venous infusion 5-fluorouracil: Topics by WorldWideScience.org

Sample records for venous infusion 5-fluorouracil

Transarterial infusion chemotherapy with a combination of gemcitabine and 5-fluorouracil in advanced pancreatic carcinoma

International Nuclear Information System (INIS)

Shi Haifeng; Jin Zhengyu; Yang Ning; Liu Wei; Pan Jie; Cai Lixing; Zhao Yupei; Zhou Zhiqiang

2002-01-01

Objective: To retrospectively analyze the effectiveness of transarterial infusion chemotherapy of gemcitabine and 5-fluorouracil in advanced pancreatic carcinoma. Methods: Twenty-two patients with advanced pancreatic carcinoma were treated with transarterial infusion chemotherapy. Gemcitabine and 5-fluorouracil was administered to the patients via an interarterial catheter. Then the tumor response rate and clinical benefit were observed. Results: A clinical benefit was obtained in 8 patients (36.4%). The tumor response rate was 13.6%. Median survival for all the patients was 6.1 months. Median time to tumor progression was 2.9 months. Conclusion: Transarterial infusion chemotherapy with a combination of gemcitabine and 5-fluorouracil appears to have good clinical benefit and may prolong the survival time of patients with advanced pancreatic carcinoma
Continuous infusion of chemotherapy: focus on 5-fluorouracil and fluorodeoxyuridine

NARCIS (Netherlands)

Poorter, R. L.; Bakker, P. J.; Veenhof, C. H.

1998-01-01

Continuous infusion of chemotherapy is one of the developments to try to improve the treatment of metastatic cancer. There is a sound theoretical rationale to deliver cytotoxic drugs as a continuous infusion. Furthermore, the development of reliable venous access devices and portable infusion pumps
Response of colo-rectal hepatic metastases to concomitant radiotherapy and intravenous infusion 5 fluorouracil

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Rotman, M.; Kuruvilla, A.M.; Choi, K.; Bhutiani, I.; Aziz, H.; Rosenthal, J.; Braverman, A.; Marti, J.; Brandys, M.

1986-12-01

Twenty-three patients with colo-rectal hepatic metastases were retrospectively reviewed after completing treatment with split course liver irradiation and continually infused concomitant intravenous 5-fluorouracil. Although no patient attained a complete response, an objective partial response was documented in 15 (Responders). The Responders had a median survival of 45 weeks whereas Non-responders had a median survival of 17 weeks. Patients with metastatic disease solely in the liver or those with a Karnofsky performance score (k.p.s) of over sixty, had a median survival of 49 weeks. Patients with multiple organ metastatic involvement had a median survival of 25 weeks and those with a Karnofsky with less than 60 had a median survival of 27 weeks. (p values of 0.006 and 0.03, respectively.) The overall survival of the group completing treatment was 30 weeks, and 19 patients (83%) achieved subjective palliation. The patients tolerated therapy well. There was minimal hematological toxicity; 3 patients developed a leucocyte count of less than 2000 and 1 developed a platelet count of 30,000. The palliation and prolongation of survival attained with minimal complications suggest that adjuvant liver irradiation with concomitant infusion 5-fluorouracil radiosensitization may be an option to offer patients identified to be at high risk of developing subclinical liver disease.
Clinical benefit response of concurrent chemoradiotherapy with protracted 5-fluorouracil infusion in patients with locally advanced pancreatic cancer

International Nuclear Information System (INIS)

Okusaka, Takuji; Okada, Shuichi; Ishii, Hiroshi

1998-01-01

Pancreatic cancer is a highly virulent disease with a poor prognosis. Although objective tumor response to chemotherapy and/or radiotherapy is low, some patients show an improvement in their symptoms after treatments, without obvious tumor regression. We assessed the clinical benefit of concurrent chemoradiotherapy with protracted 5-fluorouracil infusion in patients with locally advanced pancreatic cancer. Sixteen patients were enrolled in this study. The clinical benefit response to the chemoradiotherapy was evaluated by 2 indicators, including pain (intensity of pain and consumption of morphine) and performance status. A patient was defined to be a clinical benefit responder if 1 of these 2 variables was positive, and the other variable was positive or stable. Seven patients (44%) responded. Six patients (38%) were classified as stable, and 3 (19%) as nonresponders. The survival period in responders was significantly longer than that in nonresponders and stable patients. Concurrent external-beam radiation therapy, with protracted 5-fluorouracil infusion, may be a meaningful treatment for locally advanced pancreatic cancer. (author)
Radical radiation therapy with 5-fluorouracil infusion and mitomycin C for oesophageal squamous carcinoma

International Nuclear Information System (INIS)

Keane, T.J.; Harwood, A.R.; Elhakim, T.; Rider, W.D.; Cummings, B.J.; Ginsberg, R.J.; Cooper, J.C.

1985-01-01

Thirty-five patients with clinically staged non-metastatic squamous carcinoma of the oesophagus were treated with radiation combined with mitomycin C, and 5-fluorouracil (5-FUra) infusion. Twenty patients were planned for a split course regimen 2250-2500 cGy in 10 fractions and chemotherapy. This dose of radiation to be repeated with another course of chemotherapy after 4 weeks rest. Fifteen patients were planned for a single course 4500-5000 cGy in 20 fractions and a single course of chemotherapy. Patients were matched for age, sex, TNM stage, and total radiation dose. There was a significant difference in survival p = 0.004 and local relapse-free rate p = 0.05 for patients receiving radiation and chemotherapy. We conclude that radiation combined with mitomycin C, and 5-FUra infusion appears to have a significant benefit compared to radiation as a single modality in the management of oesophageal squamous carcinoma. (orig.)
Chemo-radiotherapy for localized pancreatic cancer: increased dose intensity and reduced acute toxicity with concomitant radiotherapy and protracted venous infusion 5-fluorouracil

International Nuclear Information System (INIS)

Poen, Joseph C.; Collins, Helen L.; Niederhuber, John E.; Oberhelman, Harry A.; Vierra, Mark A.; Bastidas, Augusto J.; Young, Harvey S.; Slosberg, Edward A.; Jeffrey, Brooke R.; Longacre, Teri A.; Goffinet, Don R.

1996-01-01

Purpose: Although concomitant radiotherapy (RT) and bolus 5-Fluorouracil (5-FU) have been shown to improve survival in patients with resectable or locally advanced pancreatic cancer, most patients will eventually succumb to their disease. Since 1994, we have attempted to improve efficacy by administering 5-FU by protracted venous infusion (PVI). This study compares the dose intensity and acute toxicity of our current regimen utilizing 5-FU by PVI with our prior regimen of radiotherapy and bolus 5-FU. Materials and Methods: Since January, 1986, 77 patients with resectable or locally advanced adenocarcinoma of the pancreas were treated with radiation therapy. Thirteen received radiation therapy alone or a planned split-course treatment and were therefore excluded from this study. The remaining 64 patients were treated with continuous course RT and concurrent 5-FU by bolus injection for 3 days during weeks 1 and 5 (n=44) or by PVI 5-FU throughout the entire course of radiotherapy (n=20). Patients were treated on 6 or 15 MV linear accelerators with 3-4 custom shaped fields to target doses of 40-50 Gy following pancreaticoduodenectomy or 50-60 Gy for locally advanced disease. 5-FU target doses were 500 mg/m 2 for bolus injection and 200-225 mg/m 2 /day for PVI. Dose intensity was assessed for both 5-FU and radiotherapy by calculating total doses (mg/m 2 and Gy, respectively) and dose/week of treatment. The Cooperative Group Common Toxicity Scale was used to score acute hematologic and gastrointestinal toxicity. Only those endpoints which could be reliably and objectively quantified (e.g. blood counts, weight loss, treatment interruption) were evaluated. Patients with resectable and locally advanced disease were jointly and independently evaluated. Results: The patient characteristics and radiotherapy treatment techniques were similar between the two treatment groups. The mean irradiated volume was 1,323 cm 3 (95% CI: 1,210-1,436). Chemotherapy and radiotherapy dose
Phase I and pharmacologic study of 72-hour infused 5-fluorouracil and hyperfractionated cyclical radiation

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Byfield, J.E.; Frankel, S.S.; Sharp, T.R.; Hornbeck, C.L.; Callipari, F.B.

1985-04-01

The authors have studied 21 patients infused for 72 hours with 5- Fluorouracil (5-FU) at progressive doses combined with hyperfractionated radiation. The schedule was chosen as being one capable of inducing 5-FU radiosensitization (RS). All patients were started at a daily 5-FU dose of 40 mg/kg/24 hours; doses were then escalated with each subsequent treatment cycle to limiting toxicity or until taken off study. Patients received between one and six infusion cycles. Every treatment cycle included coincident hyperfractionated radiation to various body areas including the abdomen, chest, and head and neck region. Radiation fractionation was invariant; 1,000 rad were delivered in four equal fractions. Two fractions of 250 rad each were given on days 1 and 2 of each three day 5-FU cycle, i.e. at approximately 0, 8, 24, and 32 hours into the drug infusion. Patients were followed for toxicity; serum 5-FU concentrations were determined using a high pressure liquid chromatographic assay. 5-FU clearances were calculated from the mean serum drug levels and the infused drug dose. The toxicity spectrum was not found to be significantly different from infused drug alone in this dose range except when the head and neck region received coincident irradiation. In that region the two anticipated toxicities combined in what appears to be a synergistic fashion to enhance mucositis. Most toxicities including gastrointestinal and bone marrow appeared dependent on the mean serum 5-FU level as did mucositis itself. 5-FU clearance was found to be non-linear in this dose region but did not appear influenced by radiation to any part of the body.
Phase I and pharmacologic study of 72-hour infused 5-fluorouracil and hyperfractionated cyclical radiation

International Nuclear Information System (INIS)

Byfield, J.E.; Frankel, S.S.; Sharp, T.R.; Hornbeck, C.L.; Callipari, F.B.

1985-01-01

The authors have studied 21 patients infused for 72 hours with 5- Fluorouracil (5-FU) at progressive doses combined with hyperfractionated radiation. The schedule was chosen as being one capable of inducing 5-FU radiosensitization (RS). All patients were started at a daily 5-FU dose of 40 mg/kg/24 hours; doses were then escalated with each subsequent treatment cycle to limiting toxicity or until taken off study. Patients received between one and six infusion cycles. Every treatment cycle included coincident hyperfractionated radiation to various body areas including the abdomen, chest, and head and neck region. Radiation fractionation was invariant; 1,000 rad were delivered in four equal fractions. Two fractions of 250 rad each were given on days 1 and 2 of each three day 5-FU cycle, i.e. at approximately 0, 8, 24, and 32 hours into the drug infusion. Patients were followed for toxicity; serum 5-FU concentrations were determined using a high pressure liquid chromatographic assay. 5-FU clearances were calculated from the mean serum drug levels and the infused drug dose. The toxicity spectrum was not found to be significantly different from infused drug alone in this dose range except when the head and neck region received coincident irradiation. In that region the two anticipated toxicities combined in what appears to be a synergistic fashion to enhance mucositis. Most toxicities including gastrointestinal and bone marrow appeared dependent on the mean serum 5-FU level as did mucositis itself. 5-FU clearance was found to be non-linear in this dose region but did not appear influenced by radiation to any part of the body
Fluorouracil continuous infusion plus alfa interferon plus oral folinic acid in advanced colorectal cancer

NARCIS (Netherlands)

Punt, C. J.; de Mulder, P. H.; Burghouts, J. T.; Wagener, D. J.

1992-01-01

Several reports on fluorouracil (5-FU) and alfa interferon (IFN-alpha) combination therapy in patients with advanced colorectal cancer have been published. In our study high-dose continuous infusion 5-FU (60 mg/kg per 48 hours), oral folinic acid (FA) (8 x 90 mg during 5-FU), and IFN-alpha three
Pilot study of continuous-infusion 5-fluorouracil, oral leucovorin, and upper-abdominal radiation therapy in patients with locally advanced residual or recurrent upper gastrointestinal or extrapelvic colon cancer

International Nuclear Information System (INIS)

Martenson, James A.; Swaminathan, Revathi; Burch, Patrick A.; Santala, Roger G.; Schroeder, Georgene; Pitot, Henry C.; Wright, Keith; Kugler, John W.; Stella, Philip J.; Garton, Graciela R.

1997-01-01

Purpose: The purpose of this study was to develop a satisfactorily tolerated regimen of radiation therapy, continuous infusion 5-fluorouracil, and leucovorin in patients with locally advanced upper-abdominal gastrointestinal cancer. Methods and Materials: Patients with locally advanced or locally recurrent gastric, pancreatic, or extrapelvic colon cancer were eligible for this study. Radiation therapy consisted of 45 Gy in 25 fractions to the tumor and regional lymph nodes, followed by 5.4-9 Gy in three to five fractions to the tumor. Treatment with leucovorin, 10 mg orally daily, and continuous infusion 5-fluorouracil was initiated on the first day of radiation therapy. 5-Fluorouracil was administered at an initial daily dose of 125 mg/m 2 , with dose escalation planned in 25-mg increments, depending on patient tolerance. Results: Twenty-one evaluable patients participated in this study. Six were treated at the initial daily 5-fluorouracil dose of 125 mg/m 2 . One patient experienced Grade 4 anorexia and nausea. No other Grade ≥3 toxicity was observed at this dose. Fifteen evaluable patients were entered at a planned 5-fluorouracil dose of 150 mg/m 2 daily; 6 of them experienced Grade 3 toxicity, and none experienced Grade ≥ 4 toxicity. Grade 3 toxicities and the number of patients who developed each were: vomiting (three patients); nausea (two patients); diarrhea (two patients); and skin toxicity, hand-foot syndrome, catheter-related infection, and stomatitis in one patient each. Four of the six patients who experienced Grade 3 toxicity developed more than one type of Grade 3 toxicity. Conclusions: In patients with upper-abdominal gastrointestinal cancer, continuous infusion 5-fluorouracil (150 mg/m 2 daily), leucovorin (10 mg orally daily), and radiation therapy (50-54 Gy) resulted in a 40% rate of severe toxicity but no life-threatening toxicity. This clinical trial excludes, with 90% confidence, a 20% risk of Grade 4 toxicity with this combination. The 40
Phase I and II trial of five-day infused 5-fluorouracil and radiation in advanced cancer of the head and neck

International Nuclear Information System (INIS)

Byfield, J.E.; Sharp, T.R.; Frankel, S.S.; Tang, S.G.; Callipari, F.B.

1984-01-01

Eighteen patients with advanced epithelial cancers of the head and neck region were studied for their tolerance and response to combined cycles of 120-hour infused 5-fluorouracil (5-FU) and external-beam radiation therapy. 5-FU infusions were given under conditions where radiosensitization would be expected at the higher infusion doses. Coincident radiation treatments were given as four sequential daily fractions of 250 rad each administered during days 1 through 4 of each five-day infusion cycle. The patients were rested for at least nine days after each cycle or longer until toxicity was resolved. The regimen was then repeated in each patient for a total of five treatment cycles. Thereafter therapy was consolidated, usually by boost radiation without drug. In sequential patient subsets the infusion load was progressively escalated in a phase I format. The complete response rate for stage IV patients was 75% with survival benefit compared to prior results. 5-FU dose-dependent combined modality loco-regional toxicity was demonstrated without significant enhancement of systemic toxicity of any form; 5-FU dose-dependent enhanced responsiveness and survival benefit is also suggested. Further scheduling and response studies of 5-FU under radiosensitizing conditions appear warranted
Cardiotoxicity in Asymptomatic Patients Receiving Adjuvant 5-fluorouracil

DEFF Research Database (Denmark)

Nielsen, Karin; Polk, Anne; Nielsen, Dorte Lisbet

2014-01-01

Evolving evidence of cardiotoxicity in cancer patients treated with 5-fluorouracil (5-FU) has been reported. We report two different clinical manifestations of asymptomatic 5-FU-associated cardiotoxicity in patients operated for colorectal cancer and treated with adjuvant chemotherapy of 5-FU...... (bolus-injection and continuous infusion for 46 hours), folinic acid and oxaliplatin (FOLFOX). For a research study evaluating cardiac events during 5-FU treatment, Holter monitoring, electrocardiogram (ECG) and echocardiography were done and cardiac markers monitored before and during the first...... and hyperlipidemia as well as an incidental finding of negative T-waves in electrocardiogram years before 5-FU treatment. No subjective cardiac symptoms were described during infusion, but approximately 12 hours after infusion she suffered from cardiac arrest but was revived. Subsequent analysis of the Holter...
Neoadjuvant Bevacizumab, Oxaliplatin, 5-Fluorouracil, and Radiation for Rectal Cancer

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Dipetrillo, Tom; Pricolo, Victor; Lagares-Garcia, Jorge; Vrees, Matt; Klipfel, Adam; Cataldo, Tom; Sikov, William; McNulty, Brendan; Shipley, Joshua; Anderson, Elliot; Khurshid, Humera; Oconnor, Brigid; Oldenburg, Nicklas B.E.; Radie-Keane, Kathy; Husain, Syed [Brown University Oncology Group, Providence, RI (United States); Safran, Howard, E-mail: hsafran@lifespan.org [Brown University Oncology Group, Providence, RI (United States)

2012-01-01

Purpose: To evaluate the feasibility and pathologic complete response rate of induction bevacizumab + modified infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX) 6 regimen followed by concurrent bevacizumab, oxaliplatin, continuous infusion 5-fluorouracil (5-FU), and radiation for patients with rectal cancer. Methods and Materials: Eligible patients received 1 month of induction bevacizumab and mFOLFOX6. Patients then received 50.4 Gy of radiation and concurrent bevacizumab (5 mg/kg on Days 1, 15, and 29), oxaliplatin (50 mg/m{sup 2}/week for 6 weeks), and continuous infusion 5-FU (200 mg/m{sup 2}/day). Because of gastrointestinal toxicity, the oxaliplatin dose was reduced to 40 mg/m{sup 2}/week. Resection was performed 4-8 weeks after the completion of chemoradiation. Results: The trial was terminated early because of toxicity after 26 eligible patients were treated. Only 1 patient had significant toxicity (arrhythmia) during induction treatment and was removed from the study. During chemoradiation, Grade 3/4 toxicity was experienced by 19 of 25 patients (76%). The most common Grade 3/4 toxicities were diarrhea, neutropenia, and pain. Five of 25 patients (20%) had a complete pathologic response. Nine of 25 patients (36%) developed postoperative complications including infection (n = 4), delayed healing (n = 3), leak/abscess (n = 2), sterile fluid collection (n = 2), ischemic colonic reservoir (n = 1), and fistula (n = 1). Conclusions: Concurrent oxaliplatin, bevacizumab, continuous infusion 5-FU, and radiation causes significant gastrointestinal toxicity. The pathologic complete response rate of this regimen was similar to other fluorouracil chemoradiation regimens. The high incidence of postoperative wound complications is concerning and consistent with other reports utilizing bevacizumab with chemoradiation before major surgical resections.
An EORTC-IDBBC phase I study of gemcitabine and continuous infusion 5-fluorouracil in patients with metastatic breast cancer resistant to anthracyclines or pre-treated with both anthracyclines and taxanes.

NARCIS (Netherlands)

Awada, A.; Biganzoli, L.; Cufer, T.; Beex, L.V.A.M.; Lohrisch, C.; Batter, V.; Hamilton, A.; Nooij, M.A.; Piccart, M.

2002-01-01

The aim of this study was to determine the maximum tolerated dose (MTD), dose-limiting toxicities (DLT), and potential activity of combined gemcitabine and continuous infusion 5-fluorouracil (5-FU) in metastatic breast cancer (MBC) patients that are resistant to anthracyclines or have been
A Phase II study of preoperative radiotherapy and concomitant weekly irinotecan in combination with protracted venous infusion 5-fluorouracil, for resectable locally advanced rectal cancer

International Nuclear Information System (INIS)

Navarro, Matilde; Dotor, Emma; Rivera, Fernando; Sanchez-Rovira, Pedro; Vega-Villegas, Maria Eugenia; Cervantes, Andres; Garcia, Jose Luis; Gallen, Manel; Aranda, Enrique

2006-01-01

Purpose: The aim of this study was to evaluate the efficacy and tolerance of preoperative chemoradiotherapy (CRT) with irinotecan (CPT-11) and 5-fluorouracil (5-FU) in patients with resectable rectal cancer. Methods and Materials: Patients with resectable T3-T4 rectal cancer and Eastern Cooperative Oncology Group performance status 2 weekly) and 5-FU (225 mg/m 2 /day continuous infusion, 5 days/week) were concurrently administered with radiation therapy (RT) (45 Gy, 1.8 Gy/day, 5 days/week), during 5 weeks. Results: A total of 74 patients were enrolled: mean age, 59 years (20-74 years; SD, 11.7). Planned treatment was delivered to most patients (median relative dose intensity for both drugs was 100%). Grade 3/4 lymphocytopenia occurred in 35 patients (47%), neutropenia in 5 (7%), and anemia in 2 (3%). Main Grade 3 nonhematologic toxicities were diarrhea (14%), asthenia (9%), rectal mucositis (8%), and abdominal pain (8%). Of the 73 resected specimens, 13.7% (95% confidence interval [CI], 6.8-23.7) had a pathologic complete response and 49.3% (95% CI, 37.4-61.3) were downstaged. Additionally, 66.7% (95% CI, 51.1-80.0) of patients with ultrasound staged N1/N2 disease had no pathologic evidence of nodal involvement after CRT. Conclusions: This preoperative CRT schedule has been shown to be effective and feasible in a large population of patients with resectable rectal cancer
Relationship between pharmacokinetics of 5-FU in plasma and in saliva, and toxicity of 5-fluorouracil/folinic acid

NARCIS (Netherlands)

Jansman, FGA; Coenen, JLLM; De Graaf, JC; Tobi, H; Sleijfer, DT; Brouwers, JRBJ

2002-01-01

Background: Dose adaptation based on pharmacokinetic parameters has been shown to decrease toxicity of some 5-fluorouracil(5-FU)-based continuous infusion regimens. Patients and Methods: In the present study the relationship between 5-FU pharmacokinetics in plasma and in saliva, and toxicity was
Capecitabine versus 5-fluorouracil in colorectal cancer: where are we now?

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Lakshmi Chintala

2011-06-01

Full Text Available Fluorouracil (5-FU remains the most widely used agent for colorectal cancer. Capecitabine is a rationally designed 5-FU pro-drug developed to mimic the continuous infusion of 5-FU while avoiding complications and inconvenience of intravenous administration. Capecitabine is absorbed intact from the gastrointestinal tract, converted enzymatically to active 5-FU, and released directly into the tumor. Capecitabine’s efficacy and safety are shown in multiple phase III trials across different disease stages and therapy lines. Three randomized phase III trials demonstrated the equivalence of capecitabine plus oxaliplatin (XELOX versus 5-FU/leucovorin (LV/oxaliplatin (FOLFOX. The safety of capecitabine compared with 5-FU depends on the regimen of 5-FU used. The adverse event rate with oxaliplatin in combination with infusional 5-FU is similar to that of capecitabine plus oxaliplatin but is associated with more neutropenia and venous thrombotic events; capecitabine plus oxaliplatinbased regimens tend to be associated with more grade 3 diarrhea and hand-foot skin reaction. Combination therapy with capecitabine and irinotecan (CapeIRI versus 5-FU/ LV and irinotecan (FOLFIRI had more variable results; some former schedules resulted in excessive treatmentrelated toxicity. More recent data show that lower capecitabine and irinotecan doses, different schedules, and combination with targeted agents (e.g, bevacizumab have resulted in more favorable outcomes.
Schedule-selective biochemical modulation of 5-fluorouracil in advanced colorectal cancer – a phase II study

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Savage Paul

2002-05-01

Full Text Available Abstract Background 5-fluorouracil remains the standard therapy for patients with advanced/metastatic colorectal cancer. Pre-clinical studies have demonstrated the biological modulation of 5-fluorouracil by methotrexate and leucovorin. This phase II study was initiated to determine the activity and toxicity of sequential methotrexate – leucovorin and 5-fluorouracil chemotherapy in patients with advanced colorectal cancer. Methods Ninety-seven patients with metastatic colorectal cancer were enrolled onto the study. Methotrexate – 30 mg/m2 was administered every 6 hours for 6 doses followed by a 2 hour infusion of LV – 500 mg/m2. Midway through the leucovorin infusion, patients received 5-fluorouracil – 600 mg/m2. This constituted a cycle of therapy and was repeated every 2 weeks until progression. Results The median age was 64 yrs (34–84 and the Eastern Cooperative Group Oncology performance score was 0 in 37%, 1 in 55% and 2 in 8% of patients. Partial and complete responses were seen in 31% of patients with a median duration of response of 6.4 months. The overall median survival was 13.0 months. The estimated 1-year survival was 53.7%. Grade III and IV toxic effects were modest and included mucositis, nausea and vomiting. Conclusions This phase II study supports previously reported data demonstrating the modest clinical benefit of 5-FU modulation utilizing methotrexate and leucovorin in patients with metastatic colorectal cancer. Ongoing studies evaluating 5-fluorouracil modulation with more novel agents (Irinotecan and/or oxaliplatin are in progress and may prove encouraging.
Extensive forearm deep venous thrombosis following a severe infliximab infusion reaction.

Science.gov (United States)

Ryan, Barbara M; Romberg, Marielle; Wolters, Frank; Stockbrugger, Reinhold W

2004-09-01

Here we describe a patient with Crohn's disease who developed a severe infliximab infusion reaction (IIR), complicated 1 day later by severe swelling of the forearm and hand ipsilateral to the site of infliximab infusion. This proved to be extensive forearm deep venous thrombosis. The site of thrombosis and the chronological relationship with the IIR implicates a hypersensitivity to infliximab in the causation of the venous thrombosis in this case. With an increasing trend towards re-treating patients with known IIRs, clinicians should be aware of this potentially serious and previously unreported complication.
Concurrent chemoradiotherapy for esophageal cancer. Comparison between intermittent standard-dose cisplatin with 5-fluorouracil and daily low-dose cisplatin with continuous infusion of 5-fluorouracil

International Nuclear Information System (INIS)

Sai, Heitetsu; Mitsumori, Michihide; Yamauchi, Chikako; Araki, Norio; Okumura, Setsuko; Nagata, Yasushi; Nishimura, Yasumasa; Hiraoka, Masahiro

2004-01-01

Although current standard treatment for advanced esophageal cancer is intermittent standard-dose cisplatin with 5-fluorouracil (5-FU) (ISD-FP), daily low-dose cisplatin with continuous infusion of 5-FU (CLD-FP) is advocated for equivalent effectiveness and lower toxicity. The feasibility of these two concurrent chemoradiotherapeutic protocols was retrospectively reviewed for local control rate, overall survival, toxicity, and compliance in a single institutional situation. Concurrent chemoradiotherapy, using 60 Gy of radiation and ISD-FP or CLD-FP was non-randomly scheduled for 29 patients between June 1994 and March 2001. Complete response in the irradiated volume at the end of primary treatment was shown by 8 of 15 and 9 of 14 patients in the ISD-FP and CLD-FP groups, respectively. The projected overall survival rate at 2 years was 55% for stage III patients and 13% for stage IV. Median survival times were 14 months versus 15 months in the ISD-FP and CLD-FP groups, with no significant difference. Toxicities were similar, including two treatment-related deaths in each group. Chemotherapy was completed for 10 of 15 and 11 of 14 patients in the ISD-FP and CLD-FP groups, respectively. Modification of the planned regimen was more often required for the CLD-FP group. CLD-FP therapy has no apparent advantage over ISD-FP therapy from the perspective of compliance and safety. A randomized phase II clinical trial comparing ISD-FP and CLD-FP, currently being performed, is expected to provide further information. (author)

Pharmacokinetics of a 5-fluorouracil liposomal delivery system.

OpenAIRE

Simmons, S T; Sherwood, M B; Nichols, D A; Penne, R B; Sery, T; Spaeth, G L

1988-01-01

A liposomal delivery system was developed in an attempt to prolong ocular levels of 5-fluorouracil for glaucoma filtering surgery. The pharmacokinetics of the 5-fluorouracil liposomal delivery system were studied in normal pigmented rabbits with 5-fluorouracil labelled with carbon-14 (C-14). 14C 5-fluorouracil was incorporated into the liposomes at a concentration of 10 g/l and injected subconjunctivally in doses of 5 and 10 mg. Concentrations of 5-fluorouracil were assayed at 10 time interva...
Early toxicity from preoperative radiotherapy with continuous infusion 5-fluorouracil for resectable adenocarcinoma of the rectum: a Phase II trial for the Trans-Tasman Radiation Oncology Group

International Nuclear Information System (INIS)

Ngan, Samuel Y.K.; Burmeister, Bryan H.; Fisher, Richard; Rischin, Danny; Schache, David J.; Kneebone, Andrew; MacKay, John R.; Joseph, David; Bell, Andrew; Goldstein, David

2001-01-01

Purpose: To assess the toxicity and the efficacy of preoperative radiotherapy with continuous infusion 5-fluorouracil (5-FU) for locally advanced adenocarcinoma of the rectum. Methods and Materials: Eligible patients had newly diagnosed localized adenocarcinoma of the rectum within 12 cm of the anal verge, Stage T3-4, and were suitable for curative resection. Eighty-two patients were treated with radiotherapy--50.4 Gy in 28 fractions in 5.6 weeks, given concurrently with continuous infusion 5-FU, using either 96-h/week infusion at 300 mg/m 2 /day or 7-days/week infusion at 225 mg/m 2 /day. Results: The median age was 59 years (range, 27-87), and 67% of patients were male. Pretreatment stages of the rectal cancer were T3, 89% and resectable T4, 11%, with endorectal ultrasound confirmation in 67% of patients. Grade 3 acute toxicity occurred in 5 of 82 patients (6%; 95% confidence interval [CI], 2-14%). Types of surgical resection were anterior resection, 61%; abdominoperineal resection, 35%; and other procedures, 4%. There was no operative mortality. Anastomotic leakage after low anterior resection occurred in 3 of 50 patients (6%; 95% CI, 1-17%). The pathologic complete response rate was 16% (95% CI, 9-26%). Pathologic Stages T2 or less occurred in 51%. Conclusion: Preoperative radiotherapy with continuous infusion 5-FU for locally advanced rectal cancer is a safe regimen, with a significant downstaging effect. It does not seem to lead to a significant increase in serious surgical complications
Continuous 5-fluorouracil infusion plus long acting octreotide in advanced well-differentiated neuroendocrine carcinomas. A phase II trial of the Piemonte Oncology Network

International Nuclear Information System (INIS)

Brizzi, Maria P; Ferretti, Benedetta; Alabiso, Oscar; Ciuffreda, Libero; Bertetto, Oscar; Papotti, Mauro; Dogliotti, Luigi; Berruti, Alfredo; Ferrero, Anna; Milanesi, Enrica; Volante, Marco; Castiglione, Federico; Birocco, Nadia; Bombaci, Sebastiano; Perroni, Davide

2009-01-01

Well-differentiated neuroendocrine carcinomas are highly vascularized and may be sensitive to drugs administered on a metronomic schedule that has shown antiangiogenic properties. A phase II study was designed to test the activity of protracted 5-fluorouracil (5FU) infusion plus long-acting release (LAR) octreotide in patients with neuroendocrine carcinoma. Twenty-nine patients with metastatic or locally advanced well-differentiated neuroendocrine carcinoma were treated with protracted 5FU intravenous infusion (200 mg/m 2 daily) plus LAR octreotide (20 mg monthly). Patients were followed for toxicity, objective response, symptomatic and biochemical response, time to progression and survival. Assessment by Response Evaluation Criteria in Solid Tumors (RECIST) criteria showed partial response in 7 (24.1%), stable disease in 20 (69.0%), and disease progression in 2 patients. Response did not significantly differ when patients were stratified by primary tumor site and proliferative activity. A biochemical (chromogranin A) response was observed in 12/25 assessable patients (48.0%); symptom relief was obtained in 9/15 symptomatic patients (60.0%). There was non significant decrease in circulating vascular epithelial growth factor (VEGF) over time. Median time to progression was 22.6 months (range, 2.7-68.5); median overall survival was not reached yet. Toxicity was mild and manageable. Continuous/metronomic 5FU infusion plus LAR octreotide is well tolerated and shows activity in patients with well-differentiated neuroendocrine carcinoma. The potential synergism between metronomic chemotherapy and antiangiogenic drugs provides a rationale for exploring this association in the future. NCT00953394
Continuous 5-fluorouracil infusion plus long acting octreotide in advanced well-differentiated neuroendocrine carcinomas. A phase II trial of the Piemonte Oncology Network

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Ciuffreda Libero

2009-11-01

Full Text Available Abstract Background Well-differentiated neuroendocrine carcinomas are highly vascularized and may be sensitive to drugs administered on a metronomic schedule that has shown antiangiogenic properties. A phase II study was designed to test the activity of protracted 5-fluorouracil (5FU infusion plus long-acting release (LAR octreotide in patients with neuroendocrine carcinoma. Methods Twenty-nine patients with metastatic or locally advanced well-differentiated neuroendocrine carcinoma were treated with protracted 5FU intravenous infusion (200 mg/m2 daily plus LAR octreotide (20 mg monthly. Patients were followed for toxicity, objective response, symptomatic and biochemical response, time to progression and survival. Results Assessment by Response Evaluation Criteria in Solid Tumors (RECIST criteria showed partial response in 7 (24.1%, stable disease in 20 (69.0%, and disease progression in 2 patients. Response did not significantly differ when patients were stratified by primary tumor site and proliferative activity. A biochemical (chromogranin A response was observed in 12/25 assessable patients (48.0%; symptom relief was obtained in 9/15 symptomatic patients (60.0%. There was non significant decrease in circulating vascular epithelial growth factor (VEGF over time. Median time to progression was 22.6 months (range, 2.7-68.5; median overall survival was not reached yet. Toxicity was mild and manageable. Conclusion Continuous/metronomic 5FU infusion plus LAR octreotide is well tolerated and shows activity in patients with well-differentiated neuroendocrine carcinoma. The potential synergism between metronomic chemotherapy and antiangiogenic drugs provides a rationale for exploring this association in the future. Trial registration NCT00953394
Concurrent 5-fluorouracil and radiotherapy in radical treatment of frail patients with deeply invasive bladder cancer

Energy Technology Data Exchange (ETDEWEB)

Fellin, G.; Mussari, S.; Graffer, U.; Caffo, O.; Valduga, F.; Tomio, L.; Luciani, L. [S. Chiara Hospital, Trento (Italy)

2004-11-01

The radical treatment of deeply invasive bladder cancer with full dose radiotherapy and concomitant 5- fluorouracil continuous infusion is feasible even in frail patients, with an acceptable toxicity and a response rate comparable to that obtained using radiotherapy and simultaneous cisplatin. Many patients can retain a functioning bladder. (author)
Pharmacokinetics of a 5-fluorouracil liposomal delivery system.

Science.gov (United States)

Simmons, S T; Sherwood, M B; Nichols, D A; Penne, R B; Sery, T; Spaeth, G L

1988-01-01

A liposomal delivery system was developed in an attempt to prolong ocular levels of 5-fluorouracil for glaucoma filtering surgery. The pharmacokinetics of the 5-fluorouracil liposomal delivery system were studied in normal pigmented rabbits with 5-fluorouracil labelled with carbon-14 (C-14). 14C 5-fluorouracil was incorporated into the liposomes at a concentration of 10 g/l and injected subconjunctivally in doses of 5 and 10 mg. Concentrations of 5-fluorouracil were assayed at 10 time intervals from 0.5 to 96 hours in cornea, sclera, and conjunctiva and at six time intervals from 0.5 to 12 hours in aqueous. Two peak concentrations were noted at approximately one and eight hours, with measurable levels present at 96 hours. This study demonstrates the ability of this liposomal delivery system to prolong levels of 5-fluorouracial in normal pigmented rabbits. PMID:3179257
Venous plasma levels of endothelin-1 are not altered immediately after nitroglycerin infusion in healthy subjects

DEFF Research Database (Denmark)

Thomsen, L L; Iversen, Helle Klingenberg; Emmeluth, C

1995-01-01

before and immediately (5-30 s) after 80 min infusion of NTG (glyceryl trinitrate) or saline in 12 healthy subjects. On two different days separated by at least 1 week, NTG in four different doses, 0.015, 0.25, 1.0, and 2.0 micrograms. kg-1. min-1, or placebo (isotonic saline) was infused successively...... for 20 min each dose. During the infusion blood pressure and heart rate were measured. NTG infusion significantly decreased systolic blood pressure from 112.4 to 103.4 mmHg and pulse pressure from 39.3 to 29.5 mmHg. Heart rate increased from 62.7 to 73.1 beats. min-1. No changes in endothelin-1 plasma...... levels were induced by NTG infusion (2.4 pg.ml-1 before NTG vs. 2.7 pg.ml-1 after NTG) and placebo infusion also did not affect plasma endothelin-1. It is concluded that venous plasma levels of endothelin-1 are not altered immediately after NTG infusion....
Improved chemical syntheses of 5,6-dihydro-5-fluorouracil.

Science.gov (United States)

LaFrate, Andrew L; Katzenellenbogen, John A

2007-10-26

5,6-dihydro-5-fluorouracil (5-DHFU) is a metabolite of the chemotherapy drug 5-fluorouracil (5-FU) of importance for biological studies. 5-DHFU has been prepared by enzymatic reduction of 5-FU and in very low yield by hydrogenation of 5-FU; however, a practical chemical synthesis is not available. Facile racemic syntheses of 5-DHFU from 5-FU or uracil, using p-methoxybenzyl protecting groups followed by L-Selectride reduction, are reported.
Concurrent cisplatin, continuous infusion fluorouracil and radiotherapy followed by tailored consolidation treatment in non metastatic anal squamous cell carcinoma

International Nuclear Information System (INIS)

Zampino, Maria G; Orecchia, Roberto; Magni, Elena; Leonardi, Maria C; Santoro, Luigi; Petazzi, Elena; Fodor, Cristiana; Petralia, Giuseppe; Trovato, Cristina; Nolè, Franco

2011-01-01

To evaluate efficacy and feasibility of chemo-radiotherapy in patients with non-metastatic anal squamous-cell-cancer. TNM staged anal squamous-cell cancer patients were treated with pelvic radiotherapy concomitant to continuous infusion fluorouracil plus cisplatin for at least 2 cycles. In T3-T4 or any T - N+ tumours or in 'slow-responder' cases, 1-2 chemotherapy courses were subsequently administered. Tumour assessment was performed at baseline and 6-8 weeks after radiotherapy to evaluate response. 29 patients were enrolled: 4 males, 25 females; median age 57 years; baseline T1/T2/T3/T4 2/12/7/8; N involvement 17. Median dose pelvic radiotherapy was 59.4 Gy (range: 54-74). In 5 patients 2 chemotherapy courses, in 12 patients three and in 12 patients four courses were performed. At first evaluation, 27 CR (93.1%; 95% CI: 78% - 98%) and 2 SD were observed. Main grade (G) 3 toxic events were neutropenia (8%), diarrhoea (8%) and dermatitis (62%). Most frequent late events G3-G4 occurred in 14 patients: proctitis (5), dermatitis (4), bladder dysfunctions (2), sexual dysfunctions (9), lower extremity venous thromboses (2), dysuria (1), stenosis (1) and tenesmus (1). Five patients reported G1 leucopoenia. The rate of colostomy was 14%. After a median follow up of 42 months (range: 4-81), 20 patients are still alive without relapse and 3 died due to PD. The estimated 7-year DFS was 83.4% (C.I.: 68.3%-98.5%) and the estimated 7-year OS was 85.7% (C.I.: 70% - 100%). The 1-year and the estimated 7-year colostomy-free survivals were 85.9% (C.I.: 73.1% - 98.7%). Concurrent cisplatin plus fluorouracil and radiotherapy is associated with favourable local control rates and acute toxicity. Future investigations will be directed towards research into molecular biomarkers related to disease progression and resistance to chemo-radiotherapy and to the evaluation of new cytotoxic agents or targeted drugs, such as anti-epidermal growth factor receptor, concomitant to RT and to
Concurrent cisplatin, continuous infusion fluorouracil and radiotherapy followed by tailored consolidation treatment in non metastatic anal squamous cell carcinoma

Directory of Open Access Journals (Sweden)

Petralia Giuseppe

2011-02-01

Full Text Available Abstract Background To evaluate efficacy and feasibility of chemo-radiotherapy in patients with non-metastatic anal squamous-cell-cancer. Methods TNM staged anal squamous-cell cancer patients were treated with pelvic radiotherapy concomitant to continuous infusion fluorouracil plus cisplatin for at least 2 cycles. In T3-T4 or any T - N+ tumours or in "slow-responder" cases, 1-2 chemotherapy courses were subsequently administered. Tumour assessment was performed at baseline and 6-8 weeks after radiotherapy to evaluate response. Results 29 patients were enrolled: 4 males, 25 females; median age 57 years; baseline T1/T2/T3/T4 2/12/7/8; N involvement 17. Median dose pelvic radiotherapy was 59.4 Gy (range: 54-74. In 5 patients 2 chemotherapy courses, in 12 patients three and in 12 patients four courses were performed. At first evaluation, 27 CR (93.1%; 95% CI: 78% - 98% and 2 SD were observed. Main grade (G 3 toxic events were neutropenia (8%, diarrhoea (8% and dermatitis (62%. Most frequent late events G3-G4 occurred in 14 patients: proctitis (5, dermatitis (4, bladder dysfunctions (2, sexual dysfunctions (9, lower extremity venous thromboses (2, dysuria (1, stenosis (1 and tenesmus (1. Five patients reported G1 leucopoenia. The rate of colostomy was 14%. After a median follow up of 42 months (range: 4-81, 20 patients are still alive without relapse and 3 died due to PD. The estimated 7-year DFS was 83.4% (C.I.: 68.3%-98.5% and the estimated 7-year OS was 85.7% (C.I.: 70% - 100%. The 1-year and the estimated 7-year colostomy-free survivals were 85.9% (C.I.: 73.1% - 98.7%. Conclusions Concurrent cisplatin plus fluorouracil and radiotherapy is associated with favourable local control rates and acute toxicity. Future investigations will be directed towards research into molecular biomarkers related to disease progression and resistance to chemo-radiotherapy and to the evaluation of new cytotoxic agents or targeted drugs, such as anti-epidermal growth
A new venous infusion path monitoring system utilizing electrostatic induced potential.

Science.gov (United States)

Ogawa, Hidekuni; Yonezawa, Yoshiharu; Maki, Hiromichi; Caldwell, W Morton

2008-01-01

A new venous infusion pathway monitoring system has been developed for hospital and home use. The system consists of linear and digital integrated circuits and a low-power 8-bit single chip microcomputer which constantly monitors the infusion pathway intactness. A 330 kHz AC voltage, which is induced on the patient's body by electrostatic coupling from a 330 kHz pulse oscillator, can be recorded by main and reference electrodes wrapped around the infusion polyvinyl chloride tube. If the injection needle or infusion tube becomes detached, then the system detects changes in the induced AC voltages and alerts the nursing station, via the nurse call system or PHS (personal handy phone system).
Development of lattice-inserted 5-Fluorouracil-hydroxyapatite nanoparticles as a chemotherapeutic delivery system.

Science.gov (United States)

Tseng, Ching-Li; Chen, Jung-Chih; Wu, Yu-Chun; Fang, Hsu-Wei; Lin, Feng-Huei; Tang, Tzu-Piao

2015-10-01

Developing an effective vehicle for cancer treatment, hydroxyapatite nanoparticles were fabricated for drug delivery. When 5-Fluorouracil, a major chemoagent, is combined with hydroxyapatite nanocarriers by interclay insertion, the modified hydroxyapatite nanoparticles have superior lysosomal degradation profiles, which could be leveraged as controlled drug release. The decomposition of the hydroxyapatite nanocarriers facilitates the release of 5-Fluorouracil into the cytoplasm causing cell death. Hydroxyapatite nanoparticles with/without 5-Fluorouracil were synthesized and analyzed in this study. Their crystallization properties and chemical composition were examined by X-ray diffraction and Fourier transforms infrared spectroscopy. The 5-Fluorouracil release rate was determined by UV spectroscopy. The biocompatibility of hydroxyapatite-5-Fluorouracil extraction solution was assessed using 3T3 cells via a WST-8 assay. The effect of hydroxyapatite-5-Fluorouracil particles which directly work on the human lung adenocarcinoma (A549) cells was evaluated by a lactate dehydrogenase assay via contact cultivation. A 5-Fluorouracil-absorbed hydroxyapatite particles were also tested. Overall, hydroxyapatite-5-Fluorouracils were prepared using a co-precipitation method wherein 5-Fluorouracil was intercalated in the hydroxyapatite lattice as determined by X-ray diffraction. Energy dispersive scanning examination showed the 5-Fluorouracil content was higher in hydroxyapatite-5-Fluorouracil than in a prepared absorption formulation. With 5-Fluorouracil insertion in the lattice, the widths of the a and c axial constants of the hydroxyapatite crystal increased. The extraction solution of hydroxyapatite-5-Fluorouracil was nontoxic to 3T3 cells, in which 5-Fluorouracil was not released in a neutral phosphate buffer solution. In contrast, at a lower pH value (2.5), 5-Fluorouracil was released by the acidic decomposition of hydroxyapatite. Finally, the results of the lactate
Compatibility of 5-fluorouracil and total parenteral nutrition solutions.

Science.gov (United States)

Hardin, T C; Clibon, U; Page, C P; Cruz, A B

1982-01-01

The physicochemical stability and availability of 0.1% 5-fluorouracil solutions in D5W and a typical total parenteral nutrition solution (hypertonic dextrose and crystalline amino acids) were studied in both glass and Viaflex delivery systems. Serial samples collected over a 48-hour period were assayed for 5-fluorouracil concentration using a high performance liquid chromatographic technique. Changes in the pH as well as precipitate formation were also investigated. There was no reduction in the amount of 5-fluorouracil at 48 hours in either the glass or plastic system, regardless of whether the drug was added to D5W or to the total parenteral nutrition solution. No pH changes or precipitates were observed. These findings indicate that 5-fluorouracil is compatible with and available from total parenteral solutions of hypertonic dextrose and amino acid in both plastic and glass containers. Use of such a system would allow for (1) a reduction in vascular access in patients receiving both treatments and (2) continued administration of nutritional support without the requirement for additional fluid volume.
Advanced colorectal carcinoma. A prospective randomized trial of sequential methotrexate, 5-fluorouracil, and leucovorin versus 5-fluorouracil alone.

Science.gov (United States)

Machiavelli, M; Leone, B A; Romero, A; Rabinovich, M G; Vallejo, C T; Bianco, A; Pérez, J E; Rodríguez, R; Cuevas, M A; Alvarez, L A

1991-06-01

One hundred and twenty-five previously untreated patients bearing metastatic or advanced recurrent (inoperable) colorectal carcinoma and measurable disease were prospectively randomized. Those in arm A received 5-fluorouracil (5-FU), 1,200 mg/m2 i.v. infusion over 2 h, while those in arm B received methotrexate (MTX), 200 mg/m2 i.v. (push injection), followed 20 h later by 5-FU, 1,200 mg/m2 i.v. infusion over 2 h, plus calcium leucovorin (LV), 25 mg i.m. every 6 h for eight doses beginning 24 h after MTX administration. Cycles were repeated every 15 days. All patients receiving treatment were evaluable for toxicity and survival, and 118 patients were evaluable for response. The objective regression rate (complete plus partial response) was 12% (7 of 58) in arm A and 28% (17 of 60) in arm B (p = 0.049). No change was observed in 24% (14 of 58) in arm A and in 35% (21 of 60) in arm B (p = 0.28), while progressive disease was registered in 64% (37 of 58) and 37% (22 of 60) in arms A and B, respectively (p = 0.006). Median duration of response was 3 months in arm A and 5 months in arm B (p = 0.39). The median survival was 8.3 months in arm A and 11.2 months in arm B (p = 0.25). No statistically significant differences were found when objective regression and survival were related to site of primary tumor, performance status, and number of involved organs. There were two drug-related deaths in arm B due to severe myelosuppression followed by mucositis and sepsis. Of nonhematologic toxicities, diarrhea was more frequently observed in arm B, as were mucositis and infectious complications. Our results indicate that the sequential schedule MTX-5-FU-LV with 20-h intervals between MTX and 5-FU is superior in terms of objective regression to 5-FU alone given at the dose and schedule used in the present study. However, MTX-5-FU-LV did not have a significant impact on survival.
Cardiotoxicity in cancer patients treated with 5-fluorouracil or capecitabine

DEFF Research Database (Denmark)

Polk, Anne; Vaage-Nilsen, Merete Bech; Vistisen, Kirsten

2013-01-01

To systematically review the incidence, manifestations and predisposing factors for cardiovascular toxicity in cancer patients treated with systemic 5-fluorouracil or capecitabine.......To systematically review the incidence, manifestations and predisposing factors for cardiovascular toxicity in cancer patients treated with systemic 5-fluorouracil or capecitabine....
Activity and toxicity of oxaliplatin and bolus fluorouracil plus leucovorin in pretreated colorectal cancer patients: a phase 2. study

Energy Technology Data Exchange (ETDEWEB)

Ferraresi, V.; Buccilli, A.; Giannarelli, D.; Ciccarese, M. [Regina Elena Cancer Institute, Rome (Italy). Dept. of Medical Oncology; Giampaolo, M.A.; Gabriele, A.; Buccilli, A.; Gamucci, T. [Azienda Sanitaria Locale, Frosinone (Italy). Complex Operative Unit of Medical Oncology

2005-06-15

The aim of the current study was to evaluate the activity and toxicity of a combination of oxaliplatin with bolus fluorouracil and leucovorin in colorectal cancer (CRC) patients pretreated for advanced disease with various schedules including continuous fluorouracil infusion. Thirty consecutive patients with pretreated advanced CRC received oxaliplatin 130 mg/m{sup 2} by 2-h infusion dl, leucovorin 100 mg/m{sup 2} by 1-h infusion followed by fluorouracil 425 mg/m{sup 2} i.v. bolus from day 1 to 3 every 3 weeks for a maximum of 6 cycles. The best overall response rate in an intent-to-treat analysis was 13% (2 complete responses and 2 partial responses) (95% CI, 1.2-25.5%) and 37% of patients obtained stable disease with a tumor growth control rate of 50% (95% CI, 32.1-67.9%). The median progression-free survival was 4.0 months (95% CI, 1.4-6.5 months) and median overall survival was 12.0 months (95% CI, 9.9-14.1 months). The independent prognostic factors for improved overall survival were a good performance status and a response/stabilization of disease to chemotherapy. Severe neutropenia was quite common (43.3% of patients and 14.4% of cycles), although complicated by fever only in one case (3.3% of patients). There was one toxic death. In conclusion, the study combination showed an interesting rate of tumor growth control in a cohort of patients previously treated for advanced disease with various schedules including continuous fluorouracil infusion.
New solid state forms of antineoplastic 5-fluorouracil with anthelmintic piperazine

Science.gov (United States)

Moisescu-Goia, C.; Muresan-Pop, M.; Simon, V.

2017-12-01

The aim of the present study was to asses the formation of solid forms between the 5-fluorouracil chemotherapy drug and the anthelmintic piperazine. Two new solid forms of antineoplastic agent 5-fluorouracil with anthelmintic piperazine were obtained by liquid assisted ball milling and slurry crystallization methods. The Nsbnd H hydrogen bonding donors and C = O hydrogen bonding acceptors of 5-fluorouracil allow to form co-crystals with other drugs delivering improved properties for medical applications, as proved for other compounds of pharmaceutical interest. Both new solid forms were investigated using X-ray powder diffraction (XRD), differential thermal analysis (DTA) and Fourier transform infrared (FTIR) spectroscopy. The XRD results show that by both methods were successfully synthesized new solid forms of 5-fluorouracil with piperazine. According to FTIR results the form prepared by lichid assisted grinding process was obtained as co-crystal and the other one, prepared by slurry method, resulted as a salt.
Sequential chemotherapy with dose-dense docetaxel, cisplatin, folinic acid and 5-fluorouracil (TCF-dd) followed by combination of oxaliplatin, folinic acid, 5-fluorouracil and irinotecan (COFFI) in metastatic gastric cancer: results of a phase II trial.

Science.gov (United States)

Dalla Chiesa, Matteo; Tomasello, Gianluca; Buti, Sebastiano; Rovere, Rodrigo Kraft; Brighenti, Matteo; Lazzarelli, Silvia; Donati, Gianvito; Passalacqua, Rodolfo

2011-01-01

To evaluate a new strategy of two sequential, intensified chemotherapy regimens in metastatic gastric cancer. Chemo-naïve patients with metastatic gastric cancer were enrolled to receive 4 cycles of TCF-dd (docetaxel initially 85 mg/m(2) and cisplatin initially 75 mg/m(2) on day 1 [later modified due to toxicity: 70 and 60 mg/m(2) respectively], l-folinic acid 100 mg/m(2) on days 1 and 2, 5-fluorouracil 400 mg/m(2) bolus and then 600 mg/m(2) as a 22 h continuous infusion on day 1 and 2, every 14 days). Subsequently, patients with CR, PR or SD received 4 cycles of COFFI (oxaliplatin 85 mg/m(2), irinotecan 140 mg/m(2), l-folinic acid 200 mg/m(2), 5-fluorouracil bolus 400 mg/m(2) on day 1 followed by 2,400 mg/m(2) as a 48 h continuous infusion, every 14 days). In both regimens pegfilgrastim 6 mg subcutaneously on day 3 was included. Forty consecutive patients were enrolled. TCF-dd regimen achieved an ORR of 55% (95% CI, 40-70). Twenty-three patients proceeded to COFFI. After this regimen the ORR was then increased to 60% (95% CI, 45-75). Among the 21 patients treated with TCF-dd after the protocol amendments, main grade 3-4 toxicities were: neutropenia (29%), thrombocytopenia (19%), asthenia (24%) and diarrhea (14%). COFFI caused grade 3-4 neutropenia (all not febrile) and diarrhea in 35% and 17% of patients respectively. A sequential strategy with TCF-dd followed by COFFI is very active and may be of special interest in selected patients.
Venous damage prevention by defibrotide in vinorelbine-treated patients.

Science.gov (United States)

Mare, M; Maisano, R; Caristi, N; Adamo, V; Altavilla, G; Carboni, R; Munaò, S; La Torre, F

2003-09-01

The aim of our study was to evaluate the incidence of venous toxicity induced by vinorelbine administration in patients who received a preventive therapy with defibrotide. From July 1996 to July 2002 we treated 203 patients with vinorelbine, 51 with vinorelbine alone and 152 with vinorelbine in combination with other drugs via peripheral vein infusion. Of the 203 patients, 123 were male and 80 female with a median age of 67 years (range 18 to 82 years), and 118 were chemotherapy-naive. Defibrotide was delivered i.v. at a dose of 400 mg in 250 ml normal saline. After infusion of 125 ml over about 15 min, vinorelbine mixed with 10 ml normal saline was delivered as quick brief repeated pulses over 5 min through the plastic tube, followed by infusion of the remaining defibrotide. The specific Rittenberg scale was used to assess venous irritation episodes. Among a total of 1336 vinorelbine infusions, with a median of five infusions per patient, the incidence of venous irritation episodes graded according to Rittenberg scale was 1.1% (15), of which 0.6% (8) were grade 2 and 0.5% (7) grade 1. Globally, 15 patients (7.3%) developed venous toxicity after a median of 3 infusions (range 1-14), but no patient had more than one event. Our findings support the use of defibrotide as an effective, safe and low-cost means for preventing vinorelbine-related venous damage.
Prevention of 5-fluorouracil-caused growth inhibition in Sordaria fimicola.

Science.gov (United States)

Schoen, H F; Berech, J

1977-02-01

Growth (dry weight accumulation) of Sordaria fimicola in standing liquid culture (sucrose-nitrate-salts-vitamins) is inhibited by the presence of 5 muM 5-fluorouracil in the medium. This inhibition is completely prevented by uracil, deoxyuridine, and 5-bromouracil, partly prevented (40 to 90% of growth observed without 5-fluorouracil) by uridine, thymidine, and 5-bromodeoxyuridine, and slightly prevented by trifluorothymine, cytosine, cytidine, deoxycytidine, and 5-methylcytosine (all at 0.5 to 1 mM). Thymidine and thymine riboside were without any apparent effect. Growth is also inhibited by 0.2 mM 6-azauracil, and this inhibition was completely prevented by uracil and uridine, partly prevented by deoxyuridine, 5-bromouracil, cytidine, and 5-methylcytosine, and slightly prevented by thymine, thymidine, 5-bromodeoxyuridine, cytosine, and deoxycytidine. The data suggest that the observed inhibition of growth by 5-fluorouracil is due to inhibition of both ribonucleic acid and deoxyribonucleic acid synthesis. The data also allow inferences concerning pyrimidine interconversions in S. fimicola; i.e., thymine can be anabolized to thymidylic acid without first being demethylated, although demethylation appears to occur also.

5-Fluorouracil:carnauba wax microspheres for chemoembolization: an in vitro evaluation.

Science.gov (United States)

Benita, S; Zouai, O; Benoit, J P

1986-09-01

5-Fluorouracil:carnauba wax microspheres were prepared using a meltable dispersion process with the aid of a surfactant as a wetting agent. It was noted that only hydrophilic surfactants were able to wet the 5-fluorouracil and substantially increased its content in the microspheres. No marked effect was observed in the particle size distribution of the solid microspheres as a function of the nature of the surfactant. Increasing the stirring rate in the preparation process decreased, first, the mean droplet size of the emulsified melted dispersion in the vehicle during the heating process, and, consequently, the mean particle size of the solidified microspheres during the cooling process. 5-Fluorouracil cumulative release from the microspheres followed first-order kinetics, as shown by nonlinear regression analysis. Although the kinetic results were not indicative of the true release mechanism from a single microsphere, it was believed that 5-fluorouracil release from the microspheres was probably governed by a dissolution process, rather than by a leaching process through the carnauba wax microspheres.
In vitro radiosensitization by oxaliplatin and 5-fluorouracil in a human colon cancer cell line

International Nuclear Information System (INIS)

Kjellstroem, Johan; Kjellen, Elisabeth; Johnsson, Anders

2005-01-01

The current study was designed to compare the radiosensitizing effects of oxaliplatin and 5-fluorouracil (5FU) in a human colon cancer cell line. A human colon cancer cell line (S1) was treated with various doses of oxaliplatin, 5FU, radiation, and combinations thereof. Various clinically used schedules were mimicked. 5FU was either incubated during 1 h ('bolus') or 24 h ('continuous infusion'). When combining oxaliplatin and 5FU, an isobologram analysis revealed synergistic effects, regardless of 5FU schedule. The IC 10 and IC 50 -doses for the drugs where then combined with radiotherapy. With equitoxic drug doses (IC 50 ), radiosensitization was observed in the following order: oxaliplatin>5FU 24 h>5FU 1 h exposure. The degree of potentiation corresponded to approximately 0.8 Gy, 0.7 Gy, and 0.2 Gy, respectively. In this experimental setting, oxaliplatin seemed to be a better radiosensitizer than 5FU, and longer incubation time with 5FU was better than short exposure
A phase II study using vinorelbine and continuous 5-fluorouracil in patients with advanced head and neck cancer

DEFF Research Database (Denmark)

Larsen, Susanne; Serup-Hansen, Eva; Andersen, Lisbeth J

2007-01-01

Seventy patients with advanced head and neck cancer were treated with vinorelbine and continuous 5-FU administered in a central venous catheter. Over all response was 36% with 9% complete responses. The most common grade 3 and 4 toxicities were stomatitis (13), infection (5), pain related...... to vinorelbine infusion (4), skin toxicity (3). Thirty one patients had grade 3 or 4 leukopenia. Treatment was complicated by venous thrombosis in the central venous catheter in one case. A majority of patients experienced dose reduction of one or both drugs or treatment delays due to toxicity. Median time...... to progression was 4.7 months and overall median survival 6.6 months. We conclude that the regimen is feasible and tolerated with moderate toxicity. Response rates and time to progression are comparable to other studies with multi agent treatment...
Double-modulation of 5-Fluorouracil by methotrexate and leucovorin in advanced colorectal-carcinoma.

Science.gov (United States)

Leone, B; Romero, A; Rabinovich, M; Vallejo, C; Bianco, A; Perez, J; Rodriguez, R; Cuevas, M; Machiavelli, M; Paris, A; Lacava, J

1993-11-01

A phase II trial was performed to evaluate the efficacy and toxicity of a double modulation of 5-fluorouracil (5-FU) by methotrexate (MTX) and leucovorin (LV) as first line chemotherapy in advanced colorectal carcinoma. Between January 1990, and April 1992, 42 patients with metastatic or advanced recurrent (inoperable) colorectal cancer were entered into the study. Therapy consisted of a sequential combination of MTX, LV and 5-FU. MTX was administered at a dose of 150 mg/m2 over 20 minutes I.V. infusion at hour (h) 0, followed 19 h later by LV 50 mg/m2 over 2 h infusion. 5-FU 900 mg/m2 was given by I.V. push injection at h 20. Starting 24 h after MTX administration all patients received LV 15 mg/m2 intramuscularly every 6 h for six doses. Treatment was repeated every 15 days until progressive disease, severe toxicity, or death. Four patients were considered not evaluable for response. Objective regression (OR) was observed in 14 of 38 patients (37%, 95% confidence interval 23-53%). Two patients (5%) obtained complete response (CR) and 12 (32%) partial response (PR). Median time to treatment failure was 6 months (range 1-21). Median survival for the whole group of patients was 13 months (range 1-27). Toxicity was within acceptable limits but one therapy-related death due to severe leukopenia and sepsis was observed. Double modulation of 5-FU with MTX and low dose of LV is an active regimen against advanced colorectal carcinoma and represents a promising strategy that should be further explored.
Choice of infusion-sampling mode for tracer studies of free fatty acid metabolism

International Nuclear Information System (INIS)

Jensen, M.D.; Rogers, P.J.; Ellman, M.G.; Miles, J.M.

1988-01-01

To determine the preferred infusion-sampling mode for isotopic studies of free fatty acid (FFA) metabolism, tracer [( 14 C]palmitate) was infused into the left ventricle of five anesthetized dogs, and tracee ([ 3 H]palmitate) was infused into three separate peripheral veins of each dog. The [ 14 C]palmitate specific activity (SA) was lower in mixed venous than arterial blood, and [ 3 H]palmitate SA was equal in both sites. The actual infusion rate of [ 3 H]palmitate [2.15 +/- 0.31 X 10(5) disintegrations/min (dpm).kg-1.min-1] could be accurately predicted (2.14 +/- 0.32 X 10(5) dpm.kg-1.min-1) using the known [ 14 C]palmitate infusion rate and the arterial plasma [ 14 C]-to-[ 3 H]palmitate ratio. In contrast, the mixed venous [ 14 C]-to-[ 3 H]palmitate ratio resulted in overestimates (P less than 0.05) of the actual [ 3 H]palmitate infusion rate. In summary, venous tracer infusion with arterial blood sampling for FFA tracer studies provides the most accurate estimates of tracee rate of appearance
Dégradation photocatalytique du 5-fluorouracile par un système UV ...

African Journals Online (AJOL)

Mots clés : 5-fluorouracile, UV-A/TiO2, eau ultra pure, eau bicarbonatée, eau usée. Photocatalytic degradation of 5-fluorouracil by a UV-A / TiO2 system: effect of catalyst concentration and pollutant, pH and dilution matrices. ABSTRACT. Residues of anticancer drugs are among the emerging micropollutants often identified ...
Design and Synthesis of New Cholesterol-Conjugated 5-Fluorouracil: A Novel Potential Delivery System for Cancer Treatment

Directory of Open Access Journals (Sweden)

Awwad A. Radwan

2014-08-01

Full Text Available Cholesterol-conjugated 5-fluorouracil prodrugs were designed to be carried in vivo via low density lipoproteins (LDL and subsequently undergo LDL-receptor-mediated internalisation into cancer cells. In vivo anti-cancer evaluation was performed using 5-fluorouracil-cholesterol conjugate in a mouse model. The obtained prodrugs were more potent than 5-fluorouracil control drug at the same 5-fluorouracil content (3 mg·kg−1.
Cytotoxicity and radiosensitising activity of synthesized dinitrophenyl derivatives of 5-fluorouracil

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Khoshayand Mohammad

2012-07-01

Full Text Available Abstract Background and the purpose of the study Dual functional agents in which nitroaromatic or nitroheterocyclic compounds are attached through a linker unit to mustards and aziridines have shown higher cytotoxicities than the corresponding counterparts to both aerobic and hypoxic cells and enhanced radiosensitizing activity. In the present investigation cytotoxicity and radiosensitizing activity of 2,4-dinitrobenzyl, 2,4-dinitrobenzoyl, and 2,4-dinitrophenacetyl derivatives of 5-fluorouracil which was assumed to release cytotoxic active quinone methidide and 5-fluorouracil under hypoxic conditions on HT-29 cell line under both aerobic and hypoxic conditions was investigated. Methods 5-fluorouracil derivative X-XIII were prepared by the reaction of the corresponding di-nitro substituted benzyl, benzoyl and phenacetyl halides with 5-fluorouracil protected at N-1 with di-t-butoxydicarbonate (BOC in dimethyl formamide (DMF in the presence of the potassium carbonate followed by hydrolysis of the blocking group by potassium carbonate in methanol. Cytotoxicity of fluorouracil VIII and tested compounds X-XIII against HT-29 cell line under both aerobic and hypoxic conditions after 48 hrs incubation were measured by determination of the percent of the survival cells using 3-(4,5-Dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay and percent of the dead cells using propidium iodide(PI-digitonine assay and results were used to calculate the corresponding IC50 values. Radiosensitization experiments were carried out by irradiation of the incubations with a 60Co source and clonogenic assay was performed to determine the cell viabilities following treatment with the tested compounds and/or radiation. Sensitization Enhancement Ratio (SER of each tested compound was obtained from the radiation survival curves in the absence and presence of each sensitizer for 37% survival respectively. Results and major conclusion Findings of the present study
Modification of the radiosensitizing effect of metronidazole by 5-fluorouracil and caffeine

International Nuclear Information System (INIS)

Esel'baeva, G.O.; Ermekova, S.A.

1986-01-01

A study was made of the combined effect of 5-fluorouracil, metronidazole, caffeine and radiation on radiosensitivity of Pliss lymphosarcoma and protein synthesis rate during the first few hours following irradiation. A complete regression of the tumor was noted in 100% of animals after a 3-fold exposure. Effective postirradiation inhibition of protein synthesis was achieved by injection of metronidazole and caffeine together with 5-fluorouracil
Dose escalation of cisplatin with 5-fluorouracil in concurrent chemoradiotherapy for esophageal carcinoma

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Lin Qiang; Gao Xianshu; Qiao Xueying; Zhou Zhiguo; Zhang Jun; Yang Xiangran; Wan Xin

2006-01-01

Objective: To define the maximum-tolerated dose (MTD) and observe the side effect of escalating cisplatin with 5-fluorouracil in concurrent chemoradiotherapy for esophageal carcinoma in Chinese, with toxicity studied. Methods: Previously untreated fifteen Chinese patients suffering from esophageal carcinoma received conventional fractionation radiotherapy, with 5 daily fractions of 2.0 Gy per week. The total radiation dose was 60 Gy. Concurrent chemotherapy dose escalation was given by the relatively safe and kidney-sparing modified Fibonacci sequence. The starting dose was cisplatin 37.5 mg/m 2 D1 and 5-fluorouracil 500 mg/m 2 D1-5, respectively. This regimen was repeated 4 times every 28 days. Escalation dose was cisplatin 7.5 mg/m 2 and 5- fluorouracil 100 mg/m 2 . Every. cohort contained at least 3 patients. If no dose-limiting toxicity(DLT) was observed, the next dose level was opened for entry. These courses were repeated until DLT appeared. MTD was declared as one dose level below which DLT appeared. Results: DLT was defined as grade 3 radiation-induced esophagitis at the level of cisplatin 60 mg/m2, 5-fluorouracil 700 mg/m 2 . MTD was defined as cisplatin 52.5 mg/m 2 , 5- fiuorouracil 700 mg/m 2 . The major side effect were radiation-induced esophagitis, leucopenia, nausea, vomiting and anorexia. Conclusion: Maximun tolerated dose of cisplatin with 5-fiuorouracil in concurrent ehemoradiotherapy in the Chinese people with esophageal carcinoma were eisplatin 52.5 mg/m2 D1,5-fluorouracil 700 mg/m 2 D1-5, repeated 4 times every 28 days. (authors)
Takotsubo Cardiomyopathy and 5-Fluorouracil: Getting to the Heart of the Matter

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Stephanie Hui-Su Lim

2013-01-01

Full Text Available Takotsubo cardiomyopathy is a rare but increasingly recognized phenomenon, which can occur as a side-effect of chemotherapeutic agents, in particular, the antimetabolite 5-fluorouracil. We describe a case of delayed Takotsubo cardiomyopathy after 3 weeks of adjuvant 5-fluorouracil for resected rectal adenocarcinoma in a 66-year-old female, supported by angiographic, electrocardiographic, and echocardiographic features. As a complication, she developed an apical mural thrombus with subsequent cerebral thromboembolic events and was successfully anticoagulated to make a full recovery. We present a review of the literature on Takotsubo cardiomyopathy secondary to 5-fluorouracil and the rare occurrence of thromboembolic complications. As this is a significant clinical phenomenon which involves a multispeciality approach to management, oncologists and cardiologists need to recognize it as a potential toxicity of a widely administered chemotherapeutic drug.
Neoadjuvant chemotherapy with cisplatin and 5-fluorouracil in advanced squamous cell carcinoma of the head and neck: a randomized Phase III study

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Lewin, Freddi; Damber, Lena; Jonsson, Haakan; Andersson, Torsten; Berthelsen, Anne; Bioerklund, Anders; Blomqvist, Erik; Evensen, Jan F.; Hansen, Hanne S.; Hansen, Olfred; Jetlund, Olav; Mercke, Claes; Modig, Hans; Overgaard, Marie; Rosengren, Bengt; Tausjoe, Johan; Ringborg, Ulrik

1997-01-01

Background and purpose: In 1986 a prospective, randomized, multi-centre trial for evaluation of neoadjuvant chemotherapy with cisplatin and 5-fluorouracil in the treatment of advanced squamous cell carcinoma of the head and neck was initiated. As survival in this group of patients is poor the purpose was to find a possible survival benefit of the chemotherapy in addition to radiotherapy compared to radiotherapy only. Methods. Four-hundred sixty-one patients from Denmark, Norway and Sweden with tumors in oral cavity, oropharynx, hypopharynx and larynx were randomized to receive either standard treatment (radiotherapy or radiotherapy followed by surgery) or neoadjuvant chemotherapy followed by standard treatment. Chemotherapy included three courses of cisplatin 100 mg/m 2 i.v. infusion on day 1 followed by 5-fluorouracil 1000 mg/m 2 per day continuous i.v. infusion for 120 hours. Radiotherapy 64-70 Gy in 2 Gy per fraction, 5 times/week, was given to patients in both treatment arms. Results: Response rate was 71% for patients randomized to chemotherapy-radiotherapy and 66% for patients randomized to standard treatment (not statistically significant). Residual tumors were excised if possible. After surgery 62% of the patients randomized to chemotherapy-radiotherapy and 60% of the patients in the standard treatment group were clinically tumor free. Conclusions: No statistically significant benefit in survival was observed for patients treated with neoadjuvant chemotherapy followed by radiotherapy. Nor was there any impact of chemotherapy on the number of patients achieving loco-regional tumor control after primary treatment
Comparative study of 5-fluorouracil and its derivative, N1-(2'-tetrahydrofuryl)-5-fluorouracil on endogenous colony forming units in spleens of mice

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Ueno, Yori

1976-01-01

The effect of intraperitoneal injection of N 1 -(2'-tetrahydrofuryl)-5-fluorouracil (FT-207) which is metabolized to 5-fluorouracil (5-FU) in vivo, on endogeneous colony forming units in the spleen (endogeneous CFU-s) was observed and compared with that of 5-FU. The 8 x 10 -4 m eqv of FT-207 injected in mice 20 minutes before x-rays irradiation of 450 rads suppressed the endogeneous CFU-s count to about 60% and about 5.5 x 10 -5 m eqv of 5-FU had the same effect. The suppression of FT-207 continued over 120 minutes and increased gradually. The effect of 5-FU was strong shortly after the injection but faded out for 120 minutes. FT-207 had almost no effect on the recovery constant (Blair) of endogeneous CFU-s for 3 days, whereas 5-FU reduced seriously, especially for the first 2 days. The differences in the effects of both compounds could not be explained on the base of the only differences in the metabolism of both compounds. (auth.)
The effect of paracetamol on 5 fluorouracil and bovine serum albumin interaction: A biophysical study

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Dahiya, Vandana; Pal, Samanwita

2018-05-01

Serum Albumin is a major carrier protein and its binding with drugs is important to examine the change in pharmacokinetic properties due to interaction amongst drugs. In the present study we have attempted to understand the relevant drug-drug interaction (DDI) between two common drugs viz, paracetamol, an anti-inflammatory and fluorouracil, an anti-cancer drug. In-vitro spectroscopic methods viz., fluorescence quenching and UV-vis absorption have been employed for the drug-bovine serum albumin (BSA) complexes studies. The binding parameters and quenching constants have been determined for BSA-Paracetamol and BSA-5Fluorouracil complex according to literature models. It is also predicted from the quenching studies that BSA-5Fluorouracil is a stronger complex than BSA-Paracetamol. On the other hand paracetamol can alter binding affinity of 5Fluorouracil towards BSA. Hence it becomes clear that although the drugs could be administered simultaneously but they influence each other's binding with protein in a concentration dependent fashion. Further these results also indicate that availability of free 5Fluorouracil in blood may increase in presence of paracetamol.
Radiochemotherapy With Cisplatin and 5-Fluorouracil After Transurethral Surgery in Patients With Bladder Cancer

International Nuclear Information System (INIS)

Weiss, Christian; Engehausen, Dirk G.; Krause, Frens S.; Papadopoulos, Thomas; Dunst, Juergen; Sauer, Rolf; Roedel, Claus

2007-01-01

Purpose: To give an update on the long-term outcome of an intensified protocol of combined radiochemotherapy (RCT) with 5-fluorouracil (5-FU) and cisplatin after initial transurethral resection of bladder tumor (TURBT) with selective organ preservation in bladder cancer. Methods and Materials: One hundred twelve patients with muscle-invading or high-risk T1 (G3, associated Tis, multifocality, diameter >5 cm) bladder cancer were enrolled in a protocol of TURBT followed by concurrent cisplatin (20 mg/m 2 /day as 30-min infusion) and 5-FU (600 mg/m 2 /day as 120-h continuous infusion), administered on Days 1-5 and 29-33 of radiotherapy. Response to treatment was evaluated by restaging TURBT 4-6 weeks after RCT. In case of invasive residual tumor or recurrence, salvage cystectomy was recommended. Results: Ninety-nine patients (88.4%) had no detectable tumor at restaging TURBT; 71 patients (72%) have been continuously free from local recurrence or distant metastasis. Superficial relapse occurred in 13 patients and muscle-invasive recurrence in 11 patients. Overall and cause-specific survival rates for all patients were 74% and 82% at 5 years, respectively. Of all surviving patients, 82% maintained their own bladder, 79% of whom were delighted or pleased with their urinary condition. Hematologic Grade 3/4 toxicity occurred in 23%/6% and Grade 3 diarrhea in 21% of patients. One patient required salvage cystectomy due to a shrinking bladder. Conclusion: Concurrent RCT with 5-FU/cisplatin has been associated with acceptable acute and long-term toxicity. Overall and cause-specific survival rates are encouraging. More than 80% of patients preserved their well-functioning bladder
Cytotoxicity and Radiosensitising Activity of Synthesized Dinitrophenyl Derivatives of 5-Fluorouracil

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Khosrou Abdi

2012-07-01

Full Text Available Background and the purpose of the study: Dual functional agents in which nitroaromatic or nitroheterocyclic compounds are attached through a linker unit to mustards and aziridines have shown higher cytotoxicities than the corresponding counterparts to both aerobic and hypoxic cells and enhanced radiosensitizing activity. In thepresent investigation cytotoxicity and radiosensitizing activity of 2,4-dinitrobenzyl, 2,4-dinitrobenzoyl, and 2,4-dinitrophenacetyl derivatives of 5-fluorouracil which was assumed to release cytotoxic active quinone methidide,and 5-fluorouracil under hypoxic conditions on HT-29 cell line under both aerobic and hypoxic conditions wasinvestigated.Methods: 5-fluorouracil derivative X-XIII were prepared by the reaction of the corresponding di-nitro substitutedbenzyl, benzoyl and phenacetyl halides with 5-fluorouracil protected at N-1 with di-t-butoxydicarbonate (BOC in dimethyl formamide (DMF in the presence of the potassium carbonate followed by hydrolysis of the blocking,group by potassium carbonate in methanol. Cytotoxicity of fluorouracil VIII and tested compounds X-XIII against HT-29cell line under both aerobic and hypoxic conditions after 48 hrs incubation were measured by determination of the percent of the survival cells using 3-(4,5-Dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay and percent of the dead cells using propidium iodide(PI-digitonine assay and results were used to calculate the corresponding IC50 values. Radiosensitization experiments were carried out by irradiation of the incubations with a 60Co source and clonogenic assay was performed to determine the cell viabilities following treatment with the tested compounds and/or radiation. Sensitization Enhancement Ratio (SER of each tested compound was obtained from the radiation survival curves in the absence and presence of each sensitizer for 37% survival respectively.Results and major conclusion: Findings of the present study showed that
Clinical experience with chronomodulated infusional 5-fluorouracil chemoradiotherapy for pancreatic adenocarcinoma

International Nuclear Information System (INIS)

Keene, Kimberly S.; Rich, Tyvin A.; Penberthy, David R.; Shepard, Robert C.; Adams, Reid; Jones, R. Scott

2005-01-01

Purpose: To evaluate retrospectively the efficacy and chronic toxicities of concurrent radiotherapy and chronomodulated infusion 5-fluorouracil (5-FU) in patients with pancreatic adenocarcinoma. Methods and Materials: Twenty-eight patients with pancreatic adenocarcinoma were treated between January 1997 and May 2000 with 5-FU chronomodulated chemoradiotherapy. Chronomodulated delivery of chemotherapy was chosen on the basis of a lower toxicity profile in the treatment of GI malignancies. The median age was 64 years. Of the 28 patients, 12 were men and 16 were women. Eight patients had unresectable disease and 20 were treated after pancreatic resection. The median radiation dose was 50.4 Gy given in 28 fractions. The median field length and width was 10.6 cm and 10.9 cm, respectively. Concurrent chemotherapy with 5-FU was administered 5 d/wk, with a median total dose of 8.4 g/m 2 (300 mg/m 2 /d). Chronomodulated 5-FU delivery consisted of a low basal infusion for 16 h followed by an 8-h escalating-deescalating infusion peaking at 10 PM. Survival and recurrence data were evaluated using Kaplan-Meier actuarial analysis. Toxicities were recorded using the Radiation Therapy Oncology Group grading system. Results: The median follow-up for all patients was 26 months (range, 4-68 months). The median overall survival for the 20 patients treated postoperatively was 34 months, with a 3- and 5-year actuarial survival rate of 40% and 21%, respectively. If the 3 patients with carcinoma of the ampulla were removed from the data set, the mean overall survival in the resected patients was 34 months, with a 3-year and 5-year actuarial survival rate of 40% and 17%, respectively. The 8 unresectable patients had a median overall survival of 14 months, and none lived past 2 years. No patient experienced Grade 3 or 4 hematologic toxicity or weight loss. Five patients had nausea and dehydration requiring i.v. fluids; only one (4%) was hospitalized. Four patients required a dose reduction
Efeito do colírio de 5-fluorouracil sobre o epitélio corneano íntegro de coelhos Effects of 5-fluorouracil eye drops on intact rabbit corneal epithelium

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Lucieni Cristina Barbarini Ferraz

2003-08-01

Full Text Available OBJETIVO: Observar os efeitos da aplicação tópica de 5-fluorouracil (5-FU sobre o epitélio corneano íntegro. MÉTODOS: Foram utilizados 10 coelhos albinos (14 olhos, divididos em: grupo controle (GC, 4 olhos nos quais não se administraram drogas, grupo 1 (G1, 5 olhos que receberam 5-fluorouracil na concentração 1,25% e grupo 2 (G2, 5 olhos que receberam 5-fluorouracil na concentração de 2,5%. A droga foi instilada 4 vezes por dia, durante 7 dias, quando os animais foram sacrificados, os olhos removidos, separando-se a córnea que foi preparada de modo convencional para estudo em microscópico eletrônico de varredura. RESULTADOS: GC: observaram-se células de formato hexagonal, claras, escuras e intermediárias, compondo o epitélio corneano de coelhos. Presença de numerosas microplicas, principalmente nas células claras. Cada célula possui cerca de 1 a 3 criptas. Nos animais do G1, observou-se maior número de células escuras, regiões com diminuição no número de criptas; alterações da superfície celular, protusão na região do núcleo e descamação de células epiteliais. Os do G2 tiveram aumento de microprojeções na superfície celular, modificações nas junções intercelulares até separação de células adjacentes; diminuição do número e variabilidade no tamanho das criptas. As alterações mais freqüentes ocorreram nas células da periferia da córnea. CONCLUSÃO: O 5-fluorouracil teve efeitos deletérios no epitélio íntegro corneano de coelhos. As alterações observadas foram mais importantes nos animais que receberam a droga mais concentrada (G2 e mais freqüentes na periferia da córnea.PURPOSE: To assess the influence of the antiproliferative agent (5-FU on the intact rabbit corneal epithelium. METHODS: 10 rabbits (14 eyes,were divided into: control group (CG, 4 eyes without drug administration; G1, 5 eyes underwent treatment with topical 12.5 mg/ml 5-fluorouracil and G2, 5 eyes received 5-fluorouracil
Electrochemical behavior of an anticancer drug 5-fluorouracil at methylene blue modified carbon paste electrode

International Nuclear Information System (INIS)

Bukkitgar, Shikandar D.; Shetti, Nagaraj P.

2016-01-01

A novel sensor for the determination of 5-fluorouracil was constructed by electrochemical deposition of methylene blue on surface of carbon paste electrode. The electrode surface morphology was studied using Atomic force microscopy and XRD. The electrochemical activity of modified electrode was characterized using cyclic voltammetry and differential pulse method. The developed sensor shows impressive enlargement in sensitivity of 5-fluorouracil determination. The peak currents obtained from differential pulse voltammetry was linear with concentration of 5-fluorouracil in the range 4 × 10 −5 –1 × 10 −7 M and detection limit and quantification limit were calculated to be 2.04 nM and 6.18 nM respectively. Further, the sensor was successfully applied in pharmaceutical and biological fluid sample analysis. - Highlights: • Electrochemical oxidation of 5-fluorouracil has been investigated for first time at methylene blue modified carbon paste electrode • The electrode process was irreversible and diffusion controlled • Probable electrochemical mechanism was proposed which involved two proton and two electron transfer reaction • The LOD and LOQ values were calculated to be 2.04 nM and 6.18 nM, respectively, with good selectivity and sensitivity. • Proposed method was applied to 5-Fluorouracil determination in pharmaceutical and spiked human urine samples
Alpha- and Beta-Cyclodextrin Inclusion Complexes with 5-Fluorouracil: Characterization and Cytotoxic Activity Evaluation

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Cristina Di Donato

2016-12-01

Full Text Available Cyclodextrins are natural macrocyclic oligosaccharides able to form inclusion complexes with a wide variety of guests, affecting their physicochemical and pharmaceutical properties. In order to obtain an improvement of the bioavailability and solubility of 5-fluorouracil, a pyrimidine analogue used as chemotherapeutic agent in the treatment of the colon, liver, and stomac cancers, the drug was complexed with alpha- and beta-cyclodextrin. The inclusion complexes were prepared in the solid state by kneading method and characterized by Fourier transform-infrared (FT-IR spectroscopy and X-ray powder diffractometry. In solution, the 1:1 stoichiometry for all the inclusion complexes was established by the Job plot method and the binding constants were determined at different pHs by UV-VIS titration. Furthermore, the cytotoxic activity of 5-fluorouracil and its complexation products were evaluated using the 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay on MCF-7 (breast cancer cell line, Hep G2 (hepatocyte carcinoma cell line, Caco-2 (colon adenocarcinoma cell line, and A-549 (alveolar basal epithelial carcinoma cell line. The results showed that both inclusion complexes increased the 5-fluorouracil capability of inhibiting cell growth. In particular, 5-fluorouracil complexed with beta-cyclodextrin had the highest cytotoxic activity on MCF-7; with alpha-cyclodextrin the highest cytotoxic activity was observed on A-549. The IC50 values were equal to 31 and 73 µM at 72 h, respectively. Our results underline the possibility of using these inclusion complexes in pharmaceutical formulations for improving 5-fluorouracil therapeutic efficacy.

Synthesis and Characterization of 5-Fluorouracil-Loaded Glutaraldehyde Crosslinked Chitosan Hydrogels

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Zehra ÖZBAŞ

2016-11-01

Full Text Available In this work, the characterization and drug release behavior of 5-fluorouracil-loaded glutaraldehyde-crosslinked chitosan hydrogels have been studied. The structure of the hydrogels were investigated by Fourier transform infrared spectroscopy, differential scanning calorimetry, and X-ray diffraction, also their properties were compared with those of the drug-unloaded hydrogels. The equilibrium swelling studies and drug release profiles were determined at 37°C in two different pHs (2.1 and 7.4. The results indicated that increased chitosan concentration in the hydrogel decreased the swelling and drug release values and the hydrogels released nearly the same amount of 5-fluorouracil in both acidic (~59% and basic medium (~50%.
A systematic review of the pathophysiology of 5-fluorouracil-induced cardiotoxicity

DEFF Research Database (Denmark)

Polk, Anne; Vistisen, Kirsten; Vaage-Nilsen, Merete

2014-01-01

BACKGROUND: Cardiotoxicity is a serious side effect to treatment with 5-fluorouracil (5-FU), but the underlying mechanisms are not fully understood. The objective of this systematic review was to evaluate the pathophysiology of 5-FU- induced cardiotoxicity. METHODS: We systematically searched Pub...
Internal radiation dosimetry of F-18-5-fluorouracil

International Nuclear Information System (INIS)

Shani, J.; Schlesinger, T.; Wolf, W.

1980-01-01

The projected internal radiations dose to different human organs per millicurie of injected F-18-5-Fluorouracil is calculated from rat distribution studies and human urinary excretion data. The calculations assume a similar distribution of labelled drug in humans as in rats, inasmuch as preliminary human distribution studies appeared to validate the use of the rat model for human dosimetry calculations. (U.K.)
Randomized phase II study of 5-fluorouracil hepatic arterial infusion with or without antineoplastons as an adjuvant therapy after hepatectomy for liver metastases from colorectal cancer.

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Yutaka Ogata

Full Text Available Antineoplastons are naturally occurring peptides and amino acid derivatives found in human blood and urine. Antineoplaston A10 and AS2-1 reportedly control neoplastic growth and do not significantly inhibit normal cell growth. Antineoplastons contain 3-phenylacetylamino-2, 6-piperidinedione (A10, phenylacetylglutamine plus phenylacetylisoglutamine (A10-I, and phenylacetylglutamine plus phenylacetate (AS2-1. This open label, non- blinded randomized phase II study compared the efficacy of hepatic arterial infusion (HAI with 5-fluorouracil,with or without antineoplastons as a postoperative therapy for colorectal metastasis to the liver.Sixty-five patients with histologically confirmed metastatic colon adenocarcinoma in liver, who had undergone hepatectomy, and/or thermal ablation for liver metastases were enrolled between 1998- 2004 in Kurume University Hospital. Patients were randomly assigned to receive systemic antineoplastons (A10-I infusion followed by per-oral AS2-1 plus HAI (AN arm or HAI alone (control arm based on the number of metastases and presence/ absence of extra-hepatic metastasis at the time of surgery. Primary endpoint was cancer-specific survival (CSS; secondary endpoints were relapse-free survival (RFS, status and extent of recurrence, salvage surgery (rate and toxicity.Overall survival was not statistically improved (p=0.105 in the AN arm (n=32. RFS was not significant (p=0.343. Nevertheless, the CSS rate was significantly higher in the AN arm versus the control arm (n=33 with a median survival time 67 months (95%CI 43-not calculated versus 39 months (95%CI 28-47 (p=0.037 and 5 year CSS rate 60% versus 32% respectively. Cancer recurred more often in a single organ than in multiple organs in the AN arm versus the control arm. The limited extent of recurrent tumours in the AN arm meant more patients remained eligible for salvage surgery. Major adverse effects of antineoplastons were fullness of the stomach and phlebitis. No
The post-occipital spinal venous sinus of the Nile crocodile (Crocodylus niloticus: Its anatomy and use for blood sample collection and intravenous infusions

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Jan G. Myburgh

2014-05-01

Full Text Available The post-occipital sinus of the spinal vein is often used for the collection of blood samples from crocodilians. Although this sampling method has been reported for several crocodilian species, the technique and associated anatomy has not been described in detail in any crocodilian, including the Nile crocodile (Crocodylus niloticus. The anatomy of the cranial neck region was investigated macroscopically, microscopically, radiographically and by means of computed tomography. Latex was injected into the spinal vein and spinal venous sinus of crocodiles to visualise the regional vasculature. The spinal vein ran within the vertebral canal, dorsal to and closely associated with the spinal cord and changed into a venous sinus cranially in the post-occipital region. For blood collection, the spinal venous sinus was accessed through the interarcuate space between the atlas and axis (C1 and C2 by inserting a needle angled just off the perpendicular in the midline through the craniodorsal cervical skin, just cranial to the cranial borders of the first cervical osteoderms. The most convenient method of blood collection was with a syringe and hypodermic needle. In addition, the suitability of the spinal venous sinus for intravenous injections and infusions in live crocodiles was evaluated. The internal diameter of the commercial human epidural catheters used during these investigations was relatively small, resulting in very slow infusion rates. Care should be taken not to puncture the spinal cord or to lacerate the blood vessel wall using this route for blood collection or intravenous infusions.
Limb venous distension evokes sympathetic activation via stimulation of the limb afferents in humans

Science.gov (United States)

Cui, Jian; McQuillan, Patrick M.; Blaha, Cheryl; Kunselman, Allen R.

2012-01-01

We have recently shown that a saline infusion in the veins of an arterially occluded human forearm evokes a systemic response with increases in muscle sympathetic nerve activity (MSNA) and blood pressure. In this report, we examined whether this response was a reflex that was due to venous distension. Blood pressure (Finometer), heart rate, and MSNA (microneurography) were assessed in 14 young healthy subjects. In the saline trial (n = 14), 5% forearm volume normal saline was infused in an arterially occluded arm. To block afferents in the limb, 90 mg of lidocaine were added to the same volume of saline in six subjects during a separate visit. To examine whether interstitial perfusion of normal saline alone induced the responses, the same volume of albumin solution (5% concentration) was infused in 11 subjects in separate studies. Lidocaine abolished the MSNA and blood pressure responses seen with saline infusion. Moreover, compared with the saline infusion, an albumin infusion induced a larger (MSNA: Δ14.3 ± 2.7 vs. Δ8.5 ± 1.3 bursts/min, P blood pressure responses. These data suggest that venous distension activates afferent nerves and evokes a powerful systemic sympathoexcitatory reflex. We posit that the venous distension plays an important role in evoking the autonomic adjustments seen with postural stress in human subjects. PMID:22707559
Degradation of the chemotherapy drug 5-fluorouracil on medical-grade silver surfaces

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Risinggård, Helene Kjær; Cooil, Simon; Mazzola, Federico; Hu, Di; Kjærvik, Marit; Østli, Elise Ramleth; Patil, Nilesh; Preobrajenski, Alexei; Andrew Evans, D.; Breiby, Dag W.; Trinh, Thuat T.; Wells, Justin W.

2018-03-01

The degradation of the chemotherapy drug 5-fluorouracil by a non-pristine metal surfaces is studied. Using density functional theory, X-ray photoelectron spectroscopy and X-ray absorption spectroscopy we show that the drug is entirely degraded by medical-grade silver surfaces, already at body temperature, and that all of the fluorine has left the molecule, presumably as HF. Remarkably, this degradation is even more severe than that reported previously for 5-fluorouracil on a pristine monocrystalline silver surface (in which case 80% of the drug reacted at body temperature) [1]. We conclude that the observed reaction is due to a reaction pathway, driven by H to F attraction between molecules on the surface, which results in the direct formation of HF; a pathway which is favoured when competing pathways involving reactive Ag surface sites are made unavailable by environmental contamination. Our measurements indicate that realistically cleaned, non-pristine silver alloys, which are typically used in medical applications, can result in severe degradation of 5-fluorouracil, with the release of HF - a finding which may have important implications for the handling of chemotherapy drugs.
Comparison between the efficacy of microneedling combined with 5-fluorouracil vs microneedling with tacrolimus in the treatment of vitiligo.

Science.gov (United States)

Mina, Mary; Elgarhy, Lamia; Al-Saeid, Hanan; Ibrahim, Zeinab

2018-03-12

Several treatment modalities had been used for the treatment of vitiligo, but the optimal treatment has not yet been identified. To study the efficacy of microneedling with 5-flurouracil vs its efficacy with tacrolimus in the treatment of vitiligo. Twenty-five patients with vitiligo were subjected to microneedling of 2 patches of vitiligo with dermapen, then application of 5-fluorouracil to 1 patch and tacrolimus on the other patch. This procedure was repeated every 2 weeks for every patient for maximum 6 months (12 sessions). The patients were followed up for 3 months after the last session. The overall repigmentation was significantly higher in 5-fluorouracil-treated patches compared with tacrolimus. Excellent improvement occurred in 48% of 5- flurouracil-treated patches while only in 16% of tacrolimus-treated patches. In the acral parts, 40% of the patches treated with 5-fluorouracil achieved excellent improvement (repigmentation >75%), while no patch in the acral parts achieved excellent improvement with tacrolimus. However, there was significant difference between the 2 drugs,regarding inflammation, ulceration, and hyperpigmentation which occurred with 5-fluorouracil. Microneedling combined with 5-fluorouracil or tacrolimus is safe and effective treatment of vitiligo. However, 5-fluorouracil achieved a greater percentage of repigmentation than tacrolimus particularly in the acral parts. © 2018 Wiley Periodicals, Inc.
Impact of application of bio-amniotic membrane immersed in 5-fluorouracil solution in trabeculectomy on rabbit retina

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Chenming Zhang

2013-01-01

Full Text Available Background : To observe the impact of application of bio-amniotic membrane immersed in 5-fluorouracil solution in trabeculectomy on the retina in a rabbit model. Materials and Methods : Healthy white New Zealand rabbits were randomly assigned into three groups with 20 in each group. Bio-amniotic membranes of 4 × 5 mm immersed in either physiological saline/water for 10 min, or 25 mg/mL 5-fluorouracil solution for 5 and 10 min, respectively, were applied on rabbit eyes during trabeculectomy. At 7, 14, 21, and 28 days of postoperation, five rabbits from each group were examined with electroretinogram (ERG. After being examined for eye pressure and bleb morphology, rabbits were sacrificed by air embolism and their retinas were collected and examined by transmission electron microscopy (TEM. In addition, 5-fluorouracil amount in bio-amniotic membranes was measured using high-performance liquid chromatography. Results: Each bio-amniotic membrane could absorb 59.004 μg and 75.828 μg 5-fluorouracil after being immersed in 5-fluorouracil solution for 5 and 10 min, respectively. Application of these bio-amniotic membranes in trabeculectomy could promote the formation of well-functioning bleb and maintain intraocular pressure, although it had no effect on retina structures as examined with ERG and TEM. Conclusion: Application of 5-FU soaked bio-amniotic membrane in rabbit eye trabeculectomy is effective and safe.
Phase II study of docetaxel in combination with epirubicin and protracted venous infusion 5-fluorouracil (ETF) in patients with recurrent or metastatic breast cancer. A Yorkshire breast cancer research group study.

Science.gov (United States)

Humphreys, A C; Dent, J; Rodwell, S; Crawford, S M; Joffe, J K; Bradley, C; Dodwell, D; Perren, T J

2004-06-01

This study was originally designed as a phase I/II study, with a dose escalation of docetaxel in combination with epirubicin 50 mg m(-2) and 5-fluorouracil (5-FU) 200 mg m(-2) day(-1). However, as dose escalation was not possible, the study is reported as a phase II study of the combination to assess response and toxicity. A total of 51 patients with locally advanced or metastatic breast cancer were treated on this phase II study, with doses of docetaxel 50 mg m(-2), epirubicin 50 mg m(-2) and infusional 5-FU 200 mg m(-2) day(-1) for 21 days. The main toxicity of this combination was neutropenia with 89% of patients having grade 3 and 4 neutropenia, and 39% of patients experiencing febrile neutropenia. Nonhaematological toxicity was mild. The overall response rate in the assessable patients was 64%, with median progression-free survival of 38 weeks, and median survival of 70 weeks. The ETF regimen was found to be toxic, and it was not possible to escalate the dose of docetaxel above the first dose level. This regimen has therefore not been taken any further, but as a development of this a new study is ongoing, combining 3-weekly epirubicin, weekly docetaxel and capecitabine, days 1-14.
In vivo Confocal Laser Microscopy for monitoring of actinic keratosis treatment: a comparison with histopathologic assessment after treatment with topical 5% 5-fluorouracil.

Science.gov (United States)

Ishioka, P; Maia, M; Rodrigues, S B; Lellis, R F; Hirata, S H

2017-11-24

Histological examination is the gold standard for actinic keratosis diagnosis; however, it is not always a feasible approach. Reflectance confocal microscopy (RCM) is a non-invasive technique that may be an alternative for monitoring actinic keratoses treatment response. Topical 5-fluorouracil is indicated for actinic keratosis multiple lesions and for field cancerization treatment. To assess the RCM accuracy, sensibility and specificity for actinic keratosis, considering as a gold standard the histopathological examination; as well as to evaluate the efficacy of 5% 5-fluorouracil treatment. This is a prospective study in actinic keratosis patients between August 2014 and November 2015. RCM analyses were performed in one randomly selected actinic keratosis lesion of the upper limbs by two independent observers before and after 5% 5-fluorouracil treatment. At the end of treatment and with clinical bleaching of treated lesions, histological examination was performed by two pathologists. A total of 50 lesions were enroled, and 40 lesions presented complete clinical bleaching after treatment and were included in the final analysis. Accuracy, sensibility and specificity means among observers were 83.8%, 84.6% and 83.3%, respectively. After 5-fluorouracil treatment, actinic keratosis was diagnosed in 45.0% (observer 1) and 32.5% (observer 2) of subjects according to RCM and in 32.5% of subjects according to histological examination. Considering RCM observers diagnosis, the concordance was substantial (k 0.637, P keratosis therapeutic response to 5-fluorouracil, presenting efficacy comparable to histological examination. Additionally, the results suggest that 5-fluorouracil may be a satisfactory option for therapeutic control of this condition. © 2017 European Academy of Dermatology and Venereology.
Triamcinolone Acetonide and 5-Fluorouracil Intralesional Combination Injection in Keloid Treatment

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Jono Hadi Agusni

2017-03-01

Full Text Available Objective: To evaluate the effectiveness of steroid and 5-fluorouracil (5-FU injection combination for keloid management. Methods: A 22-year-old female patient was presented with recurrent skin lesions. The skin lesions first appeared 10 years prior to consultation, had been surgically excised, and were given triamcinolone acetonide injection. However, no improvement was observed. A decision was made to use and evaluate treatment using an intralesional 4 mg (0.1 ml of 40 mg/ml triamcinolone acetonide and 45 mg (0.9 ml of 50 mg/ml 5-FU injection combination for 5 weeks. Results: Clinical improvements were observed in the third week as the lesions softened and pruritic sensation dinimished. At the end of the fifth week, improvements in the form of keloid lesion flattening and size reduction were observed. Conclusions: Intralesional injection using a combination of triamcinolone acetonide and 5-fluorouracil is effective for keloid lesion treatment.
5-Fluorouracil-radiation interactions in human colon adenocarcinoma cells

International Nuclear Information System (INIS)

Buchholz, Daniel J.; Lepek, Katherine J.; Rich, Tyvin A.; Murray, David

1995-01-01

Purpose: To determine the effect of cellular proliferation and cell cycle stage on the ability of postirradiation 5-fluorouracil (5-FU) to radiosensitize cultured human colon adenocarcinoma Clone A cells. Methods and Materials: Cell survival curves were generated for irradiated: (a) log- and plateau-phase Clone A cells; and (b) Clone A cells separated by centrifugal elutriation into the various phases of the cell cycle; with and without postirradiation treatment with 100 μg/ml 5-FU. Results: Postirradiation treatment with 5-FU sensitized proliferating cells to a greater degree than it sensitized cells growing in plateau phase. The β component of cell kill in log-phase cells was increased by a factor of 1.5 with a sensitizer enhancement ratio of 1.21 at the 0.01 survival level. Plateau-phase cells showed less radiosensitization (sensitizer enhancement ratio of 1.13 at the 0.01 survival level); however, there was a mild increase in both α and β kill in plateau-phase cells. Elutriated G 1 cells were the most radiosensitive, independent of treatment with 5-FU. The phase of the cell cycle had little effect on the ability of fluorouracil to radiosensitize Clone A cells. Conclusion: Proliferating cells are more susceptible to radiosensitization with 5-FU than plateau-phase cells are, but this effect appears to be independent of the phase of the cell cycle
Treatment results of nasopharyngeal carcinoma with chemotherapy (cisplatin and 5-fluorouracil) and radiation therapy

International Nuclear Information System (INIS)

Fuwa, Nobukazu; Kato, Eriko; Ito, Yosiyuki; Kikuti, Yuzo

1995-01-01

Sixteen patients with nasopharyngeal cancer were treated with a combination chemotherapy consisting of cisplatin and 5-fluorouracil and radiation therapy. Systemic chemotherapy with cisplatin (50 mg/m 2 , 2 days) and 5-fluorouracil (700 mg/m 2 , 5 days) was given successively with radiation therapy. The complications of chemotherapy were generally acceptable except one patient who was shocked by cisplatin. The survival rate was significantly improved compared with historical control cases. The main reason for this effectiveness was the improvement of localized control. The suppression of distant metastasis is the subject of future research. (author)
Synthesis, development and preclinical study of EDDA based 99mTc-5-fluorouracil for brain imaging

International Nuclear Information System (INIS)

Ahmed, N.; Nuclear Medicine, Oncology and Radiotherapy Institute; Saeed, A.M.; Fatima, S.; Irfan, J.; Zia, M.; Zia, N.; Raza, A.

2016-01-01

5-Fluorouracil is used as an antineoplastic agent in solid tumors. The study was conducted to analyze the effect of EDDA on synthesis of 5-fluorouracil with 99m Tc. The 99m Tc-5-flurouracil was formulated using stannous agent, and EDDA. This complex was stable for 4 h, with post labeling efficiency of 92 %. The distribution study in animal model showed that after 30 min 35 ± 8 % of injected dose cross the blood brain barrier and excreted through kidney with no sign of toxicity. It was concluded that the addition of EDDA modified the labeling side in 5-fluorouracil for 99m Tc, which localized in brain and hence can be used further for brain imaging study. (author)
Double modulation of 5-fluorouracil by methotrexate and high-dose L-leucovorin in advanced colorectal cancer.

Science.gov (United States)

Romero, A O; Perez, J E; Cuevas, M A; Lacava, J A; Sabatini, C L; Dominguez, M E; Rodriguez, R; Barbieri, M R; Ortiz, E H; Salvadori, M A; Acuña, L A; Acuña, J M; Langhi, M J; Amato, S; Machiavelli, M R; Leone, B A; Vallejo, C T; Lorusso, V; DeLena, M

1998-02-01

A phase II trial was performed to evaluate the efficacy and toxicity of a double modulation of 5-fluorouracil (5-FU) by methotrexate (MTX) and L-leucovorin (L-LV) in patients with advanced recurrent (inoperable) or metastatic colorectal carcinoma (ACC). Between July 1993 and October 1995, 41 patients with ACC received a regimen that consisted of MTX 150 mg/m2 i.v., infused over a 20-minute period at hour 0, followed 19 hours later by L-LV 250 mg/m2 in a 2-hour i.v. infusion. 5-FU, 900 mg/m2, was administered by i.v. push injection at hour 20. Beginning 24 hours after MTX administration, all patients received four doses of L-LV, 15 mg/m2 i.m., every 6 hours. Cycles were repeated every 15 days. Two patients were not assessable for response. Objective regression was observed in 11 of 39 (28%) patients, [95% confidence interval (CI), 14-42%]. One (2%) patient achieved complete response (CR) and 10 (26%) partial response (PR). No change was recorded in 15 (39%) patients and progressive disease was noted in 13 (33%) patients. The median time to treatment failure was 6 months and the median survival time was 10 months. Toxicity was within acceptable limits, but one therapy-related death due to severe leukopenia was observed. The dose-limiting toxicity was mucositis. Eight episodes of grade 3 or 4 stomatitis were observed, and were responsible for dosage modifications of MTX and 5-FU. In conclusion, further in experimental and clinical studies are clearly necessary in order to design the best modulatory strategy of 5-FU.
Intolerable toxicity of simultaneous 5-fluorouracil-radiotherapy in the treatment of advanced gastrointestinal tumours

International Nuclear Information System (INIS)

Higi, M.; Arndt, D.; Schmidt, C.; Schmitt, G.

1983-01-01

Simultaneous application of 5-fluorouracil and radiotherapy is generally accepted in the treatment of gastrointestinal tumours. However, in 10 patients with metastatic gastrointestinal tumours we oberseved intolerable toxicity during this combined treatment regimen. Because of gastrointestinal and haematological toxicity the combined modality was interrupted in all patients. Given sequentially, this regimen was tolerated. Our experience indicates that an intolerable high rate of toxicity has to be taken into consideration in case of the simultaneous combination of 5-fluorouracil and radiotherapy. (orig.) [de
Total body topical 5-fluorouracil for extensive non-melanoma skin cancer

NARCIS (Netherlands)

van Ruth, Serge; Jansman, Frank G. A.; Sanders, Cornelis J.

Background Topical 5-fluorouracil 5% cream is one of the treatment modalities for non-melanoma skin cancer (NMSC). There is a lack of suitable therapies to treat patients with extensive NMSC. In this paper we report two patients with extensive NMSC treated by total body application of topical
Continuous insulin administration via complex central venous catheter infusion tubing is another risk factor for blood glucose imbalance. A retrospective study.

Science.gov (United States)

Maury, Eric; Vitry, Paola; Galbois, Arnauld; Ait-Oufella, Hafid; Baudel, Jean-Luc; Guidet, Bertrand; Offenstadt, Georges

2012-06-14

We assessed the potential impact of infusion tubing on blood glucose imbalance in ICU patients given intensive insulin therapy (IIT). We compared the incidence of blood glucose imbalance in patients equipped, in a nonrandomized fashion, with either conventional tubing or with a multiport infusion device. We retrospectively analyzed the nursing files of 35 patients given IIT through the distal line of a double-lumen central venous catheter. A total of 1389 hours of IIT were analyzed for occurrence of hypoglycemic events [defined as arterial blood glucose below 90 mg/dL requiring discontinuation of insulin]. Twenty-one hypoglycemic events were noted (density of incidence 15 for 1000 hours of ITT). In 17 of these 21 events (81%), medication had been administered during the previous hour through the line connected to the distal lumen of the catheter. Conventional tubing use was associated with a higher density of incidence of hypoglycemic events than multiport infusion device use (23 vs. 2 for 1,000 hours of IIT; rate ratio = 11.5; 95% confidence interval, 2.71-48.8; p tubing carrying other medications can lead to the delivery of significant amounts of unscheduled products. Hypoglycaemia observed during IIT could be related to this phenomenon. The use of a multiport infusion device with a limited dead volume could limit hypoglycemia in patients on IIT.
OPTIMIZATION AND CHARACTERIZATION OF 5-FLUOROURACIL TRANSETHOSOMES FOR SKIN CANCER THERAPY USING RESPONSE SURFACE METHODOLOGY.

OpenAIRE

Jessy Shaji; Rinki Bajaj.

2018-01-01

The purpose of the present study was to develop, optimize and characterize 5-Fluorouracil transethosomes for skin cancer targeting. 5- Fluorouracil transethosomes were prepared by cold method using phospholipon 90G as the lipid and sodium cholate as edge activator. The size reduction was done by probe sonication. Central composite design was used for optimization procedure with different concentration of phospholipon 90G and sodium cholate as independent variables. The response variables sele...

Oral fluoropyrimidine versus intravenous 5-fluorouracil for the treatment of advanced gastric and colorectal cancer: Meta-analysis.

Science.gov (United States)

Zhang, Linlin; Xing, Xiaoli; Meng, Fanlu; Wang, Yan; Zhong, Diansheng

2018-01-01

5-Fluorouracil (5-Fu) is one of the most commonly prescribed antineoplastic agents against gastric and colorectal cancers. Continuous infusion would be the optimal way of its administration, however, may usually cause thrombosis, infection, and prolonged hospital stay. Oral fluoropyrimidines would be an attractive alternative, but their efficiency and toxicities for the treatment of gastric and colorectal cancer are still obscure as compared with infusion 5-Fu. Literature retrieval, trials selection and assessment, data collection, and statistic analysis were performed according to the Cochrane Handbook. The outcome measures were tumor response rate, progression-free survival, overall survival, and adverse effects. Twenty-nine randomized controlled trials, comprising totally 15 154 patients, were included. Meta-analysis showed similar overall outcome in terms of response rate (1.01; 95% confidence interval [CI], 0.92-1.12), progression-free survival (hazard ratio 1.00; 95%CI, 0.94-1.06), and overall survival (hazard ratio 0.96; 95%CI, 0.92-1.01) between oral fluoropyrimidine-based and intravenous 5-Fu-based regimens in gastric and colorectal cancer patients. The risk of grade 3/4 neutropenia, thrombocytopenia, and stomatitis was more prominent in intravenous 5-Fu-based regimens; while more frequent grade 3/4 hand-foot syndrome, diarrhea, and anorexia were detected in oral fluoropyrimidine-based regimens. Oral-fluoropyrimidines showed equivalent response and similar survival outcomes, but different toxicity profiles, as compared with intravenous 5-Fu. Thus, it would be a more convenient and adjustable alternative in treatment of advanced gastric and colorectal cancer. © 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.
A Phase 1/2 Study of Definitive Chemoradiation Therapy Using Docetaxel, Nedaplatin, and 5-Fluorouracil (DNF-R) for Esophageal Cancer

Energy Technology Data Exchange (ETDEWEB)

Ohnuma, Hiroyuki; Sato, Yasushi; Hirakawa, Masahiro; Okagawa, Yutaka; Osuga, Takahiro; Hayashi, Tsuyoshi; Sato, Tsutomu; Miyanishi, Koji; Kobune, Masayoshi; Takimoto, Rishu [Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, Sapporo (Japan); Sagawa, Tamotsu [Division of Gastroenterology, Hokkaido Cancer Center, Sapporo (Japan); Hori, Masakazu; Someya, Masanori; Nakata, Kensei; Sakata, Koh-ichi [Department of Radiology, Sapporo Medical University School of Medicine, Sapporo (Japan); Takayama, Tetsuji [Department of Gastroenterology and Oncology, University of Tokushima, Tokushima (Japan); Kato, Junji, E-mail: jkato@sapmed.ac.jp [Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, Sapporo (Japan)

2015-10-01

Purpose: Patient survival in esophageal cancer (EC) remains poor. The purpose of this study was to investigate a regimen of definitive chemoradiation therapy (CRT) that exerts good local control of EC. We performed a phase 1/2 study to assess the safety and efficacy of CRT with docetaxel, nedaplatin, and 5-fluorouracil (DNF-R). Methods and Materials: Eligible patients presented with stage IB to IV EC. Patients received 2 cycles of docetaxel (20, 30, or 40 mg/m{sup 2}) and nedaplatin (50 mg/m{sup 2}) on days 1 and 8 and a continuous infusion of 5-fluorouracil (400 mg/m{sup 2}/day) on days 1 to 5 and 8 to 12, every 5 weeks, with concurrent radiation therapy (59.4 Gy/33 fractions). The recommended dose (RD) was determined using a 3 + 3 design. Results: In the phase 1 study, the dose-limiting toxicities were neutropenia and thrombocytopenia. The RD of docetaxel was determined to be 20 mg/m{sup 2}. In the phase 2 study, grade 3 to 4 acute toxicities included neutropenia (42.8%), febrile neutropenia (7.14%), thrombocytopenia (17.9%), and esophagitis (21.4%). Grade 3 to 4 late radiation toxicity included esophagostenosis (10.7%). The complete response rate was 82.1% (95% confidence interval: 67.9-96.3%). Both the median progression-free survival and overall survival were 41.2 months. Conclusions: DNF-R showed good tolerability and strong antitumor activity, suggesting that it is a potentially effective therapeutic regimen for EC.
A Phase 1/2 Study of Definitive Chemoradiation Therapy Using Docetaxel, Nedaplatin, and 5-Fluorouracil (DNF-R) for Esophageal Cancer

International Nuclear Information System (INIS)

Ohnuma, Hiroyuki; Sato, Yasushi; Hirakawa, Masahiro; Okagawa, Yutaka; Osuga, Takahiro; Hayashi, Tsuyoshi; Sato, Tsutomu; Miyanishi, Koji; Kobune, Masayoshi; Takimoto, Rishu; Sagawa, Tamotsu; Hori, Masakazu; Someya, Masanori; Nakata, Kensei; Sakata, Koh-ichi; Takayama, Tetsuji; Kato, Junji

2015-01-01

Purpose: Patient survival in esophageal cancer (EC) remains poor. The purpose of this study was to investigate a regimen of definitive chemoradiation therapy (CRT) that exerts good local control of EC. We performed a phase 1/2 study to assess the safety and efficacy of CRT with docetaxel, nedaplatin, and 5-fluorouracil (DNF-R). Methods and Materials: Eligible patients presented with stage IB to IV EC. Patients received 2 cycles of docetaxel (20, 30, or 40 mg/m 2 ) and nedaplatin (50 mg/m 2 ) on days 1 and 8 and a continuous infusion of 5-fluorouracil (400 mg/m 2 /day) on days 1 to 5 and 8 to 12, every 5 weeks, with concurrent radiation therapy (59.4 Gy/33 fractions). The recommended dose (RD) was determined using a 3 + 3 design. Results: In the phase 1 study, the dose-limiting toxicities were neutropenia and thrombocytopenia. The RD of docetaxel was determined to be 20 mg/m 2 . In the phase 2 study, grade 3 to 4 acute toxicities included neutropenia (42.8%), febrile neutropenia (7.14%), thrombocytopenia (17.9%), and esophagitis (21.4%). Grade 3 to 4 late radiation toxicity included esophagostenosis (10.7%). The complete response rate was 82.1% (95% confidence interval: 67.9-96.3%). Both the median progression-free survival and overall survival were 41.2 months. Conclusions: DNF-R showed good tolerability and strong antitumor activity, suggesting that it is a potentially effective therapeutic regimen for EC
Effect of intra-hepatic arterial infusion chemotherapy for patients with liver metastasis from breast cancer

International Nuclear Information System (INIS)

Liu Dezhong; Li Huai; Zeng Huiying; Yang Ling

2001-01-01

Objective: To evaluate the efficacy of intra-hepatic arterial infusion chemotherapy for patients with liver metastasis from breast cancer. Methods: 1993-1998 years, Thirty four patients with liver metastasis from breast cancer had received epi-adriamycin, cisplatin, mitomycin and 5-fluorouracil by intrahepatic arterial infusion chemotherapy. Twelve patients had received embolization. Results: Six patients (17.65%) had a complete response, 12 patients (35.29%) had a partial response. The overall response rate was 52.94%. Cumulative survival rates at 1, 2, 3 and 4 years were 56.90%, 25.00%, 5.00% and 5.00% respectively (Kaplan-Meier method). The median overall survival time was 11.5 months. Conclusion: Intra-hepatic arterial infusion chemotherapy is safe and effective for liver metastasis from breast cancer and should be the first choice of treatment for these patients
Treatment of 29 patients with bulky squamous cell carcinoma of the cervix with simultaneous cisplatin, 5-fluorouracil, and split-course hyperfractionated radiation therapy

Energy Technology Data Exchange (ETDEWEB)

Heaton, D.; Yordan, E.; Reddy, S.; Bonomi, P.; Lee, M.S.; Lincoln, S.; Graham, J.; Dolan, T.; Miller, A.; Phillips, A. (Rush Presbyterian-St. Lukes Hospital, Chicago, IL (USA))

1990-09-01

Attempting to improve local disease control in bulky primary or recurrent pelvic tumors, 29 patients with squamous cell carcinoma of the cervix were treated with concomitant chemotherapy and split-course hyperfractionated radiation therapy between April 1983 and August 1988. Cisplatin (CDDP) and 5-fluorouracil (5-FU) have been shown to be radiation enhancers; furthermore, CDDP, radiation therapy, and continuous-infusion 5-FU have elicited high local response rates in head and neck squamous cell carcinoma. A pilot study of cyclical week on/week off CDDP, continuous-infusion 5-FU, and hyperfractionated radiation therapy was developed. Radiation was administered at 116 cGy twice daily, Days 1-5, every other week for a median dose of 4600 cGy to a pelvic field, with paraaortic extension if indicated. Concomitant chemotherapy included CDDP 60 mg/m2 IV Day 1 and 5-FU 600 mg/m2 IV continuous infusion for 96 hr following CDDP infusion. Patients received a median of four cycles of combined treatment, and intracavitary or interstitial brachytherapy followed in 21 patients. Local pelvic response was achieved in 29 of 29 (100%): complete response (CR) in 19 of 29 (66%), partial response (PR) in 10 of 29 (34%). Among CR patients 10 of 19 (53%) were without evidence of disease at a mean follow-up of 29 (range 12-76) months. Five-year actuarial disease-free survival among complete responders was 65%. Of the 10 CR patients 2 failed in the pelvis, for a local control rate of 17/19 (89%). Chemotherapy-related and acute radiation morbidity was minimal but 2 patients required surgical correction of radiation injury. Aggressive combination of split-course hyperfractionated radiation therapy with radiation enhancers resulted in promising local control of bulky pelvic tumor, with an acceptable complication rate, in this otherwise very poor prognostic group of patients.
Concurrent chemoradiotherapy with nedaplatin and 5-fluorouracil (5-FU) for locally advanced squamous cell carcinoma of the esophagus

International Nuclear Information System (INIS)

Kubo, Naoshi; Morimoto, Junya; Tanaka, Hiroaki

2009-01-01

Concurrent chemoradiotherapy (CRT) using cisplatin (CDDP) and 5-fluorouracil (5-FU) is the standard treatment for unresectable locally advanced esophageal carcinoma. Although this regimen has been widely accepted in Japan, the adverse effect of CDDP such as gastrointestinal and renal toxicity may sometimes be the cause of interruption of the treatment, especially among the elderly patients. Cis-diammine-glycolatoplatinum (nedaplatin: CDGP) is a new platinum agent, which was developed with the aim of decreasing renal and gastrointestinal toxicities but maintaining the effectiveness of CDDP. We reported the efficacy and safety of CRT using CDGP and 5-FU for locally advanced squamous cell carcinoma of the esophagus. Between January 2001 and December 2007, 65 patients with locally advanced esophageal cancer (39 patients with unresectable tumor (cT4) and 26 patients with distant lymphnode or bulky lymphnode metastasis) were eligible and given informed consent and cared by the Department of Surgical Oncology of Osaka City University. Patients received a continuous infusion of 5-FU (250 mg/body) on days 1-21. CDGP was administered at the dose of 10 mg/body by bolus infusion for 1 hour on days 1-5, 8-12 and 15-19 just before radiotherapy. Radiotherapy was delivered in 1.8 Gy fractions, 5 days/week for 4 weeks. For the effective cases of CRT, a surgical resection was followed subsequently and an additional radiotherapy at the dose of 20 Gy was performed for non-effective cases. Complete or partial response was achieved in 46 patients (71%). Hematologic toxicities such as grades 3 and 4 leucocytopenia developed in 19 patients and thrombocytopenia developed in 20 patients, which were well tolerated by conservative therapy. Gastrointestinal and renal toxicities were developed in only a few patients. There was no CRT-related death. Of all 65 patients, 25 patients underwent a surgical resection while 19 patients could receive a curative resection (R0 operation). In the resected
Concurrent cisplatin, infusional fluorouracil, and conventionally fractionated radiation therapy in head and neck cancer: Dose-limiting mucosal toxicity

Energy Technology Data Exchange (ETDEWEB)

Denham, J.W.; Abbott, R.L. (Royal Adelaide Hospital (Australia))

1991-03-01

After a preliminary dose-finding study involving 12 patients with advanced or locally recurrent head and neck cancer, 27 patients were treated on a phase II protocol, using fluorouracil 350 mg/m2/d by continuous intravenous (IV) infusion over 5 days, followed on the sixth day by a 2-hour IV infusion of cisplatin 50 mg/m2, administered during the first and fourth weeks of radiation therapy to total doses between 60 and 64 Gy, using 2 Gy daily fractions. Eight of these 27 patients had American Joint Committee on Cancer Staging (AJCC) stage III disease, and 12 had stage IV disease. Four had recurrent disease after surgery. Three-year follow-up is now available. Twenty-one (77.8%) remitted completely following treatment, and 11 remain free of local and regional relapse at 3 years. Four have developed systemic metastases. Following successful salvage treatment in two cases, estimated determinate survival at 3 years is 64%. Acute toxicity was manageable with this regime. Eleven instances of grade 3 Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG/EORTC) mucositis were observed, which caused interruptions to radiotherapy in only four cases. No late sequelae have so far been recorded. It is concluded that the protocol described is tolerable but probably did not cause a greater number of locoregional cures than would have been expected following conventional radiotherapy alone in this group of patients. The use of infusional fluorouracil with concurrent conventionally fractionated radiation therapy and cisplatin infusion results in mucositis that limits the dose of fluorouracil to levels that are probably subtherapeutic.
[Local treatment of cervical intraepithelial neoplasia with a 5 percent fluorouracil ointment].

Science.gov (United States)

Barten, G

1987-01-01

The results of treatment of histologically proven cervical intraepithelial neoplasia (CIN) in 10 women are described. Two of them had CIN I and 8 CIN III. All patients had a application of 5 g 5 per cent 5-fluorouracil cream in a cervical cup daily over a period of 12 hours for one week. All 10 patients have been examined colposcopically, cytological and by biopsy following therapy. In 8 women cone biopsie were done 6-12 months afterwards for having a final diagnosis 2 patients having CIN I pretherapeutically were follow up for 16 months with cytology, colposcopy and punch biopsy. In 6 cases we found better findings (Twice complete healing, twice only CIN I and twice CIN II as residues). In 4 cases severe dysplasia and carcinoma in situ could be found in endocervix. Based on these results were recommended more (not only one) treatment cycles for local efficient chemotherapy using 5 per cent 5-fluorouracil cream.
A novel class of antitumor prodrug, 1-(2'-oxopropyl)-5-fluorouracil (OFU001), that releases 5-fluorouracil upon hypoxic irradiation

International Nuclear Information System (INIS)

Shibamoto, Yuta; Zhou, Ling; Hatta, Hiroshi; Mori, Mayuko; Nishimoto, Sei-ichi

2000-01-01

We have been developing prodrugs of anticancer agents such as 5-fluorouracil (5-FU) that are activated by irradiation under hypoxic conditions via one-electron reduction. Among them, OFU001 [1-(2'-oxopropyl)-5-fluorouracil] is a prototype radiation-activated prodrug. In this study, we investigated the radiation chemical reactivity and the biological effects of OFU001. This prodrug is presumed to release 5-FU through incorporation of hydrated electrons into the antibonding σ * orbital of the C(1')-N(1) bond. Hydrated electrons are active species derived from radiolysis of water, but are readily deactivated by O 2 into superoxide anion radicals (O 2 - ·) under conditions of aerobic irradiation. Therefore, 5-FU release occurs highly specifically upon irradiation under hypoxic conditions. OFU001 dissolved in phosphate buffer released 5-FU with a G-value (mol number of molecules that are decomposed or produced by 1 J of absorbed radiation energy) of 1.9 x 10 -7 mol/J following hypoxic irradiation, while the G-value for 5-FU release was 1.0 x 10 -8 mol/J following aerobic irradiation. However, the G-values for decomposition of OFU001 were almost the same, i.e., 3.4 x 10 -7 mol/J following hypoxic irradiation and 2.5 x 10 -7 mol/J following aerobic irradiation. When hypoxically irradiated (7.5-30 Gy) OFU001 was added to murine SCCVII cells for 1-24 h, a significant cell-killing effect was observed. The degree of this cytotoxicity was consistent with that of authentic 5-FU at the corresponding concentrations. On the other hand, cytotoxicity was minimal when the cells were treated with aerobically irradiated or unirradiated OFU001. This compound had no radiosensitizing effect against SCCVII cells under either aerobic or hypoxic conditions when the drug was removed immediately after irradiation. Since hypoxia is generally most marked in tumors and irradiation is applied at the tumor site, this concept of prodrug design appears to be potentially useful for selective tumor
Design of Infusion Schemes for Neuroreceptor Imaging

DEFF Research Database (Denmark)

Feng, Ling; Svarer, Claus; Madsen, Karine

2016-01-01

for bolus infusion (BI) or programmed infusion (PI) experiments. Steady-state quantitative measurements can be made with one short scan and venous blood samples. The GABAA receptor ligand [(11)C]Flumazenil (FMZ) was chosen for this purpose, as it lacks a suitable reference region. Methods. Five bolus [(11)C...... state was attained within 40 min, which was 8 min earlier than the optimal BI (B/I ratio = 55 min). Conclusions. The system can design both BI and PI schemes to attain steady state rapidly. For example, subjects can be [(11)C]FMZ-PET scanned after 40 min of tracer infusion for 40 min with venous...
Molecular profile of 5-fluorouracil pathway genes in colorectal carcinoma

Czech Academy of Sciences Publication Activity Database

Kunická, T.; Procházka, Pavel; Krus, I.; Bendová, Petra; Protivová, M.; Susová, S.; Hlaváč, V.; Liška, V.; Novák, P.; Schneiderová, M.; Pitule, P.; Bruha, J.; Vyčítal, O.; Vodička, Pavel; Souček, P.

2017-01-01

Roč. 16, oct (2017), s. 795 ISSN 1471-2407 R&D Projects: GA MZd(CZ) NT14329; GA ČR(CZ) GAP304/12/1585 Institutional support: RVO:68378041 Keywords : colorectal carcinoma * 5-fluorouracil * methylation Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Biochemistry and molecular biology Impact factor: 3.288, year: 2016
Distribution of 18F-5-fluorouracil in tumor-bearing mice and rats

International Nuclear Information System (INIS)

Shani, J.; Wolf, W.; Schlesinger, T.

1978-01-01

Extensive distribution studies of 18 F-5-fluorouracil ( 18 F-5-FU) in control and tumor-bearing mice (seven lines) and rats (eight lines) that have been shown or suspected to be responsive to 5-FU treatment were investigated with 18 F-5-FU. Studies were performed as a function of time, loading dose of 5-FU, and after a pretreatment regimen of 5-FU. Following the parenteral administration of 18 F-5-FU to tumor-bearing mice and rats there was slight preferential uptake by some of the tumor types, particularly subcutaneous leukemic tumors and breast adenocarcinomas. The degree of concentration in tumor tissue in comparison with surrounding tissues (blood, Muscle) was not such as to consider the radiopharmaceutical suitable for tumor localization. However, sufficient amounts of radioactivity localized in some tumors so that it might be possible to determine if a correlation exists between tumor uptake and anti-tumor effect of 5-fluorouracil. Another possible area of use might be in regulating the method of administration of the chemotherapeutic agent. (author)
Oxaliplatin, fluorouracil, and leucovorin versus fluorouracil and leucovorin as adjuvant chemotherapy for locally advanced rectal cancer after preoperative chemoradiotherapy (ADORE): an open-label, multicentre, phase 2, randomised controlled trial.

Science.gov (United States)

Hong, Yong Sang; Nam, Byung-Ho; Kim, Kyu-Pyo; Kim, Jeong Eun; Park, Seong Joon; Park, Young Suk; Park, Joon Oh; Kim, Sun Young; Kim, Tae-You; Kim, Jee Hyun; Ahn, Joong Bae; Lim, Seok-Byung; Yu, Chang Sik; Kim, Jin Cheon; Yun, Seong Hyeon; Kim, Jong Hoon; Park, Jin-Hong; Park, Hee Chul; Jung, Kyung Hae; Kim, Tae Won

2014-10-01

The role of adjuvant chemotherapy for patients with rectal cancer is controversial, especially when used after preoperative chemoradiotherapy. Fluoropyrimidine-based adjuvant chemotherapy, including fluorouracil and leucovorin, has been widely used; however, the addition of oxaliplatin to fluorouracil and leucovorin (FOLFOX), a standard adjuvant regimen for colon cancer, has not been tested in rectal cancer. We aimed to compare the efficacy and safety of adjuvant fluorouracil and leucovorin with that of FOLFOX in patients with locally advanced rectal cancer after preoperative chemoradiotherapy. In this open-label, multicentre, phase 2, randomised trial, patients with postoperative pathological stage II (ypT3-4N0) or III (ypTanyN1-2) rectal cancer after preoperative fluoropyrimidine-based chemoradiotherapy and total mesorectal excision were recruited and randomly assigned (1:1) via a web-based software platform to receive adjuvant chemotherapy with either four cycles of fluorouracil and leucovorin (fluorouracil 380 mg/m(2) and leucovorin 20 mg/m(2) on days 1-5, every 4 weeks) or eight cycles of FOLFOX (oxaliplatin 85 mg/m(2), leucovorin 200 mg/m(2), and fluorouracil bolus 400 mg/m(2) on day 1, and fluorouracil infusion 2400 mg/m(2) for 46 h, every 2 weeks). Stratification factors were pathological stage (II vs III) and centre. Neither patients nor investigators were masked to group assignment. The primary endpoint was 3-year disease-free survival, analysed by intention to treat. This study is fully enrolled, is in long-term follow-up, and is registered with ClinicalTrials.gov, number NCT00807911. Between Nov 19, 2008, and June 12, 2012, 321 patients were randomly assigned to fluorouracil and leucovorin (n=161) and FOLFOX (n=160). 141 (95%) of 149 patients in the fluorouracil plus leucovorin group and 141 (97%) of 146 in the FOLFOX group completed all planned cycles of adjuvant treatment. Median follow-up was 38·2 months (IQR 26·4-50·6). 3-year disease
Evaluation of efficacy and safety of modified infusion of fluorouracil, leucovorin, oxaliplatin, and irinotecan (mFOLFOXIRI in treatment of metastatic colorectal cancer: a retrospective study of 21 cases

Directory of Open Access Journals (Sweden)

Xi-cheng WANG

2016-04-01

Full Text Available Objective 　To evaluate the safety and preliminary efficacy of mFOLFOXIRI (the combination of irinotecan, oxaliplatin and 5-fluorouracil with reducing dosages in first-line treatment for Chinese patients with unresectable metastatic colorectal cancer (mCRC. Methods 　A total of 21 patients received mFOLFOXIRI treatment: irinotecan 150mg/m2 on day 1, oxaliplatin 85mg/m2 on day 1, leucovorin 200mg/m2 on day 1, and 5-fluorouracil (5-FU 2800mg/m2 in a 48-h continuous infusion starting on day 1. The regimen was repeated every 2 weeks. Result 　All the 21 patients were evaluated for efficacy of the aforesaid therapeutic regimen, and the incidence of toxic effects. No death occurred in association with the treatment. The total rate of grade 3 to 4 adverse events was 42.9% (9/21 including 38.1% (8 cases with grade 3 neutropenia and 4.8% (1 case suffering from grade 3 anemia. One of 21 patients (4.8% showed grade 4 neutropenia accompanied by fever. The delivered relative dose intensity of irinotecan, oxaliplatin and 5-FU during the entire treatment course were 93.4%, 98.5% and 97.6%, respectively of planned dosage. In the intention-to-treat analysis for treatment activity, 14 patients showed remission, 6 stability, and 1 with progression of the disease. The overall response rate was 66.7%, and the disease control rate was 95.2%. Three patients (15.8% with residual liver metastases were radically resected after mFOLFOXIRI chemotherapy. Conclusions 　This mFOLFOXIRI project has manageable toxicity and is well tolerated in Chinese patients. The safety profile appears to be improved compared with standard FOLFOXIRI regimen. In addition, the antitumor activity and preliminary efficacy seem to be maintained. DOI: 10.11855/j.issn.0577-7402.2016.03.15
5-fluorocytosine-related bone-marrow depression and conversion to fluorouracil: a pilot study

NARCIS (Netherlands)

Vermes, András; Guchelaar, Henk-Jan; van Kuilenburg, Andre B. P.; Dankert, Jacob

2002-01-01

The aim of this study is to investigate whether fluorouracil (5-FU) could be responsible for bone-marrow depression occurring in fluorocytosine 5-FC) treated patients. Six 5-FC treated patients were included in this pilot study. Toxicity was monitored by means of thrombocyte and leucocyte counts.
Hematopoiesis in 5-Fluorouracil-Treated Adenosine A(3) Receptor Knock-Out Mice

Czech Academy of Sciences Publication Activity Database

Hofer, Michal; Pospíšil, Milan; Dušek, L.; Hoferová, Zuzana; Komůrková, Denisa

2015-01-01

Roč. 64, č. 2 (2015), s. 255-262 ISSN 0862-8408 Institutional support: RVO:68081707 Keywords : Adenosine A(3) receptor knock-out mice * Hematopoiesis * 5-fluorouracil-induced hematotoxicity Subject RIV: BO - Biophysics Impact factor: 1.643, year: 2015
Cardiac tamponade in an infant during contrast infusion through central venous catheter for chest computed tomography; Tamponamento cardiaco durante infusao de contraste em acesso venoso central para realizacao de tomografia computadorizada do torax em lactente

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Daud, Danilo Felix; Campos, Marcos Menezes Freitas de; Fleury Neto, Augusto de Padua [Hospital Geral de Palmas, TO (Brazil)

2013-11-15

Complications from central venous catheterization include infectious conditions, pneumothorax, hemothorax and venous thrombosis. Pericardial effusion with cardiac tamponade hardly occurs, and in infants is generally caused by umbilical catheterization. The authors describe the case of cardiac tamponade occurred in an infant during chest computed tomography with contrast infusion through a central venous catheter inserted into the right internal jugular vein. (author)
Arterio-venous anastomoses in isolated, perfused rat lungs.

Science.gov (United States)

Conhaim, Robert L; Segal, Gilad S; Watson, Kal E

2016-11-01

Several studies have suggested that large-diameter (>25 μm) arterio-venous shunt pathways exist in the lungs of rats, dogs, and humans. We investigated the nature of these pathways by infusing specific-diameter fluorescent latex particles (4, 7, 15, 30, or 50 μm) into isolated, ventilated rat lungs perfused at constant pressure. All lungs received the same mass of latex (5 mg), which resulted in infused particle numbers that ranged from 1.7 × 10 7 4 μm particles to 7.5 × 10 4 50 μm particles. Particles were infused over 2 min. We used a flow cytometer to count particle appearances in venous effluent samples collected every 0.5 min for 12 min from the start of particle infusion. Cumulative percentages of infused particles that appeared in the samples averaged 3.17 ± 2.46% for 4 μm diameter particles, but ranged from 0.01% to 0.17% for larger particles. Appearances of 4 μm particles followed a rapid upslope beginning at 30 sec followed by a more gradual downslope that lasted for up to 12 min. All other particle diameters also began to appear at 30 sec, but followed highly irregular time courses. Infusion of 7 and 15 μm particles caused transient but significant perfusate flow reductions, while infusion of all other diameters caused insignificant reductions in flow. We conclude that small numbers of bypass vessels exist that can accommodate particle diameters of 7-to-50 μm. We further conclude that our 4 μm particle data are consistent with a well-developed network of serial and parallel perfusion pathways at the acinar level. Published 2016. This article is a U.S. Government work and is in the public domain in the USA. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.
Biochemical modulation of 5-fluorouracil by methotrexate in patients with advanced gastric carcinoma.

Science.gov (United States)

Pérez, J E; Lacava, J A; Dominguez, M E; Rodriguez, R; Barbieri, M R; Ortiz, E H; Romero Acuña, L A; Langhi, M J; Romero Acuña, J M; Vallejo, C T; Leone, B A; Machiavelli, M R; Romero, A O

1998-10-01

A phase II trial was conducted to evaluate the efficacy and toxicity of a modulation of 5-fluorouracil (5-FU) by methotrexate (MTX) (with leucovorin (LV) rescue) as first-line chemotherapy in patients with locally advanced (inoperable) or metastatic gastric carcinoma. From July 1993 through August 1996, 36 patients with advanced gastric carcinoma received a regimen that consisted of: MTX 200 mg/m2 diluted in 250 ml normal saline by intravenous infusion over 20 minutes at hour 0; 5-FU 1,200 mg/m2 intravenous push injection at hour 20. Beginning 24 hours after MTX administration all patients received LV 15 mg/m2 intramuscularly every 6 hours for six doses. Cycles were repeated every 15 days. One patient was not assessable for response. Objective regression was observed in 15 of 37 patients (43%; 95% confidence interval, 26%-60%). One patient (3%) achieved complete response and 14 (40%) achieved partial response. No change was recorded in 14 patients (40%) and progressive disease was noted in six patients (17%). The median time to treatment failure was 7 months and the median survival was 12 months. Toxicity was within acceptable limits but one therapy-related death resulting from severe leukopenia occurred. The dose-limiting toxicity was mucositis. Five episodes of grade 3 or 4 stomatitis were observed and caused dosage modifications of MTX and 5-FU. Biochemical modulation of 5-FU by MTX appears as an attractive modality in patients with advanced gastric cancer. Further investigation both in experimental and clinical fields is needed to clearly define its role and to design the best modulatory strategy.
The quantitative regional cerebral blood flow measurement with autoradiography method using 123I-IMP SPECT. Evaluation of arterialized venous blood sampling as a substitute for arterial blood sampling

International Nuclear Information System (INIS)

Ohnishi, Takashi; Yano, Takao; Nakano, Shinichi; Jinnouchi, Seishi; Nagamachi, Shigeki; Flores, L. II; Nakahara, Hiroshi; Watanabe, Katsushi.

1996-01-01

The purpose of this study is validation of calibrating a standard input function in autoradiography (ARG) method by one point venous blood sampling as a substitute for that by one point arterial blood sampling. Ten and 20 minutes after intravenous constant infusion of 123 I-IMP, arterialized venous blood sampling from a dorsal vein were performed on 15 patients having ischemic cerebrovascular disease. And arterial blood sampling from radial artery was performed 10 min after 123 I-IMP infusion. The mean difference rates of integrated input function between calibrated standard input function by arterial blood sampling at 10 min and that by venous blood sampling were 4.1±3% and 9.3±5.4% at 10 and 20 min after 123 I-IMP infusion, respectively. The ratio of venous blood radioactivity to arterial blood radioactivity at 10 min after 123 I-IMP infusion was 0.96±0.02. There was an excellent correlation between ARG method CBF values obtained by arterial blood sampling at 10 min and those obtained by arterialized venous blood sampling at 10 min. In conclusion, a substitution by arterialized venous blood sampling from dorsal hand vein for artery can be possible. The optimized time for arterialized venous blood sampling was 10 min after 123 I-IMP infusion. (author)

Sympathetic responses during saline infusion into the veins of an occluded limb.

Science.gov (United States)

Cui, Jian; McQuillan, Patrick; Moradkhan, Raman; Pagana, Charles; Sinoway, Lawrence I

2009-07-15

Animal studies have shown that the increased intravenous pressure stimulates the group III and IV muscle afferent fibres, and in turn induce cardiovascular responses. However, this pathway of autonomic regulation has not been examined in humans. The aim of this study was to examine the hypothesis that infusion of saline into the venous circulation of an arterially occluded vascular bed evokes sympathetic activation in healthy individuals. Blood pressure, heart rate, and muscle sympathetic nerve activity (MSNA) responses were assessed in 19 young healthy subjects during local infusion of 40 ml saline into a forearm vein in the circulatory arrested condition. From baseline (11.8 +/- 1.2 bursts min(-1)), MSNA increased significantly during the saline infusion (22.5 +/- 2.6 bursts min(-1), P Blood pressure also increased significantly during the saline infusion. Three control trials were performed during separate visits. The results from the control trial show that the observed MSNA and blood pressure responses were not due to muscle ischaemia. The present data show that saline infusion into the venous circulation of an arterially occluded vascular bed induces sympathetic activation and an increase in blood pressure. We speculate that the infusion under such conditions stimulates the afferent endings near the vessels, and evokes the sympathetic activation.
A new venous infusion pathway monitoring system.

Science.gov (United States)

Maki, Hiromichi; Yonezawa, Yoshiharu; Ogawa, Hidekuni; Ninomiya, Ishio; Sata, Koji; Hamada, Shingo; Caldwell, W Morton

2007-01-01

A new infusion catheter pathway monitoring system employing linear integrated circuits and a low-power 8-bit single chip microcomputer has been developed for hospital and home use. The sensor consists of coaxial three-layer conductive tapes wrapped around the polyvinyl chloride infusion tube. The inner tape is the main electrode, which records an AC (alternating current) voltage induced on the patient's body by electrostatic coupling from the normal 100 volt, 60 Hz AC power line wiring field in the patient's room. The outside tape layer is a reference electrode to monitor the AC voltage around the main electrode. The center tape layer is connected to system ground and functions as a shield. The microcomputer calculates the ratio of the induced AC voltages recorded by the main and reference electrodes and if the ratio indicates a detached infusion, alerts the nursing station, via the nurse call system or low transmitting power mobile phone.
[Injection Pressure Evaluation of the New Venous Catheter with Side Holes for Contrast-enhanced CT/MRI].

Science.gov (United States)

Fukuda, Junya; Arai, Keisuke; Miyazawa, Hitomi; Kobayashi, Kyouko; Nakamura, Junpei; Suto, Takayuki; Tsushima, Yoshito

2018-01-01

The simulation study was conducted for the new venous catheter with side holes of contrast-enhanced computed tomography (CT) and magnetic resonance imaging (MRI) to evaluate the infusion pressure on four contrast media and several injection speeds. All infusion pressure of the new venous catheter with side holes were less than 15 kg/cm 2 as limitation of extension tube and also reduced the infusion pressure by 15% at the maximum compared to the catheter with single hole. The results suggest that the new venous catheter with side holes can reduce the infusion pressure by power injection of contrast-enhanced CT and MRI.
Definitive Chemoradiation Therapy With Docetaxel, Cisplatin, and 5-Fluorouracil (DCF-R) in Advanced Esophageal Cancer: A Phase 2 Trial (KDOG 0501-P2)

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Higuchi, Katsuhiko, E-mail: k.higu@kitasato-u.ac.jp [Department of Gastroenterology, Kitasato University East Hospital, Sagamihara, Kanagawa (Japan); Komori, Shouko [Department of Radiology and Radiation Oncology, Kitasato University School of Medicine, Sagamihara, Kanagawa (Japan); Tanabe, Satoshi [Department of Gastroenterology, Kitasato University East Hospital, Sagamihara, Kanagawa (Japan); Katada, Chikatoshi [Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Kanagawa (Japan); Azuma, Mizutomo [Department of Gastroenterology, Kitasato University East Hospital, Sagamihara, Kanagawa (Japan); Ishiyama, Hiromichi [Department of Radiology and Radiation Oncology, Kitasato University School of Medicine, Sagamihara, Kanagawa (Japan); Sasaki, Tohru; Ishido, Kenji [Department of Gastroenterology, Kitasato University East Hospital, Sagamihara, Kanagawa (Japan); Katada, Natsuya [Department of Surgery, Kitasato University School of Medicine, Sagamihara, Kanagawa (Japan); Hayakawa, Kazushige [Department of Radiology and Radiation Oncology, Kitasato University School of Medicine, Sagamihara, Kanagawa (Japan); Koizumi, Wasaburo [Department of Gastroenterology, Kitasato University East Hospital, Sagamihara, Kanagawa (Japan)

2014-07-15

Purpose: A previous phase 1 study suggested that definitive chemoradiation therapy with docetaxel, cisplatin, and 5-fluorouracil (DCF-R) is tolerable and active in patients with advanced esophageal cancer (AEC). This phase 2 study was designed to confirm the efficacy and toxicity of DCF-R in AEC. Methods and Materials: Patients with previously untreated thoracic AEC who had T4 tumors or M1 lymph node metastasis (M1 LYM), or both, received intravenous infusions of docetaxel (35 mg/m{sup 2}) and cisplatin (40 mg/m{sup 2}) on day 1 and a continuous intravenous infusion of 5-fluorouracil (400 mg/m{sup 2}/day) on days 1 to 5, every 2 weeks, plus concurrent radiation. The total radiation dose was initially 61.2 Gy but was lowered to multiple-field irradiation with 50.4 Gy to decrease esophagitis and late toxicity. Consequently, the number of cycles of DCF administered during radiation therapy was reduced from 4 to 3. The primary endpoint was the clinical complete response (cCR) rate. Results: Characteristics of the 42 subjects were: median age, 62 years; performance status, 0 in 14, 1 in 25, 2 in 3; TNM classification, T4M0 in 20, non-T4M1LYM in 12, T4M1LYM in 10; total scheduled radiation dose: 61.2 Gy in 12, 50.4 Gy in 30. The cCR rate was 52.4% (95% confidence interval [CI]: 37.3%-67.5%) overall, 33.3% in the 61.2-Gy group, and 60.0% in the 50.4-Gy group. The median progression-free survival was 11.1 months, and the median survival was 29.0 months with a survival rate of 43.9% at 3 years. Grade 3 or higher major toxicity consisted of leukopenia (71.4%), neutropenia (57.2%), anemia (16.7%), febrile neutropenia (38.1%), anorexia (31.0%), and esophagitis (28.6%). Conclusions: DCF-R frequently caused myelosuppression and esophagitis but was highly active and suggested to be a promising regimen in AEC. On the basis of efficacy and safety, a radiation dose of 50.4 Gy is recommended for further studies of DCF-R.
Effect of alcohol and glucose infusion on pituitary-gonadal hormones in normal females

DEFF Research Database (Denmark)

Becker, U; Gluud, C; Bennett, Patrick

1988-01-01

after 8 h. Four of the women participated in a control experiment with infusion of an equal volume of glucose 5.5%. Venous blood samples were drawn 5 times during the 24-h follow up period. Serum concentrations of sex steroids and pituitary hormones decreased in both ethanol and control experiments...... and the results did not differ significantly. The lowest hormone concentrations were observed 1-5 h after the start of infusion. Oestradiol, oestrone and oestrone-sulphate concentrations decreased 24-46% compared to basal values. 5 alpha-dihydro-testosterone levels decreased 23-31%, androstenedione...
Preoperative Capecitabine and Pelvic Radiation in Locally Advanced Rectal Cancer-Is it Equivalent to 5-FU Infusion Plus Leucovorin and Radiotherapy?

International Nuclear Information System (INIS)

Chan, Alexander K.; Wong, Alfred O.; Jenken, Daryl A.

2010-01-01

Purpose: The aim of this retrospective case-matching study was to compare the treatment outcomes and acute toxicity of preoperative radiotherapy (RT) with capecitabine vs. preoperative RT with intermittent 5-fluorouracil (5-FU) infusion, leucovorin, and mitomycin C in rectal cancer. Methods and Materials: We matched 34 patients who were treated with preoperative concurrent capecitabine and 50 Gy of RT by their clinical T stage (T3 or T4) and the tumor location (≤7 cm or >7 cm from the anal verge) with another 68 patients who were treated with preoperative intermittent 5-FU infusion, leucovorin, mitomycin C, and 50 Gy of RT for a comparison of the pathologic tumor response, local control, distant failure, and survival rates. Results: The pathologic complete response rate was 21% with capecitabine and 18% with 5-FU and leucovorin (p = 0.72). The rate of T downstaging after chemoradiation was 59% for both groups. The rate of sphincter-sparing resection was 38% after capecitabine plus RT and 43% after 5-FU plus RT (p = 0.67). At 3 years, there was no significant difference in the local control rate (93% for capecitabine and 92% for 5-FU and leucovorin), relapse-free rate (74% for capecitabine and 73% for 5-FU and leucovorin), or disease-specific survival rate (86% for capecitabine and 77% for 5-FU and leucovorin). The acute toxicity profile was comparable, with little Grade 3 and 4 toxicity. Conclusions: When administered with concurrent preoperative RT, both capecitabine and intermittent 5-FU infusion with leucovorin modulation provided comparable pathologic tumor response, local control, relapse-free survival, and disease-specific survival rates in rectal cancer.
Oral ftorafur versus intravenous 5-fluorouracil. A comparative study in patients with colorectal cancer

DEFF Research Database (Denmark)

Andersen, E; Pedersen, H

1987-01-01

The toxicities of oral Ftorafur (1 g/m2/day 1-21) and intravenous 5-fluorouracil (5-FU) (500 mg/m2/day 1-5) were compared in a prospective randomized study in patients with colorectal cancer. The treatment courses were repeated every 6th week. Leucopenia was more common after 5-FU. Leucocyte nadir...
Effects of 5-fluorouracil on the secretory process of the rat parotid gland

International Nuclear Information System (INIS)

Sandborg, R.R.

1986-01-01

Experimental animals were injected intraperitoneally with 100 mg/kg 5-fluorouracil for three days. The total volume, amylase and protein content of cannulated parotid saliva were determined following stimulation with either 5 mg/kg pilocarpine or 5 mg/kg isoproterenol in experimental, pair-fed , and control animals. Saliva from experimental animals was significantly lower in volume, amylase and protein content than both control groups. 5-fluorouracil treatment reduced the total glandular amylase per unit DNA in both unstimulated and isoproterenol-stimulated parotid glands. Decreased protein synthesis may be the mechanism underlying depleted secretory protein stores since the contents of isolated secretory granules from experimental parotid glands contained less radiolabelled protein than either control group and whole gland homogenates showed marked reductions in the activities of three lysosomal enzymes and total RNA content. Experimental animals contained less labelled protein in their secretory granules than controls, but secreted a greater proportion of their total glandular radiolabelled secretory protein into saliva relative to amylase suggesting that newly synthesized secretory proteins are preferentially secreted
Effects of 5-fluorouracil on the secretory process of the rat parotid gland

Energy Technology Data Exchange (ETDEWEB)

Sandborg, R.R.

1986-01-01

Experimental animals were injected intraperitoneally with 100 mg/kg 5-fluorouracil for three days. The total volume, amylase and protein content of cannulated parotid saliva were determined following stimulation with either 5 mg/kg pilocarpine or 5 mg/kg isoproterenol in experimental, pair-fed , and control animals. Saliva from experimental animals was significantly lower in volume, amylase and protein content than both control groups. 5-fluorouracil treatment reduced the total glandular amylase per unit DNA in both unstimulated and isoproterenol-stimulated parotid glands. Decreased protein synthesis may be the mechanism underlying depleted secretory protein stores since the contents of isolated secretory granules from experimental parotid glands contained less radiolabelled protein than either control group and whole gland homogenates showed marked reductions in the activities of three lysosomal enzymes and total RNA content. Experimental animals contained less labelled protein in their secretory granules than controls, but secreted a greater proportion of their total glandular radiolabelled secretory protein into saliva relative to amylase suggesting that newly synthesized secretory proteins are preferentially secreted.
Influence of different sugar cryoprotectants on the stability and physico-chemical characteristics of freeze-dried 5-fluorouracil plurilamellar vesicles

Directory of Open Access Journals (Sweden)

Mohamed Mahmoud Nounou

2005-07-01

Full Text Available Lyophilization increases the shelf-life of liposomes by preserving it in a dry form as lyophilized cake to be reconstituted with water immediately prior to administration. Aiming at increasing stability and availability of 5-Fluorouracil liposomal products, 5-Fluorouacil Stable Plurilamellar Vesicles were prepared. Freeze dried liposomal dispersions were prepared with or without cryoprotectants. The cryoprotectants used were glucose, mannitol or trehalose in 1, 2 and 4 grams per gram phospholipids. The results showed that lyophilized cake of liposomes without cryoprotectants was compact and difficult to reconstitute, in comparison with fluffy cakes which reconstituted easily and quickly when using cryoprotectants. The percentage of 5-Fluorouracil retained in liposomes freeze-dried without cryoprotectants was 18.29% ± 0.96% and the percentage of 5-Fluorouracil retained in stable plurilamellar vesicles was 31.22% ± 0.62% using 4 grams trehalose as cryoprotectant per gram of lipid. Physico-chemical and release stability studies showed superior potentials of the lyophilized product after reconstitution in comparison to dispersion product. It may be concluded that all tested sugars have cryoprotectant effects that stabilized liposomes in the freeze dried state, where trehalose offered the most superior cryoprotectant effect for freeze dried 5-fluorouracil liposomes.
Phase II study of modified docetaxel, cisplatin, and fluorouracil with bevacizumab in patients with metastatic gastroesophageal adenocarcinoma.

Science.gov (United States)

Shah, Manish A; Jhawer, Minaxi; Ilson, David H; Lefkowitz, Robert A; Robinson, Edric; Capanu, Marinela; Kelsen, David P

2011-03-01

To evaluate the safety and efficacy of a modified administration schedule of docetaxel, cisplatin, and fluorouracil (mDCF) with bevacizumab in patients with advanced gastroesophageal malignancies. Previously untreated patients with metastatic gastroesophageal adenocarcinoma received bevacizumab 10 mg/kg, docetaxel 40 mg/m², fluorouracil 400 mg/m², leucovorin 400 mg/m² on day 1, fluorouracil 1,000 mg/m²/d × 2 days intravenous continuous infusion beginning on day 1, and cisplatin 40 mg/m² on day 3. The primary objective was to improve 6-month progression-free survival (PFS) from 43% (historical DCF control) to 63% with the addition of bevacizumab. The target accrual was 44 patients to have 10% type I and II error rates. In total, 44 eligible patients with cancer were enrolled from October 2006 to October 2008: 22 gastric, 20 gastroesophageal junction (GEJ), and two esophagus. In 39 patients with measurable disease, the confirmed response rate was 67% (95% CI, 50% to 81%). Six-month PFS was 79% (95% CI, 63% to 88%), and median PFS was 12 months (95% CI, 8.8 to 18.2 months). With 26-month follow-up, median overall survival (OS) was 16.8 months (95% CI, 12.1 to 26.1 months), and 2-year survival was 37%. Treatment-related grade 3 to 4 toxicity was as follows: neutropenia without fever (50%), fatigue (25%), venous thromboembolism (39%), and nausea, vomiting, mucositis, neuropathy, and febrile neutropenia less than 10% each. In subset analysis, diffuse gastric cancer had significantly worse PFS and OS, and the response rate in proximal/GEJ tumors was 85% (95% CI, 62% to 97%). mDCF with bevacizumab appears tolerable and has notable patient outcomes in patients with advanced gastroesophageal adenocarcinoma. Six-month PFS was 79%, surpassing our predefined efficacy end point, and median and 2-year OS were 16.8 months and 37%, respectively.
Infusion volume control and calculation using metronome and drop counter based intravenous infusion therapy helper.

Science.gov (United States)

Park, Kyungnam; Lee, Jangyoung; Kim, Soo-Young; Kim, Jinwoo; Kim, Insoo; Choi, Seung Pill; Jeong, Sikyung; Hong, Sungyoup

2013-06-01

This study assessed the method of fluid infusion control using an IntraVenous Infusion Controller (IVIC). Four methods of infusion control (dial flow controller, IV set without correction, IV set with correction and IVIC correction) were used to measure the volume of each technique at two infusion rates. The infused fluid volume with a dial flow controller was significantly larger than other methods. The infused fluid volume was significantly smaller with an IV set without correction over time. Regarding the concordance correlation coefficient (CCC) of infused fluid volume in relation to a target volume, IVIC correction was shown to have the highest level of agreement. The flow rate measured in check mode showed a good agreement with the volume of collected fluid after passing through the IV system. Thus, an IVIC could assist in providing an accurate infusion control. © 2013 Wiley Publishing Asia Pty Ltd.
Tracer studies with aortic infusion result in improper tracer distribution

International Nuclear Information System (INIS)

Wisneski, J.A.; Brooks, G.A.; Neese, R.A.; Stanley, W.C.; Morris, D.L.; Gertz, E.W.

1986-01-01

It has been suggested that lactate turnover can be accurately assessed by infusing radioactive lactate tracer into the aorta and sampling blood in the vena cava. However, there may be streaming of newly infused tracer in the aorta, resulting in a nonuniform arterial specific activity (SA). Furthermore vena caval blood may not be representative of mixed venous blood. The authors examined this problem in 7 anesthetized dogs with sampling catheters in the pulmonary (PA), carotid (CA), and femoral (FA) arteries, and the superior (SVC) and inferior (IVC) vena cavi. [1- 14 C]lactate was continuously infused into the left ventricle through a catheter introduced through the femoral artery. The same SA (dpm/μmol) was found in the CA and FA, indicating adequate mixing of newly infused tracer with trace. Three dogs showed differences between SVC, IVC and PA, suggesting a mixed venous sample can not be obtained from the VC. When the catheter was moved into the aorta, wide differences in SA appeared between the CA and FA, clearly reflecting streaming of tracer. These differences also appeared in the SVC and IVC. In conclusion, adequate mixing does not occur between tracer and trace in arterial blood with aortic infusion. Further, VC sampling will not give a consistent mixed venous SA. Therefore, for practical reasons, aortic tracer infusion with vena caval sampling will lead to erroneous turnover values
[Home anti-cancer therapy with a venous port].

Science.gov (United States)

Muto, A; Ashino, Y; Miyazawa, M; Sato, M; Kanno, A; Kawahara, Y; Fujita, Y; Matsushiro, T

2000-12-01

Home anti-cancer chemotherapy and palliation in the terminal stage were performed for patients with advanced cancer of the digestive system, using a venous port implanted beneath the skin via the subclavian vein. Patients under 75 years of age (5 with esophageal, 61 gastric, 59 colorectal, 5 cholangio, 5 pancreatic, 1 hepatic and 1 ileal cancer) were treated. With two portable balloon pumps, continuous intravenous infusion of 5-FU (300 or 400 mg/body/day) combined low-dose injection of cisplatin (5 mg/body/day) was continued for 10 days, and repeated 3 times for 6 weeks. The response rate was 17.9% in 78 patients according to valuation of the tumor mass. In 119 patients also undergoing a tumor marker evaluation, an effect was seen in 26.1%. No severe side effects such as renal dysfunction or bone marrow suppression were seen, and no special infusion was needed. Therefore, such treatment can be continued for a long time. Use of a venous port should make easy the switchover to HPN and the amelioration of the symptoms of the terminal stage, such as pain, and helps patients cope with the worry. Therefore, the present technique is useful in a series of cancer treatments including surgery, chemotherapy and the amelioration of symptoms.
Acute diarrhea during adjuvant therapy for rectal cancer: a detailed analysis from a randomized intergroup trial

International Nuclear Information System (INIS)

Miller, Robert C.; Sargent, Daniel J.; Martenson, James A.; Macdonald, John S.; Haller, Daniel; Mayer, Robert J.; Gunderson, Leonard L.; Rich, Tyvin A.; Cha, Stephen S.; O'Connell, Michael J.

2002-01-01

Purpose: During adjuvant radiotherapy (RT) for rectal cancer, patients receiving 5-fluorouracil (5-FU) by protracted venous infusion have a higher risk of diarrhea than have patients receiving bolus 5-FU. Toxicity from a previously reported randomized clinical trial was analyzed to quantify the difference in this risk. Additionally, the persistence of diarrhea after RT was analyzed. Methods and Materials: A total of 656 patients were eligible. Patients with T3-4 N0-2 M0 or T1-2 N1-2 M0 resected, high-risk rectal cancer were randomly allocated to receive 5-FU by either protracted venous infusion or bolus during RT (50.4-54.0 Gy). Two cycles of bolus 5-FU were given before and after RT. One-half of the first 445 patients were also randomly allocated to receive lomustine in conjunction with the bolus 5-FU. The incidence and severity of diarrhea in relation to patient and treatment characteristics were evaluated. Results: The rate of diarrhea was significantly greater in patients receiving 5-FU by protracted venous infusion than in patients receiving bolus 5-FU; the difference was most pronounced for Grade 3 (severe) diarrhea (21% versus 13%, p=0.007). The incidence and magnitude of diarrhea before and after RT were similar. Patients treated with an anterior resection had a higher rate of severe or life-threatening diarrhea than did patients treated with an abdominoperineal resection (31% vs. 12%, p<0.001). Conclusions: During pelvic RT, patients who receive 5-FU by protracted venous infusion rather than by bolus have a higher risk of severe or life-threatening diarrhea during RT. This risk does not appear to persist during chemotherapy after completion of pelvic RT
Palliation of inoperable head and neck cancer: combined intra-arterial infusion chemotherapy and irradiation

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Armstrong, A.L.; Meeker, W.R.

1978-01-01

Palliation of unresectable head and neck cancer remains a difficult problem. Because of excellent results reported by others with infusion of vinblastine, methotrexate, and 5-fluorouracil into the external carotid artery followed by irradiation before curative surgery, we applied this technic to 22 patients with advanced head and neck cancer. Fifteen patients from this group who had chemotherapy infusion followed by radiation therapy are compared with 21 patients who received radiation therapy alone. Both groups were similar in distribution of primary site, histology, and TNM stage. Of 15 patients, 14 (93%) had partial or complete tumor regression after both arterial chemotherapy infusion and irradiation, while 14 of 17 patients (82%) receiving primary irradiation had partial or complete response. Drug toxicity and complications related to infusion occurred in all patients. Most patients in both groups had short survivals (mean of 14.1 months in infusion chemotherapy and radiation vs 9.1 months in primary irradiation). One patient remains alive in the infusion group and two in the control group; however, all have recurrent disease. Results indicate a slight increase in survival time with the addition of infusion chemotherapy to irradiation in palliative treatment of head and neck cancer
Venipuncture versus peripheral catheter: do infusions alter laboratory results?

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Hambleton, Victoria Lerma; Gómez, Ignacio Arribas; Andreu, Francisco A Bernabeu

2014-01-01

Our aim was to evaluate the equivalence between analytic parameters from blood samples obtained from a saline solution lock device used for the infusion of drugs and those from venipuncture. In our emergency department, patients bearing a saline solution lock device have blood extracted by venipuncture to avoid possible contamination of the sample. Adults from the emergency department with a saline solution lock device who required laboratory tests were selected as candidates for this cross-sectional observational study. Infusions were halted and flushed with 0.9% saline solution; 2 minutes later, 2 mL of blood was drawn and discarded, and the corresponding laboratory tubes were filled. Immediately after, another sample was withdrawn from the opposite extremity by venipuncture. Both samples were analyzed for hematology, biochemistry, venous blood gases, and coagulation parameters. Concordance was evaluated by use of the intraclass correlation coefficient with its 95% confidence intervals; Bland-Altman plots were used to illustrate the percentage of samples with differences exceeding 2 SDs. The mean differences were also checked to detect those exceeding the laboratory's systematic error. An intraclass correlation coefficient of over 0.9 was achieved for all parameters except for pH, partial pressure of carbon dioxide, and partial pressure of oxygen. Differences of over 2 SDs were found in fewer than 10% of all parameters. None of them exceeded 3 SDs, except for pH and venous blood gases. All parameters showed differences below the laboratory's accepted systematic error except for pH and venous blood gases. Blood samples extracted from a peripheral catheter with or without drug infusions are valid for the analysis of hematology, biochemistry, and coagulation parameters but not for venous blood gases. Nurses should know the benefits of using an existing peripheral catheter for drawing blood samples for laboratory analysis even when infusing commonly used drugs
Clinical study on external carotid artery infusion (trans-femoral) treatment of recurrent nasopharyngeal carcinoma

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Zhou Zejian; Li Chong; Luo Pengfei; Shao Peijian; Zhang Liangming; Li Weike; Li Yong; Xu Rongde; Zhuang Wenxing; Zhang Hua

2002-01-01

Objective: To evaluate the effect and safety of external carotid artery infusion treatment of recurrent nasopharyngeal carcinoma (NPC). Methods: 20 cases of recurrent NPC (13 male and 7 female, age 36-65 years, mean 50 years) diagnosed by clinical examination (including nasopharyngoscope), serology (VCA-IgA) and imaging (CT, MR) and treated by external carotid artery infusion (trans-femoral) with adriamycin (or epi-adriamycin), cisplatin (or carboplatin), Pingyangmycin and 5-Fluorouracil. Results: Of all the patients, 8 cases (40%) had a complete response (CR), 7 cases (35%) had a partial response (PR). The overall response rate (CR + PR) was 75%. Cumulative survival rates at 1, 3 years were 90% (18/20), 50%(10/20) respectively. No severe side-effects and complications found. Conclusion: External carotid artery infusion (trans-femoral) should be effective and safe in the treatment of recurrent NPC
Adjuvant chemoradiotherapy combined with cisplatin, 5-fluorouracil and folinic acid for locally advanced gastric cancer

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Muharrem Kocar

2016-04-01

Conclusion: The addition of combination chemotherapy with cisplatin, infusional 5-fluorouracil and folinic acid before and after chemoradiotherapy was found to be safe and effective in patients with operated gastric cancer.
Preserved learning and memory following 5-fluorouracil and cyclophosphamide treatment in rats

OpenAIRE

Long, Jeffrey M.; Lee, Garrick D.; Kelley-Bell, Bennett; Spangler, Edward L.; Perez, Evelyn J.; Longo, Dan L.; de Cabo, Rafael; Zou, Sige; Rapp, Peter R.

2011-01-01

Some patients experience enduring cognitive impairment after cancer treatment, a condition termed “chemofog”. Animal models allow assessment of chemotherapy effects on learning and memory per se, independent of changes due to cancer itself or associated health consequences such as depression. The present study examined the long-term learning and memory effects of a chemotherapy cocktail used widely in the treatment of breast cancer, consisting of 5-fluorouracil (5FU) and cyclophosphamide (CYP...

Melanoma or Pseudo melanoma Change in a pigmented lesion after application of topical 5-Fluorouracil

Science.gov (United States)

2017-10-26

2. REPORT TYPE 3. DATES COVERED (From - To) 10/26/2017 Poster 10/26/2017-10/29/2017 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Melanoma or Pseudo...melanoma? Change in a pigmented lesion after application of topical 5-Fluorouracil. 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d
The association of polymorphisms in 5-fluorouracil metabolism genes with outcome in adjuvant treatment of colorectal cancer

DEFF Research Database (Denmark)

Shoaib, Afzal; Gusella, Milena; Jensen, Søren Astrup

2011-01-01

The purpose of this study was to investigate whether specific combinations of polymorphisms in 5-fluorouracil (5-FU) metabolism-related genes were associated with outcome in 5-FU-based adjuvant treatment of colorectal cancer....
Pharmacokinetics and analgesic effect of ropivacaine during continuous epidural infusion for postoperative pain relief

DEFF Research Database (Denmark)

Erichsen, C J; Sjövall, J; Kehlet, H

1996-01-01

BACKGROUND: The pharmacokinetics and clinical efficacy of ropivacaine (2.5 mg/ml) during a 24-h continuous epidural infusion for postoperative pain relief in 20 patients scheduled for abdominal hysterectomy were characterized using an open-label, increasing-dose design. METHODS: Through an epidural...... catheter inserted at T10-T12, a test dose of 7.5 mg ropivacaine was given 3 min before a bolus dose of 42.5 mg and immediately followed by a 24-h continuous epidural infusion with either 10 or 20 mg/h. Peripheral venous plasma samples were collected up to 48 h after infusion, and urinary excretion...... plasma concentrations of ropivacaine increased markedly and consistently during the 24-h epidural infusion, in contrast to stable unbound concentrations. Both total and unbound plasma concentrations at the end of infusion were proportional to the total dose, although only the latter was proportional...
Targeting chemotherapy via arterial infusion for advanced gastric cancer

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Zhi-yu CAO

2011-10-01

Full Text Available Objective To evaluate the clinical effects of chemotherapy via arterial infusion in treatment of advanced gastric cancer.Methods Forty-seven patients with advanced gastric cancer were given chemotherapy via arterial infusion.Chemotherapy plan was as follows: 5-Fluorouracil(Fu 500mg/m2,cyclophosphamide(MMX 10mg/m2,Hydroxycamptothecin(HPT 20mg/m2,once per week,2 weeks as a course,a total of 2-3 courses.Results After chemotherapy via arterial infusion,complete remission(CR was achieved in 1 case,partial remission(PR in 28 cases,stabilization of disease(SD in 16 cases,progression of disease(PD was found in 2 cases,and rate with response(CR+PR was 61.7%.Four of 28 PR patients underwent tumorectomy,the pathology revealed the presence of cancer cells around the vascular vessels,manifesting karyopyknosis,karyorrhexis,coagulation and necrosis of cytoplasm,intercellular edema,hyperplasia of fibroblasts,inflammatory cell infiltration,thickening of endothelium,and thrombosis.One,two and three-year survival rates were 70.2%,14.9% and 2.1%,respectively.The average survival period was 17.2 months.Conclusion Targeting chemotherapy via arterial infusion,as a part of the combined treatment,is beneficial to the patients with unresectable advanced gastric cancer.
A modified thrombolytic scheme for the treatment of thrombosis in anatomically varied cerebral venous sinus

International Nuclear Information System (INIS)

Zhao Lin; Li Linfang; Liu Zengpin; Qin Huimin; Wang Tiegang; Zhou Cunhe

2010-01-01

Objective: To discuss the curative effect of unremitting pump infusion of microdose urokinase (100000 u / 24 h) into the cerebral venous sinus in treating thrombosis in cerebral venous sinus which had anatomical variation. Methods: Mechanical disruption of the thrombus and unremitting pump infusion of microdose urokinase (100000 u / 24 h) into the cerebral venous sinus for 48-96 hours were employed in 9 patients with thrombosis in anatomically varied cerebral venous sinus. After the procedure the original disorder was actively treated and the anticoagulant therapy was continued for 6 months. A follow-up of 6-12 months (mean 10 months) was conducted. Results: Recanalization of the previously occluded cerebral venous sinus was obtained in all 9 patients. The dose of urokinase was 100 000 u / 24 h in 8 patients. For the remaining one patient the dose of urokinase was 100000 u / 24 h in the first 48 hours, then the dose was increased to 250000 u / 24 h. Excellent result was obtained in all patients. Conclusion: Unremitting pump infusion of microdose urokinase into the cerebral venous sinus can effectively treat the thrombosis in anatomically varied cerebral venous sinus. (authors)
Effects of CO(2) pneumoperitoneum on anastomotic healing in rats receiving preoperative 5-fluorouracil neoadjuvant chemotherapy.

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Ulas, Murat; Ozer, Ilter; Ercan, Metin; Ozogul, Yusuf B; Bostanci, E Birol; Keklik, Tulay Temucin; Turkcu, Ummuhani Ozel; Bilgihan, Ayse; Akoglu, Musa

2009-01-01

When used separately, antineoplastic agents and carbon dioxide (CO(2)) pneumoperitoneum have been reported to impair anastomotic healing in experimental animals. However, the effects of their combined use have not been previously investigated. The aim of this study was to investigate the possibility that neoadjuvant chemotherapy with 5-fluorouracil followed by CO(2) pneumoperitoneum would affect the healing of anastomoses in the colon. Sprague-Dawley rats (n = 48) were given 5-fluorouracil (20 mg/kg/day) for 5 days, and were then assigned to one of the three groups. Prior to surgery, the control group received no pneumoperitoneum. The other two groups received pneumoperitoneum at 6 and 12 mmHg, respectively, for 2 hr. The large intestine was transected and anastomosis was performed via median laparotomy. On postoperative days 3 and 7, relaparotomy was performed in half of the rats in each group. From the colon, a segment including the anastomosis was excised. Tissue hydroxyproline levels were measured. For histological evaluation, the Verhofstad scale was modified and used. No significant differences in hydroxyproline levels were seen across the groups on postoperative days 3 or 7. However, by postoperative day 7, polymorphonuclear leukocytes and necrosis in the 6-mmHg group had decreased markedly, and granulation had improved. Overall, these findings suggest that preoperative 5-fluorouracil therapy followed by pneumoperitoneum at 6 or 12 mmHg does not impair anastomotic healing.
Uso do 5-fluorouracil no intra-operatório da cirurgia do pterígio Intra-operative use of 5-fluorouracil in pterygium surgery

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Silvana A. Schellini

2000-04-01

Full Text Available Objetivo: Avaliar a efetividade e as complicações com a aplicação do 5- fluorouracil (5-FLU no intra-operatório da cirurgia do pterígio. Método: Foram avaliados 28 olhos de 26 indivíduos quanto ao tipo e tamanho do pterígio, cirurgias prévias e a resposta ao tratamento cirúrgico (no 7º , 21º , 60º e 90º dia de pós-operatório. Logo após a exerese do pterígio, aplicou-se 5-FLU (25 mg/ml no leito cirúrgico, durante cinco minutos; a seguir, realizou-se a técnica de deslizamento de retalho conjuntival. Resultados: A maioria dos pacientes tinha mais de 50 anos de idade e apresentava pterígio primário (70,0%, grau II (60,7%, do tipo involutivo (60,7%. No pós-operatório observaram-se: isquemia (10,7%, deiscência da conjuntiva (7,1%, ceratite (3,5%, conjuntivite (3,5% e recidiva da lesão em 1 olho (3,5%.Conclusão: O 5-FLU se mostrou droga segura e efetiva na prevenção das recidivas, podendo ser usado como coadjuvante no tratamento do pterígio para prevenir recidivas.Purpose: To evaluate the effectiveness and the complications on intraoperative application of 5-fluorouracil (5FLU in pterygium surgery. Method: We studied 28 eyes of 26 patients with pterygium, evaluating the type and size of the pterygium, previous surgeries and the response to surgical treatment (on the 7th, 21st, 60th, 90th postoperative day. The application of 5-FLU (25 mg/ml was done soon after resection, for five minutes, followed by the sliding flap technique.Results: Most of the patients were more than 50 years old, presented with primary (70.0%, degree II (60.7%, involu-tionary type (60.7% pterygium. After surgery ischemic area (10.7%, conjunctival deiscence (7.1%, keratitis (3.5%, conjunctivitis (3.5% and lesion relapse (3.5% were observed.Conclusion: 5-FLU is a safe and effective drug and could be of help in the treatment of pterygium to prevent relapse.
Pharmacokinetic characteristics and anticancer effects of 5-Fluorouracil loaded nanoparticles

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Jiang Wenqi

2008-04-01

Full Text Available Abstract Background It is expected that prolonged circulation of anticancer drugs will increase their anticancer activity while decreasing their toxic side effects. The purpose of this study was to prepare 5-fluorouracil (5-FU loaded block copolymers, with poly(γ-benzyl-L-glutamate (PBLG as the hydrophobic block and poly(ethylene glycol (PEG as the hydrophilic block, and then examine the 5-FU release characteristics, pharmacokinetics, and anticancer effects of this novel compound. Methods 5-FU loaded PEG-PBLG (5-FU/PEG-PBLG nanoparticles were prepared by dialysis and then scanning electron microscopy (SEM and transmission electron microscopy (TEM were used to observe the shape and size of the nanoparticles, and ultraviolet spectrophotometry was used to evaluate the 5-FU in vitro release characteristics. The pharmacokinetic parameters of 5-FU/PEG-PBLG nanoparticles in rabbit plasma were determined by measuring the 5-FUby high-performance liquid chromatography (HPLC. To study in vivo effects, LoVo cells (human colon cancer cell line or Tca8113 cells (human oral squamous cell carcinoma cell line were implanted in BALB/c nude mice that were subsequently treated with 5-FU or 5-FU/PEG-PBLG nanospheres. Results 5-FU/PEG-PBLG nanoparticles had a core-shell spherical structure with a diameter of 200 nm and a shell thickness of 30 nm. The drug loading capacity was 27.1% and the drug encapsulation was 61.5%. Compared with 5-FU, 5-FU/PEG-PBLG nanoparticles had a longer elimination half-life (t1/2, 33.3 h vs. 5 min, lower peak concentration (C, 4563.5 μg/L vs. 17047.3 μg/L, and greater distribution volume (VD, 0.114 L vs. 0.069 L. Compared with a blank control, LoVo cell xenografts and Tca8113 cell xenografts treated with 5-FU or 5-FU/PEG-PBLG nanoparticles grew slower and had prolonged tumor doubling times. 5-FU/PEG-PBLG nanoparticles showed greater inhibition of tumor growth than 5-FU (p 0.05. Conclusion In our model system, 5-FU/PEG-PBLG nanoparticles
5-Fluorouracil-resistant strain of Methanobacterium thermoautortrophicum

International Nuclear Information System (INIS)

Nagle, D.P. Jr.; Teal, R.; Eisenbraun, A.

1987-01-01

Growth of Methanobacterium thermoautotrophicum Marburg is inhibited by the pyrimidine, 5-fluorouracil (FU). It was shown previously that methanogenesis is not inhibited to the same extent as growth. A spontaneously occurring FU-resistant strain (RTAE-1) was isolated from a culture of strain Marburg. The growth of both strains was inhibited by 5-fluorodeoxyuridine but not 5-fluorocytosine, and the wild type was more susceptible to inhibition by 5-azauracil and 6-azauracil than was strain RTAE-1. The cellular targets for the pyrimidine analogs are not known. When the accumulation of 14 C-labeled uracil or FU by the two strains was compared, the wilt type took up 15-fold more radiolabel per cell than did the FU-resistant strain. In the wild type, radiolabel from uracil was incorporated into the soluble pool, RNA, and DNA. The metabolism of uracil appeared to involve a uracil phosphoribosyltransferase activity. Strain Marburg extracts contained this enzyme, whereas FU-resistant strain RTAE-1 extracts had less than 1/10 as much activity. Although it is possible that a change in permeability to the compounds plays a role in the stable resistance of strain RTAE-1, the fact that it lacks the ability to metabolize pyrimidines to nucleotides is sufficient to account for its phenotype
5-Fluorouracil-resistant strain of Methanobacterium thermoautotrophicum.

Science.gov (United States)

Nagle, D P; Teal, R; Eisenbraun, A

1987-09-01

Growth of Methanobacterium thermoautotrophicum Marburg is inhibited by the pyrimidine, 5-fluorouracil (FU). It was shown previously that methanogenesis is not inhibited to the same extent as growth. A spontaneously occurring FU-resistant strain (RTAE-1) was isolated from a culture of strain Marburg. The growth of both strains was inhibited by 5-fluorodeoxyuridine but not 5-fluorocytosine, and the wild type was more susceptible to inhibition by 5-azauracil and 6-azauracil than was strain RTAE-1. The cellular targets for the pyrimidine analogs are not known. When the accumulation of 14C-labeled uracil or FU by the two strains was compared, the wild type took up 15-fold more radiolabel per cell than did the FU-resistant strain. In the wild type, radiolabel from uracil was incorporated into the soluble pool, RNA, and DNA. The metabolism of uracil appeared to involve a uracil phosphoribosyltransferase activity. Strain Marburg extracts contained this enzyme, whereas FU-resistant strain RTAE-1 extracts had less than 1/10 as much activity. Although it is possible that a change in permeability to the compounds plays a role in the stable resistance of strain RTAE-1, the fact that it lacks the ability to metabolize pyrimidines to nucleotides is sufficient to account for its phenotype.
Epithelial Downgrowth after Intraocular Surgery Treated with Intracameral 5-Fluorouracil

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Nina Ni

2015-01-01

Full Text Available Purpose. To present the clinical and histopathologic correlation of two cases of epithelial downgrowth (EDG after prior intraocular surgery. Methods. Observational case reports. Results. We present two cases of EDG occurring after intraocular surgery. In both cases, after two anterior chamber injections of 5-fluorouracil (5FU, the area of EDG initially regressed. In Case 1, a limited area of EDG eventually recurred, and penetrating keratoplasty with cryotherapy was curative. In Case 2, subsequent corneal edema required Descemet-stripping automated endothelial keratoplasty, and the patient remained clinically free of EDG without further treatment. Conclusion. Intracameral 5FU may have a role in the treatment of EDG after intraocular surgery, though its precise utilization and impact remain to be defined.
Tetrathiomolybdate sensitizes ovarian cancer cells to anticancer drugs doxorubicin, fenretinide, 5-fluorouracil and mitomycin C

International Nuclear Information System (INIS)

Kim, Kyu Kwang; Lange, Thilo S; Singh, Rakesh K; Brard, Laurent; Moore, Richard G

2012-01-01

Our recent study showed that tetrathiomolybdate (TM), a drug to treat copper overload disorders, can sensitize drug-resistant endometrial cancer cells to reactive oxygen species (ROS)-generating anticancer drug doxorubicin. To expand these findings in the present study we explore TM efficacy in combination with a spectrum of ROS-generating anticancer drugs including mitomycin C, fenretinide, 5-fluorouracil and doxorubicin in ovarian cancer cells as a model system. The effects of TM alone or in combination with doxorubicin, mitomycin C, fenretinide, or 5-fluorouracil were evaluated using a sulforhodamine B assay. Flow cytometry was used to detect the induction of apoptosis and ROS generation. Immunoblot analysis was carried out to investigate changes in signaling pathways. TM potentiated doxorubicin-induced cytotoxicity and modulated key regulators of apoptosis (PARP, caspases, JNK and p38 MAPK) in SKOV-3 and A2780 ovarian cancer cell lines. These effects were linked to the increased production of ROS, as shown in SKOV-3 cells. ROS scavenging by ascorbic acid blocked the sensitization of cells by TM. TM also sensitized SKOV-3 to mitomycin C, fenretinide, and 5-fluorouracil. The increased cytotoxicity of these drugs in combination with TM was correlated with the activity of ROS, loss of a pro-survival factor (e.g. XIAP) and the appearance of a pro-apoptotic marker (e.g. PARP cleavage). Our data show that TM increases the efficacy of various anticancer drugs in ovarian cancer cells in a ROS-dependent manner
Intravenous 5-fluorouracil versus oral doxifluridine as preoperative concurrent chemoradiation for locally advanced rectal cancer. Prospective randomized trails

International Nuclear Information System (INIS)

Kim, Nam-Kyu; Min, Jin-Sik; Park, Jea-Kun; Yun, Seong-Hyun; Sung, Jin-Sil; Jung, Hyun-Chul; Roh, Jae-Kyung

2001-01-01

Preoperative radiation treatment with concomitant intravenous infusion of 5-fluorouracil (5-FU) is known to be effective in shrinking and downstaging of tumors. However, chemotherapy has often been limited by its toxicity and poor patient compliance. Oral 5-FU is known to have several advantages over conventional intravenous 5-FU infusion such as lower toxicity and higher quality of life without compromising the efficacy of the treatment. The aim of this study was to compare intravenous 5-FU with oral doxifluridine with respect to tumor response, toxicity and quality of life. Twenty-eight patients with rectal cancer, staged as over T3N1 or T4 by transrectal ultrasonography between July 1997 and December 1998, were included in this study. Intravenous 5-FU (450 mg/m 2 ) and leucovorin (20 mg/m 2 ) were given for five consecutive days during the first and fifth weeks of radiation therapy (50.4 Gy) (n=14). Oral doxifluridine (700 mg/m 2 /day) and leucovorin (20 mg/m 2 ) were given daily during radiation treatment (n=14). Quality of life was scored according to 22 activity items (good, >77; fair, >58; poor, <57). Surgical resection was performed 4 weeks after completion of concurrent chemoradiation treatment. Tumor response was classified into CR (complete remission), PR (partial response; 50% diminution of tumor volume or downstaging) and NR (no response). Tumor response was CR 3/14 (21.4%), PR 7/14 (50%) and NR 4/14 (28.6%) in the IV arm versus CR 2/14 (14.2%), PR 6/14 (42.9%) and NR 6/14 (42.9%) in the Oral arm (p=0.16, 0.23, 0.24), respectively. The quality of life was poor (36.4% versus 33.3%), fair and good (63.6% versus 66.7%) between the IV arm and Oral arm, respectively. Gastrointestinal toxicity was 2/14 (14.3%) in the IV arm versus 5/14 (35.7%) in the Oral arm, respectively. Stomatitis was only observed in the IV arm (1/14, 7.1%). Hematological toxicity was 3/14 (21.4%) in the IV arm versus 4/14 (28.5%) in the Oral arm, respectively. Systemic recurrence
Pediatric central venous access devices: nursing interventions

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Duffy EA

2017-05-01

Full Text Available Elizabeth A Duffy, Kathryn N Nelson Department of Health Behavior and Biological Sciences, The University of Michigan School of Nursing, Ann Arbor, MI, USA Abstract: A central venous catheter (CVC is an indwelling catheter that provides permanent or temporary stable venous access for both acute and chronically ill pediatric patients. These catheters provide stable venous access that can be used for a variety of medical purposes including drawing blood, hemodynamic monitoring, infusion of intravenous medications, infusion of intravenous fluids, chemotherapy, blood products, and parenteral nutrition. Each day, nurses access and care for CVCs in infants, children, and adolescents; the precision of this care can prevent life-threatening complications. The purpose of this review and the case study is to highlight the importance and components of evidence-based nursing practice in pediatric CVC care. A historical perspective of CVC care is provided in conjunction with current national initiatives to improve patient outcomes for children with CVCs. Infection prevention, clinical practice guidelines, quality improvement, and evidence-based care bundles are discussed. Keywords: pediatric nursing, central venous catheters, central line-associated bloodstream infection, care bundles, pediatric case study
[The efficacy of the combined use of 5-fluorouracil electrophoresis and magnetotherapy in experimental pancreatitis].

Science.gov (United States)

Kents, V V; Tsympilova, T A; Mavrodiĭ, V M; Godlevskiĭ, L S

1994-01-01

As shown on the experimental model of rat acute pancreatitis, an intensive 5-fluorouracil electrophoresis course in combination with magnetotherapy significantly reduces the activity of blood trypsin, amylase, lipase and corticosterone. The treatment is thought effective in experimental pancreatitis.
Preparation of 5-fluorouracil nanoparticles by supercritical antisolvents for pulmonary delivery

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Pardis Kalantarian

2010-09-01

Full Text Available Pardis Kalantarian1,2, Abdolhosein Rouholamini Najafabadi1, Ismaeil Haririan2, Alireza Vatanara1, Yadollah Yamini3, Majid Darabi1, Kambiz Gilani11Aerosol Research Laboratory and 2Pharmaceutical Laboratory, School of Pharmacy, Tehran University of Medical Sciences, 3Department of Chemistry, Tarbiat Modarres University, Tehran, IranAbstract: This study concerns the supercritical antisolvent process which allows single-step production of 5-fluorouracil (5-FU nanoparticles. This process enhances the physical characteristics of 5-FU in order to deliver it directly to the respiratory tract. Several mixtures of methanol with dichloromethane, acetone, or ethanol were used for particle preparation, and their effects on the physical characteristics of the final products were studied. The conditions of the experiment included pressures of 100 and 150 bar, temperature of 40°C, and a flow rate of 1 mL/min. The particles were characterized physicochemically before and after the process for their morphology and crystallinity. In spite of differences in size, the particles were not very different regarding their morphology. The resulting particles were of a regular shape, partly spherical, and appeared to have a smooth surface, whereas the mechanically milled particles showed less uniformity, had surface irregularities and a high particle size distribution, and seemed aggregated. Particles of 5-FU precipitated from methanol-dichloromethane 50:50 had a mean particle size of 248 nm. In order to evaluate the aerodynamic behavior of the nanoparticles, six 5-FU dry powder formulations containing mixtures of coarse and fine lactose of different percentages were prepared. Deposition of 5-FU was measured using a twin-stage liquid impinger and analyzed using a validated high pressure liquid chromatography method. Addition of fine lactose improved the aerodynamic performance of the drug, as determined by the fine particle fraction.Keywords: supercritical antisolvent, 5
Intra-arterial cis-diamminedichloroplatinum infusion treatment for widespread hepatocellular carcinoma

International Nuclear Information System (INIS)

Park, Sung Il; Yang, Hee Chul; Lee, Do Yon; Shim, Yong Woon; Kim, Sang Heum; Kim, Myeong Jin; Lee, Jong Tae; Yoo, Hyung Sik

1997-01-01

The purpose of this study is to evaluate the therapeutic efficacy of intra-arterial infusion of Cis-diamminedichloroplatinum (C-DDP) for the treatment of hepatocellular carcinomas with widespread involvement. We retrospectively analyzed 22 patients who between July 1994 and June 1996 had undergone intra-arterial c-DDP infusion therapy for the treatment of hepatocellular carcinomas with widespread involvement. The hepatomas involved both lobes in ten, portal venous obstructions in fourteen, arterio-portal shunts in nine, and arterio-venous shunts in two. Proper hepatic artery was selected for infusion of 100 mg/BSA of C-DDP. The same procedure was repeated every 3 to 4 weeks, and the total number of infusions was 65. On the basis of WHO criteria, response was classified as complete remission, partial remission, stable, or progression of the disease. Six-month and one-year survival rates were estimated, and adverse reactions were evaluated. Although the response rate is not high, intra-arterial C-DDP infusion therapy can be used as an alternative treatment for hepatocellular carcinomas with widespread involvement; adverse reactions are tolerable. (author). 16 refs., 3 figs
Synthetic adenosine receptor agonists modulate murine haematopoiesis: a study employing the cytotoxic action of 5-fluorouracil

Czech Academy of Sciences Publication Activity Database

Hofer, Michal; Pospíšil, Milan; Vacek, Antonín; Znojil, V.; Pipalová, I.

2004-01-01

Roč. 5, Suppl. 2 (2004), s. S65 ISSN 1466-4860. [Congress of the European Hematology Association /9./. 10.06.2004-13.06.2004, Geneva] R&D Projects: GA ČR GA305/02/0423 Keywords : 5-fluorouracil * haematopoiesis * adenosine Subject RIV: BO - Biophysics
Nedaplatin and 5-fluorouracil combined with radiotherapy for advanced esophageal cancer

International Nuclear Information System (INIS)

Nakamura, Tsutomu; Ide, Hiroko; Eguchi, Reiki; Hayashi, Kazuhiko; Ota, Masaho; Narumiya, Kosuke; Takasaki, Ken

2003-01-01

We conducted a pilot study of nedaplatin+5-fluorouracil (5-FU) combined with radiotherapy for 29 patients with primary advanced (stage IV) esophageal cancer. A complete remission (CR) was obtained in 4 (14%) and a partial response in 13 patients (response rate: 59%). The median survival time and one-year survival rate were 238 days and 34.5%, respectively. Of the 29 patients, 24 (83%) completed the treatment schedule and toxicity of stomatitis and the like was infrequent. In conclusion, these results suggest that the efficacy of nedaplatin+5-FU combined with radiotherapy might not differ from that of cisplatin+5-FU combined with radiotherapy. Clearly, the usefulness of this combined therapy needs to be assessed in multicenter phase III trials. (author)
Genetic polymorphisms in 5-Fluorouracil-related enzymes predict pathologic response after neoadjuvant chemoradiation for rectal cancer.

Science.gov (United States)

Nelson, Bailey; Carter, Jane V; Eichenberger, Maurice R; Netz, Uri; Galandiuk, Susan

2016-11-01

Many patients with rectal cancer undergo preoperative neoadjuvant chemoradiation, with approximately 70% exhibiting pathologic downstaging in response to treatment. Currently, there is no accurate test to predict patients who are likely to be complete responders to therapy. 5-Fluorouracil is used regularly in the neoadjuvant treatment of rectal cancer. Genetic polymorphisms affect the activity of thymidylate synthase, an enzyme involved in 5-Fluorouracil metabolism, which may account for observed differences in response to neoadjuvant treatment between patients. Detection of genetic polymorphisms might identify patients who are likely to have a complete response to neoadjuvant therapy and perhaps allow them to avoid operation. DNA was isolated from whole blood taken from patients with newly diagnosed rectal cancer who received neoadjuvant therapy (n = 50). Response to therapy was calculated with a tumor regression score based on histology from the time of operation. Polymerase chain reaction was performed targeting the promoter region of thymidylate synthase. Polymerase chain reaction products were separated using electrophoresis to determine whether patients were homozygous for a double-tandem repeat (2R), a triple-tandem repeat (3R), or were heterozygous (2R/3R). A single nucleotide polymorphism, 3G or 3C, also may be present in the second repeat unit of the triple-tandem repeat allele. Restriction fragment length polymorphism assays were performed in patients with at least one 3R allele using HaeIII. Patients with at least 1 thymidylate synthase 3G allele were more likely to have a complete or partial pathologic response to 5-Fluorouracil neoadjuvant therapy (odds ratio 10.4; 95% confidence interval, 1.3-81.6; P = .01) than those without at least one 3G allele. Identification of rectal cancer patients with specific genetic polymorphisms in enzymes involved in 5-Fluorouracil metabolism seems to predict the likelihood of complete or partial pathologic response

Chemoprevention of Basal and Squamous Cell Carcinoma With a Single Course of Fluorouracil, 5%, Cream: A Randomized Clinical Trial.

Science.gov (United States)

Weinstock, Martin A; Thwin, Soe Soe; Siegel, Julia A; Marcolivio, Kimberly; Means, Alexander D; Leader, Nicholas F; Shaw, Fiona M; Hogan, Daniel; Eilers, David; Swetter, Susan M; Chen, Suephy C; Jacob, Sharon E; Warshaw, Erin M; Stricklin, George P; Dellavalle, Robert P; Sidhu-Malik, Navjeet; Konnikov, Nellie; Werth, Victoria P; Keri, Jonette E; Robinson-Bostom, Leslie; Ringer, Robert J; Lew, Robert A; Ferguson, Ryan; DiGiovanna, John J; Huang, Grant D

2018-02-01

Keratinocyte carcinoma (ie, cutaneous basal and squamous cell carcinoma) is the most common cancer in the United States. To determine whether topical fluorouracil could prevent surgically treated keratinocyte carcinoma. The Veterans Affairs Keratinocyte Carcinoma Chemoprevention Trial was a randomized, double-blind, placebo-controlled trial of topical fluorouracil for chemoprevention of keratinocyte carcinoma. Participants were recruited from May 2009 to September 2011 from 12 Veterans Affairs medical centers and followed until June 30, 2013. Participants were veterans (n = 932) with a history of at least 2 keratinocyte carcinomas in the past 5 years; almost all were white males and the median age was 70 years. Application of fluorouracil, 5%, (n = 468) or vehicle control cream (n = 464) to the face and ears twice daily for 2 to 4 weeks upon randomization. Surgically treated keratinocyte, basal cell, and squamous cell carcinoma risk on the face and ears in the first year after enrollment; and time to first surgically treated keratinocyte, basal cell, and squamous cell carcinoma. The a priori hypothesis was that fluorouracil would be effective in preventing these cancers. Of 932 participants (916 men [98%]; 926 white [99%]; median age, 70 years), 299 developed a basal cell carcinoma end point (95 in year 1) and 108 developed a squamous cell carcinoma end point (25 in year 1) over 4 years (median follow-up, 2.8 years). Over the entire study, there was no difference between treatment groups in time to first keratinocyte, basal cell, or squamous cell carcinoma. During the first year, however, 5 participants (1%) in the fluorouracil group developed a squamous cell carcinoma vs 20 (4%) in the control group, a 75% (95% CI, 35%-91%) risk reduction (P = .002). The 11% reduction in basal cell carcinoma risk during year 1 (45 [10%] in the fluorouracil group vs 50 [11%] in the control group) was not statistically significant (95% CI, 39% reduction to 31
Preparation of 5-fluorouracil loaded chitosan microparticle and its drug release properties

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Li Mingming

2017-01-01

Full Text Available Chitosan is one kind of good biocompatible polymer and is suitble for drug carriers. Preparation of 5-fluorouracil (5-Fu loaded chitosan (CS particles and in vitro release experiment were performed using ionic crosslinking method with sodium tripolyphosphate (TPP as crosslinker. The optimal preparing parameters were verified by 5-Fu release experiments. The drug loading, and release behavior of drug loaded microparticles in vitro were investigated. The optimal preparation conditions were: the temperature 25°C, the ratio of CS to TPP 5:1, the CS concentration 1.5g/L, stirring speed 650rpm. Under these conditions, the drug loading of particles was up to 45%.
Ramosetron for the prevention of nausea and vomiting during 5-fluorouracil-based chemoradiotherapy for pancreatico-biliary cancer

International Nuclear Information System (INIS)

Kim, Kyubo; Chie, Eui-Kyu; Jang, Jin-Young; Kim, Sun-Whe; Oh, Do-Youn; Im, Seock-Ah; Kim, Tae-You; Bang, Yung-Jue; Ha, Sung-W.

2009-01-01

The aim of the study was to evaluate the role of ramosetron for the prevention of chemoradiotherapy-induced nausea and vomiting (CRINV) in patients receiving upper abdominal irradiation with concurrent 5-fluorouracil chemotherapy. Between November 2006 and April 2007, 25 patients with pancreatico-biliary cancer underwent adjuvant chemoradiotherapy. A total dose of 40 Gy was delivered using 2 Gy/fraction, 5 days a week, with 2 weeks of planned rest after 20 Gy. Concomitant 5-fluorouracil (500 mg/m 2 /day i.v. bolus) was administered for the first 3 days of each split course. During the first course of chemoradiotherapy, all patients had prophylactic metoclopramide before treatment and those refractory to metoclopramide received rescue medication with ondansetron. During the second course of chemoradiotherapy, prophylactic ramosetron was given to patients who were refractory to ondansetron. Response to antiemetics was scored in four tiers: none, no CRINV; mild, did not interfere with normal daily life; moderate, interfered with normal daily life and severe, patient bedridden because of CRINV. Fifty-six percent of the patients (14 of 25) had moderate CRINV despite metoclopramide, and received ondansetron. Ten patients who experienced moderate CRINV despite the ondansetron had prophylactic ramosetron, and 60% of the patients (6 of 10) had the symptom improved. Ramosetron proved to be an effective alternative for the control of CRINV during upper abdominal irradiation with concurrent 5-fluorouracil chemotherapy. (author)
Pharmacokinetic characteristics and anticancer effects of 5-Fluorouracil loaded nanoparticles

International Nuclear Information System (INIS)

Li, Su; Wang, Anxun; Jiang, Wenqi; Guan, Zhongzhen

2008-01-01

It is expected that prolonged circulation of anticancer drugs will increase their anticancer activity while decreasing their toxic side effects. The purpose of this study was to prepare 5-fluorouracil (5-FU) loaded block copolymers, with poly(γ-benzyl-L-glutamate) (PBLG) as the hydrophobic block and poly(ethylene glycol) (PEG) as the hydrophilic block, and then examine the 5-FU release characteristics, pharmacokinetics, and anticancer effects of this novel compound. 5-FU loaded PEG-PBLG (5-FU/PEG-PBLG) nanoparticles were prepared by dialysis and then scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were used to observe the shape and size of the nanoparticles, and ultraviolet spectrophotometry was used to evaluate the 5-FU in vitro release characteristics. The pharmacokinetic parameters of 5-FU/PEG-PBLG nanoparticles in rabbit plasma were determined by measuring the 5-FUby high-performance liquid chromatography (HPLC). To study in vivo effects, LoVo cells (human colon cancer cell line) or Tca8113 cells (human oral squamous cell carcinoma cell line) were implanted in BALB/c nude mice that were subsequently treated with 5-FU or 5-FU/PEG-PBLG nanospheres. 5-FU/PEG-PBLG nanoparticles had a core-shell spherical structure with a diameter of 200 nm and a shell thickness of 30 nm. The drug loading capacity was 27.1% and the drug encapsulation was 61.5%. Compared with 5-FU, 5-FU/PEG-PBLG nanoparticles had a longer elimination half-life (t 1/2 , 33.3 h vs. 5 min), lower peak concentration (C, 4563.5 μg/L vs. 17047.3 μg/L), and greater distribution volume (V D , 0.114 L vs. 0.069 L). Compared with a blank control, LoVo cell xenografts and Tca8113 cell xenografts treated with 5-FU or 5-FU/PEG-PBLG nanoparticles grew slower and had prolonged tumor doubling times. 5-FU/PEG-PBLG nanoparticles showed greater inhibition of tumor growth than 5-FU (p < 0.01). In the PEG-PBLG nanoparticle control group, there was no tumor inhibition (p > 0.05). In our
Significant air embolism: A possibility even with collapsible intravenous fluid containers when used with rapid infuser system

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Deepanjali Pant

2010-01-01

Full Text Available Significant venous air embolism may develop acutely during the perioperative period due to a number of causes such as during head and neck surgery, spinal surgery, improper central venous and haemodialysis catheter handling, etc. The current trend of using self collapsible intravenous (IV infusion bags instead of the conventional glass or plastic bottles has several advantages, one of thaem being protection against air embolism. We present a 56-year-old man undergoing kidney transplantation, who developed a near fatal venous air embolism during volume resuscitation with normal saline in collapsible IV bags used with rapid infuser system. To our knowledge, this problem with collapsible infusion bags has not been reported earlier.
Significant air embolism: A possibility even with collapsible intravenous fluid containers when used with rapid infuser system

Science.gov (United States)

Pant, Deepanjali; Narani, Krishan Kumar; Sood, Jayashree

2010-01-01

Significant venous air embolism may develop acutely during the perioperative period due to a number of causes such as during head and neck surgery, spinal surgery, improper central venous and haemodialysis catheter handling, etc. The current trend of using self collapsible intravenous (IV) infusion bags instead of the conventional glass or plastic bottles has several advantages, one of thaem being protection against air embolism. We present a 56-year-old man undergoing kidney transplantation, who developed a near fatal venous air embolism during volume resuscitation with normal saline in collapsible IV bags used with rapid infuser system. To our knowledge, this problem with collapsible infusion bags has not been reported earlier. PMID:20532073
Theoretical, clinical and pharmacokinetic aspects of cancer chemotherapy administered by continuous infusion

International Nuclear Information System (INIS)

Sikic, B.I.

1986-01-01

This chapter reviews some of the theoretical and empirical aspects of the administration of anti-cancer drugs by continuous intravenous infusion in conjunction with radiation therapy. The variables contributing to schedule dependence of anti-cancer drugs are discussed. A table shows the improved therapeutic index of Bleomycin by continuous infusion in mice. The use of Cytarabine, a pyrimidine anti-metabolite which kills cells during S-phase or DNA synthesis, is examined. Fluorouracil and Doxorubicin are examined and several other drugs including vincristine, vinblastine, etoposide, and cisplatin are discussed
Tracer measured substrate turnover requires arterial sampling downstream of infusion site

International Nuclear Information System (INIS)

Stanley, W.C.; Neese, R.A.; Gertz, E.W.; Wisneski, J.A.; Morris, D.L.; Brooks, G.A.

1986-01-01

Measurement of metabolite turnover (Rt) with radioactive tracers is done by either infusing tracer venously and sampling specific activity (SA) arterially (V-A modes), or by infusing into the aorta and sampling venous blood (A-V mode). Using the Fick principle, the necessity for using the V-A mode can be demonstrated. If tracer is infused into the left ventricle, in a steady state the Rt is the product of arterial trace concentration, the cardiac output, and the tracer extraction ratio for the whole body. This is expressed as: Rt = Ca x Qx ((*Ca - *Cv)/*Ca) (Eq1) where C=trace concentration (μmol/ml), *C=tracer conc. (dpm/ml), a=arterial, v-=mixed venous, and Q=cardiac output (ml/min). Rearranging the equation: Rt = Qx(*Ca - *Cv)/SAa = F/SAa (Eq2) where SAa is *Ca/Ca, and Qx (*Ca-*Cv) equals the infusion rate (F). The authors compared Eqs1 and 2 (Rt = F/SAa) in 3 anesthetized dogs in which [1- 14 C] lactate was infused into the left ventricle, and blood was sampled arterially downstream from the infusion site and in the pulmonary artery. Eqs 1 and 2 gave similar results for Rt (45.9 vs. 43.9 μmol/kg min), while substituting SAv for SAa (A-V mode) into Eq 2 gave a higher Rt (53.6). When SAv (A-V mode) is used, the specific activity seen by the tissues (SAa) is not considered in the calculation of Rt. Therefore, only the V-A mode meets the requirements for tracer measured metabolite turnover
Design, synthesis and biological evaluation of 5-fluorouracil-derived benzimidazoles as novel type of potential antimicrobial agents.

Science.gov (United States)

Fang, Xue-Jie; Jeyakkumar, Ponmani; Avula, Srinivasa Rao; Zhou, Qian; Zhou, Cheng-He

2016-06-01

A series of 5-fluorouracil benzimidazoles as novel type of potential antimicrobial agents were designed and synthesized for the first time. Bioactive assay manifested that some of the prepared compounds exhibited good or even stronger antibacterial and antifungal activities against the tested strains in comparison with reference drugs norfloxacin, chloromycin and fluconazole. Noticeably, 3-fluorobenzyl benzimidazole derivative 5c gave remarkable antimicrobial activities against Saccharomyces cerevisiae, MRSA and Bacillus proteus with MIC values of 1, 2 and 4μg/mL, respectively. Experimental research revealed that compound 5c could effectively intercalate into calf thymus DNA to form compound 5c-DNA complex which might block DNA replication and thus exert antimicrobial activities. Molecular docking indicated that compound 5c should bind with DNA topoisomerase IA through three hydrogen bonds by the use of fluorine atom and oxygen atoms in 5-fluorouracil with the residue Lys 423. Copyright © 2016 Elsevier Ltd. All rights reserved.
Vasopressin-induced changes in splanchnic blood flow and hepatic and portal venous pressures in liver resection.

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Bown, L Sand; Ricksten, S-E; Houltz, E; Einarsson, H; Söndergaard, S; Rizell, M; Lundin, S

2016-05-01

To minimize blood loss during hepatic surgery, various methods are used to reduce pressure and flow within the hepato-splanchnic circulation. In this study, the effect of low- to moderate doses of vasopressin, a potent splanchnic vasoconstrictor, on changes in portal and hepatic venous pressures and splanchnic and hepato-splanchnic blood flows were assessed in elective liver resection surgery. Twelve patients were studied. Cardiac output (CO), stroke volume (SV), mean arterial (MAP), central venous (CVP), portal venous (PVP) and hepatic venous pressures (HVP) were measured, intraoperatively, at baseline and during vasopressin infusion at two infusion rates (2.4 and 4.8 U/h). From arterial and venous blood gases, the portal (splanchnic) and hepato-splanchnic blood flow changes were calculated, using Fick's equation. CO, SV, MAP and CVP increased slightly, but significantly, while systemic vascular resistance and heart rate remained unchanged at the highest infusion rate of vasopressin. PVP was not affected by vasopressin, while HVP increased slightly. Vasopressin infusion at 2.4 and 4.8 U/h reduced portal blood flow (-26% and -37%, respectively) and to a lesser extent hepato-splanchnic blood flow (-9% and -14%, respectively). The arterial-portal vein lactate gradient was not significantly affected by vasopressin. Postoperative serum creatinine was not affected by vasopressin. Short-term low to moderate infusion rates of vasopressin induced a splanchnic vasoconstriction without metabolic signs of splanchnic hypoperfusion or subsequent renal impairment. Vasopressin caused a centralization of blood volume and increased cardiac output. Vasopressin does not lower portal or hepatic venous pressures in this clinical setting. © 2016 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.
Enhancement of radiation effect on mouse intestinal crypt survival by timing of 5-fluorouracil administration

International Nuclear Information System (INIS)

Ho, E.; Coffey, C.; Maruyama, Y.

1977-01-01

There is a marked dependence of mouse crypt survival on the sequence of combined drug-radiation treatment and on the time lapse between irradiation and drug administration. When 5-fluorouracil is administered 6 hours after irradiation or later (up to 18 hours postirradiation), crypt survival drops significantly
Mixing in the human carotid artery during carotid drug infusion studied with PET

International Nuclear Information System (INIS)

Junck, L.; Koeppe, R.A.; Greenberg, H.S.

1989-01-01

The safety and efficacy of drug infusion into the carotid artery require adequate mixing of the infused solution with carotid blood. Using positron emission tomography (PET), we studied the mixing of solutions infused into the human carotid artery in seven patients by analyzing the distribution of [15O]H2O infused into the carotid artery and by vein. At four infusion rates ranging from 0.5 to 10 ml/min, the variability in distribution averaged 16.5-17.8% among the pixels in a large volume of interest, without dependence on the infusion rate. The overall correlation between [15O]H2O influx with arterial infusion and [15O]H2O influx with venous injection was 0.78-0.82 at the four infusion rates, with no trend toward higher correlations at the faster infusion rates. The distribution into the anterior, middle, and posterior cerebral artery territories differed from distribution throughout the entire carotid territory by an average of 6.2-9.6% at the four infusion rates, with no trend toward smaller differences at the faster infusion rates. Infusions performed into a vinyl tube simulating the carotid artery indicated that at 0.5 ml/min, the velocity of fluid exiting the catheter makes no apparent contribution to mixing. We conclude that with infusions at the carotid bifurcation, mixing in the human carotid artery is complete or nearly complete over a wide range of infusion rates. The mixing appears to result from the patterns of blood flow within the artery, and not from jet effects at the catheter tip
Insulin-induced enhancement of MCF-7 breast cancer cell response to 5-fluorouracil and cyclophosphamide.

Science.gov (United States)

Agrawal, Siddarth; Łuc, Mateusz; Ziółkowski, Piotr; Agrawal, Anil Kumar; Pielka, Ewa; Walaszek, Kinga; Zduniak, Krzysztof; Woźniak, Marta

2017-06-01

The study was designed to evaluate the potential use of insulin for cancer-specific treatment. Insulin-induced sensitivity of MCF-7 breast cancer cells to chemotherapeutic agents 5-fluorouracil and cyclophosphamide was evaluated. To investigate and establish the possible mechanisms of this phenomenon, we assessed cell proliferation, induction of apoptosis, activation of apoptotic and autophagic pathways, expression of glucose transporters 1 and 3, formation of reactive oxygen species, and wound-healing assay. Additionally, we reviewed the literature regarding theuse of insulin in cancer-specific treatment. We found that insulin increases the cytotoxic effect of 5-fluorouracil and cyclophosphamide in vitro up to two-fold. The effect was linked to enhancement of apoptosis, activation of apoptotic and autophagic pathways, and overexpression of glucose transporters 1 and 3 as well as inhibition of cell proliferation and motility. We propose a model for insulin-induced sensitization process. Insulin acts as a sensitizer of cancer cells to cytotoxic therapy through various mechanisms opening a possibility for metronomic insulin-based treatments.
The role of initial 5-fluorouracil trabeculectomy in primary glaucoma.

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Dastur Y

1994-10-01

Full Text Available Sixty-eight patients with primary glaucoma involving 68 eyes were divided into two groups: Group I eyes were subjected to trabeculectomy (n = 38 and Group II eyes underwent trabeculectomy followed by subconjunctival injections of 5-fluorouracil (35 mg (n = 30. After one year follow-up, Group I eyes exhibited reduction of mean intra-ocular tension from 45.7 mm Hg (pre-operative to 16 mm Hg; optic disc cupping remained unchanged and 24/38 eyes (63% were found to have field defects (19/38 i.e. 50% had preoperative field defects. Group II eyes showed a reduction of mean intra-ocular pressure from 47.3 mmHg to 9.3 mmHg after one year. Mean cup disc ratio was lowered from 0.50:1 to 0.46:1 and 17/30 eyes (57% which had field defects initially continued to exhibit the same. Complications in Group I and II eyes were shallow anterior chamber [8/38 eyes (21% from Group I and 8/30 eyes (26% from Group II], posterior synechiae formation in 10/38 eyes (26% and 8/30 eyes (26% and cataract progression in 13/38 eyes (34% and 12/30 eyes (40% respectively; only Group II eyes had transient superficial keratitis in 9/30 eyes (30% and thin blebs in 6/30 eyes (20%. The use of 5-fluorouracil after trabeculectomy for primary glaucoma resulted in lowering of intra-ocular pressure, eliminated the need for antiglaucoma medications post-operatively, reduced the galucomatous cup size, and prevented progression of field loss without having a significantly increased complication rate.
Vasopressin and nitroglycerin decrease portal and hepatic venous pressure and hepato-splanchnic blood flow.

Science.gov (United States)

Wisén, E; Svennerholm, K; Bown, L S; Houltz, E; Rizell, M; Lundin, S; Ricksten, S-E

2018-03-26

Various methods are used to reduce venous blood pressure in the hepato-splanchnic circulation, and hence minimise blood loss during liver surgery. Previous studies show that combination of vasopressin and nitroglycerin reduces portal pressure and flow in patients with portal hypertension, and in this study we investigated this combination in patients with normal portal pressure. In all, 13 patients were studied. Measurements were made twice to confirm baseline (C1 and BL), during vasopressin infusion 4.8 U/h (V), and during vasopressin infusion combined with nitroglycerin infusion (V + N). Portal venous pressure (PVP), hepatic venous pressure (HVP), central haemodynamics and arterial and venous blood gases were obtained at each measuring point, and portal (splanchnic) and hepato-splanchnic blood flow changes were calculated. Vasopressin alone did not affect PVP, whereas HVP increased slightly. In combination with nitroglycerin, PVP decreased from 10.1 ± 1.6 to 8.9 ± 1.3 mmHg (P HVP decreased from 7.9 ± 1.9 to 6.2 ± 1.3 mmHg (P = 0.001). Vasopressin reduced portal blood flow by 47 ± 19% and hepatic venous flow by 11 ± 18%, respectively. Addition of nitroglycerin further reduced portal- and hepatic flow by 55 ± 13% and 30 ± 13%, respectively. Vasopressin alone had minor effects on central haemodynamics, whereas addition of nitroglycerin reduced cardiac index (3.2 ± 0.7 to 2.7 ± 0.5; P < 0.0001). The arterial-portal vein lactate gradient was unaffected. The combination of vasopressin and nitroglycerin decreases portal pressure and hepato-splanchnic blood flow, and could be a potential treatment to reduce bleeding in liver resection surgery. © 2018 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.
The clinical efficacy of methotrexate and 5-fluorouracil in the interventional treatment of uterine incisional pregnancy after cesarean section: a comparative study

International Nuclear Information System (INIS)

Zhang Lei; Gu Weijin; Wan Jun; Ji Lihua; Wang Haiyun; Wang Ying; Ji Fang; Chen Qing

2012-01-01

Objective: To compare the interventional therapeutic efficacy of methotrexate (MTX) with that of 5-fluorouracil (5-FU) in treating uterine incisional pregnancy after cesarean section. Methods: A total of 92 patients with uterine incisional pregnancy after cesarean section, who were admitted to the hospital during the period from 2007 to 2010, were randomly divided into two groups: group MTX and group 5-FU. Patients in group MTX (n=46) received intra-arterial infusion of MTX (60-200) mg, which was followed by arterial embolization. Patients in group 5-FU (n=46) received intra-arterial infusion of 5-FU (1000-1250) mg, which was followed by arterial embolization. After the treatment the serum β-HCG and progesterone levels were determined daily for three succeeding days. The patients were followed up for three months. The clinical results were compared between the two groups. Results: The cure rates in group MTX and group 5-FU were 97.2% and 100%, respectively. No significant difference in cure rate existed between the two groups (P>0.05). A rapid fall in the serum β-HCG and progesterone levels within 1-3 days after the treatment were detected in 40 cases of group MTX and 38 cases of group 5-FU, and the decreasing extent was over 50%-80%, but the difference between the two groups was not significant (P>0.05). At the operation day, all patients of both groups had abdominal pain, and three patients in group MTX and 2 patients in 5-FU group had nausea and vomiting, but the difference between the two groups was not significant (P>0.05). During the follow-up period, no significant difference in the recovery time of the mental cycle and the hormone levels were found between the two groups (P>0.05). Conclusion: For the interventional treatment of uterine incisional pregnancy after cesarean section, the use of MTX has the same clinical efficacy as the use of 5-FU does. (authors)
Enhanced in Vivo Delivery of 5-Fluorouracil by Ethosomal Gels in Rabbit Ear Hypertrophic Scar Model

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Yan Wo

2014-12-01

Full Text Available Applying Ethosomal Gels (EGs in transdermal drug delivery systems has evoked considerable interest because of their good water-solubility and biocompatibility. However, there has not been an explicit description of applying EGs as a vehicle for hypertrophic scars treatment. Here, a novel transdermal EGs loaded with 5-fluorouracil (5-FU EGs was successfully prepared and characterized. The stability assay in vitro revealed that 5-FU EGs stored for a period of 30 days at 4 ± 1 °C had a better size stability than that at 25 ± 1 °C. Furthermore, using confocal laser scanning microscopy, EGs labeled with Rhodamine 6 G penetrated into the deep dermis of the hypertrophic scar within 24 h in the rabbit ear hypertrophic model suggested that the EGs were an optional delivery carrier through scar tissues. In addition, the value of the Scar Elevation Index (SEI of 5-FU EGs group in the rabbit ear scar model was lower than that of 5-FU Phosphate Buffered Saline gel and Control groups. To conclude, these results suggest that EGs delivery system loaded 5-fluorouracil is a perfect candidate drug for hypertrophic scars therapy in future.
Nitroglycerine and patient position effect on central, hepatic and portal venous pressures during liver surgery.

Science.gov (United States)

Sand, L; Lundin, S; Rizell, M; Wiklund, J; Stenqvist, O; Houltz, E

2014-09-01

To reduce blood loss during liver surgery, a low central venous pressure (CVP) is recommended. Nitroglycerine (NG) with its rapid onset and offset can be used to reduce CVP. In this study, the effect of NG on portal and hepatic venous pressures (PVP and HVP) in different body positions was assessed. Thirteen patients undergoing liver resection were studied. Cardiac output (CO), mean arterial pressure (MAP) and CVP were measured. PVP and HVP were measured using tip manometer catheters at baseline (BL) in horizontal position; during NG infusion, targeting a MAP of 60 mmHg, with NG infusion and the patient placed in 10 head-down position. NG infusion reduced HVP from 9.7 ± 2.4 to 7.2 ± 2.4, PVP from 12.3 ± 2.2 to 9.7 ± 3.0 and CVP from 9.8 ± 1.9 to 7.2 ± 2.1 mmHg at BL. Head-down tilt during ongoing NG resulted in increases in HVP to 8.2 ± 2.1, PVP to 10.7 ± 3 and CVP to 11 ± 1.9 mmHg. CO at BL was 6.3 ± 1.1, which was reduced by NG to 5.8 ± 1.2. Head-down tilt together with NG infusion restored CO to 6.3 ± 1.0 l/min. NG infusion leads to parallel reductions in CVP, HVP and PVP at horizontal body position. Thus, CVP can be used to guide NG dosage and fluid administration at horizontal position. NG infusion can be used to reduce HVP. Head-down tilt can be used during NG infusion to improve both blood pressure and CO without substantial increase in liver venous pressure. In head-down tilt, CVP dissociates from HVP and PVP. © 2014 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.
Effects of repeated administration of chemotherapeutic agents tamoxifen, methotrexate, and 5-fluorouracil on the acquisition and retention of a learned response in mice

Science.gov (United States)

Foley, John J.; Clark-Vetri, Rachel; Raffa, Robert B.

2011-01-01

Rationale A number of cancer chemotherapeutic agents have been associated with a loss of memory in breast cancer patients although little is known of the causality of this effect. Objectives To assess the potential cognitive effects of repeated exposure to chemotherapeutic agents, we administered the selective estrogen receptor modulator tamoxifen or the antimetabolite chemotherapy, methotrexate, and 5-fluorouracil, alone and in combination to mice and tested them in a learning and memory assay. Methods Swiss-Webster male mice were injected with saline, 32 mg/kg tamoxifen, 3.2 or 32 mg/kg methotrexate, 75 mg/kg 5-fluorouracil, 3.2 or 32 mg/kg methotrexate in combination with 75 mg/kg 5-fluorouracil once per week for 3 weeks. On days 23 and 24, mice were tested for acquisition and retention of a nose-poke response in a learning procedure called autoshaping. In addition, the acute effects of tamoxifen were assessed in additional mice in a similar procedure. Results The chemotherapeutic agents alone and in combination reduced body weight relative to saline treatment over the course of 4 weeks. Repeated treatment with tamoxifen produced both acquisition and retention effects relative to the saline-treated group although acute tamoxifen was without effect except at a behaviorally toxic dose. Repeated treatment with methotrexate in combination with 5-fluorouracil produced effects on retention, but the magnitude of these changes depended on the methotrexate dose. Conclusions These data demonstrate that repeated administration of tamoxifen or certain combination of methotrexate and 5-fluorouracil may produce deficits in the acquisition or retention of learned responses which suggest potential strategies for prevention or remediation might be considered in vulnerable patient populations. PMID:21537942
Infusion and sampling site effects on two-pool model estimates of leucine metabolism

International Nuclear Information System (INIS)

Helland, S.J.; Grisdale-Helland, B.; Nissen, S.

1988-01-01

To assess the effect of site of isotope infusion on estimates of leucine metabolism infusions of alpha-[4,5-3H]ketoisocaproate (KIC) and [U- 14 C]leucine were made into the left or right ventricles of sheep and pigs. Blood was sampled from the opposite ventricle. In both species, left ventricular infusions resulted in significantly lower specific radioactivities (SA) of [ 14 C]leucine and [ 3 H]KIC. [ 14 C]KIC SA was found to be insensitive to infusion and sampling sites. [ 14 C]KIC was in addition found to be equal to the SA of [ 14 C]leucine only during the left heart infusions. Therefore, [ 14 C]KIC SA was used as the only estimate for [ 14 C]SA in the equations for the two-pool model. This model eliminated the influence of site of infusion and blood sampling on the estimates for leucine entry and reduced the impact on the estimates for proteolysis and oxidation. This two-pool model could not compensate for the underestimation of transamination reactions occurring during the traditional venous isotope infusion and arterial blood sampling

Curcumin Chemosensitizes 5-Fluorouracil Resistant MMR-Deficient Human Colon Cancer Cells in High Density Cultures

OpenAIRE

Shakibaei, Mehdi; Buhrmann, Constanze; Kraehe, Patricia; Shayan, Parviz; Lueders, Cora; Goel, Ajay

2014-01-01

OBJECTIVE: Treatment of colorectal cancer (CRC) remains a clinical challenge, as more than 15% of patients are resistant to 5-Fluorouracil (5-FU)-based chemotherapeutic regimens, and tumor recurrence rates can be as high as 50-60%. Cancer stem cells (CSC) are capable of surviving conventional chemotherapies that permits regeneration of original tumors. Therefore, we investigated the effectiveness of 5-FU and plant polyphenol (curcumin) in context of DNA mismatch repair (MMR) status and CSC ac...
Molecularly Imprinted Polymers for 5-Fluorouracil Release in Biological Fluids

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Franco Alhaique

2007-04-01

Full Text Available The aim of this work was to investigate the possibility of employing Molecularly Imprinted Polymers (MIPs as a controlled release device for 5-fluorouracil (5-FU in biological fluids, especially gastrointestinal ones, compared to Non Imprinted Polymers (NIPs. MIPs were synthesized using methacrylic acid (MAA as functional monomer and ethylene glycol dimethacrylate (EGDMA as crosslinking agent. The capacity of the polymer to recognize and to bind the template selectively in both organic and aqueous media was evaluated. An in vitro release study was performed both in gastrointestinal and in plasma simulating fluids. The imprinted polymers bound much more 5-Fu than the corresponding non-imprinted ones and showed a controlled/sustained drug release, with MIPs release rate being indeed much more sustained than that obtained from NIPs. These polymers represent a potential valid system for drug delivery and this study indicates that the selective binding characteristic of molecularly imprinted polymers is promising for the preparation of novel controlled release drug dosage form.
Considerations on prevention of phlebitis and venous pain from intravenous prostaglandin E(1) administration by adjusting solution pH: in vitro manipulations affecting pH.

Science.gov (United States)

Kohno, Emiko; Nishikata, Mayumi; Okamura, Noboru; Matsuyama, Kenji

2008-01-01

Prostaglandin E(1) (PGE(1); Alprostadil Alfadex) is a potent vasodilator and inhibitor of platelet aggregation used to treat patients with peripheral vascular disease. The main adverse effects of intravenous PGE(1) administration, phlebitis and venous pain, arise from the unphysiologically low pH of infusion solutions. When PGE(1) infusion solutions with a pH value greater then 6 are used, phlebitis and venous pain are considered to be avoidable. Beginning with a PGE(1) infusion solution with pH greater than 6, we add the amount of 7% sodium bicarbonate needed to bring the solution to pH 7.4 if phlebitis or venous pain develops. In the present study we established a convenient nomogram showing the relationship between the titratable acidity of various infusion solutions and the volume of 7% sodium bicarbonate required to attain pH 7.4 for preventing the phlebitis and venous pain associated with PGE(1) infusion.
The effect of microneedles on the skin permeability and antitumor activity of topical 5-fluorouracil

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Youssef W. Naguib

2014-02-01

Full Text Available Topical 5-fluorouracil (5-FU is approved for the treatment of superficial basal cell carcinoma and actinic keratosis. However, 5-FU suffers from poor skin permeation. Microneedles have been successfully applied to improve the skin permeability of small and large molecules, and even nanoparticles, by creating micron-sized pores in the stratum corneum layer of the skin. In this report, the feasibility of using microneedles to increase the skin permeability of 5-FU was tested. Using full thickness mouse skin mounted on Franz diffusion apparatus, it was shown that the flux of 5-FU through the skin was increased by up to 4.5-fold when the skin was pretreated with microneedles (500 μm in length, 50 μm in base diameter. In a mouse model with B16-F10 mouse melanoma cells implanted in the subcutaneous space, the antitumor activity of a commercially available 5-FU topical cream (5% was significantly enhanced when the cream was applied on a skin area that was pretreated with microneedles, as compared to when the cream was simply applied on a skin area, underneath which the tumor cells were implanted, and without pretreatment of the skin with microneedles. Fluorouracil is not approved for melanoma therapy, but the clinical efficacy of topical 5-FU against tumors such as basal cell carcinoma may be improved by integrating microneedle technology into the therapy.
Chemoradiotherapy with or without consolidation chemotherapy using cisplatin and 5-fluorouracil in anal squamous cell carcinoma: long-term results in 31 patients

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Roh Jae

2008-01-01

Full Text Available Abstract Background The objectives of this study were to evaluate long-term results of concurrent chemoradiotherapy (CRT with 5-fluorouracil and cisplatin and the potential benefit of consolidation chemotherapy in patients with anal squamous cell carcinoma (ASCC. Methods Between January 1995 and February 2006, 31 patients with ASCC were treated with CRT. Radiotherapy was administered at 45 Gy over 5 weeks, followed by a boost of 9 Gy to complete or partial responders. Chemotherapy consisted of 5-fluorouracil (750 or 1,000 mg/m2 daily on days 1 to 5 and days 29 to 33; and, cisplatin (75 or 100 mg/m2 on day 2 and day 30. Twelve patients had T3–4 disease, whereas 18 patients presented with lymphadenopathy. Twenty-one (67.7% received consolidation chemotherapy with the same doses of 5-fluorouracil and cisplatin, repeated every 4 weeks for maximum 4 cycles. Results Nineteen patients (90.5% completed all four courses of consolidation chemotherapy. After CRT, 28 patients showed complete responses, while 3 showed partial responses. After a median follow-up period of 72 months, the 5-year overall, disease-free, and colostomy-free survival rates were 84.7%, 82.9% and 96.6%, demonstrating that CRT with 5-fluorouracil and cisplatin yields a good outcome in terms of survival and sphincter preservation. No differences in 5-year OS and DFS rates between patients treated with CRT alone and CRT with consolidation chemotherapy was observed. Conclusion our study shows that CRT with 5-FU and cisplatin, with or without consolidation chemotherapy, was well tolerated and proved highly encouraging in terms of long-term survival and the preservation of anal function in ASCC. Further trials with a larger patient population are warranted in order to evaluate the potential role of consolidation chemotherapy.
Prospective evaluation of fluorouracil chemotherapy based on the genetic makeup of colorectal cancer

OpenAIRE

Carethers, J M

2006-01-01

Evaluation of 5‐fluorouracil chemotherapy and survival, based on mismatch repair (MMR) status, indicates that patients with MMR proficient colorectal tumours benefit from 5‐fluorouracil treatment while patients with MMR deficient tumours do not
Novel 5-Fluorouracil Derivatives: Synthesis and Cytotoxic Activity of 2-Butoxy-4-Substituted 5-Fluoropyrimidines

International Nuclear Information System (INIS)

Sun, Jian; Zhou, Wei; Hu, Weixiao; Shan, Shang; Zhang, Shijie; Li, Haibo

2013-01-01

Twenty two new 5-fluorouracil (5-FU) derivatives, 2-butoxy-4-substituted 5-fluoropyrimidines, were synthesized and characterized by IR, 1 H NMR, MS, HRMS. All compounds were preliminarily evaluated by MTT assay on human liver BEL-7402 cancer cell line in vitro. Ten compounds were selected to test their cytotoxic activity against A549, HL-60 and MCF-7 cancer cell lines in vitro. These compounds were more sensitive to BEL-7402 than other cell lines, particularly, cytotoxic activity of compounds 6b, 6d-f, 6p, 6s-u were in sub-micromolar scale. The highest cytotoxic potency against A549, HL-60 and MCF-7 was shown by 2-butoxy-4-chloro-5-fluoropyrimidine (5) with IC 50 values of 0.10, 1.66 and 0.59 μM, respectively. Compounds 6d and 6e were effective against MCF-7 with IC 50 9.73 μM and HL-60 with IC 50 8.83 μM, respectively
N-Alkynyl Derivatives of 5-Fluorouracil: Susceptibility to Palladium-Mediated Dealkylation and Toxigenicity in Cancer Cell Culture

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Jason T Weiss

2014-07-01

Full Text Available Palladium-activated prodrug therapy is an experimental therapeutic approach that relies on the unique chemical properties and biocompatibility of heterogeneous palladium catalysis to enable the spatially-controlled in vivo conversion of a biochemically-stable prodrug into its active form. This strategy, which would allow inducing local activation of systemically administered drug precursors by mediation of an implantable activating device made of Pd(0, has been proposed by our group as a way to reduce drug’s systemic toxicity while reaching therapeutic levels of the active drug in the affected tissue / organ. In the seminal study of such an approach, we reported that propargylation of the N1 position of 5-fluorouracil suppressed the drug’s cytotoxic properties, showed high stability in cell culture and facilitated the bioorthogonal restoration of the drug’s pharmacological activity in the presence of extracellular Pd(0-functionalized resins. To provide additional insight on the properties of this system, we have investigated different N1-alkynyl derivatives of 5-fluorouracil and shown that the presence of substituents near the triple bond influence negatively on its sensitivity to palladium catalysis under biocompatible conditions. Comparative studies of the N1- versus the N3-propargyl derivatives of 5-fluorouracil revealed that masking each or both positions equally led to inactive derivatives (>200-fold reduction of cytotoxicity relative to the unmodified drug, whereas the depropargylation process occurred faster at the N1 position than at the N3, thus resulting in greater toxigenic properties in cancer cell culture.
Systemic and regional hemodynamic effects of enalaprilat infusion in experimental normotensive sepsis

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L. Rahal

Full Text Available Angiotensin-converting enzyme inhibitors have been shown to improve splanchnic perfusion in distinct shock states. We hypothesized that enalaprilat potentiates the benefits of early fluid resuscitation in severe experimental sepsis, particularly in the splanchnic region. Anesthetized and mechanically ventilated mongrel dogs received an intravenous infusion of live Escherichia coli over a period of 30 min. Thereafter, two interventions were performed: fluid infusion (normal saline, 32 mL/kg over 30 min and enalaprilat infusion (0.02 mg kg-1 min-1 for 60 min in randomized groups. The following groups were studied: controls (fluid infusion, N = 4, E1 (enalaprilat infusion followed by fluid infusion, N = 5 and E2 (fluid infusion followed by enalaprilat infusion, N = 5. All animals were observed for a 120 min after bacterial infusion. Mean arterial pressure, cardiac output (CO, portal vein blood flow (PVBF, systemic and regional oxygen-derived variables, and lactate levels were measured. Rapid and progressive reductions in CO and PVBF were induced by the infusion of live bacteria, while minor changes were observed in mean arterial pressure. Systemic and regional territories showed a significant increase in oxygen extraction and lactate levels. Widening venous-arterial and portal-arterial pCO2 gradients were also detected. Fluid replacement promoted transient benefits in CO and PVBF. Enalaprilat after fluid resuscitation did not affect systemic or regional hemodynamic variables. We conclude that in this model of normotensive sepsis inhibition of angiotensin-converting enzyme did not interfere with the course of systemic or regional hemodynamic and oxygen-derived variables.
The use of intraosseous infusions in the operating room.

Science.gov (United States)

Joseph, Gayatri; Tobias, Joseph D

2008-09-01

The use of an intraosseous (IO) infusion during the anesthetic care of an 8-month-old, 5.4-kg infant with cyanotic congenital heart disease (CHD) is presented. Previous vascular access had resulted in thrombotic occlusion of the upper and lower venous systems. When intravenous access could not be achieved, an IO needle was placed and IO access was used during the surgical procedure. The role of the IO route in the perioperative period is discussed and its adverse effect profile is reviewed.
Drug eruption (erythema multiforme type) following chemoradiotherapy with mitomycin C and 5-fluorouracil administration for squamous cell carcinoma of the anal canal

International Nuclear Information System (INIS)

Arikawa, Shunji; Uchida, Masafumi; Ogoh, Etsuyo

2010-01-01

We report a case of drug eruption (erythema multiforme type) in a 54-year-old woman, following concurrent chemoradiotherapy for squamous cell carcinoma of the anal canal. Chemotherapy comprised one cycle of mitomycin C 10 mg/m 2 /day (intravenous bolus injection) on day 1 and 5-fluorouracil (5-FU) 1, 000 mg/m 2 /day (continuous intravenous infusion) on days 1-4 of radiotherapy. External irradiation of the pelvic space was performed, using daily fractions of 1.5 Gy (total dose, 33 Gy). From day 4 after chemoradiotherapy, erythema appeared proximal to the forearm site used for drug administration. On day 6, erythema was noted on the trunk, hip and thigh. We suspected erythema multiforme based on the appearance of wheals and target lesions of the skin and a patient history of chemoradiotherapy. Steroids were administered orally, which resolved systemic eruption at week 2. The patient also experienced grade 3 leukocytopenia, neutropenia, thrombopenia, diarrhea, and anorexia. Although we could not provide sufficient chemotherapy and radiation therapy due to severe side effects, squamous cell carcinoma of the anal canal responded extremely well with a marked decrease in complete response. We surmise that the drug eruption was associated with 5-FU. Concurrent chemoradiotherapy is safe and effective for squamous cell carcinoma of the anal canal, but care is required to prevent drug eruption during treatment. (author)
Oxidative damage to guanine nucleosides following combination chemotherapy with 5-fluorouracil and oxaliplatin

DEFF Research Database (Denmark)

Afzal, Shoaib; Jensen, Søren Astrup; Sørensen, Jens Benn

2011-01-01

PURPOSE: Recent in vitro and animal studies have suggested that the cytotoxicity of 5-fluorouracil and oxaliplatin is linked to increased formation of reactive oxygen species (ROS). This prospective study was undertaken to examine the generation of oxidative stress, in 106 colorectal cancer patie...... concentrations of 8-oxoGuo and 8-oxodG and the treatment effect and the other variables. RESULTS: The analysis showed that chemotherapy increased the excretion of 8-oxoGuo and 8-oxodG around 15% (P ...
A study on radiation therapy combined with superselective intraarterial infusion therapy for maxillary sinus carcinoma

International Nuclear Information System (INIS)

Okamoto, Isaku; Ito, Hiroyuki; Shimizu, Akira; Shimizu, Shigetaka; Suzuki, Mamoru; Yoshida, Tomoyuki; Nakamura, Kazuhiro; Tsukahara, Kiyoaki

2010-01-01

The data of 14 patients with squamous cell carcinoma of the maxillary sinus who were admitted to our hospital and received radiation therapy and concurrent superselective intraarterial infusion therapy between 1998 and 2008 were analyzed to determine the effect of the primary treatment and the adverse events. The subjects were between 43 and 79 years old (median, 61 years old), and there were 10 male and 4 female patients. Superselective intraarterial infusion therapy was administered using the Seldinger method, and cisplatin (CDDP) was administered by intraarterial infusion at a total of 200 mg/m 2 . 5-fluorouracil (FU) was systemically administered by intravenous infusion at the dose of 800 mg/m 2 from day 2 to day 5. In addition, radiation therapy was given concurrently, beginning on day 2. At 4 weeks after completion of the scheduled radiation therapy combined with superselective intraarterial infusion therapy, the treatment effect was judged based on macroscopic, radiological and histopathological findings. The response rates to the primary treatment were as follows: 57.1%, complete response (CR) (8 patients) and 42.9%, partial response (PR) (6 patients). Thus, the overall response rate was 100%. As for the adverse events, while grade 4 cerebral infarction occurred in one patient, all of the other adverse events were reversible and not serious. The safety of the treatment was therefore considered to be acceptable. We are planning to investigate the long-term outcomes in a future study. (author)
Preoperative combination therapy of 5-fluorouracil suppository and radiation for carcinoma of the rectum

International Nuclear Information System (INIS)

Mizusawa, Hirokazu; Takahashi, Toshio

1983-01-01

Twelve cases of carcinoma of the rectum were treated preoperatively by combination therapy with 5-fluorouracil (5-FU) suppository (100 mg twice a day consecutively, a total dose of more than 4,000 mg) and irradiation (300 rad x 3/week, a total dose of 3,000 rad). This group was compared with 34 cases given single preoperative 5-FU therapy and 24 control cases given no preoperative adjuvant modality. The group treated by preoperative combination therapy showed marked antitumor effects macroscopically and histologically. In addition, decrease in local recurrence was expected for this group, compared with the other two groups. (Chiba, N.)
Use of Zeolite ZSM-5 for Loading and Release of 5-Fluorouracil

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Ruba A. Al-Thawabeia

2015-01-01

Full Text Available Samples of zeolite ZSM-5 have been synthesized in both the sodium form (ZSM-5 and the acid activated form (H-ZSM-5. In addition, each of these two forms was prepared in the two molar SiO2/Al2O3 ratios of 169 and 15. All samples of these ZSM-5 derivatives were characterized by X-ray diffraction (XRD, nitrogen adsorption-desorption isotherms, thermal gravimetric analysis (TGA, X-ray fluorescence (XRF, and scanning electron microscopy (SEM. The samples were successfully loaded with the anticancer drug 5-fluorouracil (5-FU with loading capacities varying from 22% (for the sodium form having the lower molar SiO2/Al2O3 ratio of 15, ZSM-5-(15 to 43% (for the corresponding acid form, H-ZSM-5-(15. Percent release of the drug-loaded ZSM-5 samples into simulated body fluid (SBF was measured at pH 7.4 and 37°C. The results showed a slight variation in the % release within the range 84–93%, while the first-order rate constant (k varied from 2.2 h−1 for ZSM-5-(15 to 3.9 h−1 for H-ZSM-5-(15. It was interesting to note that at the higher molar SiO2/Al2O3 ratios of 169, both the sodium form, ZSM-5-(169, and the acid form, H-ZSM-5-(169, exhibit an intermediate efficiency in either % loading (38% or first-order kinetic release constant (k = 2.9 h−1.
Local thrombolysis for patients of severe cerebral venous sinus thrombosis during puerperium

International Nuclear Information System (INIS)

Guo, Xin-bin; Fu, Zhenqiang; Song, Lai-jun; Guan, Sheng

2013-01-01

Objective: To explore and evaluate the efficacy of intrasinus thrombolysis (IST) in patients with cerebral venous sinus thrombosis (CVST) during postpartum period. Methods: 11 patients during postpartum period with CVST who received IST during July 2007–November 2011 were included. Urokinase was infused into the sinuses via a microcatheter. Magnetic resonance venography (MRV) was performed to assess the recanalization of venous sinuses. Results: Before discharge, the intracranial pressure in 11 patients was under 200 mmH 2 O. MRV confirmed that venous sinus of 9 patients were smooth. The cortex venous and deep venous recovered to normal. Venous sinus of 2 patients recanalized partly, and cortex venous and deep venous had compensation. 9 patients had good outcome and 2 patients had only mild deficits. Conclusion: Intrasinus thrombolysis is safe and effective in patients with severe cerebral venous sinus thrombosis during postpartum period
Elevated plasma factor VIII enhances venous thrombus formation in rabbits: contribution of factor XI, von Willebrand factor and tissue factor.

Science.gov (United States)

Sugita, Chihiro; Yamashita, Atsushi; Matsuura, Yunosuke; Iwakiri, Takashi; Okuyama, Nozomi; Matsuda, Shuntaro; Matsumoto, Tomoko; Inoue, Osamu; Harada, Aya; Kitazawa, Takehisa; Hattori, Kunihiro; Shima, Midori; Asada, Yujiro

2013-07-01

Elevated plasma levels of factor VIII (FVIII) are associated with increased risk of deep venous thrombosis. The aim of this study is to elucidate how elevated FVIII levels affect venous thrombus formation and propagation in vivo. We examined rabbit plasma FVIII activity, plasma thrombin generation, whole blood coagulation, platelet aggregation and venous wall thrombogenicity before and one hour after an intravenous infusion of recombinant human FVIII (rFVIII). Venous thrombus induced by the endothelial denudation of rabbit jugular veins was histologically assessed. Thrombus propagation was evaluated as indocyanine green fluorescence intensity. Argatroban, a thrombin inhibitor, and neutralised antibodies for tissue factor (TF), factor XI (FXI), and von Willebrand factor (VWF) were infused before or after thrombus induction to investigate their effects on venous thrombus formation or propagation. Recombinant FVIII (100 IU/kg) increased rabbit plasma FVIII activity two-fold and significantly enhanced whole blood coagulation and total plasma thrombin generation, but did not affect initial thrombin generation time, platelet aggregation and venous wall thrombogenicity. The rFVIII infusion also increased the size of venous thrombus 1 hour after thrombus induction. Argatroban and the antibodies for TF, FXI or VWF inhibited such enhanced thrombus formation and all except TF suppressed thrombus propagation. In conclusion, elevated plasma FVIII levels enhance venous thrombus formation and propagation. Excess thrombin generation by FXI and VWF-mediated FVIII recruitment appear to contribute to the growth of FVIII-driven venous thrombus.
Prospective trial of preoperative concomitant boost radiotherapy with continuous infusion 5-fluorouracil for locally advanced rectal cancer

International Nuclear Information System (INIS)

Janjan, Nora A.; Crane, Christopher N.; Feig, Barry W.; Cleary, Karen; Dubrow, Ronelle; Curley, Steven A.; Ellis, Lee M.; Vauthey, Jean-Nicolas; Lenzi, Renato; Lynch, Patrick; Wolff, Robert; Brown, Thomas; Pazdur, Richard; Abbruzzese, James; Hoff, Paulo M.; Allen, Pamela; Brown, Barry; Skibber, John

2000-01-01

Rationale: To evaluate the response to a concomitant boost given during standard chemoradiation for locally advanced rectal cancer. Methods and Materials: Concomitant boost radiotherapy was administered preoperatively to 45 patients with locally advanced rectal cancer in a prospective trial. Treatment consisted of 45 Gy to the pelvis with 18 mV photons at 1.8 Gy/fraction using a 3-field belly board technique with continuous infusion 5FU chemotherapy (300mg/m 2 ) 5 days per week. The boost was given during the last week of therapy with a 6-hour inter-fraction interval to the tumor plus a 2-3 cm margin. The boost dose equaled 7.5 Gy/5 fractions (1.5 Gy/fraction); a total dose of 52.5 Gy/5 weeks was given to the primary tumor. Pretreatment tumor stage, determined by endorectal ultrasound and CT scan, included 29 with T3N0 [64%], 11 T3N1, 1 T3Nx, 2 T4N0, 1 T4N3, and 1 with TxN1 disease. Mean distance from the anal verge was 5 cm (range 0-13 cm). Median age was 55 years (range 33-77 years). The population consisted of 34 males and 11 females. Median time of follow-up is 8 months (range 1-24 months). Results: Sphincter preservation (SP) has been accomplished in 33 of 42 (79%) patients resected to date. Three patients did not undergo resection because of the development of metastatic disease in the interim between the completion of chemoradiation (CTX/XRT) and preoperative evaluation. The surgical procedures included proctectomy and coloanal anastomosis (n = 16), low anterior resection (n = 13), transanal resection (n = 4). Tumor down-staging was pathologically confirmed in 36 of the 42 (86%) resected patients, and 13 (31%) achieved a pathologic CR. Among the 28 tumors (67%) located <6 cm from the anal verge, SP was accomplished in 21 cases (75%). Although perioperative morbidity was higher, toxicity rates during CTX/XRT were comparable to that seen with conventional fractionation. Compared to our contemporary experience with conventional CTX/XRT (45Gy; 1.8 Gy per
Ocular surface squamous neoplasia in HIV-positive and HIV-negative patients and response to 5-fluorouracil in Angola

Directory of Open Access Journals (Sweden)

Nutt RJ

2014-12-01

Full Text Available Robert J Nutt,1 John L Clements,2 William H Dean3 1Faculty of Medicine and Dentistry, University of Bristol, Bristol, UK; 2Boa Vista Eye Clinic, Benguela, Angola; 3Bristol Eye Hospital, Bristol, UK Background: Ocular surface squamous neoplasia (OSSN is becoming increasingly prevalent and aggressive in Sub-Saharan Africa. It is a phenomenon linked with human immunodeficiency virus (HIV infection, although association rates in Angola are currently unknown. A topical treatment that is effective in HIV-positive and HIV-negative individuals may be preferable to surgery in some contexts. We aimed to estimate the proportion of OSSN associated with HIV in Angola and to report on the success of topical 5-fluorouracil as a primary treatment in HIV-positive and HIV-negative patients.Methods: Photographs of OSSNs taken at presentation and following treatment with 5-fluorouracil in patients presenting to Boa Vista Eye Clinic, Angola, between October 2011 and July 2013 were grouped into HIV-positive and HIV-negative groups and analyzed to compare presenting features and treatment response. Eighty-one OSSNs were analyzed for clinical features and 24 met the inclusion criteria for analysis of treatment response.Results: Eighty-two patients presented with OSSN between October 2011 and July 2013. Twenty-one (26% were HIV-positive and typically had OSSNs that exhibited more pathological features than those in HIV-negative patients. Twenty-four (29% patients met the inclusion criteria for analysis of treatment response; of these, 26 (91% OSSNs in both groups displayed at least partial resolution after one treatment course. In the HIV-positive group, five of eight patients displayed complete resolution, two showed partial resolution, and one failed. In the HIV-negative group, five of 16 showed complete resolution, ten of 16 had partial resolution, and one failed.Conclusion: Individuals presenting with OSSN in Angola are more likely to have HIV infection compared
Test-retest reproducibility of the metabotropic glutamate receptor 5 ligand [18F]FPEB with bolus plus constant infusion in humans

International Nuclear Information System (INIS)

Park, Eunkyung; Sullivan, Jenna M.; Planeta, Beata; Gallezot, Jean-Dominique; Lim, Keunpoong; Lin, Shu-Fei; Ropchan, Jim; Huang, Yiyun; Carson, Richard E.; McCarthy, Timothy J.; Ding, Yu-Shin; Morris, Evan D.; Williams, Wendol A.

2015-01-01

[ 18 F]FPEB is a promising PET radioligand for the metabotropic glutamate receptor 5 (mGluR5), a potential target for the treatment of neuropsychiatric diseases. The purpose of this study was to evaluate the test-retest reproducibility of [ 18 F]FPEB in the human brain. Seven healthy male subjects were scanned twice, 3 - 11 weeks apart. Dynamic data were acquired using bolus plus infusion of 162 ± 32 MBq [ 18 F]FPEB. Four methods were used to estimate volume of distribution (V T ): equilibrium analysis (EQ) using arterial (EQ A ) or venous input data (EQ V ), MA1, and a two-tissue compartment model (2 T). Binding potential (BP ND ) was also estimated using cerebellar white matter (CWM) or gray matter (CGM) as the reference region using EQ, 2 T and MA1. Absolute test-retest variability (aTRV) of V T and BP ND were calculated for each method. Venous blood measurements (C V ) were compared with arterial input (C A ) to examine their usability in EQ analysis. Regional V T estimated by the four methods displayed a high degree of agreement (r 2 ranging from 0.83 to 0.99 among the methods), although EQ A and EQ V overestimated V T by a mean of 9 % and 7 %, respectively, compared to 2 T. Mean values of aTRV of V T were 11 % by EQ A , 12 % by EQ V , 14 % by MA1 and 14 % by 2 T. Regional BP ND also agreed well among the methods and mean aTRV of BP ND was 8 - 12 % (CWM) and 7 - 9 % (CGM). Venous and arterial blood concentrations of [ 18 F]FPEB were well matched during equilibrium (C V = 1.01 . C A , r 2 = 0.95). [ 18 F]FPEB binding shows good TRV with minor differences among analysis methods. Venous blood can be used as an alternative for input function measurement instead of arterial blood in EQ analysis. Thus, [ 18 F]FPEB is an excellent PET imaging tracer for mGluR5 in humans. (orig.)

The effects of 5-fluorouracil and doxorubicin on expression of human immunodeficiency virus type 1 long terminal repeat

International Nuclear Information System (INIS)

Panozzo, J.; Akan, E.; Griffiths, T.D.

1996-01-01

Previous work by many groups has documented induction of the HIV-LTR following exposure of cells to ultraviolet light and other DNA damaging agents. Our experiments set out to determine the relative activation or repression of the HIV-LTR in response to two classes of chemotherapeutic agents: Doxorubicin is a DNA-damage inducing agent, and 5-fluorouracil has an antimetabolic mode of action. Using HeLa cells stably transfected with a construct in which HIV-LTR drives expression of the chloramphenicol acetyl transferase reporter gene, we demonstrated an up to 10-fold induction following doxorubicin treatment in 24 h post-treatment. This induction was repressed by treatment with salicylic acid, suggesting a role for prostaglandin/cyclo-oxygenase pathways and/or NFKB in the inductive response. Induction by 5-fluorouracil, in contrast, was more modest (two-fold at most) though it was consistently elevated over controls
Intraosseous infusion in elective and emergency pediatric anesthesia: when should we use it?

OpenAIRE

Neuhaus, Diego

2014-01-01

PURPOSE OF REVIEW Difficulties to establish a venous access may also occur in routine pediatric anesthesia and lead to hazardous situations. Intraosseous infusion is a well tolerated and reliable but rarely used alternative technique in this setting. RECENT FINDINGS According to recent surveys, severe complications of intraosseous infusion stay a rare event. Minor complications and problems in getting an intraosseous infusion started on the other side seem to be more common than generally ...
Local thrombolysis for patients of severe cerebral venous sinus thrombosis during puerperium

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Guo, Xin-bin, E-mail: gxb3906080@sina.com [Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, 1 Jianshe Road, Zhengzhou, 450052 (China); Fu, Zhenqiang, E-mail: fuzhenqiang1005@163.com [Department of Neurology, The First Affiliated Hospital of Zhengzhou University, 1 Jianshe Road, Zhengzhou, 450052 (China); Song, Lai-jun, E-mail: laijunsong@sina.com [Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, 1 Jianshe Road, Zhengzhou, 450052 (China); Guan, Sheng, E-mail: gsradio@126.com [Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, 1 Jianshe Road, Zhengzhou, 450052 (China)

2013-01-15

Objective: To explore and evaluate the efficacy of intrasinus thrombolysis (IST) in patients with cerebral venous sinus thrombosis (CVST) during postpartum period. Methods: 11 patients during postpartum period with CVST who received IST during July 2007–November 2011 were included. Urokinase was infused into the sinuses via a microcatheter. Magnetic resonance venography (MRV) was performed to assess the recanalization of venous sinuses. Results: Before discharge, the intracranial pressure in 11 patients was under 200 mmH{sub 2}O. MRV confirmed that venous sinus of 9 patients were smooth. The cortex venous and deep venous recovered to normal. Venous sinus of 2 patients recanalized partly, and cortex venous and deep venous had compensation. 9 patients had good outcome and 2 patients had only mild deficits. Conclusion: Intrasinus thrombolysis is safe and effective in patients with severe cerebral venous sinus thrombosis during postpartum period.
5-Fluorouracil modulation of radiosensitivity in cultured human carcinoma cells

International Nuclear Information System (INIS)

Smalley, S.R.; Kimler, B.F.; Evans, R.G.

1991-01-01

We evaluated conventional pulse exposure versus continuous exposure models of 5-fluorouracil (5-FU) radiosensitization in HT-29 (human colon adenocarcinoma) and DU-145 (human prostate cancer adenocarcinoma) cell lines. Cell survival following treatment with drug and/or radiation was determined by colony formation assays. Radiation was delivered either by itself, approximately midway through a 1-hr exposure to 5-FU (10 micrograms/ml), or at various times following initiation of exposure to 5-FU (0.5 microgram/ml) present throughout the entire period of incubation. Drug concentrations were selected to approximate those achieved in vivo in humans. HT-29 cells showed a plating efficiency of 87% and similar cytotoxicity (survival reduced to 0.57-0.71) for all 5-FU conditions. The Do's of the radiation survival curves were not different for 1 hr of 5-FU exposure versus radiation alone. However, continuous exposure conditions demonstrated statistically significantly different Do's from radiation alone and pulse 5-FU exposure. DU-145 cells displayed a plating efficiency of 17% and cytotoxicities of 0.10-0.91 for the 5-FU conditions. DU-145 cells showed different radiation 5-FU interactions: 5-FU produced statistically significant changes in Do well as the differences between cell lines insofar as their radiosensitization by 5-FU underscore the caution required in extrapolating these radiobiologic models to the clinical setting
Prevention of venous pain and phlebitis caused by epirubicin hydrochloride.

Science.gov (United States)

Sugimoto, Masakazu; Matsui, Masateru; Harada, Masanori; Yamauchi, Yumiko; Moriyama, Nao; Andou, Kanae; Yamamoto, Makoto; Yamaoka, Hisayo; Ono, Chiemi; Ishikawa, Mami; Kamo, Nobuyuki; Ikeda, Tadashi; Yamaoka, Keiko

2009-06-01

Many patients complain of venous pain or develop phlebitis following treatment with epirubicin hydrochloride(EPI). To ensure effective and safe treatment with this drug, it is essential to deal with the adverse events associated with it appropriately. At our hospital, EPI was previously administered by drip infusion(diluted with 50mL of physiological saline)over 15 minutes after pretreatment(EPI main route). With this method of treatment, venous pain and phlebitis developed in 14 of 15 cases. In 3 of these 14 cases, the regimen was modified. Following this experience, EPI administration was switched to drip infusion from the fully-opened side tube used for pretreatment(EPI sub-route). Switching to this route resulted in a sharp decrease in the incidence of venous pain and phlebitis, to only 1 of 15 cases. Stimulation of vascular tunica intima by EPI has been considered a factor principally responsible for the venous pain and phlebitis seen after EPI therapy. To prevent these adverse reactions, it is necessary to modify the method of administration so that strong or long-term exposure of blood vessels to EPI can be reduced. The results of this study suggest that the EPI sub-route we devised is useful in achieving this goal.
Forearm metabolism during infusion of adrenaline

DEFF Research Database (Denmark)

Simonsen, L; Stefl, B; Bülow, J

2000-01-01

Human skeletal muscle metabolism is often investigated by measurements of substrate fluxes across the forearm. To evaluate whether the two forearms give the same metabolic information, nine healthy subjects were studied in the fasted state and during infusion of adrenaline. Both arms were...... catheterized in a cubital vein in the retrograde direction. A femoral artery was catheterized for blood sampling, and a femoral vein for infusion of adrenaline. Forearm blood flow was measured by venous occlusion strain-gauge plethysmography. Forearm subcutaneous adipose tissue blood flow was measured...... by the local 133Xe washout method. Metabolic fluxes were calculated as the product of forearm blood flow and a-v differences of metabolite concentrations. After baseline measurements, adrenaline was infused at a rate of 0.3 nmol kg-1 min-1. No difference in the metabolic information obtained in the fasting...
Synthesis and properties of Mg2Al layered double hydroxides containing 5-fluorouracil

International Nuclear Information System (INIS)

Wang Zhongliang; Wang Enbo; Gao Lei; Xu Lin

2005-01-01

A pharmaceutically active compound, 5-fluorouracil (5-FU) has been firstly intercalated into layered double hydroxide with the restructure method. Powder X-ray diffraction and spectroscopic analysis indicate that 5-FU molecule is stabilized in the host interlayer by electrostatic interaction and intermolecular interaction, and that the orientation of 5-FU is different when changing the pattern of aging treatment or the swelling agent. The release studies show that a rapid release of the drug during the first 40min is followed by a more sustained one, and that the total amount of drug released from hybrid material into the aqueous solution is almost 87% and 74% at pH 4 and 7, respectively. The studies mentioned above suggest that layered double hydroxide might be used as the basis of a tunable drug delivery carrier
Selectivity of Very High Dose Methotrexate in Mcf-7 and Normal Cells Using a Priming and Non-Toxic 5-Fluorouracil Dose

National Research Council Canada - National Science Library

Brown, Donnell

1997-01-01

...) in MCF-7 breast cancer cells versus normal tissues and (b) provide one clear basis for intracellular rescue of only host cells from MTX toxicity when high dose MTX is used in combination with 5-fluorouracil (5-FU...
Loss of Smad4 in colorectal cancer induces resistance to 5-fluorouracil through activating Akt pathway

OpenAIRE

Zhang, B; Zhang, B; Chen, X; Bae, S; Singh, K; Washington, M K; Datta, P K

2014-01-01

Background: Higher frequency of Smad4 inactivation or loss of expression is observed in metastasis of colorectal cancer (CRC) leading to unfavourable survival and contributes to chemoresistance. However, the molecular mechanism of how Smad4 regulates chemosensitivity of CRC is unknown. Methods: We evaluated how the loss of Smad4 in CRC enhanced chemoresistance to 5-fluorouracil (5-FU) using two CRC cell lines in vitro and in vivo. Immunoblotting with cell and tumour lysates and immunohistoche...
Liposome distribution after intravenous and selective intraarterial infusion in dogs

International Nuclear Information System (INIS)

Wright, K.C.; Kasi, L.P.; Jahns, M.S.; Hashimoto, S.; Wallace, S.

1990-01-01

In an effort to improve hepatic uptake of liposomes for drug delivery, empty vesicles were administered by means of selective arterial infusion. Negatively charged, multilamellar liposomes were labeled with technetium-99m and infused into healthy adult dogs. Each dog received 100 mg/m2 of lipid over 10 minutes at 2 mL/min. Liposomes were administered via the common hepatic artery after proximal occlusion of the gastroduodenal artery, via the cranial mesenteric artery, and via the cephalic vein. Distribution (liver, spleen, and lungs) was determined by computer-assisted external imaging techniques. On the average, after arterial infusion, 69.2% of the total activity was located in the liver, 3.6% in the spleen, 3.2% in the lungs, and 3.5% in the general circulation. Following venous injection, 50.7% of the radioactivity was found in the liver, 9.1% in the spleen, 8.6% in the lungs, and 6.7% in the peripheral blood. Once the liposomes entered the systemic circulation, they were cleared at the same rate (half-life beta = 21.5 hours) independent of their route of administration. Increased hepatic liposome uptake should translate into higher local and lower systemic liposomal drug levels
[Application of subserosal injection of carbon nanoparticles via infusion needle to label lymph nodes in laparoscopic radical gastrectomy].

Science.gov (United States)

Chen, Hongyuan; Wang, Yanan; Xue, Fangqin; Yu, Jiang; Hu, Yanfeng; Liu, Hao; Yan, Jun; Li, Guoxin

2014-05-01

To explore the feasibility of subserosal injection of carbon nanoparticle via venous infusion needle to label lymph node and its application value in laparoscopic radical gastrectomy. Forty patients with gastric cancer were randomly divided into two groups (carbon nanoparticle group and control group). Subserosal injection of carbon nanoparticle around the tumor was performed via venous infusion needle laparoscopically at the beginning of surgery in carbon nanoparticles group, while the patients routinely underwent laparoscopic radical gastrectomy in control group. Results of harvested lymph nodes were compared between the two groups. The perioperative complications and the side effect of carbon nanoparticle were also evaluated. The average number of harvested lymph node in carbon nanoparticle group (31.7±7.6) was significantly higher than that in control group (19.8±6.1, Pinjection of carbon nanoparticle via venous infusion needle to label lymph nodes during laparoscopic radical gastrectomy is safe and feasible. It can increase the number of harvested lymph node, especially the small node.
Chemistry of Secondary Metabolites (Production, Properties, Biological Activity, etc.: Solubility Study of the Interaction between Pamam G-3 Dendrimer and 5 Fluorouracil in Aqueous Solution

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B. PALECZ

2014-06-01

Full Text Available Poly(amidoamine dendrimers (PAMAM are polymeric macromolecules that can find their use as carriers of small ligand molecules such as cosmetics and drugs. 5- Fluorouracil is a potent oncological drug, whose usage is limited because of its relatively high toxicity.The surface and internal layer groups in PAMAM dendrimer belonging to the third (G3 generation create an open-type structure, which facilitate small ligand molecules to bind with them.The formation equilibrium of PAMAM G3 dendrimer complex with an oncologic drug such as 5 fluorouracil (FU in water at room temperature was examined. Using the results of the drug solubility in dendrimer solutions, the maximal number of drug molecules in the dendrimer-drug complex was evaluated. Solubility results show that PAMAM G3 dendrimer can transfer tens 5 fluorouracil molecules in aqueous solution.This research work was funded from the Polish budget appropriations for science in the years 2013-2015, project number IP2012 022372.
Evaluation of the therapeutic results of actinic keratosis treated with topical 5% fluorouracil by reflectance confocal laser microscopy: preliminary study*

Science.gov (United States)

Ishioka, Priscila; Maia, Marcus; Rodrigues, Sarita Bartholomei; Marta, Alessandra Cristina; Hirata, Sérgio Henrique

2015-01-01

Topical treatment for actinic keratosis with 5% fluorouracil has a recurrence rate of 54% in 12 months of follow-up. This study analyzed thirteen actinic keratoses on the upper limbs through confocal microscopy, at the time of clinical diagnosis and after 4 weeks of treatment with fluorouracil. After the treatment was established and evidence of clinical cure was achieved, in two of the nine actinic keratoses, confocal microscopy enabled visualization of focal areas of atypical honeycomb pattern in the epidermis indicating therapeutic failure. Preliminary data suggest the use of confocal microscopy as a tool for diagnosis and therapeutic control of actinic keratosis. PMID:26131881
The Effect of Combination of Radiation with 5-Fluorouracil on Mouse Jejunal Crypt Cells

International Nuclear Information System (INIS)

Huh, Seung Jae; Park, Charn Il

1985-01-01

The interaction of radiation and 5-Fluorouracil (5-FU) on mouse jejunal crypt cells was studied using the microcolony survival assay. 150mg/kg of 5-FU was injected intraperitoneally 15 minutes before irradiation and 6 hours after irradiation. Jejunal crypt cells of mouse survived more when 5-FU was given 15 minutes before irradiation than giving it 6 hours after irradiation. The mean lethal doses (Do) of each of irradiation alone group, 5-FU injection group of 15 minutes preceding irradiation, and 5-FU injection group of 6 hours post irradiation were 135, 135, and 114 rad respectively. The dose effect factor (DEF) of each of 5-FU injection groups of 15 minutes preceding irradiation and of 6 hours post irradiation were 1.13 and 1.27
Advanced colorectal cancer, refractory to infusional fluorouracil treatment: efficacy of second line fluorouracil in combination with a different biochemical modulation

NARCIS (Netherlands)

van Halteren, H. K.; Wagener, D. J.; Vreugdenhil, G.; Punt, C. J.

1997-01-01

Currently there is no standard second line treatment for patients with advanced colorectal cancer (ACC). Previous reports have demonstrated that some patients may benefit from second line infusional 5-fluorouracil (5-FU) after failing 5-FU bolus treatment. We retrospectively studied the efficacy and
The conversion of phenylalanine to tyrosine in man. Direct measurement by continuous intravenous tracer infusions of L-[ring-2H5]phenylalanine and L-[1-13C] tyrosine in the postabsorptive state

International Nuclear Information System (INIS)

Clarke, J.T.; Bier, D.M.

1982-01-01

Steady state phenylalanine and tyrosine turnover and the rate of conversion of phenylalanine of tyrosine in vivo were determined in 6 healthy postabsorptive adult volunteers. Continuous infusions of tracer amounts of L-[ring- 2 H5]phenylalanine were determined intravenously for 13-14 hr. After 9-10 hr, a priming dose followed by a continuous infusion of L-[1- 13 C]tyrosine was added and maintained, along with the [ 2 H5]phenylalanine infusion, for 4 hr. Venous plasma samples were obtained before the initiation of each infusion and every 30 min during the course of the combined [ 2 H5]phenylalanine and [ 13 C]tyrosine infusion for determination of isotopic enrichments of [ 2 H5]phenylalanine, [ 13 C]tyrosine, and [ 2 H4]tyrosine by gas chromatograph-mass spectrometric analysis of the N-trifluoroacetyl-, methyl ester derivatives of the amino acids. Calculated from the observed enrichments, free phenylalanine and tyrosine turnover rates were 36.1 +/- 5.1 mumole . kg-1 . h-1 and 39.8 +/- 3.5 mumole . kg-1 . h-1, respectively. Phenylalanine was converted to tyrosine at the rate of 5.83 +/- 0.59 mumole . kg-1 . h-1, accounting for approximately 16% of either the phenylalanine or the tyrosine flux. The results indicate that the normal basal steady state phenylalanine hydroxylase activity in vivo in man is lower than that obtained from phenylalanine loading studies. This supports the existence of some type of substance activation of the enzyme as reflected in the previously reported exponential relationship between phenylalanine concentration and phenylalanine hydroxylase activity in vitro. The use of continuous simultaneous infusions of tracer amounts of stable isotope-labeled phenylalanine and tyrosine provides a direct means for studying physiological regulation of phenylalanine hydroxylase activity in vivo
5-FU Metabolism in Cancer and Orally-Administrable 5-FU Drugs

Directory of Open Access Journals (Sweden)

Iwao Sasaki

2010-09-01

Full Text Available 5-Fluorouracil (5-FU is a key anticancer drug that for its broad antitumor activity, as well as for its synergism with other anticancer drugs, has been used to treat various types of malignancies. In chemotherapeutic regimens, 5-FU has been combined with oxaliplatin, irinotecan and other drugs as a continuous intravenous infusion. Recent clinical chemotherapy studies have shown that several of the regimens with oral 5-FU drugs are not inferior compared to those involving continuous 5-FU infusion chemotherapy, and it is probable that in some regimens continuous 5-FU infusion can be replaced by oral 5-FU drugs. Historically, both the pharmaceutical industry and academia in Japan have been involved in the development of oral 5-FU drugs, and this review will focus on the current knowledge of 5-FU anabolism and catabolism, and the available information about the various orally-administrable 5-FU drugs, including UFT, S-1 and capecitabine. Clinical studies comparing the efficacy and adverse events of S-1 and capecitabine have been reported, and the accumulated results should be utilized to optimize the treatment of cancer patients. On the other hand, it is essential to elucidate the pharmacokinetic mechanism of each of the newly-developed drugs, to correctly select the drugs for each patient in the clinical setting, and to further develop optimized drug derivatives.
Double modulation of 5-fluorouracil by trimetrexate and leucovorin in patients with advanced colorectal carcinoma.

Science.gov (United States)

Machiavelli, M R; Salum, G; Pérez, J E; Ortiz, E H; Romero, A O; Bologna, F; Vallejo, C T; Lacava, J A; Dominguez, M E; Leone, B A

2004-04-01

The purpose of this report is to evaluate the efficacy and toxicity (Tx) of a double modulation of 5-fluorouracil (5-FU) by trimetrexate (TMTX) and leucovorin (LV) in patients with advanced recurrent (inoperable) or metastatic colorectal cancer (ACC). Between December 1997 and August 2000, 36 patients were entered in this phase II study. Median age was 61 years, and 18 patients (50%) were female. Median performance status was 0 (range: 0-1), whereas primary tumor location was colon in 21 patients (58%) and rectum in 15 patients (42%). The number of metastatic sites was 1:29 patients (81%); 2:6 patients (17%) and 3:1 patient (3%). Hepatic involvement was observed in 33 patients (92%). Treatment consisted of TMTX 110 mg/m2 IV over 1 hour at hour (H) 0; LV 50 mg/m2 IV over 2 hours IV infusion starting at H 18; and 5-FU 900 mg/m2 IV bolus at H 20. LV (rescue) 15 mg/m2 orally was administered every 6 hours (total 6 doses) beginning at H 24. Cycles were repeated every 2 weeks until progressive disease (PD) or severe Tx. Thirty-four patients are assessable for response (R) (two patients refused further treatment after the first course of therapy), whereas all patients were assessable for Tx. Complete response: 1 patient (3%); partial response: 4 patients (12%), with an overall objective response rate of 15% (95% CI, 1%-25%); no change: 12 patients (35%); and progressive disease: 17 patients (50%). The median time to treatment failure was 4 months and median survival was 11 months. Tx was within acceptable limits. The dose-limiting side effect was mucositis. Eight episodes of grade II or III stomatitis were observed and were responsible for dosage modifications of TMTX and 5-FU. Leukopenia was observed in 16 patients (44%); neutropenia was registered in 19 patients (53%); anemia was seen in 18 patients (50%); emesis in 22 patients (61%); and dermatitis in 3 patients (8%). There were no therapy-related deaths. The double modulation of 5-FU by TMTX and LV showed modest
5-Fluorouracil-based chemotherapy for colorectal cancer and MTHFR/MTRR genotypes

Czech Academy of Sciences Publication Activity Database

Pardini, Barbara; Kumar, R.; Naccarati, Alessio; Prasad, R. B.; Försti, A.; Hemminki, K.; Vodička, Pavel; Bermejo, J. L.

2011-01-01

Roč. 72, č. 1 (2011), s. 162-163 ISSN 0306-5251 R&D Projects: GA ČR GAP304/10/1286; GA ČR GP305/09/P194 Institutional research plan: CEZ:AV0Z50390512 Keywords : fluorouracil * DNA-damage * nepolymorphisms Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.958, year: 2011
Rapid blood clearance and lack of long-term renal toxicity of 177Lu-DOTATATE enables shortening of renoprotective amino acid infusion

International Nuclear Information System (INIS)

Kashyap, Raghava; Eu, Peter; Jackson, Price; Hofman, Michael S.; Hicks, Rodney J.; Beauregard, Jean-Mathieu; Zannino, Diana

2013-01-01

The aim of the study was to investigate the feasibility of shortening the recommended 4-h renoprotective amino acid infusion in patients receiving peptide receptor chemoradionuclide therapy (PRCRT) using radiosensitizing 5-fluorouracil. We evaluated the clearance of radiopeptide from the blood, long-term nephrotoxicity in patients undergoing PRCRT with the conventional 4-h amino acid infusion and renal uptake in patients receiving an abbreviated infusion. The whole-blood clearance of 177 Lu-DOTA-octreotate (LuTate) was measured in 13 patients receiving PRCRT. A retrospective analysis of short-term and long-term changes in glomerular filtration rate (GFR) in 96 consecutive patients receiving a 4-h infusion was performed. Renal LuTate retention estimated using quantitative SPECT/CT in 22 cycles delivered with a 2.5-h amino acid infusion was compared with that in 72 cycles with the 4-h infusion. LuTate demonstrated biexponential blood clearance with an initial clearance half-time of 21 min. Approximately 88 % of blood activity was cleared within 2 h. With the 4-h protocol, there was no significant change in GFR (1.2 ml/min mean increase from baseline; 95 % CI -6.9 to 4.4 ml/min) and no grade 3 or 4 nephrotoxicity at the end of induction PRCRT. The long-term decline in GFR after a median follow up of 22 months was 2.2 ml/min per year. There was no significant difference in the renal LuTate retention measured in patients receiving a 2.5-h amino acid infusion compared to those who had a 4-h infusion. The greatest renal exposure to circulating radiopeptide occurs in the first 1 - 2 h after injection. This, combined with the safety of LuTate PRCRT, allows consideration of an abbreviated amino acid infusion, increasing patient convenience and reducing human resource allocation. (orig.)

Fluorouracil Topical

Science.gov (United States)

... avoid unnecessary or prolonged exposure to sunlight and UV light (such as tanning booths) and to wear protective clothing, sunglasses, and sunscreen. Fluorouracil may make your skin sensitive to sunlight.
Rapid blood clearance and lack of long-term renal toxicity of {sup 177}Lu-DOTATATE enables shortening of renoprotective amino acid infusion

Energy Technology Data Exchange (ETDEWEB)

Kashyap, Raghava; Eu, Peter [Centre for Cancer Imaging, Peter MacCallum Cancer Centre, Melbourne (Australia); Jackson, Price [Peter MacCallum Cancer Centre, Department of Physical Sciences, Melbourne (Australia); Hofman, Michael S.; Hicks, Rodney J. [Centre for Cancer Imaging, Peter MacCallum Cancer Centre, Melbourne (Australia); The University of Melbourne, Departments of Medicine and Radiology, Melbourne (Australia); Beauregard, Jean-Mathieu [Universite Laval, Department of Radiology, Quebec City (Canada); Zannino, Diana [Peter MacCallum Cancer Centre, Department of Biostatistics and Clinical Trials, Melbourne (Australia)

2013-12-15

The aim of the study was to investigate the feasibility of shortening the recommended 4-h renoprotective amino acid infusion in patients receiving peptide receptor chemoradionuclide therapy (PRCRT) using radiosensitizing 5-fluorouracil. We evaluated the clearance of radiopeptide from the blood, long-term nephrotoxicity in patients undergoing PRCRT with the conventional 4-h amino acid infusion and renal uptake in patients receiving an abbreviated infusion. The whole-blood clearance of {sup 177}Lu-DOTA-octreotate (LuTate) was measured in 13 patients receiving PRCRT. A retrospective analysis of short-term and long-term changes in glomerular filtration rate (GFR) in 96 consecutive patients receiving a 4-h infusion was performed. Renal LuTate retention estimated using quantitative SPECT/CT in 22 cycles delivered with a 2.5-h amino acid infusion was compared with that in 72 cycles with the 4-h infusion. LuTate demonstrated biexponential blood clearance with an initial clearance half-time of 21 min. Approximately 88 % of blood activity was cleared within 2 h. With the 4-h protocol, there was no significant change in GFR (1.2 ml/min mean increase from baseline; 95 % CI -6.9 to 4.4 ml/min) and no grade 3 or 4 nephrotoxicity at the end of induction PRCRT. The long-term decline in GFR after a median follow up of 22 months was 2.2 ml/min per year. There was no significant difference in the renal LuTate retention measured in patients receiving a 2.5-h amino acid infusion compared to those who had a 4-h infusion. The greatest renal exposure to circulating radiopeptide occurs in the first 1 - 2 h after injection. This, combined with the safety of LuTate PRCRT, allows consideration of an abbreviated amino acid infusion, increasing patient convenience and reducing human resource allocation. (orig.)
Metabolism of 5-fluorouracil in human liver: an in vivo 19F NMR study

International Nuclear Information System (INIS)

Mohankrishnan, P.; Sprigg, J.; Cardwell, D.; Komoroski, R.A.; Hutchins, L.; Nauke, S.; Williamson, M.R.; Jagannathan, N.R.

1999-01-01

In vivo fluorine-19 nuclear magnetic resonance ( 19 F NMR) spectroscopy was used to study the metabolism and pharmacokinetics of 5-fluorouracil (5-FU) in human liver. Nine patients received 5-FU, and additional chemotherapeutic agents (methotrexate, leucovorin, or levamisole) either prophylactically after breast cancer surgery or for colorectal cancer. The time constant for the disappearance of 5-FU from the liver in vivo varied from 5 to 17 min, while the time constant for the appearance of α-fluoro-β-alanine (the major catabolite of 5 FU) varied from 7 to 86 min. The modulators of 5-FU metabolism did not appear to affect the time constant for the disappearance of 5-FU from the liver or for the appearance of α-fluoro-β-alanine. Results obtained indicate that the pharmacokinetics of 5-FU and α-fluoro-β-alanine may vary substantially at different times in a given individual. (author)
Induction chemotherapy with nedaplatin with 5-FU followed by intensity-modulated radiotherapy concurrent with chemotherapy for locoregionally advanced nasopharyngeal carcinoma

International Nuclear Information System (INIS)

Zheng Jijun; Wang Ge; Yang, G.Y.

2010-01-01

This Phase II study was conducted to evaluate the activity and feasibility of a regimen of nedaplatin and 5-fluorouracil as induction chemotherapy, followed by intensity-modulated radiotherapy concurrent with chemotherapy in patients with locoregionally advanced nasopharyngeal carcinoma. Patients received neoadjuvant chemotherapy comprised two cycles of 5-fluorouracil at 700 mg/m 2 /day administered on days 1-4 as continuous intravenous infusion and nedaplatin (100 mg/m 2 administered intravenous (i.v.) over 2 h) given after the administration of 5-fluorouracil on day 1, repeated every 3 weeks, followed by intensity-modulated radiotherapy concurrent with nedaplatin. During intensity-modulated radiotherapy, nedaplatin was administered at a dose of 100 mg/m 2 intravenous infusion on days 1, 22 and 43, given -60 min before radiation. Fifty-nine (95.8%) of the 60 patients were assessable for response. Thirty-eight cases of complete response and 14 cases of partial response were confirmed after completion of chemoradiation, with the objective response rate of 86.7% (95% confidence interval (CI), 78.1-95.3%). The median follow-up period was 48 months (range, 30-62 months). The 3-year progression-free survival and overall survival were 75.0% (95% CI, 63.0-87.0%) and 85.5% (95% CI, 75.9-95.1%). No patient showed Grade 3 or higher renal dysfunction. The most commonly observed late effect was xerostomia, but the severity diminished over time, and the detectable xerostomia at 24 months was 10.2%. There were no treatment-related deaths during this study. Neoadjuvant chemotherapy with nedaplatin and 5-fluorouracil followed by concomitant nedaplatin and intensity-modulated radiotherapy is an effective and safe treatment for Southern China patients affected by locoregionally advanced nasopharyngeal carcinoma. (author)
Remifentanil for the insertion and removal of long-term central venous access during monitored anesthesia care.

LENUS (Irish Health Repository)

Burlacu, Crina L

2012-02-01

STUDY OBJECTIVE: To determine the analgesic efficacy of three different rates of remifentanil infusion in patients undergoing insertion or removal of long-term central venous access devices during monitored anesthesia care and local anesthetic field infiltration. DESIGN: Double-blinded, randomized, controlled study. SETTING: Operating theatre of an University hospital. PATIENTS: 44 unpremedicated, ASA physical status 1 and 2 patients, aged 18-65 years, undergoing insertion or removal of a Port-a-Cath or Hickman catheter. INTERVENTIONS: Patients sedated with a propofol target-controlled infusion were randomly allocated to three groups: Group R25 (n = 14), Group R50 (n = 15), and Group R75 (n = 15), to receive remifentanil 0.025, 0.05, and 0.075 mug\\/kg\\/min, respectively. Rescue remifentanil 0.5 mug\\/kg was administered for pain scores > 3. The remifentanil infusion rate was maintained constant unless respiratory and\\/or cardiovascular unwanted events occurred, whereupon the rate was adjusted in 0.01 mug\\/kg\\/min decrements as necessary. MEASUREMENTS: Pain scores (primary outcome), sedation, and movement scores (secondary outcomes) were assessed during local anesthetic infiltration of the anterior chest wall and 5 other procedural steps. MAIN RESULTS: All infusion rates had equal analgesic efficacy, as shown by comparable pain scores, number of rescue boluses, and number of patients requiring rescue analgesia. Excessive sedation was associated with the highest remifentanil rate such that Group R75 patients were significantly more sedated than Groups R25 or R50 at selective procedural steps (P < 0.05). More Group R75 patients (6\\/15) required remifentanil rate reduction than did patients from Group R50 (1\\/15) or Group R25 (0\\/14), P < 0.01, most commonly because of respiratory depression. CONCLUSIONS: For the insertion or removal of long-term central venous access devices, all three remifentanil infusion rates proved to be equally analgesic
Two half-sandwiched ruthenium (II compounds containing 5-fluorouracil derivatives: synthesis and study of DNA intercalation.

Directory of Open Access Journals (Sweden)

Zhao-Jun Li

Full Text Available Two novel coordination compounds of half-sandwiched ruthenium(II containing 2-(5-fluorouracil-yl-N-(pyridyl-acetamide were synthesized, and their intercalation binding modes with calf thymus DNA were revealed by hyperchromism of ultraviolet-visible spectroscopy; the binding constants were determined according to a Langmuir adsorption equation that was deduced on the base of careful cyclic voltammetry measurements. The two compounds exhibited DNA intercalation binding activities with the binding constants of 1.13×106 M-1 and 5.35 ×105 M-1, respectively.
Gemcitabine/cisplatin versus 5-fluorouracil/mitomycin C chemoradiotherapy in locally advanced pancreatic cancer: a retrospective analysis of 93 patients

Directory of Open Access Journals (Sweden)

Sauer Rolf

2011-07-01

Full Text Available Abstract Background Despite of a growing number of gemcitabine based chemoradiotherapy studies in locally advanced pancreatic cancer (LAPC, 5-fluorouracil based regimens are still regarded to be standard and the debate of superiority between the two drugs is going on. The aim of this retrospective analysis was to evaluate the effect of two concurrent chemoradiotherapy regimens using 5-fluorouracil or gemcitabine to compare their effect and tolerance. Methods We have performed a single centre retrospective analysis of 93 patients treated with conventionally fractionated radiotherapy of 55.8 Gray using either concurrent 5-fluorouracil, 1 g/m² on days 1-5 and 29-33 of radiotherapy and 10 mg/m² of mitomycin C on day 1, 29 of radiotherapy (FM group, 35 patients versus gemcitabine (300 mg/m² and cisplatin, (30 mg/m² on days 1, 8, 22, and 29 (GC group, 58 patients. Primary endpoint was the median overall survival (OS rate. Results The median OS rate was 12.7 months in the GC group and 9.7 months in the FM group. The 1-year OS rate was 53% versus 40%, respectively (p = 0.009. GC led to more grade 3 leukocytopenia and thrombocytopenia than FM, but not to more grade 4 myelosuppression. Thrombocytopenia was the most frequently observed grade 4 toxicity in both groups (11% after FM versus 12% after GC. No grade 3/4 febrile neutropenia was observed. Grade 3 nausea was more common in the FM group (20% versus 9% and grade 4 nausea was observed in one patient per group only. Conclusions GC was superior to FM for overall survival and both regimens were similar in terms of tolerance. We conclude that GC leads to encouraging results and that the use of FM for chemoradiotherapy in LAPC cannot be recommended without concerns.
The increase in the cardiodepressant activity and vasopressin concentration in the sella turcica venous blood during vagal afferents stimulation or after angiotensin II infusion

International Nuclear Information System (INIS)

Goraca, A.; Orlowska-Majdak, M.; Traczyk, W.Z.

1996-01-01

It has previously been demonstrated that the cardiodepressant activity is present in the bovine hypothalamic extract and in the fluid incubating the posterior pituitary lobe i n situ . The present study was an attempt to reveal if the cardiodepressant factor and vasopressin were simultaneously released from the pituitary into blood. The samples of venous blood flowing from the sella turcica and, for comparison, from the posterior paw were collected in anesthetized rats. Blood from the sella turcica was collected with a fine cannula inserted into the internal maxillary vein. The concentration of vasopressin in blood plasma was determined by radioimmunoassay and cardiodepressant activity-using a biological test on a spontaneously discharged pacemaker tissue of the right auricle of the right heart atrium. Stimulation of the central ends of the cut vagus nerves or intra-arterial infusion of angiotensin II simultaneously caused an increase in the cardiodepressant activity and vasopressin concentration in the sella turcica venous blood. The cardiodepressant activity and vasopressin concentration was also enhanced to some degree in blood outflowing from the posterior paw. Present results indicate that both vasopressin and the cardiodepressant factor are released into blood from the posterior pituitary lobe. (author). 37 refs, 4 figs
Initial results of a phase II trial of high dose radiation therapy, 5-fluorouracil, and cisplatin for patients with anal cancer (E4292): an eastern cooperative oncology group study

International Nuclear Information System (INIS)

Martenson, James A.; Lipsitz, Stuart R.; Wagner, Henry; Kaplan, Edward H.; Otteman, Larry A.; Schuchter, Lynn M.; Mansour, Edward G.; Talamonti, Mark S.; Benson, Al Bowen

1996-01-01

Purpose: A prospective clinical trial was performed to assess the response and toxicity associated with the use of high dose radiation therapy, 5-fluorouracil, and cisplatin in patients with anal cancer. Methods and Materials: Patients with anal cancer without distant metastasis were eligible for this study. Radiation therapy consisted of 59.4 Gy in 33 fractions; a 2 week break in treatment was taken after 36 Gy had been given. A treatment of 5-fluorouracil, 1,000 mg/m 2 per day intravenously, was given for the first 4 days of radiation therapy, and cisplatin, 75 mg/m 2 intravenously, was given on day 1 of radiation therapy. A second course of 5-fluorouracil and cisplatin was given after 36 Gy of radiation, when the radiation therapy was resumed. Results: Nineteen patients entered this study and received treatment. Thirteen (68%) had a complete response, 5 (26%) had a partial response, and 1 (5%) had stable disease. The patient with stable disease and one of the patients with a partial response had complete disappearance of tumor more than 8 weeks after completion of radiation therapy. Fifteen patients had toxicity of Grade 3 or higher: the worst toxicity was Grade 3 in eight patients, Grade 4 in six patients, and Grade 5 in one patient. The most common form of toxicity of Grade 3 or higher was hematologic. The one lethal toxicity was due to pseudomembranous colitis, which was a complication of antibiotic therapy for a urinary tract infection. Conclusion: Radiation therapy, cisplatin, and 5-fluorouracil resulted in an overall response rate of 95%. Significant toxicity occurred, an indication that this regimen is near the maximal tolerated dose. A Phase III clinical trial is planned in which radiation therapy, cisplatin, and 5-fluorouracil will be used as an experimental arm
Biomodulation with sequential intravenous IFN-alpha2b and 5-fluorouracil as second-line treatment in patients with advanced colorectal cancer.

Science.gov (United States)

Pérez, J E; Lacava, J A; Domínguez, M E; Rodríguez, R; Barbieri, M R; Romero Acuña, L A; Romero Acuña, J M; Langhi, M J; Amato, S; Marrone, N; Ortiz, E H; Leone, B A; Vallejo, C T; Machiavelli, M R; Romero, A O

1998-08-01

A phase II trial was carried out by the Grupo Oncologico Cooperativo del Sur (G.O.C.S.) to assess the efficacy and toxicity of a biochemical modulation of 5-fluorouracil (5-FU) by i.v. pretreatment with interferon (IFN)-alpha2b in patients with advanced colorectal carcinoma refractory to previous therapy with 5-FU modulated by methotrexate (MTX) or leucovorin (LV) or both. Between January 1993 and October 1995, 34 patients were entered on the study. The treatment was IFN-alpha2b 5 x 10(6)/m2 IU in a 1-h i.v. infusion, followed immediately by 5-FU 600 mg/m2 i.v. bolus injection. Courses were repeated weekly until observation of progressive disease or severe toxicity. One patient could not be assessed for response. Objective regression was observed in 2 of 33 patients (6%, 95% confidence interval, 0%-14%). No patient achieved a complete response. Two patients had partial responses (6%). No change was recorded in 14 patients (41%), and progressive disease occurred in 17 (52%). The median time to treatment failure was 3 months, and the median survival was 5 months. Toxicity was within acceptable limits. The main side effects were mucositis and diarrhea. Four episodes of grade 2 stomatitis were observed, causing dosage modifications. The most frequent toxic effects attributable to IFN-alpha2b were mild fatigue and fever. In conclusion, second-line therapy with i.v. IFN-alpha2b preceding 5-FU has shown an interesting profile of activity in a patient population with clearly unfavorable characteristics. From this perspective, further appropriately designed studies are needed to identify the greatest potential of IFN-alpha2b as a modulator of 5-FU.
Basic pharmacology of topical imiquimod, 5-fluorouracil, and diclofenac for the dermatologic surgeon.

Science.gov (United States)

Desai, Tejas; Chen, Cynthia L; Desai, Alpesh; Kirby, William

2012-01-01

Ultraviolet radiation (UVR) contributes to the vast majority of nonmelanoma skin cancer (NMSC). As the incidence of NMSC continues to rise, topical therapies will be used with increasing frequency. Topical therapies may benefit high-risk surgical candidates as an alternative treatment modality and may improve overall cosmesis. The most commonly employed topical therapies are imiquimod, 5-fluorouracil (5-FU), and diclofenac. To review the detailed mechanism of action and side-effect profiles of each topical therapy used to treat NMSC and to explore newly discovered actions. Uncommon adverse events are also presented. An extensive literature search was performed to describe the pharmacologic actions of imiquimod, 5-FU, and diclofenac. A keen understanding of the pharmacologic concepts of these topical therapies may aid the dermatologic surgeon in making sound choices before, during, and after surgery. © 2011 by the American Society for Dermatologic Surgery, Inc. Published by Wiley Periodicals, Inc.
Monitoring 5-fluorouracil in patients undergoing chemotherapy by means of F-19 MR spectroscopy

International Nuclear Information System (INIS)

Wolf, W.; Albright, M.J.; Silver, M.S.; Starewicz, P.M.; Weber, H.; Reichardt, U.; Saver, R.

1986-01-01

F-19 MR spectroscopy allows direct observation of fluorinated drugs and their metabolites in the human body without background signal from the tissue. In addition, unlike F-18, specific chemical structure information is available in vivo. The behavior of a well-known fluorinated chemotherapeutic drug, 5-fluorouracil (5-FU), and its metabolites was observed noninvasively in patients undergoing cancer chemotherapy. The time course of the drug's metabolism was examined and half-life values of the unmetabolized 5-FU in the liver were calculated from the F-19 peak intensity. Half-life values of the unmetabolized 5-FU in the liver were in the range of 15-30 minutes. Interpatient variations were correlated with the chemotherapy results. F-19 MR spectroscopy is feasible in humans and allows determination of the time course of the metabolism of fluorinated drugs in individual patients
Combinations of Polymorphisms in Genes Involved in the 5-Fluorouracil Metabolism Pathway Are Associated with Gastrointestinal Toxicity in Chemotherapy-Treated Colorectal Cancer Patients

DEFF Research Database (Denmark)

Afzal, Shoaib; Gusella, Milena; Vainer, Ben

2011-01-01

PURPOSE: The purpose of this study was to investigate whether specific combinations of polymorphisms in genes encoding proteins involved in 5-fluorouracil (5-FU) pharmacokinetics and pharmacodynamics are associated with increased risk of treatment-induced toxicity. EXPERIMENTAL DESIGN: We analyze...
Test-retest reproducibility of the metabotropic glutamate receptor 5 ligand [{sup 18}F]FPEB with bolus plus constant infusion in humans

Energy Technology Data Exchange (ETDEWEB)

Park, Eunkyung; Sullivan, Jenna M.; Planeta, Beata; Gallezot, Jean-Dominique; Lim, Keunpoong; Lin, Shu-Fei; Ropchan, Jim; Huang, Yiyun; Carson, Richard E. [Yale School of Medicine, PET Center, Department of Diagnostic Radiology, 801 Howard Avenue, PO Box 208048, New Haven, CT (United States); McCarthy, Timothy J. [Pfizer Worldwide Research and Development, Cambridge, MA (United States); Ding, Yu-Shin [New York University School of Medicine, Department of Radiology, New York, NY (United States); Morris, Evan D.; Williams, Wendol A. [Yale School of Medicine, PET Center, Department of Diagnostic Radiology, 801 Howard Avenue, PO Box 208048, New Haven, CT (United States); Yale School of Medicine, Department of Psychiatry, New Haven, CT (United States)

2015-09-15

[{sup 18}F]FPEB is a promising PET radioligand for the metabotropic glutamate receptor 5 (mGluR5), a potential target for the treatment of neuropsychiatric diseases. The purpose of this study was to evaluate the test-retest reproducibility of [{sup 18}F]FPEB in the human brain. Seven healthy male subjects were scanned twice, 3 - 11 weeks apart. Dynamic data were acquired using bolus plus infusion of 162 ± 32 MBq [{sup 18}F]FPEB. Four methods were used to estimate volume of distribution (V{sub T}): equilibrium analysis (EQ) using arterial (EQ{sub A}) or venous input data (EQ{sub V}), MA1, and a two-tissue compartment model (2 T). Binding potential (BP{sub ND}) was also estimated using cerebellar white matter (CWM) or gray matter (CGM) as the reference region using EQ, 2 T and MA1. Absolute test-retest variability (aTRV) of V{sub T} and BP{sub ND} were calculated for each method. Venous blood measurements (C{sub V}) were compared with arterial input (C{sub A}) to examine their usability in EQ analysis. Regional V{sub T} estimated by the four methods displayed a high degree of agreement (r{sup 2} ranging from 0.83 to 0.99 among the methods), although EQ{sub A} and EQ{sub V} overestimated V{sub T} by a mean of 9 % and 7 %, respectively, compared to 2 T. Mean values of aTRV of V{sub T} were 11 % by EQ{sub A}, 12 % by EQ{sub V}, 14 % by MA1 and 14 % by 2 T. Regional BP{sub ND} also agreed well among the methods and mean aTRV of BP{sub ND} was 8 - 12 % (CWM) and 7 - 9 % (CGM). Venous and arterial blood concentrations of [{sup 18}F]FPEB were well matched during equilibrium (C{sub V} = 1.01 . C{sub A}, r{sup 2} = 0.95). [{sup 18}F]FPEB binding shows good TRV with minor differences among analysis methods. Venous blood can be used as an alternative for input function measurement instead of arterial blood in EQ analysis. Thus, [{sup 18}F]FPEB is an excellent PET imaging tracer for mGluR5 in humans. (orig.)
Cost-effectiveness analysis of 5-fluorouracil 0.5%/salicylic acid 10% in the treatment of actinic keratosis in Spain.

Science.gov (United States)

Nieves, Diana; Puig-Peiró, Ruth; Ferrándiz, Carlos; Plazas, Maria Josep; Brosa, Max

2015-06-01

The aim of this study is to conduct a cost-effectiveness analysis of 5-fluorouracil 0.5%/salicylic acid 10% (5-FU/SA) in the treatment of isolated hyperkeratotic actinic keratosis lesions in Spain. An analytical decision-making model was constructed to compare whether 5-FU/SA was a cost-effective option compared with cryotherapy from the perspective of the Spanish National Health System with a time horizon of 6 months. Costs were expressed in 2014 euros. The cost of patients with hyperkeratotic actinic keratosis treated with 5-FU/SA or cryotherapy was €266 and €285, respectively. 5-FU/SA was associated with higher rates of treatment success and, consequently, more quality-adjusted life years, than cryotherapy. Therefore, 5-FU/SA was the dominant treatment, as it was associated with a lower treatment cost and greater effectiveness than cryotherapy. Economically, 5-FU/SA was a dominant option compared with cryotherapy in the treatment of isolated hyperkeratotic actinic keratosis lesions in Spain.
Infusion of sodium bicarbonate in experimentally induced metabolic acidosis does not provoke cerebrospinal fluid (CSF) acidosis in calves.

Science.gov (United States)

Abeysekara, Saman; Zello, Gordon A; Lohmann, Katharina L; Alcorn, Jane; Hamilton, Don L; Naylor, Jonathan M

2012-01-01

In a crossover study, 5 calves were made acidotic by intermittent intravenous infusion of isotonic hydrochloric acid (HCl) over approximately 24 h. This was followed by rapid (4 h) or slow (24 h) correction of blood pH with isotonic sodium bicarbonate (NaHCO(3)) to determine if rapid correction of acidemia produced paradoxical cerebrospinal fluid (CSF) acidosis. Infusion of HCl produced a marked metabolic acidosis with respiratory compensation. Venous blood pH (mean ± S(x)) was 7.362 ± 0.021 and 7.116 ± 0.032, partial pressure of carbon dioxide (Pco(2), torr) 48.8 ± 1.3 and 34.8 ± 1.4, and bicarbonate (mmol/L), 27.2 ± 1.27 and 11 ± 0.96; CSF pH was 7.344 ± 0.031 and 7.240 ± 0.039, Pco(2) 42.8 ± 2.9 and 34.5 ± 1.4, and bicarbonate 23.5 ± 0.91 and 14.2 ± 1.09 for the period before the infusion of hydrochloric acid and immediately before the start of sodium bicarbonate correction, respectively. In calves treated with rapid infusion of sodium bicarbonate, correction of venous acidemia was significantly more rapid and increases in Pco(2) and bicarbonate in CSF were also more rapid. However, there was no significant difference in CSF pH. After 4 h of correction, CSF pH was 7.238 ± 0.040 and 7.256 ± 0.050, Pco(2) 44.4 ± 2.2 and 34.2 ± 2.1, and bicarbonate 17.8 ± 1.02 and 14.6 ± 1.4 for rapid and slow correction, respectively. Under the conditions of this experiment, rapid correction of acidemia did not provoke paradoxical CSF acidosis.
Severe complications of 5-fluorouracil and cisplatin with concomitant radiotherapy in inoperable non-metastatic squamous cell oesophageal cancer after intubation - early termination of a prospective randomised trial

Energy Technology Data Exchange (ETDEWEB)

Alberts, A.S.; Friediger, D.; Nel, J. (Pretoria Univ. (South Africa). Dept. of Radiotherapy); Burger, W.; Schoeman, L.; Falkson, G. (Pretoria Univ. (South Africa). Dept. of Medical Oncology); Greeff, F.; Steyn, E.; Schmid, E.U. (Pretoria Univ. (South Africa). Dept. of Surgery)

This brief letter describes a randomized trial in which radiotherapy is added to concomitant 5- fluorouracil and cisplatin therapy in patients with inoperable non-mestastatic squamous cell oesophageal cancer after palliative intubation. An interim analysis showed that patients randomized to observation had a median survival of 19 weeks while patients treated with radiotherapy, 5- fluorouracil and cisplatin had a median survival of 11 weeks. This difference in survival was due to the toxicity of the combined chemoradiotherapy and tube which resulted in early termination of the trial. (UK).
5-Fluorouracil-induced apoptosis in cultured oral cancer cells.

Science.gov (United States)

Tong, D; Poot, M; Hu, D; Oda, D

2000-03-01

Chemotherapy is commonly used to treat advanced oral squamous cell carcinoma (SCC) and is known to kill cancer cells through apoptosis. Our hypothesis states that 5-fluorouracil (5FU) also kills cultured oral epithelial cells through programmed cell death or apoptosis. Cultured oral cancer cells were exposed to an optimum dose of 20 mg/ml of 5FU. Cells were analyzed for changes in cell cycle distribution and induction of cell death including apoptosis. Normal control, human papilloma virus-immortalized (PP), ATCC SCC cell line (CA1) and two primary oral SCC cell lines (CA3 and -4) were studied. Inhibition of apoptosis by a pan-caspase inhibitor was used. SYTO 11 flow cytometry showed increased apoptosis in all 5FU-treated cell cultures compared to untreated controls. The results show biological variation in apoptotic response. CA1 had the lowest apoptotic rate of the cancer cell lines at 1.5%. Next lowest was CA3, followed by CA4 and PP. In addition, alteration in the G1 and S phase fractions were found. Untreated CA1 showed 28% G1, 53% S compared to 43% G1, and 40% S of treated. We investigated the pathway of apoptosis using the pan-caspase inhibitor IDN-1529 by methylthiazolyl diphenyl tetrazolium bromide (MTT) colorimetric analysis. Results showed mild inhibition of cell death when cells were incubated with 50 microM IDN-1529 for 24 h. This suggests a probable caspase-dependent apoptotic pathway. In conclusion, our data suggest that 5FU induces oral cancer cell death through apoptosis and that biological variation exists between normal and cancer cells and between different types of cancer cells themselves. Our data indicate that cultures of a useful in vitro model for chemosensitivity assays are possible. Our results also suggest a caspase-dependent pathway for chemocytotoxicity in oral SCC.
Effect of combined 5-fluorouracil and radiation on murine hematopoietic tissue

International Nuclear Information System (INIS)

Nielsen, O.S.; Overgaard, J.; Von der Maase, H.

1988-01-01

The interaction of 5-fluorouracil (5-FU) and radiation in hematopoietic tissue was assessed as the survival of hematopoietic stem cells (CFUs) by means of the spleen colony assay. 5-FU was given intraperitoneally in the dose range 50-500 mg/kg body weight. In this dose range, stem cell survival decreased exponentially as a function of 5-FU dose. After 150 mg/kg of 5-FU alone, the stem cell survival rapidly decreased, reaching a minimum after 1-2 days. A similar regeneration was observed after 0.75 Gy radiation alone 5-FU given 15 min before whole-body irradiation resulted in a pronounced reduction in stem cell survival due to an increase in the slope of the radiation survival curve by a factor of 2.1. After combined 5-FU and radiation, the survival rapidly decreased to a minimum at day 1, and it showed only a slight increase within the next 7 days. After this delay, the stem cells regenerated with a doubling time of about 30 h, reaching pretreatment values on day 15. The delayed stem cell regeneration was not seen following 3.5 Gy radiation alone or 225 mg/kg 5-FU alone, which resulted in the same nadir of CFUs survival as found after the combined treatment. Thus, 5-FU greatly enhances the hematopoietic damage after radiation by reducing the number of surviving stem cells and delaying the stem cell regeneration. 24 refs.; 6 figs.; 1 table
A simple method for measurement of cerebral blood flow using 123I-IMP SPECT with calibrated standard input function by one point blood sampling. Validation of calibration by one point venous blood sampling as a substitute for arterial blood sampling

International Nuclear Information System (INIS)

Ito, Hiroshi; Akaizawa, Takashi; Goto, Ryoui

1994-01-01

In a simplified method for measurement of cerebral blood flow using one 123 I-IMP SPECT scan and one point arterial blood sampling (Autoradiography method), input function is obtained by calibrating a standard input function by one point arterial blood sampling. A purpose of this study is validation of calibration by one point venous blood sampling as a substitute for one point arterial blood sampling. After intravenous infusion of 123 I-IMP, frequent arterial and venous blood sampling were simultaneously performed on 12 patients of CNS disease without any heart and lung disease and 5 normal volunteers. The radioactivity ratio of venous whole blood which obtained from cutaneous cubital vein to arterial whole blood were 0.76±0.08, 0.80±0.05, 0.81±0.06, 0.83±0.11 at 10, 20, 30, 50 min after 123 I-IMP infusion, respectively. The venous blood radioactivities were always 20% lower than those of arterial blood radioactivity during 50 min. However, the ratio which obtained from cutaneous dorsal hand vein to artery were 0.93±0.02, 0.94±0.05, 0.98±0.04, 0.98±0.03, at 10, 20, 30, 50 min after 123 I-IMP infusion, respectively. The venous blood radioactivity was consistent with artery. These indicate that arterio-venous difference of radioactivity in a peripheral cutaneous vein like a dorsal hand vein is minimal due to arteriovenous shunt in palm. Therefore, a substitution by blood sampling from cutaneous dorsal hand vein for artery will be possible. Optimized time for venous blood sampling evaluated by error analysis was 20 min after 123 I-IMP infusion, which is 10 min later than that of arterial blood sampling. (author)

Effect of hepatic venous sphincter contraction on transmission of central venous pressure to lobar and portal pressure.

Science.gov (United States)

Lautt, W W; Legare, D J; Greenway, C V

1987-11-01

In dogs anesthetized with pentobarbital, central vena caval pressure (CVP), portal venous pressure (PVP), and intrahepatic lobar venous pressure (proximal to the hepatic venous sphincters) were measured. The objective was to determine some characteristics of the intrahepatic vascular resistance sites (proximal and distal to the hepatic venous sphincters) including testing predictions made using a recent mathematical model of distensible hepatic venous resistance. The stimulus used was a brief rise in CVP produced by transient occlusion of the thoracic vena cava in control state and when vascular resistance was elevated by infusions of norepinephrine or histamine, or by nerve stimulation. The percent transmission of the downstream pressure rise to upstream sites past areas of vascular resistance was elevated. Even small increments in CVP are partially transmitted upstream. The data are incompatible with the vascular waterfall phenomenon which predicts that venous pressure increments are not transmitted upstream until a critical pressure is overcome and then further increments would be 100% transmitted. The hepatic sphincters show the following characteristics. First, small rises in CVP are transmitted less than large elevations; as the CVP rises, the sphincters passively distend and allow a greater percent transmission upstream, thus a large rise in CVP is more fully transmitted than a small rise in CVP. Second, the amount of pressure transmission upstream is determined by the vascular resistance across which the pressure is transmitted. As nerves, norepinephrine, or histamine cause the hepatic sphincters to contract, the percent transmission becomes less and the distensibility of the sphincters is reduced. Similar characteristics are shown for the "presinusoidal" vascular resistance and the hepatic venous sphincter resistance.(ABSTRACT TRUNCATED AT 250 WORDS)
Efeito do uso tópico de capsaicina na mucosite intestinal induzida por 5-fluorouracil em camundongos Swiss

OpenAIRE

Lorrayne Gonçalves Lopes

2014-01-01

5-FU (5-Fluorouracil) é um agente quimioterápico chave no tratamento de diversos tipos de câncer, sendo amplamente usado contra o câncer colorretal. Mucosite intestinal com diarreia e vômito é um efeito adverso frequentemente dose-limitante da terapia com 5- FU, afetando a qualidade de vida dos pacientes e a continuidade da terapia. Capsaicina (trans-8-metil-N-vanílico-6-nonenamida) é um componente de várias espécies de pimenta, sendo responsável pela pungência dos frutos. Ela apresenta amplo...
Development and evaluation of nanostructured lipid carrier-based hydrogel for topical delivery of 5-fluorouracil

Directory of Open Access Journals (Sweden)

Rajinikanth PS

2016-10-01

Full Text Available Paruvathanahalli Siddalingam Rajinikanth,1,2 Jestin Chellian2 1School of Pharmacy, Taylors University, 2School of Pharmacy, International Medical University, Kuala Lumpur, Malaysia Abstract: The aim of this study was to develop a nanostructured lipid carrier (NLC-based hydrogel and study its potential for the topical delivery of 5-fluorouracil (5-FU. Precirol® ATO 5 (glyceryl palmitostearate and Labrasol® were selected as the solid and liquid lipid phases, respectively. Poloxamer 188 and Solutol® HS15 (polyoxyl-15-hydroxystearate were selected as surfactants. The developed lipid formulations were dispersed in 1% Carbopol® 934 (poly[acrylic acid] gel medium in order to maintain the topical application consistency. The average size, zeta potential, and polydispersity index for the 5-FU-NLC were found to be 208.32±8.21 nm, -21.82±0.40 mV, and 0.352±0.060, respectively. Transmission electron microscopy study revealed that 5-FU-NLC was <200 nm in size, with a spherical shape. In vitro drug permeation studies showed a release pattern with initial burst followed by sustained release, and the rate of 5-FU permeation was significantly improved for 5-FU-NLC gel (10.27±1.82 µg/cm2/h as compared with plain 5-FU gel (2.85±1.12 µg/cm2/h. Further, skin retention studies showed a significant retention of 5-FU from the NLC gel (91.256±4.56 µg/cm2 as compared with that from the 5-FU plain gel (12.23±3.86 µg/cm2 in the rat skin. Skin irritation was also significantly reduced with 5-FU-NLC gel as compared with 5-FU plain gel. These results show that the prepared 5-FU-loaded NLC has high potential to improve the penetration of 5-FU through the stratum corneum, with enormous retention and with minimal skin irritation, which is the prerequisite for topically applied formulations. Keywords: nanostructured lipid carrier, topical delivery, controlled release, 5-fluorouracil, skin penetration, skin infection
Concurrent radiation, mitomycin C and 5-fluorouracil in poor prognosis carcinoma of cervix: preliminary results of a Phase I-II study

Energy Technology Data Exchange (ETDEWEB)

Thomas, G.; Dembo, A.; Beale, F.; Bean, H.; Bush, R.; Herman, J.; Pringle, J.; Rawlings, G.; Sturgeon, J.; Fine, S.

1984-09-01

Between July 1981 and June 1983, 27 patients with advanced primary squamous cell carcinoma (SCC) of cervix and 8 with recurrent disease were treated using a pilot regimen of combination chemotherapy (CT): Mitomycin C (MIT), 5 Fluorouracil (5 FU), and radiation therapy (RT). CT and RT doses on this Phase I-II Study were escalated to the current regimen. A split course of RT was used, either pelvic RT alone or the same pelvic RT plus para-aortic RT. CT was given by continuous IV infusion days 1 through 4 of each half-course of RT. This was followed by one application of intrauterine /sup 137/Cs when possible. Three of the 8 patients with recurrence in the pelvis or para-aortic nodes had a complete response (CR) to CT-RT and are alive without disease at 19, 19 and 22 months after treatment, respectively. Twenty of the 27 (74%) primary patients had a CR. With a median duration of follow-up of 6 months 4/20 have relapsed, 1 in RT field, 2 at distant sites, and 1 in both. The acute toxicity of this regimen was tolerable: 2/35 developed transient leukopenia with one febrile episode, 9/35 developed transient thrombocytopenia without bleeding. Symptomatic sigmoid strictures developed in two patients, one requiring surgical intervention. Typically, near complete regression of tumor is noted on completion of the external RT, reproducing the dramatic responses that have been observed in SCC of the anal canal, esophagus and head and neck, with this CT-RT regimen.
Controlled 5-fluorouracil release from hydrogels of Poly (acrylamide-co-metacrylic acid) crosslinked by means Of gamma irradiation techniques

International Nuclear Information System (INIS)

Rapado, M.; Sainz, D.; Altanes, S.; Prado, S.; Padron, S.; Salivar, D.; Chong, B.

1999-01-01

This report present the results on entrapped a cytostatic 5-Fluorouracil (5-F) in polymeric matrixes named hydrogels of polyacrylamide co -metacrylic acid crosslinked by means of gamma radiation with doses of 10,30, and 30 kGy at 25 o C. The drug delivery was followed by HPLC. The behavior of 5 -Fu migration from polymeric network was analyze by Iguchi equation for plain structure systems. The diffusion coefficients were obtained and drug release was in accordance with Fickian behavior
The increase in the cardiodepressant activity and vasopressin concentration in the sella turcica venous blood during vagal afferents stimulation or after angiotensin II infusion

Energy Technology Data Exchange (ETDEWEB)

Goraca, A.; Orlowska-Majdak, M.; Traczyk, W.Z. [Akademia Medyczna, Lodz (Poland). Katedra Fizjologii

1996-12-31

It has previously been demonstrated that the cardiodepressant activity is present in the bovine hypothalamic extract and in the fluid incubating the posterior pituitary lobe {sup i}n situ{sup .} The present study was an attempt to reveal if the cardiodepressant factor and vasopressin were simultaneously released from the pituitary into blood. The samples of venous blood flowing from the sella turcica and, for comparison, from the posterior paw were collected in anesthetized rats. Blood from the sella turcica was collected with a fine cannula inserted into the internal maxillary vein. The concentration of vasopressin in blood plasma was determined by radioimmunoassay and cardiodepressant activity-using a biological test on a spontaneously discharged pacemaker tissue of the right auricle of the right heart atrium. Stimulation of the central ends of the cut vagus nerves or intra-arterial infusion of angiotensin II simultaneously caused an increase in the cardiodepressant activity and vasopressin concentration in the sella turcica venous blood. The cardiodepressant activity and vasopressin concentration was also enhanced to some degree in blood outflowing from the posterior paw. Present results indicate that both vasopressin and the cardiodepressant factor are released into blood from the posterior pituitary lobe. (author). 37 refs, 4 figs.
Irinotecan and 5-fluorouracil-co-loaded, hyaluronic acid-modified layer-by-layer nanoparticles for targeted gastric carcinoma therapy

Directory of Open Access Journals (Sweden)

Gao Z

2017-09-01

Full Text Available Zhuanglei Gao,1 Zhaoxia Li,2 Jieke Yan,3 Peilin Wang1 1Department of General Surgery, 2Department of Pediatrics, 3Department of Renal Transplantation, The Second Hospital of Shandong University, Jinan, Shandong, People’s Republic of China Abstract: For targeted gastric carcinoma therapy, hyaluronic acid (HA-modified layer-by-layer nanoparticles (NPs are applied for improving anticancer treatment efficacy and reducing toxicity and side effects. The aim of this study was to develop HA-modified NPs for the co-loading of irinotecan (IRN and 5-fluorouracil (5-FU. A novel polymer–chitosan (CH–HA hybrid formulation (HA–CH–IRN/5-FU NPs consisting of poly(D,L-lactide-co-glycolide (PLGA and IRN as the core, CH and 5-FU as a shell on the core and HA as the outmost layer was prepared. Its morphology, average size, zeta potential and drug encapsulation ability were evaluated. Human gastric carcinoma cells (MGC803 cells and cancer-bearing mice were used for the testing of in vitro cytotoxicity and in vivo antitumor efficiency of NPs. HA–CH–IRN/5-FU NPs displayed enhanced antitumor activity in vitro and in vivo than non-modified NPs, single drug-loaded NPs and drugs solutions. The results demonstrate that HA–CH–IRN/5-FU NPs can achieve impressive antitumor activity and the novel targeted drug delivery system offers a promising strategy for the treatment of gastric cancer. Keywords: gastric carcinoma, irinotecan, 5-fluorouracil, hyaluronic acid, layer-by-layer nanoparticles
Comparative study in swines' vocal cords healing after excision of fragment with CO2 laser with mitomycin and 5-fluorouracil postoperative topical application Estudo comparado da cicatrização da prega vocal de suínos após exérese de fragmento com laser de CO2 e aplicação tópica pós-operatória de mitomicina e 5-fluorouracil

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Eduardo Baptistella

2009-02-01

Full Text Available PURPOSE: To evaluate the deposition of collagen fibers at pig's vocal folds after topical use of mitomycin or 5-fluorouracil, when partial exeresis of mucosa layer had been promoted by CO2 laser. METHODS: There were used 18 Larger white pigs which were anesthetized and submitted to mucosa fragment's exeresis, bilaterally, at its free border. The animals were divided into 3 groups, each one with 6 animals: control group, without topical drug application; mitomycin group; and 5-fluorouracil group. After 30 days, the animals were subjected to euthanasia, and samples of the vocal folds were collected and stained by picrosirius red technique with polarization for quantification of total collagen deposition. RESULTS: In control group, the mean rate of right vocal fold's collagen deposition at submucosa consisted in a 3428.66 micrometers area. There was found an area whose size had, in average, 2196.36 micrometers, in mitomycin group, and 2269.19 micrometers, in 5-fluorouracil group. CONCLUSION: Mitomycin and 5-fluorouracil had promoted beneficial change in vocal fold's cicatrization with less collagen deposition, but there was no significant statistically difference when they were compared between themselves.OBJETIVO: Avaliar a deposição das fibras de colágeno total em pregas vocais suínas após o uso tópico de mitomicina ou 5-fluorouracil nas exéreses parciais de mucosa com laser de CO2. MÉTODOS: Foram utilizados 18 porcos da raça Larger white anestesiados e submetidos à exérese de fragmento de mucosa de borda livre da prega vocal direita e prega vocal esquerda. Os animais foram divididos em 3 grupos com 6 animais cada: grupo controle, sem aplicação de medicação tópica; grupo mitomicina, com uso tópico dessa substância; grupo 5-fluorouracil, uso tópico. Após 30 dias do experimento os animais foram submetidos à eutanásia, coletadas amostras das pregas vocais e coradas pela técnica do picrosirius red com polarização para a
Impact of Gemcitabine Chemotherapy and 3-Dimensional Conformal Radiation Therapy/5-Fluorouracil on Quality of Life of Patients Managed for Pancreatic Cancer

Energy Technology Data Exchange (ETDEWEB)

Short, Michala [Discipline of Medical Radiation Sciences, University of Sydney, Sydney, New South Wales (Australia); Western Australia Centre for Cancer and Palliative Care/Curtin Health Innovation Research Institute, Curtin University, Perth, Western Australia (Australia); Goldstein, David [Department of Medical Oncology, Prince of Wales Hospital, Sydney, New South Wales (Australia); Halkett, Georgia [Western Australia Centre for Cancer and Palliative Care/Curtin Health Innovation Research Institute, Curtin University, Perth, Western Australia (Australia); Reece, William [Covance Asia Pacific, Sydney, New South Wales (Australia); Borg, Martin [Adelaide Radiotherapy Centre, Adelaide, South Australia (Australia); Zissiadis, Yvonne [Department of Radiation Oncology, Royal Perth Hospital, Perth, Western Australia (Australia); Kneebone, Andrew [Northern Sydney Cancer Centre, Royal North Shore Hospital, Sydney, New South Wales (Australia); Spry, Nigel, E-mail: Nigel.Spry@health.wa.gov.au [Department of Radiation Oncology, Sir Charles Gairdner Hospital, Perth, Western Australia (Australia); Faculty of Medicine, University of Western Australia, Perth, Western Australia (Australia)

2013-01-01

Purpose: To report quality of life (QOL) results for patients receiving chemoradiation therapy for pancreatic cancer. Methods and Materials: Eligible patients (n=41 locally advanced, n=22 postsurgery) entered the B9E-AY-S168 study and received 1 cycle of induction gemcitabine (1000 mg/m{sup 2} weekly Multiplication-Sign 3 with 1-week break) followed by 3-dimensional conformal radiation therapy (RT) (54 Gy locally advanced and 45 Gy postsurgery) and concomitant continuous-infusion 5-fluorouracil (5FU) (200 mg/m{sup 2}/d throughout RT). After 4 weeks, patients received an additional 3 cycles of consolidation gemcitabine chemotherapy. Patients completed the European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-PAN26 questionnaires at baseline, before RT/5FU, at end of RT/5FU, before consolidation gemcitabine, and at treatment completion. Results: The patterns of change in global QOL scores differed between groups. In the locally advanced group global QOL scores were +13, +8, +3, and +1 compared with baseline before RT/5FU (P=.008), at end of RT/5FU, before consolidation gemcitabine, and at treatment completion, respectively. In the postsurgery group, global QOL scores were -3, +4, +15, and +17 compared with baseline at the same time points, with a significant improvement in global QOL before consolidation gemcitabine (P=.03). No significant declines in global QOL were reported by either cohort. Conclusions: This study demonstrates that global QOL and associated function and symptom profiles for pancreatic chemoradiation therapy differ between locally advanced and postsurgery patients, likely owing to differences in underlying disease status. For both groups, the treatment protocol was well tolerated and did not have a negative impact on patients' global QOL.
Impact of Gemcitabine Chemotherapy and 3-Dimensional Conformal Radiation Therapy/5-Fluorouracil on Quality of Life of Patients Managed for Pancreatic Cancer

International Nuclear Information System (INIS)

Short, Michala; Goldstein, David; Halkett, Georgia; Reece, William; Borg, Martin; Zissiadis, Yvonne; Kneebone, Andrew; Spry, Nigel

2013-01-01

Purpose: To report quality of life (QOL) results for patients receiving chemoradiation therapy for pancreatic cancer. Methods and Materials: Eligible patients (n=41 locally advanced, n=22 postsurgery) entered the B9E-AY-S168 study and received 1 cycle of induction gemcitabine (1000 mg/m 2 weekly ×3 with 1-week break) followed by 3-dimensional conformal radiation therapy (RT) (54 Gy locally advanced and 45 Gy postsurgery) and concomitant continuous-infusion 5-fluorouracil (5FU) (200 mg/m 2 /d throughout RT). After 4 weeks, patients received an additional 3 cycles of consolidation gemcitabine chemotherapy. Patients completed the European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-PAN26 questionnaires at baseline, before RT/5FU, at end of RT/5FU, before consolidation gemcitabine, and at treatment completion. Results: The patterns of change in global QOL scores differed between groups. In the locally advanced group global QOL scores were +13, +8, +3, and +1 compared with baseline before RT/5FU (P=.008), at end of RT/5FU, before consolidation gemcitabine, and at treatment completion, respectively. In the postsurgery group, global QOL scores were −3, +4, +15, and +17 compared with baseline at the same time points, with a significant improvement in global QOL before consolidation gemcitabine (P=.03). No significant declines in global QOL were reported by either cohort. Conclusions: This study demonstrates that global QOL and associated function and symptom profiles for pancreatic chemoradiation therapy differ between locally advanced and postsurgery patients, likely owing to differences in underlying disease status. For both groups, the treatment protocol was well tolerated and did not have a negative impact on patients' global QOL.
Comment: The comparison study of 5 Fluorouracil vs. cryotherpy in the treatment of the backhand resistant common wart

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Antonio Chuh

2014-07-01

Full Text Available We refer to the study conducted by Asghariazar R et al comparing the efficacy of 5-fluorouracil against cryotherapy in the management of backhand resistant common warts [1]. We congratulate their success in reporting such a high-quality study. We would humbly like to offer a few pieces of advice, which might further augment the clinical relevance and the scientific content for future studies along similar veins.
5-Fluorouracil-induced acute reversible heart failure not explained by coronary spasms, myocarditis or takotsubo

DEFF Research Database (Denmark)

Fakhri, Yama; Dalsgaard, Morten; Nielsen, Dorte

2016-01-01

A 69-year-old woman presented with arterial hypotension, pulmonary oedema and a severely depressed left ventricular ejection fraction (LVEF) of 25% only 3 days after having received her first treatment for colorectal cancer with 5-fluorouracil (5-FU)-based therapy. The ECG demonstrated widespread......, cardiac MRI scan 9 days later showed a normal LVEF with signs of neither myocardial oedema nor necrosis. Despite the high therapeutic efficacy of 5-FU in treatment of colorectal cancer, it is associated with undesired cardiac toxicities including coronary spasms, toxic inflammation and takotsubo...... ST-segment depression and echocardiography showed uniform hypokinesia of all left ventricular (LV) myocardial segments without signs of regional LV ballooning. Coronary angiography was normal and the patient gained full recovery after receiving treatment with heart failure medication. Interestingly...
Experimental and theoretical studies on the coordination chemistry of the N1-hexyl substituted pyrimidines (uracil, 5-fluorouracil and cytosine).

Science.gov (United States)

Barceló-Oliver, Miquel; Baquero, Beatriz Adriana; Bauzá, Antonio; García-Raso, Angel; Vich, Roberto; Mata, Ignasi; Molins, Elies; Terrón, Angel; Frontera, Antonio

2013-06-07

N(1)-Hexyl substituted pyrimidines were shown to present solubility properties closer to the real bases than the commonly used methyl and ethyl derivatives, yielding bi-layered structures in the solid state. The study of their coordination capabilities, mainly with Ag(I) and Hg(II), is presented in order to prove their reactivity. A series of coordination complexes, namely, [Hg(N(1)-hexyl-5-fluorouracilate)2]4·6H2O (1), (Ag(+))·[Ag(N(1)-hexyl-5-fluorouracilate)2](-) (2), [Ag(NO3)(N(1)-hexyluracil-κO(4))4] (3), [ZnBr2(N(1)-hexylcytosine)2] (4), [CdBr2(N(1)-hexylcytosine)2] (5), [HgBr2(N(1)-hexylcytosine)2] (6) and [CoBr2(N(1)-hexylcytosine)2] (7), have been synthesized in good yields and X-ray characterized. The presence of the hexyl chains and the fluorine atoms causes the formation of interesting 3D architectures in the solid state. Their structures have been further characterized by infrared spectra (IR) and elemental analyses. In addition, DFT-D3 calculations are used to study interesting noncovalent interactions observed in the solid state, like fluorine-fluorine, fluorine-π and hydrophobic interactions.
Development and evaluation of 5-fluorouracil loaded chitin nanogels for treatment of skin cancer.

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Sabitha, M; Sanoj Rejinold, N; Nair, Amrita; Lakshmanan, Vinoth-Kumar; Nair, Shantikumar V; Jayakumar, R

2013-01-02

This study focuses on development and evaluation of 5-fluorouracil (5-FU) loaded chitin nanogels (FCNGs). It formed good, stable aqueous dispersion with spherical particles in 120-140 nm size range and showed pH responsive swelling and drug release. The FCNGs showed toxicity on melanoma (A375) in a concentration range of 0.4-2.0mg/mL, but less toxicity toward human dermal fibroblast (HDF) cells by MTT assay. Confocal analysis revealed uptake of FCNGs by both cells. From skin permeation experiments, FCNGs showed almost same steady state flux as that of control 5-FU but the retention in the deeper layers of skin was found to be 4-5 times more from FCNGs. Histopathological evaluation revealed loosening of the horny layer of epidermis by interaction of cationically charged chitin, with no observed signs of inflammation and so FCNGs can be a good option for treatment of skin cancers. Copyright © 2012 Elsevier Ltd. All rights reserved.
Bimonthly 24 h infusion of high-dose 5-fluorouracil vs EAP regimen in patients with advanced gastric cancer. A randomized phase II study.

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Popov, I P; Jelić, S B; Krivokapić, Z V; Jezdić, S D; Pesko, P M; Micev, M T; Babić, D R

2008-01-01

To investigate the activity and toxicity of high dose (HD) infusional 5-FU in comparison to EAP regimen as first-line chemotherapy in patients with advanced gastric cancer. Histologically confirmed measurable advanced gastric cancer, age EAP arm: doxorubicin (40 mg/m(2)), etoposide (360 mg/m(2)), and cisplatin (80 mg/m(2)) every 28 d; HD 5-FU arm: 5-FU 2.6 g/m(2) 24 h infusion, biweekly. Sixty patients were randomized. Patient characteristics (arms EAP/HD 5-FU): Median age 57/55 yr, median PS 1/1, LAD (patients) 3/8, M1 (patients) 27/22. Median number of cycles (range): EAP arm 4 (2-8), HD 5-FU arm 2 (1-8). Worst toxicity per cycle (grade 3 and 4 in%): Neutropenia 20/3, thrombocytopenia 9/0, anemia 9/13, diarrhea 3/10, nausea 17/7, vomiting 10/0 for EAP and HD 5-FU arms, respectively. All patients were eligible for response in both arms. Confirmed response rate (95%CI): EAP arm 34% [16-50%]/HD 5-FU arm 10% (0-21%), no change: 46/40%, progression of disease: 20/50, respectively. Overall survival (range): EAP arm A 7 mo [3-27], HD 5-FU arm 6 mo (4-25). Infusional HD 5-FU showed a low incidence of severe toxicity. But given the low efficacy of 5-FU in the dosage we applied in the study, it cannot be recommended as a single treatment for further studies. Assessment of higher dose intensity and/or dose density of 5-FU, with introduction of other active drugs in combination, could be an option for further studies.
Peripheral venous distension elicits a blood pressure raising reflex in young and middle-aged adults.

Science.gov (United States)

Matthews, Evan L; Brian, Michael S; Coyle, Dana E; Edwards, David G; Stocker, Sean D; Wenner, Megan M; Farquhar, William B

2016-06-01

Distension of peripheral veins in humans elicits a pressor and sympathoexcitatory response that is mediated through group III/IV skeletal muscle afferents. There is some evidence that autonomic reflexes mediated by these sensory fibers are blunted with increasing age, yet to date the venous distension reflex has only been studied in young adults. Therefore, we tested the hypothesis that the venous distension reflex would be attenuated in middle-aged compared with young adults. Nineteen young (14 men/5 women, 25 ± 1 yr) and 13 middle-aged (9 men/4 women, 50 ± 2 yr) healthy normotensive participants underwent venous distension via saline infusion through a retrograde intravenous catheter in an antecubital vein during limb occlusion. Beat-by-beat blood pressure, muscle sympathetic nerve activity (MSNA), and model flow-derived cardiac output (Q), and total peripheral resistance (TPR) were recorded throughout the trial. Mean arterial pressure (MAP) increased during the venous distension in both young (baseline 83 ± 2, peak 94 ± 3 mmHg; P blood pressure, MSNA, and TPR were similar between young and middle-aged adults. Additionally, no correlation was found between age and the response to venous distension (all P > 0.05). These findings suggest that peripheral venous distension elicits a pressor and sympathetic response in middle-aged adults similar to the response observed in young adults. Copyright © 2016 the American Physiological Society.
Deep venous thrombosis in the lower extremity: catheter-directed thrombolysis

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Roh, Byung Suk; Kim, En A; Park, Ki Han; Yoon, Kwon Ha; So, Byung Jun; Juhng, Seon Kwan; Won, Jin Jong [School of Medicine, Wonkwang University, Iksan (Korea, Republic of)

2000-09-01

To evaluate the efficacy of catheter-directed thrombolysis in treating symptomatic deep venous thrombosis (DVT) in lower limbs. Twenty-six consecutive patients (16 male and 10 female; mean age, 55 years) with lower extremity DVT underwent thrombolytic therapy. The duration of symptoms was 1-90 (mean, 17) days: 20 days or less in 16 cases (acute DVT) and less than 20 days in ten (chronic DVT). Catheter-directed infusions of urokinase were administered via ipsilateral popliteal veins, and angioplasty or stent placement was performed after the thrombolytic procedure. Oral medication of warfarin continued for six months, and for the evaluation of venous patency, follow-up ultrasonography was performed. The total dose of infused urokinase was 1,750,000-10,000,000 (mean 4,84,000) IU, and the total procedural time was 25-115 (mean, 64) hours. Lysis was complete in 16 cases (62%, all acute DVT), partial in five (19%, chronic DVT), and failed in five (19%, chronic DVT). Eight patients with venous stenosis and two with occlusion were treated by means of angioplasty (n=3D4) or Wallstent placement (n=3D6). Minor bleeding occurred in six cases and major complications in two (one of pulmonary embolism, and one of multiorgan failure). Catheter-directed thrombolysis with urokinase is effective for the treatment of DVT in lower limbs. (author)
Deep venous thrombosis in the lower extremity: catheter-directed thrombolysis

International Nuclear Information System (INIS)

Roh, Byung Suk; Kim, En A; Park, Ki Han; Yoon, Kwon Ha; So, Byung Jun; Juhng, Seon Kwan; Won, Jin Jong

2000-01-01

To evaluate the efficacy of catheter-directed thrombolysis in treating symptomatic deep venous thrombosis (DVT) in lower limbs. Twenty-six consecutive patients (16 male and 10 female; mean age, 55 years) with lower extremity DVT underwent thrombolytic therapy. The duration of symptoms was 1-90 (mean, 17) days: 20 days or less in 16 cases (acute DVT) and less than 20 days in ten (chronic DVT). Catheter-directed infusions of urokinase were administered via ipsilateral popliteal veins, and angioplasty or stent placement was performed after the thrombolytic procedure. Oral medication of warfarin continued for six months, and for the evaluation of venous patency, follow-up ultrasonography was performed. The total dose of infused urokinase was 1,750,000-10,000,000 (mean 4,84,000) IU, and the total procedural time was 25-115 (mean, 64) hours. Lysis was complete in 16 cases (62%, all acute DVT), partial in five (19%, chronic DVT), and failed in five (19%, chronic DVT). Eight patients with venous stenosis and two with occlusion were treated by means of angioplasty (n=3D4) or Wallstent placement (n=3D6). Minor bleeding occurred in six cases and major complications in two (one of pulmonary embolism, and one of multiorgan failure). Catheter-directed thrombolysis with urokinase is effective for the treatment of DVT in lower limbs. (author)
Irinotecan plus folinic acid/continuous 5-fluorouracil as simplified bimonthly FOLFIRI regimen for first-line therapy of metastatic colorectal cancer

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Höhler Thomas

2004-07-01

Full Text Available Abstract Background Combination therapy of irinotecan, folinic acid (FA and 5-fluorouracil (5-FU has been proven to be highly effective for the treatment of metastatic colorectal cancer. However, in light of safety and efficacy concerns, the best combination regimen for first-line therapy still needs to be defined. The current study reports on the bimonthly FOLFIRI protocol consisting of irinotecan with continuous FA/5-FU in five German outpatient clinics, with emphasis on the safety and efficiency, quality of life, management of delayed diarrhea, and secondary resection of regressive liver metastases. Methods A total of 35 patients were treated for metastatic colorectal cancer. All patients received first-line treatment according to the FOLFIRI regimen, consisting of irinotecan (180 mg/m2, L-FA (200 mg/m2 and 5-FU bolus (400 mg/m2 on day 1, followed by a 46-h continuous infusion 5-FU (2400 mg/m2. One cycle contained three fortnightly administrations. Staging was performed after 2 cycles. Dosage was reduced at any time if toxicity NCI CTC grade III/IV was observed. Chemotherapy was administered only to diarrhea-free patients. Results The FOLFIRI regimen was generally well tolerated. It was postponed for one-week in 51 of 415 applications (12.3%. Dose reduction was necessary in ten patients. Grade III/IV toxicity was rare, with diarrhea (14%, nausea/vomiting (12%, leucopenia (3%, neutropenia (9% and mucositis (3%. The overall response rate was 31% (4 CR and 7 PR, with disease control in 74%. After primary chemotherapy, resection of liver metastases was achieved in three patients. In one patient, the CR was confirmed pathologically. Median progression-free and overall survival were seven and 17 months, respectively. Conclusions The FOLFIRI regimen proved to be safe and efficient. Outpatient treatment was well tolerated. Since downstaging was possible, combinations of irinotecan and continuous FA/5-FU should further be investigated in neoadjuvant
Phase II trial of interleukin 2, interferon alpha, and 5-fluorouracil in metastatic renal cell cancer: a cytokine working group study.

Science.gov (United States)

Dutcher, J P; Logan, T; Gordon, M; Sosman, J; Weiss, G; Margolin, K; Plasse, T; Mier, J; Lotze, M; Clark, J; Atkins, M

2000-09-01

The purpose of this study was to evaluate the potential efficacy of alternating two outpatient regimens for the treatment of metastatic renal cell cancer. These regimens consisted of 4 weeks of recombinant interleukin 2 (rIL-2) plus IFN-alpha2B followed by 4 weeks of 5-fluorouracil plus IFN-alpha2B. Fifty patients meeting eligibility criteria of previous Cytokine Working Group studies were treated on an outpatient basis. Patients received s.c. rIL-2 (Proleukin; Chiron, Emeryville, CA) during weeks 1-4 of the 8-week regimen. During weeks 1 and 4, the dosage for rIL-2 was 10 MIU/m2 twice daily on days 3-5, and the dosage for IFN-alpha2B (Intron; Schering Plough, Kenilworth, NJ) was 6 MIU/m2 on day 1. During weeks 2 and 3, the dosage for rIL-2 was 5 MIU/m2 on days 1, 3, and 5, and the dosage for IFN-alpha2B was 6 MIU/m2 on days 1, 3, 5. During weeks 5-8, 5-fluorouracil (750 mg/m2) was administered once weekly by i.v. infusion, and IFN-alpha2B (9 MIU/mZ) was administered as a s.c. injection three times weekly. Throughout the treatment, an assessment of quality of life was made and a symptom-distress scale was evaluated. There were two patients with complete responses (CRs) and seven with partial responses (PRs) for an objective response rate of 18% (95% confidence interval, 10-25). The median response duration was 8 months (range, 3-51+ months). The CRs lasted 5 months and 51+ months and the PRs ranged from 3+ to 18 months. After completing at least one course of treatment, eight patients (three with PR, one with minor response, four with stable disease) became CRs after surgery for remaining metastatic disease. Six remain alive at 43+ to 53+ months, and 5 remain disease-free since surgery. The median survival of the study group is 17.5 months, with a maximal follow-up of 53+ months. The range in survival is 1-53+ months. Toxicity was primarily constitutional. and treatment modifications were designed to maintain toxicity at grade 2/3. The most common toxicities during

Evaluation of the impact of tumor HPV status on outcome in patients with locally advanced unresectable head and neck squamous cell carcinoma (HNSCC) receiving cisplatin, 5-fluorouracil with or without docetaxel: a subset analysis of EORTC 24971 study

NARCIS (Netherlands)

Psyrri, A.; Fortpied, C.; Koutsodontis, G.; Avgeris, M.; Kroupis, C.; Goutas, N.; Menis, J.; Herman, L.; Giurgea, L.; Remenar, E.; Degardin, M.; Pateras, I.S.; Langendijk, J.A.; Herpen, C.M.L. van; Awada, A.; Germa-Lluch, J.R.; Kienzer, H.R.; Licitra, L.; Vermorken, J.B.

2017-01-01

Background: EORTC 24971 was a phase III trial demonstrating superiority of induction regimen TPF (docetaxel, cisplatin, 5-fluorouracil) over PF (cisplatin/5-fluorouracil), in terms of progression-free (PFS) and overall survival (OS) in locoregionally advanced unresectable head and neck squamous cell
Effect of corticosteroids on phlebitis induced by intravenous infusion of antineoplastic agents in rabbits.

Science.gov (United States)

Kohno, Emiko; Murase, Saori; Matsuyama, Kenji; Okamura, Noboru

2009-08-06

Phlebitis caused by intravenous infusion of antineoplastic agents is one of the critical problems when anticancer therapy is prolonged. We have already reported that both rapid infusion and dilution of the injection solution were effective methods for reducing phlebitis caused by vinorelbine (VNR) in rabbits. The aim of this study was to explore other practical methods for preventing phlebitis caused by VNR and doxorubicin (DXR) in a rabbit model. VNR is often used with cisplatin, and dexamethasone (DEX) has been co-administered for prevention of cisplatin-induced nausea. DXR is used with prednisolone (PSL) in the CHOP regimen for the treatment of non-Hodgkin's lymphoma. Therefore, the present study investigated the prevention of phlebitis due to VNR with DEX and that due to DXR with PSL. VNR and DXR were diluted with normal saline to prepare test solutions at concentrations of 0.6 mg/mL and 1.4 mg/mL, respectively. Each test solution was infused into the auricular veins of rabbits. Two days after VNR infusion and three days after DXR infusion, the veins were evaluated histopathologically. The effect of DEX on VNR-induced phlebitis was evaluated by infusion of DEX before or after VNR. The effect of PSL on DXR-induced phlebitis was similarly evaluated by co-infusion of PSL. The histopathological features of phlebitis caused by the antineoplastic agents differed between VNR and DXR: VNR did not cause the loss of venous endothelial cells, but caused inflammatory cell infiltration, edema, and epidermal degeneration. In contrast, DXR caused the loss of venous endothelial cells and chrondrocyte necrosis. Pre-treatment and post-treatment with DEX significantly decreased VNR-induced phlebitis compared with the control group and pre-treatment was particularly effective. Co-infusion of PSL also significantly decreased phlebitis caused by DXR, but its effect was less marked. The present findings suggested that pre-treatment with DEX may be a useful method for preventing
[Incidence of phlebitis due to peripherally inserted venous catheters: impact of a catheter management protocol].

Science.gov (United States)

Ferrete-Morales, C; Vázquez-Pérez, M A; Sánchez-Berna, M; Gilabert-Cerro, I; Corzo-Delgado, J E; Pineda-Vergara, J A; Vergara-López, S; Gómez-Mateos, J

2010-01-01

To assess the impact on the incidence of PPIVC by implementing a catheter management protocol and to determine risk factors for PPIVC development in hospitalized patients. A total of 3978 episodes of venous catheterization were prospectively included from September 2002 to December 2007. A catheter management protocol was implemented during this period of time. The incidence and variables associated to the occurrence of PPIVC were determined. The incidence of PPIVC from 2002 to 2007 was 4.8%, 4.3%, 3.6%, 2.5%, 1.3% and 1.8% (phistory of phlebitis was the only factor independently associated to phlebitis due to peripherally inserted central venous catheters (AOR 3.24; CI at 95% CI= 1.05-9.98, p=0.04). A catheter management protocol decreases the incidence of PPIVC in hospitalized patients. The risk of PPIVC increases for peripherally inserted central venous catheters when the patients have a history of phlebitis and for peripheral venous catheters when amiodarone or cefotaxime are infused. Catheterization of peripheral veins performed during morning shifts is associated with a lower incidence of PPIVC when compared with night shift catheterizations.
Combination of Drugs Elevating Extracellular Adenosine with Granulocyte Colony-Stimulating Factor Promotes Granulopoietic Recovery in the Murine Bone Marrow after 5-Fluorouracil Treatment

Czech Academy of Sciences Publication Activity Database

Hofer, Michal; Pospíšil, Milan; Weiterová, Lenka; Znojil, V.; Vácha, J.; Holá, Jiřina; Vacek, Antonín; Pipalová, Iva

2001-01-01

Roč. 50, č. 5 (2001), s. 521-524 ISSN 0862-8408 R&D Projects: GA ČR GA306/99/0027; GA AV ČR IBS5004009 Institutional research plan: CEZ:AV0Z5004920 Keywords : 5-fluorouracil * granulopoiesis * extracellular adenosine Subject RIV: BO - Biophysics Impact factor : 1.027, year: 2001
Combined Effects of Muricid Extract and 5-Fluorouracil on Intestinal Toxicity in Rats

Directory of Open Access Journals (Sweden)

Roger Yazbeck

2015-01-01

Full Text Available Chemotherapy drugs, such as 5-fluorouracil (5FU, are the standard approach for cancer and are associated with several peripheral toxicities. We previously demonstrated that Muricidae marine molluscs exhibit chemopreventive properties. This study investigated the combined effect of muricid extract derived from Dicathais orbita, with 5FU, on intestinal toxicity in rats. Groups of rats were orally gavaged water, muricid extract, or sunflower oil, with or without 5FU (150 mg/kg. Metabolic data was collected daily and small intestinal brush border enzyme activity was measured by sucrose breath test (SBT. Blood was collected by cardiac puncture for whole blood analysis. Intestinal biopsies were taken for histopathology. Neutrophil activity was measured by myeloperoxidase activity. No additional toxicity effects were observed in rats receiving the combination of 5FU and muricid extract compared to 5FU alone, as indicated by SBT, histopathology, and myeloperoxidase activity. Intestinal integrity was protected from 5FU-induced damage in the sunflower oil vehicle group, compared to controls, as measured by SBT, villus height, and crypt depth. We concluded that combination of muricid extract and 5FU did not confer any additional intestinal toxicity, further supporting its potential as a chemopreventive food product. In this model system, sunflower oil partially protected against 5FU-induced intestinal toxicity.
Pharmacokinetic properties and antitumor efficacy of the 5-fluorouracil loaded PEG-hydrogel

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Kim Bokyung

2010-05-01

Full Text Available Abstract Background We have studied the in vitro and in vivo utility of polyethylene glycol (PEG-hydrogels for the development of an anticancer drug 5-fluorouracil (5-FU delivery system. Methods A 5-FU-loaded PEG-hydrogel was implanted subcutaneously to evaluate the drug retention time and the anticancer effect. For the pharmacokinetic study, two groups of male rats were administered either an aqueous solution of 5-FU (control group/or a 5-FU-loaded PEG-hydrogel (treated group at a dose of 100 mg/kg. For the pharmacodynamic study, a human non-small-cell lung adenocarcinoma (NSCLC cell line, A549 was inoculated to male nude mice with a cell density of 3 × 106. Once tumors start growing, the mice were injected with 5-FU/or 5-FU-loaded PEG-hydrogel once a week for 4 weeks. The growth of the tumors was monitored by measuring the tumor volume and calculating the tumor inhibition rate (IR over the duration of the study. Results In the pharmacokinetic study, the 5-FU-loaded PEG-hydrogel gave a mean residence time (MRT of 8.0 h and the elimination half-life of 0.9 h; these values were 14- and 6-fold, respectively, longer than those for the free solution of 5-FU (p Conclusion We suggest that 5-FU-loaded PEG-hydrogels could provide a useful tool for the development of an anticancer drug delivery system.
A theoretical alternative intraosseous infusion site in severely hypovolemic children

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Nkhensani Mogale

2015-07-01

Full Text Available Background: Studies have shown that the venous system tends to collapse during hypovolemic shock. The use of the bone marrow space for infusions is an effective alternative, with the tibial insertion site being the norm. Objectives: This study was conducted to determine a quick intraosseous infusion method that could be an alternative to the tibial route in neonates during emergency situations. Method: A sample of 30 neonatal cadavers was dissected to explore a possible alternative to the tibial insertion site. The needle was inserted in the superolateral aspect of the humerus. The needle infusion site was then dissected to determine possible muscular and neurovascular damage that might occur during the administration of this procedure, with the greatest concern being the posterior circumflex humeral artery and axillary nerve exiting the quadrangular space. The distance of the needle insertion site was measured in relation to the soft tissue aswell as to bony landmarks. Results: The calculated 95% confidence interval shows that the needle can be safely inserted into the intraosseous tissue at the greater tubercle of the humerus 9.5 mm – 11.1 mm from the acromion. This is about a little finger’s width from the acromioclavicular joint. Conclusion: Anatomically, the described site is suggested to offer a safe alternative access point for emergency infusion in severely hypovolemic newborns and infants, without the risk of damage to any anatomical structures.
Individual fluorouracil dose adjustment in FOLFOX based on pharmacokinetic follow-up compared with conventional body-area-surface dosing: a phase II, proof-of-concept study.

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Capitain, Olivier; Asevoaia, Andreaa; Boisdron-Celle, Michele; Poirier, Anne-Lise; Morel, Alain; Gamelin, Erick

2012-12-01

To compare the efficacy and safety of pharmacokinetically (PK) guided fluorouracil (5-FU) dose adjustment vs. standard body-surface-area (BSA) dosing in a FOLFOX (folinic acid, fluorouracil, oxaliplatin) regimen in metastatic colorectal cancer (mCRC). A total of 118 patients with mCRC were administered individually determined PK-adjusted 5-FU in first-line FOLFOX chemotherapy. The comparison arm consisted of 39 patients, and these patients were also treated with FOLFOX with 5-FU by BSA. For the PK-adjusted arm 5-FU was monitored during infusion, and the dose for the next cycle was based on a dose-adjustment chart to achieve a therapeutic area under curve range (5-FU(ODPM Protocol)). The objective response rate was 69.7% in the PK-adjusted arm, and median overall survival and median progression-free survival were 28 and 16 months, respectively. In the traditional patients who received BSA dosage, objective response rate was 46%, and overall survival and progression-free survival were 22 and 10 months, respectively. Grade 3/4 toxicity was 1.7% for diarrhea, 0.8% for mucositis, and 18% for neutropenia in the dose-monitored group; they were 12%, 15%, and 25%, respectively, in the BSA group. Efficacy and tolerability of PK-adjusted FOLFOX dosing was much higher than traditional BSA dosing in agreement with previous reports for 5-FU monotherapy PK-adjusted dosing. Analysis of these results suggests that PK-guided 5-FU therapy offers added value to combination therapy for mCRC. Copyright © 2012 Elsevier Inc. All rights reserved.
Phase II study of tolerance and efficacy of hyperfractionated radiotherapy and 5-fluorouracil, cisplatin, and paclitaxel (Taxol) in stage III and IV inoperable and/or unresectable head-and-neck squamous cell carcinoma: A-2 protocol

International Nuclear Information System (INIS)

Abitbol, Andre; Abdel-Wahab, May; Lewin, Alan; Troner, Michael; Rodrigues, Maria-Amelia; Hamilton-Nelson, Kara L.; Markoe, Arnold

2002-01-01

Purpose: To determine the toxicity and efficacy of concurrent 5-fluorouracil (5-FU), cisplatin, and paclitaxel (Taxol) and hyperfractionated radiotherapy in locally advanced squamous cell carcinoma of the head and neck. Methods and Materials: Twenty-seven patients were entered into this Phase II trial. Eligible patients had Stage III or IV head-and-neck squamous cell carcinoma arising from the oral cavity, hypopharynx, oropharynx, nasopharynx, or larynx. The plan of treatment consisted of hyperfractionated radiotherapy (74.4 Gy at twice daily fractions of 1.2 Gy). Chemotherapy was given on Weeks 1, 5, and 8 as follows: 5-FU at 750 mg/m 2 as a constant infusion for 24 h for 3 days; cisplatin at 50 mg/m 2 in 250-500 mL D5 0.5 NS or NS infusion during 2-4 h, and paclitaxel at 70 mg/m 2 infused in 500 mL NS during 3 h. Results: The overall survival rate of the entire group was 81.5%, 66.7%, and 63% at 1, 2, and 3 years, respectively. The median follow-up was 40.2 months (range 30-62). Of the 27 patients, 19 (70%) had a complete response and an overall survival rate of 100% at 1 year and 94% at 2 and 3 years. The disease-free survival rate of the latter group was 95% at 1 year and 84% at 2 and 3 years. Of the 27 patients, 18 (67%) maintained the complete response until the last follow-up visit or death. Percutaneous endoscopic gastrostomy dependency occurred for a median of 7.1 months. Grade 3 and 4 mucositis occurred in 20 and 3 patients, respectively. Six patients were hospitalized for leukopenic fever. Late toxicities included L'Hermitte syndrome (n=3), osteoradionecrosis (n=1), hypothyroidism (n=4), paresthesias (n=1), aspiration pneumonia (n=3), and esophageal strictures (8 patients underwent dilation). Conclusion: Combining hyperfractionated radiotherapy concurrently with 5-FU, cisplatin, and paclitaxel results in acceptable efficacy and toxicity. However, although a locoregional control benefit is suggested by the preliminary results of this trial, it needs to be
Long-term results of the maxillary sinus carcinoma with irradiation and intraarterial infusion of 5-FU

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Sakaguchi, Masanori; Netsu, Kiminori (Shinshu Univ., Matsumoto, Nagano (Japan). Faculty of Medicine); Kawarada, Kazuo; Yachiyama, Hitoshi

1990-08-01

Therapeutic results of 33 primary cases of maxillary sinus carcinoma treated with irradiation and intraarterial infusion of 5-FU between 1972 and 1984 were analyzed. The 5-year crude survival rate for the group with stage T2 carcinoma (n=10) was 50.0%, and for those with T3 (n=15) and T4 (n=8) it was 46.7% and 25.0%, respectively. The overall 5-year crude survival rate was 42.4%. Eight patients who did not undergo maxillectomy survived for 5 years after irradiation and intraarterial infusion. Recurrence of the tumor after the irradiation and intraarterial infusion occurred in 63.6%, and was frequently observed at the ethmoidal region and the orbita. In the areas in which the tumor extended to regions such as the ethmoid sinus and orbita, which are nourished by arteries other than the maxillary artery, conventional intraarterial infusion was ineffective for complete tumor eradication. Therefore, in most of the patients with advanced maxillary sinus carcinoma, partial or total maxillectomy following combined therapy of intraarterial infusion and irradiation is necessary to improve a prognosis. (author).
Long-term results of the maxillary sinus carcinoma with irradiation and intraarterial infusion of 5-FU

International Nuclear Information System (INIS)

Sakaguchi, Masanori; Netsu, Kiminori; Kawarada, Kazuo; Yachiyama, Hitoshi.

1990-01-01

Therapeutic results of 33 primary cases of maxillary sinus carcinoma treated with irradiation and intraarterial infusion of 5-FU between 1972 and 1984 were analyzed. The 5-year crude survival rate for the group with stage T2 carcinoma (n=10) was 50.0%, and for those with T3 (n=15) and T4 (n=8) it was 46.7% and 25.0%, respectively. The overall 5-year crude survival rate was 42.4%. Eight patients who did not undergo maxillectomy survived for 5 years after irradiation and intraarterial infusion. Recurrence of the tumor after the irradiation and intraarterial infusion occurred in 63.6%, and was frequently observed at the ethmoidal region and the orbita. In the areas in which the tumor extended to regions such as the ethmoid sinus and orbita, which are nourished by arteries other than the maxillary artery, conventional intraarterial infusion was ineffective for complete tumor eradication. Therefore, in most of the patients with advanced maxillary sinus carcinoma, partial or total maxillectomy following combined therapy of intraarterial infusion and irradiation is necessary to improve a prognosis. (author)
Optimization of induction of mild therapeutic hypothermia with cold saline infusion: A laboratory experiment

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Jure Fluher

2015-11-01

Full Text Available Cold fluid infusions can be used to induce mild therapeutic hypothermia after cardiac arrest. Fluid temperature higher than 4°C can increase the volume of fluid needed, prolong the induction phase of hypothermia and thus contribute to complications. We performed a laboratory experiment with two objectives. The first objective was to analyze the effect of wrapping fluid bags in ice packs on the increase of fluid temperature with time in bags exposed to ambient conditions. The second objective was to quantify the effect of insulating venous tubing and adjusting flow rate on fluid temperature increase from bag to the level of an intravenous cannula during a simulated infusion. The temperature of fluid in bags wrapped in ice packs was significantly lower compared to controls at all time points during the 120 minutes observation. The temperature increase from the bag to the level of intravenous cannula was significantly lower for insulated tubing at all infusion rates (median temperature differences between bag and intravenous cannula were: 8.9, 4.8, 4.0, and 3.1°C, for non-insulated and 5.9, 3.05, 1.1, and 0.3°C, for insulated tubing, at infusion rates 10, 30, 60, and 100 mL/minute, respectively. The results from this study could potentially be used to decrease the volume of fluid infused when inducing mild hypothermia with an infusion of cold fluids.
Post-operative chemosensitized radiation with modulated 5-fluorouracil (5-FU) following resection of adenocarcinoma of the esophagus and esophagogastric (EG) junction

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Kurtzman, S.M.; Whittington, R.; Vaughn, D.; Rosato, E.F.; Haller, D.G.

1995-01-01

Purpose: To evaluate the survival and toxicity of post-operative chemosensitized radiation with modulated 5-FU chemotherapy in patients with resected adenocarcinomas of the esophagus and EG junction. Materials and Methods: One hundred and ninety-two patients with localized adenocarcinomas of the esophagus and EG junction were treated with single or combined modality therapy. The results in the first 165 patients treated between 1972 and 1989 demonstrated that survival was improved with chemosensitized radiation therapy following surgical resection. In the final group of patients treated between 1985 and 1989 a 96 hour inpatient 5-FU infusion was used to provide chemosensitization in those patients. Twenty-seven patients have been treated between January 1990 and December 1994 using a new outpatient regimen with modulated 5-FU chemotherapy for chemosensitization. Radiation and chemotherapy commenced within 6 weeks of surgery. The dose of radiation was 54 Gy in patients with no residual tumor, and 59.4 to 63.0 Gy in patients with positive margins or residual tumor. Modulated 5-FU using bolus 5-FU with Leukovorin +/-α-interferon (α-IFN) was given during the first and fifth week of radiation. Results: Median follow-up of surviving patients treated with modulated 5-FU is 15 months (max - 46 mos). Survival is 71% at 1 year, 45% at 2 years and 39% at 3 years. This compares favorably with the survival with 5-FU infusion, 75% - 1 year, 35% - 2 year, and 10% - 3 year. The toxicity of modulated 5-FU was no different from that observed in patients treated with 5-FU infusion. Three patients treated with modulated 5-FU leukovorin and α-IFN required intravenous hydration, and two patients experienced grade 3 leukopenia. There were two radiation related events in these patients, one case of radiation pneumonitis and one patient with pericarditis. Conclusions: Based on this experience, aggressive therapy of adenocarcinomas of the esophagus and EG junction with surgery and
A randomised controlled trial of oxytocin 5IU and placebo infusion versus oxytocin 5IU and 30IU infusion for the control of blood loss at elective caesarean section--pilot study. ISRCTN 40302163.

LENUS (Irish Health Repository)

Murphy, Deirdre J

2012-02-01

OBJECTIVE: To compare the blood loss at elective lower segment caesarean section with administration of oxytocin 5IU bolus versus oxytocin 5IU bolus and oxytocin 30IU infusion and to establish whether a large multi-centre trial is feasible. STUDY DESIGN: Women booked for an elective caesarean section were recruited to a pilot randomised controlled trial and randomised to either oxytocin 5IU bolus and placebo infusion or oxytocin 5IU bolus and oxytocin 30IU infusion. We wished to establish whether the study design was feasible and acceptable and to establish sample size estimates for a definitive multi-centre trial. The outcome measures were total estimated blood loss at caesarean section and in the immediate postpartum period and the need for an additional uterotonic agent. RESULTS: A total of 115 women were randomised and 110 were suitable for analysis (5 protocol violations). Despite strict exclusion criteria 84% of the target population were considered eligible for study participation and of those approached only 15% declined to participate and 11% delivered prior to the planned date. The total mean estimated blood loss was lower in the oxytocin infusion arm compared to placebo (567 ml versus 624 ml) and fewer women had a major haemorrhage (>1000 ml, 14% versus 17%) or required an additional uterotonic agent (5% versus 11%). A sample size of 1500 in each arm would be required to demonstrate a 3% absolute reduction in major haemorrhage (from baseline 10%) with >80% power. CONCLUSION: An additional oxytocin infusion at elective caesarean section may reduce blood loss and warrants evaluation in a large multi-centre trial.
Biodistribution and radiation dosimetry of [18F]-5-fluorouracil

International Nuclear Information System (INIS)

Hino-Shishikura, Ayako; Suzuki, Akiko; Minamimoto, Ryogo; Shizukuishi, Kazuya; Oka, Takashi; Tateishi, Ukihide; Sugae, Sadatoshi; Ichikawa, Yasushi; Horiuchi, Choichi; Inoue, Tomio

2013-01-01

Purpose: To estimate the radiation dose and biodistribution of 18 F-5-fluorouracil ([ 18 F]-5-FU) from positron emission tomography/computed tomography (PET/CT) data, and to extrapolate mouse data to human data in order to evaluate cross-species consistency. Methods: Fifteen cancer patients (head and neck cancer (n=11), colon cancer (n=4)) were enrolled. Sequential PET/CT images were acquired for 2 h after intravenous administration of [ 18 F]-5-FU, and the percent of the injected dose delivered to each organ was derived. For comparison, [ 18 F]-5-FU was administered to female BALB/cAJcl-nu/nu nude mice (n=19), and the percent of the injected dose delivered to mouse organs was extrapolated to the human model. Absorbed radiation dose was calculated using OLINDA/EXM 1.0 software. Results: In human subjects, high [ 18 F]-5-FU uptake was seen in the liver, gallbladder and kidneys. The absorbed dose was highest in the gallbladder wall. In mice, the biodistribution of [ 18 F]-5-FU corresponded to that of humans. Estimated absorbed radiation doses for all organs were moderately correlated, and doses to organs (except the gallbladder and urinary bladder) were significantly correlated between mice and humans. The mean effective [ 18 F]-5-FU dose was higher in humans (0.0124 mSv/MBq) than in mice (0.0058 mSv/MBq). Conclusion: Biodistribution and radiation dosimetry of [ 18 F]-5-FU were compared between humans and mice: biodistribution in mice and humans was similar. Data from mice underestimated the effective dose in humans, suggesting that clinical measurements are needed for more detailed dose estimation in order to ensure radiation safety. The observed effective doses suggest the feasibility of [ 18 F]-5-FU PET/CT for human studies. - Highlights: ► The radiation dose and biodistribution of [ 18 F]-5-FU were estimated from mouse and human data. ► The biodistribution of [ 18 F]-5-FU of mouse and human was corresponded. ► Estimated absorbed radiation doses for organs
5-HT causes splanchnic venodilation.

Science.gov (United States)

Seitz, Bridget M; Orer, Hakan S; Krieger-Burke, Teresa; Darios, Emma S; Thompson, Janice M; Fink, Gregory D; Watts, Stephanie W

2017-09-01

Serotonin [5-hydroxytryptamine (5-HT)] causes relaxation of the isolated superior mesenteric vein, a splanchnic blood vessel, through activation of the 5-HT 7 receptor. As part of studies designed to identify the mechanism(s) through which chronic (≥24 h) infusion of 5-HT lowers blood pressure, we tested the hypothesis that 5-HT causes in vitro and in vivo splanchnic venodilation that is 5-HT 7 receptor dependent. In tissue baths for measurement of isometric contraction, the portal vein and abdominal inferior vena cava relaxed to 5-HT and the 5-HT 1/7 receptor agonist 5-carboxamidotryptamine; relaxation was abolished by the 5-HT 7 receptor antagonist SB-269970. Western blot analyses showed that the abdominal inferior vena cava and portal vein express 5-HT 7 receptor protein. In contrast, the thoracic vena cava, outside the splanchnic circulation, did not relax to serotonergic agonists and exhibited minimal expression of the 5-HT 7 receptor. Male Sprague-Dawley rats with chronically implanted radiotelemetry transmitters underwent repeated ultrasound imaging of abdominal vessels. After baseline imaging, minipumps containing vehicle (saline) or 5-HT (25 μg·kg -1 ·min -1 ) were implanted. Twenty-four hours later, venous diameters were increased in rats with 5-HT-infusion (percent increase from baseline: superior mesenteric vein, 17.5 ± 1.9; portal vein, 17.7 ± 1.8; and abdominal inferior vena cava, 46.9 ± 8.0) while arterial pressure was decreased (~13 mmHg). Measures returned to baseline after infusion termination. In a separate group of animals, treatment with SB-269970 (3 mg/kg iv) prevented the splanchnic venodilation and fall in blood pressure during 24 h of 5-HT infusion. Thus, 5-HT causes 5-HT 7 receptor-dependent splanchnic venous dilation associated with a fall in blood pressure. NEW & NOTEWORTHY This research is noteworthy because it combines and links, through the 5-HT 7 receptor, an in vitro observation (venorelaxation) with in vivo events
Eudragit-coated dextran microspheres of 5-fluorouracil for site-specific delivery to colon.

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Rai, Gopal; Yadav, Awesh K; Jain, Narendra K; Agrawal, Govind P

2016-01-01

Objective of the present investigation was to prepare and evaluate the potential of enteric coated dextran microspheres for colon targeting of 5-fluorouracil (5-FU). Dextran microspheres were prepared by emulsification-crosslinking method and the formulation variables studied included different molecular weights of dextran, drug:polymer ratio, volume of crosslinking agent, stirring speed and time. Enteric coating (Eudragit S-100) of dextran microspheres was performed by oil-in-oil solvent evaporation method using different coat:core ratios (4:1 or 8:1). Uncoated and coated dextran microspheres were characterized by particle size, surface morphology, entrapment efficiency, DSC, in vitro drug release in the presence of dextranase and 2% rat cecal contents. The release study of 5-FU from coated dextran microspheres was pH dependent. No release was observed at acidic pH; however, the drug was released quickly where Eudragit starts solublizing there was continuous release of drug from the microspheres. Organ distribution study was suggested that coated dextran microspheres retard the release of drug in gastric and intestinal pH environment and released of drug from microspheres in colon due to the degradation of dextran by colonic enzymes.
Development of a middle cerebral artery occlusion model in the nonhuman primate and a safety study of i.v. infusion of human mesenchymal stem cells.

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Masanori Sasaki

Full Text Available Most experimental stroke research is carried out in rodents, but given differences between rodents and human, nonhuman primate (NHP models may provide a valuable tool to study therapeutic interventions. The authors developed a surgical method for transient occlusion of the M1 branch of middle cerebral artery (MCA in the African green monkey to evaluate safety aspects of intravenous infusion of mesenchymal stem cells (hMSCs derived from human bone marrow.The left Sylvian fissure was exposed by a small fronto-temporal craniotomy. The M1 branch of the MCA was exposed by microsurgical dissection and clipped for 2 to 4 hours. Neurological examinations and magnetic resonance imaging (MRI were carried out at regular post-operative course. hMSCs were infused 1 hour after reperfusion (clip release in the 3-hour occlusion model.During M1 occlusion, two patterns of changes were observed in the lateral hemisphere surface. One pattern (Pattern 1 was darkening of venous blood, small vessel collapse, and blood pooling with no venous return in cortical veins. Animals with these three features had severe and lasting hemiplegia and MRI demonstrated extensive MCA territory infarction. Animals in the second pattern (Pattern 2 displayed darkening of venous blood, small vessel collapse, and reduced but incompletely occluded venous flow and the functional deficit was much less severe and MRI indicated smaller infarction areas in brain. The severe group (Pattern 1 likely had less extensive collateral circulation than the less severe group (Pattern 2 where venous pooling of blood was not observed. The hMSC infused animals showed a trend for greater functional improvement that was not statistically significant in the acute phase and no additive negative effects.These results indicate inter-animal variability of collateral circulation after complete M1 occlusion and that hMSC infusion is safe in the developed NHP stroke model.
Extravasation of parenteral alimentation fluid into the renal pelvis--a complication of central venous catheter in a neonate.

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Nadroo, A M; al-Sowailem, A M

2001-01-01

Many complications of central venous catheters, which include perforation of the vessel walls and extravasation of the infusate into pericardial, pleural, and peritoneal cavities, have been reported. We report an infant with a central venous catheter in inferior vena cava who experienced extravasation of parenteral alimentation fluid into the right renal pelvis secondary to perforation of the renal vein. To our knowledge, this rare complication has not been reported earlier.
Postoperative subconjunctival bevacizumab injection as an adjunct to 5-fluorouracil in the management of scarring after trabeculectomy

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Freiberg FJ

2013-06-01

Full Text Available Florentina Joyce Freiberg,1 Juliane Matlach,1 Franz Grehn,1 Sabine Karl,2 Thomas Klink1 1Department of Ophthalmology, Julius Maximilian University, Wuerzburg, Germany; 2Institute of Mathematics, University of Wuerzburg, Wuerzburg, Germany Purpose: Scarring after glaucoma filtering surgery remains the most frequent cause for bleb failure. The aim of this study was to assess if the postoperative injection of bevacizumab reduces the number of postoperative subconjunctival 5-fluorouracil (5-FU injections. Further, the effect of bevacizumab as an adjunct to 5-FU on the intraocular pressure (IOP outcome, bleb morphology, postoperative medications, and complications was evaluated. Methods: Glaucoma patients (N = 61 who underwent trabeculectomy with mitomycin C were analyzed retrospectively (follow-up period of 25 ± 19 months. Surgery was performed exclusively by one experienced glaucoma specialist using a standardized technique. Patients in group 1 received subconjunctival applications of 5-FU postoperatively. Patients in group 2 received 5-FU and subconjunctival injection of bevacizumab. Results: Group 1 had 6.4 ± 3.3 (0–15 (mean ± standard deviation and range, respectively 5-FU injections. Group 2 had 4.0 ± 2.8 (0–12 (mean ± standard deviation and range, respectively 5-FU injections. The added injection of bevacizumab significantly reduced the mean number of 5-FU injections by 2.4 ± 3.08 (P ≤ 0.005. There was no significantly lower IOP in group 2 when compared to group 1. A significant reduction in vascularization and in cork screw vessels could be found in both groups (P < 0.0001, 7 days to last 5-FU, yet there was no difference between the two groups at the last follow-up. Postoperative complications were significantly higher for both groups when more 5-FU injections were applied. (P = 0.008. No significant difference in best corrected visual acuity (P = 0.852 and visual field testing (P = 0.610 between preoperative to last follow

Clinical study of suppository delivery of 5-fluorouracil and pathological effects on metastatic lymph nodes caused by preoperative combined treatment with radiation, intraluminal hyperthermia and 5-fluorouracil suppository in rectal cancer

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Tamura, Takaaki [Kyoto Prefectural Univ. of Medicine (Japan)

1997-11-01

Preoperative combined treatment with radiation, intraluminal hyperthermia, and 5-fluorouracil (5-FU) suppository has been reported effective in shrinking locally advanced rectal cancers and facilitating subsequent surgery. Suppository and intravenous 5-FU administration were compared with respect to tissue concentrations in rectal cancer cases. Just before the operation patients received 100 mg of 5-FU via suppository or intravenously. Portal and systemic blood, tumor tissue, normal mucosa and muscle layer separately at 5, 10, 15 cm in the oral direction from the tumor and the pararectal lymph node were harvested for high-performance liquid chromatography determination of 5-FU concentrations. Rectal 5-FU concentrations were significantly higher in the suppository cases compared with the intravenously administrated ones. Suppository distributed more 5-FU at pararectal lymph nodes than intravenous injection. This fact revealed 5-FU suppositories to be a useful drug delivery system for rectal cancer. The pathological effects on metastatic lymph nodes caused by combined treatment were evaluated in 22 cases. Normal lymph nodes showed congestion only. Fibrotic and necrotic changes were characteristic of damaged metastatic areas. In 6 cases (27.3%), no metastatic cells were detected on fibrotically changed areas. The down staging of the lymph node metastatic factor was carried out by preoperative combined treatment. High concentrations of 5-FU at mucosa could suggest the usefulness of 5-FU suppository administration just before operation for prevention of suture-line implantation. (author)
Clinical study of suppository delivery of 5-fluorouracil and pathological effects on metastatic lymph nodes caused by preoperative combined treatment with radiation, intraluminal hyperthermia and 5-fluorouracil suppository in rectal cancer

International Nuclear Information System (INIS)

Tamura, Takaaki

1997-01-01

Preoperative combined treatment with radiation, intraluminal hyperthermia, and 5-fluorouracil (5-FU) suppository has been reported effective in shrinking locally advanced rectal cancers and facilitating subsequent surgery. Suppository and intravenous 5-FU administration were compared with respect to tissue concentrations in rectal cancer cases. Just before the operation patients received 100 mg of 5-FU via suppository or intravenously. Portal and systemic blood, tumor tissue, normal mucosa and muscle layer separately at 5, 10, 15 cm in the oral direction from the tumor and the pararectal lymph node were harvested for high-performance liquid chromatography determination of 5-FU concentrations. Rectal 5-FU concentrations were significantly higher in the suppository cases compared with the intravenously administrated ones. Suppository distributed more 5-FU at pararectal lymph nodes than intravenous injection. This fact revealed 5-FU suppositories to be a useful drug delivery system for rectal cancer. The pathological effects on metastatic lymph nodes caused by combined treatment were evaluated in 22 cases. Normal lymph nodes showed congestion only. Fibrotic and necrotic changes were characteristic of damaged metastatic areas. In 6 cases (27.3%), no metastatic cells were detected on fibrotically changed areas. The down staging of the lymph node metastatic factor was carried out by preoperative combined treatment. High concentrations of 5-FU at mucosa could suggest the usefulness of 5-FU suppository administration just before operation for prevention of suture-line implantation. (author)
Induction Chemotherapy With Gemcitabine, Oxaliplatin, and 5-Fluorouracil/Leucovorin Followed by Concomitant Chemoradiotherapy in Patients With Locally Advanced Pancreatic Cancer: A Taiwan Cooperative Oncology Group Phase II Study

International Nuclear Information System (INIS)

Ch’ang, Hui-Ju; Lin, Yu-Lin; Wang, Hsiu-Po; Chiu, Yen-Feng; Chang, Ming-Chu; Hsu, Chih-Hung; Tien, Yu-Wen; Chen, Jen-Shi; Hsieh, Ruey-Kuen; Lin, Pin-Wen; Shan, Yan-Shen; Cheng, Ann-Lii; Chang, Jang-Yang; Whang-Peng, Jacqueline; Hwang, Tsann-Long

2011-01-01

Purpose: To evaluate the therapeutic efficacy of 3-month triplet induction chemotherapy (ICT) followed by concomitant chemoradiotherapy (CCRT) in patients with locally advanced pancreatic cancer (LAPC). Patients and Methods: Chemonaïve patients with measurable, histologically confirmed LAPC were eligible. The ICT consisted of biweekly gemcitabine (800 mg/m 2 ) infusion at a fixed dose rate (10 mg/m 2 /min), followed by 85 mg/m 2 oxaliplatin and 48-h infusion of 5-fluorouracil/leucovorin (3000/150 mg/m 2 ) for 6 cycles. Patients without disease progression 4 weeks after ICT would receive weekly 400 mg/m 2 gemcitabine and 5040 cGy radiation in 28 fractions. After CCRT, patients were subjected for surgical intervention and/or maintenance chemotherapy until progression or intolerable toxicity. Results: Between December 2004 and August 2008, 50 patients were enrolled. The best responses after ICT were partial response (PR) in 9, stable disease in 26, and progressive disease or not evaluable in 15. Among the former 35 patients, 2 had disease progression before CCRT, and 3 declined to have CCRT. Of the 30 patients receiving CCRT, an additional 4 and 1 patient(s) achieved PR at the end of CCRT and during maintenance chemotherapy, respectively. On intent-to-treat analysis, the overall best response was PR in 14 patients and stable disease in 21. The overall response rate and disease control rate were 28% (95% confidence interval [CI], 16.2–42.5%) and 70% (95% CI, 44.4–99.2%), respectively. The median time to progression and overall survival of the intent-to-treat population was 9.3 (95% CI, 5.8–12.8) months and 14.5 (95% CI, 11.9–17.1) months, respectively. One- and two-year survival rates were 68% (95% CI, 55.1–80.9%) and 20.6% (95% CI, 8.7–32.5%), respectively. Neutropenia was the most common Grade 3–4 toxicity of both ICT and CCRT, with a frequency of 28% and 26.7%, respectively. Significant sensory neuropathy occurred in 9 patients (18%). Conclusion
Induction Chemotherapy With Gemcitabine, Oxaliplatin, and 5-Fluorouracil/Leucovorin Followed by Concomitant Chemoradiotherapy in Patients With Locally Advanced Pancreatic Cancer: A Taiwan Cooperative Oncology Group Phase II Study

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Ch' ang, Hui-Ju [National Institute of Cancer Research, National Health Research Institutes, Miaoli, Taiwan (China); Department of Radiation Oncology, National Cheng Kung University Hospital, Tainan, Taiwan (China); Lin, Yu-Lin [Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan (China); Wang, Hsiu-Po [Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan (China); Chiu, Yen-Feng [Institute of Public Health Sciences, National Health Research Institutes, Miaoli, Taiwan (China); Chang, Ming-Chu [Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan (China); Hsu, Chih-Hung [Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan (China); Tien, Yu-Wen [Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan (China); Chen, Jen-Shi [Department of Internal Medicine, Chang-Gung Memorial Hospital, Chang Gung University, College of Medicine, Tao-Yuan, Taiwan (China); Hsieh, Ruey-Kuen [Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan (China); Lin, Pin-Wen; Shan, Yan-Shen [Department of Surgery, National Cheng Kung University Hospital, Tainan, Taiwan (China); Cheng, Ann-Lii [Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan (China); Chang, Jang-Yang [National Institute of Cancer Research, National Health Research Institutes, Miaoli, Taiwan (China); Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan (China); Whang-Peng, Jacqueline [National Institute of Cancer Research, National Health Research Institutes, Miaoli, Taiwan (China); Cancer Center Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan (China); Hwang, Tsann-Long, E-mail: hwangtl@adm.cgmh.org.tw [Department of Surgery, Chang-Gung Memorial Hospital, Chang Gung University, College of Medicine, Tao-Yuan, Taiwan (China); and others

2011-12-01

Purpose: To evaluate the therapeutic efficacy of 3-month triplet induction chemotherapy (ICT) followed by concomitant chemoradiotherapy (CCRT) in patients with locally advanced pancreatic cancer (LAPC). Patients and Methods: Chemonaieve patients with measurable, histologically confirmed LAPC were eligible. The ICT consisted of biweekly gemcitabine (800 mg/m{sup 2}) infusion at a fixed dose rate (10 mg/m{sup 2}/min), followed by 85 mg/m{sup 2} oxaliplatin and 48-h infusion of 5-fluorouracil/leucovorin (3000/150 mg/m{sup 2}) for 6 cycles. Patients without disease progression 4 weeks after ICT would receive weekly 400 mg/m{sup 2} gemcitabine and 5040 cGy radiation in 28 fractions. After CCRT, patients were subjected for surgical intervention and/or maintenance chemotherapy until progression or intolerable toxicity. Results: Between December 2004 and August 2008, 50 patients were enrolled. The best responses after ICT were partial response (PR) in 9, stable disease in 26, and progressive disease or not evaluable in 15. Among the former 35 patients, 2 had disease progression before CCRT, and 3 declined to have CCRT. Of the 30 patients receiving CCRT, an additional 4 and 1 patient(s) achieved PR at the end of CCRT and during maintenance chemotherapy, respectively. On intent-to-treat analysis, the overall best response was PR in 14 patients and stable disease in 21. The overall response rate and disease control rate were 28% (95% confidence interval [CI], 16.2-42.5%) and 70% (95% CI, 44.4-99.2%), respectively. The median time to progression and overall survival of the intent-to-treat population was 9.3 (95% CI, 5.8-12.8) months and 14.5 (95% CI, 11.9-17.1) months, respectively. One- and two-year survival rates were 68% (95% CI, 55.1-80.9%) and 20.6% (95% CI, 8.7-32.5%), respectively. Neutropenia was the most common Grade 3-4 toxicity of both ICT and CCRT, with a frequency of 28% and 26.7%, respectively. Significant sensory neuropathy occurred in 9 patients (18
The addition of low-dose leucovorin to the combination of 5-fluorouracil-levamisole does not improve survival in the adjuvant treatment of Dukes' C colon cancer

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Bleeker, WA; Mulder, NH; Hermans, J; Otter, R; Plukker, JT

Purpose: To assess the effect of the addition of leucovorin to the combination of 5-fluorouracil (5-FU)-levamisole on recurrence risk and overall survival in patients after a resection with curative intent of a Dukes' C colon cancer. Patients and methods: Five hundred patients with Dukes' C colon
Use of subconjunctival injections of 5-fluorouracil to rescue and prolong intraocular pressure reduction for a failing Ahmed glaucoma implant.

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Kaplowitz, Kevin; Khodadadeh, Sarah; Wang, Samantha; Lee, Daniel; Tsai, James C

2017-06-01

5-Fluorouracil (5-FU) has been well described for a failing trabeculectomy bleb, but not for aqueous shunts. We sought to determine whether subconjunctival 5-FU prolongs the intraocular pressure (IOP) efficacy of Ahmed shunts. We included all patients with Ahmed FP-7 implantation by one surgeon at Yale University. Patients with 21 on >2 medications. Five-milligram (0.1 cc) injections were made over the plate. The control group consisted of Ahmed FP-7 patients without injections. The main outcome measure was IOP. Secondary outcome was success (IOP Ahmed shunts. Outcomes between eyes receiving injections and controls were statistically similar.
A complex interplay between PGC-1 co-activators and mTORC1 regulates hematopoietic recovery following 5-fluorouracil treatment

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Sunanda Basu

2014-01-01

Full Text Available In vitro stimulation of HSCs with growth factors generally leads to their depletion. Understanding the molecular mechanisms underlying expansion of HSCs in vivo following myeloablation could lead to successful expansion of HSCs ex vivo for therapeutic purposes. Current findings show that mTORC1 is activated in HSPCs following 5-fluorouracil treatment and that mTORC1 activation is dependent on mitochondrial ETC capacity of HSPCs. Moreover, expression of PGC-1 family members, proteins that regulate mitochondrial biogenesis, in HSPCs following 5-fluorouracil treatment changes; also, these proteins play a stage specific role in hematopoietic recovery. While PRC regulates HSCs' expansion during early recovery phase, PGC-1α regulates progenitor cell proliferation and recovery of hematopoiesis during later phase. During early recovery phase, PRC expression, mitochondrial activity and mTORC1 activation are relatively higher in PGC-1α−/− HSCs compared to WT HSCs, and PGC-1α−/− HSCs show greater expansion. Administration of rapamycin, but not NAC, during early recovery phase improves WT HSC numbers but decreases PGC-1α−/− HSC numbers. The current findings demonstrate that mTOR activation can increase HSC numbers provided that the energy demand created by mTOR activation is successfully met. Thus, critical tuning between mTORC1 activation and mitochondrial ETC capacity is crucial for HSC maintenance/expansion in response to mitogenic stimulation.
Therapeutic effects of 5-fluorouracil sustained-release particles in 81 malignant pericardial effusion patients

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Yong-Li Ji

2015-02-01

Full Text Available This study aimed to investigate the clinical application value of the 5-fluorouracil (5-FU sustained-release particles implanted along the cardiac tangent direction into malignant pericardial effusion (MPCE. A total of 81 MPCE patients underwent pericardiocentesis, and were implanted with 5-FU sustained-release particles into the pericardial cavity under ultrasound guidance. The puncturing path was along the cardiac tangent direction. Ultrasound examinations were performed every week, and the efficacy was evaluated 4 weeks after treatment. The 45 patients who were treated with pericardial catheter drainage and simultaneous intracavitary chemotherapy were used as the control group. The success rate of pericardiocentesis was 100%. Ultrasound reviews performed 4 weeks after treatment showed that 71 cases achieved complete remission and eight cases achieved partial remission, while treatment was completely ineffective in two cases. The total remission rate was 97.53%, which was significantly higher than that of the control group (77.78%, p < 0.01. The implantation of 5-FU sustained-release particles along the cardiac tangent direction was safe, and demonstrated good efficacy and fewer adverse reactions. Thus, this method could be ideal for the treatment of MPCE.
Factors Associated with Continuous Low Dose Heparin Infusion for Central Venous Catheter Patency in Critically Ill Children Worldwide

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Onyeama, Sara-Jane N; Hanson, Sheila J; Dasgupta, Mahua; Hoffmann, Raymond G; Faustino, Edward Vincent S

2016-01-01

Objective To identify patient, hospital and central venous catheter (CVC) factors that may influence the use of low dose heparin infusion (LDHI) for CVC patency in critically ill-children. Design Secondary analysis of an international multicenter observational study. Setting 59 Pediatric Intensive Care Units (PICUs) over four study dates in 2012, involving 7 countries. Patients Children less than 18 years of age with a CVC, admitted to a participating unit and enrolled in the completed PROTRACT study were included. All overflow patients were excluded. Interventions None. Measurements and Main Results Of the 2,484 patients in the PROTRACT study, 1,312 patients had a CVC. 507 of those patients used LDHI. The frequency of LDHI was compared across various patient, hospital and CVC factors using chi-squared, Mann-Whitney and Fisher's exact tests. In the multivariate analysis, age was not a significant factor for LDHI use. Patients with pulmonary hypertension had decreased LDHI use while those with active surgical or trauma diagnoses had increased LDHI use. All central CVC insertion sites were more likely to use LDHI when compared to peripherally inserted CVCs. The Asia-Pacific region showed increased LDHI use, along with community hospitals and smaller ICUs (LDHI in critically ill children. Further study is needed to evaluate the efficacy and persistence of LDHI use. PMID:27362853
Phase I and II trial on infusional 5-fluorouracil and gefitinib in combination with preoperative radiotherapy in rectal cancer: 10-years median follow-up

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Maria Antonietta Gambacorta

2018-03-01

Full Text Available Purpose: The aim of this study is to evaluate the long term survival of the addition of gefitinib to chemoradiotherapy (CRT in locally advanced rectal cancer (LARC. Methods and materials: This previously published multicentre, open-label, phase I-II study, enrolled patients (pts with LARC to receive CRT with concurrent 5-fluorouracil continuous intravenous infusion and a dose escalation of orally administered gefitinib, followed 6–8 weeks later by surgery. An intra-operative radiotherapy boost of 10 Gy was planned. Adjuvant chemotherapy was administrated in ypN1-2 pts. After a median f/u of >10 years, we analyzed Local Control (LC, Metastasis Free Survival (MFS, Disease Free Survival (DFS, Disease Specific Survival (DSS and Overall Survival (OS. Predictive endpoints of clinical outcomes were tested by univariate and multivariate analysis. Variables analyzed included: age, gefitinib dose and interruptions, adjuvant CT, surgery type, ypT, ypN, and TRG grade. We have also analyzed late toxicity according to CTCAEv4. Results: Of the 41 initially enrolled pts, 39 were evaluable (27M, 12F. With a median f/u of 133 months, LC, MFS, DFS, OS and DSS at 5 years were 84%; 71%; 64%; 87% and 92%, respectively. The OS and DSS at 10 years were 61,5% and 76%, respectively. Grade 3-4 late toxicity occurred in 38% of pts: sexual (28,2% and gastrointestinal toxicities (10,2%. Conclusion: Long term outcomes and late toxicity were similar to previously reported series. The addition of gefitinib did not improve outcomes in LARC. Gefitinib is not recommended for rectal cancer patients who received 5-FU based preoperative CRT. Further studies may identify if gefitinib is beneficial in selected group of patients. Keywords: Rectal cancer, Gefitinib, Log term follow-up, Chemoradiotherapy
Front-line Bevacizumab in combination with Oxaliplatin, Leucovorin and 5-Fluorouracil (FOLFOX in patients with metastatic colorectal cancer: a multicenter phase II study

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Touroutoglou Nikolaos

2007-05-01

Full Text Available Abstract Purpose To evaluate the efficacy and the toxicity of front line FOLFOX4 combined with bevacizumab in patients with metastatsic CRC (mCRC. Patients and Methods Chemotherapy-naïve patients with mCRC, received bevacizumab (5 mg/kg every 2 weeks d1, oxaliplatin (85 mg/m2 on d1, leucovorin (200 mg/m2 on days 1 and 2 and 5-Fluorouracil (400 mg/m2 as i.v. bolus and 600 mg/m2 as 22 h i.v. continuous infusion on days 1 and 2 every 2 weeks. Results Fifty three patients (46 with a PS 0–1 were enrolled. Complete and partial response was achieved in eight (15.1% and 28 (52.8% patients, respectively (ORR: 67.9%; 95% C.I.: 53.8%–92%; 11 (20.7% patients had stable disease and six (11.3% progressive disease. With a median follow up period of 13.5 months, time to tumor progression was 11 months while the median survival has not yet been reached; the probability of 1-, 2- and 3- year survival was 79.8%, 63.8% and 58.3%, respectively; Two patients relapsed during the follow up period. Eight (15% patients underwent metastasectomy with R0 resections. Grade 3–4 neutropenia occurred in 15.1% of patients and one (1.9% of them presented febrile neutropenia. Non-hematologic toxicity included grade 3 diarrhea (7.6% and grade 2 and 3 neurotoxicity in 16.9 and 15.1% of patients, respectively. One (1.9% patient presented pulmonary embolism and one (1.9% cardiac ischaemia. There was one (1.9% sudden death after the first cycle. Conclusion The combination of FOLFOX4/bevacizumab appears to be highly effective, well tolerated and merits further evaluation in patients with mCRC.
Adjuvant radiotherapy and 5-fluorouracil after curative resection of cancer of the pancreas and periampullary region: phase III trial of the EORTC gastrointestinal tract cancer cooperative group

NARCIS (Netherlands)

J.H.G. Klinkenbijl (Jean); J. Wils; J. Jeekel (Hans); T. Sahmoud; R. van Pel; M.L. Couvreur; C.H. Veenhof; J.P. Arnaud; D. González González (Dionisio); L.Th. de Wit (Laurens); A. Hennipman

1999-01-01

textabstractOBJECTIVE: The survival benefit of adjuvant radiotherapy and 5-fluorouracil versus observation alone after surgery was investigated in patients with pancreatic head and periampullary cancers. SUMMARY BACKGROUND DATA: A previous study of adjuvant
Delivery interaction between co-infused medications: an in vitro modeling study of microinfusion.

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Tsao, Amy C; Lovich, Mark A; Parker, Michael J; Zheng, Hui; Peterfreund, Robert A

2013-01-01

To test the hypothesis that steady-state drug delivery by continuous infusion is predictably affected by a second drug infusion in the same lumen. Clinicians commonly administer two drugs by continuous infusion through one central venous catheter lumen (co-infusion). To limit fluid delivery, low flow rate carriers transport concentrated drug solutions; a method called microinfusion. How microinfusion delivery of one drug is affected by a second drug infusion has not been explored. Two water-soluble dyes, tartrazine and erioglaucine, infused at 3 ml · h(-1), modeled drug delivery through a four stopcock linear manifold and catheter lumen. A pump drove a carrier fluid (10 ml · h(-1)). After tartrazine reached steady-state delivery, erioglaucine entered downstream or upstream of the tartrazine infusion. Quantitative spectrophotometry measured dye delivery. Starting erioglaucine's infusion upstream of tartrazine's entry caused a transient tartrazine bolus (duration 10 min, peak drug delivery 20% higher than target levels). Starting erioglaucine's infusion downstream produced a similar amplitude, briefer, bolus. Stopping the erioglaucine infusion caused a transient reduction in tartrazine delivery. Measured delivery profiles were comparable to prediction models. We confirmed the hypothesis that delivery of one infused drug is transiently affected by starting or stopping a second drug infusion in the same line. The magnitude of the changes can be estimated quantitatively. The clinical impact depends on the drugs being co-infused and patient sensitivity, but could be clinically important; the findings have safety implications for infused medication delivery to critically ill or anesthetized children. We recommend minimizing infusion system dead volumes, connecting the most essential infusion(s) to the main fluid pathway as close as possible to the patient, and recognizing the potential for unintended alterations in delivery when multiple drugs co-infuse. © 2012
Therapeutic significance of a D-dimer cut-off level of >3 μg/ml in colorectal cancer patients treated with standard chemotherapy plus bevacizumab

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Mochizuki, Satoshi; Yoshino, Takayuki; Kojima, Takashi

2010-01-01

The risk of venous thromboembolism has been reported to increase when receiving bevacizumab. Many cancer patients are reported to have elevated D-dimer levels. It is not clear what D-dimer level might indicate an increased risk of venous thromboembolism in the colorectal cancer patients treated with bevacizumab-containing chemotherapy. The D-dimer levels and any event concurrent with an elevated D-dimer level were evaluated in patients receiving bevacizumab. The D-dimer cut-off level was determined using the receiver-operating characteristic analysis. The selection criteria were as follows: histologically proven metastatic and unresectable colorectal adenocarcinoma; no prior chemotherapy containing bevacizumab; D-dimer test performed repetitively on the baseline and during bevacizumab administration; no venous thromboembolism identified at the baseline; and enhanced computed tomographic scan performed every 2 months. Sixty-nine patients were included. The chemotherapy regimens with bevacizumab included the regimen of 5-fluorouracil, leucovorin and oxaliplatin (FOLFOX), the regimen of 5-fluorouracil, leucovorin and irinotecan (FOLFIRI), and leucovorin-modulated 5-fluorouracil. The median baseline D-dimer level was 1.2 μg/ml. The appropriate D-dimer cut-off level was 3 μg/ml with the negative predictive value of 98% and relative risk of 6.9. Twenty-one of 69 patients showed elevated D-dimer levels of >3 μg/ml, with 11 patients for unknown reasons, 6 with tumor progression, 3 with venous thromboembolism and 1 with sepsis. In the remaining 48 patients whose D-dimer levels were ≤3 μg/ml, only one patient developed a venous thromboembolism. A D-dimer cut-off level of 3 μg/ml might be a useful indicator level to exclude venous thromboembolism or show an increased risk for venous thromboembolism in colorectal cancer patients treated with bevacizumab-containing chemotherapy. (author)
Effects of methacholine infusion on desflurane pharmacokinetics in piglets☆

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Kozian, Alf; Kretzschmar, Moritz; Baumgardner, James E.; Schreiber, Jens; Hedenstierna, Göran; Larsson, Anders; Hachenberg, Thomas; Schilling, Thomas

2015-01-01

The data of a corresponding animal experiment demonstrates that nebulized methacholine (MCh) induced severe bronchoconstriction and significant inhomogeneous ventilation and pulmonary perfusion (V̇A/Q̇) distribution in pigs, which is similar to findings in human asthma. The inhalation of MCh induced bronchoconstriction and delayed both uptake and elimination of desflurane (Kretzschmar et al., 2015) [1]. The objective of the present data is to determine V̇A/Q̇ matching by Multiple Inert Gas Elimination Technique (MIGET) in piglets before and during methacholine- (MCh-) induced bronchoconstriction, induced by MCh infusion, and to assess the blood concentration profiles for desflurane (DES) by Micropore Membrane Inlet Mass Spectrometry (MMIMS). Healthy piglets (n=4) under general anesthesia were instrumented with arterial, central venous, and pulmonary artery lines. The airway was secured via median tracheostomy with an endotracheal tube, and animals were mechanically ventilated with intermittent positive pressure ventilation (IPPV) with a FiO2 of 0.4, tidal volume (VT)=10 ml/kg and PEEP of 5cmH2O using an open system. The determination of V.A/Q. was done by MIGET: before desflurane application and at plateau in both healthy state and during MCh infusion. Arterial blood was sampled at 0, 1, 2, 5, 10, 20, and 30 min during wash-in and washout, respectively. Bronchoconstriction was established by MCH infusion aiming at doubling the peak airway pressure, after which wash-in and washout of the anesthetic gas was repeated. Anesthesia gas concentrations were measured by MMIMS. Data were analyzed by ANOVA, paired t-test, and by nonparametric Friedman׳s test and Wilcoxon׳s matched pairs test. We measured airway pressures, pulmonary resistance, and mean paO2 as well as hemodynamic variables in all pigs before desflurane application and at plateau in both healthy state and during methacholine administration by infusion. By MIGET, fractional alveolar ventilation and
Translational Pharmacokinetic‐Pharmacodynamic Modeling and Simulation: Optimizing 5‐Fluorouracil Dosing in Children With Pediatric Ependymoma

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Daryani, VM; Patel, YT; Tagen, M; Turner, DC; Carcaboso, AM; Atkinson, JM; Gajjar, A; Gilbertson, RJ; Wright, KD

2016-01-01

We previously investigated novel therapies for pediatric ependymoma and found 5‐fluorouracil (5‐FU) i.v. bolus increased survival in a representative mouse model. However, without a quantitative framework to derive clinical dosing recommendations, we devised a translational pharmacokinetic‐pharmacodynamic (PK‐PD) modeling and simulation approach. Results from our preclinical PK‐PD model suggested tumor concentrations exceeded the 1‐hour target exposure (in vitro IC90), leading to tumor growth delay and increased survival. Using an adult population PK model, we scaled our preclinical PK‐PD model to children. To select a 5‐FU dosage for our clinical trial in children with ependymoma, we simulated various 5‐FU dosages for tumor exposures and tumor growth inhibition, as well as considering tolerability to bolus 5‐FU administration. We developed a pediatric population PK model of bolus 5‐FU and simulated tumor exposures for our patients. Simulations for tumor concentrations indicated that all patients would be above the 1‐hour target exposure for antitumor effect. PMID:27104090
Preserved learning and memory following 5-fluorouracil and cyclophosphamide treatment in rats.

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Long, Jeffrey M; Lee, Garrick D; Kelley-Bell, Bennett; Spangler, Edward L; Perez, Evelyn J; Longo, Dan L; de Cabo, Rafael; Zou, Sige; Rapp, Peter R

2011-11-01

Some patients experience enduring cognitive impairment after cancer treatment, a condition termed "chemofog". Animal models allow assessment of chemotherapy effects on learning and memory per se, independent of changes due to cancer itself or associated health consequences such as depression. The present study examined the long-term learning and memory effects of a chemotherapy cocktail used widely in the treatment of breast cancer, consisting of 5-fluorouracil (5FU) and cyclophosphamide (CYP). Eighty 5-month old male F344 rats received contextual and cued fear conditioning before treatment with saline, or a low or high dose drug cocktail (50mg/kg CYP and 75 mg/kg 5FU, or 75 mg/kg CYP and 120 mg/kg 5FU, i.p., respectively) every 30 days for 2 months. After a 2-month, no-drug recovery, both long-term retention and new task acquisition in the water maze and 14-unit T-maze were assessed. Neither dose of the CYP/5FU cocktail impaired retrograde fear memory despite marked toxicity documented by enduring weight loss and 50% mortality at the higher dose. Acquisition in the water maze and Stone maze was also normal relative to controls in rats treated with CYP/5FU. The results contribute to a growing literature suggesting that learning and memory mediated by the hippocampus can be relatively resistant to chemotherapy. Future investigation may need to focus on assessments of processing speed, executive function and attention, and the possible interactive contribution of cancer itself and aging to the post-treatment development of cognitive impairment. Copyright © 2011 Elsevier Inc. All rights reserved.
In-Line Filtration Reduces Postoperative Venous Peripheral Phlebitis Associated With Cannulation: A Randomized Clinical Trial.

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Villa, Gianluca; Chelazzi, Cosimo; Giua, Rosa; Tofani, Lorenzo; Zagli, Giovanni; Boninsegni, Paolo; Pinelli, Fulvio; De Gaudio, A Raffaele; Romagnoli, Stefano

2018-04-23

Peripheral venous cannulation is an everyday practice of care for patients undergoing anesthesia and surgery. Particles infused with intravenous fluids (eg, plastic/glass/drugs particulate) contribute to the pathogenesis of peripheral phlebitis. The aim of this study is to demonstrate the efficacy of in-line filtration in reducing the incidence of postoperative phlebitis associated with peripheral short-term vascular access. In this controlled trial, 268 surgical patients were randomly assigned to in-line filtration and standard care (NCT03193827). The incidence of phlebitis (defined as visual infusion phlebitis [VIP] score, ≥2) within 48 hours was compared between the 2 groups, as well as the onset and severity of phlebitis and the reasons for removal of the cannula. The lifespan of venous cannulae was compared for the in-line filter and no-filter groups through a Kaplan-Meier curve. The incidence of phlebitis within 48 hours postoperatively was 2.2% and 26.9% (difference, 25% [95% confidence interval {CI}, 12%-36%]; odds ratio, 0.05 [0.01-0.15]), respectively, for the in-line filter and no-filter groups (P phlebitis (hazard ratio, 0.05 [95% CI, 0.014-0.15]; P phlebitis and prolongs cannula lifespan during peripheral venous cannulation in surgical patients.
Efficacy of repeated 5-fluorouracil needling for failing and failed filtering surgeries based on simple gonioscopic examination

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Rashad MA

2012-12-01

Full Text Available Mohammad A RashadOphthalmology Department, Faculty of Medicine, Ain Shams University, Cairo, EgyptPurpose: To evaluate the success rate of a modified bleb needling technique in eyes with previous glaucoma surgery that had elevated intraocular pressure.Methods: A retrospective study of 24 eyes of 24 patients that underwent repeated bleb needling performed for failing and failed blebs on slit lamp with 5-fluorouracil (5-FU injections on demand. This was performed after gonioscopic examination to define levels of filtration block.Results: There was significant reduction of mean IOP from 36.91 mmHg to 14.73 mmHg at the final follow-up (P < 0.001. The overall success rate was 92%.Conclusion: Repeated needling with adjunctive 5-FU proved a highly effective, safe alternative to revive filtration surgery rather than another medication or surgery.Keywords: bleb, failure, 5-FU, needling, gonioscopy
Polysaccharides from Tricholoma matsutake and Lentinus edodes enhance 5-fluorouracil-mediated H22 cell growth inhibition.

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Ren, Ming; Ye, Lingyan; Hao, Xiaoshi; Ren, Zhixing; Ren, Shuping; Xu, Kun; Li, Juan

2014-06-01

Few studies have investigated the effects produced by combinations of polysaccharides and chemotherapeutic drugs in cancer treatment. We hypothesized that a combination of polysaccharides (COP) from Lentinus edodes and Tricholoma matsutake would improve the efficacy of 5-fluorouracil (5-FU)-mediated inhibition of H22 cell growth. Mice were injected H22 cells and then treated with either 5-FU, polysaccharides from Tricholoma matsutake (PTM), polysaccharides from Lentinus edodes (PL), PTM+PL, 5-FU+PTM, 5-FU+ PL, or 5-FU + COP. The tumor weight and volume, and splenic CD4 + and CD8 + T cell frequencies, were determined. Additionally, splenic natural killer (NK) cell and cytotoxic T lymphocyte (CTL) activities were assessed and the serum levels of tumor necrosis factor-alpha (TNF-alpha), Interleukin-2 (IL-2), and Interferon-gamma (IFN-gamma) were measured. Compared with mice from the control, 5-FU, PL, PTM, PTM + PL, 5-FU + PL, and 5-FU + PTM groups, mice treated with 5-FU + COP showed: (a) significantly reduced tumor weight and volume (P Lentinus edodes and Tricholoma matsutake could enhance the efficacy of 5-FU-mediated H22 cell growth inhibition.

Influence of decreased fibrinolytic activity and plasminogen activator inhibitor-1 4G/5G polymorphism on the risk of venous thrombosis.

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Vuckovic, Biljana A; Djeric, Mirjana J; Tomic, Branko V; Djordjevic, Valentina J; Bajkin, Branislav V; Mitic, Gorana P

2018-01-01

: Objective of our study is to determine whether decreased fibrinolytic activity or plasminogen activator inhibitor (PAI)-1 4G/5G polymorphism influence the risk of venous thrombosis.Our case-control study included 100 patients with venous thrombosis, and 100 random controls. When patients were compared with random controls, unconditional logistic regression was used to calculate odds ratios (ORs) with 95% confidence intervals (CIs).Decreased fibrinolytic activity yielded a 2.7-fold increase in risk for venous thrombosis than physiological fibrinolytic activity (OR 2.70; 95% CI 1.22-5.98), when comparing patients with random controls. Adjustment for several putative confounders did not change the estimate (OR 3.02; 95% CI 1.26-7.22). Analysis of venous thrombotic risk influenced by PAI-1 genotype, showed no influence of PAI-1 4G/5G gene variant in comparison with 5G/5G genotype (OR 0.57 95% CI; 0.27-1.20).Decreased fibrinolytic activity increased, whereas PAI-1 4G/5G polymorphism did not influence venous thrombosis risk in this study.
Excess portal venous long-chain fatty acids induce syndrome X via HPA axis and sympathetic activation

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Benthem, L; Keizer, Klaas-Jan; Wiegman, CH; De Boer, SF; Strubbe, JH; Steffens, AB; Kuipers, F; Scheurink, AJW

2000-01-01

We tested the hypothesis that excessive portal venous supply of long-chain fatty acids to the liver contributes to the development of insulin resistance via activation of the hypothalamus-pituitary-adrenal axis (HPA axis) and sympathetic system. Rats received an intraportal infusion of the
Postoperative Chemotherapy Followed by Conformal Concomitant Chemoradiotherapy in High-Risk Gastric Cancer

International Nuclear Information System (INIS)

Quero, Laurent; Bouchbika, Zineb; Kouto, Honorine; Baruch-Hennequin, Valerie; Gornet, Jean-Marc; Munoz, Nicolas; Cojean-Zelek, Isabelle; Houdart, Remi; Panis, Yves; Valleur, Patrice; Aparicio, Thomas; Maylin, Claude; Hennequin, Christophe

2012-01-01

Purpose: To analyze the efficacy, toxicity, and pattern of relapse after adjuvant cisplatin-based chemotherapy followed by three-dimensional irradiation and concomitant LV5FU2 chemotherapy (high-dose leucovorin and 5-fluorouracil bolus plus continuous infusion) in the treatment of completely resected high-risk gastric cancer. Methods and Materials: This was a retrospective analysis of 52 patients with high-risk gastric cancer initially treated by total/partial gastrectomy and lymphadenectomy between January 2002 and June 2007. Median age was 54 years (range, 36–75 years). Postoperative treatment consisted of 5-fluorouracil and cisplatin chemotherapy. Adjuvant chemotherapy was followed by three-dimensional conformal radiotherapy in the tumor bed and regional lymph nodes at 4500 cGy/25 fractions in association with concomitant chemotherapy. Concomitant chemotherapy consisted of a 2-h infusion of leucovorin (200 mg/m²) followed by a bolus of 5-fluorouracil (400 mg/m²) and then a 44-h continuous infusion of 5-fluorouracil (2400–3600 mg/m²) given every 14 days, for three cycles (LV5FU2 protocol). Results: Five-year overall and disease-free survival were 50% and 48%, respectively. Distant metastases and peritoneal spread were the most frequent sites of relapse (37% each). After multivariate analysis, only pathologic nodal status was significantly associated with disease-free and overall survival. Acute toxicities were essentially gastrointestinal and hematologic. One myocardial infarction and one pulmonary embolism were also reported. Eighteen patients had a radiotherapy program interruption because of acute toxicity. All patients but 2 have completed radiotherapy. Conclusion: Postoperative cisplatin-based chemotherapy followed by conformal radiotherapy in association with concurrent 5-fluorouracil seemed to be feasible and resulted in successful locoregional control.
Cardiorespiratory effects of venous lipid micro embolization in an experimental model of mediastinal shed blood reinfusion

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Dencker Magnus

2009-09-01

Full Text Available Abstract Background Retransfusion of the patient's own blood during surgery is used to reduce the need for allogenic blood transfusion. It has however been found that this blood contains lipid particles, which form emboli in different organs if the blood is retransfused on the arterial side. In this study, we tested whether retransfusion of blood containing lipid micro-particles on the venous side in a porcine model will give hemodynamic effects. Methods Seven adult pigs were used. A shed blood surrogate containing 400 ml diluted blood and 5 ml radioactive triolein was produced to generate a lipid embolic load. The shed blood surrogate was rapidly ( Results A more than 30-fold increase in pulmonary vascular resistance was observed, with subsequent increase in pulmonary artery pressure, and decrease in cardiac output and arterial pressure. This response was transient, but was followed by a smaller, persistent increase in pulmonary vascular resistance. Only a small portion of the infused triolein passed the lungs, and only a small fraction could be recirculated by increasing cardiac output and pulmonary pressure. Conclusion Infusion of blood containing lipid micro-emboli on the venous side leads to acute, severe hemodynamic responses that can be life threatening. Lipid particles will be trapped in the lungs, leading to persistent effects on the pulmonary vascular resistance.
Cetuximab in combination with irinotecan/5-fluorouracil/folinic acid (FOLFIRI) in the initial treatment of metastatic colorectal cancer: a multicentre two-part phase I/II study

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Raoul, Jean-Luc; Van Laethem, Jean-Luc; Peeters, Marc; Brezault, Catherine; Husseini, Fares; Cals, Laurent; Nippgen, Johannes; Loos, Anja-Helena; Rougier, Philippe

2009-01-01

This study was designed to investigate the efficacy and safety of the epidermal growth factor receptor (EGFR) inhibitor cetuximab combined with irinotecan, folinic acid (FA) and two different doses of infusional 5-fluorouracil (5-FU) in the first-line treatment of EGFR-detectable metastatic colorectal cancer. The 5-FU dose was selected on the basis of dose-limiting toxicities (DLTs) during part I of the study. Patients received cetuximab (400 mg/m 2 initial dose and 250 mg/m 2 /week thereafter) and every 2 weeks irinotecan (180 mg/m 2 ), FA (400 mg/m 2 ) and 5-FU (either low dose [LD], 300 mg/m 2 bolus plus 2,000 mg/m 2 46-hour infusion, n = 7; or, high-dose [HD], 400 mg/m 2 bolus plus 2,400 mg/m 2 ; n = 45). Only two DLTs occurred in the HD group, and HD 5-FU was selected for use in part II. Apart from rash, commonly observed grade 3/4 adverse events such as leucopenia, diarrhoea, vomiting and asthenia occurred within the expected range for FOLFIRI. Among 52 patients, the overall response rate was 48%. Median progression-free survival (PFS) was 8.6 months (counting all reported progressions) and the median overall survival was 22.4 months. Treatment facilitated the resection of initially unresectable metastases in fourteen patients (27%): of these, 10 patients (71%) had no residual tumour after surgery, and these resections hindered the estimation of PFS. The combination of cetuximab and FOLFIRI was active and well tolerated in this setting. Initially unresectable metastases became resectable in one-quarter of patients, with a high number of complete resections, and these promising results formed the basis for the investigation of FOLFIRI with and without cetuximab in the phase III CRYSTAL trial
Cetuximab in combination with irinotecan/5-fluorouracil/folinic acid (FOLFIRI in the initial treatment of metastatic colorectal cancer: a multicentre two-part phase I/II study

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Cals Laurent

2009-04-01

Full Text Available Abstract Background This study was designed to investigate the efficacy and safety of the epidermal growth factor receptor (EGFR inhibitor cetuximab combined with irinotecan, folinic acid (FA and two different doses of infusional 5-fluorouracil (5-FU in the first-line treatment of EGFR-detectable metastatic colorectal cancer. Methods The 5-FU dose was selected on the basis of dose-limiting toxicities (DLTs during part I of the study. Patients received cetuximab (400 mg/m2 initial dose and 250 mg/m2/week thereafter and every 2 weeks irinotecan (180 mg/m2, FA (400 mg/m2 and 5-FU (either low dose [LD], 300 mg/m2 bolus plus 2,000 mg/m2 46-hour infusion, n = 7; or, high-dose [HD], 400 mg/m2 bolus plus 2,400 mg/m2; n = 45. Results Only two DLTs occurred in the HD group, and HD 5-FU was selected for use in part II. Apart from rash, commonly observed grade 3/4 adverse events such as leucopenia, diarrhoea, vomiting and asthenia occurred within the expected range for FOLFIRI. Among 52 patients, the overall response rate was 48%. Median progression-free survival (PFS was 8.6 months (counting all reported progressions and the median overall survival was 22.4 months. Treatment facilitated the resection of initially unresectable metastases in fourteen patients (27%: of these, 10 patients (71% had no residual tumour after surgery, and these resections hindered the estimation of PFS. Conclusion The combination of cetuximab and FOLFIRI was active and well tolerated in this setting. Initially unresectable metastases became resectable in one-quarter of patients, with a high number of complete resections, and these promising results formed the basis for the investigation of FOLFIRI with and without cetuximab in the phase III CRYSTAL trial.
A new DPYD genotyping assay for improving the safety of 5-fluorouracil therapy.

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Sistonen, Johanna; Smith, Chingying; Fu, Yung-Kang; Largiadèr, Carlo R

2012-12-24

Chemotherapeutic use of 5-fluorouracil (5FU) is compromised by 10-20% of patients developing severe toxicity. Recently described genetic variation in dihydropyrimidine dehydrogenase (DPYD) has been shown to be a major predictor of 5FU toxicity. Here, we describe a new genotyping assay for routine clinical use that covers all the major DPYD risk variants. Genomic regions targeting DPYD risk variants (c.1129-5923C>G, c.1679T>G/A, c.1905+1G>A, c.2846A>T) and additional markers (c.234-123G>C, c.496A>G, c.775A>G) were amplified in a multiplex PCR reaction. The subsequent steps including allele-specific primer extension, hybridization of the primers to a microarray, scanning of the array, and data analysis were automated within the INFINITI® Analyzer (AutoGenomics). The assay was validated by analyzing 107 blood samples obtained from patients previously re-sequenced for the DPYD. The genotypes obtained with the developed assay were 100% concordant with the re-sequencing. The procedure is suitable for routine clinical use since the results are obtained within one day. For heterozygous risk variant carriers (~7% of Europeans), the treatment can be adjusted by 5FU dose reduction, whereas carriers of two risk alleles should be treated with an alternative therapy. The developed assay provides a novel tool to improve the safety of commonly used 5FU-based chemotherapies. Copyright © 2012 Elsevier B.V. All rights reserved.
RBFOX3 Regulates the Chemosensitivity of Cancer Cells to 5-Fluorouracil via the PI3K/AKT, EMT and Cytochrome-C/Caspase Pathways

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Tianze Liu

2018-04-01

Full Text Available Background/Aims: RBFOX3, an RNA-binding fox protein, plays an important role in the differentiation of neuronal development, but its role in the chemosensitivity of hepatocellular carcinoma (HCC to 5-FU is unknown. Methods: In this study, we examined the biological functions of RBFOX3 and its effect on the chemosensitivity of HCC cells to 5-FU in vitro and in a mouse xenograft model. Results: RBFOX3 was found to have elevated expression in HCC cell lines and tissue samples, and its knockdown inhibited HCC cell proliferation. Moreover, knockdown of RBFOX3 improved the inhibitory effect of 5-fluorouracil (5-FU on cell proliferation, migration and invasion, and enhanced the apoptosis induced by 5-FU. However, overexpression of RBFOX3 reduced the inhibitory effect of 5-fluorouracil (5-FU on cell proliferation, migration and invasion, and decreased the apoptosis induced by 5-FU. We further elucidated that RBFOX3 knockdown synergized with 5-FU to inhibit the growth and invasion of HCC cells through PI3K/AKT and epithelial-mesenchymal transition (EMT signaling, and promote apoptosis by activating the cytochrome-c/caspase signaling pathway. Finally, we validated that RBFOX3 regulated 5-FU-mediated cytotoxicity in HCC in mouse xenograft models. Conclusions: The findings from this study indicate that RBFOX3 regulates the chemosensitivity of HCC to 5-FU in vitro and in vivo. Therefore, targeting RBFOX3 may improve the inhibition of HCC growth and progression by 5-FU, and provide a novel potential therapeutic strategy for HCC.
Adjuvant radiotherapy and 5-fluorouracil after curative resection of cancer of the pancreas and periampullary region: phase III trial of the EORTC gastrointestinal tract cancer cooperative group

NARCIS (Netherlands)

Klinkenbijl, J. H.; Jeekel, J.; Sahmoud, T.; van Pel, R.; Couvreur, M. L.; Veenhof, C. H.; Arnaud, J. P.; Gonzalez, D. G.; de Wit, L. T.; Hennipman, A.; Wils, J.

1999-01-01

The survival benefit of adjuvant radiotherapy and 5-fluorouracil versus observation alone after surgery was investigated in patients with pancreatic head and periampullary cancers. A previous study of adjuvant radiotherapy and chemotherapy in these cancers by the Gastrointestinal Tract Cancer
19F NMR studies of 5-fluorouracil-substituted Escherichia coli transfer RNAs: solution structure and codon-anticodon interaction

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Gollnick, P.D.

1986-01-01

19 F NMR was used to study E. coli tRNA 1 /sup Val/, tRNA/sub f//sup Met/, and tRNA/sub m//Met/, in which 5-fluorouracil (FUra) has replaced uracil and uracil-derived minor bases. 19 F NMR spectra of these tRNAs resolve resonances from nearly all the incorporated FUra residues. Each of the three tRNAs can be resolved into two isoaccepting species, termed forms A and B, whose 19 F spectra differ in the shift of one 19 F peak from ca. 4.5 ppm in form B, upfield to -15 ppm in form A. Because the two isoacceptors of each tRNA differ only at one position, the peaks at 4.5 ppm in the spectra of (FUra)tRNA 1 /sup Val/ and (FUra)tRNA/sub m//sup Met/; are assigned to FUra 17 and Fura 20 respectively. Bisulfate modification and pH dependence indicate that 19 F signals in the central region of the spectrum of (FUra)tRNA 1 /sup Val/ correspond to fluorouracils in non-base-paired regions. Photoreaction with psoralen indicates upfield 19 F signals arise from residues in helical environments. Removal of magnesium or addition of NaCl produces major, reversible changes in the 19 F spectrum of fluorinated tRNAs. Studies of manganese and spermine binding to (FUra)tRNA 1 /sup Val/ allow localization of several resonances in the 18 F spectrum to regions near putative binding sites for these ions. Binding of the codon G/sub p/U/sub p/A causes an upfield shift of a 19 F resonance at 3.9 ppm in the spectrum of (FUra)tRNA 1 /sup Val/. G/sub p/U/sub p/A/sub p/A, which is complementary to the anticodon and 5'-adjacent FUra 33, shifts an additional 19 F peak at 4.5 ppm. 1 H NMR and RNase H digestion studies show that the oligonucleotides bind to the anticodon
Intraosseous infusion in elective and emergency pediatric anesthesia: when should we use it?

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Neuhaus, Diego

2014-06-01

Difficulties to establish a venous access may also occur in routine pediatric anesthesia and lead to hazardous situations. Intraosseous infusion is a well tolerated and reliable but rarely used alternative technique in this setting. According to recent surveys, severe complications of intraosseous infusion stay a rare event. Minor complications and problems in getting an intraosseous infusion started on the other side seem to be more common than generally announced. The EZ-IO intraosseous infusion system has received expanded EU CE mark approval for an extended dwell time of up to 72 h and for insertion in pediatric patients in the distal femur. Key values of blood samples for laboratory analysis can be obtained with only 2 ml of blood/marrow waste and do also offer reliable values using an I-Stat point-of-care analyzer. Most problems in using an intraosseous infusion are provider-dependent. In pediatric anesthesia, the perioperative setting should further contribute to reduce these problems. Nevertheless, regular training, thorough anatomical knowledge and prompt availability especially in the pediatric age group are paramount to get a seldom used technique work properly under pressure. More longitudinal data on large cohorts were preferable to further support the safety of the intraosseous infusion technique in pediatric patients.
Microsurgical training on an in vitro chicken wing infusion model.

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Olabe, Jon; Olabe, Javier

2009-12-01

Microneurovascular anastomosis and aneurysm clipping require extensive training before mastering the technique and are a surgical challenge. We developed the "infused chicken wing method" to provide a simple but realistic training method minimizing animal use and need for special facilities for animal care and anesthesia. Fresh chicken wings were used in this model. The main brachial artery was cannulated, and water was infused at 140 mm Hg followed by anatomical neurovascular dissection. Multiple microsurgical training exercises were performed under microscope vision including terminoterminal, lateroterminal, laterolateral vascular anastomosis, and nerve anastomosis. Different complexity aneurysms were created using venous patches, clipping, rupture, and vascular reconstruction techniques were performed. This novel training model is inexpensive, easily obtainable, and no live animals are required. The diameter and characteristics of arteries and veins used are similar to those of the human brain. Great microsurgical technique progress may be obtained. The infused chicken wing artery model presents a realistic microvascular training method. It is inexpensive and easy to set up. Such simplicity provides the adequate environment for developing microsurgical technique. Copyright 2009 Elsevier Inc. All rights reserved.
Alteration of the redox state with reactive oxygen species for 5-fluorouracil-induced oral mucositis in hamsters.

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Fumihiko Yoshino

Full Text Available Oral mucositis is often induced in patients receiving cancer chemotherapy treatment. It has been reported that oral mucositis can reduce quality of life, as well as increasing the incidence of mortality. The participation of reactive oxygen species (ROS in the pathogenesis of oral mucositis is well known, but no report has actually demonstrated the presence of ROS. Thus, the purpose of this study was thus to demonstrate the involvement of ROS and the alteration of the redox state in oral mucositis using an in vivo L-band electron spin resonance (ESR technique. An oral mucositis animal model induced by treatment of 5-fluorouracil with 10% acetic acid in hamster cheek pouch was used. Lipid peroxidation was measured as the level of malondialdehyde determined by the thiobarbituric acid reaction. The rate constants of the signal decay of nitroxyl compounds using in vivo L-band ESR were calculated from the signal decay curves. Firstly, we established the oral mucositis animal model induced by treatment of 5-fluorouracil with acetic acid in hamster cheek pouch. An increased level of lipid peroxidation in oral mucositis was found by measuring malondialdehyde using isolated hamster cheek pouch ulcer. In addition, as a result of in vivo L-band ESR measurements using our model animals, the decay rate constants of carbamoyl-PROXYL, which is a reagent for detecting the redox balance in tissue, were decreased. These results suggest that a redox imbalance might occur by excessive generation of ROS at an early stage of oral mucositis and the consumption of large quantities of antioxidants including glutathione in the locality of oral mucositis. These findings support the presence of ROS involved in the pathogenesis of oral mucositis with anti-cancer therapy, and is useful for the development of novel therapies drugs for oral mucositis.
Radiation- and Photo-induced Activation of 5-Fluorouracil Prodrugs as a Strategy for the Selective Treatment of Solid Tumors

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Sei-ichi Nishimoto

2008-10-01

Full Text Available 5-Fluorouracil (5-FU is used widely as an anticancer drug to treat solid cancers, such as colon, breast, rectal, and pancreatic cancers, although its clinical application is limited because 5-FU has gastrointestinal and hematological toxicity. Many groups are searching for prodrugs with functions that are tumor selective in their delivery and can be activated to improve the clinical utility of 5-FU as an important cancer chemotherapeutic agent. UV and ionizing radiation can cause chemical reactions in a localized area of the body, and these have been applied in the development of site-specific drug activation and sensitization. In this review, we describe recent progress in the development of novel 5-FU prodrugs that are activated site specifically by UV light and ionizing radiation in the tumor microenvironment. We also discuss the chemical mechanisms underlying this activation.
Concurrent Liposomal Cisplatin (Lipoplatin), 5-Fluorouracil and Radiotherapy for the Treatment of Locally Advanced Gastric Cancer: A Phase I/II Study

International Nuclear Information System (INIS)

Koukourakis, Michael I.; Giatromanolaki, Alexandra; Pitiakoudis, Michael; Kouklakis, George; Tsoutsou, Pelagia; Abatzoglou, Ioannis; Panteliadou, Marianthi; Sismanidou, Kyriaki M.Sc.; Sivridis, Efthimios; Boulikas, Teni

2010-01-01

Purpose: Liposomal drugs have a better tolerance profile and are highly accumulated in the tumor environment, properties that promise an optimal radiosensitization. We investigated the feasibility of the combination of 5-fluorouracil/lecovorin-based radio-chemotherapy with the administration of high weekly dose of a liposomal platinum formulation (Lipoplatin TM ). Methods and Materials: Lipoplatin was given at a dose of 120mg/m 2 /week, 5-fluorouracil at 400mg/m 2 /week (Day 1), whereas radiotherapy was given through 3.5-Gy fractions on Days 2, 3, and 4. Two groups of 6 patients received four and five consecutive cycles, respectively. Results: Minimal nephrotoxicity (18.2% Grade 1) and neutropenia (9% Grade 3) was noted. Fatigue Grade 2 appeared in 25% of cases. Abdominal discomfort was reported by 18% of patients. No liver, kidney, gastric, or intestinal severe acute or late sequellae were documented, although the median follow-up of 9 months is certainly too low to allow safe conclusions. A net improvement in the performance status (from a median of 1 to 0) was recorded 2 months after the end of therapy. The response rates assessed with computed tomography, endoscopy, and biopsies confirmed 33% (2 of 6) tumor disappearance in patients treated with four cycles, which reached 80% (4 of 5) in patients receiving five cycles. Conclusions: Lipoplatin radio-chemotherapy is feasible, with minor hematological and nonhematological toxicity. The high complete response rates obtained support the testing of Lipoplatin in the adjuvant postoperative or preoperative radio-chemotherapy setting for the treatment of gastric cancer.
Concurrent liposomal cisplatin (Lipoplatin), 5-fluorouracil and radiotherapy for the treatment of locally advanced gastric cancer: a phase I/II study.

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Koukourakis, Michael I; Giatromanolaki, Alexandra; Pitiakoudis, Michael; Kouklakis, George; Tsoutsou, Pelagia; Abatzoglou, Ioannis; Panteliadou, Marianthi; Sismanidou, Kyriaki; Sivridis, Efthimios; Boulikas, Teni

2010-09-01

Liposomal drugs have a better tolerance profile and are highly accumulated in the tumor environment, properties that promise an optimal radiosensitization. We investigated the feasibility of the combination of 5-fluorouracil/lecovorin-based radio-chemotherapy with the administration of high weekly dose of a liposomal platinum formulation (Lipoplatin). Lipoplatin was given at a dose of 120 mg/m(2)/week, 5-fluorouracil at 400mg/m(2)/week (Day 1), whereas radiotherapy was given through 3.5-Gy fractions on Days 2, 3, and 4. Two groups of 6 patients received four and five consecutive cycles, respectively. Minimal nephrotoxicity (18.2% Grade 1) and neutropenia (9% Grade 3) was noted. Fatigue Grade 2 appeared in 25% of cases. Abdominal discomfort was reported by 18% of patients. No liver, kidney, gastric, or intestinal severe acute or late sequellae were documented, although the median follow-up of 9 months is certainly too low to allow safe conclusions. A net improvement in the performance status (from a median of 1 to 0) was recorded 2 months after the end of therapy. The response rates assessed with computed tomography, endoscopy, and biopsies confirmed 33% (2 of 6) tumor disappearance in patients treated with four cycles, which reached 80% (4 of 5) in patients receiving five cycles. Lipoplatin radio-chemotherapy is feasible, with minor hematological and nonhematological toxicity. The high complete response rates obtained support the testing of Lipoplatin in the adjuvant postoperative or preoperative radio-chemotherapy setting for the treatment of gastric cancer. Copyright (c) 2010 Elsevier Inc. All rights reserved.
Suppression of Reserve MCM Complexes Chemosensitizes to Gemcitabine and 5-Fluorouracil.

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Bryant, Victoria L; Elias, Roy M; McCarthy, Susan M; Yeatman, Timothy J; Alexandrow, Mark G

2015-09-01

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest forms of cancer and is very difficult to treat with conventional chemotherapeutic regimens. Gemcitabine and 5-fluorouracil are used in the management of PDAC and act by indirectly blocking replicative forks. However, these drugs are not highly effective at suppressing disease progression, indicating a need for the development of innovative therapeutic approaches. Recent studies indicate that suppression of the MCM helicase may provide a novel means to sensitize cancer cells to chemotherapeutic agents that inhibit replicative fork progression. Mammalian cells assemble more MCM complexes on DNA than are required to start S-phase. The excess MCM complexes function as backup initiation sites under conditions of replicative stress. The current study provides definitive evidence that cosuppression of the excess/backup MCM complexes sensitizes PDAC tumor lines to both gemcitabine and 5-FU, leading to increased loss of proliferative capacity compared with drugs alone. This occurs because reduced MCM levels prevent efficient recovery of DNA replication in tumor cells exposed to drug. PDAC tumor cells are more sensitive to MCM loss in the presence of gemcitabine than are nontumor, immortalized epithelial cells. Similarly, colon tumor cells are rendered less viable when cosuppression of MCM complexes occurs during exposure to the crosslinking agent oxaliplatin or topoisomerase inhibitor etoposide. These studies demonstrate that suppressing the backup complement of MCM complexes provides an effective sensitizing approach with the potential to increase the therapeutic index of drugs used in the clinical management of PDAC and other cancers. ©2015 American Association for Cancer Research.
Identification of molecular subtypes of gastric cancer with different responses to PI3-kinase inhibitors and 5-fluorouracil.

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Lei, Zhengdeng; Tan, Iain Beehuat; Das, Kakoli; Deng, Niantao; Zouridis, Hermioni; Pattison, Sharon; Chua, Clarinda; Feng, Zhu; Guan, Yeoh Khay; Ooi, Chia Huey; Ivanova, Tatiana; Zhang, Shenli; Lee, Minghui; Wu, Jeanie; Ngo, Anna; Manesh, Sravanthy; Tan, Elisabeth; Teh, Bin Tean; So, Jimmy Bok Yan; Goh, Liang Kee; Boussioutas, Alex; Lim, Tony Kiat Hon; Flotow, Horst; Tan, Patrick; Rozen, Steven G

2013-09-01

Almost all gastric cancers are adenocarcinomas, which have considerable heterogeneity among patients. We sought to identify subtypes of gastric adenocarcinomas with particular biological properties and responses to chemotherapy and targeted agents. We compared gene expression patterns among 248 gastric tumors; using a robust method of unsupervised clustering, consensus hierarchical clustering with iterative feature selection, we identified 3 major subtypes. We developed a classifier for these subtypes and validated it in 70 tumors from a different population. We identified distinct genomic and epigenomic properties of the subtypes. We determined drug sensitivities of the subtypes in primary tumors using clinical survival data, and in cell lines through high-throughput drug screening. We identified 3 subtypes of gastric adenocarcinoma: proliferative, metabolic, and mesenchymal. Tumors of the proliferative subtype had high levels of genomic instability, TP53 mutations, and DNA hypomethylation. Cancer cells of the metabolic subtype were more sensitive to 5-fluorouracil than the other subtypes. Furthermore, in 2 independent groups of patients, those with tumors of the metabolic subtype appeared to have greater benefits with 5-fluorouracil treatment. Tumors of the mesenchymal subtype contain cells with features of cancer stem cells, and cell lines of this subtype are particularly sensitive to phosphatidylinositol 3-kinase-AKT-mTOR inhibitors in vitro. Based on gene expression patterns, we classified gastric cancers into 3 subtypes, and validated these in an independent set of tumors. The subgroups have differences in molecular and genetic features and response to therapy; this information might be used to select specific treatment approaches for patients with gastric cancer. Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.
A novel drug delivery of 5-fluorouracil device based on TiO{sub 2}/ZnS nanotubes

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Mendonça Faria, Henrique Antonio, E-mail: henrique.fisica@ifsc.usp.br [Institute of Physics and Chemistry, Federal University of Itajubá (UNIFEI), Av. BPS, 1303, Pinheirinho, Itajubá, MG, PO Box 50, CEP: 37500-903 (Brazil); Nanomedicine and Nanotoxicology Laboratory, São Carlos Institute of Physics, University of São Paulo. Av. Trabalhador São-carlense, 400, Arnold Schimidt, São Carlos, SP CEP: 13566-590 (Brazil); Alencar de Queiroz, Alvaro Antonio, E-mail: alencar@unifei.edu.br [Institute of Physics and Chemistry, Federal University of Itajubá (UNIFEI), Av. BPS, 1303, Pinheirinho, Itajubá, MG, PO Box 50, CEP: 37500-903 (Brazil)

2015-11-01

The structural and electronic properties of titanium oxide nanotubes (TiO{sub 2}) have attracted considerable attention for the development of therapeutic devices and imaging probes for nanomedicine. However, the fluorescence response of TiO{sub 2} has typically been within ultraviolet spectrum. In this study, the surface modification of TiO{sub 2} nanotubes with ZnS quantum dots was found to produce a red shift in the ultra violet emission band. The TiO{sub 2} nanotubes used in this work were obtained by sol–gel template synthesis. The ZnS quantum dots were deposited onto TiO{sub 2} nanotube surface by a micelle-template inducing reaction. The structure and morphology of the resulting hybrid TiO{sub 2}/ZnS nanotubes were investigated by scanning electron microscopy, transmission electron microscopy and X-ray diffraction techniques. According to the results of fluorescence spectroscopy, pure TiO{sub 2} nanotubes exhibited a high emission at 380 nm (3.26 eV), whereas TiO{sub 2}/ZnS exhibited an emission at 410 nm (3.02 eV). The TiO{sub 2}/ZnS nanotubes demonstrated good bio-imaging ability on sycamore cultured plant cells. The biocompatibility against mammalian cells (Chinese Hamster Ovarian Cells—CHO) suggesting that TiO{sub 2}/ZnS may also have suitable optical properties for use as biological markers in diagnostic medicine. The drug release characteristic of TiO{sub 2}/ZnS nanotubes was explored using 5-fluorouracil (5-FU), an anticancer drug used in photodynamic therapy. The results show that the TiO{sub 2}/ZnS nanotubes are a promising candidate for anticancer drug delivery systems. - Highlights: • TiO{sub 2}/ZnS nanotubes showed a redshift in fluorescence spectrum. • Cytotoxicity against mammalian cells revealed biocompatibility of the nanotubes. • TiO{sub 2}/ZnS proved an efficient delivery system for anti-tumor 5-fluorouracil.
Topical application of ointment containing 0.5% green tea catechins suppresses tongue oxidative stress in 5-fluorouracil administered rats.

Science.gov (United States)

Miyai, Hisataka; Maruyama, Takayuki; Tomofuji, Takaaki; Yoneda, Toshiki; Azuma, Tetsuji; Mizuno, Hirofumi; Sugiura, Yoshio; Kobayashi, Terumasa; Ekuni, Daisuke; Morita, Manabu

2017-10-01

The purpose of this study was to investigate the preventive effects of topical application of green tea catechins on tongue oxidative stress induced by 5-fluorouracil (5-FU) administration in rats. Male Wistar rats (n=28, 8 weeks old) were divided into four groups of seven rats each: a negative control group (saline administration and application of ointment without green tea catechins), a positive control group (5-FU administration and application of ointment without green tea catechins), and two experimental groups (5-FU administration and application of ointment containing 0.1% or 0.5% green tea catechins). Topical application of each ointment to the ventral surface of the tongue was performed once a day for 5days. The level of 8-hydroxydeoxyguanosine (8-OHdG) was determined to evaluate oxidative stress. Fluorescence staining was also performed to confirm nuclear factor erythroid 2-related factor 2 (Nrf2) translocation to the nucleus. After the experimental period, the ratios of 8-OHdG-positive cells in the ventral tongue tissue were higher in the positive control group than in the negative control group (Ptea catechin group, but not in the 0.1% green tea catechin group, were lower than the positive control group (Ptea catechin group than in the positive control group (Ptea catechins could prevent tongue oxidative stress in 5-FU administered rats, via up-regulation of the Nrf2 signaling pathway. Copyright © 2017 Elsevier Ltd. All rights reserved.

Monitoring mixed venous oxygen saturation in patients with obstructive shock after massive pulmonary embolism.

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Krivec, Bojan; Voga, Gorazd; Podbregar, Matej

2004-05-31

Patients with massive pulmonary embolism and obstructive shock usually require hemodynamic stabilization and thrombolysis. Little is known about the optimal and proper use of volume infusion and vasoactive drugs, or about the titration of thrombolytic agents in patients with relative contraindication for such treatment. The aim of the study was to find the most rapidly changing hemodynamic variable to monitor and optimize the treatment of patients with obstructive shock following massive pulmonary embolism. Ten consecutive patients hospitalized in the medical intensive care unit in the community General Hospital with obstructive shock following massive pulmonary embolism were included in the prospective observational study. Heart rate, systolic arterial pressure, central venous pressure, mean pulmonary-artery pressure, cardiac index, total pulmonary vascular-resistance index, mixed venous oxygen saturation, and urine output were measured on admission and at 1, 2, 3, 4, 8, 12, and 16 hours. Patients were treated with urokinase through the distal port of a pulmonary-artery catheter. At 1 hour, mixed venous oxygen saturation, systolic arterial pressure and cardiac index were higher than their admission values (31+/-10 vs. 49+/-12%, p<0.0001; 86+/-12 vs. 105+/-17 mmHg, p<0.01; 1.5+/-0.4 vs. 1.9+/-0.7 L/min/m2, p<0.05; respectively), whereas heart rate, central venous pressure, mean pulmonary-artery pressure and urine output remained unchanged. Total pulmonary vascular-resistance index was lower than at admission (29+/-10 vs. 21+/-12 mmHg/L/min/m2, p<0.05). The relative change of mixed venous oxygen saturation at hour 1 was higher than the relative changes of all other studied variables (p<0.05). Serum lactate on admission and at 12 hours correlated to mixed venous oxygen saturation (r=-0.855, p<0.001). In obstructive shock after massive pulmonary embolism, mixed venous oxygen saturation changes more rapidly than other standard hemodynamic variables.
Core Cross-linked Star Polymers for Temperature/pH Controlled Delivery of 5-Fluorouracil

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Elizabeth Sánchez-Bustos

2016-01-01

Full Text Available RAFT polymerization with cross-linking was used to prepare core cross-linked star polymers bearing temperature sensitive arms. The arms consisted of a diblock copolymer containing N-isopropylacrylamide (NIPAAm and 4-methacryloyloxy benzoic acid (4MBA in the temperature sensitive block and poly(hexyl acrylate forming the second hydrophobic block, while ethyleneglycol dimethacrylate was used to form the core. The acid comonomer provides pH sensitivity to the arms and also increases the transition temperature of polyNIPAAm to values in the range of 40 to 46°C. Light scattering and atomic force microscopy studies suggest that loose core star polymers were obtained. The star polymers were loaded with 5-fluorouracil (5-FU, an anticancer agent, in values of up to 30 w/w%. In vitro release experiments were performed at different temperatures and pH values, as well as with heating and cooling temperature cycles. Faster drug release was obtained at 42°C or pH 6, compared to normal physiological conditions (37°C, pH 7.4. The drug carriers prepared acted as nanopumps changing the release kinetics of 5-FU when temperatures cycles were applied, in contrast with release rates at a constant temperature. The prepared core cross-linked star polymers represent advanced drug delivery vehicles optimized for 5-FU with potential application in cancer treatment.
Subcutaneous insulin infusion: change in basal infusion rate has no immediate effect on insulin absorption rate

International Nuclear Information System (INIS)

Hildebrandt, P.; Birch, K.; Jensen, B.M.; Kuehl, C.

1986-01-01

Eight insulin-dependent diabetic patients were simultaneously given subcutaneous infusions (1.12 IU/h each) of 125 I-labeled Actrapid insulin in each side of the abdominal wall. After 24 h of infusion, the size of the infused insulin depots was measured by external counting for 5 h. The basal infusion rate was then doubled in one side and halved in the other for the next 4 h. Finally, 1.12 IU/h of insulin was given in both sides of the abdominal wall for an additional 3 h. The changes in the size of the depots were measured, and the absorption rates for each hour were calculated. During the first 5 h of infusion, the depot size was almost constant (approximately 5 IU) with an absorption rate that equaled the infusion rate. Doubling the infusion rate led to a significant increase in depot size, but the absorption rate remained unchanged for the first 3 h, and only thereafter was a significant increase seen. When the infusion rate was reduced to the initial 1.12 IU/h, the absorption rate remained elevated during the next 3 h. Correspondingly, when the infusion rate was decreased, the depot size also decreased, but the absorption rate remained unchanged for the first 3 h. The results show that a change in the basal insulin infusion rate does not lead to any immediate change in the insulin absorption rate. This should be considered when planning an insulin-infusion program that includes alteration(s) in the basal-rate setting
Stroke Volume Variation-Guided Versus Central Venous Pressure-Guided Low Central Venous Pressure With Milrinone During Living Donor Hepatectomy: A Randomized Double-Blinded Clinical Trial.

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Lee, Jiwon; Kim, Won Ho; Ryu, Ho-Geol; Lee, Hyung-Chul; Chung, Eun-Jin; Yang, Seong-Mi; Jung, Chul-Woo

2017-08-01

We previously demonstrated the usefulness of milrinone for living donor hepatectomy. However, a less-invasive alternative to central venous catheterization and perioperative contributors to good surgical outcomes remain undetermined. The current study evaluated whether the stroke volume variation (SVV)-guided method can substitute central venous catheterization during milrinone-induced profound vasodilation. We randomly assigned 42 living liver donors to receive either SVV guidance or central venous pressure (CVP) guidance to obtain milrinone-induced low CVP. Target SVV of 9% was used as a substitute for CVP of 5 mm Hg. The surgical field grade evaluated by 2 attending surgeons on a 4-point scale was compared between the CVP- and SVV-guided groups (n = 19, total number of scores = 38 per group) as a primary outcome variable. Multivariable analysis was performed to identify independent factors associated with the best surgical field as a post hoc analysis. Surgical field grades, which were either 1 or 2, were not found to be different between the 2 groups via Mann-Whitney U test (P = .358). There was a very weak correlation between SVV and CVP during profound vasodilation such as CVP ≤ 5 mm Hg (R = -0.06; 95% confidence interval, -0.09 to -0.04; P milrinone infusion might be helpful in providing the best surgical field. Milrinone-induced vasodilation resulted in favorable surgical environment regardless of guidance methods of low CVP during living donor hepatectomy. However, SVV was not a useful indicator of low CVP because of very weak correlation between SVV and CVP during profound vasodilation. In addition, factors contributing to the best surgical field such as donor age, proactive fasting, and proper dosing of milrinone need to be investigated further, ideally through prospective studies.
(Mis)placed central venous catheter in the left superior intercostal vein

International Nuclear Information System (INIS)

Padovan, Ranka Stern; Paar, Maja Hrabak; Aurer, Igor

2010-01-01

Chest X-ray is routinely performed to check the position of the central venous catheter (CVC) inserted through the internal jugular or subclavian vein, while the further evaluation of CVC malfunction is usually performed by contrast venography. In patients with superior vena cava obstruction, the tip of the catheter is often seen in collateral mediastinal venous pathways, rather than in the superior vena cava. In such cases detailed knowledge of thoracic vessel anatomy is necessary to identify the exact location of the catheter. We report a case of 32-year-old female patient with relapsing mediastinal lymphoma and previous superior vena cava obstruction with collateral azygos-hemiazygos venous pathways. The patient had CVC inserted through the left subclavian vein and its position was detected by CT to be in the dilated left superior intercostal vein and accessory hemiazygos vein. Considering that dilated accessory hemiazygos vein can tolerate infusion, the CVC was left in place and the patient had no complaints related to CVC (mal)position. Furthermore, we present anatomical and radiological observations on the azygos-hemiazygos venous system with the special emphasis on the left superior intercostal vein. Non-contrast CT scans can be a valuable imaging tool in the detection of the CVC position, especially in patients with renal insufficiency and contrast media hypersensitivity
Mathematical model of 5-[125I]iodo-2'-deoxyuridine treatment: continuous infusion regimens for hepatic metastases

International Nuclear Information System (INIS)

Sgouros, George; O'Donoghue, Joseph A.; Larson, Steven M.; Macapinlac, Homer; Larson, Justine J.; Kemeny, Nancy

1998-01-01

Purpose: Due to the cytotoxicity of DNA-bound iodine-125, 5-[ 125 I]Iodo-2'-deoxyuridine ([ 125 I]IUdR), an analog of thymidine, has long been recognized as possessing therapeutic potential. In this work, the feasibility and potential effectiveness of hepatic artery infusion of [ 125 I]IUdR is examined. Methods: A mathematical model has been developed that simulates tumor growth and response to [ 125 I]IUdR treatment. The model is used to examine the efficacy and potential toxicity of prolonged infusion therapy. Treatment of kinetically homogeneous tumors with potential doubling times of either 4, 5, or 6 days is simulated. Assuming uniformly distributed activity, absorbed dose estimates to the red marrow, liver and whole-body are calculated to assess the potential toxicity of treatment. Results: Nine to 10 logs of tumor-cell kill over a 7- to 20-day period are predicted by the various simulations examined. The most slowly proliferating tumor was also the most difficult to eradicate. During the infusion time, tumor-cell loss consisted of two components: A plateau phase, beginning at the start of infusion and ending once the infusion time exceeded the potential doubling time of the tumor; and a rapid cell-reduction phase that was close to log-linear. Beyond the plateau phase, treatment efficacy was highly sensitive to tumor activity concentration. Conclusions: Model predictions suggest that [ 125 I]IUdR will be highly dependent upon the potential doubling time of the tumor. Significant tumor cell kill will require infusion durations that exceed the longest potential doubling time in the tumor-cell population
Bronchial arterial infusion versus bronchial combined pulmonary arterial infusion for pulmonary metastatic tumors

International Nuclear Information System (INIS)

Dong Sheng; Dong Weihua; Jia Ningyang; Zhang Dianbo; Xiao Xiangsheng

2008-01-01

Objective: To evaluate the pulmonary metastatic tumor response to different ways of transcatheter arterial infusion. Methods: Thirty-five patients with pulmonary metastatic tumors were randomized divided into two groups: 15 patients with 49 lesions treated with bronchial arterial infusion (BAI) and 20 patients with 65 lesions treated with bronchial arterial infusion (BM)combined with pulmonary arterial infusion (PAI). The therapeutic response was assessed by the WHO evaluation criteria. Results: The total effective rate(CR + PR) of BAI was 65.3% (32/49), PAI + BAI was 61.5%(40/65) showing no statistical difference. The median survival time of BAI was 9 mo, BAI + PAI was 11.5 mo, demonstrating no statistical significance. Conclusions: BAI should be the primary treatment for pulmonary metastatic tumor. (authors)
Studies of hematopoietic stem cells spared by 5-fluorouracil

International Nuclear Information System (INIS)

Van Zant, G.

1984-01-01

Mouse marrow cells were exposed to 5-fluorouracil (FU) either in vivo or in vitro and the effects on the hematopoietic stem cell compartment were studied. The drug was highly toxic to bone marrow cells including the spleen colony-forming unit (CFU-S) population. The small population of stem cells surviving FU, however, caused a different pattern of spleen colony growth when injected into lethally irradiated mice. Whereas numbers of spleen colonies caused by normal marrow cells remained constant during an 8-14 d period after transplantation, spleen colonies derived from FU-treated marrow cells increased by as much as 100-fold during this time. This effect on stem cells was dose dependent both in vitro and in vivo. When FU was given in vivo, the day 14/day 8 ratio of colonies was greatest 1 d after injection and, over the next 7 d, returned to a near-normal value, that is, unity. A number of studies have shown that the stem cell compartment is heterogeneous with respect to self-replicative capacity and developmental potential. An age structure for the stem cell compartment has been proposed wherein cells with a short mitotic history are more likely to self-replicate than they are to differentiate; hence they are more primitive. I propose that the delayed spleen colony appearance in normal hosts is the result of developmental maturation of the primitive stem cell compartment that survives FU and is responsible for spleen colonies arising around day 14. This maturation, at least initially, occurs in the marrow and leads to the replenishment of the more differentiated CFU-S subsets ablated by FU, which are normally responsible for spleen colonies appearing earlier after transplantation
Thermosensitive hydrogel based on chitosan and its derivatives containing medicated nanoparticles for transcorneal administration of 5-fluorouracil

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Fabiano A

2017-01-01

Full Text Available Angela Fabiano,1 Ranieri Bizzarri,2 Ylenia Zambito1 1Department of Pharmacy, University of Pisa, 2NEST, Istituto Nanoscienze CNR (CNR-NANO and Scuola Normale Superiore, Pisa, Italy Abstract: A thermosensitive ophthalmic hydrogel (TSOH – fluid at 4°C (instillation temperature, semisolid at 35°C (eye temperature, which coupled the dosing accuracy and administration ease of eyedrops with the increased ocular bioavailability of a hydrogel – was prepared by gelling a chitosan hydrochloride (ChHCl solution (27.8 mg/mL medicated with 1.25 mg/mL 5-fluorouracil (5-FU with β-glycerophosphate 0.8 mg/mL. Polymer mixtures, where Ch was partially (10%, 15%, or 20% replaced by quaternary ammonium–chitosan conjugates (QA-Ch or thiolated derivatives thereof, were also used to modulate 5-FU-release properties of TSOH. Also, Ch-based nanoparticles (NPs; size after lyophilization and redispersion 341.5±15.2 nm, polydispersity 0.315±0.45, ζ-potential 10.21 mV medicated with 1.25 mg/mL 5-FU prepared by ionotropic cross-linking of Ch with hyaluronan were introduced into TSOH. The 5-FU binding by TSOH polymers in the sol state was maximum with plain Ch (31.4% and tended to decrease with increasing QA presence in polymer mixture. 5-FU release from TSOH with or without NPs was diffusion-controlled and linear in √t. The different TSOH polymers were compared on a diffusivity basis by comparing the slopes of √t plots. These showed a general decrease with NP-containing TSOH, which was the most marked with the TSOH, where Ch was 20% replaced by the derivative QA-Ch50. This formulation and that not containing NP were instilled in rabbits and the 5-FU transcorneal penetration was measured by analyzing the aqueous humor. Both TSOH solutions increased the area under the curve (0–8 hours 3.5 times compared with the plain eyedrops, but maximum concentration for the NP-free TSOH was about 0.65 µg/mL, followed by a slow decline, while the NP-containing one showed a
Design of Infusion Schemes for Neuroreceptor Imaging: Application to [11C]Flumazenil-PET Steady-State Study

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Ling Feng

2016-01-01

Full Text Available This study aims at developing a simulation system that predicts the optimal study design for attaining tracer steady-state conditions in brain and blood rapidly. Tracer kinetics was determined from bolus studies and used to construct the system. Subsequently, the system was used to design inputs for bolus infusion (BI or programmed infusion (PI experiments. Steady-state quantitative measurements can be made with one short scan and venous blood samples. The GABAA receptor ligand [C11]Flumazenil (FMZ was chosen for this purpose, as it lacks a suitable reference region. Methods. Five bolus [C11]FMZ-PET scans were conducted, based on which population-based PI and BI schemes were designed and tested in five additional healthy subjects. The design of a PI was assisted by an offline feedback controller. Results. The system could reproduce the measurements in blood and brain. With PI, [C11]FMZ steady state was attained within 40 min, which was 8 min earlier than the optimal BI (B/I ratio = 55 min. Conclusions. The system can design both BI and PI schemes to attain steady state rapidly. For example, subjects can be [C11]FMZ-PET scanned after 40 min of tracer infusion for 40 min with venous sampling and a straight-forward quantification. This simulation toolbox is available for other PET-tracers.
Short-lasting systemic and regional benefits of early crystalloid infusion after intravenous inoculation of dogs with live Escherichia coli

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Garrido A.G.

2005-01-01

Full Text Available We investigated the systemic and regional hemodynamic effects of early crystalloid infusion in an experimental model of septic shock induced by intravenous inoculation with live Escherichia coli. Anesthetized dogs received an intravenous infusion of 1.2 x 10(10 cfu/kg live E. coli in 30 min. After 30 min of observation, they were randomized to controls (no fluids; N = 7, or fluid resuscitation with lactated Ringer's solution, 16 ml/kg (N = 7 or 32 ml/kg (N = 7 over 30 min and followed for 120 min. Cardiac index, portal blood flow, mean arterial pressure, systemic and regional oxygen-derived variables, blood lactate, and gastric PCO2 were assessed. Rapid and progressive cardiovascular deterioration with reduction in cardiac output, mean arterial pressure and portal blood flow (~50, ~25 and ~70%, respectively was induced by the live bacteria challenge. Systemic and regional territories showed significant increases in oxygen extraction and in lactate levels. Significant increases in venous-arterial (~9.6 mmHg, portal-arterial (~12.1 mmHg and gastric mucosal-arterial (~18.4 mmHg PCO2 gradients were also observed. Early fluid replacement, especially with 32 ml/kg volumes of crystalloids, promoted only partial and transient benefits such as increases of ~76% in cardiac index, of ~50% in portal vein blood flow and decreases in venous-arterial, portal-arterial, gastric mucosal-arterial PCO2 gradients (7.2 ± 1.0, 7.2 ± 1.3 and 9.7 ± 2.5 mmHg, respectively. The fluid infusion promoted only modest and transient benefits, unable to restore the systemic and regional perfusional and metabolic changes in this hypodynamic septic shock model.
Manual Aspiration Thrombectomy with Stent Placement: Rapid and Effective Treatment for Phlegmasia Cerulea Dolens with Impending Venous Gangrene

International Nuclear Information System (INIS)

Oguzkurt, Levent; Tercan, Fahri; Ozkan, Ugur

2008-01-01

Phlegmasia cerulea dolens is an uncommon but potentially life-threatening complication of acute deep vein thrombosis. It is an emergency and delay in treatment may cause death or loss of the patient's limb. Surgical thrombectomy is the recommended treatment in venous gangrene. Catheter-directed intrathrombus thrombolysis has been reported as successful, but it may require a lengthy infusion. Manual aspiration thrombectomy may clear the entire thrombus with no need for thrombolytic administration and provide rapid and effective treatment for patients with phlegmasia cerulea dolens with impending venous gangrene
Technical note: Measurement of mammary plasma flow in sows by downstream dilution of mammary vein infused para-aminohippuric acid

DEFF Research Database (Denmark)

Larsen, Uffe Krogh; Storm, Adam Christian; Theil, Peter Kappel

2016-01-01

catheter was surgically implanted in the femoral artery, and another 2 were inserted in the right cranial mammary vein of 8 second- and third-parity sows on d 76 ± 2 SEM of gestation. On the 3rd and 17th days in milk, arterial and venous blood samples were drawn in hourly intervals from 0.5 h before until...... 6.5 h after feeding. The MPF in the right cranial mammary vein was measured by downstream dilution of infused pAH (3.0 mmol/h). Total MPF-pAH was calculated assuming that the measured flow constituted the flow from 5 out of 14 suckled glands on the basis of the anatomical structure of the mammary...
Role of Catheter-directed Thrombolysis in Management of Iliofemoral Deep Venous Thrombosis.

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Chen, James X; Sudheendra, Deepak; Stavropoulos, S William; Nadolski, Gregory J

2016-01-01

The treatment for iliofemoral deep venous thrombosis (DVT) is challenging, as the use of anticoagulation alone can be insufficient for restoring venous patency and thus lead to prolongation of acute symptoms and an increased risk of chronic complications, including venous insufficiency and postthrombotic syndrome (PTS). In these cases, earlier and more complete thrombus removal can ameliorate acute symptoms and reduce long-term sequelae. Endovascular therapies involving the use of pharmacologic, mechanical, and combined pharmacomechanical modalities have been developed to achieve these goals. The most frequently used of these techniques, catheter-directed thrombolysis (CDT), involves the infusion of a thrombolytic agent through a multiple-side-hole catheter placed within the thrombosed vein to achieve high local doses and thereby break down the clot while minimizing systemic thrombolytic agent exposure. Randomized controlled trial results have indicated decreased PTS rates and improved venous patency rates in patients treated with CDT compared with these rates in patients treated with anticoagulation. The use of newer pharmacomechanical techniques, as compared with conventional CDT, reduces procedural times and thrombolytic agent doses and is the subject of ongoing investigations. Endovascular thrombus removal techniques offer a means to improve venous valvular function and decrease the risk of debilitating long-term complications such as PTS and are a promising option for treating patients with iliofemoral DVT. (©)RSNA, 2016.
Clinical observation of needle revision and 5-fluorouracil subconjunctive injection for the dysfunctional filtering blebs

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Yan-Hua Gao

2016-07-01

Full Text Available AIM:To investigate the efficacy and safety of needle revision with 5-fluorouracil(5-FUon the dysfunctional filtering blebs after trabeculectomy and to assess the factors that may impact the success. METHODS:Eighty-three eyes in 76 patients underwent the needle revision and 5-FU subconjunctive injection for the dysfunctional blebs after trabeculectomy and were followed up for 12mo. The intraocular pressure(IOP, the number of drugs, corneal endothclium, bleb morphology and complications were observed and recorded. RESULTS:IOP decreased significantly from 35.3±5.8mmHg(1kPa=7.5mmHgof pre-needling to 17.0±4.3mmHg of post-needling(PPCI: 10.3-11.6. Statistically, there were no significant difference on needling effect with reference to the types of glaucoma, the use of mitomycin C(MMCduring the previous filtration surgery, the ages of patients, the intervals of needling operation from previous trabeculectomy, while there were significant difference on needling effect with reference to bleb appearance before needling, and the mean number of needling in patients that had surgery within 3mo were less than those who had surgery for more than 3mo. CONCLUSION: The needle revision combined with 5-FU is a safe, effective and simple method. Dysfunctional blebs should be treated early after trabeculectomy.
A Phase II Study of Docetaxel, Cisplatin and 5- Fluorouracil (TPF) In Patients with Locally Advanced Head and Neck Carcinomas.

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Ansari, M; Omidvari, S; Mosalaei, A; Ahmadloo, N; Mosleh-Shirazi, M A; Mohammadianpanah, M

2011-03-01

The combination of cisplatin and 5-fluorouracil (PF) is currently considered a standard and effective regimen for the treatment of advanced head and neck carcinomas. The aim of this study was to evaluate the efficacy and safety of docetaxel, cisplatin and 5-fluorouracil (TPF) in patients with unresectable head and neck carcinomas. Forty-six patients with previously untreated non-metastatic stage IV head and neck carcinomas were enrolled. All patients received three cycles of induction chemotherapy with docetaxel (75 mg/m(2)), cisplatin (40 mg/m(2)) (days 1-2), and 5-FU (500 mg/m(2), days 1-3), repeated every 21 days. Following induction chemotherapy, all patients underwent concurrent chemoradiotherapy using weekly cisplatin (30 mg/m(2)) and a median total dose of 70 Gy was delivered. Clinical response rate and toxicity were the primary and secondary end-points of the study. There were 31 men and 15 women. All patients had non-metastatic stage IV (T2-3N2-3 or T4N0-3) of disease. Overall and complete response rates were 74% and 24% respectively. Advanced T4 classification was associated with poorer response rate (p value=0.042). The major (grade 3-4) treatment-related toxicities were myelosuppression (78%), anorexia (13%), diarrhea (7%), emesis (11%) and stomatitis/pharyngitis (24%). In comparison with the data of historical published trials of the PF regimen, the TPF regimen was more effective. However, the TPF regimen appears to be associated with a higher incidence of major toxicities. Therefore, our limited findings support the TPF regimen as an alternative chemotherapeutic regimen for advanced head and neck carcinomas.
[Influence of an infusion of 5- or 20% glucose solution on blood glucose and inorganic phosphate concentrations in dairy cows].

Science.gov (United States)

Aldaek, T A A; Failing, K; Wehrend, A; Klymiuk, M C

2011-01-01

The study was performed to evaluate the influence of an intravenous infusion of 5% and 20% dextrose solution on the plasma concentration of glucose and inorganic phosphate in healthy, dairy cows. Ten healthy, lactating, nonpregnant 3 to 6 year-old Holstein-Friesian cows were included in this investigation. The daily milk yield was 20.3±2.7 liters. Blood plasma concentrations of inorganic phosphate and glucose were determined before, during, immediately and 60 minutes after infusion of 0.9% physiological saline, 5% or 20% dextrose solution. A statistically significant influence of dextrose infusion on blood glucose concentration was observed. After 20% dextrose infusion (200 g dextrose) the blood glucose concentration increased by approximately 13.26 mmol/l. The administration of 5% dextrose solution (50 g dextrose) yielded an increase of blood glucose concentration by 3.31 mmol/l. There was no significant correlation between plasma inorganic phosphate concentrations and infusion of 0.9% saline, 5% or 20% dextrose solution. Intravenous administration of 1000 ml of 5% or 20% dextrose solution does not induce a lasting plasma phosphate reduction and is suitable for elevating the blood glucose concentration.
A nanomedicine-promising approach to provide an appropriate colon-targeted drug delivery system for 5-fluorouracil

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Singh S

2015-11-01

Full Text Available Sima Singh,1,* Niranjan G Kotla,2,* Sonia Tomar,3 Balaji Maddiboyina,4 Thomas J Webster,5,6 Dinesh Sharma,7 Omprakash Sunnapu2 1Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi, Jharkhand, 2Technologies for the Advancement of Science, Institute for Stem Cell Biology and Regenerative Medicine, Bangalore, Karnataka, 3Department of Pharmaceutics, Ram Gopal College of Pharmacy, Rohtak, Haryana, 4Department of Pharmaceutics, Maharishi Markandeshwar University, Mullana, Ambala, Haryana, India; 5Department of Chemical Engineering, Northeastern University, Boston, MA, USA; 6Center of Excellence for Advanced Materials Research, King Abdulaziz University, Jeddah, Saudi Arabia; 7Ranbaxy Laboratory Ltd, Gurgaon, Haryana, India *These authors contributed equally to this work Abstract: Targeted drug delivery plays a significant role in disease treatment associated with the colon, affording therapeutic responses for a prolonged period of time with low side effects. Colorectal cancer is the third most common cancer in both men and women with an estimated 102,480 cases of colon cancer and 40,340 cases of rectal cancer in 2013 as reported by the American Cancer Society. In the present investigation, we developed an improved oral delivery system for existing anticancer drugs meant for colon cancer via prebiotic and probiotic approaches. The system comprises three components, namely, nanoparticles of drug coated with natural materials such as guar gum, xanthan gum (that serve as prebiotics, and probiotics. The natural gums play a dual role of protecting the drug in the gastric as well as intestinal conditions to allow its release only in the colon. In vitro results obtained from these experiments indicated the successful targeted delivery of 5-fluorouracil to the colon. Electron microscopy results demonstrated that the prepared nanoparticles were spherical in shape and 200 nm in size. The in vitro release data
Biweekly cetuximab and irinotecan as third-line therapy in patients with advanced colorectal cancer after failure to irinotecan, oxaliplatin and 5-fluorouracil

DEFF Research Database (Denmark)

Pfeiffer, P.; Nielsen, Dorte; Bjerregaard, J.

2008-01-01

-resulting in an overall treatment time of 90 min. Results: All patients had ACRC resistant to 5-fluorouracil and irinotecan and 95% to oxaliplatin. Median age was 63 years, median performance status was 0. Median duration of therapy was 4.3 months. Response rate was 25%. Median progression-free survival and overall...... survival were 5.4 months and 8.9 months, respectively, comparable to own historical controls receiving weekly CetIri. Grade 3-4 toxicity was rare (skin 7%, nail 3%, diarrhoea 10%, fatigue 3%, neutropenia 9%). One patient experienced severe allergic reaction. Conclusion: Salvage therapy with simplified...
In situ delivery of thermosensitive gel-mediated 5-fluorouracil microemulsion for the treatment of colorectal cancer

Science.gov (United States)

Wang, Lu-Lu; Huang, Shuai; Guo, Hui-Hui; Han, Yan-Xing; Zheng, Wen-Sheng; Jiang, Jian-Dong

2016-01-01

In situ administration of 5-fluorouracil (5FU) “thermosensitive” gel effectively reduced systemic side effects in treating colon rectal cancer; however, the penetration efficacy of the formulation was considerably low due to the poor lipid solubility of 5FU. The aim of this study was to develop thermosensitive gel-mediated 5FU water-in-oil microemulsion (TG-5FU-ME) for improving the infiltration of 5FU. An in vitro release test showed that TG-5FU-ME sustained the drug’s release up to 10 hours. TG-5FU-ME exhibited good stability, and the microemulsion entrapped did not show any change in morphology and 5FU content during the 4-month storage. Transportation test in the Caco-2 cell monolayer showed that TG-5FU-ME had a permeability 6.3 times higher than that of 5FU thermosensitive gel, and the intracellular uptake of 5FU increased by 5.4-fold compared to that of 5FU thermosensitive gel. In vivo tissue distribution analysis exhibited that the TG-5FU-ME group had drug levels in rectal tissue and mesenteric lymph nodes, which were significantly higher than those of 5FU thermosensitive gel group, with very low blood levels of 5FU in both groups. Furthermore, TG-5FU-ME was not associated with detectable morphological damage to the rectal tissue. Conclusively, TG-5FU-ME might be an efficient rectal delivery system to treat colorectal cancer. PMID:27660416

Chrysin Attenuates Cell Viability of Human Colorectal Cancer Cells through Autophagy Induction Unlike 5-Fluorouracil/Oxaliplatin.

Science.gov (United States)

Lin, Yueh-Ming; Chen, Chih-I; Hsiang, Yi-Ping; Hsu, Yung-Chia; Cheng, Kung-Chuan; Chien, Pei-Hsuan; Pan, Hsiao-Lin; Lu, Chien-Chang; Chen, Yun-Ju

2018-06-14

Chemotherapeutic 5-fluorouracil (5-FU) combined with oxaliplatin is often used as the standard treatment for colorectal cancer (CRC). The disturbing side effects and drug resistance commonly observed in chemotherapy motivate us to develop alternative optimal therapeutic options for CRC treatment. Chrysin, a natural and biologically active flavonoid abundant in propolis, is reported to have antitumor effects on a few CRCs. However, whether and how chrysin achieves similar effectiveness to the 5-FU combination is not clear. In this study, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), western blotting, fluorescence microscopy, and reactive oxygen species (ROS) production were assayed. We found that chrysin exhibited similar inhibition of cell viability as the 5-FU combination in a panel of human CRC cells. Furthermore, the results showed that chrysin significantly increased the levels of LC3-II, an autophagy-related marker, in CRC cells, which was not observed with the 5-FU combination. More importantly, blockage of autophagy induction restored chrysin-attenuated CRC cell viability. Further mechanistic analysis revealed that chrysin, not the 5-FU combination, induced ROS generation, and in turn, inhibited the phosphorylation of protein kinase B (Akt) and mammalian target of rapamycin (mTOR). Collectively, these results imply that chrysin may be a potential replacement for the 5-FU and oxaliplatin combination to achieve antitumor activity through autophagy for CRC treatment in the future.
Acquisition of 5-fluorouracil resistance induces epithelial-mesenchymal transitions through the Hedgehog signaling pathway in HCT-8 colon cancer cells.

Science.gov (United States)

Liu, Yanjun; DU, Fangfang; Zhao, Qiannan; Jin, Jian; Ma, Xin; Li, Huazhong

2015-06-01

Colon cancer has a high incidence in individuals >60-years-old. The commonly used chemotherapeutic agent, 5-fluorouracil (5-FU), has gradually lost its potency in treating colorectal cancer following the acquisition of resistance. Drug resistance is usually associated with epithelial-mesenchymal transitions (EMTs) in cancer cells. In the present study, the EMT phenotypes of two colon cancer cell lines, wild-type (HCT-8/WT) and 5-FU-resistant (HCT-8/5-FU), were characterized following the analysis of cellular migration, proliferation, morphology and molecular changes. In order to further clarify the mechanism of EMT in HCT-8/5-FU cells, the effect of EMT pathway inhibitors upon drug sensitivity was investigated. The results revealed that the Hedgehog signaling pathway inhibitor, GDC0449, reversed drug resistance. Therefore, inhibition of the Hedgehog pathway may provide a novel chemotherapeutic strategy for the treatment of patients with 5-FU-resistant colon cancer.
Thrombolytic treatment for acute ischemic cerebral stroke: intraarterial urokinase infusion vs. intravenous heparin and urokinase infusion

International Nuclear Information System (INIS)

Ko, Gi Young; Suh, Dae Chul; Lee, Jae Hong; Kim, Jun Hyoung; Choi, Choong Gon; Lee, Ho Kyu; Lee, Myoung Chong

1996-01-01

To evaluate the efficacy and limitation of intra-arterial urokinase (IAUK) infusion for treatment of acute cerebral stroke. Twenty-seven acute cerebral stroke patients treated with IAUK infusion within six hours of stroke onset were reviewed. All patients showed normal initial brain findings on CT. In 21 patients, urokinase(5-15 x 10 5 IU) was administered through a microcatheter placed into or proximal to occluded segment. Mechanical disruption of thrombus by guidewire was performed in 17 patients. Angiographic and clinical responses and complications after IAUK infusion, were evaluated and the results were compared with those of intravenous heparin(N=19) and urokinase infusion(N=19). Complete or partial angiographic recanalization of occluded segment was found in 18 patients (67%), and neurologic improvement was followed in 14 patients(52%). The degree of improvement on the stroke scale score after IAUK infusion was statistically more significant(p<0.05) than that shown after intravenous heparin and urokinase infusion. Complications after IAUK infusion were large(15%) and small amount intracerebral hemorrhage(15%), contrast leakage into brain parenchyma(11%), and gastrointestinal bleeding(4%). Between the IAVK and the intravenous urokinase infusion group, differences in extent and types of complications were statistically insignificant, but were significantly higher in those two groups than in the intravenous heparin infusion group. IAUK infusion may be effective for the treatment of acute cerebral stroke
Anti-mitotic potential of 7-diethylamino-3(2′-benzoxazolyl)-coumarin in 5-fluorouracil-resistant human gastric cancer cell line SNU620/5-FU

International Nuclear Information System (INIS)

Kim, Nam Hyun; Kim, Su-Nam; Oh, Joa Sub; Lee, Seokjoon; Kim, Yong Kee

2012-01-01

Highlights: ► DBC exerts antiproliferative potential against 5FU-resistant human gastric cancer cells. ► This effect is mediated by destabilization of microtubules and subsequent mitotic arrest. ► DBC enhances apoptosis via caspase activation and downregulation of antiapoptotic genes. -- Abstract: In this study, we investigate an anti-mitotic potential of the novel synthetic coumarin-based compound, 7-diethylamino-3(2′-benzoxazolyl)-coumarin, in 5-fluorouracil-resistant human gastric cancer cell line SNU-620-5FU and its parental cell SNU-620. It exerts the anti-proliferative effects with similar potencies against both cancer cells, which is mediated by destabilization of microtubules and subsequent mitotic arrest. Furthermore, this compound enhances caspase-dependent apoptotic cell death via decreased expression of anti-apoptotic genes. Taken together, our data strongly support anti-mitotic potential of 7-diethylamino-3(2′-benzoxazolyl)-coumarin against drug-resistant cancer cells which will prompt us to further develop as a novel microtubule inhibitor for drug-resistant cancer chemotherapy.
Urethro-venous intravasation during retrograde urethrography (report of 5 cases.

Directory of Open Access Journals (Sweden)

Gupta S

1991-04-01

Full Text Available Five instances of urethro-venous intravasation during retrograde urethrography are reported. Four cases were of urethral strictures and one case was of urethral hemangioma. All patients had post procedural bleeding while one patient got allergic reactions, another showed chills and rigors. Anatomy of the drainage veins is described. Factors responsible for this complication and its clinical implications are discussed. It is suggested that urethro-venous intravasation should be considered a diagnostic sign of urethral inflammation.
Analysis of the vertebral venous system in relation to cerebral venous drainage on MR angiography

International Nuclear Information System (INIS)

Baik, Seung Kug; Sohn, Chul Ho; Kim, Gab Chul; Kim, Yong Sun

2004-01-01

In the supine position, cerebral venous drainage occurs primarily through the internal jugular veins, as seen on venous phase cerebral angiography. However, in the erect position, the vertebral venous system represents the major alternative pathway of cerebral venous drainage, while outflow through the internal jugular veins is absent or negligible. The purpose of this study is to evaluate the vertebral venous system and its relationship between the surrounding venous structures using magnetic resonance angiography (MRA) in the case of subjects in the supine position. We retrospectively reviewed the results of 65 patients (M:F = 31: 34, mean age 61.6 years) who underwent multi-phase contrast-enhanced carotid MRA. The imaging studies were performed using a 3.0 T MR unit (TR: 5.2, TE: 1.1, FA: 20, 3.8 thickness, EC: 1). We analyzed the appearance and extent of the vertebral venous system (vertebral venous plexus and vertebral artery venous plexus) and the internal jugular vein on the venous phase images. We also evaluated the main drainage pattern of the cerebral venous drainage and the drainage pattern of the vertebral venous system. The visualized vertebral venous system was defined as either poor, vertebral venous plexus dominant, vertebral artery venous plexus dominant or mixed. In the vertebral venous system, the vertebral artery venous plexus was visualized in 54 cases (83%). The appearance of the visualized vertebral artery venous plexus was symmetrical in 39 cases (72%) and asymmetrical in 15 cases (28%). The extent of the visualized vertebral artery venous plexus was partial in 26 cases (48%) and complete in 28 cases (52%). The vertebral venous plexus was visualized in 62 cases (95%). The appearance of the visualized vertebral artery venous plexus was symmetrical in 43 cases (69%) and asymmetrical in 19 cases (31%). The extent of the visualized vertebral artery venous plexus was partial in 35 cases (56%) and complete in 27 cases (44%). The appearance of the
Sucralfate mouthwash for prevention and treatment of 5-fluorouracil-induced mucositis: a randomized, placebo-controlled trial.

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Nottage, Michelle; McLachlan, Sue-Anne; Brittain, Mary-Anne; Oza, Amit; Hedley, David; Feld, Ronald; Siu, Lillian L; Pond, Gregory; Moore, Malcolm J

2003-01-01

A randomized, double-blind, placebo-controlled trial was conducted to evaluate the effectiveness of a sucralfate mouthwash in preventing and alleviating oral mucositis induced by 5-fluorouracil (5FU). A total of 81 patients with colorectal cancer were enrolled. Patients were studied during their first cycle of chemotherapy with 5FU and leucovorin (LV) daily for 5 days every 4 weeks (Mayo Clinic schedule). Patients were randomly allocated to receive either a sucralfate suspension or a placebo suspension that was identical in appearance. Patients were instructed to use the suspension as a mouthwash four times daily from the beginning of the chemotherapy cycle. All patients received oral cryotherapy. Patients graded the severity of their own symptoms on a daily basis, and this was the primary outcome measure. There was no difference in the frequency or severity of oral mucositis between the sucralfate- and the placebo-treated group. Some mucositis was reported by 79% of the patient group. Assessment of mucositis by trial staff underestimated the incidence of this problem. Results of this trial do not support the hypothesis that a sucralfate mouthwash can prevent or alleviate oral mucositis induced by 5FU. Patient reporting of mucositis is a more sensitive instrument for assessment of mucositis than review by medical staff.
Cytocompatible chitosan-graft-mPEG-based 5-fluorouracil-loaded polymeric nanoparticles for tumor-targeted drug delivery.

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Antoniraj, M Gover; Ayyavu, Mahesh; Henry, Linda Jeeva Kumari; Nageshwar Rao, Goutham; Natesan, Subramanian; Sundar, D Sathish; Kandasamy, Ruckmani

2018-03-01

Biodegradable materials like chitosan (CH) and methoxy polyethylene glycol (mPEG) are widely being used as drug delivery carriers for various therapeutic applications. In this study, copolymer (CH-g-mPEG) of CH and carboxylic acid terminated mPEG was synthesized by carbodiimide-mediated acid amine reaction. The resultant hydrophilic copolymer was characterized by Fourier transform infrared spectroscopy and 1 H NMR studies, revealing its relevant functional bands and proton peaks, respectively. Blank polymeric nanoparticles (B-PNPs) and 5-fluorouracil loaded polymeric nanoparticles (5-FU-PNPs) were formulated by ionic gelation method. Furthermore, folic acid functionalized FA-PNPs and FA-5-FU-PNPs were prepared for folate receptor-targeted drug delivery. FA-5-FU-PNPs were characterized by particle size, zeta potential, and in vitro drug release studies, resulting in 197.7 nm, +29.9 mv, and sustained drug release of 88% in 24 h, respectively. Cytotoxicity studies were performed for FA-PNPs and FA-5-FU-PNPs in MCF-7 cell line, which exhibited a cell viability of 80 and 41%, respectively. In vitro internalization studies were carried out for 5-FU-PNPs and FA-5-FU-PNPs which demonstrated increased cellular uptake of FA-5-FU-PNPs by receptor-mediated transport. Significant (p drug delivery, thereby influencing better therapeutic effect.
CD133+CD24lo defines a 5-Fluorouracil-resistant colon cancer stem cell-like phenotype

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Paschall, Amy V.; Yang, Dafeng; Lu, Chunwan; Redd, Priscilla S.; Choi, Jeong-Hyeon; Heaton, Christopher M.; Lee, Jeffrey R.; Nayak-Kapoor, Asha; Liu, Kebin

2016-01-01

The chemotherapeutic agent 5-Fluorouracil (5-FU) is the most commonly used drug for patients with advanced colon cancer. However, development of resistance to 5-FU is inevitable in almost all patients. The mechanism by which colon cancer develops 5-FU resistance is still unclear. One recently proposed theory is that cancer stem-like cells underlie colon cancer 5-FU resistance, but the phenotypes of 5-FU-resistant colon cancer stem cells are still controversial. We report here that 5-FU treatment selectively enriches a subset of CD133+ colon cancer cells in vitro. 5-FU chemotherapy also increases CD133+ tumor cells in human colon cancer patients. However, sorted CD133+ colon cancer cells exhibit no increased resistance to 5-FU, and CD133 levels exhibit no correlation with colon cancer patient survival or cancer recurrence. Genome-wide analysis of gene expression between sorted CD133+ colon cancer cells and 5-FU-selected colon cancer cells identifies 207 differentially expressed genes. CD24 is one of the genes whose expression level is lower in the CD133+ and 5-FU-resistant colon cancer cells as compared to CD133+ and 5-FU-sensitive colon cancer cells. Consequently, CD133+CD24lo cells exhibit decreased sensitivity to 5-FU. Therefore, we determine that CD133+CD24lo phenotype defines 5-FU-resistant human colon cancer stem cell-like cells. PMID:27659530
Catheter-directed thrombolysis of below-knee deep venous thrombosis of the lower extremities

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Roh, Byung Suk; Sohn, Young Jun; Heo, Eun A; Cho, Hyun Sun; Park, Seong Hoon; Lee, Young Hwan [Wonkwang University Hospital, Iksan (Korea, Republic of)

2008-02-15

To evaluate the technical feasibility and clinical efficacy of the use of local thrombolysis for below-knee deep vein thrombosis (DVT). From a population of 41 patients with a lower extremity DVT, the prospective clinical trial included 11 patients (7 female, 4 male, average age 61.4 years) treated with catheter-directed thrombolysis with urokinase for below-knee DVT. After removal of the proximal ilofemoral DVT, additional interventional procedures to remove the residual thrombosis and restore the venous flow from the below-knee vein were performed in cases of continuous occlusion of venous flow from the popliteal and tibial veins. Under ultrasound (US) guidance, catheter-directed thrombolysis with urokinase was performed through the ipsilateral popliteal vein. After administration of oral anticoagulation therapy, CT and venography were performed to identify patency and the presence of a recurrent thrombosis. Successful removal of the thrombus and restoration of venous flow were achieved in all of the patients (100%). Restoration of flow with a residual thrombus occurred in one case. Focal venous stenosis was discovered in four cases. The duration of urokinase infusion was 1-4 days (average 2.36 days), which was considered long. For 15.2 months, the venous lumen of all cases was preserved without a recurrent thrombosis. Catheter-directed thrombolysis is an effective procedure for recanalization of below-knee DVT in patients with a lower extremity DVT.
Catheter-directed thrombolysis of below-knee deep venous thrombosis of the lower extremities

International Nuclear Information System (INIS)

Roh, Byung Suk; Sohn, Young Jun; Heo, Eun A; Cho, Hyun Sun; Park, Seong Hoon; Lee, Young Hwan

2008-01-01

To evaluate the technical feasibility and clinical efficacy of the use of local thrombolysis for below-knee deep vein thrombosis (DVT). From a population of 41 patients with a lower extremity DVT, the prospective clinical trial included 11 patients (7 female, 4 male, average age 61.4 years) treated with catheter-directed thrombolysis with urokinase for below-knee DVT. After removal of the proximal ilofemoral DVT, additional interventional procedures to remove the residual thrombosis and restore the venous flow from the below-knee vein were performed in cases of continuous occlusion of venous flow from the popliteal and tibial veins. Under ultrasound (US) guidance, catheter-directed thrombolysis with urokinase was performed through the ipsilateral popliteal vein. After administration of oral anticoagulation therapy, CT and venography were performed to identify patency and the presence of a recurrent thrombosis. Successful removal of the thrombus and restoration of venous flow were achieved in all of the patients (100%). Restoration of flow with a residual thrombus occurred in one case. Focal venous stenosis was discovered in four cases. The duration of urokinase infusion was 1-4 days (average 2.36 days), which was considered long. For 15.2 months, the venous lumen of all cases was preserved without a recurrent thrombosis. Catheter-directed thrombolysis is an effective procedure for recanalization of below-knee DVT in patients with a lower extremity DVT
Venous, Arterialized-Venous, or Capillary Glucose Reference Measurements for the Accuracy Assessment of a Continuous Glucose Monitoring System.

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Kropff, Jort; van Steen, Sigrid C; deGraaff, Peter; Chan, Man W; van Amstel, Rombout B E; DeVries, J Hans

2017-11-01

Different reference methods are used for the accuracy assessment of continuous glucose monitoring (CGM) systems. The effect of using venous, arterialized-venous, or capillary reference measurements on CGM accuracy is unclear. We evaluated 21 individuals with type 1 diabetes using a capillary calibrated CGM system. Venous or arterialized-venous reference glucose samples were taken every 15 min at two separate visits and assessed per YSI 2300 STAT Plus. Arterialization was achieved by heated-hand technique. Capillary samples were collected hourly during the venous reference visit. The investigation sequence (venous or arterialized-venous) was randomized. Effectiveness of arterialization was measured by comparing free venous oxygen pressure (PO2) of both visit days. Primary endpoint was the median absolute relative difference (ARD). Median ARD using arterialized-venous reference samples was not different from venous samples (point estimated difference 0.52%, P = 0.181). When comparing the three reference methods, median ARD was also not different over the full glycemic range (venous 9.0% [n = 681], arterialized-venous 8.3% [n = 684], and capillary 8.1% [n = 205], P = 0.216), nor over the separate glucose ranges. Arterialization was successful (PO2 venous 5.4 kPa vs. arterialized-venous 8.9 kPa, P reference measurements did not significantly impact CGM accuracy. Venous reference seems preferable due to its ease of operation.
Intervention of raltitrexed combined with epirubicin in hepatic arterial infusion and embolization in treatment of primary liver cancer

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WANG Baoxin

2015-05-01

Full Text Available ObjectiveTo evaluate the therapeutic effect of intervention of raltitrexed combined with epirubicin in hepatic arterial infusion and embolization in the treatment of advanced primary liver cancer. MethodsA total of 80 patients with advanced primary liver cancer who were admitted to the Central Hospital of China National Petroleum Corporation from January 2011 to May 2013 and not suitable for surgical treatment were selected and randomly divided into study group (n=40 and control group (n=40. The study group was treated with intervention of raltitrexed combined with epirubicin in hepatic arterial infusion and embolization, while the control group was treated with intervention of fluorouracil (5-FU combined with epirubicin in hepatic arterial infusion and embolization. The treatment was given once every four weeks for a total of three to six circles. The response rate (RR, disease control rate (DCR, median time to progression, survival rate, and the decreases in alpha fetoprotein (AFP, carcinoembryonic antigen (CEA, transaminase, and bilirubin of the two groups were observed. Comparison of categorical data between the two groups was made by chi-square test, and comparison of continuous data was made by t test. ResultsThe RRs of the study group and control group were 52.5% and 22.5%, respectively, and the difference was significant (χ2=7.680, P=0.006; the DCRs of the study group and control group were 87.5% and 60.0%, respectively, and the difference was significant (χ2=7.813, P=0.005; the median time to progression of the study group and control group was 12.2 and 8.0 months, respectively, and the difference was significant (t=5.118, P=0.00; the 1- and 2-year survival rates of the study group were 85.0% and 60.0%, respectively, with the control group being 65.0% and 37.5%, and the difference was significant (χ2=4.267, P=0.039; χ2=4.053, P=0.044. One month after chemoembolization, the number of patients whose AFP, transaminase, and bilirubin
5-Fluorouracil Encapsulated Chitosan Nanoparticles for pH-Stimulated Drug Delivery: Evaluation of Controlled Release Kinetics

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R. Seda Tığlı Aydın

2012-01-01

Full Text Available Nanoparticles consisting of human therapeutic drugs are suggested as a promising strategy for targeted and localized drug delivery to tumor cells. In this study, 5-fluorouracil (5-FU encapsulated chitosan nanoparticles were prepared in order to investigate potentials of localized drug delivery for tumor environment due to pH sensitivity of chitosan nanoparticles. Optimization of chitosan and 5-FU encapsulated nanoparticles production revealed 148.8±1.1 nm and 243.1±17.9 nm particle size diameters with narrow size distributions, which are confirmed by scanning electron microscope (SEM images. The challenge was to investigate drug delivery of 5-FU encapsulated chitosan nanoparticles due to varied pH changes. To achieve this objective, pH sensitivity of prepared chitosan nanoparticle was evaluated and results showed a significant swelling response for pH 5 with particle diameter of ∼450 nm. In vitro release studies indicated a controlled and sustained release of 5-FU from chitosan nanoparticles with the release amounts of 29.1–60.8% due to varied pH environments after 408 h of the incubation period. pH sensitivity is confirmed by mathematical modeling of release kinetics since chitosan nanoparticles showed stimuli-induced release. Results suggested that 5-FU encapsulated chitosan nanoparticles can be launched as pH-responsive smart drug delivery agents for possible applications of cancer treatments.
5-fluorouracil Toxicity Mechanism Determination in Human Keratinocytes: in vitro Study on HaCaT

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Jan Hartinger

2018-01-01

Full Text Available 5-fluorouracil (5-FU and capecitabine therapy is often accompanied by palmar-plantar erythrodysesthesia (PPE which is manifestation of 5-FU toxicity in keratinocytes. The main mechanisms of 5-FU action are thymidylate synthase (TS inhibition which can be abrogated by thymidine and strengthened by calciumfolinate (CF and incorporation of fluorouridinetriphosphate into RNA which can be abrogated by uridine. For proper PPE treatment 5-FU mechanism of action in keratinocytes needs to be elucidated. We used the 5-FU toxicity modulators uridine, thymidine and CF to discover the mechanism of 5-FU action in human keratinocyte cell line HaCaT. To measure the cellular viability, we used MTT test and RTCA test. CF did not augment 5-FU toxicity and 5-FU toxicity was weakened by uridine. Therefore, the primary mechanism of 5-FU toxicity in keratinocytes is 5-FU incorporation into RNA. The uridine protective effect cannot fully develop in the presence of CF. Thymidine addition to 5-FU and uridine treated cells not only prevents the toxicity-augmenting CF effect but it also prolongs the 5-FU treated cells survival in comparison to uridine only. Therefore, it can be assumed that in the presence of uridine the 5-FU toxicity mechanism is switched from RNA incorporation to TS inhibition. Although particular 5-FU toxicity mechanisms were previously described in various cell types, this is the first time when various combinations of pyrimidine nucleosides and CF were used for 5-FU toxicity mechanism elucidation in human keratinocytes. We suggest that for PPE treatment ointment containing uridine and thymidine should be further clinically tested.
Curcuminoids from Curcuma longaL. reduced intestinal mucositis induced by 5-fluorouracil in mice: Bioadhesive, proliferative, anti-inflammatory and antioxidant effects

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Edvande Xavier dos Santos Filho

Full Text Available Introduction: Intestinal mucositis is a frequent limiting factor in anticancer therapy and there is currently no broadly effective treatment targeted to cure this side effect. Objective: This study aimed to evaluate the effects of a mucoadhesive formulation containing curcuminoids (MFC from Curcuma longa L. on the pathogenesis of 5-fluorouracil (5-FU-induced intestinal mucositis. Methods: Three intraperitoneal 5-FU injections (200 mg/kg were used to induce intestinal mucositis in adult Swiss male mice. Treatment was provided orally (MFC 3.75, 7.5 and 15 mg/kg, thirty minutes before 5-FU injections, daily until euthanasia. Duodenal samples were collected to perform morphometric and histopathological analysis, to investigate the expression of Ki-67, p53, Bax and Bcl-2 by immunohistochemistry, to evaluate neutrophil activity myeloperoxidase (MPO-mediated and oxidative stress by malondialdehyde (MDA determination. Mice body weight was assessed as well. Results: As expected, 5-FU induced a significant weight loss (∼17%, P < 0.001, shortening in villi height (∼55.4% and crypts depth (∼47%, and increased (∼64% the histological severity score when compared to other groups (P < 0.05. These pathological changes were markedly alleviated by the three MFC treatment doses (P < 0.05, in special with the dose MFC 15 mg/kg. This dose also stimulated cell proliferation by ∼90% in the epithelial cells lining from villi and crypts (P < 0.05, reduced MPO levels and MDA formation by 60% and 44%, respectively (P < 0.05. Conclusions: Our data suggest the therapeutic potential of the formulation for treating intestinal mucositis in mice. Supplementary studies are underway searching for the elucidation of mechanisms involved in the protective effects of MFC in order to make this formulation a clinical tool for mucositis treatment. Keywords: Mucoadhesive formulation, Curcuminoids, Curcuma longa L, Intestinal mucositis, 5-Fluorouracil
Preoperative combination therapy of 5-fluorouracil suppository and radiation for carcinoma of the rectum

International Nuclear Information System (INIS)

Mizusawa, Hirokazu

1986-01-01

The effect of adjuvant preoperative treatments with radiation and 5-fluorouracil (5-FU) on rectal carcinomas was investigated. The radiation therapy was administered in the area including the rectum and regional lymph nodes up to the level of the promontorium with 10 doses of 300 rad in three-week periods (a total dose of 3,000 rad). The suppository containing 100 mg of 5-FU was given intrarectally twice daily in the same period (a total dose of 4,000 mg of 5-FU). The surgical procedure with either abdominoperineal excision or anterior resection was performed within 14 days after the last preoperative treatment. The resected specimens were examined microscopically. The mean thickness of excised tumor-free tissue around the rectal wall having the most extended tumor growth was 6.2 mm in 16 patients receiving the treatment with radiation and 5-FU, 3.9 mm in 31 patients with 5-FU alone and 3.7 mm in 19 patients without preoperative treatments. Lymph node metastases were detected in 3 of 17 patients (19 %) with radiation and 5-FU, in 18 of 33 patients (55 %) with 5-FU alone, and in 11 of 24 patients (46 %) without preoperative treatments. The extensive degenerative pictures of cancer cells such as nuclear picnosis, and the growth of collagen fibers in carcinoma foci were observed in resected specimens with radiation and 5-FU treatments. Those findings suggest that preoperative adjuvant therapy with moderate dose of radiation and 5-FU affected significantly rectal carcinomas. There were no adverse effects. It seems likely, thus, that this combined therapy could prevent postoperative local or intrapelvic recurrence, which was the most frequent form of recurrence after curative surgery in rectal cancer. (author)
The effect of a pre-anesthetic infusion of amino acids on body temperature, venous blood pH, glucose, creatinine, and lactate of healthy dogs during anesthesia.

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Clark-Price, Stuart C; Dossin, Olivier; Ngwenyama, Thandeka R; O'Brien, Mauria A; McMichael, Maureen; Schaeffer, David J

2015-05-01

To evaluate the effect of preanesthetic, intravenous (IV) amino acids on body temperature of anesthetized healthy dogs. Randomized, experimental, crossover study. Eight mixed-breed dogs approximately 2 years of age weighing 20.7 ± 2.1 kg. Dogs received 10% amino acid solution (AA) or 0.9% saline (SA) IV at 5 mL kg(-1) over 60 minutes. Body temperature (BT) was recorded at 5 minute intervals during infusions. Dogs were then anesthetized with sevoflurane for 90 minutes. BT was recorded at 5 minute intervals during anesthesia. Jugular blood samples were analyzed for pH, glucose, creatinine, and lactate concentrations at baseline, after infusion, after anesthesia and after 24 hours. BT at conclusion of infusion decreased -0.34 ± 0.42 °C in group AA and -0.40 ± 0.38 °C in group SA and was not different between groups (p = 0.072). BT decreased 2.72 ± 0.37 °C in group AA and 2.88 ± 0.26 °C in group SA after anesthesia and was different between groups (p dogs, preanesthetic IV infusion of amino acids attenuated heat loss compared to controls, however, the amount attenuated may not be clinically useful. Further studies are warranted to determine if nutrient-induced thermogenesis is beneficial to dogs undergoing anesthesia. © 2014 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.
Dietary emu oil supplementation suppresses 5-fluorouracil chemotherapy-induced inflammation, osteoclast formation, and bone loss.

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Raghu Nadhanan, Rethi; Abimosleh, Suzanne M; Su, Yu-Wen; Scherer, Michaela A; Howarth, Gordon S; Xian, Cory J

2012-06-01

Cancer chemotherapy can cause osteopenia or osteoporosis, and yet the underlying mechanisms remain unclear, and currently, no preventative treatments are available. This study investigated damaging effects of 5-fluorouracil (5-FU) on histological, cellular, and molecular changes in the tibial metaphysis and potential protective benefits of emu oil (EO), which is known to possess a potent anti-inflammatory property. Female dark agouti rats were gavaged orally with EO or water (1 ml·day(-1)·rat(-1)) for 1 wk before a single ip injection of 5-FU (150 mg/kg) or saline (Sal) was given. The treatment groups were H(2)O + Sal, H(2)O + 5-FU, EO + 5-FU, and EO + Sal. Oral gavage was given throughout the whole period up to 1 day before euthanasia (days 3, 4, and 5 post-5-FU). Histological analysis showed that H(2)O + 5-FU significantly reduced heights of primary spongiosa on days 3 and 5 and trabecular bone volume of secondary spongiosa on days 3 and 4. It reduced density of osteoblasts slightly and caused an increase in the density of osteoclasts on trabecular bone surface on day 4. EO supplementation prevented reduction of osteoblasts and induction of osteoclasts and bone loss caused by 5-FU. Gene expression studies confirmed an inhibitory effect of EO on osteoclasts since it suppressed 5-FU-induced expression of proinflammatory and osteoclastogenic cytokine TNFα, osteoclast marker receptor activator of nuclear factor-κB, and osteoclast-associated receptor. Therefore, this study demonstrated that EO can counter 5-FU chemotherapy-induced inflammation in bone, preserve osteoblasts, suppress osteoclast formation, and potentially be useful in preventing 5-FU chemotherapy-induced bone loss.
Development of hydrocortisone succinic acid/and 5-fluorouracil/chitosan microcapsules for oral and topical drug deliveries.

Science.gov (United States)

Lam, Pik-Ling; Lee, Kenneth Ka-Ho; Wong, Raymond Siu-Ming; Cheng, Gregory Yin Ming; Cheng, Shuk Yan; Yuen, Marcus Chun-Wah; Lam, Kim-Hung; Gambari, Roberto; Kok, Stanton Hon-Lung; Chui, Chung-Hin

2012-05-01

Recently, we demonstrated the safety use of calendula oil/chitosan microcapsules as a carrier for both oral and topical deliveries. We also reported the improved biological activity towards skin cells and Staphylococcus aureus of phyllanthin containing chitosan microcapsules. However, the possibility of both oral and topical applications was still necessary to be further studied. Here we investigated that both oral and topical applications of chitosan-based microcapsules were tested using hydrocortisone succinic acid (HSA) and 5-fluorouracil (5-FU), respectively. The drug loading efficiency, particle size, surface morphology and chemical compositions of both drug loaded microcapsules were confirmed by UV-vis spectrophotometer, particle size analyzer, scanning electron microscope and Fourier transform infrared spectroscopy. The in vitro release studies revealed that both HSA and 5-FU could be released form chitosan microcapsules. The mean adrenocorticotropic hormone concentration in HSA loaded microcapsule mice plasma was detected to be lower than that of water control. One hundred micrograms per milliliter of 5-FU containing microcapsules exhibited a stronger growth inhibition towards skin keratinocytes than that of free 5-FU. In vitro drug delivery model demonstrated the delivery of 5-FU from microcapsule treated textiles into nude mice skin. Further uses of the drug loaded microcapsules may provide an efficiency deliverable tool for both oral and topical applications. Copyright © 2012 Elsevier Ltd. All rights reserved.

Alanyl-glutamine attenuates 5-fluorouracil-induced intestinal mucositis in apolipoprotein E-deficient mice

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C.V. Araújo

2015-06-01

Full Text Available Apolipoprotein E (APOE=gene, apoE=protein is a known factor regulating the inflammatory response that may have regenerative effects during tissue recovery from injury. We investigated whether apoE deficiency reduces the healing effect of alanyl-glutamine (Ala-Gln treatment, a recognized gut-trophic nutrient, during tissue recovery after 5-FU-induced intestinal mucositis. APOE-knockout (APOE-/- and wild-type (APOE+/+ C57BL6J male and female mice (N=86 were given either Ala-Gln (100 mM or phosphate buffered saline (PBS by gavage 3 days before and 5 days after a 5-fluorouracil (5-FU challenge (450 mg/kg, via intraperitoneal injection. Mouse body weight was monitored daily. The 5-FU cytotoxic effect was evaluated by leukometry. Intestinal villus height, villus/crypt ratio, and villin expression were monitored to assess recovery of the intestinal absorptive surface area. Crypt length, mitotic, apoptotic, and necrotic crypt indexes, and quantitative real-time PCR for insulin-like growth factor-1 (IGF-1 and B-cell lymphoma 2 (Bcl-2 intestinal mRNA transcripts were used to evaluate intestinal epithelial cell turnover. 5-FU challenge caused significant weight loss and leukopenia (P<0.001 in both mouse strains, which was not improved by Ala-Gln. Villus blunting, crypt hyperplasia, and reduced villus/crypt ratio (P<0.05 were found in all 5-FU-challenged mice but not in PBS controls. Ala-Gln improved villus/crypt ratio, crypt length and mitotic index in all challenged mice, compared with PBS controls. Ala-Gln improved villus height only in APOE-/- mice. Crypt cell apoptosis and necrotic scores were increased in all mice challenged by 5-FU, compared with untreated controls. Those scores were significantly lower in Ala-Gln-treated APOE+/+ mice than in controls. Bcl-2 and IGF-1 mRNA transcripts were reduced only in the APOE-/--challenged mice. Altogether our findings suggest APOE-independent Ala-Gln regenerative effects after 5-FU challenge.
Alanyl-glutamine attenuates 5-fluorouracil-induced intestinal mucositis in apolipoprotein E-deficient mice

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Araújo, C.V. [Laboratório da Biologia da Cicatrização, Ontogenia e Nutrição de Tecidos, INCT - Instituto de Biomedicina do Semiárido Brasileiro, Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, CE (Brazil); Lazzarotto, C.R. [Laboratório de Biologia Molecular e do Desenvolvimento, Universidade de Fortaleza, Fortaleza, CE (Brazil); Aquino, C.C.; Figueiredo, I.L.; Costa, T.B.; Oliveira Alves, L.A. de [Laboratório da Biologia da Cicatrização, Ontogenia e Nutrição de Tecidos, INCT - Instituto de Biomedicina do Semiárido Brasileiro, Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, CE (Brazil); Ribeiro, R.A. [Laboratório da Inflamação e Câncer, INCT - Instituto de Biomedicina do Semiárido Brasileiro, Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, CE (Brazil); Bertolini, L.R. [Laboratório de Biologia Molecular e do Desenvolvimento, Universidade de Fortaleza, Fortaleza, CE (Brazil); Lima, A.A.M. [Laboratório de Doenças Infecciosas, INCT - Instituto de Biomedicina do Semiárido Brasileiro, Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, CE (Brazil); Brito, G.A.C. [Laboratório da Inflamação e Câncer, INCT - Instituto de Biomedicina do Semiárido Brasileiro, Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, CE (Brazil); Oriá, R.B. [Laboratório da Biologia da Cicatrização, Ontogenia e Nutrição de Tecidos, INCT - Instituto de Biomedicina do Semiárido Brasileiro, Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, CE (Brazil)

2015-04-28

Apolipoprotein E (APOE=gene, apoE=protein) is a known factor regulating the inflammatory response that may have regenerative effects during tissue recovery from injury. We investigated whether apoE deficiency reduces the healing effect of alanyl-glutamine (Ala-Gln) treatment, a recognized gut-trophic nutrient, during tissue recovery after 5-FU-induced intestinal mucositis. APOE-knockout (APOE{sup -/-}) and wild-type (APOE{sup +/+}) C57BL6J male and female mice (N=86) were given either Ala-Gln (100 mM) or phosphate buffered saline (PBS) by gavage 3 days before and 5 days after a 5-fluorouracil (5-FU) challenge (450 mg/kg, via intraperitoneal injection). Mouse body weight was monitored daily. The 5-FU cytotoxic effect was evaluated by leukometry. Intestinal villus height, villus/crypt ratio, and villin expression were monitored to assess recovery of the intestinal absorptive surface area. Crypt length, mitotic, apoptotic, and necrotic crypt indexes, and quantitative real-time PCR for insulin-like growth factor-1 (IGF-1) and B-cell lymphoma 2 (Bcl-2) intestinal mRNA transcripts were used to evaluate intestinal epithelial cell turnover. 5-FU challenge caused significant weight loss and leukopenia (P<0.001) in both mouse strains, which was not improved by Ala-Gln. Villus blunting, crypt hyperplasia, and reduced villus/crypt ratio (P<0.05) were found in all 5-FU-challenged mice but not in PBS controls. Ala-Gln improved villus/crypt ratio, crypt length and mitotic index in all challenged mice, compared with PBS controls. Ala-Gln improved villus height only in APOE{sup -/-} mice. Crypt cell apoptosis and necrotic scores were increased in all mice challenged by 5-FU, compared with untreated controls. Those scores were significantly lower in Ala-Gln-treated APOE{sup +/+} mice than in controls. Bcl-2 and IGF-1 mRNA transcripts were reduced only in the APOE{sup -/-}-challenged mice. Altogether our findings suggest APOE-independent Ala-Gln regenerative effects after 5-FU
Alanyl-glutamine attenuates 5-fluorouracil-induced intestinal mucositis in apolipoprotein E-deficient mice

International Nuclear Information System (INIS)

Araújo, C.V.; Lazzarotto, C.R.; Aquino, C.C.; Figueiredo, I.L.; Costa, T.B.; Oliveira Alves, L.A. de; Ribeiro, R.A.; Bertolini, L.R.; Lima, A.A.M.; Brito, G.A.C.; Oriá, R.B.

2015-01-01

Apolipoprotein E (APOE=gene, apoE=protein) is a known factor regulating the inflammatory response that may have regenerative effects during tissue recovery from injury. We investigated whether apoE deficiency reduces the healing effect of alanyl-glutamine (Ala-Gln) treatment, a recognized gut-trophic nutrient, during tissue recovery after 5-FU-induced intestinal mucositis. APOE-knockout (APOE -/- ) and wild-type (APOE +/+ ) C57BL6J male and female mice (N=86) were given either Ala-Gln (100 mM) or phosphate buffered saline (PBS) by gavage 3 days before and 5 days after a 5-fluorouracil (5-FU) challenge (450 mg/kg, via intraperitoneal injection). Mouse body weight was monitored daily. The 5-FU cytotoxic effect was evaluated by leukometry. Intestinal villus height, villus/crypt ratio, and villin expression were monitored to assess recovery of the intestinal absorptive surface area. Crypt length, mitotic, apoptotic, and necrotic crypt indexes, and quantitative real-time PCR for insulin-like growth factor-1 (IGF-1) and B-cell lymphoma 2 (Bcl-2) intestinal mRNA transcripts were used to evaluate intestinal epithelial cell turnover. 5-FU challenge caused significant weight loss and leukopenia (P<0.001) in both mouse strains, which was not improved by Ala-Gln. Villus blunting, crypt hyperplasia, and reduced villus/crypt ratio (P<0.05) were found in all 5-FU-challenged mice but not in PBS controls. Ala-Gln improved villus/crypt ratio, crypt length and mitotic index in all challenged mice, compared with PBS controls. Ala-Gln improved villus height only in APOE -/- mice. Crypt cell apoptosis and necrotic scores were increased in all mice challenged by 5-FU, compared with untreated controls. Those scores were significantly lower in Ala-Gln-treated APOE +/+ mice than in controls. Bcl-2 and IGF-1 mRNA transcripts were reduced only in the APOE -/- -challenged mice. Altogether our findings suggest APOE-independent Ala-Gln regenerative effects after 5-FU challenge
A modified thrombolytic scheme for the treatment of cerebral venous sinus thrombosis

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Zhao Lin; Shi Jiancheng; Liu Zengpin; Li Linfang; Wang Zhihong; Wang Tiegang; Zhou Cunhe

2009-01-01

Objective: To discuss the curative effect and safety of a modified thrombolytic scheme in the treatment of cerebral sinus thrombosis. The new scheme adopts unremitting pump infusion of microdose urokinase (100,000 IU/24 h) into the cerebral venous sinus. Methods: The new therapeutic scheme was conducted in 21 patients with cerebral sinus thrombosis. Mechanical disruption of the thrombus was applied by moving the micro guidewire back and forth in the thrombus site, and unremitting pump infusion of urokanase for 48-96 hours with the lowest dose of 100,000 u/24 h was used. A follow-up of 6-12 months was made. Results: Recanalization of the occluded cerebral venous sinus was obtained in all 21 patients. The total urokinase dose of 100,000 u/24 h was used in 12 patients. For the other 9 patients the urokinase dose was 100,000 u/24 h in the first 48 hours, then the dose was increased to 250,000 u/24 h. No serious complications occurred. All patients showed a good prognosis. Conclusion: For the treatment of cerebral sinus thrombosis, this modified thrombolytic scheme is more safe and effective with less hemorrhage as compared to the classical one, since it may avoid certain complications caused by the use of large dose of thrombolytic drug . (authors)
Infusion-related reactions to infliximab in patients with rheumatoid arthritis in a clinical practice setting: relationship to dose, antihistamine pretreatment, and infusion number.

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Wasserman, Michael J; Weber, Deborah A; Guthrie, Judith A; Bykerk, Vivian P; Lee, Peter; Keystone, Edward C

2004-10-01

We describe infusion-related reactions to infliximab (during infusion or within 1 hour postinfusion) in patients with active rheumatoid arthritis (RA) treated in a quaternary care center. We followed 113 patients for a mean of 60.6 +/- 28.9 weeks, obtaining 10.5 +/- 4.9 infusions per patient. We observed 1183 infusions resulting in 104 infusion reactions (8.8%). All reactions resolved within several hours following cessation of the infusion and none was serious enough to warrant hospitalization. Reactions included allergic reactions (pruritus, urticaria) in 4.2% of infusions, cardiopulmonary (hypotension, hypertension, tachycardia) in 3.0%, and miscellaneous reactions (headache, nausea, vomiting) in 2.0%. Reactions occurred in 8.0% of 3 mg/kg infusions and in 10.3% of 5 mg/kg infusions. Reactions occurred in 13.2% of infusions that involved antihistamine pretreatment compared to only 7.5% of infusions that involved no pretreatment. At both infliximab doses, there was a similar frequency of infusion reactions in patients pretreated due to a previous infusion (12.6%) compared to those pretreated strictly based on infusion number (14.7%). A number of the reactions involving antihistamine pretreatment may be explained by known side effects of diphenhydramine, including headache, dizziness, nausea, and palpitations. Infusion-related reactions to infliximab were infrequent, rarely severe, and easily manageable. The frequency of reactions was equivalent in patients treated with 3 mg/kg compared to 5 mg/kg. Reactions were significantly more frequent in infusions where patients were pretreated with the antihistamine diphenhydramine, compared to those not involving pretreatment.
111In-labeled platelets: effects of heparin on uptake by venous thrombi and relationship to the activated partial thromboplastin time

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Fedullo, P.F.; Moser, K.M.; Moser, K.S.; Konopka, R.; Hartman, M.T.

1982-01-01

The goal of heparin therapy in deep vein thrombosis is to prevent thrombus extension. The relationship between thrombus extension and the results of coagulation tests used to monitor heparin therapy is unclear. To explore this relationship, we studied the effect of several heparin regimens on the accretion of 111 In-labeled platelets on fresh venous thrombi, as detected by gamma imaging, and monitored the activated partial thromboplastin time (APTT). Six dogs were treated with a 300-U/kg bolus of heparin followed by a 90-U/kg/hour heparin infusion, a dose of heparin sufficient to increase the APTT to levels greater than eight times baseline (APTT ratio); platelet accretion (thrombus imaging) occurred only after the heparin effect was reversed with protamine sulfate. Nineteen dogs were treated with a 150-U/kg bolus of heparin followed by a 4-hour, 45-U/kg/hour heparin infusion; a thrombus was demonstrated only after protamine injection in 12 (mean APTT ratio 1.3 +/- 0.19) and before protamine injection in seven. In thirteen of these 19 dogs, 30 minutes separated the platelet injection from heparin therapy, while in six this duration was less than 30 minutes. In four of these six dogs, thrombi were demonstrated before protamine therapy and at APTT ratios greater than 3.0. Finally, 10 dogs were treated with a 100-U/kg bolus followed by a 3-hour, 50-U/kg/hour heparin infusion, after which the APTT was allowed to return to baseline values spontaneously. In all 10 dogs, a thrombus was demonstrated only after cessation of the heparin infusion, and at a mean APTT ratio of 1.4 +/- 0.15 times baseline. These results suggest that, except with very early platelet injection, platelet accretion by thrombi is consistently inhibited by heparin at APTT ratios greater than 2.5. Platelet accretion by venous thrombi occurs within narrow limits of heparin effect as reflected by the APTT
Effect of abomasal infusion of oligofructose on portal-drained visceral ammonia and urea-nitrogen fluxes in lactating Holstein cows.

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Røjen, B A; Larsen, M; Kristensen, N B

2012-12-01

The effects of abomasal infusion of oligofructose in lactating dairy cows on the relationship between hindgut fermentation and N metabolism, and its effects on NH(3) absorption and transfer of blood urea-N across the portal-drained viscera versus ruminal epithelia were investigated. Nine lactating Holstein cows fitted with ruminal cannulas and permanent indwelling catheters in major splanchnic blood vessels were used in an unbalanced crossover design with 14-d periods. Treatments were continuous abomasal infusion of water or 1,500 g/d of oligofructose. The same basal diet was fed with both treatments. Eight sample sets of arterial, portal, hepatic, and ruminal vein blood, ruminal fluid, and urine were obtained at 0.5h before the morning feeding and at 0.5, 1.5, 2.5, 3.5, 4.5, 5.5, and 6.5 h after feeding. It was hypothesized that an increased supply of fermentable substrate to the hindgut would increase the uptake of urea-N from blood to the hindgut at the expense of urea-N uptake to the forestomach. The study showed that abomasal oligofructose infusion decreased the total amount of urea-N transferred from the blood to the gut, NH(3) absorption, and arterial blood urea-N concentration. Subsequently, hepatic NH(3) uptake and urea-N production also decreased with oligofructose infusion. Additionally, urea-N concentration in milk and urinary N excretion decreased with oligofructose treatment. The oligofructose infusion did not affect ruminal NH(3) concentrations or any other ruminal variables, nor did it affect ruminal venous - arterial concentration differences for urea-N and NH(3). The oligofructose treatment did not affect milk yield, but did decrease apparent digestibility of OM, N, and starch. Nitrogen excreted in the feces was greater with the oligofructose infusion. In conclusion, the present data suggest that increased hindgut fermentation did not upregulate urea-N transfer to the hindgut at the expense of urea-N uptake by the rumen, and the observed reduction
Treatment with acetaminophen/paracetamol or ibuprofen alleviates post-dose symptoms related to intravenous infusion with zoledronic acid 5 mg.

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Wark, J D; Bensen, W; Recknor, C; Ryabitseva, O; Chiodo, J; Mesenbrink, P; de Villiers, T J

2012-02-01

Patients treated with intravenous zoledronic acid 5 mg for osteoporosis may experience post-dose influenza-like symptoms. Oral acetaminophen/paracetamol or ibuprofen administered 4 h post-infusion reduced the proportion of patients with increased oral temperature and worsening post-infusion symptom scores vs. placebo, thus providing an effective strategy for the treatment of such symptoms. Once-yearly intravenous zoledronic acid 5 mg is a safe and effective treatment for postmenopausal osteoporosis. This study assessed whether transient influenza-like post-dose symptoms associated with intravenous infusion of zoledronic acid can be reduced by post-dose administration of acetaminophen/paracetamol or ibuprofen. In an international, multicenter, randomized, double-blind, double-dummy parallel-group study, bisphosphonate-naïve postmenopausal women with osteopenia (n = 481) were randomized to receive zoledronic acid 5 mg + acetaminophen/paracetamol (n = 135), ibuprofen (n = 137) or placebo (n = 137), or placebo + placebo (n = 72). Acetaminophen/paracetamol and ibuprofen were administered every 6 h for 3 days beginning 4 h post-infusion. The proportion of patients with increased oral temperature (≥1°C above 37.5°C) and with worsening post-infusion symptom scores over 3 days was significantly lower in patients receiving ibuprofen (36.8% and 48.5%) or acetaminophen/paracetamol (37.3% and 46.3%) vs. those receiving placebo (63.5% and 75.9%, respectively; all p paracetamol or ibuprofen. Oral acetaminophen/paracetamol or ibuprofen effectively managed the transient influenza-like symptoms associated with zoledronic acid 5 mg.
Andrographolide enhanced 5-fluorouracil-induced antitumor effect in colorectal cancer via inhibition of c-MET pathway

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Su M

2017-11-01

Full Text Available Meng Su,1 Baoli Qin,1 Fang Liu,2 Yuze Chen,2 Rui Zhang2 1Department of Internal Medicine, 2Department of Colorectal Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Liaoning, China Abstract: Colorectal cancer (CRC is the third most common malignant neoplasm worldwide. 5-Fluorouracil (5-Fu is the most important chemotherapeutic drug used for the treatment of CRC. However, resistance to 5-Fu therapies is a growing concern in CRC clinical practice recently. Andrographolide (Andro is a main bioactive constituent of the herb Andrographis paniculata, which has various biological effects including anti-inflammation and antitumor activities. In the present study, we investigated the effects of combined Andro with 5-Fu against CRC HCT-116 cells. In vitro studies showed that Andro synergistically enhanced the anti-proliferation effect of 5-Fu on HCT-116 cells due to increased apoptotic cells. Meanwhile, results of the enzyme linked immunosorbent assay indicated that the level of phosphorylated cellular-mesenchymal to epithelial transition factor (p-MET was decreased by the combination treatment. Further study suggested that Andro promoted the antitumor effect of 5-Fu by downregulating the level of p-MET. In conclusion, these results confirmed the synergistic antitumor activity of Andro on CRC and provide evidence for possible clinical application of Andro for enhancing the antitumor effect of 5-Fu in CRC treatment. Keywords: Andro, 5-Fu, HCT-116 cells, apoptosis, p-MET
Long-term persistence of acquired resistance to 5-fluorouracil in the colon cancer cell line SW620

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Tentes, I.K., E-mail: itentes@med.duth.gr [Department of Biochemistry, Medical School, Democritus University of Thrace, 6th km Alexandroupolis-Komotini (Dragana), 68100 Alexandroupolis (Greece); Schmidt, W.M. [Center for Anatomy and Cell Biology, Waehringer Strasse 13, 1090 Vienna (Austria); Krupitza, G. [Institute of Clinical Pathology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna (Austria); Steger, G.G.; Mikulits, W. [Department of Medicine I, Medical University of Vienna, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna (Austria); Kortsaris, A. [Department of Biochemistry, Medical School, Democritus University of Thrace, 6th km Alexandroupolis-Komotini (Dragana), 68100 Alexandroupolis (Greece); Mader, R.M. [Department of Medicine I, Medical University of Vienna, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna (Austria)

2010-11-15

Treatment resistance to antineoplastic drugs represents a major clinical problem. Here, we investigated the long-term stability of acquired resistance to 5-fluorouracil (FU) in an in vitro colon cancer model, using four sub-clones characterised by increasing FU-resistance derived from the cell line SW620. The resistance phenotype was preserved after FU withdrawal for 15 weeks ({approx} 100 cell divisions) independent of the established level of drug resistance and of epigenetic silencing. Remarkably, resistant clones tolerated serum deprivation, adopted a CD133{sup +} CD44{sup -} phenotype, and further exhibited loss of membrane-bound E-cadherin together with predominant nuclear {beta}-catenin localisation. Thus, we provide evidence for a long-term memory of acquired drug resistance, driven by multiple cellular strategies (epithelial-mesenchymal transition and selective propagation of CD133{sup +} cells). These resistance phenomena, in turn, accentuate the malignant phenotype.
Comparison of cisplatinum/paclitaxel with cisplatinum/5-fluorouracil as first-line therapy for nonsurgical locally advanced esophageal squamous cell carcinoma patients

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Hu GF

2016-07-01

Full Text Available Guofang Hu,1 Zhehai Wang,2 Yuan Wang,1 Qingqing Zhang,1 Ning Tang,1 Jun Guo,2 Liyan Liu,2 Xiao Han2 1School of Medicine and Life Sciences, University of Jinan, Shandong Academy of Medical Sciences, 2Department of Oncology, Shandong Cancer Hospital, Shandong University, Jinan, Shandong, People’s Republic of China Background: To retrospectively evaluate the efficacy and toxicity of definitive concurrent chemoradiotherapy (dCRT with cisplatinum/paclitaxel versus cisplatinum/5-fluorouracil in patients with locally advanced esophageal squamous cell carcinoma (ESCC who received nonsurgical treatment. Methods: This study retrospectively evaluated 202 patients with locally advanced ESCC treated at Shandong Cancer Hospital between January 2009 and December 2013. All the patients initially received dCRT, including platinum and paclitaxel or 5-fluorouracil, with concurrent 1.8 or 2 Gy/fraction radiation (total dose, 54–60 Gy. The patient population was divided into two treatment groups: 105 patients who received the cisplatinum/paclitaxel regimen were allocated to group A, and 97 patients who received the cisplatinum/5-fluorouracil regimen were allocated to group B. We compared the progression-free survival (PFS and overall survival (OS by various clinical variables, including prior treatment characteristics, major toxicities (mainly in grade 3 and 4 hematological, and response to dCRT. We used the receiver operating curve analysis to determine the optimal cutoff value of clinical stage and radiation dose. The Kaplan–Meier method was used for survival comparison and Cox regression for multivariate analysis. Results: Median PFS and OS in group A were significantly better compared with group B (median PFS, 15.9 versus 13.0 months, P=0.016 and median OS, 33.9 versus 23.1 months, P=0.014, respectively. The 1- and 2-year survival rates of the two groups were 82.9% versus 76.3%, and 61.9% versus 47.6%, respectively. The complete response and response rate
Semi-physiological pharmacokinetic-pharmacodynamic (PK-PD) modeling and simulation of 5-fluorouracil for thrombocytopenia in rats.

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Kobuchi, Shinji; Ito, Yukako; Hayakawa, Taro; Nishimura, Asako; Shibata, Nobuhito; Takada, Kanji; Sakaeda, Toshiyuki

2015-01-01

1. The aim of this study was to develop a simple pharmacokinetic-pharmacodynamic (PK-PD) model that could characterize the complete time-course of alterations in platelet counts to predict the onset and degree of thrombocytopenia, which severely limits the use of the anticancer agent 5-fluorouracil (5-FU), in rats. 2. Platelet counts were measured in rats following the intravenous administration of various doses of 5-FU for 4 days to obtain data for an analysis of the PK-PD model. Our PK-PD model consisted of a two-compartment PK model, with three compartments for the PD model and 10 structural PK-PD model parameters. 3. After the 5-FU treatment, platelet counts transiently decreased to a nadir level, showed a rebound to above the baseline level before recovering to baseline levels. Nadir platelet counts and rebounds varied with the AUC0-∞ level. The final PK-PD model effectively characterized platelet count data and final PD parameters were estimated with high certainty. 4. This PK-PD model and simulation may represent a valuable tool for quantifying and predicting the complete time-course of alterations in blood cell counts, and could contribute to the development of therapeutic strategies with 5-FU and assessments of various novel anticancer agents that are difficult to examine in humans.
Intraosseous infusions: a review for the anesthesiologist with a focus on pediatric use.

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Tobias, Joseph D; Ross, Allison Kinder

2010-02-01

Intraosseous (IO) access is used most frequently for emergency care of critically ill infants and children when IV access cannot be rapidly achieved. Despite its efficacy in such situations, applications outside of the emergency room or resuscitation scenario have been limited. Furthermore, although the technique is emphasized in the teaching of those caring for critically ill infants and children in the emergency room or critical care setting, there is limited emphasis on its potential use in the perioperative setting. When peripheral venous access cannot be achieved in the operating room, alternative means of securing vascular access such as central line placement or surgical cutdown are generally successful; however, these techniques may be time consuming. Anyone providing anesthesia care for infants and children may want to become facile with the use of IO infusions for selected indications. We present the history of IO infusions, review the anatomy of the bone marrow space, discuss the potential role of IO infusions in the perioperative period, and analyze its adverse effect profile.
Diagnosis and endovascular treatment of multiple cerebral venous and venous sinuses thrombosis

International Nuclear Information System (INIS)

Li Baomin; Zhang Ji; Yin Ling; Huang Xusheng; Jiang Jinli; Liu Jun; Lang Senyang; Zhou Dingbiao; Zhu Ke

2000-01-01

Objective: Eighty-five cases with multiple cerebral venous and venous sinuses thrombosis including the diagnosis and endovascular therapy were reported. Methods: The long T2 and short T1 signals in the related regions of multiple venous sinuses on MRI and prolonged blood circulation time of the brain with tortuous dilatation of vein in angiography were the important characteristics for the diagnosis. Of the 85 cases, the treatment procedures were consisted of injecting urokinase intermittently via common carotid artery and intra-sinus contact thrombolysis as well as warfarin intake orally. Results: Intracranial pressure of 80 cases reduced down between 230 and 300 mm H 2 O, and clinical deficits were markedly improved within 10 days. Re-angiography of 18 cases revealed recanalization partly in 5 cases and circulation time appeared near normal i 8 cases during one week after therapy. Conclusions: Combined intraarterial thrombolysis consecutively with general anticoagulation for the treatment of multiple thrombosis in cerebral venous sinuses may be one of the effective means
Effect of early preoperative 5-fluorouracil on the integrity of colonic anastomoses in rats

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Ozel, Leyla; Ozel, M Sefa; Toros, Ahmet Burak; Kara, Melih; Ozkan, Kemal Sırrı; Tellioglu, Gurkan; Krand, Osman; Koyuturk, Meral; Berber, Ibrahim

2009-01-01

AIM: To determine the effect of chemotherapy on wound healing by giving early preoperative 5-fluorouracil (5-FU) to rats with colonic anastomoses. METHODS: Sixty Albino-Wistar male rats (median weight, 235 g) were used in this study. The rats were fed with standard laboratory food and given tap water ad libitum. The animals were divided into three groups: Group 1: Control group (chemotherapy was not administered), Group 2: Intraperitoneally (IP) administered 5-FU group (chemotherapy was administered IP to animals at a dose of 20 mg/kg daily during the 5 d preceeding surgery), Group 3: Intravenously (IV) administered 5-FU group. Chemotherapy was administered via the penil vein, using the same dosing scheme and duration as the second group. After a 3-d rest to minimize the side effects of chemotherapy, both groups underwent surgery. One centimeter of colon was resected 2 cm proximally from the peritoneal reflection, then sutured intermittently and subsequently end-to-end anastomosed. In each group, half the animals were given anaesthesia on the 3rd postoperative (PO) day and the other half on the 7th PO day, for in vivo analytic procedures. The abdominal incisions in the rats were dissected, all the new and old anastomotic segments were clearly seen and bursting pressures of each anastomotic segment, tissue hydroxyproline levels and DNA content were determined to assess the histologic tissue repair process. RESULTS: When the IV group was compared with the IP group, bursting pressures of the anastomotic segments on the 3rd and 7th PO days, were found to be significantly decreased, hydroxyproline levels at the anastomotic segment on the 7th PO day were significantly decreased (P < 0.01). CONCLUSION: In this study, we conclude that early preoperative 5-FU, administered IV, negatively affects wound healing. However, IP administered 5-FU does not negatively affect wound healing. PMID:19725150
Optimization of health-care organization and perceived improvement of patient comfort by switching from intra-venous BU four-times-daily infusions to a once-daily administration scheme in adult hematopoietic stem cell recipients.

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Xhaard, A; Rzepecki, P; Valcarcel, D; Santarone, S; Fürst, S; Serrano, D; De Angelis, G; Krüger, W; Scheid, C

2014-04-01

Previous studies have shown an equivalent pharmacokinetic profile between four-times-daily (4QD) and once-daily (QD) administration of intra-venous (IV) BU, without increased toxicity. We assess the impact of a switch in IV BU from a 4QD to a QD schedule, in terms of health-care organization, staff working conditions, quality of care dispensed and perceived patient comfort. Clinicians, nurses and pharmacists from nine allogeneic transplantation units in five European countries were interviewed face to face. Overall perception of QD versus 4QD BU was very positive. Both administration schemes were evaluated to be equally efficaciousZ. QD BU was perceived to be safer and more convenient. Clinicians and nurses perceived that patient comfort was improved, due to fewer complications associated with repeated infusions, and avoiding night infusions associated with stress, anxiety and decreased quality of sleep. Switching from 4QD to QD BU had a significant impact on health-care organization, with a better integration in the overall management and usual timelines in the pharmacies and transplantation units. Time spent to prepare and administer BU was significantly reduced, leading to potential financial savings that merit further assessment and would be of particular interest in the current economic climate.
MicroRNA-21 induces 5-fluorouracil resistance in human pancreatic cancer cells by regulating PTEN and PDCD4

International Nuclear Information System (INIS)

Wei, Xueju; Wang, Weibin; Wang, Lanlan; Zhang, Yuanyuan; Zhang, Xian; Chen, Mingtai; Wang, Fang; Yu, Jia; Ma, Yanni; Sun, Guotao

2016-01-01

Pancreatic cancer patients are often resistant to chemotherapy treatment, which results in poor prognosis. The objective of this study was to delineate the mechanism by which miR-21 induces drug resistance to 5-fluorouracil (5-FU) in human pancreatic cancer cells (PATU8988 and PANC-1). We report that PATU8988 cells resistant to 5-FU express high levels of miR-21 in comparison to sensitive primary PATU8988 cells. Suppression of miR-21 expression in 5-Fu-resistant PATU8988 cells can alleviate its 5-FU resistance. Meanwhile, lentiviral vector-mediated overexpression of miR-21 not only conferred resistance to 5-FU but also promoted proliferation, migration, and invasion of PATU8988 and PANC-1 cells. The proresistance effects of miR-21 were attributed to the attenuated expression of tumor suppressor genes, including PTEN and PDCD4. Overexpression of PTEN and PDCD4 antagonized miR-21-induced resistance to 5-FU and migration activity. Our work demonstrates that miR-21 can confer drug resistance to 5-FU in pancreatic cancer cells by regulating the expression of tumor suppressor genes, as the target genes of miR-21, PTEN and PDCD4 can rescue 5-FU sensitivity and the phenotypic characteristics disrupted by miR-21
tRNA modifying enzymes, NSUN2 and METTL1, determine sensitivity to 5-fluorouracil in HeLa cells.

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Mayumi Okamoto

2014-09-01

Full Text Available Nonessential tRNA modifications by methyltransferases are evolutionarily conserved and have been reported to stabilize mature tRNA molecules and prevent rapid tRNA decay (RTD. The tRNA modifying enzymes, NSUN2 and METTL1, are mammalian orthologs of yeast Trm4 and Trm8, which are required for protecting tRNA against RTD. A simultaneous overexpression of NSUN2 and METTL1 is widely observed among human cancers suggesting that targeting of both proteins provides a novel powerful strategy for cancer chemotherapy. Here, we show that combined knockdown of NSUN2 and METTL1 in HeLa cells drastically potentiate sensitivity of cells to 5-fluorouracil (5-FU whereas heat stress of cells revealed no effects. Since NSUN2 and METTL1 are phosphorylated by Aurora-B and Akt, respectively, and their tRNA modifying activities are suppressed by phosphorylation, overexpression of constitutively dephosphorylated forms of both methyltransferases is able to suppress 5-FU sensitivity. Thus, NSUN2 and METTL1 are implicated in 5-FU sensitivity in HeLa cells. Interfering with methylation of tRNAs might provide a promising rationale to improve 5-FU chemotherapy of cancer.
Topical Mitomycin-C versus Subconjunctival 5‑Fluorouracil for Management of Bleb Failure

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Mohammad Pakravan

2011-01-01

Full Text Available Purpose: To compare the efficacy and safety of topical mitomycin‑C (MMC drops with that of subconjunctival 5‑fluorouracil (5‑FU injections for management of early bleb failure after trabeculectomy or combined phacoemulsification and trabeculectomy with posterior chamber intraocular lens implantation (PT+PCIOL. Methods: In a randomized comparative study, 37 eyes of 37 patients with impending early bleb failure received MMC 0.02% eye drops for 2 or 4 weeks (19 eyes or subconjunctival 5‑FU injections, 5 mg per dose (18 eyes. Complete success was defined as 5 < IOP ≤ 18 mmHg without medications. Results: Baseline characteristics were comparable between the study groups. However, there were more cases of combined PT+PCIOL in the MMC group [11 (57.9% eyes versus 3 (16.7% eyes, P = 0.017]. Mean preoperative IOP was 20.5΁8.85 mmHg in the MMC group and 25.82΁11.35 mmHg in the 5‑FU group (P = 0.129, which was decreased to 13.2΁6.1 and 10.6΁4.8 mmHg respectively after 12 months (P = 0.159. There was no significant difference between the study groups in terms of bleb extent (P = 0.170, height (P = 0.178 or vascularity (P = 0.366. At the end of the study, complete success was achieved in 13 eyes (68.4% in the MMC group and 14 eyes (77.8% in the 5‑FU group (P = 0.714. The survival of success at 8 months (median follow-up was 89.5% and 86.5% in the MMC and 5‑FU groups respectively; the number of glaucoma medications (P = 0.707 and best-corrected visual acuity (P = 0.550 were also comparable. Complication rates were similar in the study groups (P = 0.140. Conclusion: Topical MMC 0.02% has comparable safety and efficacy to subconjunctival 5‑FU injections for management of early bleb failure. Topical MMC 0.02% drops are more convenient and can be initiated first, while 5‑FU injections may be reserved for eyes with an insufficient response to topical MMC.
Development and evaluation of nanostructured lipid carrier-based hydrogel for topical delivery of 5-fluorouracil.

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Rajinikanth, Paruvathanahalli Siddalingam; Chellian, Jestin

The aim of this study was to develop a nanostructured lipid carrier (NLC)-based hydrogel and study its potential for the topical delivery of 5-fluorouracil (5-FU). Precirol ® ATO 5 (glyceryl palmitostearate) and Labrasol ® were selected as the solid and liquid lipid phases, respectively. Poloxamer 188 and Solutol ® HS15 (polyoxyl-15-hydroxystearate) were selected as surfactants. The developed lipid formulations were dispersed in 1% Carbopol ® 934 (poly[acrylic acid]) gel medium in order to maintain the topical application consistency. The average size, zeta potential, and polydispersity index for the 5-FU-NLC were found to be 208.32±8.21 nm, -21.82±0.40 mV, and 0.352±0.060, respectively. Transmission electron microscopy study revealed that 5-FU-NLC was <200 nm in size, with a spherical shape. In vitro drug permeation studies showed a release pattern with initial burst followed by sustained release, and the rate of 5-FU permeation was significantly improved for 5-FU-NLC gel (10.27±1.82 μg/cm 2 /h) as compared with plain 5-FU gel (2.85±1.12 μg/cm 2 /h). Further, skin retention studies showed a significant retention of 5-FU from the NLC gel (91.256±4.56 μg/cm 2 ) as compared with that from the 5-FU plain gel (12.23±3.86 μg/cm 2 ) in the rat skin. Skin irritation was also significantly reduced with 5-FU-NLC gel as compared with 5-FU plain gel. These results show that the prepared 5-FU-loaded NLC has high potential to improve the penetration of 5-FU through the stratum corneum, with enormous retention and with minimal skin irritation, which is the prerequisite for topically applied formulations.

'Poker' association of weekly alternating 5-fluorouracil, irinotecan, bevacizumab and oxaliplatin (FIr-B/FOx) in first line treatment of metastatic colorectal cancer: a phase II study

International Nuclear Information System (INIS)

Bruera, Gemma; Ficorella, Corrado; Ricevuto, Enrico; Santomaggio, Alessandra; Cannita, Katia; Baldi, Paola Lanfiuti; Tudini, Marianna; De Galitiis, Federica; Mancini, Maria; Marchetti, Paolo; Antonucci, Adelmo

2010-01-01

This phase II study investigated efficacy and safety of weekly alternating Bevacizumab (BEV)/Irinotecan (CPT-11) or Oxaliplatin (OHP) associated to weekly 5-Fluorouracil (5-FU) in first line treatment of metastatic colorectal carcinoma (MCRC). Simon two-step design: delta 20% (p 0 50%, p 1 70%), power 80%, α 5%, β 20%. Projected objective responses (ORR): I step, 8/15 patients (pts); II step 26/43 pts. Schedule: weekly 12 h-timed-flat-infusion/5-FU 900 mg/m 2 , days 1-2, 8-9, 15-16, 22-23; CPT-11 160 mg/m 2 plus BEV 5 mg/kg, days 1,15; OHP at three dose-levels, 60-70-80 mg/m 2 , days 8, 22; every 4 weeks. Fifty consecutive, unselected pts < 75 years were enrolled: median age 63; young-elderly (yE) 24 (48%); liver metastases (LM) 33 pts, 66% Achieved OHP recommended dose, 80 mg/m 2 . ORR 82% intent-to-treat and 84% as-treated analysis. Median progression-free survival 12 months. Equivalent efficacy was obtained in yE pts. Liver metastasectomies were performed in 26% of all pts and in 39% of pts with LM. After a median follow-up of 21 months, median overall survival was 28 months. Cumulative G3-4 toxicities per patient: diarrhea 28%, mucositis 6%, neutropenia 10%, hypertension 2%. They were equivalent in yE pts. Limiting toxicity syndromes (LTS), consisting of the dose-limiting toxicity, associated or not to G2 or limiting toxicities: 44% overall, 46% in yE. Multiple versus single site LTS, respectively: overall, 24% versus 20%; yE pts, 37.5% versus 8%. Poker combination shows high activity and efficacy in first line treatment of MCRC. It increases liver metastasectomies rate and can be safely administered. Osservatorio Nazionale sulla Sperimentazione Clinica dei Medicinali (OsSC) Agenzia Italiana del Farmaco (AIFA) Numero EudraCT 2007-004946-34
Autoradiographic studies on nucleic acid synthesis of human gastric cancer cells, 2. Effects of 5-Fluorouracil on nucleic acid synthesis of cancer cells

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Inoue, K [Kobe Univ. (Japan). School of Medicine

1982-03-01

Changes in nucleic acid synthesis of gastric cancer cells by oral administration of 5-fluorouracil (5-FU) were evaluated autoradiographically. 1) Average /sup 3/H-thymidine labeling index (TLI) in the administered group (31.8%, n = 13) was a significantly high value compared with that of the control group (22.4%, n = 21). This result is considered to show that the pharmacological effects of 5-FU appeared on the cancer cells by the clinical administration of 5-FU. 2) Increase in TLI of the administered group was also found in the advanced stages. However, the degree of its increase seemed to be higher in the early stages. 3) Average /sup 3/H-uridine labeling index (89.9%) was not different from that (92.7%) of control group.
Inflammation and peripheral venous disease. The San Diego Population Study.

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Cushman, M; Callas, P W; Allison, M A; Criqui, M H

2014-09-02

The inflammatory response to healing in venous thrombosis might cause vein damage and post-thrombotic syndrome. Inflammation may also be involved in venous insufficiency apart from deep-vein thrombosis. We studied the association of inflammation markers with venous insufficiency in a general population sample. We characterised 2,404 men and women in a general population cohort for peripheral venous disease and its severity using physical exam, symptom assessment, and venous ultrasound. Inflammation markers, C-reactive protein (CRP), fibrinogen, interleukin 1-beta (IL-1-beta), IL-8, IL-10, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E-selectin, monocyte chemoattractant-1 (MCP-1) and vascular endothelial cell growth factor (VEGF) were compared in 352 case participants with peripheral venous disease and 352 controls with no venous abnormalities frequency matched to cases by age, sex and race. Associations were also evaluated including a subset of 108 cases of severe venous disease, as previously defined. Odds ratios (95% CI), for peripheral venous disease for biomarkers in the top quartile (adjusting for age, race, sex, body mass index and history of venous thrombosis) were 1.8 (1.1-3.0), 1.6 (1.0-2.5) and 1.5 (0.9-2.3) for CRP, fibrinogen and IL-10, respectively. Associations were larger considering cases of severe venous disease, with odds ratios for these three analytes of 2.6 (1.2-5.9), 3.1 (1.3-7.3) and 2.2 (1.1-4.4), and for IL-8: 2.4 (1.1-5.2). There was no association of IL-1-beta, ICAM-1, VCAM-1, E-selectin, MCP-1 or VEGF with overall cases or severe venous disease. In conclusion, a subset of inflammation markers were associated with increased risk of peripheral venous disease, suggesting potential therapeutic targets for treatment.
Mechanisms Regulating the Cardiac Output Response to Cyanide Infusion, a Model of Hypoxia

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Liang, Chang-seng; Huckabee, William E.

1973-01-01

When tissue metabolic changes like those of hypoxia were induced by intra-aortic infusion of cyanide in dogs, cardiac output began to increase after 3 to 5 min, reached a peak (220% of the control value) at 15 min, and returned to control in 40 min. This pattern of cardiac output rise was not altered by vagotomy with or without atropine pretreatment. However, this cardiac output response could be differentiated into three phases by pretreating the animals with agents that block specific activities of the sympatho-adrenal system. First, ganglionic blockade produced by mecamylamine or sympathetic nerve blockade by bretylium abolished the middle phase of the cardiac output seen in the untreated animal, but early and late phases still could be discerned. Second, beta-adrenergic receptor blockade produced by propranolol shortened the total duration of the cardiac output rise by abolishing the late phase. Third, when given together, propranolol and mecamylamine (or bretylium) prevented most of the cardiac output rise that follows the early phase. When cyanide was given to splenectomized dogs, the duration of the cardiac output response was not shortened, but the response became biphasic, resembling that seen after chemical sympathectomy. A similar biphasic response of the cardiac output also resulted from splenic denervation; sham operation or nephrectomy had no effect on the monophasic pattern of the normal response. Splenic venous blood obtained from cyanide-treated dogs, when infused intraportally, caused an increase in cardiac output in recipient dogs; similar infusion of arterial blood had no effects. These results suggest that the cardiac output response to cyanide infusion consists of three components: an early phase, related neither to the autonomic nervous system nor to circulating catecholamines; a middle phase, caused by a nonadrenergic humoral substance released from the spleen by sympathetic stimulation; and a late phase, dependent upon adrenergic receptors
Acute dimethyl sulfoxide therapy in brain edema. Part 3: effect of a 3-hour infusion.

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Del Bigio, M; James, H E; Camp, P E; Werner, R; Marshall, L F; Tung, H

1982-01-01

Albino rabbits with experimental brain edema produced by a combined cryogenic left hemisphere lesion and metabolic 6-aminonicotinamide lesion were administered a 3-hour intravenous infusion of dimethyl sulfoxide (DMSO). Simultaneous recording of intracranial pressure (ICP), systolic arterial pressure (SAP), and central venous pressure (CVP) and electroencephalography were performed while the animals were being ventilated mechanically to produce a constant Pa CO2 value (38-42 torr). At the end of the infusion, the brain water and electrolyte contents were measured. There was a persistent and progressive reduction of ICP during the infusion, the nadir occurring at 3 hours (p less than 0.005 from zero time), with no change in SAP or CVP. There was a reduction of brain water in both hemispheres when compared to untreated controls, but this was significant for the right hemisphere only (p less than 0.005). There was a significant reduction of the brain sodium content for both hemispheres, but no significant change occurred in brain potassium content. The DMSO infusion was effective not only in reducing ICP, but also in sustaining this reduction for 3 hours.
Peri-tumor administration of 5-fluorouracil sol-gel using a hollow microneedle for treatment of gastric cancer.

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Jung, Yoon Suk; Koo, Dong-Hoe; Yang, Jeong-Yoon; Lee, Hee-Young; Park, Jung-Hwan; Park, Jung Ho

2018-11-01

The aim of this study was to investigate the effectiveness of treating gastric cancer by injecting a pluronic F-127 sol-gel formulation of 5-fluorouracil (5-FU) into normal tissue surrounding the tumor using a hollow microneedle. The MTS tetrazolium assay was performed to assess the cytotoxicity of 5-FU after application to gastric cancer cells at different concentrations for 1, 5 and 10 h. Gastric cancer cells were inoculated subcutaneously into 30 male nude mice (CrjBALB/c-nu/nu mice, male); the inoculated mouse were divided into three groups. One group received no treatment, whereas the two other groups received free 5-FU gel (40 mg/kg) and 5-FU gel (40 mg/kg) for 4 days, respectively. Mean tumor volume, apoptotic index (TUNEL) and proliferative index (Ki 67) were evaluated in all groups. Cell viability was 77.3% when 1.22 g of free 5-FU was administered, whereas cell viability was 37.4% and 43.5% when 0.122 g of free 5-FU was administered per hour for 10 h and 0.244 g of free 5-FU was administered for 5 h (p sol-gel induced apoptosis and significantly inhibited cell proliferation compared to the free 5-FU (p sol-gel formulation to inoculated mice (p sol-gel formulation into normal tissue surrounding the tumor mass using a hollow microneedle is an effective method for treating gastric cancer.
Loss of Smad4 in colorectal cancer induces resistance to 5-fluorouracil through activating Akt pathway.

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Zhang, B; Zhang, B; Chen, X; Bae, S; Singh, K; Washington, M K; Datta, P K

2014-02-18

Higher frequency of Smad4 inactivation or loss of expression is observed in metastasis of colorectal cancer (CRC) leading to unfavourable survival and contributes to chemoresistance. However, the molecular mechanism of how Smad4 regulates chemosensitivity of CRC is unknown. We evaluated how the loss of Smad4 in CRC enhanced chemoresistance to 5-fluorouracil (5-FU) using two CRC cell lines in vitro and in vivo. Immunoblotting with cell and tumour lysates and immunohistochemical analyses with tissue microarray were performed. Knockdown or loss of Smad4 induced tumorigenicity, migration, invasion, angiogenesis, metastasis, and 5-FU resistance. Smad4 expression in mouse tumours regulated cell-cycle regulatory proteins leading to Rb phosphorylation. Loss of Smad4 activated Akt pathway that resulted in upregulation of anti-apoptotic proteins, Bcl-2 and Bcl-w, and Survivin. Suppression of phosphatidylinositol-3-kinase (PI3K)/Akt pathway by LY294002 restored chemosensitivity of Smad4-deficient cells to 5-FU. Vascular endothelial growth factor-induced angiogenesis in Smad4-deficient cells might also lead to chemoresistance. Low levels of Smad4 expression in CRC tissues correlated with higher levels of Bcl-2 and Bcl-w and with poor overall survival as observed in immunohistochemical staining of tissue microarrays. Loss of Smad4 in CRC patients induces resistance to 5-FU-based therapy through activation of Akt pathway and inhibitors of this pathway may sensitise these patients to 5-FU.
Fluorouracil as a treatment for corneal papilloma in a Malayan tapir.

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Karpinski, Lorraine G; Miller, Christine L

2002-09-01

A 26-year-old, wild caught, male Malayan tapir at the Miami Metrozoo with bilateral corneal papillomas was serially immobilized and given subconjunctival injections of fluorouracil. Over the course of 17 weeks five bilateral injections of 25 mg fluorouracil were given. This treatment caused regression of the corneal lesions as evidenced by decreased lesion diameter, decreased corneal vascularity, increased corneal clarity, and improved visual function. No adverse drug effects were observed.
Effects of protein-calorie malnutrition and refeeding on fluorouracil toxicity

Energy Technology Data Exchange (ETDEWEB)

Gamelli, R.L.; Foster, R.S. Jr.

1983-10-01

Mice were used to study the effects of protein-calorie malnutrition and its reversal on granulocyte-macrophage production and fluorouracil's toxic effect on bone marrow. An in vitro quantitative clonal culture technique for bone marrow granulocyte-macrophage progenitor cells (GM-CFC) was used. Animals on a protein-free but otherwise complete diet for ten days had a significant contraction in total marrow cellularity and GM-CFC numbers paralleling the animal's weight loss. The acute toxic effect of fluorouracil on bone marrow was not increased in protein-deprived animals. On refeeding, there was a biphasic response in the degree of toxic effect on marrow. Animals refed for one day had significantly increased fluorouracil-related marrow abnormalities. However, animals refed for four days, when marrows were repleted, were partially protected from the drug's cytotoxic effects. The increased sensitivity in mice refed for one day was related to more GM-CFC in active DNA synthesis.
A Comparison of the Effects of Intraosseous and Intravenous 5% Albumin on Infusion Time and Hemodynamic Measures in a Swine Model of Hemorrhagic Shock.

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Muir, Stacy L; Sheppard, Lance B; Maika-Wilson, Anne; Burgert, James M; Garcia-Blanco, Jose; Johnson, Arthur D; Coyner, Jennifer L

2016-08-01

Introduction Obtaining intravenous (IV) access in patients in hemorrhagic shock is often difficult and prolonged. Failed IV attempts delay life-saving treatment. Intraosseous (IO) access may often be obtained faster than IV access. Albumin (5%) is an option for prehospital volume expansion because of the absence of interference with coagulation and platelet function. Hypothesis/Problem There are limited data comparing the performance of IO and IV administered 5% albumin. The aims of this study were to compare the effects of tibial IO (TIO) and IV administration of 500 mL of 5% albumin on infusion time and hemodynamic measurements of heart rate (HR), mean arterial pressure (MAP), cardiac output (CO), and stroke volume (SV) in a swine model of hemorrhagic shock. Sixteen male swine were divided into two groups: TIO and IV. All subjects were anesthetized and a Class III hemorrhage was achieved by exsanguination of 31% of estimated blood volume (EBV) from a femoral artery catheter. Following exsanguination, 500 mL of 5% albumin was administered under pressurized infusion (300 mmHg) by the TIO or IV route and infusion time was recorded. Hemodynamic measurements of HR, MAP, CO, and SV were collected before and after exsanguination and every 20 seconds for 180 seconds during 5% albumin infusion. An independent t-test determined that IV 5% albumin infusion was significantly faster compared to IO (P=.01). Mean infusion time for TIO was seven minutes 35 seconds (SD=two minutes 44 seconds) compared to four minutes 32 seconds (SD=one minute 08 seconds) in the IV group. Multivariate Analysis of Variance was performed on hemodynamic data collected during the 5% albumin infusion. Analyses indicated there were no significant differences between the TIO and IV groups relative to MAP, CO, HR, or SV (P>.05). While significantly longer to infuse 5% albumin by the TIO route, the longer TIO infusion time may be negated as IO devices can be placed more quickly compared to repeated IV
Venous sinus stenting for pseudotumour cerebri with venous sinus stenosis

International Nuclear Information System (INIS)

Chen Huairui; Bai Rulin; Wu Xiaojun; Qi Xiangqian; Mei Qiyong; Lu Yicheng

2011-01-01

Objective: To explore the relation between venous sinus stenosis and pseduotumour cerebri and to discuss the efficacy and strategy of venous sinus stenting for its treatment. Methods: Venous sinus stenting was performed in a total of 9 patients with pseudotumour cerebri accompanied by dural sinus stenosis. The clinical data, including the clinical presentations, intracranial pressure, angiographic findings, pressure of dural sinus,methods of treatment and the therapeutic results, were retrospectively analyzed. Results: Bilateral disc edema was seen in all patients. The pressure gradient in the lateral sinuses was obviously high before stenting (22.67±7.25)mmHg in all patients and a reduction in intra-sinus pressure and pressure gradient was also found (5.78±3.77)mmHg. The symptoms associated with intracranial hypertension were gradually improved or disappeared in two weeks after the placement of the stent in all cases, and the intracranial pressure dropped evidently (12.78±5.97)cm H 2 O. Vision was improved in 7 cases at three months, whereas it remained poor in 2 cases despite normalized intracranial pressure. There was no other permanent procedure-related morbidity. The patients were followed up for 3 months to 5 years, and no recurrence developed. Conclusion: Lateral sinus stenting is an effective method for the treatment of pseudotumour cerebri with dural sinus stenosis. (authors)
In Vitro Synergistic Enhancement of Newcastle Disease Virus to 5-Fluorouracil Cytotoxicity against Tumor Cells

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Ahmed M. Al-Shammari

2016-01-01

Full Text Available Background: Chemotherapy is one of the antitumor therapies used worldwide in spite of its serious side effects and unsatisfactory results. Many attempts have been made to increase its activity and reduce its toxicity. 5-Fluorouracil (5-FU is still a widely-used chemotherapeutic agent, especially in combination with other chemotherapies. Combination therapy seems to be the best option for targeting tumor cells by different mechanisms. Virotherapy is a promising agent for fighting cancer because of its safety and selectivity. Newcastle disease virus is safe, and it selectively targets tumor cells. We previously demonstrated that Newcastle disease virus (NDV could be used to augment other chemotherapeutic agents and reduce their toxicity by halving the administered dose and replacing the eliminated chemotherapeutic agents with the Newcastle disease virus; the same antitumor activity was maintained. Methods: In the current work, we tested this hypothesis on different tumor cell lines. We used the non-virulent LaSota strain of NDV in combination with 5-FU, and we measured the cytotoxicity effect. We evaluated this combination using Chou–Talalay analysis. Results: NDV was synergistic with 5-FU at low doses when used as a combination therapy on different cancer cells, and there were very mild effects on non-cancer cells. Conclusion: The combination of a virulent, non-pathogenic NDV–LaSota strain with a standard chemotherapeutic agent, 5-FU, has a synergistic effect on different tumor cells in vitro, suggesting this combination could be an important new adjuvant therapy for treating cancer.
Acute Reversible Heart Failure Caused by Coronary Vasoconstriction due to Continuous 5-Fluorouracil Combination Chemotherapy

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Cornelia Dechant

2012-06-01

Full Text Available We present the case of a 51-year-old male patient who received adjuvant chemotherapy consisting of oxaliplatin, bolus and continuous 5-fluorouracil (5-FU and leucovorin after anterior resection because of locally advanced rectal cancer. Preoperative chemotherapy with capecitabine (an oral 5-FU prodrug had been well tolerated. Two days after initiation of the first course of chemotherapy, the patient reported typical chest pain. The ECG showed ST elevations and prominent T waves in almost all leads. Due to suspicion of a high-risk acute coronary syndrome, an urgent cardiac catheterization was performed. It showed a generally reduced coronary flow with multiple significant stenoses (including the ostia of the left and right coronary artery, as well as a highly reduced left ventricular function with diffuse hypokinesia. Due to the meanwhile completely stable situation of the patient after medical acute coronary syndrome treatment, no ad hoc intervention was performed to allow further discussion of the optimal management. Thereafter, the patient remained clinically asymptomatic, without any rise in cardiac necrosis parameters; only NT-pro-BNP was significantly elevated. A control cardiac catheterization 2 days later revealed a restored normal coronary artery flow with only coronary calcifications without significant stenoses, as well as a normal left ventricular ejection fraction. Cardiovascular symptoms occurred on the second day of continuous 5-FU treatment. As cardiotoxic effects seem to appear more frequently under continuous application of 5-FU, compared to the earlier established 5-FU bolus regimens, treating medical oncologists should pay special attention to occurring cardiac symptoms and immediately interrupt 5-FU chemotherapy and start a cardiologic work-up.
Characterization and evaluation of 5-fluorouracil-loaded solid lipid nanoparticles prepared via a temperature-modulated solidification technique.

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Patel, Meghavi N; Lakkadwala, Sushant; Majrad, Mohamed S; Injeti, Elisha R; Gollmer, Steven M; Shah, Zahoor A; Boddu, Sai Hanuman Sagar; Nesamony, Jerry

2014-12-01

The aim of this research was to advance solid lipid nanoparticle (SLN) preparation methodology by preparing glyceryl monostearate (GMS) nanoparticles using a temperature-modulated solidification process. The technique was reproducible and prepared nanoparticles without the need of organic solvents. An anticancer agent, 5-fluorouracil (5-FU), was incorporated in the SLNs. The SLNs were characterized by particle size analysis, zeta potential analysis, differential scanning calorimetry (DSC), infrared spectroscopy, atomic force microscopy (AFM), transmission electron microscopy (TEM), drug encapsulation efficiency, in vitro drug release, and in vitro cell viability studies. Particle size of the SLN dispersion was below 100 nm, and that of redispersed lyophilizates was ~500 nm. DSC and infrared spectroscopy suggested that the degree of crystallinity did not decrease appreciably when compared to GMS. TEM and AFM images showed well-defined spherical to oval particles. The drug encapsulation efficiency was found to be approximately 46%. In vitro drug release studies showed that 80% of the encapsulated drug was released within 1 h. In vitro cell cultures were biocompatible with blank SLNs but demonstrated concentration-dependent changes in cell viability to 5-FU-loaded SLNs. The 5-FU-loaded SLNs can potentially be utilized in an anticancer drug delivery system.
[Benefit of adjuvant 5-fluorouracil based chemotherapy for colon cancer: a retrospective cohort study].

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Mondaca, Sebastián; Villalón, Constanza; Leal, José Luis; Zúñiga, Álvaro; Bellolio, Felipe; Padilla, Oslando; Palma, Silvia; Garrido, Marcelo; Nervi, Bruno

2016-02-01

Multiple clinical trials have demonstrated the benefits of adjuvant 5-fluorouracil-based chemotherapy for patients with resectable colon cancer (CC), especially in stage III. To describe the clinical characteristics of a cohort of CC patients treated at a single university hospital in Chile since 2002, and to investigate if chemotherapy had an effect on survival rates. Review of a tumor registry of the hospital. Medical records of patients with CC treated between 2002 and 2012 were reviewed. Death certificates from the National Identification Service were used to determine mortality. Overall survival was described using the Kaplan-Meier method. A multivariate Cox proportional hazard regression model was also used. A total of 370 patients were treated during the study period (202 in stage II and 168 in stage III). Adjuvant chemotherapy was administered to 22 and 70% of patients in stage II and III respectively. The median follow-up period was 4.6 years. The 5-year survival rate for stage II patients was 79% and there was no benefit observed with adjuvant chemotherapy. For stage III patients, the 5-year survival rate was 81% for patients who received adjuvant chemotherapy, compared to 56% for those who did not receive chemotherapy (hazard ratio (HR): 0.29; 95% confidence interval (CI): 0.15-0.56). The benefit of chemotherapy was found to persist after adjustment for other prognostic variables (HR: 0.47; 95% CI: 0.23-0.94). Patients with colon cancer in stage III who received adjuvant chemotherapy had a better overall survival.
Curcumin chemosensitizes 5-fluorouracil resistant MMR-deficient human colon cancer cells in high density cultures.

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Mehdi Shakibaei

Full Text Available OBJECTIVE: Treatment of colorectal cancer (CRC remains a clinical challenge, as more than 15% of patients are resistant to 5-Fluorouracil (5-FU-based chemotherapeutic regimens, and tumor recurrence rates can be as high as 50-60%. Cancer stem cells (CSC are capable of surviving conventional chemotherapies that permits regeneration of original tumors. Therefore, we investigated the effectiveness of 5-FU and plant polyphenol (curcumin in context of DNA mismatch repair (MMR status and CSC activity in 3D cultures of CRC cells. METHODS: High density 3D cultures of CRC cell lines HCT116, HCT116+ch3 (complemented with chromosome 3 and their corresponding isogenic 5-FU-chemo-resistant derivative clones (HCT116R, HCT116+ch3R were treated with 5-FU either without or with curcumin in time- and dose-dependent assays. RESULTS: Pre-treatment with curcumin significantly enhanced the effect of 5-FU on HCT116R and HCR116+ch3R cells, in contrast to 5-FU alone as evidenced by increased disintegration of colonospheres, enhanced apoptosis and by inhibiting their growth. Curcumin and/or 5-FU strongly affected MMR-deficient CRC cells in high density cultures, however MMR-proficient CRC cells were more sensitive. These effects of curcumin in enhancing chemosensitivity to 5-FU were further supported by its ability to effectively suppress CSC pools as evidenced by decreased number of CSC marker positive cells, highlighting the suitability of this 3D culture model for evaluating CSC marker expression in a close to vivo setting. CONCLUSION: Our results illustrate novel and previously unrecognized effects of curcumin in enhancing chemosensitization to 5-FU-based chemotherapy on DNA MMR-deficient and their chemo-resistant counterparts by targeting the CSC sub-population. (246 words in abstract.
Curcumin chemosensitizes 5-fluorouracil resistant MMR-deficient human colon cancer cells in high density cultures.

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Shakibaei, Mehdi; Buhrmann, Constanze; Kraehe, Patricia; Shayan, Parviz; Lueders, Cora; Goel, Ajay

2014-01-01

Treatment of colorectal cancer (CRC) remains a clinical challenge, as more than 15% of patients are resistant to 5-Fluorouracil (5-FU)-based chemotherapeutic regimens, and tumor recurrence rates can be as high as 50-60%. Cancer stem cells (CSC) are capable of surviving conventional chemotherapies that permits regeneration of original tumors. Therefore, we investigated the effectiveness of 5-FU and plant polyphenol (curcumin) in context of DNA mismatch repair (MMR) status and CSC activity in 3D cultures of CRC cells. High density 3D cultures of CRC cell lines HCT116, HCT116+ch3 (complemented with chromosome 3) and their corresponding isogenic 5-FU-chemo-resistant derivative clones (HCT116R, HCT116+ch3R) were treated with 5-FU either without or with curcumin in time- and dose-dependent assays. Pre-treatment with curcumin significantly enhanced the effect of 5-FU on HCT116R and HCR116+ch3R cells, in contrast to 5-FU alone as evidenced by increased disintegration of colonospheres, enhanced apoptosis and by inhibiting their growth. Curcumin and/or 5-FU strongly affected MMR-deficient CRC cells in high density cultures, however MMR-proficient CRC cells were more sensitive. These effects of curcumin in enhancing chemosensitivity to 5-FU were further supported by its ability to effectively suppress CSC pools as evidenced by decreased number of CSC marker positive cells, highlighting the suitability of this 3D culture model for evaluating CSC marker expression in a close to vivo setting. Our results illustrate novel and previously unrecognized effects of curcumin in enhancing chemosensitization to 5-FU-based chemotherapy on DNA MMR-deficient and their chemo-resistant counterparts by targeting the CSC sub-population. (246 words in abstract).
Radioimmunological determination of 5a-pregnane-3,20-dione and progesterone in arterial and venous blood from the umbilical cord

International Nuclear Information System (INIS)

Tannich, E.

1985-01-01

Radioimmunological investigations of arterial and venous blood from the umbilical cord for 5a-DHP and progesterone were carried out in 60 newly delivered infants using 3 H as a tracer substance. The following findings were revealed: 1) The correlation between progesterone and 5a-DHP was better in the venous blood than in the arterial blood from the umbilical cord and the concentrations measured for the two hormones were higher in the vein. 2) Both the umbilical vein and artery showed more elevated hormone levels in male infants as compared to female infants. 3) The duration of gestation, the concentration of hydrogen ions in the fetal plasma and various other maternal and fetal factors have an influence on the height of the 5a-DHP and progesterone levels in the umbilical blood. This was also concluded from the fact that the (arterial and venous) hormone concentrations measured in infants from primiparae were higher than those in infants from multiparae. The metabolisation of 5a-DHP varies between the sexes, which does not hold true for progosterone. (TRV) [de
YB-1 facilitates basal and 5-fluorouracil-inducible expression of the human major vault protein (MVP) gene.

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Stein, Ulrike; Bergmann, Stephan; Scheffer, George L; Scheper, Rik J; Royer, Hans-Dieter; Schlag, Peter M; Walther, Wolfgang

2005-05-19

Vaults have been suggested to play a direct role in multidrug resistance (MDR) to anticancer drugs. The human major vault protein (MVP) also known as lung resistance-related protein (LRP) represents the predominant component of vaults that may be involved in the defense against xenobiotics. Here, we demonstrate that besides MDR-related cytostatics, also the non-MDR-related drug 5-fluorouracil (5-FU) was able to induce MVP mRNA and protein expression. Treatment with 5-FU amplified the binding activity and interaction of the transcription factor Y-box binding protein-1 (YB-1) with the Y-box of the human MVP gene promoter in a time-dependent manner. 5-FU also induced reporter expressions driven by a panel of newly generated MVP promoter deletion mutants. Interestingly, stably YB-1 overexpressing cell clones showed enhanced binding of YB-1 to the Y-box motif, associated with enhanced basal as well as 5-FU-inducible MVP promoter-driven reporter expressions. Moreover, transduction of YB-1 cDNA led to increased expression of endogenous MVP protein. Under physiological conditions, we observed a strong coexpression of MVP and YB-1 in human colon carcinoma specimen. In summary, our data demonstrate a direct involvement of YB-1 in controlling basal and 5-FU-induced MVP promoter activity. Therefore, YB-1 is directly linked to MVP-mediated drug resistance.
Effects of atmospheric pressure cold plasma on human hepatocarcinoma cell and its 5-fluorouracil resistant cell line

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Yang, H.; Gan, L.; Yang, X., E-mail: luxinpei@hotmail.com, E-mail: yangxl@mail.hust.edu.cn [College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei 430074 (China); Lu, R. [School Hospital of Huazhong University of Science and Technology, Wuhan, Hubei 430074 (China); Xian, Y.; Lu, X., E-mail: luxinpei@hotmail.com, E-mail: yangxl@mail.hust.edu.cn [State Key Laboratory of Advanced Electromagnetic Engineering and Technology, Huazhong University of Science and Technology, Wuhan, Hubei 430074 (China)

2015-12-15

Atmospheric pressure cold plasma showed selective killing efficiency on cancer cells in vitro and in vivo, which makes plasma a potential option for cancer therapy. However, the plasma effects on chemotherapeutic drugs-resistant cells are rarely to be found. In this paper, the effects of plasma on human hepatocellular carcinoma Bel7402 cells and 5-fluorouracil (5-FU) resistant Bel7402/5FU cells were intensively investigated. The results showed that plasma induced superior toxicity to Bel7402 cells compared with Bel7402/5FU cells. Incubation with plasma-treated medium for 20 s induced more than 85% death rate in Bel7402 cells, while the same death ratio was achieved when Bel7402/5FU cells were treated for as long as 300 s. The hydrogen peroxide in the medium played a leading role in the cytotoxicity effects. Further studies implicated that when the treatment time was shorter than 60 s, the depolarization of mitochondrial membrane potential and apoptosis occurred through the intracellular reactive oxygen species accumulation in Bel7402 cells. Molecular analysis showed an increase in the transcription factor activity for AP-1, NF-kB, and p53 in Bel7402 cells. No obvious damage could be detected in plasma-treated Bel7402/5FU cells due to the strong intracellular reactive oxygen stress scavenger system.

Effects of atmospheric pressure cold plasma on human hepatocarcinoma cell and its 5-fluorouracil resistant cell line

Science.gov (United States)

Yang, H.; Lu, R.; Xian, Y.; Gan, L.; Lu, X.; Yang, X.

2015-12-01

Atmospheric pressure cold plasma showed selective killing efficiency on cancer cells in vitro and in vivo, which makes plasma a potential option for cancer therapy. However, the plasma effects on chemotherapeutic drugs-resistant cells are rarely to be found. In this paper, the effects of plasma on human hepatocellular carcinoma Bel7402 cells and 5-fluorouracil (5-FU) resistant Bel7402/5FU cells were intensively investigated. The results showed that plasma induced superior toxicity to Bel7402 cells compared with Bel7402/5FU cells. Incubation with plasma-treated medium for 20 s induced more than 85% death rate in Bel7402 cells, while the same death ratio was achieved when Bel7402/5FU cells were treated for as long as 300 s. The hydrogen peroxide in the medium played a leading role in the cytotoxicity effects. Further studies implicated that when the treatment time was shorter than 60 s, the depolarization of mitochondrial membrane potential and apoptosis occurred through the intracellular reactive oxygen species accumulation in Bel7402 cells. Molecular analysis showed an increase in the transcription factor activity for AP-1, NF-кB, and p53 in Bel7402 cells. No obvious damage could be detected in plasma-treated Bel7402/5FU cells due to the strong intracellular reactive oxygen stress scavenger system.
Clinical applications of continuous infusion chemotherapy ahd concomitant radiation therapy

International Nuclear Information System (INIS)

Rosenthal, C.J.; Rotman, M.

1986-01-01

This book presents information on the following topics: theoretical basis and clinical applications of 5-FU as a radiosensitizer; treatment of hepatic metastases from gastro intestingal primaries with split course radiation therapy; combined modality therapy with 5-FU, Mitomycin-C and radiation therapy for sqamous cell cancers; treatment of bladder carcinoma with concomitant infusion chemotherapy and irradiation; a treatment of invasiv bladder cancer by the XRT/5FU protocol; concomitant radiation therapy and doxorubicin by continuous infusion in advanced malignancies; cis platin by continuous infusion with concurrent radiation therapy in malignant tumors; combination of radiation with concomitant continuous adriamycin infusion in a patient with partially excised pleomorphic soft tissue sarcoma of the lower extremeity; treatment of recurrent carcinoma of the paranasal sinuses using concomitant infusion cis-platinum and radiation therapy; hepatic artery infusion for hepatic metastases in combination with hepatic resection and hepatic radiation; study of simultaneous radiation therapy, continuous infusion, 5FU and bolus mitomycin-C; cancer of the esophagus; continuous infusion VP-16, bolus cis-platinum and simultaneous radiation therapy as salvage therapy in small cell bronchogenic carcinoma; and concomitant radiation, mitomycin-C and 5-FU infusion in gastro intestinal cancer
Changes in plasma calcium and in radiocalcium kinetics after termination of 5-week infusions of synthetic parathyroid peptide in dogs

International Nuclear Information System (INIS)

Stevenson, R.W.; Parsons, J.A.; Podbesek, R.D.; Reeve, J.

1983-01-01

Nine dogs were infused at constant rates with the synthetic parathyroid peptide hPTH 1-34 (initially sc) to produce consistent hypercalcaemia. Over the final week, the infusions were iv. Radioisotopic tracers were injected iv 30 days (5 dogs) and 2 days (9 dogs) before the infusions were suddenly terminated. In 5 dogs, complete urine collections were obtained via a bladder catheter over 8 h beginning 2 h before stopping the infusions. Cessation of treatment caused small rises in the urinary Ca: creatinine ratio. Plasma calcium levels fell by a mean of 0.44 mmol/l, of which total urine calcium excretion only accounted for 55%. Immediately after the PTH infusions were stopped, consistent but transient increases were seen in the ratio of ''new'' 47 Ca to ''old'' 45 Ca label, suggesting inflow of 40 Ca of high 47 Ca specific activity from a fairly rapidly exchangeable bone pool. These data confirm and extend previous evidence that the immediate response of the calcium equilibrium between bone and bloodstream to rapid changes in plasma PTH concentrations in the supra-physiological ranges is paradoxical relative to the classical later response. (author)
VENOUS INSUFFICIENCY AND THROMBOEMBOLIC DISEASE IN BARIATRIC SURGERY PATIENTS

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Bonno van BELLEN

2013-09-01

Full Text Available Context Morbid obesity is associated with various co-morbidities, including chronic venous insufficiency. Bariatric surgery is the only effective treatment for morbid obesity, but with potential risks and possible complications, including venous thromboembolism. Objective To determine the prevalence of clinical and ultrasonographic signs of chronic venous insufficiency in morbid obese patients in preparation for bariatric surgery and the incidence of post-operative venous thromboembolic disease. Methods Patients on work-up for bariatric surgery of Centro Terapêutico Especializado em Fígado (CETEFI and Pro-Gastro surgical teams of the Hospital Beneficência Portuguesa de São Paulo were included. The analysed data were pre-operative findings for venous insufficiency (CEAP - clinical, etiological, anatomical, physiopathologic - classification and venous ultrassonographic findings, type of surgery (open or laparoscopic, abdominal circumference, body mass index (BMI and post-operative ultrassonography search for venous insufficiency and deep venous thrombosis. Results Between March 2007 and December 2009, 95 patients candidates for bariatric surgery had clinical and duplex scan evaluation of the lower limbs venous system. Of the 95 patients, 53 were submitted to the surgical procedure. There was a predominance of women (77.9%, the average age was 38.5 years, average preoperative weight 124.6 kg and average BMI of 45.5 kg/m2. Regarding obesity, 16.8% were obese, and 83.1% were morbidly obese. In relation to the venous findings, 86.3% of the patients did fit CEAP classification less than 3 and 13.7% greater than or equal to 3. Among the post-operative complications, there were four cases of wound infection. Three patients developed post-operative distal venous thrombosis (7.5%, but no one had clinically manifested pulmonary embolism. Conclusion No relation between BMI, CEAP classification and venous ultrassonographic findings were found. Although
Local release of ATP into the arterial inflow and venous drainage of human skeletal muscle: insight from ATP determination with the intravascular microdialysis technique

DEFF Research Database (Denmark)

Mortensen, Stefan; Thaning, Pia; Nyberg, Michael Permin

2011-01-01

is released into plasma, we measured plasma [ATP] with the intravascular microdialysis technique at rest and during dynamic exercise (normoxia and hypoxia), passive exercise, thigh compressions and arterial ATP, tyramine and ACh infusion in a total of 16 healthy young men. Femoral arterial and venous...
In vitro cytotoxicity and genotoxicity studies of gold nanoparticles-mediated photo-thermal therapy versus 5-fluorouracil

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Gomaa, Iman E., E-mail: iman.gomaa@guc.edu.eg; Abdel Gaber, Sara A. [German University in Cairo (GUC), Faculty of Pharmacy and Biotechnology (Egypt); Bhatt, Samarth; Liehr, Thomas [Friedrich Schiller University, Jena University Hospital, Institute of Human Genetics (Germany); Glei, Michael [Friedrich Schiller University, Faculty of Biology and Pharmacy, Institute of Nutrition (Germany); El-Tayeb, Tarek A. [Cairo University, The National Institute for Laser Enhanced Sciences (NILES) (Egypt); Abdel-Kader, Mahmoud H. [German University in Cairo (GUC), Faculty of Pharmacy and Biotechnology (Egypt)

2015-02-15

This study evaluates tumour cell-killing efficacy of metallic gold nanoparticles (AuNPs)-mediated photo-thermal therapy (PTT) in comparison to 5-fluorouracil (5-FU) as a standard chemotherapeutic drug. It also focuses on the possible genetic abnormalities of both drugs in normal blood lymphocytes. Both 5-FU and light-activated spherical AuNPs of 15± nm diameter were used to target MCF-7 breast cancer cell line. Alkaline comet assay, standard karyotyping and multiplex fluorescent in situ hybridization were applied in order to investigate the respective possible genotoxic and mutagenic side effects that might result from the application of each therapeutic modality. Results showed that the LC25 of AuNPs-mediated PTT was achieved at a concentration of 100 µM for 12-h incubation and exposure to light energy of 50 J/cm{sup 2}, while the same cytotoxic effect was obtained by incubating the MCF-7 cells with the same concentration of the chemotherapeutic drug 5-FU for 24 h. On the other hand, AuNPs showed insignificant genotoxic effect of DNA damage represented by 4.6 % in comparison to 18.58 % exerted by 5-FU. The chromosomal studies resulted in normal karyotypes for cells treated with AuNPs-mediated PTT, while those treated with 5-FU showed several types of numerical as well as structural chromosomal aberrations. In conclusion, compared to 5-FU, light-activated AuNPs-mediated PTT provides considerable efficacy in breast cancer cells killing with no genetic side effects under the proposed experimental conditions.
In vitro cytotoxicity and genotoxicity studies of gold nanoparticles-mediated photo-thermal therapy versus 5-fluorouracil

International Nuclear Information System (INIS)

Gomaa, Iman E.; Abdel Gaber, Sara A.; Bhatt, Samarth; Liehr, Thomas; Glei, Michael; El-Tayeb, Tarek A.; Abdel-Kader, Mahmoud H.

2015-01-01

This study evaluates tumour cell-killing efficacy of metallic gold nanoparticles (AuNPs)-mediated photo-thermal therapy (PTT) in comparison to 5-fluorouracil (5-FU) as a standard chemotherapeutic drug. It also focuses on the possible genetic abnormalities of both drugs in normal blood lymphocytes. Both 5-FU and light-activated spherical AuNPs of 15± nm diameter were used to target MCF-7 breast cancer cell line. Alkaline comet assay, standard karyotyping and multiplex fluorescent in situ hybridization were applied in order to investigate the respective possible genotoxic and mutagenic side effects that might result from the application of each therapeutic modality. Results showed that the LC25 of AuNPs-mediated PTT was achieved at a concentration of 100 µM for 12-h incubation and exposure to light energy of 50 J/cm 2 , while the same cytotoxic effect was obtained by incubating the MCF-7 cells with the same concentration of the chemotherapeutic drug 5-FU for 24 h. On the other hand, AuNPs showed insignificant genotoxic effect of DNA damage represented by 4.6 % in comparison to 18.58 % exerted by 5-FU. The chromosomal studies resulted in normal karyotypes for cells treated with AuNPs-mediated PTT, while those treated with 5-FU showed several types of numerical as well as structural chromosomal aberrations. In conclusion, compared to 5-FU, light-activated AuNPs-mediated PTT provides considerable efficacy in breast cancer cells killing with no genetic side effects under the proposed experimental conditions
Biweekly irinotecan plus bolus 5-fluorouracil and folinic acid in patients with advanced stage colorectal cancer.

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Yalcin, Suayib; Oksuzoglu, Berna; Tekuzman, Gülten; Engin, Hüseyin; Celik, Ismail; Turker, Alev; Barista, Ibrahim; Gullu, Ibrahim; Guler, Nilufer; Altundag, Kadri; Ozisik, Yavuz; Kars, Ayse

2003-11-01

In this study, we evaluated the efficacy and tolerability of biweekly irinotecan (CPT-11) plus 5-fluorouracil (5-FU) and folinic acid (FA) regimen (IFL) in patients with advanced stage colorectal cancer. A total of 28 patients were examined. The median age was 51 years (range, 30-74 years). One treatment cycle consisted of CPT-11 180 mg/m(2) on days 1 and 15; 5-FU 425 mg/m(2) on days 1, 2, 15 and 16; and FA 20 mg/m(2) on days 1, 2, 15 and 16, every 4 weeks. A total of 119 cycles (median, 4.0 cycles) were administered. Of the 28 patients, 18 received the chemotherapy as first line treatment, seven received it as second line and three received it as third line. An overall objective response rate of 21.5% was achieved in the patient group. However, the overall response rate for the 18 patients receiving first line treatment was 27.7%. The median response duration was 10.5 months (range, 3-19 months). An additional 28.6% of the patients had stable disease for a median duration of 6.5 months (range, 3-8 months). Median time to disease progression was 4.5 months (range, 1-22+ months) and median overall survival time was 11+ months (95% confidence interval, 9-15 months). Toxicities were mild and manageable. We conclude that biweekly IFL is a practical and tolerable treatment option with a disease control rate of 50.1% in patients with advanced stage colorectal cancer.
Determination of 24-hour insulin infusion pattern by an artificial endocrine pancreas for intravenous insulin infusion with a miniature pump

DEFF Research Database (Denmark)

Kølendorf, K; Christiansen, J S; Bojsen, J

1981-01-01

UNLABELLED: Intravenous insulin infusion with a glucose controlled insulin infusion system (GCIIS) is known to restore glucose homeostasis. A simpler approach to improve blood glucose regulation is preprogrammed intravenous insulin infusion with portable pumps without sensor-mediated feedback. We...... report a study designed to evaluate whether the preprogrammed insulin infusion pattern to be used in the miniature insulin infusion pump (MIIP) could be optimized by concomitant employment of the GCIIS for blood glucose control. Six juvenile-onset insulin-dependent diabetics (mean age 31 yrs) were...... studied. Mean blood glucose (MBG) was 6.2 mmol/l +/- 0.5 (SD) during glucose controlled infusion and 5.3 +/- 0.6 during the combined MIIP + GCIIS-day. The insulin requirements calculated from the s.c. regimen (56 U +/- 10 SD) were identical to the GCIIS-measured (51 U +/- 14) and to the amounts delivered...
Tumor trapping of 5-fluorouracil: In vivo 19F NMR spectroscopic pharmacokinetics in tumor-bearing humans and rabbits

International Nuclear Information System (INIS)

Wolf, W.; Servis, K.L.; El-Tahtawy, A.; Singh, M.; Ray, M.; Shani, J.; Presant, C.A.; King, M.; Wiseman, C.; Blayney, D.; Albright, M.J.; Atkinson, D.; Ong, R.; Barker, P.B.; Ring, R. III

1990-01-01

The pharmacokinetics of 5-fluorouracil (5FU) were studied in vivo in patients with discrete tumors and in rabbits bearing VX2 tumors by using 19 F NMR spectroscopy. Free 5FU was detected in the tumors of four of the six patients and in all VX2 tumors but not in normal rabbit tissues. No other metabolites were seen in these tumors, contrary to the extensive catabolism previously documented using 19 F NMR spectroscopy in both human and animal livers. The tumor pool of free 5FU in those human tumors that trapped 5FU was determined to have a half-life of 0.4-2.1 hr, much longer than expected and significantly longer than the half-life of 5FU in blood (5-15 min), whereas the half-life of trapped 5FU in the VX2 tumors ranged from 1.05 to 1.22 hr. These studies document that NMR spectroscopy is clinically feasible in vivo, allows noninvasive pharmacokinetic analyses at a drug-target tissue in real time, and may produce therapeutically important information at the time of drug administration. Demonstration of the trapping of 5FU in tumors provides both a model for studying metabolic modulation in experimental tumors (in animals) and a method for testing modulation strategies clinically (in patients)
Chamomile infusion cryotherapy to prevent oral mucositis induced by chemotherapy: a pilot study.

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Dos Reis, Paula Elaine Diniz; Ciol, Marcia A; de Melo, Nilce Santos; Figueiredo, Paulo Tadeu de Souza; Leite, André Ferreira; Manzi, Natália de Melo

2016-10-01

The aim of this study is to compare cryotherapy made only with water and cryotherapy made with chamomile infusion for prevention and reduction of intensity of oral mucositis in patients with cancer receiving 5-fluorouracil and leucovorin. This is a randomized pilot study with two groups: cryotherapy made only with water (control group, n = 18) and cryotherapy made with chamomile infusion (chamomile group, n = 20). Both groups were instructed to swish the ice around in their oral cavity for at least 30 min during chemotherapy. Assessment of oral mucosa occurred on days 8, 15, and 22 after the first day of chemotherapy. Fifty percent of the patients in the control and 30 % in the chamomile group developed oral mucositis. Mouth pain score was higher in patients in the control group on all evaluations (p = 0.02 for day 8, p = 0.09 for day 15, and p = 0.14 for day 22). Patients in the chamomile group never developed mucositis with grade 2 or higher. Presence of ulceration was statistically significant on day 8 (16 % in the control vs. 0 % in the chamomile group, p = 0.10), but not in days 15 and 22, although 11 % still had ulcerations in the control group and none in the chamomile group. The occurrence of oral mucositis was lower in patients in the chamomile group than in the control group. When compared to the controls, the chamomile group presented less mouth pain and had no ulcerations. Cryotherapy was well tolerated by both groups, and no toxicity related to chamomile was identified.
Evaluation of methyl methanesulfonate, 2,6-diaminotoluene and 5-fluorouracil: Part of the Japanese center for the validation of alternative methods (JaCVAM) international validation study of the in vivo rat alkaline comet assay.

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Plappert-Helbig, Ulla; Junker-Walker, Ursula; Martus, Hans-Joerg

2015-07-01

As a part of the Japanese Center for the Validation of Alternative Methods (JaCVAM)-initiative international validation study of the in vivo rat alkaline comet assay (comet assay), we examined methyl methanesulfonate, 2,6-diaminotoluene, and 5-fluorouracil under coded test conditions. Rats were treated orally with the maximum tolerated dose (MTD) and two additional descending doses of the respective compounds. In the MMS treated groups liver and stomach showed significantly elevated DNA damage at each dose level and a significant dose-response relationship. 2,6-diaminotoluene induced significantly elevated DNA damage in the liver at each dose and a statistically significant dose-response relationship whereas no DNA damage was obtained in the stomach. 5-fluorouracil did not induce DNA damage in either liver or stomach. Copyright © 2015 Elsevier B.V. All rights reserved.
Propranolol, clonidine, urapidil and trazodone infusion in essential tremor: a double-blind crossover trial.

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Caccia, M R; Osio, M; Galimberti, V; Cataldi, G; Mangoni, A

1989-05-01

Accelerometric tremorgrams were recorded from 25 subjects affected by essential tremor and analysed by a Berg-Fourier frequency analyser before and during venous infusion of the following drugs: propranolol (beta-blocker), clonidine (alpha-presynaptic adrenergic agonist), urapidil (alpha-postsynaptic blocker), trazodone (adrenolytic agent) and placebo. The washout interval between infusions was 3 days. Recordings and data analyses were performed in a double-blind crossover trial. Tremor was classified as: at rest; postural (arms hyperextended); and intention (finger-nose test). Analysis of the results showed that propranolol and clonidine reduced significantly (P = 0.01 and P = 0.009, respectively) the power spectrum of postural tremor, but left at rest and intention tremors unchanged. No significant effects on the tremor power spectrum were observed after placebo, urapidil or trazodone administration. None of the drugs had any effect on tremor frequency.
Influence of Spray-dried Hydroxyapatite-5-Fluorouracil Granules on Cell Lines Derived from Tissues of Mesenchymal Origin

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Tim Scharnweber

2008-11-01

Full Text Available In our previous work we described the preparation and characterization of spray dried hydroxyapatite micro granules loaded with 5-fluorouracil (5-FU. These loaded particles are used as a model drug delivery system (DDS. In this study we examined the in vitro response of two cell lines derived from different tissues to 5-FU loaded granules (LG. Both cell lines, either L929 cells of a mouse fibroblast lineage or cells originating from a rat osteosarcoma (ROS 17/2.8 showed a dose dependent decrease in cell proliferation in response to 5-FU-, either dissolved in the culture medium or loaded onto particles. The response of the two cell lines to loaded and nonloaded particles was different. The effect of LG and of a corresponding concentration of free 5-FU was practically the same for the ROS 17/2.8 cells indicating that ROS 17/2.8 cells were not affected by the carrier material. In contrast, L929 cells showed a slight decrease in cell proliferation also in the presence of granules not loaded with 5-FU. This is thought to be attributed to the inhibition of mitogenesis by phosphocitrates, already demonstrated in fibroblasts. In summary, we found that the loaded 5-FU kept its effectivity after the spray drying process and that the response towards the granules varied with cell type. This is the first step towards a tissue specific DDS.
Comparative study of peripherally inserted central venous catheter and traditional central catheter assisted with X-ray

International Nuclear Information System (INIS)

Yu Jianchun; Wang Xiurong; Jiang Zhuming

1999-01-01

Objective: To study the feasibility, complications, mid- and long-term advantages of peripherally inserted central catheters (PICC) compared with central venous access assisted with X-ray. Methods: From Jan 1997 to Dec 1998, the authors conducted a study in 60 patients with placed PICC lines and 60 patients with central lines. Study variables included tip placement and complication rates. Results: Tere were on significant differences between PICC and CVC in the successful placement 95.0% and 88.3%, t = 1.745, P 0.19; the mean duration 13(6-98) days and 14 (7-104) days, F = 0.049, P = 0.83; the total occlusion rate 6.7% (4/60) and 5.0%(3/60), t = 0.152, P = 0.70. In PICC patients, the occlusion rate was slightly higher in 3 Fr (20-gauge) catheter (3/20, 15.0%) than in 4 Fr(18-gauge) catheters (1/20, 5.0%), t = 1.111, P=0.29. Phlebitis occurred in 5.0% of patients (3/60) and one catheter fracture was happened on the catheter hub junction (1.7%). In 3 catheter tips dislocation cases, the catheter tips were moved to the optional position assisted with X-ray image. In CVC group, pneumothorax happened in 1 case (1.7%). In 4 catheter dislocation cases, the catheters were with drawn. No catheter-related sepsis and hemo-pneumothorax happened in both group patients. Conclusions: Both PICC and CVC can be acceptable in clinical use. PICC assisted with X-ray possesses the advantages of less trauma, accurate localization preventing some possible severe complications of central venous access such as pneumothorax. The new method provides a reliable, effective venous access for mid-and long-term usage in patients receiving a variety of solutions, primarily parenteral alimentation, chemotherapy or antibiotic infusion
Experimental cystic echinococcosis therapy: In vitro and in vivo combined 5-fluorouracil/albendazole treatment.

Science.gov (United States)

Pensel, Patricia E; Elissondo, Natalia; Gambino, Guillermo; Gamboa, Gabriela Ullio; Benoit, J P; Elissondo, María C

2017-10-15

Human cystic echinococcosis is a zoonosis caused by the larval stage of the tapeworm Echinococcus granulosus sensu lato (s. l.). Although benzimidazole compounds such as albendazole (ABZ) and mebendazole have been the cornerstone of chemotherapy for the disease, there is often no complete recovery after treatment. Hence, new strategies are required to improve treatment of human cystic echinococcosis. The goals of the current study were as follows: (i) to evaluate the in vitro efficacy of the 5-fluorouracil (5-FU) and ABZ combination against E. granulosus s. l. protoscoleces and cysts, (ii) to compare the clinical efficacy of 5-FU alone or in combination with ABZ in infected mice. The combination of 5-FU+ABZ had a stronger in vitro effect against larval stage than that did both drugs alone. Even at the lowest concentration of 5-FU+ABZ combination (1μg/ml), the reduction of the viability of protoscoleces and cysts was greater than that observed with drugs alone at 10μg/ml. The results were confirmed at the ultrastructural level by scanning electron microscopy. These data helped to justify the in vivo investigations assessing the therapeutic potential of the combination of 5-FU and ABZ suspension in CF-1 mice infected with E. granulosus sensu stricto (s. s.) metacestodes. Treatment with 5-FU (10mg/kg) or 5-FU (10mg/kg) + ABZ suspension (5mg/kg) reduced the weight of cysts recovered from mice compared with control groups. Interestingly, the effect of 5-FU given weekly for 5 consecutive weeks was comparable to that observed with ABZ suspension under a daily schedule during 30days. Co-administration of 5-FU with ABZ did not enhance the in vivo efficacy of drugs alone calculated in relation to cysts weights. However, the combination provoked greater ultrastructural alterations compared to the monotherapy. In conclusion, we demonstrated the efficacy of 5-FU either alone or co-administrated with ABZ against murine experimental cystic echinococcosis. Since 5-FU treatments
An Inhalable Powder Formulation Based on Micro- and Nanoparticles Containing 5-Fluorouracil for the Treatment of Metastatic Melanoma

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Reolon, Luciano Antonio; Amaral-Machado, Lucas; Gremião, Maria Palmira Daflon; Guterres, Silvia S.

2018-01-01

Melanoma is the most aggressive and lethal type of skin cancer, with a poor prognosis because of the potential for metastatic spread. The aim was to develop innovative powder formulations for the treatment of metastatic melanoma based on micro- and nanocarriers containing 5-fluorouracil (5FU) for pulmonary administration, aiming at local and systemic action. Therefore, two innovative inhalable powder formulations were produced by spray-drying using chondroitin sulfate as a structuring polymer: (a) 5FU nanoparticles obtained by piezoelectric atomization (5FU-NS) and (b) 5FU microparticles of the mucoadhesive agent Methocel™ F4M for sustained release produced by conventional spray drying (5FU-MS). The physicochemical and aerodynamic were evaluated in vitro for both systems, proving to be attractive for pulmonary delivery. The theoretical aerodynamic diameters obtained were 0.322 ± 0.07 µm (5FU-NS) and 1.138 ± 0.54 µm (5FU-MS). The fraction of respirable particles (FR%) were 76.84 ± 0.07% (5FU-NS) and 55.01 ± 2.91% (5FU-MS). The in vitro mucoadhesive properties exhibited significant adhesion efficiency in the presence of Methocel™ F4M. 5FU-MS and 5FU-NS were tested for their cytotoxic action on melanoma cancer cells (A2058 and A375) and both showed a cytotoxic effect similar to 5FU pure at concentrations of 4.3 and 1.7-fold lower, respectively. PMID:29385692
An Inhalable Powder Formulation Based on Micro- and Nanoparticles Containing 5-Fluorouracil for the Treatment of Metastatic Melanoma

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Kelly Cristine Zatta

2018-01-01

Full Text Available Melanoma is the most aggressive and lethal type of skin cancer, with a poor prognosis because of the potential for metastatic spread. The aim was to develop innovative powder formulations for the treatment of metastatic melanoma based on micro- and nanocarriers containing 5-fluorouracil (5FU for pulmonary administration, aiming at local and systemic action. Therefore, two innovative inhalable powder formulations were produced by spray-drying using chondroitin sulfate as a structuring polymer: (a 5FU nanoparticles obtained by piezoelectric atomization (5FU-NS and (b 5FU microparticles of the mucoadhesive agent Methocel™ F4M for sustained release produced by conventional spray drying (5FU-MS. The physicochemical and aerodynamic were evaluated in vitro for both systems, proving to be attractive for pulmonary delivery. The theoretical aerodynamic diameters obtained were 0.322 ± 0.07 µm (5FU-NS and 1.138 ± 0.54 µm (5FU-MS. The fraction of respirable particles (FR% were 76.84 ± 0.07% (5FU-NS and 55.01 ± 2.91% (5FU-MS. The in vitro mucoadhesive properties exhibited significant adhesion efficiency in the presence of Methocel™ F4M. 5FU-MS and 5FU-NS were tested for their cytotoxic action on melanoma cancer cells (A2058 and A375 and both showed a cytotoxic effect similar to 5FU pure at concentrations of 4.3 and 1.7-fold lower, respectively.
THE AZYGOS VENOUS SYSTEM AND ITS ANATOMICAL VARIATIONS

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Madiki Sudhakara Rao

2016-06-01

Full Text Available AIMS AND OBJECTIVES Azygos veins are important cavocaval and portacaval junctions, which form a collateral circulation in caval vein occlusion and in portal hypertension, cirrhosis of liver. The unpaired azygos venous system consists of azygos vein, hemiazygos vein and accessory azygos vein. This system of veins, along with its mediastinal, bronchial and oesophageal tributaries drains most of the body wall of trunk, namely posterior abdominal and thoracic wall. Anatomical variations of this unpaired azygos venous system are clinically important. AIMS To study and report the occurrence of anatomical variations of the unpaired azygos venous system in the region of East Godavari District, Andhra Pradesh (India. METHODS The present study was carried out in the Department of Anatomy, KIMS & RF, Amalapuram and G.S.L. Medical College, Rajahmundry over a period of 2 years. The present study was conducted on 60 cadavers (irrespective of age and sex. The entire course of the azygos venous system in these 60 cadavers was carefully observed and documented. RESULTS Anatomical variations were present in 16.66% of cases, out of which three distinct types were identified. 6.6% exhibited two separate azygos venous systems with no communications, 5% with communication between the left brachiocephalic vein and the azygos vein and 5% presence of post-aortic venous channels. CONCLUSION Variations of azygos venous system may be wrongly dubbed as aneurysm, lymphadenopathy or other abnormalities while reporting a CT scan of mediastinum. Venous anomalies are also detected only during surgery. The most troublesome intraoperative hazard is haemorrhage, which is mainly of venous origin. To avoid such situations is to have an awareness and knowledge of the expected venous anomalies.
Comparison of external dacryocystorhinostomy and 5-fluorouracil augmented endonasal laser dacryocystorhinostomy. A Retrospective review

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Watts Patrick

2001-01-01

Full Text Available Purpose: To compare the success rates of external dacryocystorhinostomy (EXT-DCR with 5-fluorouracil (5-FU augmented endonasal laser dacryocystorhinostomy (ENL-DCR and to record the complications associated with 5-FU augmented ENL-DCR Materials and Methods: This was a retrospective non-randomised study. Forty-one patients with primary acquired nasolacrimal duct obstruction underwent an EXT-DCR (19 patients or an ENL-DCR (22 patients over a 3-year period. A Holmium YAG laser (Ho:YAG was used in the latter group of patients. Silicone tubes intubated in all patients were removed at three months. 5-FU was applied intraoperatively at the site of the ostium in the ENL-DCR patients. The median follow-up was 12 months (range 3-24 months for the ENL-DCR group and 22 months (range 6-28 months for the EXT-DCR group. The patency of the lacrimal system and the severity of epiphora were assessed at a final-review. Results: The median age of the EXT-DCR group was 77 years (range 53-87 and that of the ENL-DCR group was 71 years (range 23 to 84. There were 12 female patients in the former group and 19 in the latter. The percentage of success in the EXT-DCR group was 94.7% (95% confidence interval (CI = 75.4-99.1 = , and 63.6% in the ENL-DCR group (95% CI= 43.0-80.3. The confidence interval for the difference of 31.1% was 5.6-52.2. There was a statistically significant difference between the two groups, p=0.024 (Fisher exact test. Conclusions: These data suggest that EXT-DCR provides better results than 5-FU augmented ENL-DCR. However, ENL-DCR is the procedure of choice in certain circumstances such as in elderly, frail or medically unfit patients. Our results of 5-FU augmented ENL-DCR compare favourably with other published series.

Cadmium modifies the cell cycle and apoptotic profiles of human breast cancer cells treated with 5-fluorouracil.

Science.gov (United States)

Asara, Yolande; Marchal, Juan A; Carrasco, Esther; Boulaiz, Houria; Solinas, Giuliana; Bandiera, Pasquale; Garcia, Maria A; Farace, Cristiano; Montella, Andrea; Madeddu, Roberto

2013-08-12

Industrialisation, the proximity of factories to cities, and human work activities have led to a disproportionate use of substances containing heavy metals, such as cadmium (Cd), which may have deleterious effects on human health. Carcinogenic effects of Cd and its relationship with breast cancer, among other tumours, have been reported. 5-Fluorouracil (5-FU) is a fluoropyrimidine anticancer drug used to treat solid tumours of the colon, breast, stomach, liver, and pancreas. The purpose of this work was to study the effects of Cd on cell cycle, apoptosis, and gene and protein expression in MCF-7 breast cancer cells treated with 5-FU. Cd altered the cell cycle profile, and its effects were greater when used either alone or in combination with 5-FU compared with 5-FU alone. Cd significantly suppressed apoptosis of MCF-7 cells pre-treated with 5-FU. Regarding gene and protein expression, bcl2 expression was mainly upregulated by all treatments involving Cd. The expression of caspase 8 and caspase 9 was decreased by most of the treatments and at all times evaluated. C-myc expression was increased by all treatments involving Cd, especially 5-FU plus Cd at the half time of treatment. Cd plus 5-FU decreased cyclin D1 and increased cyclin A1 expression. In conclusion, our results indicate that exposure to Cd blocks the anticancer effects of 5-FU in MCF-7 cells. These results could have important clinical implications in patients treated with 5-FU-based therapies and who are exposed to high levels of Cd.
Cadmium Modifies the Cell Cycle and Apoptotic Profiles of Human Breast Cancer Cells Treated with 5-Fluorouracil

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Roberto Madeddu

2013-08-01

Full Text Available Industrialisation, the proximity of factories to cities, and human work activities have led to a disproportionate use of substances containing heavy metals, such as cadmium (Cd, which may have deleterious effects on human health. Carcinogenic effects of Cd and its relationship with breast cancer, among other tumours, have been reported. 5-Fluorouracil (5-FU is a fluoropyrimidine anticancer drug used to treat solid tumours of the colon, breast, stomach, liver, and pancreas. The purpose of this work was to study the effects of Cd on cell cycle, apoptosis, and gene and protein expression in MCF-7 breast cancer cells treated with 5-FU. Cd altered the cell cycle profile, and its effects were greater when used either alone or in combination with 5-FU compared with 5-FU alone. Cd significantly suppressed apoptosis of MCF-7 cells pre-treated with 5-FU. Regarding gene and protein expression, bcl2 expression was mainly upregulated by all treatments involving Cd. The expression of caspase 8 and caspase 9 was decreased by most of the treatments and at all times evaluated. C-myc expression was increased by all treatments involving Cd, especially 5-FU plus Cd at the half time of treatment. Cd plus 5-FU decreased cyclin D1 and increased cyclin A1 expression. In conclusion, our results indicate that exposure to Cd blocks the anticancer effects of 5-FU in MCF-7 cells. These results could have important clinical implications in patients treated with 5-FU-based therapies and who are exposed to high levels of Cd.
Cadmium Modifies the Cell Cycle and Apoptotic Profiles of Human Breast Cancer Cells Treated with 5-Fluorouracil

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Asara, Yolande; Marchal, Juan A.; Carrasco, Esther; Boulaiz, Houria; Solinas, Giuliana; Bandiera, Pasquale; Garcia, Maria A.; Farace, Cristiano; Montella, Andrea; Madeddu, Roberto

2013-01-01

Industrialisation, the proximity of factories to cities, and human work activities have led to a disproportionate use of substances containing heavy metals, such as cadmium (Cd), which may have deleterious effects on human health. Carcinogenic effects of Cd and its relationship with breast cancer, among other tumours, have been reported. 5-Fluorouracil (5-FU) is a fluoropyrimidine anticancer drug used to treat solid tumours of the colon, breast, stomach, liver, and pancreas. The purpose of this work was to study the effects of Cd on cell cycle, apoptosis, and gene and protein expression in MCF-7 breast cancer cells treated with 5-FU. Cd altered the cell cycle profile, and its effects were greater when used either alone or in combination with 5-FU compared with 5-FU alone. Cd significantly suppressed apoptosis of MCF-7 cells pre-treated with 5-FU. Regarding gene and protein expression, bcl2 expression was mainly upregulated by all treatments involving Cd. The expression of caspase 8 and caspase 9 was decreased by most of the treatments and at all times evaluated. C-myc expression was increased by all treatments involving Cd, especially 5-FU plus Cd at the half time of treatment. Cd plus 5-FU decreased cyclin D1 and increased cyclin A1 expression. In conclusion, our results indicate that exposure to Cd blocks the anticancer effects of 5-FU in MCF-7 cells. These results could have important clinical implications in patients treated with 5-FU-based therapies and who are exposed to high levels of Cd. PMID:23941782
Induction therapy with cetuximab plus docetaxel, cisplatin, and 5-fluorouracil (ETPF) in patients with resectable nonmetastatic stage III or IV squamous cell carcinoma of the oropharynx. A GERCOR phase II ECHO-07 study

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Chibaudel, Benoist; Lacave, Roger; Lefevre, Marine; Soussan, Patrick; Antoine, Martine; Périé, Sophie; Belloc, Jean-Baptiste; Banal, Alain; Albert, Sébastien; Chabolle, Frédéric; Céruse, Philippe; Baril, Philippe; Gatineau, Michel; Housset, Martin; Moukoko, Rachel; Benetkiewicz, Magdalena; Gramont, Aimery de; Bonnetain, Franck; Lacau St Guily, Jean

2015-01-01

Induction TPF regimen is a standard treatment option for squamous cell carcinoma (SCC) of the oropharynx. The efficacy and safety of adding cetuximab to induction TPF (ETPF) therapy was evaluated. Patients with nonmetastatic resectable stage III/IV SCC of the oropharynx were treated with weekly cetuximab followed the same day by docetaxel and cisplatin and by a continuous infusion of 5-fluorouracil on days 1-5 (every 3 weeks, 3 cycles). The primary endpoint was clinical and radiological complete response (crCR) of primary tumor at 3 months. Secondary endpoints were crCR rates, overall response, pathological CR, progression-free survival, overall survival, and safety. Forty-two patients were enrolled, and 41 received ETPF. The all nine planned cetuximab doses and the full three doses of planned chemotherapy were completed in 31 (76%) and 36 (88%) patients, respectively. Twelve (29%) patients required dose reduction. The crCR of primary tumor at the completion of therapy was observed in nine (22%) patients. ETPF was associated with a tumor objective response rate (ORR) of 58%. The most frequent grade 3–4 toxicities were as follows: nonfebrile neutropenia (39%), febrile neutropenia (19%), diarrhea (10%), and stomatitis (12%). Eighteen (44%) patients experienced acne-like skin reactions of any grade. One toxic death occurred secondary to chemotherapy-induced colitis with colonic perforation. This phase II study reports an interesting response rate for ETPF in patients with moderately advanced SCC of the oropharynx. The schedule of ETPF evaluated in this study cannot be recommended at this dosage
Unravelling the potential of a new uracil phosphoribosyltransferase (UPRT) from Arabidopsis thaliana in sensitizing HeLa cells towards 5-fluorouracil.

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Narayanan, Sharmila; Sanpui, Pallab; Sahoo, Lingaraj; Ghosh, Siddhartha Sankar

2016-10-01

In silico studies with uracil phosphoribosyltransferase from Arabidopsis thaliana (AtUPRT) revealed its lower binding energies for uracil and 5-fluorouracil (5-FU) as compared to those of bacterial UPRT indicating the prospective of AtUPRT in gene therapy implications. Hence, AtUPRT was cloned and stably expressed in cervical cancer cells (HeLa) to investigate the effect of prodrug 5-FU on these transfected cancer cells. The treatment of AtUPRT-expressing HeLa (HeLa-UPP) cells with 5-FU for 72h resulted in significant decrease in cell viability. Moreover, 5-FU was observed to induce apoptosis and perturb mitochondrial membrane potential in HeLa-UPP cells. While cell cycle analysis revealed significant S-phase arrest as a result of 5-FU treatment in HeLa-UPP cells, quantitative gene expression analysis demonstrated simultaneous upregulation of important cell cycle related genes, cyclin D1 and p21. The survival fractions of non-transfected, vector-transfected and AtUPRT-transfected HeLa cells, following 5-FU treatment, were calculated to be 0.425, 0.366 and 0.227, respectively. Copyright © 2016 Elsevier B.V. All rights reserved.
Chloroquine potentiates the anti-cancer effect of 5-fluorouracil on colon cancer cells

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Sasaki, Kazuhito; Hiyoshi, Masaya; Kaneko, Manabu; Kitayama, Joji; Takahashi, Koki; Nagawa, Hirokazu; Tsuno, Nelson H; Sunami, Eiji; Tsurita, Giichiro; Kawai, Kazushige; Okaji, Yurai; Nishikawa, Takeshi; Shuno, Yasutaka; Hongo, Kumiko

2010-01-01

Chloroquine (CQ), the worldwide used anti-malarial drug, has recently being focused as a potential anti-cancer agent as well as a chemosensitizer when used in combination with anti-cancer drugs. It has been shown to inhibit cell growth and/or to induce cell death in various types of cancer. 5-Fluorouracil (5-FU) is the chemotherapeutic agent of first choice in colorectal cancer, but in most cases, resistance to 5-FU develops through various mechanisms. Here, we focused on the combination of CQ as a mechanism to potentiate the inhibitory effect of 5-FU on human colon cancer cells. HT-29 cells were treated with CQ and/or 5-FU, and their proliferative ability, apoptosis and autophagy induction effects, and the affection of the cell cycle were evaluated. The proliferative ability of HT-29 was analyzed by the MTS assay. Apoptosis was quantified by flow-cytometry after double-staining of the cells with AnnexinV/PI. The cell cycle was evaluated by flow-cytometry after staining of cells with PI. Autophagy was quantified by flow-cytometry and Western blot analysis. Finally, to evaluate the fate of the cells treated with CQ and/or 5-FU, the colony formation assay was performed. 5-FU inhibited the proliferative activity of HT-29 cells, which was mostly dependent on the arrest of the cells to the G0/G1-phase but also partially on apoptosis induction, and the effect was potentiated by CQ pre-treatment. The potentiation of the inhibitory effect of 5-FU by CQ was dependent on the increase of p21 Cip1 and p27 Kip1 and the decrease of CDK2. Since CQ is reported to inhibit autophagy, the catabolic process necessary for cell survival under conditions of cell starvation or stress, which is induced by cancer cells as a protective mechanism against chemotherapeutic agents, we also analyzed the induction of autophagy in HT-29. HT-29 induced autophagy in response to 5-FU, and CQ inhibited this induction, a possible mechanism of the potentiation of the anti-cancer effect of 5-FU. Our
Do the lungs contribute to propofol elimination in patients during orthotopic liver transplantation without veno-venous bypass?

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Yi-Zhong Chen; Sheng-Mei Zhu; Hui-Liang He; Jian-Hong Xu; Su-Qin Huang; Qing-Lian Chen

2006-01-01

BACKGROUND: The clearance of propofol is very rapid, and its transformation takes place mainly in the liver. Some reports indicated extrahepatic clearance of the drug and that the lungs are the likely place where the process occurs. This study was undertaken to compare the plasma concentrations of propofol both in the pulmonary and radial arteries after constant infusion during the dissection, anhepatic and reperfusion phases of orthotopic liver transplantation (OLT) without veno-venous bypass, attempting to investigate extrahepatic clearance and to determine whether the human lungs take part in the elimination of propofol. METHODS: Fifteen patients undergoing OLT without veno-venous bypass were enrolled in the study, and propofol was infused via a forearm vein at a rate of 2 mg· kg-1·h-1. Blood samples were simultaneously collected from pulmonary and radial arteries at the end of the ifrst hepatic portal dissection (T0), at the clamping of the portal vein (T1), 30, and 60 minutes after the beginning of the anhepatic phase (T2, T3), and 30, 60, and 120 minutes after the unclamping of the new liver (T4, T5, T6). Plasma propofol concentrations were measured using a reversed-phase, high-performance liquid chromatographic method with lfuorescence detection. RESULTS: The concentrations of plasma propofol in the pulmonary and radial arteries at T2 and T3 rose signiifcantly compared with T0 and T1 (P CONCLUSIONS:Propofol is eliminated mainly by the liver, and also by extrahepatic organs. The lungs seem to be not a major site contributing to the extrahepatic metabolism of propofol in humans.
Fluorouracil implants caused a diaphragmatic tumor to be misdiagnosed as liver metastasis: a case report

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Shen, Yang-Yang; Qin, Hong-Wei; Zhang, Jian-Bo; Wang, Zhen-Dan; Li, Pang; Pang, Kai; Zhang, Bo; Li, Sheng; Cui, Kai

2016-01-01

Fluorouracil implants are widely used in peritoneal interstitial chemotherapy. Curative effects have been obtained, but implants have also caused some complications. We performed an analysis of a 66-year-old male patient’s case history, as well as conventional pathological analysis and Raman spectroscopic detection of the diaphragmatic tumor. We also analyzed the underlying causes of this condition to prevent complications and reduce misdiagnoses in future cases. The patient had a history of peritoneal fluorouracil implantation. Pathological analysis of the diaphragmatic mass revealed foreign particles, and Raman detection showed that the mass contained fluorouracil. Fluorouracil implants may persist due to the high concentrations of this drug used in peritoneal chemotherapy. This finding should provide guidance and improve the application of peritoneal implants. In clinical trials, and the diagnosis of liver metastasis should be based on pathological results
Acriflavine enhances the antitumor activity of the chemotherapeutic drug 5-fluorouracil in colorectal cancer cells.

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Zargar, Parisa; Ghani, Esmaeel; Mashayekhi, Farideh Jalali; Ramezani, Amin; Eftekhar, Ebrahim

2018-06-01

5-Fluorouracil (5-FU)-based chemotherapy improves the overall survival rates of patients with colorectal cancer (CRC). However, only a small proportion of patients respond to 5-FU when used as a single agent. The aim of the present study was to investigate whether the anticancer property of 5-FU is potentiated by combination treatment with acriflavine (ACF) in CRC cells. Additionally, the potential underlying molecular mechanisms of the cytotoxic effect of ACF were determined. The cytotoxic effects of ACF, 5-FU and irinotecan on different CRC cell lines with different p53 status were investigated using an MTT assay. SW480 cells that express a mutated form of p53 and two other CRC cell lines were used, HCT116 and LS174T, with wild-type p53. To determine the effect of ACF on the sensitivity of cells to 5-FU, cells were co-treated with the 30% maximal inhibitory concentration (IC 30 ) of ACF and various concentrations of 5-FU, or pretreated with the IC 30 of ACF and various concentrations of 5-FU. To assess the mechanism of action of ACF, cells were treated with IC 30 values of the compound and then the reverse transcription-quantitative polymerase chain reaction was used to evaluate mRNA levels of hypoxia-inducible factor-1α (HIF-1α) and topoisomerase 2. Results indicate that pretreatment with ACF markedly sensitized CRC cells to the cytotoxic effects of 5-FU, whereas simultaneous treatment with ACF and 5-FU were not able to alter the resistance of CRC cells to 5-FU. In comparison with irinotecan, ACF was a more potent agent for enhancing the antitumor activity of 5-FU. ACF did not alter the mRNA levels of either HIF-1α or topoisomerase 2. The results of the present study reveal for the first time that pretreatment of CRC cells with ACF markedly increases the cytotoxic effects of 5-FU, regardless of the p53 status of cells.
Combination photodynamic therapy using 5-fluorouracil and aminolevulinate enhances tumor-selective production of protoporphyrin IX and improves treatment efficacy of squamous skin cancers and precancers

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Maytin, Edward V.; Anand, Sanjay

2016-03-01

In combination photodynamic therapy (cPDT), a small-molecule drug is used to modulate the physiological state of tumor cells prior to giving aminolevulinate (ALA; a precursor for protoporphyrin IX, PpIX). In our laboratory we have identified three agents (methotrexate, 5-fluorouracil, and vitamin D) that can enhance therapeutic effectiveness of ALAbased photodynamic therapy for cutaneous squamous cell carcinoma (SCC). However, only one (5-fluorouracil; 5-FU) is FDA-approved for skin cancer management. Here, we describe animal and human studies on 5-FU mechanisms of action, in terms of how 5-FU pretreatment leads to enhanced PpIX accumulation and improves selectivity of ALA-PDT treatment. In A431 subcutaneous tumors in mice, 5-FU changed expression of heme enzyme (upregulating coproporphyrinogen oxidase, and down-regulating ferrochelatase), inhibited tumor cell proliferation (Ki-67), enhanced differentiation (E-cadherin), and led to strong, tumor-selective increases in apoptosis. Interestingly, enhancement of apoptosis by 5-FU correlated strongly with an increased accumulation of p53 in tumor cells that persisted for 24 h post- PDT. In a clinical trial using a split-body, bilaterally controlled study design, human subjects with actinic keratoses (AK; preneoplastic precursors of SCC) were pretreated on one side of the face, scalp, or forearms with 5-FU cream for 6 days, while the control side received no 5-FU. On the seventh day, the levels of PpIX in 4 test lesions were measured by noninvasive fluorescence dosimetry, and then all lesions were treated with PDT using methyl-aminolevulinate (MAL) and red light (635 nm). Relative amounts of PpIX were found to be increased ~2-fold in 5-FU pretreated lesions relative to controls. At 3 months after PDT, the overall clinical response to PDT (reduction in lesion counts) was 2- to 3-fold better for the 5-FU pretreated lesions, a clinically important result. In summary, 5-FU is a useful adjuvant to aminolevulinate-based PDT
Photo-Fenton and Fenton-like processes for the treatment of the antineoplastic drug 5-fluorouracil under simulated solar radiation.

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Koltsakidou, Α; Antonopoulou, M; Sykiotou, M; Εvgenidou, Ε; Konstantinou, I; Lambropoulou, D A

2017-02-01

In the present study, photo-Fenton and Fenton-like processes were investigated for the degradation and mineralization of the antineoplastic drug 5-fluorouracil (5-FU). For the optimization of photo-Fenton treatment under simulated solar light (SSL) radiation, the effects of several operating parameters (i.e., 5-FU concentration, Fe 3+ , and oxidant concentration) on the treatment efficiency were studied. According to the results, SSL/[Fe(C 2 Ο 4 ) 3 ] 3- /Η 2 Ο 2 process was the most efficient, since faster degradation of 5-FU and higher mineralization percentages were achieved. All the applied processes followed quite similar transformation routes which include defluorination-hydroxylation as well as pyrimidine ring opening, as demonstrated by the transformation products identified by high resolution mass spectrometry analysis. The toxicity of the treated solutions was evaluated using the Microtox assay. In general, low toxicity was recorded for the initial solution and the solution at the end of the photocatalytic treatment, while an increase in the overall toxicity was observed only at the first stages of SSL/Fe 3+ /Η 2 Ο 2 and SSL/Fe 3+ /S 2 O 8 2- processes.
5-Fluorouracil-related enhancement of adenoviral infection is Coxsackievirus-adenovirus receptor independent and associated with morphological changes in lipid membranes

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Cabrele, Chiara; Vogel, Mandy; Piso, Pompiliu; Rentsch, Markus; Schröder, Josef; Jauch, Karl W; Schlitt, Hans J; Beham, Alexander

2006-01-01

AIM: To evaluate the mechanism underlying the effects of 5-Fluorouracil (5-FU) on adenoviral infection. METHODS: Low and high Coxsackievirus-Adenovirus Receptor (CAR) expressing human colon carcinoma cell lines were treated with 5-FU and two E1-deleted adenoviral constructs, one transferring GFP (Ad/CMV-GFP) the other bax (Ad/CEA-bax). The number of infected cells were monitored by GFP expression. To evaluate the effects of 5-FU in a receptor free system, Ad/GFP were encapsulated in liposomes and treated with 5-FU. Ad/GFP release was estimated with PCR and infection of 293 cells with the supernatant. Electron microscopy of the Ad5-GFP-liposome complex was made to investigate morphological changes of the liposomes after 5-FU. RESULTS: Infection rates of all cell lines increased from 50% to 98% with emerging 5-FU concentrations. The enhanced viral uptake was independent of the CAR expression. Additionally, 5-FU treated liposomes released 2-2.5 times more adenoviruses. Furthermore, 5-FU-treated liposomes appeared irregular and porous-like. CONCLUSION: adenoviral uptake is enhanced in the presence of 5-FU irrespective of CAR and is associated with morphological changes in membranes making the combination of both a promising option in gene therapy. PMID:16937527
Strategies in the treatment for intracranial venous sinus thrombosis

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JIA Qiang

2013-03-01

Full Text Available Background Cerebral venous sinus thrombosis (CVST is a special type of cerebrovascular disease with high morbidity and mortality which often has an unpredictable outcome. It is usually misdiagnosed because of different causes and variable clinical manifestations. How to improve the diagnosis and therapy of CVST is always the hotspot in clinic. This article aims to investigate the effective and safe strategies in the treatment for CVST. Methods Clinical data of 52 patients diagnosed with CVST were retrospectively analyzed. These patients were subdivided into mild type and severe type according to the features of symptoms, signs, lumbar puncture pressure and imaging. The patients with mild type were treated with systemic anticoagulant therapy combined with intravenous thrombolysis [continuous intravenous infusion of heparin (12.50-25 × 103 U/d for 7-10 d followed by a continuous infusion of urokinase (0.50-0.75 ×106 U/d for 5-7d]. The patients with severe type were treated with endovascular thrombolysis [injection of urokinase (0.50-1 × 106 U, 0.10 × 106 U/min via carotid or vertebral artery; or intravenous infusion of urokinase 1 ×106 U/d and heparin 25 ×103 U/d for 5-7 d], and superior sagittal sinus cut-open/ intrasinus thrombolysis separately. All the patients took oral warfarin for 6-12 months, and follow-up was performed after operation by the method of magnetic resonance venography (MRV. Results Among the 27 cases of mild type receiving systemic anticoagulant agents and intravenous thrombolysis, 14 were cured; 9 were improved; 4 were ineffective. Among the 22 cases of severe type receiving systemic anticoagulant drugs and endovascular thrombolysis, 18 were cured; 3 were improved; 1 was dead. The left 3 cases with gravis type received superior sagittal sinus cut-open/intrasinus thrombolysis and were cured. The period of follow-up was between 6 months and 60 months (the median time was 36 months, and no recurrence happened. Conclusion
Role of the route of leukotrienes in an experimental model of oral mucositis induced by 5-fluorouracil 1.

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Silva, Viviane Carvalho da; Leitão, Renata Ferreira de Carvalho; Brito, Gerly Anne de Castro; Martins, Conceição da Silva; Freire, Gildenio Estevam; Aragão, Karoline Saboia; Wanderley, Carlos Wagner de Souza; Freitas, Marcos Rabelo de

2017-09-01

To investigate the participation of cysteinyl leukotrienes in the pathophysiology of oral mucositis. Oral mucositis was induced in hamsters using 5-fluorouracil (5-FU; 60 and 40 mg/kg; i.p., on days 1 and 2, respectively, and with excoriations in jugal mucosa on day 4). Montelukast (10, 20, or 40 mg/kg/d; gavage), MK886 (3 mg/kg/d, i.p.), or saline or celecoxib (7.5 mg/kg/d; i.p.) was administered 1 h prior to 5-FU and daily, until the fourth (MK886) or tenth day, when the animals were euthanized and their jugal mucosa was collected for macroscopic, histopathological, and immunohistochemical evaluation. Neither montelukast nor MK-886 prevented the oral mucositis induced by 5-FU, as observed by histopathological evaluation. In addition, we did not find significant differences in the expression of inducible nitric oxide synthase-2, cyclooxygenase-2, or interleukin (IL)-1β between the experimental and control groups. However, we did observe a significant decrease in tumor necrosis factor (TNF)-α expression for all doses of montelukast; we also observed a significant decrease in IL-10 with 40 mg/kg/d and MK 886. Cysteinyl leukotrienes do not play an important role in experimental oral mucositis induced by 5-FU. There is a modulating action specifically on TNF-α.
Peripheral Insertion of a Central Venous Access Device Under Fluoroscopic Guidance Using a Peripherally Accessed System (PAS) Port in the Forearm

International Nuclear Information System (INIS)

Hata, Yasuhiro; Morita, Sojiro; Morita, Yoshitaka; Awatani, Toshihide; Takasaki, Motohiro; Horimi, Tadashi; Ozawa, Zen

1998-01-01

Purpose: We describe the technique, efficacy, and complications of fluoroscopy-guided implantation of a central venous access device using a peripherally accessed system (PAS) port via the forearm. Methods: Beginning in July 1994, 105 central venous access devices were implanted in 104 patients for the long-term infusion of antibiotics or antineoplasmic agents, blood products, or parenteral nutrition. The devices was inserted under fluoroscopic guidance with real-time venography from a peripheral route. Results: All ports were successfully implanted. There were no procedure-related complications. No thrombosis or local infection was observed; however, in six patients catheter-related phlebitis occurred. Conclusion: Fluoroscopy-guided implantation of a central venous access device using a PAS port via the forearm is safe and efficacious, and injection of contrast medium through a peripheral IV catheter before introduction of the catheter helps to avoid catheter-related phlebitis
Concomitant bid radiotherapy with cisplatin and 5-fluorouracil in unresectable carcinoma of the pharynx: 10 year's experience at the Centre Antoine Lacassagne

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Magne, N.; Pivot, X.; Marcy, P.Y.; Chauvel, P.; Courdi, A.; Dassonville, O.; Possonnet, G.; Vallicioni, J.; Ettore, F.; Falewee, M.N.; Milano, G.; Santini, J.; Lagrange, J.L.; Schneider, M.; Demard, F.; Bensadoun, R.J.

2001-01-01

Patients suffering from locally advanced unresectable squamous cell carcinoma of the oropharynx and hypopharynx treated with radiotherapy alone have a poor prognosis. More than 70% of patients die within 5 years mainly due to local recurrences. The aim of this study was to evaluate retrospectively the Antoine Lacassagne Cancer Center's experience in a treatment by concomitant bid radiotherapy and chemotherapy. Evaluation was based on analysis of the toxicity, the response rates, the survival, and the clinical prognostic factors. From 1992 to 2000, 92 consecutive patients were treated in our single institution. All of them had stage IV, unresectable squamous cell carcinoma of the pharynx and they received continuous bid radiotherapy (two daily fractions of 1.2 Gy, 5 days a week, with a 6-h minimal internal between fractions). Total radiotherapy dose was 80.4 Gy on the oropharynx and 75.6 Gy on the hypopharynx. Two or three chemotherapy courses of cisplatin (CP)-5-fluorouracil (5FU) were given during radiotherapy at 21 -day intervals (third not delivered after the end of the radiotherapy). CP dose was 100 mg/m 2 (day 1) and 5-FU was given as 6-day continuous infusion (750 mg/m 2 /day at 1. course; 430 mg/m 2 /day at 2. and 3. courses). Special attention was paid to supportive care, particularly in terms of enteral nutrition and mucositis prevention by low-level laser energy. Acute toxicity was marked and included WHO grade III/IV mucositis (89%, 16% of them being grade IV), WHO grade III dermatitis (72%) and grade III/IV neutropenia (61%). This toxicity was significant but manageable with optimised supportive care, and never led to interruption of treatment for more than 1 week, although there were two toxic deaths. Complete global response rate at 6 months was 74%. Overall global survival at 1 and 3 years was 72% and 50% respectively, with a median follow-up of 17 months. Prognostic factors for overall were the Karnofsky index (71% survival at 3 years for patients
Is continuous infusion of imipenem always the best choice?

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Suchánková, Hana; Lipš, Michal; Urbánek, Karel; Neely, Michael N; Strojil, Jan

2017-03-01

Monte Carlo simulations allow prediction and comparison of concentration-time profiles arising from different dosing regimens in a defined population, provided a population pharmacokinetic model has been established. The aims of this study were to evaluate the population pharmacokinetics of imipenem in critically ill patients with hospital-acquired pneumonia (HAP) and to assess the probability of target attainment (PTA) and cumulative fraction of response (CFR) using EUCAST data. A two-compartment model based on a data set of 19 subjects was employed. Various dosage regimens at 0.5-h and 3-h infusion rates and as continuous infusion were evaluated against the pharmacodynamic targets of 20%fT >MIC , 40%fT >MIC and 100%fT >MIC . For the target of 40%fT >MIC , all 0.5-h infusion regimens achieved optimal exposures (CFR ≥ 90%) against Escherichia coli and Staphylococcus aureus, with nearly optimal exposure against Klebsiella pneumoniae (CFR ≥ 89.4%). The 3-h infusions and continuous infusion exceeded 97% CFR against all pathogens with the exception of Pseudomonas aeruginosa and Acinetobacter spp., where the maximum CFRs were 85.5% and 88.4%, respectively. For the 100%fT >MIC target, only continuous infusion was associated with nearly optimal exposures. Higher PTAs for the targets of 40%fT >MIC and 100%fT >MIC were achieved with 3-h infusions and continuous infusion in comparison with 0.5-h infusions; however, continuous infusion carries a risk of not reaching the MIC of less susceptible pathogens in a higher proportion of patients. In critically ill patients with HAP with risk factors for Gram-negative non-fermenting bacteria, maximum doses administered as extended infusions may be necessary. Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.
Cellular response to 5-fluorouracil (5-FU in 5-FU-resistant colon cancer cell lines during treatment and recovery

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Kravik Katherine L

2006-05-01

Full Text Available Abstract Background Treatment of cells with the anti-cancer drug 5-fluorouracil (5-FU causes DNA damage, which in turn affects cell proliferation and survival. Two stable wild-type TP53 5-FU-resistant cell lines, ContinB and ContinD, generated from the HCT116 colon cancer cell line, demonstrate moderate and strong resistance to 5-FU, respectively, markedly-reduced levels of 5-FU-induced apoptosis, and alterations in expression levels of a number of key cell cycle- and apoptosis-regulatory genes as a result of resistance development. The aim of the present study was to determine potential differential responses to 8 and 24-hour 5-FU treatment in these resistant cell lines. We assessed levels of 5-FU uptake into DNA, cell cycle effects and apoptosis induction throughout treatment and recovery periods for each cell line, and alterations in expression levels of DNA damage response-, cell cycle- and apoptosis-regulatory genes in response to short-term drug exposure. Results 5-FU treatment for 24 hours resulted in S phase arrests, p53 accumulation, up-regulation of p53-target genes on DNA damage response (ATF3, GADD34, GADD45A, PCNA, cell cycle-regulatory (CDKN1A, and apoptosis-regulatory pathways (FAS, and apoptosis induction in the parental and resistant cell lines. Levels of 5-FU incorporation into DNA were similar for the cell lines. The pattern of cell cycle progression during recovery demonstrated consistently that the 5-FU-resistant cell lines had the smallest S phase fractions and the largest G2(/M fractions. The strongly 5-FU-resistant ContinD cell line had the smallest S phase arrests, the lowest CDKN1A levels, and the lowest levels of 5-FU-induced apoptosis throughout the treatment and recovery periods, and the fastest recovery of exponential growth (10 days compared to the other two cell lines. The moderately 5-FU-resistant ContinB cell line had comparatively lower apoptotic levels than the parental cells during treatment and recovery
Both hMutSα and hMutSß DNA mismatch repair complexes participate in 5-fluorouracil cytotoxicity.

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Akihiro Tajima

Full Text Available Patients with advanced microsatellite unstable colorectal cancers do not show a survival benefit from 5-fluorouracil (5-FU-based chemotherapy. We and others have shown that the DNA mismatch repair (MMR complex hMutSα binds 5-FU incorporated into DNA. Although hMutSß is known to interact with interstrand crosslinks (ICLs induced by drugs such as cisplatin and psoralen, it has not been demonstrated to interact with 5-FU incorporated into DNA. Our aim was to examine if hMutSß plays a role in 5-FU recognition.We compared the normalized growth of 5-FU treated cells containing either or both mismatch repair complexes using MTT and clonogenic assays. We utilized oligonucleotides containing 5-FU and purified baculovirus-synthesized hMutSα and hMutSß in electromobility shift assays (EMSA and further analyzed binding using surface plasmon resonance.MTT and clonogenic assays after 5-FU treatment demonstrated the most cytotoxicity in cells with both hMutSα and hMutSß, intermediate cytotoxicity in cells with hMutSα alone, and the least cytotoxicity in cells with hMutSß alone, hMutSß binds 5-FU-modified DNA, but its relative binding is less than the binding of 5-FU-modified DNA by hMutSα.Cytotoxicity induced by 5-FU is dependent on intact DNA MMR, with relative cell death correlating directly with hMutSα and/or hMutSß 5-FU binding ability (hMutSα>hMutSß. The MMR complexes provide a hierarchical chemosensitivity for 5-FU cell death, and may have implications for treatment of patients with certain MMR-deficient tumors.
Reduction of Orc6 expression sensitizes human colon cancer cells to 5-fluorouracil and cisplatin.

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Elaine J Gavin

Full Text Available Previous studies from our group have shown that the expression levels of Orc6 were highly elevated in colorectal cancer patient specimens and the induction of Orc6 was associated with 5-fluorouracil (5-FU treatment. The goal of this study was to investigate the molecular and cellular impact of Orc6 in colon cancer. In this study, we use HCT116 (wt-p53 and HCT116 (null-p53 colon cancer cell lines as a model system to investigate the impact of Orc6 on cell proliferation, chemosensitivity and pathways involved with Orc6. We demonstrated that the down regulation of Orc6 sensitizes colon cancer cells to both 5-FU and cisplatin (cis-pt treatment. Decreased Orc6 expression in HCT-116 (wt-p53 cells by RNA interference triggered cell cycle arrest at G1 phase. Prolonged inhibition of Orc6 expression resulted in multinucleated cells in HCT-116 (wt-p53 cell line. Western immunoblot analysis showed that down regulation of Orc6 induced p21 expression in HCT-116 (wt-p53 cells. The induction of p21 was mediated by increased level of phosphorylated p53 at ser-15. By contrast, there is no elevated expression of p21 in HCT-116 (null-p53 cells. Orc6 down regulation also increased the expression of DNA damaging repair protein GADD45beta and reduced the expression level of JNK1. Orc6 may be a potential novel target for future anti cancer therapeutic development in colon cancer.

Infusion cisternography

International Nuclear Information System (INIS)

Magnaes, B.; Rootwelt, K.; Sjaastad, O.

1976-01-01

A source of error in cerebrospinal fluid (CSF) infusion tests is leakage at the dural puncture site. The addition of a bolus of radionuclide to the infusion fluid was helpful in detecting the existence of leakage as shown by increased infusion pressure in six of eight patients studied with and without scintigraphic evidence of leakage. Comparison of CSF dynamics in 26 patients studied by infusion cisternography and conventional cisternography showed similar patterns, suggesting no alteration of CSF dynamics by the artificial CSF infusion. Combining the two tests, therefore, resulted in simple identification of the leakage and saved the patient time and discomfort
Comparison of the short-term efficacy between docetaxel plus carboplatin and 5-fluorouracil plus carboplatin in locoregionally advanced nasopharyngeal carcinoma

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Lv X

2016-08-01

Full Text Available Xing Lv,1,2,* Wei-Xiong Xia,1,2,* Liang-Ru Ke,1,2 Jing Yang,1,2 Wen-Zhe Qiu,1,2 Ya-Hui Yu,1,2 Hu Liang,1,2 Xin-Jun Huang,1,2 Guo-Yin Liu,1,2 Qi Zeng,1,2 Xiang Guo,1,2 Yan-Qun Xiang1,2 1Key Laboratory of Oncology in South China, 2Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China *These authors contributed equally to this work Objective: Platinum-based chemotherapy in combination with radiotherapy is a standard treatment strategy for locoregionally advanced nasopharyngeal carcinoma (NPC. This study aimed to investigate the long-term efficacy and tolerability of inductive chemotherapy with docetaxel plus carboplatin (TC or 5-fluorouracil plus carboplatin (FC followed by concurrent radiation therapy in patients with NPC. Methods: Patients (N=88 were randomized to receive TC or FC as inductive therapy followed by concurrent radiotherapy (60–70 Gy with two cycles of carboplatin (area under the curve =5 mg·h/L. Patients were followed up for 8 years. Primary end point was progression-free survival (PFS. Secondary end points included overall survival (OS, toxicity, tumor response, distant metastasis-free survival, and local recurrence-free survival. Results: At the end of the follow-up period, 31 patients died, 32 had disease progression, eleven had cancer recurrence, and 25 had distant metastasis. Overall, there was no difference between treatment groups with regard to response or survival. We found that following induction and concurrent chemoradiotherapy, the majority of patients showed a complete response (~96%–98% for induction therapy and 82%–84% for comprehensive therapy to both therapies. PFS and OS were also similar between groups. The rate of PFS was 63.6% for both FC and TC and that of OS was 65.9% and 63.5%, respectively. The overall incidence of grade 3–4 adverse events in the TC group (20.5% was higher than in the FC group (10.7%. Neutropenia and leukopenia
5-Fluorouracil incorporation into RNA of a rat liver adenocarcinoma after hepatic artery injection together with degradable starch microspheres

International Nuclear Information System (INIS)

Teder, H.; Erichsen, C.; Christensson, P.I.; Joensson, P.E.S.; Stenram, U.

1987-01-01

The effect of degradable starch microspheres (DSM) on the cellular incorporation of 5-fluorouracil (FUra) was studied in rats with solitary liver tumors. 3 H-labelled FUra [0.78 mg (6000 nmol)/kg b.wt.] was injected with saline or mixed with DSM, into the hepatic artery. Labelling of the acid soluble fraction (ASF), RNA and DNA of tumor, liver, bone marrow and small intestine was measured 60 minutes after injection. The DSM had no significant effect on the incorporation of FUra into the ASF or RNA, neither in tumor nor liver tissue. Regarding the tumor/normal tissue ratios of specific radioactivities, there was with DSM a higher tumor/liver and a higher tumor/bone marrow ratio in the ASF, indicating an increased tumour drug exposure with DSM. However, this was not accompanied by any significant increase in drug anabolism
A prospective cohort study of patient-reported vomiting, retching, nausea and antiemetic use during neoadjuvant long-course radiation therapy and concurrent 5-fluorouracil-based chemotherapy for rectal adenocarcinoma

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Kristopher Dennis

2018-03-01

Full Text Available Background and purpose: Antiemetic guidelines suggest daily prophylaxis with a serotonin3 receptor antagonist (5-HT3RA as an option for patients receiving long-course neoadjuvant radiation therapy and concurrent 5-fluorouracil-based chemotherapy for rectal cancer, despite the risks that 5-HT3RA-induced constipation may pose. We explored the incidence of patient-reported vomiting, retching, nausea and antiemetic intake among patients in this setting to determine if these risks are justified. Materials and methods: We carried out a single-centre non-randomised prospective cohort study of adult patients receiving long-course neoadjuvant radiation therapy and concurrent 5-fluorouracil-based chemotherapy for rectal adenocarcinoma. Patients recorded symptoms and medication intake daily until 7 days following treatment completion. Results: From 33 evaluable patients, we collected 1407 days of patient-reported data. Vomiting was reported by 7 patients (21%, retching by 5(15% and nausea by 21(64%. No patients were administered prophylactic antiemetics. The median number of days with vomiting was 2, and the cumulative number of days for all affected patients was 22 (1.6% of 1407 evaluable days. There were no differences in PTV or small bowel loop V15Gy, V45Gy and V50Gy volumes between patients that did and did not vomit. Conclusions: The cumulative incidence of days with vomiting was only 1.6%. 5-HT3RA prophylaxis during long-course neoadjuvant treatment seems unnecessary. Keywords: Antiemetic, Nausea, Patient-reported outcome, Radiation therapy, Rectal cancer, Vomiting
RTOG 96-10: reirradiation with concurrent hydroxyurea and 5-fluorouracil in patients with squamous cell cancer of the head and neck

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Spencer, S.A.; Harris, J.; Wheeler, R.H.; Machtay, M.; Schultz, C.; Spanos, W.; Rotman, M.; Meredith, R.

2001-01-01

Purpose: Patients with recurrent squamous cell cancer of the head and neck (SCH and N) are generally treated with systemic chemotherapy. Improvement in survival has not occurred, despite an increased objective response rate. This study was undertaken to explore the feasibility and toxicity, and estimate the therapeutic impact of, reirradiation (RRT) with concurrent hydroxyurea and 5-fluorouracil. Methods and Materials: The eligibility requirements included SCH and N presenting as a second primary or recurrence ≥6 months after definitive RT to ≥45 Gy, with ≥75% of the tumor volume within the previous field. The cumulative spinal cord dose was limited to 50 Gy, and measurable disease was required. Four weekly cycles were given, each separated by 1 week of rest. A cycle consisted of 5 days, Monday through Friday, of 1.5-Gy twice-daily repeated RT, with the fractions separated by ≥6 h, with 1.5 g of hydroxyurea given 2 h and 300 mg/m 2 of a 5-fluorouracil IV bolus given 30 min before each second daily fraction. Results: Eighty-six patients were entered; 81 patients were assessable. The median prior radiation dose was 61.2 Gy. The 4 planned cycles were delivered in 79% of patients. Grade 3 mucositis occurred in 14% of patients, and Grade 4 in 5%. Grade 3 acute pharyngeal toxicity was seen in 17%. Grade 3 neutropenia occurred in 9%, Grade 4 in 10%, and Grade 5 in 7%. Six patients died of treatment-related toxicity. Two died of hemorrhage from the tumor site without thrombocytopenia. With a median follow-up of 16.3 months for living patients, the estimated median overall survival was 8.2 months and the estimated 1-year survival rate 41.7%. Patients treated >3 years after the previous RT had a 1-year survival rate of 48% compared with 35% for patients treated within 3 years (p=0.017). The 1-year survival rate for patients with a second primary was 54% compared with 38% for patients with recurrence (p=0.083). Conclusion: Repeated RT with concurrent chemotherapy as
Analysis of the clinical benefit of 5-fluorouracil and radiation treatment in locally advanced pancreatic cancer

International Nuclear Information System (INIS)

Fisher, Barbara J.; Perera, Francisco E.; Kocha, Walter; Tomiak, Anna; Taylor, Marianne; Vincent, Mark; Bauman, Glenn S.

1999-01-01

Purpose: To assess the palliative benefit of 5-fluorouracil (5-FU) and radiotherapy in patients with surgically unresectable localized pancreatic cancer. Methods and Materials: Twenty-five patients with locally advanced surgically unresectable symptomatic pancreatic cancer received 5-FU chemotherapy and local radiation therapy. They were retrospectively reviewed in regard to their clinical benefit response (a composite of measurement of pain assessment, weight, and Karnofsky performance status [KPS]), as well as radiological response, time to progression, and overall survival. Results: Median survival for the 25 patients was 9 months and median progression-free survival was 6 months. Thirty-two percent of patients survived in excess of 1 year. Analgesic requirements increased >50% in 2 patients and KPS deteriorated in 10 patients. Of the 13 remaining patients, 2 sustained a >7% weight loss and 2 gained weight post-treatment. Six patients improved in one parameter of analgesic consumption, weight loss or KPS without deteriorating in any others. Thus, the clinical benefit response index for 5-FU-radiation was 6/25 (24%). In terms of tumor response, 8 patients (44%) demonstrated a reduction in tumor volume post-treatment, 4 of whom (22%) experienced a >50% reduction. Four additional patients had radiologically stable disease. Conclusion: In this retrospective analysis, the clinical benefit response index for 5-FU-radiation was 24%, a value similar to the 23.8% reported for single agent gemcitabine. The median survival of 7 months was also similar to the 5.65 months reported for gemcitabine. The radiological partial response rate of 22% and the 1-year survival of 32% were higher for 5-FU-radiation than the reported values for gemcitabine. A randomized trial would be necessary to compare 5-FU-radiation to gemcitabine directly; however, from this review it did not appear that the overall palliative benefit of 5-FU-radiation was inferior to gemcitabine
Venous hemodynamic changes in lower limb venous disease

DEFF Research Database (Denmark)

Lee, Byung Boong; Nicolaides, Andrew N; Myers, Kenneth

2016-01-01

). Their aim was to confirm or dispel long-held hemodynamic principles and to provide a comprehensive review of venous hemodynamic concepts underlying the pathophysiology of lower limb venous disorders, their usefulness for investigating patients and the relevant hemodynamic changes associated with various...... forms of treatment. Chapter 1 is devoted to basic hemodynamic concepts and normal venous physiology. Chapter 2 presents the mechanism and magnitude of hemodynamic changes in acute deep vein thrombosis indicating their pathophysiological and clinical significance. Chapter 3 describes the hemodynamic...... changes that occur in different classes of chronic venous disease and their relation to the anatomic extent of disease in the macrocirculation and microcirculation. The next four chapters (Chapters 4-7) describe the hemodynamic changes resulting from treatment by compression using different materials...
Percutaneous central venous catheters versus peripheral cannulae for delivery of parenteral nutrition in neonates.

Science.gov (United States)

Ainsworth, S B; Clerihew, L; McGuire, W

2007-07-18

Parenteral nutrition for neonates may be delivered via a short peripheral cannula or a central venous catheter. The latter may either be inserted via the umbilicus or percutaneously. Because of the complications associated with umbilical venous catheter use, many neonatal units prefer to use percutaneously inserted catheters following the initial stabilisation period. The method of parenteral nutrition delivery may affect nutrient input and consequently growth and development. Although potentially more difficult to place, percutaneous central venous catheters may be more stable than peripheral cannulae, and need less frequent replacement. These delivery methods may also be associated with different risks of adverse events, including acquired systemic infection and extravasation injury. To determine the effect of infusion via a percutaneous central venous catheter versus a peripheral cannula on nutrient input, growth and development, and complications including systemic infection, or extravasation injuries in newborn infants who require parenteral nutrition. The standard search strategy of the Cochrane Neonatal Review Group was used. This included searches of the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2007), MEDLINE (1966 - February 2007), EMBASE (1980 - February 2007), conference proceedings, and previous reviews. Randomised controlled trials that compared the effect of delivering parenteral nutrition via a percutaneous central venous catheter versus a peripheral cannulae in neonates. Data were extracted the data using the standard methods of the Cochrane Neonatal Review Group, with separate evaluation of trial quality and data extraction by each author, and synthesis of data using relative risk, risk difference and mean difference. Four trials eligible for inclusion were found. These trials recruited a total of 368 infants and reported a number of different outcomes. One study showed that the use of a percutaneous
In Vivo Chemoprotective Activity of Bovine Dialyzable Leukocyte Extract in Mouse Bone Marrow Cells against Damage Induced by 5-Fluorouracil

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Erika Evangelina Coronado-Cerda

2016-01-01

Full Text Available Chemotherapy treatments induce a number of side effects, such as leukopenia neutropenia, peripheral erythropenia, and thrombocytopenia, affecting the quality of life for cancer patients. 5-Fluorouracil (5-FU is wieldy used as myeloablative model in mice. The bovine dialyzable leukocyte extract (bDLE or IMMUNEPOTENT CRP® (ICRP is an immunomodulatory compound that has antioxidants and anti-inflammatory effects. In order to investigate the chemoprotection effect of ICRP on bone marrow cells in 5-FU treated mice, total bone marrow (BM cell count, bone marrow colony forming units-granulocyte/macrophage (CFU-GM, cell cycle, immunophenotypification, ROS/superoxide and Nrf2 by flow cytometry, and histological and hematological analyses were performed. Our results demonstrated that ICRP increased BM cell count and CFU-GM number, arrested BM cells in G0/G1 phase, increased the percentage of leukocyte, granulocytic, and erythroid populations, reduced ROS/superoxide formation and Nrf2 activation, and also improved hematological levels and weight gain in 5-FU treated mice. These results suggest that ICRP has a chemoprotective effect against 5-FU in BM cells that can be used in cancer patients.
In Vivo Chemoprotective Activity of Bovine Dialyzable Leukocyte Extract in Mouse Bone Marrow Cells against Damage Induced by 5-Fluorouracil

Science.gov (United States)

Coronado-Cerda, Erika Evangelina; Franco-Molina, Moisés Armides; Mendoza-Gamboa, Edgar; Prado-García, Heriberto; Rivera-Morales, Lydia Guadalupe; Zapata-Benavides, Pablo; Rodríguez-Salazar, María del Carmen; Caballero-Hernandez, Diana; Tamez-Guerra, Reyes Silvestre; Rodríguez-Padilla, Cristina

2016-01-01

Chemotherapy treatments induce a number of side effects, such as leukopenia neutropenia, peripheral erythropenia, and thrombocytopenia, affecting the quality of life for cancer patients. 5-Fluorouracil (5-FU) is wieldy used as myeloablative model in mice. The bovine dialyzable leukocyte extract (bDLE) or IMMUNEPOTENT CRP® (ICRP) is an immunomodulatory compound that has antioxidants and anti-inflammatory effects. In order to investigate the chemoprotection effect of ICRP on bone marrow cells in 5-FU treated mice, total bone marrow (BM) cell count, bone marrow colony forming units-granulocyte/macrophage (CFU-GM), cell cycle, immunophenotypification, ROS/superoxide and Nrf2 by flow cytometry, and histological and hematological analyses were performed. Our results demonstrated that ICRP increased BM cell count and CFU-GM number, arrested BM cells in G0/G1 phase, increased the percentage of leukocyte, granulocytic, and erythroid populations, reduced ROS/superoxide formation and Nrf2 activation, and also improved hematological levels and weight gain in 5-FU treated mice. These results suggest that ICRP has a chemoprotective effect against 5-FU in BM cells that can be used in cancer patients. PMID:27191003
Intra-cerebral ventricular infusion of 5-iodo-2-deoxyuridine (IUDR) as a radiosensitizer in the treatment of a rat glioma

International Nuclear Information System (INIS)

Deutsch, M.; Rewers, A.B.; Redgate, S.; Fisher, E.R.; Boggs, S.S.

1990-01-01

The efficacy of 5-iodo-2-deoxyuridine (IUDR) as a radiosensitizer when administered by continuous infusion into the cerebral spinal fluid (CSF) of the lateral cerebral ventricle was evaluated in a 9L gliosarcoma rat brain tumor model. Stereotactic implantation of a 5 x 10(4) tumor cell suspension into the left caudate nucleus was carried out in four groups of 10 rats each. Control animals had a median survival of 16.9 days (range 16-21 days). IUDR, 8.4 mg over 7 days administered by continuous infusion into the left lateral ventricle produced a slight survival advantage (median survival 21.5 days, range 12-56). Irradiation of the entire brain, 8 Gy on days 4, 6 and 7 after tumor cell implantation also produced a slight improvement in survival (median 19.5 days, range 17-34). The combination of radiation and IUDR infusion into the CSF produced a marked survival advantage (median 30.5, range 22-54) compared to the control and single modality treatment groups. This is the first demonstration of the effectiveness of IUDR as a radiosensitizer when administered into the lateral cerebral ventricle in the treatment of an intraparenchymal brain tumor
Effects of induction docetaxel, platinum, and fluorouracil chemotherapy in patients with stage III or IVA/B nasopharyngeal cancer treated with concurrent chemoradiation therapy: Final results of 2 parallel phase 2 clinical trials.

Science.gov (United States)

Kong, Lin; Zhang, Youwang; Hu, Chaosu; Guo, Ye; Lu, Jiade J

2017-06-15

The effects of docetaxel, platinum, and fluorouracil (TPF) induction chemotherapy plus concurrent chemoradiotherapy (CCRT) on locoregionally advanced nasopharyngeal cancer (NPC) are unclear. This study examined the long-term outcomes of the addition of this regimen to CCRT for stage III and IVA/B NPC. Two parallel, single-arm phase 2 trials were performed synchronously to evaluate the efficacy and toxicity of TPF-based induction chemotherapy in patients with stage III or IVA/B NPC. The induction chemotherapy, which preceded standard intensity-modulated radiation therapy/platinum-based chemoradiation, consisted of 3 cycles of docetaxel (75 mg/m 2 on day 1), cisplatin (75 mg/m 2 on day 1), and a continuous infusion of fluorouracil (500 mg/m 2 /d on days 1-5) every 4 weeks. The primary endpoint for both trials was 5-year overall survival (OS). Between January 2007 and July 2010, 52 eligible patients with stage III NPC and 64 eligible patients with nonmetastatic stage IV NPC were accrued to the 2 trials. With a median follow-up of 67 months, the 5-year OS, progression-free survival, distant metastasis-free survival, and local progression-free survival (LPFS) rates were all improved in comparison with historical benchmarks for patients with stage III or IVA/IVB NPC. Multivariate analyses indicated that T and N classifications (T1/T2 vs T3/T4 and N3 vs N0-N2) were the only significant prognosticators for OS. The number of induction chemotherapy cycles was the only significant prognostic factor for predicting LPFS. TPF-based induction chemotherapy appears to significantly improve outcomes in comparison with historical data when it is administered before CCRT for locoregionally advanced NPC. A phase 3 trial is currently being performed to confirm this benefit. Cancer 2017;123:2258-2267. © 2017 American Cancer Society. © 2017 American Cancer Society.
Peripheral Venous Access Ports: Outcomes Analysis in 109 Patients

International Nuclear Information System (INIS)

Bodner, Leonard J.; Nosher, John L.; Patel, Kaushik M.; Siegel, Randall L.; Biswal, Rajiv; Gribbin, Christopher E.; Tokarz, Robert

2000-01-01

(p = 0.6). Aspiration occlusion occurred in 13 patients (11.7%). Intracatheter urokinase was infused in eight of these patients and successfully restored catheter function in all but two instances. These complication rates are comparable to or better than those reported with chest ports.Conclusion: Peripheral ports for long-term central venous access placed by interventional radiologists in the interventional radiology suite are as safe and as effective as chest ports
Low-dose factor VIII infusion in Chinese adult haemophilia A patients: pharmacokinetics evidence that daily infusion results in higher trough level than with every-other-day infusion with similar factor VIII consumption.

Science.gov (United States)

Hua, B; Lee, A; Fan, L; Li, K; Zhang, Y; Poon, M-C; Zhao, Y

2017-05-01

Pharmacokinetics (PK) modelling suggests improvement of trough levels are achieved by using more frequent infusion strategy. However, no clinical study data exists to confirm or quantify improvement in trough level, particularly for low-dose prophylaxis in patients with haemophilia A. To provide evidence that low dose daily (ED) prophylaxis can increase trough levels without increasing FVIII consumption compared to every-other-day (EOD) infusion. A cross-over study on 5 IU kg -1 FVIII daily vs. 10 IU kg -1 EOD infusions, each for 14 days was conducted at the PUMCH-HTC. On the ED schedule, trough (immediate prior to infusion), and peak FVIII:C levels (30 min after infusion) were measured on days 1-5; and trough levels alone on days 7, 9, 11 and 13. For the EOD schedule, troughs, peaks and 4-h postinfusion were measured on day 1; troughs and peaks on days 3, 5, and 7; troughs alone on days 9, 11 and 13 and 24-h postinfusion on days 2, 4 and 6. FVIII inhibitors were assessed on days 0 and 14 during both infusion schedules. Six patients were enrolled. PK evidence showed that daily prophylaxis achieved higher (~2 times) steady-state FVIII trough levels compared to EOD with the same total factor consumption. The daily prophylaxis had good acceptability among patients and reduced chronic pain in the joints in some patients. Our PK study shows low-dose factor VIII daily infusion results in higher trough level than with EOD infusion with similar factor VIII consumption in Chinese adult haemophilia A patients. © 2017 John Wiley & Sons Ltd.
Infusion Extractor

Science.gov (United States)

Chang-Diaz, Franklin R.

1988-01-01

Apparatus and method of removing desirable constituents from an infusible material by infusion extraction, where a piston operating in a first chamber draws a solvent into the first chamber where it may be heated, and then moves the heated solvent into a second chamber containing the infusible material, and where infusion extraction takes place. The piston then moves the solvent containing the extract through a filter into the first chamber, leaving the extraction residue in the second chamber.
Iliac Vein Interrogation Augments Venous Ulcer Healing in Patients Who Have Failed Standard Compression Therapy along with Pathological Venous Closure.

Science.gov (United States)

Mousa, Albeir Y; Broce, Mike; Yacoub, Michael; AbuRahma, Ali F

2016-07-01

Treatment of venous ulcers is demanding for patients, as well as clinicians, and the investigation of underlying venous hypertension is the cornerstone of therapy. We propose that occult iliac vein stenosis should be ruled out by iliac vein interrogation (IVI) in patients with advanced venous stasis. We conducted a systematic retrospective analysis of a consecutive series of patients who presented with CEAP (clinical, etiological, anatomical, and pathophysiological) 6 venous disease. All patients had great saphenous vein ablation, compressive treatment, wound care (including Unna boot compression), and perforator closure using ablation therapy. Iliac vein stenosis was defined as ≥50% stenosis in cross-sectional surface area on intravascular ultrasound. Primary outcomes include time of venous ulcer healing and/or measurable change in the Venous Clinical Severity Score. Twenty-two patients with CEAP 6 venous disease met the inclusion criteria (active ulcers >1.5 cm in diameter). The average age and body mass index were 62.2 ± 9.2 years and 41.7 ± 16.7, respectively. The majority were female (72.7%) with common comorbidities, such as hyperlipidemia (54.5%), hypertension (36.4%), and diabetes mellitus (27.3%). Twenty-nine ulcers with an average diameter of 3.4 ± 1.9 cm and a depth of 2.2 ± 0.5 mm were treated. The majority of the ulcers occurred on the left limb (n = 17, 58.6%). Average perforator venous reflux was 3.6 ± 0.8 sec, while common femoral reflux was 1.8 ± 1.6. The majority (n = 19, 64.5%) of the perforator veins were located at the base of the ulcer, while the remainder (n = 10, 34.5%) were within 2 cm from the base. Of the 13 patients who underwent IVI, 8 patients (61.5%) had stenosis >50% that was corrected with iliac vein angioplasty and stenting (IVAS). There was a strong trend toward shorter healing time in the IVI group (7.9 ± 9.5 weeks) than for patients in the no iliac vein interrogation (NIVI) group (20.2 ± 15
Influence of DPYD Genetic Polymorphisms on 5-Fluorouracil Toxicities in Patients with Colorectal Cancer: A Meta-Analysis

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Qiang Li

2014-01-01

Full Text Available Our meta-analysis aggregated existing results from relevant studies to comprehensively investigate the correlations between genetic polymorphisms in dihydropyrimidine dehydrogenase (DPYD gene and 5-fluorouracil (5-FU toxicities in patients with colorectal cancer (CRC. The MEDLINE (1966∼2013, the Cochrane Library Database (Issue 12, 2013, EMBASE (1980∼2013, CINAHL (1982∼2013, Web of Science (1945∼2013, and the Chinese Biomedical Database (CBM (1982∼2013 were searched without language restrictions. Meta-analyses were conducted with the use of STATA software (Version 12.0, Stata Corporation, College Station, TX, USA. Seven clinical cohort studies with a total of 946 CRC patients met our inclusion criteria, and NOS scores of each of the included studies were ≥5. Our findings showed that DPYD genetic polymorphisms were significantly correlated with high incidences of 5-FU-related toxicity in CRC patients. SNP-stratified analysis indicated that there were remarkable connections of IVS14+1G>A, 464T>A, and 2194G>A polymorphisms with the incidence of marrow suppression in CRC patients receiving 5-FU chemotherapy. Furthermore, we found that IVS14+1G>A, 496A>G, and 2194G>A polymorphisms were correlated with the incidence of gastrointestinal reaction. Ethnicity-stratified analysis also revealed that DPYD genetic polymorphisms might contribute to the development of marrow suppression and gastrointestinal reaction among Asians, but not among Caucasians. The present meta-analysis suggests that DPYD genetic polymorphisms may be correlated with the incidence of 5-FU-related toxicity in CRC patients.
Radiologically-placed venous ports in children under venous anesthesia

International Nuclear Information System (INIS)

Jang, Joo Yeon; Jeon, Ung Bae; Choo, Ki Seok; Hwang, Jae Yeon; Kim, Yong Woo; Lee, Yun Jin; Nam, Sang Ool; Lim, Young Tak

2015-01-01

To evaluate the efficacy and safety of radiologic venous port placement in children under venous anesthesia. Between April 2009 and July 2011, 44 ports were implanted in 41 children (24 boys, 17 girls). The age of patients ranged from 9 months to 19 years (mean, 6.5 years) and their body weights ranged from 6.8 kg to 56.3 kg (mean, 23.2 kg). Right internal jugular vein access was used in 42 ports, right subclavian vein in 1, and left subclavian in 1. Durability and complications of port implantation were reviewed. The technical success rate was 100%. The catheter life was 10-661 days (mean 246 days). Two patients died during the follow-up period, 21 and 6 ports were removed at the end of treatment or as a result of complications, respectively. One port was removed and replaced by a Hickmann catheter. Three ports were explanted due to port-related sepsis, one due to a catheter kink, and two for unexplained fever or insertion site pain. The overall port-related infection was 3 cases (6.8%, 0.28/1000 catheter days). Venous port placement by interventional radiologists in children under intravenous sedation is relatively safe, with a high rate of technical success and low rate of complications.
Radiologically-placed venous ports in children under venous anesthesia

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Jang, Joo Yeon; Jeon, Ung Bae; Choo, Ki Seok; Hwang, Jae Yeon; Kim, Yong Woo; Lee, Yun Jin; Nam, Sang Ool; Lim, Young Tak [Pusan National University School of Medicine, Yangsan (Korea, Republic of)

2015-02-15

To evaluate the efficacy and safety of radiologic venous port placement in children under venous anesthesia. Between April 2009 and July 2011, 44 ports were implanted in 41 children (24 boys, 17 girls). The age of patients ranged from 9 months to 19 years (mean, 6.5 years) and their body weights ranged from 6.8 kg to 56.3 kg (mean, 23.2 kg). Right internal jugular vein access was used in 42 ports, right subclavian vein in 1, and left subclavian in 1. Durability and complications of port implantation were reviewed. The technical success rate was 100%. The catheter life was 10-661 days (mean 246 days). Two patients died during the follow-up period, 21 and 6 ports were removed at the end of treatment or as a result of complications, respectively. One port was removed and replaced by a Hickmann catheter. Three ports were explanted due to port-related sepsis, one due to a catheter kink, and two for unexplained fever or insertion site pain. The overall port-related infection was 3 cases (6.8%, 0.28/1000 catheter days). Venous port placement by interventional radiologists in children under intravenous sedation is relatively safe, with a high rate of technical success and low rate of complications.
Brain SPECT by intraarterial infusion of 99mTc-HMPAO for assessing the cerebral distribution of carotid artery infusions in patient with brain tumor

International Nuclear Information System (INIS)

Kosuda, Shigeru; Kusano, Shoichi; Aoki, Shigeki

1993-01-01

In order to assess the cerebral distribution of intracarotid chemotherapy, 17 postoperative patients with brain tumor underwent brain SPECT obtrained by intraarterial infusion of 18.5 MBq of 99m Tc-d,l,-hexamethylpropyleneamine oxime ( 99m Tc-HMPAO). Injection methods were continuous (5.0 ml/min) or pulsatile infusion with supra- or infraophthalmic catheterization. The findings obtained by brain SPECT were frequently different from those of angiography and/or DSA. In supraophthalmic catheterization with continuous infusion, only 2 of 10 studies (20%) had homogeneous distribution and 5 of them (50%) had maldistribution of 99m Tc-HMPAO which appears in association with laminar flow effect. The remaining 3 studies showed localized distribution (two: tumor localization, one: healthy brain localization). On the other hand, all of 5 studies with pulsatile infusion had homogeneous distribution of 99m Tc-HMPAO. In infraophthalmic catheterization, all but one of 5 studies had homogeneous distribution with continuous infusion. These results suggest that pulsatile infusion may be effective in eliminating maldistribution of 99m Tc-HMPAO in supraophthalmic catheterization. In conclusion, we are convinced that 99m Tc-HMPAO is a useful intraarterial agent for assessing cerebral distribution of intracarotid chemotherpay. (author)

Direct venous thrombolysis and venous angioplasty in the upper extremity

International Nuclear Information System (INIS)

Hollmann, J.P.; Guenther, R.W.

1987-01-01

Venous thromboses of stenoses in the upper extremity are often the result of a compression syndrome of the shoulder girdle, the Paget-von Schroetter syndrome, vascular surgery, space-occupying lesions in the mediastinum or the result of catheterisation. Direct venous thrombolysis and venous angioplasty were performed successfully in six patients. (orig.) [de
The achievement of mass balance by simultaneous quantification of floxuridine prodrug, floxuridine, 5-fluorouracil, 5-dihydrouracil, α-fluoro-β-ureidopropionate, α-fluoro-β-alanine using LC-MS.

Science.gov (United States)

Tsume, Yasuhiro; Provoda, Chester J; Amidon, Gordon L

2011-04-15

5-Fluoro-2'-deoxyuridine (floxuridine, 5-FdUrd) and 5-fluorouracil (5-FU) are widely used for the treatment of colorectal cancers. The mechanisms of action of 5-FdUrd and 5-FU, as well as the biochemical pathway responsible for their metabolism, are well understood. Identification of every metabolite and achieving mass balance by conventional UV absorption-based HPLC analysis are not feasible because the metabolites beyond 5-FU in the 5-FdUrd metabolic pathway are undetectable by UV light. We therefore established a mass spectrometry method, designed for fast and convenient analysis, for simultaneously measuring 5-FdUrd, 5-FU, and their metabolites. Linearity, precision and accuracy were validated in the concentration ranges studied for each compound. Hydrolysis studies of 5-FdUrd and amino acid mono ester prodrugs of 5-FdUrd in Capan-2 cell homogenates were carried out and the achievement of mass balance was established with this method (recovery of 5'-O-l-leucyl-FdUrd was 96.6-108.2% and that of 5-FdUrd was 79.4-117.4%). This simple LC-MS method achieves reliable quantitation and mass balance of 5-FdUrd, 5-FU, and their metabolites and can be effectively utilized for further kinetic studies. Copyright © 2011 Elsevier B.V. All rights reserved.
Pharmacokinetics of imipenem in critically ill patients during empirical treatment of nosocomial pneumonia: a comparison of 0.5-h and 3-h infusions.

Science.gov (United States)

Lipš, Michal; Siller, Michal; Strojil, Jan; Urbánek, Karel; Balík, Martin; Suchánková, Hana

2014-10-01

In critically ill patients, pathophysiological changes alter the pharmacokinetics of antibiotics. Imipenem exhibits primarily time-dependent killing. Its administration by prolonged infusion may increase the time for which its plasma concentration exceeds the minimum inhibitory concentrations (MICs) of suspected pathogens. The objectives of this study were to compare the pharmacokinetic parameters of imipenem administered by standard short infusion (1g imipenem/1g cilastatin over 30min three times daily) and by extended infusion with a reduced total dose (0.5g imipenem/0.5g cilastatin over 3h four times daily) and to compare the target pharmacokinetic/pharmacodynamic indices, namely percentage of the dosing interval for which the free plasma concentration of imipenem exceeds the MIC and 4× MIC (%fT>MIC and %fT>4×MIC) of 0.5, 1, 2 and 4mg/L, for these two regimens in critically ill adult patients with nosocomial pneumonia on Day 2 of empirical antibiotic therapy. The study included 22 patients. Whilst no significant differences were found between both groups for %fT>MIC, %fT>4×MIC was 87.4±12.19%, 68.6±15.08%, 47.31±6.64% and 27.81±9.52% of the 8-h interval in the short infusion group for MICs of 0.5, 1, 2 and 4mg/L, respectively, and 85.15±17.57%, 53.14±27.27%, 13.55±24.47% and 0±0% of the 6-h interval for the extended infusion group. In conclusion, administration of 0.5g of imipenem by a 3-h infusion every 6h does not provide sufficient drug concentrations to treat infections caused by pathogens with a MIC of ≥2mg/L. Copyright © 2014 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.
Venous pump of the calf: a study of venous and muscular pressures.

Science.gov (United States)

Alimi, Y S; Barthelemy, P; Juhan, C

1994-11-01

Little data are available concerning the relation between the muscular pumping mechanism and the variation of superficial and deep venous pressure during normal action of the calf pump; therefore we undertook this study to determine the pressure values in three compartments of the calf and in the deep and the superficial venous system and to establish correlation between muscular and venous pressure. Nine healthy young women with a mean age of 23 years (range 19 to 28 years) were examined. In the same calf, a muscular catheter was placed in the deep posterior compartment (DPC), in the superficial posterior compartment (SPC), and in the anterior tibial compartment (ATC), and a vascular catheter was placed in the popliteal vein and in the greater saphenous vein (GSV). The five lines of pressure were simultaneously recorded in the following situations: at rest, during Valsalva maneuver, foot flexion, and foot extension. The situation was studied with the patient in the following positions: decubitus, sitting, standing, and squatting. A final continuous recording was carried out after the patient had been walking for 5 minutes. Mean values with standard errors of muscular and venous pressure were established in each situation. At rest and during Valsalva maneuver, the muscular pressures did not vary, whereas venous pressures increased significantly when the patient was sitting and standing. On the other hand, squatting was associated with a rise in the muscular and vein pressures. Foot flexion entailed a significant increase in the ATC pressure and a rise in the GSV pressure, whereas foot extension caused the DPC pressure to rise without venous pressure modifications. Walking was associated with an alternating increase in the DPC, SPC, GSV and popliteal vein pressures when the foot was compressed to floor followed by a significant decrease when the foot pressure was released. The variations in the deep and superficial venous pressures when the patient is sitting and
Post-exercise abdominal, subcutaneous adipose tissue lipolysis in fasting subjects is inhibited by infusion of the somatostatin analogue octreotide

DEFF Research Database (Denmark)

Enevoldsen, Lotte H; Polak, Jan; Simonsen, Lene

2007-01-01

.c., abdominal adipose tissue metabolism, before, during and after exercise in healthy, fasting, young male subjects. The adipose tissue net releases of fatty acids and glycerol were measured by arterio-venous catheterizations and simultaneous measurements of adipose tissue blood flow with the local Xe....... The results show that octreotide infusion during rest increased lipolysis and fatty acid release from the abdominal, s.c. adipose tissue. The exercise-induced increase in lipolysis and fatty acid release does not seem to be affected by octreotide when compared with the control study without octreotide...... infusion while the post-exercise increase in lipolysis is inhibited by octreotide, suggesting that the exercise-induced increase in GH secretion plays a role for the post-exercise lipolysis in s.c., abdominal adipose tissue....
Chemoradiotherapy with docetaxel, cisplatin and 5-fluorouracil (TPF) in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN)

International Nuclear Information System (INIS)

Katori, Hideaki; Ishitoya, Junichi; Ikeda, Yoichi; Kimura, Machiko; Hirose, Shouji; Sakuma, Yasunori; Yamamoto, Kaoru; Tsukuda, Mamoru

2004-01-01

The aim of this study was to evaluate the efficacy and toxicity of chemoradiotherapy using docetaxel (DOC), cisplatin (CDDP) and 5-fluorouracil (5-FU) in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN). Nineteen patients with previously untreated stage III-IV SCCHN were entered onto this trial. Patients received 2 cycles of chemotherapy with TPF. Radiation was targeted to begin on the first day of chemotherapy, day 1. The total radiation dose was between 63.0 and 74.0 Gy At least three patients were examined at each dose level before advancing to the next level. The maximum-tolerated dose (MTD) of this regimen was that DOC 60, CDDP 60 and 5-FU 600 mg/m 2 /day. The main toxicities were mucositis, leukocytopenia, neutropenia, anemia, liver dysfunction and renal dysfunction. The overall response rate was 100%, including 84% complete responses (CR). The high complete response rate justifies further evaluation of this chemoradiotherapy modality in advanced SCCHN patients. (author)
Chemoradiotherapy with docetaxel, cisplatin and 5-fluorouracil (TPF) in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN)

International Nuclear Information System (INIS)

Katori, Hideaki; Tsukuda, Mamoru; Mochimatu, Izumi; Ishitoya, Junichi; Mikami, Yasukazu; Tanigaki, Yuji; Ikeda, Yoichi; Taguchi, Takahide

2003-01-01

This study evaluated the efficacy and toxicity of chemoradiotherapy using docetaxel (DOC), cisplatin (CDDP) and 5-fluorouracil (5-FU) in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN). Nineteen patients with previously untreated stage III-IV SCCHN were entered onto this trial. Patients received two cycles of chemotherapy with TPF. Radiation was targeted to begin on the first day of chemotherapy, day 1. The total radiation dose was between 63.0 and 74.0 Gy. At least three patients were examined at each dose level before advancing to the next level. The maximum-tolerated dose (MTD) of this regimen was DOC 60, CDDP 60 and 5-FU 600 mg/m 2 /day. The main toxicities were mucositis, leukocytopenia, neutropenia, anemia, liver dysfunction and renal dysfunction. The overall response rate was 100%, including 84% complete responses (CR). The high complete response rate justifies further evaluation of this chemoradiotherapy modality in advanced SCCHN patients. (author)
Combined oral contraceptives: venous thrombosis.

Science.gov (United States)

de Bastos, Marcos; Stegeman, Bernardine H; Rosendaal, Frits R; Van Hylckama Vlieg, Astrid; Helmerhorst, Frans M; Stijnen, Theo; Dekkers, Olaf M

2014-03-03

Combined oral contraceptive (COC) use has been associated with venous thrombosis (VT) (i.e., deep venous thrombosis and pulmonary embolism). The VT risk has been evaluated for many estrogen doses and progestagen types contained in COC but no comprehensive comparison involving commonly used COC is available. To provide a comprehensive overview of the risk of venous thrombosis in women using different combined oral contraceptives. Electronic databases (Pubmed, Embase, Web of Science, Cochrane, CINAHL, Academic Search Premier and ScienceDirect) were searched in 22 April 2013 for eligible studies, without language restrictions. We selected studies including healthy women taking COC with VT as outcome. The primary outcome of interest was a fatal or non-fatal first event of venous thrombosis with the main focus on deep venous thrombosis or pulmonary embolism. Publications with at least 10 events in total were eligible. The network meta-analysis was performed using an extension of frequentist random effects models for mixed multiple treatment comparisons. Unadjusted relative risks with 95% confidence intervals were reported.Two independent reviewers extracted data from selected studies. 3110 publications were retrieved through a search strategy; 25 publications reporting on 26 studies were included. Incidence of venous thrombosis in non-users from two included cohorts was 0.19 and 0.37 per 1 000 person years, in line with previously reported incidences of 0,16 per 1 000 person years. Use of combined oral contraceptives increased the risk of venous thrombosis compared with non-use (relative risk 3.5, 95% confidence interval 2.9 to 4.3). The relative risk of venous thrombosis for combined oral contraceptives with 30-35 μg ethinylestradiol and gestodene, desogestrel, cyproterone acetate, or drospirenone were similar and about 50-80% higher than for combined oral contraceptives with levonorgestrel. A dose related effect of ethinylestradiol was observed for gestodene
A randomized phase II study of weekly nab-paclitaxel plus gemcitabine or simplified LV5FU2 as first-line therapy in patients with metastatic pancreatic cancer: the AFUGEM GERCOR trial.

Science.gov (United States)

Bachet, Jean-Baptiste; Chibaudel, Benoist; Bonnetain, Franck; Validire, Pierre; Hammel, Pascal; André, Thierry; Louvet, Christophe

2015-10-06

Metastatic pancreatic adenocarcinoma (PAC) prognosis remains dismal and gemcitabine monotherapy has been the standard treatment over the last decade. Currently, two first-line regimens are used in this setting: FOLFIRINOX and nab-paclitaxel plus gemcitabine. Increasing translational data on the predictive value of hENT1 for determining gemcitabine efficacy suggest that a non-gemcitabine-based regimen is favored in about 60 % of patients with PAC due to high resistance of PAC to this cytotoxic drug. This study aims to evaluate the efficacy of weekly nab-paclitaxel combined with gemcitabine or a simplified (s) LV5FU2 regimen in patients with previously untreated metastatic PAC. AFUGEM is a two-stage, open-label, randomized, multicenter, phase II trial. Patients with PAC who meet the inclusion criteria and provide written informed consent will be randomized in a 1:2 ratio to either nab-paclitaxel (125 mg/m(2)) plus gemcitabine (1000 mg/m(2)) given on days 1, 8, and 15 every 28 days or nab-paclitaxel (125 mg/m(2)) plus sLV5FU2 (leucovorin 400 mg/m(2) followed by bolus 400 mg/m(2) 5-fluorouracil and by 5-fluorouracil 2400 mg/m(2) as an 46-h intravenous infusion) given on days 1 and 15 every 28 days. A total of 114 patients will be randomized to one of the treatment arms. The primary endpoint is progression-free survival at 4 months. Secondary outcomes are rate and duration of response, disease control, overall survival, safety, and quality of life. Potential biomarkers of gemcitabine (hENT1, dCK) and 5-fluorouracil (TS) efficacy will be assessed. The AFUGEM trial is designed to provide valuable information regarding efficacy and tolerability of nab-paclitaxel plus gemcitabine and nab-paclitaxel plus sLV5FU2 regimens. Identification of potential predictive biomarkers of gemcitabine and 5-fluorouracil is likely to drive therapeutic decisions in patients with metastatic PAC. AFUGEM is registered at Clinicaltrials.gov: NCT01964534 , October 15, 2013.
Percutaneous transfemoral repositioning of malpositioned central venous catheters.

Science.gov (United States)

Hartnell, G G; Roizental, M

1995-04-01

Central venous catheters inserted by blind surgical placement may not advance into a satisfactory position and may require repositioning. Malpositioning via surgical insertion is common in patients in whom central venous catheters have previously been placed, as these patients are more likely to have central venous thrombosis and distortion of central venous anatomy. This is less of a problem when catheter placement is guided by imaging; however, even when insertion is satisfactory, central venous catheters may become displaced spontaneously after insertion (Fig. 1). Repositioning can be effected by direct manipulation using guidewires or tip-deflecting wires [1, 2], by manipulation via a transfemoral venous approach [3-5], and by injection of contrast material or saline [6]. Limitations of the direct approach include (1) the number and type of maneuvers that can be performed to effect repositioning when anatomy is distorted, (2) difficulty in accessing the catheter, and (3) the risk of introducing infection. Moreover, these patients are often immunosuppressed, and there is a risk of introducing infection by exposing and directly manipulating the venous catheter. Vigorous injection of contrast material or saline may be unsuccessful for the same reasons: It seldom exerts sufficient force to reposition large-caliber central venous catheters and may cause vessel damage or rupture if injection is made into a small or thrombosed vessel. We illustrate several alternative methods for catheter repositioning via a transfemoral venous approach.
Raltitrexed (Tomudex administration in patients with relapsed metastatic colorectal cancer after weekly irinotecan/5-Fluorouracil/Leucovorin chemotherapy

Directory of Open Access Journals (Sweden)

Vadiaka Maria

2002-01-01

Full Text Available Abstract Purpose The present study aimed at evaluating the efficacy of Raltitrexed, a specific thymidilate synthase inhibitor, in patients with advanced colorectal cancer (ACC in relapse (>8 weeks after a prior response or disease stabilization to first-line chemotherapy combination with lrinotecan+5-Fluorouracil (5-FU+Leucovorin (LV. Methods Twenty-five patients with metastatic ACC entered; 17 males/8 females, median age 61 (range: 47–70, median Karnovsky PS: 80 (70–90, and sites of metastases; liver: 21, lung: 4, lymph nodes: 7, peritoneal: 5 and a life expectancy of at least 3 months, were entered in the present pilot study. All patients had progressed after prior chemotherapy with lrinotecan+5-FU+LV. Raltitrexed was administered at a dose of 3 mg/m2 i.v. every 21 days. Results Three patients (12% achieved a partial response (PR, 8 (32% had stable disease (SD, and the remaining 14 (56% developed progressive disease (PD. Median time-to-progression (TTP was 5.5 months (range, 2–8.5, and median overall survival (OS 8 months (range, 4.0–12.5. Toxicity was generally mild; it consisted mainly of myelosuppression; neutropenia grade 1–2: 52%-grade 3: 28%, and anemia grade 1–2 only: 36%. Mild mucositis grade 1–2 occured in 13.5% of patients and was the principal non-hematologic toxicity. Conclusion Response to treatment with Raltitrexed is limited in patients with ACC failing after an initial response or non-progression to the weekly lrinotecan+5-FU+LV combination. However, it appears that a limited number of patients with PR/SD may derive clinical benefit, but final proof would require a randomized study.
Bioactive Glass Nanoparticles as a New Delivery System for Sustained 5-Fluorouracil Release: Characterization and Evaluation of Drug Release Mechanism

Directory of Open Access Journals (Sweden)

Abeer M. El-Kady

2015-01-01

Full Text Available Bioactive glass nanoparticles were synthesized and tested for the first time as a new delivery system for sustained 5-fluorouracil (5-FU release. They were characterized by TEM, DTA, TGA, and FT-IR. The porosity % and specific surface area of glass nanoparticles were 85.59% and 378.36 m2/g, respectively. The in vitro bioactivity evaluation confirmed that bioactive glass disks prepared from these nanoparticles could induce hydroxyapatite layer over their surfaces in simulated body fluid. The in vitro drug release experiment indicated that glass nanoparticles could serve as long-term local delivery vehicles for sustained 5-FU release. The release profile of 5-FU showed an initial fast release stage followed by a second stage of slower release. The initial burst release of 5-FU in the first day was about 23% (28.92 mg·L−1 of the total amount of loaded 5-FU, while the final cumulative percentage of the 5-FU released after 32 days was about 45.6% (57.31 mg·L−1 of the total amount of loaded 5-FU. The application of different mathematical models indicated that 5-FU was released by diffusion controlled mechanism and suggested that its release rate was dependent on glass particles dissolution, changes of surface area as well as diameter of glass particles, and concentration of loaded drug.
Venous anomalies and abnormalities of the posterior fossa

International Nuclear Information System (INIS)

Goulao, A.; Alvarez, H.; Garcia Monaco, R.; Pruvost, P.; Lasjaunias, P.

1990-01-01

The authors report a series of 16 patients with venous anomalies or abnormalities of the posterior fossa studied by angiography, CT and/or MRI. We believe that so-called 'venous angioma' are extreme anatomic variants that drain normal territories, and we prefer to call them developmental venous anomalies (DVA). Posterior fossa DVA, like the supra-tentorial ones are classified according to their drainage into deep and superficial type. They are exclusively located in the cerebellum or tectum. In 4 cases DVA was an incidental finding, in 3 an associated cerebral venous malformation (CVM) was found and felt to be the cause of the symptoms and only in one (Trigeminal pain) was a link between both suspected. Cavernous venous malformation (CVM) were found in frequent association with DVA (27%). 4 cases were single and 2 multiple. 5 CVM were located in the brain stem and 3 in the cerebellum. The clinical and radiological files were reviewed and a direct relationship between symptoms and localization was found in all patients with CVM. In 2 cases venous dysplasia was found: 1 Sturge-Weber and 1 First branchial arch syndrome. Both posterior fossa venous abnormalities were incidental findings. (orig.)
Double-blind, placebo-controlled, randomized study of chlorhexidine prophylaxis for 5-fluorouracil-based chemotherapy-induced oral mucositis with nonblinded randomized comparison to oral cooling (cryotherapy) in gastrointestinal malignancies

DEFF Research Database (Denmark)

Skovsgaard, T.; Bork, E.; Damstrup, L.

2008-01-01

BACKGROUND: The purpose was to evaluate prevention of oral mucositis (OM) using chlorhexidine compared with placebo and with oral cooling (cryotherapy) during fluorouracil (5-FU)-based chemotherapy in gastrointestinal (GI) cancer. METHODS: Patients with previously untreated GI cancer receiving...... bolus 5-FU/leucovorin chemotherapy were randomized to chlorhexidine mouthrinse 3 times a day for 3 weeks (Arm A), double-blind placebo (normal saline) with the same dose and frequency (Arm B), or cryotherapy with crushed ice 45 minutes during chemotherapy (Arm C). Patients self-reported on severity (CTC...... (33%) than in A (13%, Pcryotherapy. The latter is easy and inexpensive but has...
Inhibition of endogenous lactate turnover with lactate infusion in humans

International Nuclear Information System (INIS)

Searle, G.L.; Feingold, K.R.; Hsu, F.S.; Clark, O.H.; Gertz, E.W.; Stanley, W.C.

1989-01-01

The extent to which lactate infusion may inhibit endogenous lactate production, though previously considered, has never been critically assessed. To examine this proposition, single injection tracer methodology (U- 14 C Lactate) has been used for the estimation of lactate kinetics in 12 human subjects under basal conditions and with the infusion of sodium lactate. The basal rate of lactate turnover was measured on a day before the study with lactate infusion, and averaged 63.7 + 5.5 mg/kg/h. Six of these individuals received a stable lactate infusion at an approximate rate of 160 mg/kg/h, while the remaining six individuals were infused at the approximate rate of 100 mg/kg/h. It has been found that stable lactate infused at rates approximating 160 mg/kg/h consistently produced a complete inhibition of endogenous lactate production. Infusion of lactate at 100 mg/kg/h caused a lesser and more variable inhibition of endogenous lactate production (12% to 64%). In conclusion, lactate infusion significantly inhibits endogenous lactate production
Opposing effects of 5,7-DHT infusions into the orbitofrontal cortex and amygdala on flexible responding.

Science.gov (United States)

Man, M S; Dalley, J W; Roberts, A C

2010-07-01

Central serotonin is implicated in a variety of emotional and behavioral control processes. Serotonin depletion can lead to exaggerated aversive processing and deficient response inhibition, effects that have been linked to serotonin's actions in the amygdala and orbitofrontal cortex (OFC), respectively. However, a direct comparison of serotonin manipulations within the OFC and amygdala in the same experimental context has not been undertaken. This study compared the effects of infusing the serotonin neurotoxin, 5,7-dihydroxytryptamine into the OFC and amygdala of marmosets performing an appetitive test of response inhibition. Marmosets had to learn to inhibit a prepotent response tendency to choose a box containing high-incentive food and instead choose a box containing low-incentive food, to obtain reward. OFC infusions caused long-lasting reductions in serotonin tissue levels, as revealed at postmortem, and exaggerated prepotent responses. In contrast, the significantly reduced prepotent responses following amygdala infusions occurred at a time when serotonin tissue levels had undergone considerable recovery, but there remained residual reductions in extracellular serotonin, in vivo. These opposing behavioral effects of serotonin manipulations in the same experimental context may be understood in terms of the top-down regulatory control of the amygdala by the OFC.
Systemic 5-fluorouracil treatment causes a syndrome of delayed myelin destruction in the central nervous system

Directory of Open Access Journals (Sweden)

Han Ruolan

2008-04-01

Full Text Available Abstract Background Cancer treatment with a variety of chemotherapeutic agents often is associated with delayed adverse neurological consequences. Despite their clinical importance, almost nothing is known about the basis for such effects. It is not even known whether the occurrence of delayed adverse effects requires exposure to multiple chemotherapeutic agents, the presence of both chemotherapeutic agents and the body's own response to cancer, prolonged damage to the blood-brain barrier, inflammation or other such changes. Nor are there any animal models that could enable the study of this important problem. Results We found that clinically relevant concentrations of 5-fluorouracil (5-FU; a widely used chemotherapeutic agent were toxic for both central nervous system (CNS progenitor cells and non-dividing oligodendrocytes in vitro and in vivo. Short-term systemic administration of 5-FU caused both acute CNS damage and a syndrome of progressively worsening delayed damage to myelinated tracts of the CNS associated with altered transcriptional regulation in oligodendrocytes and extensive myelin pathology. Functional analysis also provided the first demonstration of delayed effects of chemotherapy on the latency of impulse conduction in the auditory system, offering the possibility of non-invasive analysis of myelin damage associated with cancer treatment. Conclusions Our studies demonstrate that systemic treatment with a single chemotherapeutic agent, 5-FU, is sufficient to cause a syndrome of delayed CNS damage and provide the first animal model of delayed damage to white-matter tracts of individuals treated with systemic chemotherapy. Unlike that caused by local irradiation, the degeneration caused by 5-FU treatment did not correlate with either chronic inflammation or extensive vascular damage and appears to represent a new class of delayed degenerative damage in the CNS.
Cyclophosphamide, methotrexate, and fluorouracil; oral cyclophosphamide; levamisole; or no adjuvant therapy for patients with high-risk, premenopausal breast cancer

DEFF Research Database (Denmark)

Ejlertsen, Bent Laursen; Mouridsen, Henning T; Jensen, Maj-Britt

2010-01-01

BACKGROUND: The Danish Breast Cancer Cooperative Group (DBCG) 77B trial examined the relative efficacy of levamisole, single-agent oral cyclophosphamide, and the classic combination of cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) against no adjuvant systemic therapy in high-risk breast...... cancer patients. The authors report the results from that trial after a potential follow-up of 25 years. METHODS: Between 1977 and 1983, 1146 premenopausal patients who had tumors >5 cm or positive axillary lymph nodes were assigned randomly to 1 of 4 options: no systemic therapy, levamisole 5 mg weekly...... for 48 weeks (the levamisole arm), oral cyclophosphamide 130 mg/m(2) on Days 1 through 14 every 4 weeks for 12 cycles (the C arm), or oral cyclophosphamide 80 mg/m(2) on Days 1 through 14 plus methotrexate 30 mg/m(2) and fluorouracil 500 mg/m(2) intravenously on Days 1 and 8 every 4 weeks for 12 cycles...
Color-flow Doppler imaging in suspected extremity venous thrombosis

International Nuclear Information System (INIS)

Foley, W.D.; Middleton, W.D.; Lawson, T.L.; Hinson, G.W.; Puller, D.R.

1987-01-01

Color-flow Doppler imaging (CFDI) (Quanatum, 5 and 7.5 MHz, linear array) has been performed on 23 extremities (nine positive for venous thrombosis, 14 negative) with venographic correlation. CFDI criteria evaluated were venous color-flow respiratory variation, augmentation, compressibility, valve competence, and intraluminal echogenic filling defects. Both CFDI and venography were evaluated independently and prospectively. CFDI and venography agreed in all six cases of femoral vein thrombosis and eight of nine cases of popliteal vein thrombosis. CFDI was negative in one instance of recanalized popliteal vein thrombosis. Recanalized femoral vein thrombosis was documented in three patients by CFDI when the vein was nonopacified on conventional venography. CFDI provides a rapid and accurate assessment of the femoral popliteal venous system and can distinguish an occluded from a recanalized thrombus. Initial experience with auxiliary subclavian venous thrombus has produced equally accurate results
Preclinical screening for drugs effective against 5-fluorouracil-resistant cells with a murine L5178Y cell line in vitro

International Nuclear Information System (INIS)

Hill, B.T.

1983-01-01

A subline of L5178Y cells has been established in vitro that exhibits a fiftyfold order of resistance to 5-fluorouracil (FUra) as compared to that of the parent line. The cytotoxic effects of 24-hour exposures to 23 antitumor drugs and to radiation were compared in the two cell lines. Four patterns of response were identified: 1) Only two drugs, mitomycin C and adriamycin, proved significantly more cytotoxic to FUra-resistant cells. 2) Four other drugs--anguidine, 4'-(9-acridinylamino)-methanesulfon-m-anisidide, melphalan, and quelamycin--showed marginal superiority against resistant cells. 3) X-radiation and the majority of drugs tested--including 5-azacytidine, 1,3-bis(2-chloroethyl)-1-nitrosourea, cisplatin, bleomycin, dibromodulcitol, razoxane, hydroxyurea, methotrexate, teniposide, etoposide, and three experimental agents, metoprine, spirogermanium HCl, and ellipticinum--proved equally cytotoxic to both cell lines. 4) Cross-resistance with FUra was exhibited with vincristine, vindesine, pyrazofurin, and indicine-N-oxide. This experimental system provides a simple method of testing agents for activity against FUra-resistant cells before phase 1 clinical studies

Early mechanism of action of arterially infused ethanol: an experimental study on the influence of infusion speed

International Nuclear Information System (INIS)

Han, Joon Koo

1988-01-01

Abdominal aortography and histopathologic examination after absolute ethanol infusion at fast (0.4cc/sec) and slow speed (0.04cc/sec) were performed on 16 rats (2 controls. 7 fast infusion group. 7 slow infusion group). Angiographic and histopathologic findings were correlated and the findings of slow and fast infusion groups were studied. The results are as follows: 1. Histopathologic findings of the fast infusion group revealed wide area of glomerular and tubular collapses, obliteration of the free space between the Bowmann's capsule and glomerulus, sloughing and loss of the endothelium, fresh thrombi attached to the wall, and cleavage of the muscle layer of the arteries. 2. Angiographic findings of the fast infusion group revealed luminal irregularity, early obstruction of the aorta and the renal arteries, and delayed circulation time. 3. Histopathologic findings of the slow infusion group revealed degenerated, coalesced red blood cell packed in the glomeruli, focal areas of severe glomerular and tubular damage on relatively normal background, endothelial and muscular damage of the arteries. 4. Angiographic findings of the slow infusion group revealed focal perfusion defect of the kidney, delayed circulation time, and mild luminal irregularity, but there was no obstruction of the major arteries. 5. In conclusion, author believes that endothelial damage and thrombus formation from the damaged vessel wall, as well as direct cytotoxicity and in situ emboli formation play a significant role in the embolic effect of absolute ethanol.
Physicochemical stability of oxaliplatin in 5% dextrose injection stored in polyvinyl chloride, polyethylene, and polypropylene infusion bags.

Science.gov (United States)

Eiden, Céline; Philibert, Laurent; Bekhtari, Khedidja; Poujol, Sylvain; Malosse, Francoise; Pinguet, Frédéric

2009-11-01

The physicochemical stability of extemporaneous dilutions of oxaliplatin in 5% dextrose injection stored in polyvinyl chloride (PVC), polypropylene, and polyethylene infusion bags was studied. Oxaliplatin 100 mg/20 mL concentrated solution was diluted in 100 mL of 5% dextrose injection in PVC, polypropylene, and polyethylene infusion bags to produce nominal oxaliplatin concentrations of 0.2 and 1.3 mg/mL. The filled bags were stored for 14 days at 20 degrees C and protected from light, at 20 degrees C under normal fluorescent light, and at 4 degrees C. A 1-mL sample was removed from each bag at time 0 and at 24, 48, 72, 120, 168, and 336 hours. The samples were visually inspected for color and clarity, and the pH values of the solutions were measured. High-performance liquid chromatography was used to assay oxaliplatin concentration. Bacterial contamination was assessed on study day 14 after incubation in trypticase soy solution for three days at 37 degrees C. Solutions of oxaliplatin 0.2 and 1.3 mg/mL in 5% dextrose injection were stable in the three container types for at least 14 days at both 4 degrees C and 20 degrees C without regard to light exposure. No color change was detected during the storage period, and pH values remained stable. No microbial contamination was detected in any samples over the study period. Oxaliplatin solutions diluted in 5% dextrose injection to 0.2 and 1.3 mg/mL were stable in PVC and PVC-free infusion bags for at least 14 days at both 4 degrees C and 20 degrees C without regard to light exposure.
Weekly oxaliplatin, 5-fluorouracil and folinic acid (OXALF) as first-line chemotherapy for elderly patients with advanced gastric cancer: results of a phase II trial

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Santini, D; Vincenzi, B; Russo, A; Caraglia, M; Virzi, V; Cascinu, S; Tonini, G; Graziano, F; Catalano, V; Di Seri, M; Testa, E; Baldelli, AM; Giordani, P; La Cesa, A; Spalletta, B

2006-01-01

Elderly patients have been often excluded from or underrepresented in the study populations of combination chemotherapy trials. The primary end point of this study was to determine the response rate and the toxicity of the weekly oxaliplatin, 5-fluorouracil and folinic acid (OXALF) regimen in elderly patients with advanced gastric cancer. The secondary objective was to measure the time to disease progression and the survival time. Chemotherapy-naive patients with advanced gastric cancer aged 70 or older were considered eligible for study entry. Patients received weekly oxaliplatin 40 mg/m2, fluorouracil 500 mg/m2 and folinic acid 250 mg/m2. All drugs were given intravenously on a day-1 schedule. A total of 42 elderly patients were enrolled. Median age was 73 years and all patients had metastatic disease. The response rate according to RECIST criteria was 45.2% (95% CIs: 30%–56%) with two complete responses, 17 partial responses, 13 stable diseases and 10 progressions, for an overall tumor rate control of 76.2% (32 patients). Toxicity was generally mild and only three patients discontinued treatment because of treatment related adverse events. The most common treatment-related grade 3/4 adverse events were fatigue (7.1%), diarrhoea (4.8%), mucositis (2.4%), neurotoxicity (2.4%) and neutropenia (4.8%). The median response duration was 5.3 months (95% CIs: 2.13 – 7.34), the median time to disease progression was 5.0 months (95% CIs: 3.75 – 6.25) and the median survival time was 9.0 months (95% CIs: 6.18 – 11.82). OXALF represents an active and well-tolerated treatment modality for elderly patients with locally advanced and metastatic gastric cancer
Weekly oxaliplatin, 5-fluorouracil and folinic acid (OXALF as first-line chemotherapy for elderly patients with advanced gastric cancer: results of a phase II trial

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Vincenzi B

2006-05-01

Full Text Available Abstract Background Elderly patients have been often excluded from or underrepresented in the study populations of combination chemotherapy trials. The primary end point of this study was to determine the response rate and the toxicity of the weekly oxaliplatin, 5-fluorouracil and folinic acid (OXALF regimen in elderly patients with advanced gastric cancer. The secondary objective was to measure the time to disease progression and the survival time. Methods Chemotherapy-naive patients with advanced gastric cancer aged 70 or older were considered eligible for study entry. Patients received weekly oxaliplatin 40 mg/m2, fluorouracil 500 mg/m2 and folinic acid 250 mg/m2. All drugs were given intravenously on a day-1 schedule. Results A total of 42 elderly patients were enrolled. Median age was 73 years and all patients had metastatic disease. The response rate according to RECIST criteria was 45.2% (95% CIs: 30%–56% with two complete responses, 17 partial responses, 13 stable diseases and 10 progressions, for an overall tumor rate control of 76.2% (32 patients. Toxicity was generally mild and only three patients discontinued treatment because of treatment related adverse events. The most common treatment-related grade 3/4 adverse events were fatigue (7.1%, diarrhoea (4.8%, mucositis (2.4%, neurotoxicity (2.4% and neutropenia (4.8%. The median response duration was 5.3 months (95% CIs: 2.13 – 7.34, the median time to disease progression was 5.0 months (95% CIs: 3.75 – 6.25 and the median survival time was 9.0 months (95% CIs: 6.18 – 11.82. Conclusion OXALF represents an active and well-tolerated treatment modality for elderly patients with locally advanced and metastatic gastric cancer.
Synergistic antitumor effect of 3-bromopyruvate and 5-fluorouracil against human colorectal cancer through cell cycle arrest and induction of apoptosis.

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Chong, Dianlong; Ma, Linyan; Liu, Fang; Zhang, Zhirui; Zhao, Surong; Huo, Qiang; Zhang, Pei; Zheng, Hailun; Liu, Hao

2017-09-01

3-Bromopyruvic acid (3-BP) is a well-known inhibitor of energy metabolism. It has been proposed as an anticancer agent as well as a chemosensitizer for use in combination with anticancer drugs. 5-Fluorouracil (5-FU) is the first-line chemotherapeutic agent for colorectal cancer; however, most patients develop resistance to 5-FU through various mechanisms. The aim of this study was to investigate whether 3-BP has a synergistic antitumor effect with 5-FU on human colorectal cancer cells. In our study, combined 3-BP and 5-FU treatment upregulated p53 and p21, whereas cyclin-dependent kinase CDK4 and CDK2 were downregulated, which led to G0/G1 phase arrest. Furthermore, there was an increase in reactive oxygen species levels and a decrease in adenosine triphosphate levels. It was also observed that Bax expression increased, whereas Bcl-2 expression reduced, which were indicative of mitochondria-dependent apoptosis. In addition, the combination of 3-BP and 5-FU significantly suppressed tumor growth in the BALB/c mice in vivo. Therefore, 3-BP inhibits tumor proliferation and induces S and G2/M phase arrest. It also exerts a synergistic antitumor effect with 5-FU on SW480 cells.
Effects of 5-fluorouracil on morphology, cell cycle, proliferation, apoptosis, autophagy and ROS production in endothelial cells and cardiomyocytes.

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Chiara Focaccetti

Full Text Available Antimetabolites are a class of effective anticancer drugs interfering in essential biochemical processes. 5-Fluorouracil (5-FU and its prodrug Capecitabine are widely used in the treatment of several solid tumors (gastro-intestinal, gynecological, head and neck, breast carcinomas. Therapy with fluoropyrimidines is associated with a wide range of adverse effects, including diarrhea, dehydration, abdominal pain, nausea, stomatitis, and hand-foot syndrome. Among the 5-FU side effects, increasing attention is given to cardiovascular toxicities induced at different levels and intensities. Since the mechanisms related to 5-FU-induced cardiotoxicity are still unclear, we examined the effects of 5-FU on primary cell cultures of human cardiomyocytes and endothelial cells, which represent two key components of the cardiovascular system. We analyzed at the cellular and molecular level 5-FU effects on cell proliferation, cell cycle, survival and induction of apoptosis, in an experimental cardioncology approach. We observed autophagic features at the ultrastructural and molecular levels, in particular in 5-FU exposed cardiomyocytes. Reactive oxygen species (ROS elevation characterized the endothelial response. These responses were prevented by a ROS scavenger. We found induction of a senescent phenotype on both cell types treated with 5-FU. In vivo, in a xenograft model of colon cancer, we showed that 5-FU treatment induced ultrastructural changes in the endothelium of various organs. Taken together, our data suggest that 5-FU can affect, both at the cellular and molecular levels, two key cell types of the cardiovascular system, potentially explaining some manifestations of 5-FU-induced cardiovascular toxicity.
Krypton 81m infusion studies. Chapter 18

International Nuclear Information System (INIS)

Kaplan, E.; Mayron, L.W.; Friedman, A.M.; Gindler, J.E.

1978-01-01

A technique is described to give a continuous, constant-rate, intravascular infusion of 81 Krsup(m). Modifications of earlier generators included production of sodium-free 81 Rb, the use of a solution of commercial sterile isotonic non-ionic 5% dextrose-in-water as an eluant, the incorporation of a constant-rate infusion pump, and the miniaturization of the generator column and catheter system. Results are presented of studies of 81 Krsup(m) distribution in dogs, using both intravenous and intra-arterial infusion. (author)
Nucleic acid labeling with [3H]orotic acid and nucleotide profile in rats in protein deprivation, enteral and parenteral essential amino acid administration, and 5-fluorouracil treatment

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Jakobsson, B.; el Hag, I.A.; Andersson, M.; Christensson, P.I.; Stenram, U.

1990-01-01

Rats were fed a 0% casein diet for 1 week, with or without enteral or parenteral administration of essential amino acids, or a 25% casein diet, in one group supplemented with 5-fluorouracil treatment. Ninety minutes before sacrifice the rats were given a tracer of [3H]orotic acid. Incorporation into the acid soluble fraction, RNA, and DNA was determined in liver, small intestine, bone marrow, and kidney. Nucleotide profile was examined in liver and intestine. Protein deficiency caused inter alia a decrease in body weight; a decrease in RNA/DNA ratio and an increase in the specific RNA labeling in liver and kidney; an altered nucleotide profile in the liver; an increase in the nucleotide/DNA and RNA/DNA ratios and a decrease in the specific labeling of the acid soluble fraction, RNA, and DNA in the bone marrow. These changes were prevented to the same extent by giving essential amino acids, either orally or intravenously. The minor changes in intestinal nucleotide profile in protein deprivation were prevented to a slightly larger extent by amino acids orally than parenterally. 5-Fluorouracil treatment gave a decrease in the RNA/DNA ratio in the liver and kidney but an increase in the nucleotide/DNA and RNA/DNA ratios in the bone marrow. Nucleotide profiles were unaltered. The amount of DNA per gram of tissue decreased in bone marrow and increased in kidney. Parenteral administration per se resulted in almost no changes
Postoperative deep venous thrombosis in Japan. Incidence and prophylaxis

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Inada, K.; Shirai, N.; Hayashi, M.; Matsumoto, K.; Hirose, M.

1983-01-01

The incidence of postoperative deep venous thrombosis was investigated using the iodine-125-fibrinogen method in 256 patients undergoing major surgery. Deep venous thrombosis was found in 49 patients (15.3 percent), and nonfatal pulmonary embolism developed in one of seven patients in whom the thrombus extended to the popliteal vein. The same investigation was performed in 110 patients who wore a graduated compression stocking on one leg, with the other leg serving as a control. Deep venous thrombosis was found in 4 of 110 stockinged legs (3.6 percent) and in 16 of 110 control legs (14.5 percent). The incidence of deep venous thrombosis decreased significantly in patients who wore the stocking. An increase in femoral venous flow velocity was found in the stockinged legs by the Doppler method. The mean velocity of venous return by xenon-133 clearance was significantly greater in the stockinged legs than in the control legs. These findings were considered to support the efficacy of graduated compression stockings for the prevention of deep venous thrombosis
Prevalence of lower extremity venous duplication

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Simpson William

2010-01-01

Full Text Available Purpose: This retrospective study was performed to determine the prevalence of lower extremity venous duplication using duplex ultrasound in the patient population of a large urban medical center. Materials and Methods: The reports of all lower extremity venous ultrasound examinations performed at our institution between January 1, 2002 and December 31, 2002 were reviewed. Ultrasound examinations that were performed for purposes other than the detection of lower extremity deep vein thrombosis were excluded. The prevalence of duplication and its specific location were recorded. In addition, the prevalence of thrombus and its specific location were also recorded. Results: A total of 3118 exams were performed in 2664 patients. Of the 2664 patients, 2311 had only one examination performed during the study period; 353 patients had more than one examination performed. We found that 10.1% of patients (270/2664 had at least one venous segment duplicated and 5.4% of patients (143/2664 had a thrombus in at least one venous segment. There was a statistically significant difference in the prevalence of both duplication and thrombus with a change in venous segment. Only 0.4% of patients (11/2664 had thrombus within a duplicated segment. Of those who had more than one examination performed, 15.3% (54/353 had the same venous segment(s seen on one examination but not another. Conclusion: Lower extremity venous duplication is a frequent anatomic variant that is seen in 10.1% of patients, but it may not be as common as is generally believed. It can result in a false negative result for deep vein thrombosis.
Promoter methylation and large intragenic rearrangements of DPYD are not implicated in severe toxicity to 5-fluorouracil-based chemotherapy in gastrointestinal cancer patients

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Savva-Bordalo, Joana; Henrique, Rui; Jerónimo, Carmen; Ramalho-Carvalho, João; Pinheiro, Manuela; Costa, Vera L; Rodrigues, Ângelo; Dias, Paula C; Veiga, Isabel; Machado, Manuela; Teixeira, Manuel R

2010-01-01

Severe toxicity to 5-fluorouracil (5-FU) based chemotherapy in gastrointestinal cancer has been associated with constitutional genetic alterations of the dihydropyrimidine dehydrogenase gene (DPYD). In this study, we evaluated DPYD promoter methylation through quantitative methylation-specific PCR and screened DPYD for large intragenic rearrangements in peripheral blood from 45 patients with gastrointestinal cancers who developed severe 5-FU toxicity. DPYD promoter methylation was also assessed in tumor tissue from 29 patients Two cases with the IVS14+1G > A exon 14 skipping mutation (c.1905+1G > A), and one case carrying the 1845 G > T missense mutation (c.1845G > T) in the DPYD gene were identified. However, DPYD promoter methylation and large DPYD intragenic rearrangements were absent in all cases analyzed. Our results indicate that DPYD promoter methylation and large intragenic rearrangements do not contribute significantly to the development of 5-FU severe toxicity in gastrointestinal cancer patients, supporting the need for additional studies on the mechanisms underlying genetic susceptibility to severe 5-FU toxicity
Promoter methylation and large intragenic rearrangements of DPYD are not implicated in severe toxicity to 5-fluorouracil-based chemotherapy in gastrointestinal cancer patients

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Savva-Bordalo Joana

2010-09-01

Full Text Available Abstract Background Severe toxicity to 5-fluorouracil (5-FU based chemotherapy in gastrointestinal cancer has been associated with constitutional genetic alterations of the dihydropyrimidine dehydrogenase gene (DPYD. Methods In this study, we evaluated DPYD promoter methylation through quantitative methylation-specific PCR and screened DPYD for large intragenic rearrangements in peripheral blood from 45 patients with gastrointestinal cancers who developed severe 5-FU toxicity. DPYD promoter methylation was also assessed in tumor tissue from 29 patients Results Two cases with the IVS14+1G > A exon 14 skipping mutation (c.1905+1G > A, and one case carrying the 1845 G > T missense mutation (c.1845G > T in the DPYD gene were identified. However, DPYD promoter methylation and large DPYD intragenic rearrangements were absent in all cases analyzed. Conclusions Our results indicate that DPYD promoter methylation and large intragenic rearrangements do not contribute significantly to the development of 5-FU severe toxicity in gastrointestinal cancer patients, supporting the need for additional studies on the mechanisms underlying genetic susceptibility to severe 5-FU toxicity.
Proanthocyanidins from Uncaria rhynchophylla induced apoptosis in MDA-MB-231 breast cancer cells while enhancing cytotoxic effects of 5-fluorouracil.

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Chen, Xiao-Xin; Leung, George Pak-Heng; Zhang, Zhang-Jin; Xiao, Jian-Bo; Lao, Li-Xing; Feng, Feng; Mak, Judith Choi-Wo; Wang, Ying; Sze, Stephen Cho-Wing; Zhang, Kalin Yan-Bo

2017-09-01

Breast cancer is the most frequently diagnosed cancer and cause of cancer death in women worldwide. Current treatments often result in systematic toxicity and drug resistance. Combinational use of non-toxic phytochemicals with chemotherapeutic agents to enhance the efficacy and reduce toxicity would be one promising approach. In this study, bioactive proanthocyanidins from Uncaria rhynchophylla (UPAs) were isolated and their anti-breast cancer effects alone and in combination with 5- fluorouracil (5-FU) were investigated in MDA-MB-231 breast cancer cells. The results showed that UPAs significantly inhibited cell viability and migration ability in a dose-dependent manner. Moreover, UPAs induced apoptosis in a dose-dependent manner which was associated with increased cellular reactive oxygen species production, loss of mitochondrial membrane potential, increases of Bax/Bcl-2 ratio and levels of cleaved caspase 3. Treatments of the cells with UPAs resulted in an increase in G2/M cell cycle arrest. Cytotoxic effects of 5-FU against MDA-MB-231 cells were enhanced by UPAs. The combination treatment of UPAs and 5-FU for 48 h elicited a synergistic cytotoxic effect on MDA-MB-231 cells. Altogether, these data suggest that UPAs are potential therapeutic agents for breast cancer. Copyright © 2017 Elsevier Ltd. All rights reserved.
Efficacy of Sucralfate Mouth Wash in Prevention of 5-fluorouracil Induced Oral Mucositis: A Prospective, Randomized, Double-Blind, Controlled Trial.

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Ala, Shahram; Saeedi, Majid; Janbabai, Ghasem; Ganji, Reza; Azhdari, Elham; Shiva, Afshin

2016-01-01

Sucralfate has been used for the prevention and treatment of radiotherapy- and chemotherapy-induced stomatitis and mucositis in a number of studies, but the results are contradictory. To answer such discrepancies, the present study was designed to evaluate the efficacy of sucralfate mouthwash in prevention of 5-fluorouracil (5-FU)-induced oral mucositis in patients with gastrointestinal malignancies. Patients with gastrointestinal cancers receiving 5-FU-based chemotherapy regimens were included in this randomized, blinded, controlled trial and were randomly allocated to either sucralfate mouthwash (every 6 h) or placebo. The patients were visited at fifth and tenth day of trial; the presence and severity of oral mucositis and the intensity of pain were assessed. The patients receiving sucralfate experienced lower frequency and severity of mucositis (76% vs. 38.5%, P = 0.005 and 84 vs. 38.5%, P < 0.001, respectively) and less intense pain (2.5 ± 2.2 vs. 5.08 ± 3.82, P = 0.004 and 1.33 ± 0.86 vs. 4.12 ± 3.5, P = 0.001, respectively) compared with the placebo group both at day 5 and day 10. Within the sucralfate group, a decrease in frequency and severity of mucositis was observed throughout the trial period, while in the placebo group no such effect was observed. Sucralfate mouthwash reduced the frequency and severity of 5-FU-induced oral mucositis in patients with gastrointestinal malignancies compared with placebo, indicating its efficacy in the prevention of chemotherapy-induced mucositis.
Effects of anisodamine on the expressions of vascular endothelial growth factor and intercellular adhesion molecule 1 in experimental infusion phlebitis.

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Zhang, Zhen-Xiang; Wang, Peng; Zhang, Qiu-Shi; Pan, Xue; Zhao, Qing-Xia; Wang, Xiao-Kai

2012-01-01

Infusion phlebitis is the most common side effect of clinical intravenous drug therapy and several clinical studies have demonstrated that anisodamine can effectively prevent the occurrence of infusion phlebitis. This study was designed to investigate effects of anisodamine on the expressions of vascular endothelial growth factor (VEGF) and intercellular adhesion molecule 1 (ICAM-1) in a rabbit model of infusion phlebitis and to analyze the mechanisms of anisodamine effect on the prevention and treatment of experimental infusion phlebitis. Twenty-four specific pathogen-free male Japanese white rabbits were randomly assigned to the control group, the model group, the magnesium sulfate group and the anisodamine group. The rabbit model of infusion phlebitis, induced by intravenous administration, was established and expressions of VEGF and ICAM-1 were determined and contrasted with the control group treated with normal saline. We evaluated expression by histopathology, immunohistochemistry, reverse transcription-polymerase chain reaction, and Western blotting assay. Pathohistological changes of the model group were observed, such as loss of venous endothelial cells, inflammatory cell infiltration, edema and thrombus. The magnesium sulfate group and the anisodamine group showed significant protective effects on vascular congestion, inflammatory cell infiltration, proliferation, swelling of endothelium and perivascular hemorrhage. The model group showed the highest expressions of VEGF and ICAM-1 of the four groups (P 0.05). Anisodamine alleviates inflammatory damage by significantly reducing the expressions of VEGF and ICAM-1, and shows significant protective effects in an animal model of infusion phlebitis.
Venous Ulcers

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Caprini, J.A.; Partsch, H.; Simman, R.

2013-01-01

Venous leg ulcers are the most frequent form of wounds seen in patients. This article presents an overview on some practical aspects concerning diagnosis, differential diagnosis and treatment. Duplex ultrasound investigations are essential to ascertain the diagnosis of the underlying venous pathology and to treat venous refluxes. Differential diagnosis includes mainly other vascular lesions (arterial, microcirculatory causes), hematologic and metabolic diseases, trauma, infection, malignancies. Patients with superficial venous incompetence may benefit from endovenous or surgical reflux abolition diagnosed by Duplex ultrasound. The most important basic component of the management is compression therapy, for which we prefer materials with low elasticity applied with high initial pressure (short-stretch bandages and Velcro-strap devices). Local treatment should be simple, absorbing and not sticky dressings keeping adequate moisture balance after debridement of necrotic tissue and biofilms are preferred. After the ulcer is healed compression therapy should be continued in order to prevent recurrence. PMID:26236636
Cost-effectiveness analysis of levobupivacaine 0.5 %, a local anesthetic, infusion in the surgical wound after modified radical mastectomy.

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Ferreira Laso, Lourdes; López Picado, Amanda; Antoñanzas Villar, Fernando; Lamata de la Orden, Laura; Ceballos Garcia, Mar; Ibañez López, Carolina; Pipaon Ruilope, Lorena; Lamata Hernandez, Felix; Valero Martinez, Cesar; Aizpuru, Felipe; Hernandez Chaves, Roberto

2015-09-01

Effective treatment of postoperative pain contributes to decreasing the rate of complications as well as the total cost of the operated patients. The aim of this study was to analyze the costs and the efficiency of use of continuous infusion of levobupivacaine 0.5 % with the help of an infusion pump in modified radical mastectomy. A cost calculation of the analgesic procedures (continuous infusion of levobupivacaine 0.5 % [levobupivacaine group (LG)] or saline [saline group (SG)] (2 ml/h 48 h) has been carried out based on the data of a previous clinical trial (double-blind randomized study) of patients who underwent modified radical mastectomy surgery. The measure of the effectiveness was the point reduction of pain derived from the verbal numeric rating scale (VNRS). The usual incremental cost-effectiveness ratio (ICER) was performed. Considering only the intravenous analgesia, overall costs were lower in LG, as less analgesia was used (EUR14.06 ± 7.89 vs. 27.47 ± 14.79; p mastectomy, therefore providing patients with a higher quality of care in the prevention of pain. clinicaltrials.gov: reference number NCT01389934. http://clinicaltrials.gov/show/NCT01389934
Systemic Venous Inflow to the Liver Allograft to Overcome Diffuse Splanchnic Venous Thrombosis

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Cristian Lupascu

2015-01-01

Full Text Available Diffuse splanchnic venous thrombosis (DSVT, formerly defined as contraindication for liver transplantation (LT, is a serious challenge to the liver transplant surgeon. Portal vein arterialisation, cavoportal hemitransposition and renoportal anastomosis, and finally combined liver and small bowel transplantation are all possible alternatives to deal with this condition. Five patients with preoperatively confirmed extensive splanchnic venous thrombosis were transplanted using cavoportal hemitransposition (4x and renoportal anastomosis (1x. Median follow-up was 58 months (range: 0,5 to 130 months. Two patients with previous radiation-induced peritoneal injury died, respectively, 18 days and 2 months after transplantation. The three other patients had excellent long-term survival, despite the fact that two of them needed a surgical reintervention for severe gastrointestinal bleeding. Extensive splanchnic venous thrombosis is no longer an absolute contraindication to liver transplantation. Although cavoportal hemitransposition and renoportal anastomosis undoubtedly are life-saving procedures allowing for ensuring adequate allograft portal flow, careful follow-up of these patients remains necessary as both methods are unable to completely eliminate the complications of (segmental portal hypertension.
[Treatment results for different categories of vaginal intraepithelial neoplasia with electrocoagulation, 5-fluorouracil and combined treatment].

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Veloz-Martínez, María Guadalupe; Quintana-Romero, Verónica; Contreras-Morales, María del Rosario Sandra; Jiménez-Vieyra, Carlos Ramón

2015-10-01

Vaginal intraepithelial neoplasia (VAIN) represents a variety of changes that initiate as an intraepithelial squamous lesion with the possibility of resulting in cancer. To compare the results of the treatment for the different categories of VAIN with electrocoagulation, 5-fluorouracil and combined treatment. Observational an analytical study. We stablished groups according to the category of VAIN evaluating and comparing remission, persistence, recurrence, or progression of the disease ac- cording to the received treatment, with a 1-year follow up. The results were compared by chi2 and Kruskal Wallis. The statistics analysis was done with the SPSS program version 20. One hundred thirty seven patients between 20 and 81 years of age (mean age: 52.49 years) were included. Seventy-four percent of the patients had a history of premalignant or malignant cervical lesions. Seventy-four patients had VAIN I, 34 patients had VAIN II, 22 patients had VAIN III and there were seven cases of vaginal carcinoma in situ. Fifty-eight patients were treated with electrocoagulation, 55 patients were treated with 5-FU, 16 patients had combined treatment, and eight patients received expectant management. Sixty three percent of patients had total remission of the lesion, 34% had persistence and 3% showed progression, and there were no cases of recurrence. Results were better in patients with VAIN I treated with 5-FU (bigger percentage of remission P .026), for the remaining categories of VAIN, no treatment showed superior results. The superior response occurs in patients with VAIN I treated with 5-FU. None of the treatments achieves a 100% remission. The VAIN frequency is high, patients with a history of malignant or premalignant cervical pathology should undergo a closer surveillance through cytocolposcopic control with respect to the remaining population.
Concomitant bid radiotherapy with cisplatin and 5-fluorouracil in unresectable carcinoma of the pharynx: 10 year's experience at the Centre Antoine Lacassagne; Radiotherapie bifractionnee et chimiotherapie par cisplatine et 5-fluoro-uracile concomitantes dans les carcinomes epidermoides localement evolues non resecables du pharynx: dix ans d'experience au centre Antoine Lacassagne

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Magne, N.; Pivot, X.; Marcy, P.Y.; Chauvel, P.; Courdi, A.; Dassonville, O.; Possonnet, G.; Vallicioni, J.; Ettore, F.; Falewee, M.N.; Milano, G.; Santini, J.; Lagrange, J.L.; Schneider, M.; Demard, F.; Bensadoun, R.J. [Centre Antoine-Lacassagne, 06 - Nice (France)

2001-08-01

Patients suffering from locally advanced unresectable squamous cell carcinoma of the oropharynx and hypopharynx treated with radiotherapy alone have a poor prognosis. More than 70% of patients die within 5 years mainly due to local recurrences. The aim of this study was to evaluate retrospectively the Antoine Lacassagne Cancer Center's experience in a treatment by concomitant bid radiotherapy and chemotherapy. Evaluation was based on analysis of the toxicity, the response rates, the survival, and the clinical prognostic factors. From 1992 to 2000, 92 consecutive patients were treated in our single institution. All of them had stage IV, unresectable squamous cell carcinoma of the pharynx and they received continuous bid radiotherapy (two daily fractions of 1.2 Gy, 5 days a week, with a 6-h minimal internal between fractions). Total radiotherapy dose was 80.4 Gy on the oropharynx and 75.6 Gy on the hypopharynx. Two or three chemotherapy courses of cisplatin (CP)-5-fluorouracil (5FU) were given during radiotherapy at 21 -day intervals (third not delivered after the end of the radiotherapy). CP dose was 100 mg/m{sup 2} (day 1) and 5-FU was given as 6-day continuous infusion (750 mg/m{sup 2}/day at 1. course; 430 mg/m{sup 2}/day at 2. and 3. courses). Special attention was paid to supportive care, particularly in terms of enteral nutrition and mucositis prevention by low-level laser energy. Acute toxicity was marked and included WHO grade III/IV mucositis (89%, 16% of them being grade IV), WHO grade III dermatitis (72%) and grade III/IV neutropenia (61%). This toxicity was significant but manageable with optimised supportive care, and never led to interruption of treatment for more than 1 week, although there were two toxic deaths. Complete global response rate at 6 months was 74%. Overall global survival at 1 and 3 years was 72% and 50% respectively, with a median follow-up of 17 months. Prognostic factors for overall were the Karnofsky index (71% survival at 3

Venous trauma in the Lebanon War--2006.

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Nitecki, Samy S; Karram, Tony; Hoffman, Aaron; Bass, Arie

2007-10-01

Reports on venous trauma are relatively sparse. Severe venous trauma is manifested by hemorrhage, not ischemia. Bleeding may be internal or external and rarely may lead to hypovolemic shock. Repair of major extremity veins has been a subject of controversy and the current teaching is to avoid venous repair in an unstable or multi-trauma patient. The aim of the current paper is to present our recent experience in major venous trauma during the Lebanon conflict, means of diagnosis and treatment in a level I trauma center. All cases of major venous trauma, either isolated or combined with arterial injury, admitted to the emergency room during the 33-day conflict were reviewed. Out of 511 wounded soldiers and civilians who were admitted to our service over this period, 12 (2.3%) sustained a penetrating venous injury either isolated (5) or combined with arterial injury (7). All injuries were secondary to high velocity penetrating missiles or from multiple pellets stored in long-range missiles. All injuries were accompanied by additional insult to soft tissue, bone and viscera. The mean injury severity score was 15. Severe external bleeding was the presenting symptom in three cases of isolated venous injury (jugular, popliteal and femoral). The diagnosis of a major venous injury was made by a CTA scan in five cases, angiography in one and during surgical exploration in six cases. All injured veins were repaired: three by venous interposition grafts, four by end to end anastomosis, three by lateral suture and two by endovascular techniques. None of the injuries was treated by ligation of a major named vein. Immediate postoperative course was uneventful in all patients and the 30-day follow-up (by clinical assessment and duplex scan) has demonstrated a patent repair with no evidence of thrombosis. Without contradicting the wisdom of ligating major veins in the setup of multi-trauma or an unstable patient, our experience indicates that a routine repair of venous trauma can
Liquid nitrogen cryotherapy for lip mucous membrane venous malformation in infants.

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Zhang, Da-Ming; Wang, You-Yuan; Lin, Zhao-Yu; Yang, Zhao-Hui; Chen, Wei-Liang

2015-03-01

Lip mucous membrane venous malformations are common benign lesions in infants. This clinical study evaluates the efficacy and safety of liquid nitrogen cryotherapy used to treat this condition. A total of 84 pediatric patients undergoing liquid nitrogen cryotherapy for venous malformations involving the lips were reviewed, with 45 males and 39 females treated. The overall median age at mucous membrane venous malformation diagnosis was 5.6 months (range 2-18 months). The venous malformations involved the vermilion of the lower lip in 44 cases, the vermilion of the upper lip in 31 cases, and both vermilions in 9 cases. No complications due to anesthesia occurred. After a follow-up period of 2-38 months (mean 25 months), 65 lesions (77.4 %) were completely involuted, 14 lesions (16.7 %) were mostly involuted, and 5 lesions (5.9 %) were partially involuted; no lesions showed a minor amount of involution. Liquid nitrogen cryotherapy is an effective, simple, and safe management tool for mucous membrane venous malformations of the lip in infants.
Comparison of 5-fluorouracil/leucovorin and capecitabine in preoperative chemoradiotherapy for locally advanced rectal cancer

International Nuclear Information System (INIS)

Kim, Dae Yong; Jung, Kyung Hae; Kim, Tae Hyun; Kim, Duck-Woo; Chang, Hee Jin; Jeong, Jun Yong; Kim, Young Hoon; Son, Seok-Hyun; Yun, Tak; Hong, Chang Won; Sohn, Dae Kyung; Lim, Seok-Byung; Choi, Hyo Seong; Jeong, Seung-Yong; Park, Jae-Gahb

2007-01-01

Purpose: To describe our experience with a bolus injection of 5-fluorouracil and leucovorin (FL) vs. capecitabine in terms of radiologic and pathologic findings in preoperative chemoradiotherapy (CRT) for locally advanced rectal cancer. Methods: The study enrolled 278 patients scheduled for preoperative CRT using two protocols with different chemotherapeutic regimens. Pelvic radiotherapy (50.4 Gy) was delivered concurrently with FL (n = 145) or capecitabine (n = 133). Surgery was performed 6 weeks after CRT completion. Tumor responses to CRT were measured using both radiologic and pathologic examination. Magnetic resonance volumetry was performed at the initial workup and just before surgery after completion of preoperative CRT. Post-CRT pathology tests were used to determine tumor stage and regression. Results: Radiologic examination showed that tumor volume decreased by 68.2% ± 20.5% in the FL group and 68.3% ± 22.3% in the capecitabine group (p = 0.970). Postoperative pathologic T stage determination showed that downstaging occurred in 44.3% of FL and 49.9% of capecitabine patients (p = 0.571). The tumor regression grades after CRT were Grade 1 (minimal response) in 22.6% and 21.0%, Grade 2 (moderate response) in 53.2% and 50.0%, Grade 3 (near-complete response) in 12.9% and 12.9%, and Grade 4 (complete response) in 11.3% and 16.1% of the FL and capecitabine groups, respectively (p = 0.758). Conclusion: In the present study, the radiologic and pathologic findings did not reveal significant differences in short-term tumor responses between preoperative FL and capecitabine CRT for locally advanced rectal cancer. Long-term results and a prospective randomized trial are needed
Pharmacokinetics and toxicology of continuously infused nitroimidazoles

International Nuclear Information System (INIS)

Eifel, P.J.; Brown, J.M.

1984-01-01

The pharmacokinetics and toxicology of misonidazole (MISO) and SR-2508 given by continuous intraperitoneal infusion were studied in female C 3 H mice. The survival (time to death) of animals receiving continuous infusions of SR-2508 and MISO was compared and related to plasma concentration, rate of infusion and total amount of drug delivered. Brain and plasma concentrations were determined by HPLC. For SR-2508, plasma concentration was directly proportional to the infusion rate. However, as the infusion rate of MISO was doubled, the plasma concentration of MISO increased approximately 6-fold, reflecting a substantial increase in the apparent half-life. The brain/plasma concentration ratio in animals infused for up to 6 days with SR-2508 remained constant, at approximately 0.09. At plasma concentrations of 0.08-1.5 mM, animals receiving SR-2508 survived approximately 3 times as long as animals exposed to a comparable plasma concentration of MISO. Even at the lowest infusion rates employed in this study, the survival of mice receiving SR-2508 was much shorter than would have been predicted if the toxicity of these two drugs were solely related to the integral brain exposure. The low brain/plasma concentration ratio of SR-2508 was maintained throughout long continuous exposures
Gold nanoparticles capped with benzalkonium chloride and poly (ethylene imine) for enhanced loading and skin permeability of 5-fluorouracil.

Science.gov (United States)

Safwat, Mohamed A; Soliman, Ghareb M; Sayed, Douaa; Attia, Mohamed A

2017-11-01

To enhance 5-fluorouracil (5-FU) permeability through the skin by loading onto gold nanoparticles (GNPs) capped with two cationic ligands, benzalkonium chloride (BC) or poly (ethylene imine) (PEI). Whereas 5-FU has excellent efficacy against many cancers, its poor permeability through biological membranes and several adverse effects limit its clinical benefits. BC and PEI were selected to stabilize GNPs and to load 5-FU through ionic interactions. 5-FU/BC-GNPs and 5-FU/PEI-GNPs were prepared at different 5-FU/ligand molar ratios and different pH values and were evaluated using different techniques. GNPs stability was tested as a function of salt concentration and storage time. 5-FU release from BC- and PEI-GNPs was evaluated as a function of solution pH. Ex vivo permeability studies of different 5-FU preparations were carried out using mice skin. 5-FU-loaded GNPs size and surface charge were dependent on the 5-FU/ligand molar ratios. 5-FU entrapment efficiency and loading capacity were dependent on the used ligand, 5-FU/ligand molar ratio and solution pH. Maximum drug entrapment efficiency of 59.0 ± 1.7% and 46.0 ± 1.1% were obtained for 5-FU/BC-GNPs and 5-FU/PEI-GNPs, respectively. 5-FU-loaded GNPs had good stability against salinity and after storage for 4 months at room temperature and at 4 °C. In vitro 5-FU release was pH- and ligand-dependent where slower release was observed at higher pH and for 5-FU/BC-GNPs. 5-FU permeability through mice skin was significantly higher for drug-loaded GNPs compared with drug-ligand complex or drug aqueous solution. Based on these results, BC- and PEI-GNPs might find applications as effective topical delivery systems of 5-FU.
Safety and Efficacy of Pegfilgrastim When Given Less Than 14 Days Before the Next Chemotherapy Cycle: Review of Every 14-Day Chemotherapy Regimen Containing 5-FU Continuous Infusion.

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Donkor, Kofi N; Selim, Julie H; Waworuntu, Ariani; Lewis, Kelsey

2017-10-01

Pegfilgrastim should not be given days from the next chemotherapy because of concerns for cytopenias. Some clinicians are prescribing pegfilgrastim to be given days in patients receiving 5-fluorouracil continuous infusion (5-FUCI) regimens. To determine the effectiveness and safety of pegfilgrastim administered days from the next chemotherapy in patients receiving 5-FUCI administered >46 hours. Single-institution retrospective cohort study of patients who received 5-FUCI administered >46 hours from June 2013 to December 2015. The unit of measurement was chemotherapy cycles. End points included the safety and efficacy of giving pegfilgrastim days from the next chemotherapy (Pegfilgrastim-Less-Than-14-Days-Group) and comparing that to pegfilgrastim given ≥14 days (Pegfilgrastim-More-Than-14-Days-Group), filgrastim only (Filgrastim-Group), and no colony stimulating factors (No-CSF-Group). Generalized estimating equations (GEEs) were used to compare mean absolute neutrophil count (ANC) and white blood cell count (WBC). Poisson regression models with GEE were used to estimate relative risk (RR) for neutropenia. There were no incidences of neutropenia, febrile neutropenia (FN), or hospitalizations for FN with the Pegfilgrastim-Less-Than-14-Days-Group. There was also a high mean ANC of 9.9 (5.7) × 10 9 /L. Mean ANC and WBC were statistically significantly less with the Filgrastim-Group, No-CSF-Group, and Pegfilgrastim-More-Than-14-Days-Group compared with the Pegfilgrastim-Less-Than-14-Days-Group. The Filgrastim-Group and the No-CSF-Group had a 32% (1.10-1.56, P = 0.002) and 8% (1.04-1.12, P Days-Group. The risk of incidence of neutropenia was the same with the Pegfilgrastim-More-Than-14-Days-Group and Pegfilgrastim-Less-Than-14-Days-Group (0.95-1.04, P = 0.821). This study shows a promising possibility that administering pegfilgrastim days from the next chemotherapy cycle could be a safe and effective practice. However, better controlled clinical trials are needed.
Radiographic signs of non-venous placement of intended central venous catheters in children

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Taylor, Erin C. [Boston Children' s Hospital, Department of Radiology, Boston, MA (United States); Taylor, George A. [Boston Children' s Hospital, Department of Radiology, Boston, MA (United States); Harvard Medical School, Department of Radiology, Boston, MA (United States)

2016-02-15

Central venous catheters (CVCs) are commonly used in children, and inadvertent arterial or extravascular cannulation is rare but has potentially serious complications. To identify the radiographic signs of arterial placement of CVCs. We retrospectively reviewed seven cases of arterially malpositioned CVCs on chest radiograph. These cases were identified through departmental quality-assurance mechanisms and external consultation. Comparison of arterial cases was made with 127 age-matched chest radiographs with CVCs in normal, expected venous location. On each anteroposterior (AP) radiograph we measured the distance of the catheter tip from the right lateral border of the thoracic spine, and the angle of the vertical portion of the catheter relative to the midline. On each lateral radiograph we measured the angle of the vertical portion of each catheter relative to the anterior border of the thoracic spine. When bilateral subclavian catheters were present, the catheter tips were described as crossed, overlapping or uncrossed. On AP radiographs, arterially placed CVCs were more curved to the left, with catheter tip positions located farther to the left of midline than normal venous CVCs. When bilateral, properly placed venous catheters were present, all catheters crossed at the level of the superior vena cava (SVC). When one of the bilateral catheters was in arterial position, neither of the catheters crossed or the inter-catheter crossover distance was exaggerated. On lateral radiographs, there was a marked anterior angulation of the vertical portion of the catheter (mean angle 37 ± 15 standard deviation [SD] in arterial catheters versus 5.9 ± 8.3 SD in normally placed venous catheters). Useful radiographic signs suggestive of unintentional arterial misplacement of vascular catheters include leftward curvature of the vertical portion of the catheter, left-side catheter tip position, lack of catheter crossover on the frontal radiograph, as well as exaggerated
Outcomes of Preoperative Chemoradiotherapy and Combined Chemotherapy with Radiotherapy Without Surgery for Locally Advanced Rectal Cancer.

Science.gov (United States)

Supaadirek, Chunsri; Pesee, Montien; Thamronganantasakul, Komsan; Thalangsri, Pimsiree; Krusun, Srichai; Supakalin, Narudom

2016-01-01

To evaluate the treatment outcomes of patients with locally advanced rectal cancer treated with preoperative concurrent chemoradiotherapy (CCRT) or combined chemotherapy together with radiotherapy (CMTRT) without surgery. A total of 84 patients with locally advanced rectal adenocarcinoma (stage II or III) between January 1st, 2003 and December 31st, 2013 were enrolled, 48 treated with preoperative CCRT (Gr.I) and 36 with combined chemotherapy and radiotherapy (CMTRT) without surgery (Gr.II). The chemotherapeutic agents used concurrent with radiotherapy were either 5fluorouracil short infusion plus leucovorin and/or capecitabine or 5fluorouracil infusion alone. All patients received pelvic irradiation. There were 5 patients (10.4%) with a complete pathological response. The 3 yearoverall survival rates were 83.2% in Gr.I and 24.8 % in Gr.II (prectal cancer demonstrated that in preoperative CCRT a sphincter sparing procedure can be performed. The results of treatment with preoperative CCRT for locally advanced rectal cancer showed comparable rates of overall survival and sphincter sparing procedures as compared to previous studies.
ENDOVASCULAR TREATMENT FOR DISORDERS OF THE VENOUS SYSTEM

Directory of Open Access Journals (Sweden)

A. G. Osiev

2015-01-01

Full Text Available The annual rate of deep vein thrombosis in general population is from 5 to 9 cases per 10 000, whereas for venous thromboembolism (deep vein thrombosis and pulmonary embolism taken together amounts to 14 cases per 10 000. To improve longterm results of therapy for thrombosis of deep veins of the lower extremities, it is important to restore venous function and outflow. Anticoagulant therapy with low weight or non-fractionated heparin preparations remains the most widely used method of management. However, total or partial thrombosis resolution under anticoagulant treatment is achieved only in 4 and 14% of cases, respectively. Thrombolysis allows for early resorption of the thrombus by means of a minimally invasive procedure with lower risk of complication. After the venous flow is restored, the aim of treatment is to prevent damage to the venous valves, venous hypertension and repeated thrombosis with development of the post-thrombotic syndrome. Compared to anticoagulation, systemic thrombolysis has the benefit of more rapid clot resorption and less damage to the venous valve. One of its serious limitations is a high bleeding risk related to higher doses of the drug administered through a peripheral vein catheter. Therefore, selective intra-clot administration of thombolytics (direct catheter thrombolysis has been suggested as an alternative. For more effective therapy with the use of lower doses of thrombolytics, the so called pharmaco-mechanical thrombectomy has been developed. Venous stenosis hindering the venous outflow is frequently seen after direct catheter or pharmaco-mechanical thrombolysis. Angioplasty with stent placement is recommended in the cases with residual venous abnormality after successful thrombolysis and thrombectomy.
Medical management of venous ulcers.

Science.gov (United States)

Pascarella, Luigi; Shortell, Cynthia K

2015-03-01

Venous disease is the most common cause of chronic leg ulceration and represents an advanced clinical manifestation of venous insufficiency. Due to their frequency and chronicity, venous ulcers have a high socioeconomic impact, with treatment costs accounting for 1% of the health care budget in Western countries. The evaluation of patients with venous ulcers should include a thorough medical history for prior deep venous thrombosis, assessment for an hypercoagulable state, and a physical examination. Use of the CEAP (clinical, etiology, anatomy, pathophysiology) Classification System and the revised Venous Clinical Severity Scoring System is strongly recommended to characterize disease severity and assess response to treatment. This venous condition requires lifestyle modification, with affected individuals performing daily intervals of leg elevation to control edema; use of elastic compression garments; and moderate physical activity, such as walking wearing below-knee elastic stockings. Meticulous skin care, treatment of dermatitis, and prompt treatment of cellulitis are important aspects of medical management. The pharmacology of chronic venous insufficiency and venous ulcers include essentially two medications: pentoxifylline and phlebotropic agents. The micronized purified flavonoid fraction is an effective adjunct to compression therapy in patients with large, chronic ulceration. Copyright © 2015 Elsevier Inc. All rights reserved.
Pharmacologic requirements for obtaining sensitization of human tumor cells in vitro to combined 5-fluorouracil or ftorafur and x rays

International Nuclear Information System (INIS)

Byfield, J.E.; Calabro-Jones, P.; Klisak, I.; Kulhanian, F.

1982-01-01

The combined effects of X ray and 5-fluorouracil (5-FU) in tissue culture have been studied using two human adenocarcinoma lines (HeLa and HT-29 cells). Both showed similar sensitivities to 5-FU, HeLa cells appearing somewhat more resistant to higher concentrations. Combined treatment of both cell types with 5-FU and X rays led to a time-dependent enhancement of cell killing (''radiosensitization''). Only post-radiation incubation had any effect, prior exposure to 5-FU being strictly additive. Enhanced cell killing by combined 5-FU and X rays could not be explained by either the infliction of additional acute damage in the immediate post-radiation period or an inhibitory effect of 5-FU on the repair of sub-lethal X ray injury. Rather, the enhanced cytotoxicity proved to be dependent on a damage expressed in time periods exceeding the duration of a cell doubling time in vitro. Overall, the data equally suggest that X rays may sensitize the cells to 5-FU. The enhanced cell killing is maximized if the cells are continuously exposed to 5-FU for 48 hours following the X ray exposure. These results indicate that clinical treatment regimens might be useful in evaluating 5-FU infusional scheduling in accordance with these unique requirements, which are not met by conventional bolus 5-FU and X ray therapy fractionation regimens. Ftorafur, a drug proposed to act as a slow release form of 5-FU, was found to show limited cytotoxic potential in vitro and did not significantly enhance cell killing after X ray exposure
Diagnosis of venous disorders

International Nuclear Information System (INIS)

Minar, E.

1993-01-01

Limited accuracy in the clinic diagnosis of deep vein thrombosis (VT) makes such diagnostic tests such as duplex sonography or venography necessary. Exact information on the age and extent of the thrombus are necessary for the clinician to optimize the therapeutric management. The correct diagnosis of calf vein thrombosis and of recurrent VT in patients with postphlebitis changes also has implications for treatment. After exclusion of thrombosis, the radiologist should evaluate the leg for other possible causes of symptoms besides VT. Investigation of the venous sytem also has a role in the diagnosis in patients with suspected pulmonary embolism. In patients with chronic venous insuffficiency the deep venous system should assessed for patency and venous valve function. The superficial veins should be differentiated in segments with sufficient or insufficient venous valves, and it is also necessary to look for insufficiency of the perforrating veins. In patients with superficial phlebitis there is risk of propagation into the deep venous system. (orig.) [de
Fluoropyrimidine-HAI (hepatic arterial infusion) versus systemic chemotherapy (SCT) for unresectable liver metastases from colorectal cancer.

Science.gov (United States)

Mocellin, Simone; Pasquali, Sandro; Nitti, Donato

2009-07-08

Although locoregional treatments such as hepatic arterial infusion (HAI) claim the advantage of delivering higher doses of anticancer agents directly into the metastatic organ as compared to systemic chemotherapy (SCT), the benefit in terms of overall survival (OS) is unclear. We quantitatively summarized the results of randomised controlled trials (RCT) comparing HAI to SCT for the treatment of unresectable liver metastatic disease from colorectal cancer (CRC). The aim of this work is to quantitatively summarize the results of RCT comparing HAI to SCT for the treatment of unresectable hepatic metastases from CRC. A systematic review of reports published until September 2008 on the findings of RCT that compared HAI to SCT for the treatment of unresectable CRC liver metastases was performed by searching the MEDLINE, Embase, Cancerlit, Cochrane and GoogleScholar electronic databases as well as other databanks collecting information on clinical trials. Inclusion criteria were patients with unresectable CRC liver metastases enrolled in RCT comparing HAI to SCT. The outcome measures were tumor response rate and overall survival. Two authors independently carried out study selection and assessment of methodological quality. A third author performed a concordance analysis in order to unravel potential systematic biases. Ten RCT were identified that met the eligibility criteria. HAI regimens were based on floxuridine (FUDR), 5-fluorouracil or either one of these two fluoropyrimidines in eight and one RCT, respectively. SCT consisted of FUDR or 5-fluorouracil in three and seven RCT, respectively. By pooling the summary data, tumor response rate resulted 42.9% and 18.4% for HAI and SCT, respectively (RR = 2.26; 95% CI, 1.80 to 2.84; P < 0.0001). Mean weighted median OS times were 15.9 and 12.4 months for HAI and SCT, respectively: the meta-risk of death was not statistically different between the two treatment groups (HR = 0.90; 95% CI, 0.76 to 1.07; P = 0.24). Currently
Curcumin and 5-Fluorouracil-loaded, folate- and transferrin-decorated polymeric magnetic nanoformulation: a synergistic cancer therapeutic approach, accelerated by magnetic hyperthermia

Directory of Open Access Journals (Sweden)

Balasubramanian S

2014-01-01

Full Text Available Sivakumar Balasubramanian,1 Aswathy Ravindran Girija,1 Yutaka Nagaoka,1 Seiki Iwai,1 Masashi Suzuki,1 Venugopal Kizhikkilot,2 Yasuhiko Yoshida,1 Toru Maekawa,1 Sakthikumar Dasappan Nair1 1Bio Nano Electronics Research Center, Graduate School of Interdisciplinary New Science, Toyo University, Kawagoe, Japan; 2Department of Respiratory Medicine, Sooriya Hospital, Chennai, India Abstract: The efficient targeting and therapeutic efficacy of a combination of drugs (curcumin and 5-Fluorouracil [5FU] and magnetic nanoparticles encapsulated poly(D,L-lactic-co-glycolic acid nanoparticles, functionalized with two cancer-specific ligands are discussed in our work. This multifunctional, highly specific nanoconjugate resulted in the superior uptake of nanoparticles by cancer cells. Upon magnetic hyperthermia, we could harness the advantages of incorporating magnetic nanoparticles that synergistically acted with the drugs to destroy cancer cells within a very short period of time. The remarkable multimodal efficacy attained by this therapeutic nanoformulation offers the potential for targeting, imaging, and treatment of cancer within a short period of time (120 minutes by initiating early and late apoptosis. Keywords: nanotechnology, curcumin, 5FU, folate, transferrin, PLGA nanoparticle, magnetic hyperthermia
Brain venous pathologies: MRI findings

International Nuclear Information System (INIS)

Salvatico, Rosana; Gonzalez, Alejandro; Yanez, Paulina; Romero, Carlos; Trejo, Mariano; Lambre, Hector

2006-01-01

Purpose: To describe MRI findings of the different brain venous pathologies. Material and Methods: Between January 2002 and March 2004, 18 patients were studied 10 males and 8 females between 6 and 63 years old; with different brain venous pathologies. In all cases brain MRI were performed including morphological sequences with and without gadolinium injection and angiographic venous sequences. Results: 10 venous occlusions were found, 6 venous angiomas, and 2 presented varices secondary to arteriovenous dural fistula. Conclusion: Brain venous pathologies can appear in many different clinical contexts, with different prognosis and treatment. In all the cases brain MRI was the best imaging study to disclose typical morphologic abnormalities. (author) [es
Cerebral venous angiomas

International Nuclear Information System (INIS)

Agnoli, A.L.; Hildebrandt, G.

1985-01-01

Clinical symptoms and radiological signs in 15 patients with cerebral venous malformations are presented and the diagnostic problems discussed. The circulation time in combination with cerebral malformations and angiomas of the scalp are described. CT findings in cases of venous malformations of the brain stem are evaluated. Spot-like enhancement, as well as sharply demarcated round shaped enhancement are characteristic for venous angiomas. Cavernous angiomas usually present as homogenous or inhomogenous round shaped enhanced areas. (Author)
A comparison of the effects of propofol and midazolam on memory during two levels of sedation by using target-controlled infusion.

Science.gov (United States)

de Roode, A; van Gerven, J M; Schoemaker, R C; Engbers, F H; Olieman, W; Kroon, J R; Cohen, A F; Bovill, J G

2000-11-01

We examined memory during sedation with target-controlled infusions of propofol and midazolam in a double-blinded five-way, cross-over study in 10 volunteers. Each active drug infusion was targeted to sedation level 1 (asleep) and level 4 (lethargic) as determined with the Observer Assessment of Alertness/Sedation scale. At the target level of sedation, drug concentration was clamped for 30 min, during which time neutral words were presented. After 2 h, explicit memory was assessed by recall, and implicit memory by using a wordstem completion test. Venous drug concentrations (mean +/- SD) were 1350 ng/mL (+/-332 ng/mL) for propofol and 208 ng/mL (+/-112 ng/mL) for midazolam during Observer Assessment of Alertness/Sedation scale level 4; and 1620 ng/mL (+/-357 ng/mL) and 249 ng/mL (+/-82 ng/mL) respectively during level 1. The wordstem completion test frequencies at low level sedation were significantly higher than spontaneous frequencies (8.7% + 2.4%; P: sedation were accompanied by small differences in venous propofol or midazolam concentrations. This indicates steep concentration-effect relationships. Neutral information is still memorized during low-level sedation with both drugs. The memory effect of propofol and midazolam did not differ significantly. Implicit memory can occur during different states of consciousness and might lead to psychological damage. In 10 volunteers, implicit memory was investigated during sedation with propofol and midazolam in a double-blinded, placebo-controlled study. To compare the effects of both drugs, they were titrated using a computer-controlled infusion system to produce similar high and low levels of sedation.
Predictors of Venous Thromboembolic Events Associated with Central Venous Port Insertion in Cancer Patients

Directory of Open Access Journals (Sweden)

Christine Hohl Moinat

2014-01-01

Full Text Available Insertion of central venous port (CVP catheter in the cancer population is associated with increased incidence of venous thromboembolic events (VTE. However, trials have shown limited benefit of antithrombotic treatment to prevent catheter-related venous thrombosis. This prospective observational cohort study was designed to assess the incidence of VTE closely related to CVP implantation in patients with cancer and undergoing chemotherapy, and to identify a high risk subgroup of patients. Between February 2006 and December 2011, 1097 consecutive cancer patients with first CVP implantation were included. Catheter-related VTE were defined as deep venous thrombosis in the arm, with or without pulmonary embolism (PE, or isolated PE. The incidence of CVP-associated VTE was 5.9% (IC95 4.4–7.3% at 3 months, and 11.3% (IC95 9.4–13.2% at 12 months. The incidence of any VTE was 7.6% (IC95 6.0–9.3% at 3 months, and 15.3% (IC95 13.1–17.6% at 12 months. High Khorana risk score and lung cancer were significant predictors of 3 month VTE. In conclusion, this large cohort study of patients with first CVP catheter implantation confirms the high incidence of VTE associated with the CVP implantation and allow identifying high risk patients who may benefit from thromboprophylaxis.
Infusion of hypertonic saline (7.5% NaCl) causes minor immunological changes in normovolaemic women

DEFF Research Database (Denmark)

Petersen, Jens Aage Kølsen; Nielsen, J O D; Bendtzen, K

2004-01-01

Haemorrhagic shock is treated effectively by infusion of hypertonic saline/colloid solutions. Furthermore, previous studies found hypertonicity to affect immune responses in animals and in human blood cell cultures. It is unknown, however, whether hypertonic saline infusion affects immune responses...
Venous ulcers -- self-care

Science.gov (United States)

... surgery to improve blood flow through your veins. Prevention If you are at risk for venous ulcers, take the steps listed above under Wound Care. ... weight if you are overweight. Manage your blood pressure and cholesterol levels. ... Venous leg ulcers - self-care; Venous insufficiency ulcers - self-care; Stasis ...

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