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Sample records for 5-fluorouracil infusion combined

  1. Treatment of Advanced Gastric Carcinoma Patients with Calcium Folinate, a 5-Fluorouracil Bolus and Continous Infusion with 5-Infusion with 5-Fluorouracil Combined with Oxaliplatin

    Institute of Scientific and Technical Information of China (English)

    Qilian Liang; Saihong Chen; Dachao Pan; Jierong Xie; Liangzhen Cai; Shujun Li

    2008-01-01

    OBJECTIVE To examine the therapeutic effects and toxicity of high-dose-folinic acid plus a 5-fluorouracil (5-FU) bolus and continuous infusion with 5-FU combined with locally produced oxaliplatin (L-HOP)in treating advanced gastric carcinoma patients.METHODS Sixty-five patients with advanced gastric carcinoma were treated with high-dose-folinic acid plus a 5-FU bolus and a 48-h continuous infusion of 5-FU combined with oxaliplatin. The effects of treatment and toxicity were observed.RESULTS There were 4 complete responses, 26 partial responses,30 with no change and 5 with progressive disease. The overall effective response rate was 46.2% (30/65). The median duration was 7 months, with the main side effects including nausea and vomiting, peripheral phlebitis, alopecia, leukopenia, dental ulcers,peripheral neuritis and diarrhea. All the side effects were tolerated and minimal.CONCLUSION The results showed that high-dose folinic acid plus a 5-FU bolus and continuous infusion of 5-FU combined with oxaliplatin appears to be a safe and effective therapy for patients with advanced gastric carcinoma. This therapeutic regimen is of value for these patients.

  2. Continuous-infusion cisplatin and bolus 5-fluorouracil in colorectal carcinoma.

    Science.gov (United States)

    Posner, M R; Belliveau, J F; Weitberg, A B; Sabbath, K; Wiemann, M C; Cummings, F J; Calabresi, P

    1987-10-01

    Twenty-one evaluable patients with metastatic colorectal carcinoma were treated with a combination of continuous-infusion cisplatin (25 mg/m2/day X 3 days) and bolus 5-fluorouracil (400 mg/m2/day X 3 days). Toxicity was minimal. Seven patients (33%) responded. All responses were observed among the 16 previously untreated patients (44%) and lasted a median of 30 weeks. The results indicate the need for phase III trials of this treatment.

  3. A Case of Hepatocellular Carcinoma With Portal Vein Tumor Thrombosis Successfully Treated by a Combination of Intra-Arterial Infusion 5-Fluorouracil, Cisplatin, and Systemic Interferon-α Therapies

    OpenAIRE

    Kobayashi, Tsutomu(Department of Physics, Rikkyo University, Toshima, Tokyo 175-8501, Japan); Suzuki, Hideki; Kubo, Norio; Watanabe, Akira; Sasaki, Shigeru; Wada, Wataru; Araki, Kenichiro; Shimura, Tatsuo; Kuwano, Hiroyuki

    2012-01-01

    A 58-year-old female with hepatitis C was referred to our hospital after computed tomography (CT) revealed a tumor in the right lobe of her liver. After thorough examination, tumor thrombosis was detected on the main trunk of the portal vein, and we decided to administer a combination of subcutaneous interferon-alfa and intra-arterial 5-fluorouracil. However, after 2 cycles of treatment, this regimen was ineffective, and thus cisplatin (CDDP) was added for the third cycle. On completion of 5 ...

  4. Adjuvant radiotherapy and concomitant 5-fluorouracil by protracted venous infusion for resected pancreatic cancer

    International Nuclear Information System (INIS)

    Purpose: To assess the toxicity and clinical benefit from adjuvant chemoradiotherapy consisting of protracted venous infusion 5-fluorouracil (5-FU) and concomitant radiotherapy in patients with resected pancreatic cancer. Methods and Materials: Between 1994 and 1999, 52 patients who underwent pancreaticoduodenectomy received adjuvant chemoradiotherapy. The tumor bed and regional nodes received a dose of 45 Gy in fractions of 1.8 Gy followed by boost to the tumor bed if the surgical margins were involved (total dose, 54 Gy). The patients also received concomitant 5-FU by protracted venous infusion (200-250 mg/m2/day, 7 days/week) during the entire radiotherapy course. Results: Fifty-two patients (30 men, 22 women) were enrolled and treated on this protocol. The median age was 63 years (range, 38-78 years), and the median Karnofsky Performance Status was 80 (range, 70-100). Thirty-five percent had involved surgical margins and 59% had involved lymph nodes. All patients completed therapy, and there were no Grade IV/V toxicities observed. With median follow-up of 24 months (range, 3-52 months) for surviving patients, the median survival is 32 months, and 2-year and 3-year survivals are 62%, and 39%, respectively. Conclusion: Radiotherapy with concomitant 5-FU by protracted venous infusion as adjuvant treatment for resected pancreatic cancer is well tolerated. This approach allows for greater dose intensity with reduced toxicity. The median survival of this cohort of patients compares favorably with our earlier experience and other published series.

  5. 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

    patients, by 5-fluorouracil and oxaliplatin combination (FOLFOX) therapy as measured by urinary excretion of 8-oxo-7,8-dihydro-2-deoxyguanosine (8-oxodG) and 8-oxo-7,8-dihydro-guanosine (8-oxoGuo). METHODS: The amounts of 8-oxoGuo and 8-oxodG were measured in 3 spot urine samples from 106 patients by using......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...

  6. CHEMOIMMUNOTHERAPY OF MURINE LIVER METASTASES WITH 5-FLUOROURACIL IN COMBINATION WITH LIPOSOME-ENCAPSULATED MURAMYL DIPEPTIDE

    NARCIS (Netherlands)

    DAEMEN, T; DONTJE, BHJ; REGTS, J; SCHERPHOF, GL

    1993-01-01

    The therapeutic effect of a combination of liposomal muramyl dipeptide (MDP) and 5-fluorouracil (5FU) was studied in a murine tumor model of hepatic metastases of the tumor cell line C26, a colon adenocarcinoma. Liposomal MDP (250 mug/kg body wt) and a low, nontoxic, dose of 5FU (10 mg/kg body wt) w

  7. Combined radiotherapy and preradiation chemotherapy with Cisplatin and 5-Fluorouracil for advanced esophageal carcinoma, 1

    International Nuclear Information System (INIS)

    Eight patients with untreated squamous cell carcinoma of the esophagus accompanying distant metastases who were treated by one to five cycles of chemotherapy consisting of Cisplatin and 120 hour infusion of 5-Fluorouracil were reported. Two patients showed complete response (CR), four partial response (PR), one minor response, and one no response. High response rate of 75% (6 of 8) was obtained. Radiation therapy was then administered to six of the patients. After definitive treatment, CR was obtained in four, and PR in two of the cases. However, relapses were noted in all four of the CR cases, with four at distant sites, and one locally. Five of the eight patients (62.5%) survived one year and two survived three years (25%). Two patients could not receive radiotherapy because of uncontrollable lung metastases or death from duodenal ulcer. Although the follow-up period is still short, the combined treatment of radiation and preradiation chemotherapy appears to be an effective treatment, and has made a major impact upon survival time in cases of disseminated esophageal carcinoma. (author)

  8. Less cytotoxicity to combination therapy of 5-fluorouracil and cisplatin than 5-fluorouracil alone in human colon cancer cell lines

    Institute of Scientific and Technical Information of China (English)

    Xiu-Xu Chen; Mao-De Lai; Yong-Liang Zhang; Qiong Huang

    2002-01-01

    AIM: Our previous studies showed increased sensitivityto 5-FU in colon cancer cell lines with microsatelliteinstability, and considered that mutations of TGFβ-RⅡ,IGF Ⅱ R, RIZ gene might enhance the potentials of cellgrowth and proliferation, which increased the sensitivityto 5-FU. Here we compared the distribution of cell cycleand P53 status between two human colon cancer cell lineswith different sensitivity to 5-FU. Because mechanisticdifferences exist between 5-FU andCD DP, we alsoanalyzed the efficacy of CDDP and combination therapyon two human colon cancer cell linesMETHODS: We compared the sensitivity to CDDP of thesetwo cell lines by MTT assay. Distribution of cell cycle undertreatment of 5-FU, CDDP alone or both was analyzed byFlow Cytometry, and expression of P53 was detected byimmunocytochemical staining.RESULTS: SW480 cells were more sensitive to CDDP thanLoVo cells at the concentrations above 16 μmol/I (Ratio ofabsorption is 0.64 and 0.79 at 16 μmol/I, respectively;P<0.01). Efficacy of combination therapy was converselylower than that of single-therapy of 5-FU (Ratio of absorptionin LoVo+5-FU, SW480+5-FU, LoVo+5-FU+CDDP andSW480+5-FU+CDDP is 0.53, 0.54, 0.72, 0.78, respectively;P<0.01). LoVo cells were negative whereas SW480 cellspositive in P53 expression. 5-FU induced G1-phase arrestin both cell lines, but LoVo cells peaked 24 hours earlierthan SW480 cells, and 48 hours earlier for an apparenthypodiploid DNA. However, CDDP showed the contrary,inducing S-phase arrest, and SW480 cells peaking 36 hoursearlier. Both cell lines showed hypodipliod nuclei 48 hoursafter CDDP treatment. Percentage of cells in G1-phase andS-phase dominated alternatively under combination therapyin both cell lines.CONCLUSION: These results suggest that colon cancercells with microsatellite instability are more sensitive to 5-FU, whereas more resistant to CDDP. Combination therapyof 5-FU and CDDP shows fewer efficacies than 5-FU single-therapy, although it can render a

  9. PREOPERATIVE CHEMOTHERAPY OF CONTINUOUS INFUSION OF 5-FLUOROURACIL, EPIRUBICIN OR PIRARUBICIN AND CYCLO-PHOSPHAMINE IN OPERABLE PRIMARY BREAST CANCER

    Institute of Scientific and Technical Information of China (English)

    李金锋; 欧阳涛; 王天峰; 林本耀

    2004-01-01

    Objective: To evaluate the feasibility and activity of continuous-infusion of fluorouracil in association with epirubicin or pirarubicin and cyclophosphamine as neoadjuvant regimen in patients with primary breast cancer. Methods: A total of 111 (including 114 breasts) were entered into the study. Chemotherapy consisted of two to six cycles of epirubicin 50 mg/(m2·d) and cyclophosphamide 500 mg/(m2·d) on day 1 and 8, and continuous intravenous administration of 5-fluorouracil 200 mg/(m2·d) from day 1 to 28 with a microinfusional elastomer (CEFci) or pirarubicin 35 mg/(m2·d) on day 1 and 8 instead of epirubicin (CTFci). Results: The overall response rate was 87.7%. Forty-five patients (39.5%) attained a complete clinical response and 27 (23.7%) attained a pathological complete response. CTFci regimen was superior to CEFci regimen in response rate, the pathological complete response rate (pCR) of former regimen was significantly higher than that of latter regimen (34.8% vs. 16.2%) (P=0.022). The pCR rate in ER/PgR negative tumor was significantly higher than that of ER/PgR positive tumor, achieving 33.3% and 7.5% respectively (P=0.001, x2=11.043). There was no relationship between HER-2 expression and tumor response. The toxicity of two regimens was well tolerated. Alopecia was mild in CTFci regimen comparing with CEFci regimen but neutropenia in CTFci regimen was higher than CEFci regimen. Conclusion: Continuous-infusion of fluorouracil in association with epirubicin or pirarubicin and cyclophosphamine is effective regimens as neoadjuvant chemotherapy for primary breast cancer and the toxicity is well tolerated. Pirarubicin regimen was superior to epirubicin regimen in response rate.

  10. Combined Effects of Muricid Extract and 5-Fluorouracil on Intestinal Toxicity in Rats

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    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.

  11. Cytotoxic action of bisabololoxide A of German chamomile on human leukemia K562 cells in combination with 5-fluorouracil.

    Science.gov (United States)

    Ogata-Ikeda, Ikuko; Seo, Hakaru; Kawanai, Takuya; Hashimoto, Erika; Oyama, Yasuo

    2011-03-15

    German chamomile (Matricaria recutita L.) is a popular ingredient in herbal teas. In previous study, micromolar bisabololoxide A, one of main constituents in German chamomile, exerted cytotoxic action on rat thymocyte, a normal non-proliferative cell. This result prompted us to study the effect of bisabololoxide A on proliferative cancer cells and to seek the possibility of its use with 5-fluorouracil, an anticancer agent. In this study, the effect of micromolar bisabololoxide A on human leukemia K562 cells was cytometrically examined. Although the incubation of K562 cells with 10 μM bisabololoxide A for 72h did not significantly increase the percentage populations of dead cells and shrunken cells, the inhibitory action on the growth was obviously observed. It was not the case for the concentrations of less than 5 μM. The threshold concentration of bisabololoxide A to exert the cytotoxic action on K562 cells was ascertained to be 5-10 μM. Bisabololoxide A at 5-10 μM did not exert cytotoxic action on normal non-proliferative cells (rat thymocytes) in our previous study. Since the antiproliferative action of micromolar bisabololoxide A on cancerous cells was expected to be beneficial to cancer treatment, the modification of antiproliferative action of 5-fluorouracil (3-30 μM) by bisabololoxide A was studied. The combination of 5-fluorouracil and bisabololoxide further inhibited the growth of K562 cells although the additive inhibition of growth by bisabololoxide A became smaller as the concentration of 5-fluorouracil increased. Therefore, it is suggested that the simultaneous application of German chamomile containing bisabololoxide A may reduce the dose of 5-fluorouracil. PMID:20863677

  12. Schedule-dependent antitumor effects of 5-fluorouracil combined with sorafenib in hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Recently, a phase II clinical trial in hepatocellular carcinoma (HCC) has suggested that the combination of sorafenib and 5-fluorouracil (5-FU) is feasible and side effects are manageable. However, preclinical experimental data explaining the interaction mechanism(s) are lacking. Our objective is to investigate the anticancer efficacy and mechanism of combined sorafenib and 5-FU therapy in vitro in HCC cell lines MHCC97H and SMMC-7721. Drug effects on cell proliferation were evaluated by cell viability assays. Combined-effects analyses were conducted according to the median-effect principle. Cell cycle distribution was measured by flow cytometry. Expression levels of proteins related to the RAF/MEK/ERK and STAT3 pathways and to cell cycle progression (cyclin D1) were determined by western blot analysis. Sorafenib and 5-FU alone or in combination showed significant efficacy in inhibiting cell proliferation in both cell lines tested. However, a schedule-dependent combined effect, associated with the order of compound treatments, was observed. Efficacy was synergistic with 5-FU pretreatment followed by sorafenib, but it was antagonistic with the reverse treatment order. Sorafenib pretreatment resulted in a significant increase in the half inhibitory concentration (IC50) of 5-FU in both cell lines. Sorafenib induced G1-phase arrest and significantly decreased the proportion of cells in S phase when administrated alone or followed by 5-FU. The RAF/MEK/ERK and STAT3 pathways were blocked and cyclin D1 expression was down regulated significantly in both cell lines by sorafenib; whereas, the kinase pathways were hardly affected by 5-FU, and cyclin D1 expression was up regulated. Antitumor activity of sorafenib and 5-FU, alone or in combination, is seen in HCC cell lines. The nature of the combined effects, however, depends on the particular cell line and treatment order of the two compounds. Sorafenib appears to reduce sensitivity to 5-FU through down regulation of cyclin

  13. Effects of Combined Intralesional 5-Fluorouracil and Topical Silicone in Prevention of Keloids: A Double Blind Randomized Clinical Trial Study

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    Hamid Reza Ghafarian Shirazi

    2011-03-01

    Full Text Available Keloids are aesthetically disfiguring and severely disabling. The optimal treatment remains undefined. This clinical study, evaluate the efficacy and side effects of combined topical silicone and 5-Fluorouracil on the prevention of keloids. In this double blind randomized clinical trial, fifty patients with keloids were randomly allocated in two groups. The control group were treated by perilesional surgical excision of keloids combined with topical silicone and the trial group were treated with adjuvant treatment of intralesional 5-Fluorouracil. All patients were examined and assessment was done by an independent observer. the data collected were analyzed by SPSS statistical software with using tables and χ square tests. 75% of the cases in the trial group were keloid free 21% have keloid partially improvement and 4% have keloid recurrence, compared to patients in the control group respectively: 43%, 35% and 22%, findings suggest that efficacy of 5-Fluorouracil combined with topical silicone used for the prevention of keloid is comparable to other modality. The lack of any serious side effects and the evidence of recurrence at one year of follow-up make this an effective tool for the prevention of keloids.

  14. Hyperthermia combined with 5-fluorouracil promoted apoptosis and enhanced thermotolerance in human gastric cancer cell line SGC-7901

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    Liu T

    2015-05-01

    Full Text Available Tao Liu,* Yan-Wei Ye,* A-li Zhu, Zhen Yang, Yang Fu, Chong-Qing Wei, Qi Liu, Chun-Lin Zhao, Guo-Jun Wang, Xie-Fu Zhang Department of Gastrointestinal Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China *These authors contributed equally to this work Abstract: This study was designed to investigate the proliferation inhibition and apo­ptosis-promoting effect under hyperthermia and chemotherapy treatment, at cellular level. Human gastric cancer cell line SGC-7901 was cultivated with 5-fluorouracil at different temperatures. Cell proliferation and apoptosis were determined, and expression of Bcl-2 and HSP70 was measured at different treatments. Cell survival rates and inhibition rates in chemotherapy group, thermotherapy group, and thermo-chemotherapy group were drastically lower than the control group (P<0.05. For tumor cells in the thermo-chemotherapy group, survival rates and inhibition rates at three different temperatures were all significantly lower than those in chemotherapy group and thermotherapy group (P<0.05. 5-Fluorouracil induced apoptosis of SGC-7901 cells with a strong temperature dependence, which increased gradually with increase in temperature. At 37°C and 43°C there were significant differences between the thermotherapy group and chemotherapy group and between the thermo-chemotherapy group and thermotherapy group (P<0.01. The expression of Bcl-2 was downregulated and HSP70 was upregulated, with increase in temperature in all groups. Cell apoptosis was not significant at 46°C (P>0.05, which was probably due to thermotolerance caused by HSP70 accumulation. These results suggested that hyperthermia combined with 5-fluorouracil had a synergistic effect in promoting apoptosis and enhancing thermotolerance in gastric cancer cell line SGC-7901. Keywords: gastric cancer, thermotherapy, 5-fluorouracil, Bcl-2, HSP70, thermotolerance

  15. [Evaluation of acute cardiotoxicity from the combination cyclophosphamide-mitoxantrone-5-fluorouracil (CMF) with Holter ECG].

    Science.gov (United States)

    Doria, G; Cangemi, F; Tosto, A; Platania, F; Circo, A; Motta, S; Tralongo, P; Aiello, R A; Failla, G

    1990-05-01

    By making use of a twenty-four hour Holter monitoring, it as been possible to compute the acute cardiotoxicity of the cyclophosphamide + mitoxantrone + 5-fluorouracil (CNF) association in twenty oncologic patients (pts) each of whom being immune from organic cardiopathy emerging clinically and at their first cycle of chemotherapy. The following parameters have been computed: meaningful changes in the heart frequency; premature atrial and ventricular depolarizations, both as a first appearance and as a clear growth in the number; the ST dislocation entity; malignant ventricular arrhythmias. The administration of CNF at the doses of: 600 mg/m2 of cyclophosphamide, 12 mg/m2 of mitoxantrone and 600 mg/m2 of 5-fluorouracil , has caused a meaningful increase in the heart frequency on 6 pts (30%), an increase of premature atrial depolarization on 4 pts (20%) with an appearance ex novo on 2 pts (10%), an increase of premature ventricular depolarization, without any passing to superior Lown classes, on 2 pts (10%) with an appearance ex novo on 3 pts (15%). Although the results in the study point out a frequency percentage of simple hyperkinetic arrhythmias equal to the 55%, the lack of more serious hyperkinetic arrhythmias and of intense disorders of ventricular repolarization testified to a synergic effect as a determining factor on the acute cardiotoxicity of the previously discussed association, in our opinion. PMID:2234455

  16. Prospective trial of concurrent chemoradiotherapy with protracted infusion of 5-fluorouracil and cisplatin for T4 esophageal cancer with or without fistula

    International Nuclear Information System (INIS)

    Purpose: A prospective trial of concurrent chemoradiotherapy (CT-RT) with a protracted infusion of 5-fluorouracil and cisplatin was performed to evaluate the safety and efficacy of this protocol for T4 esophageal cancer (UICC 1997). Methods and Materials: Between 1998 and 2000, 28 patients with T4 esophageal squamous cell carcinomas were treated with concurrent CT-RT. Of the 28 patients, 15 had Stage III, 5 Stage IVA, and 8 Stage IV disease. Five of the T4 tumors had evidence of fistula before treatment. Patients received a protracted infusion of 5-fluorouracil 300 mg/m2/24 h on Days 1-14, a 1-h infusion of cisplatin 10 mg/body on Days 1-5 and 8-12, and concurrent radiation at a dose of 30 Gy in 15 fractions during 3 weeks. This schedule was repeated twice, with a 1-week split, for a total RT dose of 60 Gy during 7 weeks for 25 patients. For the remaining 3 patients, 30 Gy of preoperative CT-RT was administered. Results: Of the 25 patients who were treated with the full dose of CT-RT, 14 (56%) completed the two courses of the CT-RT protocol, and 8 patients (32%) received the full dose of RT but a reduced dose of chemotherapy. Eight (32%) of the 25 tumors showed complete regression. Although Grade 3 hematologic toxicities were frequently noted, Grade 4 or more hematologic toxicities were few. Of the 5 T4 fistulous tumors, 2 demonstrated the disappearance of the fistula after CT-RT. However, the worsening or development of an esophageal fistula was noted in 5 patients. The 2-year survival rate for patients with Stage III was 27%, and the median survival time for those with Stage III and Stage IVA+IV was 12 and 5 months, respectively. Conclusion: Despite its significant toxicity for esophageal fistula, this concurrent CT-RT protocol of protracted 5-fluorouracil infusion and cisplatin appears feasible and effective for T4 esophageal cancer with or without fistulas

  17. A pilot study of preoperative continuous infusion 5-fluorouracil, external microwave hyperthermia, and external beam radiotherapy for treatment of locally advanced, unresectable, or recurrent rectal cancer

    International Nuclear Information System (INIS)

    Purpose: To determine the feasibility of combining external beam radiotherapy, continuous infusion 5-fluorouracil (5-FU), and external microwave hyperthermia in patients with locally advanced, unresectable, or recurrent adenocarcinoma of the rectum. Methods and Materials: From 7/95 through 2/99, 15 patients were enrolled in the study. The treatment regimen consisted of continuous infusion 5-FU 250 mg/m2/d 7 days/week beginning on day 1, external beam radiotherapy to the pelvis, 4500 cGy, 180 cGy/d 5 days/week using a 3 or 4-field technique, and external microwave hyperthermia on days 3, 8, 15, 22, and 29. Chemotherapy was stopped on the last day of radiotherapy. Surgical resection, if feasible, was scheduled 3-6 weeks after completing thermochemoradiotherapy. For this regimen to be considered feasible, no more than 2 of the 15 patients should fail to complete therapy due to life-threatening toxicity. Toxicity was scored using National Cancer Institute Criteria. Results: All patients completed the chemoradiotherapy portion of the protocol. Eleven of the 15 patients completed all 5 hyperthermia treatments. Of the 4 patients who did not receive the full course of hyperthermia, only 1 patient had treatment stopped due to life-threatening toxicity. The other 3 patients did not complete hyperthermia due to scheduling errors (n = 2) or patient request (n = 1). Five of 15 patients required a treatment interruption due to toxicity no. >=no. Grade 3. Seven patients experienced lesser degrees of toxicity which did not require treatment interruption. Three patients experienced no side effects. The most common toxicities were dermatitis and diarrhea. Of the 14 patients in whom surgery was planned, 11 (79%) were resectable. There was one pathologic complete response. Conclusions: It is feasible to deliver thermochemoradiotherapy, as prescribed in this study, to patients with locally advanced, unresectable, or recurrent rectal cancer. The therapy is moderately toxic, with one

  18. Treatment of laser resistant granuloma faciale with intralesional triamcinolone acetonide and 5-fluorouracil combination therapy

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    Diana L Norris

    2015-01-01

    Full Text Available This report describes a sixty year old male with biopsy proven Granuloma Faciale (GF. The patient had been unsuccessfully treated with multiple therapies. A mixture 0.8 ml 5-Fluorouracil (5FU and 0.2 ml Kenacort-A was trialled initially to treat this patient, followed by a more varied mixture ratio. These were given at intervals ranging from two weeks to two months. The patient received a total of twenty injections over a period of more than three years. An excellent response was noted and the patient is now able to tolerate long treatment free periods of between nine and twelve months. 5FU is a simple injection material and can be considered by clinicians as an option for treatment of GF.

  19. Long-term results of concurrent chemoradiotherapy using low-dose continuous infusion of 5-fluorouracil for stage II-III esophageal cancer

    International Nuclear Information System (INIS)

    To improve the local control of stage II-III esophageal cancer, we tried concurrent chemoradiotherapy with low-dose continuous infusion of 5-fluorouracil (5-FU) during the entire course of conventional radiotherapy. Forty-three eligible patients with stage II-III esophageal cancer were treated with conventional radiotherapy up to 60-70 Gy concurrently with continuous infusion of 5-FU (300 mg/m2 per 24 hours) for 5 days per week given over 5 to 7 weeks. All patients were followed up more than 5 years after starting the treatments. Although there were two treatment-related deaths, 88% of the patients (38/43) could complete the planned course of chemoradiotherapy. Response rate was 90%. The median survival time was 12.2 months, and the 2- and 5-year overall survival rates were 33% and 15%, respectively. Low-dose continuous infusion of 5-FU given during the entire course of conventional radiotherapy is feasible and seems to offer better results than radiotherapy alone in the treatment of stage II-III esophageal cancer. (author)

  20. 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)

    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/m2/day or 7-days/week infusion at 225 mg/m2/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

  1. Novel Resveratrol and 5-Fluorouracil Coencapsulated in PEGylated Nanoliposomes Improve Chemotherapeutic Efficacy of Combination against Head and Neck Squamous Cell Carcinoma

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    Aarti Mohan

    2014-01-01

    Full Text Available Increasing consumption of tobacco and alcohol has led to a steady increase in the incidence of head and neck cancers in Asia. The drawbacks associated with the existing chemotherapeutic and surgical interventions have necessitated the development of a safer alternative for therapy of head and neck cancers. In this study we have explored the synergistic therapeutic potential of a phytochemical and chemotherapeutic agent using PEGylated liposomes as a delivery vehicle. Resveratrol and 5-fluorouracil were successfully coencapsulated in a single PEGylated nanoliposome. The thermal analysis and the nuclear magnetic resonance results revealed that resveratrol localized near the glycerol backbone of the liposomal membrane while 5-fluorouracil localized closer to the phosphate moiety, which influenced the release kinetics of both drugs. The nanoformulation was tested in vitro on a head and neck cancer cell line NT8e and was found to exhibit a GI50 similar to that of free 5-fluorouracil. Further, gene expression studies showed that the combination of resveratrol and 5-fluorouracil exhibited different effects on different genes that may influence the net antagonistic effect. The coencapsulation of resveratrol and 5-fluorouracil in a liposomal nanocarrier improved the cytotoxicity in comparison with the free drug combination when tested in vitro.

  2. Original P53 status predicts for pathological response in locally advanced breast cancer patients treated preoperatively with continuous infusion 5-fluorouracil and radiation therapy

    International Nuclear Information System (INIS)

    Purpose/Objective: 1) To test feasibility of preoperative continuous infusion (c.i.) 5-Fluorouracil (5-FU) and radiation (RT) in locally advanced breast cancer. 2) To study clinical and pathological response rates of 5-FU and radiation. 3) To attempt preliminary correlations between biological probes and pathological response. Methods and Materials: Previously untreated, locally advanced breast cancer patients were eligible: only patients who presented with T3/T4 tumors that could not be resected with primary wound closure were eligible, while inflammatory breast cancer patients were excluded. The protocol consisted of preoperative c.i. infusion 5-FU, 200 mg/m2/day with radiotherapy, 50 Gy at 2 Gy fractions to the breast and regional nodes. At mastectomy, pathological findings were classified based on persistence of invasive cancer: pathological complete response (pCR) = no residual invasive cells in the breast and axillary contents; pathological partial response (pPR) = presence of microscopic foci of invasive cells in either the breast or nodal specimens; no pathological response (pNR) = pathological persistence of tumor. For each patient pretreatment breast cancer biopsies were analyzed by immunohistochemistry for nuclear grade, ER/PR hormonal receptors, her2/neu and p53 overexpression. Results: Thirty-five women have completed the protocol and are available for analysis. 5-FU was interrupted during radiation in 10 of 35 patients because of oral mucositis in 8 patients, cellulitis in 1, and patient choice in another. Objective clinical response rate before mastectomy was 71% (25 of 35 patients): 4 CR, 21 PR. However, in all 35 patients tumor response was sufficient to make them resectable with primary wound closure. Accordingly, all patients underwent modified radical mastectomy: primary wound closure was achieved in all patients. At mastectomy there were 7 pCR (20%), 5 pPR (14%) and the remaining 23 patients (66%) had pathological persistence of cancer (p

  3. Concurrent radiotherapy and chemotherapy with protracted continuous infusion of 5-fluorouracil in inoperable esophageal squamous cell carcinoma

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    Purpose: The feasibility of a concurrent chemoradiotherapeutic protocol for patients with inoperable esophageal squamous cell carcinoma was tested. Methods and Materials: Concurrent chemoradiotherapy using protracted low-dose continuous infusions of five-fluorouracil (5-FU; 250-300 mg/m2/24 h) and standard external beam irradiation was given to 28 patients with inoperable esophageal squamous cell carcinoma between November 1991 and June 1993. Results: For 25 patients receiving a total dose of ≥ 60 Gy and concurrent 5-FU infusion for more than 5 weeks, the complete response rate was 52%. Local progression-free rate in this chemoradiotherapy group was significantly higher than the historical controls treated by radiotherapy alone (p < 0.05). A multivariate analysis revealed the treatment scheme (concomitant chemoradiotherapy vs. radiotherapy alone) to be a significant factor in local control (p < 0.01). Swallowing pain (39%), anorexia (39%), and nausea (32%) were the most frequent early reactions. Serious late radiation complications have not been observed. Conclusion: The concurrent chemoradiotherapy using protracted low-dose continuous infusion of 5-FU and standard radiotherapy is an effective and safe method to obtain a local control in inoperable esophageal squamous cell carcinoma

  4. Length and quality of survival after external-beam radiotherapy with concurrent continuous 5-fluorouracil infusion for locally unresectable pancreatic cancer

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    Purpose: The purpose of this study was to evaluate whether external-beam radiotherapy (EBRT) with concurrent continuous 5-fluorouracil (5-FU) infusion affects the length and quality of survival in patients with locally unresectable pancreatic cancer. Methods: Thirty-one patients with histologically proven locally advanced and unresectable pancreatic cancer without distant metastases were evaluated in this prospective randomized trial. Sixteen patients received EBRT (50.4 Gy/28 fractions) with concurrent continuous infusion of 5-FU (200 mg/m2/day), whereas 15 patients received no chemoradiation. The length and quality of survival was analyzed and compared for the two groups. Results: The median survival of 13.2 months and the 1-year survival rate of 53.3% in the chemoradiation group were significantly better than the respective 6.4 months and 0% in the group without chemoradiotherapy (p=0.0009). The average monthly Karnofsky score, a quality of life indicator, was 77.1 in the chemoradiation group, which was significantly higher than the 65.5 in the group without chemoradiotherapy (p<0.0001). The number of hospital days per month of survival was significantly less in the chemoradiation than in the no-therapy group (12.3 vs. 19.0 days, p<0.05). In the chemoradiation group, 5 patients (31%) had a partial response, and 9 (56%) had radiologically stable disease at a median duration of 6.1 months. The patients who had chemoradiation had a lower rate of liver and peritoneal metastases than patients without chemoradiotherapy (31% vs. 64%). Of 10 patients who experienced pain before chemoradiation, 8 (80%) received pain relief that lasted a median of 5.2 months. Conclusions: EBRT with concurrent continuous 5-FU infusion increased the length and quality of survival as compared to no chemoradiotherapy and provided a definite palliative benefit for patients with unresectable pancreatic cancer

  5. 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)

    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/m2 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

  6. Phase I and pharmacokinetic study of the polyamine synthesis inhibitor SAM486A in combination with 5-fluorouracil/leucovorin in metastatic colorectal cancer

    NARCIS (Netherlands)

    L. van Zuylen; C. Mueller; J. Verweij (Jaap); J.A. Ledermann; J. Bridgewater; A. Sparreboom (Alex); F.A.L.M. Eskens (Ferry); P. de Bruijn (Peter); I. Sklenar; A.S.Th. Planting (André); L. Choi; D. Bootle

    2004-01-01

    textabstractPURPOSE: The purpose of our study was to determine the maximum-tolerated dose, dose-limiting toxicity, safety profile, and pharmacokinetics of the polyamine synthesis inhibitor SAM486A given in combination with 5-fluorouracil/leucovorin (5-FU/LV) in cancer patients. EXP

  7. Angiogenesis inhibition and cell cycle arrest induced by treatment with Pseudolarix acid B alone or combined with 5-fluorouracil

    Institute of Scientific and Technical Information of China (English)

    Jingtao Liu; Wei Guo; Bo Xu; Fuxiang Ran; Mingming Chu; Hongzheng Fu; Jingrong Cui

    2012-01-01

    Angiogenesis inhibitors combined with chemotherapeutic drugs have significant efficacy in the treatment of a variety of cancers.Pseudolarix acid B (PAB) is a traditional pregnancy-terminating agent,which has previously been shown to reduce tumor growth and angiogenesis.In this study,we used the high content screening assay to examine the effects of PAB on human umbilical vein endothelial cells (HUVECs).Two hepatocarcinoma 22-transplanted mouse models were used to determine PAB efficacy in combination with 5-fluorouracil (5-Fu).Our results suggested that PAB (0.156-1.250 μM) inhibited HUVECs motility in a concentration-dependent manner without obvious cytotoxicity in vitro.In vivo,PAB (25 mg/kg/day) promoted the anti-tumor efficacy of 5-Fu (5 mg/kg/2 days) in combination therapy,resulting in significantly higher tumor inhibition rates,lower microvessel density values,and prolonged survival times.It was also demonstrated that PAB acted by blocking the cell cycle at both the G1/S boundary and M phase,down-regulation of vascular endothelial growth factor,hypoxia-inducible factor 1α and cyclin E expression,and up-regulation of cdc2 expression.These observations provide the first evidence that PAB in combination with 5-Fu may be useful in cancer treatment.

  8. Effect of combined treatment with x-irradiation and 5-fluorouracil in multicellular spheroids of rat glioma

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    Kuwahara, Kenji; Katakura, Ryuichi; Suzuki, Jiro; Sasaki, Takehito; Mori, Teruaki

    1987-12-01

    The effect of combined treatment with X-irradiation and 5-fluorouracil (5-Fu) on the spheroids of rat glioma clone-6 cells was compared with that on exponentially grown monolayer cells. Isobolographic analysis showed the effect of the combined treatment to be supra-additive in both multicellular spheroids and monolayer cells when irradiation followed 24 hours of treatment with 5-Fu. X-irradiation prior to 5-Fu treatment showed an additive effect. The effect of X-irradiation on spheroids was enhanced after 3 hours of 5-Fu treatment, whereas its effect on monolayer cells was augmented only when prior 5-Fu treatment exceeded 12 hours. Potentiation of the effect of X-irradiation on spheroids by prior treatment with 5-Fu is thought to be due to reoxygenation of previously hypoxic cells and partial synchronization of proliferating cells. These results suggest that when X-irradiation is applied shortly after 5-Fu treatment the effect on solid tumors is selectively enhanced, while the effect on actively proliferating normal tissues is reduced.

  9. Systemic gemcitabine combined with intra-arterial low-dose cisplatin and 5-fluorouracil for advanced hepatocellular carcinoma: Seven cases

    Institute of Scientific and Technical Information of China (English)

    Kiminori Uka; Kazuaki Chayama; Hiroshi Aikata; Shintaro Takaki; Tomokazu Kawaoka; Hiromi Saneto; Daiki Mild; Shoichi Takahashi; Naoyuld Toyota; Katsuhide Ito

    2008-01-01

    The combination of intra-arterial low-dose cisplatin and 5-fluorouracil (5-FU) is effective against advanced hepatocellular carcinoma (HCC).Systemic gemcitabine chemotherapy seems effective in many cancers.We report the results of combination therapy with systemic gemcitabine, intra-arterial low-dose cisplatin and 5-FU (GEMFP).Seven patients with non-resectable advanced HCC were treated with GEMFP.One course of chemotherapy consisted of daily intra-arterial cisplatin (20 mg/body weight/hour on day z, 10 mg/body weight per 0.5 h on d 2-5 and 8-12), followed by 5-FU (250 mg/body weight per 5 h on d 1-5 and 8-12) via an injection port.Gemcitabine at 1000 mg/m2 was administered intravenously at 0.5 h on d 1 and 8.The objective response was 57%.The response to GEMFP was as follows: complete response (no patients), partial response (four patients), stable disease (three patients),and progressive disease (no patients).The median survival period was 8 mo (range, 5-55).With regard to the National Cancer Institute Common Toxicity Criteria (NCI-CTC) grade 3 or 4 adverse reactions, seven (100%),seven, six (86%) and one (14%) patients developed leukopenia, neutropenia, thrombocytopenia and anemia,respectively.GEMFP may potentially be effective for nonresectable advanced HCC, but it has severe hematologic toxicity.

  10. Re-evaluation of antitumor effects of combination chemotherapy with interferon-α and 5-fluorouracil for advanced hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Munechika Enjoji; Shusuke Morizono; Kazuhiro Kotoh; Motoyuki Kohjima; Yuzuru Miyagi; Tsuyoshi Yoshimoto; Makoto Nakamuta

    2005-01-01

    AIM: To evaluate the efficacy of combination chemotherapy with interferon-α (IFNα) and 5-fluorouracil (5-FU) in patients with advanced hepatocellular carcinoma (HCC).METHODS: Twenty-eight HCC patients in advanced stage were enrolled in the study. They were treated with IFNα/5-FU combination chemotherapy. One cycle of therapy lasted for 4 wk. IFNα (3× 106 units) was subcutaneously injected thrice weekly on days 1, 3, and 5 for 3 wk, and 5-FU (500 mg/d) was administered via the proper hepatic artery for 5 consecutive days per week for 3 wk. No drugs were administered during the 4th wk. The effect of combination chemotherapy was evaluated in each patient after every cycle based on the reduction of tumor volume.RESULTS: After the 1st cycle of therapy, 16 patients showed a partial response (PR, 57.1%) but none showed a complete response (CR, 0%). At the end of therapy,the number of patients who showed a CR, PR, or no response (NR) was 1, 10, and 17, respectively. The response rate for therapy (CR+PR) was 21.5%. Biochemical tests before therapy were compared between responsive (CR+PR) and non-responsive (NR) patients, but no significant differences were found for any of the parameters examined, indicating that no reasonable predictors could be identified in our analysis.CONCLUSION: Attempts should be made to discriminate between responders and non-responders by evaluating tumor size after the first cycle of IFNα/5-FU combination chemotherapy. For non-responders, therapy should not proceed to the next cycle, and instead, different combination of anticancer drugs should be explored.

  11. 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

  12. Experience with combination of docetaxel, cisplatin plus 5-fluorouracil chemotherapy, and intensity-modulated radiotherapy for locoregionally advanced nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Our aim was to evaluate the efficacy and toxicity of cisplatin, fluorouracil, and docetaxel chemotherapy plus intensity-modulated radiotherapy (IMRT) for locoregionally advanced nasopharyngeal carcinoma (NPC). Sixty patients with locoregionally advanced NPC were enrolled. Patients received IMRT plus three courses of neoadjuvant chemotherapy and two courses of adjuvant chemotherapy consisting of docetaxel (60 mg/m2/day on day 1), cisplatin (25 mg/m2/day on days 1-3), and 5-fluorouracil (500 mg/m2/day on days 1-3). The overall response rate to neoadjuvant chemotherapy was 89%. Three months after the completion of radiotherapy, 53 (93%) patients achieved complete regression, 3 (5%) achieved partial response (PR), and 1 experienced liver metastasis. However, among the 3 PR patients, 2 patients had no evidence of relapse in the follow-up. With a median follow-up of 27 months (range, 6-43), the 2-year estimated locoregional failure-free survival, distant failure-free survival, progression-free survival, and overall survival were 96.6, 93.3, 89.9, and 98.3%, respectively. Leukopenia was the main adverse effect in chemotherapy; 14 patients experienced grade 3 or grade 4 neutropenia, and 1 patient developed febrile neutropenia. The nonhematological adverse events included alopecia, nausea, vomiting, anorexia, and diarrhea. The incidence of grade 3 acute radiotherapy-related mucositis was 28.3%; no grade 4 acute mucositis was observed. No grade 3 or grade 4 hematological toxicity occurred during radiotherapy. None of the patients had interrupted radiotherapy. The common late adverse effects included xerostomia and hearing impairment. Neoadjuvant-adjuvant chemotherapy using cisplatin, fluorouracil, plus docetaxel combined with IMRT was an effective and well-tolerated alternative for advanced NPC. (author)

  13. 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.

  14. A comparison between 5-fluorouracil/mitomycin and capecitabine/mitomycin in combination with radiation for anal cancer

    Science.gov (United States)

    Wan, Dante D.; Schellenberg, Devin; Lim, Howard J.

    2016-01-01

    Background There are no randomized phase III trials comparing 5-fluorouracil/mitomycin (FM) versus capecitabine/mitomycin (CM) in combination with radiotherapy (RT) for locally advanced anal cancer. We aim to evaluate the outcomes of patients treated with FM and CM at our institution. Methods Patients with stage I–III anal cancer who initiated curative-intent RT (50–54 Gy) with either CM or FM between 1998 and 2013 at the BC Cancer Agency were reviewed. Cox proportional models were used to analyze the impact of regimen on disease-free survival (DFS) and anal cancer-specific survival (ACSS). Results A total of 300 patients were included. Baseline characteristics were well-distributed between the groups. A total of 194 patients (64.6%) received FM and 106 (35.3%) CM. The 2-year DFS was 79.7% for CM [95% confidence intervals (95% CI), 71.1–88.3%] and 78.8% for FM (95% CI, 73–84.6%); 2-year ACSS was 88.7% for CM (95% CI, 81.8–95.5%) and 87.5% for FM (95% CI, 82.8–92.2%). On multivariate analysis, only HIV status, clinical T size (≤5 vs. >5 cm), and N status (negative vs. positive) remained as significant prognostic factors for both DFS and ACSS. Chemotherapy regimen (CM vs. FM) had no impact on either DFS [P=0.995; hazard ratios (HR) =0.99; 95% CI, 0.57–1.74] or ACSS (P=0.847; HR =0.93; 95% CI, 0.46–1.86). Conclusions In our population-based study, CM and FM concomitant with RT achieved similar DFS and ACSS. Substitution of capecitabine for infusional 5-FU may therefore be a reasonable option for patients and physicians who prefer to avoid the inconvenience and potential complications of a central infusional device. PMID:27563458

  15. Irinotecan or oxaliplatin combined with 5-fluorouracil and leucovorin as first-line therapy for advanced colorectal cancer: a meta-analysis

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    LIANG Xiao-bo; HOU Sheng-huai; Li Yao-ping; WANG Li-chun; ZHANG Xin; YANG Jun

    2010-01-01

    Background To compare clinical efficacy and toxicity of irinotecan combined with 5-fluorouracil and leucovorin with those of oxaliplatin combined with 5-fiuorouracil and leucovorin as first-line therapy for advanced colorectal cancer.Methods Literature search was performed by keywords "irinotecan", "oxaliplatin" and "colorectal cancer" on all randomized controlled trails reported on irinotecan versus oxaliplatin combined with 5-fluorouracil and leucovorin as first-line therapy for advanced colorectal cancer in MEDLINE, OVID, Springer, Cochrane Controlled Trials Register (CCTR) and CBMdisc (Chinese Biology and Medicine disc) before January 2010. Two authors drew the details of trial design, characteristics of patients, outcomes, and toxicity from the studies included. Data analysis was performed by RevMan 4.2.Results According to the screening criteria, 7 clinical studies with 2095 participants of advanced colorectal cancer were included in this meta analysis. The baseline characteristics of irinotecan group were similar to those of oxaliplatin group.The response rate of oxaliplatin group was higher than that of irinotecan group (relative risk (RR)=0.82, 95% confidence interval (95%CI) (0.70, 0.96), P=0.01), and the median overall survival of oxaliplatin group was longer by 2.04 months than that of irinotecan group (95%CI (-3.54, -0.54), P=0.008). In the comparison of grade 3-4 toxicity between the two groups, the incidences of nausea, emesis, diarrhoea and alopecia in irinotecan group were higher than those in oxaliplatin group (RR=1.94, 95%CI(1.22, 3.09), P=0.005; 1.71, 95%CI (1.34, 2.18), P <0.001; 14.56, 95%CI (4.11,51.66), P <0.0001), respectively. However, the incidence of neurotoxicity, neutropenia and thrombocytopenia in irinotecan group were lower than those in oxaliplatin group (RR=0.06, 95%CI(0.03, 0.14), P <0.00001; 0.70, 95%CI(0.55, 0.91), P=0.006; 0.18, 95%CI(0.05, 0.61), P=0.006), respectively.Conclusions Both irinotecan and oxaliplatin combined

  16. Superselective intra-arterial infusion therapy with docetaxel, cisplatin and 5-fluorouracil for head and neck cancer. For tongue cancer patients in comparison patients with other therapies

    International Nuclear Information System (INIS)

    In order to cure head and neck cancer without resection, chemotherapy (superselective intra-arterial infusion therapy with docetaxel, cisplatin and fluorouracil (DCF)) was conducted by anterograde, superselective intra-arterial infusion of 50-60 mg/m2 of docetaxel (DOC) and 50-60 mg/m2 of cisplatin (CDDP) via the femoral artery on day 1 followed by continuous intravenous instillation of 600-750 mg/m2/day of 5-FU for 5 days from day 2. A total of 70 patients with advanced and recurrent cancer of the head and neck have been treated since April 2000. With the median follow-up duration of 1,017 days, the survival rate was 92.7% and the organ preservation rate was 90.1%. Almost no complications associated with this therapy were observed. Due to space limitations, here we report only cases of tongue cancer. Histological CR was obtained from all 19 patients with squamous cell cancer of the tongue. With the median follow-up duration of 1,371 days (45.7 months: 471-2,133 days), the survival rate was 94.74% and the organ preservation rate was 88.42% by the Kaplan-Meier method. For both the survival rate and organ preservation rate, extremely good results were obtained by the superselective intra-arterial infusion therapy with DCF compared to the intravenous infusion therapy using a combination of CDDP and 5-FU (five-year survival rate: 20%) as well as the superselective intra-arterial infusion of CDDP alone followed by continuous intravenous infusion of 5-FU (five-year survival rate: 28.5%) that had been conducted before. Major adverse effects observed were leukopenia and alopecia. Although patients who underwent concurrent radiation therapy developed mucositis and dermatitis, both were reversible changes. (author)

  17. 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)

    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/m2 for bolus injection and 200-225 mg/m2/day for PVI. Dose intensity was assessed for both 5-FU and radiotherapy by calculating total doses (mg/m2 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 cm3 (95% CI: 1,210-1,436). Chemotherapy and radiotherapy dose intensity

  18. THE EFFECTS OF GAMMA-INTERFERON COMBINED WITH 5-FLUOROURACIL OR 5-FLUORO-2'-DEOXYURIDINE ON PROLIFERATION AND ANTIGEN EXPRESSION IN A PANEL OF HUMAN COLORECTAL-CANCER CELL-LINES

    NARCIS (Netherlands)

    MAAS, IWHM; BOVEN, E; PINEDO, HM; SCHLUPER, HMM; Haisma, Hidde

    1991-01-01

    Gamma-Interferon (IFN-gamma) and the antimetabolites 5-fluorouracil (5-FU) and S-fluoro-2'-deoxyuridine (FUdR) were investigated as individual agents and in combination for their in vitro antiproliferative capacity and for their effect on the expression of HLA class-I antigen, carcinoembryonic antig

  19. The combination of a low-dose chemotherapeutic agent, 5-fluorouracil, and an adenoviral tumor vaccine has a synergistic benefit on survival in a tumor model system.

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    Sean M Geary

    Full Text Available Standard cancer therapies, particularly those involving chemotherapy, are in need of modifications that both reduce short-term and long-term side effects as well as improve the overall survival of cancer patients. Here we show that combining low-dose chemotherapy with a therapeutic vaccination using an adenovirus encoding a model tumor-associated antigen, ovalbumin (Ad5-OVA, had a synergistic impact on survival in tumor-challenged mice. Mice that received the combinatorial treatment of Ad5-OVA plus low-dose 5-fluorouracil (5-FU had a 95% survival rate compared to 7% and 30% survival rates for Ad5-OVA alone and 5-FU alone respectively. The presence of 5-FU enhanced the levels of OVA-specific CD8(+ T lymphocytes in the spleens and draining lymph nodes of Ad5-OVA-treated mice, a phenomenon that was dependent on the mice having been tumor-challenged. Thus 5-FU may have enhanced survival of Ad5-OVA-treated mice by enhancing the tumor-specific immune response combined with eliminating tumor bulk. We also investigated the possibility that the observed therapeutic benefit may have been derived from the capacity of 5-FU to deplete MDSC populations. The findings presented here promote the concept of combining adenoviral cancer vaccines with low-dose chemotherapy.

  20. 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

    Science.gov (United States)

    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

  1. Engineering of lipid prodrug-based, hyaluronic acid-decorated nanostructured lipid carriers platform for 5-fluorouracil and cisplatin combination gastric cancer therapy

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    Qu CY

    2015-06-01

    Full Text Available Chun-Ying Qu,1,* Min Zhou,1,* Ying-wei Chen,2 Mei-mei Chen,3 Feng Shen,1 Lei-Ming Xu11Digestive Endoscopic Diagnosis and Treatment Center, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, People’s Republic of China; 2Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, People’s Republic of China; 3Digestive Department, Xinhua Hospital, School of medicine, Shanghai Jiaotong University, Shanghai, People’s Republic of China*These authors contributed equally to this workPurpose: The first-line chemotherapy treatment protocol for gastric cancer is combination chemotherapy of 5-fluorouracil (5-FU and cisplatin (CDDP. The aim of this study was to engineer prodrug-based nanostructured lipid carriers (NLC platform for codelivery of 5-FU and CDDP to enhance therapy and decrease toxicity.Methods: First, 5-FU-stearic acid lipid conjugate was synthesized by two steps. Second, 5-FU-stearic acid prodrug and CDDP were loaded in NLC. Finally, hyaluronic acid (HA was coated onto NLC surface. Average size, zeta potential, and drug loading capacity of NLC were evaluated. Human gastric cancer cell line BGC823 (BGC823 cells was used for the testing of in vitro cytotoxicity assays. In vivo antitumor activity of NLC was evaluated in mice bearing BGC823 cells model.Results: HA-coated 5-FU-stearic acid prodrug and CDDP-loaded NLC (HA-FU/C-NLC showed a synergistic effect in combination therapy and displayed the greatest antitumor activity than all of the free drugs or uncoated NLC in vitro and in vivo.Conclusion: This work reveals that HA-coated NLC could be used as a novel carrier to codeliver 5-FU and CDDP for gastric cancer therapy. HA-FU/C-NLC could be a promising targeted and combinational therapy in nanomedicine.Keywords: gastric cancer, nanostructured lipid carriers, hyaluronic acid, combination chemotherapy, lipid prodrug

  2. SMALL-DOSE CYTOKINES IN COMBINATION WITH 5-FLUOROURACIL IN OLISSEMINATED RENAL CELL CARCINOMA: FINAL RESULTS OF A RANDOMIZED TRIAL

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    L. V. Demidov

    2009-01-01

    Full Text Available Background: High and intermediate IL-2 regimens are difficult to recommend because of great toxicity and efficacy is not sufficient. We suggest that a combination of very low-dose cytokines is effective and safe in metastatic renal cell carcinoma (MRCC patients (pts. A prospective randomized study was started in 2003. The primary end-point was a response rate. Methods: The eligibility criteria included histopathologically confirmed MRCC, ECOG PS 0-2, no autoimmune diseases, no brain metastases, and normal organ function. All pts were randomized in three arms: IL-2 alone, 1.5 MIU, iv, t.i.w., weeks 1—3 or IL-2 1.0 MIU, iv, t.i.w., weeks 1—3 plus IFN 5 MIU, sc, t.i.w, weeks 1—3 or biochemotherapy group 5-FU, 500 mg/m2, iv, once a week, weeks 1—3 plus IL-2 1.0 MIU, iv, t.i.w., weeks 1—3 plus IFN 5 MIU, sc, t.i.w., weeks 1—3. Courses were repeated every three weeks. A response was assessed according to the RECIST every 2 courses.Results: 64 pts were enrolled, of whom 63 were analyzed. Their median age was 55.4 years (range 16—74. 42.9% of the patients had pre- viously received chemo- or immunotherapy. 55.6 percent of the pts had poor prognosis (according to Motzer et al., 2002. Bone metastases were present in 52.4% of the pts. Sixteen patients treated with IL-2 alone showed no CR, PR, 2 SD, or 14 PD. Of 23 patients in the IL-2+IFN group, there were 5 PR, 8 SD, and 10 PD, with a response rate of 21.7%. Amongst 24 patients in the 5-FU+IL-2+IFN group, there were 1 CR, 3 PR, 10 SD, and 10 PD, with a response rate of 16.7%. One-year survival was 20.0%, 81.3% and 81.0%, respectively. The influenza-like syndrome was the most common side effect in the pts who received IFN (89.1%, grade 1, CTC. Hypotension associated with IL-2 (all groups was seen in 56.3% (50%, grade 1 and 6.3%, grade 2. The other adverse reactions were 12.7% grade 1 neutropenia and vomiting in 4.7% pts (Group 3.Conclusion: All regimens are well tolerated. Small-dose IL-2

  3. Clinical studies of combined photodynamic therapy using 5-fluorouracil and methyl-aminolevulinate in patients at high risk for squamous cell carcinoma

    Science.gov (United States)

    Maytin, Edward V.; Lohser, Sara; Tellez, Alejandra; Wene, Lauren; Ishak, Rim; Anand, Sanjay

    2013-03-01

    Photodynamic therapy (PDT) using aminolevulinic acid or its methyl ester, methyl-aminolevulinate (MAL), is an increasingly recognized approach for treating squamous neoplasia of the skin. Advantages of MAL-PDT include its ability to cover broad diseased areas (field treatment), and to do multiple sessions with little-to-no risk of scarring or mutagenesis. MAL-PDT is especially valuable in certain populations at high risk for skin cancer, including Caucasian patients with extensive solar damage, and organ transplant recipients (OTR) who take immunosuppressive drugs to prevent graft rejection. The latter group has a 65-200 fold increased risk of developing squamous cell carcinoma (SCC), a major cause of mortality. Therapeutic options for those patients, other than frequent surgeries, are very limited. Topical 5-Fluorouracil (5-FU), frequently prescribed in normal patients for pre-SCC of the skin, is only minimally effective in the OTR group. MAL-PDT, however, has ~40% efficacy for pre-SCC in OTR patients. Based upon our preclinical studies in mouse tumor models, which showed that preconditioning with 5-FU can drive higher accumulation of target protoporphyins (PpIX), we proposed a rational combination regimen of 5-FU and MAL-PDT in humans. A clinical trial was designed to test the hypothesis that a combination of 5-FU followed by MAL-PDT will elevate PpIX levels and achieve better clinical outcomes in high-risk OTR patients. Primary endpoints include PpIX levels and biochemical markers (p53) measured noninvasively and in skin biopsies. Lesion clearance and recurrence (via photographs and clinical exam) are secondary endpoints. Ongoing results of this clinical trial are presented.

  4. Combination chemotherapy with cyclophosphamide, epirubicin and 5-fluorouracil causes trabecular bone loss, bone marrow cell depletion and marrow adiposity in female rats.

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    Fan, Chiaming; Georgiou, Kristen R; McKinnon, Ross A; Keefe, Dorothy M K; Howe, Peter R C; Xian, Cory J

    2016-05-01

    The introduction of anthracyclines to adjuvant chemotherapy has increased survival rates among breast cancer patients. Cyclophosphamide, epirubicin and 5-fluorouracil (CEF) combination therapy is now one of the preferred regimens for treating node-positive breast cancer due to better survival with less toxicity involved. Despite the increasing use of CEF, its potential in causing adverse skeletal effects remains unclear. Using a mature female rat model mimicking the clinical setting, this study examined the effects of CEF treatment on bone and bone marrow in long bones. Following six cycles of CEF treatment (weekly intravenous injections of cyclophosphamide at 10 mg/kg, epirubicin at 2.5 mg/kg and 5-flurouracil at 10 mg/kg), a significant reduction in trabecular bone volume was observed at the metaphysis, which was associated with a reduced serum level of bone formation marker alkaline phosphatase (ALP), increased trends of osteoclast density and osteoclast area at the metaphysis, as well as an increased size of osteoclasts being formed from the bone marrow cells ex vivo. Moreover, a severe reduction of bone marrow cellularity was observed following CEF treatment, which was accompanied by an increase in marrow adipose tissue volume. This increase in marrow adiposity was associated with an expansion in adipocyte size but not in marrow adipocyte density. Overall, this study indicates that six cycles of CEF chemotherapy may induce some bone loss and severe bone marrow damage. Mechanisms for CEF-induced bone/bone marrow pathologies and potential preventive strategies warrant further investigation. PMID:26056019

  5. 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.

  6. Feasibility and Efficacy of Induction Docetaxel, Cisplatin, and 5-Fluorouracil Chemotherapy Combined With Cisplatin Concurrent Chemoradiotherapy for Nonmetastatic Stage IV Head-and-Neck Squamous Cell Carcinomas

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    Prestwich, Robin J., E-mail: Robin.Prestwich@leedsth.nhs.uk [Department of Clinical Oncology, St. James' s Institute of Oncology, Leeds (United Kingdom); Oeksuez, Didem Colpan; Dyker, Karen; Coyle, Catherine; Sen, Mehmet [Department of Clinical Oncology, St. James' s Institute of Oncology, Leeds (United Kingdom)

    2011-11-15

    Purpose: To report the experience of treating selected fit patients with locally advanced head-and-neck squamous cell carcinoma with three cycles of induction TPF (docetaxel 75 mg/m{sup 2}, cisplatin 75 mg/m{sup 2}, 5-fluorouracil 750 mg/m{sup 2}, Days 2-5) followed by concurrent three-weekly bolus cisplatin 100 mg/m{sup 2} chemoradiotherapy. Methods and Materials: Between March 2006 and February 2010, 66 patients with nonmetastatic Stage IV head-and-neck squamous cell carcinoma were treated in a single institution with three cycles of induction TPF, followed by radical radiotherapy with concurrent cisplatin 100 mg/m{sup 2}. Results: Median age was 54 years (range, 33-69 years). Median follow-up was 21 months (range, 4-55 months). During TPF, Grade 3 toxicity occurred in 18 patients (27%), dose modifications in 10 (15%), delays in 3 (5%), and unplanned admissions in 6 (9%); a clinical tumor response was documented in 60 patients (91%). Median time from the final cycle of TPF to commencing radiotherapy was 22 days. Sixty-two patients (94%) received radical radiotherapy, and all completed treatment with no delays {>=}3 days. One, two, and three cycles of concurrent cisplatin were delivered to 18 patients (29%), 38 patients (61%), and 3 patients (5%), respectively. Ninety-two percent of patients received enteral feeding; median weight loss during treatment was 7%. Forty-two patients (68%) had unplanned admissions with no on-treatment deaths. Three unrelated deaths occurred after treatment. At 1 year after treatment, 21% of patients without disease progression remained gastrostomy dependent. Of 58 assessable patients, 50 (86%) achieved a complete response after treatment. One- and 2-year progression-free survival, cause-specific survival, and overall survival were 88%, 92%, and 86% and 80%, 85%, and 80%, respectively. Conclusion: The combination of induction TPF with concurrent cisplatin chemoradiotherapy in patients with locally advanced head and neck squamous cell

  7. The Synthesis of 1-Aryl-5-Fluorouracil

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    A series of new type substituted 5-fluorouracil derivatives, 1-aryl-5-fluorouracil (4a-4f), were synthesized via diaryliodonium salts and the structure of the title compound was finally confirmed by IR, UV, 1H-NMR, MS and CHN analysis.

  8. Abdominal irradiation modulates 5-Fluorouracil pharmacokinetics

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    Shueng Pei-Wei

    2010-03-01

    Full Text Available Abstract Background Concurrent chemoradiation with 5-fluorouracil (5-FU is widely accepted for treatment of abdominal malignancy. Nonetheless, the interactions between radiation and 5-FU remain unclear. We evaluated the influence of abdominal irradiation on the pharmacokinetics of 5-FU in rats. Methods The radiation dose distributions of cholangiocarcinoma patients were determined for the low dose areas, which are generously deposited around the intrahepatic target volume. Then, corresponding single-fraction radiation was delivered to the whole abdomen of Sprague-Dawley rats from a linear accelerator after computerized tomography-based planning. 5-FU at 100 mg/kg was intravenously infused 24 hours after radiation. A high-performance liquid chromatography system equipped with a UV detector was used to measure 5-FU in the blood. Ultrafiltration was used to measure protein-unbound 5-FU. Results Radiation at 2 Gy, simulating the daily human treatment dose, reduced the area under the plasma concentration vs. time curve (AUC of 5-FU by 31.7% compared to non-irradiated controls. This was accompanied by a reduction in mean residence time and incremental total plasma clearance values, and volume of distribution at steady state. Intriguingly, low dose radiation at 0.5 Gy, representing a dose deposited in the generous, off-target area in clinical practice, resulted in a similar pharmacokinetic profile, with a 21.4% reduction in the AUC. This effect was independent of protein binding capacity. Conclusions Abdominal irradiation appears to significantly modulate the systemic pharmacokinetics of 5-FU at both the dose level for target treatment and off-target areas. This unexpected and unwanted influence is worthy of further investigation and might need to be considered in clinical practice.

  9. Combined intra-arterial infusion and systemic chemoradiotherapy for stage IV squamous cell carcinoma of the mandibular gingiva

    International Nuclear Information System (INIS)

    The purpose of this study was to show the effectiveness of combining intra-arterial infusion and systemic chemotherapy with concurrent radiotherapy for treatment of stage IV mandibular gingival cancer. A total of 23 patients with mandibular gingival cancer were treated with either docetaxel by intra-arterial infusion followed by systemic chemoradiotherapy with cisplatinum and 5-fluorouracil as a monthly regimen, or with docetaxel and cisplatinum by intra-arterial infusion followed by systemic chemoradiotherapy with 5-fluorouracil as a weekly or biweekly regimen. Tumor responses, locoregional control, overall survival, disease-specific survival, and adverse events were evaluated. Of the 23 patients enrolled in the study, 22 completed the treatment. With regard to clinical stages, 82% were diagnosed as IVA and 18% IVB. Complete and partial response was observed in 82 and 18%, respectively. Five-year overall survival, disease-specific survival, and locoregional control were 51, 70, and 72%, respectively. No statistically significant difference was seen between the monthly regimen and the weekly plus biweekly regimen, although the latter resulted in longer survival and 88% control. Combined intra-arterial infusion and systemic chemoradiotherapy may be an effective treatment for patients with stage IV mandibular gingival cancer. (author)

  10. Topical combination of diclofenac, calcipotriol, and difluoromethylornithine has beneficial effects comparable to 5-fluorouracil for the treatment of non-melanoma skin cancer in mice

    DEFF Research Database (Denmark)

    Pommergaard, Hans-Christian; Burcharth, Jakob; Rosenberg, Jacob;

    2014-01-01

    Non-melanoma skin cancer (NMSC) is the most common form of skin cancer. Owing to the significant adverse effects of existing treatments, alternatives are needed. The aim of this study was to evaluate the use of topically administered combination therapy and 5-flurouracil (5-FU) for the treatment...... of UVB induced NMSC in a mouse model. Ninety-six SKH-1 mice were randomized to one placebo group and two treatment groups (diclofenac+calcitriol+difluoromethylornithine (DFMO) and 5-FU). After UVB radiation for 20 weeks, the mice with tumours were treated topically for the following 17 weeks. Both...... treatments significantly reduced the number of tumours, number of mice with tumours as well as tumour area size compared with placebo. As the clinical use of 5-FU may induce more adverse effects, a combination of diclofenac+calcitriol+DFMO could be a promising alternative. Human studies are warranted...

  11. Combined effects of 5-Fluorouracil, Folinic acid and Oxaliplatin on the expression of carcinoembryonic antigen in human colon cancer cells: pharmacological basis to develop an active antitumor immunochemotherapy

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    De Vecchis Liana

    2008-05-01

    Full Text Available Abstract Background Five-fluorouracil (FU, mainly associated with leucovorin (L, plays an essential role in chemotherapy of colorectal carcinoma. Moreover, FU ± L has been found to increase the expression of tumor-associated carcinoembryonic antigen (CEA, that may be an important target in therapeutic protocols of active specific immunotherapy. FU + L (FUL are frequently combined with oxaliplatin (OXA in advanced colon cancer patients. Thus, we investigated whether FUL in combination with OXA according to 2 different schedules may influence CEA expression in human colon cancer cells in vitro. Methods CEA protein expression was evaluated by cytofluorimetric and western blot analysis. Relative quantification of CEA mRNA was assessed by real time RT-PCR analysis. Results Levels of CEA protein and transcript were found to be higher in FUL-treated cells than in controls. However, when target cells were exposed to OXA before but not after FUL treatment, the up-regulation of CEA was partially inhibited. Conclusion These results suggest that target cells must be exposed to OXA after but not before treatment with the fluoropyrimidine in order to exploit drug-induced up-regulation of CEA. This finding appears to provide useful information to design chemo-immunotherapy protocols based on FUL + OXA, combined with host's immunity against CEA directed cancer vaccines.

  12. Metformin synergizes 5-fluorouracil, epirubicin, and cyclophosphamide (FEC) combination therapy through impairing intracellular ATP production and DNA repair in breast cancer stem cells.

    Science.gov (United States)

    Soo, Jaslyn Sian-Siu; Ng, Char-Hong; Tan, Si Hoey; Malik, Rozita Abdul; Teh, Yew-Ching; Tan, Boon-Shing; Ho, Gwo-Fuang; See, Mee-Hoong; Taib, Nur Aishah Mohd; Yip, Cheng-Har; Chung, Felicia Fei-Lei; Hii, Ling-Wei; Teo, Soo-Hwang; Leong, Chee-Onn

    2015-10-01

    Metformin, an AMPK activator, has been reported to improve pathological response to chemotherapy in diabetic breast cancer patients. To date, its mechanism of action in cancer, especially in cancer stem cells (CSCs) have not been fully elucidated. In this study, we demonstrated that metformin, but not other AMPK activators (e.g. AICAR and A-769662), synergizes 5-fluouracil, epirubicin, and cyclophosphamide (FEC) combination chemotherapy in non-stem breast cancer cells and breast cancer stem cells. We show that this occurs through an AMPK-dependent mechanism in parental breast cancer cell lines. In contrast, the synergistic effects of metformin and FEC occurred in an AMPK-independent mechanism in breast CSCs. Further analyses revealed that metformin accelerated glucose consumption and lactate production more severely in the breast CSCs but the production of intracellular ATP was severely hampered, leading to a severe energy crisis and impairs the ability of CSCs to repair FEC-induced DNA damage. Indeed, addition of extracellular ATP completely abrogated the synergistic effects of metformin on FEC sensitivity in breast CSCs. In conclusion, our results suggest that metformin synergizes FEC sensitivity through distinct mechanism in parental breast cancer cell lines and CSCs, thus providing further evidence for the clinical relevance of metformin for the treatment of cancers. PMID:26276035

  13. Original P53 status predicts for pathological response in locally advanced breast cancer treated pre-operatively with continuous infusion (C.I.) 5-fluorouracil (5FU) during radiotherapy

    International Nuclear Information System (INIS)

    Purpose/Objective: 1) To study the pathological response at mastectomy of women treated with a combination of continuous infusion (c.i.) 5Fu during radiotherapy. 2) to explore possible correlations between initial biological parameters (p53 status, Thymidylate Synthase (TS), Her 2/neu expression etc.) and pathological responses. Materials and Methods: Previously untreated locally advanced breast cancer patients were eligible for a preoperative protocol of c.i. 5FU (200 mg/m2) during radiotherapy (50 Gy) to the breast and regional nodes. Mastectomy followed and the pathological findings were quantified as: complete pathological response (pCR) = absence of residual tumor cells both in the removed breast and axillary contents specimens; partial pathological response (pPR) = no tumor mass identified but persistent microscopic cancer cells in either the breast or nodal specimens; no pathological response (pNR) = macroscopic persistence of tumor. Pre-treatment breast cancer biopsies from each patient were analyzed by immunohistochemistry for ER/PR hormonal receptors, her2/neu, TS expression and p53 mutation expression. Results: Twenty-six women completed the protocol and are available for analysis. The combined regimen was well tolerated except for grade I oral mucositis in (9(26)) patients and in field wet desquamation in (3(26)) patients. Clinical response rate before mastectomy was 69% ((18(26)) patients). At mastectomy primary wound closure (without requiring interposition of tissue flaps) was achieved in all patients: no increase post-operative morbidity was detected. At pathological evaluation there were 5 pCR (19%), 2 pPR (8%) and the remaining nineteen patients had macroscopic persistence of cancer (pNR). No correlation was found between clinical and pathological complete response (p=1.00, Fisher exact test). p53 mutation expression was present in (13(19)) (68%) of the pNR patients and in none of the 7 patients with pCR and pPR. All the tumors expressing p53

  14. RTOG 0529: A Phase II Evaluation of Dose-Painted Intensity Modulated Radiation Therapy in Combination with 5-Fluorouracil and Mitomycin-C for the Reduction of Acute Morbidity in Carcinoma of the Anal Canal

    Science.gov (United States)

    Kachnic, Lisa A.; Winter, Kathryn; Myerson, Robert J.; Goodyear, Michael D.; Willins, John; Esthappan, Jacqueline; Haddock, Michael G.; Rotman, Marvin; Parikh, Parag J.; Safran, Howard; Willett, Christopher G.

    2012-01-01

    Purpose A multi-institutional phase II trial assessed the utility of dose-painted IMRT (DP-IMRT) in reducing grade 2+ combined acute gastrointestinal and genitourinary adverse events (AEs) of 5-fluorouracil (5FU) and mitomycin-C (MMC) chemoradiation for anal cancer by at least 15% as compared to the conventional radiation/5FU/MMC arm from RTOG 9811. Methods and Materials T2-4N0-3M0 anal cancer patients received 5FU and MMC days 1 and 29 of DP-IMRT, prescribed per stage - T2N0: 42Gy elective nodal and 50.4Gy anal tumor planning target volumes (PTVs) in 28 fractions; T3-4N0-3: 45Gy elective nodal, 50.4Gy ≤ 3cm or 54Gy > 3cm metastatic nodal and 54Gy anal tumor PTVs in 30 fractions. The primary endpoint is described above. Planned secondary endpoints assessed all AEs and the investigator’s ability to perform DP-IMRT. Results Of 63 accrued patients, 52 were evaluable. Tumor stage included: 54% II, 25% IIIA, 21% IIIB. In primary endpoint analysis, 77% experienced grade 2+ gastrointestinal/genitourinary acute AEs (9811 77%). There was, however, a significant reduction in acute grade 2+ hematologic, 73% (9811 85%, P=0.032), grade 3+ gastrointestinal, 21% (9811 36%, P=0.0082), and grade 3+ dermatologic AEs 23% (9811 49%, P<0.0001) with DP-IMRT. On initial pre-treatment review, 81% required DP-IMRT re-planning, while final review revealed only three cases with normal tissue major deviations. Conclusions Although the primary endpoint was not met, DP-IMRT was associated with significant sparing of acute grade 2+ hematologic, and grade 3+ dermatologic and gastrointestinal toxicity. While DP-IMRT proved feasible, the high pre-treatment planning revision rate emphasizes the importance of real-time radiation quality assurance for IMRT trials. PMID:23154075

  15. RTOG 0529: A Phase 2 Evaluation of Dose-Painted Intensity Modulated Radiation Therapy in Combination With 5-Fluorouracil and Mitomycin-C for the Reduction of Acute Morbidity in Carcinoma of the Anal Canal

    Energy Technology Data Exchange (ETDEWEB)

    Kachnic, Lisa A., E-mail: lisa.kachnic@bmc.org [Department of Radiation Oncology, Boston University Medical Center, Boston, Massachusetts (United States); Winter, Kathryn [Radiation Therapy Oncology Group Statistical Center, Philadelphia, Pennsylvania (United States); Myerson, Robert J. [Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri (United States); Goodyear, Michael D. [Department of Medicine, Dalhousie University, Halifax (Canada); Willins, John [Department of Radiation Oncology, Boston University Medical Center, Boston, Massachusetts (United States); Esthappan, Jacqueline [Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri (United States); Haddock, Michael G. [Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (United States); Rotman, Marvin [Department of Radiation Oncology, State University of New York—Downstate Medical Center, Brooklyn, New York (United States); Parikh, Parag J. [Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri (United States); Safran, Howard [Department of Medicine, Brown University, Providence, Rhode Island (United States); Willett, Christopher G. [Department of Radiation Oncology, Duke University, Durham, North Carolina (United States)

    2013-05-01

    Purpose: A multi-institutional phase 2 trial assessed the utility of dose-painted intensity modulated radiation therapy (DP-IMRT) in reducing grade 2+ combined acute gastrointestinal and genitourinary adverse events (AEs) of 5-fluorouracil (5FU) and mitomycin-C (MMC) chemoradiation for anal cancer by at least 15% compared with the conventional radiation/5FU/MMC arm from RTOG 9811. Methods and Materials: T2-4N0-3M0 anal cancer patients received 5FU and MMC on days 1 and 29 of DP-IMRT, prescribed per stage: T2N0, 42 Gy elective nodal and 50.4 Gy anal tumor planning target volumes (PTVs) in 28 fractions; T3-4N0-3, 45 Gy elective nodal, 50.4 Gy ≤3 cm or 54 Gy >3 cm metastatic nodal and 54 Gy anal tumor PTVs in 30 fractions. The primary endpoint is described above. Planned secondary endpoints assessed all AEs and the investigator’s ability to perform DP-IMRT. Results: Of 63 accrued patients, 52 were evaluable. Tumor stage included 54% II, 25% IIIA, and 21% IIIB. In primary endpoint analysis, 77% experienced grade 2+ gastrointestinal/genitourinary acute AEs (9811 77%). There was, however, a significant reduction in acute grade 2+ hematologic, 73% (9811 85%, P=.032), grade 3+ gastrointestinal, 21% (9811 36%, P=.0082), and grade 3+ dermatologic AEs 23% (9811 49%, P<.0001) with DP-IMRT. On initial pretreatment review, 81% required DP-IMRT replanning, and final review revealed only 3 cases with normal tissue major deviations. Conclusions: Although the primary endpoint was not met, DP-IMRT was associated with significant sparing of acute grade 2+ hematologic and grade 3+ dermatologic and gastrointestinal toxicity. Although DP-IMRT proved feasible, the high pretreatment planning revision rate emphasizes the importance of real-time radiation quality assurance for IMRT trials.

  16. Combination of the histone deacetylase inhibitor depsipeptide and 5-fluorouracil upregulates major histocompatibility complex class II and p21 genes and activates caspase-3/7 in human colon cancer HCT-116 cells.

    Science.gov (United States)

    Okada, Kouji; Hakata, Shuko; Terashima, Jun; Gamou, Toshie; Habano, Wataru; Ozawa, Shogo

    2016-10-01

    Epigenetic anticancer drugs such as histone deacetylase (HDAC) inhibitors have been combined with existing anticancer drugs for synergistic or additive effects. In the present study, we found that a very low concentration of depsipeptide, an HDAC inhibitor, potentiated the antitumor activity of 5-fluorouracil (5-FU) in a human colon cancer cell model using HCT-116, HT29, and SW48 cells via the inhibition of colony formation ability or cellular viability. Exposure to a combination of 5-FU (1.75 µM) and 1 nM depsipeptide for 24 and 48 h resulted in a 3- to 4-fold increase in activated caspase-3/7, while 5-FU alone failed to activate caspase-3/7. Microarray and subsequent gene ontology analyses revealed that compared to 5-FU or depsipeptide alone, the combination treatment of 5-FU and depsipeptide upregulated genes related to cell death and the apoptotic process consistent with the inhibition of colony formation and caspase-3/7 activation. These analyses indicated marked upregulation of antigen processing and presentation of peptide or polysaccharide antigen via major histocompatibility complex (MHC) class (GO:0002504) and MHC protein complex (GO:0042611). Compared with vehicle controls, the cells treated with the combination of 5-FU and depsipeptide showed marked induction (3- to 8.5-fold) of expression of MHC class II genes, but not of MHC class I genes. Furthermore, our global analysis of gene expression, which was focused on genes involved in the molecular regulation of MHC class II genes, showed enhancement of pro-apoptotic PCAF and CIITA after the combination of 5-FU and depsipeptide. These results may indicate a closer relationship between elevation of MHC class II expression and cellular apoptosis induced by the combination of depsipeptide and 5-FU. To the best of our knowledge, this is the first study to report that the combination of 5-FU and depsipeptide induces human colon cancer cell apoptosis in a concerted manner with the induction of MHC

  17. Targeting the microRNA-21/AP1 axis by 5-fluorouracil and pirarubicin in human hepatocellular carcinoma

    Science.gov (United States)

    He, Xiaodong; Li, Jingjing; Guo, Weidong; Liu, Wei; Yu, Jia; Song, Wei; Dong, Lei; Wang, Fang; Yu, Shuangni; Zheng, Yi; Chen, Songsen; Kong, Yan; Liu, Changzheng

    2015-01-01

    MicroRNAs function as oncomiRs and tumor suppressors in diverse cancers. However, the utility of specific microRNAs in predicting the clinical benefit of chemotherapy has not been well-established. Here, we investigated the correlation between microRNA-21 expression and hepatic arterial infusion chemotherapy with 5-fluorouracil and pirarubicin (HAIC) for hepatocellular carcinoma (HCC). We found that HCC patients with low microRNA-21 levels in tumors tended to have a longer time to recurrence and disease-free survival. We demonstrated that microRNA-21 suppression in combination with 5-fluorouracil and pirarubicin treatment inhibited tumor growth in subcutaneous xenograft mice models. Mechanistically, the AP-1 and microRNA-21-mediated axis was verified to be a therapeutic target of cytotoxic drugs and deregulation of this axis led to an enhanced cell growth in HCC. Taken together, our findings demonstrate that microRNA-21 is a chemotherapy responsive microRNA and can serve as a prognostic biomarker for HCC patients undergoing HAIC. Targeting microRNA-21 enhances the effect of chemotherapeutic drugs, thereby suggesting that microRNA-21 suppression in combination with HAIC may be a novel approach for HCC treatment. PMID:25544773

  18. Metastatic basaloid-squamous cell carcinoma of the esophagus treated by 5-fluorouracil and cisplatin

    Institute of Scientific and Technical Information of China (English)

    Yoshihiro Shibata; Hirokazu Noshiro; Takashi Yao; Shuji Nakano; Eishi Baba; Hiroshi Ariyama; Ryusuke Miki; Nobumichi Ogami; Shuji Arita; Baoli Qin; Hitoshi Kusaba; Kenji Mitsugi

    2007-01-01

    Basaloid squamous cell carcinoma (BSC) of the esophagus is a rare malignant disease. We report here a patient with recurrent esophageal BSC, who was successfully treated by systemic chemotherapy containing 5-fluorouracil (5-FU) and cisplatin (CDDP). A 57-year-old woman was diagnosed as having squamous cell carcinoma of the esophagus upon endoscopic examination. Curative esophagectomy with lymph node dissection was performed under the thoracoscope. The pathological diagnosis of the surgical specimen was BSC.Five months after operation, the patient was diagnosed as having a recurrence of the BSC with metastases to the liver and spleen, and a right paraclavicular lymph node. She was given systemic chemotherapy consisting ofcontinuous infusion of 800 mg/d of 5-FU and 3 h infusion of 20 mg/d of CDDP for 5 consecutive days every 4 wk. The metastatic lesions in the spleen and right paraclavicular lymph node disappeared, and the liver metastasis was apparently reduced in size after 2 courses of chemotherapy. The tumor regression was seen over 6 courses, with progression afterwards.Although subsequent treatment with CPT-11 and CDDP was not effective, docetaxel and vinorelbine temporarily controlled the tumor growth for 2 mo. 5-FU and CDDP combination may be useful for the patients with advanced BSC.

  19. 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....

  20. The Synthesis of 6-Alkyl-5-Fluorouracil Derivatives

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    6-alkyl-5-fluorouracil derivatives (5a~5f) were synthesized by facile alkylation of lithiation of 5-fluorouracil derivatives with mthyl iodide (MeI) or alkyl trifluoromethanesulfonate (ROTf) in yield of 42~58%. We found that the methylated product was ethyl-substituted derivatives, not methyl-substituted derivatives.

  1. A new promising treatment in systemic sclerosis: 5-fluorouracil.

    OpenAIRE

    Casas, J. A.; Subauste, C P; Alarcón, G S

    1987-01-01

    Twelve patients with systemic sclerosis according to American Rheumatism Association criteria were treated with intravenous 5-fluorouracil. Significant subjective and objective improvement occurred initially in the skin and subsequently in the involved viscera and vasculature. These preliminary results suggest that 5-fluorouracil may be an effective treatment for systemic sclerosis.

  2. 5-Fu静脉泵持续输注与口服希罗达治疗消化道肿瘤的安全性及疗效的观察%Continuous-infusion 5-Fluorouracil versus Xeloda for gastrointestinal cancer: A safety and efficacy observation

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective: We assessed the safety and efficacy of two regimens for patients with gastrointestinal cancers: continuous-infusion (CI) schedules of 5-Fluorouracil (5-Fu) plus a platinum (cisplatin or oxaiiplatin) with/or without paclitaxel (regimen A) versus Xeloda plus a platinum (cisplatin or oxaliplatin) with/or without paclitaxel for oral use (regimen B) in patients with gastrointestinal cancers. Methods: Between May 2003 and May 2005, 84 patients diagnosed in Jiangsu Cancer Hospital & Research Institute with locally advanced esophageal, gastric or colorectal cancer were registered. Regimen A and B consisted of either 5-Fu 0.375 C I days 1-14, every 28 days (n = 44), or Xeloda 1000 mg twice daily, days 1-14, every 28 days (n= 40). For both regimen A and B, Ⅳ cisplatin 25 mg/m2 was administered on day 1, 2 and 3 (or Oxaliplatin 75mg/m2 on day 1, 8 and 15) with or without paclitaxel 60-75 mg/m2 on day1, 8 and 15. Results: Patients receiving regimen B experienced significantly less stomatitis (P < 0.05) and diarrhea (P < 0.05), than those receiving regimen A. Prevalence of nausea/vomiting,alopecia, neutropenia, and hand-foot syndrome without significant difference between two regimens. No treatment related death occurred during study period. Regimen B demonstrates a similar, favorable safety profile in this study. Response rates and rates of clinical benefit for regimen A and B were 40.9%, 40.0% and 43.2%, 65.0% respectively. Conclusion: Based on its improved safety profile and improved rate of clinical benefit, Xeloda has the potential to replace CI 5-FU as an alternative treatment for patients with gastrointestinal cancers.

  3. Neoadjuvant Bevacizumab, Oxaliplatin, 5-Fluorouracil, and Radiation for Rectal Cancer

    Energy Technology Data Exchange (ETDEWEB)

    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.

  4. A Phase II Study of Docetaxel, Cisplatin and 5- Fluorouracil (TPF) In Patients with Locally Advanced Head and Neck Carcinomas

    OpenAIRE

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

    2011-01-01

    Background 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. Methods Forty-six patients with previously untreated non-metastatic stage IV head and neck carcinomas were enrolled. All patients received three cycles o...

  5. Preoperative docetaxel/cisplatin/5-fluorouracil chemotherapy in patients with locally advanced gastro-esophageal adenocarcinoma.

    Science.gov (United States)

    Bayraktar, Ulas Darda; Bayraktar, Soley; Hosein, Peter; Chen, Emerson; Koniaris, Leonidas G; Rocha-Lima, Caio Max S; Montero, Alberto J

    2012-09-01

    Perioperative chemotherapy plus surgery improves survival compared to surgery alone in GE junctional (GEJ) and gastric adenocarcinomas. The docetaxel/cisplatin/5-fluorouracil (DCF) combination is superior to CF in patients with metastatic gastric cancer. We retrospectively evaluated the safety and efficacy of preoperative DCF chemotherapy in patients with locally advanced gastric and GEJ cancer. Twenty-one gastric and 10 gastroesophageal junctional (GEJ) cancer patients received 2-3 cycles of preoperative docetaxel 75 mg/m(2) and cisplatin 75 mg/m(2) on day 1, 5-FU 750 mg/m(2) (continuous infusion) on days 1-5 every 3 weeks. Clinical response was evaluated by comparing pre- and postchemotherapy CT scans. Overall survival (OS) and progression-free survival (PFS) were calculated from the initiation of chemotherapy. None of the patients achieved complete clinical remission while 11 (35%) patients achieved partial clinical remission. Ten patients with GEJ cancer (100%) and 13 with gastric cancer (62%) underwent curative surgery (P = 0.023). Seventeen (55%) patients experienced grade 3-4 chemotherapy-related adverse events. The most common adverse events were anemia, nausea/vomiting, diarrhea, and febrile neutropenia. At a median follow-up of 17.0 months, median OS and PFS were 26.1 months (95% CI: 22.7-29.5) and 18.8 months (95% CI: 9.9-27.7), respectively. The DCF regimen is active in patients with gastric and GEJ adenocarcinoma in the preoperative setting.

  6. Quality of life of palliative chemotherapy naive patients with advanced adenocarcinoma of the stomach or esophagogastric junction treated with irinotecan combined with 5-fluorouracil and folinic acid: results of a randomised phase III trial.

    LENUS (Irish Health Repository)

    Curran, Desmond

    2009-09-01

    PURPOSE: The quality of life (QL) of advanced gastric cancer patients receiving irinotecan, folinic acid and 5-fluorouracil (5-FU) (IF arm) or cisplatin with 5-FU (CF arm) is presented. METHODS: Patients with measurable or evaluable advanced gastric cancer received IF weekly for 6\\/7 weeks or CF q4 weeks. QL was assessed using the EORTC QLQ-C30 at baseline, subsequently every 8 weeks until progression and thereafter every 3 months until death. The QL data were analysed using several statistical methods including summary measures and pattern-mixture modelling. RESULTS: A total of 333 patients were randomised and treated (IF 170, CF 163). The time-to-progression for IF and CF was 5.0 and 4.2 months (P = 0.088), respectively. The overall compliance rates for QL questionnaire completion were 60 and 56% in the IF and CF arms, respectively. Significant treatment differences were observed for the physical functioning scale (P = 0.024), nausea\\\\vomiting (P = 0.001) and EQ-5D thermometer (P = 0.020) in favour of the IF treatment arm. CONCLUSION: There was a trend in favour of IF over CF in time-to-progression. The IF group also demonstrated a better safety profile than CF and a better QL on a number of multi-item scales, suggesting that IF offers an alternative first-line platinum-free treatment option for advanced gastric cancer.

  7. Summarize Nursing Experience of the Tumor Patients by Using Auto Chemotherapy Pump Continuous Intravenous Infusion in 5-FU (5-fluorouracil)Chemotherapy%总结肿瘤患者应用全自动化疗泵持续静脉输注5-FU(5-氟尿嘧啶)化疗的护理经验

    Institute of Scientific and Technical Information of China (English)

    魏美霞

    2013-01-01

    Objective:To observe the fully automatic continuous chemotherapy pump infusion of 5-FU(5-fluorouracil)chemotherapy in tumor patients,summarize nursing experience in the use of automatic chemotherapy pump.Method:70 cases patients with using automatic chemotherapy pump continuous infusion of 5-FU chemotherapy were given clinical care packet observation,the observation group was given health education path table during chemotherapy nursing,the intervention control group was given traditional health education.Compared patients during chemotherapy toxicity and nursing satisfaction.Result:The observation group during chemotherapy toxicity was significantly less than that of the control group,the difference was satistically significant between the groups(P<0.01),discharge patient care satisfaction of the observation group was higher than that in the control group,the difference was statistically significant between the groups(P<0.01).Conclusion:Health education path table nursing intervention during chemotherapy can reduce various toxicities during chemotherapy and improve patient satisfaction with care work.%  目的:观察全自动化疗泵持续静脉输注5-FU(5-氟尿嘧啶)化疗在肿瘤患者中的应用,总结全自动化疗泵使用中的护理经验。方法:对70例使用全自动化疗泵持续静脉输注5-FU化疗的患者进行临床护理分组观察,观察组采用健康教育路径表进行化疗期间的护理干预,对照组采用传统健康宣教。对两组患者化疗过程中的毒副反应以及护理满意度进行比较。结果:观察组化疗期间出现的毒副反应明显少于对照组,比较差异有统计学意义(P<0.01),出院时患者对护理满意度观察组亦高于对照组,比较差异有统计学意义(P<0.01)。结论:采用健康教育路径表进行化疗期间的护理干预,能够减少化疗期间的各类毒副反应,并提高患者对护理工作的满意度。

  8. Sequence-dependence of cisplatin and 5-fluorouracil in advanced and recurrent gastric cancer.

    Science.gov (United States)

    Koizumi, Wasaburo; Kurihara, Minoru; Hasegawa, Koichi; Chonan, Akimichi; Kubo, Yasuhiko; Maekawa, Ryuichiro; Iwasaki, Ryozo; Sasai, Tadashi; Fukuyama, Yoshio; Ishikawa, Kunitsugu; Miyoshi, Kazuo; Yasutake, Koichi; Hayakawa, Makoto

    2004-09-01

    This randomized controlled clinical trial was designed to compare the safety and effectiveness of different sequences of treatment with cisplatin (CDDP) and 5-fluorouracil (5-FU) in patients with unresectable advanced and post-operative recurrent gastric cancer. Patients with unresectable advanced or post-operative recurrent gastric cancer were randomly assigned by a registration center to group A or B. Group A received CDDP (80 mg/m(2)) as a continuous 2-h intravenous infusion on day 1 and 5-FU (700 mg/m(2)) as a continuous intravenous infusion on days 2-5. Group B was given 5-FU (700 mg/m(2)) as a continuous intravenous infusion on days 1-4, followed by CDDP (80 mg/m(2)) as a continuous 2-h intravenous infusion on day 5. Each course of chemotherapy was repeated every 28 days. A total of 74 patients were enrolled. One patient died accidentally, and 5 could not be evaluated. Response was assessable in 68 patients. The response rate was 31.3% (10/32) in group A as compared with 13.9% (5/36) in group B. Although the response rate was higher in Group A, the difference was not significant (p=0.085). The response rate in patients with diffuse type tumors was significantly lower in group B. There was no difference between the groups in response among patients with intestinal type tumors. The median overall survival was 239 and 174 days and time to progression was 175 and 140 days in group A and group B, respectively. Although there were trends toward longer survival and time to progression in group A, the differences between the groups were not statistically significant. There was also no difference in the type or incidence of adverse reactions. The results of this controlled study indicate that the overall response rate was slightly but not significantly higher in patients who received CDDP before 5-FU. Among patients with diffuse type tumors, the response rate was significantly lower when 5-FU was administered before CDDP. Our results suggest that CDDP should be given

  9. Postoperative adjuvant radiotherapy and 5-fluorouracil chemotherapy for rectal carcinoma

    International Nuclear Information System (INIS)

    Postoperative combined modality therapy with radiotherapy and 5-fluorouracil (5FU) chemotherapy is an effective adjuvant approach that reduces locoregional and distant metastatic disease in patients with high-risk rectal carcinoma. However, this approach results in a treatment regimen of at least 6 months' duration. The present prospective study investigates the integration of radiotherapy and 5FU chemotherapy in a protocol designed to minimize toxicity and reduce the overall treatment time. A total of 40 patients with TNM stage 11 or 111 disease receives postoperative radiotherapy at four fractions per week with weekly 5FU bolus injections delivered on the fifth non radiotherapy day. Patients also received systemic chemotherapy with leucovorin both before and after pelvic irradiation, with the total treatment duration extending for only 18 weeks. Patients were able to complete radiotherapy in 90% of cases, while the delivery of full-dose chemotherapy was achievable in the vast majority. The incidence of haematologic and gastrointestinal toxicities requiring the cessation of treatment was acceptable. With a median follow-up of 20.9 months among surviving patients, the estimated progression-free and overall survival at 2 years were 71% and 79%, respectively. Copyright (1998) Blackwell Science Pty Ltd

  10. Schedule-selective biochemical modulation of 5-fluorouracil in advanced colorectal cancer – a phase II study

    Directory of Open Access Journals (Sweden)

    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.

  11. Autophagy in 5-Fluorouracil Therapy in Gastrointestinal Cancer: Trends and Challenges

    OpenAIRE

    Jia-Cheng Tang; Yi-Li Feng; Xiao Liang; Xiu-Jun Cai

    2016-01-01

    Objective: 5-Fluorouracil (5-FU)-based combination therapies are standard treatments for gastrointestinal cancer, where the modulation of autophagy is becoming increasingly important in offering effective treatment for patients in clinical practice. This review focuses on the role of autophagy in 5-FU-induced tumor suppression and cancer therapy in the digestive system. Data Sources: All articles published in English from 1996 to date those assess the synergistic effect of autophagy and 5-...

  12. Conjugation of Chitooligosaccharide-5-fluorouracil with Bovine Serum Albumin

    Institute of Scientific and Technical Information of China (English)

    Rong Min WANG; Jing Feng SONG; Yu Feng HE; Juan Juan MAO; Yan LI

    2006-01-01

    The interaction between chitooligosaccharide-5-fluorouracil (COS-5FU) and bovine serum albumin (BSA) was studied by fluorescence spectroscopy. It was found that an energy transfer between COS-5FU and BSA had been occurred. The binding constants were calculated,between the donor and acceptor, the distance between BSA and COS-5FU was determined.

  13. Changes in thymidylate synthase mRNA in blood leukocytes from patients with colorectal cancer after bolus administration of 5-fluorouracil

    DEFF Research Database (Denmark)

    Ehrnrooth, E; Sørensen, B; Poulsen, J H;

    2000-01-01

    5-fluorouracil (5-FU) is considered the standard antineoplastic drug of choice for metastatic colorectal cancer. It has been suggested that 5-FU administered as bolus infusion is cytotoxic mainly through an RNA damaging effect. We investigated the effect of i.v. bolus 5-FU 500-600 mg/m2 on the 5-FU...

  14. Combination chemotherapy with 5-fluorouracil (5FU) and 1,3-bis(2-chloro-ethyl)-1-nitrosourea (BCNU) prolongs survival of rats with dimethylhydrazine-induced colon cancer.

    OpenAIRE

    Danzi, M; Lewin, M R; Cruse, J P; Clark, C G

    1983-01-01

    The effects of combination chemotherapy with 5FU and BCNU on rats with dimethylhydrazine (DMH)-induced colon cancer were investigated in a long term survival study. Eighty Wistar rats received a colon cancer producing regimen on DMH (40 mg/kg body weight/week, subcutaneously for 10 weeks). After presenting with signs of colonic disease, all rats underwent diagnostic laparotomy and colonoscopy when colon tumours were located, measured and the extent of the disease staged. Only animals with tum...

  15. Hydrogen–water enhances 5-fluorouracil-induced inhibition of colon cancer

    Directory of Open Access Journals (Sweden)

    Joshua Runtuwene

    2015-04-01

    Full Text Available Oxidative stress is involved in cancer development. Hydrogen (H2 is a potent antioxidant and exhibits anti-inflammatory and potentially anticancer-like activities. This study aimed to investigate the role of H2 incombination with 5-fluorouracil (5-FU in cancer treatment both in vitro and in vivo using the colon 26 cell line. The survival rate was determined using the Kaplan–Meier survival test, and cell viability was assessed using cell viability imaging kit and the MTT assay, and activation of the cell apoptosis pathway (Phosphorylated adenosine monophosphate activated protein kinase (p-AMPK, Apoptosis-inducing factor (AIF and Caspase 3 were characterized by western blots. Hydrogen water administration improved the survival of mice with colon 26-induced cancer. Furthermore, hydrogen water enhanced cell apoptosis in cancer cells, resulting in a marked increase in the expression of p-AMPK, AIF and Caspase 3 in colon 26 cells. Hydrogen water also increased the inhibitory effect of 5-FU on colon 26 cells with spect to cell survival rate and anticancer functions. Additionally, high-content hydrogen water exhibited stronger antioxidative and anticancer activity than did the natural hydrogen water. In conclusion, high-content hydrogen water can inhibit colon cancer, particularly in combination with 5-fluorouracil.

  16. Hydrogen–water enhances 5-fluorouracil-induced inhibition of colon cancer

    Science.gov (United States)

    Runtuwene, Joshua; Amitani, Marie; Asakawa, Akihiro; Cheng, Kai-Chun; Inui, Akio

    2015-01-01

    Oxidative stress is involved in cancer development. Hydrogen (H2) is a potent antioxidant and exhibits anti-inflammatory and potentially anticancer-like activities. This study aimed to investigate the role of H2 incombination with 5-fluorouracil (5-FU) in cancer treatment both in vitro and in vivo using the colon 26 cell line. The survival rate was determined using the Kaplan–Meier survival test, and cell viability was assessed using cell viability imaging kit and the MTT assay, and activation of the cell apoptosis pathway (Phosphorylated adenosine monophosphate activated protein kinase (p-AMPK), Apoptosis-inducing factor (AIF) and Caspase 3) were characterized by western blots. Hydrogen water administration improved the survival of mice with colon 26-induced cancer. Furthermore, hydrogen water enhanced cell apoptosis in cancer cells, resulting in a marked increase in the expression of p-AMPK, AIF and Caspase 3 in colon 26 cells. Hydrogen water also increased the inhibitory effect of 5-FU on colon 26 cells with spect to cell survival rate and anticancer functions. Additionally, high-content hydrogen water exhibited stronger antioxidative and anticancer activity than did the natural hydrogen water. In conclusion, high-content hydrogen water can inhibit colon cancer, particularly in combination with 5-fluorouracil. PMID:25870767

  17. Hydrogen-water enhances 5-fluorouracil-induced inhibition of colon cancer.

    Science.gov (United States)

    Runtuwene, Joshua; Amitani, Haruka; Amitani, Marie; Asakawa, Akihiro; Cheng, Kai-Chun; Inui, Akio

    2015-01-01

    Oxidative stress is involved in cancer development. Hydrogen (H2) is a potent antioxidant and exhibits anti-inflammatory and potentially anticancer-like activities. This study aimed to investigate the role of H2 incombination with 5-fluorouracil (5-FU) in cancer treatment both in vitro and in vivo using the colon 26 cell line. The survival rate was determined using the Kaplan-Meier survival test, and cell viability was assessed using cell viability imaging kit and the MTT assay, and activation of the cell apoptosis pathway (Phosphorylated adenosine monophosphate activated protein kinase (p-AMPK), Apoptosis-inducing factor (AIF) and Caspase 3) were characterized by western blots. Hydrogen water administration improved the survival of mice with colon 26-induced cancer. Furthermore, hydrogen water enhanced cell apoptosis in cancer cells, resulting in a marked increase in the expression of p-AMPK, AIF and Caspase 3 in colon 26 cells. Hydrogen water also increased the inhibitory effect of 5-FU on colon 26 cells with spect to cell survival rate and anticancer functions. Additionally, high-content hydrogen water exhibited stronger antioxidative and anticancer activity than did the natural hydrogen water. In conclusion, high-content hydrogen water can inhibit colon cancer, particularly in combination with 5-fluorouracil. PMID:25870767

  18. Infliximab enhances the therapeutic effects of 5-fluorouracil resulting in tumor regression in colon cancer

    Science.gov (United States)

    Liu, Fen; Ai, Feiyan; Tian, Li; Liu, Shaojun; Zhao, Lian; Wang, Xiaoyan

    2016-01-01

    Colon cancer (CC) is among the most common malignant diseases with a dismal survival. Tumor necrosis factor-alpha (TNF-α) has been identified as a therapeutic target in various cancers, and anti-TNF-α treatment has shown promising effects in different cancer models. However, if TNF-α can be targeted in CC, the therapeutic values of anti-TNF-α treatment in CC remain unknown. Our study indicated that TNF-α is highly expressed in CC cell lines and patient tumor samples. High expression of TNF-α is an independent adverse prognosticator of CC. Targeting the TNF-α by its antibody infliximab induced antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity and enhanced apoptosis leading to cell death. The combination of infliximab with 5-fluorouracil showed better responses in vitro and in vivo than 5-fluorouracil alone. In conclusion, this study identified TNF-α as a target of CC and anti-TNF-α treatment synergized with chemotherapy leading to a better outcome in preclinical models. PMID:27757041

  19. Controlled release of 5-fluorouracil and progesterone from magnetic nanoaggregates

    Directory of Open Access Journals (Sweden)

    Ragab DM

    2012-06-01

    Full Text Available Doaa M Ragab,1 Sohrab Rohani,1 Styliani Consta21Department of Chemical and Biochemical Engineering, 2Department of Chemistry, The University of Western Ontario, London, Ontario, CanadaBackground: The potential use of magnetic nanoparticles in biomedical applications has witnessed an exponential growth in recent years.Methods: In this study, we used nanoaggregates of magnetic nanoparticles as carriers for controlled drug delivery. The nanoaggregates are formed due to the presence of the block copolymer of polyethylene oxide-polypropylene oxide (Pluronic F-68 and beta-cyclodextrin that surround the magnetic core of the nanoparticles. The administration of the drug carriers occurs by inhalation, and the drug is delivered systemically via the pulmonary route. We tested the delivery of 5-fluorouracil and progesterone, which are used as models of hydrophilic and hydrophobic drugs, respectively.Results: The estimated nanoaggregates' diameters are between 293 nm ± 14.65 nm and 90.2 nm ± 4.51 nm, respectively. In-situ and post-synthesis techniques are two approaches for drug loading. The polymer composition of nanoaggregates and initial drug concentration showed a significant effect on both the drug entrapment efficiency and release kinetics. Average drug entrapment efficiencies ranged between 16.11% and 83.25%. In-situ loaded samples showed significantly slower release rates. The drug release mechanism is investigated by mathematical curve fitting to different drug release kinetics models. In most cases, the Peppas model has shown good correlations (coefficients of correlation, R2, between 0.85 and 0.99 with the examined release profiles. The estimated release indices are below 0.5, which indicates the Fickian diffusion mechanism. For samples with an initial burst effect, the modified Peppas model can provide a better understanding of the drug release mechanism, both in the samples loaded with progesterone, or those high polymer concentrations

  20. Treatment of verruca plana with 5% 5-fluorouracil ointment.

    Science.gov (United States)

    Lee, S; Kim, J G; Chun, S I

    1980-01-01

    11 patients with verruca plana were treated with 5% 5-Fluorouracil ointment as a twice daily topical application with open dressing. The patients were chosen among those who failed to be cured with avrious topical agents such as salicylic acid, vitamin A acid and dinitrochlorobenzene (DNCB), or even with carbon dioxide cryotherapy, oral administration of methotrexate and intramuscular injection of sodium cacodylate. In 9 patients, all the treated warts completely disappeared within 3--5 weeks. 2 of these patients had recurrence after 3 weeks and 2 months, respectively. In 2 patients, some lesions disppeared while others failed to be healed. The major clinical adverse reactions were hyperpigmentation (8 cases), erythema (5 cases) and erosion (5 cases). PMID:7389971

  1. Breast Cancer Resistance Protein Expression and 5-Fluorouracil Resistance

    Institute of Scientific and Technical Information of China (English)

    JIAN-HUI YUAN; ZHI-XIONG ZHUANG; JIN-QUAN CHENG; LONG-YUAN JIANG; WEI-DONG JI; LIANG-FENG GUO; JIAN-JUN LIU; XING-YUN XU; JING-SONG HE; XIAN-MING WANG

    2008-01-01

    To filtrate breast cancer resistance protein (BCRP)-mediated resistant agents and to investigate clinical relationship between BCRP expression and drug resistance. Methods MTT assay was performed to filtrate BCRP-mediated resistant agents with BCRP expression cell model and to detect chemosensitivity of breast cancer tissue specimens to these agents. A high performance liquid chromatography (HPLC) assay was established, and was used to measure the relative dose of intracellular retention resistant agents. RT-PCR and immununohistochemistry (IHC) were employed to investigate the BCRP expression in breast cancer tissue specimens. Results MTT assay showed that the expression of BCRP increased with the increasing resistance of 5-fluorouracil (5-Fu) (P=0.8124, P<0.01). Condusion Resistance to 5-Fu can be mediated by BCRP. Clinical chemotherapy for breast cancer patients can be optimized based on BCRP-positive expression.

  2. Epithelial Downgrowth after Intraocular Surgery Treated with Intracameral 5-Fluorouracil

    Directory of Open Access Journals (Sweden)

    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.

  3. Subconjunctival sustained release 5-fluorouracil for glaucoma filtration surgery

    Institute of Scientific and Technical Information of China (English)

    Li-jun CUI; Nai-xue SUN; Xing-hua LI; Jie HUANG; Jian-gang YANG

    2008-01-01

    Aim:To determine the release characteristics of a 5-fluorouracil-loaded poly (lactic acid) disc (5-FU-PLA-DS) and the effect of sustained drug delivery on the success of glaucoma filtration surgery in rabbit eyes. Methods: A method of microspheres accumulated by excessive carriers was used in the preparation of the 5-FU-PLA-DS. The disc was characterized for drug loading, entrapment efficiency, in vitro release, and external morphology. It was then implanted sub-conjunctivally into rabbit eyes with trabeculectomy. Intraocular pressure, ocular inflammatory reaction, filtration bleb appearance, and persistence were evalu-ated up to postoperative d 90. A quantitative analysis of 5-fluorouracil (5-FU) was performed in the aqueous humor. Ultrasound biomicroscopy was used to assess the appearance of the filtering fistula. Results: The 5-FU-PLA-DS was produced with the drug-loading of 3.07±0.08 mg (mean±SD). 5-FU was released for 91 d with suppressive concentrations. The decrease in intraocular pressure from baseline was significantly more marked in the 5-FU-PLA-DS-implanted eyes during postoperative d 3-90, and the persistence of bleb and filtration fistula was longer than the control eyes (P<0.05). Corneal toxicity and hyperemia triggered by 5-FU was lower in the 5-FU-PLA-DS-implanted eyes than those exposed to 5-FU intraoperatively. The 5-FU concentration in the aqueous humor was insufficient for corneal endothelial damage. No evidence of toxic reaction was found in the conjunctival biopsy. Conclusion: 5-FU-PLA-DS displaying sustained intraocular release of 5-FU, reduced intraocular pres-sure, and prolonged bleb persistence, while significantly reducing 5-FU toxicity.

  4. Bevacizumab plus infusional 5-fluorouracil, leucovorin and irinotecan for advanced colorectal cancer that progressed after oxaliplatin and irinotecan chemotherapy: A pilot study

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To evaluate the combination of bevacizumab with infusional 5-fluorouracil (5-FU), leucovorin (LV) and irinotecan (FOLFIRI) in patients with advanced colorectal cancer (CRC) pretreated with combination regimens including irinotecan and oxaliplatin.METHODS: Fourteen patients (median age 56 years) with advanced CRC, all having progressed after oxaliplatin- and irinotecan-based combination chemotherapy, were enrolled in this study. Patients were treated with 2 h infusion of irinotecan 150 mg/m2 on d 1, plus bevacizumab 5 mg/kg iv infusion for 90 min on d 2, and iv injection of LV 20 mg/m2 followed by a bolus of 5-FU 400 mg/m2 and then 22 h continuous infusion of 600 mg/m2 given on two consecutive days every 14 d.RESULTS: The median number of cycles of chemotherapy was six (range 3-12). The response rate was 28.5%, one patient had a complete response, and three patients had a partial response. Eight patients had stable disease. The median time to progression was 3.9 mo (95% CI 2.0-8.7),and the median overall survival was 10.9 mo (95% CI 9.6-12.1). Grade 3/4 neutropenia occurred in five patients, and two of these developed neutropenic fever.Grade 3 hematuria and hematochezia occurred in one.Grade 2 proteinuria occurred in two patients. However,hypertension, bowel perforation or thromboembolic events did not occur in a total of 90 cycles.CONCLUSION: Bevacizumab with FOLFIRI is well tolerated and a feasible treatment in patients with heavily treated advanced CRC.

  5. Pharmacokinetic characteristics and anticancer effects of 5-Fluorouracil loaded nanoparticles

    Directory of Open Access Journals (Sweden)

    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

  6. 丹参联合5-氟尿嘧啶腹腔注射对大鼠胃肿瘤及其相关蛋白表达的影响%Effects of Radix Salvia Miltiorrhiza Combined with Intraperitoneal Injection of 5-Fluorouracil on Implanted Gastric Tumor and Expression of Gastric Tumor Related Proteins in Rats

    Institute of Scientific and Technical Information of China (English)

    于庆生; 王园; 潘晋方; 王汉明; 帅剑锋; 张琦; 刘举达

    2011-01-01

    Objective To explore the mechanism of Radix Salviae miltiorrhizae (RSM) enhancing antineoplasm effects of 5-fluorouracil (5-Fu) against gastric tumor. Methods The rat model of implanted gastric tumor was induced using Walker-256 cell line. Sixty male rats with gastric tumor were randomized into three groups, namely, normal saline (NS) treated group, 5-Fu treated group, and 5-Fu combined with RSM treated group. Seven days after the implantation of gastric tumor cells, each rat was daily given intraperitoneal injection of NS 40 ml/kg in NS treated group, 5-Fu 20 ml/kg in 5-Fu treated group, and 5-Fu 20 ml/kg plus RSM 60 mg/kg in 5-Fu combined with RSM treated group, respectively, during 5 successive days. After the chemotherapy, the general conditions were observed in rats with implanted gastric tumor of the three groups. The inhibition rates of gastric tumor and the prolongation rates of survival time were compared among the three groups. The expression levels of P53, CD44, H-ras, and nm23 proteins were assayed using immunohistochemistry method. Results (1) Two weeks after the implantation of gastric tumor cells, rats in NS treated group manifestated such symptoms as loss of appetite, decrement of activities, slow response to outside stimuli, gradual emaciation, and even ascites. While in 5-Fu treated group, and 5-Fu combined with RSM treated group, above-mentioned manifestations gradually appeared about 4 weeks after the implantation of gastric tumor cells. (2) Compared with those in NS treated group, the sizes of implanted gastric tumor were significantly decreased in 5-Fu treated group, and 5-Fu combined with RSM treated group. The sizes of implanted gastric tumor and the inhibition rates of tumor size were significantly lower in 5-Fu combined with RSM treated group than those in 5-Fu treated group. (3)The survival time in 5-Fu treated group, and 5-Fu combined with RSM treated group was significantly longer than that in NS treated group; compared with 5-Fu

  7. Study on liver targeting 5-fluorouracil solid lipid nanoparticles

    Institute of Scientific and Technical Information of China (English)

    Zhi Rong Zhang; Bo Tao Yu

    2000-01-01

    AIM To prepare 5-fluorouracil solid lipid nanoparticles (5-FuE-SLN) with liver targeting.METHODS 5-Fu was employed as model drug to acylate with stearyl chloride and obtain 5-Fu precurser N1-stearyl-5-Fu (5-FuE). The precurser was determined by nuclear magnetic resonance and infraredspectrometry and used to prepare 5-FuE-SLN by the method of physical agglomeration. TransmissionElectron Microscopy (TEM) was employed to study the shape, mean size and particle distribution of 5-FuE-SLN. The drug loading, and releasing characteristics in vitro, the drug distribution and pharmacokinetics invivo were also investigated by HPLC method.RESULTS The average diameter was 240.19nm, and the drug loading was 20.53%. The releasingcharacteristics in vitro was fitted to first-order pharmacokinetic model. The distribution of 5-FuE-SLN inmice showed that 5-FuE-SLN had significant liver targeting being compared with 5-Fu injection. Theconcentration of 5-FuE-SLN group in mice liver was double over that of control group. The mainpharmacokinetics parameters in rabbits were as follows: Vc = 0.04336 L·kg-1, T1/2β- 1.2834 h, CL =0.1632 L·h-1CONCLUSION 5-FuE-SLN has the characteristic of liver targeting. Using 5-Fu precurser to enhance itsliposoluble properties and the method of preparation presented in this paper seems to have significantadvantages and important reference value.

  8. Combined infusion cholecystography in patients with the postgastroresection syndromes

    International Nuclear Information System (INIS)

    Using a combined infusion cholecystography in patients with postgastroresection syndromes, the concentration, motor-evacuator function of the biliary bladder and changes in biliary tracts are studied. 71 patients (63 men and 8 women) in the age of 31-65 have been investigated. It is shown that in patients who have suffered resection, the interaction of motor-evacuator function of the gastrointestinal tract.and biliary tracts is upset which can further lead to profound pathologic changes in these organs

  9. Anti-tumor effect of L-methionine-deprived total parenteral nutrition with 5-fluorouracil administration on Yoshida sarcoma-bearing rats.

    Science.gov (United States)

    Goseki, N; Endo, M; Onodera, T; Kosaki, G

    1991-07-01

    L-methionine-deprived total parenteral nutrition (methionine-deprived TPN), infusing amino acid solution devoid of L-methionine and L-cysteine by the method of TPN as an only protein source, showed enhancement of the effect of several anti-cancer agents. In this study the combined effect of the methionine-deprived TPN with administration of 5-fluorouracil (5-FU) was examined in Yoshida Sarcoma (YS)-bearing rats, from aspects of effects on the tumor metastasis and the host animal's life span, in the following four groups treated with: methionine-deprived TPN with administration of 5-FU, methionine-deprived TPN without administration of 5-FU, L-methionine-contained TPN plus 5-FU, and L-methionine-contained TPN without 5-FU. In the first experiment, TPN was continued for 8 days in the four groups, and the anti-cancer effect of methionine-deprived TPN and administration of 5-FU based on both the growth of the primary tumor at the implanted site and the tumor metastasis was studied from the view point of pathologic findings of animals killed immediately after these treatments. In experiment 2 the survival period was examined after these treatments for 10 days with subsequent oral feeding until death. The results were as follows: proliferation of YS, transplanted subcutaneously, was markedly suppressed; particularly hematogenous metastasis, characteristic in YS, was prominently blunted then obtained an apparent longer survival period in rats treated with the methionine-deprived TPN with administration of 5-FU.

  10. Cardiotoxicity in Asymptomatic Patients Receiving Adjuvant 5-fluorouracil

    DEFF Research Database (Denmark)

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

    2014-01-01

    (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...... treatment course. Case report 1 presents a 75-year old woman with a medical history of paroxysmal atrial fibrillation, hypertension and hyperlipidemia. Holter monitoring revealed increasing paroxysms of atrial fibrillation, increased ventricular ectopic activity and episodes of sinoatrial arrest during...... 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...

  11. Combined arteriovenous thrombolytic infusion for refractory renal vein thrombosis.

    Science.gov (United States)

    Heafner, Thomas A; Scott, Daniel; Watson, J Devin; Propper, Brandon; Johnson, Chatt; Arthurs, Zachary M

    2014-08-01

    Acute renal vein thrombosis can rapidly lead to significant impairment and eventual loss of renal function. Classically presenting with flank pain, hematuria, and laboratory markers consistent with acute kidney injury, therapeutic anticoagulation is the mainstay of treatment. However, endovascular surgery offers a safe and effective alternative for renal salvage in the setting of acute renal vein thrombosis. Described is the use of combined arteriovenous thrombolytic infusion for refractory renal vein thromboses to quickly and effectively decrease clot burden in the micro- and macrovenous circulations while limiting systemic exposure.

  12. Synthesis and anticancer properties of tungstosilicic polyoxometalate containing 5-fluorouracil and neodymium

    Institute of Scientific and Technical Information of China (English)

    LIU

    2010-01-01

    A novel tungstosilicic polyoxometalate containing 5-fluorouracil and Nd,K26(C4H4FN2O2)8Nd(SiW11O39)4·SH2O(FNSW)was synthesized and its structure was characterized by using elemental analysis,FT-IR spectra,X-ray powder diffraction,UV-vis spectra and TG.The results indicated that the compound FNSW had Keggin structure of heteropolyanion and ring structure of 5-fluorouracil,and it had a good thermal stability.With 5-fluorouracil for the positive control group,the cytotoxicity tests in human renal embryonic cell HEK293 and the antitumor activity tests in hepatocellular carcinoma cell HepG-2 were carried out by the methyl thiazolyl tetrazolium method.The toxicity of the compound FNSW was lower than that of 5-fluorouracil,and compared with 5-fluorouracil the compound FNSW could inhibit HepG-2cell in vitro with significant difference.The rare earth clement Nd increased the biological activity of polyoxometalate significantly.

  13. 微波消融联合5-氟尿嘧啶瘤内注射对小鼠结肠癌移植瘤的治疗%Therapeutic effect of microwave ablation combined with injection of 5-fluorouracil in mice bearing CT26 colon carcinoma xenografts

    Institute of Scientific and Technical Information of China (English)

    林海; 王云海

    2011-01-01

    目的:研究微波消融(MA)联合5-氟尿嘧啶瘤内注射对小鼠移植性结肠癌的治疗作用.方法:Balb/c小鼠皮下接种结肠癌CT26细胞建立肿瘤模型,肿瘤分别给予瘤周注射PBS、MA、瘤周注射5-氟尿嘧啶和MA+瘤周注射5-氟尿嘧啶4种处理.测量各组肿瘤大小;观察肿瘤复发情况、动物生存期及生活状态;ELISA法检测各组小鼠外周血-TNF-α、IL-2、IL-12和IFN-γ的含量.结果:60 d生存期观察发现微波消融组47 d±1.7 d、5-氟尿嘧啶组36 d±2.1d和微波消融联合5-氟尿嘧啶组56 d±2.5 d小鼠的生存期显著高于PBS组33 d±1.4 d;微波消融联合5-氟尿嘧啶组肿瘤体积[(0.11±0.03) cm×cm×cm]较其他3组显著增大(P<0.05);联合治疗组小鼠外周血中TNF-α浓度(ng/L),IL-2浓度(n/L),IL-12浓度(ng/L),IFN-γ浓度(ng/L)显著高于其他3组(180.3±35.9 vs 62.8±12.7,96.3±25.1,136.9±49.4; 72.5±6.8 vs 20.6±7.3,27.9±10.5,46.4±9.3; 302.3±69.6 vs 123.4±13.1,153.8±35.4,278.9±57.0; 68.4±8.2 vs 29.9±4.3,36.8±4.6,59.1±9.0,均P<0.01).结论:MA联合5-氟尿嘧啶瘤内注射可以减少结肠癌移植瘤局部复发,提高治疗效果.%AIM: To evaluate the therapeutic effect of microwave ablation (MA) combined with injection of 5-fluorouracil (5-FU) in mice bearing CT26 colon carcinoma xenografts.METHODS: Balb/c mice were subcutaneously inoculated with CT26 cells to establish a xeno-graft mouse model of colon carcinoma. Model mice were divided into four groups: PBS group, MA group, 5-FU group, and MA plus 5-FU group. After treatment, the changes in tumor volume were measured; tumor recurrence, mouse survival and living status were observed; and peripheral serum levels of TNF-α, IL-2, IL-12 and IFN-γ were determined by ELISA.RESULTS: The life span of mice treated by MA, 5-FU injection, MA plus 5-FU was significantly longer than that of mice treated with PBS (47 d ± 1.7 d, 36 d ± 2.1 d, 56 d ± 2.5 d vs 33 d ± 1.4 d, all P < 0.05). Tumor

  14. Characterization of calcium alginate beads of 5-fluorouracil for colon delivery

    Directory of Open Access Journals (Sweden)

    Patel Hetal

    2008-01-01

    Full Text Available A multiparticulate system combining pH-sensitive property and specific biodegradability for colon targeted delivery of 5-fluorouracil (5-FU was examined. The purpose of this study was to prepare and evaluate the colon-specific alginate beads of 5-FU for the treatment of colon cancer. Calcium alginate beads were prepared by extruding 5-FU loaded alginate solution to calcium chloride solution, and gelled spheres were formed instantaneously by ionotropic gelation reaction using different ratios of FU and alginate, alginate and calcium chloride, stirring speeds (500-1500 rpm, and reaction time. The core beads were coated with Eudragit S-100 to prevent drug release in the stomach and provide controlled dissolution of enteric coat in the small intestine and maximum drug release in the colon. Morphology and surface characteristics of the formulation were determined by scanning electron microscopy. In vitro drug release studies were performed in conditions simulating stomach to colon transit. No significant release was observed at acidic pH, however, when it reached the pH where Eudragit S-100 starts to dissolve, drug release was observed. Also, release of drug was found to be higher in presence of rat caecal content.

  15. 5-Fluorouracil Loaded Chitosan-PVA/Na+MMT Nanocomposite Films for Drug Release and Antimicrobial Activity

    Institute of Scientific and Technical Information of China (English)

    A Babul Reddy; B Manjula; T Jayaramudu; E R Sadiku; P Anand Babu; S Periyar Selvam

    2016-01-01

    In the present study, chitosan and polyvinyl alcohol (PVA) were blended with different concentrations of sodium montmorillonite (Na?MMT) clay solution by a solvent casting method. X-ray diffraction and transition electron microscope results show that the film properties are related to the co-existence of Na?MMT intercalation/exfoliation in the blend and the interaction between chitosan–PVA and Na?MMT. 5-Fluorouracil (5-FU) was loaded with chitosan–PVA/Na?MMT nanocomposite films for in vitro drug delivery study. The antimicrobial activity of the chitosan–PVA/Na?MMT films showed significant effect against Salmonella (Gram-negative) and Staphylococcus aureus (Gram-positive), whereas 5-FU encapsulated chitosan–PVA/Na?MMT bio-nanocomposite films did not show any inhibition against bacteria. Our results indicate that combination of a flexible and soft polymeric material with high drug loading ability of a hard inorganic porous material can produce improved control over degradation and drug release. It will be an economically viable method for preparation of advanced drug delivery vehicles and biodegradable implants or scaffolds.

  16. Phase Ⅱ Study of Intensity-Modulated Radiotherapy Combined with 5-Fluorouracil and Nedaplatin Chemotherapy in Recurrent Esophageal Carcinoma after Curative Operation%食管癌术后复发患者调强放疗同步化疗(5-Fu+奈达铂)的Ⅱ期临床研究

    Institute of Scientific and Technical Information of China (English)

    陶华; 孔诚; 陆进成

    2012-01-01

    Objective To analyze the feasibility and safety of postoperative recurrent esophageal carcinoma patients treated by intensity-modulated radiotherapy combined with 5-Fluorouracil(5-Fu) and nedaplatin chemotherapy. Methods Forty-four esophageal carcinoma patients suffered recurrence after their definitive resection in our department from June 2009 to June 2010. Intensity-modulated radiotherapy combined with 5-Fu and nedaplatin chemotherapy was performed in the patients(gross tumor volume,GTV) of IMRT was prescribed to 60 Gy/ 30f ,2. 0 Gy/f and 5-Fu and nedaplatin concurrent chemotherapy was used by 5-Fu 750 mg/(m2 · d),dl — 5, nedaplatin 80 mg/(m2 · d),dl at week 1 and week 4. The primary endpoint was 1-year survival rate and the second endpoint was toxicity related to the treatment. Results The overall response rate (CR + PR) was 86% (38/44). 1- and 2-year overall survival rate was 72. 7% and 60% , respectively. 1- and 2-year progression-free survival rate was 63. 6% and 36. 6% , respectively. Univariate analysis outcome showed that only recurrent site was related with prognosis (X2 = 22. 848,P = 0. 000). All the patients undergone this treatment smoothly. Grade T , D and III leukocytopenia was observed in 16% (7/44),50% (22/44),and 34% (15/44) patients,respectively. Grade Land II digestive tract toxicity was observed in 45% (20/44),55% (24/44) patients,respectively. Grade T ,and II liver/renal toxicity was observed in 77% (34/44) ,and 23% (10/44) patients,respectively. Over grade 3 digestive tract and liver/renal toxicity were not found. All the toxicities were gone after corresponding therapy. Conclusion Concurrent chemotherapy with 5-Fu and nedaplatin plus intensity-modulated radiotherapy is an effective and feasible regimen and would be considered as a better option for postoperative recurrent esophageal carcinoma patients, which could be deserved to be applied to phase III clinical trial.%目的 评价食管癌根治术后复发

  17. Electrochemical behavior of an anticancer drug 5-fluorouracil at methylene blue modified carbon paste electrode.

    Science.gov (United States)

    Bukkitgar, Shikandar D; Shetti, Nagaraj P

    2016-08-01

    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 2.04nM and 6.18nM respectively. Further, the sensor was successfully applied in pharmaceutical and biological fluid sample analysis. PMID:27157751

  18. Takotsubo Cardiomyopathy and 5-Fluorouracil: Getting to the Heart of the Matter

    Directory of Open Access Journals (Sweden)

    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.

  19. Synthesis of different sized and porous hydroxyapatite nanorods without organic modifiers and their 5-fluorouracil release performance

    Energy Technology Data Exchange (ETDEWEB)

    Ji, Yuqin; Wang, Aili [Faculty of Chemistry and Chemical Engineering, Jiangsu University, Zhenjiang 212013 (China); Wu, Gang [Department of Stomatology, Chinese PLA 359 Hospital, Zhenjiang 212006 (China); Yin, Hengbo, E-mail: yin@ujs.edu.cn [Faculty of Chemistry and Chemical Engineering, Jiangsu University, Zhenjiang 212013 (China); Liu, Shuxin [School of Chemistry and Chemical Engineering, Mianyang Normal University, Mianyang 621000 (China); Chen, Bujun; Liu, Fanggang [Department of Orthopaedics, Chinese PLA 359 Hospital, Zhenjiang 212006 (China); Li, Xiaoyun [Faculty of Chemistry and Chemical Engineering, Jiangsu University, Zhenjiang 212013 (China)

    2015-12-01

    Porous biocompatible hydroxyapatite (HAP) nanorods of various sizes were synthesized by the combination of chemical precipitation and hydrothermal method without the use of organic modifiers. The HAP nanorod samples were characterized by powder X-ray diffraction, transmission electron microscopy, and N{sub 2} adsorption/desorption techniques. HAP nanorods with average diameters and average lengths ranging from 8.5 to 26.6 nm and from 23.1 to 49.7 nm, respectively, could be controllably synthesized via these methods. Low autoclaving temperature and high pH value favored the formation of relatively small HAP nanorods. The TEM images showed that the nanorods possessed porous structures with average pore diameters ranging from 1.6 to 2.7 nm. These HAP nanoparticles effectively prolonged the release time of 5-fluorouracil up to 24 h. The as-synthesized HAP nanorods displayed no cytotoxicity to bone marrow stem cells at low HAP concentration, indicating that these nanorod materials could serve as potential carriers for novel drug release systems. - Highlights: • Porous HAP nanorods were synthesized by chemical precipitation/hydrothermal method. • Particle sizes of HAP nanorods were tunably changed without using organic modifiers. • Porous HAP nanorods had average pore diameters of 1.6–2.7 nm measured from TEM image. • Porous HAP as drug carrier effectively prolonged the release time of 5-fluorouracil.

  20. Synthesis of different sized and porous hydroxyapatite nanorods without organic modifiers and their 5-fluorouracil release performance

    International Nuclear Information System (INIS)

    Porous biocompatible hydroxyapatite (HAP) nanorods of various sizes were synthesized by the combination of chemical precipitation and hydrothermal method without the use of organic modifiers. The HAP nanorod samples were characterized by powder X-ray diffraction, transmission electron microscopy, and N2 adsorption/desorption techniques. HAP nanorods with average diameters and average lengths ranging from 8.5 to 26.6 nm and from 23.1 to 49.7 nm, respectively, could be controllably synthesized via these methods. Low autoclaving temperature and high pH value favored the formation of relatively small HAP nanorods. The TEM images showed that the nanorods possessed porous structures with average pore diameters ranging from 1.6 to 2.7 nm. These HAP nanoparticles effectively prolonged the release time of 5-fluorouracil up to 24 h. The as-synthesized HAP nanorods displayed no cytotoxicity to bone marrow stem cells at low HAP concentration, indicating that these nanorod materials could serve as potential carriers for novel drug release systems. - Highlights: • Porous HAP nanorods were synthesized by chemical precipitation/hydrothermal method. • Particle sizes of HAP nanorods were tunably changed without using organic modifiers. • Porous HAP nanorods had average pore diameters of 1.6–2.7 nm measured from TEM image. • Porous HAP as drug carrier effectively prolonged the release time of 5-fluorouracil

  1. Clinical Efficacy of Short Contact Topical 5-Fluorouracil in the Treatment of Keratoacanthomas: A Retrospective Analysis

    OpenAIRE

    Thompson, Bobbye J.; Ravits, Margaret; Silvers, David N.

    2014-01-01

    Objective: To determine the efficacy of treating patients with a recent onset, biopsy-proven keratoacanthoma with short-contact topical 5% 5-fluorouracil cream twice daily until resolution. Design: Chart review of 10 patients who applied 5% 5-fluorouracil for the treatment of biopsy-proven keratoacanthoma. Setting: Outpatient clinic of a board-certified dermatologist. Participants: The study population was 90-percent women (9/10), 10-percent men (1/10) and ranged in ages from 52 to 92 years o...

  2. Application of 5-Fluorouracil-Polycaprolactone Sustained-Release Film in Ahmed Glaucoma Valve Implantation Inhibits Postoperative Bleb Scarring in Rabbit Eyes

    OpenAIRE

    Xiu-Zeng Bi; Wei-Hua Pan; Xin-Ping Yu; Zong-Ming Song; Zeng-Jin Ren; Min Sun; Cong-Hui Li; Kai-Hui Nan

    2015-01-01

    This study was designed to investigate whether 5-fluorouracil (5-Fu)-polycaprolactone sustained-release film in Ahmed glaucoma valve implantation inhibits postoperative bleb scarring in rabbit eyes. Eighteen New Zealand white rabbits were randomly divided into three groups (A, B and C; n = 6 per group). Group A received combined 5-Fu-polycaprolactone sustained-release film application and Ahmed glaucoma valve implantation, group B received local infiltration of 5-Fu and Ahmed glaucoma valve i...

  3. Synergy of interleukin 1 and granulocyte colony-stimulating factor: in vivo stimulation of stem-cell recovery and hematopoietic regeneration following 5-fluorouracil treatment of mice

    International Nuclear Information System (INIS)

    The human bladder carcinoma cell line 5637 produces hematopoietic growth factors [granulocyte and granulocyte/macrophage colony-stimulating factors (G-CSF and GM-CSF)] and hemopoietin 1, which synergizes with CSFs to stimulate colony formation by primitive hematopoietic stem cells in 5-fluorouracil-treated mouse bone marrow. Molecular and functional properties of hemopoietin 1 identified it as identical to interleukin 1α (IL-1α). When bone marrow cells from 5-fluorouracil-treated mice were cultured in suspension for 7 days with recombinant human IL-1α and/or G-CSF, it was found that the two factors synergized to enhance recovery of myelopoietic cells and colony-forming cells of both high and low proliferative potential. G-CSF alone did not sustain these populations, but the combination had greater-than-additive stimulating capacity. In vivo, 5-fluorouracil (150 mg/kg) produced profound myelosuppression and delayed neutrophil regeneration for up to 2 weeks in C3H/HeJ mice. Daily administration of recombinant human G-CSF or human IL-1α accelerated recovery of stem cells, progenitor cells, and blood neutrophils by up to 4 days in 5-fluorouracil-treated C3H/HeJ and B6D2F1 mice. The combination of IL-1α and G-CSF acted synergistically, reducing neutropenia and accelerating recovery of normal neutrophil numbers by up to 7 days. These results indicate the possible therapeutic potential of combination therapy with IL-1 and hematopoietic growth factors such as G-CSF in the treatment of chemotherapy- or radiation-induced myelosuppression

  4. Total body topical 5-fluorouracil for extensive non-melanoma skin cancer

    NARCIS (Netherlands)

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

    2006-01-01

    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 5-fluo

  5. Extensive hepatic replacement due to liver metastases has no effect on 5-fluorouracil pharmacokinetics

    NARCIS (Netherlands)

    Maring, JG; Piersma, H; van Dalen, A; Groen, HJM; Uges, DRA; DeVries, EGE

    2003-01-01

    Purpose: The influence of liver metastases on the pharmacokinetics of 5-fluorouracil (5-FU) and its metabolite 5,6-dihydrofluorouracil (DHFU) was studied in patients with liver metastases from gastrointestinal cancer (n = 16) and compared with a control group of patients with nonmetastatic gastroint

  6. FLOW CYTOMETRIC DETECTION OF ABNORMAL FETAL ERYTHROPOIESIS: APPLICATION TO 5-FLUOROURACIL-INDUCED ANEMIA

    Science.gov (United States)

    Previously, we observed that administration of 20-40 mg/kg 5-fluorouracil (5-FU) to pregnant rats on gestational day (GD) 14 produced fetal anemia on GD 16-17, as evidenced by dose-dependent decreases in the cell counts, hematocrit, and hemoglobin content of fetal blood obtained ...

  7. Genotype-phenotype correlations in 5-fluorouracil metabolism: a candidate DPYD haplotype to improve toxicity prediction.

    Science.gov (United States)

    Gentile, G; Botticelli, A; Lionetto, L; Mazzuca, F; Simmaco, M; Marchetti, P; Borro, M

    2016-08-01

    5-Fluorouracil is among the most widely used anticancer drug, but a fraction of treated patients develop severe toxicity, with potentially lethal injuries. The predictive power of the available pretreatment assays, used to identify patients at risk of severe toxicity, needs improvements. This study aimed to correlate a phenotypic marker of 5-fluorouracil metabolism (the individual degradation rate of 5-fluorouracil-5-FUDR) with 15 functional polymorphisms in the dihydropyrimidine dehydrogenase gene (DPYD). Single SNP (single-nucleotide polymorphism) analysis revealed that the SNPs rs1801160, rs1801265, rs2297595 and rs3918290 (splice site variant IVS14+1G>A) were significantly associated with a decreased value of 5-FUDR, and the rs3918290 causing the larger decrease. Multi-SNP analysis showed that a three-SNP haplotype (Hap7) involving rs1801160, rs1801265 and rs2297595 causes a marked decrease in 5-FUDR, comparable to that caused by the splice site variant rs3918290, which is the main pharmacogenetic marker associated with severe fluorouracil toxicity. The similar effect played by Hap7 and by the splice site variant rs3918290 upon individual 5-FUDR suggests that Hap7 could also represent a similar determinant of fluorouracil toxicity. Haplotype assessment could improve the predictive value of DPYD genetic markers aimed at the pre-emptive identification of patients at risk of severe 5-fluorouracil toxicity.The Pharmacogenomics Journal advance online publication, 28 July 2015; doi:10.1038/tpj.2015.56. PMID:26216193

  8. 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...

  9. The structural changes of the rat's lung induced by intraperitoneal injection of 5-fluorouracil

    International Nuclear Information System (INIS)

    Objective: To record the main structural changes in the rat's lung induced by administration of 5-fluorouracil. Methods: The case-control study was conducted at College of Medicine, Mosul, Iraq, from December 2012 to June 2013. Two groups of 6 rats each were used. The experimental group was given 20mg of 5-fluorouracil in 2ml normal saline per kg body weight by intraperitoneal injection for 7 consecutive days, while the other group was given 2ml normal saline per kg body weight intraperitoneally for 7 days and served as the control group. Specimens of lung tissue of the two groups were taken and prepared for light microscopic examination. Result: Structural changes were found in the experimental (5-fluorouracil) group compared to the controls, including abnormal alveolar duct, sac, and terminal bronchioles with emphysematous changes in most of the alveoli in addition to peribronchiolitis, perivasculitis, inflammatory cells infiltration and interstitial fibrosis. Conclusion: 5-fluorouracil has toxic effects on the lung tissue resulting in emphysema and interstitial fibrosis. (author)

  10. p14ARF upregulation of p53 and enhanced effects of 5-fluorouracil in pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    张群华; 倪泉兴; 甘军; 沈兆忠; 罗建民; 金忱; 张妞; 张延龄

    2003-01-01

    Objective To investigate the synergistic antitumor effects of combined use of p14ARF gene and 5-fluorouracil (5-Fu) in pancreatic cancer.Methods A human pancreatic cancer cell line PC-3 was transfected with lipofectin-mediated recombinant p14ARF gene, and was then administered with 5-Fu. Cell growth, morphological changes, cell cycle, apoptosis, and molecular changes were measured using the MTT assay, flow cytometry, RT-PCR, Western blotting, and immunocytochemical assays.Results After transfection of p14ARF, cell growth was obviously inhibited, resulting in an accumulation of cells in the G1 phase. The proportion of cells in the G1 phase was significantly increased from 58.51% to 75.92 %, and in the S and G2/M phases decreased significantly from 20.05% to 12.60%, and from 21.44% to 11.48 %, respectively, as compared with those of the control groups. PC-3/p14ARF cells that underwent 5-Fu treatment had significantly greater G2/M phase accumulation, from 11.48% to 53.47 %. The apoptopic index was increased in PC-3/p14ARF cells from 3.64% to 19.62%. The MTT assay showed p14ARF-expressing cells were significantly more sensitive to 5-Fu (0.01-10 mg/L) than those devoid of p14ARF expression (P<0.01). Western blotting showed p14ARF upregulates p53 expression. Conclusion Combined use of p14ARF gene and 5-Fu acts synergistically to inhibit pancreatic cancer cell proliferation, suggesting a new anticancer strategy.

  11. Dose escalation of cisplatin with 5-fluorouracil in concurrent chemoradiotherapy for esophageal carcinoma

    International Nuclear Information System (INIS)

    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/m2 D1 and 5-fluorouracil 500 mg/m2 D1-5, respectively. This regimen was repeated 4 times every 28 days. Escalation dose was cisplatin 7.5 mg/m2 and 5- fluorouracil 100 mg/m2. 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/m2. MTD was defined as cisplatin 52.5 mg/m2, 5- fiuorouracil 700 mg/m2. 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/m2 D1-5, repeated 4 times every 28 days. (authors)

  12. Autophagy in 5-Fluorouracil Therapy in Gastrointestinal Cancer: Trends and Challenges

    Institute of Scientific and Technical Information of China (English)

    Jia-Cheng Tang; Yi-Li Feng; Xiao Liang; Xiu-Jun Cai

    2016-01-01

    Objective: 5-Fluorouracil (5-FU)-based combination therapies are standard treatments for gastrointestinal cancer, where the modulation of autophagy is becoming increasingly important in offering effective treatment for patients in clinical practice.This review focuses on the role of autophagy in 5-FU-induced tumor suppression and cancer therapy in the digestive system.Data Sources: All articles published in English from 1996 to date those assess the synergistic effect ofautophagy and 5-FU in gastrointestinal cancer therapy were identified through a systematic online search by use of PubMed.The search terms were "autophagy" and "5-FU" and ("colorectal cancer" or"hepatocellular carcinoma" or"pancreatic adenocarcinoma" or"esophageal cancer" or"gallbladder carcinoma" or "gastric cancer").Study Selection: Critical reviews on relevant aspects and original articles reporting in vitro and/or in vivo results regarding the efficiency ofautophagy and 5-FU in gastrointestinal cancer therapy were reviewed, analyzed, and summarized.The exclusion criteria for the articles were as follows: (1) new materials (e.g., nanomaterial)-induced autophagy;(2) clinical and experimental studies on diagnostic and/or prognostic biomarkers in digestive system cancers;and (3) immunogenic cell death for anticancer chemotherapy.Results: Most cell and animal experiments showed inhibition ofautophagy by either pharmacological approaches or via genetic silencing of autophagy regulatory gene, resulting in a promotion of 5-FU-induced cancer cells death.Meanwhile, autophagy also plays a pro-death role and may mediate cell death in certain cancer cells where apoptosis is defective or difficult to induce.The dual role of autophagy complicates the use of autophagy inhibitor or inducer in cancer chemotherapy and generates inconsistency to an extent in clinic trials.Conclusion: Autophagy might be a therapeutic target that sensitizes the 5-FU treatment in gastrointestinal cancer.

  13. Pretreatment with insulin enhances anticancer functions of 5-fluorouracil in human esophageal and colonic cancer cells

    Institute of Scientific and Technical Information of China (English)

    Ke ZOU; Ji-hang JU; Hong XIE

    2007-01-01

    Aim: To investigate the effects of insulin on enhancing 5-fluorouracil (5-FU) anti-cancer functions and its mechanisms in the human esophageal cancer cell line (Eca 109) and human colonic cancer cell line (Ls-174-t). Methods: The effect of insulin/5-FU combination treatment on the growth of Eca 109 and Ls-174-t cells was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay. After insulin treatment or insulin/5-FU treatment, cell cycle distri-bution of both cell lines was analyzed by flow cytometry. Western blot assay was used to assess the expression of caspase-3 and thymidylate synthase (TS).Apoptosis was detected by flow cytometry, DNA fragmentation assay, and termi-nal transferase dUTP nick end labeling assay (TUNEL). Moreover, the changes of 5-FU uptake after insulin pretreatment were detected by HPLC assay and Western blot analysis. Results: We found that insulin enhanced the inhibitory effect of 5-FU on cell proliferation when Eca 109 cells and Ls- 174-t cells were pretreated with insulin for the appropriate time. Insulin increased the cell number of the S phase and the uptake of 5-FU. Insulin/5-FU treatment enhanced apoptosis of tumor cells and upregulated the expression of cleaved caspase-3 compared with 5-FU treatment.Moreover, insulin/5-FU treatment induced the changes of free TS and the TS ternary complex level compared with 5-FU treatment in Eca 109 and Ls-174-t cells.Conclusion: These data suggest that insulin enhances anticancer functions of 5-FU when it is treated before 5-FU for the appropriate time in human esophageal and colonic cancer cell lines.

  14. Outcomes of Chemoradiotherapy With 5-Fluorouracil and Mitomycin C for Anal Cancer in Immunocompetent Versus Immunodeficient Patients

    International Nuclear Information System (INIS)

    Purpose: Information is limited as to how we should treat invasive anal squamous cell carcinoma (SCC) in patients with chronic immunosuppression, since the majority of clinical studies to date have excluded such patients. The objective of this study is to compare treatment outcomes in immunocompetent (IC) versus immunodeficient (ID) patients with invasive anal SCC treated similarly with combined modality therapy. Methods and Materials: Between January 1999 and March 2007, a total of 36 consecutive IC and ID patients received concurrent chemoradiotherapy using three-dimensional conformal radiotherapy with infusional 5-fluorouracil and mitomycin C. The IC and ID groups consisted of 19 and 17 patients, respectively, with 14 human immunodeficiency virus-positive (HIV+) and 3 post-solid organ transplant ID patients. There were no significant differences in tumor size, T stage, N stage, chemotherapy doses, or radiation doses between the two groups. Results: With a median follow-up of 3.1 years, no differences were found in overall survival, disease-specific survival, and colostomy-free survival. Three-year overall survival was 83.6% (95% CI = 68.2-100) and 91.7% (95% CI = 77.3-100) in the IC and ID groups, respectively. In addition, there were no differences in acute and late toxicity profiles between the two groups. In the human immunodeficiency virus-positive patients, Cox modeling showed no difference in overall survival by pretreatment CD4 counts (hazard ratio = 0.994, 95% CI = 0.98-1.01). No correlation was found between CD4 counts and the degree of acute toxicities. Conclusion: Our data suggest that standard combined modality therapy with three-dimensional conformal radiotherapy and 5-fluorouracil plus mitomycin C is as safe and effective for ID patients as for IC patients.

  15. [Combination Chemotherapy Using Sorafenib and Hepatic Arterial Infusion with a Fine-Powder Formulation of Cisplatin for Advanced Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis--A Case Report].

    Science.gov (United States)

    Tsukamoto, Tadashi; Kanazawa, Akishige; Shimizu, Sadatoshi; Murata, Akihiro; Sakae, Masayuki; Kurihara, Shigeaki; Tashima, Tetsuzo; Deguchi, Sota; Nakai, Takashi; Kawasaki, Yasuko; Kioka, Kiyohide

    2015-11-01

    Sorafenib has been a standard therapy for advanced hepatocellular carcinoma (HCC) with portal vein thrombosis. Hepatic arterial infusion chemotherapy (HAIC) is still preferably performed in Japan because of its relatively good tumor-shrinking effect. We report a case of advanced multiple HCC with portal thrombus that responded to combination chemotherapy with sorafenib and repeat hepatic arterial infusion with a fine-powder formulation of cisplatin (IA-call®). A 57-year-old man presented for the treatment of HCC with alcoholic cirrhosis. Multiple HCC were found to be rapidly progressing with portal thrombosis. HAIC with IA-call® was performed, but the tumors progressed. TAE was performed 3 times thereafter and the main tumor shrunk to some extent. A month after the last TAE, the HCC was found to progress again, and oral sorafenib was administered. A reservoir and catheter were placed and HAIC with low-dose 5-fluorouracil and cisplatin was performed for 3 cycles following 1 HAIC cycle with epirubicin and mitomycin C, which was not effective. For 10 months after initial therapy, HAIC using IA-call® has been performed once for 6 weeks. After performing HAIC with IA-call® 5 times, the serum levels of HCC tumor markers AFP and PIVKA-Ⅱdecreased, and the tumors continued to shrink and were not stained on enhanced CT scan. The patient has been alive for 23 months after the initial therapy and has maintained stable disease. PMID:26805203

  16. Biological evaluation of 5-fluorouracil nanoparticles for cancer chemotherapy and its dependence on the carrier, PLGA

    Directory of Open Access Journals (Sweden)

    Lekha Nair K

    2011-08-01

    Full Text Available K Lekha Nair1, Sankar Jagadeeshan2, S Asha Nair2, GS Vinod Kumar11Chemical Biology, Molecular Medicine Division, 2Cancer Research, Rajiv Gandhi Centre for Biotechnology, Poojappura, Thiruvananthapuram, Kerala, IndiaAbstract: Nanoscaled devices have great potential for drug delivery applications due to their small size. In the present study, we report for the first time the preparation and evaluation of antitumor efficacy of 5-fluorouracil (5-FU-entrapped poly (D, L-lactic-co-glycolic acid (PLGA nanoparticles with dependence on the lactide/glycolide combination of PLGA. 5-FU-loaded PLGA nanoparticles with two different monomer combinations, 50-50 and 90-10 were synthesized using a modified double emulsion method, and their biological evaluation was done in glioma (U87MG and breast adenocarcinoma (MCF7 cell lines. 5-FU-entrapped PLGA 50-50 nanoparticles showed smaller size with a high encapsulation efficiency of 66%, which was equivalent to that of PLGA 90-10 nanoparticles. Physicochemical characterization of nanoparticles using differential scanning calorimetry and X-ray diffraction suggested the presence of 5-FU in molecular dispersion form. In vitro release studies showed the prolonged and sustained release of 5-FU from nanoparticles with both the PLGA combinations, where PLGA 50-50 nanoparticles showed faster release. Nanoparticles with PLGA 50-50 combination exhibited better cytotoxicity than free drug in a dose- and time-dependent manner against both the tumor cell lines. The enhanced efficiency of PLGA 50-50 nanoparticles to induce apoptosis was indicated by acridine orange/ethidium bromide staining. Cell cycle perturbations studied using flow cytometer showed better S-phase arrest by nanoparticles in comparison with free 5-FU. All the results indicate that PLGA 50-50 nanoparticles possess better antitumor efficacy than PLGA 90-10 nanoparticles and free 5-FU. Since, studies have shown that long-term exposure of ailing tissues to moderate

  17. A randomised phase II trial of weekly high-dose 5-fluorouracil with and without folinic acid and cisplatin in patients with advanced biliary tract carcinoma: results of the 40955 EORTC trial.

    NARCIS (Netherlands)

    Ducreux, M.; Cutsem, E. van; Laethem, J. van; Gress, T.M.; Jeziorski, K.; Rougier, P.; Wagener, T.; Anak, O.; Baron, B.; Nordlinger, B.

    2005-01-01

    Previous small phase II trials have demonstrated that the combination of 5-fluorouracil (5FU) and cisplatin(CDDP) could have clinical activity in metastatic biliary tract cancer. This randomised phase II trial was designed to assess the activity and safety of a high-dose infusional weekly 5FU alone

  18. Magnetite/poly(alkylcyanoacrylate) (core/shell) nanoparticles as 5-Fluorouracil delivery systems for active targeting.

    Science.gov (United States)

    Arias, José L; Gallardo, Visitación; Ruiz, M A Adolfina; Delgado, Angel V

    2008-05-01

    In this article, a reproducible emulsion polymerization process is described to prepare core/shell colloidal nanospheres, loaded with 5-Fluorouracil, and consisting of a magnetic core (magnetite) and a biodegradable polymeric shell [poly(ethyl-2-cyanoacrylate), poly(butylcyanoacrylate), poly(hexylcyanoacrylate), or poly(octylcyanoacrylate)]. The heterogeneous structure of these carriers can confer them both the possibility of being used as drug delivery systems and the responsiveness to external magnetic fields, allowing an active drug targeting without a concurrent systemic distribution. Zeta potential determinations as a function of ionic strength showed that the surface behaviour of the core/shell particles is similar to that of pure cyanoacrylate particles. The first magnetization curve of both magnetite and magnetite/polymer particles demonstrated that the polymer shell reduces the magnetic responsiveness of the particles, but keeps unchanged their ferrimagnetic character. Two drug loading mechanisms were studied: absorption or entrapment in the polymeric network, and surface adsorption. We found that the acidity of the medium had significant effects on the drug absorption per unit mass of polymer, and needs to be controlled to avoid formation of macroaggregates and to reach significant 5-Fluorouracil absorption. The type of polymer and the drug concentration are also main factors determining the drug incorporation to the core/shell particles. 5-Fluorouracil release evaluations showed a biphasic profile affected by the type of polymeric shell, the type of drug incorporation and the amount of drug loaded.

  19. 5-Fluorouracil induces apoptosis in rat cardiocytes through intracellular oxidative stress

    Directory of Open Access Journals (Sweden)

    Lamberti Monica

    2012-07-01

    Full Text Available Abstract Background Cardiotoxicity is a major complication of anticancer drugs, including anthracyclines and 5-fluorouracil(5-FU and it can have detrimental effects both in patients and workers involved in the preparation of chemotherapy. Methods Specifically, we have assessed the effects of increasing concentrations of 5-FU and doxorubicin (DOXO on proliferation of H9c2 rat cardiocytes and HT-29 human colon adenocarcinoma cells by MTT assay. Cells were treated for 24, 48 and 72 h with different concentrations of the two drugs alone or with 5-FU in combination with 10-4 M of levofolene (LF. Results 5-FU induced a time- and dose-dependent growth inhibition in both cell lines. The 50% growth inhibition (IC:50 was reached at 72 h with concentrations of 4 μM and 400 μM on HT-29 and H9c2, respectively. The addition of LF to 5-FU enhanced this effect. On the other hand, the IC:50 of DOXO was reached at 72 h with concentrations of 0.118 μM on H9c2 and of 0.31 μM for HT-29. We have evaluated the cell death mechanism induced by 50% growth inhibitory concentrations of 5-FU or DOXO in cardiocytes and colon cancer cells. We have found that the treatment with 400 μM 5-FU induced apoptosis in 32% of H9c2 cells. This effect was increased by the addition of LF to 5-FU (38% of apoptotic cells. Apoptosis occurred in only about 10% of HT-29 cells treated with either 5-FU or 5-FU and LF in combination. DOXO induced poor effects on apoptosis of both H9c2 and HT-29 cells (5–7% apoptotic cells, respectively. The apoptosis induced by 5-FU and LF in cardiocytes was paralleled by the activation of caspases 3, 9 and 7 and by the intracellular increase of O2− levels. Conclusions These results suggest that cardiotoxic mechanism of chemotherapy agents are different and this disclose a new scenario for prevention of this complication.

  20. Cytotoxicity and radiosensitising activity of synthesized dinitrophenyl derivatives of 5-fluorouracil

    Directory of Open Access Journals (Sweden)

    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

  1. Optimization of 5-fluorouracil solid-lipid nanoparticles: a preliminary study to treat colon cancer

    Directory of Open Access Journals (Sweden)

    Alaa Eldeen B. Yassin, Md. Khalid Anwer, Hammam A. Mowafy, Ibrahim M. El-Bagory, Mohsen A. Bayomi, Ibrahim A. Alsarra

    2010-01-01

    Full Text Available Solid lipid nanoparticle (SLNs formulae were utilized for the release of 5-fluorouracil (5-FU inside the colonic medium for local treatment of colon cancer. SLNs were prepared by double emulsion-solvent evaporation technique (w/o/w using triglyceride esters, Dynasan™ 114 or Dynasan™ 118 along with soyalecithin as the lipid parts. Different formulation parameters; including type of Dynasan, soyalicithin:Dynasan ratio, drug:total lipid ratio, and polyvinyl alcohol (PVA concentration were studied with respect to particle size and drug entrapment efficiency. Results showed that formula 8 (F8 with composition of 20% 5-FU, 27% Dynasan™ 114, and 53% soyalithicin and F14 (20% 5-FU, 27% Dynasan™ 118, and 53% soyalithicin, which were stabilized by 0.5% PVA, as well as F10 with similar composition as F8 but stabilized by 2% PVA were considered the optimum formulae as they combined small particle sizes and relatively high encapsulation efficiencies. F8 had a particle size of 402.5 nm ± 34.5 with a polydispersity value of 0.005 and an encapsulation efficiency of 51%, F10 had a 617.3 nm ± 54.3 particle size with 0.005 polydispersity value and 49.1% encapsulation efficiency, whereas formula F14 showed a particle size of 343 nm ± 29 with 0.005 polydispersity, and an encapsulation efficiency of 59.09%. DSC and FTIR results suggested the existence of the lipids in the solid crystalline state. Incomplete biphasic prolonged release profile of the drug from The three formulae was observed in phosphate buffer pH 6.8 as well as simulated colonic medium containing rat caecal contents. A burst release with magnitudes of 26%, 32% and 28.8% cumulative drug released were noticed in the first hour samples incubated in phosphate buffer pH 6.8 for both F8, F10 and F14, respectively, followed by a slow release profile reaching 50%, 46.3% and 52% after 48 hours.

  2. Optimized synthesis of glycyrrhetinic acid-modified chitosan 5-fluorouracil nanoparticles and their characteristics

    Directory of Open Access Journals (Sweden)

    Cheng M

    2014-01-01

    Full Text Available Mingrong Cheng,1,2,* Houxiang Chen,3,* Yong Wang,4,* Hongzhi Xu,5 Bing He,5 Jiang Han,1 Zhiping Zhang1 1Department of General Surgery, 2Department of Endoscopy, Pudong New Area District Zhoupu Hospital, Shanghai, People's Republic of China; 3Zhejiang Huafon Fiber Research Institute, Zhejiang Huafon Spandex Co, Ltd, Wenzhou, People's Republic of China; 4School of Materials Science and Engineering, Wuhan University of Technology, Wuhan, People’s Republic of China; 5Department of General Surgery, Shanghai Fifth People’s Hospital, Fudan University, Shanghai, People’s Republic of China *These authors contributed equally to this work Abstract: The nanoparticle drug delivery system, which uses natural or synthetic polymeric material as a carrier to deliver drugs to targeted tissues, has a broad prospect for clinical application for its targeting, slow-release, and biodegradable properties. Here, we used chitosan (CTS and hepatoma cell-specific binding molecule glycyrrhetinic acid to synthesize glycyrrhetinic acid-modified chitosan (GA-CTS. The synthetic product was confirmed by infrared (IR spectra and hydrogen-1 nuclear magnetic resonance. The GA-CTS/5-fluorouracil (5-FU nanoparticles were synthesized by combining GA-CTS and 5-FU and conjugating 5-FU onto the GA-CTS nanomaterial. The central composite design was performed to optimize the preparation process as CTS:tripolyphosphate sodium (TPP weight ratio =5:1, 5-FU:CTS weight ratio =1:1, TPP concentration =0.05% (w/v, and cross-link time =50 minutes. GA-CTS/5-FU nanoparticles had a mean particle size of 193.7 nm, a polydispersity index of 0.003, a zeta potential of +27.4 mV, and a drug loading of 1.56%. The GA-CTS/5-FU nanoparticle had a protective effect on the drug against plasma degrading enzyme, and provided a sustained release system comprising three distinct phases of quick, steady, and slow release. Our study showed that the peak time, half-life time, mean residence time and area under

  3. A phase I clinical and pharmacokinetic study of capecitabine (Xeloda®) and irinotecan combination therapy (XELIRI) in patients with metastatic gastrointestinal tumours

    OpenAIRE

    Delord, J P; Pierga, J Y; Dieras, V; Bertheault-Cvitkovic, F; Turpin, F L; Lokiec, F.; Lochon, I; Chatelut, E; Canal, P.; Guimbaud, R; Mery-Mignard, D; Cornen, X; Mouri, Z; Bugat, R

    2005-01-01

    Capecitabine is a highly active oral fluoropyrimidine that is an attractive alternative to 5-fluorouracil in colorectal cancer treatment. The current study, undertaken in 27 patients with gastrointestinal tumours, aimed to assess the toxicity and potential for significant pharmacokinetic interactions of a combination regimen incorporating capecitabine with 3-weekly irinotecan (XELIRI). Irinotecan (200 and 250 mg m−2) was administered as a 90-min infusion on day 1 in combination with escalatin...

  4. Duration and distribution of experimental muscular hyperalgesia in humans following combined infusions of serotonin and bradykinin

    DEFF Research Database (Denmark)

    Babenko, Victor; Svensson, Peter; Graven-Nielsen, Thomas;

    2000-01-01

    -infusions interval of 3 min. Infusions of isotonic saline (NaCl, 0.9%) were given as control. Pain intensity was continuously scored on a visual analogue scale (VAS), and subjects drew the distribution of the pain areas on an anatomical map. Pressure pain thresholds (PPTs) were assessed with an electronic algometer....... In addition, PPTs were significantly decreased (Peffect of bradykinin in producing experimental muscle pain and muscle hyperalgesia to mechanical stimuli. The combination of serotonin and bradykinin can produce muscle...

  5. Efficacy of sequential treatment of HCT116 colon cancer monolayers and xenografts with docetaxel, flavopiridol, and 5-fluorouracil

    Institute of Scientific and Technical Information of China (English)

    Jun GUO; An-wu ZHOU; Yu-cai FU; Udit N VERMA; Debu TRIPATHY; Eugene P FRENKEL; Carlos R BECERRA

    2006-01-01

    Aim: Clinical treatment of solid tumors with docetaxel, flavopiridol, or 5-fluorouracil (5-FU) often encounters undesirable side effects and drug resistance. This study aims to evaluate the potential role of combination therapy with docetaxel, flavopiridol, or 5-FU in modulating chemosensitivity and better understand how they might be used clinically. Methods: HCT116 colon cancer cells were treated with docetaxel, flavopiridol, and 5-FU in several different administrative schedules in vitro, either sequentially or simultaneously. Cell survival was measured by MTT assay. The activity of caspase-3 was determined by caspase-3 assays and the soft agar colony assay was used to test the colony formation of HCT116 cells in soft agar. We also established xenograft models to extend in vitro observations to an in vivo system. Results: The maximum cytotoxicity was found when human colon cancer HCT116 cells were treated with docetaxel for 1 h followed by flavopiridol for 24 h and 5-FU for another 24 h. This sequential combination therapy not only inhibits tumor cell growth more strongly compared to other combination therapies but also significantly reduces colony formation in soft agar and augments apoptosis of HCT116 cells. Sequencing of docetaxel followed 1 h later by flavopiridol, followed 24 h later by 5-FU in xenograft models, also resulted in delayed tumor growth and higher survival rate. Conclusion: These results highlight the importance of an administrative schedule when combining docetaxel with flavopiridol and 5-FU, providing a rationale explanation for its development in clinical trials.

  6. Development of Novel Ionic Liquid-Based Microemulsion Formulation for Dermal Delivery of 5-Fluorouracil

    OpenAIRE

    Goindi, Shishu; Arora, Prabhleen; Kumar, Neeraj; Puri, Ashana

    2014-01-01

    The present study was aimed at synthesizing an imidazole-based ionic liquid 1-butyl-3-methylimidazolium bromide (BMIMBr) and subsequent development of a novel ionic liquid-in-oil (IL/o) microemulsion (ME) system for dermal delivery of a poorly permeating drug 5-fluorouracil (5-FU). A significant enhancement in the solubility of 5-FU was observed in BMIMBr. IL/o MEs of 5-FU were prepared using isopropyl myristate, Tween 80/Span 20, and BMIMBr. Results of ex vivo skin permeation studies through...

  7. Synthesis and Antitumor Activity of Amino Acid Ester Derivatives Containing 5-Fluorouracil

    Directory of Open Access Journals (Sweden)

    Jing Xiong

    2009-08-01

    Full Text Available A series of amino acid ester derivatives containing 5-fluorouracil were synthesized using 1-ethyl-3-(3-dimethylaminopropylcarbodiimide hydrochloride (EDC•HCl and N-hydroxybenzotriazole (HOBt as a coupling agent. The structures of the products were assigned by NMR, MS, IR etc. The in vitro antitumor activity tests against leukaemia HL-60 and liver cancer BEL-7402 indicated that (R-ethyl 2-(2-(5-fluoro-2,4-dioxo-3,4-dihydropyrimidin-1(2H-ylacetamido-3-(4-hydroxyphenyl propanoate showed more inhibitory effect against BEL-7402 than 5-FU.

  8. Cytotoxicity and Radiosensitising Activity of Synthesized Dinitrophenyl Derivatives of 5-Fluorouracil

    Directory of Open Access Journals (Sweden)

    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

  9. Uso do 5-fluorouracil no intra-operatório da cirurgia do pterígio Intra-operative use of 5-fluorouracil in pterygium surgery

    Directory of Open Access Journals (Sweden)

    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.

  10. Antitumor effect of 5-fluorouracil is enhanced by rosemary extract in both drug sensitive and resistant colon cancer cells.

    Science.gov (United States)

    González-Vallinas, Margarita; Molina, Susana; Vicente, Gonzalo; de la Cueva, Ana; Vargas, Teodoro; Santoyo, Susana; García-Risco, Mónica R; Fornari, Tiziana; Reglero, Guillermo; Ramírez de Molina, Ana

    2013-06-01

    5-Fluorouracil (5-FU) is the most used chemotherapeutic agent in colorectal cancer. However, resistance to this drug is relatively frequent, and new strategies to overcome it are urgently needed. The aim of this work was to determine the antitumor properties of a supercritical fluid rosemary extract (SFRE), alone and in combination with 5-FU, as a potential adjuvant therapy useful for colon cancer patients. This extract has been recognized as a healthy component by the European Food Safety Authority (EFSA). The effects of SFRE both alone and in combination with 5-FU were evaluated in different human colon cancer cells in terms of cell viability, cytotoxicity, and cell transformation. Additionally, colon cancer cells resistant to 5-FU were used to assay the effects of SFRE on drug resistance. Finally, qRT-PCR was performed to ascertain the mechanism by which SFRE potentiates the effect of 5-FU. Our results show that SFRE displays dose-dependent antitumor activities and exerts a synergistic effect in combination with 5-FU on colon cancer cells. Furthermore, SFRE sensitizes 5-FU-resistant cells to the therapeutic activity of this drug, constituting a beneficial agent against both 5-FU sensitive and resistant tumor cells. Gene expression analysis indicates that the enhancement of the effect of 5-FU by SFRE might be explained by the downregulation of TYMS and TK1, enzymes related to 5-FU resistance. PMID:23557932

  11. Results of a planned interim toxicity analysis with trimodality therapy, including carboplatin AUC = 4, paclitaxel, 5-fluorouracil, amifostine, and radiation for locally advanced esophageal cancer: preliminary analyses and treatment recommendations from the North Central Cancer Treatment Group

    OpenAIRE

    Jatoi, Aminah; Martenson, James; Mahoney, Michelle R; Lair, Bradley S; Brindle, Jeffrey S; Nichols, Frank; Caron, Normand; Rowland, Kendrith; Tschetter, Loren; Alberts, Steven

    2004-01-01

    Purpose An aggressive trimodality approach from the Minnie Pearl Cancer Research Network [carboplatin AUC = 6, days 1 and 22; 5-fluorouracil 225 mg/m2 continuous infusion, days 1–42, paclitaxel 200 mg/m2, days 1 and 22; 45 Gy] has resulted in remarkable pathologic response rates but notable toxicity. This trial was designed to mitigate this toxicity by starting with a lower carboplatin dose, AUC = 4, and by adding subcutaneous amifostine. Methods This phase II trial included patients with loc...

  12. 5-Fluorouracil preferentially sensitizes mutant KRAS non-small cell lung carcinoma cells to TRAIL-induced apoptosis.

    Science.gov (United States)

    Wang, Haizhen; Yang, Tao; Wu, Xiangwei

    2015-11-01

    Mutations in the KRAS gene are very common in non-small cell lung cancer (NSCLC), but effective therapies targeting KRAS have yet to be developed. Interest in tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), a potent inducer of cell death, has increased following the observation that TRAIL can selectively kill a wide variety of human cancer cells without killing normal cells both in vitro and in xenograft models. However, results from clinical trials of TRAIL-based therapy are disappointingly modest at best and many have demonstrated a lack of therapeutic benefit. Current research has focused on selecting a subpopulation of cancer patients who may benefit from TRAIL-based therapy and identifying best drugs to work with TRAIL. In the current study, we found that NSCLC cells with a KRAS mutation were highly sensitive to treatment with TRAIL and 5-fluorouracil (5FU). Compared with other chemotherapeutic agents, 5FU displayed the highest synergy with TRAIL in inducing apoptosis in mutant KRAS NSCLC cells. We also found that, on a mechanistic level, 5FU preferentially repressed survivin expression and induced expression of TRAIL death receptor 5 to sensitize NSCLC cells to TRAIL. The combination of low-dose 5FU and TRAIL strongly inhibited xenograft tumor growth in mice. Our results suggest that the combination of TRAIL and 5FU may be beneficial for patients with mutant KRAS NSCLC.

  13. Preparation and drug releasing property of magnetic chitosan-5-fluorouracil nano-particles

    Institute of Scientific and Technical Information of China (English)

    WANG Dong-sheng; LI Jian-guo; LI He-ping; TANG Fa-qing

    2009-01-01

    In order to synthesize the targeting drug carrier system, magnetic chitosan-5-fluorouracil nano-particles were prepared by using 5-fluorouracil (5-Fu) as model drug, Fe_3O_4 nano-particles as kernel, chitosan as enveloping material and glutaraldehyde as cross linking agent through ultrasonic technique. The morphology of the magnetic chitosan-5-Fu nano-particles was observed with a transmission electron microscope(TEM). The results showed that magnetic chitosan-5-Fu nano-particles were prepared in spherical structure with a size range of 50-60 nm. The delivering capacity and drug releasing properties of magnetic chitosan-5-Fu nano-particles were investigated by UV-vis spectrum analysis. The results showed that the loading capacity was 13.4% and the cumulative release percentage in the phosphate buffer (pH=7.2) solutions was 68% in 30 h. These data indicate that the wrapped drug of magnetic chitosan-5-Fu nano-particles was slowly-released. The magnetic response of magnetic chitosan-5-Fu nano-particles was studied by UV-vis spectrometer to detect the changes of solution absorbance. Without external magnetic field, the nano-particle deposition rate was slow. When being subjected to 8 mT magnetic field, the particle sedimentation rate was increased rapidly. The results showed that magnetic chitosan-5-Fu nano-particles have a magnetic stability and strong targeting characteristics.

  14. Magnetic glass ceramics for sustained 5-fluorouracil delivery: characterization and evaluation of drug release kinetics.

    Science.gov (United States)

    Abdel-Hameed, S A M; El-Kady, A M; Marzouk, M A

    2014-11-01

    In the present study, magnetic glass ceramics in the system Fe2O3 ∙ TiO2 ∙ P2O5 ∙ SiO2 ∙ MO (M=Mg, Ca, Mn, Cu, Zn or Ce) are prepared. The effect of adding different cations on the thermal behavior, developed phases, microstructure and magnetic properties is studied using differental thermal analysis (DTA), X-ray diffraction analysis (XRD), transmission electron microscope (TEM), FT-infrared transmission (FT-IR) and vibrating sample magnetometer (VSM) respectively. The magnetic glass ceramics are tested as delivery systems for 5-fluorouracil. Modeling and analysis of release kinetics are addressed. The application of Higuchi square root of time model and the first order release model indicated that, 5-FU is released by diffusion controlled mechanisms, and that its released rate depends greatly on the concentration of loaded drug during the loading stage. The obtained results suggested that, the prepared magnetic glass ceramics can be used for cancer treatment by hyperthermia and/or by localized delivery of therapeutic doses of 5-fluorouracil.

  15. Enhanced in Vivo Delivery of 5-Fluorouracil by Ethosomal Gels in Rabbit Ear Hypertrophic Scar Model

    Directory of Open Access Journals (Sweden)

    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.

  16. Enhanced in Vivo Delivery of 5-Fluorouracil by Ethosomal Gels in Rabbit Ear Hypertrophic Scar Model

    Science.gov (United States)

    Wo, Yan; Zhang, Zheng; Zhang, Yixin; Zhang, Zhen; Wang, Kan; Mao, Xiaohui; Su, Weijie; Li, Ke; Cui, Daxiang; Chen, Jun

    2014-01-01

    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. PMID:25501333

  17. FORMULATION AND EVALUATION OF PULSED DRUG DELIVERY OF 5- FLUOROURACIL IN TREATING COLO-RECTAL CANCER

    Directory of Open Access Journals (Sweden)

    Joshi V.G

    2012-09-01

    Full Text Available The proposed work aimed to develop a time dependent programmable pulsatile drug delivery system of 5-Fluorouracil, intended for chronotherapy in colorectal cancer. Various batches of tablets were prepared by direct compression method using microcrystalline cellulose (MCC. These tablets were coated with pH sensitive polymers like Eudragit S-100, cellulose acetate succinate(CAS and Ethyl Cellulose (EC at fixed concentration with different coating level (10% & 20%.The prepared tablets were evaluated for lag time and in vitro drug release. FTIR studies revealed that there was no interaction between drug and polymer. Lag time with Eudragit S-100 at (20% coating level was 5 hrs, Cumulative drug released from the formulation ranged from 91-96% within 8-10 hrs. Drug released followed first order kinetics. The rapid release of the drug after a lag time consistent with requirement for chronotherapeutics was achieved. This approach provides a useful means for pulsatile/programmable release (with single pulse of 5-Fluorouracil and may be helpful for patients suffering from cancer.

  18. 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.

  19. Severe Encephalopathy, Lactic Acidosis, Vegetative Instability and Neuropathy with 5-Fluorouracil Treatment – Pyrimidine Degradation Defect or Beriberi

    Directory of Open Access Journals (Sweden)

    A. Rosen

    2011-08-01

    Full Text Available We present the case of a 19-year-old female with nasopharyngeal carcinoma, who received two courses of chemotherapy with 5-fluorouracil (5-FU in combination with folic acid and cisplatin. Upon developing esophageal strictures in the course of her radiotherapy, she required total parenteral nutrition. In the course of therapy, the patient developed severe multisystem failure with encephalopathy, lactic acidosis, vegetative instability and neuropathy. The treatment with 5-FU can lead to severe toxicity due to enzyme deficiencies in the degradation of pyrimidines, but it can also lead to thiamine deficiency with the classic symptoms of beriberi. Beriberi is a rare disorder, usually attributed to malnutrition or alcoholism. 5-FU has been shown to induce thiamine depletion. Reduced food intake or total parenteral nutrition devoid of vitamin supplements may aggravate symptoms. We were unable to find a genetic cause for increased 5-FU toxicity in our patient, ruling out deficiencies of dihydropyrimidine dehydrogenase, dihydropyrimidinase or β-ureidopropionase and double-strand break repair deficits. We come to the conclusion that, even without any definable enzyme deficiency, treatment with 5-FU can lead to high toxicity due to thiamine deficiency if vitamin supplementation is not undertaken.

  20. tRNA modifying enzymes, NSUN2 and METTL1, determine sensitivity to 5-fluorouracil in HeLa cells.

    Directory of Open Access Journals (Sweden)

    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.

  1. Surface Molecularly Imprinted Polymer of Chitosan Grafted Poly(methyl methacrylate) for 5-Fluorouracil and Controlled Release.

    Science.gov (United States)

    Zheng, Xue-Fang; Lian, Qi; Yang, Hua; Wang, Xiuping

    2016-01-01

    The molecular surface imprinted graft copolymer of chitosan with methyl methacrylate (MIP-CS-g-PMMA) were prepared by free radical polymerization with 5-fluorouracil (5-FU) as the template molecule using initiator of ammonium persulfate as adsorption system. MIPs were characterized by FTIR, X-ray diffraction, thermo-gravimetric analysis, (1)H NMR and SEM. The mechanism of graft copolymerization and factors affected graft reaction were studied in details, and the optimum reaction conditions (to the highest %G and %E as the standard) were obtained at [MMA] 1.2 mol/L, [Chitosan] 16.67 mol/L, [initiator] 0.0062 mol/L, temperature 60 °C and reaction time 7 h. MIPs exhibited high recognition selectivity and excellent combining affinity to template molecular. The in vitro release of the 5-FU was highly pH-dependent and time delayed. The release behavior showed that the drugs did not release in simulated gastric fluid (pH = 1.0), and the drug release was small in the simulated small intestinal fluid (pH = 6.8), and drug abrupt release will be produced in the simulated colon fluid (pH = 7.4), indicating excellent colon-specific drug delivery behavior. PMID:26892676

  2. Downregulation of Rap1 promotes 5-fluorouracil-induced apoptosis in hepatocellular carcinoma cell line HepG2.

    Science.gov (United States)

    Zha, Yong; Gan, Ping; Yao, Qian; Ran, Feng-Ming; Tan, Jing

    2014-04-01

    Recent studies have revealed that repressor/activator protein (Rap1) not only protects telomeres from sister chromatid exchange, but also functions in genomewide transcriptional regulation. Knockdown of Rap1 sensitizes breast cancer cells to adriamycin-induced apoptosis. However, little is known about the role of Rap1 in the progression of hepatocellular carcinoma (HCC). The present study aimed to investigate the functions of Rap1 in HCC progression and to determine whether targeting the Rap1 signaling pathway may be of therapeutic value against HCC. We found knockdown of Rap1 by microRNA (miRNA) interference enhanced significantly apoptosis and 5-fluorouracil (5-FU) chemosensitivity in HepG2 cell line. Rap1 miRNA downregulated nuclear factor-κB p65 (NF-κB p65) expression, and upregulated inhibitor of NF-κB (IκB) expression. In vivo, Rap1 miRNA combined with 5-FU treatment led to a significant reduction of tumor growth as compared with 5-FU alone. The results indicate that Rap1 miRNA can effectively enhance sensitivity of HepG2 cell line to 5-FU chemotherapy in vitro and in vivo. PMID:24549317

  3. Actikerall™ (5-Fluorouracil 0.5% and Salicylic Acid 10%) Topical Solution for Patient-directed Treatment of Actinic Keratoses.

    Science.gov (United States)

    Nguyen, H P; Rivers, J K

    2016-05-01

    Actinic keratosis (AK), a common cutaneous lesion with the potential to transform into squamous cell carcinoma, has traditionally been treated with ablative and/or surgical procedures. Recently, a topical formulation combining 0.5% 5-fluorouracil with 10% salicylic acid (5-FU-SA) was introduced in Europe under the trade name Actikerall™ for the treatment of grade I/II AKs. In a single randomized phase III trial, 5-FU-SA was shown to be superior to diclofenac 3% gel in hyaluronic acid, as measured by the histological clearance of one defined lesion (72% vs. 59.1%) and by complete clinical clearance (55.4% vs. 32.0%). 5-FU-SA should be applied once daily to a total area of up to 25 cm(2), which may include the lesion(s) and a small area of surrounding skin (rim of healthy skin should not exceed 0.5 cm), for up to 12 weeks. The most common side effects are local inflammation and pruritus at the application site, and no serious adverse effects have been reported to date. Now commercially available in Canada, 5-FU-SA represents a patientapplied therapeutic option for the treatment of both overt and subclinical AKs.

  4. Photocatalytic oxidation of 5-fluorouracil and cyclophosphamide via UV/TiO2 in an aqueous environment.

    Science.gov (United States)

    Lin, Hank Hui-Hsiang; Lin, Angela Yu-Chen

    2014-01-01

    Cytostatic drugs are a class of pharmaceuticals that are increasingly used in cancer therapies; 5-fluorouracil is one of the most commonly used cytostatic (antineoplastic) drugs in the world. This study applied photocatalytic oxidation to remove 5-fluorouracil. Degussa P25 showed a higher photocatalytic degradation efficiency for 5-fluorouracil removal than Aldrich TiO2 and ZnO. Under optimal conditions (20 mg L(-1) TiO2 at pH 5.8), 200 μg L(-1) 5-fluorouracil can be removed within 2 h (k = 0.0375 min(-1)). 5-fluorouracil was found to be decomposed by near-surface OH free radicals produced from valence holes (hvb(+)). At a relatively high concentration, 5-fluorouracil (27.6 mg L(-1)) is >99.9% removed within 4 h by 300 mg L(-1) Degussa P25, while 24 h is required to reach complete mineralization with 96.7% fluoride recovery. Cyclophosphamide is another widely used cancer drug that follows a similar decomposition pathway. Cyclophosphamide (27.6 mg L(-1)) was also >99.9% eliminated within 4 h, but dechlorination and mineralization reached only 79.9% and 55.1%, respectively, after 16 h of irradiation. Together with the results for Microtox(®), it is suggested that the oxidation products of cyclophosphamide are even more recalcitrant and toxic. For engineering practices, despite the fact that photocatalytic oxidation can rapidly remove target antineoplastic, it is also important to further evaluate the treatment efficiency of the photoproducts. PMID:24200004

  5. Investigations on the interactions of 5-fluorouracil with bovine serum albumin: Optical spectroscopic and molecular modeling studies

    International Nuclear Information System (INIS)

    5-Fluorouracil is clinically used as antitumor drug to treat many types of cancer, which is made available to the target tissues in conjugation with transport protein serum albumin. 5-Fluorouracil which is low toxic when compared to the other drugs of this family and hence its binding characteristics are therefore of prime interest. The steady state and time resolved fluorescence studies, Fourier transform infrared spectroscopy and circular dichroism studies were employed to explain the mode and the mechanism of interaction of 5FU with BSA. 5-Fluorouracil binding is characterized with one high affinity binding site, with the binding constant of the order of 104. The molecular distance r (∼1.5 nm) between donor (bovine serum abumin) and acceptor (5-fluorouracil) was estimated according to Forster's theory of non-radiative energy transfer. The feature of 5-fluorouracil induced structural changes of bovine serum albumin has been studied in detail by circular dichroism and Fourier transform infrared spectroscopy analysis. The binding dynamics was expounded by synchronous fluorescence spectroscopy, florescence lifetime measurements and molecular modeling elicits that hydrophobic interactions and hydrogen bonding, stabilizes the 5-fluorouracil interaction with BSA. - Highlights: • The fluorescence quenching of BSA induced by 5-FU is static at lower concentration and dynamic at higher concentration. • 5-FU binding with BSA results, there is no considerable changes in α-helix. • 5-FU binds with hydrophobic cavity in BSA (site I). • The distance between the donor and acceptor is 1.5 nm. • The main force of attraction between 5-FU in BSA are hydrophobic and hydrogen bonding

  6. Investigations on the interactions of 5-fluorouracil with bovine serum albumin: Optical spectroscopic and molecular modeling studies

    Energy Technology Data Exchange (ETDEWEB)

    Chinnathambi, Shanmugavel [Department of Medical Physics, Anna University, Chennai 600025 (India); Velmurugan, Devadasan [Bioinformatics Infrastructure Facility, University of Madras, Chennai 600025 (India); Centre of Advanced Study in Crystallography and Biophysics, University of Madras, Chennai 600025 (India); Hanagata, Nobutaka [Nanotechnology Innovation Station, National Institute for Materials Science, 1-2-1 Sengen, Tsukuba, Ibaraki 305-0047 (Japan); Graduate School of Life Science, Hokkaido University, N10W8, Kita-ku, Sapporo 060-0812 (Japan); Aruna, Prakasa Rao [Department of Medical Physics, Anna University, Chennai 600025 (India); Ganesan, Singaravelu, E-mail: sganesan@annauniv.edu [Department of Medical Physics, Anna University, Chennai 600025 (India)

    2014-07-01

    5-Fluorouracil is clinically used as antitumor drug to treat many types of cancer, which is made available to the target tissues in conjugation with transport protein serum albumin. 5-Fluorouracil which is low toxic when compared to the other drugs of this family and hence its binding characteristics are therefore of prime interest. The steady state and time resolved fluorescence studies, Fourier transform infrared spectroscopy and circular dichroism studies were employed to explain the mode and the mechanism of interaction of 5FU with BSA. 5-Fluorouracil binding is characterized with one high affinity binding site, with the binding constant of the order of 10{sup 4}. The molecular distance r (∼1.5 nm) between donor (bovine serum abumin) and acceptor (5-fluorouracil) was estimated according to Forster's theory of non-radiative energy transfer. The feature of 5-fluorouracil induced structural changes of bovine serum albumin has been studied in detail by circular dichroism and Fourier transform infrared spectroscopy analysis. The binding dynamics was expounded by synchronous fluorescence spectroscopy, florescence lifetime measurements and molecular modeling elicits that hydrophobic interactions and hydrogen bonding, stabilizes the 5-fluorouracil interaction with BSA. - Highlights: • The fluorescence quenching of BSA induced by 5-FU is static at lower concentration and dynamic at higher concentration. • 5-FU binding with BSA results, there is no considerable changes in α-helix. • 5-FU binds with hydrophobic cavity in BSA (site I). • The distance between the donor and acceptor is 1.5 nm. • The main force of attraction between 5-FU in BSA are hydrophobic and hydrogen bonding.

  7. Properties of the surface of a porous polymer modified with 5-fluorouracil, according to data of gas chromatography

    Science.gov (United States)

    Gus'kov, V. Yu.; Gainullina, Yu. Yu.; Ivanov, S. P.; Kudasheva, F. Kh.

    2014-06-01

    The effect or modification with 5-fluorouracil on the sorption activity of porous polymeric adsorbent is studied. It is demonstrated that the supramolecular structure formed on the surface is able to addition-ally contribute to the values of the specific retention volumes. It is found that the structure of 5-fluorouracil is capable of size effects corresponding to a molecular window of approximately 7-8 Å. It is concluded that surface polarity diminishes after modification, due to the shielding effect of four fluorine atoms present in the cavity.

  8. Pharmacological Study on Antitumor Activity of 5-Fluorouracil-1-Acetic Acid and Its Rare Earth Complexes

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    The antitumor activity of 5-fluorouracil-1-acetic acid(HFAA) and its lanthanide complexes(La(FAA)3, Eu(FAA)3) were studied. The results show that HFAA, La(FAA)3 and Eu(FAA)3 with the concentrations of 1.0×10-5~1.0×10-2 μg·ml-1 inhibit the colony formation of leukemia cells(L1210) and the growth of transplanted tumor sarcoma 180(S180), hepatic carcinoma(HEPA) and ehrlich ascites tumor(EC) as well. The maximum inhibitory rate of Eu(FAA)3 for S180 is 38.4%, that HFAA and La(FAA)3 for EC are 22.4% and 43.4%, respectively. The life prolongation rate of Eu(FAA)3 for HEPA bearing mice is as long as 284%.

  9. Electronic structure of uracil-like nucleobases adsorbed on Si(001): uracil, thymine and 5-fluorouracil

    Science.gov (United States)

    Molteni, Elena; Onida, Giovanni; Cappellini, Giancarlo

    2016-04-01

    We study the electronic properties of the Si(001):Uracil, Si(001):Thymine, and Si(001):5-Fluorouracil systems, focusing on the Si dimer-bridging configuration with adsorption governed by carbonyl groups. While the overall structural and electronic properties are similar, with small differences due to chemical substitutions, much larger effects on the surface band dispersion and bandgap show up as a function of the molecular orientation with respect to the surface. An off-normal orientation of the molecular planes is favored, showing larger bandgap and lower total energy than the upright position. We also analyze the localization of gap-edge occupied and unoccupied surface states. Supplementary material in the form of one pdf file available from the Journal web page at http://dx.doi.org/10.1140/epjb/e2016-70011-1

  10. Interactions of radiation and 5-fluorouracil, cyclophosphamide or methotrexate in intestinal crypt cells

    International Nuclear Information System (INIS)

    The interactions of radiation and 5-fluorouracil (5-FU), cyclophosphamide (CTX), or methotrexate (MTX) in mouse jejunal crypt cells were studied using the microcolony survival assay. 5-FU given from 48 hr before to 24 hr after irradiation resulted in an almost constant, increased cell kill except at injection 6 hr after irradiation, which resulted in a more pronounced effect. CTX enhanced the radiation effect only when given simultaneously with or up to 3 hr after irradiation. The effect of MTX, extremely dependent on the sequence and interval between drug administration and irradiation, was most prominent when administered 1 hr before irradiation. At this drug-radiation interval, the D0 surprisingly increased by a factor of 2.4, whereas MTX 15 min before irradiation displaced the survival curve to the left without changing the D0. The influence of MTX on the radiation response disappeared when the drug was given either 96 hr before or 3 hr after irradiation

  11. Inhibition of phosphoserine phosphatase enhances the anticancer efficacy of 5-fluorouracil in colorectal cancer.

    Science.gov (United States)

    Li, Xin; Xun, Zhe; Yang, Yong

    2016-09-01

    Most colorectal cancer (CRC) cell lines are identified to overexpress phosphoserine phosphatase (PSPH), which regulates the intracellular synthesis of serine and glycine, and supports tumor growth. In this study, the effect of PSPH on 5-fluorouracil (5-FU) efficacy was evaluated. CRC cells exposed to 5-FU acquire metabolic remodeling, resulting in increased glucose flux for PSPH-mediated serine synthesis. Then serine is converted into GSH, which promotes cell survival through the detoxification of 5-FU-induced reactive oxygen species (ROS). Consequently, repression of PSPH by the use of shRNAs for PSPH impaired the defense against drug-induced oxidative stress, thereby sensitizing cells to 5-FU. The importance of the PSPH in supporting tumor growth during 5-FU treatment was also demonstrated in an in vivo tumor model of CRC. These findings indicate that the PSPH could serve as a target for increasing the anticancer efficacy of conventional therapy in patients with CRC. PMID:27349874

  12. 5-Fluorouracil cardiotoxicity: reversible left ventricular systolic dysfunction with early detection.

    Science.gov (United States)

    Iskandar, Muhammad Zaid; Quasem, Wahid; El-Omar, Magdi

    2015-01-01

    A 33-year-old man presented to hospital with acute shortness of breath and evolving ST segment changes on ECG 3 days following a cycle of 5-fluorouracil (5-FU) for colon cancer. Despite no cardiac history, subsequent echocardiogram showed severe left ventricular systolic dysfunction. The patient was initially treated with heart failure medications and his coronary angiogram was normal. Chemotherapy was stopped and he was started on nitrates and calcium channel blockers. A repeat echocardiogram and cardiac MRI a week later showed complete resolution of his left ventricular dysfunction and he was discharged home. This case report summarises 5-FU cardiotoxicity, and emphasises the importance of early recognition and correct treatment, as left ventricular systolic dysfunction in this context is potentially reversible. PMID:25935919

  13. The determination of 5-fluorouracil in human plasma by a gas chromatography-mass spectrometry

    International Nuclear Information System (INIS)

    A gas chromatography-mass spectrometry method for the determination of 5-fluorouracil in human plasma is described. The method involves a single extraction procedure with 10 ml of isopropanol-eth-er(20:80) solution and pentafluoro-benzylation. Samples were injected using an automatic injector, followed by separation on a nonpolar capillary column and detection with a mass selective detector(MSD). No en-dogeneous compounds were found to interfere. The detection limit, based upon an assayed plasma volume of 0.5, was 3 ng/ml. The extraction yield was found to be above 80%. Plasma 5-FU concentrations were det-ermined by this method in about 500 plasma samples from cancer patients undergoing treatment with 5-FU. This method is suitable for monitoring of 5-FU in plasma of cancer patients

  14. CETSA screening identifies known and novel thymidylate synthase inhibitors and slow intracellular activation of 5-fluorouracil

    Science.gov (United States)

    Almqvist, Helena; Axelsson, Hanna; Jafari, Rozbeh; Dan, Chen; Mateus, André; Haraldsson, Martin; Larsson, Andreas; Molina, Daniel Martinez; Artursson, Per; Lundbäck, Thomas; Nordlund, Pär

    2016-03-01

    Target engagement is a critical factor for therapeutic efficacy. Assessment of compound binding to native target proteins in live cells is therefore highly desirable in all stages of drug discovery. We report here the first compound library screen based on biophysical measurements of intracellular target binding, exemplified by human thymidylate synthase (TS). The screen selected accurately for all the tested known drugs acting on TS. We also identified TS inhibitors with novel chemistry and marketed drugs that were not previously known to target TS, including the DNA methyltransferase inhibitor decitabine. By following the cellular uptake and enzymatic conversion of known drugs we correlated the appearance of active metabolites over time with intracellular target engagement. These data distinguished a much slower activation of 5-fluorouracil when compared with nucleoside-based drugs. The approach establishes efficient means to associate drug uptake and activation with target binding during drug discovery.

  15. 5-Fluorouracil loaded guar gum microspheres for colon delivery:preparation, characterization and in vitro release

    Institute of Scientific and Technical Information of China (English)

    KAUSHIK Dinesh; SARDANA Satish; MISHRA DN

    2009-01-01

    The present investigation is aimed to develop a new formulation containing chemically cross-linked guar gum microspheres loaded with 5-fluorouracil for targeting colorectal cancer. The emulsification polymerization method involving the dispersion of aqueous phase of guar gum in castor oil was used to prepare spherical microspheres. Various processing parameters were studied in order to optimize the formulation. Particle size and surface morphology of the microspheres were determined using optical microscopy and scanning electron microscopy. The in vitro drug release studies performed in simulated gastric fluid (SGF) for 2 h followed by intestinal fluid for 3 h, revealed the retention of the drug inside the microspheres from which only (15.27±0.56)% of the drug was released in 5 h. In vitro release rate studies were also carried out in simulated colonic fluid (SCF) in the presence of rat caecal contents, which showed improved drug release. The drug release from the formulation was found to be (41.6±3.5) % with 2% (w/v) caecal matter in 24 h as compared to control study where (25.2±3.5) % of drug was released. The drug release from the formulation with 2% and 4% rat caecal contents medium after 2 days of enzyme induction was found to be (56.3±4.1) % and (78.9±2.8) % in 24 h respectively. Similarly, (61.3±5.4) % and (90.2±2.9) % drug was released respectively with 2% and 4% rat caecal matter after 4 days of enzyme induction and (72.1±2.9) % and (90.2±3.2) % after 6 days of enzyme induction. In this way, 5-fluorouracil loaded guar gum microspheres have shown promising results in the management of colorectal cancer, warranting thorough in vivo study for scale up technology.

  16. Preparation of 5-fluorouracil nanoparticles by supercritical antisolvents for pulmonary delivery

    Directory of Open Access Journals (Sweden)

    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

  17. Vitamin D analogs enhance the anticancer activity of 5-fluorouracil in an in vivo mouse colon cancer model

    International Nuclear Information System (INIS)

    Active vitamin D analogs that are less toxic than calcitriol can be useful in the combined treatment of patients suffering from colon cancer. In the present study we demonstrate, for the first time in an in vivo model system, the biological effect of combined therapy using 5-fluorouracil (5-FU) along with vitamin D analog PRI-2191 (tacalcitol, 1,24-dihydroxyvitamin D3) or PRI-2205 (5,6-trans-isomer of calcipotriol) on colon cancer. We investigated the influence of vitamin D analogs on the anticancer activity of 5-FU or capecitabine in the treatment of mice bearing MC38 mouse colon tumors implanted subcutaneously or orthotopically. The cell cycle distribution, E-cadherin expression and caspase 3/7 activity in vitro were also evaluated. We observed that both PRI-2191 and PRI-2205 significantly enhanced the antitumor activity of 5-FU; but these results depend on the treatment regimen. Applying the optimal schedule of combined therapy we observed a significant decrease in tumor growth, metastasis and also a prolongation of the survival time of mice, in comparison with the administrations of 5-FU given alone. Both combinations indicated a synergistic effect and did not cause toxicity. Moreover, analogs applied after completed course of administration of 5-FU, prolonged the antitumor effect of the drug. Furthermore, when the prodrug of 5-FU, capecitabine, was used, potentiation of its activity was also observed. Our data suggest that vitamin D analogs (especially PRI-2191) might be potentially applied to clinical use in order to enhance the anticancer effect of 5-FU and also prolong its activity against colon cancer. The activity of PRI-2191 is realized through stopping the cells in the G0/G1 cell cycle phase and increasing the expression of E-cadherin

  18. Short-term health-related quality of life and symptom control with docetaxel, cisplatin, 5-fluorouracil and cisplatin (TPF), 5-fluorouracil (PF) for induction in unresectable locoregionally advanced head and neck cancer patients (EORTC 24971/TAX 323).

    NARCIS (Netherlands)

    Herpen, C.M.L. van; Mauer, M.E.; Mesia, R.; Degardin, M.; Jelic, S.; Coens, C.; Betka, J.; Bernier, J.; Remenar, E.; Stewart, J.S.; Preiss, J.H.; Weyngaert, D. van den; Bottomley, A.; Vermorken, J.B.

    2010-01-01

    BACKGROUND: The EORTC 24971/TAX 323, a phase III study of 358 patients with unresectable locoregionally advanced squamous cell carcinoma of the head and neck, showed an improved progression-free and overall survival (OS) with less toxicity when docetaxel (T) was added to cisplatin and 5-fluorouracil

  19. Interaction between the cytostatic effects of quercetin and 5-fluorouracil in two human colorectal cancer cell lines

    NARCIS (Netherlands)

    Boersma, H H; Woerdenbag, H J; Bauer, Joseph; Scheithauer, W; Kampinga, H H; Konings, A W

    1994-01-01

    Therapy with 5-fluorouracil (5-FU) as a single agent has only limited success in palliative treatment of cancer of the large bowel. In the current study, the effect of quercetin on the action of 5-FU in the human colorectal cancer cell lines COLO 320 DM and COLO 205 was evaluated using the MTT and c

  20. 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.

  1. Development and characterization of chitosan-polycarbophil interpolyelectrolyte complex-based 5-fluorouracil formulations for buccal, vaginal and rectal application

    Directory of Open Access Journals (Sweden)

    Pendekal Mohamed S

    2012-10-01

    Full Text Available Abstract Background of the study The present investigation was designed with the intention to formulate versatile 5-fluorouracil (5-FU matrix tablet that fulfills the therapeutic needs that are lacking in current cancer treatment and aimed at minimizing toxic effect, enhancing efficacy and increasing patient compliance. The manuscript presents the critical issues of 5-FU associate with cancer and surpasses issues by engineering novel 5-FU matrix tablets utilizing chitosan- polycarbophil interpolyelectrolyte complex (IPEC. Methods Precipitation method is employed for preparation of chitosan and polycarbophil interpolyelectrolyte complex (IPEC followed by characterization with Fourier transform infrared spectroscopy (FT-IR, Differential Scanning calorimeter (DSC and X-ray Diffraction (XRD. 5-FU tablets were prepared by direct compression using IPEC. Six formulations were prepared with IPEC alone and in combination with chitosan, polycarbophil and Sodium deoxycholate. The formulations were tested for drug content, hardness, friability, weight variation, thickness, swelling studies, in vitro drug release (buccal, vaginal and rectal pH, ex vivo permeation studies, mucoadhesive strength and in vivo studies. Results FT-IR studies represent the change in spectra for the IPEC than single polymers.DSC study represents the different thermo gram for chitosan, polycarbophil and IPEC whereas in X-ray diffraction, crystal size alteration was observed. Formulations containing IPEC showed pH independent controlled 5-FU without an initial burst release effect in buccal, vaginal and rectal pH. Furthermore, F4 formulations showed controlled release 5-FU with highest bioadhesive property and satisfactory residence in both buccal and vaginal cavity of rabbit. 3% of SDC in formulation F6 exhibited maximum permeation of 5-FU. Conclusion The suitable combination of IPEC, chitosan and polycarbophil demonstrated potential candidate for controlled release of 5-FU in buccal

  2. Effect of consecutive lower-dose cisplatin in enhancement of 5-fluorouracil cytotoxicity in experimental tumor cells in vivo.

    Science.gov (United States)

    Araki, H; Fukushima, M; Kamiyama, Y; Shirasaka, T

    2000-11-28

    It is known that cisplatin (CDDP) potentiates the cytotoxicity of 5-fluorouracil (5-FU), and that the biochemical mechanism is an increase in the intracellular reduced folate levels in the tumor cells. We investigated the effect of consecutive administration with lower-dose CDDP on intracellular accumulation of reduced folate and the activity of methionine synthase, a key enzyme in intracellular methionine synthesis. When CDDP (1 mg/kg) was administered i.p. to ascitic Yoshida sarcoma-bearing rats for 4 consecutive days, both the reduced folate levels and methionine synthase activity in the cells significantly increased, as the same as a single 5 mg/kg dose of CDDP. Furthermore, when Yoshida sarcoma-bearing rats were pre-treated with 1 mg/kg CDDP for 5 consecutive days, [14C]L-methionine incorporation into the isolated ascitic cells was significantly inhibited as compared to that in non-treated cells, suggesting that consecutive administration of lower-dose CDDP is capable of inducing the intracellular modulation of reduced folate levels and methionine synthase activity via inhibition of cellular uptake of methionine. In addition, 5-day administration of lower-dose (1 mg/kg) CDDP potentiated the antitumor effect of 5 mg/kg S-1, a new oral preparation of tegafur, given for 7 consecutive days, and this combined effect was almost similar to the antitumor effect of a combination of S-1 and a single conventional dose (5 mg/kg) of CDDP. Consecutive lower-dose CDDP also may be concluded to act as an important modulator of the enhancement of 5-FU cytotoxicity in experimental tumors.

  3. Definitive Chemoradiation Therapy With Docetaxel, Cisplatin, and 5-Fluorouracil (DCF-R) in Advanced Esophageal Cancer: A Phase 2 Trial (KDOG 0501-P2)

    International Nuclear Information System (INIS)

    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/m2) and cisplatin (40 mg/m2) on day 1 and a continuous intravenous infusion of 5-fluorouracil (400 mg/m2/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

  4. Definitive Chemoradiation Therapy With Docetaxel, Cisplatin, and 5-Fluorouracil (DCF-R) in Advanced Esophageal Cancer: A Phase 2 Trial (KDOG 0501-P2)

    Energy Technology Data Exchange (ETDEWEB)

    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.

  5. Pharmacokinetics and tissue distribution of intraperitoneal 5-fluorouracil with a novel carrier solution in rats

    Institute of Scientific and Technical Information of China (English)

    Zhi-Gang Wei; Guo-Xin Li; Xiang-Cheng Huang; Li Zhen; Jiang Yu; Hai-Jun Deng; Shan-Hua Qing; Ce Zhang

    2008-01-01

    AIM: To compare the pharmacokinetics and tissue distribution of 5-fluorouracil administered intraperitoneally with two isotonic carrier solutions: HAES-steri (neotype 6% hydroxyethyl starch), a novel carrier solution with middle molecular weight and physiologic saline (0.9%sodium chloride solution), a traditional carrier solution for intraperitoneal chemotherapy, in rats.METHODS: A total of 60 Sprague Dawley rats were randomized into groups according to the carrier solution administered. Each group was further randomized according to the intraperitoneal dwell period (1, 3, 6, 12,18 and 24 h). At the end of the procedure the rats were killed, the peritoneal fluid was withdrawn completely and quantitated. Drug concentrations in peritoneal fluid, plasma, and tissues were determined by highperformance liquid chromatography.RESULTS: The mean volumes remaining in the peritoneal cavity were significantly higher with HAESsteri than those with physiologic saline at 1, 6, 12, 18,and 24 h (P=0.047, 0.009, 0.005, 0.005 and 0.005respectively, the percentages of remaining peritoneal fluid volume were 89.9 ± 5.6 vs 83.4 ± 4.9, 79.9 ± 2.8 vs 56.2 ± 15.7, 46.8 ± 5.5 vs 24.7± 9.7, 23.0 ± 2.8 0.0 ± 0.0 and 4.2 ± 1.7 vs 0.0 ± 0.0 respectively). Mean concentrations in peritoneal fluid were significantly higher with HAES-steri than those with physiologic saline at 3,12 and 18 h (P = 0.009, 0.009 and 0.005 respectively,the concentrations were 139.2768 ± 28.2317 mg/L vs mg/L, 11.5427 ± 3.0976 mg/L vs 0.0000 ± 0.0000 mg/L and 4.7724 ± 1.0936 mg/L vs 0.0000 ± 0.0000 mg/L respectively). Mean plasma 5-fiuorouracil concentrations in portal vein were significantly higher with HAES-steri at 3, 12, 18 and 24 h (P = 0.009, 0.034, 0.005 and 0.019 respectively, the concentrations were 3.3572 ± 0.8128 mg/L vs 0.8794 ± 0.2394 mg/L, 0.6203 ± 0.9935 mg/L vs 0.0112 ± 0.0250 mg/L, 0.3725 ± 0.3871 mg/L vs 0.0000 ± 0.0000 mg/L, and 0.2469 ± 0.1457 mg/L 0.0000 ± 0.0000 mg

  6. Manganese Superoxide Dismtase Polymorphism and Breast Cancer Recurrence: A Danish Population-Based Case-Control Study of Breast Cancer Patients Treated with Cyclophosphamide Epirubicin and 5-fluorouracil

    DEFF Research Database (Denmark)

    Ording, Anne Gulbech; Cronin Fenton, Deirdre; Christensen, Mariann;

    2013-01-01

    Manganese Superoxide Dismtase Polymorphism and Breast Cancer Recurrence: A Danish Population-Based Case-Control Study of Breast Cancer Patients Treated with Cyclophosphamide Epirubicin and 5-fluorouracil......Manganese Superoxide Dismtase Polymorphism and Breast Cancer Recurrence: A Danish Population-Based Case-Control Study of Breast Cancer Patients Treated with Cyclophosphamide Epirubicin and 5-fluorouracil...

  7. Chemotherapy by superselective intraarterial infusion of nedaplatin combined with radiotherapy for oral cancer

    International Nuclear Information System (INIS)

    Nedaplatin (CDGP), which is a CDDP derivative, has been reported to be an effective anticancer agent for head and neck cancer. This study was performed to assess the feasibility of chemotherapy by superselective intraarterial infusion of nedaplatin (CDGP) in patients with oral cancers. Ten patients were treated with chemotherapy by superselective intraarterial infusion of CDGP combined with radiotherapy. The complete and partial response rates were 7/10 (70%) and 3/10 (30%), respectively. Nine patients showed grade 1-2 hematological toxicity including leukocytopenia and anemia. Thrombocytopenia of grade 4 was seen in only one patient. However, all the patients were free from renal dysfunction. From these results, it is suggested that this combination therapy might be quite effective and safe. Further study will be needed to determine its efficacy against oral cancer. (author)

  8. Cadmium Modifies the Cell Cycle and Apoptotic Profiles of Human Breast Cancer Cells Treated with 5-Fluorouracil

    Directory of Open Access Journals (Sweden)

    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.

  9. 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

    2013-01-01

    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

  10. 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

    2013-01-01

    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

  11. Fermented Wheat Germ Extract Induced Cell Death and Enhanced Cytotoxicity of Cisplatin and 5-Fluorouracil on Human Hepatocellular Carcinoma Cells

    Directory of Open Access Journals (Sweden)

    Cheng-Jeng Tai

    2013-01-01

    Full Text Available Hepatocellular carcinoma (HCC is one of the most common causes of cancer-related death worldwide. Due to the difficulties of early diagnosis, curative treatments are not available for most patients. Palliative treatments such as chemotherapy are often associated with low response rate, strong adverse effects and limited clinical benefits for patients. The alternative approaches such as fermented wheat germ extract (FWGE with anti-tumor efficacy may provide improvements in the clinical outcome of current therapy for HCC. This study aimed to clarify antitumor efficacy of FWGE and the combination drug effect of FWGE with chemotherapeutic agents, cisplatin and 5-fluorouracil (5-Fu in human HCC cells, HepG2, Hep3B, and HepJ5. The present study indicated that FWGE exhibited potential to suppress HepG2, Hep3B, and HepJ5 cells, with the half maximal inhibitory concentrations (IC50 of FWGE were 0.494, 0.371 and 1.524 mg/mL, respectively. FWGE also induced Poly (Adenosine diphosphate ribose polymerase (PARP associated cell death in Hep3B cells. Moreover, the FWGE treatment further enhanced the cytotoxicity of cisplatin in all tested HCC cells, and cytotoxicity of 5-Fu in a synergistic manner in HepJ5 cells. Collectively, the results identified the anti-tumor efficacy of FWGE in HCC cells and suggested that FWGE can be used as a supplement to effectively improve the tumor suppression efficiency of cisplatin and 5-Fu in HCC cells.

  12. Antineoplastic Effect of Calcium Channel Blocker-Verapamil and 5-Fluorouracil Intraperitoneal Chemotherapy on Hepatocarcinoma-Bearing Rats

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Objective To study the antineoplastic effect of the calcium channel blocker verapamil and 5-fluorouracil intraperitoneal chemotherapy on hepatocarcinoma-bearing rats,and examine the action between calcium channel blockers and cytotoxic drugs. Methods We adopted the method of subcapsular implantation of carcinoma tissues of walker-256 in the left liver lobe as a model of liver carcinoma-bearing rats.All experimental animals were divided into four groups.On the sixth day post implantation,in group A (control group) 6ml of saline was injected intraperitoneally once a day for 3 days.In group B(single chemotherapy group) 6ml of 5-Fu 75 mg/kg was injected intraperitoneally once a day for 3 days.In group C(combination of treatment group)both 5-Fu(75mg/kg) and verapamil (25mg/kg) were administered simultaneously as in A and B.In group D(simple verapamil group)only 6ml of verapamil(25mg/kg)was administered as above. Results Compared with groups A, B and D,The volume of cancer and the contents of liver cancer DNA and protein were significantly reduced.The rates of inhibiting cancer(89.9% in group C and 35.4% in group B)were significantly increased in groupC. Group C had significantly long survival time compared to groups A, B and D(P<0.05).By light microscopy, a number of focal necroses were found in cancer tissue in group C.Conclusion Calcium channel blockers can enhance the antineoplastic effect of 5-Fu intraperitonea chemotherapy to liver cancer;The use of verapamil can not increase the toxicity of 5-Fu.

  13. Pharmacokinetics of ketamine and propofol combination administered as ketofol via continuous infusion in cats.

    Science.gov (United States)

    Zonca, A; Ravasio, G; Gallo, M; Montesissa, C; Carli, S; Villa, R; Cagnardi, P

    2012-12-01

    The pharmacokinetics of the extemporaneous combination of low doses of ketamine and propofol, known as 'ketofol', frequently used for emergency procedures in humans to achieve safe sedation and analgesia was studied in cats. The study was performed to assess propofol, ketamine and norketamine kinetics in six female cats that received ketamine and propofol (1:1 ratio) as a loading dose (2 mg/kg each, IV) followed by a continuous infusion (10 mg/kg/h each, IV, 25 min of length). Blood samples were collected during the infusion period and up to 24 h afterwards. Drug quantification was achieved by HPLC analysis using UV-visible detection for ketamine and fluorimetric detection for propofol. The pharmacokinetic parameters were deduced by a two-compartment bolus plus infusion model for propofol and ketamine and a monocompartmental model for norketamine. Additional data were derived by a noncompartmental analysis. Propofol and ketamine were quantifiable in most animals until 24 and 8 h after the end of infusion, respectively. Propofol showed a long elimination half-life (t(1/2λ2) 7.55 ± 9.86 h), whereas ketamine was characterized by shorter half-life (t(1/2λ2) 4 ± 3.4 h) owing to its rapid biotransformation into norketamine. The clinical significance of propofol's long elimination half-life and low clearance is negligible when the drug is administered as short-term and low-dosage infusion. The concurrent administration of ketamine and propofol in cats did not produce adverse effects although it was not possible to exclude interference in the metabolism. PMID:22283551

  14. Research on the development of bioadhesive vaginal tablets containing 5-fluorouracil.

    Science.gov (United States)

    Cojocaru, Ileana; Palade, Laura; Popovici, Iuliana; Georgescu, Gabriela; Bîrsan, Magdalena

    2013-01-01

    Biomucoadhesive vaginal tablets are modern formulations used in current therapy to achieve controlled release of the active substance at the application site by maintaining the pharmaceutical preparation at that level. This can be achieved by using mucoadhesive substances with different mechanical and physical-chemical properties. Two cellulose derivatives of different viscosity, Metolose 90 SH 4000 and Metolose 90 SH 100000, and two types of polyacrylates with different cross linking degrees, Carbopol 71, low degree of cross linking, and Carbopol 974, high degree of cross linking were used. In a previous study twelve original formulations of bioadhesive vaginal tablets containing 100 mg 5-fluorouracil (5-FU)/tablet (F1-F12) were formulated, prepared and analyzed. The pharmacotechnical characterization of the bioadhesive vaginal tablets containing 5-FU was performed by determining their specific quality characteristics. For the optimization of formulations, the influence of formulation factors on some quality characteristics (mechanical strength, friability, disintegration time) which may be influenced by the nature and amount of auxiliary substances used was studied by SPSS statistical software and statistical analysis ANOVA tests. The results are in favor of formulations F1, F2 containing 20-30% Carbopol 71 and of 37-47% Microcelac. PMID:24505926

  15. Core Cross-linked Star Polymers for Temperature/pH Controlled Delivery of 5-Fluorouracil

    Directory of Open Access Journals (Sweden)

    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.

  16. Polysaccharide-based nanocomplexes for co-encapsulation and controlled release of 5-Fluorouracil and Temozolomide.

    Science.gov (United States)

    Di Martino, Antonio; Pavelkova, Alena; Maciulyte, Sandra; Budriene, Saulute; Sedlarik, Vladimir

    2016-09-20

    Polysaccharide-based nanocomplexes, intended for simultaneous encapsulation and controlled release of 5-Fluorouracil (5-FU) and Temozolomide (TMZ) were developed via the complexation method using chitosan, alginic and polygalacturonic acid. Investigation focused on the influence of polysaccharides on the properties of the system and amelioration of the stability of the drugs, in particular TMZ. The dimensions of particles and their ζ-potential were found to range between 100 and 200nm and -25 to +40mV, respectively. Encapsulation efficiency varied from 16% to over 70%, depending on the given system. The influence of pH on the release and co-release of TMZ and 5-FU was evaluated under different pH conditions. The stability of the loaded drug, in particular TMZ, after release was evaluated and confirmed by LC-MS analysis. Results suggested that the amount of loaded drug(s) and the release rate is connected with the weight ratio of polysaccharides and the pH of the media. One-way ANOVA analysis on the obtained data revealed no interference between the drugs during the encapsulation and release process, and in particular no hydrolysis of TMZ occurred suggesting that CS-ALG and CS-PGA would represent interesting carriers for multi-drug controlled release and drugs protection.

  17. Synthesis and Crystal Structure of Tetraaquacopper(II) Bis(5-fluorouracil-1-acetate) Tetrahydrate

    Institute of Scientific and Technical Information of China (English)

    WANG Wei-Dong; HU Mao-Lin

    2006-01-01

    The title compound, [Cu(C6H4N2O4F)2(H2O)4]·4(H2O) I, has been hydrothermally synthesized and structurally determined by single-crystal X-ray diffraction method. It crystallizes in monoclinic, space group P21/c with a = 8.3041(17), b = 12.045(2), c = 11.077(2) (A), β = 92.567(3)o, V = 1106.8(4)(A)3, Mr = 581.89, Z = 2, Dc = 1.746 g/cm3, F(000) = 598, μ(MoKα) = 1.090 mm-1, the final R = 0.0296 and wR = 0.0806 for 3195 observed reflections with I > 2σ(I). In the centrosymme- tric compound I, each Cu(II) ion is coordinated by six O atoms from two 5-fluorouracil-1-acetate anions and four water molecules, forming a six-coordinated octahedral environment. N-H…O and O-H…O hydrogen-bonding interactions are observed in the structure, leading to the formation of a three-dimensional network.

  18. Base excision by thymine DNA glycosylase mediates DNA-directed cytotoxicity of 5-fluorouracil.

    Directory of Open Access Journals (Sweden)

    Christophe Kunz

    2009-04-01

    Full Text Available 5-Fluorouracil (5-FU, a chemotherapeutic drug commonly used in cancer treatment, imbalances nucleotide pools, thereby favoring misincorporation of uracil and 5-FU into genomic DNA. The processing of these bases by DNA repair activities was proposed to cause DNA-directed cytotoxicity, but the underlying mechanisms have not been resolved. In this study, we investigated a possible role of thymine DNA glycosylase (TDG, one of four mammalian uracil DNA glycosylases (UDGs, in the cellular response to 5-FU. Using genetic and biochemical tools, we found that inactivation of TDG significantly increases resistance of both mouse and human cancer cells towards 5-FU. We show that excision of DNA-incorporated 5-FU by TDG generates persistent DNA strand breaks, delays S-phase progression, and activates DNA damage signaling, and that the repair of 5-FU-induced DNA strand breaks is more efficient in the absence of TDG. Hence, excision of 5-FU by TDG, but not by other UDGs (UNG2 and SMUG1, prevents efficient downstream processing of the repair intermediate, thereby mediating DNA-directed cytotoxicity. The status of TDG expression in a cancer is therefore likely to determine its response to 5-FU-based chemotherapy.

  19. Treatment of advanced esophageal cancer by means of irradiation, cisplatinum and 5-fluorouracil

    International Nuclear Information System (INIS)

    In the years 1985-1990, 30 patients with locally advanced and/or disseminated cancer of the esophagus (Stages III and IV) were treated by radiotherapy and chemotherapy containing cisplatinum and 5-fluorouracil (5-fu). The median survival of the patients was 8 months (range 2.5-39 months); 13 stage III patients survived 3-36 months respectively (median 11 months), while 17 stage IV patients survived 2.5-27 months, respectively (median 6.5 months). The survival depended statistically significantly (p<0.05) only on the presence or absence of residual tumor after therapy and not on other parameters observed. Clinical response to treatment was evaluated in 16/30 patients as follows: clinical response (CR) was obtained in 4 patients, partial response in two, and no respond in 10 patients. Median survival of 4 patients with CR was 31 months; relatively high rate of CR (4/16) could be explained by the small number of patients. However, favorable survival results in individual patients may be expected even in larger series, though the rate responders may be somewhat lower than that obtained in our study. (author)

  20. Analysis of chemotherapy drug 5-fluorouracil and its metabolites by surface-enhanced Raman spectroscopy

    Science.gov (United States)

    Gift, Alan D.; Shende, Chetan S.; Inscore, Frank E.; Farquharson, Stuart

    2004-12-01

    Chemotherapy drug dosage is based on the limited statistics of the response of previously treated patients and administered according to body surface area. Considerably better dose regulation could be performed if the drug metabolism of each patient could be monitored. Unfortunately, current technologies require multiple withdrawals of blood to determine metabolism, a precious fluid in limited supply. Saliva analysis has long been considered an attractive alternative, but unfortunately standard techniques require large quantities that are difficult to obtain. In an effort to overcome this limitation we have been investigating the ability of metal-doped sol-gels to both separate drugs and their metabolites from saliva and generate surface-enhanced Raman spectra. Surface-enhanced Raman spectroscopy has the potential to perform this analysis with just a few drops of sample due to its extreme sensitivity. Preliminary measurements are presented for the chemotherapy drug, 5-fluorouracil, and its two metabolites 5-fluorouridine and 5-fluoro-2'-deoxyuridine, and the potential of determining metabolism on a patient-by-patient basis.

  1. Raman spectroscopic investigations on the interactions of gastric cancer cells with 5-fluorouracil

    Institute of Scientific and Technical Information of China (English)

    Jianyu Guo; Weiying Cai; Jipeng Yang; Zhenrong Sun

    2008-01-01

    To study the efficacy and side effects of antitumor drug by the method of Raman spectroscopy, the cancerous (SGC-7901) and normal (GES-1) gastric cells were treated with 0, 25-, 100-, and 200-mg/L 5-fluorouracil (5-Fu) for 24 h, respectively, then Raman spectra of cells were recorded. The excitation wavelength was 514.5 nm and the Raman spectra in the region of 500 - 1800 cm-1 were recorded. For the gastric cancer cells, as the concentration of 5-Fu increases, the band at 1094 cm-1 attributed to the symmetric stretching vibration mode of PO2- in the DNA backbone gradually decreases, and the intensity ratio of the band at 1315 cm-1 to that at 1340 cm-1 (I1315/I1340) shows the ascending trend, and the ratio of the band area at 1655 cm-1 to that at 1450 cm-1 (A1655/A1450) shows the slight ascending trend. For the normal gastric cells, these peaks also appear changes, however, the changes are weaker than those for the cancer cells. In SGC-7901 cells, 5-Fu can interfere with the DNA synthesis and result in the reduction of the DNA content. Besides, it can affect the unsaturation degree of the hydrocarbon chains and alter the external environment of guanine and adenine residues in cancer cells. The changes of Raman spectra for normal gastric cells reveal the side effect of 5-Fu.

  2. Development of novel ionic liquid-based microemulsion formulation for dermal delivery of 5-Fluorouracil.

    Science.gov (United States)

    Goindi, Shishu; Arora, Prabhleen; Kumar, Neeraj; Puri, Ashana

    2014-08-01

    The present study was aimed at synthesizing an imidazole-based ionic liquid 1-butyl-3-methylimidazolium bromide (BMIMBr) and subsequent development of a novel ionic liquid-in-oil (IL/o) microemulsion (ME) system for dermal delivery of a poorly permeating drug 5-fluorouracil (5-FU). A significant enhancement in the solubility of 5-FU was observed in BMIMBr. IL/o MEs of 5-FU were prepared using isopropyl myristate, Tween 80/Span 20, and BMIMBr. Results of ex vivo skin permeation studies through mice skin indicated that the selected IL/o ME exhibited 4-fold enhancement in percent drug permeation as compared to aqueous solution, 2.3-fold as compared to hydrophilic ointment, and 1.6-fold greater permeation than water in oil (w/o) ME. The results of in vivo studies against dimethylbenz(a)anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mice skin carcinogenesis demonstrated that the IL/o ME could effectively treat skin cancer in 4 weeks. In addition, the side effects such as erythema and irritation associated with the conventional formulations were not observed. Histopathological studies showed that the use of IL/o ME caused no anatomic and pathological changes in the skin structure of mice. These studies suggest that the use of IL-based ME system can efficiently enhance the solubility and permeability of 5-FU and hence its therapeutic efficacy. PMID:24668136

  3. In vitro effect of 5-fluorouracil and paclitaxel on Echinococcus granulosus larvae and cells.

    Science.gov (United States)

    Pensel, P E; Albani, C; Gamboa, G Ullio; Benoit, J P; Elissondo, M C

    2014-12-01

    Human cystic echinococcosis is a zoonosis caused by the metacestode stage of the tapeworm Echinococcus granulosus. Although benzimidazole compounds such as albendazole and mebendazole have been the cornerstone of chemotherapy for the disease, there is often no complete recovery after treatment. Hence, in searching for novel treatment options, we examined the in vitro efficacies of 5-fluorouracil (5-FU) and paclitaxel (PTX) against E. granulosus germinal cells, protoscoleces and cysts. 5-FU or PTX inhibited the growth of E. granulosus cells in a time dependent manner. Although both treatments had a protoscolicidal effect, 5-FU had a considerably stronger effect than PTX. 5-FU produced a dose- and time-dependent effect, provoking the complete loss of viability after 24 days of incubation. Moreover, cysts did not develop following the inoculation of treated protoscoleces into mice. The loss of viability was slower in PTX treated protoscoleces, reaching to approximately 60% after 30 days. The results of the in vitro treatment with 5-FU and PTX were similar in secondary murine cysts. The employment of SEM and TEM allowed us to examine, at an ultrastructural level, the effects induced by 5-FU and PTX on E. granulosus germinal cells, protoscoleces and murine cysts. In conclusion, the data obtained clearly demonstrated that 5-FU and PTX at clinically achievable concentrations inhibit the survival of larval cells, protoscoleces and metacestodes. In vivo studies to test the antiparasitic activities of 5-FU and PTX are currently being undertaken on the murine model of cystic echinococcosis.

  4. The effect of microneedles on the skin permeability and antitumor activity of topical 5-fluorouracil

    Directory of Open Access Journals (Sweden)

    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.

  5. Role of 5 fluorouracil in the management of failed glaucoma surgery

    Directory of Open Access Journals (Sweden)

    Sood N

    1990-01-01

    Full Text Available Filtering surgery for glaucoma usually controls the intraocular pressure adequately. However, in glaucoma patients with aphakia, neovascularisation of iris, previous failed filtering surgeries and relatively young patients, results of surgery leave much scope for improvement. Most failures of filtering surgery are related to extra-ocular factors. Histopathological studies of eyes after failed filtering operations have suggested that proliferation of fibroblasts and deposition of collagen constitute a barrier to filteration. There is also a positive correlation between success of filtering surgery and inhibition of fibroblast growth by the patients aqueous humour. Thus agents inhibiting fibroblast proliferation should play an important role in increasing the success rate of filtering surgery. 5 Fluorouracil is a pyrimidine analogue which has been utilised for over 15 years as an antimetabolite in cancer therapy. Its efficiency in inhibiting fibroblast proliferation in vitro and in rabbit eyes has been proved beyond doubt. We undertook a pilot project to estimate the efficiency of the subconjunctival 5 FU to increase the changes of success in problematic cases of glaucoma in pigmented eyes.

  6. 5-Fluorouracil in the Treatment of Keloids and Hypertrophic Scars: A Comprehensive Review of the Literature.

    Science.gov (United States)

    Shah, Vidhi V; Aldahan, Adam S; Mlacker, Stephanie; Alsaidan, Mohammed; Samarkandy, Sahal; Nouri, Keyvan

    2016-06-01

    Hypertrophic (HTSs) and keloid scars are common dermatological complaints produced by disruption of the normal wound-healing process. Despite a wide array of therapeutic options available to treat these lesions, HTSs and keloids continue to pose a significant challenge to clinicians in everyday practice. The chemotherapeutic drug 5-fluorouracil (5-FU) is a well-known treatment option reserved for recalcitrant HTSs and keloid lesions. We present clinicians with a comprehensive review of the published data concerning the use of 5-FU in the treatment of HTSs and keloids. The current evidence suggests that 5-FU is a safe and practical alternative for the treatment of HTSs and keloids as it may substantially improve the appearance of proliferative scars and reduce the chance of recurrence. This therapeutic option is most effective in conjunction with adjuvant therapy such as corticosteroids. Additional randomized controlled clinical trials with large sample sizes should be conducted to corroborate the existing efficacy and safety data in patients with HTSs and keloids. PMID:27105629

  7. Efeito do colírio de 5-fluorouracil sobre o epitélio corneano íntegro de coelhos Effects of 5-fluorouracil eye drops on intact rabbit corneal epithelium

    Directory of Open Access Journals (Sweden)

    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

  8. Synthesis, Structure and Antitumor Activity of Dibutyltin Oxide Complexes with 5-Fluorouracil Derivatives. Crystal Structure of [(5-Fluorouracil-1-CH2CH2COOSn(n-Bu 2]4O2

    Directory of Open Access Journals (Sweden)

    Zhan Shi

    2001-07-01

    Full Text Available Dibutyltin (IV oxide complex reacts with the fluorouracil compounds 5-fluorouracil-1-propanonic or 5-fluorouracil-1-acetic acid (Fu to give the complexes [(5-Fu-1-(CH2nCOOSn(n-Bu2]4O2 (I, n=2; II, n=1 which were characterized by IR and 1H-NMR. The crystal structure of complex I shows that the molecular is a dimer, in which two [(5-Fu-1-CH2CH2COOSn(n-Bu2]2O units are linked by a bridging oxygen atom, and the tin atoms adopt distorted trigonal bipyramids via two carbons from a dibutyl moiety and three oxygen atoms from 5-Fu and bridging oxygen. These complexes have potential anti-tumour activity: in vitro tests showed that complexes I and II exhibit high cytotoxicity against OVCAR-3 and PC-14.

  9. Effects and mechanism analysis of combined infusion by levosimendan and vasopressin on acute lung injury in rats septic shock.

    Science.gov (United States)

    Wang, Xuebing; Ma, Shaolin; Liu, Yang; Xu, Wei; Li, Zhanxia

    2014-12-01

    This research is aimed to discover the influence and underling mechanism of combined infusion of arginine vasopressin with levosimendan on acute lung injury in rat septic shock with norepinephrine supplemented. The traditional fecal peritonitis-induced septic shock model was undergone in rats for study. It is observed that the combined infusion supplemented with norepinephrine brought about a lower mean pulmonary artery pressure; lower high-mobility group box 1 levels, pulmonary levels of interleukin-6, and arterial total nitrate/nitrite; lower apoptotic cells scores and total histological scores; but higher pulmonary gas exchange when compared with the separate infusion group and norepinephrine group. This therapy shows potential clinical beneficial assistance in sepsis-induced acute lung injury. The results suggest the mechanism of such effect is through abating pulmonary artery pressure, and more importantly suppressing inflammatory responses in lung when compared with norepinephrine infusion group and the separate infusion of levosimendan or vasopressin alone. PMID:25002345

  10. 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. PMID:27117429

  11. The Prediction of Nanoscale Drug Molecular Structure and Acid Dissociation Constants of 5-Fluorouracil in Aqueous Solution Using DFT Methods

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    Baghery SMS

    2013-09-01

    Full Text Available Background and Objective : In this work, dissociation of nano drug 5 -Fluorouracil derivatives was studied theoretically. Methodology : For this purpose, Gibbs free energy values for neutral and deprotonated forms of 5 -Fluorouracil were calculated at gas and aqueous phases by using density functional theory (DFT method. Solvent effects are taken into account by means of polarizable continuum model (PCM. Result : It was shown that, theoretically calculated pKa values are in good agreement with the existing experimental pKa values, which are determined from capillary electrophoresis, potentiometric titration and UV visible spectrophotometric measurements. Conclusion : In summary, cluster continuum method with implicit - explicit solvent molecules was used for calculation of pKa values.Total energies and molecular parameters were obtained for 5 - FUra nanoscale drug systems, at B3LYP6-31G(d level of theory for the anion, cation, and neutral species.

  12. Influences of Organic Solvents on Particle Size and Drug-loading Efficiency for 5-Fluorouracil Poly(lactic acid) Nanoparticles

    Institute of Scientific and Technical Information of China (English)

    LIUXiao-yan; CHANGJin; GUOYan-shuang; YUANXu-bo; LIXiao-rong; LIUChun-ling; SONGCun-xian

    2004-01-01

    The objective of this study was to investigate the influences of organic solvents on particle size, drug content, loading efficiency and yield for 5-Fluorouracil Poly (lactic acid) nanoparticles . The 5-Fluorouracil was entrapped into poly(lactic acid)(PLA) nanoparticles using a water-in-oil-in-water solvent evaporation technique. During the preparation process, ethyl acetate and acetone were used as organic solvents since they are less toxic than the more commonly used dichloromethane. The effect of the three solvents on particle size, drug content, loading efficiency and yield of nanopartcles was compared. When the solvent of the oil phase was acetone, the highest drug content, smallest particle size and lowest yield were obtained for the PLA nanoparticles.

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

    Energy Technology Data Exchange (ETDEWEB)

    Panozzo, J.; Akan, E. [Argonne National Lab., IL (United States); Griffiths, T.D. [Northern Illinois Univ., De Kalb, IL (United States). Dept. of Biological Sciences; Woloschak, G.E. [Argonne National Lab., IL (United States)

    1996-03-01

    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.

  14. Fourier transform infrared spectroscopy for the distinction of MCF-7 cells treated with different concentrations of 5-fluorouracil

    OpenAIRE

    WU, BI-BO; Gong, Yi-Ping; Wu, Xin-Hong; Chen, Yuan-Yuan; Chen, Fang-Fang; Jin, Li-Ting; Cheng, Bo-Ran; Hu, Fen; Xiong, Bin

    2015-01-01

    Background In order to provide personalized treatment to patients with breast cancer, an accurate, reliable and cost-efficient analytical technique is needed for drug screening and evaluation of tumor response to chemotherapy. Methods Attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) was used as a tool to assess cancer cell response to chemotherapy. MCF-7 cells (human breast adenocarcinoma cell line) were treated with different concentrations of 5-fluorouracil (5...

  15. Neoadjuvante Chemotherapie mit Paclitaxel, Cisplatin, Leucovorin und 5-Fluorouracil beim lokal fortgeschrittenen Adenokarzinom des Ösophagus

    OpenAIRE

    Bader, Franz Georg

    2005-01-01

    In einer prospektiven Phase-II-Studie wurde die Kombination Paclitaxel/Cisplatin/Leucovorin/5-Fluorouracil bei 35 Patienten mit lokal fortgeschrittenen Adenocarzinomen des Ösophagus hinsichtlich Wirksamkeit und verträglichkeit geprüft. Auf die neoadjuvante Therapie ansprechende Patientensollten anschließend in kurativer Intention operiert werden. Die Remissionsrate betrug 48%. 29 Patienten wurden reseziert mit einem Anteil von 64,5% R0-Resektionen. In 31% der Resektate betrug die Tumorregress...

  16. Controlled 5-fluorouracil release from hydrogels of Poly (acrylamide-co-metacrylic acid) crosslinked by means Of gamma irradiation techniques

    International Nuclear Information System (INIS)

    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

  17. Gefitinib, Methotrexate and Methotrexate plus 5-Fluorouracil as palliative treatment in recurrent head and neck squamous cell carcinoma

    OpenAIRE

    Kushwaha, Vandana Singh; Gupta, Seema; Husain, Nuzhat; Khan, Huma; Negi, MPS; Jamal, Naseem; Ghatak, Ashim

    2015-01-01

    This study compared the efficacy and toxicity of Gefitinib, Methotrexate and Methotrexate plus 5-Fluorouracil (5-FU) in patients of recurrent squamous cell carcinoma of head and neck (SCCHN) treated with palliative intent. Patients with recurrent SCCHN not amenable to curative treatment were randomly assigned to Gefitinib, Methotrexate or Methotrexate plus 5-FU arm. The primary end point was overall survival. Secondary end points of interest were objective response rate, toxicity and quality ...

  18. Development and characterization of chitosan-polycarbophil interpolyelectrolyte complex-based 5-fluorouracil formulations for buccal, vaginal and rectal application

    OpenAIRE

    Pendekal, Mohamed S.; Tegginamat, Pramod K

    2012-01-01

    Abstract Background of the study The present investigation was designed with the intention to formulate versatile 5-fluorouracil (5-FU) matrix tablet that fulfills the therapeutic needs that are lacking in current cancer treatment and aimed at minimizing toxic effect, enhancing efficacy and increasing patient compliance. The manuscript presents the critical issues of 5-FU associate with cancer and surpasses issues by engineering novel 5-FU matrix tablets utilizing chitosan- polycarbophil inte...

  19. Comment: The comparison study of 5 Fluorouracil vs. cryotherpy in the treatment of the backhand resistant common wart

    Directory of Open Access Journals (Sweden)

    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.

  20. Growth hormone releasing peptide 2 reverses anorexia associated with chemotherapy with 5-fluorouracil in colon cancer cell-bearing mice

    OpenAIRE

    Perboni, Simona; Bowers, Cyril; Kojima, Shinya; Asakawa, Akihiro; Inui, Akio

    2008-01-01

    The cancer-associated anorexia-cachexia syndrome is observed in 80% of patients with advanced-stage cancer, and is one of the major obstacles in chemotherapy. Ghrelin is a orexigenic hormone that has been proposed to prevent anorexia. Aim of the study was to determine whether the addition of the ghrelin agonist growth hormone releasing peptide 2 (GHRP-2) to cytotoxic therapy with 5-fluorouracil (5-FU) prevents the anorexia associated with chemotherapy in cancer cachectic mice. Thirty-three BA...

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

    OpenAIRE

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

    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 th...

  2. Synthesis, structural elucidation, biological, antioxidant and nuclease activities of some 5-Fluorouracil-amino acid mixed ligand complexes

    Science.gov (United States)

    Shobana, Sutha; Subramaniam, Perumal; Mitu, Liviu; Dharmaraja, Jeyaprakash; Arvind Narayan, Sundaram

    2015-01-01

    Some biologically active mixed ligand complexes (1-9) have been synthesized from 5-Fluorouracil (5-FU; A) and amino acids (B) such as glycine (gly), L-alanine (ala) and L-valine (val) with Ni(II), Cu(II) and Zn(II) ions. The synthesized mixed ligand complexes (1-9) were characterized by various physico-chemical, spectral, thermal and morphological studies. 5-Fluorouracil and its mixed ligand complexes have been tested for their in vitro biological activities against some pathogenic bacterial and fungal species by the agar well diffusion method. The in vitro antioxidant activities of 5-Fluorouracil and its complexes have also been investigated by using the DPPH assay method. The results demonstrate that Cu(II) mixed ligand complexes (4-6) exhibit potent biological as well as antioxidant activities compared to 5-Fluorouracil and Ni(II) (1-3) and Zn(II) (7-9) mixed ligand complexes. Further, the cleaving activities of CT DNA under aerobic conditions show moderate activity with the synthesized Cu(II) and Ni(II) mixed ligand complexes (1-6) while no activity is seen with Zn(II) complexes (7-9). Binding studies of CT DNA with these complexes show a decrease in intensity of the charge transfer band to the extent of 5-15% along with a minor red shift. The free energy change values (Δ‡G) calculated from intrinsic binding constants indicate that the interaction between mixed ligand complex and DNA is spontaneous.

  3. Up-regulation of cyclooxygenase-2-derived prostaglandin E2 in colon cancer cells resistant to 5-fluorouracil

    OpenAIRE

    Choi, Cheol Hee; Lee, Tae Bum; Lee, Yeon Ah; Choi, Suk; Kim, Kyung Jong

    2011-01-01

    Purpose It has been suggested that constitutive up-regulation of cyclooxygenase (COX)-2 is associated with resistance to apoptosis, increased angiogenesis, and increased tumor invasiveness in various cancers including colon cancer. There are many factors involved in the resistance to 5-fluorouracil (5-FU) in colon cancer. However, little is known about the role of COX-2 in acquired resistance to 5-FU in colon cancer. Methods Hence we investigated whether COX-2 contribute to acquired resistanc...

  4. Genome-wide screening of loci associated with drug resistance to 5-fluorouracil-based drugs.

    Science.gov (United States)

    Ooyama, Akio; Okayama, Yoshihiro; Takechi, Teiji; Sugimoto, Yoshikazu; Oka, Toshinori; Fukushima, Masakazu

    2007-04-01

    Resistance to chemotherapeutic agents represents the chief cause of mortality in cancer patients with advanced disease. Chromosomal aberration and altered gene expression are the main genetic mechanisms of tumor chemoresistance. In this study, we have established an algorithm to calculate DNA copy number using the Affymetrix 10K array, and performed a genome-wide correlation analysis between DNA copy number and antitumor activity against 5-fluorouracil (5-FU)-based drugs (S-1, tegafur + uracil [UFT], 5'-DFUR and capecitabine) to screen for loci influencing drug resistance using 27 human cancer xenografts. A correlation analysis confirmed that the single nucleotide polymorphism (SNP) showing significant associations with drug sensitivity were concentrated in some cytogenetic regions (18p, 17p13.2, 17p12, 11q14.1, 11q11 and 11p11.12), and we identified some genes that have been indicated their relations to drug sensitivity. Among these regions, 18p11.32 at the location of the thymidylate synthase gene (TYMS) was strongly associated with resistance to 5-FU-based drugs. A change in copy number of the TYMS gene was reflected in the TYMS expression level, and showed a significant negative correlation with sensitivity against 5-FU-based drugs. These results suggest that amplification of the TYMS gene is associated with innate resistance, supporting the possibility that TYMS copy number might be a predictive marker of drug sensitivity to fluoropyrimidines. Further study is necessary to clarify the functional roles of other genes coded in significant cytogenetic regions. These promising data suggest that a comprehensive DNA copy number analysis might aid in the quest for optimal markers of drug response. PMID:17425594

  5. Conversion of 5-fluorocytosine to 5-fluorouracil by human intestinal microflora

    International Nuclear Information System (INIS)

    5-Fluorocytosine (FC) is used to treat systemic fungal infections in man. Its clinical effectiveness has been limited by hematologic toxicity which may be secondary to the formation of 5-fluorouracil (FU). It is unclear how FU is formed since human cells lack cytosine deaminase. The present study examined if intestinal microflora (IMF) could convert FC to FU in man. An in vitro semicontinuous culture system was inoculated with human feces and maintained with sterile nutrient suspension. The microbial community was assessed for cell count and anaerobes as well as formation of volatile fatty acids and CH4. The system approximated that believed to occur in vivo. The study was initiated with addition of purified [6-14C]-FC. Unlabelled FC was then added to the system daily for 2 weeks following which [6-14C]-FC was again added. Following each addition of [6-14C]-FC, samples were removed at 2,4,8,24,48,72, and 96 hr. Utilizing HPLC, FC and FU could be separated with quantitation of radioactivity in each peak. Following the initial dose, no detectable FU was observed during the first 8 hr, but after 24 hr increasing levels were detected (9.42 μg FU/ml after 4 days). Following chronic administration of FC, increased levles of FU were noted without an 8 hr lag time in the production of FU (31.86 μg FU/ml after 4 days). In summary, these studies demonstrate that IMF can convert FC to FU possibly accounting for toxicity observed following administration of FC

  6. Use of Zeolite ZSM-5 for Loading and Release of 5-Fluorouracil

    Directory of Open Access Journals (Sweden)

    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.

  7. Reduction of Orc6 expression sensitizes human colon cancer cells to 5-fluorouracil and cisplatin.

    Directory of Open Access Journals (Sweden)

    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.

  8. Effects of 5-fluorouracil on survival and hematopoiesis in irradiated mice

    International Nuclear Information System (INIS)

    The effects of whole-body irradiation on survival and hematopoiesis were studied in mice treated with 5-fluorouracil (5-FU). Animals (ddy-SLC male mice, 8 - 10 weeks old) were injected with 5-FU (i.p.) as a single dose (150 mg/kg) at various times before or after irradiation with X-rays. In mice pretreated with 5-FU at different intervals before X-irradiation (1.9 Gy), the radiosensitivity of the CFU-S population changed day by day after the treatment. The maximal survival for femoral CFU-S was obtained in mice treated with 5-FU at 5 days before irradiation. The post-irradiation recovery for femoral and splenetic CFU-S in mice pretreated with 5-FU at 3 days before X-irradiation (1.9 Gy) was faster than in mice given irradiation alone. The pattern of change for thrombocyte counts in the circulating blood after X-irradiation (1.9 Gy) was greatly modified by the pretreatment with 5-FU at 5 days before irradiation, being effective in lessening the radiation-induced depression. For survival experiments, treatment of mice with 5-FU at 5 days before X-irradiation with graded doses (4.8 to 7.6 Gy) was the most effective in reducing for radiation lethality. The dose reduction factor was obtained as 1.24. However, treatment with 5-FU at 1 day and 2 hours before, and at times after irradiation increased the radiation lethality compared to the untreated controls. Such phenomena on the decrease or the increase of radiation lethality of 5-FU exhibited a similar pattern to the radiation-dose relation on endogenous and exogenous CFU-S. (author)

  9. Effect of early preoperative 5-fluorouracil on the integrity of colonic anastomoses in rats

    Institute of Scientific and Technical Information of China (English)

    Leyla Ozel; M Sefa Ozel; Ahmet Burak Toros; Melih Kara; Kemal S(I)rr(I) Ozkan; Gurkan Tellioglu; Osman Krand; Meral Koyuturk; Ibrahim Berber

    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 signifi-cantly 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.

  10. Development of in situ gelling and bio adhesive 5-Fluorouracil enema.

    Science.gov (United States)

    Wang, Lu-Lu; Zheng, Wen-Sheng; Chen, Shao-Hua; Fang, Xia-Qin

    2013-01-01

    In this study, a novel 5-Fluorouracil (5-FU) enema with good bio adhesion and temperature sensitivity was developed using in situ gelling technology. The preparation was formulated as a free-flowing liquid before use, while a layer of gel film was quickly formed when administered in the rectum, with a large contact surface area. It also demonstrated good biocompatibility, appropriate gel strength and bio adhesive force with excellent adhesion to rectal mucosa and prolonged action time, allowing more effective drug absorption and diffusion to surrounding tissues. Poloxamer 407 and poloxamer 188 were applied to adjust the gelling temperature. With the addition of carbopol and polycarbophil (bio adhesive substances), the solubility of 5-FU and gel strength increased, the temperature of gelation and the surface area of drug contact on mucous epithelium decreased. Decreased adhesive force between the preparation and the mucous membrane of the rectum was demonstrated with improving carbopol and polycarbophil's concentration. In vitro release demonstrated that 5-FU in situ gelling enema with different bases had a rapid and almost complete drug release. We used an optimized formulation of P407/P188/polycarbophil/5-FU (17/2.5/0.2/1.0) for animal experiments. The result showed that the drug evenly covered the surface of the rectum and there was no leakage in 6 hours. The in situ gelling enema showed significantly higher rectal tissue levels of 5-FU compared with suppository and intravenous administration, indicating that 5-FU could be well absorbed due to the enlarged releasing area, longer retention time and larger amount of dissolved active ingredients. Systemically, 5-FU levels in the enema group were similar to those in the suppository group and significantly lower than the intravenous group. The enema was not associated with morphological damage to rectal tissue. These results suggest that the bio adhesive and in situ gelling enema could be a more effective rectal

  11. Development of in situ gelling and bio adhesive 5-Fluorouracil enema.

    Directory of Open Access Journals (Sweden)

    Lu-Lu Wang

    Full Text Available In this study, a novel 5-Fluorouracil (5-FU enema with good bio adhesion and temperature sensitivity was developed using in situ gelling technology. The preparation was formulated as a free-flowing liquid before use, while a layer of gel film was quickly formed when administered in the rectum, with a large contact surface area. It also demonstrated good biocompatibility, appropriate gel strength and bio adhesive force with excellent adhesion to rectal mucosa and prolonged action time, allowing more effective drug absorption and diffusion to surrounding tissues. Poloxamer 407 and poloxamer 188 were applied to adjust the gelling temperature. With the addition of carbopol and polycarbophil (bio adhesive substances, the solubility of 5-FU and gel strength increased, the temperature of gelation and the surface area of drug contact on mucous epithelium decreased. Decreased adhesive force between the preparation and the mucous membrane of the rectum was demonstrated with improving carbopol and polycarbophil's concentration. In vitro release demonstrated that 5-FU in situ gelling enema with different bases had a rapid and almost complete drug release. We used an optimized formulation of P407/P188/polycarbophil/5-FU (17/2.5/0.2/1.0 for animal experiments. The result showed that the drug evenly covered the surface of the rectum and there was no leakage in 6 hours. The in situ gelling enema showed significantly higher rectal tissue levels of 5-FU compared with suppository and intravenous administration, indicating that 5-FU could be well absorbed due to the enlarged releasing area, longer retention time and larger amount of dissolved active ingredients. Systemically, 5-FU levels in the enema group were similar to those in the suppository group and significantly lower than the intravenous group. The enema was not associated with morphological damage to rectal tissue. These results suggest that the bio adhesive and in situ gelling enema could be a more

  12. Transcription and activity of 5-fluorouracil converting enzymes in fluoropyrimidine resistance in colon cancer in vitro.

    Science.gov (United States)

    Mader, R M; Sieder, A E; Braun, J; Rizovski, B; Kalipciyan, M; Mueller, M W; Jakesz, R; Rainer, H; Steger, G G

    1997-12-01

    Cellular resistance to 5-fluorouracil (5-FU) is not completely understood. Since 5-FU shares the pyrimidine pathway with the physiological pyrimidines, we investigated the relationship between fluoropyrimidine metabolism, nucleic acid uptake and cytotoxicity of 5-FU in eight colon tumour cell lines including 5-FU-resistant subclones. The cytotoxicity of 5-FU was increased up to 423-fold when the anabolites 5-fluorouridine (FUrd), 5-fluorodeoxyuridine (FdUrd), and 5-fluorodeoxyuridine monophosphate (FdUMP) were compared with the parent drug in vitro. The enzymes uridine phosphorylase and thymidine phosphorylase were predictive for the cytotoxicity of 5-FU in 5/7 cell lines. Inhibition of uridine phosphorylase and thymidine phosphorylase by antisense strategies effectively antagonised 5-FU, abolishing 84% and 79% of its toxicity. The importance of thymidine phosphorylase was supported by a highly restricted enzyme activity in 5-FU-resistant cells. In 5-FU naive cells, a stimulating effect of 5-FU on thymidylate synthase mRNA and ribonucleotide reductase mRNA expression was observed. In these cells, antisense oligonucleotides to ribonucleotide reductase significantly reduced cell growth. Downregulation of ribonucleotide reductase mRNA in 5-FU-resistant subclones suggests different mechanisms in primary and secondary resistance to 5-FU. Most of the intracellular 5-FU was selectively incorporated into RNA (range: 45-91%) and generally spared DNA (range: 0.2-11%). In synthesising our data, we conclude that drug resistance could be overwhelmed through bypassing limiting steps in the activation of 5-FU. In the majority of colonic tumours, the activity of uridine phosphorylase and thymidine phosphorylase may have prognostic relevance for the cytotoxicity of 5-FU in vitro.

  13. Systemic 5-fluorouracil treatment causes a syndrome of delayed myelin destruction in the central nervous system

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    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.

  14. Comparison of capecitabine and 5-fluorouracil in chemoradiotherapy for locally advanced pancreatic cancer

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    Although capecitabine has theoretical advantages in the pharmacokinetics, such as higher intratumoral and lower systemic concentration, relative to bolus 5-fluorouracil (5-FU), outcomes of chemoradiotherapy (CRT) with capecitabine or bolus 5-FU have not been directly compared in patients with locally advanced pancreatic cancer. Therefore, we retrospectively compared the outcomes, including toxicity, tumor response, and overall survival, of oral capecitabine plus radiotherapy (RT) with bolus 5-FU plus RT, in patients with locally advanced pancreatic cancer. Between August 2006 and January 2012, 98 patients with locally advanced pancreatic cancer received CRT, with 52 receiving concurrent oral capecitabine and 46 receiving bolus injection of 5-FU. Primary tumor and overall response after CRT were evaluated radiologically, and toxicity, tumor response, and overall survival (OS) were compared in the two groups. Baseline clinical parameters of the two groups were similar. The rates of ≥ Grade 3 hematologic (0% vs. 8.7%, p = 0.045) and non-hematologic (0% vs. 8.7%, p = 0.045) toxicities were significantly lower in the capecitabine group than in the 5-FU group. Primary tumor (30.7% vs. 28.2%, p = 0.658) and overall (13.7% vs. 15.2%, p = 0.273) response rates and median OS time (12.5 months vs. 11.6 months, p = 0.655) were similar in the two groups. Capecitabine plus RT may be a safe and feasible regimen for patients with locally advanced pancreatic cancer, with similar efficacy and low rates of toxicities compared with bolus 5-FU plus RT

  15. Carcinoembryonic Antigen Expression and Resistance to Radiation and 5-Fluorouracil-Induced Apoptosis and Autophagy.

    Science.gov (United States)

    Eftekhar, Ebrahim; Jaberie, Hajar; Naghibalhossaini, Fakhraddin

    2016-01-01

    Understanding the mechanism of tumor resistance is critical for cancer therapy. In this study, we investigated the effect of carcinoembryonic antigen (CEA) overexpression on UV-and 5-fluorouracil (5-FU)-induced apoptosis and autophagy in colorectal cancer cells. We used histone deacetylase (HDAC) inhibitor, NaB and DNA demethylating agent, 5-azacytidine (5-AZA) to induce CEA expression in HT29/219 and SW742 colorectal cancer cell lines. MTT assay was used to measure IC50 value of the cells exposed to graded concentrations of 5- FU with either 0.1 mM NaB or 1 μM 5-AZA for 72 h . Using CHO- and SW742-CEA transfectants, we also investigated the effect of CEA expression on UV- and 5-FU-induced apoptosis and autophagy. Treatment of HT29/219 cell line with NaB and 5-AZA increased CEA expression by 29% and 31%, respectively. Compared with control cells, the IC50 value for 5-FU of NaB and 5-AZA-treated cells increased by 40% and 57%, respectively. Treatment of SW742 cells with NaB or 5-AZA increased neither CEA expression nor the IC50 value for 5-FU. In comparison to parental cells, CEA expression also significantly protected transfected cells against UV-induced apoptosis. Decreased proportions of autophagy and apoptosis were also observed in 5-FU treated SW742- and CHO-CEA transfectants. We conclude that CEA expression can effectively protect colorectal cancer cells against radiation and drug-induced apoptosis and autophagy. PMID:27478804

  16. Concurrent chemoradiotherapy comparison of taxanes and platinum versus 5-fluorouracil and platinum in nasopharyngeal carcinoma treatment

    Institute of Scientific and Technical Information of China (English)

    Chen Xichuang; Hong Yuan; Feng Jinhua; Ye Jianlin; Zheng Panpan; Guan Xiyin; You Xiaohong

    2014-01-01

    Background Nasopharyngeal carcinoma (NPC) is a squamous-cell carcinoma especially prevailing among the natives of southern China.The regimen of concurrent chemoradiotherapy (CCRT) that include platinum and 5-fluorouracil (5-FU)is considered to be the standard treatment for NPC.However,its clinical use is limited by its toxicity.Our purpose was to evaluate the efficacy and safety of the regimen of CCRT with taxanes and platinum versus the regimen of CCRT with 5-FU and platinum in NPC treatment.Methods Medline,the Cochrane library,and the Chinese medical literature database were searched for eligible studies.Meta-analysis was performed using Review Manager (Version 5.2).Results Six random controlled trials (RCTs) including 514 patients met our criteria.Meta-analysis showed that the regimen of CCRT with taxanes and platinum had an improved significant difference in complete remission (CR) and less incidence rate in adverse reactions such as gastrointestinal impairment grades Ⅲll-Ⅳ,liver and kidney impairment grades Ⅰ-Ⅱ,and radiodermatitis grades Ⅲ-Ⅳ versus the conventional regimen of CCRT with 5-FU and platinum,while the long-term effectiveness rate of overall survival,Iocoregional failure-free survival,or distant metastasis failure-free survival between the two groups was therapeutic equivalence.Conclusions The regimen of CCRT with taxanes and platinum in NPC therapy may be more efficient and safe compared to the conventional modality of 5-FU and platinum in CCRT.However,we need more high-quality studies of multi-center and randomized double-blind clinical trials to further compare,analyze,and confirm the findings.

  17. 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.

  18. Adsorption behavior of 5-fluorouracil on pristine, B-, Si-, and Al-doped C60 fullerenes: A first-principles study

    Science.gov (United States)

    Hazrati, Mehrnoosh Khodam; Hadipour, Nasser L.

    2016-02-01

    Since C60 fullerene has been enormously studied as a drug delivery vehicle, we investigated the interaction between C60 and 5-fluorouracil drug using density functional theory calculations. The electronic and structural properties were explored in terms of binding energies, frontier molecular orbitals, DOS and NBO. To manipulate 5-fluorouracil adsorption properties on the C60, we substituted a carbon atom with boron, silicon and aluminum. In contrast to the pristine C60, the binding energy of 5-fluorouracil to the doped fullerenes is much more negative and the HOMO-LUMO gaps are significantly enlarged. Our results suggest that doping may improve C60 drug delivery properties.

  19. Effect of Lidocaine-Ketamine Infusions Combined with Morphine or Fentanyl in Sevoflurane-Anesthetized Pigs.

    Science.gov (United States)

    Re, Michela; Canfrán, Susana; Largo, Carlota; Gómez de Segura, Ignacioa A

    2016-01-01

    Providing lidocaine, ketamine, and an opioid greatly decreases the minimum alveolar concentration (MAC) of volatile anesthetics in dogs. However, the efficacy of this combination shows marked interspecies variation, and opioids are likely to be less effective in pigs than in other species. The aim of the study was to determine the effects of constant-rate infusion of lidocaine and ketamine combined with either morphine or fentanyl on the MAC of sevoflurane in pigs. In a prospective, randomized, crossover design, 8 healthy crossbred pigs were premedicated with ketamine and midazolam, and anesthesia was induced and maintained with sevoflurane. Pigs then received ketamine (0.6 mg/kg/h) and lidocaine (3 mg/kg/h) combined with either morphine (0.24 mg/kg/h; MLK) or fentanyl (0.0045 mg/kg/h; FLK) after a loading dose; the control group received Ringers lactate solution. The anesthetic-sparing action of the 2 infusion protocols was calculated according to the MAC, by using dewclaw clamping as the standard noxious stimulus. The sevoflurane MAC (mean ± 1 SD) was 2.0% ± 0.2%, 1.9% ± 0.4%, and 1.8% ± 0.2% in the control, MLK, and FLK groups, respectively. No differences among groups or treatments were found. In conclusion, the administration of MLK or FLK at the studied doses did not reduce the MAC of sevoflurane in pigs. PMID:27177566

  20. Epidural levobupivacaine alone or combined with different morphine doses in bitches under continuous propofol infusion

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    V.B. Albuquerque

    2015-08-01

    Full Text Available The aim of this study was to assess the cardiopulmonary, analgesic, adverse effects, serum concentration of cortisol and plasma levels of levobupivacaine and morphine in bitches undergoing propofol anesthesia and epidural analgesia with levobupivacaine alone or combined with morphine. This was a randomized 'blinded' prospective clinical study using 32 adult bitches weighing 9.8±4.1kg that were admitted for elective ovariohysterectomy. Twenty minutes after administration of acepromazine and midazolam, anesthesia was induced with propofol (4mg kg-1 and maintained by a continuous rate infusion (CRI. Each animal was randomly assigned to one of four epidural groups: GL = levobupivacaine alone (0.33mg kg-1; GLM0.1 = levobupivacaine and morphine (0.1mg kg-1; GLM0.15 = levobupivacaine and morphine (0.15mg kg-1; and GLM0.2 = levobupivacaine and morphine (0.2mg kg-1. Variables obtained during anesthesia were heart rate, respiratory rate, systolic, mean and diastolic arterial blood pressures, oxyhemoglobin saturation, inspired oxygen fraction, end-tidal carbon dioxide tension, blood gases, serum cortisol, and plasma levels of levobupivacaine and morphine. The onset and duration times of the blockade were recorded. Arterial pressures were significantly increased in all groups at the times of ovarian pedicle clamping. There was a decrease in pH, together with an increase in both PaO2and PaCO2 over time. Serum cortisol levels were increased in TESu compared to TB, T30 and TR. Limb spasticity, muscle tremors, opisthotonos and diarrhea were observed in some animals during propofol infusion and ceased with the end of CRI. Reactions happened at different moments and lasted for different periods of time in each individual. Epidural with levobupivacaine alone or combined with morphine allowed for ovariohysterectomy to be performed under low propofol infusion rates, with minimal changes in cardiovascular variables and in serum cortisol levels. Adverse effects were

  1. 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 radiotherapy

  2. Is taxane/platinum/5 fluorouracil superior to taxane/platinum alone and does docetaxel trump paclitaxel in induction therapy for locally advanced oral cavity cancers?

    Directory of Open Access Journals (Sweden)

    V Noronha

    2015-01-01

    Full Text Available Background: Cisplatin and 5 fluorouracil drug combination is inferior to the combination of taxane with these 2 drugs. However, often in clinical practice at our center giving TPF (docetaxel, cisplatin, 5 fluorouracil is difficult in view of logistics and tolerance issues. In such a scenario, we prefer to use the 2 drugs combination of platinum and taxane. However, no study has addressed whether a 2 drugs combination, which includes taxane is inferior to the 3 drugs combination and which the taxane of choice is in the 2 drugs combination of taxane and platinum. Methods: This is a retrospective analysis of prospectively collected data of patients undergoing induction chemotherapy (IC in oral cavity cancers from 2010 to 2012. We chose for analysis those patients who had a baseline scan done within 4 weeks of starting therapy and a follow-up scan done within 2 weeks of completion of the second cycle of IC. Response was scored in accordance with RECIST version 1.1. Chi-square analysis was done to compare response rates (RRs between regimens. Results: Two hundred and forty-five patients were identified. The median age was 45 years (24–70 years, 208 (84.9% were male patients, and 154 patients (62.9% had primary in the Buccal mucosa. The regimens received were TPF 22 (9%, docetaxel + cisplatin 97 (39.6%, paclitaxel + cisplatin 89 (36.3%, docetaxel + carboplatin 16 (6.5% and paclitaxel + carboplatin 21 (8.6%. The overall RRs were complete response, partial response, stable disease and progressive disease in 4 (1.6%, 56 (22.9%, 145 (59.2% and 40 (16.3%. The 3 drugs regimen (TPF had 50% RR as compared to 22% RR with 2 drugs regimen (P = 0.004. Docetaxel containing regimens had 30.3% RR as compared to 17.2% RR with paclitaxel containing regimens (P = 0.094. Conclusions: TPF has better RR than a 2 drugs taxane-containing regimen and docetaxel leads to a better RR than paclitaxel for IC in locally advanced oral cavity cancers.

  3. Orotate phosphoribosyl transferase mRNA expression and the response of cholangiocarcinoma to 5-fluorouracil

    Institute of Scientific and Technical Information of China (English)

    Chariya Hahnvajanawong; Jariya Chaiyagool; Wunchana Seubwai; Vajarabhongsa Bhudhisawasdi; Nisana Namwat; Narong Khuntikeo; Banchob Sripa

    2012-01-01

    AIM:To determine whether expression of certain enzymes related to 5-fluorouracil (5-FU) metabolism predicts 5-FU chemosensitivity in cholangiocarcinoma (CCA).METHODS:The histoculture drug response assay (HDRA) was performed using surgically resected CCA tissues.Tumor cell viability was determined morphologically with hematoxylin and eosin-and terminal deoxynucleotide transferase-mediated dUTP nick-end labeling-stained tissues.The mRNA expression of thymidine phosphorylase (TP),orotate phosphoribosyl transferase (OPRT),thymidylate synthase (TS),and dihydropyrimidine dehydrogenase (DPD) was determined with realtime reverse transcriptase-polymerase chain reaction.The levels of gene expression and the sensitivity to 5-FU were evaluated.RESULTS:Twenty-three CCA tissues were obtained from patients who had been diagnosed with intrahepatic CCA and who underwent surgical resection at Srinagarind Hospital,Khon Kaen University from 2007 to 2009.HDRA was used to determine the response of these CCA tissues to 5-FU.Based on the dose-response curve,200 μg/mL 5-FU was selected as the test concentration.The percentage of inhibition index at the median point was selected as the cut-off point to differentiate the responding and non-responding tumors to 5-FU.When the relationship between TP,OPRT,TS and DPD mRNA expression levels and the sensitivity of CCA tissues to 5-FU was examined,only OPRT mRNA expression was significantly correlated with the response to 5-FU.The mean expression level of OPRT was significantly higher in the responder group compared to the non-responder group (0.41 ± 0.25 vs 0.22 ± 0.12,P < 0.05).CONCLUSION:OPRT mRNA expression may be a useful predictor of 5-FU chemosensitivity of CCA.Whether OPRT mRNA could be used to predict the success of 5-FU chemotherapy in CCA patients requires confirmation in patients.

  4. 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.

  5. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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

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

    International Nuclear Information System (INIS)

    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

  8. Anti-hepatocarcinoma effects of 5-fluorouracil encapsulated by galactosylceramide liposormes in vivo and in vitro

    Institute of Scientific and Technical Information of China (English)

    Yong Jin; Jun Li; Long-Fu Rong; Yuan-Hai Li; Lin Guo; Shu-Yun Xu

    2005-01-01

    AIM: To study the anti-hepatocarcinoma effects of 5fluorouracil (5-Fu) encapsulated by galactosylceramide liposomes (5-Fu-GCL)in vivo and in vitro. METHODS: Tumor-bearing animal model and HepA cell line were respectively adopted to evaluate the anti-tumor effects of 5-Fu-GCL in vivo and in vitro. Tumor cell growth inhibition effects of 5-Fu-GCL in vitro were assessed bycell viability assay and MTT assay. In vivo experiment, the inhibitory effects on tumor growth were evaluated by tumor inhibition rate and animal survival days. High performance liquid chromatography was used to detect the concentration-time course of 5-Fu-GCL in intracellular fluidin vitro and the distribution of 5-Fu-GCL in liver tumor tissues in vivo. Apoptosis and cell cycle of tumor cells were demonstrated by flow cytometry.RESULTS: In vitro experiment, 5-Fu-GCL (6.25-100 μmol/L) and free 5-Fu significantly inhibited HepA cell growth. Furthermore, IC50 of 5-Fu-GCL (34.5 μmol/L) was lower than that of free 5-Fu (51.2 μrnol/L). In vivo experiment, 5-Fu-GCL (20, 40, 80 mg/kg) significantly suppressed the tumor growth in HepA bearing mice model. Compared with free 5-Fu, the area under curve of 5-Fu-GCL in intracellular fluid increased 2.6 times. Similarly, the distribution of 5-Fu-GCL in liver tumor tissues was significantly higher than that of free 5-Fu. After being treated with 5-Fu-GCL, the apoptotic rate and the proportion of HepA cells in the S phase increased, while the proportion in the G0/G1 and G2/M phases decreased. CONCLUSION: 5-Fu-GCL appears to have anti-hepatocarcinoma effects and its drug action is better than free 5-Fu. Its mechanism is partly related to increased drug concentrations in intracellular fluid and liver tumor tissues, enhanced tumor cell apoptotic rate and arrest of cell cycle in S phase.

  9. A comparative study of 5-Fluorouracil release from chitosan/silver and chitosan/silver/MWCNT nanocomposites and their cytotoxicity towards MCF-7.

    Science.gov (United States)

    E A K, Nivethaa; S, Dhanavel; A, Rebekah; V, Narayanan; A, Stephen

    2016-09-01

    5-Fluorouracil encapsulated chitosan/silver and chitosan/silver/multiwalled carbon nanotubes were synthesized to comparatively study the release profile and cytotoxicity of the systems towards MCF-7 cell line. The triclinic structure of 5-Fluorouracil, face centered cubic structure of silver and the semi-crystalline nature of chitosan were elucidated using the XRD pattern. The XRD pattern of Chitosan/silver/multiwalled carbon nanotube consisted of (002) reflection of graphitic carbon from carbon nanotube. The evident splitting of NH2 and NH3(+) and a variation in the intensity of OH peaks in the FTIR pattern were indicative of the binding of moieties like silver, carbon nanotube and 5-Fluorouracil to chitosan. The encapsulation of 5-Fluorouracil was evident from elemental mapping and from the presence of reflections corresponding to 5-Fluorouracil in the SAED pattern. The release profile showed a prolonged release for 5-Fluorouracil encapsulated Chitosan/silver/multiwalled carbon nanotube and a better cytotoxicity with a IC50 of 50μg/ml was observed for the same.

  10. A comparative study of 5-Fluorouracil release from chitosan/silver and chitosan/silver/MWCNT nanocomposites and their cytotoxicity towards MCF-7.

    Science.gov (United States)

    E A K, Nivethaa; S, Dhanavel; A, Rebekah; V, Narayanan; A, Stephen

    2016-09-01

    5-Fluorouracil encapsulated chitosan/silver and chitosan/silver/multiwalled carbon nanotubes were synthesized to comparatively study the release profile and cytotoxicity of the systems towards MCF-7 cell line. The triclinic structure of 5-Fluorouracil, face centered cubic structure of silver and the semi-crystalline nature of chitosan were elucidated using the XRD pattern. The XRD pattern of Chitosan/silver/multiwalled carbon nanotube consisted of (002) reflection of graphitic carbon from carbon nanotube. The evident splitting of NH2 and NH3(+) and a variation in the intensity of OH peaks in the FTIR pattern were indicative of the binding of moieties like silver, carbon nanotube and 5-Fluorouracil to chitosan. The encapsulation of 5-Fluorouracil was evident from elemental mapping and from the presence of reflections corresponding to 5-Fluorouracil in the SAED pattern. The release profile showed a prolonged release for 5-Fluorouracil encapsulated Chitosan/silver/multiwalled carbon nanotube and a better cytotoxicity with a IC50 of 50μg/ml was observed for the same. PMID:27207060

  11. 低剂量氟脲嘧啶输注顺铂腹腔灌注联合热疗治疗恶性肿瘤肝转移疗效观察%A Study of Efficacy and Side-Effect of Infusion 5-Fluorouracil and Cisplatin (DDP) Interperitoneal Chemoperfasin Combined with Hyperthermia to Cure the Hepatic Metastasis of Malignant Tumor

    Institute of Scientific and Technical Information of China (English)

    张阳; 张彦华; 曹旸; 朱眉; 孔天东; 姚丽鸽

    2005-01-01

    目的观察5-氟脲嘧啶静脉输注,顺铂腹腔灌注联合全身热疗治疗恶性肿瘤肝转移的客观疗效及毒副反应.方法顺铂30mg/m2+生理盐水2000~3 000mL腹腔灌注,d1、dg,腹腔穿刺采用单次直接腹腔穿刺法.术后应用国产UHR-2000型微波热疗机进行深部热疗90min,5-氟脲嘧啶300mg/(m2.d)静脉输注,d2~6、d9~13,28天为一周期,2个周期以上评价疗效.结果全组16例,CR1例、PR 9例,近期有效率62.5%,无明显毒副反应.结论低剂量5-氟脲嘧啶静脉输注,顺铂腹腔灌注加全身热疗治疗恶性肿瘤肝转移是低毒有效的方法,值得临床推广应用.

  12. CF101, An Agonist to the A3 Adenosine Receptor, Enhances the Chemotherapeutic Effect of 5-Fluorouracil in a Colon Carcinoma Murine Model

    Directory of Open Access Journals (Sweden)

    Sara Bar-Yehuda

    2005-01-01

    Full Text Available NF-κB and the upstream kinase PKB/Akt are highly expressed in chemoresistance tumor cells and may hamper the apoptotic pathway. CF101, a specific agonist to the A3 adenosine receptor, inhibits the development of colon carcinoma growth in cell cultures and xenograft murine models. Because CF101 has been shown to downregulate PKB/Akt and NF-κB protein expression level, we presumed that its combination with chemotherapy will enhance the antitumor effect of the cytotoxic drug. In this study, we utilized 3-[4,5Dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT and colony formation assays and a colon carcinoma xenograft model. It has been shown that a combined treatment of CF101 and 5-fluorouracil (5-FU enhanced the cytotoxic effect of the latter on HCT-116 human colon carcinoma growth. Downregulation of PKB/Akt, NF-κB, and cyclin D1, and upregulation of caspase-3 protein expression level were observed in cells and tumor lesions on treatment with a combination of CF101 and 5-FU. Moreover, in mice treated with the combined therapy, myelotoxicity was prevented as was evidenced by normal white blood cell and neutrophil counts. These results show that CF101 potentiates the cytotoxic effect of 5-FU, thus preventing drug resistance. The myeloprotective effect of CF101 suggests its development as an add-on treatment to 5-FU.

  13. N-Alkynyl Derivatives of 5-Fluorouracil: Susceptibility to Palladium-Mediated Dealkylation and Toxigenicity in Cancer Cell Culture

    Directory of Open Access Journals (Sweden)

    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.

  14. PERIPANCREATIC ARTERIAL LIGATION COMBINED WITH ARTERIAL INFUSION REGIONAL CHEMOTHERAPY FOR TREATING PATIENTS WITH ADVANCED PANCREATIC CARCINOMA

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective To find out a new treatment method for advanced pancreatic carcinoma. Methods Twenty-nine patients with advanced pancreatic carcinoma and liver metastases were randomly divided into 2 groups.Group A (n=11) underwent bilio-enterostomy and/or gastro-enterostomy combined with systemic chemotherapy after operation;Group B(n=18) underwent bilio-enterostomy and/or gastro-enterostomy combined with peripancreatic arterial ligation and arterial infusion regional chemotherapy.The alleviation of clinical symptom,the change of carcinoma volume by BUS and CT scan,survival period and serum CEA were observed in two groups. Results The symptoms were alleviated apparently in most cases in Group B;BUS and CT scan showed that the tumor volume decreased apparently in Group B;The response rate was 67.7% in Group B,and 18.2% in Group A,respectively(P<0.01);the mean survival period was (4.8±0.6) months in Group A,and (12.5±1.2) months in Group B,respectively(P<0.01),there was significant difference between the two groups.The decrease of serum CEA was 54% in Group A and 60% in Group B,but the difference was not significant(P>0.05). Conclusion Peripancreatic arterial ligation combined with arterial infusion regional chmotherapy is believed to be effective against both pancreatic carcinoma and liver metastases,and it can alleviate the clinical symptoms,postpone the growth speed of tumor,and prolong the survival period.

  15. Effects of Caloric Intake on Intestinal Mucosal Morphology and Immune Cells in Rats Treated with 5-Fluorouracil

    OpenAIRE

    Murakami, Mariko; Sato, Norifumi; Tashiro, Katsufumi; Nakamura, Tsuyoshi; Masunaga, Hiroaki

    2009-01-01

    Anticancer drugs have been reported to damage the intestinal mucosa. We evaluated the effects of caloric intake on the mucosal morphology and immune cells in rats treated with 5-fluorouracil (5-FU). Rats were received a liquid diet plus 5-FU treatment for 8 days as follows: Low calorie group (25 kcal/day with 5-FU), Normal calorie group (50 kcal/day with 5-FU), and Control group (50 kcal/day with saline). The mucosal morphology, cell numbers and phenotypes of spleen and intraepithelial lympho...

  16. 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.

  17. Severe adverse effects of 5-fluorouracil in S-1 were lessened by haemodialysis due to elimination of the drug.

    Science.gov (United States)

    Inoue, Kazunori; Nagasawa, Yasuyuki; Yamamoto, Ryohei; Omori, Hiroki; Kimura, Tomonori; Tomida, Kodo; Furumatsu, Yoshiyuki; Imai, Enyu; Isaka, Yoshitaka; Rakugi, Hiromi

    2009-04-01

    S-1 and cisplatin are used as one of the first-line chemotherapies for gastric cancer in Japan. The plasma concentration of 5-fluorouracil (5-FU) is increased in patients with renal dysfunction because gimeracil in S-1 inhibits the degradation of 5-FU and about 50% of gimeracil is excreted in the urine. We describe a 35-year-old man with acute kidney injury while taking S-1 and cisplatin for advanced gastric cancer and who presented severe adverse effects of 5-FU. This case report describes the evolution of the plasma concentrations of 5-FU with haemodialysis along with a decrease in the adverse drug effects.

  18. Surviving cells after treatment with gemcitabine or 5-fluorouracil for the study of de novo resistance of pancreatic cancer.

    Science.gov (United States)

    Liu, Qing-Hua; Zhang, Jing; Zhao, Chen-Yan; Yu, Dang-Hui; Bu, Hai-Ji; Chen, Ying; Ni, Can-Yong; Zhu, Ming-Hua

    2012-01-01

    One of the hallmarks of pancreatic cancer is its inherent insensitivity to chemotherapy. This study was undertaken to develop a cell model for the study of de novo resistance of pancreatic cancer. The surviving pancreatic cancer cells after a 3-day exposure to gemcitabine or 5-fluorouracil followed by another 7-day recovery were potentially drug-resistant. They had similar morphology and comparable growth and tumorigenic potentials to their untreated parental cells. Repeated subculture affected the cell-cycle profile and growth characteristics of the surviving cells. Our data suggest that surviving pancreatic cancer cells after drug treatment are a useful model for exploring intrinsic resistance.

  19. Enhancing effect of N-dodecyl-2-pyrrolidone on the percutaneous absorption of 5-fluorouracil derivatives.

    Science.gov (United States)

    Sato, S; Hirotani, Y; Ogura, N; Sasaki, E; Kitagawa, S

    1998-05-01

    The enhancing effects of N-dodecyl-2-pyrrolidone (NDP) on the percutaneous absorption of doxifluridine (DOX), 5-fluorouracil (5-FU), tegafur (TEG) and carmofur (CAR) were examined using an in vitro penetration technique and rat skin. Phosphate buffered isotonic saline (PBS), propylene glycol (PG) and PG containing 0.4M NDP (PGNDP) were applied as the donor solution. The correlation between the n-octanol/water partition coefficients and the permeability coefficients of DOX, 5-FU and TEG was investigated using both logarithmic plots. It was determined that the permeability coefficients are significantly correlated with their n-octanol/water partition coefficients on PBS. This result suggested that the non-polar stratum corneum lipid lamella in the skin might act as a rate limiting step on the skin penetration of DOX, 5-FU and TEG. The permeability coefficient of DOX, 5-FU and TEG was increased on PGNDP. The enhancing effect of NDP on the permeability coefficient was more effective at higher hydrophilic drugs, the values of the permeability coefficient had almost the same values on PGNDP and the dependency of the permeability coefficient on the n-octanol/water partition coefficient disappeared in the presence of NDP. These results indicated that the enhancing effect of NDP on the percutaneous absorption of DOX, 5-FU and TEG might be closely related to the perturbation of stratum corneum lipid lamella. Since it has been well recognized that CAR is decomposed into 5-FU in neutral and alkaline solution, the decomposition rate of CAR was measured using PBS solution and was found to be very rapid (Kd = 3.17 h-1, t1/2 = 13.1 min). The total concentrations of CAR plus 5-FU in the acceptor compartment were used to determine the permeability coefficient of CAR. The obtained value of the permeability coefficient of CAR on PG was almost the same as that of TEG on PG (CAR: 1.11 x 10(-3) cm/h, TEG: 1.24 x 10(-3) cm/h), while that of CAR on PGNDP was smaller than that of TEG on

  20. 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)

    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/m2 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/m2/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.

  1. 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.

  2. Transarterial infusion chemotherapy combined with high intensity focused ultrasound for the treatment of pancreatic carcinomas: a clinical study

    International Nuclear Information System (INIS)

    Objective: To assess the clinical value of transarterial infusion chemotherapy combined with high intensity focused ultrasound (HIFU) for the treatment of pancreatic carcinomas. Methods: A total of 64 patients with inoperable pancreatic carcinomas were randomly divided into study group (n=32) and control group (n=32). Transarterial infusion chemotherapy combined with HIFU was employed in patients of study group, while simple transarterial infusion chemotherapy was conducted in patients of control group. The effective rate, the clinical benefit rate (CBR), the occurrence of side effect and the survival time of the two groups were recorded. The results were compared between the two groups. Results: The effective rate (PR + MR), the median survival time and the one-year survival rate of the study group were 55.56%, 13.0 months and 68.75% respectively, while the effective rate (PR + MR), the median survival time and the one-year survival rate of the control group were 28.57%, 9.0 months and 43.75% respectively. Both the effective rate and the one-year survival rate of the study group were significantly higher than those of the control group (P<0.05). Conclusion: Compared with pure transarterial infusion chemotherapy, transarterial infusion chemotherapy combined with HIFU can significantly improve the short-term efficacy and increase the one-year survival rate for patients with advanced pancreatic carcinomas. (authors)

  3. l-carnosine dipeptide overcomes acquired resistance to 5-fluorouracil in HT29 human colon cancer cells via downregulation of HIF1-alpha and induction of apoptosis.

    Science.gov (United States)

    Iovine, Barbara; Guardia, Francesca; Irace, Carlo; Bevilacqua, Maria Assunta

    2016-08-01

    Hypoxia-inducible factor (HIF-1α) protein is over-expressed in many human cancers and is a major cause of resistance to drugs. HIF-1α up-regulation decreases the effectiveness of several anticancer agents, including 5-fluorouracil (5-FU), because it induces the expression of drug efflux transporters, alters DNA repair mechanisms and modifies the balance between pro- and antiapoptotic factors. These findings suggest that inhibition of HIF-1α activity may sensitize cancer cells to cytotoxic drugs. We previously reported that l-carnosine reduces HIF-1α expression by inhibiting the proliferation of colon cancer cells. In the present study we investigated the effect of l-carnosine on HT29 colon cancer cells with acquired resistance to 5-FU. We found that l-carnosine reduces colon cancer cell viability, decreases HIF-1α and multi-drug resistant protein MDR1-pg expression, and induces apoptosis. Moreover, the l-carnosine/5-FU combination lowers the expression of some chemoresistance markers. The combination index evaluated in vitro on the HT29-5FU cell line by median drug effect analysis reveals a significant synergistic effect. PMID:27234614

  4. Up-regulation of stem cell markers by P21-activated kinase 1 contributes to 5-fluorouracil resistance of colorectal cancer.

    Science.gov (United States)

    Huynh, Nhi; Shulkes, Arthur; Baldwin, Graham; He, Hong

    2016-08-01

    Cancer stem cells (CSC) are tumorigenic and resistant to chemotherapy. In colorectal cancer (CRC), CSCs have been identified by the expression of specific markers, including CD44, Bmi1 and Nanog. Although p21-activated kinase 1 (PAK1), acting downstream of Ras, stimulates Wnt/β-catenin signaling and is known to play an important role in CRC development and progression, the role of PAK1 in the expression of CSC markers has not previously been investigated. The effect of PAK1 over-expression, knockdown or inhibition on the expression or alteration (in the case of CD44) of CSC markers in human CRC cell lines was measured by immunofluorescence and Western blotting. The effect of PAK1 modulation on tumorigenesis, and on resistance to treatment with 5-fluorouracil (5-FU), was measured by sphere formation in vitro and by growth of xenografted tumors in vivo. The results show that PAK1 activity correlated with the expression of CSC markers and the CD44 isoform profile, and with tumor growth both in vitro and in vivo. Furthermore PAK overexpression partially overcame the inhibition of CRC growth by 5-FU, and PAK inhibition was synergistic with 5-FU treatment. Our findings lay the foundation for a combination therapy in which PAK1 inhibitors targeting CSCs may be combined with conventional 5-FU-based chemotherapy for the treatment of CRC.

  5. 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

    2013-06-01

    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.

  6. Oral 5-fluorouracil colon-specific delivery through in vivo pellet coating for colon cancer and aberrant crypt foci treatment.

    Science.gov (United States)

    Bose, A; Elyagoby, A; Wong, T W

    2014-07-01

    In situ coating of 5-fluorouracil pellets by ethylcellulose and pectin powder mixture (8:3 weight ratio) in capsule at simulated gastrointestinal media provides colon-specific drug release in vitro. This study probes into pharmacodynamic and pharmacokinetic profiles of intra-capsular pellets coated in vivo in rats with reference to their site-specific drug release outcomes. The pellets were prepared by extrusion-spheronization technique. In vitro drug content, drug release, in vivo pharmacokinetics, local colonic drug content, tumor, aberrant crypt foci, systemic hematology and clinical chemistry profiles of coated and uncoated pellets were examined against unprocessed drug. In vivo pellet coating led to reduced drug bioavailability and enhanced drug accumulation at colon (179.13 μg 5-FU/g rat colon content vs 4.66 μg/g of conventional in vitro film-coated pellets at 15 mg/kg dose). The in vivo coated pellets reduced tumor number and size, through reforming tubular epithelium with basement membrane and restricting expression of cancer from adenoma to adenocarcinoma. Unlike uncoated pellets and unprocessed drug, the coated pellets eliminated aberrant crypt foci which represented a putative preneoplastic lesion in colon cancer. They did not inflict additional systemic toxicity. In vivo pellet coating to orally target 5-fluorouracil delivery at cancerous colon is a feasible therapeutic treatment approach.

  7. Transcriptional activation and cell cycle block are the keys for 5-fluorouracil induced up-regulation of human thymidylate synthase expression.

    Directory of Open Access Journals (Sweden)

    Alessio Ligabue

    Full Text Available BACKGROUND: 5-fluorouracil, a commonly used chemotherapeutic agent, up-regulates expression of human thymidylate synthase (hTS. Several different regulatory mechanisms have been proposed to mediate this up-regulation in distinct cell lines, but their specific contributions in a single cell line have not been investigated to date. We have established the relative contributions of these previously proposed regulatory mechanisms in the ovarian cancer cell line 2008 and the corresponding cisplatin-resistant and 5-FU cross-resistant-subline C13*. METHODOLOGY/PRINCIPAL FINDINGS: Using RNA polymerase II inhibitor DRB treated cell cultures, we showed that 70-80% of up-regulation of hTS results from transcriptional activation of TYMS mRNA. Moreover, we report that 5-FU compromises the cell cycle by blocking the 2008 and C13* cell lines in the S phase. As previous work has established that TYMS mRNA is synthesized in the S and G(1 phase and hTS is localized in the nuclei during S and G(2-M phase, the observed cell cycle changes are also expected to affect the intracellular regulation of hTS. Our data also suggest that the inhibition of the catalytic activity of hTS and the up-regulation of the hTS protein level are not causally linked, as the inactivated ternary complex, formed by hTS, deoxyuridine monophosphate and methylenetetrahydrofolate, was detected already 3 hours after 5-FU exposure, whereas substantial increase in global TS levels was detected only after 24 hours. CONCLUSIONS/SIGNIFICANCE: Altogether, our data indicate that constitutive TYMS mRNA transcription, cell cycle-induced hTS regulation and hTS enzyme stability are the three key mechanisms responsible for 5-fluorouracil induced up-regulation of human thymidylate synthase expression in the two ovarian cancer cell lines studied. As these three independent regulatory phenomena occur in a precise order, our work provides a feasible rationale for earlier observed synergistic combinations of 5

  8. Glycyrrhetinic acid-modified chitosan nanoparticles enhanced the effect of 5-fluorouracil in murine liver cancer model via regulatory T-cells

    Directory of Open Access Journals (Sweden)

    Cheng M

    2013-10-01

    Full Text Available Mingrong Cheng,1,2,* Hongzhi Xu,3,* Yong Wang,4,* Houxiang Chen,5 Bing He,3 Xiaoyan Gao,6 Yingchun Li,2 Jiang Han,1 Zhiping Zhang1 1Department of General Surgery, 2Department of Endoscopy, Pudong New Area District Zhoupu Hospital, Shanghai, People’s Republic of China; 3Department of General Surgery, Shanghai Fifth People’s Hospital, Fudan University, Shanghai, People’s Republic of China; 4School of Materials Science and Engineering, Wuhan University of Technology, Wuhan, People’s Republic of China; 5Zhejiang Huafon Fiber Research Institute, Zhejiang Huafon Spandex Co, Ltd, Wenzhou, People’s Republic of China; 6Department of Plastic Surgery, Pudong New Area District Zhoupu Hospital, Shanghai, People’s Republic of China *These authors contributed equally to this work Abstract: Modified chitosan nanoparticles are a promising platform for drug, such as 5-fluorouracil (5-FU, gene, and vaccine delivery. Here, we used chitosan and hepatoma cell-specific binding molecule glycyrrhetinic acid (GA to synthesize glycyrrhetinic acid-modified chitosan (GA-CTS. The synthetic product was confirmed by infrared spectroscopy and hydrogen nuclear magnetic resonance. By combining GA-CTS and 5-FU, we obtained a GA-CTS/5-FU nanoparticle, with a particle size of 193.7 nm, drug loading of 1.56%, and a polydispersity index of 0.003. The GA-CTS/5-FU nanoparticle provided a sustained-release system comprising three distinct phases of quick, steady, and slow release. In vitro data indicated that it had a dose- and time-dependent anticancer effect. The effective drug exposure time against hepatic cancer cells was increased in comparison with that observed with 5-FU. In vivo studies on an orthotropic liver cancer mouse model demonstrated that GA-CTS/5-FU significantly inhibited cancer cell proliferation, resulting in increased survival time. The antitumor mechanisms for GA-CTS/5-FU nanoparticle were possibly associated with an increased expression of regulatory T

  9. Clinical application of radiofrequency ablation combined with bronchial artery infusion of docetaxel in treating non-small cell lung cancer

    International Nuclear Information System (INIS)

    Objective: To discuss the clinical application of radiofrequency ablation combined with bronchial artery infusion of docetaxel in treating non-small cell lung cancer and to summarize the experience of using this therapy in clinical practice. Methods: Radiofrequency ablation was performed in twenty-one patients with lung cancer. The diagnosis was confirmed by CT-guided percutaneous needle biopsy or bronchoscopic biopsy in all patients. One week after radiofrequency ablation treatment, bronchial artery infusion of docetaxel was conducted. The therapeutic results were observed and evaluated. Results: After the treatment, the lesion's size was markedly reduced and the clinical symptoms were dramatically improved in all patients. Conclusion: Radiofrequency ablation combined with bronchial artery infusion of docetaxel is a safe, effective and simple technique with excellent therapeutic results for the treatment of non-small cell lung cancer. It is really worth popularizing this technique in clinical practice. (authors)

  10. 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)

    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)

  11. Therapeutic effect of transarterial licartin infusion in combination with transcatheter arterial chemoembolization for advanced hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Objective: To investigate the short term effect of licartin transarterial infusion in combination with chemoembolization (LTACE) and compare its effect with conventional transcatheter arterial chemoembolization (TACE) for advanced hepatocellular carcinoma (HCC). Methods: Seventy-two cases of advanced HCC were included in this analysis. There were 50 males and 22 females with the average age of (58 ± 12) yrs (range 34-86 yrs). Twenty-nine patients received LTACE treatment while the other forty three patients received conventional TACE treatment. Before intervention, there was no variation (P>0.05) in gender (χ2=0.202), Child-Pugh grading for hepatic function (χ2=2.428), as well as in white blood cell count (t=1.101) and platelet count (t=0.080) between the two groups except for age and portal vein thrombosis. For LTACE group, 30 minutes after the infusion of licartin (27.75 MBq/kg) into proper hepatic artery, an emulsion of 40 mg pharmorubicin and 30 ml ultrafluid lipidol was infused until hemostasis within target artery. For TACE group, only an emulsion of 40 mg pharmorubicin and 30ml ultrafluid lipidol was infused until hemostasis within target artery. Following these interventions, the two groups were given the same treatment to stabilize hepatic function and relief embolization-relating symptoms; Patients' follow-up included clinical symptoms and signs, hepatic and renal function, peripheral blood test, CT and radionuclide study(ECT). All data were analyzed with SPSS 11.5. Measurement data were expressed with mean and processed by t test; numeration data were processed by Chi square test and Fisher precise test; Kaplan-Meier analysis and log-rank test were applied for comparing the survival rate of the two groups. P0.05]. ECT imaging demonstrated a 55.17% (16/29) uptake ratio of licartin within tumor areas by the time of 7-days follow-up study. The lesions in both LTACE and TACE groups exhibited a decrease in their size and statistically significant

  12. Retrospective comparison between a regular and a split-dose protocol of 5-fluorouracil, cisplatin, and mitoxantrone for the treatment of far advanced hepatocellular carcinoma

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    Pan Kuang-Tse

    2011-03-01

    Full Text Available Abstract Background In patients with advanced hepatocellular carcinoma (HCC, combination chemotherapy using 5- fluorouracil, cisplatin, and mitoxantrone (FMP could achieve a response rate > 20%, but the beneficial effect was compromised by formidable adverse events. Chemotherapy given in a split-dose manner was associated with reduced toxicities. In this retrospective study, we compared the efficacies and side effects between a regular and a split-dose FMP protocol approved in our medical center. Methods From 2005 to 2008, the clinical data of 84 patients with far advanced HCC, who had either main portal vein thrombosis and/or extrahepatic metastasis, were reviewed. Of them, 65 were treated by either regular (n = 27 or split-dose (n = 38 FMP and had completed at least one therapeutic course. The remaining 19 patients were untreated. Clinical parameters, therapeutic responses, survivals and adverse events were compared. Results The median overall survival was 6.0, 5.2, and 1.5 months, respectively, in patients receiving regular FMP, split-dose FMP, and no treatment (regular versus split-dose group, P = 0.447; regular or split-dose versus untreated group; P Conclusions Comparable overall survival was observed between patients receiving regular and split-dose FMP therapies. Patients receiving split-dose therapy had a significantly lower risk of grade 3/4 neutropenia. Positive anti-hepatitis C virus antibody, smaller tumor size, and absence of previous anti-cancer therapy were independent predictors for successful disease control.

  13. 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

  14. Performance and acceptability of a combined device for insulin infusion and glucose sensing in the home setting

    DEFF Research Database (Denmark)

    Nørgaard, K.; Shin, J.; Welsh, J. B.;

    2015-01-01

    connected to insulin pumps over 15 days (3 days/device) and test capillary blood glucose (SMBG) 7 times/day. The primary endpoint was the percentage of sensor-SMBG paired values within 20% of one another. Subject experiences were assessed via questionnaires. Overall, 74.8% of sensor-SMBG paired values were......The use of sensor-augmented insulin pump (SAP) therapy is increasing. Currently, glucose sensors and insulin infusion cannulas are inserted separately. A new device, MiniMed Duo, combines sensing and infusion capabilities on the same platform and is intended to simplify device insertion and site...

  15. Formulation, in vitro drug release and in vivo human X-ray investigation of polysaccharide based drug delivery systems for targeting 5-fluorouracil to the colon

    OpenAIRE

    Sidramappa Mallikarjun Chickpetty; Baswaraj Veerappa Raga

    2013-01-01

    The purpose of this research study was to develop 5-fluorouracil compression coated tablets by using biodegradable polysaccharide polymer locust bean gum (LBG) and hydroxyl propyl methyl cellulose (HPMC) as coating materials. The fast disintegrating core tablets containing 50 mg of 5-fluorouracil were compression coated with LBG and HPMC in different ratios (8:1, 7:2 and 6:3) with a coat weight of 300, 400 and 500 mg. In vitro dissolution data indicated that the formulation (CLH63) with a coa...

  16. Impact of heterophil granulocyte depletion caused by 5-fluorouracil on infectious bursal disease virus infection in specific pathogen free chickens

    DEFF Research Database (Denmark)

    Kabell, Susanne; Igyarto, Botond-Zoltan; Magyar, Attila;

    2006-01-01

    The purpose of this study was to investigate the influence of the cytostatic drug, 5-fluorouracil (5-FU), which causes depletion of heterophil granulocytes, on clinical symptoms and histological lesions during the progress of infectious bursal disease virus ( IBDV) infection in chickens. The aim...... inoculated with the classical IBDV strain F52/70. Bursae of Fabricius were sampled at fixed intervals, and the progress of the infection was monitored by various histological techniques and reverse transcriptase-polymerase chain reaction (RT-PCR). We found correlation between histological observations and RT......-PCR results. In the 5-FU pretreated chickens, IBDV caused only mild clinical symptoms, even though histological alterations similar to alterations caused by IBDV were still observed. The 5-FU pretreatment resulted in severe heterophil granulocyte depletion by days 2 and 3 after infection (post inoculation...

  17. Efficacy of repeated 5-fluorouracil needling for failing and failed filtering surgeries based on simple gonioscopic examination

    Directory of Open Access Journals (Sweden)

    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

  18. 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.

  19. Treatment of malignant digestive tract obstruction by combined intraluminal stent installation and intra-arterial drug infusion

    Institute of Scientific and Technical Information of China (English)

    Ai-Wu Mao; Zhong-Du Gao; Jia-Yu Xu; Ren-Jie Yancg; Xiang-Seng Xiao; Ting-Hui Jiang; Wei-Jun Jiang

    2001-01-01

    AIM To study the palliative treatment of malignant obstrution of digestive tract with placement of intraluminal stent combined with intra-arterial infusion of chemotherapeutic drugs. METHODS A total of 281 cases of digestive tract malignant obstruction were given per oral (esophagus,stomach, duodenum and jejunum), per anal (colon and rectum ) and percutaneous transhepatic ( biliary )installation of metallic stent. Among them, 205 cases received drug infusion by cannulation of tumor supplying artery with Seldingers technique. RESULTS Altogether 350 stents were installed in 281 cases, obstructive symptoms were relieved or ameliorated after installation. Occurrence of restenotic obstruction was 8 - 43 weeks among those with intraarterial drug infusion, which was later than 4 - 26 weeks in the group with only stent installation. The average survival time of the former group was 43 (3 - 105) weeks,which was significantly longer than 15 (3- 24) weeks of the latter group. CONCLUSION Intraluminal placement of stent combined with intra-arterial infusion chemotherapy is one of the effective palliative therapies for malignant obstruction of the digestive tract with symptomatic as well as etiological treatment.

  20. Experience in treatment of patients with locally advanced or recurrent breast cancer. Intraarterial infusion chemotherapy combined with radiotherapy

    International Nuclear Information System (INIS)

    For the purpose of local control and breast conservation, intraarterial infusion chemotherapy combined with radiotherapy has been indicated in patients with locally advanced breast cancer both in primary and recurrent cases. The present series, evaluated during the past 4 years, consisted of 15 patients 35-83 years of age, with invasive ductal carcinoma, including 10 with primary breast cancer (stage IIIb: 1, IV: 9) and 5 with postoperative recurrence (stage IIIb: 2, IV: 3). Intraarterial chemotherapy is started, basically infusing ADM 50 mg, MMC 10 mg and CDDP 50 mg into the internal thoracic and/or subclavian artery 1-3 times, followed by reduction surgery (quadrantectomy: 4, wide resection: 2) and radiotherapy to the breast, supraclavicular, parasternal and cervical regions according to tumor extent. Local response after arterial infusion was CR: 2, PR: 10, NC: 3 (response rate: 73% ). The response rate of distant metastases after arterial infusion was 73%. Of 10 patients with primary breast cancer, recurrence was noted in 1. Breast conservation was successful in 8 of 10 patients. One of them, in stage IIIb, has survived for 4.5 years with no evidence of disease and with breast conservation. Five patients with postoperative recurrence showed CR with no recurrence after intraarterial chemotherapy and radiotherapy. Acute skin reaction occurred in 6 patients, and was especially frequent in patients with postoperative recurrence (4 of 5). According to these results, combined therapy affords breast conservation even in patients with locally advanced breast cancer, and improves patient's QOL in stage IV. (author)

  1. 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.)

  2. 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)

    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 177Lu-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.)

  3. Concomitant bid radiotherapy with cisplatin and 5-fluorouracil in unresectable carcinoma of the pharynx: 10 year's experience at the Centre Antoine Lacassagne

    International Nuclear Information System (INIS)

    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/m2 (day 1) and 5-FU was given as 6-day continuous infusion (750 mg/m2/day at 1. course; 430 mg/m2/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 with a

  4. Is the therapeutic index better with gemcitabine-based chemoradiation than with 5-fluorouracil-based chemoradiation in locally advanced pancreatic cancer?

    International Nuclear Information System (INIS)

    Purpose: To retrospectively compare the toxicity and efficacy of concurrent gemcitabine-based chemoradiation with that of concurrent 5-fluorouracil (5-FU)-based chemoradiation in patients with unresectable pancreatic cancer. Patients and Methods: Between September 1996 and May 2000, 114 patients with localized unresectable adenocarcinoma of the pancreas were treated with concurrent chemoradiation. Locally advanced unresectable disease was defined as low-density tumor in contact with the superior mesenteric artery (SMA) or celiac artery, or occlusion of the superior mesenteric-portal venous confluence. Fifty-three patients were selected to receive gemcitabine in 7 weekly cycles (250-500 mg/m2) with concurrent radiotherapy (median dose 30 Gy, range 30-33 Gy in 10-11 fractions). The remaining 61 patients received continuous-infusion 5-FU (200-300 mg/m2) with concurrent radiotherapy (30 Gy in 10 fractions). Radiotherapy was delivered to the primary tumor and regional lymphatics. Patients receiving gemcitabine and those receiving 5-FU had a similar mean Karnofsky performance status (KPS, 89% vs. 86%), distribution of tumor grade (43% vs. 33% poorly differentiated), and percent weight loss (all p=NS). However, patients treated with gemcitabine had a significantly larger median maximum cross-sectional tumor area (TA, 8.8 cm2 vs. 5.7 cm2, p=0.046) and were significantly younger (median age 60 vs. 68 years, p10 cm2 (p=0.03) and poor differentiation (p=0.07) were associated with a worse survival duration; however, other factors, such as KPS and weight loss >10% and age did not influence OS. Conclusion: Despite the selection of healthier patients to receive gemcitabine, there was a significantly higher severe toxicity rate than with 5-FU. The median and 1-year survivals were not significantly different with the use of concurrent gemcitabine; however, the tumors treated were significantly larger. Additionally, a small number of patients with minimal arterial involvement whose

  5. 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.

  6. Integrated analysis of overall survival in two randomised studies comparing 5-fluorouracil/leucovorin with or without trimetrexate in advanced colorectal cancer

    NARCIS (Netherlands)

    Punt, CJA; Blanke, CD; Zhang, J; Hammershaimb, L

    2002-01-01

    Background: Two randomised studies were performed with trimetrexate (TMTX) as a biochemical modulator of 5-fluorouracil (5-FU)/leucovorin (LV) in advanced colorectal cancer (ACC), one in Europe and one in the United States. Both studies were similarly designed to detect a statistically significant d

  7. Endoscopic Resection and Topical 5-Fluorouracil as an Alternative Treatment to Craniofacial Resection for the Management of Primary Intestinal-Type Sinonasal Adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Simon Mackie

    2010-01-01

    Conclusion. Trans-nasal endoscopic resection and topical 5-Fluorouracil could potentially offer an acceptable alternative treatment to the standard of cranio-facial resection. This should be investigated in trials with a longer followup period than this paper in order to directly compare the two treatment modalities.

  8. Formulation, in vitro drug release and in vivo human X-ray investigation of polysaccharide based drug delivery systems for targeting 5-fluorouracil to the colon

    Directory of Open Access Journals (Sweden)

    Sidramappa Mallikarjun Chickpetty

    2013-06-01

    Full Text Available The purpose of this research study was to develop 5-fluorouracil compression coated tablets by using biodegradable polysaccharide polymer locust bean gum (LBG and hydroxyl propyl methyl cellulose (HPMC as coating materials. The fast disintegrating core tablets containing 50 mg of 5-fluorouracil were compression coated with LBG and HPMC in different ratios (8:1, 7:2 and 6:3 with a coat weight of 300, 400 and 500 mg. In vitro dissolution data indicated that the formulation (CLH63 with a coat weight of 500 mg containing LBG and HPMC in the ratio 6:3 gave the best release profile (0% in first 5 hour and 96.18% in 24 hours. DSC and FTIR results indicated no possibility of interaction between drug and polymers or other excipients. In vivo human X-ray studies revealed that formulation CLH63 was able to resist breakdown in the stomach and small intestine. The disintegration of the tablet occurred in the colon between 8 to 16 hours of post dose. By the present study, it can be concluded that the LBG and HPMC based compression coated tablets of 5-fluorouracil will be useful strategy for colonic delivery of 5-fluorouracil without being released in upper gastrointestinal region for the safe and effective management of colon cancer.

  9. Down-regulation of Sonic hedgehog signaling pathway activity is involved in 5-fluorouracil-induced apoptosis and motility inhibition in Hep3B cells

    Institute of Scientific and Technical Information of China (English)

    Qiyu Wang; Shuhong Huang; Ling Yang; Ling Zhao; Yuxia Yin; Zhongzhen Liu; Zheyu Chen; Hongwei Zhang

    2008-01-01

    The Sonic hedgehog (SHh) pathway plays a critical role in normal embryogenesis and carcinogenesis, but its function in cancer cells treated with 5-fluorouracil (5-FU) remains unknown. We examined the expression of a subset of SHh signaling pathway genes, including SHh, SMO, PTC1, Su(Fu) and HIP in human hepatocellular carcinoma (HCC) cell lines,Hep3B and HepG2, treated with 5-FU by reverse transcriptionpolymerase chain reaction. Using trypan blue analysis,3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and terminal deoxynucleotidyl transferase-mediated digoxigenin-dUTP nick-end labeling assay, we also detected the apoptosis of Hep3B cells resulting from the transfection of pCS2-Gli1 expression vector combined with 5-FU treatment.The motility of the cells was detected by scratch wound closure assay. The expression and subcellular location of PTC1 protein in Hep3B cells treated by 5-FU were also investigated by Western blot analysis and immunofluorescent microscopy. The results indicated that the expression of SHh pathway target molecules at both messenger RNA and protein levels are evidently down-regulated in Hep3B cells treated with 5-FU. The overexpression of Gli1 restores cell viability and, to some extent, the migration abilities inhibited by 5-FU.Furthermore, 5-FU treatment affects the subcellular localization of PTC1 protein, a key member in SHh signaling pathway. Our data showed that the down-regulation of SHh signaling pathway activity was involved in 5-FU-induced apoptosis and the inhibition of motility in hedgehog-activated HCC cell lines. This implies that the combination of SHh signaling pathway inhibitor and 5-FU-based chemotherapy might represent a more promising strategy against HCC.

  10. Paricalcitol Enhances the Chemopreventive Efficacy of 5-Fluorouracil on an Intermediate-Term Model of Azoxymethane-Induced Colorectal Tumors in Rats.

    Science.gov (United States)

    El-Shemi, Adel Galal; Refaat, Bassem; Kensara, Osama Adnan; Mohamed, Amr Mohamed; Idris, Shakir; Ahmad, Jawwad

    2016-06-01

    Colorectal cancer is a common cancer with high mortality rate. Despite being the standard anti-colorectal cancer drug, 5-fluorouracil (5-FU) exhibits only limited therapeutic benefits. Herein, we investigated whether paricalcitol, a synthetic vitamin D analogue with potential antitumor properties, would enhance the chemopreventive efficacy of 5-FU on an intermediate-term (15 weeks) model of colorectal tumors induced by azoxymethane (AOM) in rats. After AOM injection, 5-FU was administered during the 9th and 10th weeks (12 mg/kg/day for 4 days, then 6 mg/kg every other day for another 4 doses), whereas paricalcitol (2.5 μg/kg/day; 3 days/week) was given from the 7th to the 15th week. At week 15, the animals were euthanized and their resected colons were examined macroscopically and microscopically. Quantitative RT-PCR was used to measure the transcription activities of Wnt, β-catenin, DKK-1, CDNK-1A, NF-κB, and COX-2 genes, and ELISA was used to quantify the protein levels of β-catenin, COX-2, HSP90, and VEGF. IHC was additionally used to measure β-catenin, HSP90, and inducible nitric oxide synthase (iNOS). Compared with their individual therapy, combination of 5-FU and paricalcitol showed more significant reducing effect on numbers of grown tumors and large aberrant crypts foci. Mechanistically, paricalcitol and 5-FU had cooperated together to repress the expression of procancerous Wnt, β-catenin, NF-κB, COX-2, iNOS, VEGF, and HSP-90 more, and to upregulate the expression of antitumorigenesis DKK-1 and CDNK-1A, compared with their monotherapies. Our findings suggest that combined use of paricalcitol with 5-FU exhibits an augmenting chemopreventive effect against colorectal tumors, and might potentially be useful for chemoprevention in colorectal cancer patients. Cancer Prev Res; 9(6); 491-501. ©2016 AACR. PMID:27020656

  11. Indication for shunt operation of normal pressure hydrocephalus. Combined assessment of infusion test and dynamic CT scan

    Energy Technology Data Exchange (ETDEWEB)

    Jinnai, Takahiro; Nagao, Seigo [Kagawa Medical Univ., Miki (Japan); Kuyama, Hideyuki

    2000-03-01

    Normal pressure hydrocephalus (NPH) is one of the diseases that causes a neuro-surgically treatable form of dementia. Although patients with NPH can be treated with shunt operation, reliable indications for the surgery are not yet established. In this study, 20 NPH patients diagnosed by clinical symptoms were subjected to combined assessment by infusion test and dynamic CT scan, a useful diagnostic tool to select a shunt responsive cases. Patients were evaluated by measuring sequential changes in the density of the periventricular lucency (PVL) using dynamic CT scan and continuous lumbar subdural pressure monitoring during an infusion manometric test at a rate of 0.8 ml/min for 30 min. The average lumbar subdural pressure during infusion manometric test in the shunt responsive group was 18.4{+-}5.8 mmHg, which was significantly higher than that in the shunt non-responsive group which was 10.0{+-}4.0 mmHg (p<0.01). The relative changes in PVL density in the dynamic CT was also significantly higher in the shunt responsive group (0.99{+-}0.61 HU) compared to the shunt non-responsive group (0.15{+-}0.32) (p<0.01). Dynamic CT scan with infusion manometric test is useful in the selection of patients with NPH who are likely to respond to shunt surgery. (author)

  12. Indication for shunt operation of normal pressure hydrocephalus. Combined assessment of infusion test and dynamic CT scan

    International Nuclear Information System (INIS)

    Normal pressure hydrocephalus (NPH) is one of the diseases that causes a neuro-surgically treatable form of dementia. Although patients with NPH can be treated with shunt operation, reliable indications for the surgery are not yet established. In this study, 20 NPH patients diagnosed by clinical symptoms were subjected to combined assessment by infusion test and dynamic CT scan, a useful diagnostic tool to select a shunt responsive cases. Patients were evaluated by measuring sequential changes in the density of the periventricular lucency (PVL) using dynamic CT scan and continuous lumbar subdural pressure monitoring during an infusion manometric test at a rate of 0.8 ml/min for 30 min. The average lumbar subdural pressure during infusion manometric test in the shunt responsive group was 18.4±5.8 mmHg, which was significantly higher than that in the shunt non-responsive group which was 10.0±4.0 mmHg (p<0.01). The relative changes in PVL density in the dynamic CT was also significantly higher in the shunt responsive group (0.99±0.61 HU) compared to the shunt non-responsive group (0.15±0.32) (p<0.01). Dynamic CT scan with infusion manometric test is useful in the selection of patients with NPH who are likely to respond to shunt surgery. (author)

  13. Radical resection for low rectal carcinoma combined with infusion pump chemotherapy via internal iliac artery

    Directory of Open Access Journals (Sweden)

    Bo YANG

    2011-10-01

    Full Text Available Objective To evaluate the effects and practicability of radical resection for low rectal carcinoma with infusion pump chemotherapy via internal iliac artery,and explore the correlation factors influencing the therapeutic effects.Methods Data of 316 patients with low rectal carcinoma,admitted from Oct.1997 to Mar.2008,were retrospectively analyzed and assigned into 2 groups according to the treatment: Patients received infusion pump chemotherapy via internal iliac artery to target area combined with intravenous systemic chemotherapy were assigned into group A(n=249,and those receiving systemic chemotherapy alone following radical resection were assigned to group B(n=67.The timing of pump chemotherapy to target area in group A was set at day 12 after recovery of digestive function,with regimen of 5-FU at 0.5g per dose plus hydroxycamptothecin at 10-15mg per dose,twice a week,four times as a treatment course for a total of 6 courses,and it was followed by intravenously systemic chemotherapy with a regimen of FOLFIRI or FOLFOX.In group B,at day 12 right after recovery of digestive function,the intravenous sytemic chemotherapy was started with the same regimen as in group A.The local recurrence rate,metastasis rate and survival rate after 1,3 and 5 years in the two groups were respectively observed and compared,and the correlation between the clinicopathological features and the 5 year local recurrence rates and survival rates was analyzed in patients of group A.Results In group A,the local recurrence rate at year 1,3 and 5 was 0,1.68%(4/238 and 3.79%(8/211,respectively,the metastasis rate was 0.80%(2/249,4.62%(11/238 and 10.90%(23/211,respectively,and the survival rate was 100%,77.73%(185/238 and 72.04%(152/211,respectively.In group B,the local recurrence rate at year 1,3 and 5 was 0,9.52%(6/63 and 16.36%(9/55,respectively,the metastasis rate was 1.49%(1/67,15.87%(10/63 and 27.27%(15/55,respectively,and the survival rate was 100

  14. Postoperative subconjunctival bevacizumab injection as an adjunct to 5-fluorouracil in the management of scarring after trabeculectomy

    Directory of Open Access Journals (Sweden)

    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

  15. A novel drug delivery of 5-fluorouracil device based on TiO{sub 2}/ZnS nanotubes

    Energy Technology Data Exchange (ETDEWEB)

    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.

  16. A nanomedicine-promising approach to provide an appropriate colon-targeted drug delivery system for 5-fluorouracil

    Directory of Open Access Journals (Sweden)

    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

  17. Herb-Drug Pharmacokinetic Interaction of a Traditional Chinese Medicine Jia-Wei-Xiao-Yao-San with 5-Fluorouracil in the Blood and Brain of Rat Using Microdialysis

    Directory of Open Access Journals (Sweden)

    Meng-Hsuan Chiang

    2015-01-01

    Full Text Available According to a survey from the National Health Insurance Research Database (NHIRD, Jia-Wei-Xiao-Yao-San (JWXYS is the most popular Chinese medicine for cancer patients in Taiwan. 5-Fluorouracil (5-FU is a general anticancer drug for the chemotherapy. To investigate the herb-drug interaction of JWXYS on pharmacokinetics of 5-FU, a microdialysis technique coupled with a high-performance liquid chromatography system was used to monitor 5-FU in rat blood and brain. Rats were divided into four parallel groups, one of which was treated with 5-FU (100 mg/kg, i.v. alone and the remaining three groups were pretreated with a different dose of JWXYS (600, 1200, or 2400 mg/kg/day for 5 consecutive days followed by a combination with 5-FU. This study demonstrates that 5-FU with JWXYS (600 mg/kg/day or 1200 mg/kg/day has no significant effect on the pharmacokinetics of 5-FU in the blood and brain. However, JWXYS (2400 mg/kg/day coadministered with 5-FU extends the elimination half-life and increases the volume of distribution of 5-FU in the blood. The elimination half-life of 5-FU in the brain for the pretreatment group with 2400 mg/kg/day of JWXYS is significantly longer than that for the group treated with 5-FU alone and also reduces the clearance. This study provides practical dosage information for clinical practice and proves the safety of 5-FU coadministered with JWXYS.

  18. Herb-Drug Pharmacokinetic Interaction of a Traditional Chinese Medicine Jia-Wei-Xiao-Yao-San with 5-Fluorouracil in the Blood and Brain of Rat Using Microdialysis

    Science.gov (United States)

    Chiang, Meng-Hsuan; Chang, Li-Wen; Wang, Ju-Wen; Lin, Lie-Chwen; Tsai, Tung-Hu

    2015-01-01

    According to a survey from the National Health Insurance Research Database (NHIRD), Jia-Wei-Xiao-Yao-San (JWXYS) is the most popular Chinese medicine for cancer patients in Taiwan. 5-Fluorouracil (5-FU) is a general anticancer drug for the chemotherapy. To investigate the herb-drug interaction of JWXYS on pharmacokinetics of 5-FU, a microdialysis technique coupled with a high-performance liquid chromatography system was used to monitor 5-FU in rat blood and brain. Rats were divided into four parallel groups, one of which was treated with 5-FU (100 mg/kg, i.v.) alone and the remaining three groups were pretreated with a different dose of JWXYS (600, 1200, or 2400 mg/kg/day for 5 consecutive days) followed by a combination with 5-FU. This study demonstrates that 5-FU with JWXYS (600 mg/kg/day or 1200 mg/kg/day) has no significant effect on the pharmacokinetics of 5-FU in the blood and brain. However, JWXYS (2400 mg/kg/day) coadministered with 5-FU extends the elimination half-life and increases the volume of distribution of 5-FU in the blood. The elimination half-life of 5-FU in the brain for the pretreatment group with 2400 mg/kg/day of JWXYS is significantly longer than that for the group treated with 5-FU alone and also reduces the clearance. This study provides practical dosage information for clinical practice and proves the safety of 5-FU coadministered with JWXYS. PMID:25861367

  19. 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

    Directory of Open Access Journals (Sweden)

    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.

  20. Dose-volume relationships between enteritis and irradiated bowel volumes during 5-fluorouracil and oxaliplatin based chemoradiotherapy in locally advanced rectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Gunnlaugsson, Adalsteinn; Kjellen, Elisabeth; Bendahl, Paer-Ola; Johnsson, A nders [Dept. of Oncology, Lund Univ. Hospital, Lund (Sweden); Nilsson, Per [Dept. o f Radiation Physics, Lund Univ. Hospital, Lund (Sweden); Willner, Julian [Dept. of Radiology, Lund Univ. Hospital, Lund (Sweden)

    2007-10-15

    Purpose. Radiation enteritis is the main acute side-effect during pelvic irradiation. The aim of this study was to quantify the dose-volume relationship between irradiated bowel volumes and acute enteritis during combined chemoradiotherapy for rectal cancer. Material and methods. Twenty-eight patients with locally advanced rectal cancer received chemoradiotherapy. The radiation therapy was given with a traditional multi-field technique to a total dose of 50 Gy, with concurrent 5-Fluorouracil (5-FU) and oxaliplatin (OXA) based chemotherapy. All patients underwent three-dimensional CT-based treatment planning. Individual loops of small and large bowel as well as a volume defined as 'whole abdomen' were systematically contoured on each CT slice, and dose-volume histograms were generated. Diarrhea during treatment was scored retrospectively according to the NCI Common Toxicity Criteria scale. Results. There was a strong correlation between the occurrence of grade 2+diarrhea and irradiated small bowel volume, most notably at doses >15 Gy. Neither irradiated large bowel volume, nor irradiated 'whole abdomen' volume correlated significantly with diarrhea. Clinical or treatment related factors such as age, gender, hypertension, previous surgery, enterostomy, or dose fractionation (1.8 vs. 2.0 Gy/fraction) did not correlate with grade 2+diarrhea. Discussion. This study indicates a strong dose-volume relationship between small bowel volume and radiation enteritis during 5-FU-OXA-based chemoradiotherapy. These findings support the application of maneuvers to minimize small bowel irradiation, such as using a 'belly board' or the use of IMRT technique aiming at keeping the small bowel volume receiving more than 15 Gy under 150 cc.

  1. Synthesis of Glycyrrhetinic Acid-Modified Chitosan 5-Fluorouracil Nanoparticles and Its Inhibition of Liver Cancer Characteristics in Vitro and in Vivo

    Directory of Open Access Journals (Sweden)

    Jiang Han

    2013-09-01

    Full Text Available Nanoparticle drug delivery (NDDS is a novel system in which the drugs are delivered to the site of action by small particles in the nanometer range. Natural or synthetic polymers are used as vectors in NDDS, as they provide targeted, sustained release and biodegradability. Here, we used the chitosan and hepatoma cell-specific binding molecule, glycyrrhetinic acid (GA, to synthesize glycyrrhetinic acid-modified chitosan (GA-CTS. The synthetic product was confirmed by Fourier transformed infrared spectroscopy (FT-IR and 1H-nuclear magnetic resonance (1H-NMR. By combining GA-CTS and 5-FU (5-fluorouracil, we obtained a GA-CTS/5-FU nanoparticle, with a particle size of 217.2 nm, a drug loading of 1.56% and a polydispersity index of 0.003. The GA-CTS/5-FU nanoparticle provided a sustained release system comprising three distinct phases of quick, steady and slow release. We demonstrated that the nanoparticle accumulated in the liver. In vitro data indicated that it had a dose- and time-dependent anti-cancer effect. The effective drug exposure time against hepatic cancer cells was increased in comparison with that observed with 5-FU. Additionally, GA-CTS/5-FU significantly inhibited the growth of drug-resistant hepatoma, which may compensate for the drug-resistance of 5-FU. In vivo studies on an orthotropic liver cancer mouse model demonstrated that GA-CTS/5-FU significantly inhibited tumor growth, resulting in increased survival time.

  2. Intraduodenal infusion of a combination of tastants decreases food intake in humans

    NARCIS (Netherlands)

    Avesaat, Van Mark; Troost, F.J.; Ripken, Dina; Peters, Jelmer; Hendriks, H.F.J.; Masclee, A.A.M.

    2015-01-01

    Background: Taste receptors are expressed not only in taste buds but also in the gastrointestinal tract. It has been hypothesized that these receptors may play a role in satiety and food intake. Objective: This study investigated the effect of intraduodenal tastant infusions (bitter, sweet, and u

  3. Intraduodenal infusion of a combination of tastants decreases food intake in humans

    NARCIS (Netherlands)

    Avesaat, M. van; Troost, F.J.; Ripken, D.; Peters, J.; Hendriks, H.F.J.; Masclee, A.A.M.

    2015-01-01

    Background: Taste receptors are expressed not only in taste buds but also in the gastrointestinal tract. It has been hypothesized that these receptors may play a role in satiety and food intake. Objective: This study investigated the effect of intraduodenal tastant infusions (bitter, sweet, and umam

  4. Decreased Oxygen Transfer Capacity of Erythrocytes as a Cause of 5-Fluorouracil Related Ischemia

    Directory of Open Access Journals (Sweden)

    Ivan Spasojević

    2008-12-01

    Full Text Available cisplatin have similar effects on the erythrocyte membrane, thus eliminating those changes as a potential source of cardiotoxicity. On the contrary, 31P-NMR and polarography showed that the effects of these cytostatics on the intracellular milieu differ significantly. 5-FU provoked a pronounced decrease of the O2 level in blood and affected the metabolism of phosphate compounds, while cisplatin had no such effects. When combined these two drugs showed synergistic effects, which matches the higher frequency of cardiotoxicity of the combination relative to the sole application of 5-FU. Preliminary results acquired on blood of patients receiving cisplatin/5-FU therapy verified observations obtained ex vivo. These results open a possibility of applying NMR in preclinical trials of new drugs in order to predict their ischemic potential.

  5. 5-Fluorouracil-induced acute reversible heart failure not explained by coronary spasms, myocarditis or takotsubo: lessons from MRI.

    Science.gov (United States)

    Fakhri, Yama; Dalsgaard, Morten; Nielsen, Dorte; Lav Madsen, Per

    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 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, 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 cardiomyopathy. However, our patient did not fulfil the diagnostic criteria for the aforementioned complications. Based on this case report, we discuss alternative mechanisms including myocardial adenosine triphosphate depletion suggested from animal experiments. PMID:27251602

  6. Assam Bora rice starch based biocompatible mucoadhesive microsphere for targeted delivery of 5-fluorouracil in colorectal cancer.

    Science.gov (United States)

    Ahmad, Mohammad Zaki; Akhter, Sohail; Anwar, Mohammed; Ahmad, Farhan Jalees

    2012-11-01

    The aim of this study was to develop novel colon targeted mucoadhesive microspheres (MAMs) for site specific delivery of 5-fluorouracil (5-FU) to colon without the drug being released in the stomach or small intestine. MAMs were prepared using Assam Bora rice starch, a natural mucoadhesive polymer, by a double emulsion solvent evaporation method. The microspheres were characterized for their shape, size, surface morphology, size distribution, incorporation efficiency, and in vitro and in vivo drug release studies. The release study confirmed the insignificant release of 5-FU in physiological condition of stomach and small intestine and major drug release in the cecal content. In vivo release study of the optimized MAMs was compared with immediate release (IR) 5-FU. 5-FU was distributed predominantly in the upper GI tract from the IR, whereas 5-FU was distributed primarily to the lower part of the GI tract from the MAM formulation. Enhanced levels of liver enzymes were found in animals given IR 5-FU as well as augmented levels of serum albumin, creatinine, leucocytopenia and thrombocytopenia was also observed. Thus to sum up, it can be appropriately established that the 5-FU release pattern from MAMs exhibits slow and extended release over longer periods of time with reduced systemic side effects. PMID:22994847

  7. 5-fluorouracil 0.5% cream for multiple actinic or solar keratoses of the face and anterior scalp.

    Science.gov (United States)

    Gupta, A K; Weiss, J S; Jorizzo, J L

    2001-06-01

    Carac (5-fluorouracil 0.5% cream, Aventis Pharma) was approved by the US FDA in October 2000, for the treatment of multiple actinic or solar keratoses involving the face and anterior scalp. The cream should be applied in a thin film once daily to the skin where actinic keratoses (AKs) are present. When it is applied for 1, 2, or 4 weeks, it is significantly more effective than a vehicle in the management of patients with five or more AKs at pretherapy. Pooled data from the two pivotal trials (n=384) indicate that following 4 weeks of therapy the number of subjects with total AK clearance in the Carac and vehicle groups was 52.9% and 1.6% respectively (p<0.001). Furthermore, the corresponding reduction of AK lesion counts in the Carac and vehicle groups was 82.5% and 19.3%, respectively (p<0.001). Treatment should be continued up to 4 weeks as tolerated by the patient. The most common adverse-effect is facial irritation. PMID:11550079

  8. 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

  9. In Vivo Chemoprotective Activity of Bovine Dialyzable Leukocyte Extract in Mouse Bone Marrow Cells against Damage Induced by 5-Fluorouracil

    Directory of Open Access Journals (Sweden)

    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.

  10. Radiation could induce p53-independent and cell cycle - unrelated apoptosis in 5-fluorouracil radiosensitized head and neck carcinoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Didelot, C.; Mirjolet, J.F.; Barberi-Heyob, M.; Ramacci, C.; Merlin, J.L. [Centre Alexis Vautrin, Lab. de Recherche en Oncologie, Vandoeuvre-les-Nancy CEDEX (France)

    2002-07-01

    The effect of chemoresistance induction in radio sensitivity and cellular behavior after irradiation remains misunderstood. This study was designed to understand the relationship between radiation-induced cell cycle arrest, apoptosis, and radiosensitivity in KB cell line and KB3 subline selected after 5-fluorouracil (5FU) exposure. Exposure of KB cells to 5FU led to an increase in radiosensitivity. G{sub 2}/M cell cycle arrest was observed in the two cell lines after irradiation. The radioresistant KB cell line reached the maximum arrest two hours before KB3. The cellular exit from this arrest was found to be related to the wild type p53 protein expression induction. After irradiation, only KB3 cell line underwent apoptosis. This apoptosis induction seemed to be independent of G{sub 2}/M arrest exit, which was carried out later. The difference in radiosensitivity between KB and KB3 subline may result therefore from both a difference in apoptosis induction and a difference in G{sub 2}/M arrest maximum duration. Moreover, 5FU exposure has led to an increase in constitutive p53 protein expression, which may be associated with an increase in basal apoptosis cell fraction. Given the existing correlation between radiosensitivity and the percentage of basal apoptosis. the constitutive p53 protein expression may be related to intrinsic radiosensitivity in our cellular model. (author)

  11. Methacrylic-based nanogels for the pH-sensitive delivery of 5-Fluorouracil in the colon

    Directory of Open Access Journals (Sweden)

    Ashwanikumar N

    2012-11-01

    Full Text Available N Ashwanikumar,1,* Nisha Asok Kumar,2,* S Asha Nair,2 GS Vinod Kumar11Chemical Biology, 2Cancer Research Programme, Rajiv Gandhi Center for Biotechnology, Poojappura, Thiruvananthapuram, Kerala, India *These authors contributed equally to this workAbstract: Methacrylic-based copolymers in drug-delivery systems demonstrate a pH-sensitive drug-releasing behavior in the colon. In this study, copolymers of methacrylic acid and 2-ethyl hexyl acrylate were prepared using a microemulsion polymerization technique. The purified copolymer was characterized by Fourier transform infrared spectroscopy, proton nuclear magnetic resonance spectroscopy, and differential scanning calorimetry. 5-Fluorouracil (5-FU was entrapped within methacrylic-based copolymers by a solvent evaporation method. The size of the nanogels formed was characterized by transmission electron microscopy and atomic force microscopy. In vitro drug-release studies using phosphate-buffered saline at different pH levels demonstrated the sustained release of 5-FU and its pH dependence. Cell proliferation assay of a human colon tumor colon cancer cell line (HCT-116 was performed and showed that the nanogels containing 5-FU exhibited considerable cytotoxicity in comparison with free 5-FU. Cell uptake of the nanogels was also monitored using confocal microscopy. Western blot analysis and flow cytometry studies confirmed that the nanogels could be successfully used as an efficient vector for pH-sensitive and controlled delivery of drugs specifically targeted to the colon.Keywords: 5-FU, methacrylic polymer, colon cancer, nanogel

  12. Is early post-operative treatment with 5-fluorouracil possible without affecting anastomotic strength in the intestine?

    Science.gov (United States)

    van der Kolk, B M; de Man, B M; Wobbes, T; Hendriks, T

    1999-01-01

    Early post-operative local or systemic administration of 5-fluorouracil (5-FU) is under investigation as a means to improve outcome after resection of intestinal malignancies. It is therefore quite important to delineate accurately its potentially negative effects on anastomotic repair. Five groups (n = 24) of rats underwent resection and anastomosis of both ileum and colon: a control group and four experimental groups receiving daily 5-FU, starting immediately after operation or after 1, 2 or 3 days. Within each group, the drug (or saline) was delivered either intraperitoneally (n = 12) or intravenously (n = 12). Animals were killed 7 days after operation and healing was assessed by measurement of anastomotic bursting pressure, breaking strength and hydroxyproline content. In all cases, 5-FU treatment from the day of operation or from day 1 significantly (P < 0.025) and severely suppressed wound strength; concomitantly, the anastomotic hydroxyproline content was reduced. Depending on the location of the anastomosis and the route of 5-FU administration, even a period of 3 days between operation and first dosage seemed insufficient to prevent weakening of the anastomosis. The effects of intravenous administration, though qualitatively similar, were quantitatively less dramatic than those observed after intraperitoneal delivery. Post-operative treatment with 5-FU, if started within the first 3 days after operation, is detrimental to anastomotic strength and may compromise anastomotic integrity. © 1999 Cancer Research Campaign PMID:10027328

  13. 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.

  14. Effects of smoking and alcohol consumption on 5-fluorouracil-related metabolic enzymes in oral squamous cell carcinoma.

    Science.gov (United States)

    Yamashita, Tomomi; Kato, Keizo; Long, Nguyen Khanh; Makita, Hiroki; Yonemoto, Kazuhiro; Iida, Kazuki; Tamaoki, Naritaka; Hatakeyama, Daijiro; Shibata, Toshiyuki

    2014-05-01

    Lifestyle, particularly smoking and alcohol consumption, may induce and/or inhibit drug metabolism. In order to reveal the effects of smoking and alcohol consumption on the 5-fluorouracil (5-FU)-related metabolic enzymes, namely thymidylate synthase, dihydropyrimidine dehydrogenase (DPD; a sole catabolic enzyme of 5-FU), orotate phosphoribosyl transferase (OPRT) and thymidine phosphorylase, in oral squamous cell carcinomas, the mRNA expression of these enzymes was investigated in 29 surgical specimens and compared by the Brinkman index and drinking years. The surgical specimens were divided into normal and tumor regions and were independently analyzed using quantitative reverse transcription-polymerase chain reaction. There was a significantly positive correlation between DPD mRNA expression in these tissues and Brinkman index/drinking years, with OPRT mRNA expression being significantly correlated to the Brinkman index in tumor tissues. These results revealed that lifestyle habits, including smoking and alcohol consumption, may vary the activity of the 5-FU-related metabolic enzymes. DPD is the initial and rate-limiting enzyme in the catabolic pathway of 5-FU. Therefore, smoking and alcohol consumption may reduce the anticancer activity of 5-FU, possibly through the induction of DPD activity. PMID:24772313

  15. Assessment of surface concentrations in resorbable ocular implants: controlled drug delivery devices for 5-fluorouracil (5-FU)

    Science.gov (United States)

    Milne, Peter J.; Gautier, Sandrine; Parel, Jean-Marie A.; Jallet, Valerie

    1997-05-01

    The antineoplastic drug 5-fluorouracil (5-fluoro- 2,4,(1H,3H)-pyrimidinedione; 5-FU) has been used to control proliferation of penetrating fibroblasts and to prevent channel closure following glaucoma filtration surgery (trabeculectomy) or laser sclerectomy. Because of the toxicity of the drug, administration of low dosages slowly over time, at the site of the desired treatment, is indicated for optimum efficacy. Repeated injections of low dosages of the drug represent an undesirable intervention and may also result in unwanted toxicity to the corneal epithelium. A suitable biocompatible and resorbable polymer matrix composed of a poly (D,L-lactic-co-glycolic acid: PLGA) has been admixed with varying amounts of 5-FU and cast as shapes suitable for intracorneal implantation. Slow biodegradation of this polymer over a one to two week period has been shown to result in an acceptably slow drug release mechanism. An issue arising during the clinical evaluation of the efficacy of this drug delivery system was how best to quantify the concentration of 5-FU and its distribution spatially in the solid implant. FT-IR and FT-Raman spectroscopies distinguishes between the drug and the polymer matrix and were used to differentiate and quantitate the 5-FU concentration of the implants.

  16. Studies on In Vitro Slow-Release Characteristics and Anticancer Effect of 5-Fluorouracil-Loaded Immuno-Nanoparticles

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    OBJECTIVE To investigate slow-release features of biodegradable anticancer 5-fluorouracil-loaded immunonanoparticles (5-FU INPs), and to assess their tumor cell killing activity in vitro.METHODS The method of vibrating dialysis at a constant temperature,and first-order derivative ultraviolet spectrophotometry were used to determine the drug-releasing character of 5-FU INPs. The methyl thiazolyl tetrazolium (MTT) colorimetric method was employed to assay the killing activity of 5-FU INPs on 5 tumor cell lines at different phases.RESULTS The 5-FU INPs had a favorable slow-release function, with a t1/2 release time of 10.4 days. The 5-FU INPs had a rather strong lethal effect on 5 tumor cell lines resulting in a positive correlativity between the killing activity and the action time and amount of the drug released.CONCLUSION The drug disposition is uniform from the 5-FU INPs,and there is no impact on efficacy of the 5-FU during preparation and degradation of the 5-FU INPs. The 5-FU INPs have a favorable function for drug release, and can maintain an effective killing activity over a long period of time.

  17. A designed 5-fluorouracil-based bridged silsesquioxane as an autonomous acid-triggered drug-delivery system.

    Science.gov (United States)

    Giret, Simon; Théron, Christophe; Gallud, Audrey; Maynadier, Marie; Gary-Bobo, Magali; Garcia, Marcel; Wong Chi Man, Michel; Carcel, Carole

    2013-09-16

    Two new prodrugs, bearing two and three 5-fluorouracil (5-FU) units, respectively, have been synthesized and were shown to efficiently treat human breast cancer cells. In addition to 5-FU, they were intended to form complexes through H-bonds to an organo-bridged silane prior to hydrolysis-condensation through sol-gel processes to construct acid-responsive bridged silsesquioxanes (BS). Whereas 5-FU itself and the prodrug bearing two 5-FU units completely leached out from the corresponding materials, the prodrug bearing three 5-FU units was successfully maintained in the resulting BS. Solid-state NMR ((29) Si and (13) C) spectroscopy show that the organic fragments of the organo-bridged silane are retained in the hybrid through covalent bonding and the (1) H NMR spectroscopic analysis provides evidence for the hydrogen-bonding interactions between the prodrug bearing three 5-FU units and the triazine-based hybrid matrix. The complex in the BS is not affected under neutral medium and operates under acidic conditions even under pH as high as 5 to deliver the drug as demonstrated by HPLC analysis and confirmed by FTIR and (13) C NMR spectroscopic studies. Such functional BS are promising materials as carriers to avoid the side effects of the anticancer drug 5-FU thanks to a controlled and targeted drug delivery. PMID:23929826

  18. Dynamical Interactions of 5-Fluorouracil Drug with Dendritic Peptide Vectors: The Impact of Dendrimer Generation, Charge, Counterions, and Structured Water.

    Science.gov (United States)

    De Luca, Sergio; Seal, Prasenjit; Ouyang, Defang; Parekh, Harendra S; Kannam, Sridhar Kumar; Smith, Sean C

    2016-06-30

    Molecular dynamics simulations are utilized to investigate the interactions between the skin cancer drug 5-fluorouracil (5FU) and peptide-based dendritic carrier systems. We find that these drug-carrier interactions do not conform to the traditional picture of long-time retention of the drug within a hydrophobic core of the dendrimer carrier. Rather, 5FU, which is moderately soluble in its own right, experiences weak, transient chattering interactions all over the dendrimer, mediated through multiple short-lived hydrogen bonding and close contact events. We find that charge on the periphery of the dendrimer actually has a negative effect on the frequency of drug-carrier interactions due to a counterion screening effect that has not previously been observed. However, charge is nevertheless an important feature since neutral dendrimers are shown to have a significant mutual attraction that can lead to clustering or agglomeration. This clustering is prevented due to charge repulsion for the titrated dendrimers, such that they remain independent in solution. PMID:27267604

  19. Risk associated with renal toxicity and hyponatremia in patients with esophageal cancer receiving chemoradiotherapy, including 5-fluorouracil and platinum

    International Nuclear Information System (INIS)

    The purpose of this study was to analyze the risk factors for renal toxicity and hyponatremia after primary chemoradiotherapy (CRT), including 5-fluorouracil and platinum in 87 (78 male, 9 female; median age 63.5 years) patients with esophageal cancer, and to prepare a risk classes. The rate of renal toxicity and hyponatremia were 12.6%, 87.4%, respectively. At multivariate analysis, risk factors for renal toxicity were baseline nausea/vomiting and serum creatinine, and for hyponatremia were baseline sodium and C-reactive protein (P<0.05). The toxicity index (TI) consisted of risk factors and regression coefficient. We were stratified patients into three groups according to TI that was calculated for each patient. The group with high value was found to include patients with renal toxicity and hyponatremia with a significantly higher frequency than the group with low value (renal toxicity; 3.4% vs 46.2%, hyponatremia; 2.1% vs 80.0%, P<0.001). This risk classes could be useful to identify patients at high risk for CRT-induced renal toxicity and hyponatremia. (author)

  20. Hyperfractionated Radiotherapy with Concurrent Cisplatin/5-Fluorouracil for Locoregional Advanced Head and Neck Cancer: Analysis of 105 Consecutive Patients

    Directory of Open Access Journals (Sweden)

    David Zaboli

    2012-01-01

    Full Text Available Objective. We reviewed a cohort of patients with previously untreated locoregional advanced head and neck squamous cell carcinoma (HNSCC who received a uniform chemoradiotherapy regimen. Methods. Retrospective review was performed of 105 patients with stage III or IV HNSCC treated at Greater Baltimore Medical Center from 2000 to 2007. Radiation included 125 cGy twice daily for a total 70 Gy to the primary site. Chemotherapy consisted of cisplatin (12 mg/m2/h daily for five days and 5-fluorouracil (600 mg/m2/20 h daily for five days, given with weeks one and six of radiation. All but seven patients with N2 or greater disease received planned neck dissection after chemoradiotherapy. Primary outcomes were overall survival (OS, locoregional control (LRC, and disease-free survival (DFS. Results. Median followup of surviving patients was 57.6 months. Five-year OS was 60%, LRC was 68%, and DFS was 56%. Predictors of increased mortality included age ≥55, female gender, hypopharyngeal primary, and T3/T4 stage. Twelve patients developed locoregional recurrences, and 16 patients developed distant metastases. Eighteen second primary malignancies were diagnosed in 17 patients. Conclusions. The CRT regimen resulted in favorable outcomes. However, locoregional and distant recurrences cause significant mortality and highlight the need for more effective therapies to prevent and manage these events.

  1. Hyperfractionated Radiotherapy with Concurrent Cisplatin/5-Fluorouracil for Locoregional Advanced Head and Neck Cancer: Analysis of 105 Consecutive Patients

    Science.gov (United States)

    Zaboli, David; Tan, Marietta; Gogineni, Hrishikesh; Lake, Spencer; Fan, Katherine; Zahurak, Marianna L.; Messing, Barbara; Ulmer, Karen; Zinreich, Eva S.; Levine, Marshall A.; Tang, Mei; Pai, Sara I.; Blanco, Ray G.; Saunders, John R.; Best, Simon R.; Califano, Joseph A.; Ha, Patrick K.

    2012-01-01

    Objective. We reviewed a cohort of patients with previously untreated locoregional advanced head and neck squamous cell carcinoma (HNSCC) who received a uniform chemoradiotherapy regimen. Methods. Retrospective review was performed of 105 patients with stage III or IV HNSCC treated at Greater Baltimore Medical Center from 2000 to 2007. Radiation included 125 cGy twice daily for a total 70 Gy to the primary site. Chemotherapy consisted of cisplatin (12 mg/m2/h) daily for five days and 5-fluorouracil (600 mg/m2/20 h) daily for five days, given with weeks one and six of radiation. All but seven patients with N2 or greater disease received planned neck dissection after chemoradiotherapy. Primary outcomes were overall survival (OS), locoregional control (LRC), and disease-free survival (DFS). Results. Median followup of surviving patients was 57.6 months. Five-year OS was 60%, LRC was 68%, and DFS was 56%. Predictors of increased mortality included age ≥55, female gender, hypopharyngeal primary, and T3/T4 stage. Twelve patients developed locoregional recurrences, and 16 patients developed distant metastases. Eighteen second primary malignancies were diagnosed in 17 patients. Conclusions. The CRT regimen resulted in favorable outcomes. However, locoregional and distant recurrences cause significant mortality and highlight the need for more effective therapies to prevent and manage these events. PMID:22778748

  2. MEK5/ERK5 signaling inhibition increases colon cancer cell sensitivity to 5-fluorouracil through a p53-dependent mechanism

    Science.gov (United States)

    Pereira, Diane M.; Simões, André E. S.; Gomes, Sofia E.; Castro, Rui E.; Carvalho, Tânia; Rodrigues, Cecília M. P.; Borralho, Pedro M.

    2016-01-01

    The MEK5/ERK5 signaling pathway is emerging as an important contributor to colon cancer onset, progression and metastasis; however, its relevance to chemotherapy resistance remains unknown. Here, we evaluated the impact of the MEK5/ERK5 cascade in colon cancer cell sensitivity to 5-fluorouracil (5-FU). Increased ERK5 expression was correlated with poor overall survival in colon cancer patients. In colon cancer cells, 5-FU exposure impaired endogenous KRAS/MEK5/ERK5 expression and/or activation. In turn, MEK5 constitutive activation reduced 5-FU-induced cytotoxicity. Using genetic and pharmacological approaches, we showed that ERK5 inhibition increased caspase-3/7 activity and apoptosis following 5-FU exposure. Mechanistically, this was further associated with increased p53 transcriptional activation of p21 and PUMA. In addition, ERK5 inhibition increased the response of HCT116 p53+/+ cells to 5-FU, but failed to sensitize HCT116 p53−/− cells to the cytotoxic effects of this chemotherapeutic agent, suggesting a p53-dependent axis mediating 5-FU sensitization. Finally, ERK5 inhibition using XMD8-92 was shown to increase the antitumor effects of 5-FU in a murine subcutaneous xenograft model, enhancing apoptosis while markedly reducing tumor growth. Collectively, our results suggest that ERK5-targeted in hibition provides a promising therapeutic approach to overcome resistance to 5-FU-based chemotherapy and improve colon cancer treatment. PMID:27144434

  3. 5-Fluorouracil Encapsulated Chitosan Nanoparticles for pH-Stimulated Drug Delivery: Evaluation of Controlled Release Kinetics

    Directory of Open Access Journals (Sweden)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  5. Anticancer activity of an extract from needles and twigs of Taxus cuspidata and its synergistic effect as a cocktail with 5-fluorouracil

    Directory of Open Access Journals (Sweden)

    Shang Weihu

    2011-12-01

    Full Text Available Abstract Background Botanical medicines are increasingly combined with chemotherapeutics as anticancer drug cocktails. This study aimed to assess the chemotherapeutic potential of an extract of Taxus cuspidata (TC needles and twigs produced by artificial cuttage and its co-effects as a cocktail with 5-fluorouracil (5-FU. Methods Components of TC extract were identified by HPLC fingerprinting. Cytotoxicity analysis was performed by MTT assay or ATP assay. Apoptosis studies were analyzed by H & E, PI, TUNEL staining, as well as Annexin V/PI assay. Cell cycle analysis was performed by flow cytometry. 5-FU concentrations in rat plasma were determined by HPLC and the pharmacokinetic parameters were estimated using 3p87 software. Synergistic efficacy was subjected to median effect analysis with the mutually nonexclusive model using Calcusyn1 software. The significance of differences between values was estimated by using a one-way ANOVA. Results TC extract reached inhibition rates of 70-90% in different human cancer cell lines (HL-60, BGC-823, KB, Bel-7402, and HeLa but only 5-7% in normal mouse T/B lymphocytes, demonstrating the broad-spectrum anticancer activity and low toxicity to normal cells of TC extract in vitro. TC extract inhibited cancer cell growth by inducing apoptosis and G2/M cell cycle arrest. Most interestingly, TC extract and 5-FU, combined as a cocktail, synergistically inhibited the growth of cancer cells in vitro, with Combination Index values (CI ranging from 0.90 to 0.26 at different effect levels from IC50 to IC90 in MCF-7 cells, CI ranging from 0.93 to 0.13 for IC40 to IC90 in PC-3M-1E8 cells, and CI TC extract did not affect the pharmacokinetics of 5-FU in rats. Conclusions The combinational use of the TC extract with 5-FU displays strong cytotoxic synergy in cancer cells and low cytotoxicity in normal cells. These findings suggest that this cocktail may have a potential role in cancer treatment.

  6. Population pharmacokinetics of oxaliplatin (85 mg/m2) in combination with 5-fluorouracil in patients with advanced colorectal cancer.

    Science.gov (United States)

    Kho, Yuhan; Jansman, Frank G A; Prins, Nicolaas H; Neef, Cees; Brouwers, Jacobus R B J

    2006-04-01

    Pharmacokinetic (PK) studies of oxaliplatin, using a dose regimen of 85 mg/m, are lacking. A PK model may be used in future studies to investigate the relationship between pharmacokinetics and dose limiting toxicity. The purpose of this study was to construct a population PK model to describe platinum (Pt) concentrations in plasma in 33 patients with colorectal cancer. The secondary objective was to determine the relationship between the amount of Pt in 24-hour urine and the amount of Pt in fractionated urine collection periods. Plasma and urine samples were collected from patients during their first oxaliplatin treatment course. Population PK analysis was performed with WinNonMix. The model that best described the Pt concentrations in plasma was a two-compartment PK model. The elimination clearance (CL) and the elimination clearance of the peripheral compartment (CL2) (median +/- SE) were 25.2 +/- 6.3 L/hr and 68 +/- 24.8 L/hr, respectively. The median volume of distribution (V1) was determined to be 41.6 +/- 9.4 L and the median volume of distribution of the peripheral compartment (V2) was 452.5 +/- 96.4 L. The relationship between the cumulative amount of Pt in urine in the first 12 hours compared with the amount of Pt in 24 hours urine was reflected by a correlation coefficient (r2) of 0.95. The cumulative Pt concentration in urine in the first 10 hours and the first 8 hours compared with 24 hours was reflected by correlation coefficients r2 = 0.93 and r2 = 0.897, respectively. This PK model could be useful in identifying predictors for PK and pharmacodynamic variability to individualize dosing. The results of this study suggest that fractionated urine samples can replace 24-hour urine collection. PMID:16628132

  7. Low molecular weight procyanidins from grape seeds enhance the impact of 5-Fluorouracil chemotherapy on Caco-2 human colon cancer cells.

    Directory of Open Access Journals (Sweden)

    Ker Y Cheah

    Full Text Available OBJECTIVE: Grape seed procyanidins (PC are flavan-3-ol oligomers and polymers known for their biological activity in the gut. Grape seed extract (GSE have been reported to reduce intestinal injury in a rat model of mucositis. We sought to investigate effects of purified PC fractions differing in mean degree of polymerization (mDP combined with 5-Fluorouracil (5-FU chemotherapy on the viability of colon cancer cells (Caco-2. DESIGN: SixPC fractions (F1-F6 were isolated from Cabernet Sauvignon seeds at two ripeness stages: pre-veraison unripe (immature and ripe (mature, utilizing step gradient, low-pressure chromatography on a Sephadex LH-20 resin. Fractions were tested on Caco-2 cells, alone and in combination with 5-FU. Eluted fractions were characterized by phloroglucinolysis and gel permeation chromatography. Cell viability was determined by the 3-(4,5-Dimethylthiazol-2yl-2,5-diphenyl-tetrazolium bromide (MTT assay. RESULTS: All isolated fractions significantly reduced Caco-2 cell viability compared to the control (P<0.05, but F2 and F3 (mDP 2-6 were the most active fractions (immature F2 = 32% mDP 2.4, F3 = 35% mDP 5.8 and mature F2 = 13% mDP 3.6 and F3 = 17% mDP 5.9; percentage of viable cells remaining on Caco-2 cells. When combined with 5-FU, immature fractions F1-F3 enhanced the cell toxicity effects of 5-FU by 27-73% (P<0.05. Mature seed PC fractions (F1-F4 significantly enhanced the toxicity of 5-FU by 60-83% against Caco-2 cells (P<0.05. Moreover, some fractions alone were more potent at decreasing viability in Caco-2 cells (P<0.05; immature fractions = 65-68% and mature fractions = 83-87% compared to 5-FU alone (37%. CONCLUSIONS: PCs of mDP 2-6 (immature F1-F3 and mature F1 and F4not only enhanced the impact of 5-FU in killing Caco-2 cells, but also surpassed standard 5-FU chemotherapy as an anti-cancer agent.The bioactivity of PC is therefore attributed primarily to lower molecular weight PCs.

  8. TPF (Paclitaxel, Cisplatin, 5-fluorouracil) 療法を施行した進行性陰茎癌の1例

    OpenAIRE

    高本, 大路; 春日, 純; 湯村, 寧; 小泉, 充之; 花井, 孝宏; 石田, 寛明; 服部, 裕介; 寺西, 淳一; 三好, 康秀; 近藤, 慶一; 野口, 和美

    2014-01-01

    54-year-old male was introduced to our hospital in January 2012 for surgical treatment and chemotherapy. The pathological examination revealed well differentiated squamous cell carcinoma of the penis. Computed tomography and magnetic resonance imaging indicated right inguinal and pelvic lymphadenopathy. We diagnosed the tumor to be unresectable radically and administered paclitaxel, cisplatin and 5-fluorouracil (TPF) as neoadjuvant chemotherapy. After 3 courses of chemotherapy, the size of ly...

  9. Tolerance and toxicity of neoadjuvant docetaxel, cisplatin and 5 fluorouracil regimen in technically unresectable oral cancer in resource limited rural based tertiary cancer center

    OpenAIRE

    V M Patil; Chakraborty, S; P K Shenoy; A Manuprasad; Sajith Babu, T. P.; T Shivkumar; Babu, S.; A Bhatterjee; S Balasubramanian

    2014-01-01

    Background: Recent studies indicate neoadjuvant chemotherapy (NACT) can result in R0 resection in a substantial proportion of patients with technically unresectable oral cavity cancers. However, data regarding the efficacy and safety of docetaxel, cisplatin and 5 fluorouracil (TPF) NACT in our setting is lacking. The present audit was proposed to evaluate the toxicities encountered during administration of this regimen. It was hypothesized that TPF NACT would be considered feasible for routin...

  10. Loss of Runt-related transcription factor 3 induces resistance to 5-fluorouracil and cisplatin in hepatocellular carcinoma.

    Science.gov (United States)

    Kataoka, Junro; Shiraha, Hidenori; Horiguchi, Shigeru; Sawahara, Hiroaki; Uchida, Daisuke; Nagahara, Teruya; Iwamuro, Masaya; Morimoto, Hiroki; Takeuchi, Yasuto; Kuwaki, Kenji; Onishi, Hideki; Nakamura, Shinichiro; Takaki, Akinobu; Nouso, Kazuhiro; Yagi, Takahito; Yamamoto, Kazuhide; Okada, Hiroyuki

    2016-05-01

    Runt-related transcription factor 3 (RUNX3) is known to function as a tumor suppressor in gastric cancer and other types of cancers, including hepatocellular carcinoma (HCC). However, its role has not been fully elucidated. In the present study, we aimed to evaluate the role of RUNX3 in HCC. We used the human HCC cell lines Hep3B, Huh7 and HLF; RUNX3 cDNA was introduced into Hep3B and Huh7 cells, which were negative for endogenous RUNX3 expression, and RUNX3 siRNA was transfected into HLF cells, which were positive for endogenous RUNX3. We analyzed the expression of RUNX3 and multidrug resistance-associated protein (MRP) by immunoblotting. MTT assays were used to determine the effects of RUNX3 expression on 5-fluorouracil (5-FU) and cisplatin (CDDP) sensitivity. Finally, 23 HCC specimens resected from patients with HCC at Okayama University Hospital were analyzed, and correlations among immunohistochemical expression of RUNX3 protein and MRP protein were evaluated in these specimens. Exogenous RUNX3 expression reduced the expression of MRP1, MRP2, MRP3 and MRP5 in the RUNX3-negative cells, whereas knockdown of RUNX3 in the HLF cells stimulated the expression of these MRPs. An inverse correlation between RUNX3 and MRP expression was observed in the HCC tissues. Importantly, loss of RUNX3 expression contributed to 5-FU and CDDP resistance by inducing MRP expression. These data have important implications in the study of chemotherapy resistance in HCC. PMID:26985715

  11. miR-139-5p sensitizes colorectal cancer cells to 5-fluorouracil by targeting NOTCH-1.

    Science.gov (United States)

    Liu, Heyong; Yin, Yuan; Hu, Yaling; Feng, Yuyang; Bian, Zehua; Yao, Surui; Li, Min; You, Qingjun; Huang, Zhaohui

    2016-07-01

    Multidrug resistance (MDR), a phenomenon that often occurs with drug treatment and is characterized by relapse or attenuation of drug efficacy, is almost unavoidable in colorectal cancer (CRC) patients receiving 5-fluorouracil (5-FU)-based chemotherapy. MicroRNAs (miRNAs) are small noncoding RNAs that post-transcriptionally regulate gene expression. Our previous study has identified miR-139-5p as a potential tumor suppressor in CRC, but its role in chemoresistance of CRC has not been elucidated. In this study, we demonstrated that miR-139-5p was down-regulated either in CRC tumors receiving chemotherapy or in 5-FU-resistant CRC cell lines (HCT-8/5-FU and HCT-116/5-FU). Ectopic expression of miR-139-5p sensitized CRC cells to 5-FU by increasing 5-FU-induced apoptosis. In addition, miR-139-5p inhibited the expression of the miR-139-5p target gene NOTCH-1 and its downstream molecules MRP-1 and BCL-2, two key MDR-associated genes. Furthermore, silencing NOTCH-1 expression promoted the chemotherapeutic effects of 5-FU, and up-regulation of NOTCH-1 abrogated miR-139-5p-mediated sensitization to 5-FU in LoVo and HCT-116 cells. Taken together, our data indicate a new role of miR-139-5p/NOTCH-1 pathway in the drug resistance of CRC cells to 5-FU, which may be a promising therapeutic target for the anti-MDR treatment of CRC. PMID:27173050

  12. In vitro cytotoxicity and genotoxicity studies of gold nanoparticles-mediated photo-thermal therapy versus 5-fluorouracil

    International Nuclear Information System (INIS)

    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/cm2, 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

  13. Neuroprotective effects of intravenous transplantation of bone marrow mononuclear cells from 5-fluorouracil pre-treated rats on ischemic stroke.

    Science.gov (United States)

    Li, Y; Mao, W W; Zhang, C G; Wan, L; Jing, C H; Hua, X M; Li, S T; Cheng, J

    2016-03-15

    Our previous findings showed bone marrow mononuclear cells (BMMNCs) from 5- fluorouracil (5-FU) pre-treated rats (named BMRMNCs) had a better therapeutic efficacy in ischemia/reperfusion rats as compared to BMMNCs from untreated rats. This study was undertaken to explore the potential mechanisms underlying the neuroprotective effects of BMRMNCs in middle cerebral artery occlusion (MCAO) rat model. Rats were intravenously pre-treated with 5-FU and BMRMNCs were collected at different time points. The contents of growth factors in the supernatant and CXCR4 expression were detected by ELISA and flow cytometry, respectively. MCAO was introduced to rats, and BMMNCs and BMRMNCs collected at 7 days after 5-FU pre-treatment were independently transplanted via the tail vein 24h later. The neurological function was evaluated before cell transplantation and at 24h, 7d and 14d after cell transplantation. Rats were sacrificed at 14d after cell transplantation, the brains were collected for TTC staining, infarct volume detection, NISSL staining, counting of viable cells in the CA1 region, and observation of transplanted cells. BMRMNCs had elevated expressions of growth factors as well as CXCR4 expression. Our results confirmed the better therapeutic effects of BMRMNCs in MCAO rats, demonstrated by reduction in infarct volume, improvement of neurological function and more viable cells in the hippocampus. In addition, more transplanted cells were found after BMRMNCs transplantation at 7 days and 14 days although there was no marked difference at 14 days. These findings indicate that BMRMNCs transplantation may protect ischemic stroke, at least partially, via increasing the secretion of growth factors and migration to the injured site.

  14. Biomechanical and Macroscopic Evaluations of the Effects of 5-Fluorouracil on Partially Divided Flexor Tendon Injuries in Rabbits

    Institute of Scientific and Technical Information of China (English)

    Shkelzen B Duci; Hysni M Arifi; Hasan R Ahmeti; Suzana Manxhuka-Kerliu; Burim Neziri; Agon Y Mekaj; Shpetim Lajqi

    2015-01-01

    Background:The main goals of flexor tendon surgery are to restore digital motion by providing tendon healing and to preserve tendon gliding.Our purpose was to investigate the effects of 5-fluorouracil (5-FU) on tendon adhesions in partially divided profundus flexor tendons (flexor digitorum profundus [FDPs]) following surgical repair and in partially divided FDPs without surgical repair,and to compare the results of the repair versus the nonrepair of zone two injuries via macroscopic and biomechanical evaluations of tendon adhesions.Methods:We used 32 adult male European rabbits (Oryctolagus cunniculus) weighing from 2.5 to 3.5 kg.The study was performed on the deep flexor tendons of the second and third digits of the right hind paws of the rabbits;thus,a total of 64 tendons were examined in this study.Results:Based on the results achieved in our experimental study,the load (N) significantly increased in subgroup 1a in which the tendons were surgically repaired and were not treated with 5-FU compared with subgroup 2a in which tendons were surgically repaired and treated with 5-FU.Conclusions:The load (N) significantly increased in subgroup 1 a in which the tendons were surgically repaired and were not treated with 5-FU compared to subgroup 2a in which the tendons were surgically repaired and treated with 5-FU.Therefore,these results revealed a decrease in adhesion formation in the subgroup that was treated with 5-FU due to increased resistance to tendon adhesions during their excursion through the tendon sheath,which in this case required greater traction force.

  15. Does radiation prevent 5-fluorouracil-induced colitis in the early phase of radiochemotherapy? A case report and literature review

    International Nuclear Information System (INIS)

    Case Report: A 43-year-old man with T3 N2 M0 adenocarcinoma of the lower rectum was admitted for preoperative radiochemotherapy (RCT). Daily fractions of 1.8 Gy (planned total dose: 50.4 Gy) and concomitant chemotherapy consisting of 5-fluorouracil (5-FU), leucovorin, and mitomycin C (MMC) were administered. On day 10, the patient developed abdominal pain and massive diarrhea. Computed tomography, endoscopy, histopathologic and serologic tests revealed severe colitis confined to the upper abdomen and most probably related to 5-FU. Unexpectedly, the bowel inflammation was restricted to areas not irradiated. 4 months later, during the course of disease, relapse with pulmonary metastases occurred. A palliative chemotherapy with 5-FU, oxaliplatin, and leucovorin was started. Again, the patient suffered from severe diarrhea and dose reduction was necessary. Discussion: It was speculated that in the early phase of RCT the well-known anti-inflammatory nature of low-dose radiation prevented exacerbation of colitis. To the authors' knowledge, this observation has not been published before. With respect to the current literature and the clinical findings it is discussed that both increased leukocyte/endothelial cell adhesion and altered release of reactive oxygen species or inducible nitric oxide synthase (iNOS) may play a role in 5-FU-induced colitis. Conclusion: This observation led to the hypothesis that the anti-inflammatory effect of low-dose irradiation may attenuate 5-FU-induced colitis in the very early phase of RCT. It appears worthwhile to separate side effects of RCT into radiation- and chemotherapy-induced effects, which requires a detailed diagnostic work-up. This differentiation has an impact on planning individual therapy: the authors did not saw conclusive evidence of an increased radiosensitivity but chemosensitivity in their patient and therefore continued radiotherapy. This assumption was confirmed when the patient received palliative 5-FU

  16. Efficacy of Adjuvant 5-Fluorouracil Therapy for Patients with EMAST-Positive Stage II/III Colorectal Cancer

    Science.gov (United States)

    Hamaya, Yasushi; Guarinos, Carla; Tseng-Rogenski, Stephanie S.; Iwaizumi, Moriya; Das, Ritabrata; Jover, Rodrigo; Castells, Antoni; Llor, Xavier; Andreu, Montserrat; Carethers, John M.

    2015-01-01

    Elevated Microsatellite Alterations at Selected Tetranucleotide repeats (EMAST) is a genetic signature found in up to 60% of colorectal cancers (CRCs) that is caused by somatic dysfunction of the DNA mismatch repair (MMR) protein hMSH3. We have previously shown in vitro that recognition of 5-fluorouracil (5-FU) within DNA and subsequent cytotoxicity was most effective when both hMutSα (hMSH2-hMSH6 heterodimer) and hMutSβ (hMSH2-hMSH3 heterodimer) MMR complexes were present, compared to hMutSα > hMutSβ alone. We tested if patients with EMAST CRCs (hMutSβ defective) had diminished response to adjuvant 5-FU chemotherapy, paralleling in vitro findings. We analyzed 230 patients with stage II/III sporadic colorectal cancers for which we had 5-FU treatment and survival data. Archival DNA was analyzed for EMAST (>2 of 5 markers mutated among UT5037, D8S321, D9S242, D20S82, D20S85 tetranucleotide loci). Kaplan-Meier survival curves were generated and multivariate analysis was used to determine contribution to risk. We identified 102 (44%) EMAST cancers. Ninety-four patients (41%) received adjuvant 5-FU chemotherapy, and median follow-up for all patients was 51 months. Patients with EMAST CRCs demonstrated improved survival with adjuvant 5FU to the same extent as patients with non-EMAST CRCs (P<0.05). We observed no difference in survival between patients with stage II/III EMAST and non-EMAST cancers (P = 0.36). There is improved survival for stage II/III CRC patients after adjuvant 5-FU-based chemotherapy regardless of EMAST status. The loss of contribution of hMSH3 for 5-FU cytotoxicity may not adversely affect patient outcome, contrasting patients whose tumors completely lack DNA MMR function (MSI-H). PMID:25996601

  17. A nanomedicine-promising approach to provide an appropriate colon-targeted drug delivery system for 5-fluorouracil.

    Science.gov (United States)

    Singh, Sima; Kotla, Niranjan G; Tomar, Sonia; Maddiboyina, Balaji; Webster, Thomas J; Sharma, Dinesh; Sunnapu, Omprakash

    2015-01-01

    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 indicated that the maximum release occurs at pH 7.2 and 7.4 with 93% of the drug released in the presence of 4% (w/v) of rat cecal content. In vivo results conclude a practical mechanism to maintain the integrity and intactness of the intestinal/colonic microflora, in the face of a "chemical attack" by oral colon-targeted drug delivery for colon cancer treatment. PMID:26648721

  18. In vitro cytotoxicity and genotoxicity studies of gold nanoparticles-mediated photo-thermal therapy versus 5-fluorouracil

    Energy Technology Data Exchange (ETDEWEB)

    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.

  19. Does radiation prevent 5-fluorouracil-induced colitis in the early phase of radiochemotherapy? A case report and literature review

    Energy Technology Data Exchange (ETDEWEB)

    Rischke, H.C.; Momm, F.; Henke, M.; Frommhold, H. [University Hospital Freiburg (Germany). Dept. of Radiotherapy; Wiech, T. [University Hospital Freiburg (Germany). Dept. of General Pathology and Pathologic Anatomy

    2007-08-15

    Case Report: A 43-year-old man with T3 N2 M0 adenocarcinoma of the lower rectum was admitted for preoperative radiochemotherapy (RCT). Daily fractions of 1.8 Gy (planned total dose: 50.4 Gy) and concomitant chemotherapy consisting of 5-fluorouracil (5-FU), leucovorin, and mitomycin C (MMC) were administered. On day 10, the patient developed abdominal pain and massive diarrhea. Computed tomography, endoscopy, histopathologic and serologic tests revealed severe colitis confined to the upper abdomen and most probably related to 5-FU. Unexpectedly, the bowel inflammation was restricted to areas not irradiated. 4 months later, during the course of disease, relapse with pulmonary metastases occurred. A palliative chemotherapy with 5-FU, oxaliplatin, and leucovorin was started. Again, the patient suffered from severe diarrhea and dose reduction was necessary. Discussion: It was speculated that in the early phase of RCT the well-known anti-inflammatory nature of low-dose radiation prevented exacerbation of colitis. To the authors' knowledge, this observation has not been published before. With respect to the current literature and the clinical findings it is discussed that both increased leukocyte/endothelial cell adhesion and altered release of reactive oxygen species or inducible nitric oxide synthase (iNOS) may play a role in 5-FU-induced colitis. Conclusion: This observation led to the hypothesis that the anti-inflammatory effect of low-dose irradiation may attenuate 5-FU-induced colitis in the very early phase of RCT. It appears worthwhile to separate side effects of RCT into radiation- and chemotherapy-induced effects, which requires a detailed diagnostic work-up. This differentiation has an impact on planning individual therapy: the authors did not saw conclusive evidence of an increased radiosensitivity but chemosensitivity in their patient and therefore continued radiotherapy. This assumption was confirmed when the patient received palliative 5-FU

  20. Hyperoxia increases the uptake of 5-fluorouracil in mammary tumors independently of changes in interstitial fluid pressure and tumor stroma

    Directory of Open Access Journals (Sweden)

    Salvesen Gerd S

    2009-12-01

    Full Text Available Abstract Background Hypoxia is associated with increased resistance to chemo- and radiation-therapy. Hyperoxic treatment (hyperbaric oxygen has previously been shown to potentiate the effect of some forms of chemotherapy, and this has been ascribed to enhanced cytotoxicity or neovascularisation. The aim of this study was to elucidate whether hyperoxia also enhances any actual uptake of 5FU (5-fluorouracil into the tumor tissue and if this can be explained by changes in the interstitium and extracellular matrix. Methods One group of tumor bearing rats was exposed to repeated hyperbaric oxygen (HBO treatment (2 bar, pO2 = 2 bar, 4 exposures à 90 min, whereas one group was exposed to one single identical HBO treatment. Animals housed under normal atmosphere (1 bar, pO2 = 0.2 bar served as controls. Three doses of 5FU were tested for dose response. Uptake of [3H]-5FU in the tumor was assessed, with special reference to factors that might have contributed, such as interstitial fluid pressure (Pif, collagen content, oxygen stress (measured as malondialdehyd levels, lymphatics and transcapillary transport in the tumors. Results The uptake of the cytostatic agent increases immediately after a single HBO treatment (more than 50%, but not 24 hours after the last repeated HBO treatment. Thus, the uptake is most likely related to the transient increase in oxygenation in the tumor tissue. Factors like tumor Pif and collagen content, which decreased significantly in the tumor interstitium after repeated HBO treatment, was without effect on the drug uptake. Conclusion We showed that hyperoxia increases the uptake of [3H]-5FU in DMBA-induced mammary tumors per se, independently of changes in Pif, oxygen stress, collagen fibril density, or transendothelial transport alone. The mechanism by which such an uptake occur is still not elucidated, but it is clearly stimulated by elevated pO2.

  1. Bcl-XL Small Interfering RNA Enhances Sensitivity of Hepg2 Hepatocellular Carcinoma Cells to 5-Fluorouracil and Hydroxycamptothecin

    Institute of Scientific and Technical Information of China (English)

    Xiao-Yong LEI; Miao ZHONG; Lan-Fang FENG; Bing-Yang ZHU; Sheng-Song TANG; Duan-Fang LIAO

    2006-01-01

    Changes in drug sensitivity in Bcl-XL small interfering RNA (siRNA) transfected Hepg2 hepatocellular carcinoma cells were investigated in this study. Bcl-XL siRNA and negative siRNA expression vector were constructed and stably transfected into Hepg2 cells. Reverse transcription (RT)-PCR, western blot and immunofluorescence were used to detect the target gene expression at mRNA and protein levels.Drug sensitivity of the cells to 5-fluorouracil (5-FU) and hydroxycamptothecin (HCPT) were evaluated with MTT. The Bcl-XL mRNA and protein expression levels in Bcl-XL siRNA transfectants were reduced compared with negative siRNA transfectants or mock cells. MTT results showed that Bcl-XL siRNA transfected cells have a higher cell inhibition rate than negative vector transfected cells or untreated cells after treatment with 13, 130, 1300 and 13,000 mg/L of 5-FU. Bcl-XL siRNA transfected cells also showed increased drug-sensitivity compared with negative vector transfected cells or untreated cells after treatment with 0.18, 0.36, 0.72 and 1.44 mg/L HCPT. Flow cytometry (FCM) results demonstrated that the sub-G1 population increased in the Bcl-XL siRNA group, compared with the negative siRNA group and untreated control group, after the addition of 5-FU (1300 mg/L) and HCPT (0.72 mg/L). siRNA targeting Bcl-XL gene can specifically down-regulate Bcl-XL expression in Hepg2 cells, and can increase spontaneous cell apoptosis and sensitize cells to 5-FU or HCPT.

  2. Phase I Trial of Escalating-dose Cisplatin with 5-fluorouracil and Concurrent Radiotherapy in Chinese Patients with Esophageal Cancer

    Directory of Open Access Journals (Sweden)

    Zhao,Yan-Nan

    2008-02-01

    Full Text Available We defined the maximum-tolerated dose (MTD of chemoradiotherapy (cisplatin (CDDP with 5-fluorouracil (5-FU and concurrent chemoradiotherapy for Chinese patients with esophageal cancer. Twenty-one previously untreated patients with primary esophageal cancer were entered into this study. Escalating doses of CDDP with 5-FU were administered in a modified Fibonacci sequence, with concurrent conventional fractionation radiotherapy (CFR of 60 Gy or 50 Gy. The starting doses were CDDP 37.5 mg/m2 on day 1, and 5-FU 500 mg/m2 on days 1-5, respectively. The regimen was repeated 4 times every 28 days. If no dose-limiting toxicity (DLT was observed, the next dose level was applied. The procedures were repeated until DLT appeared. The MTD was declared to be 1 dose level below the level at which DLT appeared. DLT was grade 3 radiation-induced esophagitis at a dose level of CDDP 60 mg/m2 with 5-FU 700 mg/m2 and concurrent 60 Gy CFR. MTD was defined as CDDP 52.5 mg/m2 with 5-FU 700 mg/m2 and concurrent 50 Gy CFR. The MTD of CDDP with 5-FU and in concurrent chemoradiotherapy for Chinese patients with esophageal cancer is CDDP 52.5 mg/m2 on day 1 and 5FU 700 mg/m2 on days 1-5, repeated 4 times every 28 days, and concurrent 50 Gy CFR. Further evaluation of this regimen in a prospective phase II trial is ongoing.

  3. A Bmi1-miRNAs cross-talk modulates chemotherapy response to 5-fluorouracil in breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Jiang Yin

    Full Text Available The polycomb group transcriptional modifier Bmi1 is often upregulated in numerous cancers and is intensely involved in normal and cancer stem cells, and importantly is as a prognostic indicator for some cancers, but its role in breast cancer remains unclear. Here, we found Bmi1 overexpression in 5-Fu (5-fluorouracil-resistant MCF-7 cells (MCF-7/5-Fu derived from MCF-7 breast cancer cells, MDA-MB-231 and MDA-MB-453 breast cancer cells compared to MCF-7 cells, was related with 5-Fu resistance and enrichment of CD44(+/CD24(- stem cell subpopulation. Bmi1 knockdown enhanced the sensitivity of breast cancer cells to 5-Fu and 5-Fu induced apoptosis via mitochondrial apoptotic pathway, and decreased the fraction of CD44(+/CD24(- subpopulation. In addition, our analysis showed inverse expression pattern between Bmi1 and miR-200c and miR-203 in selected breast cancer cell lines, and miR-200c and miR-203 directly repressed Bmi1 expression in protein level confirmed by luciferase reporter assay. MiR-200c and miR-203 overexpression in breast cancer cells downregulated Bmi1 expression accompanied with reversion of resistance to 5-Fu mediated by Bmi1. Inversely, Bmi1 overexpression inhibited miR-200c expression in MCF-7 cells, but not miR-203, however ectopic wild-type p53 expression reversed Bmi1 mediated miR-200c downregulation, suggesting the repressive effect of Bmi1 on miR-200c maybe depend on p53. Thus, our study suggests a cross-talk between Bmi1 and miR-200c mediated by p53, and Bmi1 interference would improve chemotherapy efficiency in breast cancer via susceptive apoptosis induction and cancer stem cell enrichment inhibition.

  4. No effect of 5-fluorouracil on the properties of purified. cap alpha. -amylase from barley half-seeds

    Energy Technology Data Exchange (ETDEWEB)

    Rodaway, S.J.; Kende, H.

    1978-01-01

    Amylase has been purified from de-embryonated seeds of barley (Horedeum vulgare L. cv. Betzes) which have been incubated on 10/sup 6/M gibberellic acid (GA/sub 3/) following 3 days of imbibition in buffer. Incubation of the half-seeds in up to 10/sup -2/ M 5-fluorouracil (5-FU) during the entire incubation period, including imbibition, had no effect on any of the following characteristics of purified ..cap alpha..-amylase: thermal stability in the absence of calcium, molecular weight of the enzyme, isozyme composition, specific activity, or the amount of ..cap alpha..-amylase synthesized by the aleurone tissue. The synthesis of rRNA and tRNA was strongly inhibited by 5-FU, indicating that the analog had entered the aleurone cells. These results are not in agreement with those of Carlson (Nature New Biology 237: 39-41 (1972)) who found that treatment of barley aleurone with 10/sup -4/ M 5-FU to the addition of GA/sub 3/ resulted in decreased thermal stability of GA/sub 3/-induced ..cap alpha..-amylase and who interpreted this as evidence that the mRNA for ..cap alpha..-amylase was synthesized during the imbibition of the aleurone tissue and independently of gibberellin action. Results of the present experiments indicate that the thermal stability of highly purified ..cap alpha..-amylase is not altered by treatment of barley half-seeds with 5-FU, and that 5-FU cannot be used as a probe to examine the timing of ..cap alpha..-amylase mRNA synthesis.

  5. 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

    Directory of Open Access Journals (Sweden)

    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.

  6. Studies of variation in inherent sensitivities to radiation, 5-fluorouracil and methotrexate in a series of human and murine tumor cell lines in vitro

    International Nuclear Information System (INIS)

    Clinical studies have reported reduced response rates to subsequent chemotherapy in certain tumors recurring after radiotherapy. These authors have investigated whether there are any correlations between radiation and drug responses in vitro using a range of murine and human tumor cell lines. They have compared sensitivities to X-irradiation and to 24 hr exposures to two widely used antitumor drugs, methotrexate and 5-fluorouracil. The 4 murine lines selected showed a range of radiation responses with Do values of 0.48-0.76 Gy. Methotrexate sensitivities also exhibited an 800-fold difference which appeared to correlate inversely with radiation response. Sensitivity to 5-FU was less variable in these cells and was unrelated to radiation response. In contrast, in the human lines tested, no correlations were observed between drug sensitivities and radiation response. The six lines tested showed a range of radiation responses with Do values of 0.66-1.59 Gy. Methotrexate sensitivities ranged only over a 150-fold concentration but, contrasting with data from the murine cells, no correlation with radiation response was apparent. Similarly, no correlations between response to 5-fluorouracil and radiation or 5-fluorouracil and methotrexate were noted, which is inconsistent with results using murine cells

  7. In-vitro differential metabolism and activity of 5-fluorouracil between short-term, high-dose and long-term, low-dose treatments in human squamous carcinoma cells.

    Science.gov (United States)

    Qin, Baoli; Tanaka, Risa; Ariyama, Hiroshi; Shibata, Yoshihiro; Arita, Shuji; Kusaba, Hitoshi; Baba, Eishi; Harada, Mine; Nakano, Shuji

    2006-04-01

    Although continuous infusion of 5-fluorouracil (5-FU) has been clinically demonstrated to be superior to bolus administration, the mechanistic difference between the treatments still remains unclear. Here, we investigated in vitro whether there were any differences in the metabolism and activity of 5-FU between these schedules. To simulate bolus and infusional treatments of 5-FU, HST-1 human squamous carcinoma cells were treated with short-term, high-doses and long-term, low-doses so that the area under the curve (AUC) of 5-FU became equivalent between both schedules, and compared the cytotoxicity, fluorinated RNA (F-RNA) levels, 5-fluorodeoxyuridine monophosphate (FdUMP) content and thymidylate synthase (TS) activity. F-RNA and FdUMP were measured by capillary gas chromatography-mass spectrometry and competitive ligand-binding assay, respectively. The [H]FdUMP binding site in TS was determined as an index of the amount of TS using the radio-binding assay. Long-term, low-dose treatment of 5-FU was found to be 1.3-1.7 times more cytotoxic than the short-term, high-dose treatment. F-RNA content increased as the AUC of 5-FU was increased and was 2-4 times significantly higher in the cells treated with the long-term, low-dose than those with the short-term, high-dose schedule, indicating that the levels of F-RNA are AUC and schedule dependent. In contrast, there were no significant differences in FdUMP levels, TS activity and TS inhibition rate between the schedules. These data suggest that the superior activity of 5-FU administered long-term, low-dose over short-term, high-dose could be explained by more 5-FU incorporated into RNA during a long-term, low-dose exposure, thus providing a strategic rationale for the clinical advantage of continuous infusion over bolus administration. PMID:16550002

  8. Effect of L-histidinol on the metabolism of 5-fluorouracil in the BALB/c x DBA/8 F1 murine tumor system.

    Science.gov (United States)

    Sawyer, R C; Stolfi, R L; Martin, D S

    1988-12-01

    L-Histidinol, a structural analogue of histidine, which transiently inhibits proliferation, can protect cells from the toxic effects of proliferation-dependent chemotherapeutic agents such as 5-fluorouracil (FUra). In the BALB/c x DBA/8 F1 (hereafter called CD8F1) murine tumor system, L-histidinol protected mice from FUra-induced leukopenia, weight loss, and mortality; however, the therapeutic index was not improved since L-histidinol also protected the tumor against the toxic effects of FUra. In order to understand the mechanism of this protection, we examined the effects of L-histidinol on the metabolism of FUra. Results indicate that L-histidinol had no effect on the phosphoribosyl pyrophosphate levels in tumor, the activation of FUra to nucleotides or levels of free 5-fluorodeoxyuridine monophosphate in either tumor or bone marrow. L-Histidinol (7 mg/mouse, every 2 h for 5 doses) reduced RNA and DNA synthesis, as measured by 32P incorporation in vivo, by approximately one-half in tumor, and by 70% in bone marrow. This in turn resulted in reduced incorporation of FUra into RNA in both tumor and bone marrow. At 2 h, 4 h, and 24 h after FUra administration the level of FUra in RNA was 24-37% less in both tumor and bone marrow of mice that received L-histidinol with FUra. Using 32P as a monitor of overall RNA synthesis, the [3H]FUra/32P ratio remained unchanged, suggesting that the reduction of FUra incorporation into RNA was due to decreased RNA synthesis rather than a decrease in the number of FUra molecules per RNA chain. In contrast, L-histidinol had no effect on the in vivo inhibition of thymidylate synthetase by 5-fluorodeoxyuridine monophosphate as measured by the incorporation of [3H]-2'-deoxyuridine into DNA or on the percentages of thymidylate synthetase in the free versus 5-fluorodeoxyuridine monophosphate-bound state. We conclude that L-histidinol reduces FUra toxicity by reducing FUra incorporation into RNA. Since the major mechanism of action in the

  9. Clinical trial of combination therapy using systemic interleukin-2 infusion and low-dose tumor irradiation for advanced hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Although recent progress in surgical techniques and interventional radiology enables patients with hepatocellular carcinoma (HCC) to survive longer, there are still many who cannot receive them due to disease progression. We are currently investigating the therapeutic efficacy of the combination of systemic recombinant interleukin-2 (IL-2) administration and local tumor irradiation for HCC patients in the advanced stage. First, the results of the basic experiment to analyze the optimal dose and timing of IL-2 infusion were demonstrated. Intensive administration of high-dose IL-2 caused acute death, whereas intermittent low-dose IL-2 administration resulted in complete tumor regression followed by the acquisition of tumor-specific immunity. Our data suggested that the tumor-bearing state increased the responsiveness to IL-2 treatment, and that an excessively high-dose regimen is not prerequisite for the optimal IL-2 treatment. With regard to the effectiveness of radiotherapy for HCC, human hepatoma cells exhibited apoptotic death when hepatoma cells were cocultured with LAK cells, or were irradiated in vitro with relatively low-dose irradiation. These results suggested the possible synergistic effect of killer cells and low-dose irradiation. Finally, we presented six eligible cases of advanced HCC treated by combination therapy of IL-2 infusion and local low-dose tumor irradiation. Direct anti-tumor effects were one CR, one MR, two NC, and two PD. One CR case and a NC case have survived now for longer than 40 months. In all cases, NK cell activity increased prominently, and side effects wee mild flu-like symptoms except macroscopic hematuria and moderate VLS-like symptoms in two cases in which therapy was continued for longer than 2 years. Hepatic reserve function like prothrombin time or hepaplastic time improved. The apparent clinical effectiveness of the combination therapy presented here might give promising hints for a new therapeutic strategy for HCC. (author)

  10. Effect of Oxyntomodulin, Glucagon, GLP-1 and Combined Glucagon +GLP-1 Infusion on Food Intake, Appetite and Resting Energy Expenditure

    DEFF Research Database (Denmark)

    Bagger, Jonatan I; Holst, Jens J; Hartmann, Bolette;

    2015-01-01

    ], and glucagon+GLP-1 688 [606, 769]). Oxygen uptake did not change significantly from baseline in response to any peptide infusion compared with saline. Conclusions: Oxyntomodulin, GLP-1, and glucagon decreased food intake but with no additional effect of combining GLP-1 and glucagon. - See more at: http......Context: The gut hormone, oxyntomodulin, is a proglucagon product with body weight-lowering potential. It binds to both the glucagon-like peptide-1 (GLP-1) receptor and the glucagon receptor; however, the mechanism behind the body weight-lowering effect remains elusive. Objective: We wanted.......86 pmol × kg−1 × min−1), oxyntomodulin (3 pmol × kg−1 × min−1), or glucagon+GLP-1 (same doses). Main Outcome Measures: We evaluated resting energy expenditure (measured as oxygen uptake, gastric emptying (GE), composite appetite scores (CAS), and food intake. Results: Oxyntomodulin, GLP-1, and GLP-1...

  11. Combined modality preoperative therapy for unresectable rectal cancer.

    Science.gov (United States)

    Percarpio, B; Bitterman, J; Sabbath, K; Alfano, F; Ruszkowski, R; Bowen, J

    1992-01-01

    Locally advanced rectal cancer has been a surgical challenge because of fixation of the primary tumor to the boney pelvis or to other pelvic soft tissues. During a 12-month period seven patients with locally advanced adenocarcinoma of the rectum were treated preoperatively with simultaneous pelvic irradiation (4500-5040 cGy) and infusion chemotherapy (5-fluorouracil 1000 mg per m2 per day over 96 hours and mitomycin 10 mg per m2. Tolerance was reasonable and all patients underwent successful resection of the primary lesion. Two patients had a complete response to preoperative combined modality therapy with no cancer found in the surgical specimen. With a short follow-up period, all patients have experienced satisfactory healing and none have suffered local or distant recurrence. The results of this limited series are encouraging for future clinical trials.

  12. 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.

  13. Associations between gene polymorphisms of thymidylate synthase with its protein expression and chemosensitivity to 5-fluorouracil in pancreatic carcinoma cells

    Institute of Scientific and Technical Information of China (English)

    ZHANG Qiang; ZHAO Yu-pei; LIAO Quan; HU Ya; XU Qiang; ZHOU Li; SHU Hong

    2011-01-01

    Background Thymidylate synthase (TS) is a key regulatory enzyme for de novo DNA synthesis.TS activity is also an important determinant of the response to chemotherapy with fluoropyrimidine prodrugs,and its expression may be affected by gene polymorphisms.In this study,we investigated the associations between polymorphisms of the TS gene and its protein expression,and the implications on the efficacy of 5-fluorouracil (5-FU) in pancreatic cancer cells.Methods Genotypes based on the 28-bp TS tandem repeat for pancreatic cell lines were determined by electrophoretic analysis of PCR products.A single nucleotide polymorphism (SNP) at nucleotide 12 of the second 28-bp repeat of the 3R allele was determined by nucleotide sequencing.The chemosensitivity of pancreatic carcinoma cells to 5-FU in vitro was evaluated using Cell Counting Kit-8 (CCK-8).TS protein expression was analyzed by Western blotting.Results Seven pancreatic carcinoma cell lines had different genotypes in terms of the 28-bp TS tandem repeat,as follows:homozygous 2R/2R (T3M4 and BxPC-3 cells),heterozygous 2R/3R (AsPC-1,Capan-1,and SU86.86),and homozygous 3R/3R (PANC-1 and COLO357).The optical density ratio of genotypes 3R/3R,2R/2R and 2R/3R was 1.393±0.374,0.568±0.032 and 0.561±0.056,respectively.Cells with the 2R/3R or 3R/3R genotypes were further analyzed for the G to C SNP at nucleotide 12 of the second 28-bp repeat of the 3R allele,yielding heterozygous 2R/3Rc (AsPC-1,Capan-1,and SU86.86),homozygous 3Rg/3Rg (COLO357) and homozygous 3Rc/3Rc (PANC-1).The optical density ratio of homozygous 3Rg/3Rg cells and homozygous 3Rc/3Rc cells was 1.723±0.062 and 1.063±0.134,respectively,and this difference was statistically significant (P <0.05).Cells with the 2R/2R and 2R/3R genotypes of TS were hypersensitive to 5-FU in vitro as compared with those with the 3R/3R cells.Conclusions Polymorphisms in the TS gene influenced its protein expression and affected sensitivity of 5-FU in seven pancreatic cancer cell

  14. Preparation of ethosomes and deformable liposomes encapsulated with 5-fluorouracil and their investigation of permeability and retention in hypertrophic scar.

    Science.gov (United States)

    Wo, Yan; Zhang, Zhen; Zhang, Yixin; Wang, Danru; Pu, Zheming; Su, Weijie; Qian, Yunliang; Li, Yunwu; Cui, Daxiang

    2011-09-01

    With the aim of comparing scar penetration efficiency and retention between ethosomes and deformable liposomes both encapsulated with 5-fluorouracil (5-FU), the 5-FU ethosomal suspensions (5-FU ES, 81.74 +/- 9.37 nm) and the 5-FU Deformable Liposomal Suspensions (5-FU DS, 73.7 +/- 9.45 nm) were prepared respectively by Touitou method and Cevc method, their sizes were determined by Particle Sizer System (PSS), and their entrapment Efficiency (EE) was detected by ultracentrifugation and microcolumn centrifugation. Their transdermal delivery experiments were done in hypertrophic scars in vitro. The permeated amount of 5-FU and retention contents of 5-FU were both calculated by High Performance Liquid Chromatography (HPLC). Fluorescence intensities of ES and DS labeled with Rodanmin 6GO (Rho) were measured by Laser Scanning Microscopy (LSM). The control groups such as the 5-FU and empty ethosomal vesicles (5-FU + EEV), the 5-FU and empty deformable liposomal vesicles (5-FU + EDV) and 5-FU PBS Solution (5-FU Sol) were set up. Results showed that, prepared 5-FU ES was 81.74 +/- 9.37 nm in size, 5-FU DS was 73.7 +/- 9.45 nm, EE of 5-FU ES was 10.95%, EE of 5-FU DS was 15.05%. Within 24 hours, in the group of 5-FU ES, the penetration amount of 5-FU in scar was 14.12 +/- 0.1 microg/mL/cm2, the retention contents of 5-FU was 10.74 +/- 1.17 microg/cm2, and the fluorescence intensity of Rho in hypertrophic scar tissues were 182 +/- 18.3; in the group of 5-FU DS: the penetration amount of 5-FU was 12.35 +/- 1.21 microg/mLcm2; the retention contents of 5-FU was 17.48 +/- 0.82 microg/cm2, and the fluorescence intensity of Rho was 241.45 +/- 7.63; there existed statistical difference between penetration amount in the group of 5-FU ES and that in the group of 5-FU DS as well as control groups (P < 0.05, P < 0.01), the penetration amount in the group of ES is markedly higher than DS group or control groups. Conversely, the retention contents of 5-FU and the fluorescence intensity of

  15. 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

    International Nuclear Information System (INIS)

    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

  16. Adjuvant continuous infusion 5-FU, whole-abdominal radiation, and tumor bed boost in high-risk stage III colon carcinoma: a southwest oncology group pilot study

    International Nuclear Information System (INIS)

    Purpose: Results of a combined modality adjuvant pilot program of low-dose continuous-infusion 5-fluorouracil, whole-abdominal radiation, and tumor bed boost in patients with colon cancer with involved nodes and serosal involvement are presented. Methods and Materials: Forty-one eligible patients with completely resected T3N1-2M0 colon cancer (modified Astler-Coller C2) were treated with 5-fluorouracil (5-FU) at a dose of 200 mg/m2/day by continuous infusion and 30 Gy of concomitant whole-abdominal radiation in 1 Gy fractions. An additional 16 Gy boost to the tumor bed was administered in 1.6 Gy fractions. After completion of combined modality treatment and a 21-day rest period, patients received 4 days of 5-FU at a dose of 1000 mg/m2 by continuous infusion every 28 days for nine cycles. Results: Five-year disease-free and overall survival estimates were 58 and 67%, respectively, for all T3N1-2 patients. Five-year disease-free and overall survival estimates for the 19 patients with four or fewer nodes were both 61%. Five-year disease-free survival and overall survival estimates for the 20 patients with more than four involved nodes were 55% and 74%, respectively (the exact number of involved nodes were unknown for two patients). Disease-free and overall survival estimates for patients treated with 5-FU and radiation compare favorably to the 5-FU plus levamisole arm of the intergroup adjuvant colon study (Int 0035/SWOG 8591) in patients with more than four positive nodes where the 5-year disease-free and overall survival estimates were 35% and 39%, respectively. Disease-free and overall survival estimates for patients with four or fewer nodes in the 5-FU plus levamisole arm of the intergroup study were 64 and 68%, which is not markedly different from results obtained with radiation and 5-FU in the current study. There were no treatment-related fatalities. Seventeen percent of patients had severe and 7% had life-threatening toxicity of any kind. One patient had an

  17. EMJH medium with 5-fluorouracil and nalidixic acid associated with serial dilution technique used to recover Leptospira spp from experimentally contaminated bovine semen Meio de EMJH com 5-fluorouracil e ácido nalidíxico associado a técnica das diluições seriadas usados para recuperar Leptospira spp do sêmen bovino experimentalmente contaminado

    OpenAIRE

    Fabiana Miraglia; Zenaide Maria Moraes; Priscilla Anne Melville; Ricardo Augusto Dias; Silvio Arruda Vasconcellos

    2009-01-01

    Bovine semen experimentally contaminated with Leptospira santarosai serovar Guaricura was submitted to the modified EMJH medium with 5-fluorouracil (300mg/L) and nalidixic acid (20mg/L), named as "selective medium" and using the serial dilution technique, in order to evaluate the percentage of recovery of the added microorganism. The selective EMJH medium was found with higher percentage of recovery of leptospiras and minor losses of samples due to contamination with opportunistic microorgani...

  18. Combined strategy of endothelial cells coating, Sertoli cells coculture and infusion improves vascularization and rejection protection of islet graft.

    Directory of Open Access Journals (Sweden)

    Yang Li

    Full Text Available Improving islet graft revascularization and inhibiting rejection become crucial tasks for prolonging islet graft survival. Endothelial cells (ECs are the basis of islet vascularization and Sertoli cells (SCs have the talent to provide nutritional support and exert immunosuppressive effects. We construct a combined strategy of ECs coating in the presence of nutritious and immune factors supplied by SCs in a co-culture system to investigate the effect of vascularization and rejection inhibition for islet graft. In vivo, the combined strategy improved the survival and vascularization as well as inhibited lymphocytes and inflammatory cytokines. In vitro, we found the combinatorial strategy improved the function of islets and the effect of ECs-coating on islets. Combined strategy treated islets revealed higher levels of anti-apoptotic signal molecules (Bcl-2 and HSP-32, survival and function related molecules (PDX-1, Ki-67, ERK1/2 and Akt and demonstrated increased vascular endothelial growth factor receptor 2 (KDR and angiogenesis signal molecules (FAk and PLC-γ. SCs effectively inhibited the activation of lymphocyte stimulated by islets and ECs. Predominantly immunosuppressive cytokines could be detected in culture supernatants of the SCs coculture group. These results suggest that ECs-coating and Sertoli cells co-culture or infusion synergistically enhance islet survival and function after transplantation.

  19. Quality by design case study 1: Design of 5-fluorouracil loaded lipid nanoparticles by the W/O/W double emulsion - Solvent evaporation method.

    Science.gov (United States)

    Amasya, Gulin; Badilli, Ulya; Aksu, Buket; Tarimci, Nilufer

    2016-03-10

    With Quality by Design (QbD), a systematic approach involving design and development of all production processes to achieve the final product with a predetermined quality, you work within a design space that determines the critical formulation and process parameters. Verification of the quality of the final product is no longer necessary. In the current study, the QbD approach was used in the preparation of lipid nanoparticle formulations to improve skin penetration of 5-Fluorouracil, a widely-used compound for treating non-melanoma skin cancer. 5-Fluorouracil-loaded lipid nanoparticles were prepared by the W/O/W double emulsion - solvent evaporation method. Artificial neural network software was used to evaluate the data obtained from the lipid nanoparticle formulations, to establish the design space, and to optimize the formulations. Two different artificial neural network models were developed. The limit values of the design space of the inputs and outputs obtained by both models were found to be within the knowledge space. The optimal formulations recommended by the models were prepared and the critical quality attributes belonging to those formulations were assigned. The experimental results remained within the design space limit values. Consequently, optimal formulations with the critical quality attributes determined to achieve the Quality Target Product Profile were successfully obtained within the design space by following the QbD steps. PMID:26780593

  20. The performance of a target-controlled infusion of propofol in combination with remifentanil : A clinical investigation with two propofol formulations

    NARCIS (Netherlands)

    Wietasch, JKG; Scholz, M; Zinserling, J; Kiefer, N; Frenkel, C; Knufermann, P; Brauer, U; Hoeft, A

    2006-01-01

    Target-controlled infusion (TCI) incorporates the pharmacokinetic variables of an IV drug to facilitate safe and reliable administration. In this clinical study we investigated the performance of propofol TCI in combination with remifentanil. Fifty-four adult patients scheduled for general surgery l

  1. 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...

  2. 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)

    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/m2) infusion at a fixed dose rate (10 mg/m2/min), followed by 85 mg/m2 oxaliplatin and 48-h infusion of 5-fluorouracil/leucovorin (3000/150 mg/m2) for 6 cycles. Patients without disease progression 4 weeks after ICT would receive weekly 400 mg/m2 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: Three months

  3. 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

    Energy Technology Data Exchange (ETDEWEB)

    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

  4. Radiation therapy and arterial infusion chemotherapy for advanced gallbladder cancer

    International Nuclear Information System (INIS)

    The standard therapy is not yet established for the unresectable advanced gallbladder cancer (AGC). Here described is the outcome of authors' therapeutic protocol for AGC during the time Jan., 1989-Dec., 2008. Subjects are 73 patients (M 32/F 41, average age 65 y) with AGC of Stage IV. One shot arterial infusion (AI) of EEP regimen (etoposide (VP16)/4'epiadriamycin (EPIR)/cisplatin (CDDP)) is conducted via hepatic artery proper or common at the first angiography and one week later, external radiation therapy (RT), with about 30-50 Gy/6 fractions (actually, 12-61.6 Gy). AI is weekly done with FP regimen (CDDP/5-fluorouracil (FU)) through the reservoir indwelled in the gastroduodenal artery for 6 months where a metal stent for the stegnosis of bile duct is used if necessary after RT, and in recent days, additionally with biweekly CDDP/gemcitabin (GEM) regimen depending on patient's state after FP. As a result, RT is conducted to 62 cases (RT alone 8 cases), AI, 64 (alone, 10), and RT+AI, 54. Response is found to be 49% (CR 7 cases and PR, 28). Survivals 1- and 3-year are 39 and 6%, respectively, and average survival time, 408 days. Survival rate in (RT+AI) is significantly superior to that in AI alone and in RT alone. Prognosis in patients with jaundice, hepatic or duodenal invasion is significantly inferior to those without the symptom, and in non-responded cases, to responded cases. Complications like hepatic abscess are seen in 4 cases at 6 months after treatment. Four actual case-reports are presented in details with their images. Combination of RT+AI is suggested to be of utility for AGC, of which multi-center trial is awaited with addition of newer anti-cancers developed recently. (K.T.)

  5. Comparison of cisplatinum/paclitaxel with cisplatinum/5-fluorouracil as first-line therapy for nonsurgical locally advanced esophageal squamous cell carcinoma patients

    Directory of Open Access Journals (Sweden)

    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

  6. Comparison of cisplatinum/paclitaxel with cisplatinum/5-fluorouracil as first-line therapy for nonsurgical locally advanced esophageal squamous cell carcinoma patients

    Science.gov (United States)

    Hu, Guofang; Wang, Zhehai; Wang, Yuan; Zhang, Qingqing; Tang, Ning; Guo, Jun; Liu, Liyan; Han, Xiao

    2016-01-01

    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 were 17.1% versus 7.2% (P=0.032) and 52.4% versus 30.9% (P=0.042) in group A and B, respectively. Meanwhile, group B was associated with a significantly lower rate of grade 3/4 overall toxicity than group A (P=0.039). Conclusion Our data showed that patients with locally advanced ESCC in group A had longer PFS and OS compared with

  7. 乳腺癌耐受蛋白介导5-氟脲嘧啶的耐受及机制探讨%Breast Cancer Resistance Protein Mediates 5-Fluorouracil Resistance and Its Mechanism

    Institute of Scientific and Technical Information of China (English)

    袁建辉; 贺智敏; 吕辉; 余艳辉; 陈主初

    2005-01-01

    AIM To filtrate breast cancer resistance protein(BCRP)-mediated resistance agents and investigate the mechanism,so as to provide valuable datum for optimization clinical chemotherapy scheme to tumor with evaluation marker of BCRP expression. METHODS MTT assay was used to filtrate BCRP-mediated resistance agents with PA317/Tet-on/TRE-BCRP cell of different expression levels of BCRP after treated with different concentration anticancer agents. High performance liquid chromatography(HPLC) was applied to measure relative dose of intracellular retention resistance agents. Nuclear DNA fluorescence dye,Hochest 33258, staining and flow cytometry were adopted to detect apoptotic cells after treated with drugs. RESULTS There were shown increasing durg-resistance to 5-fluorouracil,methotrexate, doxirubicin, pirarubicin,etoposide and mitoxantrone followed with increasing expression of BCRP on PA317/Tet-on/TRE-BCRP cells(P<0.05, n=3),but shown sensitive to paclitaxel, cisplatin, vincristine, mitomycin and vindesine. There also was shown significant negative correlation between the intracellular retention dose of 5-fluorouracil with different expression of BCRP(r=-0.885, P<0.05, n=3).There were shown parallel results of that decreasing cellular apoptotic rate with increasing cellular expression of BCRP after treated with 5-fluorouracil by fluorescence dye staining and flow cytometry(P<0.05, n=3),and also shown significate rise of the apoptotic rate of BCRP expression cells after treated with Ko143 (P<0.05, n=3). Every group of cells could be different extently blocked in phase of G0/G1 treated with 5-fluorouracil. CONCLUSION Resistance of 5-fluorouracil could be especially mediated by conjugated with BCRP and acted as drug exclude-pump substrate. Cellular ability resistant to 5-fluorouracil-induced apoptosis could be reinforced by BCRP expression.

  8. Partial splenic embolization combined with vincristine infusion for the treatment of refractory idiopathic thrombocytopenic purpura and Evans syndrome: observation of its long-term efficacy

    International Nuclear Information System (INIS)

    Objective: To observe the long-term efficacy of partial spleen embolization combined with vincristine infusion in treating refractory idiopathic thrombocytopenic purpura (ITP) and Evans syndrome. Methods: During the period of 2000-2007, partial spleen embolization together with vincristine infusion was carried out in 30 patients with refractory idiopathic thrombocytopenic purpura (n=24) or Evans syndrome (n=6). Vincristine infusion (2 mg) via splenic artery was performed before partial spleen embolization procedure. The long-term effectiveness was observed and analyzed. Results: One week after the treatment, the platelet count was increased from preoperative (10.23±8.28) × 109/L to (140.28±85.45) × 109/L in patients with ITP, while the platelet count was increased from preoperative (12±8) × 109/L to (210±60) × 109/L in patients with Evans syndrome. Meanwhile, the hemoglobin level showed an increase in different degrees, from preoperative (63.00±13.62) g/L to postoperative (123.00±13.14) g/L. The therapeutic effectiveness was 100%. During the follow-up time lasting for 3-5 years, recurrence was seen in 11 patients (36.7%) and the overall efficacy rate was 63.3%. Conclusion: For the treatment of refractory idiopathic thrombocytopenic purpura and Evans syndrome, partial spleen embolization combined with vincristine infusion carries reliable long-term efficacy. (author)

  9. The combination of liquid chromatography/tandem mass spectrometry and chip-based infusion for improved screening and characterization of drug metabolites.

    Science.gov (United States)

    Staack, Roland F; Varesio, Emmanuel; Hopfgartner, Gérard

    2005-01-01

    An approach has been developed for drug metabolism studies of non-radiolabeled compounds using on-line liquid chromatography/tandem mass spectrometry (LC/MS/MS) combined with chip-based infusion following fraction collection. The potential of this approach, which improves the data quality compared with only LC/MS analysis, has been investigated for the analysis of in vitro metabolites of tolcapone and talinolol, two compounds with well-characterized metabolism. The information-dependent LC/MS/MS analysis enables the characterization of the major metabolites while the chip-based infusion is used to obtain good product ion spectra for lower level metabolites, to generate complementary MS information on potential metabolites detected in the LC/MS trace, or to screen for unexpected metabolites. Fractions from the chromatographic analysis are collected in 20 second steps, into a 96-well plate. The fractions of interest can be re-analyzed with chip-based infusion on a variety of mass spectrometers including triple quadrupole linear ion trap (QqLIT or Q TRAP) and QqTOF systems. Acquiring data for several minutes using multi-channel acquisition (MCA), or signal averaging while infusing the fractions at approximately 200 nL/min, permits about a 50 times gain in sensitivity (signal-to-noise) in MS/MS mode. A 5-10 microL sample fraction can be infused for more than 30 min allowing the time to perform various MS experiments such as MS(n), precursor ion or neutral loss scans and accurate mass measurement, all in either positive or negative mode. Through fraction collection and infusion, a significant gain in data quality is obtained along with a time-saving benefit, because the original sample needs neither to be re-analyzed by re-injection nor to be pre-concentrated. Therefore, a novel hydroxylated talinolol metabolite could be characterized with only one injection. PMID:15685686

  10. 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

    Background: Standard weekly cetuximab and irinotecan (CetIri) is an effective regimen in heavily pretreated patients with advanced colorectal cancer (ACRC). Inspired by a pharmacokinetic study demonstrating no differences between weekly and biweekly cetuximab, we present the results of 74......-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...

  11. Inhibition of Bcl-2 expression by a novel tumor-specific RNA interference system increases chemosensitivity to 5-fluorouracil in Hela cells

    Institute of Scientific and Technical Information of China (English)

    Sheng-lin HUANG; Yi WU; Hai YU; Ping ZHANG; Xing-qian ZHANG; Lei YING; Han-fang ZHAO

    2006-01-01

    Aim: RNA interference (RNAi) has been proposed as a potential treatment for cancer, but the lack of cellular targets limits its use in cancer gene therapy. No current technology has achieved direct tumor-specific gene silencing using RNAi.In the present study we attempt to develop a tumor-specific RNAi system using the human telomerase reverse transcriptase (hTERT) promoter; furthermore, we analyzed its inhibitive effect on Bcl-2 expression. Methods: The vectors containing a small hairpin RNA (shRNA) to target exogenous reporters [firefly luciferase and enhanced green fluorescent protein (EGFP)] and endogenous gene (Bcl-2)were constructed. Luciferase expression was determined by dual luciferase assay.Reverse transcription-polymerase chain reaction (RT-PCR), fluorescence microscopy and fluorescence-activated cell sorting (FACS) were used to measure EGFP expression. Inhibition of Bcl-2 was evaluated by RT-PCR and Western blotting.Cell proliferation and viability were measured by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. FACS was used to analyze the cell cycle distribution profile. Results: We showed that with the hTERT promoter directly driving shRNA transcription, expression of the exogenous reporters (LUC and EGFP) in tumor cells, but not normal cells, was specifically inhibited in vitro. The hTERT promoter-driven shRNA also depressed the expression of Bcl-2. Inhibition of Bcl-2 did not affect cell proliferation, but increased the chemosensitivity of HeLa cells to 5-fluorouracil. Conclusion: The present study describes an efficient RNAi system for gene silencing that is specific to tumor cells using the hTERT promoter. Suppression of Bcl-2 by using this system sensitized HeLa cells to 5-fluorouracil. This system may be useful for RNAi therapy.

  12. Tolerance and toxicity of neoadjuvant docetaxel, cisplatin and 5 fluorouracil regimen in technically unresectable oral cancer in resource limited rural based tertiary cancer center

    Directory of Open Access Journals (Sweden)

    V M Patil

    2014-01-01

    Full Text Available Background: Recent studies indicate neoadjuvant chemotherapy (NACT can result in R0 resection in a substantial proportion of patients with technically unresectable oral cavity cancers. However, data regarding the efficacy and safety of docetaxel, cisplatin and 5 fluorouracil (TPF NACT in our setting is lacking. The present audit was proposed to evaluate the toxicities encountered during administration of this regimen. It was hypothesized that TPF NACT would be considered feasible for routine administration if an average relative dose intensity (ARDI of ≥0.90 or more in at least 70% of the patients. Materials and Methods: Technically unresectable oral cancers with Eastern Cooperative Oncology Group PS 0-2, with biopsy proven squamous cell carcinoma underwent two cycles of NACT with TPF regimen. Toxicity and response rates were noted following the CTCAE 4.03 and RECIST criteria. Descriptive analysis of completion rates (completing 2 cycles of planned chemotherapy with ARDI of 0.85 or more, reason for delay, toxicity, and response are presented. Results: The NACT was completed by all patients. The number of subjects who completed all planned cycles of chemotherapy are with the ARDI of the delivered chemotherapy been equal to or >0.85 was 11 (91.67%. All toxicity inclusive Grade 3-5 toxicity was seen in 11 patients (91.67%. The response rate of chemotherapy was 83.33%. There were three complete response, seven partial response, and two stable disease seen post NACT in this study. Conclusion: Docetaxel, cisplatin and 5 fluorouracil regimen can be routinely administered at our center with the supportive care methods and precautionary methods used in our study.

  13. Gemcitabine, oxaliplatin, levofolinate, 5-fluorouracil, granulocyte-macrophage colony-stimulating factor, and interleukin-2 (GOLFIG) versus FOLFOX chemotherapy in metastatic colorectal cancer patients: the GOLFIG-2 multicentric open-label randomized phase III trial.

    Science.gov (United States)

    Correale, Pierpaolo; Botta, Cirino; Rotundo, Maria S; Guglielmo, Annamaria; Conca, Raffaele; Licchetta, Antonella; Pastina, Pierpaolo; Bestoso, Elena; Ciliberto, Domenico; Cusi, Maria G; Fioravanti, Antonella; Guidelli, Giacomo M; Bianco, Maria T; Misso, Gabriella; Martino, Elodia; Caraglia, Michele; Tassone, Pierfrancesco; Mini, Enrico; Mantovani, Giovanni; Ridolfi, Ruggero; Pirtoli, Luigi; Tagliaferri, Pierosandro

    2014-01-01

    The GOLFIG-2 phase III trial was designed to compare the immunobiological activity and antitumor efficacy of GOLFIG chemoimmunotherapy regimen with standard FOLFOX-4 chemotherapy in frontline treatment of metastatic colorectal cancer (mCRC) patients. This trial was conceived on the basis of previous evidence of antitumor and immunomodulating activity of the GOLFIG regimen in mCRC. GOLFIG-2 is a multicentric open/label phase III trial (EUDRACT: 2005-003458-81). Chemo-naive mCRC patients were randomized in a 1:1 ratio to receive biweekly standard FOLFOX-4 or GOLFIG [gemcitabine (1000 mg/m(2), day 1); oxaliplatin (85 mg/m(2), day 2); levofolinate (100 mg/m(2), days 1-2), 5-fluorouracil (5-FU) (400 mg/m(2) in bolus followed by 24 h infusion at 800 mg/m(2),days 1-2), sc. GM-CSF (100 μg, days 3-7); sc. aldesleukin (0·5 MIU bi-daily, days 8-14 and 17-30)] treatments. The study underwent early termination because of poor recruitment in the control arm. After a median follow-up of 43.83 months, GOLFIG regimen showed superiority over FOLFOX in terms of progression-free survival [median 9·23 (95% confidence interval (CI), 6·9-11.5) vs. median 5.70 (95% CI, 3.38-8.02) months; hazard ratio (HR): 0.52 (95% CI, 0.35-0.77), P=0·002] and response rate [66.1% (95% CI, 0.41-0.73) vs. 37·0% (95% CI, 0.28-0.59), P=0.002], with a trend to longer survival [median 21.63 (95% CI, 18.09-25.18) vs. 14.57 mo (95% CI, 9.07-20.07); HR: 0·79 (95% CI, 0.52-1.21); P=0.28]. Patients in the experimental arm showed higher incidence of non-neutropenic fever (18.5%), autoimmunity signs (18.5%), an increase in the number of monocytes, eosinophils, CD4(+) T lymphocytes, natural killer cells, and a decrease in immunoregulatory (CD3(+)CD4(+)CD25(+)FoxP3(+)) T cells. Taken together, these findings provide proof-of-principle that GOLFIG chemoimmunotherapy may represent a novel reliable option for first-line treatment of mCRC. PMID:24316553

  14. High-dose 5-fluorouracil plus low dose methotrexate plus or minus low-dose PALA in advanced colorectal cancer : a randomised phase II-III trial of the EORTC Gastrointestinal Group

    NARCIS (Netherlands)

    Wils, J; Blijham, GH; Wagener, T; De Greve, J; Jansen, RLH; Kok, TC; Nortier, JWR; Bleiberg, H; Couvreur, ML; Genicot, B; Baron, B

    2003-01-01

    The aim of this study was to investigate whether N-(phosphonacetyl)-L-aspartic acid (PALA) can enhance the activity of low-dose methotrexate (LD-MTX) modulated infusional 5-fluorouracil (5-FU) in patients with advanced colorectal cancer. 198 patients were randomised either to (i) 5-FU 60 mg/kg as a

  15. Effect of infusion of spices into the oil vs. combined malaxation of olive paste and spices on quality of naturally flavoured virgin olive oils.

    Science.gov (United States)

    Caponio, Francesco; Durante, Viviana; Varva, Gabriella; Silletti, Roccangelo; Previtali, Maria Assunta; Viggiani, Ilaria; Squeo, Giacomo; Summo, Carmine; Pasqualone, Antonella; Gomes, Tommaso; Baiano, Antonietta

    2016-07-01

    Olive oil flavouring with aromatic plants and spices is a traditional practice in Mediterranean gastronomy. The aim of this work was to compare the influence of two different flavouring techniques (infusion of spices into the oil vs. combined malaxation of olives paste and spices) on chemical and sensory quality of flavoured olive oil. In particular, oxidative and hydrolytic degradation (by routine and non-conventional analyses), phenolic profiles (by HPLC), volatile compounds (by SPME-GC/MS), antioxidant activity, and sensory properties (by a trained panel and by consumers) of the oils were evaluated. The obtained results evidenced that the malaxation method was more effective in extracting the phenolic compounds, with a significantly lower level of hydrolysis of secoiridoids. As a consequence, antioxidant activity was significantly lower in the oils obtained by infusion, which were characterized by a higher extent of the oxidative degradation. The volatile compounds were not significantly influenced by changing the flavouring method, apart for sulfur compounds that were more abundant in the oils obtained by the combined malaxation method. From a sensory point of view, more intense bitter and pungent tastes were perceived when the infusion method was adopted.

  16. Effect of infusion of spices into the oil vs. combined malaxation of olive paste and spices on quality of naturally flavoured virgin olive oils.

    Science.gov (United States)

    Caponio, Francesco; Durante, Viviana; Varva, Gabriella; Silletti, Roccangelo; Previtali, Maria Assunta; Viggiani, Ilaria; Squeo, Giacomo; Summo, Carmine; Pasqualone, Antonella; Gomes, Tommaso; Baiano, Antonietta

    2016-07-01

    Olive oil flavouring with aromatic plants and spices is a traditional practice in Mediterranean gastronomy. The aim of this work was to compare the influence of two different flavouring techniques (infusion of spices into the oil vs. combined malaxation of olives paste and spices) on chemical and sensory quality of flavoured olive oil. In particular, oxidative and hydrolytic degradation (by routine and non-conventional analyses), phenolic profiles (by HPLC), volatile compounds (by SPME-GC/MS), antioxidant activity, and sensory properties (by a trained panel and by consumers) of the oils were evaluated. The obtained results evidenced that the malaxation method was more effective in extracting the phenolic compounds, with a significantly lower level of hydrolysis of secoiridoids. As a consequence, antioxidant activity was significantly lower in the oils obtained by infusion, which were characterized by a higher extent of the oxidative degradation. The volatile compounds were not significantly influenced by changing the flavouring method, apart for sulfur compounds that were more abundant in the oils obtained by the combined malaxation method. From a sensory point of view, more intense bitter and pungent tastes were perceived when the infusion method was adopted. PMID:26920288

  17. Biodistribution and pharmacokinetics of 188Re-liposomes and their comparative therapeutic efficacy with 5-fluorouracil in C26 colonic peritoneal carcinomatosis mice

    Directory of Open Access Journals (Sweden)

    Tsai CC

    2011-10-01

    Full Text Available Chia-Che Tsai1, Chih-Hsien Chang1, Liang-Cheng Chen1, Ya-Jen Chang1, Keng-Li Lan2, Yu-Hsien Wu1, Chin-Wei Hsu1, I-Hsiang Liu1, Chung-Li Ho1, Wan-Chi Lee1, Hsiao-Chiang Ni1, Tsui-Jung Chang1, Gann Ting3, Te-Wei Lee11Institute of Nuclear Energy Research, Taoyuan, 2Cancer Center, Taipei Veterans General Hospital, Taipei, 3National Health Research Institutes, Taipei, Taiwan, ROCBackground: Nanoliposomes are designed as carriers capable of packaging drugs through passive targeting tumor sites by enhanced permeability and retention (EPR effects. In the present study the biodistribution, pharmacokinetics, micro single-photon emission computed tomography (micro-SPECT/CT image, dosimetry, and therapeutic efficacy of 188Re-labeled nanoliposomes (188Re-liposomes in a C26 colonic peritoneal carcinomatosis mouse model were evaluated.Methods: Colon carcinoma peritoneal metastatic BALB/c mice were intravenously administered 188Re-liposomes. Biodistribution and micro-SPECT/CT imaging were performed to determine the drug profile and targeting efficiency of 188Re-liposomes. Pharmacokinetics study was described by a noncompartmental model. The OLINDA|EXM® computer program was used for the dosimetry evaluation. For therapeutic efficacy, the survival, tumor, and ascites inhibition of mice after treatment with 188Re-liposomes and 5-fluorouracil (5-FU, respectively, were evaluated and compared.Results: In biodistribution, the highest uptake of 188Re-liposomes in tumor tissues (7.91% ± 2.02% of the injected dose per gram of tissue [%ID/g] and a high tumor to muscle ratio (25.8 ± 6.1 were observed at 24 hours after intravenous administration. The pharmacokinetics of 188Re-liposomes showed high circulation time and high bioavailability (mean residence time [MRT] = 19.2 hours, area under the curve [AUC] = 820.4%ID/g*h. Micro-SPECT/CT imaging of 188Re-liposomes showed a high uptake and targeting in ascites, liver, spleen, and tumor. The results were correlated with

  18. In silico analysis of the three-dimensional structures of the homodimer of uridine phosphorylase from Yersinia Pseudotuberculosis in the ligand-free state and in a complex with 5-fluorouracil

    Energy Technology Data Exchange (ETDEWEB)

    Lashkov, A. A., E-mail: alashkov83@gmail.com; Sotnichenko, S. E.; Mikhailov, A. M. [Russian Academy of Sciences, Shubnikov Institute of Crystallography (Russian Federation)

    2013-03-15

    Pseudotuberculosis is an acute infectious disease characterized by a lesion of the gastrointestinal tract. A positive therapeutic effect can be achieved by selectively suppressing the activity of uridine phosphorylase from the causative agent of the disease Yersinia pseudotuberculosis. The synergistic effect of a combination of the chemotherapeutic agent 5-fluorouracil and antimicrobial drugs, which block the synthesis of pyrimidine bases, on the cells of pathogenic protozoa and bacteria is described in the literature. The three-dimensional structures of uridine phosphorylase from Yersinia pseudotuberculosis (YptUPh) both in the ligand-free state and in complexes with pharmacological agents are unknown, which hinders the search for and design of selective inhibitors of YptUPh. The three-dimensional structure of the ligand-free homodimer of YptUPh was determined by homology-based molecular modeling. The three-dimensional structure of the subunit of the YptUPh molecule belongs to {alpha}/{beta} proteins, and its topology is a three-layer {alpha}/{beta}/{alpha} sandwich. The subunit monomer of the YptUPh molecule consists of 38% helices and 24% {beta} strands. A model of the homodimer structure of YptUPh in a complex with 5-FU was obtained by the molecular docking. The position of 5-FU in the active site of the molecule is very consistent with the known data on the X-ray diffraction structures of other bacterial uridine phosphorylases (the complex of uridine phosphorylase from Salmonella typhimurium (StUPh) with 5-FU, ID PDB: 4E1V and the complex of uridine phosphorylase from Escherichia coli (EcUPh) with 5-FU and ribose 1-phosphate, ID PDB: 1RXC).

  19. Water extract of Hedyotis Diffusa Willd suppresses proliferation of human HepG2 cells and potentiates the anticancer efficacy of low-dose 5-fluorouracil by inhibiting the CDK2-E2F1 pathway.

    Science.gov (United States)

    Chen, Xu-Zheng; Cao, Zhi-Yun; Chen, Tuan-Sheng; Zhang, You-Quan; Liu, Zhi-Zhen; Su, Yin-Tao; Liao, Lian-Ming; Du, Jian

    2012-08-01

    Hedyotis Diffusa Willd (HDW), a Chinese herbal medicine, has been widely used as an adjuvant therapy against various cancers, including hepatocellular carcinoma (HCC). However, the underlying anticancer mechanisms are yet to be elucidated. In the present study, the anticancer effects of HDW were evaluated and the efficacy and safety of HDW combined with low-dose 5-fluorouracil (5-FU) were investigated. HepG2 cells were cultured in vitro and nude mouse xenografts were established in vivo. The proliferation of HepG2 cells was measured using the MTT method and flow cytometry. The mRNA and protein expression levels of cyclin-dependent kinase 2 (CDK2), cyclin E and E2F1 were examined using relative quantitative real-time PCR and western blot analysis, respectively. The results showed that water extract of HDW remarkably inhibited HepG2 cell proliferation in a dose-dependent manner via arrest of HepG2 cells at the G0/G1 phase and induction of S phase delay. This suppression was accompanied by a great decrease of E2F1 and CDK2 mRNA expression. In addition, HDW remarkably potentiated the anticancer effect of low-dose 5-FU in the absence of overt toxicity by downregulating the mRNA and protein levels of CDK2, cyclin E and E2F1. Our findings support the use of HDW as adjuvant therapy of chemotherapy and suggest that HDW may potentiate the efficiency of low-dose 5-FU in treating HCC. PMID:22641337

  20. Effects of music on target-controlled infusion of propofol requirements during combined spinal-epidural anaesthesia.

    Science.gov (United States)

    Zhang, X W; Fan, Y; Manyande, A; Tian, Y K; Yin, P

    2005-10-01

    The sedative effects of music were evaluated using the bispectral index (BIS) during target-controlled infusion (TCI) propofol. A total of 110 women undergoing hysterectomy were randomly allocated to receive either music or no music. Propofol was administered using target-controlled infusion and the concentration adjusted gradually to achieve an observer's assessment of alertness/sedation (OAA/S) score of 3 intra-operatively. The haemodynamic and bispectral index values during the sedation phase were recorded. Interleukin-6 was evaluated before, immediately after and 1 h following intervention. The music group had a significant reduction in mean (SD) induction time of sedation: 12 (12) min vs. 18 (12) min, p music on the induction time of sedation, concentration and level of propofol during surgery, and suggest sedative benefits of music. PMID:16179044

  1. Use of Adjuvant 5-Fluorouracil and Radiation Therapy After Gastric Cancer Resection Among the Elderly and Impact on Survival

    International Nuclear Information System (INIS)

    Purpose: In randomized trials patients with resected nonmetastatic gastric cancer who received adjuvant chemotherapy and radiotherapy (chemoRT) had better survival than those who did not. We investigated the effectiveness of adjuvant chemoRT after gastric cancer resection in an elderly general population and its effects by stage. Methods and Materials: We identified individuals in the Surveillance, Epidemiology, and End Results-Medicare database aged 65 years or older with Stage IB through Stage IV (M0) gastric cancer, from 1991 to 2002, who underwent gastric resection, using multivariate modeling to analyze predictors of chemoRT use and survival. Results: Among 1,993 patients who received combined chemoRT or no adjuvant therapy after resection, having a later year of diagnosis, having a more advanced stage, being younger, being white, being married, and having fewer comorbidities were associated with combined treatment. Among 1,476 patients aged less than 85 years who survived more than 4 months, the 313 who received combined treatment had a lower mortality rate (hazard ratio, 0.83; 95% confidence interval, 0.71-0.98) than the 1,163 who received surgery alone. Adjuvant therapy significantly reduced the mortality rate for Stages III and IV (M0), trended toward improved survival for Stage II, and showed no benefit for Stage IB. We observed trends toward improved survival in all age categories except 80 to 85 years. Conclusions: The association of combined adjuvant chemoRT with improved survival in an overall analysis of Stage IB through Stage IV (M0) resected gastric cancer is consistent with clinical trial results and suggests that, in an elderly population, adjuvant chemoradiotherapy is effective. However, our observational data suggest that adjuvant treatment may not be effective for Stage IB cancer, is possibly appropriate for Stage II, and shows significant survival benefits for Stages III and IV (M0) for those aged less than 80 years.

  2. Celecoxib attenuates 5-fluorouracil-induced apoptosis in HCT-15 and HT-29 human colon cancer cells

    Institute of Scientific and Technical Information of China (English)

    Yun Jeong Lim; Jong Chul Rhee; Young Mee Bae; Wan Joo Chun

    2007-01-01

    AIM: To investigate the combined chemotherapeutic effects of celecoxib when used with 5-FU in vitro.METHODS: Two human colon cancer cell lines (HCT-15and HT-29) were treated with 5-FU and celecoxib, alone and in combination. The effects of each drug were evaluated using the MTT (3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, flow cytometry,and western blotting.RESULTS: 5-FU and celecoxib showed a dosedependent cytotoxic effect. When treated with 10-3mol/L 5-FU (IC50) and celecoxib with its concentration ranging from 10-8 mol/L to 10-4 mol/L of celecoxib,cells showed reduced cytotoxic effect than 5-FU(10-3 mol/L) alone. Flow cytometry showed that celecoxib attenuated 5-FU induced accumulation of cells at subG1 phase. Western blot analyses for caspase-3 and poly (ADP-ribose) polymerase (PARP) cleavage showed that celecoxib attenuated 5-FU induced apoptosis. Western blot analyses for cell cycle molecules showed that G2/M arrest might be possible cause of 5-FU induced apoptosis and celecoxib attenuated 5-FU induced apoptosis via blocking of cell cycle progression to the G2/M phase,causing an accumulation of cells at the G1/S phase.CONCLUSION: We found that celecoxib attenuated cytotoxic effect of 5-FU. Celecoxib might act via inhibition of cell cycle progression, thus preventing apoptosis induced by 5-FU.

  3. Promoter methylation and large intragenic rearrangements of DPYD are not implicated in severe toxicity to 5-fluorouracil-based chemotherapy in gastrointestinal cancer patients

    International Nuclear Information System (INIS)

    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

  4. Carbogen Breathing Differentially Enhances Blood Plasma Volume and 5-Fluorouracil Uptake in Two Murine Colon Tumor Models with a Distinct Vascular Structure

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    Hanneke W.M. van Laarhoven

    2006-06-01

    Full Text Available For the systemic treatment of colorectal cancer, 5-fluorouracil (FU-based chemotherapy is the standard. However, only a subset of patients responds to chemotherapy. Breathing of carbogen (95% O2 and 5% CO2 may increase the uptake of FU through changes in tumor physiology. This study aims to monitor in animal models in vivo the effects of carbogen breathing on tumor blood plasma volume, pH, and energy status, and on FU uptake and metabolism in two colon tumor models C38 and C26a, which differ in their vascular structure and hypoxic status. Phosphorus-31 magnetic resonance spectroscopy (MRS was used to assess tumor pH and energy status, and fluorine-19 MRS was used to follow FU uptake and metabolism. Advanced magnetic resonance imaging methods using ultrasmall particles of iron oxide were performed to assess blood plasma volume. The results showed that carbogen breathing significantly decreased extracellular pH and increased tumor blood plasma volume and FU uptake in tumors. These effects were most significant in the C38 tumor line, which has the largest relative vascular area. In the C26a tumor line, carbogen breathing increased tumor growth delay by FU. In this study, carbogen breathing also enhanced systemic toxicity by FU.

  5. Accelerated split-course radiotherapy and simultaneous cis-dichlorodiammine-platinum and 5-fluorouracil chemotherapy with folinic acid enhancement for unresectable carcinoma of the head and neck

    International Nuclear Information System (INIS)

    Thirty-four (6 stage III, 28 stage IV) patients with advanced squamous cell carcinoma of the head and neck were treated by simultaneous radio-chemotherapy. Treatment was divided into three cycles. Chemotherapy consisted of cis-diamminedichloroplatinum(II) (cis-DDP) 60 mg/sqm i.v., 5-fluorouracil (5-FU) 350 mg/sqm i.v. and folinic acid (FA)-50 mg/sqm i.v. on day 2 and 5-FU 350 mg/sqm per 24 h and FA 100 mg/sqm/24 h on days 2-5. Radiotherapy consisted of 23.4 Gy/9 days divided in 13 fractions of 1.8 Gy delivered twice a day from day 3 through day 11. This regimen was repeated on days 22 and 44. Total radiation dose amounted to 70.2 Gy/51 days. Mean follow-up of surviving patients was 21 (14-34) months. 28/32 patients achieved complete response, 4/32 partial response. Actuarial one and two years survival were 88 and 58% including two early deaths from tumour bleeding. Local control rates at one and two years were 87 and 81%, respectively. This protocol produces excellent palliation and the chance of improved long term tumour control. Two patients developed distant metastases. Overall toxicity was tolerable. Since the treatment breaks were inserted after low radiation doses, acute mucositis healed rapidly and was not a limiting factor. 39 refs.; 3 figs.; 3 tabs

  6. Safety of implanting sustained-release 5-fluorouracil into hepatic cross-section and omentum majus after primary liver cancer resection.

    Science.gov (United States)

    Chen, Jiangtao; Zhang, Junjie; Wang, Chenyu; Yao, Kunhou; Hua, Long; Zhang, Liping; Ren, Xuequn

    2016-09-01

    This study was designed to evaluate the short-term safety of implanting sustained-release 5-fluorouracil (5-FU) into hepatic cross-section and omentum majus after primary liver cancer resection and its impact on related indexes of liver. Forty patients were selected and divided into an implantation group (n = 20) and a control group (n = 20). On the first day after admission, first week after surgery, and first month after surgery, fasting venous blood was extracted from patients for measuring hematological indexes. The reduction rate of alpha fetoprotein (AFP) on the first week and first month after surgery was calculated, and moreover, drainage volume of the abdominal cavity drainage tube, length of stay after surgery, and wound healing condition were recorded. We found that levels of alanine aminotransferase, aspartate amino transferase, blood urea nitrogen, creatinine, total bilirubin, albumin, and white blood cells measured on the first week and first month after surgery, length of stay, and wound healing of patients in the two groups had no significant difference (P >0.05). Drainage volume and reduction rate of AFP of two groups were significantly different on the first week and first month after surgery (P <0.05). Implanting sustained-release 5-FU into hepatic cross-section and omentum majus after primary liver cancer resection is proved to be safe as it has little impact on related indexes. PMID:27207445

  7. Safety of implanting sustained-release 5-fluorouracil into hepatic cross-section and omentum majus after primary liver cancer resection.

    Science.gov (United States)

    Chen, Jiangtao; Zhang, Junjie; Wang, Chenyu; Yao, Kunhou; Hua, Long; Zhang, Liping; Ren, Xuequn

    2016-09-01

    This study was designed to evaluate the short-term safety of implanting sustained-release 5-fluorouracil (5-FU) into hepatic cross-section and omentum majus after primary liver cancer resection and its impact on related indexes of liver. Forty patients were selected and divided into an implantation group (n = 20) and a control group (n = 20). On the first day after admission, first week after surgery, and first month after surgery, fasting venous blood was extracted from patients for measuring hematological indexes. The reduction rate of alpha fetoprotein (AFP) on the first week and first month after surgery was calculated, and moreover, drainage volume of the abdominal cavity drainage tube, length of stay after surgery, and wound healing condition were recorded. We found that levels of alanine aminotransferase, aspartate amino transferase, blood urea nitrogen, creatinine, total bilirubin, albumin, and white blood cells measured on the first week and first month after surgery, length of stay, and wound healing of patients in the two groups had no significant difference (P >0.05). Drainage volume and reduction rate of AFP of two groups were significantly different on the first week and first month after surgery (P <0.05). Implanting sustained-release 5-FU into hepatic cross-section and omentum majus after primary liver cancer resection is proved to be safe as it has little impact on related indexes.

  8. Preclinical screening for drugs effective against 5-fluorouracil-resistant cells with a murine L5178Y cell line in vitro

    International Nuclear Information System (INIS)

    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

  9. In Vitro and In Vivo Evaluation of a Folate-Targeted Copolymeric Submicrohydrogel Based on N-Isopropylacrylamide as 5-Fluorouracil Delivery System

    Directory of Open Access Journals (Sweden)

    José M. Teijón

    2011-07-01

    Full Text Available Folate-targeted poly[(p-nitrophenyl acrylate-co-(N-isopropylacrylamide] nanohydrogel (F-SubMG was loaded with 5-fluorouracil (5-FU to obtain low (16.3 ± 1.9 μg 5-FU/mg F-SubMG and high (46.8 ± 3.8 μg 5-FU/mg F-SubMG load 5-FU-loaded F-SubMGs. The complete in vitro drug release took place in 8 h. The cytotoxicity of unloaded F-SubMGs in MCF7 and HeLa cells was low; although it increased for high F-SubMG concentration. The administration of 10 μM 5-FU by 5-FU-loaded F-SubMGs was effective on both cellular types. Cell uptake of F-SubMGs took place in both cell types, but it was higher in HeLa cells because they are folate receptor positive. After subcutaneous administration (28 mg 5-FU/kg b.w. in Wistar rats, F-SubMGs were detected at the site of injection under the skin. Histological studies indicated that the F-SubMGs were surrounded by connective tissue, without any signs of rejections, even 60 days after injection. Pharmacokinetic study showed an increase in MRT (mean residence time of 5-FU when the drug was administered by drug-loaded F-SubMGs.

  10. Temperature and magnetism bi-responsive molecularly imprinted polymers: Preparation, adsorption mechanism and properties as drug delivery system for sustained release of 5-fluorouracil.

    Science.gov (United States)

    Li, Longfei; Chen, Lin; Zhang, Huan; Yang, Yongzhen; Liu, Xuguang; Chen, Yongkang

    2016-04-01

    Temperature and magnetism bi-responsive molecularly imprinted polymers (TMMIPs) based on Fe3O4-encapsulating carbon nanospheres were prepared by free radical polymerization, and applied to selective adsorption and controlled release of 5-fluorouracil (5-FU) from an aqueous solution. Characterization results show that the as-synthesized TMMIPs have an average diameter of about 150 nm with a typical core-shell structure, and the thickness of the coating layer is approximately 50 nm. TMMIPs also displayed obvious magnetic properties and thermo-sensitivity. The adsorption results show that the prepared TMMIPs exhibit good adsorption capacity (up to 96.53 mg/g at 25 °C) and recognition towards 5-FU. The studies on 5-FU loading and release in vitro suggest that the release rate increases with increasing temperature. Meanwhile, adsorption mechanisms were explored by using a computational analysis to simulate the imprinted site towards 5-FU. The interaction energy between the imprinted site and 5-FU is -112.24 kJ/mol, originating from a hydrogen bond, Van der Waals forces and a hydrophobic interaction between functional groups located on 5-FU and a NIPAM monomer. The electrostatic potential charges and population analysis results suggest that the imprinted site of 5-FU can be introduced on the surface of TMMIPs, confirming their selective adsorption behavior for 5-FU.

  11. A reduction in the interstitial fluid pressure per se, does not enhance the uptake of the small molecule weight compound 5-fluorouracil into 4T1 mammary tumours

    Directory of Open Access Journals (Sweden)

    Charlotte Jevne

    2011-05-01

    Full Text Available The tumour interstitium represents a major barrier to drug delivery and modification of the tumour extracellular matrix (ECM is one strategy that could promote better delivery. We have focused upon three factors in the tumour interstitium that could influence drug uptake into the tumour tissue; the interstitial fluid pressure (Pif, collagen content and the tumour blood vessel density (TBVD. Two treatment groups were used: repeated hyperbaric oxygen (HBO and single HBO (both to 2.5 bar, 100% O2, à 90 min. The controls were exposed to normal atmosphere (1 bar, 21% O2. Pif, angiogenesis, collagen content and uptake of [H3]-5FU ([5-fluorouracil was investigated. Pif and TBVD significantly decreased after hyperoxic treatment, without any change in collagen content. Uptake of 5FU was not affected by hyperoxic treatment. Reduction in Pif per se does not enhance the uptake of 5FU in 4T1 mammary tumours. The fibrotic ECM (unaltered collagen content together with a less dense microvasculature might help explain this.

  12. Simultaneous Integrated Boost Using Intensity-Modulated Radiotherapy Compared With Conventional Radiotherapy in Patients Treated With Concurrent Carboplatin and 5-Fluorouracil for Locally Advanced Oropharyngeal Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Clavel, Sebastien, E-mail: sebastien.clavel@umontreal.ca [Department of Radiation Oncology, Centre Hospitalier de l' Universite de Montreal, Montreal, QC (Canada); Nguyen, David H.A.; Fortin, Bernard [Department of Radiation Oncology, Hopital Maisonneuve-Rosemont, Montreal, QC (Canada); Despres, Philippe [Department of Radiation Oncology, Centre Hospitalier de l' Universite de Montreal, Montreal, QC (Canada); Khaouam, Nader [Department of Radiation Oncology, Hopital Maisonneuve-Rosemont, Montreal, QC (Canada); Donath, David [Department of Radiation Oncology, Centre Hospitalier de l' Universite de Montreal, Montreal, QC (Canada); Soulieres, Denis [Department of Medical Oncology, Centre Hospitalier de l' Universite de Montreal, Montreal, QC (Canada); Guertin, Louis [Department of Head and Neck Surgery, Centre Hospitalier de l' Universite de Montreal, Montreal, QC (Canada); Nguyen-Tan, Phuc Felix [Department of Radiation Oncology, Hopital Maisonneuve-Rosemont, Montreal, QC (Canada)

    2012-02-01

    Purpose: To compare, in a retrospective study, the toxicity and efficacy of simultaneous integrated boost using intensity-modulated radiotherapy (IMRT) vs. conventional radiotherapy (CRT) in patients treated with concomitant carboplatin and 5-fluorouracil for locally advanced oropharyngeal cancer. Methods and Materials: Between January 2000 and December 2007, 249 patients were treated with definitive chemoradiation. One hundred patients had 70 Gy in 33 fractions using IMRT, and 149 received CRT at 70 Gy in 35 fractions. Overall survival, disease-free survival, and locoregional control were estimated using the Kaplan-Meier method. Results: Median follow-up was 42 months. Three-year actuarial rates for locoregional control, disease-free survival, and overall survival were 95.1% vs. 84.4% (p = 0.005), 85.3% vs. 69.3% (p = 0.001), and 92.1% vs. 75.2% (p < 0.001) for IMRT and CRT, respectively. The benefit of the radiotherapy regimen on outcomes was also observed with a Cox multivariate analysis. Intensity-modulated radiotherapy was associated with less acute dermatitis and less xerostomia at 6, 12, 24, and 36 months. Conclusions: This study suggests that simultaneous integrated boost using IMRT is associated with favorable locoregional control and survival rates with less xerostomia and acute dermatitis than CRT when both are given concurrently with chemotherapy.

  13. Effect of Gender on Coagulation Functions: A Study in Metastatic Colorectal Cancer Patients Treated with Bevacizumab, Irinotecan, 5-Fluorouracil, and Leucovorin

    Directory of Open Access Journals (Sweden)

    Cemil Bilir

    2014-01-01

    Full Text Available Introduction. We designed this study to evaluate how coagulation parameters are changed in metastatic colorectal cancer (mCRC patients treated with bevacizumab, irinotecan, 5-fluorouracil, and leucovorin (FOLFIRI. Methods. A total of 48 mCRC patients who initially received bevacizumab with FOLFIRI were eligible for this study. Thirty-four patients were analyzed at baseline and on the 4th, 8th, and 12th cycles of chemotherapy. Results. There were 19 male and 15 female patients. Baseline characteristics of the groups were similar, but women had better overall survival than men (14 months versus 12 months, P=0.044. D-dimer levels decreased significantly after the 12th cycle compared with baseline in men but not in women. Men and women had increased levels of serum fibrinogen at the early cycles, but these increased fibrinogen levels continued after the 4th cycle of chemotherapy only in women. In addition, serum fibrinogen levels did not significantly change, but aPTT levels decreased in men. Discussion. The major finding of this study is that bevacizumab-FOLFIRI chemotherapy does not promote changes in the coagulation system. If chemotherapy treatment and the possible side effects of FOLFIRI-bevacizumab treatment are well managed, then alterations of the coagulation cascade will not have an impact on overall survival and mortality.

  14. A Type II Arabinogalactan from Anoectochilus formosanus for G-CSF Production in Macrophages and Leukopenia Improvement in CT26-Bearing Mice Treated with 5-Fluorouracil

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    Li-Chan Yang

    2013-01-01

    Full Text Available Anoectochilus formosanus is an herb well known in Asian countries. The polysaccharide isolated from A. formosanus consists of type II arabinogalactan (AGAF, with branched 3,6-Gal as the major moiety. In this study, AGAF was examined for the granulocyte colony-stimulating factor (G-CSF production and related protein expression in RAW 264.7 murine macrophages. The signaling pathway of G-CSF production involves AGAF and mitogen-activated protein kinases (MAPKs inhibitors and pattern-recognition receptor antibodies. AGAF was evaluated to ease the leukopenia in CT26-colon-cancer-bearing mice treated with 5-fluorouracil (5-FU. The results of this study showed that AGAF was a stimulant for Toll-like receptor 2 and Dectin-1 and that it induced G-CSF production, through p38 and ERK MAPK, and NF-κB pathways. In vivo examination showed that the oral administration of AGAF mitigated the side effects of leukopenia caused by 5-FU in colon-cancer-bearing mice. In conclusion, the botanic type II AGAF in this study was a potent G-CSF inducer in vivo and in vitro.

  15. Analysis of the Thymidylate Synthase Gene Structure in Colorectal Cancer Patients and Its Possible Relation with the 5-Fluorouracil Drug Response

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    A. Calascibetta

    2010-01-01

    Full Text Available Thymidylate synthase (TS catalyzes methylation of dUMP to dTMP and it is the target for the 5-Fluorouracil (5-FU activity. Barbour et al. showed that variant structural forms of TS in tumour cell lines confer resistance to fluoropyrimidines. We planned to perform the whole TS gene structure by means of sequencing techniques in human colorectal cancer (CRC samples to try to identify the presence of any possible TS variant form that could be responsible of fluoropyrimidines drug resistance and of the worse prognosis. We performed the TS-DNA gene sequence in 68 CRC from patients of A, B, and C Dukes' stages and different histological grade, but we did not find any mutation in the TS-DNA structure. In the future we intend to widen the TS structure analysis to the metastatic CRCs, because due to their higher genomic instability, they could present a TS variant form responsible of the fluoropyrimidines drug resistance and the worse prognosis.

  16. Synthesis, characterization and in vitro cytotoxicity analysis of a novel cellulose based drug carrier for the controlled delivery of 5-fluorouracil, an anticancer drug

    Science.gov (United States)

    Anirudhan, Thayyath S.; Nima, Jayachandran; Divya, Peethambaran L.

    2015-11-01

    The present investigation concerns the development and evaluation of a novel drug delivery system, aminated-glycidylmethacrylate grafted cellulose-grafted polymethacrylic acid-succinyl cyclodextrin (Cell-g-(GMA/en)-PMA-SCD) for the controlled release of 5-Fluorouracil, an anticancer drug. The prepared drug carrier was characterized by FT-IR, XRD and SEM techniques. Binding kinetics and isotherm studies of 5-FU onto Cell-g-(GMA/en)-PMA-SCD were found to follow pseudo-second-order and Langmuir model respectively. Maximum binding capacity of drug carrier was found to be 149.09 mg g-1 at 37 °C. Swelling studies, in vitro release kinetics, drug loading efficiency and encapsulation efficiency of Cell-g-(GMA/en)-PMA-SCD were studied. The release kinetics was analyzed using Ritger-Peppas equation at pH 7.4. Cytotoxicity analysis on MCF-7 (human breast carcinoma) cells indicated that the drug carrier shows sustained and controlled release of drug to the target site. Hence, it is evident from this investigation that Cell-g-(GMA/en)-PMA-SCD could be a promising carrier for 5-FU.

  17. In vivo reflectance confocal microscopy characterization of field-directed 5-fluorouracil 0.5%/salicylic acid 10% in actinic keratosis.

    Science.gov (United States)

    Ulrich, Martina; Alarcon, Ivette; Malvehy, Josep; Puig, Susana

    2015-01-01

    Actinic keratosis (AK), a frequently diagnosed cutaneous neoplasm in individuals with chronic sun exposure or fair skin, is a risk factor for squamous cell carcinoma. AK presents as clinically visible lesions and/or as subclinical lesions where an entire field of area (field cancerization) contains lesions of various grades. The diagnosis and surveillance of subclinical AK is challenging. We report a new AK management approach, including subclinical AK, with noninvasive in vivo reflectance confocal microscopy (RCM) monitoring of field-directed topical 5-fluorouracil 0.5%/salicylic acid 10.0% (5-FU/SA; currently approved for single lesions). In this case series, eight patients with primarily recurrent, multiple AKs received ≤ 6 weeks of field-directed 5-FU/SA; complete clearance of clinical/subclinical AKs on various body areas was shown in most patients using RCM. RCM facilitated the detection/characterization of subclinical AKs in the setting of field cancerization. Topical field-directed 5-FU/SA monitored with RCM is a promising management approach for subclinical AKs.

  18. Effect of intra-hepatic arterial infusion chemotherapy for patients with liver metastasis from breast cancer

    International Nuclear Information System (INIS)

    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

  19. Clinical study on external carotid artery infusion (trans-femoral) treatment of recurrent nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    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

  20. The Investigation for Antifungal Effect of Medicinal Plants, Combination Infusion of Piper Bettle Leaves, Punica Granatum Fructus Cortec, Curcuma Domestica Rhizome

    OpenAIRE

    Berna Elya; Atiek Soemiati

    2002-01-01

    The tested demartophyta used Candida albicans. This research using dilution method to determine of minimum inhibitory concentration (MIC) and difusion method to determine zone inhibition around of disc. The results of determination of MIC showed that combination infusion Piper bettle leaves with Punica granatum Fructus Cortex against C. albicans respectively, 31,2 mg/ml : 7,8 mg/ml; 15,6 mg/ml : 15,6 mg/ml and 7,8 mg/ml : 31,2 mg/ml. The determination for zone inhibition from 3 concentration ...

  1. The DSA diagnosis, artery embolization combined with low dose of vasopressin infusion treatment for lower digestive tract hemorrhage

    International Nuclear Information System (INIS)

    Objective: To evaluate the clinical value of digital subtraction angiography (DSA) diagnosis and interventional treatment for lower digestive tract hemorrhage of unknown reasons. Methods: DSA was performed in 32 patients with unknown etiologic lower digestive tract hemorrhage. The locations and causes of hemorrhage were determined by angiography according to the demonstration of contrast medium extravasation, abnormal vasculature and tumor staining. Superselective arterial embolization was performed with retaining catheter of low dose vasopressin infusion for 12 hours of hemostasis. Results: Seventy-five percent of the lesions were identified by DSA with 2 cases of intestinal typhoid, 1 intestinal tuberculosis, 14 cases of vascular malformation and 7 cases of tumor. Hemostasis was succeeded in 20 of 24 patients. The rate of success was 83.3%. Conclusions: DSA and interventional therapy are of great value in diagnosing and treating patients with lower digestive tract hemorrhage of unknown reasons and even those undergone unsuccessful conservative treatment. Low dose vasopressin infusion through retained catheter is safe and efficient after superselective arterial embolization. (authors)

  2. Comparison of the effectiveness and toxicity of neoadjuvant chemotherapy regimens, capecitabine/epirubicin/cyclophosphamide vs 5-fluorouracil/epirubicin/cyclophosphamide, followed by adjuvant, capecitabine/docetaxel vs docetaxel, in patients with operable breast cancer

    OpenAIRE

    Zhang MM; Wei W; Liu JL; Yang HW; Jiang Y; Tang W; Li QY; Liao XM

    2016-01-01

    Minmin Zhang,* Wei Wei,* Jianlun Liu, Huawei Yang, Yi Jiang, Wei Tang, Qiuyun Li, Xiaoming Liao Department of Breast Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China *These authors contributed equally to this work Abstract: The aim of this study was to compare the effectiveness and toxicity of neoadjuvant chemotherapy regimens, xeloda/epirubicin/cyclophosphamide (XEC) vs 5-fluorouracil/epirubicin/cyclophosphamide (FEC)...

  3. Hedyotis diffusa Willd overcomes 5-fluorouracil resistance in human colorectal cancer HCT-8/5-FU cells by downregulating the expression of P-glycoprotein and ATP-binding casette subfamily G member 2

    OpenAIRE

    LI, QIONGYU; Wang, Xiangfeng; SHEN, ALING; Zhang, Yuchen; Chen, Youqin; Sferra, Thomas J.; LIN, JIUMAO; Peng, Jun

    2015-01-01

    Previous studies have demonstrated that Hedyotis diffusa Willd (HDW), a traditional Chinese herbal medicine, exhibits potent anticancer activity in models of colorectal cancer (CRC). Aggressive forms of CRC exhibit resistance to widely used chemotherapeutic drugs, including the antimetabolite, 5-fluorouracil (5-FU); however, less is known with regard to the activity of HDW against 5-FU-resistant cancer. In the present study, the mechanism of action and the potency of ethanol extracts of HDW (...

  4. A comparative study of the safety and efficacy effect of 5-fluorouracil or mitomycin C mounted biological delivery membranes in a rabbit model of glaucoma filtration surgery

    Directory of Open Access Journals (Sweden)

    Wu ZH

    2013-03-01

    Full Text Available Zhihong Wu,1 Shuning Li,2 Ningli Wang,2 Wanshun Liu,3 Wen Liu3 1General Hospital of Armed Police Forces, Beijing, People’s Republic of China; 2Beijing Tongren Eye Center, Capital Medical University, Beijing, People’s Republic of China 3Ocean University of China, Qingdao, People’s Republic of China Purpose: To investigate the potential usage of biological delivery membranes containing mitomycin C (MMC or 5-fluorouracil (5-FU in the construction of glaucoma-filtering blebs, and to evaluate their safety and efficacy. Methods: Chitosan was selected as the biological membrane carrier to prepare sustained-released membranes. Twelve micrograms of 5-FU or MMC was covalently conjugated onto the membranes by solvent volatilization. Rabbits underwent glaucoma filtration surgery and were randomly allocated into one of the four treatment regimens: glaucoma filtration operation with no implantation of chitosan membrane group (as control, drug-free chitosan membrane implantation group (blank/placebo group, membrane containing 5-FU treatment group (5-FU group, and membrane containing MMC treatment group (MMC group. Each group consisted of 12 rabbits. Intraocular pressure (IOP was measured and evaluated over a 28-day period follow-up preoperatively, then after surgery on days 1, 3, 5, 7, 14, 21, and 28 by Tono-Pen. The aqueous humor was analyzed in each experimental and control groups at days 4, 6, 8, 10, 12, 14, 16, and 20 after operation. Bleb survival and anterior segment were examined with a slit lamp microscope and photographed simultaneously. Two rabbits from each group were killed on day 28 and eight eye samples obtained for histopathological study. Corneas and lenses were examined by transmission and scanning electron microscopy. Results: Both 5-FU and MMC significantly prolonged bleb survival compared with control groups. The filtering bleb’s survival period was significantly more prolonged in the MMC and 5-FU groups (maintained 14 days than the

  5. Radiochemotherapy including cisplatin alone versus cisplatin + 5-fluorouracil for locally advanced unresectable stage IV squamous cell carcinoma of the head and neck

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    Tribius, Silke; Kilic, Yasemin [Dept. of Radiation Oncology, Univ. Medical Center Hamburg-Eppendorf, Hamburg (Germany); Kronemann, Stefanie [Dept. of Radiation Oncology, Univ. Hospital Schleswig-Holstein, Campus Luebeck (Germany); Schroeder, Ursula [Dept. of Head and Neck Surgery, Univ. Hospital Schleswig-Holstein, Campus Luebeck (Germany); Hakim, Samer [Dept. of Oro-Maxillo-Facial Surgery, Univ. Hospital Schleswig-Holstein, Campus Luebeck (Germany); Schild, Steven E. [Dept. of Radiation Oncology, Mayo Clinic, Scottsdale, AZ (United States); Rades, Dirk [Dept. of Radiation Oncology, Univ. Medical Center Hamburg-Eppendorf, Hamburg (Germany); Dept. of Radiation Oncology, Univ. Hospital Schleswig-Holstein, Campus Luebeck (Germany)

    2009-10-15

    Background and purpose: the optimal radiochemotherapy regimen for advanced head-and-neck cancer is still debated. This nonrandomized study compares two cisplatin-based radiochemotherapy regimens in 128 patients with locally advanced unresectable stage IV squamous cell carcinoma of the head and neck (SCCHN). Patients and methods: concurrent chemotherapy consisted of either two courses cisplatin (20 mg/m{sup 2}/d1-5 + 29-33; n = 54) or two courses cisplatin (20 mg/m{sup 2}/d1-5 + 29-33) + 5-fluorouracil (5-FU; 600 mg/m{sup 2}/d1-5 + 29-33; n = 74). Results: at least one grade 3 toxicity occurred in 25 of 54 patients (46%) receiving cisplatin alone and in 52 of 74 patients (70%) receiving cisplatin + 5-FU. The latter regimen was particularly associated with increased rates of mucositis (p = 0.027) and acute skin toxicity (p = 0.001). Seven of 54 (13%) and 20 of 74 patients (27%) received only one chemotherapy course due to treatment-related acute toxicity. Late toxicity in terms of xerostomia, neck fibrosis, skin toxicity, and lymphedema was not significantly different. The 2-year locoregional control rates were 67% after cisplatin alone and 52% after cisplatin + 5-FU (p = 0.35). The metastases-free survival rates were 79% and 69%, respectively (p = 0.65), and the overall survival rates 70% and 51%, respectively (p = 0.10). On multivariate analysis, outcome was significantly associated with performance status, T-category, N-category, hemoglobin level prior to radiotherapy, and radiotherapy break > 1 week. Conclusion: two courses of fractionated cisplatin (20 mg/m{sup 2}/day) alone appear preferable, as this regimen resulted in similar outcome and late toxicity as two courses of cisplatin + 5-FU, but in significantly less acute toxicity. (orig.)

  6. Vaccination of colorectal cancer patients with TroVax given alongside chemotherapy (5-fluorouracil, leukovorin and irinotecan) is safe and induces potent immune responses.

    Science.gov (United States)

    Harrop, Richard; Drury, Noel; Shingler, William; Chikoti, Priscilla; Redchenko, Irina; Carroll, Miles W; Kingsman, Susan M; Naylor, Stuart; Griffiths, Richard; Steven, Neil; Hawkins, Robert E

    2008-07-01

    Modified vaccinia Ankara (MVA) encoding the tumor antigen 5T4 (TroVax) has been evaluated in an open label phase II study in metastatic colorectal cancer patients. The primary objective was to assess the safety and immunogenicity of TroVax injected before, during and after treatment with 5-fluorouracil, leukovorin and irinotecan. TroVax was administered to 19 patients with metastatic colorectal cancer. Twelve patients had blood samples taken following each of the six injections and were considered to be evaluable for assessment of immunological responses. Both antibody and cellular responses specific for the tumor antigen 5T4 and the viral vector MVA were monitored throughout the study. Administration of TroVax alongside chemotherapy was safe and well tolerated with no SAEs attributed to the vaccine and no enhancement of chemo-related toxicity. Of the 12 patients who were evaluable for assessment of immune responses, ten mounted 5T4-specific antibody responses with titers ranging from 10 to > 5,000. IFNgamma ELISPOT responses specific for 5T4 were detected in 11 patients with frequencies exceeding one in 1,000 PBMCs in five patients. Eight patients presented with elevated circulating CEA concentrations, six of whom showed decreases in excess of 50% during chemotherapy and four had CEA levels which remained stable for > 1 month following completion of chemotherapy. Of the 19 intention to treat (ITT) patients, one had a CR, six had PRs and five had SD. Potent 5T4-specific cellular and/or humoral immune responses were induced in all 12 evaluable patients and were detectable in most patients during the period in which chemotherapy was administered. These data demonstrate that TroVax can be layered on top of chemotherapy regimens without any evidence of enhanced toxicity or reduced immunological or therapeutic efficacy. PMID:18060404

  7. Comparative study of the effects of PEGylated interferon-α2a versus 5-fluorouracil on cancer stem cells in a rat model of hepatocellular carcinoma.

    Science.gov (United States)

    Motawi, Tarek Kamal; El-Boghdady, Noha Ahmed; El-Sayed, Abeer Mostafa; Helmy, Hebatullah Samy

    2016-02-01

    Cancer stem cells (CSCs) in hepatocellular carcinoma (HCC) possess tumor-initiating, metastatic, and drug resistance properties. This study was conducted to evaluate the effects of PEGylated interferon-α2a (PEG-IFN-α2a) and 5-fluorouracil (5-FU) on the expression of CSC markers and on specific pathways that contribute to the propagation of CSCs in HCC. HCC was initiated in rats using a single intraperitoneal dose of diethylnitrosamine (DENA) (200 mg/kg) and promoted by weekly subcutaneous injections of carbon tetrachloride (CCl4) for 6 weeks. After the appearance of dysplastic nodules, the animals received PEG-IFN-α2a or 5-FU for 8 weeks. CSC markers (OV6, CD90) and molecules related to transforming growth factor β (TGF-β) and other signaling pathways were assessed in hepatic tissues. The PEG-IFN-α2a treatment effectively suppressed the hepatic expression of OV6 and CD90, ameliorated the diminished hepatic expression of TGF-β receptor II (TGF-βRII) and β2-spectrin (β2SP), and significantly reduced the elevated hepatic expression of TGF-β1, interleukin6 (IL6), signal transducer and activator of transcription3 (STAT3), and vascular endothelial growth factor (VEGF). In contrast, the 5-FU treatment failed to reduce the overexpression of CSC markers and barely affected the disrupted TGF-β signaling. Furthermore, it had no effect on angiogenesis or nitrosative stress. PEG-IFN-α2a, but not 5-FU, could reduce the propagation of CSCs during the progression of HCC by upregulating the disrupted TGF-β signaling, suppressing the IL6/STAT3 pathway and reducing angiogenesis. PMID:26304505

  8. Preventive effect of Daiokanzoto (TJ-84 on 5-fluorouracil-induced human gingival cell death through the inhibition of reactive oxygen species production.

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    Kaya Yoshida

    Full Text Available Daiokanzoto (TJ-84 is a traditional Japanese herbal medicine (Kampo formulation. While many Kampo formulations have been reported to regulate inflammation and immune responses in oral mucosa, there is no evidence to show that TJ-84 has beneficial effects on oral mucositis, a disease resulting from increased cell death induced by chemotherapeutic agents such as 5-fluorouracil (5-FU. In order to develop effective new therapeutic strategies for treating oral mucositis, we investigated (i the mechanisms by which 5-FU induces the death of human gingival cells and (ii the effects of TJ-84 on biological events induced by 5-FU. 5-FU-induced lactate dehydrogenase (LDH release and pore formation in gingival cells (Sa3 cell line resulted in cell death. Incubating the cells with 5-FU increased the expression of nucleotide-binding domain and leucine-rich repeat containing PYD-3 (NLRP3 and caspase-1. The cleavage of caspase-1 was observed in 5-FU-treated cells, which was followed by an increased secretion of interleukin (IL-1β. The inhibition of the NLRP3 pathway slightly decreased the effects of 5-FU on cell viability and LDH release, suggesting that NLRP3 may be in part involved in 5-FU-induced cell death. TJ-84 decreased 5-FU-induced LDH release and cell death and also significantly inhibited the depolarization of mitochondria and the up-regulation of 5-FU-induced reactive oxygen species (ROS and nitric oxide (NO production. The transcriptional factor, nuclear factor-κB (NF-κB was not involved in the 5-FU-induced cell death in Sa3 cells. In conclusion, we provide evidence suggesting that the increase of ROS production in mitochondria, rather than NLRP3 activation, was considered to be associated with the cell death induced by 5-FU. The results also suggested that TJ-84 may attenuate 5-FU-induced cell death through the inhibition of mitochondrial ROS production.

  9. The Effect of Analogues of 1α,25-Dihydroxyvitamin D₂ on the Regrowth and Gene Expression of Human Colon Cancer Cells Refractory to 5-Fluorouracil.

    Science.gov (United States)

    Neska, Jacek; Swoboda, Paweł; Przybyszewska, Małgorzata; Kotlarz, Agnieszka; Bolla, Narasimha Rao; Miłoszewska, Joanna; Grygorowicz, Monika Anna; Kutner, Andrzej; Markowicz, Sergiusz

    2016-01-01

    This study aimed to evaluate the capacity of hypocalcemic analogues of 1α,25-dihydroxyvitamin D₂ (1,25D2) and 1α,25-dihydroxyvitamin D₃ (1,25D3) to inhibit regrowth and regulate the stemness-related gene expression in colon cancer cells undergoing renewal after exposure to 5-fluorouracil (5-FU). All of the tested analogues of 1,25D2 equally potently decreased the clonogenicity and the proliferative activity of HT-29 cells which survived the exposure to 5-FU, but differently regulated gene expression of these cells during their renewal. 1,25D2 and analogues (PRI-1907 and PRI-1917), as well as 1,25D3 and analogue PRI-2191, decreased the relative expression level of several stemness-related genes, such as NANOG, OCT3/4, PROM1, SOX2, ALDHA1, CXCR4, in HT-29/5-FU cells during their renewal, in comparison to untreated HT-29/5-FU cells. The other 1,25D2 analogues (PRI-1906 and PRI-1916) were not capable of downregulating the expression of these stemness-related genes as the analogues PRI-1907 and PRI-1917 did. All of the tested vitamin D analogues upregulated CDH1, the gene encoding E-cadherin associated with epithelial phenotype. Out of the series of analogues studied, side-chain branched analogues of 1,25D2 (PRI-1907, PRI-1917) and the analogue of 1,25D3 (PRI-2191) might be used to target cancer cells with stem-like phenotypes that survive conventional chemotherapy. PMID:27314328

  10. The Effect of Analogues of 1α,25-Dihydroxyvitamin D2 on the Regrowth and Gene Expression of Human Colon Cancer Cells Refractory to 5-Fluorouracil

    Directory of Open Access Journals (Sweden)

    Jacek Neska

    2016-06-01

    Full Text Available This study aimed to evaluate the capacity of hypocalcemic analogues of 1α,25-dihydroxyvitamin D2 (1,25D2 and 1α,25-dihydroxyvitamin D3 (1,25D3 to inhibit regrowth and regulate the stemness-related gene expression in colon cancer cells undergoing renewal after exposure to 5-fluorouracil (5-FU. All of the tested analogues of 1,25D2 equally potently decreased the clonogenicity and the proliferative activity of HT-29 cells which survived the exposure to 5-FU, but differently regulated gene expression of these cells during their renewal. 1,25D2 and analogues (PRI-1907 and PRI-1917, as well as 1,25D3 and analogue PRI-2191, decreased the relative expression level of several stemness-related genes, such as NANOG, OCT3/4, PROM1, SOX2, ALDHA1, CXCR4, in HT-29/5-FU cells during their renewal, in comparison to untreated HT-29/5-FU cells. The other 1,25D2 analogues (PRI-1906 and PRI-1916 were not capable of downregulating the expression of these stemness-related genes as the analogues PRI-1907 and PRI-1917 did. All of the tested vitamin D analogues upregulated CDH1, the gene encoding E-cadherin associated with epithelial phenotype. Out of the series of analogues studied, side-chain branched analogues of 1,25D2 (PRI-1907, PRI-1917 and the analogue of 1,25D3 (PRI-2191 might be used to target cancer cells with stem-like phenotypes that survive conventional chemotherapy.

  11. Comparative therapeutic efficacy of rhenium-188 radiolabeled-liposome and 5-fluorouracil in LS-174T human colon carcinoma solid tumor xenografts.

    Science.gov (United States)

    Hsu, Chin-Wei; Chang, Ya-Jen; Chang, Chih-Hsien; Chen, Liang-Cheng; Lan, Keng-Li; Ting, Gann; Lee, Te-Wei

    2012-10-01

    Nanoliposomes are important carriers capable of packaging drugs for various delivery applications. Rhenium-188-radiolabeled liposome ((188)Re-liposome) has potential for radiotherapy and diagnostic imaging. To evaluate the targeting of (188)Re-liposome, biodistribution, microSPECT/CT, whole-body autoradiography (WBAR), and pharmacokinetics were performed in LS-174T human tumor-bearing mice. The comparative therapeutic efficacy of (188)Re-liposome and 5-fluorouracil (5-FU) was assessed according to inhibition of tumor growth and the survival ratio. The highest uptake of (188)Re-liposome in LS-174T tumor was found at 24 hours by biodistribution and microSPECT/CT imaging, showing a positive correlation for tumor targeting of (188)Re-liposome using the Pearson's correlation analysis (r=0.997). Pharmacokinetics of (188)Re-liposome showed the properties of high circulation time and high bioavailability (mean residence time [MRT]=18.8 hours, area under the curve [AUC]=1371%ID/g·h). For therapeutic efficacy, the tumor-bearing mice treated with (188)Re-liposome (80% maximum tolerated dose [MTD], 23.7 MBq) showed better tumor growth inhibition and longer survival time than those treated with 5-FU (80% MTD, 144 mg/kg). The median survival time for mice treated with (188)Re-liposome (58.5 days; p0.05) and normal saline-treated mice (43.63 days). Dosimetry study revealed that the (188)Re-liposome did not lead to high absorbed doses in normal tissue, but did in small tumors. These results of imaging and biodistribution indicated the highly specific accumulation of tumor after intravenous (i.v.) injection of (188)Re-liposome. The therapeutic efficacy of radiotherapeutics of (188)Re-liposome have been confirmed in a LS-174T solid tumor animal model, which points to the potential benefit and promise of passive nanoliposome delivered radiotherapeutics for cancer treatment.

  12. [The mechanism of potentiation of the antitumor effect of 5-fluorouracil by methionine-free intravenous amino acid solution (AO-90) in rats].

    Science.gov (United States)

    Hibino, Y; Kawarabayashi, Y; Kohri, H; Ueda, N; Tsukagoshi, S

    1994-09-01

    AO-90, a methionine-free intravenous amino acid solution (7.43%) showed to potentiate the antitumor effect of 5-fluorouracil (5-FU) when concomitantly used as the nitrogen source in total parenteral nutrition (TPN) in Yoshida sarcoma (YS)-bearing rats. In the present experiment, this potentiation mechanism was studied by determining the serum methionine level and tumor methylenetetrahydrofolate (CH2FH4) content in YS-bearing Donryu rats given AO-90 (nitrogen 0.73g/kg on the 1st day and 1.46g/kg for the remaining 6 days) by TPN for 1 week. The rats were subcutaneously inoculated with 10(4) YS cells in the dorsum 3 days before the start of TPN. Inhibition of thymidylate synthase activity in tumor tissue after dosing of AO-90 (nitrogen 0.68g/kg on the 1st day and 1.36 g/kg for the remaining 6 days) by TPN along with daily intraperitoneal dosing of 5-FU (10 mg/kg) was also evaluated with the inoculation of 10(6) tumor cells. The results were compared with those in tumor-bearing rats given TPN with a commercially available amino acid solution containing methionine. On day 5 of TPN, the tumor-bearing rats given AO-90 showed a significantly lower serum methionine level than the control rats: 101 +/- 11 mumol/l versus 29 +/- 14 mumol/l (p methionine-containing TPN and 5-FU: 2.66 +/- 0.91 versus 5.12 +/- 2.11 (p < 0.05).

  13. Formation and characterization of β-cyclodextrin (β-CD) - polyethyleneglycol (PEG) - polyethyleneimine (PEI) coated Fe3O4 nanoparticles for loading and releasing 5-Fluorouracil drug.

    Science.gov (United States)

    Prabha, G; Raj, V

    2016-05-01

    In this work, β-cyclodextrin (β-CD) - polyethyleneglycol (PEG) - polyethyleneimine (PEI) coated iron oxide nanoparticles (Fe3O4-β-CD-PEG-PEI) were developed as drug carriers for drug delivery applications. The 5- Fluorouracil (5-FU) was chosen as model drug molecule. The developed nanoparticles (Fe3O4-β-CD-PEG-PEI) were characterized by various techniques such as Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), Scanning electron microscopy (SEM), transmission electron microscopy (TEM) and vibrating sample magnetometry (VSM). The average particles size range of 5-FU loaded Fe3O4-β-CD, Fe3O4-β-CD-PEG and Fe3O4-β-CD-PEG-PEI nanoparticles were from 151 to 300nm and zeta potential value of nanoparticles were from -43mV to -20mV as measured using Malvern Zetasizer. Finally, encapsulation efficiency (EE), loading capacity (LC) and in-vitro drug release performance of 5-FU drug loaded Fe3O4-β-CD, Fe3O4-β-CD-PEG and Fe3O4-β-CD-PEG-PEI nanoparticles was evaluated by UV-vis spectroscopy. In-vitro cytotoxicity tests investigated by MTT assay indicate that 5-FU loaded Fe3O4-β-CD-PEG-PEI nanoparticles were toxic to cancer cells and non-toxic to normal cells. The in-vitro release behavior of 5-FU from drug (5-FU) loaded Fe3O4-β-CD-PEG-PEI composite at different pH values and temperature was studied. It was found that 5-FU was released faster in pH 6.8 than in the acidic mediums (pH 1.2), and the released quantity was higher. Therefore, the newly prepared Fe3O4-β-CD-PEG-PEI carrier exhibits a promising potential capability for anticancer drug delivery in tumor therapy.

  14. Degradation of cyclophosphamide and 5-fluorouracil by UV and simulated sunlight treatments: Assessment of the enhancement of the biodegradability and toxicity.

    Science.gov (United States)

    Lutterbeck, Carlos Alexandre; Wilde, Marcelo Luís; Baginska, Ewelina; Leder, Christoph; Machado, Ênio Leandro; Kümmerer, Klaus

    2016-01-01

    The presence of pharmaceuticals in the environment has triggered concern among the general population and received considerable attention from the scientific community in recent years. However, only a few publications have focused on anticancer drugs, a class of pharmaceuticals that can exhibit cytotoxic, genotoxic, mutagenic, carcinogenic and teratogenic effects. The present study investigated the photodegradation, biodegradation, bacterial toxicity, mutagenicity and genotoxicity of cyclophosphamide (CP) and 5-fluorouracil (5-FU). The photodegradation experiments were performed at a neutral to slight pH range (7-7.8) using two different lamps (medium-pressure mercury lamp and a xenon lamp). The primary elimination of the parent compounds was monitored by means of liquid chromatography tandem mass spectrometry (LC-IT-MS/MS). NPOC (non-purgeable organic carbon) analyses were carried out in order to assess mineralization rates. The Closed Bottle Test (CBT) was used to assess ready biodegradability. A new method using Vibrio fischeri was adopted to evaluate toxicity. CP was not degraded by any lamp, whereas 5-FU was completely eliminated by irradiation with the mercury lamp but only partially by the Xe lamp. No mineralization was observed for the experiments performed with the Xe lamp, and a NPOC removal of only 18% was registered for 5-FU after 256 min using the UV lamp. Not one of the parent compounds was readily biodegradable in the CBT. Photo transformation products (PTPs) resulting from photolysis were neither better biodegradable nor less toxic than the parent compound 5-FU. In contrast, the results of the tests carried out with the UV lamp indicated that more biodegradable and non-toxic PTPs of 5-FU were generated. Three PTPs were formed during the photodegradation experiments and were identified. The results of the in silico QSAR predictions showed positive mutagenic and genotoxic alerts for 5-FU, whereas only one of the formed PTPs presented positive alerts

  15. Radiochemotherapy including cisplatin alone versus cisplatin + 5-fluorouracil for locally advanced unresectable stage IV squamous cell carcinoma of the head and neck

    International Nuclear Information System (INIS)

    Background and purpose: the optimal radiochemotherapy regimen for advanced head-and-neck cancer is still debated. This nonrandomized study compares two cisplatin-based radiochemotherapy regimens in 128 patients with locally advanced unresectable stage IV squamous cell carcinoma of the head and neck (SCCHN). Patients and methods: concurrent chemotherapy consisted of either two courses cisplatin (20 mg/m2/d1-5 + 29-33; n = 54) or two courses cisplatin (20 mg/m2/d1-5 + 29-33) + 5-fluorouracil (5-FU; 600 mg/m2/d1-5 + 29-33; n = 74). Results: at least one grade 3 toxicity occurred in 25 of 54 patients (46%) receiving cisplatin alone and in 52 of 74 patients (70%) receiving cisplatin + 5-FU. The latter regimen was particularly associated with increased rates of mucositis (p = 0.027) and acute skin toxicity (p = 0.001). Seven of 54 (13%) and 20 of 74 patients (27%) received only one chemotherapy course due to treatment-related acute toxicity. Late toxicity in terms of xerostomia, neck fibrosis, skin toxicity, and lymphedema was not significantly different. The 2-year locoregional control rates were 67% after cisplatin alone and 52% after cisplatin + 5-FU (p = 0.35). The metastases-free survival rates were 79% and 69%, respectively (p = 0.65), and the overall survival rates 70% and 51%, respectively (p = 0.10). On multivariate analysis, outcome was significantly associated with performance status, T-category, N-category, hemoglobin level prior to radiotherapy, and radiotherapy break > 1 week. Conclusion: two courses of fractionated cisplatin (20 mg/m2/day) alone appear preferable, as this regimen resulted in similar outcome and late toxicity as two courses of cisplatin + 5-FU, but in significantly less acute toxicity. (orig.)

  16. Fluoxetine counteracts the cognitive and cellular effects of 5-fluorouracil in the rat hippocampus by a mechanism of prevention rather than recovery.

    Directory of Open Access Journals (Sweden)

    Laura Lyons

    Full Text Available 5-Fluorouracil (5-FU is a cytostatic drug associated with chemotherapy-induced cognitive impairments that many cancer patients experience after treatment. Previous work in rodents has shown that 5-FU reduces hippocampal cell proliferation, a possible mechanism for the observed cognitive impairment, and that both effects can be reversed by co-administration of the antidepressant, fluoxetine. In the present study we investigate the optimum time for administration of fluoxetine to reverse or prevent the cognitive and cellular effects of 5-FU. Male Lister-hooded rats received 5 injections of 5-FU (25 mg/kg, i.p. over 2 weeks. Some rats were co-administered with fluoxetine (10 mg/kg/day, in drinking water for 3 weeks before and during (preventative or after (recovery 5-FU treatment or both time periods (throughout. Spatial memory was tested using the novel location recognition (NLR test and proliferation and survival of hippocampal cells was quantified using immunohistochemistry. 5-FU-treated rats showed cognitive impairment in the NLR task and a reduction in cell proliferation and survival in the subgranular zone of the dentate gyrus, compared to saline treated controls. These impairments were still seen for rats administered fluoxetine after 5-FU treatment, but were not present when fluoxetine was administered both before and during 5-FU treatment. The results demonstrate that fluoxetine is able to prevent but not reverse the cognitive and cellular effects of 5-FU. This provides information on the mechanism by which fluoxetine acts to protect against 5-FU and indicates when it would be beneficial to administer the antidepressant to cancer patients.

  17. 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

    Directory of Open Access Journals (Sweden)

    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

  18. Determination of phthalate esters in polyvinyl chloride infusion bag by stir bar sorptive extraction combined with GC.

    Science.gov (United States)

    Sun, Meng; Dai, Jinna; Wang, Xiaofan; Zhao, Xu; Bi, Kaishun; Chen, Xiaohui

    2012-12-01

    A novel, efficient, and sensitive stir bar sorptive extraction method coupled with GC for the detection of four kinds of phthalate esters in plasticized polyvinyl chloride infusion bag has been developed and validated. Some experimental parameters including stirring speed, stirring time, pH value, salt concentration, desorption mode, desorption solvents, and desorption time were investigated and optimized. Under optimum condition, the validated assay was found to be linear (r > 0.9945) and LODs were between 1.07 and 2.67 ng for the four analytes. The method exhibited excellent precision with RSD varied from 4.5 to 6.1% (n = 5). The recoveries of the four phthalate esters at two different concentrations ranged from 80.5 to 93.4%. The results showed that the validated method could meet the need of determination of targets and was successfully applied to the analysis of phthalate esters in real samples.

  19. Combined postoperative radiotherapy and weekly cisplatin infusion for locally advanced head and neck carcinoma: final report of a randomized trial

    International Nuclear Information System (INIS)

    Purpose: To report the final results of a prospective randomized trial that aimed to evaluate efficacy and toxicity of concomitant postoperative radiotherapy and Cisplatin infusion in patients with Stage III or IV squamous cell carcinoma of the head and neck and histological evidence of extracapsular spread of tumor in lymph node metastase(s). Methods and Materials: Radiotherapy was delivered using a daily dose of 1.7 Gy for the first 54 Gy and 1.8 to 2 Gy until the completion of the treatment. Cisplatin 50 mg i.v. with forced hydratation was given or not every week (i.e., seven to nine cycles) concurrently with radiotherapy. A total of 44 patients were treated by irradiation only (RT group) and 39 by irradiation with chemotherapy (CM group). Results: The RT group displayed a higher rate of loco-regional failures as compared to CM group (41 vs. 23%; p = 0.08). The overall survival, the survival corrected for deaths by intercurrent disease, and the disease-free survival were better in CM group as compared to RT group with statistically significant differences. Survival without loco-regional treatment failure was better in the CM group, the difference being close to the level of significance (p = 0.05). Survival without distant metastases were comparable in the two therapeutic groups. Ten severe late complications were observed, four in the RT group (17%) and six in the CM group (22%). Cox univariate analysis confirmed the importance of the therapeutic modality in predicting the overall survival, the survival corrected for deaths by intercurrent disease, and the disease-free survival. Conclusions: The present final report of this phase III study confirms preliminary results. The concomitant use of 50 mg weekly Cisplatin infusion and postoperative radiation improved loco-regional control and survival. No significant increase of late radiation complications was observed in the CM group

  20. INFUSION LOUNGE

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Infusion Lounge——颇具亚洲风情的的夜店——坐落于旧金山市区大受追捧的联合广场之上,福森酒店之下。此夜店兼具了酒吧与餐厅的功能,它将提供加州与亚洲风味融为一体的佳肴及优雅的环境和一流的服务。Infusion Lounge不仅为旧金山当地,也将为整个行业重新定义高消费夜生活的概念。

  1. Biomarker analysis of cetuximab plus oxaliplatin/leucovorin/5-fluorouracil in first-line metastatic gastric and oesophago-gastric junction cancer: results from a phase II trial of the Arbeitsgemeinschaft Internistische Onkologie (AIO

    Directory of Open Access Journals (Sweden)

    Luber Birgit

    2011-12-01

    Full Text Available Abstract Background The activity of the epidermal growth factor receptor (EGFR-directed monoclonal antibody cetuximab combined with oxaliplatin/leucovorin/5-fluorouracil (FUFOX was assessed in first-line metastatic gastric and oesophago-gastric junction (OGJ cancer in a prospective phase II study showing a promising objective tumour response rate of 65% and a low mutation frequency of KRAS (3%. The aim of the correlative tumour tissue studies was to investigate the relationship between EGFR gene copy numbers, activation of the EGFR pathway, expression and mutation of E-cadherin, V600E BRAF mutation and clinical outcome of patients with gastric and OGJ cancer treated with cetuximab combined with FUFOX. Methods Patients included in this correlative study (n = 39 were a subset of patients from the clinical phase II study. The association between EGFR gene copy number, activation of the EGFR pathway, abundance and mutation of E-cadherin which plays an important role in these disorders, BRAF mutation and clinical outcome of patients was studied. EGFR gene copy number was assessed by FISH. Expression of the phosphorylated forms of EGFR and its downstream effectors Akt and MAPK, in addition to E-cadherin was analysed by immunohistochemistry. The frequency of mutant V600E BRAF was evaluated by allele-specific PCR and the mutation profile of the E-cadherin gene CDH1 was examined by DHPLC followed by direct sequence analysis. Correlations with overall survival (OS, time to progression (TTP and overall response rate (ORR were assessed. Results Our study showed a significant association between increased EGFR gene copy number (≥ 4.0 and OS in gastric and OGJ cancer, indicating the possibility that patients may be selected for treatment on a genetic basis. Furthermore, a significant correlation was shown between activated EGFR and shorter TTP and ORR, but not between activated EGFR and OS. No V600E BRAF mutations were identified. On the other hand, an

  2. Intra-lateral septal infusions of folic acid alone or combined with various antidepressant drugs produce antidepressant-like actions in male Wistar rats forced to swim.

    Science.gov (United States)

    Molina-Hernández, Miguel; Téllez-Alcántara, N Patricia; Olivera-López, Jorge I; Jaramillo, M Teresa

    2012-01-10

    Intra-cerebral administrations of folic acid produce antidepressant-like effects; either alone or combined with several antidepressant drugs. However, the specific limbic structures implied in the antidepressant-like actions of folic acid are un-known. Thus, intra-lateral septal infusions of folic acid (5.0 nmol, Pimmobility by increasing swimming behavior in the forced swimming test (FST) of male Wistar rats. Conversely, desipramine (10.0 mg/kg, Pimmobility by increasing climbing behavior. Subthreshold doses of folic acid (2.5 nmol/intra-LSN) combined with subthreshold doses of folic acid (25.0 mg/kg, p.o., Pimmobility in the FST. These antidepressant-like actions, probably, were due to modifications of the serotonergic system since swimming behavior was increased and these effects were canceled by ketanserin.

  3. TIMP-1 Is Significantly Associated with Objective Response and Survival in Metastatic Colorectal Cancer Patients Receiving Combination of Irinotecan, 5-Fluorouracil, and Folinic Acid

    DEFF Research Database (Denmark)

    Sørensen, Nanna M; Byström, Per; Christensen, Ib Jarle;

    2007-01-01

    that patients with low plasmaTIMP-1had higher probability of obtaining an objective response [odds ratio (OR), 3.5; 95% confidence interval (95% CI), 1.4-8.5,P =0.007].CEAtreatedas a continuous variablewas also a statistically significantpredictorof no response (OR,1.3; 95%CI,1.0-1.7, P = 0.02, areaunder...

  4. The bioenergetic signature of isogenic colon cancer cells predicts the cell death response to treatment with 3-bromopyruvate, iodoacetate or 5-fluorouracil

    Directory of Open Access Journals (Sweden)

    Cuezva José M

    2011-02-01

    Full Text Available Abstract Background Metabolic reprogramming resulting in enhanced glycolysis is a phenotypic trait of cancer cells, which is imposed by the tumor microenvironment and is linked to the down-regulation of the catalytic subunit of the mitochondrial H+-ATPase (β-F1-ATPase. The bioenergetic signature is a protein ratio (β-F1-ATPase/GAPDH, which provides an estimate of glucose metabolism in tumors and serves as a prognostic indicator for cancer patients. Targeting energetic metabolism could be a viable alternative to conventional anticancer chemotherapies. Herein, we document that the bioenergetic signature of isogenic colon cancer cells provides a gauge to predict the cell-death response to the metabolic inhibitors, 3-bromopyruvate (3BrP and iodoacetate (IA, and the anti-metabolite, 5-fluorouracil (5-FU. Methods The bioenergetic signature of the cells was determined by western blotting. Aerobic glycolysis was determined from lactate production rates. The cell death was analyzed by fluorescence microscopy and flow cytometry. Cellular ATP concentrations were determined using bioluminiscence. Pearson's correlation coefficient was applied to assess the relationship between the bioenergetic signature and the cell death response. In vivo tumor regression activities of the compounds were assessed using a xenograft mouse model injected with the highly glycolytic HCT116 colocarcinoma cells. Results We demonstrate that the bioenergetic signature of isogenic HCT116 cancer cells inversely correlates with the potential to execute necrosis in response to 3BrP or IA treatment. Conversely, the bioenergetic signature directly correlates with the potential to execute apoptosis in response to 5-FU treatment in the same cells. However, despite the large differences observed in the in vitro cell-death responses associated with 3BrP, IA and 5-FU, the in vivo tumor regression activities of these agents were comparable. Conclusions Overall, we suggest that the

  5. MicroRNA-149 Increases the Sensitivity of Colorectal Cancer Cells to 5-Fluorouracil by Targeting Forkhead Box Transcription Factor FOXM1

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    Xiaobei Liu

    2016-07-01

    Full Text Available Background/Aims: Previously, we have shown that microRNA (miR-149 suppresses the migration and invasion of colorectal cancer (CRC cells by targeting forkhead box transcription factor (FOXM1. However, the roles of miR-149 in the chemoresistance of CRC cells to 5-Fluorouracil (5-FU is unclear. The aim of this study is to investigate whether miR-149 targets FOXM1 to regulate the 5-FU resistance of CRC. Methods: The qRT-PCR assay was performed to detect the expression of miR-149 in 5-FU-resistant CRC cells (HCT-8/5-FU and LoVo/5-FU and their parental CRC cells (HCT-8 and LoVo. Also, the effects of miR-149 expression on the sensitivity of CRC cells to 5-FU were determined by gain- and loss-of-function assays. Finally, whether miR-149 regulates the 5-FU resistance of CRC cells by targeting the mammalian Forkhead Box M1 (FOXM1 was investigated. Results: The expression of miR-149 was significantly downregulated in 5-FU-resistant CRC cells in comparison with their parental CRC cells. Re-expression of miR-149 could enhance the 5-FU sensitivity of 5-FU-resistant CRC cells by increasing 5-FU-inducing apoptosis, while downregulation of miR-149 could decrease the 5-FU sensitivity of parental CRC cells by decreasing 5-FU-inducing apoptosis. In addition, the luciferase assay indicated that miR-149 could bind to the 3'-UTR sequence of FOXM1 mRNA. The silencing of FOXM1 could mimic the effect of miR-149 upregulation on the 5-FU resistance of 5-FU-resistant CRC cells. Furthermore, the expression of miR-149 in the 5-FU-responding CRC tissues was significantly higher than that in the non-responding tissues and inversely correlated with FOXM1 mRNA level. Conclusions: MiR-149 reverses the resistance of CRC cells to 5-FU by directly targeting FOXM1. Thus, targeting miR-149/FOXM1 signaling will be a potential strategy in the treatment of 5-FU-chemoresistant CRC.

  6. Intra-arterial infusion of radiosensitizer (BUdR) combined with hypofractionated irradiation and chemotherapy for primary treatment of osteogenic sarcoma

    International Nuclear Information System (INIS)

    Combined modality treatment was given in nine patients of osteogenic sarcoma wherein the tumor was unresectable because of location or amputation was refused. This alternative to massive surgery comprised hypofractionated irradiation, intra-arterial infusion of the radiosensitizer 5'-bromodeoxyuridine (BUdR) and adjuvant systemic chemotherapy. Local control was achieved in seven of the nine patients. Four survived, all without evidence of disease at 6, 7.1, 8.8, and 10.5 years after completion of irradiation. Pulmonary metastases developed in six patients - of whom one survives, following high-dose pulmonary irradiation and additional chemotherapy. Significant soft-tissue injury occurred in five patients. On the basis of our experience, the authors believe that new approaches using modifications of external beam irradiation with different fractionation schedules or better radiosensitizing compounds may hold promise for patients with non-resectable osteosarcoma

  7. Bronchial artery infusion of Gemcitabine and Cisplatin combined with systemic chemotherapy for advanced non-small cell lung cancer: its short-term efficacy

    International Nuclear Information System (INIS)

    Objective: To assess the short-term efficacy of bronchial artery infusion (BAI) of Gemcitabine (GEM) plus Cisplatin (DDP) combined with systemic chemotherapy of GEM for advanced non-small cell lung cancer (NSCLC). Methods: A total of 60 patients with pathologically proved primary NSCLC were randomly selected. BAI with GEM (1000 mg/m2) and DDP (DDP 50 mg/m2) was performed on the first day, and systemic chemotherapy of GEM (1000 mg/m2) was carried out on the eighth day. The clinical results were analyzed. Results: Of the 60 patients, CR, PR, SD and PD were obtained in 3, 35, 17 and 5, respectively, with an overall effective rate of 63%. Twenty-two patients had adenocarcinoma and the effective rate of them was 45%. Thirty-eight patients had squamous cell carcinoma and their effective rate was 74%. The difference in the effective rate between the above two pathologic types was significant (P<0.05). Central type lung cancer was seen in 37 cases, their effective rate was 73%. The peripheral type lung cancer was seen in the remaining 23 patients and the effective rate was 48%. The difference in the effective rate was statistically significant between the central type and the peripheral type (P<0.05). Conclusion: The combination of bronchial artery infusion with systemic chemotherapy by using GP plan is an effective, feasible approach in the treatment of advanced non-small cell lung cancer. The short-term efficacy of the treatment bears a close relationship to the anatomical location and pathological type of the cancer. (authors)

  8. Early evaluation for treatment efficacy of 5-fluorouracil and hyperthermia on HCT-116 colon cancer cells by fluorine-18-fluorodeoxyglucose uptake

    Institute of Scientific and Technical Information of China (English)

    WANG Zhen-xin; ZHANG Bin; DENG Sheng-ming; CHEN Shao-ji

    2012-01-01

    Backgroud Fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography imaging can be used to assess the treatment efficacy of chemotherapy and prognosis.The aim of this study was to determine the uptake rate of 18F-FDG in colon cancer HCT-116 cells,and to evaluate the treatment efficacy of chemotherapy,hyperthermia and thermo-chemotherapy through the uptake inhibition rate of 18F-FDG.Methods The uptake rate of 18F-FDG in HCT-116 ceils was determined at various experimental conditions.The inhibition rate of cell growth,uptake rate of 18F-FDG and uptake inhibition rate of l8F-FDG in HCT-116 cells treated with 5-fluorouracil (5-FU) at various concentrations were determined.In HCT-116 cells subjected to chemotherapy (5-FU,100 μg/ml),hyperthermia (43℃,40 minutes) and thermo-chemotherapy for 24 hours,the inhibition rate of cell growth and uptake inhibition rate of 18F-FDG were determined; early apoptosis,the morphology and ultrastructure of HCT-116 cells were examined; and the contents of glucose and lactate dehydrogenase (LDH) in the cell culture medium of HCT-116 cells were determined.One-way analysis of variance (ANOVA) and correlation analyses were conducted by using SPSS 16.0 software.Results The uptake rate of 18F-FDG in HCT-116 cells was (44.25±2.19)%.Under the condition of adding 5-FU at various concentrations for 24 hours,the uptake rate of 18F-FDG was negatively correlated with 5-FU dosage (r=-0.879,P <0.01); the inhibition rate of cell growth revealed a positive correlation with the uptake inhibition rate of 18F-FDG (r=0.831,P <0.01).In HCT-116 cells subjected to hyperthermia,chemotherapy,and thermo-chemotherapy for 24 hours,the uptake inhibition rates of 18F-FDG were (12.94±2.80)%,(28.25±4.59)%,and (21.60±3.68)%,respectively.The early apoptotic rates of HCT-116 cells were (9.80±0.16)%,(19.80±2.40)%,and (15.70±1.80)%,respectively.Moreover,the contents of glucose and LDH in cell culture medium of HCT-116 cells after

  9. Reduction of the minimum alveolar concentration of isoflurane in dogs using a constant rate of infusion of lidocaine-ketamine in combination with either morphine or fentanyl.

    Science.gov (United States)

    Aguado, Delia; Benito, Javier; Gómez de Segura, Ignacio A

    2011-07-01

    The objective of this study was to determine the effects of a constant rate of infusion of lidocaine and ketamine in combination with either morphine or fentanyl on the minimum alveolar concentration of isoflurane (MAC(ISO)) during ovariohysterectomy in dogs. Female dogs (n=44) were premedicated with acepromazine and midazolam. Anaesthesia was induced with propofol and maintained with isoflurane. Dogs received ketamine (0.6 mg/kg/h) and lidocaine (3 mg/kg/h) together with morphine (0.24 mg/kg/h; MLK) or fentanyl (0.0036 mg/kg/h; FLK). The control group received Ringer's lactate solution. A skin incision was used as the noxious stimulus. The MAC(ISO) value was obtained with Dixon's up-and-down method. MAC(ISO) was 0.7±0.0 vol.% in the control group, 0.3±0.0 vol.% in the MLK group (45% MAC reduction) and 0.0±0.0 vol.% in the FLK group (97% MAC reduction). A combination of fentanyl with lidocaine and ketamine decreased the MAC(ISO) in dogs; this decrease was more pronounced than that produced by morphine, lidocaine and ketamine. PMID:20594878

  10. [A long-surviving patient with Stage IV breast cancer with no recurrence after combined therapy of medroxy progesterone acetate (MPA) and intra-arterial infusion chemotherapy].

    Science.gov (United States)

    Yamada, Takeshi; Yuyama, Yuichi; Okazaki, Yutaka

    2004-09-01

    The patient is a 42-year-old woman who had advanced (Stage IV) right breast cancer with contralateral supraclavicular lymph node metastasis. She was treated with the combined use of MPA and the intra-arterial infusion chemotherapy. We administered EPI into the left subclavian artery and the right internal thoracic artery. Total dose of EPI was 210 mg. MPA was administered po at 1,200 mg/day daily. During the chemotherapy, she experienced only grade 2 alopecia. After the chemotherapy, the regressive change was noted in the primary lesion. The clinical response was evaluated CR. She underwent right modified mastectomy and the resection of contralateral supraclavicular lymph nodes. Although the clinical response was very good, the pathological effect was only Grade 1b. Eight years have passed since the operation, and the patient is still alive with no sign of recurrence. It is suggested that this combination therapy may be useful for advanced breast cancer and the like. PMID:15446562

  11. EMJH medium with 5-fluorouracil and nalidixic acid associated with serial dilution technique used to recover Leptospira spp from experimentally contaminated bovine semen Meio de EMJH com 5-fluorouracil e ácido nalidíxico associado a técnica das diluições seriadas usados para recuperar Leptospira spp do sêmen bovino experimentalmente contaminado

    Directory of Open Access Journals (Sweden)

    Fabiana Miraglia

    2009-03-01

    Full Text Available Bovine semen experimentally contaminated with Leptospira santarosai serovar Guaricura was submitted to the modified EMJH medium with 5-fluorouracil (300mg/L and nalidixic acid (20mg/L, named as "selective medium" and using the serial dilution technique, in order to evaluate the percentage of recovery of the added microorganism. The selective EMJH medium was found with higher percentage of recovery of leptospiras and minor losses of samples due to contamination with opportunistic microorganisms than the non-selective EMJH medium: 151/376 (40.0% of positive growth; and 38/376 (10.0% contamination and 58/376 (15% and 129/376 (34.0%, respectively. These results were statistically significant (pSêmen bovino experimentalmente contaminado com a estirpe Leptospira santarosai Sorovar Guaricura foi utilizado para verificar a porcentagem de recuperação de leptospiras, utilizando o meio de EMJH com 5-fluorouracil (300 mg/L e ácido nalidíxico (20 mg/L, denominado "meio seletivo", associado à técnica das diluições seriadas. O meio seletivo EMJH foi encontrado com porcentagem de recuperação mais elevada e com menos perda de amostras devido à contaminação com microorganismos oportunistas quando comparado com o meio EMJH não seletivo, que foram encontrados, respectivamente, com 151/376 (40.0% de crescimento positivo e 38/376 (10.0% de contaminação, 58/376 (15% e 129/376 (34.0%. Estes resultados foram estatíticamente significantes (p<0, 0001; Fisher. Diferenças foram encontradas quando as freqüências de leptospiras recuperadas foram comparadas com a técnica de diluição seriada (10-1 a 10-4 e entre os meios seletivo e não-seletivo, em diferentes níveis de diluição. À diluição de 1/10, as porcentagens encontradas foram (0%, 0/80 e (38%, 30/80; à diluição 1/100, (3%, 2/80 e (49%, 39/80; e à diluição 1/1000, (25%, 20/80 e (50%, 40/80, respectivamente. A porcentagem de recuperação de leptospiras foi diretamente proporcional

  12. Effect of Infusions of Non-Antibiotic Antibacterials Alone and in Combination with Cephradine on Milk Yield of Buffaloes Affected with Clinical Mastitis

    Directory of Open Access Journals (Sweden)

    M. Yousaf*, G. Muhammad1, M. Z. Khan2 and S. U. Rahman3

    2010-01-01

    Full Text Available The objective of the present study was to evaluate the effect of four non-antibiotic antibacterials alone or in combination with cephradine in buffaloes on milk yield of mastitis affected quarters. For this purpose, 270 clinically mastitic quarters were grouped in randomized pattern. Non-antibiotic antibacterials viz., 2.5% chlorpromazine (2 ml, 4% lidocaine (10 ml, 10% povidone-iodine (10 ml and 99.5% dimethylsulphoxide (20 ml alone and in combination with first generation cephalosporin (cephradine 500 mg were instilled into clinically mastitic quarters daily for five days. The group administered cephradine alone served as control. Mean milk yield (L/quarter per day was recorded before administration of treatment and over a period of 4 weeks post initiation of treatment. Among the 4 non-antibiotic antibacterials tested alone, chlorpromazine (CPZ showed significantly higher (P<0.05 recuperative effect on the milk yield of clinically mastitic quarters of dairy buffaloes. However, dimethylsulphoxide (DMSO when infused alone, further aggravated (P<0.05 the milk yield loss, indicating negative effect on milk yield improvement. Adjuncting cephradine with each of the non-antibiotic antibacterials, the lidocaine-cephradine group showed the highest effect (p<0.05 on net recovery of milk yield on day 28 post initiation of treatment. It was concluded that that CPZ can be used in clinical mastitis in buffaloes as a low cost alternative to expensive branded antibiotics. Further, the use of lidocaine with cepheradnie was superior to all other combination regimens in milk yield recovery.

  13. Orthotopic liver transplantation after the combined use of locoregional therapy and sorafenib for advanced hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Yoo EJ

    2013-06-01

    Full Text Available Eun Jin Yoo,1,* Hye Sun Shin,1,* Seung Up Kim,1,2,7 Dong Jin Joo,3,4 Jun Yong Park,1,2,7 Gi Hong Choi,3 Do Young Kim,1,2,7 Sang Hoon Ahn,1,2,7 Jinsil Seong,5 Myung Joo Koh,6 Kwang-Hyub Han,1,2,7 Chae Yoon Chon1,2,7 1Department of Internal Medicine, 2Institute of Gastroenterology, 3Department of Surgery, 4Research Institute for Transplantation, 5Department of Radiation Oncology, 6Department of Pathology, Yonsei University College of Medicine, Seoul, South Korea; 7Liver Cirrhosis Clinical Research Center, Seoul, South Korea *These authors contributed equally to this work Abstract: We herein report a patient with advanced hepatitis B virus-related hepatocellular carcinoma (HCC beyond the Milan criteria. He underwent orthotopic liver transplantation after successful HCC downstaging that satisfied the University of California, San Francisco criteria, using concurrent chemoradiation therapy with a combination of repeated hepatic arterial infusion chemotherapy (HAIC and sorafenib. A 52-year-old male was diagnosed with advanced hepatitis B virus-related HCC beyond the Milan criteria. He underwent concurrent chemoradiation therapy (50 Gy with 20 fractions over 5 weeks with HAIC using 5-fluorouracil at a dose of 500 mg/day, which was administered during the first and fifth weeks of radiation therapy as an initial treatment modality. This was followed by the combined use of HAIC using 5-fluorouracil (500 mg/m2 for 5 hours on days 1–3 and cisplatin (60 mg/m2 for 2 hours on day 2 every 4 weeks (twelve cycles and sorafenib (from the third to the twelfth cycle of HAIC to treat the remaining HCC. Because a remarkable decrease in the tumor burden that satisfied the University of California, San Francisco criteria was observed after these combination treatments, the patient underwent orthotopic liver transplantation with curative aim and survived for 11 months without evidence of HCC recurrence. Keywords: hepatocellular carcinoma, liver transplantation

  14. Combined MTX{center_dot}5-FU{center_dot}CDGP for the treatment of head and neck cancer

    Energy Technology Data Exchange (ETDEWEB)

    Sakoda, Takema; Kitano, Hiroya [Tottori Univ., Yonago (Japan). Faculty of Medicine; Saitoh, Yuko; Ikeda, Hiroki; Dake, Yoshihiro; Enomoto, Tadao [Japanese Red Cross Society Wakayama Medical Center (Japan); Seno, Satoshi [Shiga Univ. of Medical Science, Otsu (Japan); Kawano, Atsushi [Tokyo Medical Coll. (Japan)

    2003-05-01

    Combination chemotherapy including 5-fluorouracil (5-FU) and nedaplatin (CDGP) with methotrexate (MTX) and leucovorin (LV) was administered for modulation in patients with head and neck cancer. We treated 19 patients with MTX{center_dot}5-FU{center_dot}CDGP consisting of 150 mg/body of MTX on day 1 followed by a 3-day continuous infusion of 5-FU at 3,500 mg/m{sup 2} and 17 injections of LV at 15 mg and infusion of CDGP at 100 mg/m{sup 2}. Six patients had recurrent head and neck cancer, and 13 had newly diagnosed disease. Eleven of the new patients were concurrently treated with radiation therapy. Treatment-associated toxicity was significant, including mucositis and myelosuppression, but acceptable. Sixteen patients were eligible for evaluation of response. The overall complete response rate was 75.0% (12/16). Patients treated with radiotherapy had a 90.0% (9/10) overall complete response rate. (author)

  15. Usefulness of thallium-201 myocardial SPECT using dipyridamole infusion combined with low level exercise for the detection of the ischemic heart disease

    International Nuclear Information System (INIS)

    To evaluate the usefulness of thallium-201 myocardial SPECT using dipyridamole infusion combined with low level exercise (Dp-method) for the detection of the ischemic heart disease, we performed both Dp-method and maximum physical exercise SPECT (Ex-method) in the same patients, and compared the results obtained by the two methods. In the visual evaluation, the detectability of each stenotic coronary territory by Dp-method tended to be higher than that by Ex-method (accuracy 71% vs 67%). The severity of the defect and the degree of the redistribution were higher by Dp-method than those by Ex-method. The washout rate (WR) analysis in 14 angina pectoris patients showed the detectability (accuracy) by Dp-method to be significantly higher than that by Ex-method (86% vs 64%; p<0.05). In comparison of mean WR values in normal subjects (10 cases for Dp-method and other 8 cases for Ex-method), mean WR by Dp-method was as high as that by Ex-method and the deviation of WR value among subjects was very small. This was probably due to the effect of the low level exercise. These results suggested that Dp-method was more excellent than Ex-method in the evaluation of the ischemic heart disease, and was a useful method of the daily routine work. The incidence of chest symptom and the electrocardiographic ST-depression was as high by Dp-method as that by Ex-method. The filling defects in Dp-method were thought to be induced not only by the difference in the relative increase of the myocardial perfusion, but also by the myocardial ischemia. (author)

  16. Failure of low-dose recombinant human IL-2 to support the survival of virus-specific CTL clones infused into severe combined immunodeficient foals: lack of correlation between in vitro activity and in vivo efficacy

    OpenAIRE

    Mealey, Robert H.; Littke, Matt H.; Leib, Steven R.; Davis, William C.; McGuire, Travis C.

    2007-01-01

    Although CTL are important for control of lentiviruses, including equine infectious anemia virus (EIAV), it is not known if CTL can limit lentiviral replication in the absence of CD4 help and neutralizing antibody. Adoptive transfer of EIAV-specific CTL clones into severe combined immunodeficient (SCID) foals could resolve this issue, but it is not known whether exogenous IL-2 administration is sufficient to support the engraftment and proliferation of CTL clones infused into immunodeficient ...

  17. Continuous hepatic arterial infusion therapy for nonresectable liver metastases from colorectal carcinoma

    International Nuclear Information System (INIS)

    Objective: To evaluate the efficacy of continuous hepatic arterial infusion chemotherapy to nonresectable liver metastases from colorectal carcinoma. Methods: Sixty-two patients with nonresectable liver metastases from colorectal carcinoma had been treated with radical operation, and the patients were divided into 2 groups. (1) Group A: 32 patients received continuous hepatic arterial infusion of 5-Fluorouracil (5-Fu)/Calcium Folinate (CF) and dexamethasone via drug delivery system (DDS) implanted percutaneously for 5 days every month. (2) Group B: 30 patients were treated through one bolus arterial infusion of 5-Fu-CF each month. Results: The response rate (CR + PR) of group A and B was 50.0% and 23.3%, respectively (P < 0.05); the survival rate for 1 and 2 years in group A was 65.6% and 39.3%, respectively, but that in group B was 36.7% and 11.5%, respectively (P < 0.05); the toxic reaction at liver, biliary, and gastrointestinal tract in group A was significantly lower than that in group B. Conclusion: Continuous hepatic arterial infusion of 5-Fu/CF and dexamethasone via DDS can prolong the survival rate and improve quality of life in patients with nonresectable liver metastases from colorectal carcinoma

  18. 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

  19. Thrombotic thrombocytopenic purpura-like syndrome associated with systemic lupus erythematosus--combined treatment with plasmapheresis and fresh frozen plasma infusion.

    OpenAIRE

    Lim, G. T.; Kim, S. S.; Park, S. H.; Choo, W. O.; Kang, D. H.; Park, I. S.; Chang, Y S; Y. S. YOON; Bang, B. K.

    1992-01-01

    We report on a patient with systemic lupus erythematosus, who, during the course of the illness, developed thrombotic thrombocytopenic purpura. In this case, the coexistence of these two conditions was confirmed by laboratory and pathologic findings. The infusion of fresh frozen plasma with plasmapheresis reversed the course of thrombotic thrombocytopenic purpura.

  20. 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

    Energy Technology Data Exchange (ETDEWEB)

    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

  1. 啤酒酵母RNA对5-氟尿嘧啶处理小鼠免疫功能的影响%Effects of Brewer's Yeast RNA on Immune Function in Mice Treated with 5-Fluorouracil

    Institute of Scientific and Technical Information of China (English)

    曾伶; 薛存宽; 何学斌; 陈艳雯; 许明旺; 李颖

    2009-01-01

    Objective To investigate the effects of brewer's yeast RNA on immune insufficiency in mice treated with 5-flu-orouracil. Methods The spleen and thymus index.phagocytosis rate of peritoneal macrophages,levels of serum hemolysin,contents of serum TNF-α and IL-2,and lymphocyte transformation rate were measured after mice were treated with 5-fluorouracil [25 mg/(kg ? d)] and/or brewer's yeast RNA [100 mg/(kg ? d) ,300 mg/(kg ? d) ,respectively] for 14 days. Results The phagocytosis rate of peritoneal macrophages, levels of serum TNF-α and IL-2. and spleen and thymus index in brewer' s yeast RNA-treated groups were significantly higher than those in 5-fluorouracil-treated group (P<0. 05,or P<0. 01). As compared with 5-fluorouracil-treated group,the levels of serum hemolysin and lymphocyte transformation rate were notably increased in brewer's yeast RNA-treated groups (P<0. 05,or P<0. 01). Conclusion Brewer's yeast RNA may increase the immune function of the mice with immune insufficiency.%目的 探讨啤酒酵母RNA对5-氟尿嘧啶(5-Fu)处理小鼠免疫功能的影响.方法 将小鼠随机分为空白组,5-氟尿嘧啶组,啤酒酵母RNA小剂量组、大剂量组[分别以啤酒酵母RNA 100 mg/(kg·d)、300 mg/(kg·d)灌胃给药];除空白组外,其余各组均以5-Fu 25 mg/(kg·d)灌胃.检测腹腔巨噬细胞吞噬率,血清溶血素形成水平、肿瘤坏死因子-α(TNF-α)及白细胞介素-2(IL-2)的含量和淋巴细胞转化率,计算脾指数及胸腺指数.结果 啤酒酵母RNA大、小剂量组均可明显提高5-氟尿嘧啶处理小鼠腹腔巨噬细胞吞噬率、血清TNF-α、IL-2水平,逆转脾指数、胸腺指数的萎缩,与5-氟尿嘧啶组相比差异具有统计学意义(P<0.05或P<0.01);啤酒酵母RNA大、小剂量组对5-氟尿嘧啶所致的血清溶血素形成水平低下和淋巴细胞转化率低下有明显的拮抗作用(P<0.05或P<0.01).结论 啤酒酵母RNA可提高免疫功能低下机体的免疫功能.

  2. Treatment of locally advanced carcinomas of head and neck with intensity-modulated radiation therapy (IMRT in combination with cetuximab and chemotherapy: the REACH protocol

    Directory of Open Access Journals (Sweden)

    Simon Christian

    2010-11-01

    Full Text Available Abstract Background Primary treatment of carcinoma of the oro-/hypopharynx or larynx may consist of combined platinum-containing chemoradiotherapy. In order to improve clinical outcome (i.e. local control/overall survival, combined therapy is intensified by the addition of the EGFR inhibitor cetuximab (Erbitux®. Radiation therapy (RT is carried out as intensity-modulated RT (IMRT to avoid higher grade acute and late toxicity by sparing of surrounding normal tissues. Methods/Design The REACH study is a prospective phase II study combining chemoradiotherapy with carboplatin/5-Fluorouracil (5-FU and the monoclonal epidermal growth factor-receptor (EGFR antibody cetuximab (Erbitux® as intensity-modulated radiation therapy in patients with locally advanced squamous-cell carcinomas of oropharynx, hypopharynx or larynx. Patients receive weekly chemotherapy infusions in the 1st and 5th week of RT. Additionally, cetuximab is administered weekly throughout the treatment course. IMRT is delivered as in a classical concomitant boost concept (bid from fraction 16 to a total dose of 69,9 Gy. Discussion Primary endpoint of the trial is local-regional control (LRC. Disease-free survival, progression-free survival, overall survival, toxicity, proteomic and genomic analyses are secondary endpoints. The aim is to explore the efficacy as well as the safety and feasibility of this combined radioimmunchemotherapy in order to improve the outcome of patients with advanced head and neck cancer. Trial registration ISRCTN87356938

  3. Failure of low-dose recombinant human IL-2 to support the survival of virus-specific CTL clones infused into severe combined immunodeficient foals: lack of correlation between in vitro activity and in vivo efficacy.

    Science.gov (United States)

    Mealey, Robert H; Littke, Matt H; Leib, Steven R; Davis, William C; McGuire, Travis C

    2008-01-15

    Although CTL are important for control of lentiviruses, including equine infectious anemia virus (EIAV), it is not known if CTL can limit lentiviral replication in the absence of CD4 help and neutralizing antibody. Adoptive transfer of EIAV-specific CTL clones into severe combined immunodeficient (SCID) foals could resolve this issue, but it is not known whether exogenous IL-2 administration is sufficient to support the engraftment and proliferation of CTL clones infused into immunodeficient horses. To address this question we adoptively transferred EIAV Rev-specific CTL clones into four EIAV-challenged SCID foals, concurrent with low-dose aldesleukin (180,000U/m2), a modified recombinant human IL-2 (rhuIL-2) product. The dose was calculated based on the specific activity on equine PBMC in vitro, and resulted in plasma concentrations considered sufficient to saturate high affinity IL-2 receptors in humans. Despite specific activity on equine PBMC that was equivalent to recombinant equine IL-2 and another form of rhuIL-2, aldesleukin did not support the engraftment and expansion of infused CTL clones, and control of viral load and clinical disease did not occur. It was concluded that survival of Rev-specific CTL clones infused into EIAV-challenged SCID foals was not enhanced by aldesleukin at the doses used in this study, and that in vitro specific activity did not correlate with in vivo efficacy. Successful adoptive immunotherapy with CTL clones in immunodeficient horses will likely require higher doses of rhuIL-2, co-infusion of CD4+ T lymphocytes, or administration of equine IL-2. PMID:17727961

  4. 甘草次酸修饰壳聚糖5-氟尿嘧啶对肝癌的抑制作用%The inhibition of synthe sis of glycyrrhetinic acid-modified chitosan 5-fluorouracil nanoparticles on liver cancer

    Institute of Scientific and Technical Information of China (English)

    徐宏智; 程明荣; 王勇; 何秉

    2014-01-01

    Objective It is to observe the targeting of glycyrrhetinic acid -modified chitosan 5 -fluorouracil nanoparti-cles ( GA-CTS/5-FU) to liver cancer in vitro and their inhibition on liver cancer cells in vivo .Methods The glycyrrhetinic acid -modified chitosan nano -materials ( GA-CTS) were synthesized glycyrrhetinic acid ( GA) combined with chitosan (CTS), GA-CTS/5-FU nanoparticles were GA -CTS combined with 5-fluorouracil (5-FU).The nanomaterials of tar-geting liver cancer were observed experimentally by confocal , the drug distribution of 5-FU were performed via liver cancer model, and their inhibitory effect on liver cancer cells in vitro .Results GA-CTS was successful synthesized with GA and GTS, which was confirmed by IR spectra and 1H-NMR.Combining GA-CTS and 5-FU (5-fluorouracil), we obtained GA-CTS/5-FU nanoparticle, with particle size of 193.7 nm, drug loading of 1.56% and polydispersity index of 0.003. GA-CTS/5-FU nanoparticle was a sustained release system showing three phases as quick , steady and slow release .The nanoparticle was observed to accumulate in liver .In vitro data demonstrated it had dose and time -dependent anti -cancer effect, and increased effective time against hepatic cancer cells was observed for GA -CTS/5-FU compared with 5-FU. Conclusion The GA-CTS/5-FU nanoparticles have sustained release effect , targeted therapy , and obvious inhibition of liv-er cancer .%目的:观察甘草次酸修饰壳聚糖5-氟尿嘧啶纳米粒的体内外肝癌的靶向性及其对肝癌细胞的抑制作用。方法将甘草次酸( GA)和壳聚糖( CTS)合成甘草次酸修饰的壳聚糖纳米材料甘草次酸修饰的壳聚糖(GA-CTS),并与5-氟尿嘧啶(5-Fu)合成GA-CTS/5-Fu纳米粒,通过共聚焦实验观察该纳米材料的肝癌靶向性,在原位肝癌模型中的药物分布,及其对肝癌细胞的体外抑制作用。结果 GA和CTS成功合成GA-CTS,并通过红外光谱和核磁共

  5. 晶状体脱位微创玻璃体灌注人工晶状体缝线固定术%Microinvasive vitreous infusion combined with transscleral suture fixation of intraocular lens for lens luxation

    Institute of Scientific and Technical Information of China (English)

    郭乾乾; 冯文国

    2015-01-01

    Objective To investigate the surgical skills and complications of microivasive vitreous infusion combined with transscleral suture fixation of intraocular lens for lens luxation.Methods Eight eye of 8 cases of lens luxation received vitreous infusion combined with intraocular lens suspension.The patients were followed up for 3-6 months,and the clinical efficacy was good.Results The intraocular lens was fixed to sulcus successfully in all eight cases and was in right position.The postoperative visual acuity was improved obviously,and no serious complications occurred.Conclusion Microinvasive vitreous infusion combined with primary intraocular lens suspension surgery for severe luxation of lens is safe and effective,but the operation skills and operation indications should be paid attention to.%目的 探讨晶状体脱位微创玻璃体灌注联合一期人工晶状体睫状沟缝线固定术的技巧和并发症.方法 8例(8眼)晶状体脱位,行微创玻璃体灌注联合一期人工晶状体睫状沟缝线固定术,术后随访3~6个月,临床疗效良好.结果 8例均1次睫状沟缝线固定成功,术后人工晶状体位正,视力明显提高,未见严重并发症.结论 微创玻璃体灌注联合一期人工晶状体睫状沟缝线固定式术治疗晶状体脱位安全有效,但应注意适应证和术中手术技巧.

  6. Determination of Bisphenol A in Infusion Used Combined Cover and Bisphenol A Migration into Infusion by HPLC%输液袋用聚碳酸酯组合盖中双酚A含量及双酚A向输液中迁移量的测定

    Institute of Scientific and Technical Information of China (English)

    王丹丹; 金宏

    2012-01-01

    目的 建立输液袋用聚碳酸酯组合盖中双酚A含量及双酚A向输液中迁移量的高效液相色谱测定法.方法 采用Diamosil-C18(4.6 mm×250 mm,5μm)色谱柱;流动相为甲醇-水(80∶20),检测波长为227 nm,流速1.0 mL·min-1.结果 双酚A在1.354~27.08 ng内呈良好的线性关系(r=0.9999);聚碳酸酯组合盖中双酚A含量和双酚A向输液中迁移量测定的平均回收率分别为91.7%(RSD=2.3%)和93.9%(RSD=1.8%).结论 该方法准确、灵敏、简便,适用于对输液袋用聚碳酸酯组合盖中双酚A含量及双酚A向输液中迁移量的测定.%OBJECTIVE To develop a method for determination of bisphenol A in Infusion Used Combined Cover and bisphenol A migration into infusion by HPLC. METHODS A Diamosil-C18column(4.6 mm×250 mm, 5 μm) and a DAD detector was adopted with methanol and water(80 : 20) as mobile phase. The wavelength was 227 nm, the flow rate was 1.0 mL·min‐1. RESULTS The method had a linear range in 1.354-27.08 ng (r=0.999 9). The average recovery of bisphenol A and bisphenol A migration was 91.7%(RSD=2.3%) and 93.9%(RSD=1.8%), respectively. CONCLUSION This method is accurate, sensitive, simple, and can be used for determination of bisphenol A and bisphenol A migration into infusion from Infusion Used Combined Cover.

  7. Simultaneous chemo-radiotherapy with Cisplatin/5-Fluorouracil/Leucovorin and hyperfractionated radiation for patients with advanced unresectable head and neck cancer

    Energy Technology Data Exchange (ETDEWEB)

    Reitmeier, M.; Pohlmann, H.; Schorer, H.; Hartenstein, R. [Munich-Harlaching City Hospital, Dept. of medicine IV, Munich (Germany)

    1994-12-31

    Thirty-one previously untreated patients with unresectable stage 3rd and 4th squamous cell carcinoma of the head and neck were treated with a simultaneous chemo-radiotherapy consisting of a cisplatin/5-fluoroucil/leucovorin-combination and of an accelerated split course radiotherapy. severe mucositis (77 %) and weight loss of 10 % or more (48 %) were the most common toxic effects. The overall response rate was 81 % with a 45 % complete response rate and a 36 % partial response rate. Median follow up time of the surviving patients was 50 %, the actuarial survival probability at 2 years was 63 % (Kaplan-Meier estimates).

  8. Simultaneous chemo-radiotherapy with Cisplatin/5-Fluorouracil/Leucovorin and hyperfractionated radiation for patients with advanced unresectable head and neck cancer

    International Nuclear Information System (INIS)

    Thirty-one previously untreated patients with unresectable stage 3rd and 4th squamous cell carcinoma of the head and neck were treated with a simultaneous chemo-radiotherapy consisting of a cisplatin/5-fluoroucil/leucovorin-combination and of an accelerated split course radiotherapy. severe mucositis (77 %) and weight loss of 10 % or more (48 %) were the most common toxic effects. The overall response rate was 81 % with a 45 % complete response rate and a 36 % partial response rate. Median follow up time of the surviving patients was 50 %, the actuarial survival probability at 2 years was 63 % (Kaplan-Meier estimates)

  9. Accelerated split-course radiotherapy and concomitant cis-platinum and 5-fluorouracil chemotherapy with folinic acid enhancement in unresectable head and neck cancer

    International Nuclear Information System (INIS)

    In patients suffering from locally advanced, unresectable squamous cell carcinoma (SCC) of the base of the tongue, the floor of the mouth, the mobile part of the tongue, the tonsils, the hypopharynx and the larynx radiotherapy yields poor results, due to local failure rather than to distant metastases. Since toxicity of radiotherapy and cytotoxic chemotherapy do not overlap entirely efforts were made to achieve better results combining these two treatment modalities. Clinical trials on simultaneous radiotherapy/chemotherapy focussed on two cytotoxic agents: Cis-dichlorodiammineplatinum(II) (cis-DDP) and 5-flourouracil (5-FU). Another approach to overcome the radioresistance of large SCC adopts accelerated fractionation. The potential tumor doubling time of sqamous cell carcinomas is about four days, and thus repopulation of surviving clonogenic tumor cells during fractionated radiotherapy may be the cause of poor treatment results. In this pilot study a twice daily fractionated split-course radiotherapy is combined with simultaneous administration of cis-DDP and 5-FU with folinic acid (FA) enhancement. (orig.)

  10. Accelerated split-course radiotherapy and concomitant cis-platinum and 5-fluorouracil chemotherapy with folinic acid enhancement in unresectable head and neck cancer

    Energy Technology Data Exchange (ETDEWEB)

    Wendt, T.G.; Wustrow, T.P.U.; Hartenstein, R.C.; Trott, K.R.

    1988-01-01

    In patients suffering from locally advanced, unresectable squamous cell carcinoma (SCC) of the base of the tongue, the floor of the mouth, the mobile part of the tongue, the tonsils, the hypopharynx and the larynx radiotherapy yields poor results, due to local failure rather than to distant metastases. Since toxicity of radiotherapy and cytotoxic chemotherapy do not overlap entirely efforts were made to achieve better results combining these two treatment modalities. Clinical trials on simultaneous radiotherapy/chemotherapy focussed on two cytotoxic agents: Cis-dichlorodiammineplatinum(II) (cis-DDP) and 5-flourouracil (5-FU). Another approach to overcome the radioresistance of large SCC adopts accelerated fractionation. The potential tumor doubling time of sqamous cell carcinomas is about four days, and thus repopulation of surviving clonogenic tumor cells during fractionated radiotherapy may be the cause of poor treatment results. In this pilot study a twice daily fractionated split-course radiotherapy is combined with simultaneous administration of cis-DDP and 5-FU with folinic acid (FA) enhancement.

  11. THERMAL-SENSITIVE BETA-CYCLODEXTRIN-CONTAINING POLY(N-ISOPROPYLACRYLAMIDE) HYDROGELS CROSSLINKED BY Si-O-Si BONDS -SYNTHESIS, CHARACTERIZATION AND PROLONGING IN VITRO RELEASE OF 5-FLUOROURACIL

    Institute of Scientific and Technical Information of China (English)

    Jian-tao Zhang; Shi-wen Huang; Ya-nan Xue; Ji Liu; Ren-xi Zhuo

    2005-01-01

    A series of novel p(N-isopropylacrylamide) (PNIPAM) hydrogels were synthesized by radical copolymerization of N-isopropylacrylamide (NIPAM) and 3-methacryloxypropyltrimethoxysilane (MPTMS). The copolymers were then crosslinked through hydrolysis of the siloxane in acetic acid/water mixed solvent. Beta-cyclodextrin (Beta-CD) was introduced into the polymeric networks by condensation of 3-glycidoxypropyltrimethoxysilane derived beta-cyclodextrin (KH560-beta-CD) with MPTMS under acidic condition. These gels were heterogeneous, porous and exhibited fast deswelling kinetics when the temperature was elevated to above lower critical solution temperature (LCST). The swelling ratios of the gels containing beta-CD at room temperature were higher than that of the normal PNIPAM hydrogel, which was caused by the lower crosslinking density in beta-CD contained gels. In comparison to that of the normal PNIPAM gel, the amount of loaded-drug in the hydrogel containing beta-CD was higher, and the release time of 5-fluorouracil (5-Fu) was prolonged, which was attributed to the formation of inclusion compounds between 5-Fu and beta-CD in gel network.

  12. Synthesis of 5-Fluorouracil conjugated LaF{sub 3}:Tb{sup 3+}/PEG-COOH nanoparticles and its studies on the interaction with bovine serum albumin: spectroscopic approach

    Energy Technology Data Exchange (ETDEWEB)

    Mangaiyarkarasi, Rajendiran; Chinnathambi, Shanmugavel; Aruna, Prakasarao; Ganesan, Singaravelu, E-mail: sganesan@annauniv.edu, E-mail: ganesansingaravelu@gmail.com [Anna University, Department of Medical Physics (India)

    2015-03-15

    The luminescent lanthanide-doped nanoparticles have gathered considerable attention in many fields especially in biomedicine. In this work, the lanthanum fluoride-doped terbium nanoparticles (LaF{sub 3}:Tb{sup 3+} NPs) via simple chemical precipitation method has been synthesized and functionalized with polyethylene glycol. The size and the shape of the nanoparticles are confirmed using X-ray diffraction and transmission electron microscopy. The conjugation of 5-Fluorouracil (5-FU) and thus synthesized nanoparticles (NPs) were confirmed using various spectroscopic methods such as UV–Visible spectroscopy, fluorescence steady state, and excited state spectroscopy studies. The enhancement in fluorescence emission (λ = 543 nm) of drug-conjugated nanoparticles confirms the Vander Waals force of attraction due to F–F bonding between the drug and the nanoparticles. Further, the effects of 5FU-NPs in carrier protein were investigated using bovine serum albumin as a protein model. The 5FU–LaF{sub 3}:Tb{sup 3+} nanoparticles binding is illustrated with binding constant and number of binding sites. The structural change of bovine serum albumin has been studied using circular dichroism and Fourier transform infrared spectroscopy analysis.

  13. Production of truncated MBD4 protein by frameshift mutation in DNA mismatch repair-deficient cells enhances 5-fluorouracil sensitivity that is independent of hMLH1 status.

    Science.gov (United States)

    Suzuki, Satoshi; Iwaizumi, Moriya; Tseng-Rogenski, Stephanie; Hamaya, Yasushi; Miyajima, Hiroaki; Kanaoka, Shigeru; Sugimoto, Ken; Carethers, John M

    2016-07-01

    Methyl-CpG binding domain protein 4 (MBD4) is a DNA glycosylase that can remove 5-fluorodeoxyuracil from DNA as well as repair T:G or U:G mismatches. MBD4 is a target for frameshift mutation with DNA mismatch repair (MMR) deficiency, creating a truncated MBD4 protein (TruMBD4) that lacks its glycosylase domain. Here we show that TruMBD4 plays an important role for enhancing 5-fluorouracil (5FU) sensitivity in MMR-deficient colorectal cancer cells. We found biochemically that TruMBD4 binds to 5FU incorporated into DNA with higher affinity than MBD4. TruMBD4 reduced the 5FU affinity of the MMR recognition complexes that determined 5FU sensitivity by previous reports, suggesting other mechanisms might be operative to trigger cytotoxicity. To analyze overall 5FU sensitivity with TruMBD4, we established TruMBD4 overexpression in hMLH1-proficient or -deficient colorectal cancer cells followed by treatment with 5FU. 5FU-treated TruMBD4 cells demonstrated diminished growth characteristics compared to controls, independently of hMLH1 status. Flow cytometry revealed more 5FU-treated TruMBD4 cells in S phase than controls. We conclude that patients with MMR-deficient cancers, which show characteristic resistance to 5FU therapy, may be increased for 5FU sensitivity via secondary frameshift mutation of the base excision repair gene MBD4.

  14. Docetaxel, cisplatin and 5-fluorouracil induction chemotherapy followed by chemoradiotherapy or chemoradiotherapy alone in stage III-IV unresectable head and neck cancer. Results of a randomized phase II study

    Energy Technology Data Exchange (ETDEWEB)

    Takacsi-Nagy, Zoltan; Polgar, Csaba; Major, Tibor; Fodor, Janos [National Institute of Oncology, Center of Radiotherapy, Budapest (Hungary); Hitre, Erika [National Institute of Oncology, Department of Chemotherapy and Clinical Pharmacology, Budapest (Hungary); Remenar, Eva; Kasler, Miklos [National Institute of Oncology, Department of Head and Neck and Maxillofacial Surgery, Budapest (Hungary); Oberna, Ferenc [Bacs-Kiskun County Hospital, Department of Oral, Maxillofacial and Head and Neck Surgery, Kecskemet (Hungary); Goedeny, Maria [National Institute of Oncology, Department of Radiology, Budapest (Hungary)

    2015-08-15

    Concurrent chemoradiotherapy (CRT) is the standard treatment for advanced head and neck squamous cell carcinoma. In this phase II randomized study, the efficacy and toxicity of docetaxel, cisplatin and 5-fluorouracil induction chemotherapy (ICT) followed by concurrent CRT was compared with those after standard CRT alone in patients with locally advanced, unresectable head and neck cancer. Between January 2007 and June 2009, 66 patients with advanced (stage III or IV) unresectable squamous cell carcinoma of the head and neck (oral cavity, oropharynx, hypopharynx, and larynx) were randomly assigned to two groups: one receiving two cycles of docetaxel, cisplatin, and 5-fluorouracil ICT followed by CRT with three cycles of cisplatin and one treated by CRT alone. Response rate, local tumor control (LTC), locoregional tumor control (LRTC), overall survival (OS), progression-free survival (PFS), and toxicity results were assessed. Three patients from the ICT + CRT group did not appear at the first treatment, so a total of 63 patients were evaluated in the study (30 ICT + CRT group and 33 CRT group). Three patients died of febrile neutropenia after ICT. The median follow-up time for surviving patients was 63 months (range 53-82 months). The rate of radiologic complete response was 63 % following ICT + CRT, whereas 70 % after CRT alone. There were no significant differences in the 3-year rates of LTC (56 vs. 57 %), LRTC (42 vs. 50 %), OS (43 vs. 55 %), and PFS (41 vs. 50 %) in the ICT + CRT group and in the CRT group, respectively. The rate of grade 3-4 neutropenia was significantly higher in the ICT + CRT group than in the CRT group (37 and 12 %; p = 0.024). Late toxicity (grade 2 or 3 xerostomia) developed in 59 and 42 % in the ICT + CRT and CRT groups, respectively. The addition of ICT to CRT did not show any advantage in our phase II trial, while the incidence of adverse events increased. The three deaths as a consequence of ICT call attention to the importance of

  15. 5-氟尿嘧啶纳米微球复合材料填充骨缺损及抗肿瘤作用★%Antitumor effect of 5-fluorouracil microsphere composite on bone defect repairs

    Institute of Scientific and Technical Information of China (English)

    冯伟; 靳安民; 刘纪恩; 勾瑞恩; 关春辉; 梁祁枫; 辛若冰

    2013-01-01

      背景:前期研究成功制备了纳米羟基磷灰石-聚羟基丁酸戊酯/聚乙二醇-5-氟尿嘧啶材料。目的:观察纳米羟基磷灰石-聚羟基丁酸戊酯/聚乙二醇-5-氟尿嘧啶的填充骨缺损和抗肿瘤作用。方法:取72只新西兰兔建立右膝关节 VX2骨肿瘤模型,切除部分胫骨形成骨缺损,且使骨缺损与肿瘤相邻,造模后随机分为实验组与对照组,分别于骨缺损处植入纳米羟基磷灰石-聚羟基丁酸戊酯/聚乙二醇-5-氟尿嘧啶与纳米羟基磷灰石-聚羟基丁酸戊酯/聚乙二醇人工骨。结果与结论:①无机质含量:两组均随时间的延长逐渐降低,尤以实验组明显。②X 射线检查:实验组术后24周材料体积较植入初期变小,肿瘤开始变小。对照植入材料体积始终无明显变化,肿瘤体积进行性增大。③生物力学检测:术后24周,实验组下肢标本最大扭转强度明显高于对照组(P <0.01)。④骨密度检测:术后2-24周,两组均呈先减低后增加趋势,以实验组明显。⑤肿瘤体积变化:术后24周,实验组减小,对照组增加。表明纳米羟基磷灰石-聚羟基丁酸戊酯/聚乙二醇-5-氟尿嘧啶复合材料能很好填充骨缺损并有明显抑制肿瘤生长的作用。%BACKGROUND: Previous studies have successful y prepared nano-hydroxyapatite-poly(3-hydroxybutyrate-hydroxyvalerate)/polyethylene glycol-5-fluorouracil. OBJECTIVE: To discuss the effect of nano-hydroxyapatite-poly(3-hydroxybutyrate-hydroxyvalerate)/polyethylene glycol-5-fluorouracil composite on bone defect repair and against bone tumor. METHODS: Bone tumor models were induced by injection of VX2 carcinoma cellsuspension into the medul ary cavity of right tibias in 72 New Zealand white rabbits through the knee joints. Partial resection of the tibia was performed to form bone defects that were adjacent to bone tumors. After modeling, al the rabbits were randomized into

  16. Anti-mitotic potential of 7-diethylamino-3(2 Prime -benzoxazolyl)-coumarin in 5-fluorouracil-resistant human gastric cancer cell line SNU620/5-FU

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Nam Hyun [Department of Pharmacology, Kwandong University College of Medicine, Gangneung 210-701 (Korea, Republic of); Kim, Su-Nam [KIST Gangneung Institute, Gangneung 210-340 (Korea, Republic of); Oh, Joa Sub [College of Pharmacy, Dankook University, Cheonan 330-714 (Korea, Republic of); Lee, Seokjoon [Department of Basic Science, Kwandong University College of Medicine, Gangneung 210-701 (Korea, Republic of); Kim, Yong Kee, E-mail: yksnbk@sookmyung.ac.kr [College of Pharmacy, Sookmyung Women' s University, Seoul 140-742 (Korea, Republic of)

    2012-02-24

    Highlights: Black-Right-Pointing-Pointer DBC exerts antiproliferative potential against 5FU-resistant human gastric cancer cells. Black-Right-Pointing-Pointer This effect is mediated by destabilization of microtubules and subsequent mitotic arrest. Black-Right-Pointing-Pointer 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 Prime -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 Prime -benzoxazolyl)-coumarin against drug-resistant cancer cells which will prompt us to further develop as a novel microtubule inhibitor for drug-resistant cancer chemotherapy.

  17. Effects of 5-FU combined compound Ginseng and Astragalus on biological behavior of human gastric cancer MGC-803 cells

    Institute of Scientific and Technical Information of China (English)

    韦尉元

    2013-01-01

    Objective To observe the in vitro effects of 5-fluorouracil(5-FU) combined Compound Ginseng and Astragalus(CGA) on the biological behaviors such as the proliferation,the cloning,apoptosis and migration of human gastric cancer MGC-803 cells. Methods The cell proliferation inhibition rate was detected by MTT assay,

  18. 动脉持续灌注化疗与静脉全身化疗治疗中晚期胰腺癌的疗效分析%A clinical study on continuous transarterial infusion chemotherapy and systemic venous chemotherapy with gemcitabine and 5-fiuorouracil in treating patients with advanced pancreatic carcinoma

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective: To compare the curative effectiveness of continuous transarterial infusion chemotherapy and systemic venous chemotherapy in treating patients with advanced pancreatic cancer, and to evaluate the value of selective continuous transarterial infusion chemotherapy in treating advanced pancreatic cancer. Methods: Of the 51 patients with advanced pancreatic cancer receiving chemotherapy with gemcitabine and 5-fluorouracil, 25 patients were treated with selective continuous transarterial infusion chemotherapy, 26 were treated with systemic venous chemotherapy, and curative effectiveness was analyzed retrospectively. Curative effectiveness included tumor volume, clinical benefit response (CBR), acute and subacute toxic reactions of antitumor drugs, survival rate and median survival time. Results: The objective effective rate in transarterial group was 32.0% versus 23.1% in systemic group without any significant difference (P = 0.475). Clinical benefit rates in transarterial group and systemic group were 80.0% and 50.0% respectively (P = 0.025). The 6-, 9- and 12-month accumulated survival rates and median survival time in transarterial group were higher than those of the systemic group (P = 0.002), the differences were statistically significant. However, the adverse reactions between the two groups were not statistically significant. Conclusion: Compared with systemic chemotherapy, continuous transarterial infusion chemotherapy with gemcitabine and 5-fluorouracil could improve clinical benefit rate and survival time of patients with advanced pancreatic cancer, it is safe and reliable, and the adverse reactions is less.

  19. FEASIBILITY OF INDUCTION DOCETAXEL, CISPLATIN, 5-FLUOROURACIL, CETUXIMAB (TPF-C FOLLOWED BY CONCURRENT CETUXIMAB RADIOTHERAPY FOR LOCALLY ADVANCED HEAD AND NECK SQUAMOUS CELL CARCINOMA

    Directory of Open Access Journals (Sweden)

    Nikolaos eCharalambakis

    2013-01-01

    Full Text Available Purpose: To report our experience with a sequential regimen of induction TPF-C followed by radioimmunotherapy with cetuximab in patients with locally advanced head and neck squamous cell carcinoma (HNSCC. Patients and Methods: Toxicity and outcome was retrospectively analyzed in 22 patients receiving sequential therapy with induction TPF-C followed by radioimmunotherapy between October 2008 and December 2011. Outcome was estimated using Kaplan-Meier analyses. In addition, we performed mutation analysis for PIK3CA genes and high-risk HPV-DNA detection using PCR. Results: Median follow-up was 16 months. Six patients were TNM Stage III, 15 patients IV (IVA or IVB and 1 patient Stage II with bulky disease. During TPF-C, Grade 3 and 4 toxicities occurred in 8 patients (36.4%, dose modifications in 7 (31.8%, delays in 1 (4.5%, and unplanned admissions in 5 (22.7%. Clinical tumor response was documented in 18 of the 21 patients who completed at least 3 cycles of TPF-C (85.7% with 3 patients developing complete response and 15 partial responses. Grade 3/4 mucositis was observed in 6 (31.6% patients. At a median follow up of 19 months, 13 patients were alive and 9 (40.9% had died including 7 patients as a result of disease persistence or recurrence and two as a result of unrelated causes. PIK3CA mutations were not identified and our 2 oropharynx cases were HPV negative.Conclusions: The combination of induction TPF-C with concurrent cetuximab radioimmunotherapy in patients with locally advanced HNSCC is tolerable, with encouraging efficacy.Keywords: HNSCC, TPF-C, cetuximab radiotherapy, toxicity and outcome, mutation analysis, PIK3CA, HPV-DNA.

  20. A randomized phase III multicenter trial comparing irinotecan in combination with the Nordic bolus 5-FU and folinic acid schedule or the bolus/infused de Gramont schedule (Lv5FU2) in patients with metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Glimelius, B; Sørbye, H; Balteskard, L;

    2008-01-01

    BACKGROUND: To compare irinotecan with the Nordic 5-fluorouracil (5-FU) and folinic acid (FA) bolus schedule [irinotecan 180 mg/m(2) on day 1, 5-FU 500 mg/m(2) and FA 60 mg/m(2) on day 1 and 2 (FLIRI)] or the Lv5FU2 schedule [irinotecan 180 mg/m(2) on day 1, FA 200 mg/m(2), 5-FU bolus 400 mg/m(2......). RESULTS: Patient characteristics were well balanced. PFS did not differ between groups (median 9 months, P = 0.22). Overall survival (OS) was also similar (median 19 months, P = 0.9). Fewer objective responses were seen in the FLIRI group (35% versus 49%, P = 0.001) but the metastatic resection rate did...

  1. Preparation of Folic Acid-modified Dextran-5-Fluorouracil and Its Cytotoxicity%叶酸-葡聚糖-5-氟尿嘧啶靶向药物的合成及细胞毒性研究

    Institute of Scientific and Technical Information of China (English)

    赵玉玺; 谭澈; 陈莹; 李建林; 潘黎军; 王驰

    2013-01-01

    目的 制备叶酸-葡聚糖-5-氟尿嘧啶靶向药物(FA-DEX-5-Fu)并考察其对叶酸受体(FR)高表达的肿瘤细胞的毒性作用.方法 以葡聚糖(DEX)为大分子载体与抗肿瘤药物5-氟尿嘧啶(5-Fu)合成5-Fu-DEX,再与靶向配体叶酸(FA)偶联,制备FA-DEX-5-Fu.采用UV、IR、ESI-MS进行结构确证;利用UV测定复合物中FA及5-Fu的含量;采用MTT检测游离5-Fu、5-Fu-DEX、FA-DEX-5-Fu对高表达FR的人宫颈癌Hela细胞及低表达FR的人肺癌A549细胞的细胞毒性作用.结果 UV、IR、ESI-MS分析表明,5-Fu和FA成功连接到DEX上.通过测定FA-DEX-5-Fu中5-Fu与FA的含量,计算出在复合物中5-Fu与FA的摩尔比为2.7:1.MTT实验结果表明,FA-DEX-5-Fu对Hela细胞的增殖抑制作用明显高于A549细胞;相同浓度的FA-DEX-5-Fu对Hela细胞的增殖抑制作用明显强于5-Fu及5-Fu-DEX.结论 本实验成功合成了FA-DEX-5Fu,且该复合物对FR高表达的肿瘤细胞有明显的靶向作用.%OBJECTIVE To synthesize folic acid-modified dextran-5-fluorouracil (FA-DEX-5-Fu) conjugates and investigate its cytotoxicity on cells with folate receptors.METHODS Dextran (DEX) was selected as the macromolecular carrier and the anti-cancer drug 5-fluorouracil (5-Fu) was selected as a model drug to synthesize 5-Fu-DEX,and then folic acid (FA) was linked into 5-FuDEX as the targeting ligand to obtain the conjugate,FA-DEX-5-Fu.UV spectra,IR and ESI-MS were used to identify the structure.UV spectrophotometry was used to determine the contents of FA and 5-Fu in the conjugate.MTT assay was applied to examine the cytotoxicity of free 5-Fu,5-Fu-DEX and FA-DEX-5-Fu on the Human cervical carcinoma cell line Hela (overexpressing folate receptors) and human lung carcinoma cell line A549 (folate receptor deficient,as negative group).RESULTS 5-Fu and FA were successfully linked with 5-Fu-DEX as confirmed by UV,IR and ESI-MS spectra.The molar ratio of 5-Fu and FA in the conjutate was 2.7:1 as determined by UV

  2. A Retrospective, Multicenter Study of the Tolerance of Induction Chemotherapy With Docetaxel, Cisplatin, and 5-Fluorouracil Followed by Radiotherapy With Concomitant Cetuximab in 46 Cases of Squamous Cell Carcinoma of the Head and Neck

    International Nuclear Information System (INIS)

    Purpose: To investigate, in a multicenter study, the tolerance of induction chemotherapy (ICT) and external radiotherapy (ERT) with concomitant cetuximab in the treatment of patients with squamous cell carcinoma of the head and neck (SCCHN). Patients and Methods: Clinical data from 46 patients with Stage III or IV nonmetastatic SCCHN who received docetaxel, cisplatin, and 5-fluorouracil as ICT, followed by ERT with concomitant cetuximab, were retrospectively analyzed. Clinical safety (weight, allergy, mucositis, and dermatitis) and paraclinical safety (levels of hemoglobin, polynuclear neutrophils, and creatinine clearance) were studied. The primary objective was the proportion of patients who completed the protocol. Results: The percentage of patients completing ICT was 73.9%, ERT 93.5%, and cetuximab 69.6%. Induction chemotherapy was better tolerated than that previously reported. The rates of temporary suspensions of radiation (39.1%, mean duration of 13 days) and hospitalization (26.1%) during ERT with concomitant cetuximab were high. Weight loss during treatment (21.4% of patients lost >10% of their body weight), radiodermatitis, and radiomucositis were the main causes of temporary suspension of treatment, although Grade 4 dermatitis was not experienced. There were no allergic reactions to cetuximab. Conclusion: The completed protocol rate for SCCHN patients receiving ICT and ERT with concomitant cetuximab is high and the toxicity acceptable. Future improvements to protocol will be possible through early action and systematic implementation of nutritional support coupled with antibiotic treatment upon the first signs of radiodermatitis. These data could be useful for prospective studies on the safety and efficacy of this protocol.

  3. Comparison of the effectiveness and toxicity of neoadjuvant chemotherapy regimens, capecitabine/epirubicin/cyclophosphamide vs 5-fluorouracil/epirubicin/cyclophosphamide, followed by adjuvant, capecitabine/docetaxel vs docetaxel, in patients with operable breast cancer

    Science.gov (United States)

    Zhang, Minmin; Wei, Wei; Liu, Jianlun; Yang, Huawei; Jiang, Yi; Tang, Wei; Li, Qiuyun; Liao, Xiaoming

    2016-01-01

    The aim of this study was to compare the effectiveness and toxicity of neoadjuvant chemotherapy regimens, xeloda/epirubicin/cyclophosphamide (XEC) vs 5-fluorouracil/epirubicin/cyclophosphamide (FEC), followed by adjuvant chemotherapy regimens, capecitabine/taxotere (XT) vs taxotere (T), in axillary lymph node (LN)-positive early-stage breast cancer. In this randomized, Phase III trial, 137 patients with operable primary breast cancer (T2-0, N0-1) who were tested axillary LN positive through aspiration biopsy of axillary LNs were randomized (1:1) to four 3-weekly cycles of XEC or FEC. Patients underwent surgery within 4–6 weeks after the fourth cycle, followed by four adjuvant cycles of 3-weekly XT or T. The primary end point was tumor pathological complete response. Toxicity profiles were secondary objectives. In total, 131 patients had clinical and radiological evaluation of response and underwent surgery. Treatment with XEC led to an increased rate of pathological complete response in primary tumor (18% vs 6%, respectively, P=0.027) and objective remission rate (87% vs 73%, P=0.048) compared to FEC. Clinical complete response occurred in 20% and 7% for XEC and FEC, respectively. Compared to FEC, XEC was associated with more hand-foot syndrome (57% vs 11%, P<0.001) and 3/4 grade nausea/vomiting/diarrhea (30% vs 14%, P=0.034) but less phlebitis (3% vs 14%, P=0.035). XT and T adjuvant chemotherapy regimens were well tolerated: treatment-related 3/4 grade adverse events occurred in 28% and 17% of patients receiving XT and T, respectively. PMID:27354816

  4. Efficacy of intensified hyperfractionated and accelerated radiotherapy and concurrent chemotherapy with carboplatin and 5-fluorouracil: Updated results of a randomized multicentric trial in advanced head-and-neck cancer

    International Nuclear Information System (INIS)

    Purpose: To prove an expected benefit of concurrent radiochemotherapy (RCT), a two-arm randomized multicentric study was performed. In a subgroup analysis the influence of pretherapeutical hemoglobin level (p-Hb) on survival under locoregional control (SLC) was tested. Patients and Methods: The study included primarily untreated Stage III/IV (International Union Against Cancer [UICC]) oropharyngeal and hypopharyngeal carcinomas. Patients were randomized to receive either hyperfractionated (hf) and accelerated (acc) RCT with two cycles 5-fluorouracil (600 mg/m2/day) and carboplatin (70 mg/m2/day) on Days 1-5 and 29-33 or hf-acc radiotherapy (RT) alone. Total RT dose in both arms was 69.9 Gy in 38 days in concomitant boost technique. Results: After a median follow-up time of 57 months, SLC is significantly better in RCT than in RT (p = 0.01), with median SLC of 17 months and 11 months, respectively. Also overall survival (OS) shows a benefit for RCT (p 0.016), with a median survival of 23 months for RCT and 16 months for RT. However, the benefit in SLC and OS is not seen in hypopharyngeal carcinomas. In a multivariate analysis of oropharyngeal cancer patients, p-Hb levels lower than 12.7 g/dL resulted in lower SLC compared with higher p-Hb levels up to 13.8 g/dL. P-Hb levels >13.8 g/dL did not further improve SLC. Conclusions: Hyperfractionated-accelerated RCT is superior to hf-acc RT in oropharyngeal carcinomas. P-Hb levels >13.8 g/dL do not further improve SLC

  5. Mechanical characterisation of hybrid composite laminates based on basalt fibres in combination with flax, hemp and glass fibres manufactured by vacuum infusion

    International Nuclear Information System (INIS)

    Highlights: ► For the first time, hybrid laminates with three different fibres were produced. ► Concerns are confirmed on the brittleness of hybrid laminates with basalt fibre core. ► An optimal configuration (FHB) for flexural properties was singled out. ► Differences between tensile and flexural properties of hybrids were identified. ► In general, the specific mechanical properties of the hybrids are quite high. - Abstract: This work concerns the production by vacuum infusion and the comparison of the properties of different hybrid composite laminates, based on basalt fibre composites as the inner core, and using also glass, flax and hemp fibre laminates to produce symmetrical configurations, all of them with a 21–23% fibre volume, in an epoxy resin. The laminates have been subjected to tensile, three-point flexural and interlaminar shear strength tests and their fracture surfaces have been characterised by scanning electron microscopy. The mechanical performance of all the hybrid laminates appears superior to pure hemp and flax fibre reinforced laminates and inferior to basalt fibre laminates. Among the hybrids, the best properties are offered by those obtained by adding glass and flax to basalt fibre reinforced laminates. Scanning electron microscopy (SEM) observation of hybrid laminates showed the diffuse presence of fibre pull-out in hemp and flax fibre reinforced layers and a general trend of brittle failure

  6. Long-Term Follow-Up of a Phase II Trial of High-Dose Radiation With Concurrent 5-Fluorouracil and Cisplatin in Patients With Anal Cancer (ECOG E4292)

    Energy Technology Data Exchange (ETDEWEB)

    Chakravarthy, A. Bapsi, E-mail: bapsi.chak@vanderbilt.edu [Vanderbilt University Medical Center, Nashville, TN (United States); Catalano, Paul J. [Dana-Farber Cancer Institute, Boston, MA (United States); Martenson, James A. [Mayo Clinic, Rochester, MN (United States); Mondschein, Joshua K. [Vanderbilt University Medical Center, Nashville, TN (United States); Wagner, Henry [Pennsylvania State Hershey Cancer Institute, Hershey, PA (United States); Mansour, Edward G. [Case Western Reserve University, Cleveland, OH (United States); Talamonti, Mark S. [University of Chicago Pritzker School of Medicine, Evanston, IL (United States); Benson, Al Bowen [Northwestern University, Chicago, IL (United States)

    2011-11-15

    Purpose: Although chemoradiation using 5-fluorouracil (5-FU) and mitomycin-C (MMC) is the standard of care in the treatment of anal cancer, many patients are unable to tolerate MMC. This Phase II clinical trial was performed to determine whether cisplatin could replace MMC in the treatment of anal cancer. Methods and Materials: Thirty-three patients with localized anal cancer were enrolled. One patient registered but never received any assigned therapy and was excluded from all analyses. Between February 1, 1993, and July 21, 1993, 19 patients were accrued to Cohort 1. Radiation consisted of 45 Gy to the primary tumor and pelvic nodes, followed by a boost to the primary and involved nodes to 59.4 Gy. A planned 2-week treatment break was used after 36 Gy. Concurrent chemotherapy consisted of 5-FU 1,000 mg/m{sup 2}/day on Days 1 to 4 and cisplatin 75 mg/m{sup 2} on Day 1. A second course of 5-FU and cisplatin was given after 36 Gy, when the patient resumed radiation therapy. Between April 4, 1996, and September 23, 1996, an additional 13 patients (Cohort 2) were accrued to the study and received the same treatment except without the planned treatment break. Results: Complete response was seen in 78% (90% CI, 63-89) of patients and was higher in patients who did not get a planned treatment break (92% vs. 68%). The overall Grade 4 toxicity rate was 31%. One treatment-related death (Grade 5) occurred in a patient who developed sepsis. The 5-year overall survival was 69%. Conclusions: Radiation therapy, cisplatin, and 5-FU resulted in an overall objective response (complete response + partial response) of 97%. Although the 5-year progression-free survival was only 55%, the overall 5-year survival was 69%. Given the excellent salvage provided by surgery, this study affirms that cisplatin-based regimens may be an alternative for patients who cannot tolerate the severe hematologic toxicities associated with mitomycin-based chemoradiation regimens.

  7. Let-7 miRNA-binding site polymorphism in the KRAS 3′UTR; colorectal cancer screening population prevalence and influence on clinical outcome in patients with metastatic colorectal cancer treated with 5-fluorouracil and oxaliplatin +/− cetuximab

    Directory of Open Access Journals (Sweden)

    Kjersem Janne B

    2012-11-01

    Full Text Available Abstract Background Recent studies have reported associations between a variant allele in a let-7 microRNA complementary site (LCS6 within the 3′untranslated region (3′UTR of KRAS (rs61764370 and clinical outcome in metastatic colorectal cancer (mCRC patients receiving cetuximab. The variant allele has also been associated with increased cancer risk. We aimed to reveal the incidence of the variant allele in a colorectal cancer screening population and to investigate the clinical relevance of the variant allele in mCRC patients treated with 1st line Nordic FLOX (bolus 5-fluorouracil/folinic acid and oxaliplatin +/− cetuximab. Methods The feasibility of the variant allele as a risk factor for CRC was investigated by comparing the LCS6 gene frequencies in 197 CRC patients, 1060 individuals with colorectal polyps, and 358 healthy controls. The relationship between clinical outcome and LCS6 genotype was analyzed in 180 mCRC patients receiving Nordic FLOX and 355 patients receiving Nordic FLOX + cetuximab in the NORDIC-VII trial (NCT00145314. Results LCS6 frequencies did not vary between CRC patients (23%, individuals with polyps (20%, and healthy controls (20% (P = 0.50. No statistically significant differences were demonstrated in the NORDIC-VII cohort even if numerically increased progression-free survival (PFS and overall survival (OS were found in patients with the LCS6 variant allele (8.5 (95% CI: 7.3-9.7 months versus 7.8 months (95% CI: 7.4-8.3 months, P = 0.16 and 23.5 (95% CI: 21.6-25.4 months versus 19.5 months (95% CI: 17.8-21.2 months, P = 0.31, respectively. Addition of cetuximab seemed to improve response rate more in variant carriers than in wild-type carriers (from 35% to 57% versus 44% to 47%, however the difference was not statistically significant (interaction P = 0.16. Conclusions The LCS6 variant allele does not seem to be a risk factor for development of colorectal polyps or CRC. No statistically significant effect of the

  8. Early prediction of survival following induction chemotherapy with DCF (docetaxel, cisplatin, 5-fluorouracil) using FDG PET/CT imaging in patients with locally advanced head and neck squamous cell carcinoma

    International Nuclear Information System (INIS)

    Locally advanced head and neck squamous cell carcinoma (HNSCC) has a high rate of recurrence. Induction chemotherapy with DCF (docetaxel, cisplatin, 5-fluorouracil) before chemoradiotherapy could lead to the best disease control of inoperable stage III/IV HNSCC but with an increased risk of acute toxicity. Early assessment of therapeutic efficacy is a key issue in considering the benefit of escalation in a poor prognosis population. Patients with stage III/IV HNSCC, in whom DCF induction chemotherapy followed by concurrent chemoradiotherapy had been validated by a multidisciplinary team, were prospectively included in the study. FDG PET/CT scans were performed in all patients before and after two of the three cycles of DCF. EORTC99 criteria were used to evaluate PET responses as follows: group 1 (metabolic responders) showing a complete response (CR) or partial response (PR), and subgroup 0 (metabolic nonresponders) showing stable disease (SD) or progressive disease (PD). The primary endpoint for monitoring patients was event-free survival (EFS). EFS probabilities between the two groups were estimated by the Kaplan-Meier method and statistically compared using the log-rank test. Fifteen consecutive patients (14 men, 1 woman; age 57.5 ± 6.2 years, mean ± SD) were analysed. Therapeutic assessment by PET/CT demonstrated CR in four patients, PR in six, SD in four and PD in one. Among the ten patients with a metabolic response (group 1), none had relapsed at the time of this report, while four of five patients with no metabolic response (group 0) showed recurrence within an average of 9.0 ± 1.6 months. Median EFS was, respectively, 18.9 months (3.8-25.3 months) and 10.2 months (7.5-12.7 months) in group 1 and group 0. The corresponding 1-year EFS rates were 100 % and 20 %, respectively. The difference in EFS between the two groups was statistically significant (p = 0.0014). Early therapeutic response demonstrated on FDG PET/CT after two cycles of induction

  9. Comparison of the effectiveness and toxicity of neoadjuvant chemotherapy regimens, capecitabine/epirubicin/cyclophosphamide vs 5-fluorouracil/epirubicin/cyclophosphamide, followed by adjuvant, capecitabine/docetaxel vs docetaxel, in patients with operable breast cancer

    Directory of Open Access Journals (Sweden)

    Zhang MM

    2016-06-01

    Full Text Available Minmin Zhang,* Wei Wei,* Jianlun Liu, Huawei Yang, Yi Jiang, Wei Tang, Qiuyun Li, Xiaoming Liao Department of Breast Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China *These authors contributed equally to this work Abstract: The aim of this study was to compare the effectiveness and toxicity of neoadjuvant chemotherapy regimens, xeloda/epirubicin/cyclophosphamide (XEC vs 5-fluorouracil/epirubicin/cyclophosphamide (FEC, followed by adjuvant chemotherapy regimens, capecitabine/taxotere (XT vs taxotere (T, in axillary lymph node (LN-positive early-stage breast cancer. In this randomized, Phase III trial, 137 patients with operable primary breast cancer (T2-0, N0-1 who were tested axillary LN positive through aspiration biopsy of axillary LNs were randomized (1:1 to four 3-weekly cycles of XEC or FEC. Patients underwent surgery within 4–6 weeks after the fourth cycle, followed by four adjuvant cycles of 3-weekly XT or T. The primary end point was tumor pathological complete response. Toxicity profiles were secondary objectives. In total, 131 patients had clinical and radiological evaluation of response and underwent surgery. Treatment with XEC led to an increased rate of pathological complete response in primary tumor (18% vs 6%, respectively, P=0.027 and objective remission rate (87% vs 73%, P=0.048 compared to FEC. Clinical complete response occurred in 20% and 7% for XEC and FEC, respectively. Compared to FEC, XEC was associated with more hand-foot syndrome (57% vs 11%, P<0.001 and 3/4 grade nausea/vomiting/diarrhea (30% vs 14%, P=0.034 but less phlebitis (3% vs 14%, P=0.035. XT and T adjuvant chemotherapy regimens were well tolerated: treatment-related 3/4 grade adverse events occurred in 28% and 17% of patients receiving XT and T, respectively. Keywords: breast cancer, capecitabine, docetaxel, neoadjuvant chemotherapy, curative effect, toxic side effects

  10. Long-Term Follow-Up of a Phase II Trial of High-Dose Radiation With Concurrent 5-Fluorouracil and Cisplatin in Patients With Anal Cancer (ECOG E4292)

    International Nuclear Information System (INIS)

    Purpose: Although chemoradiation using 5-fluorouracil (5-FU) and mitomycin-C (MMC) is the standard of care in the treatment of anal cancer, many patients are unable to tolerate MMC. This Phase II clinical trial was performed to determine whether cisplatin could replace MMC in the treatment of anal cancer. Methods and Materials: Thirty-three patients with localized anal cancer were enrolled. One patient registered but never received any assigned therapy and was excluded from all analyses. Between February 1, 1993, and July 21, 1993, 19 patients were accrued to Cohort 1. Radiation consisted of 45 Gy to the primary tumor and pelvic nodes, followed by a boost to the primary and involved nodes to 59.4 Gy. A planned 2-week treatment break was used after 36 Gy. Concurrent chemotherapy consisted of 5-FU 1,000 mg/m2/day on Days 1 to 4 and cisplatin 75 mg/m2 on Day 1. A second course of 5-FU and cisplatin was given after 36 Gy, when the patient resumed radiation therapy. Between April 4, 1996, and September 23, 1996, an additional 13 patients (Cohort 2) were accrued to the study and received the same treatment except without the planned treatment break. Results: Complete response was seen in 78% (90% CI, 63–89) of patients and was higher in patients who did not get a planned treatment break (92% vs. 68%). The overall Grade 4 toxicity rate was 31%. One treatment-related death (Grade 5) occurred in a patient who developed sepsis. The 5-year overall survival was 69%. Conclusions: Radiation therapy, cisplatin, and 5-FU resulted in an overall objective response (complete response + partial response) of 97%. Although the 5-year progression-free survival was only 55%, the overall 5-year survival was 69%. Given the excellent salvage provided by surgery, this study affirms that cisplatin-based regimens may be an alternative for patients who cannot tolerate the severe hematologic toxicities associated with mitomycin-based chemoradiation regimens.

  11. Pharmacokinetics and pharmacodynamics of ch14.18/CHO in relapsed/refractory high-risk neuroblastoma patients treated by long-term infusion in combination with IL-2.

    Science.gov (United States)

    Siebert, Nikolai; Eger, Christin; Seidel, Diana; Jüttner, Madlen; Zumpe, Maxi; Wegner, Danilo; Kietz, Silke; Ehlert, Karoline; Veal, Gareth J; Siegmund, Werner; Weiss, Michael; Loibner, Hans; Ladenstein, Ruth; Lode, Holger N

    2016-04-01

    Ch14.18 manufactured in Chinese hamster ovary (CHO) cells is currently being evaluated in clinical trials. Short-term infusion (STI) (8-20 h/day; 4-5 days) of 100 mg/m2 ch14.18/CHO (dinutiximab β) per cycle in combination with cytokines is standard treatment of neuroblastoma (NB) patients. As pain is a limiting factor, we investigated a novel delivery method by continuous long-term infusion (LTI) of 100 mg/m2 over 10 days. 53 NB patients were treated with 5-6 cycles of 6 × 106 IU/m2 subcutaneous interleukin-2 (d 1-5, 8-12), LTI of 100 mg/m2 ch14.18/CHO (d 8-18) and 160 mg/m2 oral 13-cis-retinoic acid (d 22-35). Human anti-chimeric antibody (HACA), antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity were determined. With LTI, we observed a maximum concentration of ch14.18/CHO (Cmax) of 12.56 ± 0.68 µg/ml and a terminal half-life time (t1/2 β) of 32.7 ± 16.2 d. The clearance values for LTI and STI of 0.54 ± 0.13 and 0.41 ± 0.29 L/d m2 and area under the serum concentration-time curve (AUC) values of 189.6 ± 41.4 and 284.8 ± 156.8 µg×d/ml, respectively, were not significantly different. Importantly, we detected ch14.18/CHO trough concentration of ≥ 1 µg/ml at time points preceding subsequent antibody infusions after cycle 1, allowing a persistent activation of antibody effector mechanisms over the entire treatment period of 6 months. HACA responses were observed in 10/53 (19%) patients, similar to STI (21%), indicating LTI had no effect on the immunogenicity of ch14.18/CHO. In conclusion, LTI of ch14.18/CHO induced effector mechanisms over the entire treatment period, and may therefore emerge as the preferred delivery method of anti-GD2 immunotherapy to NB patients. PMID:26785755

  12. 5-Fluorouracil-loaded polylactic acid nanoparticles have a killing effect on gastric cancer cell lines in vitro%5-氟尿嘧啶聚乳酸载药纳米微粒对胃癌细胞株的体外杀伤作用

    Institute of Scientific and Technical Information of China (English)

    李晓利; 牛敏; 张铭; 张娜娜; 施瑶

    2015-01-01

    背景:5-氟尿嘧啶在胃癌治疗中占据重要地位,但是长期服用容易出现骨髓抑制、白细胞减少等不良反应。聚乳酸及共聚物载药微粒材料生物相容性较高,分解物不会在机体内发生聚集。  目的:探讨聚乳酸载药纳米微粒对胃癌细胞株的体外杀伤作用机制。  方法:选取10只小鼠进行实验,利用超声乳化方法制备5-氟尿嘧啶聚乳酸载药纳米微粒,并采用噻唑蓝比色法配制1×10-7,1×10-6,1×10-5,1×10-4 mol/L的5-氟尿嘧啶聚乳酸载药纳米微粒,检测其对小鼠胃癌细胞的体外杀伤效应,并且计算出药物的抑制率浓度以及对胃癌细胞的生长抑制能力等以及凋亡的诱导作用。  结果与结论:透射电镜下观察5-氟尿嘧啶聚乳酸载药纳米微粒:形态完好,分布相对均匀,不出现粘连等现象,用药24 h药物浓度可达到50%,72 h后能够达到62.9%;不同浓度下单一5-氟尿嘧啶和5-氟尿嘧啶聚乳酸载药纳米微粒和小鼠胃癌细胞联合培养48 h后,细胞的活性随着药物浓度的提高出现下降趋势,并且5-氟尿嘧啶聚乳酸载药纳米微粒细胞抑制能力显著高于5-氟尿嘧啶(P OBJECTIVE:To investigate the in vitro cytotoxicity mechanism of 5-fluorouracil-loaded polylactic acid nanoparticles on gastric cancer cel lines. METHODS:Ten mice were selected in this study. 5-fluorouracil-loaded polylactic acid nanoparticles (1×10-7, 1×10-6, 1×10-5, 1×10-4 mol/L) were prepared using ultrasonic emulsification method. Kiling effect of polylactic acid nanoparticles on gastric cancer cel lines in vitrowere detected. Then, the inhibition rate was calculated at different concentrations. RESULTS AND CONCLUSIONS: Under the transmission electron microscope, 5-fluorouracil-loaded polylactic acid nanoparticles had good shape and relatively evenly distributed with no adhesions. After drug administration, the drug concentration was

  13. Effects of Liraglutide Combined with Short-Term Continuous Subcutaneous Insulin Infusion on Glycemic Control and Beta Cell Function in Patients with Newly Diagnosed Type 2 Diabetes Mellitus: A Pilot Study.

    Science.gov (United States)

    Ke, Weijian; Liu, Liehua; Liu, Juan; Chen, Ailing; Deng, Wanping; Zhang, Pengyuan; Cao, Xiaopei; Liao, Zhihong; Xiao, Haipeng; Liu, Jianbin; Li, Yanbing

    2016-01-01

    The objective of this paper is to investigate the effects of liraglutide in combination with short-term continuous subcutaneous insulin infusion (CSII) therapy on glycemic control and beta cell function in patients with newly diagnosed type 2 diabetes mellitus (T2DM). Thirty-nine eligible newly diagnosed T2DM patients were recruited and randomized to receive either of two therapies: short-term CSII alone (CSII alone group) or CSII in combination with liraglutide (CSII + Lira group) for 12 weeks. Blood glucose control, homeostasis model assessment (HOMA) indices, and acute insulin response (AIR) were compared between the two groups. The patients in CSII + Lira group achieved euglycemia with equivalent insulin dosage in shorter time (1 (0) versus 2 (3) days, P = 0.039). HbA1c at the end of study was comparable between two groups (6.3 ± 0.7% versus 6.0 ± 0.5%, for CSII alone group and CSII + Lira group, resp., P = 0.325). The increment of AIR was higher in CSII + Lira group (177.58 (351.57) μU · min/mL versus 58.15 (51.30) μU · min/mL, P < 0.001). However, after stopping liraglutide, its effect on beta cell function disappeared completely. Liraglutide combined with short-term CSII was effective in further improving beta cell function, but the beneficial effects did not sustain after suspension of the therapy.

  14. Assessment of Retrograde Coronary Venous Infusion of Mesenchymal Stem Cells Combined with Basic Fibroblast Growth Factor in Canine Myocardial Infarction Using Strain Values Derived from Speckle-Tracking Echocardiography.

    Science.gov (United States)

    Sun, Qi-Wei; Zhen, Lei; Wang, Qin; Sun, Yan; Yang, Jiao; Li, Yi-Jia; Li, Rong-Juan; Ma, Ning; Li, Zhi-An; Wang, Lu-Ya; Nie, Shao-Ping; Yang, Ya

    2016-01-01

    Speckle-tracking echocardiography was used to assess retrograde coronary venous infusion of mesenchymal stem cells (MSCs) combined with basic fibroblast growth factor (bFGF) in a canine model of acute myocardial infarction (AMI). AMI was induced by ligation of the left anterior descending coronary artery. Coronary venous retroperfusion was performed at 1 wk after AMI. Twenty-eight animals were randomized into four groups: saline, bFGF+saline, saline+MSCs and bFGF+MSCs. Echocardiography was performed before AMI, at 7 d post-AMI and 40 d after retroperfusion. Apoptotic cardiomyocytes in the border zone of the ischemic region were evaluated by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling. Vascular endothelial growth factor and factor VIII concentrations were measured by western blotting. The left ventricular end-systolic volume increased significantly, whereas the left ventricular ejection fraction and global and segmental strain values decreased significantly after AMI. After retroperfusion, the strain values of the infarct zone, but not conventional echocardiographic parameters, were significantly different between control and bFGF+MSC groups. Cardiomyocyte apoptosis decreased, whereas vascular endothelial growth factor and factor VIII concentrations were higher in the bFGF+MSC, bFGF and MSC groups. Cardiomyocyte apoptosis was well correlated with the strain values. Although retrograde coronary venous infusion of bFGF and MSCs promoted neo-vascularization of the infarcted myocardium and inhibited apoptosis, there was only a slight strain improvement without a substantial increase in global cardiac functions.

  15. Inhibitory Effects of Ethosomes Encapsulated with 5-Fluorouracil on Human Hypertrophic Scar Fibroblasts%5-氟尿嘧啶醇脂体抑制瘢痕成纤维细胞的实验研究

    Institute of Scientific and Technical Information of China (English)

    张铮; 沃雁; 张振; 毛小慧; 苏薇洁; 濮哲铭; 张艳; 章一新

    2014-01-01

    目的:构建纳米级载5-氟尿嘧啶醇脂体(5-FU ES),观察其对瘢痕成纤维细胞的抑制作用。方法采用Touitou法制备5-FU ES悬液并进行质量评价。体外培养增生性瘢痕成纤维细胞,荧光素RhoB标记醇脂体,进行体外透细胞实验,以水醇溶液为对照。激光共聚焦显微镜(CLSM)观察不同作用时间后细胞内荧光分布和强度。CCK-8检测不同浓度5-FU ES对成纤维细胞活性的影响,计算载5-FU ES对成纤维细胞活性的半数抑制浓度(IC50)。CCK-8检测醇脂体对瘢痕成纤维细胞生长的影响。结果制备所得5-FU ES粒径为(87.5±5.4) nm,分散系数为0.151±0.27,包封率为(10.03±2.12)%。 CLSM图像显示,醇脂体促进RhoB进入细胞内,可见荧光分布和强度均较水醇溶液组增多增强;经Image-Pro Plus 6.0图像分析软件计算单位面积光密度值,RhoB标记醇脂体组(Rho ES)细胞内荧光光密度显著高于水醇溶液组(Rho HA)(P<0.01)。随着5-FU浓度增加,5-FU HA 和5-FU ES对成纤维细胞的生长抑制率逐渐增强;5-FU ES和5-FU HA对成纤维细胞的半数抑制浓度(IC50)分别为(9.2582±1.2329)μg/mL和(18.0352±2.3145)μg/mL,差异具有统计学意义(P<0.05);同时,醇脂体本身对细胞活性无明显抑制作用。结论醇脂体可有效携带5-FU向瘢痕成纤维细胞内递送,促进5-FU对成纤维细胞的活性抑制作用。醇脂体作为经皮给药载体,是一种安全有效的透细胞药物载体。%Objective To establish ethosomes encapsulated with 5-Fluorouracil and to explore the inhibitory effects of 5-FU on human hypertrophic scar fibroblasts. Methods Ethosomes encapsulated with 5-Fluorouracil was prepared by Touitou method and was evaluated. Human hypertrophic scar fibroblasts were cultured in vitro, the penetration of the fluorescent probes into fibroblasts was examined by CLSM, and hydroalcoholic solution was

  16. Radiochemotherapy in combination with regional hyperthermia in preirradiated patients with recurrent rectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Milani, V.; Issels, R.D.; Buecklein, V. [Ludwig-Maximilians-Univ., Muenchen (Germany). Univ. Hospital Grosshadern, Dept. of Internal Medicine III; Institute of Molecular Immunology, Muenchen (Germany). KKG Hyperthermie GSF-Haematologikum; Pazos, M.; Schaffer, P.; Wilkowski, R.; Duehmke, E. [Ludwig-Maximilians-Univ., Muenchen (Germany). Univ. Hospital Grosshadern, Dept. of Radiation Oncology; Rahman, S.; Tschoep, K.; Schaffer, M. [Ludwig-Maximilians-Univ., Muenchen (Germany). Univ. Hospital Grosshadern, Dept. of Internal Medicine III

    2008-03-15

    Background and Purpose: Encouraging results of phase II studies combining chemotherapy with radiotherapy have been published. In this study, the results of a multimodal salvage therapy including radiochemotherapy (RCT) and regional hyperthermia (RHT) in preirradiated patients with recurrent rectal cancer are reported. Patients and Methods: All patients enrolled had received previous pelvic irradiation (median dose 50.4 Gy). The median time interval between prior radiotherapy and the onset of local recurrence was 34 months. The combined treatment consisted of reirradiation with a median dose of 39.6 Gy (30.0-45.0 Gy), delivered in fractions of 1.8 Gy/day. 5-fluorouracil was given as continuous infusion 350 mg/m2/day five times weekly, and RHT (BSD-2000 system) was applied twice a week within 1 h after radiotherapy. The primary endpoint was local progression-free survival (LPFS); secondary endpoints were overall survival, symptom control, and toxicity. Results: 24 patients (median age 59 years) with a previously irradiated locally recurrent adenocarcinoma of the rectum were enrolled. The median LPFS was 15 months (95% confidence interval 12-18 months) with a median follow-up of 27 months (16-37 months). The overall 1-year and 3-year survival rates were 87% and 30%, respectively. Pain was the main symptom in 17 patients. Release of pain was achieved in 12/17 patients (70%). No grade 3 or 4 hematologic or skin toxicity occurred. Grade 3 gastrointestinal acute toxicity was observed in 12.5% of the patients. Paratumoral thermometry revealed a homogeneous distribution of temperatures. Conclusion: RCT combined with RHT is an efficient salvage therapy showing high efficacy with acceptable toxicity and can be recommended as treatment option for this unfavorable group of preirradiated patients with local recurrence of rectal cancer. (orig.)

  17. PET physiological measurements using constant infusion

    International Nuclear Information System (INIS)

    A wide range of study designs can be used with positron emission tomography methods to provide quantitative measurements of physiological parameters. While bolus injection of tracer is the conventional approach, use of combined bolus plus constant infusion provides a number of advantages for receptor-binding tracers. Of recent interest is the use of this approach to dynamically follow the displacement of tracer during in vivo changes in neurotransmitter concentrations. This paper provides an overview of the tradeoffs in using bolus/infusion methods versus conventional bolus injection for receptor binding studies