Sample records for adenocarcinoma receiving 5-fu

  1. An open label randomized multicentre phase IIIb trial comparing parenteral substitution versus best supportive nutritional care in subjects with pancreatic adenocarcinoma receiving 5-FU plus oxaliplatin as 2nd or higher line chemotherapy regarding clinical benefit - PANUSCO

    Rötzer Ingeborg


    Full Text Available Abstract Background Pancreatic cancer is an extremely aggressive malignancy. Subjects are afflicted with a variety of disconcerting symptoms, including profound cachexia. Recent data indicate that the outcome of oncological patients suffering from cancer cachexia could be improved by parenteral nutrition and that parenteral nutrition results in an improvement of quality of life and in prolonged survival. Currently, there is no recommendation of routine use of parenteral nutrition. Furthermore, there is no clear recommendation for 2nd line therapy (or higher for pancreatic adenocarcinoma but often asked for. Methods/Design PANUSCO is an open label, controlled, prospective, randomized, multicentre phase IIIb trial with two parallel arms. All patients will be treated with 5-fluorouracil, folinic acid and oxaliplatin on an outpatient basis at the study sites. Additionally, all patients will receive best supportive nutritional care (BSNC. In the experimental group BSNC will be expanded with parenteral nutrition (PN. In contrast, patients in the control group obtain solely BSNC. Parenteral nutrition will be applied overnight and at home by experienced medical staff. A total of 120 patients are planned to be enrolled. Primary endpoint is the comparison of the treatment groups with respect to event-free survival (EFS, defined as the time from randomization till time to development of an event defined as either an impairment (change from baseline of at least ten points in EORTC QLQ-C30, functional domain total score or withdrawal due to fulfilling the special defined stopping criteria for chemotherapy as well as for nutritional intervention (NI or death from any cause (whichever occurs first. Discussion The aim of this clinical trial is to evaluate whether parenteral nutrition in combination with defined 2nd line or higher chemotherapy has an impact on quality of life for patients suffering from pancreatic adenocarcinoma. Trial registration Current

  2. Phase II study of neoadjuvant 5-FU + leucovorin + CPT-11 in patients with resectable liver metastases from colorectal adenocarcinoma

    Bigam David


    Full Text Available Abstract Background Following resection of liver metastases from colorectal cancer, 5-year survivals are reportedly 30 – 39%. It can be assumed that this clinical situation represents systemic disease. Therefore, it is postulated that systemic chemotherapy would improve outcomes, particularly in those whose disease is sensitive to the agents administered. One potential advantage of neoadjuvant chemotherapy is that it provides in vivo chemosensitivity data. Response to neoadjuvant chemotherapy could therefore guide adjuvant chemotherapy following resection of liver metastases from colorectal cancer. Methods and design This is a prospective Phase II evaluation of outcomes in patients with potentially resectable liver metastases. Patients will receive neoadjuvant chemotherapy and will undergo resection. Postoperative chemotherapy will be directed by the degree of response to preoperative chemotherapy. All patients with Stage IV colorectal adenocarcinoma isolated to the liver that have disease that is amenable to complete ablation by resection, radiofrequency ablation, and/or cryoablation will be candidates for the trial. Patients will receive CPT-11 180 mg/m2 IV (over 90 minutes on day 1 with 5-FU 400 mg/m2 bolus and 600 mg/m2 by 22 hour infusion and calcium folinate 200 mg/m2 on days 1 and 2, every 2 weeks. Altogether, six cycles of chemotherapy will be administered. Patients will then undergo resection and/or radiofrequency ablation. Patients who had stable disease or a clinical response with preoperative chemotherapy will receive an additional 12 cycles of CPT-11 180 mg/m2 IV (over 90 minutes on day 1 with 5-FU 400 mg/m2 bolus and 600 mg/m2 by 22 hour infusion and calcium folinate 200 mg/m2 on days 1 and 2 (given every 2 weeks. Patients with resectable disease who had progressive disease during neoadjuvant chemotherapy will receive best supportive care or an alternative agent, at the discretion of the treating physician. Those patients who are

  3. Phase III trial of postoperative cisplatin, interferon alpha-2b, and 5-FU combined with external radiation treatment versus 5-FU alone for patients with resected pancreatic adenocarcinoma – CapRI: study protocol [ISRCTN62866759

    Schmitz-Winnenthal H


    Full Text Available Abstract After surgical intervention with curative intention in specialised centres the five-year survival of patients with carcinoma of the exocrine pancreas is only 15%. The ESPAC-1 trial showed an increased five-year survival of 21% achieved with adjuvant chemotherapy. Investigators from the Virginia Mason Clinic have reported a 5-year survival rate of 55% in a phase II trial evaluating adjuvant chemotherapy, immunotherapy and external-beam radiation. Design The CapRI study is an open, controlled, prospective, randomised multi-centre phase III trial. Patients in study arm A will be treated as outpatients with 5-Fluorouracil; Cisplatin and 3 million units Interferon alpha-2b for 5 1/2 weeks combined with external beam radiation. After chemo-radiation the patients receive continuous 5-FU infusions for two more cycles. Patients in study arm B will be treated as outpatients with intravenous bolus injections of folinic acid, followed by intravenous bolus injections of 5-FU given on 5 consecutive days every 28 days for 6 cycles. A total of 110 patients with specimen-proven R0 or R1 resected pancreatic adenocarcinoma will be enrolled. An interim analysis for patient safety reasons will be done one year after start of recruitment. Evaluation of the primary endpoint will be performed two years after the last patients' enrolment. Discussion The aim of this study is to evaluate the overall survival period attained by chemo-radiotherapy including interferon alpha 2b administration with adjuvant chemotherapy. The influence of interferon alpha on the effectiveness of the patients' chemoradiation regimen, the toxicity, the disease-free interval and the quality of life are analysed. Different factors are tested in terms of their potential role as predictive markers.

  4. Effects of 5-FU.

    Wigmore, Peter M; Mustafa, Sarah; El-Beltagy, Maha; Lyons, Laura; Umka, Jariya; Bennett, Geoff


    5-fluorouracil (5-FU) is a chemotherapeutical agent used to treat cancers including breast and colorectal. Working as an antimetabolite to prevent cell proliferation, it primarily inhibits the enzyme thymidylate synthase blocking the thymidine formation required for DNA synthesis. Although having a relatively short half-life (fog" These accounts have come primarily from patients undergoing treatment for breast cancer who report symptoms including confusion and memory impairment, which can last for months to years. Psychometric studies of patients have suffered from confounding variables, which has led to the use of rodent models to assess the cognitive effects of this drug. Researchers have used behavioral and physiological tests including the Morris water maze, novel object location/recognition tests, shock motivated T-maze, sensory gating and conditioning, to investigate the effect of this drug on cognition. The variety of cognitive tests and the difference in dosing and administration of 5-FU has led to varied results, possibly due to the different brain regions associated with each test and the subtlety of the drug's effect, but overall these studies indicates that 5-FU has a negative effect on memory, executive function and sensory gating. 5-FU has also been demonstrated to have biochemical and structural changes on specific regions of the brain. Evidence shows it can induce apoptosis and depress cell proliferation in the neurogenic regions of the adult brain including the sub granular zone (SGZ) within the hippocampus and in oligodendrocyte precursor populations within white matter tracts. Furthermore, investigations indicate levels ofdoublecortin, a marker for newly formed neurons and brain derived neurotrophic factor, a cell survival modulator, are also reduced by 5-FU in the SGZ. Thus, 5-FU appears to have a lasting negative impact on cognition and to affect cellular and biochemical markers in various brain regions. Further work is needed to understand the

  5. Preliminary observations indicate variable patterns of plasma 5-fluorouracil (5-FU) levels during dose optimization of infusional 5-FU in colorectal cancer patients.

    Kline, Christina Leah; Sheikh, Hassan S; Scicchitano, Angelique; Gingrich, Rebecca; Beachler, Cheryl; Finnberg, Niklas K; Liao, Jason; Sivik, Jeffrey; El-Deiry, Wafik S


    Efforts to improve efficacy and minimize toxicity have led to pharmacokinetic monitoring of plasma 5-Fluorouracil (5-FU) levels in colorectal cancer patients undergoing chemotherapy. We observed variation in basal 5-FU levels in 21 patients and significant variation during subsequent dose optimization. Tumor KRAS, BRAF mutations and TS mRNA levels were determined. Regimens included FOLFOX6 + Avastin (N = 8), FOLFOX6 (N = 11), FOLFIRI (N = 1) and FOLFOX4 (N = 1). Mutations identified in tumors included G12V KRAS (N = 2), G12A KRAS (N = 1), and V600E BRAF (N = 3). Six-of-eleven patients with normalized tumor TS mRNA levels 5-FU AUC of 20 mg.h/L or greater, and 80% of patients (4 of 5) with TS levels > 4.0 had a plasma 5-FU AUC of less than or equal to 20 mg.h/L. Approximately 2/3 of patients achieved therapeutic 5-FU AUC levels with 0-2 dose adjustments while a sub-group of ~1/3 of patients slowly achieved therapeutic levels (> 3-4 dose increases leading to supra-therapeutic 5-FU and subsequent reductions to lesser than original doses). Liver metastases and tumor TS levels did not fully account for variable 5-FU AUC optimization patterns. The 5-FU level during continuous infusion was half-therapeutic in one patient who received FOLFOX4. The observed heterogeneous patterns at baseline and during dose optimization of 5-FU levels suggest variations in 5-FU metabolism among treated patients. Physiological and/or genetic differences underlying heterogeneity in 5-FU levels during dose optimization require further study of patient demographics, single nucleotide polymorphisms in Dihydropyrimidine Dehydrogenase (DPD), TS, or other genes that impact 5-FU metabolism and gene expression changes in liver after 5-FU therapy.

  6. 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

    Glimelius, B; Sørbye, H; Balteskard, L


    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......) and infused 5-FU 600 mg/m(2) on day 1 and 2 (Lv5FU2-IRI)] due to uncertainties about how to administrate 5-FU with irinotecan. PATIENTS AND METHODS: Patients (n = 567) with metastatic colorectal cancer were randomly assigned to receive FLIRI or Lv5FU2-IRI. Primary end point was progression-free survival (PFS...... and OS comparable to irinotecan with the Lv5FU2 schedule. Neutropenia and alopecia are more prevalent, but both regimens are equally well tolerated....

  7. 5FU and oxaliplatin-containing chemotherapy in two dihydropyrimidine dehydrogenase-deficient patients

    Reerink, O; Mulder, NH; Szabo, BG; Hospers, GAP


    Patients with a germline mutation leading to a deficiency of the dihydropyrimidine dehydrogenase (DPD) enzyme are at risk from developing severe toxicity on the administration of 5FU-containing chemotherapy. We report on the implications of this inborn genetic error in two patients who received 5FU

  8. 5-FU Metabolism in Cancer and Orally-Administrable 5-FU Drugs

    Iwao Sasaki


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

  9. Lack of survival advantage in patients with advanced, resectable squamous cell carcinoma of the oral cavity receiving induction chemotherapy with cisplatin (CDDP), docetaxel (TXT) and 5-fluorouracil (5FU).

    Umeda, Masahiro; Komatsubara, Hideki; Ojima, Yasutaka; Minamikawa, Tsutomu; Shigeta, Takashi; Shibuya, Yasuyuki; Yokoo, Satoshi; Komori, Takahide


    Cisplatin-based neoadjuvant chemotherapy (NAC) has been reported to increase survival of patients with nasopharyngeal carcinoma, and organ preservation in those with laryngeal carcinoma, but its efficacy for other head and neck carcinomas is still controversial. We examined the effects of NAC for patients with stage III-IV squamous cell carcinoma of the oral cavity. The patients were divided into two groups; 9 patients who underwent NAC consisting of one course of cisplatin (CDDP), docetaxel (TXT) and 5-fluorouracil (5FU) followed by surgery (NAC group), and 18 patients who underwent surgery alone (control group). Complete response (CR) was not observed, but partial response (PR) was obtained in 6 of 9 patients (33%) of the NAC group. The 3-year survival rate was 29.6% in the NAC group and 81.5% in the control group. Although any valid conclusions could not be drawn because of the small number of patients examined here, NAC with CDDP, TXT and 5FU offered no advantages over standard treatment for advanced oral cancer in terms of survival.

  10. 5-fluorouracil (5FU) treatment does not influence invasion and metastasis in microsatellite unstable (MSI-H) colorectal cancer.

    Warusavitarne, Janindra; Ramanathan, Palaniappan; Kaufman, Anthony; Robinson, Bruce G; Schnitzler, Margaret


    Microsatellite instability is a recognised pathway of colorectal carcinogenesis responsible for about 15% of all sporadic colorectal cancers. Recent evidence has suggested that these tumours may not have the same response as microsatellite stable colon cancers to 5-fluorouracil (5FU)-based chemotherapy. The response to 5FU in four microsatellite unstable (MSI-H) cell lines was examined by cell viability assays and invasion assays. Flow cytometry was used to assess the effect of 5FU on MSI-H cell lines. In vivo response to 5FU was assessed by intraperitoneal injection of 5FU or control to 80 nude mice that had received intrasplenic injections of an MSI-H cell line KM12C prior to commencing treatment. There was inhibition of cell growth in MSI-H cell lines when treated with 5FU. There was no difference in invasiveness in the MSI-H cell lines when treated with 5FU. Primary tumours formed in 27 of the untreated and 25 of the 5FU treated mice (p=NS). There was a 36% reduction in splenic weight in those mice treated with 5FU (p5FU treatment of MSI-H tumours results in a reduction in growth but does not result in a reduction in invasion or metastasis.

  11. 5FU and oxaliplatin-containing chemotherapy in two dihydropyrimidine dehydrogenase-deficient patients.

    Reerink, O; Mulder, N H; Szabo, B G; Hospers, G A P


    Patients with a germline mutation leading to a deficiency of the dihydropyrimidine dehydrogenase (DPD) enzyme are at risk from developing severe toxicity on the administration of 5FU-containing chemotherapy. We report on the implications of this inborn genetic error in two patients who received 5FU and oxaliplatin. A possible co-medication effect of oxaliplatin is considered, as are the consequences of screening for DPD deficiency.

  12. Tegafur Substitution for 5-Fu in Combination with Actinomycin D to Treat Gestational Trophoblastic Neoplasm.

    Mei Peng

    Full Text Available Although 5-fluorouracil (5-Fu combination chemotherapy provides a satisfactory therapeutic response in patients with gestational trophoblastic neoplasms (GTNs, it has severe side effects. The current study analyzed the therapeutic effects and side effects of tegafur plus actinomycin D (Act-D vs. 5-Fu plus Act-D for the treatment of GTNs based on controlled historical records. A total of 427 GTN cases that received tegafur and Act-D combination chemotherapy at the Second Xiangya Hospital of XiangYa Medical School between August 2003 and July 2013 were analyzed based on historical data. A total of 393 GTN cases that received 5-Fu plus Act-D between August 1993 and July 2003 at the same hospital were also analyzed, which constituted the control group. The therapeutic effects, toxicity and side effects after chemotherapy were compared between the groups. The overall response rate was 90.63% in the tegafur+Act-D group (tegafur group and 92.37% in the 5-Fu+Act-D group (5-Fu group; these rates were not significantly different (P > 0.05. However, the incidence rates of myelosuppression (white blood cell decline, gastrointestinal reactions (nausea, vomiting, dental ulcer, and diarrhea, skin lesions and phlebitis were lower in the tegafur group than in the 5-Fu group (P < 0.05. The results of this study may provide useful data for the clinical application of tegafur in GTN treatment.

  13. White light-mediated Cu (II)-5FU interaction augments the chemotherapeutic potential of 5-FU: an in vitro study.

    Chibber, Sandesh; Farhan, Mohd; Hassan, Iftekhar; Naseem, Imrana


    5-Fluorouracil (5-FU) is a potent photosensitizer used in colon and rectal cancers. 5-FU on galvanostatic electrolysis or radiation-induced oxidation of aqueous solution yields N(1)-C(5)-linked dimmer hydrate of 5-FU. Copper is presently associated with chromatin; in cancer cells the concentration of copper is very high. It has been shown to be capable of mediating the action of several anticancer drugs through the production of reactive oxygen species (ROS). The objective of the present study is to determine the Cu (II)-mediated anticancer mechanism of 5-FU under photo-illumination as well as 5-FU alone. We have shown that a pro-oxidant action was enhanced when Cu (II) was used with 5-FU as compared to 5-FU alone. This may be due to the inhibition of dimerization of 5-FU when present in combination with Cu (II) under photo-illumination. It was also shown that 5-FU alone as well as in combination with Cu (II) was able to generate oxidative stress in lymphocyte which is inhibited by scavengers of ROS. Moreover, the results of Fourier-transformed infrared spectra lead to the conclusion that the dimerization of 5-FU was inhibited when used in combination with Cu (II). It was due to the interaction of 5-FU with Cu (II). Hence, we propose that during chemoradiotherapy with 5-FU, the endogenous copper is mobilized by 5-FU, leading to the generation of ROS which cause oxidative stress and possibly cancer cell death by apoptosis.

  14. Phase III study of 5FU, etoposide and leucovorin (FELV) compared to epirubicin, cisplatin and 5FU (ECF) in previously untreated patients with advanced biliary cancer.

    Rao, S; Cunningham, D; Hawkins, R E; Hill, M E; Smith, D; Daniel, F; Ross, P J; Oates, J; Norman, A R


    The purpose of this study was to determine whether epirubicin, cisplatin and infused 5FU (ECF) improves overall survival (OS) compared to 5FU, etoposide and leucovorin (FELV) in patients with previously untreated advanced biliary cancer in a prospective randomised study. Patients were randomly assigned to receive epirubicin, cisplatin and infused 5FU ECF or bolus 5FU etoposide and leucovorin (FELV). The primary end point was OS with secondary end points of objective response rate (ORR), failure-free survival (FFS), quality of life (QOL) and toxicity. In all, 54 patients were recruited with 27 randomly assigned to each arm. The median OS for ECF was 9.02 months (95% confidence interval (CI): 6.46-11.51) and FELV 12.03 months (95% CI: 9.3-14.7), P=0.2059. Objective response rates were similar for both arms: ECF 19.2% (95% CI: 6.55-39.3); FELV 15% (95% CI: 3.2-37.9), P=0.72. There was significantly increased grade 3/4 neutropenia with FELV vs ECF (53.8 vs 29.5%, respectively, P=0.020). Symptom resolution was impressive for both regimens. This is the largest reported randomised study to date in this setting. ECF did not improve OS compared to FELV, but was associated with less acute toxicity. These data suggest that chemotherapy can prolong OS and achieve good symptomatic relief in advanced biliary cancer.

  15. Phenytoin toxicity due to fluoropyrimidines (5FU/capecitabine): three case reports.

    Brickell, K; Porter, D; Thompson, P


    Interactions between phenytoin and the fluoropyrimidine derivatives, 5 fluorouracil (5FU) and capecitabine, are not commonly documented or widely recognised. As more people with significant medical comorbidities are now being considered for chemotherapy, it is increasingly likely that people receiving phenytoin will be prescribed treatment with fluoropyrimidines. We present two cases of clinical phenytoin toxicity occurring after starting treatment with 5-fluorouracil/folinic acid (5FU/FA) and a third who developed clinical phenytoin toxicity after starting capecitabine (an orally administered prodrug of fluorouracil).

  16. Randomised phase III study of biweekly 24-h infusion of high-dose 5FU with folinic acid and oxaliplatin versus monthly plus 5-FU/folinic acid in first-line treatment of advanced colorectal cancer

    Hospers, GAP; Schaapveld, M; Nortier, JWR; Wils, J; van Bochove, A; de Jong, RS; Creemers, GJ; Erjavec, Z; de Gooyer, DJ; Slee, PHTJ; Gerrits, CJH; Smit, J.M.; Mulder, NH


    Background: A phase III study was started to compare oxaliplatin/5FU/LV in the first-line with bolus FU/LV in metastatic colorectal cancer. Patients and methods: 302 patients were randomised and received bolus 5-FU 425 mg/m(2) day 1-5, FA 20 mg/m(2) day 1-5, q 4 wk or oxaliplatin 85 mg/m(2), 2 h-inf

  17. Synthesis and characterization of HPMA copolymer-5-FU conjugates

    Fang Yuan; Fu Chen; Qing Yu Xiang; Xuan Qin; Zhi Rong Zhang; Yuan Huang


    N-(2-Hydroxypropyl)methacrylamide copolymer-5-fluorouracil (PHPMA-FU)conjugates were synthesized by a novel and simplified synthetic mute,and characterized by UV,FTIR and HPLC analyses.The conjugated content of 5-fluorouracil (5-FU)was 3.41 ± 0.07 wt%.The stabilities of PHPMA-FU conjugates under different conditions were studied.The results showed that HPMA copolymer was a potential carrier for tumor-targeting delivery of 5-FU.

  18. Cellular response to 5-fluorouracil (5-FU in 5-FU-resistant colon cancer cell lines during treatment and recovery

    Kravik Katherine L


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

  19. [A successful resected case of advanced esophageal cancer with early gastric cancer responding to neoadjuvant chemotherapy of docetaxel, CDDP and 5-FU].

    Matsutani, Takeshi; Yoshida, Hiroshi; Sasajima, Koji; Maruyama, Hiroshi; Yokoyama, Tadashi; Matsushita, Akira; Hirakata, Atsushi; Takao, Yoshimune; Umakoshi, Michinobu; Hayakawa, Tomohiro; Katayama, Hironori; Hosone, Masaru; Uchida, Eiji


    A 72-year-old male with a chief complaint of dysphagia was admitted to our hospital. Upper gastrointestinal endoscopic examination showed double cancers with thoracic esophageal cancer in the middle esophagus and gastric cancer in the antrum. Pathological examinations of the double cancer revealed the first one to be moderately-differentiated squamous cell carcinoma and the second to be well-differentiated adenocarcinoma. Computed tomography (CT) of the chest and abdomen showed no distant or lymph node metastases. Clinical stagings of the double cancer were stage II (T2N0M0)in esophageal cancer and stage I A (T1N0M0) in gastric cancer. The patient received neoadjuvant chemotherapy using docetaxel, CDDP and 5-FU. After 2 courses of chemotherapy, the adverse event was grade 2 in leucopenia and grade 2 in alopecia. Repeated macroscopic and histological examinations after chemotherapy revealed that the esophageal cancer had significant reductions in the size of tumors, leading to a partial response, and the gastric cancer had disappeared, leading to a complete response. He underwent thoracoscopy-assisted esophagectomy in the prone position, and laparoscopy-assisted gastric tube reconstruction. This neoadjuvant chemotherapy of docetaxel, CDDP and 5-FU might be effective and tolerable as with patients with double cancer of esophageal and gastric cancers.

  20. MFL-P Chemotherapy for Pretreated Metastatic Breast Cancer Patients: A Regimen with Triple Biochemical Modulation by MTX-5FU, LV-5FU and 5FU-CDDP.

    Kan; Honda


    BACKGROUND: Chemotherapeutic regimens, such as cyclophosphamide + doxorubicin + 5FU (CAF) or cyclophosphamide + methotrexate + 5FU (CMF), are sometimes used in combination with endocrine or radiotherapy as a standard first line of treatment for recurrent or metastatic breast cancer. However, many cases are, or become, refractory to these treatments. METHODS: Twenty-one women with recurrent or metastatic breast cancer who previously underwent treatment were administered our original regimen of combinationchemotherapy, MFL-P: Day 1, bolus methotrexate (MTX) 50 mg/body (median dose, 33 mg/m(2); range, 29-35 mg/m(2)) and 4 hours later 5-fluorouracil (5FU) 750 mg/body/h (median dose, 497 mg/m(2)/h; range, 441-528 mg/m(2) /h); Days 2-3, bolus leucovorin(LV) 15 mg/body every 8 h x 3; Days 2-5, 72 hours continuous 5FU 750 mg/body/24h; Day 6, cisplatin (CDDP) 50 mg/body/h (median dose, 33 mg/m(2)/h; range, 29-35 mg/m(2) /h) with sufficient hydration. The subjects ranged in age from 26 to 63 years (mean age, 51.3 years). RESULTS: One complete and 9 partial responses were achieved among the 20 patients (response rate, 50%). In 1 patient, diffuse liver metastasis was not measurable. Among various metastatic sites, a higher response rate was observed especially for soft tissue lesions (skin, chest wall and lymph nodes; 9 responders among 11 lesions). On the other hand, in visceral or skeletal metastases, the response rate was poor. The adverse effects were tolerable in all patients, except for common low-grade stomatitis or anorexia. CONCLUSION: MFL-P is useful as a second or third line of therapy for patients with refractory, recurrent or metastatic breast cancer with soft tissues lesions.

  1. 5-FU-induced peripheral neuropathy: a rare complication of a well-known drug.

    Laarhoven, H.W.M. van; Verstappen, C.C.P.; Beex, L.V.A.M.; Kappelle, A.C.; Punt, C.J.A.


    Peripheral neuropathy is a rare complication of the commonly used cytotoxic drug 5-fluorouracil (5-FU). We report a case of 5-FU-induced peripheral neuropathy in a patient with metastatic colorectal carcinoma. Discontinuation of 5-FU therapy is recommended in case of 5-FU-related neurotoxicity.

  2. [Modeling 5-FU clearance during a chronomodulated infusion].

    Kwiatkowski, F; Chevalier, V; Chevrier, R; Richard, D; Cure, H; Chollet, P


    Drugs pharmacokinetic control is a usual practice in case of flat continuous infusions. It enables among others, to modulate delivered doses when drug concentrations in blood appear too high. With chronotherapy, this possibility becomes more difficult because of sinusoidal outflows of infusion. We propose here a method that enables this follow-up, established through the study of 21 metastatic colorectal cancer patients, treated with a chronomodulated infusion of high dose 5-fluoro-uracil (5-FU) and folinic acid. This pharmacokinetic follow-up permitted the modelisation of 5-FU clearance and the calculation of an index, which was, in our study, correlated to the treatment response and also to main encountered toxicities.

  3. Cell Line Derived 5-FU and Irinotecan Drug-Sensitivity Profiles Evaluated in Adjuvant Colon Cancer Trial Data

    Buhl, Ida Kappel; Gerster, Sarah; Delorenzi, Mauro


    PURPOSE: This study evaluates whether gene signatures for chemosensitivity for irinotecan and 5-fluorouracil (5-FU) derived from in vitro grown cancer cell lines can predict clinical sensitivity to these drugs. METHODS: To test if an irinotecan signature and a SN-38 signature could identify...... patients who benefitted from the addition of irinotecan to 5-FU, we used gene expression profiles based on cell lines and clinical tumor material. These profiles were applied to expression data obtained from pretreatment formalin fixed paraffin embedded (FFPE) tumor tissue from 636 stage III colon cancer...... patients enrolled in the PETACC-3 prospective randomized clinical trial. A 5-FU profile developed similarly was assessed by comparing the PETACC-3 cohort with a cohort of 359 stage II colon cancer patients who underwent surgery but received no adjuvant therapy. RESULTS: There was no statistically...

  4. Slug-dependent upregulation of L1CAM is responsible for the increased invasion potential of pancreatic cancer cells following long-term 5-FU treatment.

    Kaja Lund

    Full Text Available Pancreatic adenocarcinoma is a lethal disease with 5-year survival of less than 5%. 5-fluorouracil (5-FU is a principal first-line therapy, but treatment only extends survival modestly and is seldom curative. Drug resistance and disease recurrence is typical and there is a pressing need to overcome this. To investigate acquired 5-FU resistance in pancreatic adenocarcinoma, we established chemoresistant monoclonal cell lines from the Panc 03.27 cell line by long-term exposure to increasing doses of 5-FU.5-FU-resistant cell lines exhibited increased expression of markers associated with multidrug resistance explaining their reduced sensitivity to 5-FU. In addition, 5-FU-resistant cell lines showed alterations typical for an epithelial-to-mesenchymal transition (EMT, including upregulation of mesenchymal markers and increased invasiveness. Microarray analysis revealed the L1CAM pathway as one of the most upregulated pathways in the chemoresistant clones, and a significant upregulation of L1CAM was seen on the RNA and protein level. In pancreatic cancer, expression of L1CAM is associated with a chemoresistant and migratory phenotype. Using esiRNA targeting L1CAM, or by blocking the extracellular part of L1CAM with antibodies, we show that the increased invasiveness observed in the chemoresistant cells functionally depends on L1CAM. Using esiRNA targeting β-catenin and/or Slug, we demonstrate that in the chemoresistant cell lines, L1CAM expression depends on Slug rather than β-catenin.Our findings establish Slug-induced L1CAM expression as a mediator of a chemoresistant and migratory phenotype in pancreatic adenocarcinoma cells.

  5. Selective protection by uridine of growth inhibition by 5-fluorouracil (5FU) mediated by 5FU incorporation into RNA, but not the thymidylate synthase mediated growth inhibition by 5FU-leucovorin.

    Codacci-Pisanelli, G; Noordhuis, P; van der Wilt, C L; Peters, G J


    Fluorouracil (5FU) acts by RNA-incorporation and inhibition of thymidylate synthase; the first action is counteracted by uridine, and the second is enhanced by leucovorin (LV). Growth inhibition of C26-10 colon cancer cells by 5FU was enhanced by LV and rescued by uridine, but 5FU-LV was only partially rescued by uridine. In WiDr cells, 5FU sensitivity was not enhanced by LV, while both 5FU and 5FU-LV were rescued by uridine. Intermediate trends were found in SW948 and HT29 cells. Uridine rescue in mice allowed 1.5-fold increase in 5FU dose, leading to 2-fold increase in the antitumor effect and thymidylate synthase inhibition in resistant Colon-26 tumors. In the sensitive Colon-26-10 tumor, uridine rescue decreased 5FU-RNA incorporation > 10-fold, without affecting the antitumor activity. The use of LV and uridine can differentiate between two mechanisms of action of 5FU.

  6. Quality of life in patients with advanced gastric cancer: a randomized trial comparing docetaxel, cisplatin, 5-FU (TCF with epirubicin, cisplatin, 5-FU (ECF

    Montazeri Ali


    Full Text Available Abstract Background Health related quality of life (HRQOL is an important outcome after treatment for upper gastrointestinal carcinoma. This study aimed to compare HRQOL in patients with advanced gastric cancer (GC receiving either a standard or an experimental treatment. Methods Seventy-one patients have been treated in Cancer Institute (Tehran, Iran with docetaxel, cisplatin, 5 FU (TCF or epirubicin, cisplatin, 5-FU (ECF and were followed from Jan 2002 to Jan 2005. End points were response rate, HRQOL and survival. HRQOL was assessed using the EORCT QLQ-C30 at baseline and after the third cycle of chemotherapy. Results The baseline HRQOL scores were comparable between two groups. After treatment improvement was seen in a number of items and domains except for cognitive functioning, and diarrhoea. Pain decreased and physical functioning improved in both groups. However, only the TCF group showed statistically and clinically meaningful improvement in global QOL (P = 0.001. Surgical and pathologic response was better with TCF but there was no difference in survival rate between two groups. Conclusion Docetaxel based treatment (TCF showed better palliation and improvement of global QOL as compared with epirubicin based treatment (ECF. However, it seems that regardless of treatment offered, effective chemotherapy was the most important factor affecting QOL in these patients.

  7. High response rates following paclitaxel/5-FU and simultaneous radiotherapy in advanced head and neck carcinoma; Hohe Remissionsraten unter simultaner Radio- und Chemotherapie mit Paclitaxel/5-FU in der Behandlung fortgeschrittener Kopf-Hals-Tumoren

    Schroeder, M.; Westerhausen, M. [St.-Johannes-Hospital, Duisburg (Germany). Medizinische Klinik II; Makoski, H.B. [Staedtische Kliniken, Duisburg (Germany). Radioonkologie; Sesterhenn, K. [St. Anna-Krankenhaus, Duisburg (Germany). HNO-Klinik; Schroeder, R. [Bristol Myers Squibb, Muenchen (Germany). Dept. of Oncology


    The main stay of treatment for head and neck cancer patients with advanced disease has been chemotherapy with Cisplatin/5-FU and simultaneous applied radiotherapy. With this multimodality treatment including radical surgery after two cycles of neoadjuvant chemotherapy and 40 Gy radiotherapy we reported 60% complete remission after 5 years for patients with stage III/IV of head and neck cancer. Paclitaxel, a new plant product, has demonstrated significant antineoplastic activity in head and neck tumors (ECOG-Study: 40% RR). Therefore we performed a trial with Taxol/5-FU and simultaneous radiation in a neoadjuvant and postoperative adjuvant setting of stage III/IV squamous cell carcinoma of the head and neck with pre-existent contraindication against Cisplatin. Patients and Methods: 30 patients with a primarily inoperable stage III/IV of SCC of the head and neck were enrolled to receive day 1 and 29 Taxol 175 mg/m{sup 2} as a 3-hour-infusion, followed by 120-hour-cvi of 1000 mg/m{sup 2}/d 5-FU. Locally irradiation was given ad 40 Gy (2 Gy/d/day 1-26). Radical surgery followed about day 56. Postoperatively patients received again 2 cycles of Taxol/5-FU and simultaneous irradiation with 30 Gy. Results: So far 30 patients were treated and all patients reached a CR after complete treatment, ongoing for 23/30 patients for 6 till 34 months: 4 patients developed a second neoplasia, and 3 patients gloved a local relapse. The principal toxicity was moderate (neutropenia, peripheral neuropathy, arthralgia/myalgia) and sensible with supportive care (e.g. PEG). Conclusions: The results suggest that the treatment of SCC of the head and neck with Taxol/5-FU and simultaneous radiation and radical surgery is a highly effective schedule and comparable with the treatment with Cisplatin/5-FU. (orig.) [Deutsch] Der Standard in der Behandlung weit forgeschrittener, primaer inoperabler Kopf-Hals-Tumoren stellte die Cisplatinhaltige Chemotherapiekombination mit 5-FU dar mit simultan

  8. Study on synthesis and distribution in vivo of 5-Fu-cholic acid conjugate

    Jie Li; Li Hai; Wei Jia Liu; Xiao Chun Wu; Yong Wu


    A series of hepatic targeting drugs,5-Fu-cholic acid conjugate T1-T5,were synthesized.5-Fu and cholic acid was selected as starting material,after N-hydroxymethylation,condensation,hydrogenolysis to obtain carboxylated 5-Fu 5a--e.Carboxylated 5-Fu 5a--e were eondensated with intermediate 3-hydroxyethyl cholic acid benzyl ester 6 to get 7a-e,7a-e were deproteeted to get T1-T5.

  9. Predictive value of Ki67 and p53 in locally advanced rectal cancer: Correlation with thymidylate synthase and histopathological tumor regression after neoadjuvant 5-FU-based chemoradiotherapy

    Christiane Jakob; Torsten Liersch; Wolfdietrich Meyer; Heinz Becker; Gustavo B Bare; Daniela E Aust


    AIM:To investigate the predictive value of Ki67 and p53 and their correlation with thymidylate synthase(TS) gene expression in a rectal cancer patient cohort treated according to a standardized recommended neoadjuvant treatment regimen.METHODS:Formalin fixed,paraffin embedded pretherapeutical tumor biopsies (n=22) and posttherapeutical resection specimens(n=40)from patients with rectal adenocarcinoma (clinical UICC stage Ⅱ/Ⅲ)receiving standardized neoadjuvant 5-fiuorouracil(5-FU)based chemoradiotherapy were studied for Ki67 and p53 expression by immunohistochemistry and correlated with TS mRNA expression by quantitative TaqMan realtime PCR after laser microdissection.The results were compared with histopathological tumor regression according to a standardized semiquantitative score grading system.RESULTS:Responders(patients with high tumor regression)showed a significantly lower Ki67 expression than non-responders in the pre-therapeutical tumor biopsies (81.2% vs16.7%;P<0.05) as well as in the post-therapeutical resection specimens (75.8%vs14.3%;P<0.01).High TS mRNA expression was significantly correlated with a high Ki67 index and low TS mRNA expression was significantly correlated with a low Ki67 index in the pre-therapeutical tumor biopsies (corr.coef.=0.46;P<0.01)as well as in the posttherapeutical resection specimens (corr.coef.=0.40;P<0.05).No significant association was found between p53 and TS mRNA expression or tumor regression.CONCLUSION:Ki67 has,like TS,predictive value in rectal cancer patients after neoadjuvant 5-FU based chemoradiotherapy.The close correlation between Ki67 and TS indicates that TS is involved in active cell cycle processes.

  10. Adjuvant 5FU plus levamisole in colonic or rectal cancer: improved survival in stage II and III.

    Taal, B G; Van Tinteren, H; Zoetmulder, F A


    Based on the first favourable results of adjuvant therapy of 5FU plus levamisole in Dukes C colonic cancer in 1990, we conducted a prospective trial. 1029 patients were randomised to receive one year 5FU plus levamisole or no further treatment following curative surgery for stage II or III colon (n = 730) or rectal cancer (n = 299). 45% were in stage II and 55% in stage III. With a median follow-up of 4 years and 9 months a significant reduction in odds of death (25%, SD 9%, P = 0.007) was observed for those with adjuvant treatment (65% at 5 year) compared to the observation group (55%). Improved relative survival was present in stage III (56% vs 44%), and in stage II patients (78% vs 70%). In rectal cancer a non-significant difference in disease-free or overall survival was observed. Distant metastases developed in 76%, while local recurrence alone occurred in 14%. An early start of adjuvant treatment (5FU plus levamisole was 69%. Severe toxicity did not occur. In conclusion, one year 5FU plus levamisole was of benefit in stage II and III colonic cancer; in rectal cancer a significant positive effect could not be demonstrated.

  11. Mitomycin-C and 5- FU in ophthalmology: review article

    M Jabbarvand Behrouz


    Full Text Available "nThe response of living tissues to the surgical trauma is associated with varying degrees of tissue repair and involves two distinct processes including replacement and regeneration. Replacement results in scar tissue formation instead of restoration of the normal architecture. However, regeneration leads to restoration of the original architecture leaving no sign of injury. Anti-proliferative agents are used to inhibit tissue responses to surgical trauma. Among them mitomycin- C and 5- FU had gained increasing applications in ophthalmic surgeries, including filtering glaucoma surgeries, laser vision correction with excimer laser by ablative surface refractive surgery, reconstructive surgeries for ocular surface disorders and removal of neoplastic tissues and secondary operations on nasolacrimal ducts. In this review article, the various aspects of applications of these agents including their mechanism of action, function, mode of application and complications in different ophthalmology fields are discussed.

  12. Neo-adjuvant chemotherapy with cisplatin and short infusional 5-FU in advanced head and neck malignancies

    Aich Ranen Kanti


    Full Text Available Background: Combination of radical surgery and radiotherapy is the standard management of head and neck malignancies. But due to considerable morbidity of surgery and associated cosmetic and functional deficiencies, often aggravated by adjuvant radiotherapy, many patients prefer only radiotherapy with its′ decreased chance of survival. Proper surgical facilities are also not accessible to most of our patients. Neo-adjuvant chemotherapy and loco-regional management by surgery and / or radiotherapy have emerged as a viable alternative. Aims: The purpose of this study is to find out the survival outcome as well as toxicity profile of Neo-adjuvant chemotherapy with cisplatin and short infusional (3 hours 5-FU followed by radiotherapy in advanced head and neck malignancies. Materials and Methods: From June 2002 to December 2003, seventy four patients with advanced head and neck malignancies were planned to be treated with Cisplatin (50 mg / sq. meter on Days 1 and 2 and 5 - FU (600 mg / sq. meter on Days 1, 2 and 3 by 3 hour infusion on Day care basis. On completion of four cycles of chemotherapy at 21 days interval, all patients were destined to receive 6000 cGy of radiotherapy to the loco - regional site. Results: At one year follow up on completion of therapy, 57% patients were alive and 31% patients were disease free. These 31% patients enjoyed a good quality of life in terms of cosmetic and functional deficits. Toxicities were moderate and easily manageable. Conclusion: The study indicated that neo-adjuvant chemotherapy with Cisplatin and short infusional 5 - FU may be delivered on day care basis and results are comparable with Cisplatin and 96 hours continuous infusional 5 - FU. Thus avoiding the continuous infusional 5 - FU, 7 to 10 days in-patient hospitalization during each cycle may be avoided which is a constrain in developing countries like us.

  13. Inoperable esophageal carcinoma managed by combined chemotherapy (CBDCA, 5FU and VDS) and radiotherapy

    Morishima, Yuichi; Tashiro, Tsuguhiko; Yamamori, Hideo [Chiba Univ. (Japan). School of Medicine] [and others


    Eleven inoperable patients with advanced esophageal carcinoma were treated with chemotherapy (carboplatin, 5-FU, vindesine) and concomitant radiotherapy. Two patients (T2) received this treatment due to their poor general condition and refusal of operation, and 9 patients for infiltration of tumor into the adjacent organs (T4). Administration of carboplatin (30 mg/body) and 5-FU (250 mg/body) together with radiotherapy (1.8 Gy/d) for 5 days a week was performed. This chemoradiation therapy was carried out for 5 consecutive weeks. In addition, vindesine (1-3 mg/body) was administered in the 1st and 4th week. After evaluation, endoscopic balloon dilatation was performed in 6 patients with stenosis of the esophagus. The general response rate was 80%. CR was noted in 2 patients of T2 but 1 patient of T4 developed severe leucopenia and immunosuppression, and died of septic MOF. All but the MOF case could take enough food orally following the endoscopic dilatation. The 1-year survival rate in the T4 group (45%) was significantly better than the non-treatment group (0%). In conclusion, this treatment is beneficial for patients with inoperable esophageal carcinoma to obtain a satisfactory QOL and survival rate. (author)

  14. Chromosomal imbalance maps of human 5FU-resistant colorectal cancer cell lines: implications in the analysis of 5FU-acquired resistance mechanisms.

    Plasencia, C; Rooney, P H; Taron, M; Martinez-Balibrea, E; McLeod, H L; Abad, A


    Thymidylate synthase (TS), a critical enzyme in the de novo synthesis of thymidylate, is an important target for fluoropyrimidines and folate-based TS inhibitors. Overexpression of TS has been correlated to 5-fluorouracil (5FU)-resistance. Because 5FU still remains a basic component of the treatment of colorectal cancer, circumvention of resistance is of vital importance. A panel of sensitive (HT29 and LoVo) and 5FU-resistant colorectal cancer cell lines (HT29-5FUR and LoVo-5FUR) were subjected to comparative genomic hybridization (CGH) analysis to identify possible amplified/deleted regions associated with 5FU-resistance in colon tumours. We have identified chromosomal gains at 5p, 6, 7p, 7q and 8q and one loss at 3q in 5FU-resistant cells as compared to corresponding sensitive cell lines. Neither chromosomal gains at 18p nor gene amplification of TS were observed in our resistant cell lines although an overexpression of TS gene exists (at mRNA level) in these cell lines as compared with corresponding parental cells. Most of the chromosomal gains identified in this study occur frequently in sporadic colorectal tumours and has been associated to a poor prognosis and a greater progression of the tumour and could be related to a worse chemotherapy response. The chromosomal imbalance profile detected in 5FU-resistant cell lines should provide a basis for interpreting mechanisms of 5FU-resistance in colorectal cancer and also possibly in other tumours treated with this agent. This study also identified new genes potentially implicated in 5FU-resistance and suggests new targets that could be useful for the chemotherapy treatment of colorectal cancer.

  15. Concomitant radiochemotherapy with 5-FU and cisplatin for invasive bladder cancer. Acute toxicity and first results

    Birkenhake, S.; Leykamm, S.; Sauer, R. [Friedrich-Alexander Univ., Erlangen-Nuernberg (Germany). Dept. of Radiooncology; Martus, P. [Friedrich-Alexander Univ., Erlangen-Nuernberg (Germany). Dept. of Medical Statistics


    Purpose: To evaluate acute toxicity and efficacy of simultaneous radiochemotherapy for invasive urothelial cancer of the bladder. Patients and Methods: From September 1993 to July 1997, 61 patients with invasive bladder cancer were treated with a transurethral resection (TURB) followed by radiochemotherapy (RCT). Twenty-five received a combination of 5-FU and cisplatin. The prescribed doses were 600 mg/m{sup 2} 5-FU daily as continuous infusion over 5 days each in the 1st and 5th treatment week and 20 mg/m{sup 2} cisplatin daily at the same days as a short infusion. The pelvis was irradiated with 54 Gy, the bladder with 59.4 Gy and the paraortic nodes in 7 cases with 45 Gy, respectively. Six to 8 weeks after RCT a second TURB was performed for reasons of restaging. Results: Twenty out of 25 patients received at least 80% of the prescribed chemotherapy, in 13 cases the full dose could be given. Gastrointestinal toxicity of Grade I and II occurred in 10 cases, 1 patient developed severe diarrhea (Grade VI). After the 1st course of chemotherapy 7 patients had leuco- or thrombopenia of Grade III. One patient had a leucopenia of Grade IV. After the 2nd course 4 patients developed Grade III leuko- and thrombopenia, 1 of Grade IV. Two Grade II anemia were found. All more severe toxicities and necessary dose reductions were related to radiation of the paraaortic nodes. No life threatening infections, bleedings or cardiotoxicity was found. Restaging TURBs resulted in 22 complete remissions, 1 patient had a de-novo-carcinoma (Tis) at this time, 2 were non-responders (8%). After a median follow-up of 38 months 20 patients are alive (80%). Conclusions: 1. If irradiation of paraaortic nodes is necessary, 5-FU should not be applied, because the gastrointestinal toxicity is too extensive. In all other cases side effects are tolerable and can be managed by supportive care. 2. The first results are promising and should be evaluated in a prospective study. (orig.) [Deutsch

  16. Adenovirus KH901 promotes 5-FU antitumor efficacy and S phase in LoVo cells.

    Peng, Wei; Li, Jin; Yin, X G; Xu, J F; Cheng, L Z


    A combination of oncolytic and chemotherapeutic agents has been used to kill cancer cells. However, the effect of oncolytic adenoviruses on the cell cycle remains to be determined. Cytotoxicity assays were performed to determine cell death in cells treated with 5-fluorouracil (5-FU) alone or in combination with the oncolytic adenovirus KH901. Dynamic changes in the cell cycle, cell proliferation, and apoptosis-related proteins including p-AKT, Bcl-2, Bax, and caspase 3 were investigated after treatment with 5-FU with or without KH901. A higher proportion of S-phase cells were observed after treatment with KH901 and 5-FU than with 5-FU alone. p-AKT, Bcl-2, and Bax expression was increased upon treatment with KH901, whereas the expression of caspase-3 was not induced upon treatment with KH901 with or without 5-FU. KH901 exhibited significant potential as an oncolytic adenovirus and increased cell death in combination with 5-FU in LoVo cells, as compared to 5-FU alone. In conclusion, KH901 stimulates LoVo cells to enter the S-phase by activation of p-AKT, which could partly explain its synergistic effect with 5-FU on LoVo cell cytotoxicity.

  17. Randomized adjuvant study comparing two schemes of 5-fluorouracil and leucovorin in stage B2 and C colon adenocarcinoma: study design and preliminary safety results. Groupe d'Etude et de Recherche Clinique en Oncologie Radiotherapies.

    André, T; Colin, P; Louvet, C; Gamelin, E; Bouche, O; Achille, E; Colbert, N; Boaziz, C; Piedbois, P; Tubiana-Mathieu, N; Boutan-Laroze, A; Flesch, M; Billiau, V; Buyse, M; Gramont, A


    The aim of this randomized open-label study was to compare a bimonthly with a monthly regimen of 5-fluorouracil (5-FU) and leucovorin for the adjuvant treatment of colon and high-rectum adenocarcinoma. The bimonthly regimen was administered for 2 consecutive days every 14 days as d,L-leucovorin 200 mg/m2 or L-leucovorin 100 mg/m2 as a 2-hour infusion followed by 5-FU bolus of 400 mg/m2 and a 600 mg/m2 5-FU 22-hour continuous infusion (LVSFU2). In the monthly regimen, d,L-leucovorin 200 mg/m2 or L-leucovorin 100 mg/m2 15-minute infusion followed by a 400 mg/m2 15 minute 5-FU bolus was administered for 5 consecutive days every 28 days (FUFOL). Nine hundred five patients with recently resected stage B2 or C colon or high-rectum adenocarcinoma (inferior pole of the tumor subperitoneal) were recruited into the study. Patients were randomized in a 2 x 2 factorial design to receive either LV5FU2 or FUFOL for 24 or 36 weeks. Characteristics of the patients in the two different treatment groups were similar at baseline. Compliance was good. Mean 5-FU dose intensities were 930 mg/ m2/wk and 463 mg/m2/wk for LVSFU2 and FUFOL, respectively. The incidence of maximal grade III-IV toxicities for LVSFU2 and FUFOL was neutropenia 6% and 16% (P < .001), diarrhea 4% and 10% (P < .001), and mucositis 2% and 7% (P < .001), respectively. Maximum grade III-IV toxicities in the LV5FU2 treatment group were significantly lower than in the FUFOL group (10% v 26%; P < .001). Although patients in the LV5FU2 group received twice the dose of 5-FU compared with those in the FUFOL group, LV5FU2 was shown to be less toxic. Efficacy data will be available in 2001.

  18. 5-FU-hydrogel inhibits colorectal peritoneal carcinomatosis and tumor growth in mice

    Shi Huashan


    Full Text Available Abstract Background Colorectal peritoneal carcinomatosis (CRPC is a common form of systemic metastasis of intra-abdominal cancers. Intraperitoneal chemotherapy is a preferable option for colorectal cancer. Here we reported that a new system, 5-FU-loaded hydrogel system, can improve the therapeutic effects of intraperitoneal chemotherapy. Methods A biodegradable PEG-PCL-PEG (PECE triblock copolymer was successfully synthesized. The biodegradable and temperature sensitive hydrogel was developed to load 5-FU. Methylene blue-loaded hydrogel were also developed for visible observation of the drug release. The effects and toxicity of the 5-FU-hydrogel system were evaluated in a murine CRPC model. Results The hydrogel system is an injectable flowing solution at ambient temperature and forms a non-flowing gel depot at physiological temperature. 5-FU-hydrogel was subsequently injected into abdominal cavity in mice with CT26 cancer cells peritoneal dissemination. The results showed that the hydrogel delivery system prolonged the release of methylene blue; the 5-FU-hydrogel significantly inhibited the peritoneal dissemination and growth of CT26 cells. Furthermore, intraperitoneal administration of the 5-FU-hydrogel was well tolerated and showed less hematologic toxicity. Conclusions Our data indicate that the 5-FU-hydrogel system can be considered as a new strategy for peritoneal carcinomatosis, and the hydrogel may provide a potential delivery system to load different chemotherapeutic drugs for peritoneal carcinomatosis of cancers.

  19. [Coma following chemotherapy: is 5FU implicated? Discussion about on case-report].

    Heluwaert, Frédéric; Santre, Charles; Martin, Claude; Hilleret, Marie-Noëlle; Martin, Denis


    5FU is one of the most frequently used antioncogenic and cytostatic drug in digestive oncology. It may cause severe adverse events, such as encephalopathy, possibly based on hyperammoniemia, and may lead to coma. We report here the case of a coma with a favorable outcome following 5FU chemotherapy. As any other etiologic findings came to light, hyperammoniemia was discussed as a credible cause.

  20. Enhanced DNA-directed effects of FdUMP[10] compared to 5FU.

    Gmeiner, William H; Trump, Eric; Wei, Cui


    FdUMP[N] molecules and conjugates are much more effective at inhibiting the proliferation of human tumor cells than is the widely used anticancer drug 5-fluorouracil (5FU). We have evaluated the inhibition of thymidylate synthase (TS), the extent of DNA damage, cell cycle arrest, and the induction of apoptosis by FdUMP[10] and 5FU in the human colorectal cancer cell line HT29. The magnitude and duration of TS inhibition following exposure of HT29 cells to FdUMP[10] at 1 x 10(-8) M was greater than that which occurred following exposure of these cells to 5FU at 1 x 10(-6) M. FdUMP[10] exposure also resulted in much more extensive DNA damage to HT29 cells than occurred following exposure to 100-fold higher concentrations of 5FU. Although exposure of HT29 cells to both drugs resulted in S-phase arrest, more complete accumulation of cells in S-phase was achieved following FdUMP[10] exposure at much lower drug concentrations. FdUMP[10] was also much more effective at inducing apoptosis in HT29 cells than was 5FU. The results are consistent with FdUMP[10] being much more efficient that 5FU at inducing DNA damage that results in apoptotic cell death in colon cancer cells.

  1. Resistance of colorectal cancer cells to radiation and 5-FU is associated with MELK expression

    Choi, Seungho [Laboratory of Cell Biology, Cancer Research Institute, Seoul National University College of Medicine, Seoul 110-799 (Korea, Republic of); Ku, Ja-Lok, E-mail: [Laboratory of Cell Biology, Cancer Research Institute, Seoul National University College of Medicine, Seoul 110-799 (Korea, Republic of)


    Highlights: {yields} MELK expression significantly increased when the cells are exposed to radiation or 5-FU. {yields} Suppression of MELK caused cell cycle changes and decrease in proliferation. {yields} Radiation or 5-FU treatment after MELK suppression by siRNA induced growth inhibition. -- Abstract: It was reported that the local recurrence would be caused by cancer stem cells acquiring chemo- and radio-resistance. Recently, one of the potential therapeutic targets for colorectal and other cancers has been identified, which is maternal embryonic leucine zipper kinase (MELK). MELK is known as an embryonic and neural stem cell marker, and associated with the cell survival, cell proliferation, and apoptosis. In this study, SNU-503, which is a rectal cancer cell line, was treated with radiation or 5-fluorouracil (5-FU), and elevation of the MELK expression level was observed. Furthermore, the cell line was pre-treated with small interfering RNA (siRNA) against MELK mRNA before treatment of radiation or 5-FU and its effects on cell cycle and proliferation were observed. We demonstrated that knockdown of MELK reduced the proliferation of cells with radiation or 5-FU treatment. In addition, MELK suppression caused changes in cell cycle. In conclusion, MELK could be associated with increased resistance of colorectal cancer cells against radiation and 5-FU.

  2. Inhibitory effect of silibinin combined with 5-FU treatment on malignant biological behaviors of gastric cancer cell lines MGC803

    Yang Wang; Chang-Lin Li


    Objective:To study the inhibitory effect of silibinin combined with 5-FU treatment on malignant biological behaviors of gastric cancer cell lines MGC803.Methods:Gastric cancer cell lines MGC803 were cultured, divided into NC group, 5-Fu group and SB+5-Fu group and treated with different conditions, and then the number of apoptotic cells, the number of invasive cells as well as the expression of proliferation and invasion-related genes were detected.Results:At 6 h, 12 h, 18 h and 24 h after treatment, the number of apoptotic cells of 5-Fu group and SB+5-Fu group was significantly more than that of NC group, the number of invasive cells was significantly less than that of NC group, the number of apoptotic cells of SB+5-Fu group was significantly more than that of 5-Fu group, and the number of invasive cells was significantly less than that of 5-Fu group; mRNA contents of Vav3, PTP1B, GOLPH3, RUNX3, Sipa1, UbcH10, NEDD9, Mig-7, CD157, AEP and Galectin-1 of 5-Fu group and SB+5-Fu group were lower than those of NC group; mRNA contents of Vav3, PTP1B, GOLPH3, UbcH10, NEDD9, Mig-7, CD157, AEP and Galectin-1 of SB+5-Fu group were lower than those of 5-Fu group, and mRNA contents of RUNX3 and Sipa1 were not different from those of 5-Fu group. Conclusion:Compared with single 5-FU treatment, silibinin combined with 5-FU treatment can more effectively promote gastric cancer cell apoptosis, inhibit gastric cancer cell invasion and regulate the expression of proliferation and invasion-related genes.

  3. Are capecitabine and the active metabolite 5-Fu CNS penetrable to treat breast cancer brain metastasis?

    Zhang, Jinqiang; Zhang, Lingli; Yan, Yumei; Li, Shaorong; Xie, Liang; Zhong, Wei; Lv, Jing; Zhang, Xiuhua; Bai, Yu; Cheng, Ziqiang


    Brain metastasis (BM) is increasingly diagnosed in Her2 positive breast cancer (BC) patients. Lack of effective treatment to breast cancer brain metastases (BCBMs) is probably due to inability of the current therapeutic agents to cross the blood-brain barrier. The central nervous system (CNS) response rate in BCBM patients was reported to improve from 2.6%-6% (lapatinib) to 20%-65% (lapatinib in combination with capecitabine). Lapatinib is a poor brain penetrant. In this study, we evaluated the CNS penetration of capecitabine and hoped to interpret the mechanism of the improved CNS response from the pharmacokinetic (PK) perspective. Capecitabine does not have antiproliferative activity and 5-fluorouracil (5-FU) is the active metabolite. Capecitabine was orally administered to mouse returning an unbound brain-to-blood ratio (Kp,uu,brain) at 0.13 and cerebrospinal fluid (CSF)-to-unbound blood ratio (Kp,uu,CSF) at 0.29 for 5-FU. Neither free brain nor CSF concentration of 5-FU can achieve antiproliferative concentration for 50% of maximal inhibition of cell proliferation of 4.57 µM. BCBM mice were treated with capecitabine monotherapy or in combination with lapatinib. The Kp,uu,brain value of 5-FU increased to 0.17 in the brain tumor in the presence of lapatinib, which is still far below unity. The calculated free concentration of 5-FU and lapatinib in the brain tumor did not reach the antiproliferative potency and neither treatment showed antitumor activity in the BCBM mice. The CNS penetration of 5-FU in human was predicted based on the penetration in preclinical brain tumor, CSF, and human PK and the predicted free CNS concentration was below the antiproliferative potency. These results suggest that CNS penetration of 5-FU and lapatinib are not desirable and development of a true CNS penetrable therapeutic agent will further improve the response rate for BCBM.

  4. In vitro and in vivo antitumor effect of 5-FU combined with piplartine and piperine.

    Bezerra, Daniel P; de Castro, Fernanda O; Alves, Ana Paula N N; Pessoa, Cláudia; de Moraes, Manoel Odorico; Silveira, Edilberto R; Lima, Mary Anne S; Elmiro, Francisca Juliana M; de Alencar, Nylane M N; Mesquita, Rodney O; Lima, Michael W; Costa-Lotufo, Letícia V


    It has been reported that piplartine and piperine, alkaloid/amide compounds from Piper species, show antitumor activities. In the present paper, the effects of the combination of 5-fluorouracil (5-FU) with piplartine or piperine was determined using in vitro and in vivo experimental models. Hematological and biochemical analyses, as well as histopathological and morphological analyses of the tumor and the organs, including liver, spleen and kidney, were performed in order to evaluate the toxicological aspects associated with different treatments. The incubation of tumor cell lines with 5-FU in the presence of piplartine or piperine produced an increase in growth inhibition, as observed by lower IC50 values for 5-FU. These effects were also observed in vivo, where the combination with piplartine but not piperine with 5-FU led to a higher tumor growth inhibition. The results indicated that either piplartine- or 5-FU-treated animals showed a low inhibition rate when they were used individually at low doses of 28.67% and 47.71%, respectively, but when they were combined at the same dose, the inhibition rate increased significantly to 68.04%. The histopathological analysis showed that the livers and the kidneys of treated animals were only slightly and reversibly affected. Neither the enzymatic activity of transaminases nor the urea levels were significantly modified when compared with the control group. Hematological analysis showed leukopenia after 5-FU treatment, which was reversed by the combined use of piplartine and piperine. These findings indicate that piplartine may enhance the therapeutic effectiveness of chemotherapeutic drugs, and moreover, this combination could improve immunocompetence hampered by 5-FU.

  5. Effect of resveratrol and in combination with 5-FU on murine liver cancer

    Sheng-Li Wu; Zhong-Jie Sun; Liang Yu; Ke-Wei Meng; Xing-Lei Qin; Cheng-En Pan


    AIM: To study the anti-tumor effect of resveratrol and in combination with 5-FU on murine liver cancer.METHODS: Transplantable murine hepatoma22 model was used to evaluate the anti-tumor activity of resveratrol (RES)alone or in combination with 5-FU in vivo. H22 cell cycles were analyzed with flow cytometry.RESULTS: Resveratrol could inhibit the growth of murine hepatoma22, after the mice bearing H22 tumor were treated with 10 mg/kg or 15 mg/kg resveratrol for ten days, and the inhibition rates were 36.3% (n = 10) and 49.3% (n = 9),respectively, which increased obviously compared with that in control group (85±22 vs 68±17, P<0.01). RES could induce the S phase arrest of H22 cells, and increase the persentage of cells in S phase from 59.1% (n = 9) to 73.5% (n = 9) in a dose-dependent manner (P<0.05). The enhanced inhibition of tumor growth by 5-FU was also observed in hepatoma22 bearing mice when 5-FU was administered in combination with 10 mg/kg resveratrol. The inhibition rates for 20 mg/kg or 10 mg/kg 5-FU in combination with 10 mg/kg resveratrol were 77.4% and 72.4%, respectively, compared with the group of 20 mg/kg or 10 mg/kg 5-FU alone, in which the inhibition rates were 53.4% and 43.8%, respectively (n = 8). There was a statistical significance between the combination group and 5-FU group.CONCLUSION: RES could induce the S phase arrest of H22cells and enhance the anti-tumor effect of 5-FU on murine hepatoma22 and antagonize its toxicity markedly. These results suggest that resveratrol, as a biochemical modulator to enhance the therapeutic effects of 5-FU, may be potentially useful in cancer chemotherapy.

  6. Up-regulation of insulin-like growth factor-binding protein 3 by 5-fluorouracil (5-FU) leads to the potent anti-proliferative effect of androgen deprivation therapy combined with 5-FU in human prostate cancer cell lines.

    Kawabata, Rumi; Oie, Shinji; Takahashi, Masayuki; Kanayama, Hiroomi; Oka, Toshinori; Itoh, Kohji


    In this study, we investigated the synergistic mechanism of anti-androgen and 5-fluorouracil (5-FU) combination therapy against castration-resistant prostate cancer (CRPC). Four prostate cancer cell lines, LNCaP, 22Rv1, DU145 and PC3, were examined for their growth dependency on androgens and the insulin-like growth factor 1 (IGF1). We assessed the expression changes of certain growth factor receptors and regulating proteins when treated with 5-FU, and found that 5-FU increased the expression of the IGF-binding protein 3 (IGFBP3). Furthermore, 5-FU inhibited the phosphorylation of Akt and p70 S6K, while the knockdown of IGFBP3 reduced the levels of poly (ADP-ribose) polymerase cleaved by 5-FU in PC3 cells. Therefore, the up-regulation of IGFBP3 by 5-FU not only inhibits cell growth by reducing the IGF1 signal but also induces apoptosis in PC3 cells. The synergistic effect of bicalutamide and 5-FU on 22Rv1 cells was reduced by IGFBP3 gene silencing using small-interfering RNA. These results suggest that the up-regulation of IGFBP3 induced by 5-FU plays an important role in the potent anti-tumor effect of 5-FU combined with anti-androgens on CRPC. Androgen-deprivation therapy combined with 5-FU could therefore be an appropriate therapy for CRPC patients.

  7. Life expectancy with perioperative chemotherapy and chemoradiotherapy for locally advanced gastric adenocarcinoma

    Sadighi S


    Full Text Available "nBackground: Although postoperative chemoradiotherapy should be considered for all patients at high risk for recurrence of adenocarcinoma of the stomach, curative surgery occurs in less than 50% of nonmetastatic gastric cancers. A regimen of docetaxel, cisplatin and infusional fluorouracil improves survival of patients with incurable locally-advanced gastric adenocarcinoma. So we assessed the perioperative regimen of docetaxel, cisplatin and infusions 5FU (TCF and postoperative chemoradiotherapy to improve outcomes in patients with potentially resectable gastric adenocarcinoma. "nMethods: Between March 2005 and March 2008, we 100 enrolled patients with stage II to IV (M0 adenocarcinoma of the stomach who had not been treated previously. Treatment consisted of three preoperative and one postoperative cycles of TCF followed by chemoradiotherapy. The primary end point was overall survival. The secondary end points were progression-free survival and toxicity of treatment. "nResults: A total of 100 patients participated, 83 of whom received neoadjuvant and 17 received adjuvant chemotherapy. Seventy-five patients underwent at least D0 gastrectomy. After chemotherapy, tumor stages were significantly lower than before beginning the protocol. Out of 100 patients, 44 had stage IV before chemotherapy versus 15 after the treatment. Three patients showed complete pathologic response. The median survival time was 25 months. "nConclusion: Docetaxel, cisplatin and 5FU combination chemotherapy is an active preoperative treatment in locally advanced gastric cancer. Perioperative chemoradio-therapy should be considered as an option to lengthen patient survival.

  8. In vivo biodistribution for tumor targeting of 5-fluorouracil (5-FU) loaded N-succinyl-chitosan (Suc-Chi) nanoparticles.

    Yan, Chengyun; Gu, Jiwei; Guo, Yuzhi; Chen, Dawei


    5-Fluorouracil-loaded N-succinyl-chitosan nanoparticles (5-FU-Suc-Chi/NP) were prepared by emulsification solvent diffusion. Biodistribution and tumor targeting were evaluated after i.v. administration of 5-Fu-Suc-Chi/NPs in Sarcoma 180-bearing mice. Also, pharmacokinetic profiles were evaluated after intravenous injection of 5-Fu-Suc-Chi/NP via the tail vein to rats. Our experimental results showed the 5-FU-Suc-Chi/NPs could be sustained at a high level in the blood for a very long time, implying its long systemic retention in the circulation. 5-FU-Suc-Chi/NPs were distributed mainly in tumors and liver, with small quantities being found in kidney and spleen. 5-FU-Suc-Chi/NPs accumulated only slightly in the heart and lung, and lowered the toxic effect of 5-FU in the heart and lung. Pharmacokinetic analysis in plasma showed the area under plasma concentration-time curve (AUC), elimination half-life (t(1/2)), and residence time (MRT) were increased 2.5-fold, 10.98-fold, and 10.8-fold for 5-FU-Suc-Chi/NP compared with that of free 5-FU, respectively. These results indicate that a long half-life in the circulation and tumor targeting of 5-FU-Suc-Chi/NPs are possible.

  9. Wild type p53 increased chemosensitivity of drug-resistant human hepatocellular carcinoma Be17402 / 5-FU cells

    Yu-xiuLI; Zhi-binLIN; Huan-ranTAN


    AIM: To study the effect of wild type (wt) p53 gene transfection on drug resistant human hepatocellular carcinoma(HCC) cells induced by 5-Fluorouracil (5-FU). METHODS: The cytotoxicity of anticancer drugs on Be17402 and Be17402/5-FU cells was assessed using SRB assay, p53 expression was detected at its mRNA level by RT-PCR assay and at its protein level Western blot or immunocytochemistry assay in Be17402/5-FU cells transfected with either control vector or wt p53. AnnexinV-FITC/PI double labeled assay was performed to detect apoptosis. The chemosensitivity of Be17402/5-FU cells transfected with wt p53 was assessed using SRB assay. RESULTS: Be17402/5-FU cells exhibited cross-resistance to vincristine, doxorubicin, paclitaxel, and so on. wt p53 gene transfection upregulated the expression of p53 in Be17402/5-FU cells, wt p53 was able to greatly inhibit cell proliferation and significantly induce apoptosis in Be17402/5-FU cells. Moreover, wt p53 gene transfection increased the chemosensitivity of Be17402/5-FU cells to some anticancer drugs. CONCLUSION: These results indicated that the wt p53 gene transfection not only induced suppression of cell growth, but also increased the sensitivity of Be17402/5-FU cells to 5-FU, vincristine, and doxorubicin.

  10. Preparation and evaluation of chitosan based thermoreversible gels for intraperitoneal delivery of 5-fluorouracil (5-FU).

    Depani, Bhavesh P; Naik, Anuja A; Nair, Hema A


    Sterile thermoreversibly gelling systems based on chitosan- glycerol phosphate were developed for intraperitoneal delivery of the antineoplastic agent 5-FU. The formulation was evaluated for gelling characteristics and in vitro drug release. Drug free gels were evaluated for in vitro cytotoxicity in L-929 mouse fibroblast cells. Drug loaded gels were subjected to acute toxicity studies in Swiss albino mice via intraperitoneal route and efficacy studies via intratumoral injections in subcutaneous colon carcinoma bearing BALB/c mice. The formulations gelled reversibly in 8 min at 37 °C and provided prolonged release of the drug. Drug free systems showed dose dependent cytotoxicity in fibroblast cells, while in vivo studies revealed a 2.8-fold increase in LD50 of 5-FU administered intraperitoneally as the developed system. Tumor volume measurements showed comparable efficacy of 5-FU administered as gel and commercial injection with a greatly improved safety profile of the former as adjudged from mortality and body weight measurements.

  11. "Long term results of intraoperative 5-FU in Glaucoma filtering procedures "

    "Hashemian MN


    Full Text Available This prospective study evaluated the long-term results of intraoperative 5-FU in glaucoma patients undergoing trabeculectomy. 14 patients categorized as high risk or medium risk underwent trabeculectomy with 5-FU and were followed for a mean period of 32 months. Patients were evaluated for visual acuity, cup-disc ratio and intraocular pressure (IOP; the number of medications was also taken into consideration. 78% (11 of patients achieved controlled IOP (< 21 mmHg with or without medication. There was statistically significant reduction of IOP and number of medications after the operation. There were no significant complications observed during the follow-up period.

  12. Targeting distribution of PEG-5-FU-MAMS in colorectal carcinoma tissue of nude mice%PEG-5-FU-MAMS靶向治疗裸鼠大肠癌的实验研究

    房玉海; 张春林; 洪志飞


    目的 研究聚乙二醇(polyethylene glycol,PEG)修饰的5-氟尿嘧啶磁性白蛋白微球(PEG-modified 5-FU magnetic albumin microsphere,PEG-5-FU-MAMS)和5-氟尿嘧啶磁性白蛋白微球(5-FU-MAMS)对大肠癌组织的被动靶向性,为实现大肠癌的主动靶向治疗,减少化疗药物的不良反应寻找新的途径.方法 30只人大肠癌裸鼠随机分为3组:(1)游离5-FU组;(2) 5-FU-MAMS组;(3) PEG-5-FU-MAMS组.每组10只,分别将3种不同的制剂(按5-FU 8mg/kg)经尾静脉给药,30分钟后,经眼眶采血,处死裸鼠,用HPLC法测定血清、肿瘤、肾脏、肝脏组织5-FU的浓度.结果 (1)PEG-5-FU-MAMS组、5-FU-MAMS组和游离5-FU组肿瘤组织中的药物浓度分别为(51.2±2.1) mg/L、(33.1 ±8.2)mg/L和(20.3±1.9) mg/L,PEG-5-FU-MAMS组肿瘤组织中药物浓度明显高于5-FU-MAMS和游离5-FU组(P<0.01);而在血清中药物浓度相反,PEG-5-FU-MAMS组[(1.7±0.5)mg/L]明显低于5-FU-MAMS[(6.8±0.2)mg/L]和游离5-FU组[(7.1±0.8)mg/L] (P <0.01);PEG-5-FU-MAMS组肝、肾脏中药物浓度[(22.7±2.4) mg/L和(21.1±2.3)mg/L]明显低于5-FU-MAMS[(44.3±6.7)mg/L和(38.2±4.9) mg/L]和游离5-FU组[(45.9 ±7.8)mg/L和(39.7±3.2)mg/L] (P <0.05).(2)PEG-5-FU-MAMS对裸鼠大肠癌的抑瘤率明显高于游离5-FU和5-FU-MAMS(45.3% vs 15.0%、30.1%,P<O.05).结论 PEG-5-FU-MAMS对大肠癌组织的靶向作用明显强于5-FU-MAMS和游离5-FU,但肝、肾脏的被动靶向作用明显减弱,有效地减轻药物对肝、肾脏的不良反应.PEG-5-FU-MAMS的抗结直肠癌作用明显强于游离5-FU和5-FU-MAMS.PEG-5-FU-MAMS有望成为肿瘤主动靶向治疗的有效药物.

  13. A prospective randomized study of irinotecan (CPT-11), leucovorin (LV) and 5-fluorouracil (5FU) versus leucovorin and 5-fluorouracil in patients with advanced colorectal carcinoma.

    Gennatas, C; Papaxoinis, G; Michalaki, V; Mouratidou, D; Andreadis, C; Tsavaris, N; Pafiti, A


    The purpose of this study was to compare the activity and toxicity of an irinotecan (CPT-11), leucovorin (LV) and 5-fluorouracil (5FU) combination with a standard regimen of 5FU and LV, in patients with advanced colorectal carcinoma. One hundred and sixty patients were randomized; 80 patients (group A) received LV 20 mg/m(2) bolus i.v. and 5FU 425 mg/m(2) bolus i.v. on days 1-5, every 28 days; 80 patients (group B) received CPT-11 80 mg/m(2) (30-90 min i.v. infusion), followed by LV 20 mg/m(2) bolus i.v. and 5FU 425 mg/m(2) bolus i.v. on days 1, 8, 15, 22, 29, and 36, every 8 weeks. The overall response rate was 30% and 47.5% in groups A and B respectively. Progression-free survival was significantly higher in the triple-drug combination arm (median 7.5 vs. 4.5 months; p= 0. 0335). However, overall survival did not differ significantly between the two arms (15 months vs. 14 months for the groups B and A respectively; p=0.3531). The main grade 3 adverse events were diarrhea (19%, in group A vs. 35% in group B; p=0.032) and mucositis (2% vs. 14%; p=0.017). The regimen containing irinotecan showed activity in advanced colorectal cancer. The overall safety data confirm this combination as a well-tolerated treatment.

  14. Evaluation of 5-FU pharmacokinetics in cancer patients with DPD deficiency using a Bayesian limited sampling strategy

    Van Kuilenburg, A.; Hausler, P.; Schalhorn, A.; Tanck, M.; Proost, J.H.; Terborg, C.; Behnke, D.; Schwabe, W.; Jabschinsky, K.; Maring, J.G.


    Aims: Dihydropyrimidine dehydrogenase (DPD) is the initial enzyme in the catabolism of 5-fluorouracil (5FU) and DPD deficiency is an important pharmacogenetic syndrome. The main purpose of this study was to develop a limited sampling strategy to evaluate the pharmacokinetics of 5FU and to detect dec

  15. Relationship between pharmacokinetics of 5-FU in plasma and in saliva, and toxicity of 5-fluorouracil/folinic acid

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


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

  16. A pilot study of first-line chemotherapy with 5-FU and Platinum in advanced and recurrent cancer of the cervix

    Ghaemmaghami F


    Full Text Available This study was designed to assess the role of first-line chemotherapy with 5-FU and platinum in the treatment of advanced or recurrent cervical cancer, ten patients with advanced or recurrent cancer of the cervix, with no prior chemotherapy were entered in phase II trial, from Oct. 2000 to Nov. 2001. Eight patients were treated with cis-platinum (50 mg/m2 over 60 minutes in first day followed by 5-FU (1 g/m2 over 24 hours for 4 days and two patients with impaired renal function were treated with carboplatin (300 mg/m2 over 15 minutes in first day followed by 5-FU (1 g/m2 over 24 hours for 4 days every three weeks, until progression of disease or prohibitive toxicity had been observed. Median age was 52 years (range: 28-70 years. Ten patients received a total of 42 cycles of chemotherapy. The mean number of chemotherapy cycles was 4.2 (median 4, range: 3-7. Three patients had partial response (30%, CI, 1.7%-58.5%. Mean response duration was 198 days (range: 122-273 days. Four patients required red blood cell transfusions; three of them had grade II and one of them grade III nausea and vomiting Two had fever and neutropenia (one developed acute renal insufficiency, and there wee no treatment related mortalities. First-line chemotherapy with platinum and 5-FU for advanced recurrent cervical cancer is promising and deserves consideration for large phase III trials.

  17. Evaluation of preoperative radiation therapy in combination with low dose carboplatin and 5FU

    Yokomizo, Michinori; Tada, Hiroyuki; Ishikawa, Kazuo; Togawa, Kiyoshi [Akita Univ. (Japan). School of Medicine; Okamoto, Yoshitaka; Matsuzaki, Zensei


    A comparative study was performed to evaluate difference in the histological effects and side effects between a group of tongue cancer and hypopharyngeal cancer patients treated with 5FU (250 mg x 3 days/week) and 60 Gy radiation, and those treated with CBDCA (50-80 mg x 1 day/week) followed by 5FU (250 mg x 2 days/week) and 40 Gy radiation. In the tongue cancer patients, there was no significant change in histological effects according to Shimosato`s classification system. A decrease in leukocytes was found in the CBDCA group, which was not statistically significant. In cases with hypopharyngeal cancer, the number of leukocytes was significantly decreased in the CBDCA group. However the number of platelets and degree of stomatitis was not significantly altered. (author)


    Ardeshir Ghavamzadeh


    Full Text Available This study was undertaken to assess the effectiveness of 5-FU plus epirubicin in the treatment of the advanced gastric cancer. For this purpose, 22 patients with no previous treatment were studied. All of the patients were unoperable or metastatic. Follow up checking continued for 24 months. Our selected therapeutic regimen consisted of a combination of 500 mg/m2 5-FU dialy for five days, and 75 mg/m2 epirubicin for one day. The response rate in this study was 47.4% and the mean survival rate was 9.7 months. By far, the most common complication was gastrointestinal disturbances and no carditoxicity was seen. Having presented the results of this study and comparing it with the other therapeutic regimens like FAM combination, this selected two drug combination seems to be a useful therapeutic protocol.

  19. Discovery of Multi-target Anticancer Agents Based on HDAC Inhibitor MS-275 and 5-FU.

    Jiang, Yuqi; Li, Xiaoguang; Li, Xiaoyang; Hou, Jinning; Ding, Yongzheng; Zhang, Jian; Xu, Wenfang; Zhang, Yingjie


    Histone deacetylases (HDACs) inhibitors have multiple effects targeting the cancer cells and have become one of the promising cancer therapeutics with possibly broad applicability. Combination of HDAC inhibitors with the cytotoxic fluorouracil (5-FU) showed additive and synergistic effects both in vitro and in vivo. To explore the possibility in cancer therapy of a bivalent agent that combines two bioactive groups within a single molecular architecture, we designed and synthesized new dual-acting compounds by combining the bioactive fragment of MS-275, a clinical HDACs inhibitor, with cytotoxic agent 5-FU. The target compounds 9a and 9b showed comparable HDACs inhibition with MS-275 and moderate antiproliferative acitivities against six cancer cells lines.

  20. [A case of recurrent biliary cystadenocarcinoma successfully treated with 5FU/CDDP systemic chemotherapy].

    Iyama, Satoshi; Takahashi, Yasuo; Shintani, Naoaki; Fujikawa, Koshi; Ohkubo, Syunichi; Sato, Yasushi; Sato, Tsutomu; Sato, Yasuhiro; Ohnuma, Keisuke; Niitsu, Yoshiro


    We report a case of biliary cystadenocarcinoma which recurred 41 months postoperatively. A 60-year-old woman was admitted for further examination of multiple metastatic tumors and a large amount of ascites. Systemic administration of 5FU and CDDP caused her CEA level to decrease gradually and abdominal computed tomography revealed considerable reduction of the metastatic tumors and ascites. Since her general condition had improved, chemotherapy was continued in the outpatient clinic.

  1. Effect of 5-FU on modulation of disarrangement of immuneassociated cytokines in experimental acute pancreatitis

    Xiao-Li Chen; Sang-Zhu Ciren; Hui Zhang; Li-Geng Duan; Alexander J Wesley


    AIM: To investigate the effects of 5-Fluorouracil (5-FU)on modulation of pro-inflammatory and anti-inflammatory cytokines in acute pancreatitis and the mechanism of it in the treatment of acute pancreatitis.METHODS: Male Sprague Dawley rats were assigned to 3 Groups: Group A, sham operated rats as controls ( n = 7); Group B, acute pancreatitis induced by ductal injection with 5% sodium cholate at a volume of 1.0 mL/kg without any other treatment; Group C, after the pancreatitis was induced as in Group B, the rats were injected intravenously with 5-FU 40 mg/kg. The animals in Groups B and C were killed at 2, 6 and 24 h after operation ( n = 7), and blood samples were taken for measurement of tumor necrosis factor-α (TNF-α),interleukin-1 (IL-1), interleukin-6 (IL-6) (by bioassay),and interleukin-10 (IL-10), transforming growth factor-β (TGF-β) (by ELISA). The wet weight of pancreatic tissue, serum amylase levels and white blood cells were also measured.RESULTS: Four rats in Group B and one in Group C died after pancreatitis was induced. Both pro-inflammatory cytokines (TNF-α, IL-1, IL-6) at the 2 and 6 h period and the anti-inflammatory cytokines (IL-10,TGF-β) at 24 h increased significantly ( P < 0.05) in rats of Group B. After treatment with 5-FU, TNF-α, IL-1, and IL-6 in serum of rats of Group C were inhibited at 2 and 6 h after operation ( P < 0.05), and IL-10, TGF-β were inhibited at 24 h compared to Group B ( P < 0.05). Obvious improvements in the severity of the acute pancreatitis,including the amylase levels, wet weight of pancreatic tissue and neutrophil counts, were also observed after treatment with 5-FU.

  2. Development and characterization of 5-FU bearing ferritin appended solid lipid nanoparticles for tumour targeting.

    Jain, Sanjay K; Chaurasiya, Akash; Gupta, Yashwant; Jain, Anekant; Dagur, Pradeep; Joshi, Beenu; Katoch, Vishwa M


    Ferritin coupled solid lipid nanoparticles were investigated for tumour targeting. Solid lipid nanoparticles were prepared using HSPC, cholesterol, DSPE and triolien. The SLNs without ferritin which has similar lipid composition were used for comparison. SLNs preparations were characterized for shape, size and percentage entrapment. The average size of SLNs was found to be in the range 110-152 nm and maximum drug entrapment was found to be 34.6-39.1%. In vitro drug release from the formulations is obeying fickian release kinetics. Cellular uptake and IC50 values of the formulation were determined in vitro in MDA-MB-468 breast cancer cells. In vitro cell binding of Fr-SLN exhibits 7.7-folds higher binding to MDA-MB-468 breast cancer cells in comparison to plain SLNs. Ex-vivo cytotoxicity assay on targeted nanoparticles gave IC50 of 1.28 microM and non-targeted nanoparticles gave IC50 of 3.56 microM. In therapeutic experiments, 5-FU, SLNs and Fr-SLNs were administered at the dose of 10 mg 5-FU/kg body weight to MDA-MB-468 tumour bearing Balb/c mice. Administration of Fr-SLNs formulation results in effective reduction in tumour growth as compared with free 5-FU and plain SLNs. The result demonstrates that this delivery system possessed an enhanced anti-tumour activity. The results warrant further evaluation of this delivery system.

  3. The Recovery Process of Murine Tracheal Epithelium Injured by 5-FU and Its Microarray Analysis

    Jingru ZHANG


    Full Text Available Background and objective Although there are increasing reports on localization of tracheal stem cells, the mechanism of proliferation and differentiation of tracheal stem cells remains unclear. Methods In this study, we developed an ex vivo model of murine tracheal epithelial injury and regeneration induced by 5-FU. The regenerationprocess of murine tracheal epithelium was observed and analyzed by morphological, immunofluorescence and microarray methods. Results After treatment with 5-FU, the differentiated mature cells were dead and desquamated. Only a few cells remained in G0 phase and located on the basement membrane. After being put back in normal culture media, the cells became flat, cubic and restored as pseudostratified epithelium at last. These G0 phase cells were ABCG2 positive. We detected the differences of stem cell genes between normal tracheal epithelial cells and regenerated epithelial cells at 24 h and 48 h after injured by 5-FU using stem cell differentiation gene microarray. At 24 h, 8 genes were up-regulated and 31 genes were down-regulated. At 48 h, 5 genes were up-regulated and 42 genes were down-regulated. Conclusion The differently expressed genes were mainly associated with cell cycle regulation, intercellular junction, FGF, BMP, Notch and Wnt signaling pathways, which suggested these alterations might be closely associated with the proliferation and differentiation of tracheal stem cells.

  4. Oncoprotein expression of E6 and E7 does not prevent 5-fluorouracil (5FU) mediated G1/S arrest and apoptosis in 5FU resistant carcinoma cell lines.

    Didelot, C; Mirjolet, J-F; Barberi-Heyob, M; Ramacci, C; Teiten, M-H; Merlin, J L


    5-Fluorouracil (5FU) exposure can lead to both G1/S arrest and apoptosis induction which are dependent of P53 induction. The human papilloma virus oncoproteins (HPV), E6 and E7, inactivate respectively P53 and Rb. P53 degradation by E6 protein, leads to lack of G1/S arrest after genotoxic stress. Overexpression of E7 protein prevents P53-induced G1/S arrest following DNA damage. However, few studies have described 5FU effect and efficacy on cancer cell lines presenting HPV 18 positive status. KB cell line and KB3 subline presented wild-type P53 status and difference in 5FU sensitivity. During 5FU exposure, P53 gene and protein expression was increased in both cell lines. E6 and E7 mRNA and protein expression was decreased in KB and KB3. P53 and E6 protein expressions were inversely correlated. 5FU exposure, induced a G1/S arrest which can be maintained or intensified by P53 via P21 induction expression. 5FU exposure has led to apoptosis induction related to P53 induction. In the present study, 5FU exposure was shown to induce G1/S arrest and apoptosis by P53-dependent molecular pathway, in HPV 18 positive cells.

  5. Concurrent hyperfractionated accelerated radiotherapy with 5-FU and once weekly cisplatin in locally advanced head and neck cancer. The 10-year results of a prospective phase II trial

    Budach, V.; Boehmer, D.; Badakhshi, H.; Jahn, U.; Stromberger, C. [Campus Virchow Klinikum, Charite Universitaetsmedizin Berlin, Department for Radiooncology, Clinic for Radiooncology, Berlin (Germany); Becker, E.T. [Charite Universitaetsmedizin, Department of Otorhinolaryngology, Berlin (Germany); Wernecke, K.D. [Sostana Statistics GmbH, Charite Universitaetsmedizin Berlin, Berlin (Germany)


    In this study, the acute toxicity and long-term outcome of a hyperfractionated accelerated chemoradiation regimen with cisplatin/5-fluorouracil (5-FU) in patients with locally advanced squamous cell carcinomas of head and neck were evaluated. From 2000-2002, 38 patients with stage III (5.3 %) and stage IV (94.7 %) head and neck cancer were enrolled in a phase II study. Patients received hyperfractionated-accelerated radiotherapy with 72 Gy in 15 fractions of 2 Gy followed by 1.4 Gy twice daily with concurrent, continuous infusion 5-FU of 600 mg/m{sup 2} on days 1-5 and 6 cycles of weekly cisplatin (30 mg/m{sup 2}). Acute toxicities (CTCAEv2.0), locoregional control (LRC), metastases-free (MFS), and overall survival (OS) were analyzed and exploratively compared with the ARO 95-06 trial. Median follow-up was 11.4 years (95 % CI 8.6-14.2) and mean dose 71.6 Gy. Of the patients, 82 % had 6 (n = 15) or 5 (n = 16) cycles of cisplatin, 5 and 2 patients received 4 and 3 cycles, respectively. Grade 3 anemia, leukopenia, and thrombocytopenia were observed in 15.8, 15.8, and 2.6 %, respectively. Grade 3 mucositis in 50 %, grade 3 and 4 dysphagia in 55 and 13 %. The 2-, 5-, and 10-year LRC was 65, 53.6, and 48.2 %, the MFS was 77.5, 66.7, and 57.2 % and the OS 59.6, 29.2, and 15 %, respectively. Chemoradiation with 5-FU and cisplatin seems feasible and superior in terms of LRC and OS to the ARO 95-06C-HART arm at 2 years. However, this did not persist at the 5- and 10-year follow-ups. (orig.) [German] Untersuchung der Akuttoxizitaet und des Langzeitueberlebens einer hyperfraktioniert-akzelerierten simultanen Radiochemotherapie mit Cisplatin/5-Fluorouracil (5-FU) bei Patienten mit lokal fortgeschrittenen Kopf-Hals-Tumoren. Von 2000 bis 2002 wurden 38 Patienten mit Plattenepithelkarzinomen der Kopf-Hals-Region im Stadium III (5,3 %) und IV (94,7 %) eingeschlossen. Es erfolgte eine simultane hyperfraktionierte akzelerierte Radiochemotherapie mit 72 Gy in 15 Fraktionen a 2 Gy

  6. A prospective evaluation of treatment with Selective Internal Radiation Therapy (SIR-spheres in patients with unresectable liver metastases from colorectal cancer previously treated with 5-FU based chemotherapy

    Smith D


    Full Text Available Abstract Background To prospectively evaluate the efficacy and safety of selective internal radiation (SIR spheres in patients with inoperable liver metastases from colorectal cancer who have failed 5FU based chemotherapy. Methods Patients were prospectively enrolled at three Australian centres. All patients had previously received 5-FU based chemotherapy for metastatic colorectal cancer. Patients were ECOG 0–2 and had liver dominant or liver only disease. Concurrent 5-FU was given at investigator discretion. Results Thirty patients were treated between January 2002 and March 2004. As of July 2004 the median follow-up is 18.3 months. Median patient age was 61.7 years (range 36 – 77. Twenty-nine patients are evaluable for toxicity and response. There were 10 partial responses (33%, with the median duration of response being 8.3 months (range 2–18 and median time to progression of 5.3 mths. Response rates were lower (21% and progression free survival shorter (3.9 mths in patients that had received all standard chemotherapy options (n = 14. No responses were seen in patients with a poor performance status (n = 3 or extrahepatic disease (n = 6. Overall treatment related toxicity was acceptable, however significant late toxicity included 4 cases of gastric ulceration. Conclusion In patients with metastatic colorectal cancer that have previously received treatment with 5-FU based chemotherapy, treatment with SIR-spheres has demonstrated encouraging activity. Further studies are required to better define the subsets of patients most likely to respond.

  7. A randomised phase III trial of adjuvant radio-chemotherapy comparing Irinotecan, 5FU and Leucovorin to 5FU and Leucovorin in patients with rectal cancer: a Hellenic Cooperative Oncology Group Study.

    Kalofonos, H P; Bamias, A; Koutras, A; Papakostas, P; Basdanis, G; Samantas, E; Karina, M; Misailidou, D; Pisanidis, N; Pentheroudakis, G; Economopoulos, T; Papadimitriou, C; Skarlos, D V; Pectasides, D; Stavropoulos, M; Bafaloukos, D; Kardamakis, D; Karanikiotis, C; Vourli, G; Fountzilas, G


    The primary objective was to compare the 3-year survival of rectal cancer patients randomised postoperatively to irinotecan (IRI), Leucovorin (LV) and bolus 5-fluorouracil (5FU) or LV-bolus 5FU with radiotherapy. Secondary objectives included disease-free survival, local relapse and toxicity. The study included 321 eligible patients. The treatment consisted of weekly administration of IRI 80 mg/m(2) intravenously (IV), LV 200 mg/m(2) and 5FU 450 mg/m(2) bolus (arm A) versus LV 200 mg/m(2) and 5FU 450 mg/m(2) IV bolus (arm B). One cycle included four infusions and treatment was continued for a total of six cycles. The first cycle was followed by pelvic irradiation plus 5FU. There were no differences between the arms in 3-year overall, disease-free and local relapse-free survival. Grades 3 and 4 toxicity was similar in both the arms with the exception of leucopaenia, neutropaenia and alopecia, which were higher in the IRI arm. IRI added to adjuvant radiochemotherapy with LV and bolus 5FU was not shown to improve survival, whereas the incidence of severe leucopaenia was significantly higher in the IRI arm.

  8. Saddle pulmonary embolus and bronchiolitis obliterans with organizing pneumonia develop simultaneously after first cyclophosphamide, methotrexate, 5FU chemotherapy for breast cancer.

    Al-Hameed, Fahad M


    A 62-year-old woman underwent a right mastectomy with axillary node dissection for a poorly differentiated ductal carcinoma. One month later, she underwent a left nephrectomy for a renal cell carcinoma. Two weeks after, she received her first cycle of cyclophosphamide, methotrexate, and 5FU (CMF) as a part of her breast cancer treatment. We describe an unusual case of non-occlusive saddle pulmonary embolus with extensive bilateral deep vein thrombosis and severe bronchiolitis obliterans with organizing pneumonia developing simultaneously after the first CMF chemotherapy for breast cancer.

  9. [Label-free monitoring 5-FU induced SW 620 cells apoptosis using FTIR microspectroscopy].

    Liu, Dong; Sun, Xue-Jun; Zhang, Chao; He, Sai; Du, Jun-Kai; Huo, Xiong-Wei; Zheng, Jian-Bao; Zhang, Shi-Yun; Zhang, Yuan-Fuz; Xu, Yi-Zhuang; Wu, Jin-Guang


    The aim of the present study was to evaluate Fourier transform infrared spectroscopy (FTIR) monitoring of biochemical changes in apoptosis cells. Different concentrations of 5-fluorouracil (5-FU) treated colon cancer cell lines SW620 were used to determine the optimum concentration of 5-FU IC50 by means of MTT assay. Cell starvation and 5-Fu synergistic cell cycle arrest was in G1 and S phase. FTIR combined with flow cytometry was applied to analysis of SW 620 cells and SW620 cells treated with 5-FU for 12h, 24h (early apoptosis) and 48 h (late apoptosis) respectively. The peak position and the intensity of all bands were measured and comparison was made between the SW620 and apoptotic SW620 cells. Apoptosis cells have following characteristics compared with SW620 cells (1) The band at 1 740 cm-1 is an C=O stretching vibration. Changes in these bands can reflect lipid changes, and relative peak intensity ratio 11740/11460 significantly increased (p<0. 05), indicating that the relative contents of lipid in apoptosis cells increased. (2) The band at the 1 410 cm-1 peak represents that C-H stretching related was increased to amino acid residues and shifted to higher wave numbers compared to other groups. I1410o/I 460 at early and late death phase was significantly increased, which suggests that the relative contents of amino acid residues in apoptosis cells increased (p <0. 05). New vibrational bands at 1 120 cm-1 appeared at 24 h and increased at 48 h compared with other groups. The 1 120 cm-1 absorption band is mainly due to ser, serine and threonine C-O(H) stretching vibration, and I1120/I 1460 significantly increased (p<0. 05), indicating that the relative quantity of amino acid residues in apoptosis cells increased due to that DNA unwinds the double helix. (3) 1 240 cm-1 is mainly due to the asymmetric stretching modes of phosphodiester groups shifting to higher wave number, illustrating that nucleic acid conformation was changed in apoptosis cells. (4) The band

  10. Clinical outcomes of amniotic membrane loaded with5-FU PLGA nanoparticles in experimental trabeculectomy

    Fang; Hu; Xiang-Yun; Zeng; Zhao-Lian; Xie; Lin-Lin; Liu; Liang; Huang


    AIM: To evaluate the effect of amniotic membrane loaded with 5-fluorouracil poly(lactic-co-glycolic acid)(PLGA) nanoparticles(5-FU-NPs) in the surgical outcomes of experimental trabeculectomy in rabbits.METHODS: Thirty-two New Zealand white rabbits were randomly categorized into four groups with 8 rabbits in each group. Group 1, the control group, performed traditional trabeculectomy without adjuvant treatment.While the experimental groups performed compound trabeculectomy with different implantations including amniotic membrane(group 2), 5-FU-NPs(group 3) and amniotic membrane loaded with 5-FU-NPs(group 4).Clinical evaluations including IOP measurement and filtration bleb analysis were performed in all groups postoperatively.RESULTS: There is no significant difference of mean IOP in all groups at first 7d after surgery. While at P14,mean IOPs of experimental group 2(9.8 ±2.1 mm Hg),groups 3(8.9 ±2.8 mm Hg) and group 4(7.6 ±2.3 mm Hg)were significantly reduced compared to control group(12.4 ±2.6 mm Hg; n =8, P <0.05). At P21, mean IOPs of groups 3(11.7±3.2 mm Hg) and group 4(9.9±1.6 mm Hg)were significantly decreased compare to control group(17.9±1.6 mm Hg) and group 2(16.6 ±2.8 mm Hg; n =8,P <0.05). At P28, mean IOPs of groups 3(13.8±3.3 mm Hg)and group 4(10.6 ±2.0 mm Hg) were also significantly reduced compare to control group(19.4±2.3 mm Hg) and group 2(18.5 ±2.4 mm Hg; n =8, P <0.05). Meanwhile mean IOP of group 4 is significantly decreased compared to group 3 at P28(n =8, P <0.05). Survival analysis of functional filtration blub in all groups revealed the longest survival time in group 4(24.9±5.1d) compared to that in group 3(20.6 ±4.3d), group 2(15.0 ±5.2d) and control group(10.1±5.7d).CONCLUSION: Amniotic membrane loaded with 5-FuNPs may function as an effective anti-scarring implant and provides improved long-term surgical outcomes for experimental trabeculectomy in rabbits.

  11. Effects of Streptococcus thermophilus TH-4 on intestinal mucositis induced by the chemotherapeutic agent, 5-Fluorouracil (5-FU).

    Whitford, Eleanor J; Cummins, Adrian G; Butler, Ross N; Prisciandaro, Luca D; Fauser, Jane K; Yazbeck, Roger; Lawrence, Andrew; Cheah, Ker Y; Wright, Tessa H; Lymn, Kerry A; Howarth, Gordon S


    Beneficial bacteria (probiotics) and probiotic-derived factors have the potential to ameliorate disorders of the intestine. The aim of this study was to compare live Streptococcus thermophilus TH-4 (TH-4), dead TH-4 and TH-4 supernatant in rats treated with 5-Fluorouracil. Rats were randomly allocated to five treatment groups (n=8-10): Saline+Water; 5-FU+Skim Milk; 5-FU+Live TH-4; 5-FU+Supernatant TH-4; and 5-FU+Dead TH-4. 5-FU ( was administered by a single intraperitoneal injection on day 0; animals were killed on day 4. Treatments were administered daily from days -2 to 3 via oro-gastric gavage. Metabolic parameters were measured daily. Blood was obtained by cardiac puncture, and intestinal tissues removed for quantitative and qualitative histological assessment, including: villous height and area; crypt depth and area, mitotic count and crypt fission; biochemical determination of sucrase and myeloperoxidase (MPO) activity; and disease severity scoring. One-way ANOVA statistical analyses were conducted for the majority of outcome measures. Live TH-4 significantly reduced disease severity score by 13% (p5-FU+Skim milk controls. Live and supernatant TH-4 reduced crypt fission by 69% and 48% (p5-FU+Skim Milk controls. No significant differences (p> 0.05) in the occurrence of bacteraemia were evident across all groups. Live TH-4 partially normalised mitotic count and histological severity score in 5-FU treated rats. The inhibitory effect of live TH-4 and TH-4 supernatant on crypt fission suggests therapeutic utility in the prevention of disorders characterised by increased crypt fission, such as colorectal carcinoma.

  12. RPR-115135, a farnesyltransferase inhibitor, increases 5-FU- cytotoxicity in ten human colon cancer cell lines: role of p53.

    Russo, Patrizia; Malacarne, Davide; Falugi, Carla; Trombino, Sonya; O'Connor, Patrick M


    A new non peptidic farnesyltransferase inhibitor, RPR-115135, in combination with 5-FU was studied in 10 human colon cancer cell lines (HCT-116, RKO, DLD-1, Colo-320, LoVo, SW-620, HT-29, HCT-15, Colo-205 and KM-12) carrying several mutations but well characterized for p53 and Ras status. We found that there was a slight tendency (not statistically significant) for the p53 inactivated cells to be less sensitive to 5-FU after 6 days continuous treatment. Simultaneous administration of RPR-115135 and 5-FU, at subtoxic concentrations, resulted in a synergistic enhancement of 5-FU cytotoxicity in the p53 wildtype cells (HCT-116, RKO, DLD-1, Colo-320, LoVo). In the p53 mutated cells (SW-620, HT-29, HCT-15, Colo-205, KM-12) the effect was very complicated. In HCT-15 the combination resulted in antagonism, in KM-12 in antagonism or in synergy (at different concentrations) and in SW-620, HT-29 and Colo-205 cells in synergy but only when 5-FU was administered at high concentrations. Growth inhibition could be accounted for on the basis of a specific cell cycle arrest phenotype (G2-M arrest), as assayed by flow cytometry, only in the p53 functioning cell lines. The combination RPR-115135 + 5-FU increases apoptotic events only in these cell lines. In the mutated cell lines no major alterations on cell cycle arrest phenotype and no induction of apoptosis was observed. Although RPR-115135 can potentiate the effect of 5-FU in cells in which p53 function is disrupted, these data suggest strongly that RPR-115135 significantly enhances the efficacy of 5-FU only when p53 is functioning.

  13. Concurrent chemoradiotherapy with daily low dose CDDP/5FU for locally unresectable head and neck cancer

    Kohno, Naoyuki; Kitahara, Satoshi; Tamura, Etsuyo; Tanabe, Tetsuya [Kyorin Univ., Mitaka, Tokyo (Japan). School of Medicine; Murata, Yasuhiro [National Defence Medical Coll., Tokorozawa, Saitama (Japan)


    To improve the local control rate and the prognosis of locally unresectable head and neck cancer patients, we studied the concurrent chemoradiotherapy. Between September 1996 and September 2000, thirty-eight patients with locally unresectable head and neck cancer were administered concurrent chemoradiotherapy consisting of low-dose and long-term treatment with cisplatin (CDDP) plus 5-fluorouracil (5FU), or (L-CF); the L-CF regimen consisted of CDDP, 3 mg/m{sup 2} on 5 days of the week and 5FU, 150 mg/m{sup 2} as a 24-hour infusion on 5 days of the week. Concurrently, conventional radiotherapy was given up to total dose of around 60 Gy. In the 36 patients evaluable for response, 19 complete and 10 partial responses were noted, with an overall response rate of 81%. Oral mucositis and myelosuppression were the major side effects and dose limiting toxicity. This study demonstrates increase in survival among the responders (complete+partial) in the concurrent chemoradiotherapy setting. We concluded that this treatment strategy was beneficial. Further studies for patients with locally unresectable head and neck cancer are warranted. (author)

  14. Laser sclerectomy and 5-FU controlled-drug-release biodegradable implant for glaucoma therapy

    Villain, Franck L.; Parel, Jean-Marie A.; Kiss, Katalin; Parrish, Richard K.; Kuhne, Francois; Takesue, Yoshiko; Hostyn, Patrick


    Laser sclerectomy, a simple filtering procedure performed to alleviate high intraocular pressure in glaucoma patients, was taught to offer longer lasting effect and therefore improve the patient's outcome when compared with the standard trabeculectomy procedure. Recent clinical trials have shown that this was not the case and pharmacologic wound healing modulation is also required with this new procedure. Five-Fluorouracil (5-FU) is useful as an adjunct treatment for glaucoma filtering surgery. However, efficacy depends upon maintaining sustained drug levels, currently achieved by repeated daily injection of the drug for several weeks. To overcome this limitation, we designed a biodegradable implant for the sustained release of 5-FU. After laser sclerectomy, the implant is inserted through the same 1 mm wide conjunctival snip incision and positioned below the open channel. Implantation takes less than a minute. The implant releases the drug for over 15 days and totally biodegrades in less than 100 days. The combined laser surgery and implantation procedure show great potentials for the treatment of glaucoma.

  15. A phase II experience with neoadjuvant irinotecan (CPT-11, 5-fluorouracil (5-FU and leucovorin (LV for colorectal liver metastases

    Bigam David


    Full Text Available Abstract Background Chemotherapy may improve survival in patients undergoing resection of colorectal liver metastases (CLM. Neoadjuvant chemotherapy may help identify patients with occult extrahepatic disease (averting unnecessary metastasectomy, and it provides in vivo chemosensitivity data. Methods A phase II trial was initiated in which patients with resectable CLM received CPT-11, 5-FU and LV for 12 weeks. Metastasectomy was performed unless extrahepatic disease appeared. Postoperatively, patients with stable or responsive disease received the same regimen for 12 weeks. Patients with progressive disease received either second-line chemotherapy or best supportive care. The primary endpoint was disease-free survival (DFS; secondary endpoints included overall survival (OS and safety. Results 35 patients were accrued. During preoperative chemotherapy, 16 patients (46% had grade 3/4 toxicities. Resection was not possible in 5 patients. One patient died of arrhythmia following surgery, and 1 patient had transient liver failure. During the postoperative treatment phase, 12 patients (55% had grade 3/4 toxicities. Deep venous thrombosis (DVT occurred in 11 patients (34% at various times during treatment. Of those who underwent resection, median DFS was 23.0 mo. and median OS has not been reached. The overall survival from time of diagnosis of liver metastases was 51.6 mo for the entire cohort. Conclusion A short course of chemotherapy prior to hepatic metastasectomy may serve to select candidates best suited for resection and it may also direct postoperative systemic treatment. Given the significant incidence of DVT, alternative systemic neoadjuvant regimens should be investigated, particularly those that avoid the use of a central venous line. Trial Registration NCT00168155.

  16. Development and Characterization of Novel Site Specific Hollow Floating Microspheres Bearing 5-Fu for Stomach Targeting

    Peeyush Bhardwaj


    Full Text Available Multiple-unit-type oral floating hollow microspheres of 5-fluorouracil (5-Fu were developed using modified solvent evaporation technique to prolong gastric residence time, to target stomach cancer, and to increase drug bioavailability. The prepared microspheres were characterized for micromeritic properties, floating behavior, entrapment efficiency, and scanning electron microscopy (SEM. The in vitro drug release and floating behavior were studied in simulated gastric fluid (SGF at pH 1.2. The yield of microspheres was obtained up to 84.46±6.47%. Microspheres showed passable flow properties. Based on optical microscopy, particle size was found to be ranging from 158.65±12.02 to 198.67±17.45 μm. SEM confirmed spherical size, perforated smooth surface, and a hollow cavity inside the microspheres. Different kinetic models for drug release were also applied on selected batches.

  17. Moderate intensity static magnetic fields affect mitotic spindles and increase the antitumor efficacy of 5-FU and Taxol.

    Luo, Yan; Ji, Xinmiao; Liu, Juanjuan; Li, Zhiyuan; Wang, Wenchao; Chen, Wei; Wang, Junfeng; Liu, Qingsong; Zhang, Xin


    Microtubules are the fundamental components in mitotic spindle, which plays essential roles in cell division. It was well known that purified microtubules could be affected by static magnetic fields (SMFs) in vitro because of the diamagnetic anisotropy of tubulin. However, whether these effects lead to cell division defects was unknown. Here we find that 1T SMFs induce abnormal mitotic spindles and increase mitotic index. Synchronization experiments show that SMFs delay cell exit from mitosis and cause mitotic arrest. These mimic the cellular effects of a microtubule-targeting drug Paclitaxel (Taxol), which is frequently used in combination with 5-Fluorouracil (5-FU) and Cisplatin in cancer treatment. Using four different human cancer cell lines, HeLa, HCT116, CNE-2Z and MCF7, we find that SMFs increase the antitumor efficacy of 5-FU or 5-FU/Taxol, but not Cisplatin, which indicates that the SMF-induced combinational effects with chemodrugs are drug-specific. Our study not only reveals the effect of SMFs on microtubules to cause abnormal mitotic spindles and delay cells exit from mitosis, but also implies the potential applications of SMFs in combination with chemotherapy drugs 5-FU or 5-FU/Taxol, but not with Cisplatin in cancer treatment.

  18. Failure to Adhere to Protocol Specified Radiation Therapy Guidelines Was Associated With Decreased Survival in RTOG 9704-A Phase III Trial of Adjuvant Chemotherapy and Chemoradiotherapy for Patients With Resected Adenocarcinoma of the Pancreas

    Abrams, Ross A., E-mail: [Rush University Medical Center, Chicago, IL (United States); Winter, Kathryn A. [Radiation Therapy Oncology Group Statistical Center, Philadelphia, PA (United States); Regine, William F. [University of Maryland, Baltimore, MD (United States); Safran, Howard [Brown University, Providence, RI (United States); Hoffman, John P. [Fox Chase Cancer Center, Philadelphia, PA (United States); Lustig, Robert [Radiation Therapy Oncology Group Statistical Center, Philadelphia, PA (United States); Konski, Andre A. [Wayne State Medical Center, Detroit, MI (United States); Benson, Al B. [Northwestern University, Chicago, IL (United States); Macdonald, John S. [St. Vincent' s Cancer Care Center, New York, NY (United States); Rich, Tyvin A. [University of Virginia, Charlottesville, VA (United States); Willett, Christopher G. [Duke University, Durham, NC (United States)


    Purpose: In Radiation Therapy Oncology Group 9704, as previously published, patients with resected pancreatic adenocarcinoma received continuous infusion 5-FU and concurrent radiotherapy (5FU-RT). 5FU-RT treatment was preceded and followed by randomly assigned chemotherapy, either 5-FU or gemcitabine. This analysis explored whether failure to adhere to specified RT guidelines influenced survival and/or toxicity. Methods and Materials: RT requirements were protocol specified. Adherence was scored as per protocol (PP) or less than per protocol (adenocarcinoma to evaluate the impact of adherence to specified RT protocol guidelines on protocol outcomes. Failure to adhere to specified RT guidelines was associated with reduced survival and, for patients receiving gemcitabine, trend toward increased nonhematologic toxicity.

  19. Failure to Adhere to Protocol Specified Radiation Therapy Guidelines Was Associated With Decreased Survival in RTOG 9704 - A Phase III Trial of Adjuvant Chemotherapy and Chemoradiotherapy for Patients with Resected Adenocarcinoma of the Pancreas

    Abrams, Ross A.; Winter, Kathryn A.; Regine, William F.; Safran, Howard; Hoffman, John P.; Lustig, Robert; Konski, Andre A.; Benson, Al B.; Macdonald, John S.; Rich, Tyvin A.; Willett, Christopher G.


    Purpose In RTOG 9704, as previously published, patients with resected pancreatic adenocarcinoma received continuous infusion 5-FU and concurrent radiotherapy (5FU-RT). 5FU-RT treatment was preceded and followed by randomly assigned chemotherapy, either 5-FU or gemcitabine. This analysis explored whether failure to adhere to specified RT guidelines influenced survival and/or toxicity. Methods and Materials RT requirements were protocol specified. Adherence was scored as per protocol (PP) or less than per protocol (adenocarcinoma to evaluate the impact of adherence to specified RT protocol guidelines on protocol outcomes. Failure to adhere to specified RT guidelines was associated with reduced survival and, for patients receiving gemcitabine, trend toward increased non-hematologic toxicity. PMID:21277694

  20. CDDP-5Fu-PYM化疗方案用于舌鳞癌的综合治疗

    王贺伟; 任玉英; 苏平; 杜申钊; 许云


    目的:对于34例舌部鳞癌病人使用CDDP-5Fu-PYM化疗方案作为手术或放疗前的诱导化疗.方法:CDDP 80mg/m2,5Fu 3.0g,PYM 40mg在5天内按顺序给予.结果:7例原发灶消失,21例原发灶缩小50%以上,总有效率82.4%.结论:CD-DP-5Fu-PYM联合使用可以产生更加积极的抗肿瘤作用,取得满意的临床效果,为进一步治疗提供了良好的基础,有明显的优点和实用性.

  1. Potentially functional SNPs (pfSNPs as novel genomic predictors of 5-FU response in metastatic colorectal cancer patients.

    Jingbo Wang

    Full Text Available 5-Fluorouracil (5-FU and its pro-drug Capecitabine have been widely used in treating colorectal cancer. However, not all patients will respond to the drug, hence there is a need to develop reliable early predictive biomarkers for 5-FU response. Here, we report a novel potentially functional Single Nucleotide Polymorphism (pfSNP approach to identify SNPs that may serve as predictive biomarkers of response to 5-FU in Chinese metastatic colorectal cancer (CRC patients. 1547 pfSNPs and one variable number tandem repeat (VNTR in 139 genes in 5-FU drug (both PK and PD pathway and colorectal cancer disease pathways were examined in 2 groups of CRC patients. Shrinkage of liver metastasis measured by RECIST criteria was used as the clinical end point. Four non-responder-specific pfSNPs were found to account for 37.5% of all non-responders (P<0.0003. Five additional pfSNPs were identified from a multivariate model (AUC under ROC = 0.875 that was applied for all other pfSNPs, excluding the non-responder-specific pfSNPs. These pfSNPs, which can differentiate the other non-responders from responders, mainly reside in tumor suppressor genes or genes implicated in colorectal cancer risk. Hence, a total of 9 novel SNPs with potential functional significance may be able to distinguish non-responders from responders to 5-FU. These pfSNPs may be useful biomarkers for predicting response to 5-FU.

  2. 5 Fu/CF联合 HCFU治疗晚期大肠癌%5-Fluorouracil,Leucovorin and Carmofur Combination in Treatment for Advanced Large intestinal Cancer

    司海运; 岳晓婷


    [目的 ]观察 5 Fu/CF联合口服卡莫氟 (HCFU)与单用 5 Fu/CF治疗晚期大肠癌的近期疗效 . [方法 ]对 1998年 10月~ 2001年 4月收治的 36例大肠癌随机分为两组 , 治疗组 : 5 Fu/CF联合口服 HCFU; 对照组为 5 Fu/CF. [结果 ]治疗组总有效率 55.5% , 对照组总有效率 27.7% . [结论 ]5 Fu/CF联合口服 HCFU治疗晚期大肠癌较单用 5 Fu/CF方案化疗为好 .

  3. Pilot study of postoperative adjuvant chemoradiation for advanced gastric cancer: Adjuvant 5-FU/cisplatin and chemoradiation with capecitabine

    Hyung-Sik Lee; Min-Chan Kim; Youngmin Choi; Won-Joo Hur; Hyo-Jin Kim; Hyuk-Chan Kwon; Sung-Hyun Kim; Jae-Seok Kim; Jong-Hoon Lee; Ghap-Joong Jung


    AIM: To evaluate the efficacy and toxicity of postoperative chemoradiation using FP chemotherapy and oral capecitabine during radiation for advanced gastric cancer following curative resection.METHODS: Thirty-one patients who had underwent a potentially curative resection for Stage Ⅲ and Ⅳ (MO) gastric cancer were enrolled. Therapy consists of one cycle of FP (continuous infusion of 5-FU 1000 mg/m2 on d 1 to 5 and cisplatin 60 mg/m2 on d 1) followed by 4500 cGy (180 cGy/d) with capecitabine (1650 mg/m2 daily throughout radiotherapy). Four wk after completion of the radiotherapy, patients received three additional cycles of FP every three wk. The median follow-up duration was 22.2 mo.RESULTS: The 3-year disease free and overall survival in this study were 82.7% and 83.4%, respectively. Four patients (12.9%) showed relapse during follow-up. Eight patients did not complete all planned adjuvant therapy.Grade 3/4 toxicities included neutropenia in 50.2%, anemia in 12.9%, thrombocytopenia in 3.2% and nausea/vomiting in 3.2%. Neither grade 3/4 hand foot syndrome nor treatment related febrile neutropenia or death were observed.CONCLUSION: These preliminary results suggest that this postoperative adjuvant chemoradiation regimen of FP before and after capecitabine and concurrent radiotherapy appears well tolerated and offers a comparable toxicity profile to the chemoradiation regimen utilized in INT-0116. This treatment modality allowed successful loco-regional control rate and 3-year overall survival.

  4. Supra-additive antitumor activity of 5FU with tumor necrosis factor-related apoptosis-inducing ligand on gastric and colon cancers in vitro.

    Shimoyama, Shouji; Mochizuki, Yoshino; Kusada, Osamu; Kaminishi, Michio


    We investigated supra-additive cytotoxic effects of 5-fluorouracil (5FU) on gastric and colon cancer cells with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in vitro. p53 wild- and mutant-type gastric and colon cancer cell lines were treated by 5FU alone, TRAIL alone, and a combination of 5FU and TRAIL, and cell viability after each treatment was determined by MTT assay. The p53 wild-type cells were more sensitive to 5FU alone or to TRAIL alone than p53 mutant-type cells. The cell growth inhibitory effects of the combined treatment were supra-additive and more significant in proportion to the increasing concentrations of TRAIL as compared with 5FU alone both in p53 wild- and mutant-type cells. Furthermore, TRAIL could cause a decrease in 5FU IC(50) to within the range of clinically relevant doses, particularly in p53 wild-type cells. This is the first demonstration of the supra-additive antitumor activity of 5FU with TRAIL on gastric cancer cells, giving evidence that TRAIL can reduce the requirement for 5FU that ultimately results in minimizing risks for systemic side effects while increasing the antitumor activity of 5FU, suggesting the clinical applicability of this combination for gastric and colon cancers.

  5. TS Gene Polymorphisms Are Not Good Markers of Response to 5-FU Therapy in Stage III Colon Cancer Patients

    A. Fariña-Sarasqueta


    Full Text Available Aim: Although the predictive and prognostic value of thymidylate synthase (TS expression and gene polymorphism in colon cancer has been widely studied, the results are inconclusive probably because of methodological differences. With this study, we aimed to elucidate the role of TS gene polymorphisms genotyping in therapy response in stage III colon carcinoma patients treated with 5-FU adjuvant chemotherapy.

  6. Toxicity during l-LV/5FU adjuvant chemotherapy as a modified RPMI regimen for patients with colorectal cancer.

    Hotta, Tsukasa; Takifuji, Katsunari; Arii, Kazuo; Yokoyama, Shozo; Matsuda, Kenji; Higashiguchi, Takashi; Tominaga, Toshiji; Oku, Yoshimasa; Yamaue, Hiroki


    l-leucovorin (LV)/5-fluorouracil (5FU) may play an important role, as an adjuvant chemotherapy, in improving the survival of patients with stage III colorectal cancer. However, severe toxicity of the chemotherapeutic agent could be fatal. Adverse effects, including bone marrow suppression, liver damage, renal damage, and glucose tolerance, were evaluated daily during 3 courses of l-LV/5FU-modified RPMI regimen adjuvant chemotherapy for 22 patients with stage III colorectal cancer. Decrease in the serum levels of neutrophils and platelets occurred in the 1st course, which became more obvious after three or four administrations of l-LV/5FU in the 1st course. Furthermore, serum levels of leukocytes, neutrophils, and platelets on the re-start day of this chemotherapy after 2-week intervals were lower than those on the start day of this chemotherapy. In the evaluation of liver damage, renal damage, and glucose tolerance; serum alanine aminotransferase level in the 2nd course, serum total bilirubin (T.Bil) level in the 1st course, and serum creatinine level in the 1st course deteriorated during the course. T.Bil levels on the re-start day of this chemotherapy after 2-week intervals were especially high compared to that on the start day. The more courses of this chemotherapy we perform, the more attention we must pay to bone marrow suppression and hyperbilirubinemia. Thus, we clarified the attentive point of side effect of l-LV/5FU adjuvant chemotherapy for colorectal cancer.

  7. Effect of cholesterol on behavior of 5-fluorouracil (5-FU) in a DMPC lipid bilayer, a molecular dynamics study.

    Khajeh, Aboozar; Modarress, Hamid


    In this work, molecular dynamics (MD) simulations were performed to investigate the effects of cholesterol on the interaction between the hydrophilic anticancer drug, 5-FU, and fully hydrated 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) bilayer. Several structural and dynamical parameters of DMPC bilayers with varying amounts of cholesterol (0, 25, and 50mol%) in the presence and absence of drug molecules were calculated. Moreover, the free energy barriers for translocation of one 5-FU molecule from water to the lipid bilayer were determined by using the potential of mean force (PMF). PMF studies indicated that the location of the maximum free energy barrier was in the hydrophobic middle region of bilayer, while the minimums of the barrier were located at the hydrophilic part of bilayer at the interface with water. The minimum and maximum of the free energy profiles were independent of cholesterol concentration and suggested that the drug molecules 5-FU were accumulated in the vicinity of the polar head group of lipid bilayers. Moreover, the results showed that with increasing cholesterol concentration in the bilayer, the free energy barrier for translocation of 5-FU across the bilayer also increases which can be attributed to the condensing effect of the cholesterol on the bilayer.

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

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


    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.

  9. Synthesis and characterization of insulin-5-Fu conjugate,enabling insulin as multi-drug carder via dendritic approach

    Juan Huang; Jian Wei Wang; Tao Gong; Zhi Rong Zhang


    To enable insulin as multi-drug carrier, we designed and synthesized dendritic linker molecule bearing three 5-fluorouracil residues at the branch ends. The new conjugate showed excellent water solubility. The stabilities under different conditions were investigated. The results showed that the conjugate was a potential prodrug to release free 5-Fu.

  10. Effects of 5-FU combined compound Ginseng and Astragalus on biological behavior of human gastric cancer MGC-803 cells



    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,

  11. Optimization of LDL targeted nanostructured lipid carriers of 5-FU by a full factorial design

    Sare Andalib


    Full Text Available Background: Nanostructured lipid carriers (NLC are a mixture of solid and liquid lipids or oils as colloidal carrier systems that lead to an imperfect matrix structure with high ability for loading water soluble drugs. The aim of this study was to find the best proportion of liquid and solid lipids of different types for optimization of the production of LDL targeted NLCs used in carrying 5-Fu by the emulsification-solvent evaporation method. Materials and Methods: The influence of the lipid type, cholesterol or cholesteryl stearate for targeting LDL receptors, oil type (oleic acid or octanol, lipid and oil% on particle size, surface charge, drug loading efficiency, and drug released percent from the NLCs were studied by a full factorial design. Results: The NLCs prepared by 54.5% cholesterol and 25% of oleic acid, showed optimum results with particle size of 105.8 nm, relatively high zeta potential of −25 mV, drug loading efficiency of 38% and release efficiency of about 40%. Scanning electron microscopy of nanoparticles confirmed the results of dynamic light scattering method used in measuring the particle size of NLCs. Conclusions: The optimization method by a full factorial statistical design is a useful optimization method for production of nanostructured lipid carriers.

  12. Concomitant chemoradiotherapy with CDDP and 5FU for nasopharyngeal carcinoma. The initial evaluation and side effects

    Takeuchi, Yousuke; Suzuki, Haruhiko; Shigehara, Takeo; Omura, Ken; Shimada, Fumiyuki; Hatano, Kazuo; Sekiya, Yuichi; Togawa, Takashi [Chiba Cancer Center Hospital (Japan)


    Concomitant chemoradiotherapy with CDDP and 5FU was given to 18 patients with nasopharyngeal carcinoma during January 1994-October 1996. One and 17 were in Stages III-IV respectively. None had distant metastasis. The median duration of follow-up of all patients was 23.5 months (6-45). Objective response (CR+PR) of the primary lesion and the regional nodes was 18/18 (100%), whereas CR was 2/18 (11%). CR+PR and CR at the primary lesion were 18/18 (100%) and 5/18 (28%) respectively. Two patients died of disease at T site. One patient was alive with disease. The remaining 15 (83%) patients were relapse free alive. There were 2 relapses, 1 at T+M, and 1 at T+N sites. Side effects, especially myelosuppression and mucositis, were severe. Leukopenia and mucositis in grade 3-4 were 78% and 89% respectively. In conclusion, this regimen has been effective in short term follow-up. However, because of severe side effects, further modifications are required. Long term follow-up are required to define final effectiveness of this regimen. (author)

  13. Layered inorganic nanocomposites: a promising carrier for 5-fluorouracil (5-FU).

    Kevadiya, Bhavesh D; Patel, Tapan A; Jhala, Devendrasinh D; Thumbar, Rahul P; Brahmbhatt, Harshad; Pandya, Maharshi P; Rajkumar, Shalini; Jena, Prasant K; Joshi, Ghanshyam V; Gadhia, Pankaj K; Tripathi, C B; Bajaj, Hari C


    We report here the intercalation of 5-fluorouracil (5-FU), an anticancer drug in interlayer gallery of Na(+) clay (Montmorillonite, MMT), with the assistance of biopolymer (chitosan, CS). The X-ray diffraction patterns, thermal and spectroscopic analyses indicated the drug intercalation into the clay interlayer space in support of CS and stabilized in the longitudinal monolayer by electrostatic interaction. In vitro drug release showed controlled release pattern. The genotoxic effect of drug was in vitro evaluated in human lymphocyte cell culture by comet assay, and results indicated significant reduction in DNA damage when drug was intercalated with clay and formulated in composites. The results of in vitro cell viability assay in cancer cells pointed at decreased toxicity of drug when encapsulated in Na(+)-clay plates than the pristine drug. In vivo pharmacokinetics, biodistribution, hepatotoxicity markers, e.g., SGPT and SGOT, and liver/testicular histology in rats showed plasma/tissue drug levels were within therapeutic window as compared to pristine drug. Therefore, drug-clay hybrid and composites can be of considerable value in chemotherapy of cancer with reduced side effects.

  14. The effect on the small bowel of 5-FU and oxaliplatin in combination with radiation using a microcolony survival assay

    Kjellén Elisabeth


    Full Text Available Abstract Background In locally advanced rectal cancer, 5-Fluorouracil (5-FU-based chemoradiation is the standard treatment. The main acute toxicity of this treatment is enteritis. Due to its potential radiosensitizing properties, oxaliplatin has recently been incorporated in many clinical chemoradiation protocols. The aim of this study was to investigate to what extent 5-FU and oxaliplatin influence the radiation (RT induced small bowel mucosal damage when given in conjunction with single or split dose RT. Methods Immune competent balb-c mice were treated with varying doses of 5-FU, oxaliplatin (given intraperitoneally and total body RT, alone or in different combinations in a series of experiments. The small bowel damage was studied by a microcolony survival assay. The treatment effect was evaluated using the inverse of the slope (D0 of the exponential part of the dose-response curve. Results In two separate experiments the dose-response relations were determined for single doses of RT alone, yielding D0 values of 2.79 Gy (95% CI: 2.65 - 2.95 and 2.98 Gy (2.66 - 3.39, for doses in the intervals of 5-17 Gy and 5-10 Gy, respectively. Equitoxic low doses (IC5 of the two drugs in combination with RT caused a decrease in jejunal crypt count with significantly lower D0: 2.30 Gy (2.10 - 2.56 for RT+5-FU and 2.27 Gy (2.08 - 2.49 for RT+oxaliplatin. Adding both drugs to RT did not further decrease D0: 2.28 Gy (1.97 - 2.71 for RT+5-FU+oxaliplatin. A clearly higher crypt survival was noted for split course radiation (3 × 2.5 Gy compared to a single fraction of 7.5 Gy. The same difference was seen when 5-FU and/or oxaliplatin were added. Conclusion Combining 5-FU or oxaliplatin with RT lead to an increase in mucosal damage as compared to RT alone in our experimental setting. No additional reduction of jejunal crypt counts was noted when both drugs were combined with single dose RT. The higher crypt survival with split dose radiation indicates a

  15. Gelam honey and ginger potentiate the anti cancer effect of 5-FU against HCT 116 colorectal cancer cells.

    Hakim, Luqman; Alias, Ekram; Makpol, Suzana; Ngah, Wan Zurinah Wan; Morad, Nor Azian; Yusof, Yasmin Anum Mohd


    The development of chemopreventive approaches using a concoction of phytochemicals is potentially viable for combating many types of cancer including colon carcinogenesis. This study evaluated the anti-proliferative effects of ginger and Gelam honey and its efficacy in enhancing the anti-cancer effects of 5-FU (5-fluorouracil) against a colorectal cancer cell line, HCT 116. Cell viability was measured via MTS (3-(4,5-dimethylthiazol-2- yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulphenyl)-2H-tetrazolium) assay showing ginger inhibiting the growth of HCT 116 cells more potently (IC50 of 3mg/mL) in comparison to Gelam honey (IC50 of 75 mg/mL). Combined treatment of the two compounds (3mg/mL ginger+75 mg/mL Gelam honey) synergistically lowered the IC50 of Gelam honey to 22 mg/mL. Combination with 35 mg/mL Gelam honey markedly enhanced 5-FU inhibiting effects on the growth of HCT 116 cells. Subsequent analysis on the induction of cellular apoptosis suggested that individual treatment of ginger and Gelam honey produced higher apoptosis than 5-FU alone. In addition, treatment with the combination of two natural compounds increased the apoptotic rate of HCT 116 cells dose- dependently while treatment of either ginger or Gelam honey combined with 5-FU only showed modest changes. Combination index analysis showed the combination effect of both natural compounds to be synergistic in their inhibitory action against HCT 116 colon cancer cells (CI 0.96 5-FU against colorectal cancer.

  16. Nal-IRI With 5-fluorouracil (5-FU) and Leucovorin or Gemcitabine Plus Cisplatin in Advanced Biliary-tract Cancer


    Adenocarcinoma Metastatic; Biliary Tract Cancer; Adenocarcinoma of the Biliary Tract; Adenocarinoma Locally Advanced; Non-Resectable Hepatocellular Carcinoma; Intrahepatic Bile Duct Carcinoma; Extrahepatic Bile Duct Carcinoma

  17. Overcoming acquired drug resistance in colorectal cancer cells by targeted delivery of 5-FU with EGF grafted hollow mesoporous silica nanoparticles

    Chen, Lijue; She, Xiaodong; Wang, Tao; He, Li; Shigdar, Sarah; Duan, Wei; Kong, Lingxue


    Acquired drug resistance (ADR) can be developed in colorectal cancer cells after 5-fluorouracil (5-FU) treatment and diminish the effectiveness of chemotherapy. In this work, acquired 5-FU resistance in the colorectal cancer cell line SW480 was obtained with the up-regulation of dihydropyrimidine dehydrogenase (DPYD) gene expression which can convert 5-FU to its inactive metabolite. To overcome ADR in colorectal cancer, hollow mesoporous silica nanoparticles (HMSNs) grafted with epidermal growth factor (EGF) were used as nanocarriers to deliver 5-FU to colorectal cancer cells with acquired drug resistance. The effect and mechanism of 5-FU loaded EGF grafted HMSNs (EGF-HMSNs-5-FU) in overcoming acquired drug resistance in SW480/ADR cells were studied. The EGF-HMSNs were demonstrated to be specifically internalized in EGFR overexpressed SW480/ADR cells via a receptor-mediated endocytosis and can escape from endo-lysosomes. The EGF-HMSNs-5-FU exhibited much higher cytotoxicity on SW480/ADR cells than HMSNs-5-FU and free 5-FU while the plain HMSNs did not show significant cytotoxicity. The mechanism of EGF-HMSNs-5-FU in overcoming drug resistance in SW480/ADR cells could be attributed to the specific internalization of EGF-HMSNs-5-FU in EGFR overexpressed cells which can lead to high intracellular drug accumulation and cause cell death through S phase arrest.Acquired drug resistance (ADR) can be developed in colorectal cancer cells after 5-fluorouracil (5-FU) treatment and diminish the effectiveness of chemotherapy. In this work, acquired 5-FU resistance in the colorectal cancer cell line SW480 was obtained with the up-regulation of dihydropyrimidine dehydrogenase (DPYD) gene expression which can convert 5-FU to its inactive metabolite. To overcome ADR in colorectal cancer, hollow mesoporous silica nanoparticles (HMSNs) grafted with epidermal growth factor (EGF) were used as nanocarriers to deliver 5-FU to colorectal cancer cells with acquired drug resistance. The

  18. Low levels of Caspase-3 predict favourable response to 5FU-based chemotherapy in advanced colorectal cancer: Caspase-3 inhibition as a therapeutic approach.

    Flanagan, L; Meyer, M; Fay, J; Curry, S; Bacon, O; Duessmann, H; John, K; Boland, K C; McNamara, D A; Kay, E W; Bantel, H; Schulze-Bergkamen, H; Prehn, J H M


    Colorectal cancer (CRC) is one of the most common cancers in the Western world. 5-Fluorouracil (5FU)-based chemotherapy (CT) remains the mainstay treatment of CRC in the advanced setting, and activates executioner caspases in target cells. Executioner caspases are key proteins involved in cell disassembly during apoptosis. Activation of executioner caspases also has a role in tissue regeneration and repopulation by stimulating signal transduction and cell proliferation in neighbouring, non-apoptotic cells as reported recently. Tissue microarrays (TMAs) consisting of tumour tissue from 93 stage II and III colon cancer patients were analysed by immunohistochemistry. Surprisingly, patients with low levels of active Caspase-3 had an increased disease-free survival time. This was particularly pronounced in patients who received 5FU-based adjuvant CT. In line with this observation, lower serum levels of active Caspase-3 were found in patients with metastasised CRC who revealed stable disease or tumour regression compared with those with disease progression. The role of Caspase-3 in treatment responses was explored further in primary human tumour explant cultures from fresh patient tumour tissue. Exposure of explant cultures to 5FU-based CT increased the percentage of cells positive for active Caspase-3 and Terminal Deoxynucleotidyl Transferase dUTP Nick end Labelling (TUNEL), but also the expression of regeneration and proliferation markers β-Catenin and Ki-67, as well as cyclooxygenase-2 (COX-2). Of note, selective inhibition of Caspase-3 with Ac-DNLD-CHO, a selective, reversible inhibitor of Caspase-3, significantly reduced the expression of proliferation markers as well as COX-2. Inhibition of COX-2 with aspirin or celecoxib did not affect Caspase-3 levels but also reduced Ki-67 and β-Catenin levels, suggesting that Caspase-3 acted via COX-2 to stimulate cell proliferation and tissue regeneration. This indicates that low levels of active Caspase-3 may represent a




    While investigating the effects of 5-fluorouracil (5FU) and 5-fluoro-2'-deoxyuridine (FUdR) on the tumoricidal state of rat liver macrophages activated in vitro by means of liposome-encapsulated muramyl dipeptide (MDP), we observed that 5FU in combination with macrophages produced substantially high

  20. Synthesis of liver-targeting dual-ligand modified GCGA/5-FU nanoparticles and their characteristics in vitro and in vivo.

    Cheng, Mingrong; Gao, Xiaoyan; Wang, Yong; Chen, Houxiang; He, Bing; Li, Yingchun; Han, Jiang; Zhang, Zhiping


    Nanoparticle drug delivery systems using polymers hold promise for clinical applications. We synthesized dual-ligand modified chitosan (GCGA) nanoparticles using lactic acid, glycyrrhetinic acid, and chitosan to target the liver in our previous studies. We then synthesized the GCGA/5-FU nanoparticles by conjugating 5-fluorouracil (5-FU) onto the GCGA nanomaterial, which had a mean particle size of 239.9 nm, a polydispersity index of 0.040, a zeta potential of +21.2 mV, and a drug loading of 3.90%. GCGA/5-FU nanoparticles had good slow release properties, and the release process could be divided into five phases: small burst release, gentle release, second burst release, steady release, and slow release. Inhibitory effects of GCGA/5-FU on tumor cells targeted the liver, and were time and dose dependent. GCGA nanoparticles significantly prolonged the efficacy of 5-FU on tumor cells, and alleviated the resistance of tumor cells to 5-FU. GCGA/5-FU nanoparticles were mostly concentrated in the liver, indicating that the GCGA nanoparticles were liver targeting. GCGA/5-FU nanoparticles significantly suppressed tumor growth in orthotopic liver transplantation mouse model, and improved mouse survival.

  1. Absorption and distribution characteristics of 5-fluorouracil (5-FU) after an application to the liver surface in rats in order to reduce systemic side effects.

    Kodama, Yukinobu; Fumoto, Shintaro; Nishi, Junya; Nakashima, Mikiro; Sasaki, Hitoshi; Nakamura, Junzo; Nishida, Koyo


    The present study was undertaken to elucidate the absorption and distribution characteristics of 5-fluorouracil (5-FU) after its application to the liver surface in rats to examine the possibility of reducing the systemic side effects of this agent. 5-FU was applied to the surface of the liver by employing a cylindrical diffusion cell. Approximately 69% of the dose was absorbed in 360 min. The time course of the change in the amount of 5-FU remaining in the diffusion cell obeyed first-order kinetics. Also, a linear relationship was observed between the apparent permeability coefficient, P app, and the reciprocal of the square root of the molecular weight of several compounds including 5-FU. The estimated P app value of 5-FU was in good agreement with the experimental value. The plasma concentration of 5-FU was low (5-FU was rapidly eliminated from the plasma and could not be detected at 120 min. In the analysis of tissue distribution, the liver was divided into three sites; the region under the diffusion cell attachment site (site 1), the treated lobe excluding site 1 (site 2), and untreated lobes (site 3). After being administered i.v., 5-FU mainly distributed in the kidney, and the concentration in the liver was significantly lower than that in kidney, spleen, or heart. After its application to the liver surface, however, 5-FU preferentially distributed at site 1, and was not detected at the other sites or in other tissues. Thus, these results suggested the possibility of a reduction in the systemic side effect of 5-FU on its application to the liver surface.

  2. Enteric coated HPMC capsules plugged with 5-FU loaded microsponges: a potential approach for treatment of colon cancer

    Ankita Gupta


    Full Text Available The work was aimed at developing novel enteric coated HPMC capsules (ECHC plugged with 5 Florouracil (5-FU loaded Microsponges in combination with calcium pectinate beads. Modified quasi-emulsion solvent diffusion method was used to formulate microsponges based on 32 factorial design and the effects of independent variables (volume of organic solvent and Eudragit RS100 content on the dependent variables (Particle size, %EE & % CDR were determined. The optimized microsponges (F4 were characterized by SEM, PXRD, TGA and were plugged along with calcium pectinate beads in HPMC capsules and the HPMC capsules were further coated with enteric polymer Eudragit L 100 (Ed-L100 and/ or Eudrgit S 100 (Ed-S 100 in different proportions. In vitro release study of ECHC was performed in various release media sequentially SGF for 2 h, followed by SIF for the next 6 h and then in SCF (in the presence and absence of pectinase enzyme for further 16 h. Drug release was retarded on coating with EdS-100 in comparison to blend of EdS-100: EdL-100 coating. The percentage of 5-FU released at the end of 24 h from ECHC 3 was 97.83 ± 0.12% in the presence of pectinase whereas in control study it was 40.08 ± 0.02% drug. The optimized formulation was subjected to in vivo Roentgenographic studies in New Zealand white rabbits to analyze the in vivo behavior of the developed colon targeted capsules. Pharmacokinetic studies in New Zealand white rabbits were conducted to determine the extent of systemic exposure provided by the developed formulation in comparison to 5-FU aqueous solutions. Thus, enteric coated HPMC capsules plugged with 5-FU loaded microsponges and calcium pectinate beads proved to be promising dosage form for colon targeted drug delivery to treat colorectal cancer.

  3. Proliferation rate but not mismatch repair affects the long-term response of colon carcinoma cells to 5FU treatment.

    Choudhary, B; Hanski, M L; Zeitz, M; Hanski, C


    The role of mismatch repair (MMR) in the response of colon carcinoma cells to 5-fluorouracil (5FU) is not well understood. In most of the in vitro studies only short-term response was investigated. We focussed here on the influence of MMR status on the mechanism of the short- and long-term response to clinically relevant 5FU concentrations by using isogenic or semiisogenic cell line pairs expressing/nonexpressing the hMLH1 protein, an important component of the MMR system. We show that the lower survival of MMR-proficient than of MMR-deficient cells in the clonogenic survival assay is due to a more frequent early cell arrest and to subsequent senescence. By contrast, the long-term cell growth after treatment, which is also affected by long-term arrest and senescence, is independent from the MMR status. The overall effect on the long-term cell growth is a cumulative result of cell proliferation rate-dependent growth inhibition, apoptosis and necrotic cell death. The main long-term cytotoxic effect of 5FU is the inhibition of growth while apoptosis and the necrotic cell death are minor contributions.

  4. Adverse immunoregulatory effects of 5FU and CPT11 chemotherapy on myeloid-derived suppressor cells and colorectal cancer outcomes.

    Kanterman, Julia; Sade-Feldman, Moshe; Biton, Moshe; Ish-Shalom, Eliran; Lasry, Audrey; Goldshtein, Aviya; Hubert, Ayala; Baniyash, Michal


    Colorectal cancer is associated with chronic inflammation and immunosuppression mediated by myeloid-derived suppressor cells (MDSC). Although chemotherapy reduces tumor burden at early stages, it tends to have limited effect on a progressive disease, possibly due to adverse effects on the immune system in dictating disease outcome. Here, we show that patients with advanced colorectal cancer display enhanced MDSC levels and reduced CD247 expression and that some conventional colorectal cancer chemotherapy supports the immunosuppressive tumor microenvironment. A FOLFOX combined therapy reduced immunosuppression, whereas a FOLFIRI combined therapy enhanced immunosuppression. Mechanistic studies in a colorectal cancer mouse model revealed that FOLFIRI-like therapy including the drugs CPT11 and 5-fluorouracil (5FU) damaged host immunocompetence in a manner that limits treatment outcomes. CPT11 blocked MDSC apoptosis and myeloid cell differentiation, increasing MDSC immunosuppressive features and mouse mortality. In contrast, 5FU promoted immune recovery and tumor regression. Thus, CPT11 exhibited detrimental immunoregulatory effects that offset 5FU benefits when administered in combination. Our results highlight the importance of developing therapeutic regimens that can target both the immune system and tumor towards improved personalized treatments for colorectal cancer.

  5. Combined MTX{center_dot}5-FU{center_dot}CDGP for the treatment of head and neck cancer

    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)


    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)

  6. A predicted protein, KIAA0247, is a cell cycle modulator in colorectal cancer cells under 5-FU treatment

    Chen Yan-Chu


    Full Text Available Abstract Background Colorectal cancer (CRC is the predominant gastrointestinal malignancy and the leading cause of cancer death. The identification of genes related to CRC is important for the development of successful therapies and earlier diagnosis. Methods Molecular analysis of feces was evaluated as a potential method for CRC detection. Expression of a predicted protein with unknown function, KIAA0247, was found in feces evaluated using specific quantitative real-time polymerase chain reaction. Its cellular function was then analyzed using immunofluorescent staining and the changes in the cell cycle in response to 5-fluorouracil (5-FU were assessed. Results Gastrointestinal tissues and peripheral blood lymphocytes ubiquitously expressed KIAA0247. 56 CRC patients fell into two group categories according to fecal KIAA0247 mRNA expression levels. The group with higher fecal KIAA0247 (n = 22; ≥ 0.4897 had a significantly greater five-year overall survival rate than the group with lower fecal KIAA0247 (n = 30; p = 0.035, log-rank test. Fecal expression of KIAA0247 inversely related to CRC tumor size (Kendall's tau-b = -0.202; p = 0.047. Immunofluorescent staining revealed that the cytoplasm of CRC cells evenly expresses KIAA0247 without 5-FU treatment, and KIAA0247 accumulates in the nucleus after 40 μM 5-FU treatment. In HCT116 p53-/- cells, which lack p53 cell cycle control, the proportion of cells in the G2/M phase was larger (13% in KIAA0247-silent cells than in the respective shLuc control (10% and KIAA0247-overexpressing cells (7% after the addition of low dose (40 μM 5-FU. Expression of three cyclin genes (cyclin A2, cyclin B1, and cyclin B2 also downregulated in the cells overexpressing KIAA0247. Conclusions This is the first description of a linkage between KIAA0247 and CRC. The study's data demonstrate overexpression of KIAA0247 associates with 5-FU therapeutic benefits, and also identify the clinical significance of fecal KIAA0247

  7. 复方斑蝥胶囊联合CPT-11+CF+5Fu治疗晚期大肠癌的临床观察%Comparative study on treatment of advanced colorectal cancer by Banmao capsule combined with CPT-11+CF+5Fu regimen and by CPT-11+CF+5Fu regimen alone

    林燕; 陆明


    Objective To evaluate the therapeutic efficacy and adverse reaction of Banmao capsule combined with CPT-11+CF+5Fu regimen for treatment of patients with advanced colorectal cancer and controlled with those of CPT-11 + CF+5Fu regimen alone. Methods 87 patients were randomly devided into two groups. All the patients received CPT-11 + CF+5Fu regimen,I , e. CPT-11 150-180 mg/m2 intravenous dropping in on day 1,C F 200 mg/m2 intravenous dropping and 5-FU 40 mg/m2 intravenous injection followed with 600 mg/m2 continuous infusion by micro-pump in 22 h on day 1 and 2,14 days as one course. Besides,to the treatment group (47 patients ), Banmao capsules was PO for 15 successive days,while to the control group(40 patients),no additional medication was given. Results The response rate in the treatment group was 44. 81% and in the control group 33. 6% (P = 0. 3355). The KPS score improving rate in the two groups was 65. 96% and 40%, respectively (P<0. 005). The lyear survival rate was 53. 19% and 40. 38% , respectively (P=0. 2193),and the adverse reaction presented in the treatment group was greatly less than that in the control group (P<0. 05). Conclusion Banmao capsules in combining with CPT-11+CF+5Fu regimen can enhance the efficacy, reduce the adverse reaction of chemotherapy in treating advanced colorectal cancer, and could also improve the quality of life and prolong the survival time of patients.%目的 观察复方斑蝥胶囊联合CPT-11+CF+5Fu化疗治疗晚期大肠癌的近期疗效和不良反应,方法将87例大肠癌患者随机分两组,对照组40例,单用CPT-11+CF+5Fu化疗方案,用法:CPT-11150~180 mg/m2,第1、8天,亚叶酸钙200 mg/m2静脉滴注2h,第1、2天,5-氟脲嘧啶300mg/m2静脉推注,第1、2天,600mg/m2持续微泵推入22 h,第1、2天,21天为1个周期;治疗组47例,在对照组治疗基础上加用复方斑蝥胶囊0.75 g,2次/日,连用15天.结果 治疗组和对照组有效率分别是44.81%和33.6%,差异无显著性(P=0

  8. Effect of viscous additives on the absorption and hepatic disposition of 5-fluorouracil (5-FU) after application to liver surface in rats.

    Kodama, Yukinobu; Horishita, Miyuki; Fumoto, Shintaro; Mine, Toyoharu; Miyamoto, Hirotaka; Yoshikawa, Naoki; Hirata, Haruna; Sasaki, Hitoshi; Nakamura, Junzo; Nishida, Koyo


    Objectives  The aim was to study the effect of viscous additives on the absorption and hepatic disposition of 5-fluorouracil (5-FU) after application to the liver surface in rats. Methods  5-FU solution with or without viscous additives was applied to the rat liver surface with a cylindrical diffusion cell. Then, blood and the remaining solution in the diffusion cell were collected at selected times, followed by excision of the liver. The excised liver was divided into three sites and assayed for 5-FU content. Key findings  The absorption rate of 5-FU from the liver surface was decreased in the presence of carboxymethylcellulose sodium (CMC-Na) and polyvinyl alcohol (PVA) as compared with the control. The k(a) values of PVA 15% and CMC-Na 1% were reduced to about 80 and 67% of the control. The maximum plasma concentration of 5-FU was decreased by incorporation of viscous additives. The 5-FU concentration at the diffusion cell attachment site of the liver (site 1) plateaued at 180 min in the absence of viscous additives. On the other hand, the concentration of 5-FU at site 1 increased in a time-dependent manner until 360 min in the presence of viscous additives. Conclusion  Viscous additives might be useful for retaining drugs at their application site and controlling the rate of absorption from the liver surface.

  9. Preparation and in vitro evaluation of 5-flourouracil loaded magnetite-zeolite nanocomposite (5-FU-MZNC) for cancer drug delivery applications.

    Sağir, Tuğba; Huysal, Merve; Durmus, Zehra; Kurt, Belma Zengin; Senel, Mehmet; Isık, Sevim


    In this work, super paramagnetic magnetite nanoparticles were synthesized onto/into zeolite, then loaded with anti-cancer drug 5-fluorouracil (5-FU). The physical properties of the prepared nanocomposite and drug loaded nanocomposite were characterized using different techniques. The drug loading and releasing behavior of the magnetic nanocarrier was investigated and the drug-loaded nanoparticles exhibited a sustained release of drug without any burst release phenomenon. Furthermore, 5-FU loaded MZNC were evaluated for its biological characteristics. The functional 5-FU-MZNC has been triggered intra-cellular release of the cancer therapeutic agent 5-fluorouracil (5-FU). Cytotoxic effects of 5-FU loaded MZNC on human gastric carcinoma (AGS) cells were determined by real time cell analysis and colorimetric WST-1 cell viability assay. Apoptosis of cells was further investigated by Annexin-V staining which indicates the loss of cell membrane integrity. According to our results, 5-FU-MZNC showed a concentration-dependent cell proliferation inhibitory function against AGS cells. Morphologic and apoptotic images were consistent with the cytotoxicity results. In conclusion, 5-FU loaded MZNC efficiently inhibit the proliferation of AGS cells in vitro through apoptotic mechanisms, and may be a beneficial agent against cancer, however further animal study is still required.

  10. Extracellular Disposal of Tumor-Suppressor miRs-145 and -34a via Microvesicles and 5-FU Resistance of Human Colon Cancer Cells

    Yukihiro Akao


    Full Text Available The dysregulation of microRNA (miRNA expression causes various kinds of diseases. Especially, alterations in miRNA expression levels are frequently observed in human tumor cells and are associated with cancer pathogenesis. Earlier we established Fluorouracil (5-FU-resistant human colon cancer DLD-1 cells (DLD-1/5FU from parental 5-FU- sensitive DLD-1 cells. In the present study, we examined the expression of miRNA in each cell line and in its extracellular microvesicles (MVs before and after treatment with 5-FU. The nascent RNAs of anti-oncogenic miR-34a and -145 labeled with EU in both cells were proved to be transferred into MVs in both cell lines. The levels of miR-34a and -145 in the cells and in their MVs were not largely different in the two cell lines, and a substantial amount of both miRNAs was secreted by both cell lines even in the steady-state condition. The exposure of both cell lines to 5-FU significantly increased the intracellular levels of miR-145 and miR-34a in the 5-FU-sensitive DLD-1 cells, whereas the level of neither miR was elevated in the DLD-1/5FU cells. Interestingly, the amount of miR-145 detected in the small MVs shed into the medium of the parental cells was reduced after the treatment with 5-FU. On the other hand, the intracellular expression of miR-34a in the DLD-1/5FU cells was down-regulated compared with that in the parental DLD-1 cells even in the steady-state condition. As to the miR-34a secreted into MVs, the increase in the level in DLD-1/5FU cells was greater than that in the parental DLD-1 cells after the treatment with 5-FU. Thus, the intra- and extracellular miR-145 and -34a were closely associated with 5-FU resistance, and the resistance was in part due to the enhanced secretion of miR-145 and -34a via MVs, resulting in low intracellular levels of both miRNAs.

  11. HSP27在调控人胃癌细胞系5-FU 耐药中的作用机制%The Mechanism of HSP27 Regulation of 5-FU Resistant in Human Gastric Cancer Cell Lines

    宋荣峰; 张慧卿; 熊彦; 王艳华; 万以叶


    目的:探讨热休克蛋白27(HSP27)在调控人胃癌细胞系5-FU耐药中的作用机制。方法培养人胃癌细胞株HGC27、BGC823、SGC7901、MKN28,采用CCK法筛选5-FU敏感株和耐药株,采用流式细胞仪和western blot 检测4株胃癌细胞株中HSP27表达水平,转染HSP27-siRNA,观察siRNA干扰后5-FU敏感株和耐药株中HSP27蛋白表达,并将两细胞株分别与不同浓度5-Fu共培养,采用CCK法检测细胞的半数抑制浓度( IC50)。结果 CCK法显示SGC7901细胞系是4株胃癌细胞中5-Fu相对耐药株,而HCG27是5-Fu相对敏感株。流式细胞仪显示SGC7901细胞株中HSP27表达水平最高为(72.10±1.89)%,而在HGC27细胞株中的表达水平最低为(22.12±1.33)%,各株表达水平比较差异有统计学意义( P<0.05)。转染HSP27-siRNA 后,各两株细胞HSP27蛋白表达水平均下降明显。与5-Fu共培养后, SGC7901细胞株转染组细胞半数抑制浓度降低,药物敏感性增强,与未转染组比较差异有统计学意义( P<0.05)。结论HSP27参与了SGC79015-FU耐药株中的细胞耐药,是诱导细胞多药耐药的重要分子机制,可以作为临床治疗靶点来提高胃癌患者对化疗的敏感性。%Objective To investigate the mechanism of HSP 27 of 5-FU resistant in human gastric cancer cell lines . Methods Human gastric cancer cell lines(HGC27,BGC823,SGC7901,MKN28)were cultured,and the cells which were resist-ant to 5-FU were selected by CCK assay and flow cytometry .The expression of HSP27 in these cells were detected by Western Blotting.And 2 cell lines were co-cultured with different concentration of 5-Fu,then the half inhibition concentration was detected by CCK assay.Results CCK assay showed that SGC7901 cell line was relatively resistant to 5-Fu,and the HCG27 cell line was relatively sensitive to 5-Fu.The flow cytometry results suggested that the expression of HSP 27 in the SGC7901 cells was

  12. [Preliminary clinical evaluation of low-dose cisplatin and continuous infusion of 5-FU (LFP) chemotherapy after weekly high-dose 5-FU therapy for the treatment of liver metastases from colorectal cancer].

    Itoh, Satoshi; Morita, Sojiro; Ohnishi, Takenao; Tsuji, Akihito; Takamatsu, Masahiro; Horimi, Tadashi


    In this study, we evaluate the efficacy of low-dose cisplatin and continuous 5-FU infusion systemic chemotherapy (LFP therapy) for the treatment of unresectable and recurrent liver metastases from colorectal cancer after weekly high-dose 5-FU therapy via the hepatic artery (WHF therapy). At the start of chemotherapy, 12 patients with multiple extrahepatic lesions were treated with the LFP therapy (LFP group), and 18 patients with none or a few extrahepatic lesions were treated with the WHF therapy followed by the LFP therapy (LFP after WHF group). In the LFP group, the response rate was 50.0% (PR 6) and the one-year survival rate was 50.0%. On the contrary, in the LFP after WHF group, the response rate was 38.9% (CR 1, PR 6) and the one-year survival rate after LFP started was 46.0%. We conclude that the LFP therapy may be effective for the treatment of liver metastases from colorectal cancer even after the WHF therapy.

  13. Synthesis of liver-targeting dual-ligand modified GCGA/5-FU nanoparticles and their characteristics in vitro and in vivo

    Chen M


    Full Text Available Mingrong Cheng,1,2,* Xiaoyan Gao,3,* Yong Wang,4,* Houxiang Chen,5 Bing He,6 Yingchun Li,2 Jiang Han,1 Zhiping Zhang11Department of General Surgery, Pudong New Area District Zhoupu Hospital, Shanghai, People’s Republic of China; 2Department of Endoscopy, 3Department of Plastic Surgery, Pudong New Area District Zhoupu Hospital, 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 General Surgery, Shanghai Fifth People’s Hospital, Fudan University, Shanghai, People's Republic of China *These authors equally contributed to this research Abstract: Nanoparticle drug delivery systems using polymers hold promise for clinical applications. We synthesized dual-ligand modified chitosan (GCGA nanoparticles using lactic acid, glycyrrhetinic acid, and chitosan to target the liver in our previous studies. We then synthesized the GCGA/5-FU nanoparticles by conjugating 5-fluorouracil (5-FU onto the GCGA nanomaterial, which had a mean particle size of 239.9 nm, a polydispersity index of 0.040, a zeta potential of +21.2 mV, and a drug loading of 3.90%. GCGA/5-FU nanoparticles had good slow release properties, and the release process could be divided into five phases: small burst release, gentle release, second burst release, steady release, and slow release. Inhibitory effects of GCGA/5-FU on tumor cells targeted the liver, and were time and dose dependent. GCGA nanoparticles significantly prolonged the efficacy of 5-FU on tumor cells, and alleviated the resistance of tumor cells to 5-FU. GCGA/5-FU nanoparticles were mostly concentrated in the liver, indicating that the GCGA nanoparticles were liver targeting. GCGA/5-FU nanoparticles significantly suppressed tumor growth in orthotopic liver transplantation mouse model, and improved

  14. Research Progress on 5-FU Derivatives%5-氟尿嘧啶及其衍生物的研究进展

    袁吉; 倪孟祥


    5-FU is an antimetabolite, which possesses activity against a wide range of solid tumors. The main mechanism of 5-FU is interfering with DNA synthesis and mRNA translation. However,because of the nonspecific cytotoxicity of 5-FU,the patients display several side effects. Numerous modifications of the 5-FU structure have been performed in order to overcome these disadvantages. In this paper,the mechanism and pharmacokinetics of 5-FU are briefly introduced, then several 5-FU derivatives including oral 5-FU prodrugs are presented ,finally the new innovative methods of increasing bioavailability of 5-FU and derivatives are described. All these will provide the theoretical basis for rational administration.%尿嘧啶的氟化类似物5-FU是一种抗代谢物,它对很多实体肿瘤有较好活性.5-FU抗肿瘤活性是通过干扰DNA合成和mRNA翻译来实现的.然而,由于5-FU具有非特异性细胞毒性,故采用5-FU治疗的患者表现出多种副作用.为了改善这些缺点,研究者们对5-FU的结构展开了大量的修饰工作.文章综述了5-FU的作用机理以及药代动力学情况,介绍了5-FU的几种新型修饰衍生物.最后,对提高5-FU衍生物生物利用度的研究进展进行了综述,为5-FU衍生药物的合理使用提供了理论依据.

  15. Wheat germ allutinin functionalized crosslinked polyelectrolyte microparticles for local colon delivery of 5-FU: In vitro efficacy and in vivo gastrointestinal distribution

    Glavas-Dodov, Marija; Steffansen, Bente; Crcarevska, Maja


    We have previously reported the development and characterisation of wheat germ agglutinin (WGA)-functionalised chitosan-Ca-alginate (CTS-Ca-ALG) microparticles (MPs) loaded with acid-resistant particles of 5-fluorouracil (5-FU). In the present work, our goal was to evaluate the potential...... of these carriers for efficient treatment of colon cancer by studying in vitro permeability and cell association of 5-FU and [methyl-³H]thymidine uptake in Caco-2 cells, as well as in vivo gastrointestinal distribution. The amount of 5-FU permeated through Caco-2 cells was 15.1, 7.7 and 6.5% for 5-FU solution, CTS......-Ca-ALG MPs and WGA conjugates. The concentration of 5-FU associated with Caco-2 cells was significantly greater when delivered from MPs. By incorporation of 5-FU into MPs and further decoration with WGA, an increased [methyl-³H]thymidine uptake was observed few hours after continuous drug treatment followed...

  16. Wheat germ agglutinin-functionalised crosslinked polyelectrolyte microparticles for local colon delivery of 5-FU: in vitro efficacy and in vivo gastrointestinal distribution.

    Glavas-Dodov, Marija; Steffansen, Bente; Crcarevska, Maja S; Geskovski, Nikola; Dimchevska, Simona; Kuzmanovska, Sonja; Goracinova, Katerina


    We have previously reported the development and characterisation of wheat germ agglutinin (WGA)-functionalised chitosan-Ca-alginate (CTS-Ca-ALG) microparticles (MPs) loaded with acid-resistant particles of 5-fluorouracil (5-FU). In the present work, our goal was to evaluate the potential of these carriers for efficient treatment of colon cancer by studying in vitro permeability and cell association of 5-FU and [methyl-³H]thymidine uptake in Caco-2 cells, as well as in vivo gastrointestinal distribution. The amount of 5-FU permeated through Caco-2 cells was 15.1, 7.7 and 6.5% for 5-FU solution, CTS-Ca-ALG MPs and WGA conjugates. The concentration of 5-FU associated with Caco-2 cells was significantly greater when delivered from MPs. By incorporation of 5-FU into MPs and further decoration with WGA, an increased [methyl-³H]thymidine uptake was observed few hours after continuous drug treatment followed by significantly reduced uptake after 6 h. Gastrointestinal distribution was in favour of increased localisation and concentration of the particles in colon region.

  17. 藤黄酸合用氟尿嘧啶抗肿瘤活性的研究%Anti-tumor Activity of Gambogic Acid Combined with 5-Fu

    骞秀芳; 郭喆; 史小四; 刘丹


    目的:探讨藤黄酸(GA)与氟尿嘧啶(5-Fu)联合应用的抗肿瘤活性.方法:MTT法观察GA合用5-Fu对刀豆蛋白A诱导的小鼠脾细胞增殖的影响;小鼠接种S180肉瘤,分为模型组、GA组(20 mg·kg-1)、5-Fu组(20 mg·kg-1)、GA合用5-Fu组(GA 20 mg · kg-1 + 5-Fu 20 mg·kg-1),每组10只,腹腔注射给药10 d后,各组称体质量,取瘤体、脾脏和胸腺称质量,计算抑瘤率、脾指数、胸腺指数.结果:GA合用5-Fu对淋巴细胞增殖表现出较强的抑制活性(P<0.01),抑制作用随药物浓度的增加而提高.GA合用5-Fu组的瘤质量与模型组、GA组、5-Fu组相比明显降低(P<0.01),抑瘤率达62.4%,明显大于单用GA或5-Fu.与5-Fu组相比,GA合用5-Fu可明显提高脾指数和胸腺指数(P<0.05).结论:GA合用5-Fu具备良好的体内外抗肿瘤活性,有协同作用.%Objective:To investigate the anti-tumor activity of gambogic acid (GA) combined with 5-fluorouracil (5-Fu).Method:The effect of GA plus 5-Fu on the mouse spleen lymphocyte proliferation in vitro was determined by an MTT assay.The mice were transplanted tumor S180,then divided into 4 groups randomly:GA group (20 mg · kg-1),5-Fu group (20 mg · kg-1),GA plus 5-Fu group (20 mg· kg-1 +20 mg · kg-1) and the model group(n =10).All mice were with intraperitoneal injection for ten days.After body-weighting,the effect of GA plus 5-Fu on tumor growth,spleen index and thymus index was determined.Result:GA plus 5-Fu significantly inhibited the proliferation of lymphocytes induced by ConA in a dose-dependent manner(P <0.01).The tumor growth in GA plus 5-Fu group was notablyinhibited compared with that in the model group (P < 0.01).The S180 inhibition rate in GA plus 5-Fu group reached 62.4%,which was higher than that in GA and 5-Fu group.In addition,GA plus 5-Fu had a protective effect on immune suppression caused by 5-Fu.Conclusion:GA plus 5-Fu can inhibit tumor growth effectively with a synergism.

  18. TJ-41 Induces Apoptosis and Potentiates the Apoptotic Effects of 5-FU in Breast Cancer Cell Lines

    Suresh Volate


    Full Text Available Recent studies suggest that TJ-41, a herbal drug, possesses chemotherapeutic effects. Accordingly, this study was undertaken to investigate the anticarcinogenic effects of TJ-41 on human breast cancer cells lines. TJ-41 inhibited the proliferation of human breast cancer cell lines dose dependently. Flow cytometric analysis showed that this decrease in DNA synthesis is to be associated with induction of apoptosis. In both cell lines, apoptosis was abolished by caspase-9 inhibitor Z-LEHD-fmk but was weakly inhibited by caspase-8 inhibitor Z-IETD-fmk, indicating that caspase-9 activation was involved in TJ-41 induced apoptosis. Additionally, TJ-41 stimulated phosphorylation of c-Jun NH2-terminal kinase (JNK and pretreatment of breast cancer cells with JNK inhibitor SP600125 completely abolished TJ-41 induced apoptosis. Our data also demonstrate that combined treatment of TJ-41 and 5-FU significantly potentiates the apoptotic effects of 5-FU in both breast cancer cell lines. Taken together, these data suggest that TJ-41 might provide a novel chemotherapeutic treatment for breast cancer.

  19. The Combination of the PARP Inhibitor Rucaparib and 5FU Is an Effective Strategy for Treating Acute Leukemias.

    Falzacappa, Maria Vittoria Verga; Ronchini, Chiara; Faretta, Mario; Iacobucci, Ilaria; Di Rorà, Andrea Ghelli Luserna; Martinelli, Giovanni; Meyer, Lüder Hinrich; Debatin, Klaus-Michael; Orecchioni, Stefania; Bertolini, Francesco; Pelicci, Pier Giuseppe


    The existing treatments to cure acute leukemias seem to be nonspecific and suboptimal for most patients, drawing attention to the need of new therapeutic strategies. In the last decade the anticancer potential of poly ADP-ribose polymerase (PARP) inhibitors became apparent and now several PARP inhibitors are being developed to treat various malignancies. So far, the usage of PARP inhibitors has been mainly focused on the treatment of solid tumors and not too much about their efficacy on leukemias is known. In this study we test, for the first time on leukemic cells, a combined therapy that associates the conventional chemotherapeutic agent fluorouracil (5FU), used as a source of DNA damage, and a PARP inhibitor, rucaparib. We demonstrate the efficacy and the specificity of this combined therapy in killing both acute myeloid leukemia and acute lymphoid leukemia cells in vitro and in vivo. We clearly show that the inhibition of DNA repair induced by rucaparib is synthetic lethal with the DNA damage caused by 5FU in leukemic cells. Therefore, we propose a new therapeutic strategy able to enhance the cytotoxic effect of DNA-damaging agents in leukemia cells via inhibiting the repair of damaged DNA.

  20. AT101 exerts a synergetic efficacy in gastric cancer patients with 5-FU based treatment through promoting apoptosis and autophagy.

    Wei, Xi; Duan, Wei; Li, Ying; Zhang, Sheng; Xin, Xiaojie; Sun, Lei; Gao, Ming; Li, Qing; Wang, Dong


    Gastric cancer remains a disease with a high mortality rate despite of multiple therapeutic strategies. So far, it is very important to develop new treatment approaches to improve current therapeutic efficacy in gastric cancer. Apurinic/apyrimidinic endonuclease (APE1) involves in DNA base excision repair (BER) during DNA damage pathway. APE1 was found to be associated with poor overall survival with gastric cancer patients. In the in vitro experiment, we tested APE1 inhibitor-AT101 could potently inhibit gastric cancer cell growth and further induce cancer cell apoptosis and autophagy through p53-dependent pathway. Downregulation of APE1 by AT101 has ability to suppress gastric cancer cell migration and renewal through inhibition of CD133, Nanog and LC3expression. Based on findings that Her-2 positive expression cases has poor prognosis from our dataset and TCGA database, we investigated the role of AT101 in synergetic efficacy with 5-FU treatment in Her-2 overexpression gastric cancer in vivo, indicating that AT101 is able to enhance 5-FU in the shrinkage of xenograft mice tumor and induction of cell apoptosis. In summary, the data obtained from our study showed APE1 is guided as a potential therapeutic target for gastric cancer. AT101 could be regarded as a potent inhibitor to promote chemotherapeutic sensitivity in patients with gastric cancer.

  1. AT101 exerts a synergetic efficacy in gastric cancer patients with 5-FU based treatment through promoting apoptosis and autophagy

    Wei, Xi; Duan, Wei; Li, Ying; Zhang, Sheng; Xin, Xiaojie; Sun, Lei; Gao, Ming; Li, Qing; Wang, Dong


    Gastric cancer remains a disease with a high mortality rate despite of multiple therapeutic strategies. So far, it is very important to develop new treatment approaches to improve current therapeutic efficacy in gastric cancer. Apurinic/apyrimidinic endonuclease (APE1) involves in DNA base excision repair (BER) during DNA damage pathway. APE1 was found to be associated with poor overall survival with gastric cancer patients. In the in vitro experiment, we tested APE1 inhibitor-AT101 could potently inhibit gastric cancer cell growth and further induce cancer cell apoptosis and autophagy through p53-dependent pathway. Downregulation of APE1 by AT101 has ability to suppress gastric cancer cell migration and renewal through inhibition of CD133, Nanog and LC3expression. Based on findings that Her-2 positive expression cases has poor prognosis from our dataset and TCGA database, we investigated the role of AT101 in synergetic efficacy with 5-FU treatment in Her-2 overexpression gastric cancer in vivo, indicating that AT101 is able to enhance 5-FU in the shrinkage of xenograft mice tumor and induction of cell apoptosis. In summary, the data obtained from our study showed APE1 is guided as a potential therapeutic target for gastric cancer. AT101 could be regarded as a potent inhibitor to promote chemotherapeutic sensitivity in patients with gastric cancer. PMID:27144437

  2. Inhibitory effect of sil ibinin combined with 5-FU treatment on mal ignant biological behaviors of gastric cancer cell l ines MGC803%水飞蓟宾联合5-FU 对胃癌细胞株 MGC803恶性生物学行为的抑制作用研究

    王阳; 李昌林


    目的::研究水飞蓟宾联合5-FU 处理对胃癌细胞株 MGC803恶性生物学行为的抑制作用.方法:培养胃癌细胞株 MGC803,分为 NC 组、5-Fu 组、SB+5-Fu 组并用不同条件进行处理,检测凋亡细胞数目、侵袭细胞数目以及增殖、侵袭相关基因的表达量.结果:处理后6h、12h、18h、24h 时,5-Fu 组、SB+5-Fu 组凋亡细胞的数目显著多于 NC 组、侵袭数目显著少于 NC 组,SB+5-Fu 组凋亡细胞的数目显著多于5-Fu 组、侵袭数目显著少于5-Fu 组(P <0.05);5-Fu 组、SB+5-Fu 组细胞中 Vav3、PTP1B、GOLPH3、RUNX3、Sipa1、UbcH10、NEDD9、Mig-7、CD157、AEP、Galectin-1的 mRNA 含量低于 NC组(P <0.05);SB+5-Fu 组细胞中 Vav3、PTP1B、GOLPH3、UbcH10、NEDD9、Mig-7、CD157、AEP、Galectin-1的 mRNA 含量低于5-Fu 组(P <0.05),RUNX3、Sipa1的 mRNA 含量与5-Fu 组差异无统计学意义(P >0.05).结论:与5-FU 单药处理相比,水飞蓟宾联合5-FU 处理能够更为有效的促进胃癌细胞凋亡、抑制胃癌细胞侵袭、调节增殖和侵袭相关基因的表达.%Objective:To study the inhibitory effect of silibinin combined with 5-FU treatment on malignant biological behaviors of gastric cancer cell lines MGC803.Methods:Gastric cancer cell lines MGC803 were cultured,divided into NC group,5-Fu group and SB+5-Fu group and treated with different conditions,and then the number of apoptotic cells,the num-ber of invasive cells as well as the expression of proliferation and invasion-related genes were detected.Results:6 h,12 h,18 h and 24 h after treatment,the number of apoptotic cells of 5-Fu group and SB+5-Fu group was significantly more than that of NC group,the number of invasive cells was significantly less than that of NC group,the number of apoptotic cells of SB+5-Fu group was significantly more than that of 5-Fu group,and the number of invasive cells was significantly less than that of 5-Fu group;mRNA contents of Vav3

  3. A phase II study of LFP therapy (5-FU (5-fluorourasil continuous infusion (CVI and Low-dose consecutive (Cisplatin CDDP in advanced biliary tract carcinoma

    Horimi Tadashi


    Full Text Available Abstract Background Unresectable biliary tract carcinoma is known to demonstrate a poor prognosis. We conducted a single arm phase II study of LFP therapy (5-FU (5-fluorourasil continuous infusion (CVI and Low-dose consecutive (Cisplatin CDDP for advanced biliary tract malignancies basically on an outpatient basis. Methods Between February 1996 and September 2003, 42 patients were enrolled in this trial. LFP therapy By using a total implanted CV-catheter system, 5-FU (160 mg/m2/day was continuously infused over 24 hours for 7 consecutive days and CDDP (6 mg/m2/day was infused for 30 minutes twice a week as one cycle. The administration schedule consisted of 4 cycles as one course. RESIST criteria (Response evaluation criteria for solid tumors and NCI-CTC (National Cancer Institute-Common Toxicity Criteria (ver.3.0 were used for evaluation of this therapy. The median survival time (MST and median time to treatment failure (TTF were calculated by the Kaplan-Meier method. Results Patients characteristics were: mean age 66.5(47–79: male 24 (54%: BDca (bile duct carcinoma 27 GBca (Gallbladder carcinoma 15: locally advanced 26, postoperative recurrence 16. The most common toxicity was anemia (26.2%. Neither any treatment related death nor grade 4 toxicity occurred. The median number of courses of LFP Therapy which patients could receive was two (1–14. All the patients are evaluable for effects with an over all response rates of 42.9% (95% confidence interval C.I.: 27.7–59.0 (0 CR, 18 PR, 13 NC, 11 PD. There was no significant difference regarding the anti tumor effects against both malignant neoplasms. Figure 2 Shows the BDca a longer MST and TTF than did GBca (234 vs 150, 117 vs 85, respectively, but neither difference was statistically significant. The estimated MST and median TTF were 225 and 107 days, respectively. The BDca had a longer MST and TTF than GBca (234 vs 150, 117 vs 85, respectively, but neither difference was statistically

  4. S-1 in combination with docetaxel and oxaliplatin in patients with advanced gastro-esophageal adenocarcinoma

    Pfeiffer, Per; Qvortrup, Camilla; Krogh, Merete


    BACKGROUND: Docetaxel in combination with cisplatin and 5-fluorouracil (5-FU) is one of several standard chemotherapy regimens for patients with advanced gastro-esophageal adenocarcinoma (aGEA) in Europe. To enable outpatient treatment, we evaluated the maximum tolerated dose (MTD), recommended...

  5. Comparison of MACT and 5Fu+ACT-D chemotherapy regimens in the treatment of low-risk gestational trophoblastic neoplasia.

    Wang, Yu; Miao, Jin-Wei; Wang, Tong; Wang, Yan; Wu, Yu-Mei; Kong, Wei-Min; Su, Li; Duan, Wei


    The study aimed to compare the efficacy of methotrexate (MTX) cervical injections + actinomycin-D (ACT-D)(MACT) and 5-fluorouracil (5-Fu) + actinomycin-D (5-Fu plus ACT-D) chemotherapy regimens for low-risk gestational trophoblastic neoplasia (LR-GTN). Clinical data from 66 LR-GTN patients, admitted to the Beijing Obstetrics and Gynecology Hospital from January 2010 to April 2012, were analysed retrospectively. In total, 32 patients were treated with a MACT therapeutic regimen and the remaining 34 with a 5Fu + ACT-D therapeutic regimen. Complete remission rates (CR), duration of treatment, hospital stay and toxicity effects were compared. There was no statistical difference in CR for the MACT (90.63%) or the 5-Fu plus ACT-D (100%) therapeutic regimens (p = 0.0676) or in the duration of treatment [MACT (3.50) or 5-Fu plus ACT-D (3.71; p = 0.2021)]. Moreover, the hospital stay in the 5-Fu plus ACT-D group (32.88 days) was significantly longer than for the MACT group (22.09 days; p < 0.001). Furthermore, the degree of myelosuppression, nausea and vomiting, diarrhoea, stomatitis and alopecia was more severe in the 5Fu + ACT-D group (p < 0.01). However, there was no statistical difference in the severity of liver function damage between the two groups. A shorter hospital stay, lower hospitalization cost and slightly more toxic effects were observed in LR-GTN patients treated with the MACT therapeutic regimen. We suggest that the MACT regimen should be used as first-line chemotherapy for LR-GTN.

  6. MiR-122 increases sensitivity of drug-resistant BEL-7402/5-FU cells to 5-fluorouracil via down-regulation of bcl-2 family proteins.

    Yin, Jie; Tang, Hui Fang; Xiang, Qiong; Yu, Jia; Yang, Xiao Yang; Hu, Nan; Lei, Xiao Yong


    To investigate the changes in drug sensitivity of miR-122 transfected BEL-7402/5-FU cells. MiR-122 and negative miRNA expression vectors were constructed and stably transfected into BEL-7402/5-FU cells. Real-time RT-PCR was used to detect the level of miR-122, Bcl-XL, Bcl-2 and P53 mRNA. Western Blotting was used to detect Bcl-2, Bcl-XL and P53 protein expression. Drug sensitivity of the cells to 5-fluorouracil (5-FU) was analyzed with MTT and flow cytometry. Compared with negative miRNA transfectants or untreated cells, mRNA and protein expression level of Bcl-2, Bcl-XL in stable miR-122 transfectants were decreased. Accordingly, P53 protein expression showed a significant up-regulation; MTT results showed that after incubation with 5-FU, miR-122 transfectants had higher cell inhibitory rates than negative miRNA or untreated cells; flow cytometry results demonstrated that apoptosis rate increased in miR-122 transfected cells, compared with negative miRNA or untreated cells. After addition of 5-FU (10 and 100 micromol/I), miR-122 transfected cells showed higher apoptosis rate than negative miRNA or untreated cells. MiR-122 can specifically down-regulate the expression of Bcl-2 and Bcl-XL, and increase P53 activity in BEL-7402/5-FU cells, which increased cells spontaneous apoptosis and sensitize cells to 5-FU. Therefore, MiR-122 can be used as a potential therapy agent against human hepatoblastoma.

  7. Resveratrol synergistically augments anti-tumor effect of 5-FU in vitro and in vivo by increasing S-phase arrest and tumor apoptosis.

    Dun, Jiening; Chen, Xueyan; Gao, Haixia; Zhang, Yan; Zhang, Huajun; Zhang, Yongjian


    Many studies have shown that natural dietary agents, in combination with chemical agents, can improve the therapeutic response of cancers to chemotherapy and reduce the associated side-effects. In the present study, we investigated the therapeutic potential and mechanisms of anticancer effects for the combination of 5-fluorouracil (5-FU) and resveratrol (Res). In these studies, we employed the cancer cell lines TE-1 and A431 and an animal model of skin cancer. The presented results provide the first evidence that Res can enhance the anti-tumor potency of 5-FU by inducing S-phase arrest. The combination of Res and 5-FU demonstrates synergistic efficacy, causing tumor regression in a two-stage model of mouse skin carcinogenesis induced by DMBA and TPA. There was clear evidence of Res augmenting the growth inhibitory effect of 5-FU on the TE-1 and A431 cancer cells in vitro. In the in vivo studies, the tumor regression rate in the combination group increased significantly after four weeks of treatment (P 5-FU and Res significantly increased the percentage of apoptotic cells and the level of activated caspase-3, cleaved PARP and p53 proteins as well as increased the Bax/Bcl-2 ratio. In conclusion, the 5-FU/Res combination enabled a more effective inhibition of cell growth and the induction of apoptosis in cancer cells than 5-FU alone. The results of this study suggest that chemotherapy using natural dietary agents with chemical agents represents a superior cancer treatment option.

  8. Antimyosin antibody scintigraphy in patients treated with 5-fluorouracil (5-FU) and cis-platinum (CDDP); Scintigraphie aus anticorps antimyosine chez les patients traites par 5-fluorouracil (5-FU) et cis-platine (CDDP)

    Muratet, J.P; Gameli, E.; Maillard, P.; Lortholary, A.; Delva, R.; Larra, P. [Centre Paul Papin, 2, rue Moll, 49033 Angers cedex 01 (France)


    The 5-FU in continuous perfusion over 96 h associated to CDDP can induce cardiac secondary effects for which a toxic myocardial origin is discussed. To locate anomalies related to myocarditis and consequently to adjust the dosing, a scintigraphy with antimyosin antibodies labelled with {sup 111}In (ScAM) was performed 7 days before the chemotherapy initiation and at the second day of it (with films at 4 d) in 14 patients, which besides benefited by clinical surveillance, ECG and FEVG (angio-scintigraphy before and at 48 h from the beginning of treatment). No clinical or ECG alteration and no significant variation of FEVG were found. The cardio-pulmonary fixation ratio (CPR) measured together with ScAM was not modified: 1.57 {+-} 0.21 [1.28 - 1.97] before treatment vs 1.54 {+-} 0.16 [1.30 - 1.90], during the treatment. The average intra-individual variation of CPR was as absolute value 8.12% {+-} 9.89% [0.60 - 29.71], only 2 patients presenting a variation larger than 20%. In absence, of clinical alteration, ECG or FEVG, the ScAM under 5-FU + CDDP does not show anomalies related to a asymptomatic myocardial affliction. Consequently, the exploration by ScAM appears to be reserved to symptomatic patients and/or to cases of asymptomatic break down by FEVG. Due to an inter-individual relatively limited dispersion of the values (m {+-} 2 ds 1.56 {+-} 0.37, in our series), establishing previously a reference individual CPR might be not indispensable

  9. Long-term outcome of mitomycin C- and 5-FU-based primary radiochemotherapy for esophageal cancer

    Wolf, Maria; Zehentmayr, Franz; Niyazi, Maximilian; Ganswindt, Ute; Haimerl, Wolfgang; Belka, Claus [Dept. of Radiation Oncology, Univ. Hospital Munich, LMU (Germany); Schmidt, Michael [Inst. for Biometry and Epidemiology, Univ. Hospital Munich, LMU (Germany); Hoelzel, Dieter [Tumor Registry Munich, Univ. Hospital Munich, LMU (Germany)


    Background and purpose: for definitive radiochemotherapy, 5-fluorouracil/cisplatin protocols have been considered the standard of care for esophageal carcinoma over the last 2 decades. By contrast, most patients treated at the University Hospital, LMU Munich, Germany, received 5-fluorouracil/mitomycin C. The objective of this retrospective analysis was to determine the value of 5-fluorouracil/mitomycin-C-based therapy. Patients and methods: tumor stage, treatment received, and outcome data of patients treated for esophageal cancer between 1982 and 2007 were collected; endpoint of the analysis was overall survival. Results: 298 patients with inoperable cancer of the esophagus were identified (16.8% adenocarcinoma, 77.5% squamous cell carcinoma). At diagnosis, 61.7% (184/298) had UICC stage III-IV, 54.4% (162/298) positive lymph nodes, and 26.5% (79/298) metastatic disease. 74.5% of all patients (222/298) received radiation doses between 55 and 65 Gy, 65.8% (196/298) were subjected to concomitant chemotherapy. The median follow-up period (patients alive) was 4.1 years. A significant increase of overall survival (p < 0.0001) in the radiochemotherapy versus the radiotherapy=alone group was observed. 52% (102/196) in the 5-fluorouracil/mitomycin C group had tumor stages comparable to the RTOG 85-01 study cohort (T1-3 N0-1 M0). The median survival in this subgroup was 18.2 months, 3- and 5-year survival rates were 22.7% (21/102) and 15.0% (13/102), respectively. Conclusion: despite being nominally inferior to platinum-based radiochemotherapy, the overall survival rates are in a similar range. Thus, the mitomycin-C-based radiochemotherapy approach may considered to be as effective as the standard therapy. However, there is no randomized trial available in order to prove the equality. (orig.)

  10. 白花蛇舌草注射液逆转人肝癌细胞BEL-7402/5-FU 的多药耐药作用%Effect of Hedyotic diffusa injection in reversing multi-drug resistance of human hepatoma BEL-7402/5-FU cells

    廖作庄; 韦丽美; 徐灵源; 梁钢


    Objective To study the effect and mechanism of Hedyotic diffusa injection in reversing multi-drug resistance of BEL-7402/5-FU cells.Methods The IC50 of BEL-7402/5-FU cells was examined by MTT,apoptosis was detected by flow cytometry,and the content of tyrosine kinase in total protein of tumor cells was detected by enzyme-linked immunosorbent assay (ELISA).Results The IC50 of Hedyotic diffusa injection (6 μL/mL ) combined with 5-FU (636.5 μmol/L)decreased significantly compared with that of 5-FU applied alone (1 071.6 6μmol/L). The reversal on BEL-7402/5-FU was 1.68-fold.After injection of 5-FU plus Hedyotic diffusa ,the apoptosis rate of BEL-7402/5-FU cells was increased significantly and the tyrosine kinases of BEL-7402/5-FU cells decreased significantly.Conclusion Hedyotic diffusa injection plays a certain role in reversing multi-drug resistance of BEL-7402/5-FU cells,which may be related to decreasing their tyrosine kinases.%目的:研究白花蛇舌草注射液对 BEL-7402/5-FU 细胞多药耐药的逆转作用,并探讨其作用机制。方法四甲基偶氮唑蓝(MTT)法检测药物对 BEL7402/5-FU 细胞的半数抑制浓度(IC50);流式细胞仪检测细胞凋亡;ELISA 双抗体一步夹心法测定酪氨酸激酶含量。结果无毒剂量的白花蛇舌草注射液(6μL/mL)联合5-FU 对 BEL-7402/5-FU细胞的 IC50为636.5μmol/L,比单独应用5-FU 的 IC50(1071.6μmol/L)明显下降,逆转倍数为1.68;加白花蛇舌草注射液后,5-FU 对 BEL-7402/5-FU 细胞的凋亡比例明显增加,且显著下调 BEL-7402/5-FU 细胞的酪氨酸激酶含量。结论白花蛇舌草注射液对 BEL-7402/5-FU 细胞的多药耐药性具有一定的逆转作用,其机制可能与下调酪氨酸激酶有关。

  11. HSP90 inhibition downregulates thymidylate synthase and sensitizes colorectal cancer cell lines to the effect of 5FU-based chemotherapy.

    Nagaraju, Ganji Purnachandra; Alese, Olatunji B; Landry, Jerome; Diaz, Roberto; El-Rayes, Bassel F


    Cell cycle progression and DNA synthesis are essential steps in cancer cell growth. Thymidylate synthase (TS) is a therapeutic target for 5FU. We tested the hypothesis that HSP90 transcriptional and functional inhibition can inhibit cell cycle progression, downregulate TS levels and sensitize colorectal cancer (CRC) cell lines to the effects of 5FU. Treatment with ganetespib (50 nM) for 24 hours inhibited cyclin D1 and pRb at the transcriptional and translational levels and induced p21, leading to G0/G1 cell cycle arrest in both CRC cell lines (HCT-116 and HT-29). This was associated with downregulation of E2F1 and its target gene TS. In addition, ganetespib inhibited PI3K/Akt and ERK signalling pathways. Similar effects were observed with HSP90 knockdown in both cell lines. Ganetespib sensitized CRC cell lines to the effects of oxaliplatin and 5FU. Similar effects were also observed in tumors from animals treated with ganetespib, oxaliplatin and 5FU. In this study, we present in vitro and animal data supporting that the targeting of HSP90 decreases CRC cell survival and proliferation. Ganetespib sensitizes CRC cell lines to the effects of 5FU-based chemotherapy. Combining HSP90 inhibitors with chemotherapy is a rational approach for future drug development in CRC.

  12. Application and Immune Effect of Nutrison-5Fu on Perioperative Patients with Progressive Gastrointestinal Cancer%进展期胃肠癌患者围手术期能全素-5Fu的应用及对免疫状态的影响

    马利林; 陈玉泉; 沈洪薰; 徐青; 朱建伟; 周广军; 陈瑞新


    Objectives To investigate and evaluate the effect of Nutrison-5Fu o n immune function of perioperative patients with progressive gastrointestin al cancer,and simultaneously we also recommended the methods of application of N utris on-5Fu.Methods Seventy eight cases were equally divided at random into three groups,26 cases in each group.⑴Nutrison-5Fu group:the patients were treated with Nutrison-5Fu.⑵Chemotherapy group:the patients only received 5-Fu.⑶Control gr ou p:there were not any chemotherapy and immunetherapy during the pe rioperati on.The values of CD3,CD4,CD8 and NKCC were determined in all cases. Results Values of CD3,CD4,CD/CD8 ratio and NKCC in most patients w ere distinctly l ow,but the condition rapid improved by giving them Nutrison-5Fu. On the contrary,the values declined further after chemotherapy alone.Concl usion The treatment of Nutrison-5Fu not only can repress the development of the tumor, but also can improve the dystrophic status and immune function of the patients w ith cancer.%目的 研究与评价能全素-5Fu治疗对进展期胃肠癌患者围手术 期免疫状态的影响并介 绍其应用方法。方法 确立免疫指标及正常值,将78例患者随机分为⑴能全 素-5Fu组:给予 能全素-5Fu治疗;⑵单纯化疗组:给予5-Fu治疗;⑶对照组:围手术期内不予化疗与免疫治 疗。三组分别测定围手术期各阶段T细胞亚群与NKCC值。结果 各组治疗前C D3、CD4、C D4/CD8、NKCC值均有明显下降,应用能全素-5Fu后,上述数值均明显升高,单纯化疗者 则明显下降。结论 能全素-5Fu治疗既可抑制肿瘤的生长,又可改善患者的 营养不良状况与免疫功能。

  13. MicroRNA-302b Enhances the Sensitivity of Hepatocellular Carcinoma Cell Lines to 5-FU via Targeting Mcl-1 and DPYD

    Donghui Cai


    Full Text Available MiR-302b is a member of miR-302-367 cluster. The miR-302-367 cluster played important roles in maintaining pluripotency in human embryonic stem cells (hESCs and has been proved to be capable of suppressing cell growth in several types of cancer cell lines including Hepatocellular Carcinoma (HCC Cell lines. However, the role that miR-302b plays in the 5-Fluorouracil (5-FU sensitivity of HCC has not been known. This study showed that miR-302b could enhance the sensitivity to 5-FU in HCC cell lines and verified its two putative targeted genes responsible for its 5-FU sensitivity.

  14. MicroRNA-302b Enhances the Sensitivity of Hepatocellular Carcinoma Cell Lines to 5-FU via Targeting Mcl-1 and DPYD.

    Cai, Donghui; He, Kang; Chang, Su'e; Tong, Dongdong; Huang, Chen


    MiR-302b is a member of miR-302-367 cluster. The miR-302-367 cluster played important roles in maintaining pluripotency in human embryonic stem cells (hESCs) and has been proved to be capable of suppressing cell growth in several types of cancer cell lines including Hepatocellular Carcinoma (HCC) Cell lines. However, the role that miR-302b plays in the 5-Fluorouracil (5-FU) sensitivity of HCC has not been known. This study showed that miR-302b could enhance the sensitivity to 5-FU in HCC cell lines and verified its two putative targeted genes responsible for its 5-FU sensitivity.

  15. Effects of Artemis on DNA damage of human hepatic carcinoma cell line BEL-7402/5FU%Artemis对人肝癌细胞系BEL-7402/5FU DNA损伤的影响

    张雪; 李大玉; 祝小波; 范芳; 刘云; 李长福


    目的 探讨转染shArtemis干扰质粒对人肝癌细胞BEL-7402/5FU DNA损伤的影响.方法 将人肝癌细胞分为正常对照组、脂质体对照组、空质粒对照组和转染shArtemis干扰质粒实验组(shArtemis实验组);建立DNA损伤模型,分别用0.625、1.25、2.5、5.0和10.0 μg/mL的丝裂霉素C作用BEL-7402/5FU细胞24和48 h,MTT法检测细胞活性,Western blot观察磷酸化组蛋白H2AX(γ-H2AX)的表达;转染Artemis干扰质粒,检测Artemis、γ-H2AX表达;彗星实验检测DNA的损伤.结果 0.625、1.25、2.5、5.0和10.0 μg/mL的丝裂霉素C作用48h后肝癌细胞活力明显下降(P<0.05);丝裂霉素C刺激细胞48 h后,γ-H2AX的表达量随着药物浓度的增加而增加;转染shArtemis干扰质粒后,γ-H2AX的表达量较正常对照组增加(P<0.05);shArtemis实验组较正常对照组拖尾DNA量增加(P<0.05).结论 丝裂霉素C能够诱导肝癌细胞损伤;转染shArtemis干扰质粒促进丝裂霉素C诱导的人肝癌细胞BEL-7402/5FU DNA损伤.

  16. 羟基喜树碱联合5Fu/CF治疗晚期大肠癌临床研究%Clinical study on HCPT combined with 5Fu/CF chemotherapy in treating patients with advanced colorectal cancer

    段家华; 王继红; 霍丹


    目的观察应用羟基喜树碱联合5Fu/CF化疗治疗晚期大肠癌的近期疗效及不良反应.方法将24例晚期大肠癌随机分为两组.治疗组:羟基喜树碱(HCPT)8mg/m2 iv.d1~5,甲酰四氢叶酸钙200mg iv d1~5,5-氟尿嘧啶500mg/m2 iv d1~5,对照组:5F+CF用法用量同治疗组.以上方案每四周重复.结果治疗组有效率41.6%,对照组有效率33.3%,主要不良反应为消化系统,血液系统,多为Ⅰ、Ⅱ度,患者耐受好.结论HCPT联合方案治疗晚期大肠癌安全有效,值得临床进一步观察研究.

  17. Comparison of Targeting Distribution of PEG-5-Fu-MAMS and 5-Fu-MAMS in Pancreas under Magnetic Field%两种5-Fu磁性白蛋白微球对胰腺磁靶向性的比较

    刘建刚; 刘志超; 孙诚谊; 钱志勇; 喻超; 王玉芝


    目的 比较磁导向下PEG修饰的5-氟尿嘧啶磁性白蛋白微球(PEG-5-Fu-MAMS)和5-氟尿嘧啶磁性白蛋白微球(5-Fu-MAMS)对胰腺的磁靶向性,以寻求一种对胰腺癌的磁导向化疗更有效的新途径.方法 取Wistar大鼠18只,每组6只,分为5-Fu组、5-Fu-MAMS组和PEG-5-Fu-MAMS组;分别将三种不同的制剂(按5-Fu 8mg/kg)经胃左动脉注入胃十二指肠动脉,进入循环.并在胰腺表面加一表面强度为4250GS的磁场,30min后,处死大鼠取胰腺.用HPLC法检测其药物浓度.结果 PEG-5-Fu-MAMS组胰腺中的药物浓度为76.18±4.09μg/ml;5-Fu-MAMS组为57.95±6.39μg/ml;5-Fu组为16.58±3.19μg/ml.PEG-5-Fu-MAMS组的药物浓度明显高于5-Fu-MAMS组和5-Fu组,差异具有显著统计学意义(P<0.01);5-Fu-MAMS组的药物浓度明显高于5-Fu组,差异具有显著统计学意义(P<0.01).结论 PEG修饰的磁性白蛋白微球具有更好的磁靶向性和亲水性,为实现胰腺癌的主动靶向治疗提供了一种新途径.

  18. Comparison of Targeting Distribution of PEG-5-Fu-MAMS and 5-Fu-MAMS in liver%两种5-氟尿嘧啶磁性白蛋白微球对肝脏靶向性的研究

    刘志超; 刘建刚; 孔霞


    目的:研究聚乙二醇(PEG)修饰的5-氟尿嘧啶磁性白蛋白微球(PEG-5-5-Fu-MAMS)和5-氟尿嘧啶磁性白蛋白微球(5-Fu-MAMS)对肝脏的被动靶向性,为实现肿瘤的主动靶向治疗,减少化疗药物对肝脏的毒副作用寻找新的途径.方法:取Wistar大鼠侣只,每组6只,分为游离5-Fu组、5-Fu-MAMS组和PEG-5-Fu-MAMS组;分别将3种不同的制剂(按5-Fu 8 mg/kg)经尾静脉给药,30 min后,经眼眶采血,处死大鼠,取其肝脏.用高效液相色谱法(HPLC)法分别检测血液和肝脏中的药物浓度.结果:PEG-5-Fu-MAMS组、5-Fu-MAMS组和游离5-Fu组肝脏中的药物浓度分别为(25.21±2.98)μg/mL、(48.03±10.28)μg/mL和(15.31±2.81)μg/mL.PEG-5-Fu-MAMS组和5-Fu-MAMS组肝脏中药物浓度明显高于游离5-Fu组(P0.05).结论:PEG-5-Fu-MAMS对肝脏的被动靶向作用明显减弱,有效地减轻了药物对肝脏的毒副作用,为实现肿瘤的主动靶向治疗提供了一条新途径.

  19. Ultrasound-activated agents comprised of 5FU-bearing nanoparticles bonded to microbubbles inhibit solid tumor growth and improve survival.

    Burke, Caitlin W; Alexander, Eben; Timbie, Kelsie; Kilbanov, Alexander L; Price, Richard J


    Nanoparticle (NP) drug delivery vehicles may eventually offer improved tumor treatments; however, NP delivery from the bloodstream to tumors can be hindered by poor convective and/or diffusive transport. We tested whether poly(lactic-co-glycolic acid) NP delivery can be improved by covalently linking them to ultrasound (US)-activated microbubbles in a "composite-agent" formulation and whether drug 5-fluorouracil (5FU)-loaded NPs delivered in this fashion inhibit the growth of tumors that are typically not responsive to intravenously administered 5FU. After intravenous composite-agent injection, C6 gliomas implanted on Rag-1(-/-) mice were exposed to pulsed 1 MHz US, resulting in the delivery of 16% of the initial NP dose per gram tissue. This represented a five- to 57-fold increase in NP delivery when compared to multiple control groups. 5FU-bearing NP delivery from the composite-agent formulation resulted in a 67% reduction in tumor volume at 7 days after treatment, and animal survival increased significantly when compared to intravenous soluble 5FU administration. We conclude that NP delivery from US-activated composite agents may improve tumor treatment by offering a combination of better targeting, enhanced payload delivery, and controlled local drug release.

  20. Modulation of thymidilate synthase and p53 expression by HDAC inhibitor vorinostat resulted in synergistic antitumor effect in combination with 5FU or raltitrexed.

    Di Gennaro, Elena; Bruzzese, Francesca; Pepe, Stefano; Leone, Alessandra; Delrio, Paolo; Subbarayan, Pochi R; Avallone, Antonio; Budillon, Alfredo


    Despite the introduction of several novel anticancer agents almost 50% of colorectal cancer (CRC) patients die for cancer suggesting the necessity of new therapeutical approaches. In this study we demonstrated that the HDAC inhibitor vorinostat exerted potent antiproliferative effect in a panel of mut- and wt-p53 human CRC cell lines. Moreover, in combination with 5-fluorouracil modulated by folinic acid (5FU-FA) or with Raltitrexed (RTX), both commonly used in the treatment of this disease, it showed a clear schedule-dependent synergistic antiproliferative interaction as demonstrated by calculating combination indexes. Only simultaneous, or 24 h pretreatment with vorinostat followed by either agent, produced synergistic effect paralleled by evident cell cycle perturbations with major S-phase arrest. Moreover, we provided for the first time evidences that vorinostat can overcome resistance to both 5FU and RTX. Downmodulation of Thymidilate synthase (TS) protein induced by vorinostat within 24 h, represented a key factor in enhancing the effects of both drugs in sensitive as well as resistant tumor cells. Furthermore, p53, whose wild-type expression is critical for sensitivity to 5FU and RTX, was upregulated by vorinostat in wt- and downregulated in mut-p53 cells, suggesting an additional mechanism of the antiproliferative synergistic interactions observed. Overall these data add new insights in the mechanism of vorinostat antitumor effect and suggested that the association of vorinostat plus 5FU-FA and/or RTX should be clinically explored.

  1. Mismatch repair status may predict response to adjuvant chemotherapy in resectable pancreatic ductal adenocarcinoma.

    Riazy, Maziar; Kalloger, Steve E; Sheffield, Brandon S; Peixoto, Renata D; Li-Chang, Hector H; Scudamore, Charles H; Renouf, Daniel J; Schaeffer, David F


    Deficiencies in DNA mismatch repair have been associated with inferior response to 5-FU in colorectal cancer. Pancreatic ductal adenocarcinoma is similarly treated with pyrimidine analogs, yet the predictive value of mismatch repair status for response to these agents has not been examined in this malignancy. A tissue microarray with associated clinical outcome, comprising 254 resected pancreatic ductal adenocarcinoma patients was stained for four mismatch repair proteins (MLH1, MSH2, MSH6 and PMS2). Mismatch repair deficiency and proficiency was determined by the absence or presence of uniform nuclear staining in tumor cells, respectively. Cases identified as mismatch repair deficient on the tissue microarray were confirmed by immunohistochemistry on whole slide sections. Of the 265 cases, 78 (29%) received adjuvant treatment with a pyrimidine analog and 41 (15%) showed a mismatch repair-deficient immunoprofile. Multivariable disease-specific survival in the mismatch repair-proficient cohort demonstrated that adjuvant chemotherapy, regional lymph-node status, gender, and the presence of tumor budding were significant independent prognostic variables (P≤0.04); however, none of the eight clinico-pathologic covariates examined in the mismatch repair-deficient cohort were of independent prognostic significance. Univariable assessment of disease-specific survival revealed an almost identical survival profile for both treated and untreated patients with a mismatch repair-deficient profile, while treatment in the mismatch repair-proficient cohort conferred a greater than 10-month median disease-specific survival advantage over their untreated counterparts (P=0.0018). In this cohort, adjuvant chemotherapy with a pyrimidine analog conferred no survival advantage to mismatch repair-deficient pancreatic ductal adenocarcinoma patients. Mismatch repair immunoprofiling is a feasible predictive marker in pancreatic ductal adenocarcinoma patients, and further prospective

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

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


    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.

  3. E2F1/TS Immunophenotype and Survival of Patients with Colorectal Cancer Treated with 5FU-Based Adjuvant Therapy.

    Sulzyc-Bielicka, Violetta; Domagala, Pawel; Bielicki, Dariusz; Safranow, Krzysztof; Rogowski, Wojciech; Domagala, Wenancjusz


    The predictive value of thymidylate synthase (TS) expression alone for 5FU-based treatment of colorectal cancer (CRC) has not been clinically confirmed. Little is known on the association of expression of E2F1, which controls the transcription of genes encoding proteins engaged in DNA synthesis including TS, and survival of patients with CRC. The purpose of this study is to assess the correlation between expression of both E2F1 and TS in CRCs and survival of patients administered adjuvant 5FU-based chemotherapy, in order to find a better predictor of treatment outcome than expression of TS or E2F1 alone. Nuclear TS and E2F1 were detected by immunohistochemistry in tissue microarrays from 190 CRCs (Astler-Coller stage B2 or C). Multivariate analysis identified significant association of the combined E2F1+TS+ immunophenotype with worse OS (HR = 3,78, P = 0,009) and DFS (HR = 2,30, P = 0,03) of patients with colon cancer. There were significant differences between E2F1+TS+ and E2F1-TS- Kaplan-Meier survival curves in relation to DFS (P = 0.008) and OS (P = 0.01). About 37 and 31 % difference in 3-year DFS and OS respectively were seen between patients with E2F1+TS+ vs. E2F1-TS- colon cancer immunophenotype. The E2F1+TS+ immunophenotype may be a marker of poor prognosis (the worst DFS and OS) of patients with colon cancer treated with 5FU-based adjuvant therapy. A subgroup of patients with this immunophenotype may require different and perhaps more aggressive treatment than 5FU-based chemotherapy. Thus, the combined E2F1/TS immunophenotype could be a potential indicator of colon cancer sensitivity to 5FU.

  4. Combined 5-FU and ChoKα inhibitors as a new alternative therapy of colorectal cancer: evidence in human tumor-derived cell lines and mouse xenografts.

    Ana de la Cueva

    Full Text Available BACKGROUND: Colorectal cancer (CRC is the third major cause of cancer related deaths in the world. 5-fluorouracil (5-FU is widely used for the treatment of colorectal cancer but as a single-agent renders low response rates. Choline kinase alpha (ChoKα, an enzyme that plays a role in cell proliferation and transformation, has been reported overexpressed in many different tumors, including colorectal tumors. ChoKα inhibitors have recently entered clinical trials as a novel antitumor strategy. METHODOLOGY/PRINCIPAL FINDINGS: ChoKα specific inhibitors, MN58b and TCD-717, have demonstrated a potent antitumoral activity both in vitro and in vivo against several tumor-derived cell line xenografts including CRC-derived cell lines. The effect of ChoKα inhibitors in combination with 5-FU as a new alternative for the treatment of colon tumors has been investigated both in vitro in CRC-tumour derived cell lines, and in vivo in mouse xenografts models. The effects on thymidilate synthase (TS and thymidine kinase (TK1 levels, two enzymes known to play an essential role in the mechanism of action of 5-FU, were analyzed by western blotting and quantitative PCR analysis. The combination of 5-FU with ChoKα inhibitors resulted in a synergistic effect in vitro in three different human colon cancer cell lines, and in vivo against human colon xenografts in nude mice. ChoKα inhibitors modulate the expression levels of TS and TK1 through inhibition of E2F production, providing a rational for its mechanism of action. CONCLUSION/SIGNIFICANCE: Our data suggest that both drugs in combination display a synergistic antitumoral effect due to ChoKα inhibitors-driven modulation of the metabolization of 5-FU. The clinical relevance of these findings is strongly supported since TCD-717 has recently entered Phase I clinical trials against solid tumors.

  5. In vivo {sup 19}F-MRS observation of 5-FU metabolism in fatty liver induced by choline-deficient diet

    Otsuka, Hideki; Harada, Masafumi; Nishitani, Hiromu [Tokushima Univ. (Japan). School of Medicine; Koga, Keiko


    Using {sup 19}F-MRS, 5-FU metabolism was investigated in rat fatty liver. Fatty liver was induced by choline-deficient diet (CD diet). This study showed differences in 5-FU metabolism between normal and fatty liver. After laparotomy, a surface coil was placed directly on the liver surface. Spectra were continuously obtained after injection of 5-FU 100 mg/kg body weight via a catheter inserted into femoral vein. We made MRI and {sup 1}H-MRS study to examine the lipid accumulation. Histological study was also performed using HE (hematoxylin-eosin) and oil red stain. The livers of rats fed a CD diet showed very high intensity on T{sub 1}-WI. {sup 1}H-MRS was very useful in deteminating the fat content because the fat ratio demonstrated by {sup 1}H-MRS is well correlated to histological findings. In {sup 19}F-MRS, we recognized the following four peaks: 5-FU, FBAL, Fnct (fluoronucleotide) and FUPA. The decrease of 5-FU was not very apparent, but compared to the normal liver, the formation of Fnct increased and the formation of FBAL was suppressed in fatty liver. The rats fed a CD diet for four weeks showed a higher Fnct peak and lower FBAL peak compared with the results of rats fed a CD diet for two weeks. In a CD diet group, liver cell degeneration and necrotic changes were observed histologically. It is reported that cell degeneration is followed by cell proliferation in fatty liver induced by a choline deficient diet, and the high Fnct peak found in our study may reflect this phenomenon. The high Fnct peak on {sup 19}F-MRS may correspond to recovering reaction from liver injury like fatty liver. (author)

  6. Human papillomavirus oncoproteins differentially modulate epithelial-mesenchymal transition in 5-FU-resistant cervical cancer cells.

    Vishnoi, Kanchan; Mahata, Sutapa; Tyagi, Abhishek; Pandey, Arvind; Verma, Gaurav; Jadli, Mohit; Singh, Tejveer; Singh, Sukh Mahendra; Bharti, Alok C


    Etiological role of viral proteins E6 and E7 of high-risk HPV in cervical carcinogenesis is well established. However, their contribution in chemoresistance and epithelial-mesenchymal transition (EMT) that leads to advanced metastatic lesions and chemoresistance is poorly defined. In the present study, contribution of viral oncoproteins in acquisition of EMT character during onset of chemoresistance was assessed. A chemoresistant cell line (SiHaCR) was developed from an established HPV16-positive cervical cancer cell line, SiHa, by escalating selection pressure of 5-fluorouracil (5-FU). Expression of Survivin, ABCG2, Snail, Slug, Twist, and Vimentin was examined in SiHa and SiHaCR cells by reverse transcriptase-PCR (RT-PCR) and immunoblotting assays. Mesenchymal phenotype in SiHaCR cells was confirmed by assessment of migration and invasion potentials. SiHaCR cells displayed elevated level of functional and molecular markers associated with chemoresistance (Survivin, ABCG2) and EMT (Snail, Slug, Twist, Vimentin) and reduced E-cadherin. SiHaCR also showed increased levels of HPV16 E6 and E7 transcripts. Specific silencing of HPV16 E6, but not E7 using corresponding siRNA, demonstrated a differential involvement of HPV oncogenes in manifestation of EMT. HPV16 E6 silencing resulted in reduction of Slug and Twist expression. However, the expression of Snail and Vimentin was only marginally affected. In contrast, there was an increase in the expression of E-cadherin. A reduced migration and invasion capabilities were observed only in E6-silenced SiHaCR cells, which further confirmed functional contribution of HPV16 E6 in manifestation of EMT. Taken together, our study demonstrated an active involvement of HPV16 E6 in regulation of EMT, which promotes chemoresistance in cervical cancer.

  7. Fluorouracil selectively enriches stem-like cells in the lung adenocarcinoma cell line SPC.

    Shi, Mu-mu; Xiong, Yan-lei; Jia, Xin-shan; Li, Xin; Zhang, Li; Li, Xiao-lei; Wang, En-Hua


    Most adult stem cells are in the G0 or quiescent phase of the cell cycle and account for only a small percentage of the cells in the tissue. Thus, isolation of stem cells from tissues for further study represents a major challenge. This study sought to enrich cancer stem cells and explore cancer stem-like cell clones using 5-fluorouracil (5-FU) in the lung adenocarcinoma cell line, SPC. Proliferation inhibition was analyzed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays, according to which half maximal inhibitory concentration values were calculated. Expression levels of stem cell markers after treatment with 5-FU were examined using immunofluorescence and Western blotting. Additionally, side population (SP) cells were sorted using FACS. Properties of SP cells were evaluated by using Transwell, colony-forming assays, and tumor formation experiments. 5-FU greatly inhibits proliferation, especially of cells in S phase. SP cells possess greater invasive potential, higher clone-forming potential, and greater tumor-forming ability than non-SP cells. Treatment with 5-FU enriches the SP cells with stem cell properties in human lung adenocarcinoma cell lines.

  8. Chemotherapy or radio-chemotherapy for advanced adenocarcinoma of the oesophagus and cardiac orifice; Adenocarcinomes du bas oesophage et du cardia: quelle chimiotherapie ou chimioradiotherapie dans le traitement des recidives et des metastases

    Seitz, J.F.; Duffaud, F.; Dahan, L.; Ries, P.; Ville, E.; Laugier, R. [Centre Hospitalier Universitaire de la Timone, 13 - Marseille (France)


    Adenocarcinomas of esophagus and cardia represent in France approximately 20 to 40% of the esophagus cancers. They have a high risk to develop lymph nodes metastases and liver metastases. Currently, only 50 to 70% of patients may benefit from surgical curative resection at diagnosis, but more than 50% of them will recur. The standard of treatment of these metastatic adenocarcinomas is chemotherapy. Three large randomized comparative studies, between chemotherapy and supportive care, showed that chemotherapy significantly extends the median of survival (from 3-4 months to 10-12 months) and improves the quality of life. Currently, the combination of epirubicin-cisplatin-continuous 5FU (ECF) is the most effective regimen but it is difficult to administer and tolerate because of the long continuous 5FU infusion. In France, the most commonly used combination regimen still associates 5FU and cisplatin. New drugs (such as docetaxel, CPT11, oxaliplatin) used alone or in combination, especially with 5U, are very promising. Radio-chemotherapy is the preferred treatment for locoregional recurrences, because it improves dysphagia and enables to obtain complete tumor responses. Current results from concomitant radio-chemotherapy studies for esophagus cancer, based on 5FU alone, 5FU-cisplatin or 5FU-mitomycin, given as preoperative treatment or as exclusive treatment, support to use radio-chemotherapy for the treatment of loco-regional recurrences after surgical resection. Nevertheless, the optimal radio-chemotherapy schedule still remain to be defined (dose, duration, splitting of radiotherapy, choice of anticancer drugs). (authors)

  9. RGO/AuNR/HA-5FU nanocomposite with multi-stage release behavior and efficient antitumor activity for synergistic therapy.

    Yang, Ying; Wang, Yunlong; Zhu, Manzhou; Chen, Yan; Xiao, Yazhong; Shen, Yuhua; Xie, Anjian


    A reduced graphene oxide (RGO)/gold nanorod (AuNR)/hydroxyapatite (HA) nanocomposite was designed and successfully synthesized for the first time. An anticancer drug, 5-fluorouracil (5FU), was chosen as a model drug to be loaded in RGO/AuNR/HA. The fabricated RGO/AuNR/HA-5FU showed robust, selective targeting and penetrating efficiency against HeLa cells due to the good compatibility and nontoxicity of HA, and showed excellent synergetic antitumor effects through combined chemotherapy (CT) by 5FU and photothermal therapy (PTT) by both RGO and AuNRs under near-infrared (NIR) laser irradiation. More importantly, this synergistic dual therapy based on RGO/AuNR/HA can also minimize side effects in normal cells and exhibits greater antitumor activity because of a multi-stage drug release ability triggered by the pH sensitivity of HA in the first stage and the combined photothermal conversion capabilities of RGO and AuNRs by means of the NIR laser irradiation in the second stage. This study suggests that the novel RGO/AuNR/HA multi-stage drug delivery system may represent a promising potential application of multifunctional composite materials in the biomedical field.

  10. Clinical Research on Use of Oxaliplcrtin in Combination with HCPT, LV and 5FU in a Regimen for Advanced Gastric Cancer

    GuoqingHu; QiangFu; MaolinJin; JieLi; LiangxiPan; YuxianBai; HuaijinWang; JianweiZhang; DingYu


    OBJECTIVE To observe the effects and adverse reactions of a OXA-HCPT LV/5FU 3 regimen for patients with advanced gastric cancer.METHODS OHLF3 regimen: OXA 130 mg/m2iv d 1, HCPT6 mg/m2, iv d 1-5, LV 200 mg/m2iv 2 h followed by a 5FU 400 mg/m2 iv bolus and 5FU 600mg/m2 iv d 1-3, were given, every 21 days as 1 cycle. Assessment of the tumor was conducted after 3 cycles and the effective cases were confirmed after 4 weeks.RESULTS Among 39 patients, 36 were actually evaluable. Overall response rates (CR + PR} were 50%' the major adverse reactions were mild hematological toxicity, nausea and vomiting and peripheral nerve abnormalities.CONCLUSION The OHLF 3 regimen using OXA and HCPT is effective and results in mild toxicity when used in combined chemotherapy for advanced gastric cancer.

  11. Complete response and prolonged disease-free survival in a patient with recurrent duodenal adenocarcinoma treated with bevacizumab plus FOLFOX6

    Nagaraj, Gayathri; Zarbalian, Yousef; Flora, Karin; Tan, Benjamin R.


    Small bowel adenocarcinoma is an uncommon gastrointestinal malignancy with limited data on effective chemotherapy in the adjuvant setting, as well as for advanced disease. We present a case report of a patient with recurrent duodenal adenocarcinoma after resection and adjuvant chemotherapy who experienced a complete response to bevacizumab with oxaliplatin and 5FU (FOLFOX) followed by bevacizumab/capecitabine maintenance therapy for 2 years. The patient continues to be disease-free 8 years af...

  12. A DPYD variant (Y186C) specific to individuals of African descent in a patient with life-threatening 5-FU toxic effects: potential for an individualized medicine approach.

    Saif, Muhammad Wasif; Lee, Adam M; Offer, Steven M; McConnell, Kathleen; Relias, Valerie; Diasio, Robert B


    5-Fluorouracil (5-FU) is commonly administered as a therapeutic agent for the treatment of various aggressive cancers. Severe toxic reactions to 5-FU have been associated with decreased levels of dihydropyrimidine dehydrogenase (DPD) enzyme activity. Manifestations of 5-FU toxicity typically include cytopenia, diarrhea, stomatitis, mucositis, neurotoxicity, and, in extreme cases, death. A variety of genetic variations in DPYD, the gene encoding DPD, are known to result in decreased DPD enzyme activity and to contribute to 5-FU toxic effects. Recently, it was reported that healthy African American individuals carrying the Y186C DPYD variant (rs115232898) had significantly reduced DPD enzyme activity compared with noncarriers of Y186C. Herein, we describe for the first time, to our knowledge, an African American patient with cancer with the Y186C variant who had severe toxic effects after administration of the standard dose of 5-FU chemotherapy. The patient lacked any additional toxic effect-associated variations in the DPYD gene or the thymidylate synthase (TYMS) promoter. This case suggests that Y186C may have contributed to 5-FU toxicity in this patient and supports the use of Y186C as a predictive marker for 5-FU toxic effects in individuals of African ancestry.

  13. Suppression of microRNA-31 increases sensitivity to 5-FU at an early stage, and affects cell migration and invasion in HCT-116 colon cancer cells

    Sun Xiao-Feng


    Full Text Available Abstract Background MicroRNAs (miRNAs are endogenously expressed noncoding RNAs with important biological and pathological functions. Although several studies have shown that microRNA-31 (miR-31 is obviously up-regulated in colorectal cancer (CRC, there is no study on the functional roles of miR-31 in CRC. Methods Anti-miR™ miRNA 31 inhibitor (anti-miR-31 is a sequence-specific and chemically modified oligonucleotide to specifically target and knockdown miR-31 molecule. The effect of anti-miR-31 transfection was investigated by real-time PCR. HCT-116p53+/+ and HCT-116p53-/-colon cancer cells were treated by anti-miR-31 with or without 5-fluorouracil (5-FU, cell proliferation was determined by MTT assay; apoptosis was detected by DAPI staining; cell cycle was evaluated by flow cytometry; colony formation, migration and invasion assays were performed to investigate the effect of suppression of miR-31 on the cell lines. Results Real-time PCR results showed that anti-miR-31 was efficiently introduced into the cells and reduced miR-31 levels to 44.1% in HCT-116p53+/+ and 67.8% in HCT-116p53-/-cell line (p = 0.042 and 0.046. MTT results showed that anti-miR-31 alone had no effect on the proliferation of HCT-116p53+/+ or HCT-116p53-/-. However, when combined with 5-FU, anti-miR-31 inhibited the proliferation of the two cell lines as early as 24 h after exposure to 5-FU (p = 0.038 and 0.044. Suppression of miR-31 caused a reduction of the migratory cells by nearly 50% compared with the negative control in both HCT-116p53+/+ and HCT-116p53-/-(p = 0.040 and 0.001. The invasive ability of the cells were increased by 8-fold in HCT-116p53+/+ and 2-fold in HCT-116p53-/- (p = 0.045 and 0.009. Suppression of miR-31 had no effect on cell cycle and colony formation (p > 0.05. Conclusions Suppression of miR-31 increases sensitivity to 5-FU at an early stage, and affects cell migration and invasion in HCT-116 colon cancer cells.

  14. 5-FU/CDDP療法中に多発脳梗塞を発症した進行胃癌の一例

    成清, 道博; 山田, 行重; 中島, 祥介


    A 64-year-old man visited our hospital with a chief complaint of appetiteloss and epigastralgia. Upper GI series and an endoscopic examination revealed type 3carcinoma on the upper third. Abdominal CT scan showed enlargement of the paraaorticlymph nodes that had invaded the pancreas. Preoperative diagnosis was cStage Ⅳgastric cancer, and we considered a curative operation impossible. Therefore,chemotherapy with a combination therapy of 5-fluorouracil (5-FU) and low-dose cisplatin(CDDP) was pl...

  15. Identification of colorectal cancer patients with tumors carrying the TP53 mutation on the codon 72 proline allele that benefited most from 5-fluorouracil (5-FU based postoperative chemotherapy

    Tsuchiya Eiju


    Full Text Available Abstract Background Although postoperative chemotherapy is widely accepted as the standard modality for Dukes' stage C or earlier stage colorectal cancer (CRC patients, biomarkers to predict those who may benefit from the therapy have not been identified. Previous in vitro and clinical investigations reported that CRC patients with wild-type p53 gene (TP53-tumors benefit from 5-fluorouracil (5-FU based chemotherapy, while those with mutated TP53-tumors do not. However, these studies evaluated the mutation-status of TP53 by immunohistochemistry with or without single-strand conformation polymorphism, and the mutation frequency was different from study to study. In addition, the polymorphic status at p53 codon 72, which results in arginine or proline residues (R72P and is thought to influence the function of the protein significantly, was not examined. Methods To evaluate the significance of the TP53 mutation as a molecular marker to predict the prognosis of CRC patients, especially those who received postoperative chemotherapy, we examined the mutation by direct sequencing from fresh CRC tumors and evaluated the R72P polymorphism of the mutated TP53 by a combined mutant allele- and polymorphic allele-specific polymerase chain reaction (PCR. Results The TP53 mutation occurred in 147 (70% of 211 Japanese CRC tumors. The mutation was observed in 93 (63% tumors on the R72 allele and in 54 (37% tumors on the P72 allele. Although the alterations to TP53 have no prognostic significance for CRC patients overall, we found that Dukes' stage C CRC patients who did not receive postoperative chemotherapy and carried the mutated TP53-R72 showed significantly longer survival times than those with the mutated TP53-P72 when evaluated by overall survival (p = 0.012. Conclusion Using a combined mutant allele- and polymorphic allele-specific PCR, we defined the codon 72 polymorphic status of the TP53 mutated allele in Japanese CRC patients. We raised a possibility

  16. Clinical implications of thymidylate synthetase, dihydropyrimidine dehydrogenase and orotate phosphoribosyl transferase activity levels in colorectal carcinoma following radical resection and administration of adjuvant 5-FU chemotherapy

    Ishikawa Masashi


    Full Text Available Abstract Bckground A number of studies have investigated whether the activity levels of enzymes involved in 5-fluorouracil (5-FU metabolism are prognostic factors for survival in patients with colorectal carcinoma. Most reports have examined thymidylate synthetase (TS and dihydropyrimidine dehydrogenase (DPD in unresectable or metastatic cases, therefore it is unclear whether the activity of these enzymes is of prognostic value in colorectal cancer patients treated with radical resection and adjuvant chemotherapy with 5-FU. Methods This study examined fresh frozen specimens of colorectal carcinoma from 40 patients who had undergone curative operation and were orally administered adjuvant tegafur/uracil (UFT chemotherapy. TS, DPD and orotate phosphoribosyl transferase (OPRT activities were assayed in cancer tissue and adjacent normal tissue and their association with clinicopathological variables was investigated. In addition, the relationships between TS, DPD and OPRT activities and patient survival were examined to determine whether any of these enzymes could be useful prognostic factors. Results While there was no clear relationship between pathological findings and TS or DPD activity, OPRT activity was significantly lower in tumors with lymph node metastasis than in tumors lacking lymph node metastasis. Postoperative survival was significantly better in the groups with low TS activity and/or high OPRT activity. Conclusion TS and OPRT activity levels in tumor tissue may be important prognostic factors for survival in Dukes' B and C colorectal carcinoma with radical resection and adjuvant chemotherapy with UFT.


    王晶敏; 陈建华; 缪云翔


    目的 通过测定细胞内5-Fu浓度的变化,判断5-Fu进入细胞的通道.方法 细胞培养至2×107后,分为ENT非阻断组和ENT阻断组,前者培养基中仅加入100 ng/L的5-Fu,后者培养基中加入100μmol/L潘生丁和100 ng/L的5-Fu,分别作用15、30、1 h、2 h、4 h后收集细胞,测定细胞中5-Fu含量,并计算单细胞中5-Fu的浓度.结果 ENT非阻断组和ENT阻断组细胞内5-Fu的含量,在五个位点上均有较大的差异性(P<0.01).结论 5-Fu既可通过ENT进入细胞,又可通过CNT进入细胞.

  18. Dual drug delivery of 5-fluorouracil (5-FU) and methotrexate (MTX) through random copolymeric nanomicelles of PLGA and polyethylenimine demonstrating enhanced cell uptake and cytotoxicity.

    Ashwanikumar, N; Kumar, Nisha Asok; Nair, S Asha; Kumar, G S Vinod


    We now report the synthesis of a random copolymer of poly-lactic-co-glycolic acid (PLGA) grafted branched polyethylenimine (BPEI) and the use of it as a multi drug delivery system (DDS). The methotrexate (MTX) was conjugated to BPEI through DCC/NHS chemistry. The copolymer-drug conjugate (PBP-MTX) was characterised by FT-IR and (1)H NMR spectroscopy. The PBP-MTX was converted into nanomicelles with entrapped 5-fluorouracil (5-FU) through nanoprecipitation technique. The size, shape, morphology and surface charge of the nanomicelles were confirmed using different techniques. The thermal behaviour and distribution of both conjugated and entrapped drug through the polymeric matrix were assessed by differential scanning calorimetry (DSC) and powder X-ray diffraction analysis (PXRD). In vitro drug release pattern of the nanomicelles was examined to ascertain the release pattern of two drugs namely 5-FU and MTX. The cellular uptake studies demonstrated higher uptake of the nanomicelles in colon cancer cell line HCT 116. Further the cytotoxicity evaluation of nanomicelles illustrated promising action which confirms the use of the system as a potential DDS to colon cancer.

  19. Attachment of an anti-MUC1 monoclonal antibody to 5-FU loaded BSA nanoparticles for active targeting of breast cancer cells.

    Kouchakzadeh, Hasan; Shojaosadati, Seyed Abbas; Mohammadnejad, Javad; Paknejad, Malihe; Rasaee, Mohammad Javad


    With PR81 as a murine monoclonal antibody (mAb) that was prepared against the human breast cancer, the MUC1 receptor specific targeting is possible. In this study, PR81-conjugated bovine serum albumin (BSA) nanoparticles loaded with anticancer drug 5-fluorouracil (5-FU) were developed. Enzyme linked immunosorbant assay (ELISA) results showed high immunoreactivity of PR81 mAb conjugated to nanoparticles towards MUC1 related peptide or native cancerous MUC1 and almost no cross-reaction to non-specific proteins. In vitro experiments were performed to determine the ability of this new drug delivery system on overcoming MCF-7 breast cancer cells in comparison with four other systems. The results revealed that these cell-type specific drug loaded nanoparticles could achieve more cell death as compared to when the 5-FU was used with no carriers. Stability studies of produced drug delivery system proved high immunoreactivity of conjugated PR81 even after 11 days of storage in room temperature.

  20. The clinical comparison of effects of PEA regimen and 5-Fu + KSM regimen for treatment of gestational trophoblastic neoplasms%PEA方案与5-Fu+KSM方案治疗妊娠滋养细胞肿瘤疗效比较

    马晓琳; 王欣彦; 李秀琴


    目的 探讨PEA方案是否可以作为妊娠滋养细胞肿瘤联合化疗一线选择.方法 回顾性分析中国医科大学附属盛京医院2004年7月至2013年5月62例妊娠滋养细胞肿瘤患者,评价顺铂+足叶乙甙+更生霉素(PEA方案,30例)与氟尿嘧啶+更生霉素(5-Fu+KSM,32例)方案的疗效和毒副反应.结果 PEA方案治疗妊娠滋养细胞肿瘤完全缓解率为93.33%,高于5-Fu+KSM方案组(90.63%)(P>0.05).副反应PEA组Ⅲ~Ⅳ度粒细胞减少、口腔溃疡和腹泻情况明显少于5-Fu+KSM组,差异有统计学意义(P<0.05).PEA组恶心呕吐和肝功能损伤的发生率及严重程度均低于5-Fu+KSM组(P>0.05).结论 两方案治疗妊娠滋养细胞肿瘤疗效相当,PEA方案副反应小、疗程短、费用少,可以作为妊娠滋养细胞肿瘤联合化疗一线选择之一.

  1. Effective inhibition of colon cancer cell growth with MgAl-layered double hydroxide (LDH loaded 5-FU and PI3K/mTOR dual inhibitor BEZ-235 through apoptotic pathways

    Chen J


    Full Text Available Jiezhong Chen,1,2 Renfu Shao,3 Li Li,4 Zhi Ping Xu,4 Wenyi Gu4 1School of Biomedical Sciences, University of Queensland, St Lucia, Queensland, 2Faculty of Science, Medicine and Health, University of Wollongong, Wollongong, New South Wales, 3GeneCology Research Centre, Faculty of Science, Health, Education and Engineering, University of the Sunshine Coast, Maroochydore, Queensland, 4Australian Institute of Bioengineering and Nanotechnology, University of Queensland, St Lucia, Queensland, Australia Abstract: Colon cancer is the third most common cancer and the third largest cause of cancer-related death. Fluorouracil (5-FU is the front-line chemotherapeutic agent for colon cancer. However, its response rate is less than 60%, even in combination with other chemotherapeutic agents. The side effects of 5-FU also limit its application. Nanoparticles have been used to deliver 5-FU, to increase its effectiveness and reduce side effects. Another common approach for colon cancer treatment is targeted therapy against the phosphoinositide 3-kinase (PI3K/protein kinase B (Akt pathway. A recently-invented inhibitor of this pathway, BEZ-235, has been tested in several clinical trials and has shown effectiveness and low side effects. Thus, it is a very promising drug for colon cancer treatment. The combination of these two drugs, especially nanoparticle-packed 5-FU and BEZ-235, has not been studied. In the present study, we demonstrated that nanoparticles of layered double hydroxide (LDH loaded with 5-FU were more effective than a free drug at inhibiting colon cancer cell growth, and that a combination treatment with BEZ-235 further increased the sensitivity of colon cancer cells to the treatment of LDH-packed 5-FU (LDH-5-FU. BEZ-235 alone can decrease colon cancer HCT-116 cell viability to 46% of the control, and the addition of LDH-5-FU produced a greater effect, reducing cell survival to 8% of the control. Our data indicate that the combination therapy of

  2. S-1 plus cisplatin versus fluorouracil plus cisplatin in advanced gastric or gastro-esophageal junction adenocarcinoma patients: a pilot study.

    Li, Yu Hong; Qiu, Miao Zhen; Xu, Jian Ming; Sun, Guo Ping; Lu, Hui Shan; Liu, Yun Peng; Zhong, Mei Zuo; Zhang, He Long; Yu, Shi Ying; Li, Wei; Hu, Xiao Hua; Wang, Jie Jun; Cheng, Ying; Zhou, Jun Tian; Guo, Zeng Qing; Guan, Zhon Gzhen; Xu, Rui Hua


    The safety and efficacy of S-1 plus cisplatin in Chinese advanced gastric cancer patients in first line setting is unknown. In this pilot study, patients with advanced gastric or gastro-esophageal junction adenocarcinoma were enrolled and randomly assigned in a 1:1 ratio to receive S-1 plus cisplatin (CS group) or 5-FU plus cisplatin (CF group). The primary endpoint was time to progression (TTP). Secondary end points included overall survival (OS) and safety. This study was registered on ClinicalTrials. Gov, number NCT01198392. A total of 236 patients were enrolled. Median TTP was 5.51 months in CS group compared with 4.62 months in CF group [hazard ratio (HR) 1.028, 95% confidential interval (CI) 0.758-1.394, p = 0.859]. Median OS was 10.00 months and 10.46 months in CS and CF groups (HR 1.046, 95%CI 0.709-1.543, p = 0.820), respectively. The most common adverse events in both groups were anemia, leukopenia, neutropenia, nausea, thrombocytopenia, vomiting, anorexia and diarrhea. We find that S-1 plus cisplatin is an effective and tolerable option for advanced gastric or gastro-esophageal junction adenocarcinoma patients in China.

  3. Fluorouracil Based Chemoradiation with Either Gemcitabine or Fluorouracil Chemotherapy Following Resection of Pancreatic Adenocarcinoma: 5-Year Analysis of the US Intergroup/RTOG 9704 Phase III Trial

    Regine, William F.; Winter, K.A.; Abrams, R.; Safran, H.; Hoffman, J.P.; Konski, A.; Benson, A.B.; Macdonald, J.S.; Rich, T.A.; Willett, C.G.


    Background The impact of the addition of gemcitabine (G) to 5-FU chemoradiation (CRT) on 5-year overall survival (OS) in resected pancreatic adenocarcinoma are presented with updated results of a phase III trial. Methods Following resection of pancreatic adenocarcinoma patients were randomized to pre and post CRT 5-FU vs. pre and post CRT G. 5-FU = continuous (CI) at 250 mg/m2/day. G = 1000 mg/m2 weekly; both given over 3 weeks pre and 12 weeks post - CRT. CRT = 50.4 Gy with CI 5-FU. Primary endpoint was survival for all patients and for pancreatic head tumor patients. Results Four hundred and fifty-one patients were eligible. Univariate analysis showed no difference in OS. Pancreatic head tumor patients (n=388) had a median survival and 5-year OS of 20.5 months and 22% with G vs. 17.1 months and 18% with 5-FU. On multivariate analysis, patients on the G arm with pancreatic head tumors experienced a trend towards improved OS (p=0.08). First site of relapse local recurrence in 28% of patients vs. distant relapse in 73%. Conclusion(s) The sequencing of 5-FU CRT with G as done in this trial is not associated with a statistically significant improvement in OS. Despite local recurrence being approximately half of that reported in previous adjuvant trials, distant disease relapse still occurs in ≥ 70% of patients. These findings serve as the basis for the recently activated EORTC/US Intergroup RTOG 0848 phase III adjuvant trial evaluating the impact of CRT after completion of a full course of G. PMID:21499862

  4. Prostate apoptosis response protein 4 sensitizes human colon cancer cells to chemotherapeutic 5-FU through mediation of an NFκB and microRNA network

    Weirauch Matthew T


    Full Text Available Abstract Background Diminished expression or activity of prostate apoptosis response protein 4 (Par-4 has been demonstrated in a number of cancers, although reports on Par-4 expression during colon cancer progression are lacking. An understanding of the molecular events in conjunction with the genetic networks affected by Par-4 is warranted. Results Colon cancer specimens derived from patients have significantly diminished expression of Par-4 mRNA relative to paired normal colon. Hence, the functional consequences of reintroducing Par-4 into HT29 colon cancer cells were assessed. Overexpression augmented the interaction of Par-4 with NFκB in the cytosol but not nucleus, and facilitated apoptosis in the presence of 5-fluorouracil (5-FU. Analogous findings were obtained when AKT1 pro-survival signaling was inhibited. Transcriptome profiling identified ~700 genes differentially regulated by Par-4 overexpression in HT29 cells. Nearly all Par-4-regulated genes were shown by promoter analysis to contain cis-binding sequences for NFκB, and meta-analysis of patient expression data revealed that one-third of these genes exist as a recurrent co-regulated network in colon cancer specimens. Sets of genes involved in programmed cell death, cell cycle regulation and interestingly the microRNA pathway were found overrepresented in the network. Noteworthy, Par-4 overexpression decreased NFκB occupancy at the promoter of one particular network gene DROSHA, encoding a microRNA processing enzyme. The resulting down-regulation of DROSHA was associated with expression changes in a cohort of microRNAs. Many of these microRNAs are predicted to target mRNAs encoding proteins with apoptosis-related functions. Western and functional analyses were employed to validate several predictions. For instance, miR-34a up-regulation corresponded with a down-regulation of BCL2 protein. Treating Par-4-overexpressing HT29 cells with a miR-34a antagomir functionally reversed both

  5. Complete response and prolonged disease-free survival in a patient with recurrent duodenal adenocarcinoma treated with bevacizumab plus FOLFOX6.

    Nagaraj, Gayathri; Zarbalian, Yousef; Flora, Karin; Tan, Benjamin R


    Small bowel adenocarcinoma is an uncommon gastrointestinal malignancy with limited data on effective chemotherapy in the adjuvant setting, as well as for advanced disease. We present a case report of a patient with recurrent duodenal adenocarcinoma after resection and adjuvant chemotherapy who experienced a complete response to bevacizumab with oxaliplatin and 5FU (FOLFOX) followed by bevacizumab/capecitabine maintenance therapy for 2 years. The patient continues to be disease-free 8 years after his recurrence. This case highlights the potential of vascular endothelial growth factor (VEGF) inhibitors to enhance chemotherapeutic regimens for advanced small bowel adenocarcinoma.

  6. Tumor lysis syndrome in a patient with metastatic colon cancer after treatment with oxaliplatin and 5-Fu

    Ruo-Han Tseng


    Full Text Available Tumor lysis syndrome in solid tumors is a rare occurrence, with a poor prognosis. We present the case of a patient of recurrent colon cancer who received chemotherapy with FOLFOX regimen (lencovorin, fluorouracil, and oxaliplatin with subsequent tumor lysis. We present a recurrent rectal cancer patient suffered from tumor lysis syndrome after salvage FOLFOX regimen. After treat with CVVH with improved conscious status. In this case report, we had review the tumor lysis in solid tumor.

  7. Decreased [{sup 18}F]fluoro-2-deoxy-D-glucose incorporation and increased glucose transport are associated with resistance to 5FU in MCF7 cells in vitro

    Smith, Tim A.D. [PET Unit, Department of Biomedical Physics, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD (United Kingdom)], E-mail:; Sharma, Rituka I. [PET Unit, Department of Biomedical Physics, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD (United Kingdom); Wang, Weiguang G. [Department of Medicine and Therapeutics, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD (United Kingdom); School of Applied Sciences, University of Wolverhampton, City Campus-South, Wolverhampton WV1 1SB (United Kingdom); Welch, Andy E.; Schweiger, Lutz F. [PET Unit, Department of Biomedical Physics, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD (United Kingdom); Collie-Duguid, Elaina S.R. [Department of Medicine and Therapeutics, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD (United Kingdom)


    Introduction: Tumor refractoriness to chemotherapy is frequently due to the acquisition of resistance. Resistant cells selected by exposure to chemotherapy agents may exhibit differences in [{sup 18}F]fluoro-2-deoxy-D-glucose (FDG) incorporation, as compared with sensitive cells. Methods: FDG incorporation, hexokinase (HK) activity, glucose transport and ATP content were determined in clones of 5-fluorouracil (5FU)-resistant MCF7 cells, established by long-term exposure to increasing 5FU concentrations, and in parental MCF7 cells. Results: FDG incorporation was decreased in MCF7 cells resistant to 5FU; HK activity was similar in the resistant and sensitive cells, while glucose transport was increased, as compared with sensitive cells. Treatment of cells with the glucose efflux inhibitor phloretin increased FDG incorporation to similar levels in the resistant and sensitive cells. Analysis of microarray data demonstrated the expression of GLUT1, 8 and 10 transporters in MCF7 cells. GLUT8 and 10 expression was decreased in the resistant cells, while GLUT1 was only increased in cells resistant to the lowest 5FU concentration. Conclusion: FDG incorporation in 5FU-resistant MCF7 cells is decreased, as compared with sensitive cells. Our findings also suggest that this may be due to high rates of membrane glucose transport in the resistant cells resulting in enhanced efflux of FDG. We believe that this is the first demonstration that facilitative glucose transporters can actually decrease the incorporation of FDG.

  8. Gemcitabine with a specific conformal 3D 5FU radiochemotherapy technique is safe and effective in the definitive management of locally advanced pancreatic cancer.

    Goldstein, D; Van Hazel, G; Walpole, E; Underhill, C; Kotasek, D; Michael, M; Shapiro, J; Davies, T; Reece, W; Harvey, J; Spry, N


    The aim of this phase II study was to assess the feasibility and efficacy of a specific three-dimensional conformal radiotherapy technique with concurrent continuous infusion of 5-fluorouracil (CI 5FU) sandwiched between gemcitabine chemotherapy in patients with locally advanced pancreatic cancer. Patients with inoperable cancer in the pancreatic head or body without metastases were given gemcitabine at 1000 mg m(-2) weekly for 3 weeks followed by a 1-week rest and a 6-week period of radiotherapy and concurrent CI 5FU (200 mg m(-2) day(-1)). The defined target volume was treated to 54 Gy in 30 daily fractions of 1.8 Gy. After 4 weeks' rest, gemcitabine treatment was re-initiated for three cycles (days 1, 8, 15, q28). Forty-one patients were enrolled. At the end of radiotherapy, one patient (2.4%) had a complete response and four patients (9.6%) had a partial response; at the end of treatment, three patients (7.3%) had a complete response and two patients (4.9%) had a partial response. Median survival time was 11.7 months, median time to progression was 7.1 months, and median time to failure of local control was 11.9 months. The 1- and 2-year survival rates were 46.3 and 9.8%, respectively. Treatment-related grade 3 and 4 toxicities were reported by 16 (39.0%) and four (9.8%) patients, respectively. Sixteen out of 41 patients did not complete the planned treatment and nine due to disease progression. This approach to treatment of locally advanced pancreatic cancer is safe and promising, with good local control for a substantial proportion of patients, and merits testing in a randomised trial.

  9. [Ocular metastasis heralding gastric adenocarcinoma].

    Chekrine, T; Tawfiq, N; Bouchbika, Z; Benchakroun, N; Jouhadi, H; Sahraoui, S; Benider, A


    Ocular metastasis is a rare presenting feature of gastric adenocarcinoma. We report a 48-year-old woman who presented with a decrease in visual acuity of the right eye leading to the discovery of an ocular metastasis. Diagnostic work-up identified a gastric adenocarcinoma with pulmonary metastases. She received four cycles of chemotherapy combining epirubicin, cisplatin and fluorouracil. The patient died 6 months after the diagnosis of respiratory failure.

  10. Randomised trial comparing three different schedules of infusional 5FU and raltitrexed alone as first-line therapy in metastatic colorectal cancer. Final results of the Fédération Francophone de Cancérologie Digestive (FFCD) 9601 trial.

    Ducreux, M; Bouche, O; Pignon, J P; Mousseau, M; Raoul, J L; Cassan, P; Leduc, B; Berger, C; Dunant, A; Fournet, J; Bedenne, L


    LV5FU2 with high-dose leucovorin (LV), weekly infusional 5-fluorouracil (5FU) (AIO schedule) and raltitrexed have been demonstrated to be active agents in first-line treatment of colorectal cancer. We performed a 4-arm randomised trial to compare (1) a low-dose intravenous bolus of LV (20 mg/m2), followed by an intravenous bolus of 5FU (400 mg/m2), followed by a 22-hour continuous infusion of 5FU (600 mg/m2) on day 1 and day 2/2 weeks (ldLV5FU2 arm), (2) a weekly continuous infusion of high-dose 5FU (2.6 g/m2/week) for 6 weeks followed by a rest week (HD-FU arm) and (3) raltitrexed (Tomudex arm; 3 mg/m2/3 weeks) to standard LV5FU2. From 1997 to 2001, 294 patients were included. The 4 arms were well balanced for sex ratio, age, WHO performance status, the primary tumour site and prior adjuvant chemotherapy. Treatment was stopped due to low accrual. Two toxicity-related deaths were observed in the Tomudex arm. The treatments gave rise to different rates of grade 3-4 neutropenia (3, 4, 11 and 14% of the patients in the LV5FU2, ldLV5FU2, HD-FU and Tomudex arms, respectively, p = 0.028), leucopenia and vomiting. At least one episode of grade 3-4 toxicity was observed in 27, 25, 38 and 47% of the patients in the LV5FU2, ldLV5FU2, HD-FU and Tomudex arms, respectively (p = 0.016). An objective response was observed in 28, 21, 22 and 10% of the patients in the LV5FU2, ldLV5FU2, HD-FU and Tomudex arms, respectively (p = 0.04). Progression-free survival (PFS) of the patients in the Tomudex arm was statistically lower compared to that of patients treated with LV5FU2 or ldLV5FU2 (combined group; p = 0.013, log rank test). In conclusion, Tomudex is more toxic and yields shorter PFS than infusional 5FU. Despite the early closure of the study and the lack of power of the comparison, it seems that ldLV5FU2 could be considered as an active, easier and less expensive option for the treatment of metastatic colorectal cancer compared to classic LV5FU2 or weekly HD-FU.

  11. Wild type p53 increased chemosensitivity of drug-resistant human hepatocellular carcinoma Be17402 / 5-FU cells%野生型p53增强药物耐药的人肝癌细胞Bel7402/5-FU的化疗敏感性

    李玉秀; 林志彬; 谭焕然


    AIM: To study the effect of wild type (wt) p53 gene transfection on drug resistant human hepatocellular carcinoma (HCC) cells induced by 5-Fluorouracil (5-FU). METHODS: The cytotoxicity of anticancer drugs on Be17402 and Be17402/5-FU cells was assessed using SRB assay. p53 expression was detected at its mRNA level by RT-PCR assay and at its protein level Western blot or immunocytochemistry assay in Be17402/5-FU cells transfected with either control vector or wt p53. AnnexinV-FITC/PI double labeled assay was performed to detect apoptosis. The chemosensitivity of Be17402/5-FU cells transfected with wt p53 was assessed using SRB assay. RESULTS: Be17402/5-FU cells exhibited cross-resistance to vincristine, doxorubicin, paclitaxel, and so on. wt p53 gene transfection upregulated the expression of p53 in Be17402/5-FU cells. wt p53 was able to greatly inhibit cell proliferation and significantly induce apoptosis in Bel7402/5-FU cells. Moreover, wt p53 gene transfection increased the chemosensitivity of Be17402/5-FU cells to some anticancer drugs. CONCLUSION: These results indicated that the wt p53 gene transfection not only induced suppression of cell growth, but also increased the sensitivity of Be17402/5-FU cells to 5-FU, vincristine, and doxorubicin.

  12. 与食管癌5-FU化疗效果相关分子标记的研究进展%Researc progress on molecular markers of esophageal canccer treated by 5-FU

    严爱婷; 钱晓萍; 刘宝瑞


    Persons suffering from esophageal cancer have different therapeutic effect treated by 5 - FU.With the rapid development of pharmacogenetics and pharmacogenomics, individualized chemotherapy for esophageal cancer is possible.This paper will make a review on the effect of esophageal cancer -5 - FU - related molecular markers .%不同个体的食管癌对氟尿嘧啶(Fluorouracil,5-FU)药物疗效存在差异.药物遗传学和药物基因组学的快速发展,使得分子标记指导下的食管癌个体化化疗成为可能,本文对食管癌5-FU疗效预测相关分子标记作一综述.

  13. 内质网应激对乳腺癌细胞5-FU化疗敏感性影响的观察%Effect on the chemotherapy sensitivity of breast cancer cells to 5-FU via endoplasmic reticulum stress

    贾小婷; 尹江; 郑国沛; 刘季芳; 罗凯; 贺智敏


    目的:探讨内质网应激(endoplasmic reticulum stress,ERS)状态对乳腺癌细胞5-氟尿嘧啶(5-FU)化疗敏感性的影响.方法:MTS试验比较乳腺癌MCF-7细胞及其衍生的5-FU耐受细胞(MCF-7/5-FU)对5-FU的敏感性,电子显微镜观察MCF-7及MCF-7/5-FU细胞中的内质网含量情况,Real-time RT-PCR法检测MCF-7及MCF-7/5-FU细胞中基础水平的内质网应激标志的表达情况,5-FU刺激MCF-7和MCF-7/5-FU细胞后,Real-time RT-PCR法检测内质网应激标志的表达变化以反映内质网的应激状态.结果:耐药细胞MCF-7/5-FU对5-FU的耐药指数为16.相比于亲本细胞MCF-7细胞,MCF-7/5-FU细胞中的内质网含量明显更为丰富.GRP94和CHOP在MCF-7/5-FU中的表达量分别是MCF-7中表达量的2.1(t=9.288,P=0.003)和1.8倍(t=6.057,P=0.008).比较最高剂量5-FU诱导和未加5-FU时CHOP和GRP94的表达量.在MCF-7细胞中,分别上调12.23(t=15.082,P=0.001)和2.54倍(t=6.196,P=0.038);在MCF-7/5-FU细胞中,分别上调5.45(t=15.451,P=0.003)和2.38倍(t=7.218,P=0.007).比较在5-FU刺激下72和0h时CHOP以及GRP94的表达量.在MCF-7细胞中,分别上调12.04(t=15.093,P=0.001)和3.15(t=4.540,P=0.032)倍;在MCF-7/5-FU细胞中,分别上调4.20(t=4.363,P=0.005)和1.88倍(t=2.875,P=0.041).说明5-FU能以剂量依赖性和时间依赖性上调CHOP和GRP94的表达,且在MCF-7细胞中诱导上调更为明显.结论:内质网应激参与乳腺癌细胞对5-FU化疗的敏感性,轻度的应激参与化疗耐受,而较强的应激则有利于化疗效果.%OBJECTIVE:To research for the sensitivity of breast cancer cells to 5-FU,whieh was caused by ERS.METHODS:Through MTS test,the sensitivity to 5-FU between breast cancer cell MCF-7 and its derivative 5-FU resistant cell-MCF-7/5-FU were compared.The abundance of endoplasmic reticulum in MCF-7 and MCF-7/5-FU cells were observed by electron microscope.The basal expression levels of ERS markers in MCF-7 and MCF-7/5-FU cells were measured,using Real-time RT

  14. Simultaneous quantification of 5-FU, 5-FUrd, 5-FdUrd, 5-FdUMP, dUMP and TMP in cultured cell models by LC-MS/MS.

    Carli, Delphine; Honorat, Mylène; Cohen, Sabine; Megherbi, Mehdi; Vignal, Bruno; Dumontet, Charles; Payen, Léa; Guitton, Jérôme


    To specifically quantify several metabolites of 5-fluorouracil (5-FU) and two endogenous monophosphate nucleotides, we developed an original method based on a liquid chromatography-tandem mass spectrometry (LC-MS/MS). This assay allowed the determination of: (i) the intracellular production of 5-fluoro-2'-deoxyuridine-5'-monophosphate (5-FdUMP) from 5-FU or 5-fluoro-2'-deoxyuridine (5-FdUrd), (ii) the impact of 5-FdUMP concentration on the intracellular 2'-deoxyuridine-5'-monophosphate (dUMP)/thymidine-5'-monophosphate (TMP) ratio, and (iii) the secretion extent of 5-FdUMP and 5-FU from human cultured cells by ABC transporters. Under our experimental conditions, cells were incubated with 5-FU or 5-FUrd. Then, cellular proteins were precipitated by methanol. This procedure provided high extraction recovery. In addition, to measure 5-FU and 5-FdUMP secretion from cells, we carried out quantification of these molecules in culture medium. Media were either directly injected (5-FU) or underwent a solid phase extraction using Oasis Wax extraction cartridge (5-FdUMP). Separation of analytes was performed on a dC18 Atlantis 3.5microm, (100mmx2.1mm i.d) column with isocratic mode using ammonium formate buffer/methanol/water (5/5/90, v/v) as mobile phase. The run time did not exceed 6.2min. The analytes were ionized in an electrospray interface under negative ion mode. We validated the method over a range of 2.5-150ngmL(-1) according to the compounds. Intra- and inter-assay variability was lower than 10% over seven days. All compounds were stable in cells or in culture medium when samples were stored at -20 degrees C for at least two weeks, and after three freeze-thaw cycles. No matrix effect was observed in both media.

  15. [Transcatheter Arterial Chemoembolization with Super absorbent Polymer Microspheres for a Large Lung Cystic Adenocarcinoma in the Left Pulmonary Cavity].

    Kennoki, Norifumi; Hori, Shinichi; Yuki, Takeo; Sueyoshi, Satoshi; Hori, Atsushi


    A 57-year-old woman presented with lung adenocarcinoma and carcinomatous pleurisy in January 2013. The primary lesion had been treated with 60-Gy radiation therapy. She, however, showed a recurrence of the tumor in her pulmonary cavity. She received systemic chemotherapy for 1 year but did not show any improvement. She visited our clinic in March 2014. Her performance level was 3. Her hemoglobin level was 8.5 g/dL. The CT scan showed that the size of the cystic tumor was 200 × 144 × 143 mm. The tumor severely compressed her heart. We performed TACE using a spherical embolic agent. The microcatheter was guided through the left bronchial artery; left intercostal artery 9, 10, and 11; and the left inferior phrenic artery. The anticancer drugs selected were CDDP and 5-FU. The embolic material used was SAP-MS. After 3 therapy sessions, the CT scan showed shrinkage of the target lesion to 100 × 93 × 54 mm. Her hemoglobin level increased to 13.8 g/dL; furthermore, the severity of dyspnea decreased, and she showed a performance status of 0. TACE with SAP-MS was successfully performed for the large cystic tumor in the pulmonary cavity that metastasized from the lung cancer and was refractory to standard treatments. After the treatment, the tumor size decreased and the patient's symptoms alleviated.

  16. Combination chemotherapy with paclitaxel, cisplatin and fluorouracil for patients with advanced and metastatic gastric or esophagogastric junction adenocarcinoma: a multicenter prospective study

    Xiao-Dong Zhang; Cheng-Ye Guo; Lin Shen; Mao-Lin Jin; Yong-Qian Shu; Jun Liang; Feng-Chun Zhang; Xue-Zhen Ma; Jian-Jin Huang; Li Chen; Gen-Ming Shi; Wei-Guo Cao


    Objective:To evaluate the efficacy and toxicity of the combination regimen of paclitaxel,cisplatin and 5-FU (PCF) as first-line or second-line therapy in patients with advanced gastric and esophagogastric junction (EGJ) adenocarcinoma in China.Methods:The patients were treated with paclitaxel 150 mg/m2 on d1; fractionated cisplatin 15 mg/m2 and continuous infusion 5-FU 600 mg/(m2·d) intravenously on d1-d5 of a 21-d cycle until disease progression or unacceptable toxicities.Results:Seventy-five patients have been enrolled,among which,41 received PCF regimen as the first-line therapy (group A) and 34 received the regimen as the second-line therapy (group B) with the median age of 59 years old and Karnofsky performance status (KPS) score ≥80.Toxicities were analyzed in all 75 patients.Seventy-one patients were evaluable for efficacy.The median overall survival (mOS) was 12.0 months (95% CI:7.9-16.2 months) in group A and 7.3 months (95% CI:4.3-10.3 months) in group B,respectively.The median progression-free survival (mPFS) was 5.7 months (95% CI:4.1-7.2 months) and 5.0 months (95% CI:3.1-6.9 months),respectively.The response rate (CR+PR) was 40% (16/40; 95% CI:24.9-56.7%) in group A and 22.6% (7/31; 95% CI:9.6-41.1%) in group B.Major grade 3 or 4 adverse events include neutropenia (41.3%),febrile neutropenia (9.3%),nausea/anorexia (10.7%),and vomiting (5.3%).There was no treatment-related death.Conclusions:The combination chemotherapy with PCF is active and tolerable as first-line and second-line therapy in Chinese patients with advanced gastric and EGJ adenocarcinoma.The response and survival of PCF are same as those of DCF,but the tolerance is much better.

  17. FOLFIRI regimen in metastatic pancreatic adenocarcinoma resistant to gemcitabine and platinum-salts

    Cindy Neuzillet; Olivia Hentic; Beno(i)t Rousseau; Vinciane Rebours; Lé(i)la Bengrine-Lefèvre; Franck Bonnetain; Philippe Lévy


    AIM:To evaluate the efficacy and safety of the FOLFIRI regimen in patients with metastatic pancreatic adenocarcinoma (PAC) after the failure of gemcitabine and platinum salts.METHODS:All consecutive patients with histologically confirmed,metastatic PAC and World Health Organization performance status (PS) ≤ 2 received FOLFIRI-1 [irinotecan 180 mg/m2 on day 1 and leucovorin 400 mg/m2 followed by 5-fluorouracil (5-FU) 400 mg/m2 bolus,then 5-FU 2400 mg/m2 as a 46-h infusion,biweekly] or FOLFIRI-3 (irinotecan 100 mg/m2 on day 1 and leucovorin 400 mg/m2,then 5-FU 2400 mg/m2 as a 46-h infusion and irinotecan 100 mg/m2 repeated on day 3,biweekly) after failure of gemcitabine and platinum-based chemotherapies as a systematic policy in two institutions between January 2005 and May 2010.Tumor response,time to progression (TTP),overall survival rate (OS) and grade 3-4 toxicities were retrospectively studied.Subgroup analyses were performed to search for prognostic factors.RESULTS:Sixty-three patients (52.4% male,median age 59 years) were analyzed.Among them,42.9% were PS 0,38.1% were PS 1 and 19.0% were PS 2.Fifty one patients (81.0%) had liver metastases.Before the FOLFIRI regimen,patients had received 1 line (n =19),2 lines (n =39) or 3 lines (n =5) of chemotherapy.Median TTP obtained with the line before FOLFIRI was 3.9 mo (95% CI:3.4-5.3 mo).A total of 480 cycles was completed (median:6 cycles,range:1-51 cycles).The main reason for discontinuing FOLFIRI was tumor progression (90.3%).Tumor control was achieved in 25 patients (39.7%) (partial response:n =5,stable disease:n =20) with FOLFIRI.Median TTP was 3.0 mo (95% CI:2.1-3.9 mo) and median OS was 6.6 mo (95% CI:5.3-8.1 mo).Dose adaptation was required in 36 patients (57.1%).Fifteen patients (23.8%) had grade 3-4 toxicities,mainly hematological (n =11) or digestive (n =4).Febrile neutropenia occurred in 3 patients.There was no toxic death.PS 2 was significantly associated with poor TTP [hazard

  18. 5-氟尿嘧啶与肠外营养液配伍制剂的体外稳定性和体内抗肿瘤活性%Stability in vitro and antitumor activity in vivo of preparations of 5-Fu mixed with parenteral nutrition solution

    刘广宣; 赵茜; 隋月; 关丁越; 孙博; 朱丹彤; 齐先福


    Objective To observe the compatible stability in vitro and antitumor activity in vivo of preparations of 5-fluorouracil (5-Fu) mixed with total parenteral nutrition (TPN) solution (5-Fu and TPN solution) and to provide the basis for its clinical application .Methods The blank parenteral nutrition solution and 5-Fu and TPN solution were mixed at room temperature for 24 h.The appearances were observed and the mean diameter ( MD) and coefficient of variation ( CV) of fat particles , pH value and osmotic pressure was evaluated .The stability of 5-Fu in the 5-Fu and TPN solution was deter-mined by HPLC.The H22 transplanted models of mice were established .Sixty mice were divided into six groups:5-FU-TPN-L (30 mg/kg), 5-FU-TPN-M (65 mg/kg), 5-FU-TPN-H (130 mg/kg), 5-FU-NS (65 mg/kg), TPN and the con-trol group, each group had 10 mice.On the day 3 after being inoculated with H22 tumor cells, the mice in the six groups were intraperitoneally injected with the above six kinds of liquids , separately, once every other day for 5 times.On day 2 after the last administration , mice were killed and antitumor rate was calculated .Results Compared with the blank paren-teral nutrition solution, there were no significant changes in the appearances , MD, CV, pH value, osmotic pressure and the contents of 5-Fu within 24 h of 5-Fu and TPN solution (all P>0.05).The antitumor rates of the 5-FU-TPN-L, 5-FU-TPN-M, 5-FU-NS, and TPN groups were 24.3%, 91.8%, 78.7% and 14.6%, the antitumor rate of the 5-FU-TPN-M and 5-FU-NS groups were higher than those of the 5-FU-TPN-L and TPN groups, and the antitumor rate of 5-FU-TPN-M group was higher than that of the 5-FU-NS group, significant difference was found between every two groups ( all P <0.01).The toxicity of 5-FU-TPN-H was strong, and 6 mice died, so no statistics were carried out.Conclusion 5-Fu in TPN solution is stable within 24 h and the antitumor effect of 5-Fu at 65 mg/mL is better than single administration of 5-Fu.%目的:观察5-

  19. Reversal of 5-flouroucial resistance by adenovirus-mediated transfer of wild-type p53 gene in multidrug-resiatant human colon carcinoma LoVo/5-FU cells

    Zhi-Wei Yu; Peng Zhao; Ming Liu; Xin-Shu Dong; Ji Tao; Xue-Qin Yao; Xin-Hua Yin; Yu Li; Song-Bin Fu


    AIM: To observe the reversal effects of wide-type p53 gene on multi-drug resistance to 5-FU (LOVO/5-FU).METHODS: After treatment with Ad-p53, LOVO/5-FU sensitivity to 5-Fu was investigated using tetrazolium dye assay. Multidrug resistance gene-1 (MDR1) gene expression was assayed by semi-quantitative reverse transcriptionpolymerase chain reaction and the expression of p53 protein was examined by Western blotting.RESULTS: The reversal activity after treatment with widetype p53 gene was increased up to 4.982 fold at 48 h. The expression of MDR1 gene decreased significantly after treatment with wide-type p53 gene, and the expression of p53 protein lasted for about 5 d, with a peak at 48 h, and began to decrease at 72 h.CONCLUSION: Wide-type p53 gene has a remarkable reversal activity for the high expression of MDR1 gene in colorectal cancers. The reversal effects seem to be in a time dependent manner. It might have good prospects in clinical application.

  20. A proliferation-inducing ligand-binding peptide improves chemo-sensitivity of 5-FU on colorectal LO-VO cells%sAPRIL结合肽对LOVO细胞5-FU化疗敏感性的影响

    何小庆; 柳芳; 许雯; 何美蓉


    目的:增殖诱导配体(APRIL)与结直肠癌细胞对5-氟尿嘧啶(5-FU)的耐药性密切相关。我们前期已利用噬菌体随机肽库技术成功筛选并人工合成与sAPRIL有高亲和力的结合肽。本研究旨在探讨sAPRIL结合肽对结直肠癌LOVO细胞5-FU化疗敏感性的影响。方法将LOVO细胞分为PBS组、5-FU组、sAPRIL结合肽+5-FU组。采用CCK-8法检测细胞增殖、流式细胞仪测定细胞周期及细胞凋亡。结果5-FU组和sAPRIL结合肽+5-FU组增殖抑制率分别为(37.62±7.07)%、(63.05±2.15)%;流式细胞仪检测各组的细胞周期显示5-FU组阻滞在S期,sAPRIL结合肽+5-FU组阻滞在G0/G1期和S期,且S期阻滞效应显著强于5-FU组;三组细胞凋亡率分别为(0.21±0.09)%、(12.80±0.30)%、(17.1±0.66)%。结论 sAPRIL结合肽能增强结直肠癌LOVO细胞对5-FU的化疗敏感性,有望成为结直肠癌靶向治疗的新型候选制剂。%Objective This study aimed to verify if the sAPRIL-binding peptide can enhance chemo-sensitivity of 5-FU on colorectal cancer cells. Methods LOVO cells were divided into three groups: PBS, 5-FU, and sAPRIL-binding peptide plus 5-FU. The cell growth inhibition rate was detected by CCK-8 assay, and the cell cycle and cell apoptosis were detected by flow cytometry. Results The cell growth inhibition rate was (0±0)%in PBS group, (37.62±7.07)%in 5-FUgroup, (63.05±2.15)%in sAPRIL-binding peptide plus 5-FU group, respectively. In 5-FU group, cell cycle was arrested at S phase;and in sAPRIL-binding peptide plus 5-FU group, in sAPRIL-binding peptide plus 5-FU group, cell cycle was arrested at both G0/G1 and S phases ( more markedly at S phase compared with 5-FU alone). The percentage of early apoptotic cells was (0.21±0.09)%in PBS group, (12.80±0.30)%in 5-FUgroup, and (17.1±0.66)%in sAPRIL-binding peptide plus 5-FU group, respectively. Conclusions The sAPRIL-binding peptide can enhance chemo-sensitivity of 5-FU

  1. 5-FU结合大黄(庶虫)虫汤诱导胃癌细胞凋亡的实验研究%Apoptosis of Gastric Cancer Cells Induced by Combination of 5-Fu and Dahuang Zhechong Decoction



    Objective:To study the apoptosis of gastric cancer cells induced by combination of 5-Fu and Dahuang Zhechong Decoction.Methods:Xenotransplanted human gastric carcinoma model was established by BGC 823 cell line,and was divided into 4 groups randomly (12 for each group):5-Fu plus Dahuang Zhechong Decoction group,Dahuang Zhechong Decoction group,5-Fu group,saline group,treated with 3 weeks continuously.Tumor growth inhibitory rate of each group was calculated by the end of experiments when the animals were sacrificed,flow cytometry was for analyzing the apoptosis rate of xenotrasplanted,RT-PCR assays were used to detect the levels of Caspase-3.Results:Tumor growth inhibitory rate of 5-Fu plus Dahuang Zhechong Decoction group was significantly higher than that of Dahuang Zhechong Decoction group or 5-Fu group(P < 0.01).The apoptosis rare of 5-Fu plus Dahuang Zhechong Decoction group was apparent than that of Dahuang Zhechong Decoction group or 5-Fu group (P < 0.01,P < 0.05).There were significant differences between three groups in the levels of Caspase-3,the levels of Caspase-3 was highest of 5-Fu plus Dahuang Zhechong Decoction group,compared with Dahuang Zhechong Decoction group and 5-FU group (P <0.01,P < 0.05).Conclusion:5-Fu plus Dahuang Zhechong Decoction can significantly improve the apoptosis rate and inhibit the growth of gastric cancer cells.%目的:探讨5-FU结合大黄(庶虫)虫汤诱导胃癌细胞凋亡的作用.方法:将人胃癌BGC-823细胞裸鼠移植瘤动物模型,随机分为4组(每组12只):5-FU结合大黄(庶虫)虫汤组,大黄(庶虫)虫汤组,5-FU组,生理盐水组.连续用药3周,用药结束后脱颈处死裸鼠,统计各组抑瘤率;流式细胞仪检测移植瘤细胞凋亡率,RT-PCR检测凋亡关键因子Caspase-3表达.结果:5-FU结合大黄(庶虫)虫汤组抑瘤率高于大黄(庶虫)虫汤组、5-FU组(P<0.01);5-FU结合大黄(庶虫)虫汤组胃癌细胞凋亡率明显高于大黄(庶虫)虫汤组、5-FU

  2. 保护性自噬对5-FU诱导的胃癌细胞凋亡的抑制作用%Protective autophagy inhibits 5-FU-induced apoptosis in human gastric cancer cell line MGC803

    徐玲; 曲秀娟; 刘云鹏; 刘静; 丁小娣; 侯科佐; 张晔


    目的:明确5-FU处理胃癌MGC803细胞后自噬的存在,并探讨自噬在5-FU诱导凋亡中的作用.方法:5-FU处理胃癌MGC803细胞.MTT检测细胞增殖能力.流式细胞术检测细胞凋亡.Western blot检测蛋白表达.荧光显微镜观察自噬的发生.结果:0.1-1000mg/L的5-FU作用MGC803细胞48h,抑制细胞增殖50%的药物浓度(IC50)为2.07mg/L±1.14mg/L.2mg/L和5mg/L的5-FU作用细胞48h,细胞凋亡率分别为22.46%±3.21%和32.27%±4.52%.同时,5-FU诱导细胞自噬的发生,观察到LC3的点状聚集和LC3-Ⅱ蛋白的提高.并且,5-FU抑制了PI3K/Akt/mTOR通路的活性.用氯喹抑制自噬明显提高了5-FU诱导的细胞调亡(P<0.05).结论:5-FU诱导保护性自噬并阻止了胃癌MGC803细胞的凋亡.5-FU和自噬抑制剂的联合应用可能是很有希望的胃癌治疗策略.%AIM: To investigate whether 5-fluorouracil (5-FU)induces autophagy in human gastric cancer cell line MGC803 and to identify the role of autophagy in 5-FU -induced cell apoptosis.METHODS: After cultured MGC803 ceils were treated with 5-FU, cell proliferation was measured using MTT assay; cell apoptosis was determined by flow cytometry; protein expression was detected by Western blot; and autophagy was observed by fluorescent microscopy.RESULTS: The concentration of 5-FU inducing a 50% inhibition of cell proliferation (IC50) was 2.07 mg/L ± 1.14 mg/L in MGC803 cells. After treatment with 2 and 5 mg/L 5-FU for 48 h, the rates of cell apoptosis were 22.46% ± 3.21% and 32.27% ± 4.52%, respectively. Autophagy, characterized by an increase in the number of punctate LC3 dots and the level of LC3-Ⅱ protein,was observed in cells treated with 5-FU. The activity of the PI3K/Akt/mTOR pathway was inhibited by 5-FU treatment. Inhibition of autophagy with chlorochine significantly enhanced 5-FU -induced apoptosis (P < 0.05).CONCLUSION: 5-FU-induced protective autophagy prevents MGC803 cells from apoptosis.Combination therapy with 5-FU and

  3. Aktinik şelitis tedavisinde 5-fluorourasıl (5-fu kullanımı: derleme ve iki olgunun sunumu

    Taha Unal


    Full Text Available

    Actinic (solar cheilitis is an epithelial precancerous lesion with a predilection of lower lip rather than upper lip. Clinically they may be undistinguishable from squamous cell carcinomas. Therefore actinic cheilitis should not be left untreated and the effected area should be protected from exposure to excess sun light. Two patients complaining of chronic ulcers and burning sensation on their lower lips were referred to the oral surgery clinic. Clinical examination revealed keratotic areas and superficial ulcers on lower lip vermillion. Patients’ history and the clinical findings led us to a clinical diagnosis of actinic cheilitis in both cases. The diagnoses were confirmed histopathologically, treatment was with topical 5-FU and one of the cases is still under our review. Clinical appearance of actinic cheilitis can be similar to lip carcinomas and there is the risk of transformation to squamous cell carcinoma. For this reason it is imperative that a biopsy is taken promptly to confirm the diagnosis. Recurrence is possible after treatment and this necessitates regular review appointments. Patient compliance is a must, and to improve this, treatment options should be discussed with the patient and their preferences should be considered.


    Aktinik (solar şelitis daha çok alt dudakta görülen epitelyal prekanseröz bir oluşumdur. Klinik olarak, skuamoz hücreli karsinomdan ayrılması güç olabilir. Bu nedenle aktinik şelitis tedavisiz bırakılmamalı ve etkilenen bölge güneş ışığından korunmalıdır. Alt dudaklarında iyileşmeyen yara ve yanma şikayeti olan 2 olgu, Ağız Diş Çene Hastalıkları ve Cerrahisi Anabilim Dalı kliniğine başvurmuşlardır. Muayenede alt dudak vermilyonlarında iyileşmeyen yüzeyel ülserler ve keratotik alanlar içeren lezyonlar saptanmıştır. Her iki olgunun da hikayeleri ve klinik muayeneleri sonucunda aktinik şelitis

  4. Expression of p21WAF1 in Astler-Coller stage B2 colorectal cancer is associated with survival benefit from 5FU-based adjuvant chemotherapy.

    Sulzyc-Bielicka, Violetta; Domagala, Pawel; Urasinska, Elzbieta; Bielicki, Dariusz; Safranow, Krzysztof; Domagala, Wenancjusz


    In several, but not all, previous studies, positive p21(WAF1) expression has been suggested as an indicator of a good prognosis in patients with stage III/IV colorectal cancer. However, it is not known whether the same is true for stage B2 patients. The purpose of this study is to assess the influence of p21(WAF1) expression in tumor cells on disease-free survival (DFS) and overall survival (OS) of Astler-Coller stage B2 and C patients with colorectal cancer who underwent 5-fluorouracil-based adjuvant chemotherapy. Nuclear p21(WAF1) was detected by immunohistochemistry in tissue microarrays from 275 colorectal cancers. The expression of p21(WAF1) was associated with DFS (p = 0.025) and OS (p = 0.008) in the subgroup of stage B2 patients that was treated with adjuvant chemotherapy. In multivariate analysis, it remained the only independent prognostic parameter in relation to DFS and OS (p = 0.035 and p = 0.02, respectively). In the subgroup of 72 stage B2 patients with positive p21(WAF1) expression but not in the subgroup of 61 stage B2 patients with negative p21(WAF1) expression, adjuvant chemotherapy was associated with better DFS (85% 5-year survival versus 65% without chemotherapy, p = 0.03) and OS (96% versus 82%, p = 0.014). In the combined stage B2 and C group of patients treated with adjuvant chemotherapy, positive p21(WAF1) expression was also associated with better DFS and OS (p = 0.03, p = 0.002, respectively). Expression of p21(WAF1) in colorectal tumor cells identifies a subgroup of Astler-Coller stage B2 patients who could benefit significantly from 5FU-based chemotherapy and may improve the selection of patients for adjuvant chemotherapy.

  5. Research in effect of hirudoid on phlebitis prevention initiated by continuous infusion of 5-Fu with Baxter infusor%喜疗妥预防便携式百特泵持续输注5-Fu所致静脉炎的方法研究

    胡莲英; 冯惠霞; 钟文欢


    目的 探讨喜疗妥外涂对便携式百特泵输注5-Fu所致静脉炎的预防作用.方法 选择60例2007年12月至2009年8月住院的鼻咽癌初治患者,按随机分配原则分成实验组32例和对照组28例,实验组在开始输注5-Fu时沿静脉走向外涂喜疗妥并轻轻按摩,对照组不做任何处理,观察2组静脉炎发生情况.结果 实验组静脉炎的发生率明显低于对照组,且程度较轻.结论 喜疗妥能降低便携式百特泵输注5-Fu所致静脉炎的发生率,并能减轻静脉炎的症状,是预防和治疗静脉炎的有效药物.%Objective We observed the effect of topical application of mucopolyccharide polysulfate cream (hirudoid) on phlebitis prevention initiated by continuous infusion of 5-Fu with Baxter infusor. Methods 60 untreated patients with nasopharyngeal carcinoma were selected and randomly divided into the control group (28 patients) and the experimental group (32 patients). The patients of the experimental group were gently massaged with hirudoid along the infusion vein since the beginning of 5-Fu infusion, while the control group received no intervention. The incidence of phlebitis was observed in the two groups. Results The incidence of phlebitis in the experimental group was lower and the degree was lighter compared with the control group. Conclusions Hirudoid can decrease the incidence and released the symptoms of phlebitis initiated by continuous infusion of 5-Fu with Baxter infusor, and is effective to prevent and treat phlebitis.

  6. Autophagy enhances chemotheragy resistance of CD133 + colon cancer stem cells to 5-FU%自噬增强结肠癌CD133+细胞对5-FU的化疗抵抗

    司晓丽; 刘伟; 杨爱军; 王晨昱; 李敏


    Objective To observe the autophagy of CD133 + CSCs induced by 5-FU,and explore the effect of autophagy on the chemotherapy. Methods The cell proliferative inhibition rates and IC50 of 5-FU on human colon cancer cell lines SW480 were measured by MT1 assay. CD133 + CSCs were purified with MACS( magnetic activated cell-sorting system) CD133 cell isolation kit. Then the morphplpgical features of cells were observed using transmission election microscopy( TEM), and the autophagic vacuoles ( AV ) was observed using fluorescent microscope by monodansylcadaverin(MDC) staining. The effect of autophagy on the chemotherapey was evaluated by cell viability assay and colony-forming test. Results The vibility of human colon cancer cell line SW480 was obviously inhibited with different contrations of 5-FU, 50% inhibition concentration ( IC50 ) value was ( 1.09 ± 0. 18 ) μg/mL.Autophagsomes and autophagy vesica were observed in CD133 + CSCs. The combination treatment of 5-FU and 3-MA significantly decreased the viability of CD133 +CSCs from (81.8 ±4. 6)% to (56. 3 ±5.5)% (P <0. 05),and the colony-forming efficiency from (81.1 ±3.4)% to (64.4 ±4. 8)% (P <0.05), compared with 5-FU alone. Conclusion 5-FU may induce autophagy in CD133 + CSCs. Inhibition of autophagy may be employed to increase the cytotoxic effect of CD133 + CSCs to 5-FU.%目的 对5-FU诱导结肠癌CD133+细胞发生自噬的过程进行观察,初步探讨自噬对化疗的影响.方法 用MTT法检测细胞增殖抑制率及IC50;用免疫磁珠分选CD133+细胞;用透射电子显微镜(TEM)观察细胞的超微结构,用MDC染色,荧光显微镜观察自噬囊泡;联合应用细胞活性实验、集落形成实验研究自噬对化疗的影响.结果 不同浓度5-FU处理后,人结肠癌SW480细胞活性明显受到抑制,其半数抑制浓度IC50为(1.09±0.18)μg/mL.CD133+胞质出现大量的自噬体及自噬囊泡;相比较单独给予5-FU,联合给予5-FU及3-MA,CD133+细胞活性由(81

  7. Survivin siRNA协同5-FU抑制MCF-7细胞的增殖%Synergism between a siRNA targeted to survivin and 5-FU in inhibiting MCF-7 cell proliferation in vitro

    张淑群; 张淑慧; 薛兴欢; 王西京; 姜建涛


    Objective To investigate the role of small interfering RNA (siRNA) targeted to survivin in combination with 5-fluorouracil (5-FU) in inhibiting the proliferation of MCF-7 cells. Methods A siRNA targeted to survivin was synthesized and transfected into MCF-7 cells via lipofectin. Changes of the cell growth activity in response to combined treatment with survivin siRNA and 5-FU or 5-FU treatment alone was evaluated by MTT assay. The Q method of Jin Zhenjun was used to evaluated synergism between the synthesized siRNA and 5-FU. Results Treatment with 5 nmol/L siRNA reduced the IC50 of 5-FU from 4.42 to 1.18 μg/ml, and the inhibitory effect of combined treatment on MCF-7 cells was higher than that of 5-FU alone (F=26.74, P<0.01). Synergism effect (Q ≥ 1.15) was observed between 5-FU at lower concentrations and survivin siRNA. Conclusion siRNA may enhance the effectiveness of 5-FU in inhibiting the proliferation of MCF-7 cells.%目的研究以survivin为靶标的小干扰RNA(siRNA)与化疗药5-FU联合应用抑制MCF-7细胞增殖的作用.方法利用T7 RNA聚合酶体外转录合成siRNA并筛选出一条RNA干扰survivin基因的靶序列.以脂质体为载体,将survivin siRNA转染至人乳腺癌MCF-7细胞中,用四氮唑盐(MTT)法染色并计算siRNA联用5-FU对MCF-7细胞的抑制率,用SAS统计软件及金正均Q值法进行统计分析.结果单用5-FU处理细胞,其IC50为4.42 μg/ml,而加入5 nmol/L siRNA后,其IC50降为1.18 μg/ml,siRNA与5-FU联用对MCF-7细胞的抑制作用较单用5-FU明显增强(F=26.74,P<0.01);Q值分析表明survivin siRNA与中低浓度的5-FU联用,有较好的协同作用(Q≥1.15).结论survivinsiRNA可显著增强5-FU对MCF-7细胞增殖的抑制,提高肿瘤细胞对化疗药物的敏感性,克服耐药性的产生.

  8. 运用羟基喜树碱与5-FU治疗恶性胸腔积液的对照观察%Control observation on HCPT and 5-FU therapy for malign pleural effusion

    张本亮; 庞学武; 曹弟勇


    目的:探讨羟基喜树碱(HCPT)治疗恶性胸腔积液的疗效.方法 :57例恶性胸腔积液病人分为两组.29例接受羟基喜树碱(HCPT)治疗,28例接受5-FU治疗. 结果:羟基喜树碱(HCPT)组完全控制率27.6%,部分控制率55.2%,总有效率82.8%. 而运用5-FU组分别为17.9%,28.5%,46.4%.结论:羟基喜树碱(HCPT)疗效明显优于5-FU(p<0.01).副作用低于5-FU.


    王安训; 温映萍; 李苏; 黄洪章


    目的研究顺铂(cisplatin, CDDP)和5-氟脲嘧啶(5-fluorouracil, 5-FU)联合化疗对口腔鳞癌(Tca8113 细胞株)的体内外抗瘤作用.方法应用CDDP和5-FU单独或联合治疗口腔鳞癌细胞(Tca8113 细胞系)及其裸鼠移植瘤,采用MTT法检测其体外杀伤作用;观察移植瘤的生长情况及组织病理学改变;高效液相色谱法(HPLC)检测血液及移植瘤内5-FU的浓度.结果 CDDP和5-FU均对口腔鳞癌细胞具有强的体外杀伤作用,其IC50分别为:0.59μmol/L和2.33μmol/L.与对照组比较,移植瘤经CDDP和5-FU单独或联合治疗后生长均明显受到抑制(P<0.001),其抑瘤率分别为:57.0%(5-FU)、84.4%(CDDP)和97.2%(5-FU+CDDP),CDDP和5-FU存在协同的抑瘤作用(P<0.001);组织病理学显示各治疗组移植瘤内出现囊性变和灶性坏死;肿瘤组织和血液中可检测到高浓度的5-FU.结论 CDDP和5-FU联合化疗可能是口腔鳞癌有效的化疗方案.

  10. Degradation of 5-FU by means of advanced (photo)oxidation processes: UV/H2O2, UV/Fe2+/H2O2 and UV/TiO2--Comparison of transformation products, ready biodegradability and toxicity.

    Lutterbeck, Carlos Alexandre; Wilde, Marcelo Luís; Baginska, Ewelina; Leder, Christoph; Machado, Ênio Leandro; Kümmerer, Klaus


    The present study investigates the degradation of the antimetabolite 5-fluorouracil (5-FU) by three different advanced photo oxidation processes: UV/H2O2, UV/Fe(2+)/H2O2 and UV/TiO2. Prescreening experiments varying the H2O2 and TiO2 concentrations were performed in order to set the best catalyst concentrations in the UV/H2O2 and UV/TiO2 experiments, whereas the UV/Fe(2+)/H2O2 process was optimized varying the pH, Fe(2+) and H2O2 concentrations by means of the Box-Behnken design (BBD). 5-FU was quickly removed in all the irradiation experiments. The UV/Fe(2+)/H2O2 and UV/TiO2 processes achieved the highest degree of mineralization, whereas the lowest one resulted from the UV/H2O2 treatment. Six transformation products were formed during the advanced (photo)oxidation processes and identified using low and high resolution mass spectrometry. Most of them were formed and further eliminated during the reactions. The parent compound of 5-FU was not biodegraded, whereas the photolytic mixture formed in the UV/H2O2 treatment after 256 min showed a noticeable improvement of the biodegradability in the closed bottle test (CBT) and was nontoxic towards Vibrio fischeri. In silico predictions showed positive alerts for mutagenic and genotoxic effects of 5-FU. In contrast, several of the transformation products (TPs) generated along the processes did not provide indications for mutagenic or genotoxic activity. One exception was TP with m/z 146 with positive alerts in several models of bacterial mutagenicity which could demand further experimental testing. Results demonstrate that advanced treatment can eliminate parent compounds and its toxicity. However, transformation products formed can still be toxic. Therefore toxicity screening after advanced treatment is recommendable.

  11. Curcumin potentiates the antitumor effects of 5-FU in treatment of esophageal squamous carcinoma cells through downregulating the activation of NF-κB signaling pathway in vitro and in vivo

    Fang Tian; Tianli Fan; Yan Zhang; Yanan Jiang; Xiaoyan Zhang


    Although constitutive activation of nuclear factor-kappaB (NF-κB) signaling pathway has been reported in multiple different human tumors,the role of NF-κB pathway in esophageal squamous ceil carcinoma (ESCC) remains illdefined.Abundant sources have provided interesting insights into the multiple mechanisms by which curcumin may mediate chemotherapy and chemopreventive effects on cancer.In this study,we first analyzed the status of NF-κB pathway in the two ESCC cell lines Eca109 and EC9706,and then further investigated whether curcumin alone or in combination with 5-fluorouracil (5-FU) could modulate NF-κB pathway in vitro and in vivo.The results showed that NF-κB signaling pathway was constitutively activated in the ESCC cell lines.Curcumin suppressed the activation of NF-κB via the inhibition of IκBα phosphorylation,and downregulated the expressions of Bcl-2 and CyclinD1 in ESCC cell lines.Curcumin combined with 5-FU led to the lower cell viability and higher apoptosis than 5-FU treated alone.In a human ESCC xenograft model,curcumin or 5-FU alone reduced the tumor volume,but their combination had the strongest anticancer effects.Besides,curcumin could also inhibit NF-κB signaling pathway through downregulation of the IκBα phosphorylation and induction of cell apoptosis in vivo.Overall,our results indicated that constitutively activated NF-κB signaling pathway exists in the two ESCC cells and the chemopreventive effects of curcumin were associated with downregulation of NF-κB signaling pathway and its downstream genes.

  12. Irinotecan Plus S-1 Followed by Hepatectomy for a Patient with Initially Unresectable Colorectal Liver Metastases, Who Showed Severe Drug Rash with Oxaliplatin Plus 5-FU and Leucovorin (FOLFOX

    Hiroyuki Komori


    Full Text Available For unresectable colorectal liver metastases (CRLM, hepatic resection with or without chemotherapy is the only curative treatment that sufficiently achieves long-term survival. However, occasional severe allergic responses to anticancer drugs necessitate treatment discontinuation. A 45-year-old woman presented with metachronous unresectable colorectal liver metastases. Chemotherapy with oxaliplatin plus 5-FU and leucovorin (FOLFOX was initiated, but severe allergic dermatitis developed after the second cycle. Although she reported no prior history of adverse reactions to tegafur-uracil, a drug lymphocyte stimulation test showed an allergic response to 5-FU. We subsequently replaced with Irinotecan plus S-1 (IRIS chemotherapy which was well tolerated and resulted in a partial response after 3 cycles. As a result, right trisectionectomy was successfully performed and no recurrence was detected in the following 3 years. A severe allergic reaction to intravenous 5-FU-containing drug regimens can be successfully alleviated by switching to S-1-containing regimens such as IRIS or S-1 plus oxaliplatin (SOX.

  13. 蝎毒抗癌多肽(APBMV)与5-Fu序贯用药治疗小鼠肝癌%Effect of APBMV and 5- Fu Administered in Sequence on the Mice bearing H22

    宋红霞; 杨建斌; 董伟华; 孔天翰


    目的:探讨蝎毒抗癌多肽(APBMV)与5-Fu序贯用药对小鼠肝癌治疗效果的影响.方法:以小鼠腹水型肝癌H22(Hepatoma 22)的荷瘤模型观察了APBMV与5-Fu序贯用药的体内抑瘤作用.结果:APBMV与5-Fu同时用药组、5-Fu-APBMV序贯用药均对H22荷瘤小鼠有显著的生命延长作用(P<0.002或P<0.001),以APBMV和5-Fu同时用药组的生命延长率最高,达253.40%(P<0.001);5-Fu-APBMV序贯用药组次之为80.89%(P<0.002);5-Fu单用组较低,只有30.24%(P<0.05),与前二者比较有显著差异(P<0.001或P<0.05).5-Fu-APBMV组治疗效果最差.结论:APBMV与5-Fu用药时相配合显著影响疗效.

  14. [Preliminary clinical evaluation of continuous infusion of 5-FU and low-dose Cisplatin (LFP) therapy alone and combined with radiation therapy for treatment of advanced or recurrent esophageal cancer].

    Itoh, Satoshi; Morita, Sojiro; Ohnishi, Takenao; Tsuji, Akihito; Takamatsu, Masahiro; Horimi, Tadashi


    We evaluated the clinical effect of 5-FU and low-dose Cisplatin (LFP) therapy alone and LFP therapy combined with radiation therapy in patients with advanced or recurrent esophageal cancer. From March 1995 to September 2000, 11 patients with inoperable esophageal cancer, 8 patients with adjuvant chemotherapy post operation, and 14 patients with recurrent esophageal cancer were treated with LFP therapy. 5-FU (160 mg/m2/day) was continuously infused over 24 hours, and CDDP (3-7 mg/m2/day) was infused for 30 minutes. The administration schedule consisted of 5-FU for 7 consecutive days and CDDP for 5 days followed by a 2-day rest, each for four weeks. We combined radiation therapy for the patients with all lesions that could be included in the radiation field. Of 30 patients with measurable lesions the response rates of LFP therapy alone and LFP therapy combined with radiation therapy were 33% and 60%, respectively. Toxicity over grade 3 appeared in 3 of 15 patients with LFP therapy combined with radiation therapy. There was no significant difference between LFP therapy alone and LFP therapy combined with radiation therapy with regard to survival rate of inoperable and recurrent esophageal cancer. In conclusion, LFP therapy alone may be effective for esophageal cancer.

  15. Preliminary clinical evaluation of continuous infusion of 5-FU and low-dose cisplatin (LFP) therapy alone and combined with radiation therapy for treatment of advanced or recurrent esophageal cancer

    Itoh, Satoshi; Morita, Sojiro; Ohnishi, Takenao; Tsuji, Akihito; Takamatsu, Masahiro; Horimi, Tadashi [Kochi Municipal Central Hospital, Nankoku (Japan). Cancer Research Center


    We evaluated the clinical effect of 5-FU and low-dose Cisplatin (LFP) therapy alone and LFP therapy combined with radiation therapy in patients with advanced or recurrent esophageal cancer. From March 1995 to September 2000, 11 patients with inoperable esophageal cancer, 8 patients with adjuvant chemotherapy post operation, and 14 patients with recurrent esophageal cancer were treated with LFP therapy. 5-FU (160 mg/m{sup 2}/day) was continuously infused over 24 hours, and CDDP (3-7 mg/m{sup 2}/day) was infused for 30 minutes. The administration schedule consisted of 5-FU for 7 consecutive days and CDDP for 5 days followed by a 2-day rest, each for four weeks. We combined radiation therapy for the patients with all lesions that could be included in the radiation field. Of 30 patients with measurable lesions the response rates of LFP therapy alone and LFP therapy combined with radiation therapy were 33% and 60%, respectively. Toxicity over grade 3 appeared in 3 of 15 patients with LFP therapy combined with radiation therapy. There was no significant difference between LFP therapy alone and LFP therapy combined with radiation therapy with regard to survival rate of inoperable and recurrent esophageal cancer. In conclusion, LFP therapy alone may be effective for esophageal cancer. (author)

  16. 5-Fu to Translation Combined Curettage in the Treatment of Multiple Verruca Vulgaris Curative Effect Observation and Nursing%5-Fu联合刮除术治疗多发性寻常疣疗效观察及护理



    Objective To discuss the 5-Fu combined curet age curative ef ect for the treatment of multiple verruca vulgaris. Methods Two groups were treated with curettage, the treatment group while injected 5-Fu. Results Treatment group ef ectiveness is higher than the control group. Significantly reduce the recurrence. Conclusion 5-Fu combined curet age in the treatment of multiple verruca vulgaris can improve the curative ef ect to reduce the recurrence rate.%目的探讨5-Fu联合刮除术治疗多发性寻常疣的疗效。方法两组均用刮除术治疗,治疗组同时注射5Fu。结果治疗组有效率高于对照组。明显减少复发。结论5-Fu联合刮除术治疗多发性寻常疣可提高疗效降低复发率。

  17. 周剂量多西他赛联合顺铂、5-FU治疗晚期食管癌的临床观察%Weekly docetaxel combined with cisplatin and 5-Fu in patients with advanced esophageal carcinoma

    陆向东; 张汀荣


    Objective: To evaluate the clinical efficacy and toxicity of weekly docetaxel combined with cisplatin and 5 -FU in patients with advanced esophageal carcinoma.Methods: Total of 47 patients with advanced esophageal carcinoma received docetaxel 30mg/m2 iv d1 ,8,15 , cisplatin 20mg/m2 iv d1-5 , 5 - FU 500mg/m2 iv d1-5.Treatments were repeated every 28 days.The clinical responses were assessed after two cycles.Toxicity was assessed every cycle.Results: All of the 47 patients were assessable for response,3 case of complete response and 21 cases of partial response were confirmed, eith an overall response rate of 51.06%.The median time to progression( TTP ) was 149 days and the median survival time( MST ) was 274 days.The major toxicity was myelosuppression, neutropenia of grade Ⅲ/Ⅳ occurred in 13 patients ( 27.7% ),thrombocytopenia of grade Ⅲ in 3 patients( 6.4% ) and anemia of Ⅲ in 5 patients( 10.6% ).There was no treatment - related death.Conclusion: Weekly docetaxel combined with cisplatin and 5 - FU is effective and well tolerated for patients with advanced esophageal carcinoma.%目的:观察周剂量多西他赛联合顺铂、5-FU治疗晚期食管癌的临床疗效及不良反应.方法:47例晚期食管癌患者,应用多西他赛30mg/m2 静脉滴注第1、8、15天,顺铂20mg/m2 静脉滴注第1-5天,5-FU 500mg/m2 静脉滴注第1-5天,每28天重复.治疗2个周期评价疗效,每周期评价毒性.结果:47例患者均可评价疗效.获CR 3例,PR 21例,总有效率(CR+PR)为51.06%.所有患者中位疾病进展时间为149天,中位生存时间274天.主要不良反应为骨髓抑制,出现Ⅲ/Ⅳ度中性粒细胞减少13例(27.7%),Ⅲ度血小板减少3例(6.4%),Ⅲ度贫血5例(10.6%),无治疗相关性死亡.结论:周剂量多西他赛联合顺铂、5-FU治疗晚期食管癌疗效较好,毒性可以耐受,值得临床进一步研究.

  18. 己酮可可碱对人食管癌细胞EC9706的5-Fu化疗增敏作用%Pentoxifylline enhances chemotherapy sensitization of 5-Fu in human esophageal carcinoma EC9706 cell

    宋慧琴; 李道明


    目的 探讨己酮可可碱对人食管癌细胞EC9706的5-Fu化疗增敏作用.方法 采用MTT法测定5-Fu及己酮可可碱联合5-Fu对EC9706细胞的抑制作用.结果 不同浓度的己酮可可碱联合5-Fu作用于EC9706 12、24、48、72 h,同一时间各组抑制率差异有统计学意义(P均<0.01),同一5-Fu浓度,随着己酮可可碱药物浓度的增加,5-Fu对己酮可可碱细胞的抑制作用也增强(P均<0.01).25 μg/mL 5-Fu联合己酮可可碱(0.5 mg/mL、1.0mg/mL)与50μg/mL 5-Fu对EC9706细胞抑制作用,在24、48、72 h无统计学差异(P均>0.05).结论 己酮可可碱可以增加EC9706细胞对5-Fu的敏感性,减少5-Fu的剂量.%Objective To investigate Pentoxifylline effect on chemotherapy sensitization of 5-Fu in human esophageal carcinoma EC9706 cell. Methods MTT method was used to determine the inhibition effects of 5-Fu and PTX uniting S-Fu to EC9706 Cell line. Results The EC9706 cells were treated by different concentration of 5-Fu and S-Fu uniting PTX for 12 h, 24 h, 48 h and 72 h. There were significant difference in inhibition rates in each group at the same time(P0.05). Conclusion PTX makes the EC9706 cells more sensitive to 5-Fu, and decrease dose of 5-Fu.

  19. Unintentional Long-Term Esophageal Stenting due to a Complete Response in a Patient with Stage UICC IV Adenocarcinoma of the Gastroesophageal Junction

    Paeschke, Anna; Bojarski, Christian; Küpferling, Susanne; Hucklenbroich, Thomas; Siegmund, Britta; Daum, Severin


    Endoscopic stent implantation is a common short-treatment option in palliative settings in patients with esophageal cancer. Advanced disease is associated with low survival rates; therefore, data on the long-term outcome are limited. So far, cases of long-term remission or even cure of metastasized adenocarcinoma of the gastroesophageal junction or stomach (AGS) have only been reported from Asia. A 51-year-old male patient primarily diagnosed with metastasized adenocarcinoma of the gastroesophageal junction (GEJ) [type I, cT3cN+cM1 (hep), CEA positive, UICC stage IV] received palliative esophageal stenting with a self-expandable metal stent. As disease progressed after four cycles with epirubicin, oxaliplatin, and capecitabin, treatment was changed to 5-FU and Irinotecan. The patient did not return after 5 cycles of FOLFIRI, but presented 4 years later with mild dysphagia. Endoscopy surprisingly revealed no relevant stenosis or stent migration. Repeated histological analyses of a residual mass at the GEJ did not detect malignancy. Since the initially diagnosed hepatic metastases were no longer detectable by computed tomography, cure from esophageal cancer was assumed. Dysphagia was ascribed to esophageal motility disorder by a narrowed esophageal lumen after long-term stenting. Thus, endoscopic stent implantation is an important method in palliative treatment of dysphagia related to AGS. New systemic treatment strategies like trastuzumab in Her2neu positive cases or new VEGF-inhibitors like ramucirumab will lead to more long-time survivors with AGS. In conclusion, future endoscopic treatment strategies in AGS represent a challenge for the development of new stent techniques in either extraction or programmed complete dissolution. PMID:27462189

  20. 5-FU增强TRAIL诱导的胃癌BGC823细胞凋亡的实验研究%TRAIL-induced apoptosis enhanced by 5-FU in gastric cancer BGC823 cells

    徐玲; 曲秀娟; 刘云鹏; 刘静; 于萍; 石晶; 侯科佐


    目的 观察5-FU对TRAIL诱导的胃癌BGC823细胞凋亡的影响,明确死亡受体5(DR5)在5-FU和TRAIL诱导凋亡中的作用.方法 采用MTT法测定细胞活力、流式细胞仪检测细胞凋亡、免疫印迹检测蛋白表达.结果 TRAIL可导致BGC823细胞轻度的增殖抑制和少量的细胞凋亡.与单药TRAIL和5-FU相比,TRAIL联合5-FU对细胞的增殖抑制和诱导凋亡作用明显增强(P<0.05).免疫印迹结果显示,TRAIL没有改变DR5的蛋白表达,而5-FU作用BGC823细胞48 h后,DR5蛋白表达上调(P<0.05).TRAIL和5-FU联合作用后,DR5蛋白表达同样明显上调(P均<0.05).结论 5-FU通过上调DR5蛋白表达提高了BGC823细胞对TRAIL的敏感性.%Objective To observe the inhibition effect of 5-FU on tumor necrosis factor-related apoptosis-inducing lig-and(TRAIL)-induced apoptosis in gastric cancer BGC823 cells, and identify the action of death receptor 5(DR5) in 5-FU and TRAIL-induced apoptosis. Methods Cell proliferation was measured using MTT assay. Cell apoptosis was determined by flow cytometry. Expression of protein was analyzed by western blot. Results Treatment with 100 ng/mL TRAIL for 48 h slightly resulted in the inhibition of cell proliferation and a little cell apoptosis in BGC823 cells. Treatment with TRAIL (100 ng/mL) and 5-FU(5.55 g/mL, IC50 dose of 48 h) leaded to a dramatic increase in the inhibitiong of cell proliferation and cell apoptosis compared to treatment with 5-FU or TRAIL alone(P < 0. 05). TRAIL alone did not change the expression of DR5, while 5.55 g/mL 5-FU significantly upregulated the expressions of DR5 in BGC823 cells after 48 h (P < 0.05). Treatment with 5-FU and TRAIL also resulted in the upregulation of DR5 (all P <0.05). Conclusion 5-FU enhance TRAIL-induced apoptosis in gastric cancer BGC823 cells by the upregulation of DR5.

  1. In vitro anti-HIV activity of [Ln(Phen)2(5-Fu)3(NO3)](NO3)2%[Ln(Phen)2(5-Fu)3(NO3)](NO3)2的体外抗艾滋病毒活性

    钟文远; 陈顺方; 范春兰; 崔永春



  2. Evaluation of two preoparative chemotherapy regimens for complete operability of advanced gastric adenocarcinoma: a clinical trial

    S. Sedighi


    Full Text Available Background: This prospective phase III study was designed to compare the activity of two combinations chemotherapy drugs in advanced gastric adenocarcinoma Methods: In a double blinded clinical trial, From Jan. 2002 to Jan. 2005, ninety patients with advanced gastric adenocarcinoma were randomly assigned to 1 Cisplatin and continuous infusion of 5FU and Epirubicin (ECF, and 2 Cisplatin and continuous infusion of 5FU with Docetaxel (TCF. Reduction in tumor mass, overall survival (OS, time to progression (TTP, and safety were measured outcome. Results: About 90% of patients had stage III or IV disease and the most common sites of tumor spread were peritoneal surfaces, liver and Paraaortic lymph nodes in either group. The objective clinical response rate (more than 50% decreases in tumor mass was 38% and 43% in ECF and TCF group respectively. Global quality of life increased (p=0 002 and symptoms of pain and insomnia decreased after chemotherapy. Patients in TCF had more grade one or two skin reactions, neuropathy and diarrhea. Fourteen patients underwent surgery. Complete microscopic (R0 resection had done in two of ECF and six of TCF tumors (p=0.015. Two cases in TCF group showed complete pathologic response. Median TTP was nine months and 10 months in ECF and TCF group respectively. Median OS was 12 months in both groups. Conclusion: Although there wasn’t statistically significant difference regarded to clinical response or survival between two groups, TCF showed more complete pathologic response.

  3. Berberine inhibits the growth of human colorectal adenocarcinoma in vitro and in vivo.

    Cai, Yuchen; Xia, Qing; Luo, Rongzhen; Huang, Peiyu; Sun, Yueli; Shi, Yanxia; Jiang, Wenqi


    Berberine is an alkaloid isolated from the Chinese herbal medicine Huanglian, and has long been used as an antibiotic. Its antineoplastic properties were subsequently discovered in vitro. The purpose of this study was to investigate the effects of berberine on the growth of human colorectal carcinoma cells in vitro and in vivo. The results showed that berberine inhibited human colorectal adenocarcinoma (LoVo) cell growth in a time- and dose-dependent manner. A WST-1 assay showed that the IC50 value after 72 h was 40.79 ± 4.11 μM. Cell cycle analysis of 40 μM berberine-treated LoVo cells by flow cytometry showed accumulation of cells in the G2/M phase. The inhibition of LoVo cell growth by berberine was associated with the suppression of cyclin B1, cdc2, and cdc25c proteins. Berberine at a dose of 50 mg kg(-1) day(-1) showed inhibitory rates of 45.3% in a human colorectal adenocarcinoma xenograft in nude mice. The combination of berberine and 5-fluorouracil (5-FU) had a higher inhibitory rate (59.8%) than the berberine group (36.4%, P = 0.01), but no significant difference was observed between the 5-FU group (43.0%, P = 0.06) and the combination group. These results support the possibility that berberine may be useful as an alternative therapy for colorectal carcinoma.

  4. Pemetrexed had significantly better clinical efficacy in patients with stage IV lung adenocarcinoma with susceptible EGFR mutations receiving platinum-based chemotherapy after developing resistance to the first-line gefitinib treatment

    Yang CJ


    Full Text Available Chih-Jen Yang,1–4 Ming-Ju Tsai,2,4 Jen-Yu Hung,2,3 Ta-Chih Liu,3,5 Shah-Hwa Chou,3,6 Jui-Ying Lee,6 Jui-Sheng Hsu,3,7 Ying-Ming Tsai,1,2,4 Ming-Shyan Huang,2–4 Inn-Wen Chong2,3 1Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, 2Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, 3Faculty of Medicine, College of Medicine, 4Graduate Institute of Medicine, College of Medicine, 5Division of Hematology and Oncology, Department of Internal Medicine, Kaohsiung Medical University Hospital, 6Division of Chest Surgery, Department of Surgery, Kaohsiung Medical University Hospital, 7Department of Medical Imaging, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan Background: Increased evidences show that epidermal growth factor receptor (EGFR-tyrosine kinase inhibitors such as gefitinib could prolong progression-free survival (PFS compared with cytotoxic chemotherapy for metastatic lung nonsquamous cell carcinoma harboring susceptible EGFR mutation, and gefitinib was served as the first-line therapy. However, acquired resistance is inevitable, but the salvage therapies are still unclear.Patients and methods: We designed a retrospective study of the salvage therapy and enrolled patients with stage IV lung adenocarcinoma who had mutated EGFR and developed an acquired resistance to the first-line gefitinib in two university-affiliated hospitals in Taiwan during June 2011 to December 2014. Age, sex, smoking history, EGFR gene mutation, performance statuses, response rate, PFS2 (the PFS in salvage therapy, and overall survival (OS2, the OS in salvage therapy were recorded.Results: Two hundred and nine patients with mutated EGFR and who took gefitinib as first-line therapy were identified in the period, and a total of 98 patients who had been treated with salvage therapy with cytotoxic chemotherapy or erlotinib were eligible for this

  5. DHA 联合5-FU 对人胃癌细胞增殖的抑制及线粒体呼吸链膜蛋白复合体的表达变化%The effect of combination of docosahexaenoic acid and 5-fluorouracil on the proliferation of human gastric cancer cell line AGS and the expression of mitochondrial respiratory membrane protein complexes

    王曙逢; 赵志浩; 刘竹君; 高琨; 李幼芬


    Objective To investigate the inhibitory effects of docosahexaenoic acid (DHA)and 5-fluorouracil (5-FU)in combination on human gastric cancer cell line AGS in vitro .Methods Human gastric cancer line AGS was treated with different concentrations of DHA and 5-FU alone or in combination.The inhibition of cell proliferation was evaluated by MTT assay.Dose of median (IC50 )of drugs (alone or in combination)and the combination index (CI)were calculated using the median-effect equation and the combination index equation of Chou-Talalay.Flow cytometry was used to detect the cell cycle distribution.The expression of mitochondrial respiratory membrane protein complex in AGS cells was analyzed with Western blot.Results DHA and 5-FU alone or in combination could markedly suppress the proliferation of AGS in significantly time-dependent and dose-dependent manners (P <0.05).IC50 values with DHA or 5-FU administered for 24 h and 48 h were 5 1.60 μg/mL (DHA:24 h),34.82 μg/mL (DHA:48 h),45.90 μg/mL (5-FU:24 h),and 1 6.86 μg/mL (5-FU:48 h), respectively.DHA remarkably strengthened the inhibitory effect of 5-FU and decreased IC50 of 5-FU by 3.56 -2.1 5 folds.The combination of DHA and 5-FU showed synergism.Flow cytometry showed that AGS cells treated with DHA and 5-FU were arrested in G0/G1 phase and the proportion of AGS cells in G0/G1 phase increased compared with that in the control group,DHA group and 5-FU group,while the proportion of the cells in S phase decreased significantly (P < 0.05 ).Western blot showed after treatment with DHA and 5-FU for 48 h,the expression of mitochondrial respiratory membrane protein complex was significantly decreased compared with control group,DHA group and 5-FU group (P <0.05).Conclusion DHA could act synergistically with 5-FU in inhibiting the growth of gastric carcinoma cells,and meanwhile decrease the dose of 5-FU.The mechanism may be associated with cell cycle arrest in G0/G1 phase and interference in the energy metabolism of AGS cells

  6. Genistein combined with 5-FU inhibits cell proliferation in human hepatocellular cancer cell line MHCC97-L%Genistein与5-FU联合对人肝癌细胞MHCC97-L的抗增殖作用

    刘丹; 赵忠新


    AIM: To explore whether genistein and 5-FU has synergistic inhibitory effect on the proliferation of human hepatic cancer cells (MHCC97-L). METHODS: MTT method was used to assay the biological activities of different concentrations of genistein and 5-FU in MHCC97-L cells. The inverted microscope was used to observe the influence of combined genistein and 5-FU on the morphological changes of MHCC97-L cells. After the cells were stained with Hoechst 33342 and observed under a fluorescence microscope, apop- tosis index was calculated. RESULTS: Both genistein and 5-FU could effectively inhibit the proliferation of MHCC97-L cells in a dose- and time-dependent manner. When used alone, the IQo (48 h) of genistein and 5-FU for MHCC97-L cells was 174.17 umol/L and 40.02 umol/L, respectively. When used in combination, the IC50 of genistein and 5-FU was 66.03 umol/L and 16.51 umol/L. The cell density in the combination group was lower than the two monotherapy groups. Morphologic characteristics of apoptotic cells, such as cyto-plasmic clouding, cell shrinkage and cytoplas-mic vacuolation, were observed. Typical apop-tosis was confirmed by fluorescence microscopy. The apoptosis index was 17.55% in the genistein group, 15.63 in the 5-FU group, and 30.38% in the combination group. CONCLUSION: Genistein and 5-FU can exert synergistic inhibitory effects on the growth of MHCC97-L cells possibly via mechanism associated with inducing apoptosis.%目的:探讨Genistein与5-FU联合对人肝癌MHCC97-L细胞凋亡的诱导作用.方法:采用MTT法、倒置显微镜、Hoechst 33342荧光染色技术研究Genistein、5-FU、Genistein与5-FU联合3组药物不同浓度作用于体外培养的人肝癌MHCC97-L细胞后生长抑制及诱导凋亡的形态学变化.结果:Genistein、5-FU单用及联用可抑制肝癌MHCC97-L细胞的增殖,其抑制率与药物剂量和作用时间呈依赖关系;48h单用时的IC50(Genistein)为174.17 μmol/L,IC50(5-FU)为40.02 μmol/L; 48 h

  7. Preparation of Modified 5-FU Liposomes with Cholesterol and Its Penetration Study in Hypertrophic Scar Penetration%胆固醇改性5-FU脂质体的制备及透瘢痕实验

    毛小慧; 沃雁; 章一新; 贺蓉; 崔大祥


    为了解脂质体抗瘢痕药物在增生性瘢痕中的透皮作用,应用胆固醇对5-FU脂质体进行改性处理.应用挤出仪控制粒径的大小后,观察粒径对包封率的影响,并进行体外透瘢痕实验,观察粒径对于渗透深度的影响作用.结果表明:脂质体成均一的大单层球形结构,包封率随粒径的变小而增大.粒径越小,透瘢痕能力越强.本实验证明经胆固醇改性之后的小粒径脂质体是一种较好的抗瘢痕药物载体,它的透瘢痕机制主要是变形作用和融合作用.%To investigate liposomes anti-scarring drug's ability in hypertrophic scar penetration, the 5-FU liposomes were modified with cholesterol. After the sizes of liposomes were controlled by extrusion equipment , the encapsulation efficiency of 5-FU in the liposomes was then investigated and observed. In vitro experiments of the liposomes to penetrate into human skin and scar were performed to find out whether the sizes of the liposomes would affect the depth of scar-penetration. The results show that with the decrease of the vesicle size, the encapsulation efficiency of 5-Fu increases gradually. The smaller the size of liposomes is, the stronger its permeating ability would be. The experiment proves that the modified smallsized liposomes are fine anti-scar drug carrier which can enhance their ability to penetrate into scar by the deformation and integration mechanisms.

  8. Definitive conformation radiotherapy combined with chemo-hormonal therapy in the treatment of adenocarcinoma of the prostate

    Karasawa, Katsuyuki; Kodaira, Takeshi [Tokyo Metropolitan Komagome Hospital (Japan); Nakagawa, Keiichi; Onogi, Yuzo; Hara, Hiroshi; Matsumoto, Hidetsugu; Sasaki, Yasuhito


    To ascertain the clinical benefits of photon conformation radiotherapy, since 1988 we have been conducting a clinical trial of photon conformation radiotherapy for adenocarcinoma of the prostate, and we have analyzed the findings thus far. Between 1988 and 1993, 33 evaluable patients with prostate cancer were treated with definitive radiotherapy at the Dept. of Radiology, Social Health Insurance Medical Center. Their ages ranged from 54 to 86, and averaged 69.3 y.o. (median 67). Their stages were as follows: 3 stage-B, 25 stage-C, and 5 stage-D cases. The minimum follow-up period was 1 year. Patients received 40 to 50 Gy (fraction dose ranged from 1.8 Gy to 2 Gy) to the pelvis using the AP-PA technique followed by a 20 to 30 Gy conformal boost (fraction dose 2 Gy) to the prostate gland. Total dose ranged from 68 Gy to 70.4 Gy, with an average of 70 Gy. Systemic multiagent chemotherapy with CDDP, ADR, MTX, 5FU, and CPM was administered concurrently and adjuvantly. Hormonal therapy was also adjuvantly administered. Overall survival rates at 3 years for stage B, C, and D were 100%, 100%, and 60%, respectively. and was 85% at 5 years for stage C. Relapse-free survival rates at 3 years for stage B and C were 100% and 96%, respectively, and was 61% at 5 years for stage C. Regarding stage C cases, the initial site of recurrence was bone in 5 cases. As for complications, there were 5 (15%) grade 1, 4 (12%) grade 2, and 1 (3%) grade 3 rectal complications. Although the number of cases is rather small and the follow-up period is rather short, definitive conformal radiotherapy with adjuvant chemo-hormonal therapy appears promising in the treatment of prostate cancer by improving survival rates with acceptable normal tissue toxicity. (author)

  9. Synthesis of Ru Cl3-en or Phen-5-Fu in vitro and antineoplastic activity%钌-乙二胺或邻菲罗啉-氟尿嘧啶配合物的合成及体外抗肿瘤活性

    钟文远; 崔永春; 范春兰; 胡智兴; 李玛琳



  10. Pseudomyxoma retropentonei due to the primary appendiceal mucinous adenocarcinoma

    LIUZhou-Lu; JIANGYan-Yong


    Aim Pseudomyxoma retroperitonei is a rare conditioncharacterized by mucinous implants in the retroperitonealspace. It is commonly associated with cystadenoma orcystadenocarcinoma of a retrocecal appendix.Methods A case of patient with pseudomyxomaretroperitonei and reviewed the literature was reported.Results A 68-year lady was operated for a presumedappendix abscess. A large amount of mucin was found in thefight hemi-retroperitoneal space during the operation.Appendectomy was performed together with the removal ofmucin . In addition intraoperative chemotherapy was used.Histologic diagnosis showed mucinous adenocarcinoma of theappendix. She was given systemic chemotherapypostoperatively (5-FU, MMC). Half a year later, she wasreferred to our hospital with an elevated CEA and CTrevealed a mass within the right hemi-retroperitoneal space.During exploration, the lesion was found to be encapsulatedand was completely removed . She remains disease-free nowfor 3 years since the last operation.Conclusion Primary mucinous adenocarcinoma is a diseasedifficult to diagnose, it has a relatively good prognosis evenwith pseudomyxoma peritonei or retroperitonei.Appendectomy with removal of all mucin tissue is a suitablechoice of treatment for some patients. Chemotherapy,especially intraoperative chemotherapy is recommended to improve survival.

  11. Her2+ and b-HCG Producing Undifferentiated Gastric Adenocarcinoma.

    Eivaz-Mohammadi, Sahar; Gonzalez-Ibarra, Fernando; Abdul, Waheed; Tarar, Omer; Malik, Khurram; Syed, Amer K


    A 25-year-old Hispanic female with a history of anemia, schizoaffective disorder, and psychosis was admitted for anemia associated with fatigue, weakness, shortness of breath, night sweats, weight loss, and abdominal and lower back pain for the past two months. On routine management, she was found to have a positive serum b-HCG of 80.4 (0-5 mIU/mL) but the patient denied any sexual activity in her life. During her admission, U/S of the pelvis was noncontributory. CT angiogram of the chest was significant for prominent mediastinal and hilar lymph nodes, diffusely thickened stomach suggesting gastric malignancy with multiple hypoenhancing lesions in the liver and diffuse lytic lesions in the spine and sacrum suspicious for metastatic disease. The MRI of the abdomen confirmed the CT angiogram findings. After these findings, EGD was performed which showed lesions in the antrum, body of the stomach, fundus, and cardia on the lesser curvature of the stomach body correlating with carcinoma. The biopsy was positive for Her2, b-HCG producing poorly differentiated gastric adenocarcinoma. Patient underwent one successful round of chemotherapy with Taxotene, Cisplatin, and 5-FU for Stage IV gastric adenocarcinoma.

  12. Anti-mitotic potential of 7-diethylamino-3(2 Prime -benzoxazolyl)-coumarin in 5-fluorouracil-resistant human gastric cancer cell line SNU620/5-FU

    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: [College of Pharmacy, Sookmyung Women' s University, Seoul 140-742 (Korea, Republic of)


    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.

  13. In vitro antiproliferative characteristics of flavonoids and diazepam on SNU-C4 colorectal adenocarcinoma cells.

    Lee, Sang-Woo; Lee, Jae-Tae; Lee, Maan-Gee; Lee, Ho Won; Ahn, Sohn Joo; Lee, Yong Jin; Lee, You La; Yoo, Jeongsoo; Ahn, Byeong-Cheol; Ha, Jeoung-Hee


    The need for beneficial use of sedatives in oncologic patients is increasing. Therefore, in this study, antiproliferative characteristics of herbal and synthetic sedatives were examined in vitro in SNU-C4 human colorectal adenocarcinoma cells. Apigenin (50% inhibition concentration, IC(50) = 1.8 +/- 0.5 microM) and diazepam (IC(50) = 7.0 +/- 0.5 microM) showed concentration-dependent inhibition of SNU-C4 cancer cell survival. Efficacy of cancer cell survival inhibition by apigenin and diazepam was much lower than that of 5-fluorouracil (5-FU), a known chemotherapeutic drug. However, 10(-6) M concentration of apigenin and diazepam potentiated 5-FU-induced cytotoxicity. In SNU-C4 cells, 10(-6) M concentrations of diazepam, flumazenil (Ro15-1788), Ro5-4864, or PK11195, all ligands for central- or peripheral-type benzodiazepine (BZD) receptors, inhibited cell survival like the flavonoid apigenin (4',5,7-trihydroxyflavone) and fisetin (3,7,3',4'-tetrahydroxyflavone). Also like the plant flavonoids, treatment with 10(-6) M concentration of diazepam for 3 days hardly affect the peripheral-type BZD receptor (PBR) messenger RNA (mRNA) expression and inhibited glucose utilization of SNU-C4 cells. Treatment with flavonoids or diazepam for 6 days upregulated PBR mRNA expression and cell cytotoxicity of SNU-C4 cells. Furthermore, treatment with 10(-6) M concentration of apigenin, a natural sedative material originating from traditional herbs, positively modulated BZD-induced antiproliferative cytotoxicity in SNU-C4 cells. Overall, the in vitro antiproliferative activity on SNU-C4 cancer cells of herbal sedatives, such as apigenin, plus additive enhancement of synthetic BZD- and 5-FU-induced antiproliferative activities, were shown. In conclusion, this study provides experimental basis for advanced trial in the future.

  14. Establishment and Characterization of 5-Fu-resistant Variant of Human Pancreatic Cancer Cell Line%人胰腺癌5-Fu耐药细胞株的诱导建立及细胞学特性研究

    宋鸿安; 赵翰林; 傅赞


    目的 建立稳定传代的抵抗5-Fu的人胰腺癌细胞株MiaPaca2-5-Fu, 并对细胞生物学特性进行研究.方法 逐步增加培养基中5-Fu的浓度,建立对5-Fu耐药的人胰腺癌细胞株MiaPaca2-5-Fu;采用WST法计算出MiaPaca2和MiaPaca 2-5-Fu的半数抑制浓度(IC50)和耐药指数(RI);检测MiaPaca2和MiaPaca2-5-Fu的生长曲线,计算2个细胞系的倍增时间并进行比较,用流式细胞仪技术检测其细胞周期.结果 5-Fu对MiaPaca2和MiaPaca2-5-Fu的IC50分别为(4.29±0.15) μg/mL、(41.55±2.79) μg/mL, RI为9.68(P=0.0019).根据生长曲线计算出MiaPaca2和MiaPaca2-5-Fu的倍增时间分别为(39.52±0.32) h、(43.27±0.33) h (P=0.0069), 2细胞株的G0/G1期、S期、G2/M期均存在显著性差异(P<0.01).结论 成功建立了对5-Fu耐药的人胰腺癌细胞系MiaPaca2-5-Fu, 耐药性能明显、稳定,适合于胰腺癌中5-Fu耐药机制的研究.

  15. Synchronous rectal adenocarcinoma and anal canal adenocarcinoma

    GU Jin; LI Jiyou; YAO Yunfeng; LU Aiping; WANG Hongyi


    It is difficult to distinguish a tectal carcinoma with anal metastases from coexistent synchronous anorectal carcinomas.The therapeutic strategy for rectal and anal carcinoma is so different that it should be clearly identified.Here,we report on the case of a 63-year-old man who presented with an upper-third rectal adenocarcinoma.Five months after resection,he developed an adenocarcinoma in the anal canal.The histological slides of both tumors were reviewed and immunohistochemical studies for cytokeratins(CKs)7 and 20 were performed.The index tumor demonstrated CK 7-/CK 20+and the second showed CK7+/CK20+.For this reason,we believe the present case had synchronous adenocarcinomas arising from anal canal and the rectum separately.It is very important to difierentiate the anorectal lesions pathologically because of the impact on the therapeutic options available,especially for the lesion arising in the anal canal.

  16. 刺参酸性黏多糖对5-FU治疗小鼠肝癌的减毒增效作用%Attenuated and synergized action of stichopus japonicus acid mucopolysaccharide combined with 5-FU on hepatocarcinoma22-bearing mouse

    代海华; 宋扬; 陈丹丹


    目的 探讨刺参酸性黏多糖(stichopus japonicus acid mucopolysaccharide,SJAMP)联合5-FU对肝癌小鼠肿瘤生长及免疫功能的影响,了解其对化疗药的减毒增效作用.方法 将60只小鼠随机分为正常对照组(生理盐水)、空白对照组(生理盐水)、5-FU组[5-FU 20 mg/(kg·d)]、SJAMP组[SLAMP 25 mg/(kg·d)]、SJAMP+低5-FU组[SLAMP 25 mg/(kg· d)和5-FU 10 mg/(kg·d)]和SJAMP+高5-FU组[SLAMP 25 mg/(kg·d)和5-FU20mg/(kg· d)].除正常对照组外其他各组均于右腋皮下接种H22 (Hepatocarcinoma22)细胞.接种后第2天开始给药,连续给药12 d后处死小鼠,计算抑瘤率、胸腺指数和脾脏指数,ELISA检测血清TNF-α和IL-2含量,中性红法检测腹腔巨嗜细胞吞噬功能,CCK-8法测定脾脏淋巴细胞增殖能力,MTT法测NK细胞杀伤功能,流式细胞术检测小鼠外周血T细胞亚群.结果 各干预组小鼠肿瘤生长明显受到抑制,SJAMP+高5-FU组抑瘤率(62.73%)高于5-FU组(55.53%),P=1.000.SJAMP组和SJAMP+低5-FU组小鼠脾脏指数显著高于其他组,P值均<0.05.SJAMP组和SJAMP+低5-FU组小鼠胸腺指数分别为(2.19±1.18)和(2.13±1.00) mg/g,高于5-FU组的(1.14±0.53)mg/g,P值分别为0.026和0.048;也高于SJAMP+高5-FU组的(1.07±0.49)mg/g,P值分别为0.011和0.020.各药物干预组TNF-α较空白对照组均降低,P值均<0.001.和空白对照组(33.27±6.13)相比,5-FU组(23.52±3.31)血清IL-2水平明显降低,P<0.001;SJAMP组(39.56±2.39)血清IL-2水平显著提高,P=0.001.与5-FU组相比,SJAMP组和联合用药组IL-2明显提高,P值均<0.001.SJAMP组和SJAMP+低5-FU组腹腔巨嗜细胞吞噬中性红能力显著高于正常对照组、空白对照组、5-FU组和SJAMP+高5-FU组,P值均<0.001;SJAMP+高5-FU组与5-FU组相比明显提高,P=0.012.SJAMP组和SJAMP+低5-FU组脾脏淋巴细胞增殖能力显著高于正常对照组(P值均<0.001)、空白对照组(P值均<0.001)、5-FU组(P值均<0.001)和SJAMP+高5-FU

  17. Clinical study of weekly taxol combined with cisplatin and 5-Fu in the treatment of advanced gastric carcinoma%周剂量紫杉醇联合DDP、5FU治疗晚期胃癌

    徐珍; 孔颖泽; 徐建忠


    目的 评价周剂量紫杉醇联合DDP、5FU治疗晚期胃癌的近期疗效和毒性反应.方法 紫杉醇60g/m2 d1.8.15,DDP25mg/m2 d1.8.15 ,5FU 500mg/m2 d1.8.15,四周为一周期,2周期评价疗效.结果 31例患者CR 1例,PR 12例,SD 11例,PD 7例,不良反应主要为骨髓抑制、脱发、恶心呕吐.结论 周剂量紫杉醇联合DDP、5FU治疗晚期胃癌疗效较好,不良反应可耐受.

  18. Study on the pharmacokinetics of longcirculating liposomal 5-FU in rats by HPLC%HPLC研究5-FU长循环脂质体大鼠体内药动学

    张奇; 邓英杰; 罗国安


    @@ 5-氟尿嘧啶(5-FU)长循环PEG化脂质体是一种控释、靶向制剂.它可以克服普通脂质体在生物体循环中存留时间短、易被肝脾巨噬细胞吞噬的缺点,延长5-FU在血中的作用时间.本实验对5-FU长循环脂质体在生物体内的药动学过程进行考察,并与5-FU水溶液进行比较,验证5-FU长循环脂质体的长循环性.

  19. Inhibition of proliferation of 5-FU combined with thermotherapy in human hepatoma cell line%5-氟尿嘧啶联合热疗对人肝癌细胞株的增殖抑制作用

    刘贤英; 徐茂凤; 金春香; 张巍; 李香俊; 杨慧慧; 孙寒


    目的 探讨5-氟尿嘧啶(5-FU)联合热疗诱导人肝癌细胞株(SSMC7721细胞)的增殖抑制率,细胞凋亡率及其对细胞周期进程的影响,旨在为肝细胞癌的综合治疗提供理论依据.方法 应用MTT比色法检测不同条件下对SSMC7721细胞的增殖抑制率,流式细胞仪检测细胞周期进程的变化及凋亡率,电子显微镜检测亚细胞结构改变.结果 单纯热疗组、5-FU组及联合组对SSMC7721细胞抑制率分别为18.4%、28.3%和52.7%,与对照组相比差异均有统计学意义(P均<0.01).流式细胞仪结果显示:G1期细胞增多,S期细胞减少、G2/M期细胞相对增多,细胞凋亡率升高,组间比较差异均有统计学意义(P<0.01或P<0.05),电子显微镜结果显示细胞核染色质趋边凝集、线粒体肿胀.结论 5-FU联合热疗能显著提高SSMC7721细胞的增殖抑制率,抑制SSMC7721细胞G1期向S期转化进程,诱导SSMC7721细胞凋亡及亚细胞结构改变.%Objective To investigate the inhibition rate of cell proliferation, cell apoptosis rate and their effects on the cell cycle proceeding of the SSMC7721 cell line when 5-FU combined with thermotherapy is induced into the cells, and then provide theoretical bases to the combined therapy of hepatocellular carcinoma. Methods The inhibition rate of cell proliferation was detected by the MTT under different conditions, the cell cycle proceeding and the cell apoptosis rate was detected by flow cytometry and the subcellular structure was detected by the electronmicroscope. Results The cell inhibition rate of the thermotherapy group, 5-FU group and the combinedgroup were 18.4% ,28. 3% and 52. 7% ,respectively. The inhibition rates in the latter two groups were significantly different to the thermotherapy group. The results of flow cytometry showed that the cell numbers increased in G1 stage decreased in S stage,and increased in G2/M stage;the cell apoptosis rate increased. There was significant difference between

  20. IDH1 R132H Mutation Enhances Cell Migration by Activating AKT-mTOR Signaling Pathway, but Sensitizes Cells to 5-FU Treatment as NADPH and GSH Are Reduced

    Qiu, Jiangdong; Huang, Keting; Wu, Mindan; Xia, Chunlin


    Aim of study Mutations of isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) gene were recently discovered in vast majority of World Health Organization (WHO) grade II/III gliomas. This study is to understand the effects of IDH1 R132H mutation in gliomagenesis and to develop new strategies to treat glioma with IDH1 R132H mutation. Materials and methods Over expression of IDH1 R132H in U87MG cells was done by transfecting cells with IDH1 R132H plasmid. MTT assay, scratch repair assay and western blot were performed to study effects of IDH1 R132H mutation on cell proliferation, migration, regulating AKT-mTOR signaling pathway and cell death respectively. NADP+/NADPH and GSH quantification assays were performed to evaluate effects of IDH1 R132H mutation on the production of antioxidant NADPH and GSH. Results We found that over expression of IDH1 R132H mutation decreased cell proliferation consistent with previous reports; however, it increased cell migration and enhanced AKT-mTOR signaling pathway activation. Mutations in isocitrate dehydrogenase (IDH) 1 also change the function of the enzymes and cause them to produce 2-hydroxyglutarate and not produce NADPH. We tested the level of NADPH and GSH and demonstrated that IDH1 R132H mutant stable cells had significantly low NADPH and GSH level compared to control or IDH1 wild type stable cells. The reduced antioxidants (NADPH and GSH) sensitized U87MG cells with IDH R132H mutant to 5-FU treatment. Conclusion Our study highlights the important role of IHD1 R132H mutant in up- regulating AKT-mTOR signaling pathway and enhancing cell migration. Furthermore, we demonstrate that IDH1 R132H mutation affects cellular redox status and sensitizes gliomas cells with IDH1 R132H mutation to 5FU treatment. PMID:28052098

  1. CD/5-FU联合亚叶酸钙对直肠癌细胞杀伤作用的研究%Antitumor Effects of Calcium Folinate and CD/5-FU on Human Rectal Carcinoma in Vitro

    陈纲; 李世拥; 于波; 安萍; 蔡慧芸; 郭文华


    目的:探讨亚叶酸钙(CF)联合5-氟胞嘧啶(5-FU)对转染胞嘧啶脱氨酶(CD)基因的直肠癌细胞的杀等作用方法:构建含CD基因的真核表达载体pCDA.应用四唑盐(MTT)比色试验检测瘤细胞的存活率,观察CF 联合5-氟尿嘧啶(5-FU)对CD阴性细胞及CF联合5-FU对CD阳性细胞的杀伤作用,同时观察CF对CD/5-FU旁观者效应的影响.结果:CF增强5-FU对8348细胞的杀伤作用.单独CD/5-FU和CD/5-FU联合CF对8348细胞的IC50分别为0.8 mmol/L、0.3 mmol/L,CF明显降低5-FU的IC50(P<0.01).CF对CD/5-FU系统的旁观者效应也有增强作用.结论:CF明显增强CD/5-FU系统对直肠癌细胞的杀伤效能,可作为一种增效剂应用于CD自杀基因治疗直肠癌.

  2. Long-term outcomes of trimodality treatment for squamous cell carcinoma of the esophagus with cisplatin and/or 5-FU. More than 20 years' experience at a single institution

    Fakhrian, Khashayar [Ruhr-Universitaet Bochum, Department of Radiation Oncology, Marien Hospital Herne and Sankt Josef Hospital Bochum, Bochum (Germany); Technische Universitaet Muenchen, Department of Radiation Oncology, Klinikum rechts der Isar, Munich (Germany); Universitaetsklinikum der Ruhr-Universitaet Bochum, Klinik fuer Strahlentherapie und Radio-Onkologie, Marienhospital Herne, Herne (Germany); Ordu, Arif Deniz; Molls, Michael [Technische Universitaet Muenchen, Department of Radiation Oncology, Klinikum rechts der Isar, Munich (Germany); Lordick, Florian [University Clinic Leipzig, University Cancer Center Leipzig (UCCL), Leipzig (Germany); Technische Universitaet Muenchen, Department of Internal Medicine III (Hematology/Oncology), Munich (Germany); Theisen, Joerg [Technische Universitaet Muenchen, Department of Surgery, Klinikum rechts der Isar, Munich (Germany); Haller, Bernhard [Technische Universitaet Muenchen, Institute for Medical Statistics and Epidemiology, Klinikum rechts der Isar, Munich (Germany); Omrcen, Tomislav [Technische Universitaet Muenchen, Department of Radiation Oncology, Klinikum rechts der Isar, Munich (Germany); University Hospital Split, Center of Oncology and Radiotherapy, Split (Croatia); Nieder, Carsten [Department of Oncology and Palliative Medicine, Nordland Hospital Trust, Bodoe (Norway); University of Tromsoe, Institute of Clinical Medicine, Faculty of Health Sciences, Tromsoe (Norway); Geinitz, Hans [Technische Universitaet Muenchen, Department of Radiation Oncology, Klinikum rechts der Isar, Munich (Germany); Krankenhaus der Barmherzigen Schwestern Linz, Department of Radiation Oncology, Linz (Austria)


    The purpose of this article is to report the outcome of neoadjuvant radiochemotherapy (N-RCT) + surgery in patients with squamous cell carcinoma of the esophagus at a single institution. We retrospectively reviewed data from patients who were referred to our department for N-RCT. From 1988-2011, 103 patients were treated with N-RCT with cisplatin and/or 5-fluorouracil (5-FU). Group 1: (n = 55) from 1988-2006 with 39.6-40 Gy and 5-FU with (n = 17) or without cisplatin (n = 38). Group 2: from 2003-2010 with 44-45 Gy and 5-FU with (n = 40) or without cisplatin (n = 8). All patients underwent radical resection with reconstruction according to tumor location and 2-field lymph node dissection. The degree of histomorphologic regression was defined as grade 1a (pCR, 0 % residual tumor), grade 1b (pSTR, < 10 % residual tumor), grade 2 (10-50 % residual tumor), and grade 3 (> 50 % residual tumor). Median follow-up time from the start of N-RCT was 100 months (range 2-213 months). The median overall survival (OS) for the whole cohort was 42 months and the 5-year OS was 45 ± 5 %. In the multivariate analysis, worse ECOG performance status (p < 0.001), weight loss > 10 % before the start of the N-RCT (p = 0.025), higher pT category (p = 0.001), and grade 2/3 pathologic remission (p < 0.001) were significantly associated with a poor OS. PCR and pSTR rates for group 1 were 36 % and 18 % compared to 53 % and 22 % for group 2 (p = 0.011). There was a tendency for a better outcome in group 2 patients without statistical significance. The 5-year OS, disease-free survival and recurrent-free survival were 36 ± 7 %, 35 ± 6, and 36 ± 7 % for group 1 and 55 ± 7, 49 ± 7, and 53 ± 7 in group 2 (p = 0.117, p = 0.124, and p = 0.087). There was no significant difference between the two groups considering the postoperative morbidity and mortality. Higher radiation doses and more use of simultaneous cisplatin lead to higher pathologic response rates to N-RCT and may be associated with

  3. Study on association of polymorphism of CYP450 2D6 with head and neck cancer and treatment response in patients receiving neoadjuvant chemotherapy paclitaxel, cisplatin, 5fu (TPF followed by chemoradiation

    Divyesh Kumar


    Results: Patients with CYP 2D6 1 showed good response to the therapy given, while CYP 2D6 4 and 10 were poor responders. Conclusion: There is a strong association of polymorphs of CYP 2D6 with occurrence of head and neck cancer. Response to treatment (TPF--CT-RT is polymorph graded. Our study thus provides an insight in to the concept of and ldquo;Right therapy to the right patient and rdquo;. [Int J Res Med Sci 2014; 2(2.000: 585-591

  4. 姜黄素对Bel7402/5-Fu细胞系多药耐药逆转作用的实验研究%Reversing Effects of Curcumin on Multi-drug Resistance of Bel7402/5-Fu Cell Line

    曹仕琼; 尹太勇; 扬盛力


    目的 研究姜黄素对肝癌耐药细胞系Bel7402/5-Fu多药耐药的逆转作用.方法 采用5-氟脲嘧啶( fluorouracil,Fu)药物浓度梯度递增法诱导建立肝癌耐药细胞亚系Bel7402/5 -Fu;四甲基偶氮唑盐比色(methyl thiazolyl tetrazolium,MTT)法检测肝癌细胞系Bel7402和肝癌耐药细胞系Bel7402/5-Fu对6种化疗药物的敏感性,计算两组细胞系对6种化疗药物的半数抑制剂量( IC50)和耐药指数(RI);MTT法检测姜黄素、5-Fu、姜黄素和5-Fu合用对肝癌耐药细胞系Bel7402/5-Fu抑制率的差异;流式细胞仪检测姜黄素、5-Fu、姜黄素和5-Fu合用对肝癌耐药细胞系Bel7402/5-Fu凋亡的影响.结果 肝癌耐药细胞系Bel7402/5-Fu对多种化疗药物表现出耐药性,其中对5-Fu耐药指数最高,为(109.55±14.30)倍.5、10、20μg/mL浓度的姜黄素联合5-Fu(1/2 IC50浓度)对细胞的抑制率分别为(21.47±1.49)%、(27.10±2.32)%、(59.37±2.45)%.5、10、20μg/mL浓度的姜黄素联合5-Fu作用后Bel7402/5-Fu的凋亡率分别为(30.92±2.10)%、(44.87±2.24)%、(50.36±2.58)%,明显高于姜黄素组和5-Fu组,且姜黄素浓度在0~20 μg/mL范围内,凋亡率随姜黄素浓度增加而增大.结论 姜黄素能促进肝癌耐药细胞系Bel7402/5-Fu的凋亡,同时具有良好的逆转其耐药性的效果.%Objective To investigate the reversing effects of curcumin on hepatocellular carcinoma drug resistance Bel7402/5-Fu cell line. Methods Through the exposure to gradual increased concentrations of 5-fluoroura-cii (5-Fu), the cell line Bel7402 was induced to establish a multi-drug resistant sub-cell line Bel7402/5-Fu. The sensitivity to 6 chemotherapeutics of Bel7402 and Bel7402/5-Fu were detected using methyl thiazolyl tetrazolium (MTT) assay. The 50% inhibitory concentration (IC50) and resistant index (Rl) were calculated. The differences of the inhibition ratio of Bel7402/5-Fu by curcumin, 5-Fu, curcumin combined with 5-Fu were detected using

  5. Genetic polymorphisms at TIMP3 are associated with survival of adenocarcinoma of the gastroesophageal junction.

    Morteza Bashash

    Full Text Available The poor survival of adenocarcinomas of the gastroesophageal junction (GEJ makes them clinically important. Discovery of host genetic factors that affect outcome may guide more individualized treatment. This study tests whether constitutional genetic variants in matrix metalloproteinases (MMP and tissue inhibitors of metalloproteinases (TIMP genes are associated with outcome of GEJ adenocarcinoma. Single nucleotide polymorphisms (SNPs at four TIMP (TIMP1-4 and three MMP genes (MMP2, MMP7 and MMP9 were genotyped in DNA samples from a prospective cohort of patients with primary adenocarcinoma of the GEJ admitted to the British Columbia Cancer Agency. Cox proportional hazards regression, with adjustment for patient, disease and treatment variables, was used to estimate the association of SNPs with survival. Genotypes for 85 samples and 48 SNPs were analyzed. Four SNPs across TIMP3, (rs130274, rs715572, rs1962223 and rs5754312 were associated with survival. Interaction analyses revealed that the survival associations with rs715572 and rs5754312 are specific and significant for 5FU+cisplatin treated patients. Sanger sequencing of the TIMP3 coding and promoter regions revealed an additional SNP, rs9862, also associated with survival. TIMP3 genetic variants are associated with survival and may be potentially useful in optimizing treatment strategies for individual patients.

  6. 血管生成抑制剂YH-16和氟尿嘧啶(5-FU)联合应用对结直肠癌肝转移的抑制作用%Inhibitory Effect of Angiogenesis Inhibitor YH-16 and 5-FU on Liver Metastasis of Colorectal Cancer

    韩芸; 杨桄权; 李智


    目的探讨分析血管生成抑制剂YH-16和5-氟尿嘧啶(5-FU)联合应用对结直肠癌肝转移的抑制作用。方法构建好结直肠癌肝转移动物模型,将42只裸鼠,随机分为四组:分别为生理盐水组12只、YH-16组10只、5-Fu组10只、YH-16联合5-Fu组10只,给药14d后处死。观察四组裸鼠各分级肝脏转移灶数及脾脏肿瘤的大小。结果 YH-16联合5-Fu组脾脏肿瘤体积小于生理盐水组、YH-16组、5-Fu组,具有差异性,有统计学意义(<0.05);YH-16组、5-Fu组、YH-16联合5-Fu组Ⅲ级肝脏转移灶数目低于生理盐水组,有统计学意义(<0.05)。YH-16联合5-Fu组Ⅱ、Ⅲ级肝脏转移灶低于YH-16组、5-Fu组,有统计学意义(<0.05)。结论血管生成抑制剂YH-16具有抑制结直肠癌转移作用,YH-16和5-FU具有协同抑制转移的作用,抑制效果比两者单独使用显著。%Objective To investigate the angiogenesis inhibitors YH-16 and 5-fluorouracil (5-FU)combined inhibition of colorectal cancer liver metastasis.Methods To build a good animal model of colorectal liver metastases to 42 nude mice,were randomly divided into 4 groups:normal saline group and 12,respectively,YH-16 10,5-Fu group 10,YH-16 joint 5-Fu group of 10,only for 14 days to be put to death.To observe the classification number of liver metastases and four groups of nude mice spleen tumor size.Results The YH-16 joint 5-Fu spleen tumor volume less than physiological saline group,YH-16,5-Fu group,has the difference was statistically significant ( <0.05);YH-16,5-Fu group,YH-16 joint number5-Fu groupⅢliver metastases is lower than the normal saline group,with statistical significance ( <0.05).YH-16 joint 5-Fu groupII,Ⅲliver metastases is lower than the YH-16,5-Fu group,with statistical significance ( <0.05).Conclusion Angiogenesis inhibitors can inhibit YH-16 colorectal cancer metastasis,YH-16 and 5-FU have the function of the synergistic inhibition transfer,significant inhibition

  7. 丹参注射液联合5-氟脲嘧啶腹腔化疗抗鼠胃肿瘤的实验研究%Experimental Study on Resistance to Implanted Gastric Tumor in Rats with Radix Salviae Miltiorrhizae and 5-Fu by Intraperitoneal Chemotherapy

    于庆生; 王汉明; 卢业才; 沈毅


    目的:观察丹参注射液对5-氟脲嘧啶(5-FU)抗肿瘤活性的增强作用及其对5-FU毒性和不良反应的减轻作用,为中药对抗肿瘤药的增效减毒作用提供实验依据.方法:应用Walker-256细胞株建立鼠种植性胃肿瘤模型,将60只Wistar雄性胃肿瘤大鼠随机分为3组:9.0 g/L氯化钠注射液(NS)组、5-FU组、5-FU+丹参组.接种后第7天,NS组每只每天腹腔注入NS,5-FU组每只每天腹腔注入5-FU,5-FU+丹参组每只每天腹腔注入5-FU+丹参,3组均连用5 d.于腹腔化疗结束后第7天每组处死10只大鼠.观察肿瘤体积抑制率、血常规、肝肾功能、细胞凋亡、大鼠生存时间.结果:①5-FU组和5-FU+丹参组鼠胃肿瘤生长明显缓慢,肿瘤体积较NS组明显减小(P﹤0.05,P﹤0.01),肿瘤体积抑制率分别为36.57%、59.44%(P﹤0.05);5-FU组和5-FU+丹参组鼠生存时间明显延长,生存时间延长率分别为23.7%、38.7%(P﹤0.05).②与NS组相比,5-FU组和5-FU+丹参组外周血WBC、PLT明显减少,血清ALT、AST、Cr、BUN明显升高,差异均有显著性(P﹤0.05,P﹤0.01);与5-FU组相比,5-FU+丹参组WBC、PLT显著升高,而ALT、AST、Cr、BUN显著下降(P﹤0.05,P﹤0.01).③与NS组相比,5-FU组和5-FU+丹参组凋亡面积增大,光密度明显升高(P﹤0.05,P﹤0.01);而5-FU+丹参组与5-FU组比较,差异也有显著性(P﹤0.05,P﹤0.01).结论:丹参注射液可增强5-FU诱导肿瘤细胞分化与凋亡,并能减轻5-FU所致的骨髓抑制和肝肾功能损害.


    Arockiasamy Babiya Infant


    Full Text Available BACKGROUND Primary adenocarcinoma of cervix constitutes 10-15% of all cases of carcinoma of cervix, which is the second most common carcinoma next to squamous cell carcinoma. Endocervical adenocarcinoma have a considerable morphological overlap with endometrial adenocarcinoma though they differ in their aetiologies, behaviour, and treatments. This makes their diagnosis very difficult particularly in biopsy or curetting specimens or when a fractional dilation and curettage specimens show adenocarcinoma in both components of it. This study was done in the aim to suggest the possible origin of the tumour with the help of immunohistochemistry. AIMS AND OBJECTIVES To identify the incidence, distribution, clinicopathological, histomorphological features of endocervical adenocarcinomas and to determine the immunohistochemical expression of CEA, Vimentin, ER and PR in endometrioid type of adenocarcinoma detected in endocervical biopsies, fractional dilation and curettage specimens (Both the components showing similar morphology, and in hysterectomy specimens to suggest the site of origin of tumour. MATERIALS AND METHODS It is a retrospective descriptive study of cervical adenocarcinomas conducted in the Institute of Obstetrics and Gynaecology, Madras Medical College, Chennai for a period of 4 years during the period between 2009 November to 2013 October. The statistical analysis was performed using statistical package for social science software version 11.5 the clinicopathological profile of the tumour were calculated using Student t-test and chi-square test. OBSERVATION AND RESULTS Among the total 13499 cases received during the study period, 2489 were cervical malignancies comprising 148 adenocarcinoma. It includes 101 mucinous (Endocervical type, 44 endometrioid type, 2 serous type, and 1 clear cell type. Among the 30 cases of endometrioid type, 16 cases showed definite immunophenotype of cervical origin, 9 cases of endometrial origin and in the

  9. 生脉注射液对5-FU增效减毒作用的实验研究%Experimental study on effects of Shengmai Injection: enhancing 5-FU anti-tumor efficacy and reducing its toxicity

    陈震; 王鹏; 黄雯霞; 刘鲁明


    目的:观察生脉注射液对5-氟尿嘧啶(5-fluorouracil, 5-FU)抗肿瘤的增效减毒作用.方法:建立H22肝癌荷瘤鼠模型后,将50只小鼠随机分为5组:对照组、5-FU组和生脉注射液(大、中、小剂量)联合 5-FU组,每组10只.造模次日开始进行干预处理:对照组、5-FU组和生脉注射液(大、中、小剂量)联合 5-FU组分别腹腔注射等容量生理盐水、5-FU、生脉注射液(大、中、小剂量)联合5-FU,共14 d.停药次日处死小鼠,观察瘤重抑制率、免疫功能、肝肾功能及外周血细胞变化.结果:生脉注射液联合5-FU各组小鼠的肿瘤生长抑制率明显高于5-FU组和对照组(P<0.05);与对照组相比,5-FU组CD3、CD4、CD4/CD8、IgG、IgM值明显降低(P<0.05),而各生脉注射液联合5-FU组CD3、CD4、CD4/CD8、IgG、IgM值升高(P<0.05);与对照组相比,5-FU组的血丙氨酸氨基转移酶升高、白细胞和血小板数量降低(P<0.05);而各生脉注射液联合5-FU组血丙氨酸氨基转移酶与对照组比较无明显变化,白细胞数下降程度较轻.结论:生脉注射液可增加5-FU的抑瘤效果,提高机体免疫功能,减轻化疗毒副反应.

  10. Synergistic antitumor effect of TRAIL and 5-Fu on the colon carcinoma cell line HT-29%5-Fu与TRAIL联用抗结肠癌细胞株HT-29效应的实验研究

    毛淑华; 于水静; 晏菊芳; 姬玲玲; 黄英


    目的 观察肿瘤坏死因子相关凋亡诱导配体(TRAIL)与5-氟尿嘧啶(5-Fu)联用对结肠癌细胞株HT-29体外生长增殖、凋亡的影响,评价其联用效果.方法 体外培养HT-29细胞,采用磺基罗丹明B(SRB)法测定细胞的存活率,Webb系数法判断联用是否具协同作用,流式细胞FITC-Annexin V/PI双染法检测细胞的凋亡.结果 结肠癌细胞株HT-29对TRAIL不敏感(IC50>10 μg·mL-1),对5-Fu敏感(IC50<10 μg·mL-1);0.1、1、10 μg·mL-1 TRAIL分别与0.05、0.1、0.5 μg·mL-1 5-Fu联用48 h,除0.1 μg·mL-1 TRAIL与0.5 μg·mL-1 5-Fu联用组外,其余联用组细胞存活率均明显低于TRAIL单用组或5-Fu单用组水平;0.1 μ·mL-1 TRAIL及0.5 μg·mL-1 5-Fu单用或联用时,HT-29细胞凋亡率分别为8.6%、18.1%和30.8%.结论 5-Fu 与TRAIL联用具有协同的细胞毒和细胞凋亡作用.

  11. Synthesis of Sensitive Polyelectrolyte Complex Nanoparticles and the Controlled Release of 5-FU%敏感性聚电解质纳米粒子的制备及对5-FU的控制释放

    戚旻熠; 于娜娜; 李桂英


    以壳聚糖( CS)和海藻酸钠( SA)为原料,通过接枝共聚制备了壳聚糖接枝聚N-乙烯基吡烙烷酮( CS-g-PVP)和海藻酸钠接枝聚N-乙烯基吡烙烷酮(SA-g-PVP),然后利用静电自组装得到了pH敏感性聚电解质纳米粒子,研究了纳米粒子对5-氟尿嘧啶的负载及释放性能的影响。傅立叶红外光谱验证了聚合物的结构。当CS-g-PVP与SA-g-PVP体积比为3∶7时,形成的纳米粒子结构最稳定。透射电镜表明纳米粒子具有较规则的球形结构,尺寸在30~50 nm左右。聚电解质纳米粒子对5-FU表现出较高的负载能力,环境pH值和离子强度等因素对5-FU的释放有影响。%pH-sensitive polyelectrolyte complex nanoparticles assembled from chitosan-graft-poly ( 1-vinyl-2-pyrrolidone) (CS-g-PVP) and sodium alginate-graft-poly(1-vinyl-2-pyrrolidone) (SA-g-PVP) were prepared for entrapment and release of 5-fluorouracil ( 5-FU ) . The structure of polymers was determined by fourier-transformed infrared spectroscopy ( FTIR) . The highly aggregated nanoparticle was formed at the weight ratio of CS-g-PVP and SA-g-PVP is 3∶7 with a core formed from positively charged CS and negatively charged SA and a shell formed from hydrophilic PVP. The size and morphology of the nanoparticles was observed by transmis-sion electron microscopy ( TEM) . The dried particles gave the normally spheres with an average diameter of 30~50 nm. The CS-g-PVP/SA-g-PVP polyelectrolyte complex nanoparticles exhibited high drug loading content and encapsulation efficiency for 5-FU. Decreasing pH to weak acid or increasing ionic strength of nanoparticles solution,a sustained and controlled drug release was observed due to the deformation of nanoparticles.

  12. Anticancer Effect of 5-Florouracil Combined with Extract of Rosa roxburghii Tratt on Human Endometrial Adenocarcinoma%刺梨提取物联合5-氟尿嘧啶抗人子宫内膜腺癌作用

    戴支凯; 杨小生; 余丽梅


    Objective To investigate anticancer effects of 5-florouracil (5-FU) combined with CL, extract of Rosa roxburghii Tratt on human endometrial adenocarcinoma cell line (JEC). Methods JEC cells cultured in vitro in the logarithmic growth phase were seeded in the culture plate and divided into the control group (RPMI 1640), the positive group (10~4 mol/L 5-FU), the CL groups (at the dose of 0.01, 0.1, 1, 10, and 100 ug/mL), and the CL (0. 01, 0.1, 1, 10, and 100 ug/mL) combined with 5-FU groups. Effects of 5-FU combined with CL on JEC cell growth were drawn and measured by MTT and growth curves. Effects of CL combined with 5-FU on the JEC cell differentiation was analyzed by detecting the reduction capability of nitrobenzene thiocyanate (NBT) and lactate dehydrogenase (LDH) contents in the cultured medium. Effects of CL combined with 5-FU on the JEC cell apoptosis and cell proliferation cycle were detected by acridine orange (AO)/ethidium bromide (EB) fluorescent staining and flow cytometry (FCM). Results The proliferation inhibitory effect of CL combined with 5-FU on JEC cells was enhanced when compared with that of CL or 5-FU alone (P<0.05). The percentages of NBT positive JEC cells and apoptotic JEC cells increased in the 5-FU combined with CL groups when compared with 5-FU group or the CL group alone (P<0.05). The LDH concentration of the JEC cell culture supemate decreased in 5-FU combined with CL groups (P<0.05). Furthermore, the percentage of G0-G1 phase JEC cells treated by 5-FU combined with CL was higher than that of 5-FU or CL alone (P <0.05). Conclusion CL could enhance anticancer effects of 5-FU. Its mechanisms might be correlated with reinforcing the cytotoxicity of 5-FU, inducing cell differentiation and apoptosis, and inhibiting cell proliferation and division.%目的 探讨刺梨提取物(CL)联合5-氟尿嘧啶(5-florouracil,5-FU)的抗子宫内膜腺癌细胞株(JEC)作用.方法 将体外培养的指数生长期细胞接种于培

  13. Improved survival for hepatocellular carcinoma with portal vein tumor thrombosis treated by intra-arterial chemotherapy combining etoposide, carboplatin, epirubicin and pharmacokinetic modulating chemotherapy by 5-FU and enteric-coated tegafur/uracil: A p


    AIM: To investigate the poor prognosis of HCC with PVTT, we evaluated the efficacy by a new combination chemotherapy for advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT).METHODS: From 2002 to 2007, a total of 10 consecutive patients with Stage IVA HCC accompanied by PVTT were studied prospectively to examine the efficacy of treatment by intra-arterial infusion of a chemotherapeutic agents consisting of etoposide, carboplatin, epirubicin and pharmacokinetic modulating chemotherapy by 5-FU and enteric-coated tegafur/uracil.RESULTS: The mean course of chemotherapy was 14.4 (range, 9-21) mo. One patient showed complete response (CR) with disappearance of HCC and PVTT after treatment, and the two patients showed partialresponse (PR), response rate (CR + PR/All cases 30%).The median survival time after the therapy was 457.2 d. The one-year survival rate was 70%. Adverse reactions were tolerable.CONCLUSION: Although the prognosis of most patients with Stage IVA HCC by PVTT is poor, our combination chemotherapy may induces long-term survival and is an effective treatment and produced anti-tumor activity with tolerable adverse effects in patients for advanced Stage IVA HCC accompanied by PVTT.

  14. ADM与5Fu可抑制MDA-MB231乳癌细胞的SNCG表达%ADM and 5Fu inhibit the synuclein-γexpression of MDA-MB231 breast cancer cells

    袁光波; 张幸平; 何金花; 唐卫军; 陈睿


    目的 研究乳癌临床常用化疗药物顺铂(ciaplalin or DDP),阿霉素(adriamycin,ADM),氟尿嘧啶(fluorouradl,5Fu)对MDA-MB231乳癌细胞SNCG表达的干扰效应.方法 通过RT-PCR及免疫组织化学法检测上述药物处理组和阴性对照组MDA-MB231细胞的SNCG表达状况,用Quantity One软件及北航真彩色医学图像处理系统(CM-20008)分别对各组SNCG mR-NA和蛋白相对表达水平进行分析.结果 ADM和5Fu处理组与阴性对照组比较,MDA-MB231细胞的SNCG mRNA及蛋白表达水平差异均有统计学意义(P值均小于0.05),而DDP处理组表达水平与对照组无差别.结论 ADM和5Fu可抑制MDA-MB231细胞的SNCG表达.

  15. Synergistic Inhibitory Effect of survivin siRNA in Combination with 5-Fu on Inhibiting Proliferation of MCF-7 Cells%靶向survivin siRNA与5-Fu协同抑制MCF-7细胞增殖

    薛兴欢; 张淑群; 姜建涛; 王西京; 薛锋杰; 刘晓旭


    目的 研究以survivin为靶标的小干扰RNA(siRNA)与化疗药5-Fu联合应用抑制MCF-7细胞增殖的作用.方法 以脂质体为载体,将survivin siRNA转染至MCF-7细胞中,用四氮唑盐(MTT)法染色并计算siRNA联用5-Fu对MCF-7细胞的抑制率,用SAS统计软件及金正均Q值法进行统计分析.结果 单用5-Fu,TC50为4.42μg/ml;加入5 nmol/L siRNA后,IC50降为1.18μg/ml;siRNA与5-Fu联用的抑制作用较单用5-Fu强(F=26.74,P<0.01);Q值分析表明survivin siRNA与中低浓度的5-Fu联用,有较好的协同作用(Q≥1.15).结论 survivin siRNA与5-Fu联用,可显著增强对MCF-7细胞增殖的抑制,提高肿瘤细胞对化疗药物的敏感性.

  16. Adjuvant post-operative radiotherapy vs radiotherapy plus 5-FU and levamisole in patients with TNM stage II-III resectable rectal cancer. A phase III randomized clinical trial

    Cafiero, F.; Gipponi, M.; Di Somma, C. [Istituto Nazionale per la Ricerca sul Cancro, Geneo (Italy). Istituto di Oncologia Clinica] [and others


    Loco-regional and distant relapses contribute to impair the outcome of rectal cancer patients. As to the former, either pre-or post-operative radiation therapy (RT) significantly reduce loco-regional recurrence; post-operative chemotherapy (CT), alone or in different combinations with RT, is effective in improving both disease-free survival and survival. However, many drawbacks still exist regarding the method of RT delivery as well as the toxicity of combination adjuvant chemotherapy. The aim of this trial is to assess the effectiveness and toxicity of adjuvant post-operative RT vs combined RT and CT (5-FU plus levamisole) in patients with TNM stage II-III resectable rectal cancer (pT3-4, pN0, M0; pT1-4, pN1-3, M0). The primary endpoint is overall survival; secondary endpoints are disease-free survival rate of loco-regional recurrence, and treatment-related toxicity/morbidity. (author).

  17. Effect of 5-FU,ADM combined with X-ray irradiation on livin expression and apoptosis of breast cancer cell line MCF-7%5-FU、ADM联合X线外照射对乳腺癌MCF-7细胞Livin表达及凋亡的影响

    周涛琪; 张幸平; 程丽; 蒋骞; 饶明月


    目的:观察抗肿瘤药物氟尿嘧啶(5-fluorouracil,5-FU)、阿霉素(Adriamycin,ADM)联合X线外照射对人乳腺癌MCF-7细胞Livin基因表达的干扰效应及对细胞凋亡的影响.方法:用MTT法分别测定5-FU、ADM 2种药物作用MCF-7细胞72 h的半数抑制浓度(Half maximal inhibitory concentration of a substance,IC50).实验分为空白对照组、单纯照射组、5-FU+照射组、ADM+照射组.通过免疫组化法及RT-PCR法检测各组细胞Livin蛋白及mRNA的表达,同时应用流式细胞术检测细胞的凋亡率.结果:与空白对照组比较,单纯照射组、5-Fu+照射组、ADM+照射组的Livin蛋白、mRNA的表达均减少而凋亡率增加(P<0.05),5-FU+照射组、ADM+照射组的Livin蛋白、mRNA的表达较单纯照射组减少明显,且前2组细胞的凋亡率增加,差异具有统计学意义(P<0.05).结论:5-FU、ADM联合X线外照射可提高乳腺癌MCF-7细胞的凋亡率,具有放射增敏作用,其作用机制可能与下调Livin基因的表达有关.%Objective:To observe 5-FU, ADM combined with X-ray irradiation on intefferring gene expression of Livin and apeptosis of human breast cancer cell line MCF-7. Methods :The IC50 of 5-FU, ADM were detected by MTT in the time of 72 h. The experiment had four groups: blank control group, irradiation group, 5-FU + irradiation group, ADM + irradiation group. The Immunohistochemistry and RT-PCR were used to evaluate the Livin protein and mRNA expression,the apoptosis rate was analysed by flow cytometry. Results: Compare the blank control group with other groups, the Livin protein and mRNA expression of irradiation group ,5-FU + irradiation group, ADM + irradiation group were reduced,and apoptosis rate increased (P<O.O5).While the effect of 5-FU, ADM combined with irradiation inhibited Livin protein, mRNA expression significantly compared with the irradiation group, and the apoptosis rate were increased, the differences were statistically significant (P<O.O5

  18. 5-FU乙醇脂质体制备及局部植入治疗家兔喉气管狭窄的效果分析%Preparation of Ethosomes encapsulated with 5-fluorouracil and the effect of local administered 5-FU ethosomeon on laryngotracheal stenosis of rabbit

    杨希之; 敖华飞; 程雪峰; 顾健; 孔德秋; 毛小慧


    Objective;To evaluate the efficacy of Ethosomes encapsulated with 5-FU in treatment of laryngotracheal stenosis in rabbit models. Method;The 5-FU ethosome was prepared by the thin film hydration method, and the size distribution and the encapsulation efficiency was investigated. The tracheal mucosa was scraped about 0. 5 cm in width with a nylon brush to induce the scar formation in the airway,then animals were divided into three groups:5-FU ethosome group,5-FU group and saline group. Drugs were injected into scar by paracentesis under endoscope in each group respectively. The severity of stenosis was observed under laryngofiberoscope immediately, 7,14,21 days after administration. Result; Airway stenosis of 5-FU ethosome group was not significantly different compared with 5-FU group at 7 days after administration, but 5-FU ethosome significantly reduced the airway stenosis at 21 days after administration when compared with 5-FU group and no restenosis was noticed during the observation period. Conclusion;Ethosomes encapsulated with 5-FU was effective for laryngotracheal stenosis. It is a ptentially new method for ameliorating airway stenosis originated from granulation tissue.%目的:评价5-氟尿嘧啶(5 FU)脂质体对家兔瘢痕性喉气管狭窄的治疗效果.方法:利用薄膜分散法制备5-FU乙醇脂质体,并检测脂质体形态、包封率等特性.采用刮擦法制备喉气管狭窄模型,环形刮除气管黏膜约0.5cm宽度,诱导气管内瘢痕形成,将诱导瘢痕性喉气管狭窄成功的模型动物随机分为3组:5-FU乙醇脂质体组(A组)、5-FU水溶液组(B组)和生理盐水组(C组),各组分别在内镜监视下经皮穿刺将药物注射入瘢痕内部,并记录此时狭窄度,记为0d,其后,在用药后7、14、21d纤维喉镜下观察记录气管狭窄情况.结果:治疗初期A组和B组并无差别,21d时A组狭窄度明显小于B组,并在观察期间没有出现再狭窄.结论:5-FU脂质体对家兔瘢痕型喉气管

  19. Study on Salviae Miitiorrhizae Injection in Combination with 5-Fu for the Apoptosis of Lewis Lung Tumor Mice%丹参注射液联合5-氟尿嘧啶对小鼠Lewis 肺癌细胞凋亡的影响

    冯俭; 余晓颖; 谢萍; 秦银花; 孙川; 张煜华; 张梦云; 杨张婧; 莫小宇; 王倩


    目的 探讨丹参注射液联合5-氟尿嘧啶(5-Fu)对小鼠Lewis肺癌细胞凋亡的作用.方法 将60只Lewis肺癌荷瘤C57BL/6小鼠随机分为模型组,丹参高、低剂量组(丹高组、丹低组),5-Fu组,丹参高、低剂量联合5-Fu组(丹低+5-Fu组、丹高+ 5-Fu组),每组10只.各组于接种第2日起每天腹腔注射给药0.2ml/只,5-Fu组连续给药5天,联合组先给5-Fu及丹参注射液混合液5天,后继续给予丹参注射液5天.其余各组均连续给药10天.末次给药24h后摘眼球取血再脱颈椎处死,观察血常规、瘤体重量、肺癌细胞凋亡指数、主要脏器转移灶数目及病理改变.结果 丹参低剂量组和丹参高剂量组瘤体重量较模型组降低(P<0.05),5-Fu组、丹参低剂量+5-Fu、高剂量+5- Fu组较模型组瘤体重量明显减轻(P<0.01).丹参高剂量组、5-Fu组、丹参低剂量+5-Fu组及丹参高剂量+5-Fu组瘤体细胞凋亡指数与模型组比均增高(P<0.05).结论 丹参注射液能够增强5-Fu对肿瘤的抑制,有增强小鼠Lewis肺癌细胞凋亡作用的趋势.%Objective To observe the effect of Danshen (Radix Salviae Miltiorrhizae ) Injection used together with 5-flu-orouracil (5-Fu) on the apoptosis of Lewis lung tumor mice. Methods Sixty C57BL/6 mice with Lewis lung tumors were randomized into model control group, Danshen high-dose group and low-dose group, 5-Fu group, Danshen high-dose with 5-Fu group, and Danshen low-dose with 5-Fu group, with 10 in each. All mice were intraperitoneally injected 0. 2ml everyday from the second day of inoculation. The 5-Fu group was injected for 5 days in succession, the united 5-Fu groups were given the mixture of 5-Fu and Danshen injection first for 5 days and then Danshen injection in continuation for 5 days, and the other groups were all given medicine for 10 days in succession. Twenty-four hours after the last administration, the eyeballs of mice were removed for collecting the orbital blood, and then were

  20. Synchronous gastric adenocarcinoma and pancreatic ductal adenocarcinoma

    Mirko Muroni; Francesco D'Angelo; Massimo Pezzatini; Simone Sebastiani; Samantha Noto; Emanuela Pilozzi; Giovanni Ramacciato


    BACKGROUND: The association between gastric and pancreatic carcinoma is a relatively rare condition. In gastric carcinoma patients, the prevalence of second tumors varies 2.8% to 6.8% according to the reported statistics. Gastric cancer associated with pancreatic cancer is uncommon. METHODS: We report a case of a 73-year-old patient hospitalized for vomiting and weight loss. Esophagogastro-duodenoscopy demonstrated an ulcerative lesion of the gastric antrum. Computed tomography and magnetic resonance showed a gastric thickening in the antral and pyloric portion and a nodular mass (3×1.7 cm) in the uncinate portion of the pancreas. RESULTS: The patient underwent pancreaticoduoden-ectomy according to Whipple regional typeⅠFortner. Histological examination of the specimen demonstrated a moderately differentiated adenocarcinoma of the stomach and a poorly differentiated ductal adenocarcinoma of the pancreas. CONCLUSIONS: Long survival is rare in patients with associated gastric and pancreatic cancer. Surgical resection remains the only potentially curative treatment.

  1. Apocrine adenocarcinoma of the vulva

    Babita Kajal


    Full Text Available Cutaneous vulvar carcinomas are predominantly of squamous cell carcinoma type. Primary vulvar adenocarcinomas are rare with a poorly understood histogenesis. They are classified into extramammary Paget’s disease, sweat gland carcinomas, and breast-like adenocarcinomas of the vulva. Adenocarcinomas, originating from Bartholin glands, can also present as vulvar adenocarcinoma. Rare adenocarcinomas with apocrine features have been described in the literature. The origin of these neoplasms from the native apocrine sweat glands or from anogenital mammary-like glands is still debatable. We report herein a case of a 67 year old female with a rare primary apocrine carcinoma of the vulva.

  2. 沙利度胺口服联合5-FU和顺铂腹腔灌注治疗恶性腹水%Thalidomide combined with 5-FU Cisplatin in the treatment of malignant ascites

    李亚星; 孙根林


    目的 探讨沙利度胺治疗恶性腹水的疗效及其可能机制.方法 选择胃癌20例、直肠癌10例、卵巢癌10例,经腹水细胞学证实为恶性腹腔积液病例,对照组采用顺铂60mg加入生理盐水250 mL,5-FU 500 mg加入生理盐水250 mL腹腔灌注,而实验组在上述腹腔灌注的基础上加用沙利多胺8 mg/(kg?d)口服每晚1次.采集腹水用ELISA法检测腹水中VEGF、MMP-9、TNF-a的浓度.结果 实验组和对照组相比腹水中TNF-a、VEGF和MMP-9均有下降,P值分别<0.01、0.05和0.05.实验组和对照组相比CR、NC无差异,PR、PD有差异(P<0.05),CR+ PR+ NC有差异(P<0.05).结论 沙利度胺抑制TNF-a表达从而抑制VEGF和MMPs表达,抑制腹水的生成.%Objective To observe effect of Thalidomide in the treatment of malignant as cites and its possible mechanism. Methods Twenty patients with gastric cancer, 10 cases with rec tal cancer, 10 cases of ovarian cancer were confirmed with malignant ascites by ascites cytology cas es. In the control group, Cisplatin 60 mg, 5 - FU 500 mg, together with 250 mL normal saline were perfused intraperiton. But in the experimental group, oral Salle polyamine 8 mg/(kg·d) was added one night on the basis of the intraperitoneal infusion. Ascites was collected to determine con centrations of VEGF, MMP - 9, and TNF- a in ascites by EL1SA. Results Compared with the control group, TNF- a, VEGF and MMP - 9 in ascites of the experimental group were decreased. P values were less than 0.01, 0.05 and 0.05. CR and NC had no significant difference (P>0.05) in the two groups. PR differed from PD (P<0.05), CR + PR + NC were different (P<0.05). Conclusion Thalidomide inhibits TNF - a expression and thus inhibits the expression of VEGF and MMPs, and eventually inhibits the formation of ascites.

  3. 脂质体介导Clusterin反义寡核苷酸抑制胰腺癌细胞侵袭力及增强5—FU化疗敏感性的实验研究%Liposome-mediated clusterin antisense oligodeoxynucleotides inhibit invasion and chemosensitize human pancreatic cancer cells

    迟绍云; 焦学龙; 王宝泉; 刘春生; 王蕾; 贾旭亮; 牛珉


    目的 研究Clusterin反义寡聚脱氧核苷酸(Clusterin ASO)对胰腺癌细胞侵袭力及5-FU化疗敏感性的影响.方法 采用脂质体法将Clusterin ASO转染PANC-1细胞24 h,然后将该细胞暴露于不同浓度的5-FU中,TUNEL法检测72 h后的细胞凋亡指数,MTT检测细胞增殖并计算IC50.观察Clusterin ASO转染对PANC-1细胞体外侵袭力的抑制作用.采用免疫组化,Western blot和RT-PCR技术检测不同处理组细胞中Clusterin和其mRNA和蛋白表达.结果 Clusterin ASO转染可有效沉默PANC-1细胞内Clusterin mRNA及蛋白表达;PANC-1细胞的5-FU IC50为9±0.7,PANC-1/Clusterin ASO的5-FU IC50为1.06±0.3,敏感性增加了9倍.5-FU以剂量依赖方式诱导PANC-1细胞凋亡,但对PANC-1/Clusterin ASO细胞所诱导的凋亡比PANC-1细胞更明显.重组细胞基膜侵袭实验显示,PANC-1细胞与PANC-1/Clusterin ASO细胞的穿透基膜细胞数分别为213±18个和43±8个/高倍镜(×200),差异有统计学意义(P<0.05).结论 靶向Clusterin抑制胰腺癌细胞侵袭力和增殖,并增强胰腺癌细胞对5-FU的化疗敏感性.%Purpose To investigate whether clusterin gene silencing by antisense clusterin oligodeoxynucleotides ( ASO ) can inhibit invasion and metastasis and chemosensitize 5-FU in human pancreatic cancer cell line PNAC-1. Methods Clusterin ASO was transfected into PANC-1 cells for 24 h by Lipofectamine 2000 methods, and then the cells in different groups were treated with serial concentrations ( 0. 01 ~ 100 μmol/L ) of 5-FU for 72 h. The 50% inhibitory drug concentration ( IC50 ) was obtained by MTT assay. The apoptosis was assessed by TUNEL staining. The inhibitory effects of clusterin ASO on invasion and metastasis were detected by Transwell motility assay. RT-PCR and Western blot were used to detect the clusterin protein and mRNA in PANC-1 cells in vitro. Results Clusterin expression was inhibited in PANC-1 cells in clusterin ASO groups. The inhibitory effect of cell growth was seen

  4. Sensitity of LOVO cells to 5-FU can be improved by silencing survivin gene with RNAi technology%RNA干扰沉默survivin基因提高大肠癌LOVO细胞对5-FU敏感性的研究

    郑欣; 郭文


    目的 研究以survivin为靶标的小十扰RNA(siRNA)与化疗药5-氟尿嘧啶(5-FU)联合应用抑制LOVO细胞增殖的作用.方法 利用筛选出的有效siRNA干扰survivin基因的靶序列.以脂质体为载体,将survivin siRNA转染至人大肠癌LOVO细胞中,用cell counting kit-8(CCK-8)法染色并计算5-FU及siRNA联用5-Fu时LOVO细胞的抑制率.结果 单用5-Fu处理细胞,其IC50为0.56μg/mL.而加入5 pmol siRNA后,其IC50降为0.28μg/mL,siRNA与5-Fu联用对LOVO细胞的抑制作用较单用5-FU明显增强(F=28.4,P<0.01);Q值分析表明survivin siRNA与中低浓度的5-Fu联用,有较好的协同作用(Q≥1.15).结论 survivin siRNA可显著增强5-FU对LOVO细胞增殖的抑制,提高肿瘤细胞对化疗药物的敏感性,克服耐药性的产生.

  5. Establishment and characterization of a cisplatin-resistant cell line (IGSK-1) from a poorly differentiated gastric adenocarcinoma.

    Ohi, Satoshi; Takahashi, Naoto; Ninomiya, Kouzou; Nakajima, Masako; Hashimoto, Hisashi; Tachibana, Toshiaki; Yanaga, Katsuhiko; Ishikawa, Hiroshi


    We successfully established a spontaneously cisplatin-resistant tumor cell line (designated as IGSK-1) derived from original gastric carcinoma. The patient was a 75-year-old Japanese woman. The histopathological diagnosis was gastric poorly differentiated adenocarcinoma accompanied with metastatic foci in lymph nodes, pT3, N2 M0, stage IIIB. The IGSK-1 cells grew as adhesive and monolayered cultures on the bottom of dishes. The susceptibility of the IGSK-1 cells to anti-cancer drugs was examined using oxygen electrode apparatus (Daikin, Tsukuba, JPN), and the results suggested TXL was effective, and CDDP, CPT-11 and 5-FU were not effective. Gastrin and somatostatin secretions were confirmed by immunohistochemical staining and also radioimmunoassay. Immunohistochemistry and radioimmunoassay for serotonin suggested the IGSK-1 cells might incorporate serotonin from the growth media. Spontaneously cisplatin-resistant gastric carcinoma cell line secreted gastrin and somatostatin is very important material for chemotherapy.

  6. Preparation and Preliminary Exploration of Antitumor Activity of mPEG/BSA/5-FU%单甲氧聚乙二醇/牛血清白蛋白/5-氟尿嘧啶的制备及其抑瘤活性初探

    罗晓琴; 戴会群; 朱颖杰; 张武雄; 朱亮


    目的:制备单甲氧聚乙二醇/牛血清白蛋白/5-氟尿嘧啶(mPEG/BSA/5-FU)偶联物,以延长5-FU的半衰期并降低其达峰浓度,同时初步探讨偶联物的抑瘤活性.方法:通过在5-FU的N-1处引入乙酸基后再制成活性酯并与BSA偶联,用mPEG修饰偶联物而得mPEG/BSA/5-FU.60只小鼠皮下注射H22肝癌细胞腹水建立实体瘤模型后随机分为生理盐水组、5-FU(25 mg·kg-1·d-1)组、BSA/5-FU组(以5-FU计25mg·kg-1·d-1)及mPEG/BSA/5-FU(以5-FU计50、25、12.5mg·kg-1·d-1)剂量组共6组.分别腹腔注射相应试药10 d后处死,计算各组抑瘤率等.结果:得到了偶联率为32.89%的BSA/5-FU,修饰度为48.37%的mPEG/BSA/5-FU.同等5-FU剂量下mPEG/BSA/5-FU组、5-FU组、BSA/5-FU组的抑瘤率分别为40.51%、33.63%、20.54%(P<0.01).结论:制备mPEG/BSA/5-FU偶联物的偶联反应及修饰反应的工艺简单,抑瘤实验显示所得目标产物的抑瘤率明显高于5-FU组和BSA/5-FU组.

  7. The anticancer effect of (1S,2S,3E,7E,11E)-3,7,11, 15-cembratetraen-17,2-olide(LS-1) through the activation of TGF-β signaling in SNU-C5/5-FU, fluorouracil-resistant human colon cancer cells.

    Kim, Eun-Ji; Kang, Jung-Il; Kwak, Jeon-Won; Jeon, Chan-Hee; Tung, Nguyen-Huu; Kim, Young-Ho; Choi, Cheol-Hee; Hyun, Jin-Won; Koh, Young-Sang; Yoo, Eun-Sook; Kang, Hee-Kyoung


    The anticancer effect of (1S,2S,3E,7E,11E)-3,7,11,15-cembratetraen-17,2-olide (LS-1) from Lobophytum sp. has been already reported in HT-29 human colorectal cancer cells. In this study, we examined the effect of LS-1 on the apoptosis induction of SNU-C5/5-FU, fluorouracil-resistant human colon cancer cells. Furthermore, we investigated whether the apoptosis-induction effect of LS-1 could arise from the activation of the TGF-β pathway. In SNU-C5/5-FU treated with LS-1 of 7.1 μM (IC50), we could observe the various apoptotic characteristics, such as the increase of apoptotic bodies, the increase of the sub-G1 hypodiploid cell population, the decrease of the Bcl-2 level, the increase of procaspase-9 cleavage, the increase of procaspase-3 cleavage and the increase of poly(ADP-ribose) polymerase cleavage. Interestingly, the apoptosis-induction effect of LS-1 was also accompanied by the increase of Smad-3 phosphorylation and the downregulation of c-Myc in SNU-C5/5-FU. LS-1 also increased the nuclear localization of phospho-Smad-3 and Smad-4. We examined whether LS-1 could downregulate the expression of carcinoembryonic antigen (CEA), a direct inhibitor of TGF-β signaling. LS-1 decreased the CEA level, as well as the direct interaction between CEA and TGF-βR1 in the apoptosis-induction condition of SNU-C5/5-FU. To examine whether LS-1 can induce apoptosis via the activation of TGF-β signaling, the SNU-C5/5-FU cells were treated with LS-1 in the presence or absence of SB525334, a TGF-βRI kinase inhibitor. SB525334 inhibited the effect of LS-1 on the apoptosis induction. These findings provide evidence demonstrating that the apoptosis-induction effect of LS-1 results from the activation of the TGF-β pathway via the downregulation of CEA in SNU-C5/5-FU.

  8. The Anticancer Effect of (1S,2S,3E,7E,11E-3,7,11, 15-Cembratetraen-17,2-olide(LS-1 through the Activation of TGF-β Signaling in SNU-C5/5-FU, Fluorouracil-Resistant Human Colon Cancer Cells

    Eun-Ji Kim


    Full Text Available The anticancer effect of (1S,2S,3E,7E,11E-3,7,11,15-cembratetraen-17,2-olide (LS-1 from Lobophytum sp. has been already reported in HT-29 human colorectal cancer cells. In this study, we examined the effect of LS-1 on the apoptosis induction of SNU-C5/5-FU, fluorouracil-resistant human colon cancer cells. Furthermore, we investigated whether the apoptosis-induction effect of LS-1 could arise from the activation of the TGF-β pathway. In SNU-C5/5-FU treated with LS-1 of 7.1 μM (IC50, we could observe the various apoptotic characteristics, such as the increase of apoptotic bodies, the increase of the sub-G1 hypodiploid cell population, the decrease of the Bcl-2 level, the increase of procaspase-9 cleavage, the increase of procaspase-3 cleavage and the increase of poly(ADP-ribose polymerase cleavage. Interestingly, the apoptosis-induction effect of LS-1 was also accompanied by the increase of Smad-3 phosphorylation and the downregulation of c-Myc in SNU-C5/5-FU. LS-1 also increased the nuclear localization of phospho-Smad-3 and Smad-4. We examined whether LS-1 could downregulate the expression of carcinoembryonic antigen (CEA, a direct inhibitor of TGF-β signaling. LS-1 decreased the CEA level, as well as the direct interaction between CEA and TGF-βR1 in the apoptosis-induction condition of SNU-C5/5-FU. To examine whether LS-1 can induce apoptosis via the activation of TGF-β signaling, the SNU-C5/5-FU cells were treated with LS-1 in the presence or absence of SB525334, a TGF-βRI kinase inhibitor. SB525334 inhibited the effect of LS-1 on the apoptosis induction. These findings provide evidence demonstrating that the apoptosis-induction effect of LS-1 results from the activation of the TGF-β pathway via the downregulation of CEA in SNU-C5/5-FU.

  9. Degradation of 5-FU by means of advanced (photo)oxidation processes: UV/H{sub 2}O{sub 2}, UV/Fe{sup 2+}/H{sub 2}O{sub 2} and UV/TiO{sub 2} — Comparison of transformation products, ready biodegradability and toxicity

    Lutterbeck, Carlos Alexandre, E-mail: [Sustainable Chemistry and Material Resources, Institute of Sustainable and Environmental Chemistry, Faculty of Sustainability, Leuphana University of Lüneburg, Scharnhorststraße 1/C13, DE-21335 Lüneburg (Germany); Graduate Program in Environmental Technology, Universidade de Santa Cruz do Sul — UNISC, Av. Independência, 2293, CEP 96815-900 Santa Cruz do Sul, Rio Grande do Sul (Brazil); Wilde, Marcelo Luís, E-mail: [Sustainable Chemistry and Material Resources, Institute of Sustainable and Environmental Chemistry, Faculty of Sustainability, Leuphana University of Lüneburg, Scharnhorststraße 1/C13, DE-21335 Lüneburg (Germany); Baginska, Ewelina, E-mail: [Sustainable Chemistry and Material Resources, Institute of Sustainable and Environmental Chemistry, Faculty of Sustainability, Leuphana University of Lüneburg, Scharnhorststraße 1/C13, DE-21335 Lüneburg (Germany); Leder, Christoph, E-mail: [Sustainable Chemistry and Material Resources, Institute of Sustainable and Environmental Chemistry, Faculty of Sustainability, Leuphana University of Lüneburg, Scharnhorststraße 1/C13, DE-21335 Lüneburg (Germany); Machado, Ênio Leandro, E-mail: [Graduate Program in Environmental Technology, Universidade de Santa Cruz do Sul — UNISC, Av. Independência, 2293, CEP 96815-900 Santa Cruz do Sul, Rio Grande do Sul (Brazil); and others


    The present study investigates the degradation of the antimetabolite 5-fluorouracil (5-FU) by three different advanced photo oxidation processes: UV/H{sub 2}O{sub 2}, UV/Fe{sup 2+}/H{sub 2}O{sub 2} and UV/TiO{sub 2}. Prescreening experiments varying the H{sub 2}O{sub 2} and TiO{sub 2} concentrations were performed in order to set the best catalyst concentrations in the UV/H{sub 2}O{sub 2} and UV/TiO{sub 2} experiments, whereas the UV/Fe{sup 2+}/H{sub 2}O{sub 2} process was optimized varying the pH, Fe{sup 2+} and H{sub 2}O{sub 2} concentrations by means of the Box–Behnken design (BBD). 5-FU was quickly removed in all the irradiation experiments. The UV/Fe{sup 2+}/H{sub 2}O{sub 2} and UV/TiO{sub 2} processes achieved the highest degree of mineralization, whereas the lowest one resulted from the UV/H{sub 2}O{sub 2} treatment. Six transformation products were formed during the advanced (photo)oxidation processes and identified using low and high resolution mass spectrometry. Most of them were formed and further eliminated during the reactions. The parent compound of 5-FU was not biodegraded, whereas the photolytic mixture formed in the UV/H{sub 2}O{sub 2} treatment after 256 min showed a noticeable improvement of the biodegradability in the closed bottle test (CBT) and was nontoxic towards Vibrio fischeri. In silico predictions showed positive alerts for mutagenic and genotoxic effects of 5-FU. In contrast, several of the transformation products (TPs) generated along the processes did not provide indications for mutagenic or genotoxic activity. One exception was TP with m/z 146 with positive alerts in several models of bacterial mutagenicity which could demand further experimental testing. Results demonstrate that advanced treatment can eliminate parent compounds and its toxicity. However, transformation products formed can still be toxic. Therefore toxicity screening after advanced treatment is recommendable. - Highlights: • Full primary elimination of 5-FU was

  10. Docetaxel- and 5-FU-concurrent radiotherapy in patients presenting unresectable locally advanced pancreatic cancer: a FNCLCC-ACCORD/0201 randomized phase II trial's pre-planned analysis and case report of a 5.5-year disease-free survival

    Peiffert Didier


    Full Text Available Abstract Background To explore possible improvement in the treatment of locally advanced pancreatic carcinoma (LAPC we performed a randomized, non-comparative phase II study evaluating docetaxel - plus either daily continuous 5 FU or weekly cisplatin concurrent to radiotherapy. We report here the results of the docetaxel plus 5 FU regimen stopped according to the interim analysis. The docetaxel plus cisplatin arm was continued. Methods Forty (40 chemotherapy-naive patients with unresectable LAPC were randomly assigned (1:1 to either continuous fluorouracil (5-FU 200 mg/m2/day (protracted IV and docetaxel (DCT 20 mg/m2/week or DCT 20 mg/m2 and cisplatin (CDDP 20 mg/m2, plus concurrent radiotherapy for a period of 6 weeks. The radiation dose to the primary tumor was 54 Gy in 30 fractions. The trial's primary endpoint was the 6-month crude non-progression rate (NPR. Secondary endpoints were tolerance, objective response rate, and overall survival. Accrual was to be stopped if at 6 months more than 13 disease progressions were observed in 20 patients. Results Eighteen (18 progressions occurred at 6 months in the 5-FU-DCT arm. Six-month NPR was 10% (95%CI: 0-23. Six and 12-month survivals were 85% (95%CI: 64-95 and 40% (95%CI: 22-61; median overall survival was 10.1 months. Median progression-free survival was 4.3 months. We report the case of one patient who was amenable to surgery and has been in complete response (CR for 5.5 years. Toxicities grade ≥ 3 were reported in 75% of patients; no treatment-related death occurred. Severe toxicities were mainly vomiting (35%, abdominal pain (10% and fatigue (10%. Conclusions Combination of 5-FU, docetaxel and radiotherapy has inadequate efficacy in the treatment of LAPC despite good tolerance for the 5-FU-DCT regimen. Trial Registration NCT00112697

  11. Adenocarcinoma of the cervical esophagus arising in heterotopic gastric mucosa: exclusive chemoradiotherapy following a mucosal resection

    Jestin-Letallec, V.; Muller, M.; Metges, J.P.; Bouchekoua, M.; Albarghach, N.; Pradier, O. [Departement de Cancerologie, 29 - Brest (France)


    Esophagus adenocarcinomas developing within heterotopic gastric mucosa are very rare and described to be found endoscopically in a prevalence of .29%. We report a case of cervical adenocarcinoma arising in ectopic gastric mucosa in a fifty-four year old man. The patient underwent a mucosal resection followed with exclusive chemoradiotherapy because of infiltration of the sub mucosa layer. A radiotherapy dose of 60 Gy ( 2 Gy/Fr, 30 Fr) was realized with a reduction of the fields at 50 Gy associated with a continuous 5FU-cisplatin combination after eliminating known mutation in the dihydro-pyrimidine of the dehydrogenase gene. for this tumor, surgery is the main treatment, (oesophagectomy associated with laryngo-pharyngectomy) and has an important repercussion on the quality of life. Because of the refusal of our patient, after a mucosal resection attempt, we proposed our patient a chemoradiotherapy. For the first time in the literature, we report the results of radio chemotherapy for this rare tumor. Eighteen months after the treatment, the patient is alive without sign of recurrence. The radio chemotherapy could be a safety treatment for this rare tumor associated with a good quality of life. A review of the literature since 1950 will be shown. (authors)

  12. The experiment study on the effects and mechanisms of resveratrol combined with As2O3 and 5-FU in inducing apoptosis and inhibiting proliferation of SGC-7901 cell%白藜芦醇联合化疗药物抑制胃癌SGC-7901细胞增殖作用研究

    张红; 周静; 姜政


    Objective To investigate the effects and mechanisms of Resveratrol (Res) combined with 5-FU on the proliferation and apoptosis of the gastric cancer lines SGC-7901 ,to provide experimental and theoretical foundation in clinical tumortherapies of Res.Methods Having processed SGC-7901 cell with a series of concentration including 5-FU alone or combined with Res for 211 h,48 h and 72 h respectively,the inhibition rate of cell proliferation were detected at different periods by methyhhiazdyl tetrazolium ( MTT) method , and the effective concentration fo 5-FU alone or 5-FU combined with Res for inhibition of cell proliferation was cal culated.Results The IC50 was 11.44[ μg/mL when SGC-7901 cell was processed by 5-FU alone,while it was 6.65 μg/mL when both 5-FU and 150 μmol/L of Res were used.It was shown that there was synergistic effect when Res was used combined with 5-FU.The apoptosis rate of SGC7901 cells in Res combined with 5-FU group (15.68%) was higher than that with 5FU alone (11.60% ) (P<0.05) .Karyopycnosis , nuclear chromosomal condensation and segmentation were observed in Res combined with 5-FU group by TUNFL.Conclusion Res could significantly intensified the effects of 5-FU in inhibiting the proliferation, inducing and promoting apoptosis of tumor cell and there was synergistic effect when Res was combined with 5-FU.%目的 分别探讨白藜芦醇(Res)联合5-氟尿嘧啶(5-FU)在体外对胃癌SGC-7901细胞增殖和凋亡的作用及其机制,为将来临床上以Res基础的联合用药提供理论和实验依据.方法 分别采用不同浓度的5-FU单独或与半抑制浓度(IC50)的Res联合处理SGC-7901细胞24、48、72 h后,采用3-(4,5-二甲基噻唑-2)-2,5-二苯基四氮唑溴盐(MTT)法检测细胞增殖抑制率,计算5-FU单独或与Res联合处理对SGC-7901细胞增殖抑制的中效浓度,以检测二者有无联合增效作用;以MTT法检测细胞增殖抑制率;以流式细胞仪(FCM)检测细胞凋亡率;原位末端标

  13. Cutaneous metastasis in anorectal adenocarcinoma

    Krishnendra Varma


    Full Text Available Cutaneous metastasis in anorectal adenocarcinoma is a rare entity. Here, we report the case of a 40-year-old female who presented with yellowish-brown, irregular, solid, elevated rashes over the pubis with a recent history off palliative colostomy for anorectal adenocarcinoma. Clinically, we suspected metastasis that was proved on biopsy. We report this case due to the rare presenting site (i.e., perineum of a metastatic adenocarcinoma.

  14. A case with primary signet ring cell adenocarcinoma of the prostate and review of the literature

    Orcun Celik


    Full Text Available Primary signet cell carcinoma of the prostate is a rare histological variant of prostate malignancies. It is commonly originated from the stomach, colon, pancreas, and less commonly in the bladder. Prognosis of the classical type is worse than the adenocarcinoma of the prostate. Primary signet cell adenocarcinoma is diagnosed by eliminating the adenocarcinomas of other organs such as gastrointestinal tract organs. In this case report, we present a case with primary signet cell adenocarcinoma of the prostate who received docetaxel chemotherapy because of short prostate specific antigen doubling time.

  15. 关节腔内注射5氟脲嘧啶对兔膝关节炎的疗效评价%Evaluation of intraarticular 5Fu injection in the treatment of rabbit osteoarthritis

    王巨; 李伟; 肖德明; 伍晓


    目的 评价关节腔内注射5氟脲嘧啶(5Fu)对兔膝骨性关节炎的疗效.方法 24只兔制成骨关节炎模型动物后随机分成5Fu组、透明质酸(HA)组和对照组3组,5Fu组按2mg/kg关节腔内注射,HA组关节腔内注射HA,对照组注射等量的生理盐水,每周一次连续4次,最后一次治疗后1周处死.观察3组滑膜、软骨组织的光镜改变及MMP-1免疫组化改变,比较关节液、血液中IL-1 β的浓度及Mankin's评分.结果 5Fu组较之HA组、对照组,软骨病理片显示软骨细胞凋亡减少,软骨基质结构完整、黏多糖含量多;滑膜细胞减少,滑膜下层的纤维增生减轻;血、膝关节滑液IL-1浓度降低(P<0.01),关节软骨中MMP-1表达明显减弱(P<0.01),Mankin's评分有明显改善(P<0.01).结论 关节腔内注射5Fu治疗兔膝关节炎能减轻骨性关节炎的病理过程,保护软骨基质,减轻了滑膜增生,它可能成为治疗骨性关节炎一种新的药物.

  16. Results of the phase II EORTC 22971 trial evaluating combined accelerated external radiation and chemotherapy with 5FU and cisplatin in patients with muscle invasive transitional cell carcinoma of the bladder

    Poortmans, Philip M. (Dept. of Radiation Oncology, Dr. Bernard Verbeeten Inst., Tilburg (NL)); Van Der Hulst, Marleen; Richaud, Pierre (Dept. of Radiation Oncology, Inst. Bergonieacute, Bordeaux (France)); Collette, Laurence; Pierart, Marianne (Statistics Dept., EORTC Data Center, Brussels (Belgium)); Ho Goey, S. (Dept. of Medical Oncology, TweeSteden Hospital, Tilburg (NL)); Bolla, Michel (Dept. of Radiation Oncology, CHU, Grenoble (France))


    Introduction. We prospectively evaluated concomitant radiotherapy and chemotherapy for advanced bladder cancer in a phase II EORTC trial to test whether it could be further studied as a potential treatment of bladder cancer. Patients and methods. Patients up to 75 years of age with invasive transitional-cell carcinoma of the bladder up to 5 cm, stage pT2 to pT3b, N0M0, without residual macroscopical tumour after transurethral excision were eligible. Radiotherapy consisted of 2 fractions of 1.2 Gy daily up to 60 Gy delivered in a period of 5 weeks. During the first and the last week, cisplatin 20 mg/m2/day and 5 FU 375 mg/m2/day were given concomitantly. Results. The study was interrupted early due to poor recruitment. Nine patients of the originally 43 planned were treated. Mean age was 63 years. Five patients had tumour stage pT2, 1 stage pT3a and 3 stage pT3b. All patients completed radiotherapy and chemotherapy as scheduled. Only one grade 3 and no grade 4 toxicity was seen. All patients were evaluated 3 months after treatment: eight patients had no detectable tumour and one had para-aortic lymph nodes. During further follow-up, a second patient got lymph node metastases and two patients developed distant metastases (lung in the patient with enlarged lymph nodes at the first evaluation and abdominal in one other). Those three patients died at respectively 19, 14, and 18 months after registration. Late toxicity was limited and often temporary. After 26 to 57 months of follow-up, no local recurrences were seen. Six patients remained alive without disease. Discussion. Despite the small cohort, this combination of concomitant chemotherapy and accelerated hyperfractionated radiotherapy for invasive bladder cancer seemed to be well tolerated and to result in satisfactory local control with limited early and late toxicity. It could therefore be considered for study in further clinical trials

  17. Intramucosal adenocarcinoma of the ileum originated 40 years after ileosigmoidostomy

    Sameshima Shinichi


    Full Text Available Abstract Background Small bowel adenocarcinomas (SBAs are rare carcinomas. They are asymptomatic and usually neither endoscopy nor contrast studies are performed for screening Case presentation A 72-year-old Japanese male had a positive fecal occult blood test at a regular check-up in 2006. He suffered appendicitis and received an ileosigmoidostomy in 1966. A colonoscopy revealed an irregular mucosal lesion with an unclear margin at the ileum side of the anastomosis. A mucosal biopsy specimen showed adenocarcinoma histopathologically. Excision of the anastomosis was performed for this patient. The resected specimen showed a flat mucosal lesion with a slight depression at the ileum adjacent to the anastomosis. Histological examination revealed a well differentiated intramucosal adenocarcinoma (adenocarcinoma in situ. Immunohistological staining demonstrated the overexpression of p53 protein in the adenocarcinoma. Conclusion Adenocarcinoma of the ileum at such an early stage is a very rare event. In this case, there is a possibility that the ileosigmoidostomy resulted in a back flow of colonic stool to the ileum that caused the carcinogenesis of the small intestine.

  18. 2011版《NCCN胰腺癌临床实践指南》中若干问题的探讨%The discussion on the issues related to NCCN clinical practice guidelines in oncology for pancreatic adenocarcinoma ( V2011 )

    刘子文; 赵玉沛


    《NCCN胰腺癌临床实践指南》2011中国版已修订完成,新版指南在原有内容基础上结合近年来临床研究进展,在胰腺癌的诊断和治疗路线、原则、循证医学证据上进行了细微更新,并在理念上有了新的阐述,本文就更新中的相关问题进行探讨.《NCCN胰腺癌临床实践指南》2011版中针对胰腺癌的诊断提出了多学科评估的理念,治疗上重视肿瘤可切除性判定标准,化疗中对于体力状态好的患者可选用FOLFIRINOX方案,强调了吉西他滨和5-氟尿嘧啶(5-FU)均作为胰腺癌化疗的Ⅰ类证据.%The revision of the Chinese version of NCCN clinical practice guidelines in oncology for pancreatic adenocarcinoma ( V2011) has been completed. Based on the clinical research in recent years, the new version of the guidelines expressed new ideas and made minor updates on the diagnosis, treatment, and evidence based medicine of pancreatic adenocarcinoma. This article discusses issues related to these new updates. NCCN pancreatic adenocarcinoma guidelines (V2011) presented the concept of multidisciplinary review and emphasized the criteria defining resectability status in treatment. In addition, greater emphasis was placed on the principles of chemotherapy. FOLFIRINOX therapy was recommended for patients in good physical condition. Gemcitabine and 5 - FU were also highlighted as Category 1 evidence for chemotherapy of pancreatic adenocarcinoma.

  19. 5-Fu对低氧下胃癌SGC7901细胞系中SP细胞比例及HIF-2α、ABCG2表达的影响%Effect of 5-Fu on the ratio of SP cells and expression of HIF-2α and ABCG2 in human gastric cancer cell line SGC7901 under hypoxia

    张小茜; 冯玉光; 吴美英; 朱芸; 白红霞; 王西艳


    AIM: To investigate the mechanism of resistance to 5-fluorouracil (5-Fu) chemotherapy in gastric cancer cells under hypoxia.METHODS: The proliferative activity of SGC7901 cells was determined by MTT assay, and the half maximal inhibitory concentration (IC50) of 5-Fu under normoxia and hypoxia was calculated. After 5-Fu at a concentration of IC50 was incubated with cells for 24, 48 or 72 h under hypoxia, the percentage of SP cells was detected by Hoechst 33342 staining, the expression of HIF-2α protein was detected by immunocyto-chemistry, and the expression of ABCG2 was detected by fluorescence immunocytochemistry.RESULTS: 5-Fu inhibited the proliferation of SGC7901 cells in a dose- and time-dependent manner under normoxia and hypoxia. The IC50 of 5-Fu under normoxia and hypoxia was 100 mg/L and 200 mg/L, respectively. The ratio of SP cells in SGC7901 cells was 1.87% under nomoxia, and significantly increased after induction by hypoxia for 24, 48, and 72 h. Treatment with 5-Fu had no significant impact on the proportion of SP cells under normoxia, but gradually increased SP cell proportion under hypoxia. The expression levels of HIF-2α and ABCG2 proteins in SGC7901 cells were lower under normoxia. Treatment with 5-Fu had no significant impact on the expression of HIF-2α and ABCG2 proteins under normoxia, but gradually increased their expression under hypoxia.CONCLUSION: The mechanism underlying the resistance of SGC7901 cells to 5-Fu under hypoxia may be related to inducing HIF-2α and ABCG2 expression and promoting sternness.%目的:探讨低氧下5-Fu化疗抵抗的机制.方法:MTT检测常氧和低氧下的细胞活力,并计算5-Fu的半数抑制浓度(IC50).以IC50的5-Fu分别作用细胞常氧和低氧组细胞24、48和72h后,收集标本,Hoechst33342染色法检测侧群(side population,SP)细胞的比例,免疫细胞化学法检测低氧诱导因子(hypoxiainducible factor-2α,HIF-2α),荧光免疫细胞化学法检测ABCG2(ATP-binding cassette

  20. Intensity-Modulated Radiotherapy for Pancreatic Adenocarcinoma

    Abelson, Jonathan A.; Murphy, James D.; Minn, Ann Yuriko; Chung, Melody [Department of Radiation Oncology, Stanford University, Stanford, CA (United States); Fisher, George A.; Ford, James M.; Kunz, Pamela [Department of Medical Oncology, Stanford University, Stanford, CA (United States); Norton, Jeffrey A.; Visser, Brendan C.; Poultsides, George A. [Department of Surgical Oncology, Stanford University, Stanford, CA (United States); Koong, Albert C. [Department of Radiation Oncology, Stanford University, Stanford, CA (United States); Chang, Daniel T., E-mail: [Department of Radiation Oncology, Stanford University, Stanford, CA (United States)


    Purpose: To report the outcomes and toxicities in patients treated with intensity-modulated radiotherapy (IMRT) for pancreatic adenocarcinoma. Methods and Materials: Forty-seven patients with pancreatic adenocarcinoma were treated with IMRT between 2003 and 2008. Of these 47 patients, 29 were treated adjuvantly and 18 definitively. All received concurrent 5-fluorouracil chemotherapy. The treatment plans were optimized such that 95% of the planning target volume received the prescription dose. The median delivered dose for the adjuvant and definitive patients was 50.4 and 54.0 Gy, respectively. Results: The median age at diagnosis was 63.9 years. For adjuvant patients, the 1- and 2-year overall survival rate was 79% and 40%, respectively. The 1- and 2-year recurrence-free survival rate was 58% and 17%, respectively. The local-regional control rate at 1 and 2 years was 92% and 80%, respectively. For definitive patients, the 1-year overall survival, recurrence-free survival, and local-regional control rate was 24%, 16%, and 64%, respectively. Four patients developed Grade 3 or greater acute toxicity (9%) and four developed Grade 3 late toxicity (9%). Conclusions: Survival for patients with pancreatic cancer remains poor. A small percentage of adjuvant patients have durable disease control, and with improved therapies, this proportion will increase. Systemic therapy offers the greatest opportunity. The present results have demonstrated that IMRT is well tolerated. Compared with those who received three-dimensional conformal radiotherapy in previously reported prospective clinical trials, patients with pancreatic adenocarcinoma treated with IMRT in our series had improved acute toxicity.

  1. Vesical metastasis of gastric adenocarcinoma

    Alberto A. Antunes


    Full Text Available Metastatic vesical tumors are rare, and constitute approximately 1% of all neoplasias affecting this organ. The authors report the case of a 63-year old woman with vesical metastasis of gastric adenocarcinoma. Patient presented signs of cachexia and complained of left lumbar pain and dysuria unresponsive to antibiotic therapy for approximately 5 months. She reported a previous partial gastrectomy due to ulcerative undifferentiated gastric adenocarcinoma 1 year and 9 months before. Cystoscopy revealed an extensive vegetative lesion in bladder, occupying its entire mucosal surface. The biopsy revealed metastatic signet-ring cell adenocarcinoma.

  2. Anemia and long-term outcome in adjuvant and neoadjuvant radiochemotherapy of stage II and III rectal adenocarcinoma: The Freiburg experience (1989-2002)

    Christian Weissenberger; Michael Henke; Michael Geissler; Florian Otto; Annette Barke; Karl Henne; Georg von Plehn; Alex Rein; Christine Müller; Susanne Bartelt


    AIM: To evaluate the long-term outcome of standard 5-FU based adjuvant or neoadjuvant radiochemotherapy and to identify the predictive factors, especially anemia before and after radiotherapy as well as hemoglobin increase or decrease during radiotherapy.METHODS: Two hundred and eighty-six patients with Union International Contre Cancer (UICC) stage Ⅱ and Ⅲ rectal adenocarcinomas, who underwent resection by conventional surgical techniques (low anterior or abdominoperineal resection), received either postoperative (n = 233) or preoperative (n = 53)radiochemotherapy from January 1989 until July 2002.Overall survival (OAS), cancer-specific survival (CSS),disease-free survival (DFS), local-relapse-free (LRS) and distant-relapse-free survival (DRS) were evaluated using Kaplan-Meier, Log-rank test and Cox's proportional hazards as statistical methods. Multivariate analysis was used to identify prognostic factors. Median follow-up time was 8 years.RESULTS: Anemia before radiochemotherapy was an independent prognostic factor for improved DFS (risk ratio 0.76, P=0.04) as well as stage, grading, R status (free radial margins), type of surgery, carcinoembryonic antigen (CEA) levels, and gender. The univariate analysis revealed that anemia was associated with impaired LRS (better local control) but with improved DFS. In contrast,hemoglobin decrease during radiotherapy was an independent risk factor for DFS (risk ratio 1.97, P = 0.04).During radiotherapy, only 30.8% of R0-resected patients suffered from hemoglobin decrease compared to 55.6% if R1/2 resection was performed (P=0.04). The 5-year OAS, CSS, DFS, LRS and DRS were 47.0%, 60.0%,41.4%, 67.2%, and 84.3%, respectively. Significant differences between preoperative and postoperative radiochemotherapy were not found.CONCLUSION: Anemia before radiochemotherapy and hemoglobin decrease during radiotherapy have no predictive value for the outcome of rectal cancer. Stage,grading, R status (free radial margins), type of

  3. 粉防己碱逆转大肠癌耐药细胞株LOVO/5-Fu多药耐药性的实验研究%Reversal of multidrug resistance in human colon carcinoma LOVO/5-Fu cells by tetrandrine

    王开雷; 李乐平; 靖昌庆


    目的 探讨粉防己碱(tetrandrine,Tet)逆转人大肠癌多药耐药细胞LOVO/5-Fu的多药耐药性(multidrug resistance,MDR)及其机制.方法 Tet作用于LOVO/5-Fu细胞48 h后,用噻唑蓝法检测LOVO/5-Fu细胞耐药性,流式细胞术检测细胞凋亡、周期变化及其p-糖蛋白(P-glycoprotein,P-gp)的表达水平,实时荧光定量PCR检测各组细胞MDR1 mRNA表达水平,Western blot检测各组细胞P-gp蛋白的表达水平.结果 经过Tet作用48 h后,大肠癌LOVO/5-Fu细胞株的IC50降低为(4.15±0.31)μg/ml(P<0.05),细胞凋亡率增加为(3.44%±0.28%)(P<0.05),MDR1 mRNA转录水平降低为(570 ±85)(P<0.05),P-gp的表达水平下降.结论 Tet能逆转大肠癌多药耐药细胞LOVO/5-Fu的MDR,其机制可能是抑制MDR1基因的表达,使P-gp的表达降低,从而增强了LOVO/5-Fu细胞对5-Fu的敏感性.%Objective To explore the reversal effect on MDR1 gene-mediated multidrug resistance in human colon carcinoma LOVO/5-Fu cells by tetrandrine ( Tet) and to clarify its molecular mechanism.Methods LOVO/5-Fu cells were treated for 48 h with Tet.Drug sensitivity was measured by MTT.The cell cycle, apoptosis of cells and expression of P-glycoprotein (P-gp) were determined by flow cytometry assay.Expression of MDR1 mRNA was detected by real-time quantitative PCR (real-time PCR).P-gp expression was detected by Western blot.Results After LOVO/5-Fu cells were treated for 48 h with Tet, the IC50 of 5-Fu decreased to ( 4.15 ± 0.31 ) μg/ml ( P < 0.05 ) ; and the apoptotic rate increased to (3.44% ± 0.28% ) ( P < 0.05) ; the expression of MDR1 mRNA reduced to (570 ± 85) (P < 0.05 ).Conclusions Tetrandrine reverses MDR1 gene-mediated multidrug resistance in human colon carcinoma LOVO/5-Fu cells possibly by inhibiting the expression of MDR1, decreasing the expression of P-gp, thus enhancing the sensitivity of LOVO/5-Fu cells to 5-fluorouracil.

  4. Primary adenocarcinoma of ureter: A rare histopathological variant

    Prekshi Chaudhary


    Full Text Available Primary carcinoma of ureter is an uncommon malignancy. Of which, mostly are transitional cell carcinomas followed by squamous cell carcinomas and adenocarcinomas being the rarest histopathology encountered. We report a case of adenocarcinoma ureter in a middle-aged male along with its clinical scenario. A 62-year-old male, presented with complaints of lower urinary tract symptoms. Computerized tomography urogram showed a soft tissue lesion at the right ureterovesical junction. Cystoscopic biopsy reported villous adenoma. Diethylene triamine pentaacetic acid scan reported nonfunctioning right kidney. He underwent laparoscopic right nephroureterectomy, and histopathology reported adenocarcinoma of the right lower third of ureter, with positive distal and close radial margins. The patient received external beam radiation to the postoperative bed and lymph nodes, and he is disease-free till date.

  5. 阻断MDR1基因表达逆转结肠癌LoVo/5-Fu敏感性的研究%Multidrug resistance gene MDR1 silencing inverses human colon carcinoma LoVo/5-Fu cell sensitivity

    王小文; 吕端


    This study was designed to investigate the reversal effect on MDR1 gene-mediated multidrug resistance in human colon carcinoma LoVo/5-Fu cells with RNAi technology. We designed three groups in the study: group 1 (normal group) was the normal cultured LoVo/5 -Fu cells; group 2 was the LoVo/5 -Fu cells transfected with MDRl-RNAi plasmid vector; group 3 was the LoVo/5-Fu cells transfected empty plasmid vector as negative control. Compared with the un-transfected group, shRNA-MDRI transfected group demonstrated lower level of MDR1 mRNA expression (P<0.05), 5-Fu IC50 value, and resistance indexes in LoVo/5-Fu cells (P<0.05). The relative reverse rate of sensitivity of LoVo/5 -Fu cells to 5-Fu was 71.2%. We also found that the colon formations of L0V0 cells in the experimental group were decreased. In group 2, the apoptosis rate of LoVo/5-Fu cells increased significantly, and the ratios of cells in d phase increased by 8.59%, that in S phase decreased by 8.9%, and those in apoptosis increased by 9.2% (P<0.01). Furthermore, the expression of caspase-3 was increased, while the expression of P-gp was decreased (P<0.05) in group 2. Results in this study suggest that MDR1 shRNA effectively inhibit expression of MDR1, thus reverse MDR1 gene-mediated multidrug resistance in human colon carcinoma LoVo/5—Fu cells.%目的 探讨沉默多药耐药基因MDR1逆转大肠癌耐药细胞株LoVo/5-Fu细胞对5-Fu的耐药性.方法 实验分为3组,转染组(干扰质粒转染人大肠癌耐药细胞株LoVo/5 -Fu细胞)、对照质粒组(转染无关质粒)和未转染对照组.构建靶向MDR1的短发夹RNA (shRNA-MDR1)重组质粒后,转染LoVo/5-Fu细胞,实时荧光定量PCR检测靶细胞MDR1基因表达抑制效果,MTT法检测LoVo/5-Fu细胞对5-Fu的敏感性,流式细胞仪检测细胞周期及细胞凋亡情况.平板克隆形成试验检测细胞克隆形成能力,免疫印迹法检测caspase-3及P-gp蛋白表达.结果 与未转染组相比,转染组细胞MDR1 m

  6. 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

    陶华; 孔诚; 陆进成


    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

  7. The therapy function of low concentration 5-Fu associate with steroid to hypertrophic scar%低浓度5-氟尿嘧啶联合糖皮质激素在增生性瘢痕的应用观察



    目的 观察低浓度5-氟尿嘧啶与糖皮质激素联合局部注射治疗增生性瘢痕的疗效及安全性.方法 研究分两组,单纯激素治疗组48例增生性瘢痕患者进行单纯曲安奈德注射瘢痕内注射,1次/2周.联合治疗组42例增生性瘢痕患者将0.6 m1 5-FU与5 ml曲安奈德、1ml 2%利多卡因混合后局部注射于瘢痕全层,1次/2~4周.瘢痕完全萎缩后逐渐降低药物浓度并延长注射间歇期.结果 在治疗6个月以上的患者中,5-氟尿嘧啶联合糖皮质激素治疗增生性瘢痕的总有效率为97.62%,其中完全缓解者占45.23%,极大缓解者占47.62%,部分缓解者占4.72%,未缓解者为2.38%.结论 低浓度5-氟尿嘧啶与糖皮质激素联合局部注射治疗增生性瘢痕的疗效显著.%Objective To monitor the therapeutic action and security of 5-FU associate with steroid injected to hypertrophic scar. Methods 48 patients was treated merely with corticosteroid injection to hypertrophic scar, once/2weeks. The other 42 patients around sternal area were treated with intralesional injection of a mixture of 0.6 ml 5-FU ,5 ml corticosteroid and 1 ml 2% lidocaine once per 2-4 weeks. After hypertrophic scar became flattened, drug concentration was decreased with prolonged intermission of drug injection. Results The total therapy efficacy of 5-FU associate with steroid to hypertrophic scar is 97.62%. Of them the complete remission percentage is 45.23%, the large remission percentage is 47.62%, part remission percentage is 4.72%, and the inefficacy percentage is 2.38%. Conclusion It is more effective that the combination therapy to hypertrophic scar of low concentration 5-FU and steroid.

  8. Inducing effect of Genistein and 5-FU on apoptosis of human hepatocellular carcinoma cell and their mechanism%Genistein与5-FU诱导肝癌细胞凋亡协同作用机制研究

    王钰粟; 梅庆步; 郑立红; 王玉; 刘丹


    目的 探讨染料木黄酮(genistein,Gen)与氟尿嘧啶(5-Fluorouracil,5-FU)诱导人肝癌MHCC97 L细胞凋亡的协同作用及机制.方法 Gen与5-FU单用和联用处理MHCC97-L细胞48 h,以培养液处理该细胞作为对照.MTT法检测2种药物加药顺序不同对细胞生长的影响,透射电镜观察细胞形态学变化,流式细胞术检测细胞凋亡率,蛋白质印迹法检测Bax/Bcl 2蛋白表达的变化.结果 对照组、Gen组、5 FU组、先加Gen联用组、先加5-FU联用组和同时加药组对MHCC97-L细胞生长抑制率分别为(0±5.60)%、(9.73±2.01)%、(15.97±1.75)%、(27.13±2.20)%、(31.52±2.75)%和(29.29±2.82)%,Gen与5-FU单药组可明显抑制MHCC97 L细胞增殖(P<0.001),但两药间无明显交互效应(P>0.05),加药顺序不同对药效无明显影响,P>0.05.各药物组均发生细胞凋亡及细胞坏死的形态学变化,Gen组的细胞改变多为凋亡,5-FU组和联用组的细胞改变多为坏死.Gen组、5-FU组和联用组细胞凋亡率分别为(12.03±2.02)%、(8.55±3.25)%和(14.17±0.69)%,均较对照组(2.05±1.16)%高,P值均<0.05;联用组的最高,Gen组次之,5-FU组最低,联用组明显高于5-FU组(P=0.009),但联用组与Gen组、Gen组与5 FU组之间差异无统计学意义,P>0.05.Gen组、5-FU组和联用组Bax/Bcl-2蛋白表达分别为6.65±0.56、1.77±0.20和1.33±0.05,均较对照组0.339±0.004高,P值均<0.05;联用组上调Bax/Bcl-2作用低于Gen组(P<0.001),而联用组与5 FU组之间差异无统计学意义(P>0.05),Gen组上调Bax/Bcl-2作用最强,Gen组与5-FU组差异有统计学意义,P<0.001.结论 Gen能明显增强5-FU诱导MHCC97-L细胞凋亡的作用;同时加药可作为Gen与5-FU联用首选的加药方式之一;Gen诱导MHCC97-L细胞凋亡可能与上调Bax/Bcl-2有关.

  9. Noninvasive Assessment of Losartan-Induced Increase in Functional Microvasculature and Drug Delivery in Pancreatic Ductal Adenocarcinoma

    Vidhya Kumar


    Full Text Available PURPOSE: Losartan, an angiotensin II receptor blocker, can reduce desmoplasia and enhance drug delivery and efficacy through improving interstitial transport and vascular perfusion in pancreatic ductal adenocarcinoma (PDAC models in mice. The purpose of this study was to determine whether magnetic resonance imaging (MRI of magnetic iron oxide nanoparticles (MNPs and micro–positron emission tomography (PET measurements could respectively detect improvements in tumor vascular parameters and drug uptake in orthotopic PDAC in mice treated with losartan. METHOD AND MATERIALS: All experiments were approved by the local Institutional Animal Care and Use Committee. FVB mice with orthotopic PDAC were treated daily with an i.p. injection of losartan (70 mg/kg or saline (control vehicle for 5 days. In order to calculate the fractional blood volume, vessel size index, and vessel density index, MRI was performed at 4.7 T following the injection of 3 mg/kg iron ferumoxytol (i.v.. Dynamic PET images were also acquired for 60 minutes using an 18F-5FU tracer dose of 200 μCi and analyzed for time activity curves normalized to muscle. Statistical analyses compared both cohorts using an unpaired two-tailed t test. RESULTS: In comparison to the control treatment, the losartan administration significantly increased the fractional blood volume (mean ± SEM [12.1 ± 1.7 (n = 19 vs 6.7 ± 1.1 (n = 20; P < .02] and vessel size index (128.2 ± 35.6 vs 57.5 ± 18; P < .05. Losartan also induced a significant increase in the intratumoral uptake of 18F-5FU by 53% (P < .0001. CONCLUSION: MRI using FDA-approved MNPs provides a noninvasive, translatable means of assaying microvascular parameters induced by losartan in pancreatic cancer. PET measurements demonstrated that losartan significantly increased the uptake of 18F-5FU.

  10. Toxicity and survival results of a phase II study investigating the role of postoperative chemoradioimmunotherapy for gastric adenocarcinoma

    Bese, N.S.; Yildirim, A.; Oeber, A. [Dept. of Radiation Oncology, Istanbul Univ., Cerrahpasa Medical School, Istanbul (Turkey); Bueyuekuenal, E.; Oezgueroglu, M.; Demir, G.; Mandel, N.M.; Demirelli, F.; Serdengecti, S. [Dept. of Internal Medicine, Medical Oncology Section, Istanbul Univ., Cerrahpasa Medical School, Istanbul (Turkey)


    Background and purpose: to investigate the role of postoperative concomitant chemoradioimmunotherapy in gastric adenocarcinoma patients. Patients and methods: 59 pateints, who underwent total or subtotal gastrectomy, with lymph node involvement, positive microscopic surgical margins or serosal involvement were included in the study. Radiotherapy started concomitantly with chemotherapy and levamisole. Extended-field radiotherapy was given to gastric bed and regional lymphatics via two anterior-posterior/posterior-anterior fields. A total dose of 45 Gy in 25 fractions with a fraction size of 1.8 Gy was planned. In 28 patients (48%) with positive surgical margins a 10-Gy boost dose was given to the anastomosis site. An adjuvant i.v. bolus of 450 mg/m{sup 2}/day 5-fluorouracil (5-FU) was administered concomitantly during the first 3 days and at the 20th day of irradiation. After completion of radiotherapy, i.v. boluses of 450 mg/m{sup 2}/day 5-FU and 25 mg/m{sup 2}/day rescuvorin were continued for 6 months once a week. Levamisole 40 mg/day orally was started at the 1st day of radiotherapy and also continued for 6 months. Median follow-up was 37 months (7-112 months). Results: median survival was 23 months. Overall 3- and 5-year survival rates amounted to 35% and 14%, respectively. Median survival of the patients with positive surgical margins was 22 months. The 3- and 5-year locoregional control rates were 59% and 55%, respectively. The most common toxicity was upper gastrointestinal system toxicity, which was observed in 42 patients (71%). Four patients (7%) died on account of early toxic effects, and six (10%) could not complete treatment. Conclusion: although 48% of the study population involved patients with microscopic residual disease, the survival results as a whole were satisfactory. However, due to high toxicity, radiotherapy must be delivered with the most proper techniques along with adequate nutrition and supportive care. (orig.)

  11. 索拉非尼联合5-氟尿嘧啶对人肝癌细胞株MHCCLM3增殖的抑制作用及其机制%Anti-proliferation effect of sorafenib in combination with 5-FU for hepatocellular carcinoma in vitro: antagonistic performance and mechanism

    邓丽芬; 王艳红; 贾庆安; 任正刚; 沈沪佳; 孙晓静; 李璟寰


    Objective To investigate the anti-cancer efficacy and mechanism of sorafenib and 5-fluorouracil (5-FU) therapy in vitro using the HCC cell line MHCCLM3.Methods The effects of somfenib and 5-FU,alone or in combination,on the proliferation of MHCCLM3 cells were evaluated by cell viability assays.Combined-effects analyses were conducted according to the median-effect principle established by Chou and Talalay.Effects on cell cycle distributions were tested by flow cytometry and expression of proteins related to the RAF/MEK/ERK and STAT3 signaling pathways and cyclinD1 were tested by western blotting.Results Sorafenib and 5-FU alone or in combination displayed significant efficacy in inhibiting proliferation of the MHCCLM3 cells,with the following inhibition rates:somfenib:46.16% ± 2.52%,5-FU:28.67% ± 6.16%,and sorafenib + 5-FU:22.59% ± 6.89%.The somfenib + 5-FU combination did not provide better results than treatment with either drag alone.The combination index values of the sorafenib and 5-FU treatments were mainly greater than 1,indicating that the two agents induced antagonistic,instead of synergistic,effects on the MHCCLM3 cells.In addition,the MHCCLM3 cells were less semitive to 5-FU when administrated in combination with sorafenib,as evidenced by the half inhibitory concentration (IC50) significantly increasing from (102.86 ± 27.84) mg/L to (178.61 ± 20.73) mg/L (P =0.003).Sorafenib alone induced G1 phase arrest (increasing from 44.73% ± 1.63% to 65.80% ± 0.56%; P < 0.001) and significantly decreased the proportion of cells in S phase (decreasing from 46.63% ± 0.65% to 22.83% ± 1.75%; P < 0.01),as well as down-regulated cyclinD1 expression (0.57 ± 0.03-fold change vs.untreated control group; P < 0.01).5-FU alone up-regulated cyclinD1 expression (1.45 ± 0.12-fold change vs.untreated control group; P < 0.01).Moreover,somfenib alone significantly inhibited the RAF/MEK/ERK and STAT3 pathways,with the fold-changes of p

  12. Clinicopathological features and prognosis of primary appendiceal adenocarcinoma%原发性阑尾腺癌的临床病理特征和预后分析

    梁建伟; 王征; 周志祥; 张兴茂; 胡俊杰; 赵平


    Objective To explore the clinicopathological characteristics and prognostic factors of primary appendiceal adenocarcinoma.Methods The clinicopathological data of 42 patients with primary appendiceal adenocarcinoma treated in the Cancer Hospital of Chinese Academy of Medical Sciences between March 1994 and October 2009 were retrospectively analyzed. The survival analysis was conducted using Kaplan-Meier method.The factors influencing survival were analyzed using univariate (Log-rank) and multivariate (Cox) models.Results A total of 42 patients (29 female and 13 males,median age 56 years)with appendiceal adenocarcinoma were included in this study. Of them,26 (61.9%) were mucinous adenocarcinoma,12 ( 28.6% ) were intestinal-type adenocarcinoma and 4 ( 9.5% ) were signet cell carcinoma.18 patients underwent curative resection,20 patients received cytoreductive surgery,and 4 patients underwent biopsy only.Thirty patients received systemic chemotherapy (5-Fu-based regimens ).One patient who died of postoperative pulmonary embolism on day 8 was excluded from the survival analysis.The overall 1-,3-,and 5-year survival rate was 80.3%,46.0% and 38.3%,respectively. Univariate analysis revealed that presence of symptoms of acute appendicitis,curative resection,histological grade,histological subtype,preoperative CEA level,systematic chemotherapy,and stage were all significant factors affecting the survival.Multivariate analysis showed that the preoperative CEA level (P =0.01 ),histological grade (P =0.001 ),and stage (P=0.001) were independent prognostic factors.Conclusions High level of CEA,G2/3 grade,and advanced stage are associated with poor prognosis in patients with primary appendiceal adenocarcinoma.%目的 探讨原发性阑尾腺癌的临床病理特征和预后因素.方法 回顾性分析1994年3月至2009年10月收治的、随访资料完整的42例原发性阑尾腺癌患者的临床病理资料,采用Kaplan-Meier法进行生存分析,预后因

  13. 5氟脲嘧啶关节腔注射治疗兔膝骨性关节炎的实验研究%Study of intra-articular injection with 5Fu in the treatment of rabbit knee osteoarthritis

    王巨; 肖德明; 李伟; 林博文; 徐忠世; 陈蓟; 吕猛


    [目的]评价5氟脲嘧啶(5-Fluorouracil,5Fu)关节腔注射治疗兔膝骨性关节炎(osteoarthritis,OA)的疗效.[方法]24只兔子制成骨关节炎模型随机分成OA组、5Fu组和对照组,OA组立即处死,5Fu组按5Fu 2mg/kg关节腔注射,每周1次连续4次,对照组注射等量生理盐水,最后1次治疗后1周处死.观察3组滑膜组织的光镜、电镜改变及软骨的光镜、MMP-1免疫组化改变,比较软骨Mankin's评分及关节液中IL-1的浓度.[结果]5Fu组可见软骨破坏减轻,滑膜炎症明显抑制,Mankin,s评分明显改善(P<0.01);关节液IL-1浓度降低(P<0.05),关节软骨中MMP-1表达减弱.[结论]5Fu关节腔内注射能抑制滑膜炎症,缓解软骨的破坏.

  14. 沉默热休克蛋白27基因增强大肠癌细胞对5-FU化疗敏感性%Silencing gene of heat shock protein 27 increases the sensitivity to 5-FU in colorectal cancer cells

    黄崇杰; 刘长宝; 郑晨果; 蔡锚


    目的:探讨不同大肠癌细胞热休克蛋白(HSP27)蛋白表达水平及其与5-氟尿嘧啶(5-FU)化疗敏感性的关系,同时通过RNA干扰抑制HSP27基因的表达,初步探讨沉默该基因对5-FU抗肿瘤作用的影响。方法:Western blot法检测各大肠癌细胞中HSP27蛋白的表达水平,CCK-8法测定不同浓度5-FU对各细胞株的抑制率,分析各组细胞HSP27蛋白表达水平与IC50的关系。设计合成3对针对不同靶点的HSP27小干扰RNA,通过脂质体转染SW480细胞,激光共聚焦显微镜观察转染效率,Real-time PCR及Western blot法检测转染后HSP27 mRNA及蛋白表达水平。CCK-8法检测HSP27-siRNA对细胞的生长抑制作用及沉默HSP27基因细胞对5-FU化疗敏感性的变化。结果:各组细胞中HSP27的表达水平与5-FU的敏感性呈负相关性。Real-time PCR及Western blot法结果显示有两对靶向HSP27-siRNA能有效抑制HSP27 mRNA及蛋白水平的表达;CCK-8法检测结果显示HSP27-siRNA转染可增强SW480细胞对5-FU的敏感性,半数抑制浓度(IC50)明显下调。HSP27在大肠癌细胞中的表达水平与5-FU化疗药IC50值呈正相关。结论:靶向HSP27的siRNA能有效抑制大肠癌SW480细胞HSP27蛋白的表达,增强5-FU化疗药物的敏感性。%Objective:To investigate the relationship between the HSP27 expression level and the sensiti-zation to 5-FU in different kinds of colon cancer cells, and then explore the effect of HSP27 gene down-regulated by siRNA interference, and the sensitive of 5-FU. Methods:The HSP27 expression level in different kinds of colon cancer cells were detected by Western blot, and the inhibition rates of different concentration of 5-FU were determined by CCK-8 method, then the relationship between the relative level and IC50 of 5-FU was analyzed by Linear correlation. Three siRNA sequences targeted on special sequence of HSP27 gene were designed, All siRNAs were transfected by lipofectamine

  15. Combination of Hydroxycamptothecine with oxaliplatin in induction of drug-resistant colorectal cancer cell line LoVo/5-FU and mechanism of apoptosis%羟基喜树碱联合奥沙利铂诱导人大肠癌耐药细胞株LoVo/5-FU的凋亡机制

    韩坤; 孙元珏; 姚阳


    目的:体外观察羟基喜树碱(HCPT)联合奥沙利铂(L-OHP)对人大肠癌耐药细胞株LoVo/5-FU增殖抑制及诱导凋亡作用,并初步探讨其诱导凋亡方面机制.方法:MTT法测定HCPT联合L-OHP对LoVo/5-FU细胞增殖抑制作用,并根据中效原理判断两药合用时的效应.流式细胞仪观察两药对LoVo/5-FU细胞的凋亡诱导作用.半定量RT-PCR方法检测单药及联合作用后X染色体连锁的凋亡抑制蛋白(XIAP) mRNA表达变化.结果:HCPT联合L-OHP对LoVo/5-FU细胞有明显的抑制增殖作用,细胞增殖的抑制率与药物浓度呈正相关.在抑制率(fa)>0.18时合用指数(CI)<1,两药表现为协同作用.HCPT浓度分别为0.02、0.04和0.08 mg/L.作用48 h后,LoVo/5-FU细胞凋亡率分别为5.92±0.58、9.93±0.62和3.76±0.45.当0.04 mg/L HCPT联合L-OHP作用48 h后,其凋亡率为18.44±0.57,联合组与单药组比较差异有统计学意义,P<0.05.耐药细胞LoVo/5-FU较亲本细胞LoVo高表达XIAP mRNA(0.88±0.03 vs 0.11±0.02,P<0.01),两药联合作用后XIAP mRNA降低明显为0.21±0.03,P<0.01.结论:HCPT联合L-OHP能够协同抑制LoVo/5-FU细胞增殖,其机制可能与诱导细胞凋亡有关,抑制XIAP表达发挥作用.%OBJECTIVE: To investigate the possible mechanism of proliferation inhibition and apoptosis induced by hydroxycamptothecine (HCPT) and oxaliplatin (L-OHP) on cell line LoVo/5-FU in vitro. METHODS: Proliferation inhibition induced by HCPT and L-OHP on cell line LoVo/5-FU was tested by MTT method . Flow cytometry observed the role of HCPT as a single drug and in combination with L-OHP to induce the apoptosis in LoVo/5-FU cell line. Semi quantitative RT-PCR test was done to determine the expression of mRNA of X-linked inhibitor of apoptosis protein (XIAP) in LoVo/5-FU and LoVo cells after using HCPT and L-OHP as individual drug and in combination.RESULTS: HCPT combined with L-OHP significantly inhibited LoVo/5-FU cell proliferation, cell proliferation inhibition rate was

  16. Impact of Chemotherapy on Normal Tissue Complication Probability Models of Acute Hematologic Toxicity in Patients Receiving Pelvic Intensity Modulated Radiation Therapy

    Bazan, Jose G.; Luxton, Gary; Kozak, Margaret M.; Anderson, Eric M.; Hancock, Steven L.; Kapp, Daniel S.; Kidd, Elizabeth A.; Koong, Albert C.; Chang, Daniel T., E-mail:


    Purpose: To determine how chemotherapy agents affect radiation dose parameters that correlate with acute hematologic toxicity (HT) in patients treated with pelvic intensity modulated radiation therapy (P-IMRT) and concurrent chemotherapy. Methods and Materials: We assessed HT in 141 patients who received P-IMRT for anal, gynecologic, rectal, or prostate cancers, 95 of whom received concurrent chemotherapy. Patients were separated into 4 groups: mitomycin (MMC) + 5-fluorouracil (5FU, 37 of 141), platinum ± 5FU (Cis, 32 of 141), 5FU (26 of 141), and P-IMRT alone (46 of 141). The pelvic bone was contoured as a surrogate for pelvic bone marrow (PBM) and divided into subsites: ilium, lower pelvis, and lumbosacral spine (LSS). The volumes of each region receiving 5-40 Gy were calculated. The endpoint for HT was grade ≥3 (HT3+) leukopenia, neutropenia or thrombocytopenia. Normal tissue complication probability was calculated using the Lyman-Kutcher-Burman model. Logistic regression was used to analyze association between HT3+ and dosimetric parameters. Results: Twenty-six patients experienced HT3+: 10 of 37 (27%) MMC, 14 of 32 (44%) Cis, 2 of 26 (8%) 5FU, and 0 of 46 P-IMRT. PBM dosimetric parameters were correlated with HT3+ in the MMC group but not in the Cis group. LSS dosimetric parameters were well correlated with HT3+ in both the MMC and Cis groups. Constrained optimization (0received. Patients receiving P-IMRT ± 5FU have better bone marrow tolerance than those receiving irradiation concurrent with either Cis or MMC. Treatment with MMC has a lower TD{sub 50} and more steeply rising normal tissue complication probability curve compared with treatment with Cis. Dose tolerance of PBM and the LSS subsite may be lower for

  17. The proapoptotic effect of combination PI3K p85α depletion and 5-FU treatment on colorectal cancer cells%PI3K p85α蛋白表达缺失联合5-FU对大肠癌细胞的促凋亡作用

    孙嫣; 王林; 曾晖


    Objective To investigate the proapoptotic effect of combination PI3K p85α depletion via RNA interference and 5-FU treatment on colorectal cancer cells. Methods PI3K p85α/RNAi-LoVo cells and LoVo control cells were recovered and cultured in RPMII640, supplemented with 10% fetal calf serum and 500 μg/mL G418. Western blot analysis was used to determine the RNA interference effect. The 50% inhibitory concentration (IC50) value of 5-FU was evaluated by MTT assay. Annexin V-FITC Kit was used to determine the apoptosis. Results Western blot analysis showed that the inhibited rate of PI3K p85α protein was 59%. Compared with the control cells, IC50 of 5-FU in PI3K p85α/RNAi-LoVo cells obviously decreased (P = 0. 000). Depletion of PI3K p85α sensitized LoVo cells to 5-FU induced apoptosis (P =0. 000). Conclusion Combination PI3K p85α depletion and 5-FU treatment could promote apoptosis of LoVo cells. It may be a new therapeutic strategy for gene therapy and chemotherapy of colorectal cancer.%探讨RNA干扰靶向抑制PI3K p85α蛋白表达联合5-FU对大肠癌LoVo细胞的促凋亡作用.方法 复苏培养PI3K p85α干扰组LoVo细胞(PI3Kp85ɑ/RNAi-LoVo)和LoVo对照组细胞,Western blot鉴定干扰效果,MTT法检测5-FU对两组细胞的半数抑制浓度(IC50),Annexin-FITC标记法检测细胞凋亡.结果 Western blot结果显示LoVo干扰组细胞PI3K p85α蛋白抑制率为59%,MTT结果显示干扰组细胞5-FU的IC50值(4.57±0.16)μmol/L明显低于对照组细胞5-FU的IC50值(8.07±0.30)μmol/L (P=0.000),细胞凋亡实验显示,干扰组细胞对5-FU诱导凋亡的敏感性增加(P=0.000).结论 PI3K p85α蛋白表达缺失联合5-FU可促进大肠癌LoVo细胞凋亡,为基因治疗和化学药物联合治疗大肠癌提供新的策略.

  18. 低浓度5-氟尿嘧啶与糖皮质激素联合激光治疗瘢痕疙瘩的疗效%The therapy function of low concentration 5-Fu and steroid associate with laser to keloid

    王旭东; 武晓莉


    目的 观察低浓度5-氟尿嘧啶(5-Fu)与糖皮质激素局部注射联合激光治疗瘢痕疙瘩的疗效及安全性.方法 瘢痕疙瘩70例,102处病灶,平均病史8.6年,平均治疗时间为10.29个月.70例瘢痕疙瘩患者108处病灶进行单纯瘢痕内注射,0.6 ml 5-Fu与5 ml曲安奈德、1 ml 2%利多卡因混合后局部注射于瘢痕全层注射,每2~4周1次,瘢痕完全萎缩后逐渐降低药物浓度并延长注射间歇期.另一组70例瘢痕疙瘩患者102处病灶将三联药物局部注射半个月后Nd:YAG激光照射,每2~4周1次.结果 在治疗6个月以上的患者中,5-氟尿嘧啶与糖皮质激素联合激光治疗瘢痕疙瘩的总有效率为97.06%,其中完全缓解者占45.10%,极大缓解者占49.02%,部分缓解者占2.94%,未缓解者为2.94%.结论 低浓度5-氟尿嘧啶与糖皮质激素局部注射联合激光治疗瘢痕疙瘩的疗效显著.%Objective To monitor the therapeutic action and security of 5-Fu and steroid injected associate with laser to keloid. Methods One hundred and two keloid focuses of 70 patients have the average 8.6 years history and the average therapy period of 10.29 months. Among them,70 patients with total 108 keloid were treated merely with intralesional injection of a mixture of 0.6 ml 5-Fu,5 ml corticosteroid and 1 ml 2% lidocaine once per 2-4 weeks. The other 70 patients with total 102 keloid around sternal area were treated with the mixture once per 2-4 weeks. And they were irradiated with apulsed Nd:YAG laser(wavelength 1064 nm)at 35-140 energy density levels after 15 days. After keloid became flattened,drug concentration was decreased with prolonged intermission of drug injection. Results The total therapy efficacy of 5-Fu associate with steroid to keloid was 97.06%. Of them, the complete remission percentage was 45.10%,the large remission percentage was 49.02%,part remission percentage was 2.94%,and the inefficacy percentage was 2.94%. Conclusions It is more effective that the

  19. The expression of EIF5A2 in colorectal cancer cells and its role in 5-Fu chemoresistance%EIF5A2在结直肠癌细胞中的表达及在5-Fu化疗抵抗中的作用

    范永胂; 畅银娟


    目的:探讨EIF5A2在结直肠癌细胞中的表达及在化疗抵抗中的作用。方法:培养对数生长期的人结直肠癌细胞系LOVO、SW480及DLD1,用Western blot法测定三种结直肠癌细胞系中EIF5A2的表达。将人结直肠癌LOVO细胞在浓度为0.2μg/L的5-Fu中培养48 h,用Westernblot法测定EIF5A2的表达。EIF5A2-siRNA转染LOVO细胞,将转染后的LOVO细胞及结直肠癌LOVO细胞在0.2μg/L的5-Fu中培养48 h,用MTT法测定细胞生长抑制率。结果:EIF5A2在三种结直肠癌细胞系中均有表达,在LOVO细胞中表达量最高(P<0.05)。结直肠癌LOVO细胞在5-Fu中培养48 h后 EIF5A2表达明显增强(P<0.05)。EIF-5A2-siRNA转染LOVO细胞后增加了5-Fu的细胞抑制率(P<0.05)。结论:EIF5A2在人结直肠癌细胞中有表达,并且增强了5-Fu的化疗抵抗力。%Objective: To research EIF-5A2 overexpression in colorectal cancer and its effect on chemo-therapy.Methods: EIF5A2 expression in colorectal carcinoma (CRC) line (LOVO, SW48 and DLD1) was mea-sured by Western-blot. LOVO cells were cultured in 5-Fu for 48 hours, and EIF5A2 expression was measured by Western-blot. LOVO cells were treated with EIF5A2-siRNA and exposed to 0.2 μg/L 5-Fu for 48 hours. Cell tox-icity was assayed by MTT.Results: EIF5A2 was expressed in all three different CRC and was highest in LOVO cells (P<0.05). 5-Fu treatment led to elevated EIF5A2 expression (P<0.05). The transfection of EIF5A2-siRNA could improve the inhibit rate of LOVO to 5-Fu (P<0.05).Conclusion: EIF5A2 is expressed in CRC lines and it can enhance the chemoresistance of 5-Fu.

  20. Safety study of adjuvant chemotherapy with oxaliplatin and 5-Fu and CF after liver transplantation for hepatocellular carcinoma%进展期肝癌肝移植术后采用奥沙利铂联合氟尿嘧啶-甲酰四氢叶酸钙辅助化疗的安全性

    王乐天; 张庆; 陈虹; 田彦; 毛莎; 白兰


    目的 探讨进展期肝癌肝移植术后采用"奥沙利铂(Oxaliplatin,OXA/ L-OHP) +氟尿嘧啶(5-Fu)+甲酰四氢叶酸钙(CF)"辅助化疗的临床安全性分析.方法 分析我院施行了原位肝移植手术的58例进展期原发性肝癌(HCC)伴肝硬化患者,其中治疗组为26例不符合米兰标准的肝癌患者,术后进行辅助化疗;其余32例行单纯手术治疗.采用"OXA/ L-OHP+5-Fu+ CF"化疗方案,每次化疗间隔21 d,共6个周期.治疗期间及治疗后记录患者的不良反应和生存情况.结果 化疗患者术后3年的生存率为78.8%;未化疗患者术后3年的生存率为53.6%.化疗不良反应以骨髓抑制为主.27例出现骨髓抑制的患者中,24例出现白细胞减少,其中12例接受重组人粒细胞集落刺激因子治疗;7例出现血小板减少,其中仅4例接受重组人血小板生成素治疗.无1例出现排异反应以及发生与治疗相关的死亡及感染.无1例患者因化疗毒副反应中断化疗.结论 进展期肝癌肝移植术后采用"OXA/ L-OHP +5-Fu +CF"辅助化疗是安全,可行的.%Objective To evaluate the safety of postoperative adjuvant chemotherapy on the recurrence rate and survival of patients for hepatocellular carcinoma ( HCC) after liver transplantation ( LT) . Methods Fifty - eight consecutive HCC patients with liver cirrhosis who did not conform Milancriteria underwent LT. Twenty - six invasive HCC patients were entered into a prospective prophylactic protocol with three week cycles of oxaliplatin plus 5 - fluorouracil(5 - Fu) and calcium formyltetrahydrofolat ( CF) for a maximum of six cycles. The adverse reactions and survival were recorded during treatment and after completion of treatment. Results The 3 - year survival in the non - Milan HCC patients with post - LT chemotherapy was 86. 2% , and that in the non - Milan HCC patients without post - LT chemotherapy was 53. 6% . Myelosuppression was noted in 27 patients, 24 patients had leukope-nia and 12 of

  1. Precision prevention of oesophageal adenocarcinoma.

    Vaughan, Thomas L; Fitzgerald, Rebecca C


    The incidence of oesophageal adenocarcinoma has risen rapidly over the past four decades. Unfortunately, treatments have not kept pace; unless their cancer is identified at a very early stage, most patients will not survive a year after diagnosis. The beginnings of this widespread problem were first recognized over 25 years ago, yet rates have continued to rise against a backdrop of much improved understanding and management of oesophageal adenocarcinoma. We estimate that only ∼7% of the 10,000 cases of oesophageal adenocarcinoma diagnosed annually in the USA are identified through current approaches to cancer control, and trace pathways by which the remaining 93% are 'lost'. On the basis of emerging data on aetiology and predictive factors, together with new diagnostic tools, we suggest a five-tier strategy for prevention and control that begins with a wide population base and triages individuals into progressively higher risk strata, each with risk-appropriate prevention, screening and treatment options.

  2. Unusual presentation of metastatic adenocarcinoma

    Mudan Satvinder


    Full Text Available Abstract Background The most common tumours of the adrenal gland are adenoma, pheochromocytoma, adrenocortical carcinoma, and metastases. Although the imaging features of these tumours are established, the imaging characteristics of uncommon adrenal masses are less well known. In patients with extradrenal tumour, incidental discovery of an adrenal mass necessitates excluding the possibility of metastatic malignancy. Case presentation A 52 year-old female was diagnosed with oesophageal adenocarcinoma and treated with oesophagectomy and adjuvant chemotherapy. Sixteen months later on staging CT scan a 2 × 2 cm adrenal mass was detected, which increased in size over a period of time to 3 × 3 cm in size. Adrenalectomy was performed and histological examination revealed metastatic adenocarcinoma within an adrenal adenoma. Conclusion The present case highlights the unusual behaviour of an oesophageal adenocarcinoma causing metastasis to an adrenocortical adenoma.

  3. Identification of ubiquinol cytochrome c reductase hinge (UQCRH) as a potential diagnostic biomarker for lung adenocarcinoma

    Gao, Feng; Liu, Qicai; Li, Guoping; Dong, Feng; Qiu, Minglian; Lv, Xiaoting; Zhang, Sheng; Guo, Zheng


    Ubiquinol cytochrome c reductase hinge (UQCRH) is a novel protein that localizes in the mitochondrial membrane and induces mitochondrial reactive oxygen species (ROS) generation. It had a high expression rate of 87.10% (108/124) in lung adenocarcinoma. Moreover, serum UQCRH level in patients with lung adenocarcinoma was significantly increased compared with that of pneumonia patients (p < 0.0001) and normal control subjects (p < 0.0001). Receiver operating characteristic curve analysis using ...

  4. 表没食子儿茶素没食子酸酯在逆转胃癌细胞耐药中的作用及机制探讨%Role and mechanism research on reversal of 5-fluorouracil resistance by epigallocatechin gallate in gastric cancer drug-resistance cells lines SGC-7901/5-FU

    唐鸿生; 张相良; 崔书中; 王进; 阮强; 黄永红; 杨定华


    Objective To study the role and molecular mechanism of epigallocatechin gallate (EGCG) in reversing drug-resistance to 5-fluorouracil (5-FU) in gastric cancer drug-resistant cell line SGC-7901/5-FU. Methods Drug-resistance gastric cancer cell line (SGC-7901/5-FU) was established by high doses of repeated impact joint drug concentration increment methods. The cell viability of the parent cell line and the drug-resistance cell line were determined by standard MTT assay. Cell survival rate of drug-resistance was calculated by the formula [(A490 of the treatment group / A490 of the control group) × 100%]. Cell half inhibitory concentration (IC50) and resistance index (RI) were calculated by the Graphpad prime 6.0 software ( RI = IC50 value of drug-resistance cells / IC50 value of parent cells). The apoptosis rate of SGC-7901/5-FU cells was quantified by flow cytometry after staining with annexin-V and PI. Western blot was used to detect the protein expression of drug-resistance-related proteins (ABCG2, P-gp, MDR-1 and GST-π) and apoptosis-related proteins (PARP, Survivin, Bax and bcl-2). Results IC50 value was significantly increased in drug-resistant cells compared with parental cells [(64.7 ± 3.9) mg/L and (4.1±0.3) mg/L, respectively, t = 26.46, P=0.000], and the RI was 15.6. Proliferation activity in the drug-resistant cells was higher than that in parental cells at different 5-FU concentrations (all P <0.05). In drug-resistant cells, the IC50 value of 5-FU combined with EGCG group obviously decreased compared with 5-FU group [(7.3 ± 0.1) mg/L and (63.1 ± 1.4) mg/L respectively, t = 40.84, P = 0.000], and the RI was 0.12. Proliferation activity in drug-resistant cells was significantly decreased after EGCG treatment at different 5-FU concentrations (all P < 0.05). Cell apoptosis rates in control group, 5-FU group, EGCG group and 5-FU combined with EGCG group were (3.0 ± 1.0)%, (7.0 ± 1.3)%, (6.0 ± 1.2)%and (18.0 ± 1.4)%, while apoptosis rate in 5-FU

  5. Adenocarcinoma of the esophagus and Barrett's esophagus

    Bytzer, P; Christensen, P B; Damkier, P


    OBJECTIVE: We described incidence rates of esophageal adenocarcinoma in Denmark in a 20-yr period and determined the proportion of patients diagnosed with esophageal adenocarcinoma who had a previous diagnosis of Barrett's esophagus, making them potential candidates for endoscopic surveillance. M......'s esophagus, but these screening programs are not likely to reduce the death rate from esophageal adenocarcinomas in the general population....

  6. Combination of 5-FU and trichostatin on the expression of PLK1 gene and the growth of human gastric cancer SGC-7901 cells%曲古菌素A联合5-FU对人胃癌SGC-7901细胞生长及其PLK1基因表达的影响

    程海燕; 沈哲; 陈卫昌; 严苏


    目的:探讨曲古菌素A (TSA)与5-氟尿嘧啶(5-FU)对人胃癌细胞(SGC-7901细胞)生长及其Polo样激酶1(PLK1)基因表达的影响.方法:将实验设为对照组、TSA 150 ng/mL组(TSA组)、5-FU 20μg/mL组(5-FU组)、TSA 150 ng/mL+5-FU 20 μg/mL组(TSA+5-FU组)四组,用MTT比色法测定各组对SGC-7901细胞的生长影响,流式细胞仪分析细胞周期,RT-PCR分析SGC-7901细胞PLK1 mRNA表达,Western Blot法检测PLK1蛋白表达.结果:TSA和(或)5-FU分别作用24、48、72 h后均能抑制胃癌细胞生长,TSA+5-FU组较TSA组或5-FU组生长抑制作用显著增强,且随着药物作用时间的延长,抑制作用增强更明显;流式细胞术检测显示干预胃癌细胞48 h后,TSA+5-FU组G0/G1期比率为(85.23±2.17)%,较TSA组或5-FU组显著增多;TSA和(或)5-FU干预胃癌细胞48 h后,TSA+5-FU组较TSA组或5-FU组显著减弱PLK1基因mRNA转录及蛋白表达.结论:TSA联合5-FU干预,抑制人胃癌SGC-7901细胞生长,阻止细胞周期于G0/G1期,癌基因PLK1mRNA转录及蛋白表达减少均较TSA组或5-FU组明显.

  7. Cutaneous Metastases From Esophageal Adenocarcinoma

    Triantafyllou, Stamatina; Georgia, Doulami; Gavriella-Zoi, Vrakopoulou; Dimitrios, Mpistarakis; Stulianos, Katsaragakis; Theodoros, Liakakos; Georgios, Zografos; Dimitrios, Theodorou


    The aim of this study is to present 2 rare cases of cutaneous metastases originated from adenocarcinoma of the gastro-esophageal junction, thus, underline the need for early diagnosis and possible treatment of suspicious skin lesions among patients with esophageal malignancy. Metastatic cancer to the skin originated from internal malignancies, mostly lung cancer, breast cancer, and colorectal cancer, constitute 0.5 to 9% of all metastatic cancers.5,8,15 Skin metastases, mainly from squamous cell carcinomas of the esophagus, are rarely reported. Cutaneous metastasis is a finding indicating progressiveness of the disease.17 More precisely, median survival is estimated approximately 4.7 months.2,14 This study is a retrospective review of 2 cases of patients with adenocarcinoma of the esophagus and a review of the literature. Two patients aged 60 and 32 years old, respectively, underwent esophagectomy. Both pathologic reports disclosed adenocarcinoma of the gastro-esophageal junction staged T3 N2 M0 (stage IIIB). During follow-up time, the 2 patients were diagnosed with cutaneous metastases originated from the primary esophageal tumor 11 and 4 months after surgery, respectively. The first patient is alive 37 months after diagnosis, while the second one died 16 months after surgery. Cutaneous metastasis caused by esophageal adenocarcinoma is possible. Therefore, follow-up of patients who were diagnosed with esophageal malignancy and underwent esophagectomy is mandatory in order to reveal early surgical stages. PMID:25785344

  8. IQGAP1 in rectal adenocarcinomas

    Holck, Susanne; Nielsen, Hans Jørgen; Hammer, Emilie;


    Treatment of rectal adenocarcinoma includes total mesorectal excision, which is preceded by radiochemotherapy (RCT) in cases of advanced disease. The response to RCT varies from total tumor regression to no effect but this heterogeneous response is unexplained. However, both radiation and treatme...

  9. Interphase cytogenetics of prostatic adenocarcinoma

    J.C. Alers (Janneke)


    textabstractIn the first part of this chapter an overview will be presented on the structural, histological and functional aspects of the normal human prostate. The second part describes the epidemiological and clinicopathological features of prostatic adenocarcinoma. Further, a state of the art of

  10. Trastuzumab for the treatment of HER2-positive metastatic adenocarcinoma of the stomach or gastro-oesophageal junction.

    Norman, G; Rice, S; Spackman, E; Stirk, L; Danso-Appiah, A; Suh, D; Palmer, S; Eastwood, A


    This paper presents a summary of the evidence review group (ERG) report into trastuzumab for the treatment of human epidermal growth factor receptor 2 (HER2)-positive metastatic adenocarcinoma of the stomach (mGC) or gastro-oesophageal junction. HER2 positivity is defined by immunohistochemistry (IHC)3+ or IHC2+/fluorescence in situ hybridisation (FISH)+. The decision problem addressed was the testing of the whole mGC population with IHC and, for IHC2+ patients, also with FISH, followed by treatment of HER2-positive patients with trastuzumab combined with cisplatin and either capecitabine or 5-fluorouracil (5-FU) [HCX (trastuzumab, cisplatin, capecitabine)/fluorouracil (F)] compared with current standard NHS therapy. The manufacturer's submission contained direct evidence from the ToGA trial, a well-conducted, multinational, phase III randomised controlled trial (RCT) that compared HCX/F with cisplatin and a fluoropyrimidine alone [cisplatin, capecitabine (CX)/F]. HCX/F showed statistically significantly better overall survival in the European Medicines Agency-licensed population subgroup (74%) (hazard ratio 0.65, 95% confidence interval 0.51 to 0.83), corresponding to median survival of 16 months versus 11.8 months. No other evidence exists for the efficacy of any therapy in a known HER2-positive mGC population; other comparisons extrapolate from trials in mixed HER2 status populations. The ERG accepted the manufacturer's view that a meaningful network meta-analysis to establish a comparison for HCX/F compared with current standard NHS therapy [epirubicin, cisplatin, capecitabine (ECX)/epirubicin, oxaliplatin, capecitabine (EOX)/epirubicin, cisplatin, 5-FU (ECF)] was not possible, but was unconvinced by arguments advanced in the alternative narrative synthesis. These involved disregarding evidence from a meta-analysis and interpreting non-significant results of small RCTs comparing epirubicin-containing triplets with cisplatin, 5-FU (CF)/capecitabine (X) doublets

  11. PUMA基因转染胰腺癌AsPC-1细胞增强对5-FU致凋亡的敏感性%PUMA gene transfection increases sensitivity of pancreatic cancer cell line AsPC-1 to 5-FU-induced apoptosis

    张克君; 李德春; 朱东明


    目的:探讨PUMA基因转染是否增强胰腺癌AsPC-1细胞对5-FU致凋亡的敏感性.方法: 采用脂质体转染法将PUMA-pCEP4和空载体pCEP4质粒转染入胰腺癌AsPC-1细胞中,G418筛选阳性细胞.将系列浓度(0.01~100 μmol/L)的5-FU 分别作用于AsPC-1、AsPC-1/PUMA和AsPC-1/pCEP4细胞72 h,MTT法测定各组细胞的存活率并计算IC50, FCM、断裂DNA琼脂糖凝胶电泳和TUNEL法检测细胞凋亡情况,Western blotting检测各组细胞PUMA蛋白表达的变化.结果: AsPC-1、AsPC-1/PUMA和AsPC-1/pCEP4细胞的5-FU IC50分别为(12±1.9)、(1.6±0 4)和(10.4±1.6)μmol/L,AsPC-1/PUMA细胞对5-FU作用的敏感性增加了7.5倍.5-FU以剂量依赖方式诱导AsPC-1细胞凋亡,但对AsPC-1/PUMA细胞所诱导的凋亡比AsPC-1和AsPC-1/pCEP4 更明显.低浓度5-FU(0.1 μmol/L)轻微引起AsPC-1/pCEP4[(1.14±0.28)%]和AsPC-1细胞凋亡[(0.9±0.23)%],但能诱导AsPC-1/PUMA细胞明显凋亡[(6.47±1.42)%];高浓度5-FU (1μmol/L)诱导各组细胞凋亡,但AsPC-1/PUMA细胞凋亡率[(34.54±9.36)%]明显高于AsPC-1[(12.8±3.74)%]和AsPC-1/pCEP4细胞[(15.8±5.15)%],差异均有统计学意义(P<0.01);FCM、断裂DNA琼脂糖凝胶电泳和TUNEL方法检测显示相同的结果.PUMA蛋白在AsPC-1/PUMA细胞中的表达明显高于AsPC-1和AsPC-1/pCEP4细胞.结论: PUMA基因转染明显地增强了胰腺癌AsPC-1细胞对5-FU致凋亡作用的敏感性.

  12. Protective effect of 5F,an extract from Pteris semipinnata L,in combine with 5 - Fu,on development of lung cancer in A/J mice%半边旗提取物5F联合5-Fu对A/J小鼠诱发性肺癌的影响

    叶华; 刘义; 吴科锋; 李立; 郑学宝


    目的:研究半边旗提取物5F 与5-氟尿嘧啶合用对 A/ J 小鼠诱发性肺癌的影响。方法以苯并[a]芘和甲基亚硝胺吡啶基丁酮混合剂灌胃,每周1次,连续8周,诱发小鼠肺癌。从第9周开始,分别腹腔注射5F、5-氟尿嘧啶或(5F + 5- 氟尿嘧啶),连续给药14周后处死小鼠。观察肺癌数量,计算肿瘤抑制率,检测肝脏系数、肾脏系数,检测血清丙氨酸氨基转移酶、天门冬氨酸氨基转移酶、尿素氮和血肌酐水平,检测超氧化物歧化酶和丙二醛的含量变化。结果5F 与5-氟尿嘧啶联合用药显著抑制 A/ J 小鼠诱发性肺癌,具有协同效应,且对肝肾功能无明显毒副作用,还可以提高血清超氧化物歧化酶水平。结论5F 与5-氟尿嘧啶合用可协同抑制 A/ J 小鼠诱发性肺癌。%Objective To investigate the effect of 5F,an extract from Pteris semipinnata L,in combine with 5 - Fu,on the model of induced A/ J mice lung cancer. Methods Intragastric administration was conducted on all mice using mixed re-vulsant of B[a]P and NNK. The aforementioned operation was performed once per week and continued for 8 weeks. 5F and 5- Fu,alone or in combination,were injected into mice from the ninth week and continued for 14 weeks. Count the number of lung cancer and calculate the tumor inhibition rate. Weight the liver and kidney,and calculate the organ index. The levels of ALT,AST,BUN,Scr,SOD and MDA were also detected. Results The combined application of 5F and 5 - Fu significantly suppressed the development of B[a]P and NNK - induced lung cancer in vivo with minimal side effects,and increase the level of serum SOD. Conclusion 5F combined with 5 - Fu had a synergistic effect on the induced lung cancer in A/ J mice.

  13. Development and characterization of 5-fluorouracil resistant human lung cancer cell line H460/5-FU%人肺癌细胞5-氟脲嘧啶耐药株的建立及其生物学特性分析

    陈侃; 丁陈峰; 李东冬; 裴梦蝶


    建立人肺癌5-氟脲嘧啶(5-Fluorouracil,5-FU)的耐药细胞株H460/5-FU,并对其生物学特性进行分析.实验采用浓度梯度递增法诱导肺癌细胞耐药,建立肺癌细胞耐药模型.采用四甲基偶氮唑蓝法(MTT),计算H460和H460/5-FU的半数抑制浓度(IC50)及耐药系数(RI);通过流式细胞仪分析H460和H460/5-FU的细胞周期分布;光镜观察细胞形态变化;通过流式细胞仪进行SP(side population)细胞检测,比较SP细胞所占比例;做细胞生长曲线和集落形成实验观察细胞生长及倍增情况.结果表明5-FU对H460和H460/5-FU的IC50分别为28.7 μg/mL和90.44 μg/mL,RI为3.15;H460/5-FU细胞倍增时间缓慢,DNA复制时间延长,且含有更多的SP细胞.

  14. A Randomized Multicentre Phase II Trial Comparing Adjuvant Therapy in Patients with Interferon Alpha-2b and 5-FU Alone or in Combination with Either External Radiation Treatment and Cisplatin (CapRI or Radiation alone regarding Event-Free Survival – CapRI-2

    Friess Helmut


    Full Text Available Abstract Background The 5-year survival of patients with resected pancreatic adenocarcinoma is still unsatisfying. The ESPAC-1 and the CONKO 001 trial proofed that adjuvant chemotherapy improves 5-year survival significantly from approximately 14% to 21%. In parallel, investigators from the Virginia Mason Clinic reported a 5-year survival rate of 55% in a phase II trial evaluating a combination of adjuvant chemotherapy, immunotherapy and external beam radiation (CapRI-scheme. Two other groups confirmed in phase II trials these results to a certain extent. However, these groups reported severe gastrointestinal toxicity (up to 93% grade 3 or 4 toxicity. In a randomized controlled phase III trial, called CapRI, 110 patients were enrolled from 2004 to 2007 in Germany and Italy to check for reproducibility. Interestingly, much less gastrointestinal toxicity was observed. However, dose-reduction due to haematological side effects had to be performed in nearly all patients. First clinical results are expected for the end of 2009. Methods/Design CapRI-2 is an open, controlled, prospective, randomized, multicentre phase II trial with three parallel arms. A de-escalation of the CapRI-scheme will be tested in two different modifications. Patients in study arm A will be treated as outpatients with the complete CapRI-scheme consisting of cisplatin, Interferon alpha-2b and external beam radiation and three cycles of 5-fluorouracil continuous infusion. In study arm B the first de-escalation will be realised by omitting cisplatin. Next, patients in study arm C will additionally not receive external beam radiation. A total of 135 patients with pathologically confirmed R0 or R1 resected pancreatic adenocarcinoma are planned to be enrolled. Primary endpoint is the comparison of the treatment groups with respect to six-month event-free-survival. An event is defined as grade 3 or grade 4 toxicity, objective tumour recurrence, or death. Discussion The aim of this

  15. Adenocarcinoma of the paraurethral glands: a case report.

    Massari, Francesco; Ciccarese, Chiara; Modena, Alessandra; Maines, Francesca; Segala, Diego; Luchini, Claudio; Marcolini, Lisa; Cavicchioli, Francesca; Cavalleri, Stefano; Bria, Emilio; Brunelli, Matteo; Martignoni, Guido; Artibani, Walter; Tortora, Giampaolo


    Adenocarcinoma of the paraurethral glands represents a very rare neoplasm of the urinary tract. Due to the rarity of this disease, there is no standard therapeutic approach. We report a case of adenocarcinoma of the paraurethral glands in a 56-year-old woman, presenting with abnormal serous vaginal discharges. The radiologic examination revealed a 5-cm mass around the urethra, which underwent surgical resection. After surgical resection, the histology revealed a moderately differentiated adenocarcinoma, probably arising from the paraurethral glands. One month later, a pelvic recurrent mass was radiologically diagnosed; consequently, an anterior pelvic exenteration with lymph node dissection was performed. Histological examination revealed a moderately differentiated adenocarcinoma, with glandular and micropapillary architecture, with multiple lymph node metastases. The absence of modifications such as urethritis cystic glandularis on the urethral mucosa, as well as the lack of a lesion in situ, associated with the immunohistochemical expression of PAX8 and negativity for GATA3 and S100p, suggested that the adenocarcinoma originated from the paraurethral glands rather than from the urethral mucosa. Post-surgery CT scans revealed no evidence of metastatic disease. The patient received 6 courses of adjuvant chemotherapy with carboplatin and paclitaxel. One year after the pelvic exenteration, because of inguinal lymph node progression, an inguinal lymphadenectomy was performed. Four months later, a TC-PET revealed a multidistrectual lymph node and a lung micronodule disease progression. Invasive micropapillary carcinomas have been characterized as a rare distinctive variant of carcinomas in several anatomic sites and are distinguished by a marked tendency to lymphovascular invasion, justifying the association with high-stage disease and poor prognosis. In the present case, both the poor prognosis connected with micropapillary structure and the lymph node involvement

  16. Cardiotoxicity in Asymptomatic Patients Receiving Adjuvant 5-fluorouracil

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


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

  17. Cytostatic activity of the duplex drug linking 2'-deoxy-5-fluorouridine (5FdU) with 3'-C-ethynylcytidine (ECyd) against gastric adenocarcinoma cell lines.

    Weinreich, Jürgen; Schott, Sarah; Königsrainer, Ingmar; Zieker, Derek; Königsrainer, Alfred; Schott, Herbert


    The cytostatic potential of the new duplex drug 2'-deoxy-5-fluorouridylyl-(5'5')-3'-C-ethynylcytidine (5FdU(5'-5')ECyd) was evaluated in comparison to those of 5-fluorouracil (5FU), 2'-deoxy-5-fluorourindine (5FdU), 3'-C-ethynylycytidine (ECyd), cisplatin, an equimolar mixture of 5FdU + ECyd and a three component-mixture of 0.75 μM epirubicin/0.90 μM cisplatin/3.0 μM 5FU (ECF) by incubation of the two human gastric adenocarcinoma cell lines 23132/87 and MKN-45. The molar composition of ECF was taken from data of a triple combination chemotherapy for human gastric cancer. Time and dose depending inhibition of cell growth was determinated using the CASY technology. A growth decrease of both cell lines from 100% to about 20% was observed by treatment with ECF over a course of 14 days. This result provided basis to estimate the cytostatic potential of all tested drugs and combinations thereof. Corresponding high activities in respect to ECF were achieved by incubation of 23132/87 cells with single drugs 49 μM 5FU, 10 μM cisplatin, 3.4 μM 5FdU, 0.65 μM ECyd, the mixture 0.32 μM 5FdU + 0.32 μM ECyd and 0.32 μM 5FdU(5'-5')ECyd. The less sensitive MKN-45 cells require a 1.5-4 fold higher dose of the standard chemotherapeutics in order to achieve an equivalent cytostatic effect, in respect to the 23132/87 cell line,. However, the effect of the duplex drugs on MKN-45 cells was gained with a 5-fold lower dose than ECF. Due to its high cytostatic potential the duplex drug, which covalently links two active anticancer compounds, could be a new therapeutic alternative for chemotherapy in gastric cancer, currently treated with different combinations.

  18. Hepatoid Adenocarcinoma of the Urachus

    Daniel Fernando Gallego


    Full Text Available Hepatoid adenocarcinoma of the urachus is a rare condition. We present the case of a 51-year-old female who developed abdominal pain and hematuria. Pelvic magnetic resonance imaging (MRI reported an urachal mass with invasion to the bladder that was resected by partial cystectomy. On light microscopy the tumor resembled liver architecture, with polygonal atypical cells in nest formation and trabecular structures. Immunochemistry was positive for alfa-fetoprotein (AFP and serum AFP was elevated. Hepatoid adenocarcinomas have been reported in multiple organs, being most commonly found in the stomach and the ovaries. Bladder compromise has been rarely described in the literature, and it has been associated with poor prognosis, low remission rates, and early metastasis.

  19. Adenocarcinoma of the uterine cervix.

    Rutledge, F N; Galakatos, A E; Wharton, J T; Smith, J P


    From January 1, 1947, through December 31, 1971, 219 patients with primary adenocarcinoma of the intact uterine cervix were treated at the M.D. Anderson Hospital and Tumor Institute. Two modes of therapy were primarily used, namely, irradiationtherapy alone and irradiation therapy plus operation. The 5 year survival resultsare 83.7 per cent for patients with Stage i disease, 48.0 per cent for patients with Stage ii disease, 29.2 per cent for patients with Stage iii disease, and 0.0 per cent for patients with Stage iv disease. The group with irradiation plus operation had a better over-all survival rate. In addition, the incidence of central and pelvic recurrent disease was remarkably lower (fourfold difference). The urologic and bowel complications are discussed. This review lends support for our practice of preoperative irradiation followed by simple (constructive) hysterectomy for selected patients eith adenocarcinoma of the uterine cervix.

  20. Oncocytic Adenocarcinoma of the Orbit.

    Harris, Gerald J; Paul, Sean; Hunt, Bryan C

    Oncocytic adenocarcinoma of the orbit is a rare tumor, with 1 case of nonlacrimal sac, nonlacrimal gland origin, and a poor outcome previously reported. An 85-year-old man with a 2-month history of left-sided epiphora, enlarging eyelid nodules, and diplopia in left gaze was found on imaging to have a poorly circumscribed, nodular mass of uniform radiodensity in the inferomedial orbit. Incisional biopsy revealed morphologic and immunohistochemical features of oncocytic adenocarcinoma with origin in the caruncle suspected, and CT of the neck, chest, abdomen, and pelvis showed no metastases or remote primary tumor source. Based on multidisciplinary consensus, orbital exenteration with adjuvant radiation therapy was performed, and there was no evidence of residual or recurrent tumor 2 years after treatment.

  1. Vitiligo associated with esophageal adenocarcinoma

    Ali Asilian


    Full Text Available Vitiligo is a disease that results in depigmented areas in the skin. It may develop at any age but the average age at onset is 20 years. Association of vitiligo and melanoma has been commonly reported, but malignancies other than melanoma have been rarely associated with vitiligo. We report a 73-year-old patient with new onset vitiligo who developed esophageal adenocarcinoma in the following years.

  2. Optimal lymphadenectomy for esophageal adenocarcinoma.

    Oezcelik, A


    Recently published data have shown that an extended lymphadenectomy during the en bloc esophagectomy leads to a significant increased long-term survival for esophageal adenocarcinoma. On the other hand some studies indicate that the increased survival is based on stage migration and that the surgical complication rate is increased after extended lymphadenectomy. The aim of this review was to give an overview about all aspects of an extended lymphadenectomy in patients with esophageal adenocarcinoma. The review of the literature shows clearly that the number of involved lymph nodes is an independent prognostic factor in patients with esophageal adenocarcinoma. Furthermore, an extended lymphadenectomy leads to an increased long-term survival. Some studies describe that 23 lymph nodes should be removed to predict survival; other studies 18 lymph nodes or 15 lymph nodes. Opponents indicate that the survival benefit is based on stage migration. The studies with a large study population have performed a Cox regression analyzes and identified the number of lymph nodes removed as an independent factor for improved survival, which means it is significant independently from other parameters. Under these circumstances is stage migration not an option to explain the survival benefit. An important difficulty is, that there is no standardized definition of an extended lymphadenectomy, which means the localization and number of removed lymph nodes differ depending from the performing centre. The controversies regarding the survival benefit of the lymphadenectomy is based on the lack of standardisation of the lymphadenectomy. The main goal of further studies should be to generate a clear definition of an extended lymphadenectomy in patients with esophageal adenocarcinoma.

  3. Interphase cytogenetics of prostatic adenocarcinoma

    Alers, Janneke


    textabstractIn the first part of this chapter an overview will be presented on the structural, histological and functional aspects of the normal human prostate. The second part describes the epidemiological and clinicopathological features of prostatic adenocarcinoma. Further, a state of the art of (cyto)genetic aberrations occurring in prostatic cancer is given. The third part of this introduction will discuss methodological aspects of this thesis, i.e., the development and methodology of no...

  4. Ductal adenocarcinoma of the prostate: immunohistochemical findings and clinical significance

    Sha JJ


    Full Text Available Jianjun Sha,1,2 Juanjie Bo,1 Jiahua Pan,1 Lianhua Zhang,1 Hanqing Xuan,1 Wei Chen,1 Dong Li,1 Zhaoliang Wang,1 Dongming Liu,1 Yiran Huang1,2 1Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 2School of Biomedical Engineering, Shanghai Jiaotong University, Shanghai, People's Republic of China Introduction: To investigate the clinical features, diagnosis, treatment, and prognosis of ductal adenocarcinoma of the prostate. Methods: The clinicopathological and immunohistochemical data of seven patients with ductal adenocarcinoma of the prostate were retrospectively analyzed. All patients underwent physical examination, magnetic resonance imaging (MRI, bone scan, cystoscopy, and computed tomography (CT scan. The level of prostate-specific antigen (PSA before and after surgery was assessed. Different prostate cancer markers were used for immunohistochemical staining. Results: The mean age of the seven patients diagnosed with prostatic ductal adenocarcinoma in this study was 76.2 years (range 57–88. Five patients presented with intermittent and painless gross hematuria, one patient with progressive dysuria, and one patient with elevated serum PSA on routine health examination. The level of PSA before surgery ranged from 1.3 to 45.0 ng/mL. Immunohistochemical staining results of the prostatic ductal adenocarcinoma confirmed positivity for PSA, prostatic acid phosphatase, androgen receptor, and alpha-methyacyl co-enzyme A (CoA-reductase markers. Two of the patients underwent bilateral orchiectomy combined with anti-androgen therapy, three underwent transurethral resection of prostate, one received radical prostatectomy, and one received medical castration therapy. The clinical outcomes of all patients were satisfactory, based on follow-up data. The symptoms of hematuria and dysuria were ameliorated well, and the postoperative PSA level decreased below 4.0 ng/mL. Recurrence or metastasis of disease was

  5. Unusual presentation of metastatic adenocarcinoma of the lung

    Blerina Resuli; Roberto Lisi; Daniela Musio; Vincenzo Tombolini


    On September 2013, a 62-year-old man with metastatic adenocarcinoma of the lung complained tenderness and pain of the first terminal phalange of his right hand. The biopsy confirmed metastatic adenocarcinoma of the lung to the finger. A single 8-Gy fraction of palliative radiotherapy was delivered to the patient's right hand. The patient received magnetic resonance-guided focused ultrasound surgery treatment to the phalange because he showed few improvement of clinical symptoms and persistence of moderate pain after radiotherapy. After magnetic resonance-guided focused ultrasound surgery, the clinical symptoms improved significantly. No serious adverse effects were reported and the patient compliance was very high. Our patient showed improvement of clinical symptoms after combined treatment. The patient remains in good health conditions.

  6. Unusual presentation of metastatic adenocarcinoma of the lung

    Blerina Resuli; Roberto Lisi; Daniela Musio; Vincenzo Tombolini


    On September 2013, a 62-year-old man with metastatic adenocarcinoma of the lung complained tenderness and pain of the first terminal phalange of his right hand. The biopsy confirmed metastatic adenocarcinoma of the lung to the finger. A single 8-Gy fraction of palliative radiotherapy was delivered to the patient’s right hand. The patient received magnetic resonance-guided focused ultrasound surgery treatment to the phalange because he showed few improvement of clinical symptoms and persistence of moderate pain after radiotherapy. After magnetic resonance-guided focused ultrasound surgery, the clinical symptoms improved significantly. No serious adverse effects were reported and the patient compliance was very high. Our patient showed improvement of clinical symptoms after combined treatment. The patient remains in good health conditions.

  7. Nonspecific granulomatous prostatitis with prostatic adenocarcinoma

    Murugan Paari


    Full Text Available Granulomatous prostatitis is an infrequently seen entity in routine practice. One of its most common subtypes is nonspecific granulomatous prostatitis (NSGP, the etiology of which is still under debate. Such cases may be mistaken for adenocarcinoma clinically and radiologically. Histological resemblance to adenocarcinoma may arise when there is a xanthogranulomatous pattern or a prominence of epithelioid histiocytes. However, NSGP may rarely coexist with adenocarcinoma and it is critical to sample these cases thoroughly to exclude the presence of malignancy.

  8. Clinicopathologial features of gastric hepatoid adenocarcinoma

    Cheng-Yu Lin


    Full Text Available Background: Gastric hepatoid adenocarcinoma (GHA, a rare type of primary gastric cancer, is characterized by hepatocellular carcinoma-like histology. As details of this disease remain unknown, the aim of this study was to evaluate the clinicopathological features of GHA. Methods: From January 2001 to December 2010, 4563 patients were diagnosed with primary gastric cancer at Chang Gung Memorial Hospital, Linkou Medical Center. Ten (0.22% of these patients were diagnosed with GHA. The clinicopathological characteristics of these patients were collected retrospectively. Results: The median age at diagnosis was 65.5 years, and six patients (60% were male. Seven patients had lymph node metastasis and five had distant metastasis, with the liver as the most common site (four cases. Serum alpha-fetoprotein (AFP levels were elevated in seven of eight patients (median: 359.2 ng/ml; range: 4.3-6535.6 ng/ml. Endoscopically, six tumors were classified as Borrmann's type III cancer with the appearance of fungating mass lesion with a purple, berry-like surface. Of the five patients without distant metastasis, all received curative-intent surgery and four received adjuvant chemotherapy. Four patients with distant metastasis received either palliative operation or chemotherapy, and one patient received neither operation nor chemotherapy due to a poor performance status. The median survival time was 7.2 months (range: 0.7-131.8 months, and the 5-year survival rate was 20%. There was survival benefit in the chemotherapy groups. Conclusions: GHA is a rare subtype of gastric cancer which is prone to lymph node and liver metastasis. Most GHAs appear as Borrmann's type III fungating mass lesion with a purple, berry-like surface. Although the prognosis of advanced stage GHA is poor, chemotherapy might provide some benefit.

  9. 5-氮杂胞苷调控TIP30基因表达对人结直肠癌细胞氟尿嘧啶敏感性的影响%Effects of 5-Aza-dC on 5-Fu chemosensitivity by modulating TIP30 gene expression in human colorectal cancer cells

    陈小兵; 陈贝贝; 李剑; 王新锋; 马一杰; 罗素霞; 吕慧芳


    目的 探讨5-氮杂胞苷(5-Aza-dC)对结直肠癌细胞中TIP30基因表达的影响,并探讨其与氟尿嘧啶(5-Fu)敏感性的关系.方法 5-Aza-dC处理结直肠癌HCT116细胞,采用甲基化特异性PCR (MSP)方法检测TIP30基因启动子CpG岛甲基化状态,逆转录PCR检测TIP30 mRNA表达,Western blot法检测TIP30蛋白的表达,四甲基偶氮唑蓝(MTT)法检测HCT116细胞对5-Fu的敏感性.结果 未经5-Aza-dC处理的HCT116细胞中,TIP30基因启动子完全甲基化.5-Aza-dC处理HCT116细胞3d后去除5-Aza-dC,HCT116细胞TIP30基因非甲基化产物阳性,启动子去甲基化.随着5-Aza-dC去除时间的延长,HCT116细胞中TIP30基因启动子甲基化产物和非甲基化产物均为阳性,即启动子部分甲基化,部分非甲基化;去除5-Aza-dC第10天,TIP30基因启动子甲基化产物阳性,TIP30基因启动子重新甲基化.未经5-Aza-dC处理的结直肠癌HCT116细胞TIP30 mRNA和蛋白不表达.5-Aza-dC处理结直肠癌HCT116细胞3d后去除5-Aza-dC,TIP30 mRNA和蛋白表达明显增强.随着5-Aza-dC去除时间的延长,TIP30 mRNA和蛋白表达水平逐渐降低,第10天达到最低水平.在5-Aza-dC处理前、5-Aza-dC处理后去除5-Aza-dC的第0、10天,5-Fu作用于HCT116细胞的半数抑制浓度(IC50)分别为41.62、33.17和4.96 μg/ml.结论 TIP30基因表达差异可能与其启动子甲基化状态有关,且TIP30基因启动子甲基化差异与结直肠癌细胞对化疗药物的敏感性相关.%Objective To investigate the effect of 5-Aza-2'-deoxycytidine (5-Aza-dC) on TIP30 gene expression and the relationship between TIP30 expression and the sensitivity to 5-fluouracil (5-Fu) in colorectal cancer cells.Methods The methylation profile of TIP30 gene in HCT116 colorectal cancer cells was determined by methylation-specific PCR.The levels of TIP30 mRNA and protein were determined by RT-PCR and Western blot after the 5-Aza-dC treatment.MTT assay was used to detect the chemosensitivity of HCT116

  10. Relationship between Dihydropyrimidine Dehydrogenase(DPD) Activity and Toxicity of 5-FU-based Adjuvant Chemotherapy in Colorectal Cancer Patients%二氢嘧啶脱氢酶活性与结直肠癌患者5-FU辅助化疗毒性关系的研究

    周志伟; 王国强; 万德森; 潘志忠; 李苏; 陈功; 廖海


    背景与目的:5-氟尿嘧啶(5-FU)应用于不同的患者中,它的毒性及疗效均不同,个体差异较大.现发现二氢嘧啶脱氢酶(Dihydropyrimidine dehydrogenase,DPD)在其中起重要作用.本研究测定结直肠癌患者血DPD活性,并评价其与结直肠癌患者5-FU辅助化疗毒性及5-FU血药浓度之间的关系.方法:入选符合标准的结直肠癌患者30例,术前采用高效液相色谱法(HPLC)法测定血内源性二氢尿嘧啶(UH2)/尿嘧啶(U)值代表血DPD活性,术后2周行甲酰四氢叶酸(CF)60 mg/m2,2 h静脉滴注,5-FU 425 mg/m2,2 h静脉滴注,连续5天方案,辅助化疗.第1天刚滴完5-FU时和第5天刚滴完5-FU时抽血查5-FU血药浓度.评价患者血DPD活性和患者5-FU化疗毒性及其与5-FU血药浓度之间的相关性.结果:30例结直肠癌患者行5-FU/CF方案辅助化疗.化疗前查血DPD活性为4.09±1.21,最低2.14,最高6.7,呈正态分布,个体差异较大.第1天刚滴完5-FU时5-FU血药浓度为(2079.12±621.41)μg/L(1200.10~3554.80 μg/L);第5天刚滴完5-FU时5-FU血药浓度为(2197.64±606.78)μg/L(1259.00~3441.03μg/L),亦呈正态分布,个体差异较大.Pearson相关分析显示,血DPD活性与第1天刚滴完5-FU时5-FU血药浓度(r=-0.773,P=0.00)及第5天刚滴完5-FU时5-FU血药浓度(r=-0.833,P=0.00)呈负相关.t检验显示第1天刚滴完5-FU时5-FU血药浓度及第5天刚滴完5-FU时5-FU血药浓度没有差异(P=0.458).Spearman相关分析统计显示,5-FU致恶心呕吐、腹泻、骨髓抑制级别与血DPD活性呈负相关,与5-FU血药浓度呈正相关(P<0.05).结论:检测血DPD活性可以推断5-FU化疗时5-FU血药浓度及预测5-FU化疗的毒性,为结直肠癌的个体化治疗提供了理论依据.

  11. 血管生成抑制剂YH-16联合氟尿嘧啶抑制结直肠癌肝转移的研究%Inhibitory effect of angiogenesis inhibitor YH-16 in combination with 5-FU on liver metastasis of colorectal cancer

    周志伟; 万德森; 王国强; 任镜清; 卢震海; 唐绍贤; 叶燕丽; 陈功; 林素暇



  12. Transcriptomic Microenvironment of Lung Adenocarcinoma.

    Bossé, Yohan; Sazonova, Olga; Gaudreault, Nathalie; Bastien, Nathalie; Conti, Massimo; Pagé, Sylvain; Trahan, Sylvain; Couture, Christian; Joubert, Philippe


    Background: Tissues surrounding tumors are increasingly studied to understand the biology of cancer development and identify biomarkers.Methods: A unique geographic tissue sampling collection was obtained from patients that underwent curative lobectomy for stage I pulmonary adenocarcinoma. Tumor and nontumor lung samples located at 0, 2, 4, and 6 cm away from the tumor were collected. Whole-genome gene expression profiling was performed on all samples (n = 5 specimens × 12 patients = 60). Analyses were carried out to identify genes differentially expressed in the tumor compared with adjacent nontumor lung tissues at different distances from the tumor as well as to identify stable and transient genes in nontumor tissues with respect to tumor proximity.Results: The magnitude of gene expression changes between tumor and nontumor sites was similar with increasing distance from the tumor. A total of 482 up- and 843 downregulated genes were found in tumors, including 312 and 566 that were consistently differentially expressed across nontumor sites. Twenty-nine genes induced and 34 knocked-down in tumors were also identified. Tumor proximity analyses revealed 15,700 stable genes in nontumor lung tissues. Gene expression changes across nontumor sites were subtle and not statistically significant.Conclusions: This study describes the transcriptomic microenvironment of lung adenocarcinoma and adjacent nontumor lung tissues collected at standardized distances relative to the tumor.Impact: This study provides further insights about the molecular transitions that occur from normal tissue to lung adenocarcinoma and is an important step to develop biomarkers in nonmalignant lung tissues. Cancer Epidemiol Biomarkers Prev; 26(3); 389-96. ©2016 AACR.

  13. MiR-129-5p can increase colorectal cancer cell sensitivity to 5-Fu by targeting TYMS%MiR-129-5p通过靶定胸苷酸合成酶调节结肠癌细胞对5-氟尿嘧啶的敏感性

    胡俊华; 喻琴; 杨艳果; 王琦; 卢光新


    目的 研究miR-129-5p通过靶定胸苷酸合成酶(TYMS)调控结肠癌细胞对5-氟尿嘧啶(5-Fu)敏感性的分子机制.方法 构建结肠癌耐药细胞株LoVo/5-Fu,并用实时荧光定量聚合酶链反应(PCR)检测miR-129-5p的表达水平.流式细胞术和MTT毒性实验检测过表达miR-129-5p对LoVo/5-Fu凋亡和半数致死剂量(IC50)的影响.构建TYMS 3'UTR区荧光素酶报告载体,验证miR-129-5p对TYMS的靶向调控作用.Western Blot检测转染miR-129-5p后LoVo/5-Fu细胞中TYMS的蛋白表达.在LoVo/5-Fu内转染miR-129-5P siRNA,抑制其表达,检测LoVo/5-Fu细胞的IC50和凋亡.结果 过表达miR-129-5p后,LoVo/5-Fu细胞用5-Fu处理后凋亡增加,IC50降低.荧光素酶活性检测表明miR-129-5p能够抑制TYMS的荧光素酶活性.在LoVo/5-Fu细胞中miR-129-5p与TYMS的表达呈负相关.敲减TYMS后,LoVo/5-Fu细胞用5-Fu处理后凋亡增加,IC50降低.结论 MiR-129-5p能够通过靶定TYMS而增加结肠癌细胞对5-Fu的敏感性.

  14. Adenocarcinoma uretral em uma cadela Urethral adenocarcinoma in a bitch

    Marcia Cristina da Silva


    Full Text Available Tumores primários de uretra são raros em animais e há poucos relatos em cães. A ocorrência é maior em cadelas idosas, não havendo predileção por raça. Disúria, estrangúria e hematúria são sinais clínicos associados a esses tumores. É relatado um caso de adenocarcinoma primário de uretra em um cadela Poodle de 12 anos de idade que apresentava aumento de volume no membro pélvico esquerdo. Na necropsia, foram encontradas metástases na articulação femorotibial esquerda, na glândula adrenal e no rim.Urethral primary tumors are rare in animals and there are only few reports in dogs. They are more frequent in old bitches and have no breed predilection. Clinical signs associated with urethral primary tumors include dysuria, strangury and hematuria. We report a case of primary urethral adenocarcinoma in a 12-year-old female Poodle that was presented with localized volume enlargement in the left pelvic limb. At necropsy metastasis were found at the left femorotibial joint, adrenal gland and kidney.

  15. Sigmoid adenocarcinoma with renal metastasis

    Carini Dagnoni


    Full Text Available We report a case of a 75-year-old man submitted to a rectosigmoidectomy and partial cystectomy because of a sigmoid cancer and colovesical fistula. Seven months later and after four cycles of adjuvant chemotherapy, a lesion was detected in the kidney. Histology revealed tubular adenocarcinoma, which meant sigmoid cancer metastasis. Kidney metastases are very rare in colorectal cancer (CRC, but may be generally associated with an unfavorable prognosis. Thus, patients with metastatic CRC and kidney tumors are a diagnostic and therapeutic challenge.

  16. Neurological manifestation of colonic adenocarcinoma

    Uzair Chaudhary


    Full Text Available Paraneoplastic neurologic disorders are extremely rare in cancer patients and are most commonly associated with certain tumors, such as ovarian cancer, small cell lung cancer, and breast cancer. We report here a paraneoplastic neurological syndrome in a 53-year-old man with colonic adenocarcinoma with a solitary liver metastasis. His paraneoplastic syndrome was successfully treated by methylprednisolone and primary oncologic therapies including neoadjuvant chemotherapy and definitive surgery. This is also the first documented case of simultaneous manifestation of a sensory neuropathy and limbic encephalitis with colon cancer.

  17. MYC and gastric adenocarcinoma carcinogenesis

    Danielle Queiroz Calcagno; Mariana Ferreira Leal; Paulo Pimentel Assumpcao; Marilia de Arruda Cardoso Smith; Rommel Rodriguez Burbano


    MYC is an oncogene involved in cell cycle regulation, cell growth arrest, cell adhesion, metabolism, ribosome biogenesis, protein synthesis, and mitochondrial function. It has been described as a key element of several carcinogenesis processes in humans. Many studies have shown an association between MYC deregulation and gastric cancer. MYC deregulation is also seen in gastric preneoplastic lesions and thus it may have a role in early gastric carcinogenesis. Several studies have suggested that amplification is the main mechanism of MYC deregulation in gastric cancer. In the present review, we focus on the deregulation of the MYC oncogene in gastric adenocarcinoma carcinogenesis, including its association with Helicobacter pylori (H pylori) and clinical applications.

  18. A Case of Gingival Candidiasis with Bone Destruction on Gastric Cancer Patient Receiving Cytotoxic Chemotherapy

    Seungtaek Lim


    Full Text Available We herein report a case of gingival candidiasis in an advanced gastric cancer patient while receiving palliative cytotoxic chemotherapy. A 46-year-old male patient admitted to our hospital for known advanced gastric cancer with newly developed multiple liver metastases. While receiving 2nd line cytotoxic chemotherapy with 5FU, leucovorin, and paclitxel, he complained of gingival swelling accompanied by pain and whitish plaque. Due to lack of response to the conservative oral care, incisional biopsy of gingiva was done and the pathology confirmed gingival candidiasis. Although the lesion healed apparently after two-week antifungal therapy, pain as well as bony destruction remains. By presenting this case report, we intend to emphasize the immunocompromising effect of cancer while being on systemic chemotherapy.

  19. Inhibitive effect of CTLs, actived by dendritic cells, associated with 5 - FU on carcinoma cervicis in vitro and in nude mice%树突状细胞活化的CTLs联合5-FU在裸鼠体内外对子宫颈癌的抑制作用

    张莉; 王雪峰



  20. Protection effect of arginine/glutamine on intestinal barrier in rats receiving 5-FU chemotherapy%精氨酸、谷氨酰胺对氟尿嘧啶腹腔化疗后大鼠肠屏障的保护作用

    雷福明; 段学宁; 任志忠


    目的 观察精氨酸(Arg)、谷氨酰胺(Gin)对腹腔注射氟尿嘧啶化学药物疗法(化疗)后大鼠肠黏膜屏障的保护作用.方法 40只接受氟尿嘧啶化疗的健康雄性SD大鼠,随机分为4组:STD组:肠内营养;Arg组:肠内营养+Arg;Gin组:肠内营养+Gin;Chow组:自由进食.化疗前后测定各组大鼠体重、尿乳果糖/甘露醇比值(L/M),并在第8天时测定门静脉血内毒素,进行门静脉血和淋巴结细菌培养并测定回肠绒毛高度、回肠和结肠肠壁厚度.结果 和STD组相比,Arg、Gin组大鼠体重增加,L/M比值增加幅度减少,内毒素水平降低,回肠绒毛高度、回肠和结肠肠壁厚度增加.和Chow组相比,Gin组体重增加,尿L/M增加幅度降低、内毒素水平降低,回肠绒毛高度、回肠肠壁厚度增加;Arg组内毒素水平降低.各组间门静脉血和淋巴结细菌培养结果差异无统计学意义.Gin组内毒素水平低于Arg组.结论 Arg、Gin对腹腔注射氟尿嘧啶化疗后大鼠肠屏障具有保护作用,其作用要优于自由进食;并且Gin的保护作用略强于Arg.

  1. MicroRNA expression profiles associated with pancreatic adenocarcinoma and ampullary adenocarcinoma

    Schultz, Nicolai A; Werner, Jens; Willenbrock, Hanni;


    MicroRNAs have potential as diagnostic cancer biomarkers. The aim of this study was (1) to define microRNA expression patterns in formalin-fixed parafin-embedded tissue from pancreatic ductal adenocarcinoma, ampullary adenocarcinoma, normal pancreas and chronic pancreatitis without using micro......, normal pancreas and duodenal adenocarcinoma. In all, 43 microRNAs had higher and 41 microRNAs reduced expression in pancreatic cancer compared with normal pancreas. In all, 32 microRNAs were differently expressed in pancreatic adenocarcinoma compared with chronic pancreatitis (17 higher; 15 reduced......-dissection and (2) to discover new diagnostic microRNAs and combinations of microRNAs in cancer tissue. The expression of 664 microRNAs in tissue from 170 pancreatic adenocarcinomas and 107 ampullary adenocarcinomas were analyzed using a commercial microRNA assay. Results were compared with chronic pancreatitis...

  2. [An unusual secondary localization of bronchial adenocarcinoma].

    Mirallie, E; Courant, O; Sagan, C; Letessier, E; Paineau, J; Visset, J


    The authors report a rare case of metastatic carcinoma of the large bowel, secondary to a primary bronchogenic adenocarcinoma. Abdominal pain developed in a 44-year old man 5 months after lobectomy for lung adenocarcinoma. The diagnosis of a large caecal extraluminal mass was established by means of sonography, scanner and laparoscopy. Palliative resection (brain metastases) was performed. Postoperative histological examination revealed the resected tumor to be identical to the lung adenocarcinoma. The patient eventually died 4 months after resection (complication of intracranial hypertension). Diagnosis and therapeutic features of metastatic extra-thoracic lung carcinoma are discussed.

  3. [Why oesophageal adenocarcinoma is occurring more frequently].

    Doorakkers, Eva; Brusselaers, Nele


    The incidence of oesophageal adenocarcinoma has increased rapidly over the past decades in the Western world. The prognosis is poor with a mean 5-year survival rate of 19% in the Netherlands. Important risk factors that might account for this rising incidence are reflux, obesity and the absence of Helicobacter pylori. Oesophageal adenocarcinoma is 9 times more likely in men than in women. The reason for this much higher incidence of adenocarcinoma in men is still unclear, but sex hormones may play a role.

  4. Preoperative evaluation of oesophageal adenocarcinoma.

    Khanna, Lauren G; Gress, Frank G


    The preoperative evaluation of oesophageal adenocarcinoma involves endoscopic ultrasound (EUS), computed tomography (CT), and positron emission tomography (PET). With routine Barrett's oesophagus surveillance, superficial cancers are often identified. EUS, CT and PET have a limited role in the staging of superficial tumours. Standard EUS has limited accuracy, but high frequency ultrasound miniprobes are valuable for assessing tumour stage in superficial tumours. However, the best method for determining depth of invasion, and thereby stage of disease, is endoscopic mucosal resection. In contrast, in advanced oesophageal cancers, a multi-modality approach is crucial. Accurate tumour staging is very important since the treatment of advanced cancers involves a combination of chemotherapy, radiation, and surgery. EUS is very useful for staging of the tumour and nodes. High frequency ultrasound miniprobes provide the ability to perform staging when the lesion is obstructing the oesophageal lumen. CT and PET provide valuable information regarding node and metastasis staging.

  5. Rare coexistence of sarcoidosis and lung adenocarcinoma

    Amit Girish Kachalia


    Conclusion: While evidence is still lacking regarding association between sarcoidosis and lung adenocarcinoma, it is important for clinicians to exclude metastatic malignancy in patients exhibiting clinical and radiographic findings consistent with sarcoidosis.

  6. Rb and p53 gene deletions in lung adenocarcinomas from irradiated and control mice

    Zhang, Y.; Woloschak, G.E. [Argonne National Lab., IL (United States). Center for Mechanistic Biology and Biotechnology


    This study was conducted on mouse lung adenocarcinoma tissues that were formalin-treated and paraffin-embedded 25 years ago to investigate the large gene deletions of mRb and p53 in B6CF{sub 1} male mice. A total of 80 lung tissue samples from irradiated mice and 40 lung samples from nonirradiated controls were randomly selected and examined in the mRb portion of this study. The results showed a significant (P < 0.05) higher percentage of mRb deletions in lung adenocarcinomas from mice exposed to 60 once-weekly {gamma}-ray doses than those from mice receiving 24 once-weekly {gamma}-ray doses at low doses and low dose rates; however, the percentage was not significantly different (P > 0.05) from that for spontaneous lung adenocarcinomas or lung adenocarcinomas from mice exposed to single-dose {gamma} irradiation at a similar total dose. mRb fragments 3 (71%) and 5 (67%), the parts of the gene that encoded the pocket binding region of Rb protein to adenovirus E1A and SV40 T-antigen, were the most frequently deleted fragments. p53 gene deletion analysis was carried out on normal lungs and lung adenocarcinomas that were initially found to bear mRb deletions. Exons 1,4,5,6, and 9 were chosen to be analyzed.

  7. Superoxide dismutase prevents development of adenocarcinoma in a rat model of Barrett's esophagus

    Elena Piazuelo; Carmelo Cebrián; Alfredo Escartín; Pilar Jiménez; Fernando Soteras; Javier Ortego; Angel Lanas


    AIM: To test whether antioxidant treatment could prevent the progression of Barrett's esophagus to adenocarcinoma.METHODS: In a rat model of gastroduodenoesophageal reflux by esophagojejunal anastomosis with gastric preservation, groups of 6-10 rats were randomized to receive treatment with superoxide dismutase (SOD) or vehicle and followed up for 4 mo. Rat's esophagus was assessed by histological analysis, superoxide anion and peroxinitrite generation, SOD levels and DNA oxidative damage.RESULTS: All rats undergoing esophagojejunostomy developed extensive esophageal mucosal ulceration and inflammation by mo 4. The process was associated with a progressive presence of intestinal metaplasia beyondthe anastomotic area (9% 1st mo and 50% 4th mo) (94% at the anastomotic level) and adenocarcinoma(11% 1st mo and 60% 4th mo). These changes were associated with superoxide anion and peroxinitrite mucosal generation, an early and significant increase of DNA oxidative damage and a significant decrease in SOD levels (P<0.05). Exogenous administration of SOD decreased mucosal superoxide levels, increased mucosal SOD levels and reduced the risk of developing intestinal metaplasia beyond the anastomotic area (odds ratio = 0.326; 95%CI: 0.108-0.981; P = 0.046),and esophageal adenocarcinoma (odds ratio = 0.243;95%CI: 0.073-0.804; P = 0.021).CONCLUSION: Superoxide dismutase prevents the progression of esophagitis to Barrett's esophagus and adenocarcinoma in this rat model of gastrointestinal reflux, supporting a role of antioxidants in the chemoprevention of esophageal adenocarcinoma.

  8. Henoch Schönlein purpura associated with pulmonary adenocarcinoma

    Tetsuka Takafumi


    Full Text Available Abstract Introduction Henoch-Schönlein purpura is a common immunoglobulin A-mediated vasculitis syndrome in children. Henoch-Schönlein purpura can also affect adults and is probably related to malignancy. Case presentation We report the case of a 61-year-old Japanese man who presented for examination after an abnormal shadow was detected by chest radiography. He received a diagnosis of pulmonary adenocarcinoma, stage IV. Purpura on the legs, abdominal pain, diarrhea, hematuria and proteinuria developed at this time. Henoch-Schönlein purpura was diagnosed, base on the clinical symptoms and histological findings of biopsy specimens of the skin, which showed vasculitis with immunoglobulin A deposits. Our patient received chemotherapy with gemcitabine after successful steroid therapy for the Henoch-Schönlein purpura. Conclusion Although hematological malignancies are well-known causes of vasculitides, cases of Henoch-Schönlein purpura associated with lung adenocarcinoma are rare. Our patient was treated with corticosteroid therapy, which cleared the purpura and cytotoxic chemotherapy for the non-small cell lung cancer. However, he died from heart failure due to cardiac tamponade.

  9. Inhibition of miR-141 increases sensitivity of colon cancer cells to 5-Fu%miR-141表达抑制增强结肠癌细胞对5-Fu药物敏感性的研究

    马一楠; 金迎迎; 王亚利; 陈青娟; 卫阳


    目的 建立人结肠癌5-氟尿嘧啶(5-Fu)耐药细胞株,并探讨miR-141靶向作用PPP2 R1B介导结肠癌细胞对5-Fu耐药的机制. 方法 通过药物敏感性实验,选取5-Fu敏感细胞COLO-320细胞株采取大剂量冲击联合剂量递增法,诱导筛选5-Fu耐药结肠癌细胞株,稳定传代.四甲基偶氮唑盐法(MTT)检测耐药细胞和亲本细胞的半数抑制浓度(IC50).PCR的微阵列技术比较亲本细胞和5-Fu耐药细胞差异表达的miRNA分子,从中筛选出1个差异表达的miR-141分子.利用数据库Targetscan和miRBase database预测miR-141的靶基因为PPP2R1B,利用双荧光素酶报告基因检测进行鉴定.基因敲除miR-141后分析miR-141对PPP2R1B的调控作用. 结果 COLO-320细胞株经大剂量冲击联合剂量递增的方法诱导后可在5.0μmol/L的5-Fu培养液中稳定增殖,具有耐药性,命名为COLO-320/5-Fu,该细胞株5-Fu的IC50显著高于亲代细胞(P<0.05).芯片结果显示共有13个miRNAs在耐药细胞株中差异性表达,其中miRNA-141表达增加最为显著(P<0.05).敲除该miR-141后,耐药细胞的5-Fu敏感性显著增加,凋亡比例增加(P<0.05).结果显示,PPP2R1B为miR-141的靶基因,miRNA-141表达抑制显著上调PPP2R1B的表达水平并进而影响Akt磷酸化过程. 结论 本实验成功构建COLO-320/5-Fu耐药细胞株,miR-141可能通过靶向调控PPP2R1B,进而参与调控结肠癌细胞对5-Fu的耐药.

  10. Isolated Supraclavicular Lymph Node Metastasis in Pancreatic Adenocarcinoma: A Report of Three Cases and Review of the Literature

    Arundhati D Soman


    Full Text Available Context Supraclavicular lymph nodes represent a rare site of metastasis in pancreatic cancer. We report three cases of pancreatic adenocarcinoma with metastases to supraclavicular lymph nodes. Case report A 51-year-old male was diagnosed with locally advanced pancreatic adenocarcinoma on computed tomography (CT scan. He was recommended neoadjuvant chemotherapy followed by chemoradiation therapy. However, positron emission tomography (PET/CT scans and subsequent fine needle aspiration cytology showed supraclavicular lymph node metastasis. The patient received systemic chemotherapy for metastatic pancreatic adenocarcinoma. The second patient, a 66-year-old female with pancreatic adenocarcinoma, underwent pancreaticoduodenectomy and was found to have peripancreatic lymph node involvement. She received adjuvant chemotherapy and was followed-up with surveillance CT scans, which did not reveal any metastasis. However, the patient complained of neck swelling. PET/CT scan and biopsy revealed supraclavicular lymph node metastasis from a pancreatic adenocarcinoma primary. The third patient, a 79-year-old male with a past history of thyroid carcinoma who was treated with partial thyroidectomy, developed neck swelling 4 years after his surgery. Fine needle aspiration cytology was consistent with known papillary thyroid carcinoma. Staging evaluations revealed a pancreatic mass for which he underwent subtotal pancreatectomy and splenectomy. Histopathology revealed grade 3 pancreatic adenocarcinoma. Excisional biopsy of a supraclavicular lymph node showed metastatic pancreatic adenocarcinoma. PET/CT results were consistent with these findings. Conclusion In patients with pancreatic adenocarcinoma, supraclavicular lymph node metastasis represents an uncommon, but clinically significant finding that can lead to changes in treatment planning. PET imaging represents a valuable tool in the detection and follow up of these patients.

  11. The mechanism by which pancreatic cancer cells acquire drug resistance against 5-FU and gemcitabine%胰腺癌细胞对5氟脲嘧啶和健择的获得性耐药机制的研究

    石欣; 高乃荣; 等


    目的探讨胰腺癌细胞对5氟脲嘧啶(5-FU)和健择产生获得性耐药的机制.方法用磺酰罗丹明B蛋白染色法检测细胞毒性作用,根据药物剂量与细胞生存的关系计算50%抑制浓度(IC50);用RNA酶保护分析和Western blot法来检测Bcl-xL和mcl-1的表达水平.结果5-FU和健择对3株胰腺癌细胞均产生了细胞毒性作用.5-FU长期作用后,Capan-1细胞 IC50上升了2.1倍(P<0.05);健择长期作用后,Capan-1细胞IC50上升了1.8倍(P<0.05);而Mia-Paca-2细胞在5-FU和健择作用前后IC50明显降低 (P<0.05).产生获得性耐药细胞的Bcl-xL和mcl-1的表达均上调.结论胰腺癌细胞对5-FU相对耐药,而对健择较为敏感.化疗药物长期作用后,抑凋亡基因Bcl-xL和mcl-1的表达上调,胰腺癌细胞产生了获得性耐药.

  12. Survivin反义寡核苷酸对5-FU诱导人红白血病细胞系K562凋亡的影响%Survivin antisense oligodeoxy-nucleotid enhances 5-FU- induced apoptosis of leukemic cell line K562

    靳秋月; 王瑞珉; 谢红; 陈立军


    [目的]探讨survivin反义寡核苷酸(Antisense Oligodeoxy-nucleotid,ASODN)对5-FU(5-氟尿嘧啶)诱导人红白血病细胞系K562细胞凋亡的影响.[方法]体外培养K562细胞,合成survivin ASODN并经脂质体转染至K562细胞内,MTT法观察survivin ASODN组、5-FU组及5-FU联合survivin ASODN的细胞毒作用,Hoechst33342/PI双荧光染色观察各组细胞核形态,镜下计算各组细胞凋亡率.[结果]400、600、800、1000nmol/L survivin ASODN处理K562细胞44h后,IC50为800 nmol/L;与单独使用survivin ASODN或5-FU相比,5-FU联合800 nmol/L survivin ASODN后细胞生长明显受到抑制(P<0.01);Hoechest33342/PI双荧光染色可观察到survivin ASODN组、5-FU组及5-FU联合survivin ASODN组均出现明显核固缩、凝集等细胞凋亡表现.镜下细胞计数,survivin ASODN组、5-FU组及5-FU联合survivin ASODN组细胞凋亡率分别为54.55%、53.85%、86.70%.[结论]Survivin ASODN可增强K562细胞对5-FU的敏感性.

  13. Hyperfractionated Accelerated Radiation Therapy (HART) of 70.6 Gy With Concurrent 5-FU/Mitomycin C Is Superior to HART of 77.6 Gy Alone in Locally Advanced Head and Neck Cancer: Long-term Results of the ARO 95-06 Randomized Phase III Trial

    Budach, Volker, E-mail: [Department of Radiation Oncology, Charité Universitätsmedizin Berlin (Germany); Stromberger, Carmen [Department of Radiation Oncology, Charité Universitätsmedizin Berlin (Germany); Poettgen, Christoph [Department of Radiation Oncology, University Hospital of Essen (Germany); Baumann, Michael [Department of Radiation Oncology, University Hospital of Dresden (Germany); Budach, Wilfried [Department of Radiation Oncology, Heinrich Heine Universität Düsseldorf (Germany); Grabenbauer, Gerhard [Department of Radiation Oncology, University Hospitals of Erlangen (Germany); Marnitz, Simone [Department of Radiation Oncology, Charité Universitätsmedizin Berlin (Germany); Olze, Heidi [Department of Head and Neck Surgery, Charité Universitätsmedizin Berlin (Germany); Wernecke, Klaus-Dieter [Sostana GmbH, Berlin (Germany); Ghadjar, Pirus [Department of Radiation Oncology, Charité Universitätsmedizin Berlin (Germany)


    Purpose: To report the long-term results of the ARO 95-06 randomized trial comparing hyperfractionated accelerated chemoradiation with mitomycin C/5-fluorouracil (C-HART) with hyperfractionated accelerated radiation therapy (HART) alone in locally advanced head and neck cancer. Patients and Methods: The primary endpoint was locoregional control (LRC). Three hundred eighty-four patients with stage III (6%) and IV (94%) oropharyngeal (59.4%), hypopharyngeal (32.3%), and oral cavity (8.3%) cancer were randomly assigned to 30 Gy/2 Gy daily followed by twice-daily 1.4 Gy to a total of 70.6 Gy concurrently with mitomycin C/5-FU (C-HART) or 16 Gy/2 Gy daily followed by twice-daily 1.4 Gy to a total dose of 77.6 Gy alone (HART). Statistical analyses were done with the log-rank test and univariate and multivariate Cox regression analyses. Results: The median follow-up time was 8.7 years (95% confidence interval [CI]: 7.8-9.7 years). At 10 years, the LRC rates were 38.0% (C-HART) versus 26.0% (HART, P=.002). The cancer-specific survival and overall survival rates were 39% and 10% (C-HART) versus 30.0% and 9% (HART, P=.042 and P=.049), respectively. According to multivariate Cox regression analysis, the combined treatment was associated with improved LRC (hazard ratio [HR]: 0.6 [95% CI: 0.5-0.8; P=.002]). The association between combined treatment arm and increased LRC appeared to be limited to oropharyngeal cancer (P=.003) as compared with hypopharyngeal or oral cavity cancer (P=.264). Conclusions: C-HART remains superior to HART in terms of LRC. However, this effect may be limited to oropharyngeal cancer patients.

  14. 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.

    Curran, Desmond


    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.

  15. Urothelial-Type adenocarcinoma of the prostate mimicking metastatic colorectal adenocarcinoma

    Brian P. Adley


    Full Text Available Adenocarcinoma arising in urinary bladder or prostatic urethra is uncommon. When they occur, the tumor can be mistaken for metastatic lesions, especially from the colon. Here we report the fifth case of a primary urothelial-type adenocarcinoma arising in the prostate which showed enteric differentiation. The patient was a 55 year-old male whose prostatic needle core biopsy showed a high grade adenocarcinoma which was initially thought to be metastatic colon cancer. A follow-up colonoscopy was unremarkable. Subsequent prostatectomy revealed a high grade adenocarcinoma which was positive for cytokeratins 7 and 20, carcinoembryonic antigen, CDX2, and high molecular weight cytokeratin, and negative for prostate specific antigen, prostate specific acid phosphatase and AMACR. A diagnosis of urothelial-type adenocarcinoma of the prostate was rendered. We review the literature regarding this entity, and discuss the differential diagnosis, emphasizing utility of immunohistochemistry in making the diagnosis. Finally, we speculate on the behavior of these rare tumors.

  16. Oesophageal adenocarcinoma: the new epidemic in men?

    Rutegård, Martin; Lagergren, Pernilla; Nordenstedt, Helena; Lagergren, Jesper


    The last decades have witnessed an unprecedented rise in the incidence of oesophageal adenocarcinoma. This rise has mainly affected men, and current male-to-female sex ratio estimates range from 7-10 to 1. Major risk factors for oesophageal adenocarcinoma are gastro-oesophageal reflux disease and obesity, especially in combination. The prevalence of these risk factors has increased during the last decades, but there does not seem to be a marked differential distribution among men and women. However, reflux among men is more often associated with erosive reflux disease than it is among women. There is also evidence that male-type obesity, with a prominent abdominal distribution of fat, confers a greater risk increase for oesophageal adenocarcinoma than the female equivalent. Due to the marked male predominance and the finding that women tend to develop specialized intestinal metaplasia (Barrett's oesophagus) and adenocarcinoma at a later age than men, interest has been directed towards a potential aetiological role of reproductive factors and sex hormones. Breastfeeding has been found to be a protective factor for the development of adenocarcinoma, while no association has hitherto been established with other reproductive factors. Taken together, the male predominance in the incidence of oesophageal adenocarcinoma may partly be explained by the differential effect of the major risk factors reflux disease and obesity, but the mechanisms whereby this occurs need to be elucidated. Moreover, the association with breastfeeding indicates a need for extensive epidemiological studies to clarify a possible role of sex hormonal influence in the aetiology of oesophageal adenocarcinoma.

  17. TAK1-regulated expression of BIRC3 predicts resistance to preoperative chemoradiotherapy in oesophageal adenocarcinoma patients

    Piro, G; Giacopuzzi, S; Bencivenga, M; Carbone, C; Verlato, G; Frizziero, M; Zanotto, M; Mina, M M; Merz, V; Santoro, R; Zanoni, A; De Manzoni, G; Tortora, G; Melisi, D


    Background: About 20% of resectable oesophageal carcinoma is resistant to preoperative chemoradiotherapy. Here we hypothesised that the expression of the antiapoptotic gene Baculoviral inhibitor of apoptosis repeat containing (BIRC)3 induced by the transforming growth factor β activated kinase 1 (TAK1) might be responsible for the resistance to the proapoptotic effect of chemoradiotherapy in oesophageal carcinoma. Methods: TAK1 kinase activity was inhibited in FLO-1 and KYAE-1 oesophageal adenocarcinoma cells using (5Z)-7-oxozeaenol. The BIRC3 mRNA expression was measured by qRT–PCR in 65 pretreatment frozen biopsies from patients receiving preoperatively docetaxel, cisplatin, 5-fluorouracil, and concurrent radiotherapy. Receiver operator characteristic (ROC) analyses were performed to determine the performance of BIRC3 expression levels in distinguishing patients with sensitive or resistant carcinoma. Results: In vitro, (5Z)-7-oxozeaenol significantly reduced BIRC3 expression in FLO-1 and KYAE-1 cells. Exposure to chemotherapeutic agents or radiotherapy plus (5Z)-7-oxozeaenol resulted in a strong synergistic antiapoptotic effect. In patients, median expression of BIRC3 was significantly (P<0.0001) higher in adenocarcinoma than in the more sensitive squamous cell carcinoma subtype. The BIRC3 expression significantly discriminated patients with sensitive or resistant adenocarcinoma (AUC-ROC=0.7773 and 0.8074 by size-based pathological response or Mandard's tumour regression grade classifications, respectively). Conclusions: The BIRC3 expression might be a valid biomarker for predicting patients with oesophageal adenocarcinoma that could most likely benefit from preoperative chemoradiotherapy. PMID:26291056

  18. Hepatic Artery Chemotherapy for Advanced Adenocarcinoma of the Pancreas

    Robert Levin


    Full Text Available Context Seventy patients with adenocarcinoma of the pancreas with liver metastases, received chemotherapy every four weeks and their outcomes are reported in this retrospective series. Objective Advanced adenocarcinoma of the pancreas has a poor prognosis with only 2% 5-year survival reported by SEER (Surveillance, Epidemiology and End Results of the NCI. Chemotherapy given as intra-arterial perfusions is more intense than intravenous chemotherapy. Responses in perfused tumor is expected to be better than that obtained with only intravenous chemotherapy. Design Hepatic artery therapy is given monthly as a 5 hour perfusion of the hepatic artery using DDP and MIC. Also given is monthy Intravenous (IV therapy with four hours of Leucovorin (LV, with an injection of FUDR during the last hour of LV, daily x 5 days. Setting all therapy was given at Midwestern Regional Medical Center. Patients Thirty seven patients had no prior chemotherapy, while 33 patients had progressed after prior IV chemotherapy. Intervention Hepatic artery therapy with IV LV-FUDR was given for up to six months depending upon marrow tolerance and response. At that point, if response was ongoing or improving, therapy was continued monthly with only IV LV-FUDR; all therapy was stopped whenever progressive disease was evident. Results of those without prior chemotherapy, the mean overall survival (OS was 17.3 ± 30.2 months (mean±SD, ranging up to 13 years. Six patients survived more than three years with four are living in continuing complete remission for more than five years. Conclusion This therapy offers the opportunity for long term survival in a subset of patients with metastatic adenocarcinoma of the pancreas who have liver metastases, and some patients can be cured.

  19. EGFR Mutation Status in Uighur Lung Adenocarcinoma Patients

    Li SHAN


    Full Text Available Background and objective Epidermal growth factor receptor (EGFR, a transmembrane protein, is a member of the tyrosine kinase family. Gefitinib, an EGFR tyrosine-kinase inhibitors, has shown a high response rate in the treatment of lung cancer in patients with EGFR mutation. However, significant differences in EGFR mutations exist among different ethnic groups. The aim of this study is to investigate the prevalence of EGFR mutations in Uighur lung adenocarcinoma patients by using a rapid and sensitive detection method and to analyze EGFR mutation differences compared with Han lung adenocarcinoma patients. Methods We examined lung adenocarcinoma tissues from 138 patients, including 68 Uighur lung adenocarcinoma patients and 70 Han lung adenocarcinoma patients, for EGFR mutations in exons 18, 19, 20, and 21 by using the amplification refractory mutation system (ARMS PCR method. The mutation differences between Uighur and Han lung adenocarcinoma were compared by using the chi-square test method. Results EGFR mutations were detected in 43 (31.2% of the 138 lung adenocarcinoma patients. EGFR mutations were detected in 11 (16.2% of the 68 Uighur lung adenocarcinoma patients and in 32 (45.7% of the 70 Han lung adenocarcinoma patients. Significant differences were observed in the EGFR mutations between Uighur lung adenocarcinoma patients and Han lung adenocarcinoma patients (P<0.001. Conclusion Our results indicate that the EGFR mutation in Uighur lung adenocarcinoma patients (16.2% is significantly lower than that in Han lung adenocarcinoma patients (45.7%.

  20. Correlation between Gli2, FAK expression in colonic adenocarcinoma tissue with different clinical pathological characteristics and cancer cell proliferation, invasion

    Zhe Su


    Objective:To study the correlation between glioma-associated oncogene homologue 2 (Gli2), focal adhesion kinase (FAK) expression in colonic adenocarcinoma tissue with different clinical pathological characteristics and cancer cell proliferation, invasion.Methods: 56 patients with colonic adenocarcinoma who received surgical resection in our hospital between May 2012 and December 2015 were selected, cancer tissue and para-carcinoma tissue were collected respectively, immunohistochemical staining was used to detect the Gli2 and FAK protein-positive rate, and fluorescence quantitative PCR was used to determine the mRNA expression of Gli2 and FAK as well as the proliferation and invasionn genes.Results:Gli2 and FAK mRNA expression and protein-positive rate in colonic adenocarcinoma tissues were significantly higher than those in para-carcinoma tissues (P<0.05); Gli2 and FAK mRNA expression and protein-positive rate in colonic adenocarcinoma tissues with low differentiation, no differentiation, extraserosal infiltration and Dukes stage D were significantly higher than those in colonic adenocarcinoma tissues with high differentiation, medium differentiation, intraserosal infiltration, Dukes stage B-C (P<0.05); CyclinD1, CDK4, c-myc, N-cadherin and vimentin mRNA expression in Gli2- and FAK-positive colonic adenocarcinoma tissues were significantly higher than those in Gli2- and FAK-negative colonic adenocarcinoma tissues (P<0.05).Conclusions:Gli2 and FAK expression are high in colonic adenocarcinoma tissues and associated with the clinical pathological staging of tumor, and highly expressed Gli2 and FAK can promote cell proliferation and invasion.

  1. Locally advanced pancreatic adenocarcinoma. Chemoradiotherapy, reevaluation and secondary resection; Adenocarcinomes pancreatiques localement evolues. Chimioradiotherapie, reevaluation et resection secondaire?

    Delpero, J.R.; Turrini, O. [Institut Paoli-Calmettes, Dept. de chirurgie, 13 - Marseille (France)


    Induction chemoradiotherapy (CRT) may down-stage locally advanced pancreatic tumors but secondary resections are unfrequent. However some responders' patients may benefit of a RO resection. Patients and methods. We report 18 resections among 29 locally advanced pancreatic cancers; 15 patients were treated with neo-adjuvant 5-FU-cisplatin based (13) or taxotere based (2 patients) chemoradiotherapy (45 Gy), and 3 patients without histologically proven adenocarcinoma were resected without any preoperative treatment. Results. The morbidity rate was 28% and the mortality rate was 7%; one patient died after resection (5.5%) and one died after exploration (9%). The RO resection rate was 50%. The median survival for the resected patients was not reached and the actuarial survival at 3 years was 59%. Two specimens showed no residual tumor and the two patients were alive at 15 and 46 months without recurrence; one specimen showed less than 10% viable tumoral cells and the patient was alive at 36 months without recurrence. A mesenteric infarction was the cause of a late death at 3 years in a disease free patient (radiation induced injury of the superior mesenteric artery). The median survival of the 11 non-resected patients was 21 months and the actuarial survival at 2 years was 0%. When the number of the resected patients (18) was reported to the entire cohort of the patients with locally advanced pancreatic cancer treated during the same period in our institution, the secondary resectability rate was 9%. Conclusion. Preoperative chemoradiotherapy identifies poor surgical candidates through observation and may enhance the margin status of patients undergoing secondary resection for locally advanced tumors. However it remains difficult to evaluate the results in the literature because of the variations in the definitions of resectability. The best therapeutic strategy remains to be defined, because the majority of patients ultimately succumb with distant metastatic

  2. Identification of distinct phenotypes of locally advanced pancreatic adenocarcinoma.

    Teo, Minyuen


    A significant number of pancreatic ductal adenocarcinoma present as locally advanced disease. Optimal treatment remains controversial. We sought to analyze the clinical course of locally advanced pancreatic adenocarcinoma (LAPC) in order to identify potential distinct clinical phenotypes.

  3. Effect of hepatic targeting drug Gal-HSA-5-FU on proliferation and cell cycle of human hepatocarcinoma cells (Bel-7402)%肝靶向药物Gal-HSA-5-FU对Bel-7402肝癌细胞增殖和细胞周期的影响

    李育超; 周克元; 蔡春; 张海涛


    目的 了解合成的肝靶向药物半乳糖化人血清白蛋白与5-氟尿嘧啶偶联物(galactosylated human serum albumin 5-fluorouracil conjugate,Gal-HSA-5-FU)对肝癌细胞Bel-7402细胞增殖和细胞周期的影响.方法 采用MTT法(噻唑蓝还原法)检测Gal-HSA-5-FU对细胞生长的抑制率和IC50,流式细胞术分析细胞周期变化,荧光染色法观察细胞凋亡.结果 0.953~30.500mg·L-1 Gal-HSA-5-FU分别处理Bel-7402细胞24、48、72h,细胞增殖被抑制,其增殖抑制率随药物质量浓度的增加和作用时间的延长而增高,其IC50值分别为(20.957±0.752)、(11.793±0.546)、(5.843±0.735)mg·L-1,48、72h的IC50值明显低于24h的IC50值,差异均有统计学意义 (P<0.01).相同质量浓度5-FU与Gal-HSA-5-FU作用24h,其IC50值差异无统计学意义 (P>0.05).Gal-HSA-5-FU作用Bel-7402 24h,S期细胞明显升高,G2/M期细胞明显下降.荧光染色偶见凋亡细胞.结论 Gal-HSA-5-FU能抑制Bel-7402细胞增殖,且抑制作用具有剂量和时间依赖性;一定剂量的Gal-HSA-5-FU可能通过阻滞Bel-7402于S期而抑制其增殖.

  4. shMRE11质粒转染对BEL7402/5-FU肝癌细胞耐药性的影响%Effect of plasmid transfected shMRE11 on the drug-resistance of BEL7402/5-FU hepatoma cells

    范芳; 耿磊; 李长福


    目的 研究减数分裂重组蛋白11(MRE11)基因沉默对5-氟尿嘧啶(5-FU)耐药的肝癌细胞株Bel7402/5-FU的化疗敏感性及耐药相关蛋白1(MRP1)表达的影响,探讨MRE11与肝癌耐药性的关系.方法 采用阳离子脂质体法将shMRE11干扰质粒转染BEL7402/5-FU细胞,实时定量PCR(qRT-PCR)及Western blot法检测沉默效率;MTT法检测转染后BEL7402/5-FU细胞对化疗药物顺铂(DDP)、丝裂霉素(MMC)、阿霉素(ADM)、5-FU的敏感性,qRT-PCR及Western blot法分别检测转染后BEL7402/5-FU细胞中耐药相关蛋白MRP1 mRNA水平及蛋白水平的变化.结果 qRT-PCR及Western blot法检测显示MRE11mRNA及蛋白水平的沉默效率分别为78.0%、56.1%.MTT结果显示,shMRE 11转染BEL7402/5-FU细胞后,shMRE11实验组对DDP、MMC、ADM、5-FU的IC50均低于对照组(P<0.05).qRT-PCR及Western blot法检测结果显示shMRE11实验组MRP1mRNA及蛋白水平的表达与对照组相比均有所降低(P<0.05).结论 shMRE11能够提高肝癌耐药细胞BEL7402/5-FU对化疗药物的敏感性,降低耐药相关蛋白MRP1的表达.

  5. RNA干扰抑制MDR1表达并逆转Bel7402/5-Fu肝癌细胞耐药性的研究%Suppression of MDR1 expression and restoration of sensitivity to chemotherapy in multidrug-resistant hepatocellular carcinoma cell line Bel7402/5-Fu by RNA interference



    目的:研究小片段RNA干扰对肝癌耐药细胞系Bel7402/5-Fu中多药耐药基因(multidrug resistance 1,MDR1)及其蛋白产物P-gp表达的抑制作用和逆转其耐药性的效果.方法:合成针对MDR1启动子区域的RNA干扰小片段,转染肝癌耐药细胞Bel7402/5-Fu.通过RT-PCR和Western blot方法,在mRNA和蛋白水平评价RNA干扰对MDR1表达的影响.MTT法检测RNA干扰逆转Bel7402/5-Fu细胞耐药性的效果,按实验组和对照组细胞的半数抑制剂量(IC50)计算RNA干扰对细胞耐药倍数的改变和RNA干扰组细胞的耐药逆转倍数.以流式细胞仪比较各组细胞在相同浓度化疗药物作用时细胞的凋亡情况.结果:在耐药肝癌细胞Bel7402/5-Fu中,RNA干扰明显抑制了MDR1 mRNA和蛋白产物P-gp的表达水平,其表达仅为对照组细胞的22.55%和25.49%(P<0.01).在相同浓度化疗药物的作用下,RNA干扰组Bel7402/5-Fu细胞凋亡比例显著高于对照组(P<0.01),表明细胞耐药性显著下降,对5-Fu的耐药逆转倍数为14.88倍.结论:肝癌耐药细胞Bel7402/5-Fu中,RNA干扰对MDR1 mRNA及其蛋白产物P-gp的表达水平有显著抑制作用,具有良好的逆转耐药性的效果.

  6. 全反式维甲酸和5-Fu对胃癌细胞端粒酶活性和细胞生长的影响%The effects of ATRA and 5-Fu on telomerase activity and cell growth of gastric cancer cells in vitro

    朱兆华; 夏忠胜; 何守搞


    目的观察ATRA,5-Fu单独和联合应用对体外培养的胃癌细胞端粒酶活性及细胞生长的影响.方法分别用ATRA,5-Fu单独和联合处理胃癌MGC-803细胞,采用MTT法测定细胞活力,采用端粒重复序列扩增法测定端粒酶活性.结果胃癌细胞活力随ATRA,5-Fu浓度增高、作用时间的延长其细胞活力逐渐下降,ATRA d1,d3,d 5的IC50分别为>40μmol/L,(20~40)μmol/L,(10~20)μmol/L;5-Fu d1,d3,d5的IC50分别为>25μmol/L,(2~5)μmol/L,(2~5)μmol/L;40μmol/L ATRA,5μmol/L 5-Fu及40μmol/LATRA+5μmol/L 5-Fu处理胃癌细胞3 d其细胞活力分别为46%,47%,8%(P<0.01),端粒酶活性分别为45.68%(P<0.01),100.00%,46.10%(P<0.01).结论ATRA,5-Fu均能抑制胃癌细胞的生长,其抑制作用具有时间和浓度依赖性,且二者合用具有协同抑制作用;ATRA能抑制胃癌细胞端粒酶活性,而5-Fu对胃癌细胞端粒酶活性无影响,二者合用对胃癌细胞端粒酶活性无协同抑制作用.抑制端粒酶活性可能是ATRA抗癌机制之一.

  7. Preliminary study of microRNA expression in colon cancer drug-resistant cell line LoVo/5-Fu%结肠癌耐药细胞株LoVo/5-Fu中microRNA表达的初步研究

    何冬雷; 谢小明; 刘玉; 夏立平; 许荣华


    目的 建立结肠癌细胞耐药模型LoVo/5-FU并初步筛选可能的耐药相关的microRNA.方法 采用5-FU浓度递增法建立人结肠癌细胞耐药模型LoVo/5-FU,观察其生长规律并绘制细胞生长曲线;用MTT法鉴定耐药细胞株耐药性并计算耐药指数(RI);用microRNA芯片技术检测耐药细胞株LoVo/5-FU与其亲本细胞株LoVo中mi-croRNA的表达谱,筛选差异表达的microRNA;用实时荧光定量PCR方法对筛选出的部分差异microRNA在耐药细胞及其亲本细胞中的表达情况进行验证.结果 LoVo/5-FU细胞与LoVo细胞相比,生长缓慢,细胞体积增大,耐药株LoVo/5-FU细胞相对于其亲本LoVo细胞的耐药倍数为8.08.microRNA芯片的结果显示,耐药株LoVo/5-FU细胞与亲本LoVo细胞比较,有10个microRNA表达上调,13个microRNA表达下调;实时荧光定量pcr的结果进一步证实mir-210、mir196a、mir-1281在LoVo/5-FU中显著上调,而let-7fmir-1228显著下调,其中mir-210在LoVo/5-FU与LoVo中的表达有明显差异.结论 LoVo/5-FU细胞株耐药性稳定,筛选获得的差异miRNA可能通过调控其靶基因而参与人结肠癌细胞对5-Fu的耐药,为进一步研究microRNA在结肠癌耐药机制中的作用奠定基础.

  8. Effects of polypeptide extract from scorpion venom on immune function of H22 hepatocarcinoma-bearing mice intervened by 5-Fu%蝎毒多肽提取物对5-Fu干预H22荷瘤小鼠免疫功能的影响

    王朝霞; 王兆朋; 贾青; 张月英; 韩琛; 张钰; 王恒孝


    目的 探讨蝎毒多肽提取物(PESV)对5-Fu干预H22荷瘤小鼠免疫功能的影响.方法 Balb/c小鼠随机分为对照组、模型组、化疗组及PESV高、低剂量组,模型组接种H22肝癌,化疗组ip 20 mg/kg 5-Fu,PESV组化疗同时ig 40、10 mg/kgPESV,连续干预28 d后处死,计算瘤质量、抑瘤率、脾脏指数和胸腺指数.采用鸡红细胞吞噬实验检测H22荷瘤小鼠腹腔巨噬细胞吞噬功能;流式细胞术检测小鼠脾细胞中T细胞亚群、NK细胞和NKT细胞的变化;采用ELISA法检测小鼠外周血中IFN-γ和IL-4的分泌水平.结果 与化疗组比较,PESV高剂量组瘤质量明显减轻(P<0.05);低、高剂量组的脾脏指数、高剂量组胸腺指数、腹腔巨噬细胞吞噬率和吞噬指数、高剂量组CD4+T/CD8+T值及高、低剂量组NK/NKT细胞均显著升高(P<0.05、0.01、0.001).与化疗组比较,PESV高、低剂量组小鼠血清中IFN-γ水平明显增高,IL-4水平显著降低(P<0.05、0.01).结论 PESV可逆转5-Fu干预H22荷瘤小鼠导致的免疫抑制作用.

  9. Adenocarcinoma of Meckel's cave: case report.

    Tacconi, L; Arulampalam, T; Johnston, F; Symon, L


    A rare localization of adenocarcinoma in Meckel's cave is reported in a 58-year-old woman, who had a 5-month history of pain and altered sensation in the second division of the left trigeminal nerve. Removal of the lesion was achieved by a subtemporal route. Histology showed this to be an adenocarcinoma. The patient underwent investigations for a primary tumor; the investigations were all negative, and the patient was subsequently treated with a course of radiotherapy. At 4-month follow-up, there was no evidence of recurrence, and she remains symptomatically well. The various mechanisms of secondary localization are discussed.

  10. Spinal cord compression due to ethmoid adenocarcinoma.

    Johns, D R; Sweriduk, S T


    Adenocarcinoma of the ethmoid sinus is a rare tumor which has been epidemiologically linked to woodworking in the furniture industry. It has a low propensity to metastasize and has not been previously reported to cause spinal cord compression. A symptomatic epidural spinal cord compression was confirmed on magnetic resonance imaging (MRI) scan in a former furniture worker with widely disseminated metastases. The clinical features of ethmoid sinus adenocarcinoma and neoplastic spinal cord compression, and the comparative value of MRI scanning in the neuroradiologic diagnosis of spinal cord compression are reviewed.

  11. Generalized Lymphadenopathy: Unusual Presentation of Prostate Adenocarcinoma

    Bulent Cetin


    Full Text Available Generalized lymphadenopathy is a rare manifestation of metastatic prostate cancer. Here, we report the case of a 59-year-old male patient with supraclavicular, mediastinal, hilar, and retroperitoneal and inguinal lymphadenopathy, which suggested the diagnosis of lymphoma. There were no urinary symptoms. A biopsy of the inguinal lymph node was compatible with adenocarcinoma, whose prostatic origin was shown by immunohistochemical staining with PSA. The origin of the primary tumor was confirmed by directed prostate biopsy. We emphasize that a suspicion of prostate cancer in men with adenocarcinoma of undetermined origin is important for an adequate diagnostic and therapeutic approach.

  12. Skin Metastasis from an Occult Esophageal Adenocarcinoma

    F Fereidooni


    Full Text Available Metastases to the skin from carcinoma arising in other organs are uncommon, yet they may be the first presentation of neoplastic disease. They usually originate from primary tumours in the breast, lung or colon. Skin metastases from esophageal adenocarcinoma are extremely rare. A unique case of an otherwise healthy patient who presented with a small, painless, mobile, clinically localized facial skin nodule is reported. A biopsy revealed metastatic adenocarcinoma, and subsequent investigations detected the primary tumour in the esophagus, despite no symptoms.

  13. Strategies for the prevention of oesophageal adenocarcinoma.

    Almond, L Max; Old, Oliver; Barr, Hugh


    The incidence of oesophageal adenocarcinoma has increased by 500% over the past 30 years [1]. Improved understanding of the mechanisms of neoplastic progression provides an opportunity to reverse this trend. A thorough review of emerging strategies aiming to prevent the formation of oesophageal malignancy is presented. These include dietary modification, chemoprevention, early endoscopic identification and treatment of premalignant disease, and the potential for a non-endoscopic screening test. Oesophageal adenocarcinoma has become a major public health problem in the West and it is essential that clinicians are fully informed of risk reduction strategies so that they can be actively promoted in the community.

  14. Clinical outcomes in pancreatic adenocarcinoma associated with BRCA-2 mutation.

    Vyas, Ojas; Leung, Keith; Ledbetter, Leslie; Kaley, Kristin; Rodriguez, Teresa; Garcon, Marie C; Saif, Muhammad W


    Patients with BRCA-1 and BRCA-2 germ line mutations are at an increased risk of developing pancreatic adenocarcinoma (PAC). In particular, the BRCA-2 mutation has been associated with a relative risk of developing PAC of 3.51. The BRCA-2 protein is involved in repair of double-stranded DNA breaks. Recent reports have suggested that in the setting of impaired DNA repair, chemotherapeutic agents that induce DNA damage, such as platinum-based antineoplastic drugs (platins) and poly(ADP-ribose) polymerase inhibitors (PARP inhibitors), have improved efficacy. However, because of the relative rarity of BRCA-related PAC, studies evaluating such agents in this setting are scarce. Patients with a known BRCA-2 mutation and PAC were retrospectively reviewed. Ten patients with PAC and BRCA-2 mutation were identified. Four patients (40%) were of Ashkenazi Jewish descent. Seven patients (70%) received platinum agents, two (20%) received mitomycin-C, one (10%) received a PARP inhibitor, and seven (70%) received a topoisomerase-I inhibitor. Overall, chemotherapy was well tolerated with expected side effects. Patients with a BRCA-2 mutation and PAC represent a group with a unique biology underlying their cancer. Chemotherapies such as platinum derivatives, mitomycin-C, topoisomerase-I inhibitors, and PARP inhibitors targeting DNA require further investigation in this population. Genetic testing may guide therapy in the future.

  15. MiR-145 expression accelerates esophageal adenocarcinoma progression by enhancing cell invasion and anoikis resistance.

    Mathieu Francois Derouet

    Full Text Available BACKGROUND: Carcinoma of the esophagus has a high case fatality ratio and is now the 6th most common cause of cancer deaths in the world. We previously conducted a study to profile the expression of miRNAs in esophageal adenocarcinoma (EAC pre and post induction therapy. Of the miRNAs differentially expressed post induction chemoradiation, miR-145, a known tumor suppressor miRNA, was upregulated 8-fold following induction therapy, however, its expression was associated with shorter disease-free survival. This unexpected result was explored in this current study. METHODS: In order to study the role of miR-145 in EAC, miRNA-145 was overexpressed in 3 EAC cell lines (OE33, FLO-1, SK-GT-4 and one ESCC cell line (KYSE-410. After validation of the expression of miR-145, hallmarks of cancer such as cell proliferation, resistance to chemotherapy drugs or anoikis, and cell invasion were analyzed. RESULTS: There were no differences in cell proliferation and 5 FU resistance between miR145 cell lines and the control cell lines. miR-145 expression also had no effect on cisplatin resistance in two of three cell lines (OE33 and FLO-1, but miR-145 appeared to protect SK-GT-4 cells against cisplatin treatment. However, there was a significant difference in cell invasion, cell adhesion and resistance to anoikis. All three EAC miR-145 cell lines invaded more than their respective controls. Similarly, OE33 and SK-GT-4 miR-145 cell lines were able to survive longer in a suspension state. DISCUSSION: While expression of miR-145 in ESCC stopped proliferation and invasion, expression of miR-145 in EAC cells enhanced invasion and anoikis resistance. Although more work is required to understand how miR-145 conveys these effects, expression of miR-145 appears to promote EAC progression by enhancing invasion and protection against anoikis, which could in turn facilitate distant metastasis.

  16. Treatment and survival in a population-based sample of patients diagnosed with gastroesophageal adenocarcinoma

    Deirdre P Cronin-Fenton; Margaret M Mooney; Limin X Clegg; Linda C Harlan


    AIM:To examine the extent of use of specific therapies in clinical practice,and their relationship to therapies validated in clinical trials.METHODS:The US National Cancer Institutes' Patterns of Care study was used to examine therapies and survival of patients diagnosed in 2001 with histologically-confirmed gastroesophageal adenocarcinoma (n = 1356).The study re-abstracted data and verified therapy with treating physicians for a population-based stratified random sample.RESULTS:Approximately 62% of patients had stomach adenocarcinoma (SAC),while 22% had gastric-cardia adenocarcinoma (GCA),and 16% lower esophageal adenocarcinoma (EAC).Stage IV/ unstaged esophageal cancer patients were most likely and stage I -111 stomach cancer patients least likely to receive chemotherapy as all or part of their therapy;gastric-cardia patients received chemotherapy at a rate between these two.In multivariable analysis by anatomic site,patients 70 years and older were significantly less likely than younger patients to receive chemotherapy alone or chemoradiation for all three anatomic sites.Among esophageal and stomach cancer patients,receipt of chemotherapy was associated with lower mortality;but no association was found among gastric-cardia patients.CONCLUSION:This study highlights the relatively low use of clinical trials-validated anti-cancer therapies in community practice.Use of chemotherapy-based treatment was associated with lower mortality,dependent on anatomic site.Findings suggest that physicians treat lower esophageal and SAC as two distinct entities,while gastric-cardia patients receive a mix of the treatment strategies employed for the two other sites.

  17. Adenocarcinoma of lung masquerading as systemic auto-immune disease.

    Naha, Kushal; Thakare, Sayali; Vivek, G; Prabhu, Mukhyaprana


    A 40-year-old previously healthy male presented with acute onset painless dimness of vision in both eyes since the past week and low-grade fever, anorexia and weight loss for the past 1 month. He had been evaluated at a local hospital and diagnosed to have a posterior cerebral artery territory infarct on the left side on the strength of cranial CT. Shortly after receiving antiplatelets and warfarin he had developed severe coagulopathy as evidenced by haematemesis, epistaxis and haematuria. Preliminary investigation revealed prolonged clotting parameters, renal failure and anaemia. Cerebral MRI showed multiple areas of cortical haemorrhage. In the course of his hospital stay, he developed further stigmata of auto-immunity including Coomb's positive haemolytic anaemia, recurrent venous thromboses and a palpable purpuric truncal rash. He was eventually diagnosed to have an adenocarcinoma of the lung, and was subsequently referred to an oncologist for further therapy.

  18. Does St. John's Wort cause regression in gastrointestinal system adenocarcinomas?

    Karaarslan, Serap; Cokmert, Suna; Cokmez, Atilla


    St. John's Wort (SJW) is an old herb which has long been consumed widely for its anti-inflammatory, antiviral, and anti-depressive properties. Here we present a detailed clinical evaluation of three cases (two colon and one duodenal adenocarcinoma) with remarkable and intensive lymphoplasmocytic host reaction, at the basal part of tumor, intensive fibrosis, giant cells, plasma cell increase in lymph nodes and few giant cells in germinal centers in resection specimens. The observation of similar host reaction in those tumors having otherwise usual appearance was interesting. None of the cases received neoadjuvant chemoradiotherapy or additional treatment before surgery but only SJW. These cases are presented to increase the awareness about such cases. Further research is needed to reveal the possible effect of SJW, which has long been consumed for different treatment purposes, on human tumors.

  19. Pancreatic ductal adenocarcinoma screening: New perspectives

    Raffaele Pezzilli; Dario Fabbri; Andrea Imbrogno


    Pancreatic ductal adenocarcinoma accounts for more than 90% of all pancreatic cancers and its incidence has increased significantly worldwide.Patients with pancreatic ductal adenocarcinoma have a poor outcome and more than 95% of the people affected die from the disease within 12 mo after diagnosis.Surgery is the first-line treatment in the case of resectable neoplasm,but only 20% of patients are candidates for this approach.One of the reasons there are few candidates for surgery is that,during the early phases of the disease,the symptoms are poor or non-specific.Early diagnosis is of crucial importance to improve patient outcome; therefore,we are looking for a good screening test.The screening test must identify the disease in an early stage in order to be effective; having said this,a need exists to introduce the concept of "early" ductal adenocarcinoma.It has been reported that at least five additional years after the occurrence of the initiating mutation are required for the acquisition of metastatic ability of pancreatic adenocarcinoma and patients die an average of two years thereafter.We have reviewed the most recent literature in order to evaluate the present and future perspectives of screening programs of this deadly disease.

  20. Epidemiology and risk factors for oesophageal adenocarcinoma.

    Lepage, Côme; Drouillard, Antoine; Jouve, Jean-Louis; Faivre, Jean


    Oesophageal adenocarcinoma will soon cease to be a rare form of cancer for people born after 1940. In many Western countries, its incidence has increased more rapidly than other digestive cancers. Incidence started increasing in the Seventies in England and USA, 15 years later in Western Europe and Australia. The cumulative risk between the ages of 15 and 74 is particularly striking in the UK, with a tenfold increase in men and fivefold increase in women in little more than a single generation. Prognosis is poor with a 5-year relative survival rate of less than 10%. The main known risk factors are gastro-oesophageal reflux, obesity (predominantly mediated by intra-abdominal adipose tissues) and smoking. Barrett's oesophagus is a precancerous lesion, however, the risk of degeneration has been overestimated. In population-based studies the annual risk of adenocarcinoma varied between 0.12% and 0.14% and its incidence between 1.2 and 1.4 per 1000 person-years. Only 5% of subjects with Barrett's oesophagus die of oesophageal adenocarcinoma. On the basis of recent epidemiological data, new surveillance strategies should be developed. The purpose of this review is to focus on the epidemiology and risk factors of oesophageal adenocarcinoma.

  1. Afatinib in Treatment-Naive Patients With EGFR-Mutated Lung Adenocarcinoma With Brain Metastasis: A Case Series.

    Li, Shih-Hong; Hsieh, Meng-Heng; Fang, Yueh-Fu


    Tyrosine kinase inhibitors (TKIs) of epidermal growth factor receptor (EGFR) were previously the standard first-line treatments for lung cancers with activating EGFR mutations. The first-generation reversible EGFR TKIs, gefitinib and erlotinib, demonstrated substantial efficacy in the treatment of brain metastases from EGFR-mutated lung adenocarcinoma. However, the efficacy of afatinib, the second-generation irreversible EGFR TKI, as the first-line treatment in lung adenocarcinoma patients with brain metastasis has yet to be evaluated.Here, we report cases of 3 patients who received afatinib alone as the first-line treatment in combination with whole-brain radiotherapy or following surgical resection of brain metastases. All 3 patients had EGFR L858R mutation. The first patient had lung adenocarcinoma with brain metastasis and no neurologic symptoms. After consultation, she received afatinib as a first-line treatment. Chest computed tomography and brain magnetic resonance imaging (MRI) showed partial response. The second patient had lung adenocarcinoma accompanied with a metastatic brain lesion associated with seizures. This patient received whole-brain radiotherapy and afatinib treatment following brain MRI and subsequently showed significant regression of the brain metastasis. The third patient had strabismus of the right eye, and brain MRI showed a single tumor at the cerebellar pontine angle. This patient underwent surgical resection of the tumor followed by afatinib treatment. He refused adjuvant radiotherapy after surgery for brain metastasis. The brain MRI showed no recurrent brain metastasis, and the patient had relatively less neurologic deficiency.This series of 3 cases indicate that afatinib may be an appropriate first-line treatment alternative in patients having lung adenocarcinoma with EGFR mutations. Further retrospective analyses and prospective clinical trials are required to substantiate the efficacy of afatinib in the treatment of brain

  2. Electronic warfare receivers and receiving systems

    Poisel, Richard A


    Receivers systems are considered the core of electronic warfare (EW) intercept systems. Without them, the fundamental purpose of such systems is null and void. This book considers the major elements that make up receiver systems and the receivers that go in them.This resource provides system design engineers with techniques for design and development of EW receivers for modern modulations (spread spectrum) in addition to receivers for older, common modulation formats. Each major module in these receivers is considered in detail. Design information is included as well as performance tradeoffs o

  3. [P53 protein in adenocarcinoma of the large intestine].

    Paluszkiewicz, P; Pawłowska-Wakowicz, B; Cybulski, M; Berbeć, H


    P53 gen mutations play significant role in neoplastic transformation of colorectal mucosa. We investigated p53 immunostaining in 80 cases of spontaneous human colorectal adenocarcinomas (with monoclonal DO7 antibody and LSAB+ kit). We found positive, nuclear p53 immunostaining in 64% of nonmucinous adenocarcinoma tissues and in 19% of mucinous adenocarcinomas tissues. P53 protein deposits were most often found in colorectal adenocarcinomas localised in rectum (66.67%) and in advanced (Dukes C, D) colorectal adenocarcinomas (59.38%) as well. There was no statistical significance between the p53 positive immunostaining and the histological differentiation of the colorectal adenocarcinomas. The overall survival of patients with tumours positive for p53 protein was significantly shorter than that of patients with colorectal cancers negative for p53 protein. We conclude that p53 immunohistochemical analysis may be treated as a supplementary prognostic marker for patients with colorectal adenocarcinoma, especially it may be useful for adjuvant therapy selection.

  4. A rare tumoral combination, synchronous lung adenocarcinoma and mantle cell lymphoma of the pleura

    Foroulis Christophoros N


    Full Text Available Abstract Background Coexistence of adenocarcinoma and mantle cell lymphoma in the same or different anatomical sites is extremely rare. We present a case of incidental discovery of primary lung adenocarcinoma and mantle cell lymphoma involving the pleura, during an axillary thoracotomy performed for a benign condition. Case presentation A 73-year old male underwent bullectomy and apical pleurectomy for persistent pneumothorax. A bulla of the lung apex was resected en bloc with a scar-like lesion of the lung, which was located in proximity with the bulla origin, by a wide wedge resection. Histologic examination of the stripped-off parietal pleura and of the bullectomy specimen revealed the synchronous occurrence of two distinct neoplasms, a lymphoma infiltrating the pleura and a primary, early lung adenocarcinoma. Immunohistochemical and fluorescence in situ hybridization assays were performed. The morphologic, immunophenotypic and genetic findings supported the diagnosis of primary lung adenocarcinoma (papillary subtype coexisting with a non-Hodgkin, B-cell lineage, mantle cell lymphoma involving both, visceral and parietal pleura and without mediastinal lymph node involvement. The neoplastic lymphoid cells showed the characteristic immunophenotype of mantle cell lymphoma and the translocation t(11;14. The patient received 6 cycles of chemotherapy, while pulmonary function tests precluded further pulmonary parenchyma resection (lobectomy for his adenocarcinoma. The patient is alive and without clinical and radiological findings of local recurrence or distant relapse from both tumors 14 months later. Conclusion This is the first reported case of a rare tumoral combination involving simultaneously lung and pleura, emphasizing at the incidental discovery of the two coexisting neoplasms during a procedure performed for a benign condition. Any tissue specimen resected during operations performed for non-tumoral conditions should be routinely sent for

  5. Follistatin is a novel biomarker for lung adenocarcinoma in humans.

    Fangfang Chen

    Full Text Available Follistatin (FST, a single chain glycoprotein, is originally isolated from follicular fluid of ovary. Previous studies have revealed that serum FST served as a biomarker for pregnancy and ovarian mucinous tumor. However, whether FST can serve as a biomarker for diagnosis in lung adenocarcinoma of humans remains unclear.The study population consisted of 80 patients with lung adenocarcinoma, 40 patients with ovarian adenocarcinoma and 80 healthy subjects. Serum FST levels in patients and healthy subjects were measured using ELISA. The results showed that the positive ratio of serum FST levels was 51.3% (41/80, which was comparable to the sensitivity of FST in 40 patients with ovarian adenocarcinoma (60%, 24/40 using the 95th confidence interval for the healthy subject group as the cut-off value. FST expressions in lung adenocarcinoma were examined by immunohistochemical staining, we found that lung adenocarcinoma could produce FST and there was positive correlation between the level of FST expression and the differential degree of lung adenocarcinoma. Furthermore, the results showed that primary cultured lung adenocarcinoma cells could secrete FST, while cells derived from non-tumor lung tissues almost did not produce FST. In addition, the results of CCK8 assay and flow cytometry showed that using anti-FST monoclonal antibody to neutralize endogenous FST significantly augmented activin A-induced lung adenocarcinoma cells apoptosis.These data indicate that lung adenocarcinoma cells can secret FST into serum, which may be beneficial to the survival of adenocarcinoma cells by neutralizing activin A action. Thus, FST can serve as a promising biomarker for diagnosis of lung adenocarcinoma and a useful biotherapy target for lung adenocarcinoma.

  6. Adenocarcinoma of the Rectum with Cutaneous Metastases

    Nohad Hanbala


    Full Text Available Cutaneous metastases of rectal carcinoma is a rare event. It occurs in fewer than 4% of all patients with rectal cancer. When present, it typically signifies a disseminated disease with a poor prognosis. Early detection and proper diagnosis of metastatic rectal cancer can significantly alter treatment and prognosis. We report a 70-year-oldmale who underwent rectal resection with permanent colostomy for rectal adenocarcinoma since seven years. The patient recently developed multiple skin nodules, mainly in his face, scalp, and upper trunk, associated with itching. Fine needle aspiration cytology from a face nodule was done which revealed metastatic adenocarcinoma associated with severe inflammation. Cutaneous metastasis of rectaladenocarcinoma is an unusual event that presents mainly in the form of skin nodules and could be the first sign of metastasis. Early diagnosis of cutaneous metastasis in these patients is important because it can alter treatment and prognosis.

  7. Bone and brain metastases from ampullary adenocarcinoma

    Ioannis A Voutsadakis; Stergios Doumas; Konstantinos Tsapakidis; Maria Papagianni; Christos N Papandreou


    Ampullary carcinoma is the second most common cancer of the peri-ampullary area after pancreatic carcinoma and metastasizes mostly intra-abdominally and to the liver. Extra-abdominal metastases are less frequent. In this report we describe the case of a patient with resected adenocarcinoma of the ampulla of Vater who developed skeletal metastases in the lower extremity and brain metastases. We briefly discuss aspects of this comparatively rare gastrointestinal malignancy.

  8. Appendiceal Adenocarcinoma Presenting as a Rectal Polyp

    Erin Fitzgerald


    Full Text Available Appendiceal adenocarcinoma typically presents as an incidentally noted appendiceal mass, or with symptoms of right lower quadrant pain that can mimic appendicitis, but local involvement of adjacent organs is uncommon, particularly as the presenting sign. We report on a case of a primary appendiceal cancer initially diagnosed as a rectal polyp based on its appearance in the rectal lumen. The management of the patient was in keeping with standard practice for a rectal polyp, and the diagnosis of appendiceal adenocarcinoma was made intraoperatively. The operative strategy had to be adjusted due to this unexpected finding. Although there are published cases of appendiceal adenocarcinoma inducing intussusception and thus mimicking a cecal polyp, there are no reports in the literature describing invasion of the appendix through the rectal wall and thus mimicking a rectal polyp. The patient is a 75-year-old female who presented with spontaneous hematochezia and, on colonoscopy, was noted to have a rectal polyp that appeared to be located within a diverticulum. When endoscopic mucosal resection was not successful, she was referred to colorectal surgery for a low anterior resection. Preoperative imaging was notable for an enlarged appendix adjacent to the rectum. Intraoperatively, the appendix was found to be densely adherent to the right lateral rectal wall. An en bloc resection of the distal sigmoid colon, proximal rectum and appendix was performed, with pathology demonstrating appendiceal adenocarcinoma that invaded through the rectal wall. The prognosis in this type of malignancy weighs heavily on whether or not perforation and spread throughout the peritoneal cavity have occurred. In this unusual presentation, an en bloc resection is required for a complete resection and to minimize the risk of peritoneal spread. Unusual appearing polyps do not always originate from the bowel wall. Abnormal radiographic findings adjacent to an area of

  9. Treatment of urachal adenocarcinoma-case report

    Mekić-Abazović Alma


    Full Text Available In this case, we have presented a 55-year old patient with dysuria and bloody urine. He was hospitalized at the Urology Department of County Zenica Hospital due to obstructive uropathy. Diagnostics showed the cause is a large bleeding mass in prostatic part of urethra. After cystectomy, immunohistochemistry revealed urachal adenocarcinoma, rare type of urogenital carcinomas, presented only in 5% of all cancer types. He was treated with dual modality, chemotherapy and radiotherapy

  10. Barrett's oesophagus and oesophageal adenocarcinoma: time for a new synthesis.

    Reid, Brian J; Li, Xiaohong; Galipeau, Patricia C; Vaughan, Thomas L


    The public health importance of Barrett's oesophagus lies in its association with oesophageal adenocarcinoma. The incidence of oesophageal adenocarcinoma has risen at an alarming rate over the past four decades in many regions of the Western world, and there are indications that the incidence of this disease is on the rise in Asian populations in which it has been rare. Much has been learned of host and environmental risk factors that affect the incidence of oesophageal adenocarcinoma, and data indicate that patients with Barrett's oesophagus rarely develop oesophageal adenocarcinoma. Given that 95% of oesophageal adenocarcinomas arise in individuals without a prior diagnosis of Barrett's oesophagus, what strategies can be used to reduce late diagnosis of oesophageal adenocarcinoma?

  11. Gastric choriocarcinoma admixed with an α-fetoprotein-producing adenocarcinoma and separated adenocarcinoma

    Bang Wool Eom; So-Youn Jung; Hongman Yoon; Myeong-Cherl Kook; Keun Won Ryu; Jun Ho Lee; Young-Woo Kim


    We report a case of gastric choriocarcinoma admixed with an α-fetoprotein (AFP)-producing adenocarcinoma .A 70-year-old man was hospitalized for gastric cancer that was detected during screening by esophagogastroduodenoscopy (EGD). Initial laboratory data showed the increased serum level of AFP and EGD revealed a 5-cm ulcerofungating mass in the greater curvature of the gastric antrum.The patient underwent radical subtotal gastrectomy with D2 lymph node dissection and Billroth Ⅱ gastrojejunostomy. Histopathological evaluation confirmed double primary gastric cancer: gastric choriocarcinoma admixed with an AFP-producing adenocarcinoma and separated adenocarcinoma. At 2 wk postoperatively, his human chorionic gonadotropin and AFP levels had reduced and six cycles of adjuvant chemotherapy were initiated. No recurrence or distant metastasis was observed at 4 years postoperatively.

  12. Association of visceral adiposity with oesophageal and junctional adenocarcinomas.

    Beddy, P


    BACKGROUND: Obesity is associated with an increased incidence of oesophageal and oesophagogastric junction adenocarcinoma, in particular Siewert types I and II. This study compared abdominal fat composition in patients with oesophageal\\/junctional adenocarcinoma with that in patients with oesophageal squamous cell carcinoma and gastric adenocarcinoma, and in controls. METHOD: In total, 194 patients (110 with oesophageal\\/junctional adenocarcinoma, 38 with gastric adenocarcinoma and 46 with oesophageal squamous cell carcinoma) and 90 matched control subjects were recruited. The abdominal fat area was assessed using computed tomography (CT), and the total fat area (TFA), visceral fat area (VFA) and subcutaneous fat area (SFA) were calculated. RESULTS: Patients with oesophageal\\/junctional adenocarcinoma had significantly higher TFA and VFA values compared with controls (both P < 0.001), patients with gastric adenocarcinoma (P = 0.013 and P = 0.006 respectively) and patients with oesophageal squamous cell carcinoma (both P < 0.001). For junctional tumours, the highest TFA and VFA values were seen in patients with Siewert type I tumours (respectively P = 0.041 and P = 0.033 versus type III; P = 0.332 and P = 0.152 versus type II). CONCLUSION: Patients with oesophageal\\/junctional adenocarcinoma, in particular oesophageal and Siewert type I junctional tumours, have greater CT-defined visceral adiposity than patients with gastric adenocarcinoma or oesophageal squamous cell carcinoma, or controls.

  13. File list: Pol.Lng.05.AllAg.Lung_adenocarcinoma [Chip-atlas[Archive

    Full Text Available Pol.Lng.05.AllAg.Lung_adenocarcinoma mm9 RNA polymerase Lung Lung adenocarcinoma ...

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    Full Text Available DNS.Lng.05.AllAg.Lung_adenocarcinoma mm9 DNase-seq Lung Lung adenocarcinoma ...

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    Full Text Available Unc.Lng.20.AllAg.Lung_adenocarcinoma mm9 Unclassified Lung Lung adenocarcinoma http...:// ...

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    Full Text Available Unc.Lng.10.AllAg.Lung_adenocarcinoma mm9 Unclassified Lung Lung adenocarcinoma http...:// ...

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    Full Text Available Unc.Lng.50.AllAg.Lung_adenocarcinoma mm9 Unclassified Lung Lung adenocarcinoma http...:// ...

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    Full Text Available DNS.Lng.20.AllAg.Lung_adenocarcinoma mm9 DNase-seq Lung Lung adenocarcinoma ...

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    Full Text Available Unc.Lng.05.AllAg.Lung_adenocarcinoma mm9 Unclassified Lung Lung adenocarcinoma http...:// ...

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    Full Text Available DNS.Lng.10.AllAg.Lung_adenocarcinoma mm9 DNase-seq Lung Lung adenocarcinoma ...

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    Full Text Available Pol.Lng.20.AllAg.Lung_adenocarcinoma mm9 RNA polymerase Lung Lung adenocarcinoma ...

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    Full Text Available Pol.Lng.10.AllAg.Lung_adenocarcinoma mm9 RNA polymerase Lung Lung adenocarcinoma ...

  5. Intensity-Modulated Radiation Therapy With Concurrent Chemotherapy as Preoperative Treatment for Localized Gastric Adenocarcinoma

    Chakravarty, Twisha; Crane, Christopher H. [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (United States); Ajani, Jaffer A. [Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (United States); Mansfield, Paul F. [Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (United States); Briere, Tina M.; Beddar, A. Sam [Department of Radiation Physics, University of Texas MD Anderson Cancer Center, Houston, TX (United States); Mok, Henry; Reed, Valerie K.; Krishnan, Sunil; Delclos, Marc E. [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (United States); Das, Prajnan, E-mail: [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (United States)


    Purpose: The goal of this study was to evaluate dosimetric parameters, acute toxicity, pathologic response, and local control in patients treated with preoperative intensity-modulated radiation therapy (IMRT) and concurrent chemotherapy for localized gastric adenocarcinoma. Methods: Between November 2007 and April 2010, 25 patients with localized gastric adenocarcinoma were treated with induction chemotherapy, followed by preoperative IMRT and concurrent chemotherapy and, finally, surgical resection. The median radiation therapy dose was 45 Gy. Concurrent chemotherapy was 5-fluorouracil and oxaliplatin in 18 patients, capecitabine in 3, and other regimens in 4. Subsequently, resection was performed with total gastrectomy in 13 patients, subtotal gastrectomy in 7, and other surgeries in 5. Results: Target coverage, expressed as the ratio of the minimum dose received by 99% of the planning target volume to the prescribed dose, was a median of 0.97 (range, 0.92-1.01). The median V{sub 30} (percentage of volume receiving at least 30 Gy) for the liver was 26%; the median V{sub 20} (percentage of volume receiving at least 20 Gy) for the right and left kidneys was 14% and 24%, respectively; and the median V{sub 40} (percentage of volume receiving at least 40 Gy) for the heart was 18%. Grade 3 acute toxicity developed in 14 patients (56%), including dehydration in 10, nausea in 8, and anorexia in 5. Grade 4 acute toxicity did not develop in any patient. There were no significant differences in the rates of acute toxicity, hospitalization, or feeding tube use in comparison to those in a group of 50 patients treated with preoperative three-dimensional conformal radiation therapy with concurrent chemotherapy. R0 resection was obtained in 20 patients (80%), and pathologic complete response occurred in 5 (20%). Conclusions: Preoperative IMRT for gastric adenocarcinoma was well tolerated, accomplished excellent target coverage and normal structure sparing, and led to appropriate

  6. Gastric neo-adenocarcinoma arising in a gastric tube after Ivor Lewis oesophagectomy for oesophageal adenocarcinoma.

    Hanif, Faisal; Kerr, Joana; Going, James J; Fullarton, Grant


    A 69-year-old man, seven years post Ivor-Lewis oesophagectomy for oesophageal adenocarcinoma, was diagnosed to have a moderately differentiated 4 cm, malignant ulcer within the gastric tube remnant on an endoscopic biopsy. His original presentation was with a T1N0 oesophageal adenocarcinoma, histologically intestinal in type with inflammatory features. He presented with anaemia and melena due to a malignant ulcer in the mid body of his gastric tube on an endoscopy which was confirmed to be a gastric neo-adenocarcinoma on biopsy. He underwent right posterolateral thoracotomy and a wedge resection of the gastric tube including the tumour. Pathology confirmed a T3 N0 (0/7 lymph nodes) with clear margins moderately differentiated adenocarcinoma of intestinal phenotype with papillary features and was reported to be a histopathologically new tumour. Proposed surgical treatments in such patients are dependent on patient's fitness for major resection and may vary from Endoscopic Mucosal Resection to partial resection with preservation of right gastroepiploic vessels or total gastrectomy with intestinal interposition via a retromediastinal route. We suggest that regular endoscopic surveillance may be indicated in such post-oesophagectomy patients as the number of patients developing gastric tube cancers may increase with improve survival of those patients.

  7. Study of mast cells in prostate lesions: Adenocarcinoma compared with hyperplasia

    Vittal Rakshith


    Full Text Available Background: (1 To study and correlate the mast cell numbers in benign prostatic hyperplasia (BPH and prostate carcinoma lesions. (2 To compare mast cell numbers of intratumoral and peritumoral regions in prostate adenocarcinomas. (3 To ascertain a relationship between the number of mast cells and age, prostate-specific antigen (PSA levels, and Gleason Grade. Subjects and Methods: One-hundred cases of prostate lesions, consisting of 75 cases of BPH and 25 cases of prostatic adenocarcinoma, received in the form of transurethral resection of prostate chips in the Department of Pathology, were included in the study. After histopathological diagnosis, the paraffin sections were stained with toluidine blue. Results: The mean value of mast cell count per mm2 in benign and malignant lesion was 37.05 and 92.20, respectively. The difference in mean mast cell count in BPH and prostatic adenocarcinoma was found to be statistically significant (P = 0.001. The correlation between mast cell count and Gleason Grade was found to be statistically significant (P: Grades I–III - 0.043; 0.002; 0.012. However, no correlation was found between mast cell count with age and PSA levels. Conclusion: In this study, an increase in the number of mast cells was observed in patients with prostate cancer than in benign lesions. This suggests a stimulating role of mast cells in the progression of cancer.

  8. Endometrial Adenocarcinoma Presenting in a Premenopausal Patient with Tuberous Sclerosis

    Jaffe, J. S.; Chambers, J. T.


    Background: Endometrial adenocarcinoma is very uncommon in women under 40 years of age. Case: A 39-year-old woman with tuberous sclerosis and severe intellectual disability presented with irregular bleeding unresponsive to oral contraceptive therapy. She was subsequently found to have a deeply invasive endometrial adenocarcinoma. Conclusion:…

  9. Laparoscopic treatment of mucinous urachal adenocarcinoma with mucocele.

    Oberndoerfer, Marine; Bucher, Pascal; Caviezel, Alessandro; Platon, Alexandra; Ott, Vincent; Egger, Jean-François; Morel, Philippe


    We present a case of an asymptomatic 76-year-old woman treated laparoscopically for an urachal mucocele owing to a nonmetastatic urachal mucinous adenocarcinoma. Since laparoscopic en bloc resection of the urachus and partial cystectomy, the patient has been healthy and disease-free for 12 months. Modern surgical treatment of urachal adenocarcinoma is discussed in the light of this case.

  10. Prostate adenocarcinoma with unusual first presentation-A case report

    Fariba Binesh; Shokouh Taghipour-zahir; Saeedeh Zare


    Prostate adenocarcinoma most often metastasis to the bones of spine and pelvis. Metastasis to the supradia-phragmatic lymph nodes as uncommon presentation of this disease has been increasingly reported. Here we reported a 61 years old man with prostatic adenocarcinoma who presented with generalized lymphadenopathy.

  11. Primary Papillary Mucinous Adenocarcinoma of the Ureter Mimicking Genitourinary Tuberculosis

    Hanni Gulwani


    Full Text Available Primary adenocarcinomas of the renal pelvis and ureter are rare and account for less than 1% of all malignancies at this site. We report a case of primary papillary mucinous adenocarcinoma of the ureter that clinically mimicked genitourinary tuberculosis. Early diagnosis is important for the better outcome.

  12. Erlotinib Versus Radiation Therapy for Brain Metastases in Patients With EGFR-Mutant Lung Adenocarcinoma

    Gerber, Naamit K.; Yamada, Yoshiya; Rimner, Andreas [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Shi, Weiji [Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Riely, Gregory J. [Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Beal, Kathryn [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Yu, Helena A. [Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Chan, Timothy A. [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Zhang, Zhigang [Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Wu, Abraham J., E-mail: [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States)


    Purpose/Objectives: Radiation therapy (RT) is the principal modality in the treatment of patients with brain metastases (BM). However, given the activity of EGFR tyrosine kinase inhibitors in the central nervous system, it is uncertain whether upfront brain RT is necessary for patients with EGFR-mutant lung adenocarcinoma with BM. Methods and Materials: Patients with EGFR-mutant lung adenocarcinoma and newly diagnosed BM were identified. Results: 222 patients were identified. Exclusion criteria included prior erlotinib use, presence of a de novo erlotinib resistance mutation, or incomplete data. Of the remaining 110 patients, 63 were treated with erlotinib, 32 with whole brain RT (WBRT), and 15 with stereotactic radiosurgery (SRS). The median overall survival (OS) for the whole cohort was 33 months. There was no significant difference in OS between the WBRT and erlotinib groups (median, 35 vs 26 months; P=.62), whereas patients treated with SRS had a longer OS than did those in the erlotinib group (median, 64 months; P=.004). The median time to intracranial progression was 17 months. There was a longer time to intracranial progression in patients who received WBRT than in those who received erlotinib upfront (median, 24 vs 16 months, P=.04). Patients in the erlotinib or SRS group were more likely to experience intracranial failure as a component of first failure, whereas WBRT patients were more likely to experience failure outside the brain (P=.004). Conclusions: The survival of patients with EGFR-mutant adenocarcinoma with BM is notably long, whether they receive upfront erlotinib or brain RT. We observed longer intracranial control with WBRT, even though the WBRT patients had a higher burden of intracranial disease. Despite the equivalent survival between the WBRT and erlotinib group, this study underscores the role of WBRT in producing durable intracranial control in comparison with a targeted biologic agent with known central nervous system activity.

  13. The predictive and prognostic values of factors associated with visceral pleural involvement in resected lung adenocarcinomas

    Zhang HB


    Full Text Available Huibiao Zhang,1 Chen Lu,2 Yingjie Lu,1 Bo Yu,2 Fanzhen Lv,1 Zhenghong Zhu1 1Department of Thoracic Surgery, 2Department of Pathology, Huadong Hospital, Fudan University, Shanghai, People’s Republic of China Background: The predictive and prognostic impact of factors associated with visceral pleural invasion (VPI on survival and recurrence in patients with resected lung adenocarcinomas is not clearly defined.Patients and methods: A total of 505 consecutive patients with stage Ia–IIIa lung adenocarcinomas treated with radical resection were included. The predominant growth pattern was classified according to the new classification system for lung adenocarcinoma proposed by the International Association for the Study of Lung Cancer, the American Thoracic Society, and the European Respiratory Society. The correlations of VPI with clinical and pathologic parameters were analyzed.Results: The incidence of VPI was significantly lower in lepidic predominant group (15.5% vs 4.5%, P<0.001 and higher in solid and micropapillary predominant group (28.6% vs 17.6%, P=0.004 and 14.7% vs 4.2%, P<0.001, respectively. VPI correlated with higher risk in regional postoperative recurrence (hazard ratio, 2.341; 95% confidence interval, 1.564–3.504 and distant recurrence (hazard ratio, 2.193; 95% confidence interval, 1.665–2.89 in surgically resected lung adenocarcinomas. However, when growth patterns of adenocarcinoma were lumped into multivariate analysis, VPI was not a significant independent predictive factor for survival (P=0.854 for overall survival [OS] and P=0.575 for disease-free survival [DFS] and recurrence (P=0.38 for regional recurrence and P=0.089 for distant recurrence. Of the 95 patients with stage Ib, those who received adjuvant chemotherapy had longer DFS and OS than the patients who received no chemotherapy after surgery. However, these differences in DFS and OS did not reach statistical significance (P=0.063 for DFS, P=0.85 for OS

  14. [Pseudo-mesotheliomatous adenocarcinoma of the lung].

    Aumann, K; Günter, J; Freudenberg, N


    Both pathologists and clinicians are challenged by the diagnosis of a particular variant of the peripheral adenocarcinoma with involvement of the pleura parietalis, the so-called pseudo-mesotheliomatous adenocarcinoma of the lung (PMAC), which is hard to differentiate from epithelioid mesothelioma on imaging and cytology, macroscopically as well as histologically. However, the exact diagnosis is not only crucial for the patient's therapy but also for insurance matters. Immunohistochemical evaluation represents a quick and a relatively cheap tool for which a few antibody panels have been proposed in recent years as being suitable to distinguish between these two entities. One of the positive markers for epithelioid mesothelioma most often suggested seems to be calretinin. We would like to report on a case of PMAC with the special feature of positive calretinin immunohistochemical staining. Using histochemistry and a few additional antibodies we were able to reliably characterize the tumor and provide the patient with appropriate therapy. This article gives a short overview of the possibilities available for distinguishing between these two entities in the context of a case report.

  15. Metastasis of Prostate Adenocarcinoma to the Testis

    Campara, Zoran; Simic, Dejan; Aleksic, Predrag; Spasic, Aleksandar; Milicevic, Snjezana


    Introduction: Prostate carcinoma is the most frequently diagnosed carcinoma in the male population. The most typical places of the metastases are pelvic lymphatic glands, bones and lungs, and very rarely it metastasizes into a testis. The prognostic importance of testicular metastasis of prostate cancer is not yet well-known, due to a very few published cases. According to the known facts, it is certain that a metastasis of the prostate carcinoma into a testis is a sign of an advanced disease. Case report: This work presents a 48-year-old patient, to whom an adenocarcinoma of the prostate has been proven by the pathohistological finding of transrectal biopsy, performed due to the elevated level of prostate-specific antigen (PSA). Nine years after the initial diagnosis, due to a gradual rise of PSA and tumorous enlargement of the left testis, left inguinal orchectomy and right orchectomy were performed. Metastatic dissemination of prostate adenocarcinoma into a testis was determined by a pathohistological analysis of the left testis. Conclusion: The metastasis of the prostate carcinoma into a testis, as a rare localization of the metastatic dissemination, after additionally performed orchectomy along with further oncological therapy, can provide a continuation of a good life quality as well as a control of the disease in a longer time period. PMID:27703299

  16. Highly Sensitive Optical Receivers

    Schneider, Kerstin


    Highly Sensitive Optical Receivers primarily treats the circuit design of optical receivers with external photodiodes. Continuous-mode and burst-mode receivers are compared. The monograph first summarizes the basics of III/V photodetectors, transistor and noise models, bit-error rate, sensitivity and analog circuit design, thus enabling readers to understand the circuits described in the main part of the book. In order to cover the topic comprehensively, detailed descriptions of receivers for optical data communication in general and, in particular, optical burst-mode receivers in deep-sub-µm CMOS are presented. Numerous detailed and elaborate illustrations facilitate better understanding.

  17. Concomitant gastric adenocarcinoma and stromal tumor in a woman with polymyalgia rheumatica

    Panteleimon Kountourakis; Niki Arnogiannaki; Ilias Stavrinides; Nikiforos Apostolikas; Gerasimos Rigatos


    Gastrointestinal stromal tumors (GISTs) are rare neoplasms (1%) of the gastrointestinal tract and to our knowledge only rare cases of synchronous presentation of gastric carcinomas and GISTs are reported in the literature.A 72-year-old female with a simultaneous presentation of gastric adenocarcinoma and GIST is presented.Moreover,due to polymyalgia rheumatica the patient received corticosteroids as treatment for the last 3 years.The concomitant occurrence of these neoplasms may involve common carcinogenic factors and there could be an association with polymyalgia rheumatica either as a paraneoplastic presentation or due to its treatment with corticosteroids.

  18. Lymph node dissection for Siewert II esophagogastric junction adenocarcinoma

    Duan, Xiao-Feng; Yue, Jie; Tang, Peng; Shang, Xiao-Bin; Jiang, Hong-Jing; Yu, Zhen-Tao


    Abstract The present study was aimed to investigate the application of right thansthoracic Ivor–Lewis (IL), left transthoracic (LTT), and left thoracoabdominal (LTA) approach in Siewert type II adenocarcinoma of esophagogastric junction (AEG). The data of 196 patients with Siewert type II AEG received surgical resection in our cancer center between January 2014 and April 2016 was retrospectively analyzed. Finally, 136 patients met the inclusion criteria were enrolled in the study and divided into the IL (47 cases), LTT (51 cases), and LTA group (38 cases). Clinical and short-term treatment effects were compared among the 3 groups. The patients with weight loss, diabetes, and heart disease increased in the LTT group (P = 0.054, P = 0.075, and P = 0.063, respectively). Operation time was significantly longest in the IL group (P  0.05), but the dissection rate of the hepatic artery, splenic artery, and celiac trunk lymph nodes was significantly highest in the IL group (P  0.05). Compared with the traditional left transthoracic approach, the Ivor–Lewis approach did not increase the perioperative mortality and complication rates in Siewert type II AEG, but obtained satisfactory length of the proximal surgical margin, and was better than the left transthoracic approach in thoracic and abdominal lymph node dissection. However, the advantages of Ivor–Lewis procedure requires further follow-up and validation through prospective randomized controlled trials. PMID:28207537

  19. Calpain regulates thymidylate synthase-5-fluoro-dUMP complex levels associated with response to 5-fluorouracil in gastric cancer cells.

    Nabeya, Yoshihiro; Suzuki, Takao; Furuya, Aki; Koide, Naoki; Ohkoshi, Motohiro; Takiguchi, Masaki; Ochiai, Takenori; Matsubara, Hisahiro; Hiwasa, Takaki


    Thymidylate synthase (TS) plays a major role in the response to 5-fluorouracil (5-FU) by binding directly to the 5-FU metabolite, 5-fluoro-dUMP (FdUMP). The change in the TS expression levels after 5-FU administration was examined in parallel to 5-FU responsiveness in six human gastric adenocarcinoma cell lines to elucidate the source of variability of 5-FU sensitivity. MKN-1, SH-10-TC and MKN-74 cells were more resistant to 5-FU than MKN-28, KATO III and MKN-45 cells. Western blotting analysis revealed that the 5-FU sensitivity of these cells did not correlate with the basal TS expression levels but did correlate with rapid detection of the TS-FdUMP complex after exposure to 5-FU. In 5-FU-resistant cells, very low levels of the TS-FdUMP complex early after 5-FU exposure were elevated by pretreatment with calpain inhibitors such as benzyloxycarbonyl-leucyl-leucinal (ZLLH), benzyloxycarbonyl-leucyl-leucyl-leucinal (ZLLLH) and ALLN, but not by other protease inhibitors. In contrast, ONO-3403, which causes calpain activation, stimulated downregulation of the TS-FdUMP complex in 5-FU-sensitive cells. The expression levels of calpastatin, an endogenous calpain inhibitor, were higher in 5-FU-sensitive cells than in 5-FU-resistant cells. ZLLH increased the 5-FU sensitivity of 5-FU-resistant cells, whereas ONO-3403 decreased the sensitivity of 5-FU-sensitive cells. In addition, knockdown of m-calpain by siRNA increased the 5-FU sensitivity in 5-FU-resistant cells, while knockdown of calpastatin reduced the sensitivity in 5-FU-sensitive cells. These results suggest that calpain might reduce the chemosensitivity of human gastric cancer cells to 5-FU possibly by rapid degradation of the TS-FdUMP complex, a finding that is considered to have novel therapeutic implications.

  20. Expression of p53 protein in Barrett’s adenocarcinoma and adenocarcinoma of the gastric cardia and antrum

    Jovanović Ivan


    Full Text Available Background/Aim. Most studies of esophageal and gastric adenocarcinomas have shown a very high rate of p53 gene mutation and/or protein overexpression, but the influence of the tumor site upon the frequency of p53 protein expression has not been evaluated (gastroesophageal junction, Barret's esophagus, and antrum. The aim of our study was to analyze the correlation between the selected clinico-pthological parameters, and p53 protein overexpression in regards to the particular tumor location. Methods. The material comprised 66 surgical specimens; 10 were Barrett’s carcinomas, 25 adenocarcinomas of the gastric cardia (type II adenocarcinoma of the esophagogastric junction - EGJ, and 31 adenocarcinomas of the antrum. Immunostaining for p53 protein was performed on formalin-fixed, paraffin-embedded tissue sections, using the alkaline phosphatase - antialkaline phosphatase (APAAP method. The cases were considered positive for p53 if at least 5% of the tumor cells expressed this protein by immunostaining. Results. There was no significant difference observed between the studied groups in regards to age, sex, Lauren’s classification and tumor differentiation. There was, however, a significant difference observed in the depth of tumor invasion between Barrrett’s adenocarcinoma and adenocarcinoma of the cardia compared with the adenocarcinoma of the antrum. Namely, at the time of surgery, both Barrett’s adenocarcinomas and adenocarcinomas of the cardia, were significantly more advanced comparing with the adenocarcinomas of the antrum. Overexpression of p53 was found in 40% (4/10 of Barrett’s adenocarcinomas, 72% (18/25 of adenocarcinoma of the cardia and 65% (20/31 of adenocarcinoma of the antrum. No significant differences in p53 expression in relation to sex, type (Lauren of tumor, depth of invasion, lymph node involvement, or tumor differentiation were observed in any of the analyzed groups of tumors. Patients with more advanced Barrett

  1. Systematic review of the value of chemoradiotherapy in the management of locally advanced pancreatic adenocarcinoma; Interet de la chimioradiotherapie dans la prise en charge des denocarcinomes du pancreas localement avances: revue systematique

    Azria, D. [Centre de Lutte Contre le Cancer Val d' Aurelle, 34 Montpellier (France); Seblain-El Guerche, C. [Institut National du Cancer, 92 - Boulogne-Billancourt (France); Girard, N. [Centre Hospitalier Lyon-Sud, 69 - Pierre-Benite (France); Hennequin, C. [Hopital Saint-Louis, 75 - Paris (France); Huguet, F. [Hopital Tenon, 75 - Paris (France)


    dose of 50 to 60 Gy in association with 5-fluorouracil (5-FU). The study of radiotherapy associated drugs shows that 5-FU is the reference (B1) and the value of gemcitabine must be proved in randomized trials. Finally, the study of sequences chemotherapy-C.R.T. has recently showed that induction chemotherapy before C.R.T. improves survival (C). Validation of this strategy in a randomized trial is warranted. Conclusion: The use of C.R.T. for locally advanced pancreatic adenocarcinoma is based on a few randomized trials even if this treatment appears superior in terms of survival compared to best supportive care and radiotherapy alone. This review shows the need to conduct other specific randomized trials in order to validate the value of C.R.T., especially compared to chemotherapy alone. (authors)

  2. Progressive silencing of p14ARF in oesophageal adenocarcinoma.

    Huang, Yinghui; Peters, Christopher J; Fitzgerald, Rebecca C; Gjerset, Ruth A


    The frequency of oesophageal adenocarcinoma is increasing in Western countries for unknown reasons, and correlates with a corresponding increase in the pre-malignant condition, Barrett's Oesophagus, which raises the risk of adenocarcinoma by some 40- to 125-fold. We have examined how disease progression correlates with changes in expression of the p14ARF (ARF) tumour suppressor, a key regulator of the p53 tumour suppressor pathway that is silenced in some 30% of cancers overall, but for which a role in oesophageal cancer is unclear. We have used quantitative PCR, RT-PCR, methylation-specific PCR and chromatin-immunoprecipitation to examine the regulation and function of ARF in oesophageal adenocarcinoma tissue specimens and cell lines. We find highly significant reductions (Poesophageal epithelium to Barrett's Oesophagus to adenocarcinoma, with 57/76 (75%) adenocarcinomas displaying undetectable levels of ARF expression. Retention of ARF expression in adenocarcinoma is a highly significant indicator of increased survival (Padenocarcinoma cell lines and can be reversed by 5-aza-2'-deoxycytidine. The results suggest that silencing of ARF is involved in the pathogenesis of oesophageal adenocarcinoma and show that either DNA or histone methylation can provide the primary mechanism for ARF gene silencing. Silencing of ARF could provide a useful marker for increased risk of progression and poor prognosis.

  3. Low complexity MIMO receivers

    Bai, Lin; Yu, Quan


    Multiple-input multiple-output (MIMO) systems can increase the spectral efficiency in wireless communications. However, the interference becomes the major drawback that leads to high computational complexity at both transmitter and receiver. In particular, the complexity of MIMO receivers can be prohibitively high. As an efficient mathematical tool to devise low complexity approaches that mitigate the interference in MIMO systems, lattice reduction (LR) has been widely studied and employed over the last decade. The co-authors of this book are world's leading experts on MIMO receivers, and here they share the key findings of their research over years. They detail a range of key techniques for receiver design as multiple transmitted and received signals are available. The authors first introduce the principle of signal detection and the LR in mathematical aspects. They then move on to discuss the use of LR in low complexity MIMO receiver design with respect to different aspects, including uncoded MIMO detection...

  4. Screening of the different TNM stage-associated genes in lung adenocarcinoma by genomewide gene expression profile analysis in the Chinese population



    Objective To screen for the differentially expressed genes associated with various TNM stages in lung adenocarcinoma of Chinese by comparing the expression profiles in tumor samples of different TNM stages.Methods This study was a case-case study.Lung adenocarcinoma specimens were collected from total of 240 patients receiving thoracic surgery in our hospital from May of 2008to October of 2011.There were 90 samples(30 each for stageⅠ,ⅡandⅢA)for the gene array,and 150 samples(50 and may

  5. Comparative Label-free LC-MS/MS Analysis of Colorectal Adenocarcinoma and Metastatic Cells Treated with 5-Fluorouracil

    Bauer, Kerry M.; Lambert, Paul A.; Hummon, Amanda B.


    A label-free mass spectrometric strategy was used to examine the effect of 5-fluorouracil (5-FU) on the primary and metastatic colon carcinoma cell lines, SW480 and SW620, with and without treatment. 5-FU is the most common chemotherapeutic treatment for colon cancer. Pooled biological replicates were analyzed by nanoLC-MS/MS and protein quantification was determined via spectral counting. Phenotypic and proteomic changes were evident and often similar in both cell lines. The SW620 cells were...

  6. MRI findings of a huge cyst adenocarcinoma of the palate

    Choi, Jin Woo [School of Dentistry, Seoul National University, Seoul (Korea, Republic of)


    Cyst adenocarcinoma of the salivary glands is a very rare, slow growing, and low-grade malignant neoplasm. It is characterized by predominantly cystic growth with or without the intraluminal papillary component. However, it lacks of any additional specific histopathologic features that characterize other types of salivary carcinomas showing cystic growth. Therefore, definite diagnosis of the cyst adenocarcinoma is difficult and it is often misdiagnosed. It is conceptually the malignant counterpart of the benign cyst adenoma. We present a cyst adenocarcinoma on the palate of a 49-year-old man with special emphasis on magnetic resonance imaging.

  7. Effect of anthralin on cell viability in human prostate adenocarcinoma.

    Raevskaya, A A; Gorbunova, S L; Savvateeva, M V; Severin, S E; Kirpichnikov, M P


    The study revealed the key role of serine protease hepsin activity in transition of in situ prostate adenocarcinoma into the metastasizing form. Inhibition of hepsin activity suppresses the invasive growth of the tumor. Hepsin is an convenient target for pharmacological agents, so the study of its inhibitory mechanisms is a promising avenue in drug development. Assay of proteolytic activity in various tumor cell lines in vitro showed that this activity in prostate adenocarcinoma cells significantly surpasses proteolytic activity in other examined tumor cell lines. Selective cytotoxic action of anthralin, an inhibitor of hepsin activity, on human adenocarcinoma cells was demonstrated in comparison with other tumor cell lines.

  8. Delphi Accounts Receivable Module -

    Department of Transportation — Delphi accounts receivable module contains the following data elements, but are not limited to customer information, cash receipts, line of accounting details, bill...

  9. Targeting Pancreatic Ductal Adenocarcinoma Acidic Microenvironment

    Cruz-Monserrate, Zobeida; Roland, Christina L.; Deng, Defeng; Arumugam, Thiruvengadam; Moshnikova, Anna; Andreev, Oleg A.; Reshetnyak, Yana K.; Logsdon, Craig D.


    Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer death in the USA, accounting for ~40,000 deaths annually. The dismal prognosis for PDAC is largely due to its late diagnosis. Currently, the most sensitive diagnosis of PDAC requires invasive procedures, such as endoscopic ultrasonography, which has inherent risks and accuracy that is highly operator dependent. Here we took advantage of a general characteristic of solid tumors, the acidic microenvironment that is generated as a by-product of metabolism, to develop a novel approach of using pH (Low) Insertion Peptides (pHLIPs) for imaging of PDAC. We show that fluorescently labeled pHLIPs can localize and specifically detect PDAC in human xenografts as well as PDAC and PanIN lesions in genetically engineered mouse models. This novel approach may improve detection, differential diagnosis and staging of PDAC.


    Apeksha Kakkar


    Full Text Available Being the 4th leading cause of cancer deaths in the U.S. and with a global increase in incidence, above 80% of pancreatic cancers are locally advanced or metastatic at the time of diagnosis. As surgical resection is the only hope for a cure, the answer is probably in early screening, proper classification and right therapy. The advancing research will likely lead to a better understanding of Pancreatic Ductal Adenocarcinoma (PDAC as well as enhance the techniques for screening, diagnosis, accurate subtyping and enable the use of targeted therapy. Thus, instead of clubbing together various subtypes of PDAC for trials, improving the subcategorization will ensure statistical significance for the academicians, and the clinicians would avoid administration of placebo drug to a vast number of patients.

  11. Orthovoltage intraoperative radiation therapy for pancreatic adenocarcinoma

    Kapp Daniel S


    Full Text Available Abstract Purpose To analyze the outcomes of patients from a single institution treated with surgery and orthovoltage intraoperative radiotherapy (IORT for pancreatic adenocarcinoma. Methods We retrospectively reviewed 23 consecutive patients from 1990-2001 treated with IORT to 23 discrete sites with median and mean follow up of 6.5 and 21 months, respectively. Most tumors were located in the head of the pancreas (83% and sites irradiated included: tumor bed (57%, vessels (26%, both the tumor bed/vessels (13% and other (4%. The majority of patients (83% had IORT at the time of their definitive surgery. Three patients had preoperative chemoradiation (13%. Orthovoltage X-rays (200-250 kVp were employed via individually sized and beveled cone applicators. Additional mean clinical characteristics include: age 64 (range 41-81; tumor size 4 cm (range 1.4-11; and IORT dose 1106 cGy (range 600-1500. Post-operative external beam radiation (EBRT or chemotherapy was given to 65% and 76% of the assessable patients, respectively. Outcomes measured were infield control (IFC, loco-regional control (LRC, distant metastasis free survival (DMFS, overall survival (OS and treatment-related complications. Results Kaplan-Meier (KM 2-year IFC, LRC, DMFS and OS probabilities for the whole group were 83%, 61%, 26%, and 27%, respectively. Our cohort had three grade 3-5 complications associated with treatment (surgery and IORT. Conclusions Orthovoltage IORT following tumor reductive surgery is reasonably well tolerated and seems to confer in-field control in carefully selected patients. However, distant metastases remain the major problem for patients with pancreatic adenocarcinoma.

  12. A case report of a duodenal adenocarcinoma: a complication with Crohn's disease.

    Sakakibara, Yuko; Yamada, Takuya; Kimura, Keiichi; Iwasaki, Ryuichirou; Iwasaki, Tetsuya; Ishihara, Akio; Nakazuru, Shoichi; Ishida, Hisashi; Kodama, Yoshinori; Mita, Eiji


    The prevalence of Crohn's disease (CD) in Japan is increasing, and so is the incidence of colorectal and small bowel cancers associated with CD. However, few reports have described the malignant transformation of duodenal lesions; moreover, such a diagnosis is rarely possible preoperatively. We present a case of malignant degeneration in the duodenal mucosa associated with CD. A 54-year-old man had been receiving treatment for CD for more than 20 years. Seven years ago, he was diagnosed with duodenal stenosis related to CD. He was asymptomatic, and biopsy results from the proximal stricture showed inflammatory changes without malignant transformation. The lesion was then monitored during follow-up. In 2013, he underwent an endoscopy, which revealed an ulcerated, nodular mucosa, immediately proximal to a high-grade obstruction of the descending duodenum. A biopsy of the ulcer lesion confirmed a diagnosis of adenocarcinoma. The patient then underwent duodenopancreatectomy. Histopathological results from the resected duodenum confirmed a poorly differentiated adenocarcinoma that had invaded the subserosa. The patient recovered, and no recurrence has been observed. Although the duodenum can be accessed without difficulty during endoscopy, it is challenging to preoperatively diagnose malignant transformation. There are only four reported cases of duodenal cancer stemming from CD-associated stricture, and only one of them received a preoperative diagnosis of malignancy based on endoscopic biopsy results. Progressive duodenal narrowing and ulceration in patients with CD should indicate a need for careful endoscopic evaluation and biopsy in order to exclude malignant degeneration of Crohn's duodenitis. Early diagnosis of cases of CD-associated cancers is necessary. We report the features of a rare and illustrative case of duodenal adenocarcinoma in a patient with CD.

  13. Primary adenocarcinoma of lung: A pictorial review of recent updates

    Gaikwad, Anand, E-mail: [Department of Diagnostic Imaging, The Ottawa Hospital, University of Ottawa, Ottawa, ON (Canada); Gupta, Ashish, E-mail: [Department of Diagnostic Imaging, The Ottawa Hospital, University of Ottawa, Ottawa, ON (Canada); Hare, Sam, E-mail: [Department of Diagnostic Imaging, The Ottawa Hospital, University of Ottawa, Ottawa, ON (Canada); Gomes, Marcio, E-mail: [Department of Pathology and Laboratory Medicine, The Ottawa Hospital, University of Ottawa, Ottawa, ON (Canada); Sekhon, Harman, E-mail: [Department of Pathology and Laboratory Medicine, The Ottawa Hospital, University of Ottawa, Ottawa, ON (Canada); Souza, Carolina, E-mail: [Department of Diagnostic Imaging, The Ottawa Hospital, University of Ottawa, Ottawa, ON (Canada); Inacio, Joao, E-mail: [Department of Diagnostic Imaging, The Ottawa Hospital, University of Ottawa, Ottawa, ON (Canada); Lad, Shilpa, E-mail: [Department of Diagnostic Imaging, The Ottawa Hospital, University of Ottawa, Ottawa, ON (Canada); Seely, Jean, E-mail: [Department of Diagnostic Imaging, The Ottawa Hospital, University of Ottawa, Ottawa, ON (Canada)


    Primary adenocarcinoma of lung has replaced squamous cell carcinoma as the commonest histological subtype of lung cancer and the incidence of primary lung adenocarcinoma appears to be rising. Although the main factors behind this ‘epidemic-like’ situation are largely undiscovered, filter cigarettes appear to significantly contribute to this shift in the histopathological spectrum. The new multidisciplinary classification of adenocarcinoma of lung was introduced to address advances in clinical, pathological, radiological and molecular sciences. The purpose of this essay is to discuss various classes of lung adenocarcinoma in the new classification with their classical imaging features on computed tomography and summarise the recent advances in the field of radiology and review radiology recommendations.

  14. Coexistent adenocarcinoma and microcystic adenoma of the pancreas.

    Posniak, H V; Olson, M C; Demos, T C


    A case with coexistent pancreatic adenocarcinoma and microcystic adenoma is presented. These diagnoses were suspected on the basis of their computed tomography (CT) appearances and confirmed with CT-guided fine-needle aspiration.

  15. Ovarian recurrence after radical trachelectomy for adenocarcinoma of the cervix.

    Piketty, Mathilde; Barranger, Emmanuel; Najat, Mourra; François, Paye; Daraï, Emile


    Radical trachelectomy is an effective fertility-sparing treatment for women with early-stage cervical cancer. We describe the first reported ovarian recurrence after radical trachelectomy for stage IB1 adenocarcinoma cervical cancer.

  16. Discovery of new molecular subtypes in oesophageal adenocarcinoma.

    Berg, Daniela; Wolff, Claudia; Langer, Rupert; Schuster, Tibor; Feith, Marcus; Slotta-Huspenina, Julia; Malinowsky, Katharina; Becker, Karl-Friedrich


    A large number of patients suffering from oesophageal adenocarcinomas do not respond to conventional chemotherapy; therefore, it is necessary to identify new predictive biomarkers and patient signatures to improve patient outcomes and therapy selections. We analysed 87 formalin-fixed and paraffin-embedded (FFPE) oesophageal adenocarcinoma tissue samples with a reverse phase protein array (RPPA) to examine the expression of 17 cancer-related signalling molecules. Protein expression levels were analysed by unsupervised hierarchical clustering and correlated with clinicopathological parameters and overall patient survival. Proteomic analyses revealed a new, very promising molecular subtype of oesophageal adenocarcinoma patients characterised by low levels of the HSP27 family proteins and high expression of those of the HER family with positive lymph nodes, distant metastases and short overall survival. After confirmation in other independent studies, our results could be the foundation for the development of a Her2-targeted treatment option for this new patient subgroup of oesophageal adenocarcinoma.

  17. Estrogen, male dominance and esophageal adenocarcinoma: Is there a link?

    Huiqi Yang; Olga A Sukocheva; Damian J Hussey; David I Watson


    Esophageal adenocarcinoma is a cancer with poor prognosis, and its incidence has risen sharply over recent decades. Obesity is a major risk factor for developing this cancer and there is a clear male gender bias in the incidence that cannot be fully explained by known risk factors. It is possible that a difference in the expression of estrogen, or its signaling axes, may contribute to this gender bias. We undertook a comprehensive literature search and analyzed the available data regarding estrogen and estrogen receptor expression, and the possible sex-specific links with esophageal adenocarcinoma development. Potentially relevant associations between visceral vs subcutaneous fat deposition and estrogen expression, and the effect of crosstalk between estrogen and leptin signaling were identified. We also found limited studies suggesting a role for estrogen receptor β expression in esophageal adenocarcinoma development. The current literature supports speculation on an etiological role for estrogen in the male gender bias in esophageal adenocarcinoma, but further studies are required.

  18. Asymptomatic ileal adenocarcinoma in the setting of undiagnosed Crohn's disease

    Vikram B Reddy; Harold Aslanian; Namsoo Suh; Walter E Longo


    A 53-year old previously healthy male underwent a screening colonoscopy for detection of a potential colorectal neoplasm. The terminal ileum was intubated and a mass was noted. Examination of the colon was normal. The biopsy of the ileal mass was consistent with an adenocarcinoma arising from the terminal ileum. His father who had never been previously ill from gastrointestinal disease died of natural causes,but was found to have Crohn's disease postmortem.The patient underwent exploratory laparotomy and aright hemicolectomy with a 30 cm section of terminal ileum in continuity. Findings were consistent with ileal adenocarcinoma in the setting of Crohn's disease. Thepatient made an uneventful recovery. The pathology was stage 1 adenocarcinoma. This is a unique case in that on a screening colonoscopy, a favorable ileal adenocarcinoma was discovered in the setting of asymptomatic, undiagnosed ileal Crohn's disease in a patient whose father had Crohn's disease diagnosed postmortem.

  19. Adenocarcinoma of the Minor Duodenal Papilla: Report of a Case

    Kazuhiro Takami


    Full Text Available An 81-year-old male was found to have a duodenal tumor by screening upper gastrointestinal endoscopy. The tumor was located in the minor duodenal papilla. Pathological examination of the biopsy specimen revealed adenocarcinoma, and endoscopic ultrasound showed an elevated hypoechoic mass in the minor duodenal papilla. The preoperative diagnosis was therefore considered to be either adenocarcinoma of the minor duodenal papilla or duodenal cancer. We performed a subtotal stomach-preserving pancreaticoduodenectomy. Histopathological examination of the resected specimen showed the tumor cells to be primarily located in the submucosa of the minor duodenal papilla, with slight invasion into the pancreatic parenchyma through the accessory pancreatic duct. We therefore diagnosed a primary adenocarcima of the minor duodenal papilla. Adenocarcinoma of the minor duodenal papilla is considered to be a rare disease, but it may be underestimated because of the difficulty in distinguishing advanced adenocarcinoma of the minor duodenal papilla from primary duodenal cancer and cancer of the pancreatic head.

  20. Discovery of new molecular subtypes in oesophageal adenocarcinoma.

    Daniela Berg

    Full Text Available A large number of patients suffering from oesophageal adenocarcinomas do not respond to conventional chemotherapy; therefore, it is necessary to identify new predictive biomarkers and patient signatures to improve patient outcomes and therapy selections. We analysed 87 formalin-fixed and paraffin-embedded (FFPE oesophageal adenocarcinoma tissue samples with a reverse phase protein array (RPPA to examine the expression of 17 cancer-related signalling molecules. Protein expression levels were analysed by unsupervised hierarchical clustering and correlated with clinicopathological parameters and overall patient survival. Proteomic analyses revealed a new, very promising molecular subtype of oesophageal adenocarcinoma patients characterised by low levels of the HSP27 family proteins and high expression of those of the HER family with positive lymph nodes, distant metastases and short overall survival. After confirmation in other independent studies, our results could be the foundation for the development of a Her2-targeted treatment option for this new patient subgroup of oesophageal adenocarcinoma.

  1. Curative surgical management of isolated adrenal recurrence of oesophageal adenocarcinoma.

    O'Sullivan, K E


    Adrenal metastases of oesophageal adenocarcinoma are rarely detected in the clinical setting, more frequently being found as an incidental postmortem finding in the presence of widespread metastases. With improvements in the sensitivity of radiological diagnostic modalities, the incidence of adrenal tumour detection is on the rise. We report herein a particularly rare case of primary operative management by adrenalectomy for an isolated right-sided adrenal metastasis secondary to oesophageal adenocarcinoma, with a long-term survival.

  2. [Gastric signet ring cell adenocarcinoma: A distinct entity].

    Tabouret, Tessa; Dhooge, Marion; Rouquette, Alexandre; Brezault, Catherine; Beuvon, Frédéric; Chaussade, Stanislas; Coriat, Romain


    Gastric signet ring cell carcinoma (GSRC) is a distinct entity. Their incidence is increasing. The pathologist plays a central role in the identification of this entity. Diagnosis is based on an adenocarcinoma containing a majority of signet ring cells (above 50 %). The prognosis of GSRC is the same as gastric adenocarcinoma while GSRC appeared more aggressive. Signet ring cells present a low sensitivity to chemotherapy. This review aimed to discuss the histological, the prognostic and the therapeutic aspect of this entity.

  3. Sulindac Prevents Esophageal Adenocarcinomas Induced by Gastroduodenal Reflux in Rats

    Kim, Sung Wook; Jang, Tae Jung; Jung, Ki Hoon; Suh, Jung Il


    Purpose It is known that cyclooxygenase (COX)-2 expression is increased in Barrett's esophagus and esophageal adenocarcinomas. We studied COX-2 expression and the effect sulindac has on the genesis of Barrett's esophagus and adenocarcinoma in rats undergoing esophagogastroduodenal anastomosis (EGDA). Materials and Methods Fifty-one rats were divided into a control group (n = 27), a 500 ppm sulindac-treated group (n = 15) and 1000 ppm sulindac-treated group (n = 9). Randomly selected rats were...

  4. Transcriptomic Profiles Differentiate Normal Rectal Epithelium and Adenocarcinoma


    Adenocarcinoma is a histologic diagnosis based on subjective findings. Transcriptional profiles have been used to differentiate normal tissue from disease and could provide a means of identifying malignancy. The goal of this study was to generate and test transcriptomic profiles that differentiate normal from adenocarcinomatous rectum. Comparisons were made between cDNA microarrays derived from normal epithelium and rectal adenocarcinoma. Results were filtered according to standard deviation ...

  5. Multiple urinary bladder masses from metastatic prostate adenocarcinoma

    Richard Choo


    Full Text Available We present an unusual case of metastatic prostate adenocarcinoma that manifested with multiple exophytic intravesical masses, mimicking a multifocal primary bladder tumor. Biopsy with immunohistochemical analysis confirmed metastatic prostate adenocarcinoma. The patient was treated palliatively with external beam radiotherapy to prevent possible symptoms from local tumor progression. This case illustrates that when a patient with known prostate cancer presents with multifocal bladder tumors, the possibility of metastatic prostate cancer should be considered.

  6. Curative surgical management of isolated adrenal recurrence of oesophageal adenocarcinoma.

    O'Sullivan, K E; Moriarty, A R; Larkin, J O; Reynolds, J V


    Adrenal metastases of oesophageal adenocarcinoma are rarely detected in the clinical setting, more frequently being found as an incidental postmortem finding in the presence of widespread metastases. With improvements in the sensitivity of radiological diagnostic modalities, the incidence of adrenal tumour detection is on the rise. We report herein a particularly rare case of primary operative management by adrenalectomy for an isolated right-sided adrenal metastasis secondary to oesophageal adenocarcinoma, with a long-term survival.

  7. Analysis of Imp3 Expression in Prostate Adenocarcinomas



    Full Text Available Objective: Prostate cancer is the second most common cause of male cancer deaths after lung cancer in developed countries. The prognostic factors currently identified for prostate carcinoma include preoperative serum PSA, TNM staging system, histological grade and surgical margin status and are composed of the clinically most important and useful parameters. However, all the markers studied have not been applied in clinical practice. The oncofetal protein Insulin-Like Growth Factor II has been demonstrated to be associated with aggressive tumor behavior in many organs including urothelial tumors and renal cell carcinoma. Our aim was to investigate the expression status of Insulin-Like Growth Factor II in benign prostate glands, high grade PIN and prostate adenocarcinoma, and to determine the role of Insulin-Like Growth Factor II in pathogenesis of prostate adenocarcinoma.Material and Method: A total of 70 prostate adenocarcinoma cases accompanied by high grade PIN and benign prostate glands were evaluated by immunohistochemistry for the expression of Insulin-Like Growth Factor II.Results: Insulin-Like Growth Factor II expression was not seen in any of the 70 prostate adenocarcinoma and high grade PIN cases and benign prostate glands.Conclusion: Although the number of our cases was limited, our results suggested that Insulin-Like Growth Factor II protein expression was not included in the pathogenesis of the prostate adenocarcinomas and Insulin-Like Growth Factor II expression status cannot be used for diagnosis of prostate adenocarcinomas.

  8. Adenocarcinoma primário do duodeno



    Full Text Available OBJETIVO: Revisar a literatura especializada a respeito dos adenocarcinomas duodenais primários e comparar os dados com os aspectos observados nesta casuística. MÉTODOS: Seis doentes com esta neoplasia, excluídas as lesões peri-ampulares, foram operados na Área de Estômago e Duodeno do Departamento de Cirurgia da Santa Casa de São Paulo, entre 1991 e 1999. Houve predominância do tumor no sexo masculino e na 6feminine década de vida. Os sinais e sintomas mais freqüentes foram o emagrecimento (83,3% e a obstrução intestinal crônica (66,6%, com média de duração de seis meses. A gastroduodenoscopia fez o diagnóstico, posteriormente confirmado pela histologia. Utilizamos a tomografia computadorizada e a ultra-sonografia para determinar o estádio da doença. Em três pacientes com lesão restrita à parede do órgão, praticou-se a ressecção duodenal segmentar curativa, e nos outros três, a derivação duodenal paliativa, pois o tumor infiltrava órgãos adjacentes. RESULTADOS: O tempo de internação pós-operatória variou de 5 a 9 dias, com média de 7,3 dias. A mortalidade operatória foi 16,6% (um doente. Não indicamos tratamento complementar com quimio ou radioterapia. O acompanhamento ambulatorial vem ocorrendo em períodos que variam de 15 a 20 meses. Os três pacientes submetidos à ressecção cirúrgica curativa estão sem evidências de recidiva até o 15masculine, 16masculine e 18masculine mês de pós-operatório. Houve seguimento de um e três meses nos dois pacientes submetidos a cirurgias paliativas, depois do que se perderam. CONCLUSÃO: O pequeno número de casos relatados não permitiu conclusões mais consistentes a respeito dos adenocarcinomas duodenais.

  9. 蝎毒提取物抑制Lewis肺癌化疗期间再增殖实验研究%Inhibition of polypeptide extract from scorpion venom on repopulation in Lewis lung adenocarcinoma during chemotherapy

    王兆朋; 张维东; 武利存; 贾青; 王朝霞; 张月英; 张俊平


    目的 观察转移性Lewis肺癌在5-Fu化疗期间再增殖加速现象及蝎毒提取物(PESV)对再增殖的抑制作用.方法 C57BL/6小鼠尾iv Lewis肺癌细胞,从第7天开始,每隔7天ip 5-Fu 1次,建立Lewis肺痛化疗期间冉增殖模型,以PESV干预,每隔7天处死6只动物,统计肺转移灶数目和肺质量,并以免疫组织化学方法检测Lewis肺癌增殖细胞核抗原(proliferating cell nuclear antigen,PCNA)、血管内皮生长因子(vascular endothelial growth factor,VEGF)表达水平和微血管密度(microvessel dentity,MVD).结果 模型组从第21天到第28天,大肿瘤转移灶数目平均增加2.5个,而从第14~21天仅平均增加0.8个;模型组肺质量增加在第21~28天显著大于第14~21天:模型组PCNA表达在第21天表达最低,在第28天最高,但第28天与第14天差异无显著性,PESV高、低剂量组在第28天表达水平皆低于模型组,以PESV高剂量组作用显著.模型组VEGF表达在第28天显著上调(与模型组第21天相比,P<0.01).与模型组相比,PESV高剂量组在第21、28天肿瘤组织VEGF表达下调,尤其是在第28天表达显著下调(JP<0.01),而PESV低剂量组仪在第28天与模型组差异存在显著性(P<0.05).MVD计数显示,模犁组在第21天最低,在第28天最高,但在第28天和第14天差异无显著性.而在PESV高剂量组,第14天高于第21天,第21天高于第28天,差异均有显著性.在PESV低剂量组,第14天高于第21天,但第21天与第28天差异无显著性.结论 在5-Fu对Lewis肺癌化疗期间存在再增殖加速现象,PESV可有效抑制此Lewis肺癌再增殖,作用机制之一是通过抑制肿瘤新生血管生成来抑制肿瘤细胞再增殖.%Objective To identify the repopulation in metastatic Lewis lung adenocarcinoma during 5-Fu chemotherapy and observe the inhibition ofpolypeptide extract from scorpion venom (PESV) on the repopulation. Methods To make repopulation model, Lewis cells were iv injected into caudal vein of

  10. Cytoreductive Surgery and Heated Intraperitoneal Chemotherapy for Peritoneal Carcinomatosis Secondary to Mucinous Adenocarcinoma of the Appendix

    Sparks, David S.; Morris, Bradley; Xu, Wen; Fulton, Jessica; Atkinson, Victoria; Meade, Brian; Lutton, Nicholas


    Cytoreductive surgery (CRS) followed by hyperthermic intraperitoneal chemotherapy (HIPEC) is a radical but effective treatment option for select peritoneal malignancies. We sought to determine our early experience with this method for peritoneal carcinomatosis secondary to mucinous adenocarcinomas of appendiceal origin. As such, we performed a retrospective clinical study of 30 consecutive patients undergoing CRS with planned HIPEC at the Princess Alexandra Hospital, between June 2009 to December 2012, with mucinous adenocarcinomas of the appendix. CRS was performed in 30 patients, 13 received HIPEC intraoperatively and 17 received early postoperative intra-peritoneal chemotherapy (EPIC) in addition. Mean age was 52.3 years and median hospital stay was 26 days (range 12–190 days). Peritoneal cancer index scores were 0–10 in 6.7% of patients, 11–20 in 20% of patients and >20 in 73.3% of patients. Complete cytoreduction was achieved overall in 21 patients. In total, 106 complications were observed in 28 patients. Ten were grade 3-A, five were grade 3-B and one grade-5 secondary to a fatal PE on day 97. In patients who received HIPEC, there was no difference in disease-free survival (P = 0.098) or overall survival (P = 0.645) between those who received EPIC versus those who did not. This study demonstrates that satisfactory outcomes with regards to morbidity and survival can be achieved with CRS and HIPEC, at a single-centre institution with growing expertise in the technique. Our results are comparable with outcomes previously described in the international literature. PMID:25594636

  11. Comprehensive molecular characterization of gastric adenocarcinoma

    Bass, Adam J.; Thorsson, Vesteinn; Shmulevich, Ilya; Reynolds, Sheila M.; Miller, Michael; Bernard, Brady; Hinoue, Toshinori; Laird, Peter W.; Curtis, Christina; Shen, Hui; Weisenberger, Daniel J.; Schultz, Nikolaus; Shen, Ronglai; Weinhold, Nils; Kelsen, David P.; Bowlby, Reanne; Chu, Andy; Kasaian, Katayoon; Mungall, Andrew J.; Robertson, A. Gordon; Sipahimalani, Payal; Cherniack, Andrew; Getz, Gad; Liu, Yingchun; Noble, Michael S.; Pedamallu, Chandra; Sougnez, Carrie; Taylor-Weiner, Amaro; Akbani, Rehan; Lee, Ju-Seog; Liu, Wenbin; Mills, Gordon B.; Yang, Da; Zhang, Wei; Pantazi, Angeliki; Parfenov, Michael; Gulley, Margaret; Piazuelo, M. Blanca; Schneider, Barbara G.; Kim, Jihun; Boussioutas, Alex; Sheth, Margi; Demchok, John A.; Rabkin, Charles S.; Willis, Joseph E.; Ng, Sam; Garman, Katherine; Beer, David G.; Pennathur, Arjun; Raphael, Benjamin J.; Wu, Hsin-Ta; Odze, Robert; Kim, Hark K.; Bowen, Jay; Leraas, Kristen M.; Lichtenberg, Tara M.; Weaver, Stephanie; McLellan, Michael; Wiznerowicz, Maciej; Sakai, Ryo; Getz, Gad; Sougnez, Carrie; Lawrence, Michael S.; Cibulskis, Kristian; Lichtenstein, Lee; Fisher, Sheila; Gabriel, Stacey B.; Lander, Eric S.; Ding, Li; Niu, Beifang; Ally, Adrian; Balasundaram, Miruna; Birol, Inanc; Bowlby, Reanne; Brooks, Denise; Butterfield, Yaron S. N.; Carlsen, Rebecca; Chu, Andy; Chu, Justin; Chuah, Eric; Chun, Hye-Jung E.; Clarke, Amanda; Dhalla, Noreen; Guin, Ranabir; Holt, Robert A.; Jones, Steven J.M.; Kasaian, Katayoon; Lee, Darlene; Li, Haiyan A.; Lim, Emilia; Ma, Yussanne; Marra, Marco A.; Mayo, Michael; Moore, Richard A.; Mungall, Andrew J.; Mungall, Karen L.; Nip, Ka Ming; Robertson, A. Gordon; Schein, Jacqueline E.; Sipahimalani, Payal; Tam, Angela; Thiessen, Nina; Beroukhim, Rameen; Carter, Scott L.; Cherniack, Andrew D.; Cho, Juok; Cibulskis, Kristian; DiCara, Daniel; Frazer, Scott; Fisher, Sheila; Gabriel, Stacey B.; Gehlenborg, Nils; Heiman, David I.; Jung, Joonil; Kim, Jaegil; Lander, Eric S.; Lawrence, Michael S.; Lichtenstein, Lee; Lin, Pei; Meyerson, Matthew; Ojesina, Akinyemi I.; Pedamallu, Chandra Sekhar; Saksena, Gordon; Schumacher, Steven E.; Sougnez, Carrie; Stojanov, Petar; Tabak, Barbara; Taylor-Weiner, Amaro; Voet, Doug; Rosenberg, Mara; Zack, Travis I.; Zhang, Hailei; Zou, Lihua; Protopopov, Alexei; Santoso, Netty; Parfenov, Michael; Lee, Semin; Zhang, Jianhua; Mahadeshwar, Harshad S.; Tang, Jiabin; Ren, Xiaojia; Seth, Sahil; Yang, Lixing; Xu, Andrew W.; Song, Xingzhi; Pantazi, Angeliki; Xi, Ruibin; Bristow, Christopher A.; Hadjipanayis, Angela; Seidman, Jonathan; Chin, Lynda; Park, Peter J.; Kucherlapati, Raju; Akbani, Rehan; Ling, Shiyun; Liu, Wenbin; Rao, Arvind; Weinstein, John N.; Kim, Sang-Bae; Lee, Ju-Seog; Lu, Yiling; Mills, Gordon; Laird, Peter W.; Hinoue, Toshinori; Weisenberger, Daniel J.; Bootwalla, Moiz S.; Lai, Phillip H.; Shen, Hui; Triche, Timothy; Van Den Berg, David J.; Baylin, Stephen B.; Herman, James G.; Getz, Gad; Chin, Lynda; Liu, Yingchun; Murray, Bradley A.; Noble, Michael S.; Askoy, B. Arman; Ciriello, Giovanni; Dresdner, Gideon; Gao, Jianjiong; Gross, Benjamin; Jacobsen, Anders; Lee, William; Ramirez, Ricardo; Sander, Chris; Schultz, Nikolaus; Senbabaoglu, Yasin; Sinha, Rileen; Sumer, S. Onur; Sun, Yichao; Weinhold, Nils; Thorsson, Vésteinn; Bernard, Brady; Iype, Lisa; Kramer, Roger W.; Kreisberg, Richard; Miller, Michael; Reynolds, Sheila M.; Rovira, Hector; Tasman, Natalie; Shmulevich, Ilya; Ng, Santa Cruz Sam; Haussler, David; Stuart, Josh M.; Akbani, Rehan; Ling, Shiyun; Liu, Wenbin; Rao, Arvind; Weinstein, John N.; Verhaak, Roeland G.W.; Mills, Gordon B.; Leiserson, Mark D. M.; Raphael, Benjamin J.; Wu, Hsin-Ta; Taylor, Barry S.; Black, Aaron D.; Bowen, Jay; Carney, Julie Ann; Gastier-Foster, Julie M.; Helsel, Carmen; Leraas, Kristen M.; Lichtenberg, Tara M.; McAllister, Cynthia; Ramirez, Nilsa C.; Tabler, Teresa R.; Wise, Lisa; Zmuda, Erik; Penny, Robert; Crain, Daniel; Gardner, Johanna; Lau, Kevin; Curely, Erin; Mallery, David; Morris, Scott; Paulauskis, Joseph; Shelton, Troy; Shelton, Candace; Sherman, Mark; Benz, Christopher; Lee, Jae-Hyuk; Fedosenko, Konstantin; Manikhas, Georgy; Potapova, Olga; Voronina, Olga; Belyaev, Smitry; Dolzhansky, Oleg; Rathmell, W. Kimryn; Brzezinski, Jakub; Ibbs, Matthew; Korski, Konstanty; Kycler, Witold; ŁaŸniak, Radoslaw; Leporowska, Ewa; Mackiewicz, Andrzej; Murawa, Dawid; Murawa, Pawel; Spychała, Arkadiusz; Suchorska, Wiktoria M.; Tatka, Honorata; Teresiak, Marek; Wiznerowicz, Maciej; Abdel-Misih, Raafat; Bennett, Joseph; Brown, Jennifer; Iacocca, Mary; Rabeno, Brenda; Kwon, Sun-Young; Penny, Robert; Gardner, Johanna; Kemkes, Ariane; Mallery, David; Morris, Scott; Shelton, Troy; Shelton, Candace; Curley, Erin; Alexopoulou, Iakovina; Engel, Jay; Bartlett, John; Albert, Monique; Park, Do-Youn; Dhir, Rajiv; Luketich, James; Landreneau, Rodney; Janjigian, Yelena Y.; Kelsen, David P.; Cho, Eunjung; Ladanyi, Marc; Tang, Laura; McCall, Shannon J.; Park, Young S.; Cheong, Jae-Ho; Ajani, Jaffer; Camargo, M. Constanza; Alonso, Shelley; Ayala, Brenda; Jensen, Mark A.; Pihl, Todd; Raman, Rohini; Walton, Jessica; Wan, Yunhu; Demchok, John A.; Eley, Greg; Mills Shaw, Kenna R.; Sheth, Margi; Tarnuzzer, Roy; Wang, Zhining; Yang, Liming; Zenklusen, Jean Claude; Davidsen, Tanja; Hutter, Carolyn M.; Sofia, Heidi J.; Burton, Robert; Chudamani, Sudha; Liu, Jia


    Gastric cancer is a leading cause of cancer deaths, but analysis of its molecular and clinical characteristics has been complicated by histological and aetiological heterogeneity. Here we describe a comprehensive molecular evaluation of 295 primary gastric adenocarcinomas as part of The Cancer Genome Atlas (TCGA) project. We propose a molecular classification dividing gastric cancer into four subtypes: tumours positive for Epstein–Barr virus, which display recurrent PIK3CA mutations, extreme DNA hypermethylation, and amplification of JAK2, CD274 (also known as PD-L1) and PDCD1LG2 (also knownasPD-L2); microsatellite unstable tumours, which show elevated mutation rates, including mutations of genes encoding targetable oncogenic signalling proteins; genomically stable tumours, which are enriched for the diffuse histological variant and mutations of RHOA or fusions involving RHO-family GTPase-activating proteins; and tumours with chromosomal instability, which show marked aneuploidy and focal amplification of receptor tyrosine kinases. Identification of these subtypes provides a roadmap for patient stratification and trials of targeted therapies. PMID:25079317

  12. MicroRNAs in pancreatic ductal adenocarcinoma

    Jong Y Park; James Helm; Domenico Coppola; Donghwa Kim; Mokenge Malafa; Seung Joon Kim


    Ductal adenocarcinoma of the pancreas is a lethal cancer for which the only chance of long-term survival belongs to the patient with localized disease in whom a potentially curative resection can be done.Therefore,biomarkers for early detection and new therapeutic strategies are urgently needed.miRNAs are a recently discovered class of small endogenous non-coding RNAs of about 22 nucleotides that have gained attention for their role in downregulation of mRNA expression at the posttranscriptional level.miRNAs regulate proteins involved in critical cellular processes such as differentiation,proliferation,and apoptosis.Evidence suggests that deregulated miRNA expression is involved in carcinogenesis at many sites,including the pancreas.Aberrant expression of miRNAs may upregulate the expression of oncogenes or downregulate the expression of tumor suppressor genes,as well as play a role in other mechanisms of carcinogenesis.The purpose of this review is to summarize our knowledge of deregulated miRNA expression in pancreatic cancer and discuss the implication for potential translation of this knowledge into clinical practice.

  13. High-resolution array comparative genomic hybridization in sporadic and celiac disease-related small bowel adenocarcinomas.

    Diosdado, B.; Buffart, T.E.; Watkins, R.; Carvalho, B.; Ylstra, B.; Tijssen, M.; Bolijn, A.S.; Lewis, F.; Maude, K.; Verbeke, C.; Nagtegaal, I.D.; Grabsch, H.; Mulder, C.J.; Quirke, P.; Howdle, P.; Meijer, G.A.


    PURPOSE: The molecular pathogenesis of small intestinal adenocarcinomas is not well understood. Understanding the molecular characteristics of small bowel adenocarcinoma may lead to more effective patient treatment. EXPERIMENTAL DESIGN: Forty-eight small bowel adenocarcinomas (33 non-celiac disease

  14. Adjuvant chemo-radiation for gastric adenocarcinoma: an institutional experience

    Ghosn Marwan G


    Full Text Available Abstract Background Studies have shown that surgery alone is less than satisfactory in the management of early gastric cancer, with cure rates approaching 40%. The role of adjuvant therapy was indefinite until three large, randomized controlled trials showed the survival benefit of adjuvant therapy over surgery alone. Chemoradiation therapy has been criticized for its high toxicity. Methods 24 patients diagnosed between September 2001 and July 2007 were treated with adjuvant chemoradiation. 18 patients had the classical MacDonald regimen of 4500 cGy of XRT and chemotherapy with 5-fluorouracil (5FU and leucovorin, while chemotherapy consisted of 5FU/Cisplatin for 6 patients. Results This series consisted of non-metastatic patients, 17 females and 7 males with a median age of 62.5 years. 23 patients (96% had a performance status of 0 or 1. The full course of radiation therapy (4500 cGy was completed by 22 patients (91.7%. Only 7 patients (36.8% completed the total planned courses of chemotherapy. 2 local relapses (10%, 2 regional relapses (10% and 2 distant relapses (10% were recorded. Time to progression has not been reached. 9 patients (37.5% died during follow-up with a median overall survival of 75 months. Patients lost a mean of 4 Kgs during radiation therapy. We recorded 6 episodes of febrile neutropenia and the most frequent toxicity was gastro-intestinal in 17 patients (70.8% with 9 (36% patients suffering grade 3 or 4 toxicity and 5 patients (20% suffering from grade 3 or 4 neutropenia. 4 (17% patients required total parenteral nutrition for a mean duration of 20 days. 4 patients suffered septic shock (17% and 1 patient developed a deep venous thrombosis and a pulmonary embolus. Conclusions Adjuvant chemo-radiation for gastric cancer is a standard at our institution and has resulted in few relapses and an interesting median survival. Toxicity rates were serious and this remains a harsh regimen with only 36.8% of patients completing the

  15. Wideband CMOS receivers

    Oliveira, Luis


    This book demonstrates how to design a wideband receiver operating in current mode, in which the noise and non-linearity are reduced, implemented in a low cost single chip, using standard CMOS technology.  The authors present a solution to remove the transimpedance amplifier (TIA) block and connect directly the mixer’s output to a passive second-order continuous-time Σ∆ analog to digital converter (ADC), which operates in current-mode. These techniques enable the reduction of area, power consumption, and cost in modern CMOS receivers.

  16. Zero-power receiver

    Brocato, Robert W.


    An unpowered signal receiver and a method for signal reception detects and responds to very weak signals using pyroelectric devices as impedance transformers and/or demodulators. In some embodiments, surface acoustic wave devices (SAW) are also used. Illustrative embodiments include satellite and long distance terrestrial communications applications.

  17. Prognostic role of sex steroid receptors in pancreatic adenocarcinoma.

    Georgiadou, Despoina; Sergentanis, Theodoros N; Sakellariou, Stratigoula; Vlachodimitropoulos, Dimitris; Psaltopoulou, Theodora; Lazaris, Andreas C; Gounaris, Antonia; Zografos, George C


    From the available literature, it is unclear what proportion of pancreatic adenocarcinomas express estrogen receptors (ERα, ERβ), progesterone receptors (PR), and androgen receptors (AR), and if any of these markers have prognostic significance. We aimed to assess (1) the expression and (2) the correlation of the aforementioned markers with clinicopathological parameters and prognosis in patients with pancreatic adenocarcinoma. During a five-year period, 60 patients with pancreatic ductal adenocarcinoma underwent surgical resection at a single institution. Immunohistochemical stains of the studied markers were quantified by Image analysis system. ERα expression was positively associated with PR expression. Moreover, ERβ was inversely associated with the presence of metastases, whereas no significant associations implicated AR. As far as the prognostic significance of the studied receptors is concerned, higher ERα expression correlated with poorer survival at the univariate analysis, but the finding dissipated at the multivariate approach. No significant associations with overall survival were noted regarding the other receptors. The role of sex hormone receptors in the survival from pancreatic adenocarcinoma seems rather limited. Further prospective studies assessing those receptors should ideally be designed in order to confirm our results and possibly outline additional correlations between other steroid receptors and features of pancreatic adenocarcinoma.

  18. ATM protein is deficient in over 40% of lung adenocarcinomas.

    Villaruz, Liza C; Jones, Helen; Dacic, Sanja; Abberbock, Shira; Kurland, Brenda F; Stabile, Laura P; Siegfried, Jill M; Conrads, Thomas P; Smith, Neil R; O'Connor, Mark J; Pierce, Andrew J; Bakkenist, Christopher J


    Lung cancer is the leading cause of cancer-related mortality in the USA and worldwide, and of the estimated 1.2 million new cases of lung cancer diagnosed every year, over 30% are lung adenocarcinomas. The backbone of 1st-line systemic therapy in the metastatic setting, in the absence of an actionable oncogenic driver, is platinum-based chemotherapy. ATM and ATR are DNA damage signaling kinases activated at DNA double-strand breaks (DSBs) and stalled and collapsed replication forks, respectively. ATM protein is lost in a number of cancer cell lines and ATR kinase inhibitors synergize with cisplatin to resolve xenograft models of ATM-deficient lung cancer. We therefore sought to determine the frequency of ATM loss in a tissue microarray (TMA) of lung adenocarcinoma. Here we report the validation of a commercial antibody (ab32420) for the identification of ATM by immunohistochemistry and estimate that 61 of 147 (41%, 95% CI 34%-50%) cases of lung adenocarcinoma are negative for ATM protein expression. As a positive control for ATM staining, nuclear ATM protein was identified in stroma and immune infiltrate in all evaluable cases. ATM loss in lung adenocarcinoma was not associated with overall survival. However, our preclinical findings in ATM-deficient cell lines suggest that ATM could be a predictive biomarker for synergy of an ATR kinase inhibitor with standard-of-care cisplatin. This could improve clinical outcome in 100,000's of patients with ATM-deficient lung adenocarcinoma every year.

  19. Clinicopathologic features of incidental prostatic adenocarcinoma in radical cystoprostatectomy specimens

    Vuruskan Hakan


    Full Text Available Abstract Background The aim of this study is to review all features of incidentally discovered prostate adenocarcinoma in patients undergoing radical cystoprostatectomy for bladder cancer. Methods The medical charts of 300 male patients who underwent radical cystoprostatectomy for bladder cancer between 1997 and 2005 were retrospectively reviewed. The mean age of the patients was 62 (range 51-75 years. Results Prostate adenocarcinoma was present in 60 (20% of 300 specimens. All were acinar adenocarcinoma. Of these, 40 (66.7% were located in peripheral zone, 20 (33.3% had pT2a tumor, 12 (20% had pT2b tumor, 22(36.7% had pT2c and, 6 (10% had pT3a tumor. Gleason score was 6 or less in 48 (80% patients. Surgical margins were negative in 54 (90% patients, and tumor volume was less than 0.5 cc in 23 (38.3% patients. Of the 60 incidentally detected cases of prostate adenocarcinoma 40 (66.7% were considered clinically significant. Conclusion Incidentally detected prostate adenocarcinoma is frequently observed in radical cystoprostatectomy specimens. The majority are clinically significant.

  20. Molecular mechanisms of bortezomib resistant adenocarcinoma cells.

    Erika Suzuki

    Full Text Available Bortezomib (Velcade™ is a reversible proteasome inhibitor that is approved for the treatment of multiple myeloma (MM. Despite its demonstrated clinical success, some patients are deprived of treatment due to primary refractoriness or development of resistance during therapy. To investigate the role of the duration of proteasome inhibition in the anti-tumor response of bortezomib, we established clonal isolates of HT-29 adenocarcinoma cells adapted to continuous exposure of bortezomib. These cells were ~30-fold resistant to bortezomib. Two novel and distinct mutations in the β5 subunit, Cys63Phe, located distal to the binding site in a helix critical for drug binding, and Arg24Cys, found in the propeptide region were found in all resistant clones. The latter mutation is a natural variant found to be elevated in frequency in patients with MM. Proteasome activity and levels of both the constitutive and immunoproteasome were increased in resistant cells, which correlated to an increase in subunit gene expression. These changes correlated with a more rapid recovery of proteasome activity following brief exposure to bortezomib. Increased recovery rate was not due to increased proteasome turnover as similar findings were seen in cells co-treated with cycloheximide. When we exposed resistant cells to the irreversible proteasome inhibitor carfilzomib we noted a slower rate of recovery of proteasome activity as compared to bortezomib in both parental and resistant cells. Importantly, carfilzomib maintained its cytotoxic potential in the bortezomib resistant cell lines. Therefore, resistance to bortezomib, can be overcome with irreversible inhibitors, suggesting prolonged proteasome inhibition induces a more potent anti-tumor response.

  1. Pathophysiological mechanisms linking obesity and esophageal adenocarcinoma

    Leo; Alexandre; Elizabeth; Long; Ian; LP; Beales


    In recent decades there has been a dramatic rise in the incidence of esophageal adenocarcinoma(EAC) in the developed world. Over approximately the same period there has also been an increase in the prevalence of obesity. Obesity, especially visceral obesity, is an important independent risk factor for the development of gastro-esophageal reflux disease, Barrett’s esophagus and EAC. Although the simplest explanation is that this mediated by the mechanical effects of abdominal obesity promoting gastro-esophageal reflux, the epidemiological data suggest that the EAC-promoting effects are independent of reflux. Several, not mutually exclusive, mechanisms have been implicated, which may have different effects at various points along the refluxBarrett’s-cancer pathway. These mechanisms include a reduction in the prevalence of Helicobacter pylori infection enhancing gastric acidity and possibly appetite byincreasing gastric ghrelin secretion, induction of both low-grade systemic inflammation by factors secreted by adipose tissue and the metabolic syndrome with insulin-resistance. Obesity is associated with enhanced secretion of leptin and decreased secretion of adiponectin from adipose tissue and both increased leptin and decreased adiponectin have been shown to be independent risk factors for progression to EAC. Leptin and adiponectin have a set of mutually antagonistic actions on Barrett’s cells which appear to influence the progression of malignant behaviour. At present no drugs are of proven benefit to prevent obesity associated EAC. Roux-en-Y reconstruction is the preferred bariatric surgical option for weight loss in patients with reflux. Statins and aspirin may have chemopreventative effects and are indicated for their circulatory benefits.

  2. Metastatic primary duodenal adeno-carcinoma responding to metronomic oral cyclophosphamide chemotherapy

    Anis Bandyopadhyay


    Full Text Available Primary adenocarcinoma of duodenum is a very rare tumour with a prevalence of only 0.3 to 1% of among all the tumours of gastrointestinal tracts. Localised tumours, if resected have good prognosis but those with metastates entails a poor prognosis, where generally palliation may be the only feasible option. Low dose continous cytotoxic treatment or metronomic chemotherapy prevents neoangiogenesis and chemoresistance thereby, provides excellent symptom relief and palliation in many advanced heavily pretreated solid malignancies. It offers as an affordable, less toxic therapy with moderate to good efficacy. Here we report a case of a 52 year female who, presented with history of maleana, pallor and pedal edema for last 2 months. Her performance status was poor (KPS 40 and she had enlarged left supraclavicular lymph node, palpable liver and vague mass in paraumbilical region. Upper GI endoscopy revealed large ulceroproliferative growth in the D2 segment and HPE showed moderately differentiated adenocarcinoma. CT scan revealed paratracheal and retroperitoneal lymphadenopathy and bone scan revealed vertebral metastasis. Patient received oral cyclophosphamide and hematinic and vitamin support, along with radiation to spine. There was near complete clinical response, and progression free period of about 32 weeks. Thus, single agent cyclophosphamide in the present case provided near total clinical response and prolonged period of freedom from disease progression with excellent palliation of symptoms. Hence in patient of advanced and metastatic small bowel cancer, with poor performance status metronomic therapy with single agent cyclophosphamide may provide viable option both for treatment and palliation.

  3. Breast metastasis from a pulmonary adenocarcinoma: Case report and review of the literature.

    Sanguinetti, Alessandro; Puma, Francesco; Lucchini, Roberta; Santoprete, Stefano; Cirocchi, Roberto; Corsi, Alessia; Triola, Roberta; Avenia, Nicola


    Breast metastasis from extra-mammary malignancy is rare. An incidence of 0.4-1.3% has been reported in the literature. The primary malignancies most commonly metastasizing to the breast are leukemia, lymphoma and malignant melanoma. We present a case of metastasis to the breast from a pulmonary adenocarcinoma, diagnosed concomitantly with the primary tumor. A 43-year-old female presented with dyspnea and a dry cough of 3 weeks' duration. A subsequent chest radiograph revealed a massive pleural effusion. Additionally, on physical examination, a poorly defined mass was noted in the upper outer quadrant of the right breast. The patient underwent bronchoscopy, simple right mastectomy and medical thoracoscopy. Following cytology, histology and immunohistochemistry, primary lung adenocarcinoma with metastasis to the breast and parietal pleura was diagnosed. Histologically, both the primary and metastatic anatomic sites demonstrated a micropapillary component, which has recently been recognized as an important prognostic factor. Although the patient received chemotherapy, she succumbed to her condition within 8 months. Accurate differentiation of metastasis from primary carcinoma is very important as the treatment and prognosis of the two differ significantly.

  4. Breast metastasis from a pulmonary adenocarcinoma: Case report and review of the literature



    Breast metastasis from extra-mammary malignancy is rare. An incidence of 0.4–1.3% has been reported in the literature. The primary malignancies most commonly metastasizing to the breast are leukemia, lymphoma and malignant melanoma. We present a case of metastasis to the breast from a pulmonary adenocarcinoma, diagnosed concomitantly with the primary tumor. A 43-year-old female presented with dyspnea and a dry cough of 3 weeks’ duration. A subsequent chest radiograph revealed a massive pleural effusion. Additionally, on physical examination, a poorly defined mass was noted in the upper outer quadrant of the right breast. The patient underwent bronchoscopy, simple right mastectomy and medical thoracoscopy. Following cytology, histology and immunohistochemistry, primary lung adenocarcinoma with metastasis to the breast and parietal pleura was diagnosed. Histologically, both the primary and metastatic anatomic sites demonstrated a micropapillary component, which has recently been recognized as an important prognostic factor. Although the patient received chemotherapy, she succumbed to her condition within 8 months. Accurate differentiation of metastasis from primary carcinoma is very important as the treatment and prognosis of the two differ significantly. PMID:23255943

  5. Vandetanib Treatment in Refractory Advanced Lung Adenocarcinoma Patients: 
Five Cases and Review of Literature

    Lili GUO


    Full Text Available Background and objective Vandetanib is a once-daily oral multi-target inhibitor of vascular endothelial growth factor receptor, epidermal growth factor receptor, and rearranged during transfection (RET tyrosine kinases. The current study aimed to evaluate the effect and safety of vandetanib administered in refractory advanced lung adenocarcinoma patients. Methods Five patients who accepted chemotherapy and Tarceva therapy as first- and second-line treatments received vandetanib (300 mg, oral, once daily. Results The effects are stable disease on two patients (40% and progressive disease on three patients (60%. With a median follow-up of 36 months, one patient remained on follow-up. The median progression free survival (PFS is 2 months, and the mean overall survival is 22.6 months. The adverse events include rash (n=2, skin change (n=2, paronychia (n=2, asymptomatic QTc prolongation (n=2, ST-T change (n=1, diarrhea (n=1, and increased transaminase (n=1. Conclusion There were lower incidences of severe side effects with vandetanib therapy in refractory advanced lung adenocarcinoma patients. The results of effect and safety of vandetanib are similar with the related reviewed articles.

  6. Medroxyprogesterone in Treating Patients With Endometrioid Adenocarcinoma of the Uterine Corpus


    Endometrial Adenocarcinoma; Endometrial Adenosquamous Carcinoma; Endometrial Endometrioid Adenocarcinoma, Variant With Squamous Differentiation; Recurrent Uterine Corpus Carcinoma; Stage I Uterine Corpus Cancer; Stage II Uterine Corpus Cancer; Stage III Uterine Corpus Cancer; Stage IV Uterine Corpus Cancer

  7. Frequent alterations in cytoskeleton remodelling genes in primary and metastatic lung adenocarcinomas

    Wu, Kui; Zhang, Xin; Li, Fuqiang


    The landscape of genetic alterations in lung adenocarcinoma derived from Asian patients is largely uncharacterized. Here we present an integrated genomic and transcriptomic analysis of 335 primary lung adenocarcinomas and 35 corresponding lymph node metastases from Chinese patients. Altogether 13...

  8. Outcome of pancreaticoduodenectomy with extended retroperitoneal lymphadenectomy for adenocarcinoma of the head of the pancreas

    YANG Yin-mo; WAN Yuan-lian; TIAN Xiao-dong; ZHUANG Yan; HUANG Yan-ting


    Background Nowadays, there is a remarkable rise in resectability rate of periampullary adenocarcinoma and the mortality and morbidity of the pancreaticoduodenectomy procedure have been reduced remarkably, while the 5 year survival rates of patients with carcinoma of the head of the pancreas are still below 25%. We conducted this retrospective study to evaluate the clinical outcome of radical pancreaticoduodenectomy with extended retroperitoneal lymphadenectomy as a surgical therapy for adenocarcinoma of the head of the pancreas.Methods Twenty cases with adenocarcinoma of the head of the pancreas were treated by standard pancreaticoduodenectomy (removing only the peripancreatic lymph nodes en bloc with the tumour) from 1994 to 1997, and 46 cases with the same disease underwent extended retroperitoneal lymphadenectomy associated with standard pancreaticoduodenectomy from 1998 to 2002. The patients for whom there were insufficient follow-up data, or who had received postoperative adjuvant therapy, were excluded from the analysis. Clinical and pathological parameters of both groups were reviewed. The postoperative morbidity, mortality and survival data were compared statistically. Results Demographic and histopathological characteristics were similar in the two groups of patients. Performance of the extended lymphadenectomy lengthened the procedure. The mean total number of lymph nodes resected was significantly higher in the radical group (P< 0.05). Of the 46 cases in the radical group, 26% (12/46) had metastatic adenocarcinoma in the resected retroperitoneal lymph nodes. There was one perioperative death in the standard group, and two in the radical group. Postoperative diarrhoea and lymphatic leakage were only observed in the radical group. Transfusion requirements and postoperative morbidity rates did not differ between the two groups. The 1-, 2- and 3-year survival rates were 63%, 32% and 21% respectively in the standard group, and 66%, 38% and 21% in the radical

  9. The prevalence and prognostic significance of KRAS mutation subtypes in lung adenocarcinomas from Chinese populations

    Zheng DF


    Full Text Available Difan Zheng,1,2,* Rui Wang,1,2,* Yang Zhang,1,2 Yunjian Pan,1,2 Xinghua Cheng,3 Chao Cheng,1,2 Shanbo Zheng,1,2 Hang Li,1,2 Ranxia Gong,1,2 Yuan Li,2,4 Xuxia Shen,2,4 Yihua Sun,1,2 Haiquan Chen1–3,51Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, 2Department of Oncology, Shanghai Medical College, Fudan University, 3Shanghai Chest Hospital, Shanghai Jiao Tong University, 4Department of Pathology, Fudan University Shanghai Cancer Center, 5Institutes of Biomedical Sciences, Fudan University, Shanghai, People’s Republic of China*These authors contributed equally to this workBackground: We performed this retrospective study to identify the prevalence of KRAS mutation in Chinese populations and make a comprehensive investigation of the clinicopathological features of KRAS mutation in these patients.Patients and methods: Patients from 2007 to 2013 diagnosed with primary lung adenocarcinoma who received a radical resection were examined for KRAS, EGFR, HER2, BRAF mutations, and ALK, RET, and ROS1 fusions. Clinicopathological features, including sex, age, tumor–lymph node–metastasis stage, tumor differentiation, smoking status, histological subtypes, and survival information were analyzed.Result: KRAS mutation was detected in 113 of 1,368 patients. Nine different subtypes of KRAS mutation were identified in codon 12, codon 13, and codon 61. KRAS mutation was more frequently found in male patients and former/current smoker patients. Tumors with KRAS mutation had poorer differentiation. Invasive mucinous adenocarcinoma predominant and solid predominant subtypes were more frequent in KRAS mutant patients. No statistical significance was found in relapse-free survival or overall survival between patients with KRAS mutation and patients with other mutations.Conclusion: In Chinese populations, we identified KRAS mutation in 8.3% (113/1,368 of the patients with lung adenocarcinoma. KRAS mutation defines a molecular subset of

  10. Predicting adenocarcinoma recurrence using computational texture models of nodule components in lung CT

    Depeursinge, Adrien, E-mail: [Department of Radiology, Stanford University School of Medicine, Stanford, California 94305 and Business Information Systems, University of Applied Sciences Western Switzerland (HES-SO), Sierre 3960 (Switzerland); Yanagawa, Masahiro [Department of Radiology, Stanford University School of Medicine, Stanford, California 94305 and Department of Radiology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871 (Japan); Leung, Ann N.; Rubin, Daniel L. [Department of Radiology, Stanford University School of Medicine, Stanford, California 94305 (United States)


    Purpose: To investigate the importance of presurgical computed tomography (CT) intensity and texture information from ground-glass opacities (GGO) and solid nodule components for the prediction of adenocarcinoma recurrence. Methods: For this study, 101 patients with surgically resected stage I adenocarcinoma were selected. During the follow-up period, 17 patients had disease recurrence with six associated cancer-related deaths. GGO and solid tumor components were delineated on presurgical CT scans by a radiologist. Computational texture models of GGO and solid regions were built using linear combinations of steerable Riesz wavelets learned with linear support vector machines (SVMs). Unlike other traditional texture attributes, the proposed texture models are designed to encode local image scales and directions that are specific to GGO and solid tissue. The responses of the locally steered models were used as texture attributes and compared to the responses of unaligned Riesz wavelets. The texture attributes were combined with CT intensities to predict tumor recurrence and patient hazard according to disease-free survival (DFS) time. Two families of predictive models were compared: LASSO and SVMs, and their survival counterparts: Cox-LASSO and survival SVMs. Results: The best-performing predictive model of patient hazard was associated with a concordance index (C-index) of 0.81 ± 0.02 and was based on the combination of the steered models and CT intensities with survival SVMs. The same feature group and the LASSO model yielded the highest area under the receiver operating characteristic curve (AUC) of 0.8 ± 0.01 for predicting tumor recurrence, although no statistically significant difference was found when compared to using intensity features solely. For all models, the performance was found to be significantly higher when image attributes were based on the solid components solely versus using the entire tumors (p < 3.08 × 10{sup −5}). Conclusions: This study

  11. Mesonephric adenocarcinoma of the cervix: Case report and literature review

    A. Dierickx


    Full Text Available A mesonephric adenocarcinoma of the cervix is a very rare tumor deriving from remnants of the mesonephric duct. Differential diagnosis from other cervical carcinomas is difficult and little is known regarding its biological behavior, prognosis, and the optimal management strategy. We present a case of a mesonephric adenocarcinoma of the cervix with a comprehensive review of the existing literature. In this case a 66-year-old woman presented with postmenopausal vaginal bleeding. She was diagnosed with a FIGO stage IIB mesonephric adenocarcinoma of the cervix and treated with neoadjuvant chemoradiotherapy and a Wertheim hysterectomy. The recovery from surgery was uneventful and the patient remains with no evidence of disease with 2 years of follow-up.

  12. Endometrial Adenocarcinoma and Mucocele of the Appendix: An Unusual Coexistence

    Ioannis Kalogiannidis


    Full Text Available Appendiceal mucocele is a rare clinical entity, which is however quite often associated with mucinous ovarian tumor. The coexistence of mucinous cystadenoma of the appendix and endometrial adenocarcinoma has not been reported before. A 49-year-old woman presented to our clinic with postmenopausal bleeding and no other symptom. Endometrial biopsy revealed endometrial adenocarcinoma of endometrioid type (grade I. Preoperative CT scanning revealed an appendiceal mucocele, and a colonoscopy confirmed the diagnosis. The patient underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy and appendectomy. The final histopathological examination showed a mucinous cystadenoma of the appendix and confirmed the diagnosis of endometrioid endometrial adenocarcinoma. The coexistence of appendiceal mucocele and female genital tract pathology is rare. However, gynecologists should keep a high level of suspicion for such possible coexistence. Both the diagnostic approach and the therapeutic management should be multidisciplinary, most importantly with the involvement of general surgeons.

  13. Current Standards and Novel Treatment Options for Metastatic Pancreatic Adenocarcinoma.

    Weinberg, Benjamin A; Yabar, Cinthya S; Brody, Jonathan R; Pishvaian, Michael J


    Pancreatic cancer is one of the most lethal solid tumors. The prognosis of metastatic pancreatic adenocarcinoma remains dismal, with a median survival of less than 1 year, due in large part to the fact that pancreatic adenocarcinoma is notoriously refractory to chemotherapy. However, there recently have been significant improvements in outcomes for patients with pancreatic adenocarcinoma: ongoing trials have shown promise, and these may lead to still further progress. Here we review the current treatment paradigms for metastatic disease, focusing on ways to ameliorate symptoms and lengthen survival. We then summarize recent advances in our understanding of the molecular and cellular aspects of pancreatic cancer. Finally, we outline new approaches currently under development for the treatment of metastatic disease, arising from our improved understanding of the genetic and nongenetic alterations within pancreatic cancer cells-and of interactions between cancer cells, the tumor microenvironment, and the immune system.

  14. Adenocarcinoma involving the tongue and the epiglottis in a horse.

    Laus, Fulvio; Rossi, Giacomo; Paggi, Emanuele; Bordicchia, Matteo; Fratini, Margherita; Tesei, Beniamino


    Tumors involving the oral cavity of the horse are uncommon. No cases of equine adenocarcinoma on the dorsum of the tongue have been reported in the literature. We report a case of adenocarcinoma located on the dorsum of the posterior one-third of the tongue in a 29-year-old gelding with severe dysphagia. Endoscopy revealed an epiglottis involvement, and histology was consistent with adenocarcinoma arising from minor salivary glands, which was associated with a severe fungal colonization of affected tissues. The goals of this report are to present an uncommon case of dorsum of the tongue-associated neoplasia and to highlight the association with atypical fungal colonization, to review the literature and to discuss possible clinical approach and prognosis.

  15. Mitochondrial genome instability in colorectal adenoma and adenocarcinoma.

    de Araujo, Luiza F; Fonseca, Aline S; Muys, Bruna R; Plaça, Jessica R; Bueno, Rafaela B L; Lorenzi, Julio C C; Santos, Anemari R D; Molfetta, Greice A; Zanette, Dalila L; Souza, Jorge E S; Valente, Valeria; Silva, Wilson A


    Mitochondrial dysfunction is regarded as a hallmark of cancer progression. In the current study, we evaluated mitochondrial genome instability and copy number in colorectal cancer using Next Generation Sequencing approach and qPCR, respectively. The results revealed higher levels of heteroplasmy and depletion of the relative mtDNA copy number in colorectal adenocarcinoma. Adenocarcinoma samples also presented an increased number of mutations in nuclear genes encoding proteins which functions are related with mitochondria fusion, fission and localization. Moreover, we found a set of mitochondrial and nuclear genes, which cooperate in the same mitochondrial function simultaneously mutated in adenocarcinoma. In summary, these results support an important role for mitochondrial function and genomic instability in colorectal tumorigenesis.

  16. Gastric signet-ring adenocarcinoma presenting with breast metastasis

    Anastasios L Boutis; Charalambos Andreadis; Frideriki Patakiouta; Despina Mouratidou


    Breast metastases from gastric cancer are extremely rare. A case report of a 37-year-old female with breast inflammatory invasion and ascites is described. Breast biopsy revealed carcinomatous invasion of the lymphatics from adenocarcinoma cells with signet-ring features.Estrogen (ER) and progesterone receptors (PR) and c-erb-B2 were negative. Upper gastrointestinal endoscopy revealed a prepyloric ulcerative mass. Histopathologic examination of the lesion showed infiltration from a highgrade adenocarcinoma, identical with that of the breast.Immunostaining was positive for cytokeratins CK-7 and CK-20 and CEA and negative for ER and PR. Ascitic fluid cytology was positive for adenocarcinoma cells. Mammography was not diagnostic. Abdominal CT scanning revealed large ovarian masses suggestive of metastases (Krukenberg's tumor). A cisplatin-based regimen was given but no objective response was observed. The patient died six months after initial diagnosis. A review of the literature is performed.

  17. Duodenal adenocarcinoma: Advances in diagnosis and surgical management

    Jordan M Cloyd; Elizabeth George; Brendan C Visser


    Duodenal adenocarcinoma is a rare but aggressive malignancy. Given its rarity, previous studies have traditionally combined duodenal adenocarcinoma(DA) with either other periampullary cancers or small bowel adenocarcinomas, limiting the available data to guide treatment decisions. Nevertheless, management primarily involves complete surgical resection when technically feasible. Surgery may require pancreaticoduodenectomy or segmental duodenal resection; either are acceptable options as long as negative margins are achievable and an adequate lymphadenectomy can be performed. Adjuvant chemotherapy and radiation are important components of multi-modality treatment for patients at high risk of recurrence. Further research would benefit from multiinstitutional trials that do not combine DA with other periampullary or small bowel malignancies. The purpose of this article is to perform a comprehensive review of DA with special focus on the surgical management and principles.

  18. Absorption spectra of adenocarcinoma and squamous cell carcinoma cervical tissues

    Ivashko, Pavlo; Peresunko, Olexander; Zelinska, Natalia; Alonova, Marina


    We studied a methods of assessment of a connective tissue of cervix in terms of specific volume of fibrous component and an optical density of staining of connective tissue fibers in the stroma of squamous cancer and cervix adenocarcinoma. An absorption spectra of blood plasma of the patients suffering from squamous cancer and cervix adenocarcinoma both before the surgery and in postsurgical periods were obtained. Linear dichroism measurements transmittance in polarized light at different orientations of the polarization plane relative to the direction of the dominant orientation in the structure of the sample of biotissues of stroma of squamous cancer and cervix adenocarcinoma were carried. Results of the investigation of the tumor tissues showed that the magnitude of the linear dichroism Δ is insignificant in the researched spectral range λ=280-840 nm and specific regularities in its change observed short-wave ranges.

  19. Gastric adenocarcinoma of fundic gland type: Endoscopicand clinicopathological features


    Gastric adenocarcinoma of fundic gland type (GA-FG)with chief cell differentiation was recently proposed asan extremely rare type of gastric adenocarcinoma. Here,we report 4 cases of GA-FG with chief cell differentiation.Endoscopic features included a submucosal tumor shapeor a flat shape, whitish discolorationand dilated vesselson the surface. The tumors were located in the upper ormiddle third of the stomach. All cases were preoperativelydiagnosed as GA-FG by biopsy, and endoscopic submucosaldissection was performed. Resected specimensrevealed well-differentiated adenocarcinomas resemblingchief cells. Tumor cells were diffusely positive for pepsinogen-Ⅰ,but partially positive for H+/K+-ATPase inscattered locations around the tumor margin. Despitethe presence of minimal invasion of the carcinoma intothe submucosal layer, which was observed in two cases,neither lymphatic nor venous invasion was detected inany of the cases. Finally, all cases showed less aggressiveclinical behavior with low grade malignancy.

  20. Adenocarcinoma in an ano-vaginal fistula in Crohn's disease

    Alfa-Wali, Maryam; Atinga, Angela; Mohsen, Yasser; Anthony, Andrew; Myers, Alistair


    INTRODUCTION Fistulas are a relatively common occurrence in Crohn's disease (CD), and often present early in the disease process. Additionally, patients suffering from either CD or ulcerative colitis are shown to have an increased risk of colorectal malignancies compared with the general population. PRESENTATION OF CASE We present a case of adenocarcinoma in an ano-vaginal fistula in a patient with longstanding CD. DISCUSSION Various pathogenic mechanisms for the development of carcinoma in fistulas have been suggested, but there is no consensus and indeed this risk may be cumulative. In this case report, we also discuss the pathogenesis of mucinous adenocarcinoma in fistulas secondary to CD. CONCLUSION Better detection of adenocarcinoma in patients presenting with persistent non-resolving fistulas in the presence of CD should be undertaken with regular biopsies following examinations under anaesthetic of the anorectum. PMID:23702362

  1. Pancreatic adenocarcinoma in type 2 progressive familial intrahepatic cholestasis

    Green Richard M


    Full Text Available Abstract Background BSEP disease results from mutations in ABCB11, which encodes the bile salt export pump (BSEP. BSEP disease is associated with an increased risk of hepatobiliary cancer. Case Presentation A 36 year old woman with BSEP disease developed pancreatic adenocarcinoma at age 36. She had been treated with a biliary diversion at age 18. A 1.7 × 1.3 cm mass was detected in the pancreas on abdominal CT scan. A 2 cm mass lesion was found at the neck and proximal body of the pancreas. Pathology demonstrated a grade 2-3 adenocarcinoma with invasion into the peripancreatic fat. Conclusions Clinicians should be aware of the possibility of pancreatic adenocarcinoma in patients with BSEP disease.

  2. Efficacy of Gefitinib for Young Patients with Unknown EGFR Gene Mutation 
in Advanced Lung Adenocarcinoma

    Yutao LIU


    Full Text Available Background and objective Lung cancer in young patients (less or equal to 45 years is relatively rare. We explored the efficacy and survival of Gefitinib for young patients with unknown epidermal growth factor receptor (EGFR gene mutation of advanced lung adenocarcinoma. Methods The clinical data of 55 young patients with unknown EGFR gene mutation in advanced lung adenocarcinoma referred to the Cancer Hospital & Institute, Chinese Academy of Medical Sciences from Jan 2006 through Dec 2010 were analyzed retrospectively. Results Of 55 young patients enrolled, the median age was 41 years. The objective response rate and disease control rate were 43.6% and 90.9%, respectively.. The median progression-free survival (PFS was 9.0 months. Among the factors analyzed, brain metastasis had significant effect on PFS (P=0.017. The median overall survival (OS was 24.0 months. The independent prognostic factors to significantly improve OS included non-smoking history (P=0.028 and receiving other anti-cancer treatment after Gefitinib therapy (P<0.001. Conclusion The median PFS and OS of the young patients with Unknown EGFR gene mutation in advanced lung adenocarcinoma were similar with general population.

  3. Tratamento paliativo do adenocarcinoma gástrico Palliative treatment of gastric adenocarcinoma

    Fernando de Oliveira Souza


    Full Text Available INTRODUÇÃO: Embora decrescendo nos países do chamado primeiro mundo, o adenocarcinoma gástrico mantém-se como terceiro tumor mais frequente no sexo masculino mundialmente. Sua mortalidade é muito elevada, fruto do diagnóstico tardio em lesões muito avançadas, o que frequentemente torna paliativo seu tratamento, motivos pelos quais se justificam estudos no sentido de melhorar estes resultados. MÉTODO: Revisão da literatura através do portal de periódicos da CAPES indicados por busca no sites da Bireme e PubMed. Além disso, foram consultados os sumários do 8º Congresso Internacional de Câncer Gástrico em 2009. Foi apresentada uma sugestão de algoritmo de atendimento destes pacientes. CONCLUSÕES: O surgimento de novas drogas anticancer, mais efetivas, está propiciando novas alternativas para a ressecção gástrica como tratamento paliativo. Novos protocolos estão surgindo mostrando boas perspectivas para melhorar os resultados desta doença.INTRODUCTION: Although decreasing in the well developed countries, gastric adenocarcinoma still represents the third most common cancer in males worldwide. Its mortality is very high because of the lateness of its diagnosis over advanced lesions, which turns palliative its treatment in the majority of the cases. METHOD: Literature review using CAPES, PubMed and Bireme sites as well as the abstracts of the 8 º International Gastric Cancer Congress which was held in Krakow in 2009. CONCLUSIONS: The release of new anticancer drugs against gastric cancer is providing a revival of gastrectomy as an effective palliative treatment of advanced gastric cancer. New protocols are being published, showing better results i