SEARCH · Search PubMed
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Growth inhibition of Bacillus cereus by 5-fluorouracil is abolished by the addition of uracil without the inhibition of DNA synthesis being relieved. The growth rate, protein, and RNA content of cells grown in the presence of 5-fluorouracil and uracil are unaffected until the cells contain only about 25 percent of their normal DNA content.
Johnson, Russell C. (University of Minnesota, Minneapolis), and Palmer Rogers. 5-Fluorouracil as a selective agent for growth of leptospirae. J. Bacteriol. 87:422-426. 1964.-The use of 5-fluorouracil (FU) as a selective agent for the growth of leptospirae was investigated. Both the growth rate and the final cell yield of Leptospira pomona were unaltered with FU added to the medium at concentrations varying from 50 to 1,000 mug/ml. Growth of this organism was initiated with as few as five organisms per ml in the FU medium. With C(14)-FU, it was demonstrated that FU was not incorporated into L. pomona nucleic acids. Other leptospirae tested grew normally in the presence of FU. By use of the FU medium, L. canicola was successfully isolated from contaminated urine of experimentally infected dogs. Also, contaminated cultures of leptospirae were purified by passage through the FU medium.
De Repentigny, J. (University of Montreal, Montreal, Quebec, Canada), S. Sonea, and A. Frappier. Differentiation by immunodiffusion and by quantitative immunofluorescence between 5-fluorouracil-treated and normal cells from a toxinogenic Staphylococcus aureus strain. J. Bacteriol. 88:444-448. 1964.-Immunodiffusion and quantitative immunofluorescence can both detect antigenic changes produced by 5-fluorouracil (FU) in Staphylococcus aureus Wood 46 strain. When FU is added to the cultures in their logarithmic phase of growth, a number of bacterial antigens are no longer detectable by immuno-diffusion and the intensity of the total immuno-fluorescence of bacteria is diminished; thus, these antigens are either profoundly modified or no longer synthesized. Uracil and, less effectively, thymine can reverse the FU inhibitory effect on the synthesis of antigens, and the number of precipitin lines remains closer to controls. The immunochemical approach provides a new way of obtaining information on the action of this pyrimidine analogue on metabolic processes in pathogenic bacteria. Microscopic quantitative immunofluorescence seems to be adaptable to give indirect information on changes in the metabolism or synthesis or antigens of a single bacterial cell.
Bodmer, Walter F. (Stanford University School of Medicine, Palo Alto, Calif.), and Susan Grether. Uptake and incorporation of thymine, thymidine, uracil, uridine, and 5-fluorouracil into the nucleic acids of Bacillus subtilis. J. Bacteriol. 89:1011-1014. 1965.-From 55 to 95% of uracil, uridine, or 5-fluorouracil (FU) added to the culture medium is incorporated into the acid-insoluble fraction of cells of Bacillus subtilis strains SB 19 (prototroph) and SB 503 (FU-resistant). Thymine is poorly incorporated (less than 1%); thus, the incorporation of thymidine is limited (less than 12%) by the rapid degradation of the nucleoside to thymine, probably by the enzyme thymidine phosphorylase. Uracil, uridine, and FU were not incorporated into the deoxyribonucleic acid (DNA) of either strain, whereas all the incorporated thymidine was found in the DNA.
A 62-year-old woman with metastatic gastric carcinoma was treated with fluorouracil for her malignant neoplasm. Nail plate-nail bed separation was noted in the fingers and toes after two months of weekly chemotherapy and appeared to be caused by the fluorouracil.
Fluorouracil is given for a variety of neoplasms by various administrative routes. Toxicity of susceptible normal tissue limits systemic dosage, but at this level intraocular tissue may not receive tumor-inhibiting concentrations. Subconjunctival administration of 6.25 mg of 14C-fluorouracil in 0.5-mL dosages resulted in a peak anterior chamber concentration of 69.5 micrograms/mL and a peak vitreous concentration of 10.5 micrograms/mL over the 12 hours tested. This resulted in no visible ocular damage. The intraocular levels achieved were greater than the concentration reported to inhibit selected tumors. The total dosage administered was considerably below the level of systemic toxicity.
Proliferating human Tenon's capsule fibroblasts were exposed for 5 minutes to a wide range of concentrations of fluorouracil, floxuridine, and mitomycin. High concentrations of all three agents had prolonged effects on cell proliferation and morphologic characteristics compared with untreated control cells up to 36 days. The highest concentrations of both floxuridine (15,000 micrograms/mL) and mitomycin (1000 micrograms/mL) had an apparent cidal effect, reducing cell numbers below initial cell density. In contrast, although the highest concentration of fluorouracil (25,000 micrograms/mL) inhibited cell proliferation by more than 50% relative to the untreated control cells at 36 days, the cell numbers still increased fourfold compared with the initial cell density. These results demonstrate that 5-minute treatments with high concentrations of these drugs have prolonged effects on the proliferation of human Tenon's capsule fibroblasts in vitro. Single-dose regimens using high concentrations of these drugs at the time of operation may achieve results similar to those of protocols that involve repeated applications.
Rabbits undergoing full-thickness glaucoma filtering surgery were exposed for 5 minutes to one of three intraoperative treatments: (1) distilled water; (2) fluorouracil, 50 mg/mL; or (3) mitomycin C, 0.4 mg/mL. Tissue samples were taken from the subconjunctival and scleral tissues at the treated area and 90 degrees and 180 degrees from the center of the treated area and the adjacent cornea 2 mm from the limbus, 1 hour, 5 days, and 30 days postoperatively. The biopsy specimens were then placed in tissue culture media and the fibroblast outgrowths measured. Five-minute intraoperative treatments with fluorouracil resulted in a reversible delay of fibroblast outgrowths from treated subconjunctival and scleral tissues of just over 1 week in this model, whereas treatment with mitomycin C, 0.4 mg/mL, resulted in prolonged inhibition of at least 30 days. These effects were localized to the area treated. The many clinical implications of these findings are discussed.
OBJECTIVE: To report the rate of pathological complete response after induction chemotherapy with the docetaxel, cisplatin, and fluorouracil (TPF) combination. DESIGN: Retrospective cohort analysis. SETTING: Tertiary care academic cancer center, between June 1999 and May 2004. PATIENTS: Seventy-two patients with newly diagnosed squamous cell carcinoma of the head and neck; 68 (95%) of the patients had stage IV, locally advanced disease. INTERVENTIONS: Three cycles of induction chemotherapy followed by a biopsy of the primary site. All patients subsequently underwent chemotherapy with 3 cycles of TPF. MAIN OUTCOME MEASURE: Rate of pathological complete response at the primary site after induction chemotherapy with 3 cycles of TPF. RESULTS: Biopsy results were negative for cancer in 64 patients (89%) and positive in 8 patients (11%). The median follow-up was 2 years. In the positive biopsy result group, 2 (25%) of 8 patients died of disease vs 3 (4%) of 64 patients in the negative biopsy result group. Twenty-nine neck dissections were performed; results were positive in 7 patients (all alive with no evidence of disease) and negative in 22 patients (21 alive with no evidence of disease). The overall 2- and 5-year progression-free survival is currently projected at 85% and 85%, respectively; the overall 2- and 5-year survival, at 95% and 90%, respectively. Importantly, T4 presentation did not predict a positive biopsy result at the primary site or a positive neck dissection result (P = .60 and P = .56, respectively). N3 presentation (12 patients) did not predict a positive biopsy result at the primary site (P = .87) but did correlate with positive neck dissection results in 6 of 12 patients (P<.001). CONCLUSIONS: Induction chemotherapy with the TPF regimen results in a high pathological complete response rate (89%). This rate is higher than with the cisplatin plus fluorouracil combination therapy, which was reported to be between 25% and 50% in previous studies. Chemoradiotherapy is currently an accepted standard of care, but induction chemotherapy continues to be investigated. Based on recent phase 3 trial results and the data presented herein, we propose that the 3-drug combination be used as the new platform when administering induction chemotherapy.
OBJECTIVE: To evaluate the activity and toxicity of the drug combination cisplatin, fluorouracil by continuous infusion, and high-dose oral leucovorin calcium (PFL) as induction chemotherapy in patients with advanced and untreated squamous cell head and neck (SCHN) cancer. DESIGN: Nonrandomized, prospective trial. SETTING: Referral center (comprehensive cancer center). PATIENTS: Twenty-two patients with stage III (n = 7) and IV (n = 15) M0 SCHN cancer of the larynx (n = 13), hypopharynx (n = 7), and oropharynx (n = 2) whose standard treatment would have required total laryngectomy. INTERVENTIONS: Three cycles of PFL were administered prior to local-regional therapy (concomitant cisplatin and radiation and/or neck dissection, with total laryngectomy reserved for nonresponse or relapse). Chemotherapy included cisplatin (100 mg/m2) on day 1 by short intravenous infusion; fluorouracil (800 mg/m2) on days 1 through 5 by continuous infusion; and leucovorin (100 mg) every 4 hours by mouth for 30 doses. The PFL combination was administered every 21 days. MAIN OUTCOME MEASURES: Clinical response to chemotherapy and observed toxic effects during chemotherapy. RESULTS: Five patients were inevaluable for response, with three early deaths (infection in two and sudden death in one), one cerebrovascular accident, and one patient declining further chemotherapy. Of the remaining 17 patients, 10 had a major response to chemotherapy, but in only five patients (29%) was this complete (95% confidence interval, 8% to 51%). Other significant toxic effects included grade 3 to 4 mucositis in eight patients and grade 3 to 4 neutropenia in 10. CONCLUSIONS: While PFL is active in patients with SCHN cancer, we were unable to reproduce the high complete response rates reported by other centers. Its use can be associated with significant toxic effects. We do not recommend the use of PFL for the treatment of patients with SCHN cancer outside the context of a clinical trial until there is further critical assessment of its activity and toxicity.
Seventy-four patients with liver metastasis from proved colorectal primary adenocarcinoma were entered into a prospective, randomized clinical trial to evaluate treatment with intra-arterial floxuridine compared with standard outpatient therapy with fluorouracil delivered by intravenous bolus injection. Eligible patients were randomized to hepatic arterial chemotherapy with an implanted infusion pump or systemic chemotherapy. No crossover between treatment arms was permitted, and patients were followed up to progression and death. Objective tumor response was observed in 48% of patients receiving intra-arterial floxuridine and in 21% of patients receiving intravenous fluorouracil. Time to hepatic progression was significantly longer in the group given intra-arterial therapy: 15.7 vs 6.0 months. However, time to overall progression (6.0 vs 5.0 months) and survival (12.6 vs 10.5 months) were not statistically different. Based on these data, we cannot recommend treatment with intra-arterial floxuridine as given in this study for metastatic colorectal cancer to the liver.
BACKGROUND AND OBJECTIVES: Since the prognosis of patients with T4 squamous cell carcinoma (SCC) of the esophagus is extremely poor, an effective multimodal treatment needs to be established. METHODS: Forty-five patients with SCC of the esophagus at the T4 classification of the disease but no hematogenous metastasis were treated with concurrent chemoradiation therapy followed by surgical resection. Twenty-eight patients were treated with a regimen (protocol A) of 5-fluorouracil 750 mg/m2 on days 1-5 and 22-26, and cisplatin 70 mg/m2 on days 1 and 22. The remaining 17 patients were treated with a modified regimen (protocol B) of 5-fluorouracil 400 mg/m2 and cisplatin 10 mg/m2 on days 1-5, 8-12, 15-19, and 22-26. Radiation was delivered daily for 5 days/week for 4 weeks at the rate of 2 Gy/day to a total dose of 40 Gy in both protocols. RESULTS: A major clinical response was observed in 29 [3 complete response (CR) and 26 partial response (PR)] patients (64.4%). Twenty-eight patients (62.2%) underwent esophagectomy with no postoperative death. The median survival time of the resected patients (959 days) was significantly longer than that of the non-resected patients (178 days). Protocol B showed significantly higher pathologic effectiveness than protocol A. The pathologic CR rate for the main tumors was 1 (6.3%) of 16 patients for protocol A and 7 (58.3%) of 12 patients for protocol B. The pathologic CR rate for metastasized lymph nodes was 4/11 (36.4%) for protocol A and 5/5 (100%) for protocol B. Good histological response of the main tumors correlated well with long survival. The treatments were well tolerated except for one treatment-related death. CONCLUSIONS: Concurrent chemoradiation therapy followed by surgery is an effective and safe multimodal therapy for patients with primary inoperable T4 SCC of the esophagus.
BACKGROUND: There have been no reports of creatine phosphokinase (CK) elevation during levamisole administration. There is only one prior report of CK elevation of noncardiac origin associated with 5-fluorouracil. METHODS: A 41-year-old man was diagnosed with Stage B2 colon carcinoma and underwent extensive surgical resection. Adjuvant therapy with 5-fluorouracil and levamisole was initiated after surgery. A complete hematologic and chemistry profile was obtained during weekly clinic visits. RESULTS: The patient's serum CK levels were normal prior to the initiation of chemotherapy but began to rise after 4 weeks of therapy, Isoenzyme analysis revealed that the CK was 100% from skeletal muscle. When the CK level surpassed 1,000 U/L, chemotherapy was discontinued. The CK levels began to decline immediately, falling to normal within 2 months. All attempts to identify a known cause of the enzyme elevation were negative. CONCLUSIONS: The temporal relationship between chemotherapy administration, enzyme elevation, and the rapid fall in enzyme levels upon discontinuation of treatment argue strongly in favor of chemotherapy as the etiology of CK elevation in the patient.
BACKGROUND: The results of chemotherapy for patients with esophagogastric carcinoma have generally been modest but regimens developed more recently have produced higher response rates, and rekindled interest in neoadjuvant chemotherapy. One such regimen is epirubicin, cisplatin, and 5-fluorouracil (ECF). This study evaluates its efficacy, toxicity, impact on quality of life (QL), and impact on survival in a large consecutive series of patients with metastatic and locally advanced disease (LAD). METHODS: Patients with histologically confirmed esophagogastric carcinoma were treated with ECF (epirubicin 50 mg/m2 and cisplatin 60 mg/m2 every 3 weeks with continuous infusion of 5-fluorouracil (5-FU) 200 mg/m2/d). Responses were evaluated with computed tomography (CT) scan and endoscopy. QL was assessed using the European Organization for Research and Treatment of Cancer QLQ-C30 questionnaire. RESULTS: A total of 235 patients were treated, 173 with metastatic disease and 62 with LAD. The mean number of cycles delivered was 6 (range: 1-11) and patients were followed-up for a median of 8 months. Response was observed in 135 of 220 (61%) evaluable patients, with a complete response (C(R)), 11% of the patients and a partial response in 50% of the patients. Patients with moderately differentiated adenocarcinomas and LAD responded most favorably. Symptomatic improvement was achieved in the majority of cases (63-78% depending on the symptom). Toxicity was generally only mild to moderate, with severe non hematologic toxicity in less than 12% of the patients and only 6 (2.5%) treatment related deaths. QL assessment showed no significant negative impact on emotional functioning and good symptomatic control. Surgery following response to ECF was performed in 29 of the LAD patients, and in 19 cases (66%) a potentially curative resection was possible, with histologic CR in 32% of the patients. CONCLUSIONS: ECF is a highly active regimen with acceptable toxicity in patients with esophagogastric adenocarcinoma. In a proportion of patients with LAD, chemotherapy enabled potentially curative surgery to be performed. The results justify further investigation of this regimen in a neoadjuvant setting.
BACKGROUND: In 1989, the authors began a randomized trial to determine whether 5-fluorouracil and high dose folinic acid (HD-FUFA) would increase the event free and overall survival of patients with resectable Dukes B and C (AJCC/UICC Stage II and Stage III) colon carcinoma, and to assess the toxicity of the treatment and its impact on selected health-related quality-of-life indicators. Early results were published as a part of an international multicenter pooled analysis (IMPACT) in 1995. The purpose of this report is to update the survival data for patients enrolled in the trial and describe their reported perceptions of their own health and quality of life. METHODS: The trial involved multiple treatment centers, with a centralized randomization between surgery alone and surgery with chemotherapy. The HD-FUFA regimen employed consisted of 5-fluorouracil (370 mg/m2) plus folinic acid (200 mg/m2) administered daily for 5 days every 4 weeks for 6 cycles. Patients' perceptions of their own health status were obtained by means of 3 self-administered questionnaires, which were completed by patients at the time of discharge from the treatment center and at 6 and 24 months after randomization. RESULTS: Overall, 888 patients with resected Dukes B2 and C colon carcinoma were enrolled in the trial. HD-FUFA significantly reduced mortality by 25% (95% confidence interval, 5-41%; P=0.02) and events by 31% (95% confidence interval, 14-45%; P < or = 0.001). Compliance with treatment was good; more than 80% of patients completed the planned therapy. Toxicity was mild, and oral mucositis was the main side effect. None of the health-related quality-of-life parameters investigated (emotional status, worry about the future, changes in social life, impact of the disease, follow-up, and global quality of life) seemed to be affected by the treatment to which patients were allocated. A positive trend in the evolution of patients' psychologic status was observed. CONCLUSIONS: Long term results of this SITAC study confirm that HD-FUFA is a well-tolerated, effective 6-month adjuvant regimen for patients with colon carcinoma that has no detrimental effect on their quality of life.
BACKGROUND: The aim of this study was to evaluate the toxicity and efficacy of the combination of 5-fluorouracil, bleomycin, epirubicin, and cisplatin (FBEC) in the treatment of patients with undifferentiated carcinoma of nasopharyngeal type (UCNT). The study included patients with metastatic or recurrent disease (Group A) and previously untreated patients with locally advanced nonmetastatic disease (T >/= 3 or any T, N >/= 2, M0, according to 1987 criteria of the International Union Against Cancer and the American Joint Committee on Cancer (Group B). METHODS: From January 1992 to November 1996, 49 patients with histologically proven UCNT were treated with intravenous (i.v.) 5-fluorouracil (700 mg/m(2)/day by continuous infusion for 4 days), epirubicin (70 mg/m(2) i.v. on Day 1), Bleomycin (10 mg i.v. bolus on Day 1 followed by 12 mg/m(2)/day by continuous infusion for 4 days), and cisplatin (100 mg/m(2) on Day 5); this regimen was repeated every 21 days. Six cycles were given to Group A (26 patients), with bleomycin omitted during the last 3 cycles. In Group B (23 patients), only 3 cycles were given, followed by conventional radiotherapy (70 gray for 7 weeks). RESULTS: Of the 26 patients entered in Group A, 23 were evaluable for response. Nine complete responses (CRs) and 9 partial responses (PRs) were assessed, for a 78% objective response rate (ORR) (95% CI: 56-92). Three patients are alive with no evidence of disease after 43, 61, and 73 months, respectively. These patients achieved a CR with chemotherapy followed by consolidating radiotherapy to their target lesions. In Group B, the ORR was 91.5%, with 5 CRs (22%) and 16 PRs (69.5%) assessed in the 23 patients. Three months after the end of radiotherapy, the ORR was 87% (20 patients). After a median follow-up of 51 months (range, 24-67 months), 15 patients (65%) are alive without evidence of disease. Forty percent of cycles (51% in Group A, 25% in Group B) resulted in Grade 4 neutropenia, with fever and/or sepsis in 9.5%. Mucositis was seen in 42% of pretreated patients. There were 3 treatment-related deaths (2 from complications of infection and 1 bleomycin fibrosis at a total dose of 160 mg/m(2)), all of them in Group A. CONCLUSIONS: The FBEC regimen has good activity, with durable responses in patients with locally advanced, metastatic, or recurrent UCNT. This regimen is safe for patients with locally advanced disease, but close follow-up and supportive measures are needed when it is used to treat those with metastatic or recurrent disease.
BACKGROUND: The current treatment of advanced urothelial carcinoma generates high response rates but is associated with poor overall survival. The current study evaluated the efficacy and toxicity of a new combination of active drugs in the treatment of urothelial carcinoma. METHODS: Twenty-four patients with muscle invasive or metastatic urothelial carcinoma were enrolled. Fifteen patients (63%) had metastatic disease whereas 9 patients had T2-T4 disease. Three patients were unevaluable for response because of significant toxicity. Patients were treated every 28 days with methotrexate, 60 mg/m(2), intravenously (i.v.) on Day 1; cisplatin, 25 mg/m(2)/day, by continuous i.v. infusion on Days 2-6; 5-flurouracil (5-FU) 800 mg/m(2)/day by continuous i.v. infusion on Days 3-6; and leucovorin, 500 mg/m(2)/day, by continuous i.v. infusion on Days 2-6. Dosage in subsequent cycles was adjusted according to toxicity. RESULTS: The median follow-up was 81 months (range, 53-97+ months). The overall response rate (complete response + partial response) for all 24 patients was 63% (95% confidence interval, 41-81%). The median survival was 65 months in the patients with muscle invasive disease and 17 months in the patients with metastatic disease. The duration of response in patients with metastatic disease was 6 months (range, 4-19 months). Toxicity was significant, with 82% of patients experiencing Common Toxicity Criteria Grade 3 or 4 neutropenia and 63% experiencing Grade 3 or 4 thrombocytopenia. However, only three patients developed febrile neutropenia and gastrointestinal and neurologic toxicity was moderate. CONCLUSIONS: The combination of methotrexate, cisplatin, 5-fluorouracil, and leucovorin represents an active regimen in the treatment of urothelial carcinoma with a moderate toxicity profile. As new drugs are found to treat urothelial carcinoma, further studies will be needed to evaluate the role of traditional agents such as 5-fluorouracil and methotrexate in new combination chemotherapeutic regimens.
Adaptation of HT-29 cells to increasing concentrations of methotrexate (MTX) results in the selection of differentiated populations which show sequential dose-dependent changes of their differentiated phenotype with, at the highest concentrations (0.1 and 1 mM), a shift of differentiation from a mucus-secreting to an enterocytic phenotype coinciding with an amplification of the DHFR gene. We show here that DHFR gene amplification itself does not play a role in the shift of differentiation. An alternative explanation is the presence, within the mucus-secreting population, of an undetectable minor population of cells committed to enterocytic differentiation and able to develop resistance to higher concentrations of MTX. This was confirmed by cloning the population of cells resistant to 10 microM MTX. Out of 19 isolated clones, 17 were found to be mucus-secreting and 2 enterocytic. We tested 9 of these clones for their ability to develop resistance to 0.1 mM MTX: only 1 of enterocytic phenotype, was found to develop resistance to this higher concentration and to amplify the DHFR gene. The ability of enterocytic cells to develop resistance to elevated MTX concentration through amplification of the DHFR gene was demonstrated in another enterocytic HT-29 population selected by glucose deprivation. Enterocytic cells resistant to 10 microM MTX were also found, unlike mucus-secreting cells, to be readily adaptable to 5-fluorouracil, this occurring without amplification of the thymidylate synthase gene. Together these results highlight a previously uncharacterized relationship between commitment to enterocytic differentiation of colon-cancer cells and their ability to develop resistance to MTX and 5-fluorouracil.