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At least 865 records · Page 48Linked to original sources
PubMed1999

Docetaxel compared with sequential methotrexate and 5-fluorouracil in patients with advanced breast cancer after anthracycline failure: a randomised phase III study with crossover on progression by the Scandinavian Breast Group.

The aim of this study was to compare the efficacy and tolerability of docetaxel to methotrexate and 5-fluorouracil in advanced breast cancer after anthracycline failure. A randomised multicentre trial was conducted in 283 patients with advanced breast cancer who had failed previous anthracycline treatment. Docetaxel at a dose of 100 mg/m2 every 3 weeks (n = 143) was compared with sequential methotrexate and 5-fluorouracil (MF; n = 139) given at day 1 and 8 every 3 weeks at dosages of 200 mg/ m2 and 600 mg/m2, respectively. After progression, crossover to the alternative treatment group was recommended. There was a significantly higher overall response rate in the docetaxel 42% (CR 8% + PR 34%) than in the MF arm 21% (CR 3% + PR 18%) (P < 0.001). The median time to progression (TTP) was 6.3 months in the docetaxel arm and 3.0 months in the MF arm (P < 0.001). Docetaxel also had a significantly higher response rate of 27% following crossover compared with MF (12%). Significantly more side-effects (leucopenia, infections, neuropathy, oedema, asthenia, skin, nail changes, alopecia) were seen in the docetaxel than in the MF group. However, grade 3 and 4 side-effects were infrequent with both drugs, with the exception of fatigue, alopecia and infections. Median overall survival (OS) including crossover phase was 10.4 months in the docetaxel and 11.1 months in the MF arm (P = 0.79). Based on the response rate and the primary endpoint of TTP, docetaxel is superior to sequential methotrexate and 5-fluorouracil in advanced breast cancer after anthracycline failure.

Adult↗
PubMedDate not supplied

Treatment of refractory urothelial carcinoma with alternating paclitaxel, methotrexate, cisplatin (TMP) and 5-fluorouracil, alpha-interferon, cisplatin (FAP).

We assessed the activity and safety of a biochemotherapy regimen in which courses of paclitaxel, methotrexate, and cisplatin were alternated with courses of 5-fluorouracil, alpha-interferon, and cisplatin in the treatment of refractory urothelial carcinoma. Forty patients were enrolled in the study. In the phase I portion, 15 patients were treated according to an escalating dosage regimen designed to determine the maximum tolerated dose. A total of 30 patients received treatment according to the maximum tolerated dose regimen: methotrexate (30 mg/m(2)) given iv on days 1 and 22; paclitaxel (175 mg/m(2)) given iv over 3 h on day 1; cisplatin (70 and 25 mg/m(2)) administered iv on days 1 and 22, respectively; 5-fluorouracil (400 mg/m(2)) given iv by continuous infusion daily for 5 days beginning on day 22; and alpha-interferon (4 mIU/m(2)) given SC daily for 5 days simultaneously with the 5-fluorouracil infusions. The regimen was repeated at 42-day intervals. The 40 treated patients had an overall response rate of 43%, a complete response rate of 18%, and a median survival time of 44 weeks. Most of the toxic effects were hematologic: Grade 4 neutropenia occurred in 30% of patients (12 patients) and Grade 3 thrombocytopenia in 20% (8 patients). Even though this alternating biochemotherapy regimen was active for patients with refractory urothelial carcinoma, its activity was not better than that of certain single cytotoxic agents. Furthermore, the complicated dosing schedule and toxic effects of the regimen precluded its routine use in the treatment of urothelial carcinoma.

Aged↗
PubMed1988

Partial assignment of resonances in the 19F nuclear magnetic resonance spectra of 5-fluorouracil-substituted transfer RNAs.

Features of the 19F nuclear magnetic resonance (NMR) spectra of three purified 5-fluorouracil-(FUra-) substituted Escherichia coli tRNAs, tRNA(1Val), tRNA(mMet), and tRNA(fMet), are compared. Each of the tRNA species can be resolved into two isoaccepting forms, A and B, whose 19F NMR spectra differ in the shift of one peak from the 4.5 to 4.8 parts per million (ppm) range (FUra = O) in the spectrum of isoacceptor B upfield to ca. -15 ppm in that of isoacceptor A. Because the sequences of the two isoacceptors of each tRNA differ only at one position in the D loop, that normally occupied by a dihydrouridine residue, we assign the 4.5 ppm peak in the spectrum of fluorine-labeled tRNA(1Val) to FUra17 and the resonance at 4.6 ppm in the spectrum of fluorouracil-substituted tRNA(mMet) to FUra20. A reciprocal 19F[19F] nuclear Overhauser effect is observed between the downfield peaks A and B in the 19F NMR spectrum of 19F-labeled tRNA(1Val). Assuming that fluorine-labeled tRNA(1Val) has a structure similar to that of yeast tRNA(Phe), only FUra54 and -55 are close enough (4-5 A) to give an appreciable 19F homonuclear Overhauser effect. Peaks A and B have therefore been assigned to FUra54 and -55. As the temperature is raised from 30 to 45 degrees C, the intensity of peak B (6.6 ppm) in the spectrum of 19F-labeled tRNA(1Val) gradually shifts upfield to 6.4 ppm (Tm = 36 degrees C), indicating a temperature-dependent slow exchange of the corresponding 5-fluorouracil residue between two magnetically distinct environments.(ABSTRACT TRUNCATED AT 250 WORDS)

Escherichia coli↗
PubMed1980

Fluorinated pyrimidine nucleosides. 4. Synthesis and antitumor testing of a series of 2',5'-dideoxy- and 2',3',5'-trideoxynucleosides of 5-fluorouracil.

Dideoxy- and trideoxynucleosides of 5-fluorouracil have been synthesized for antitumor evaluation. 2',5'-Dideoxy-5-fluorouridine (3) was prepared from 2'-deoxy-5-fluorouridine (1) by iodination using methyltriphenoxyphosponium iodide, followed by catalytic reduction. 1-(2',5'-Dideoxy-beta-D-threo-pentofuranosyl)5-fluorouracil (4) was prepared from 3 by mesylation, followed by alkaline hydrolysis. 2',3',5'-Trideoxy-5-fluorouridine (13), a methyl homologue of Ftorafur (17), was synthesized by two routes: Treatment of the 3'-mesylate 8 with potassium tert-butoxide yielded the 2',3'-unsaturated derivative 12, which on hydrogenation yielded 13. Alternatively, treatment of 1 with a large excess of methyltriphenoxyphosphonium iodide produced several products, including two 3'-epimeric diiodo compounds (14 and 15), each of which could be hydrogenated to 13. The major product from this iodination reaction was characterized 3-(2',3'-anhydro-2',5'-dideoxy-5'-iodo-beta-D-threo-pentofuranosyl)-5-fluorouracil (5), presumably produced by rearrangement of the corresponding 1-isomer 9. The dideoxy compounds 3 and 4, as well as the trideoxy compound 13, were tested against sarcoma 180 in mice in comparison with 5-flourouracil, FUDR (1), and Ftorafur (17).

Animals↗
PubMed1977

Studies of antitumor agents. 1. Resolution of racemic 1-(tetrahydro-2-furanyl)-k-fluorouracil into the R and S isomers and examination of the biological activities of the isomers.

1-(Tetrahydro-2-furanyl)-5-fluorouracil (Thf-FU), which is named Ftorafur or FT-207 and is used clinically as an antitumor agent, was conveniently synthesized by condensation of the trimethylsilyl derivative of 5-fluorouracil with 2-acetoxytetrahydrofuran using NaI as a catalyst. This optically inactive Thf-FU was resolved into optically active (R)-(+)- and (S)-(-)-Thf-FU in high optical purity and excellent yield by formation of diastereoisomers with brucine. 13C NMR data were obtained on Thf-FU and related compounds and the antibacterial activities and in vivo antitumor activities of these isomers were tested. The degradations of these isomers to 5-fluorouracil by liver microsomes were also examined. No significant differences were found in any of these properties of these isomers.

Animals↗
PubMed2006

Excited-state structural dynamics of 5-fluorouracil.

5-Fluorouracil is an analogue of thymine and uracil, nucleobases found in DNA and RNA, respectively. The photochemistry of thymine is significant; UV-induced photoproducts of thymine in DNA lead to skin cancer and other diseases. In previous work, we have suggested that the differences in the excited-state structural dynamics of thymine and uracil arise from the methyl group in thymine acting as a mass barrier, localizing the vibrations at the photochemical active site. To further test this hypothesis, we have measured the resonance Raman spectra of 5-fluorouracil at wavelengths throughout its 267 nm absorption band. The spectra of 5-fluorouracil and thymine are very similar. Self-consistent analysis of the resulting resonance Raman excitation profiles and absorption spectrum using a time-dependent wave packet formalism suggests that, at most, 81% of the reorganization energy upon excitation is directed along photochemically relevant modes. This compares well with what was found for thymine, supporting the mass barrier hypothesis.

Absorption↗
PubMed2006

Experimental and theoretical investigation of the electronic structure of 5-fluorouracil compounds.

We present a comparison between experimental and theoretical X-ray absorption spectroscopy (XAS) and X-ray emission spectroscopy (XES) of 5-fluorouracil compounds, with an emphasis on the effects of the inclusion of nickel in the structure. By focusing on the 1s thresholds of carbon, nitrogen, oxygen, and fluorine it was possible to provide a complete picture of the occupied and unoccupied partial density of states of the 5-fluorouracil systems. Spectra calculated using density functional theory are compared to experimental results. Most experimental results agree well with our theoretical calculations for the XAS and XES of the compounds. All spectral features are assigned. Our results reveal that the nickel in the compound is coordinated with the nitrogen sites of the 5-fluorouracil ligands.

Antimetabolites, Antineoplastic↗
PubMed1997

Phase I-II study of vinorelbine in combination with 5-fluorouracil and folinic acid as first-line chemotherapy in metastatic breast cancer: a regimen with a low subjective toxic burden.

BACKGROUND: Vinorelbine, is an active drug in the treatment of metastatic breast cancer and has a favorable toxicity profile. Its combination with other effective and well-tolerated cytotoxics may thus be beneficial. We investigated the therapeutic effect of a combination of vinorelbine plus 5-fluorouracil and folinic acid as first-line treatment in patients with metastatic breast cancer. PATIENTS AND METHODS: Forty-five patients with advanced or metastatic breast cancer were enrolled in this phase I-II study and treated with 5-fluorouracil (350 mg/m2 i.v. on day 1 to 3), folinic acid (100 mg/m2 i.v. on day 1 to 3) and vinorelbine given on days 1 and 3 at the dose of 25 mg/m2 (dose level 1), or 30 mg/m2 (dose level 2). Therapy was given on an outpatient basis every three weeks. RESULTS: Phase I: Dose limiting toxicity (DLT) occurred at the second dose level of vinorelbine (30 mg/m2), with two out of three patients developing severe constipation ('ileus-like syndrome' grade 4), and fever (grade 2). Consequently, the dose evaluated in the phase II study was 25 mg/m2. Phase II: Objective responses were observed in 24 of 39 evaluable patients (95% confidence interval (95% CI), 47% to 77%). There were seven complete responses (18%), 17 partial responses (44%), and for nine patients (23%) disease was stable. Only six patients (15%) experienced disease progression. The median response duration was 10 months (range 6 to 24+) and the median time to progression was eight months (range 2 to 24+). Granulocytopenia was the most frequently observed side effect, with a grade 4 nadir being observed in 30 patients (77%), with four hospital admissions due to febrile neutropenia. Nausea, vomiting, and anorexia were mild to moderate and reported by less than half of the patients. Alopecia was moderate and occurred in about one-third of the patients. The other side effects were mild and easily manageable. CONCLUSIONS: This effective combination chemotherapy of vinorelbine, 5-fluorouracil and folinic acid is comparable to other first-line regimens in terms of efficacy, and is subjectively well tolerated, thus deserving a test in randomized trials in the advanced and adjuvant settings.

Adult↗
PubMed2000

Early secondary acute myelogenous leukemia in breast cancer patients after treatment with mitoxantrone, cyclophosphamide, fluorouracil and radiation therapy.

BACKGROUND: The topoisomerase II-targeted drugs, epipodophyllotoxins and anthracyclines, have been shown to induce therapy-related AML (t-AML) characterized by a short latency period after chemotherapy, the absence of prior myelodysplastic syndrome and stereotyped chromosome aberrations. Few reports have been published on patients treated with the anthracenedione mitoxantrone which also targets topoisomerase II. We observed 10 cases of such t-AML over a 7-year-period in breast cancer patients treated with mitoxantrone combined with fluorouracil, cyclophosphamide and regional radiotherapy, and in three cases with vindesine. PATIENTS AND METHODS: We retrospectively analyzed patients referred to our hospital for AML with a past history of polychemotherapy for breast cancer, including mitoxantrone, either as adjuvant (8 patients)/neoadjuvant (1 patient) therapy or for metastatic disease (1 patient). We studied the probability of developing t-AML in a prospective series of 350 patients treated with an adjuvant FNC regimen (mitoxantrone, fluorouracil, cyclophosphamide) and radiation therapy. RESULTS: The median age was 45 years (range 35-67). t-AML developed 13-36 months (median 16) after beginning chemotherapy for breast cancer, and 4-28 months (median 10.5) after ending treatment. As described in t-AML following treatment with epipodophyllotoxins or anthracyclines, we found a majority of FAB M4, M5 and M3 phenotypes (7 of 10), and characteristic karyotype abnormalities that also can be found in de novo AML: breakpoint on chromosome 11q23 (3 patients), inv(16)(p13q22) (2 patients), t(15;17)(q22;q11) (1 patient), t(8;21)(q22;q22) (1 patient) and del(20q)(q11) (1 patient). The prognosis was poor. All patients died of AML shortly after diagnosis. Since two patients had been enrolled in a prospective trial for the treatment of breast cancer which included 350 patients, the probability of developing t-AML was calculated to be 0.7% from 25-40 months, using the Kaplan-Meier method (95%, confidence interval (95% CI): 0.1-4.5). CONCLUSIONS: The combination of mitoxantrone with cyclophosphamide, fluorouracil, and radiation therapy can induce t-AML, as with other topoisomerase II-targeted drugs. Despite a low incidence, the prognosis appears to be poor.

Adult↗
PubMed1995

Autoradiographic imaging of the distribution of 5-fluorouracil through cervical tissue following in vitro surface application of a bioadhesive cervical patch.

The distribution of 5-fluorouracil through cervical tissue has been assessed following the in vitro application of a bioadhesive patch to excised human cervix. The bioadhesive matrix contained a total of 20 mg of 5-fluorouracil spiked with 5-fluorouracil-6-3H and was applied for fixed periods of either 4 or 24 hours. Tissue slices were sectioned perpendicular to the plane of the applied patch and the autoradiographic image developed by placing a frozen tissue slice on Hyperfilm with subsequent instant thawing and refreezing, the resulting bilayer being maintained at -18 degrees C for 24 hours. The developed image was analysed by scanning densitometry and raster scans were visualised with three-dimensional contouring software. The autoradiograms showed darker areas surrounding tissue ducts, suggesting that 5-FU was spilling from the lumen into the surrounding stroma. Transport of 5FU via aqueous channels may thus make an important contribution to the rapid penetration of the drug through the cervical stroma. Three-dimensional autoradiographic images showed that, for a 4-hour patch application, there were areas of relatively low drug concentration within the upper 5 mm of tissue, where CIN lesions can exist in the glandular tissue or cervical crypts. However, extending the application time to 24 hours produced areas of high drug concentration extending throughout this region.

Antimetabolites, Antineoplastic↗
PubMed2003

A phase II trial of weekly paclitaxel, 5-fluorouracil, and leucovorin as first-line treatment for metastatic breast cancer.

PURPOSE: This phase II multicenter trial evaluated the efficacy and toxicity of weekly paclitaxel, 5-fluorouracil, and leucovorin administered as first-line therapy for metastatic breast cancer. PATIENTS AND METHODS: The study enrolled 155 women with pathologically confirmed and measurable metastatic adenocarcinoma of the breast. Treatment consisted of paclitaxel 80 mg/m2, 5-fluorouracil 425 mg/m2, and leucovorin 20 mg/m2 administered weekly 4 x per 4-week cycle in the first 40 patients enrolled (group 1), and weekly 3 x per 4-week cycle in the subsequent 115 patients (group 2) enrolled. Hematologic growth factor support was not routinely used. Twenty patients with hepatic dysfunction were enrolled to assess the tolerability of the regimen in this population. All therapies were delivered in an outpatient setting. RESULTS: The overall response rate was 48%, with 12-month estimated survival rates of 53% and 65% for treatment groups 1 and 2, respectively. Response rates were not statistically different between the two treatment schedules. Therapy was well tolerated when delivered on the every 3 of 4-week schedule, including patients with hepatic involvement and those age > or = 65. CONCLUSION: Weekly therapy with paclitaxel and 5-fluorouracil with leucovorin is active as first-line therapy for metastatic breast cancer. Use of this regimen should be given consideration, particularly in patients who are not candidates for anthracycline-based therapy.

Adenocarcinoma↗
PubMed1994

Cisplatin, 5-fluorouracil and interferon alpha 2b for recurrent or metastatic head and neck cancer.

On the basis of preclinical data suggesting the possibility of maximising the efficacy of 5-fluorouracil and cisplatin by interferon, a pilot clinical trial was initiated in recurrent and/or metastatic head and neck cancer. Thirty-four patients were treated with cisplatin at 100 mg m-2, followed by 5-fluorouracil at 1,000 mg m-2 by continuous infusion for 5 days. Interferon alpha 2b was administered at the dose of 3 million U i.m. daily for 7 days, beginning the day before chemotherapy. Courses were repeated every 3 weeks. Two patients achieved a complete remission, six a partial response, 14 had stable disease and 12 progressed on therapy, for an overall response rate of 23% (95% confidence interval 10-36%). Median survival time was 5 months. Toxicity was severe. Stomatitis, diarrhoea and myelosuppression were the most common side-effects. Because of the poor response rate and the presence of severe toxicity, in our opinion further clinical trials in head and neck cancer should be attempted only after a better definition in preclinical studies of interactions among 5-fluorouracil, cisplatin and interferon.

Adult↗
PubMed1995

Continuous infusion of 5-fluorouracil with alpha 2b interferon for advanced colorectal carcinoma.

Thirty patients with symptomatic colorectal carcinoma were commenced on treatment with 5-fluorouracil (2.5 g week-1) administered by continuous intravenous infusion and alpha 2b interferon (3 x 10(6) U s.c. three times a week). Six out of 30 patients (20%) achieved a partial response. Three patients (10%) had stable disease and 21 patients (70%) progressed on treatment. Twenty patients (67%) completed ten or more weeks of treatment. In nine patients, treatment was withdrawn after 2-9 weeks because of disease progression or death. One patient's treatment was interrupted by emergency surgery. The median survival for all patients was 210 days (7 months). The principal side-effects were oral mucositis (12/30 patients), nausea (8/30 patients) and transient diarrhoea (4/30 patients), and initial constitutional symptoms due to alpha 2b interferon. The combination of low-dose continuous infusional 5-fluorouracil and low-dose alpha 2b interferon is well tolerated but has no obvious advantage over alternative infusional regimens using 5-fluorouracil as a single agent.

Adult↗
PubMed1995

High-dose folinic acid and 5-fluorouracil bolus and continuous infusion in advanced colorectal cancer: poor response rate in unselected patients.

We have conducted a retrospective study of high-dose folinic acid and 5-fluorouracil in 96 patients with advanced colorectal cancer. Patients received 200 mg m-2 (maximum 300-350 mg) folinic acid by infusion over 2 h followed by an i.v. bolus of 5-fluorouracil 400 mg m-2 then an infusion of 5-fluorouracil 600 mg m-2 over 22 h. This was repeated over the next 24 h. The schedule was given every 2 weeks for four cycles; thereafter patients with objective response continued to a maximum of eight cycles. The overall response rate was 10.6% in 85 evaluable patients. The median duration of response was 11 months. The median survival was 6 months. Toxicity was low, only one patient experiencing toxicity greater than WHO grade II (grade IV platelet toxicity). Diarrhoea, nausea, vomiting and mucositis also occurred but were mild and infrequent. Our low response rate may be related to factors such as patient characteristics or duration of treatment.

Adult↗
PubMed1998

Randomized trial comparing protracted infusion of 5-fluorouracil with weekly doxorubicin and cyclophosphamide with a monthly bolus FAC regimen in metastatic breast carcinoma (SPM90).

Infusional 5-fluorouracil in advanced breast cancer has been associated with improved clinical response rates when compared with conventional bolus therapy. As a first line of chemotherapy in proven metastatic breast carcinoma, 258 women were randomly assigned to receive FAC consisting of 5-fluorouracil (F) 600 mg m(-2) intravenously (i.v.) over 1 h on days 1, 2 and 3, doxorubicin (A) 50 mg m(-2) i.v. bolus on day 1 and cyclophosphamide (C), 400 mg m(-2) i.v. bolus on days 1, 2 and 3 or 'FULON' consisting of 5-fluorouracil 250 mg m(-2) day(-1) continuously infused from day 1 to day 22, doxorubicin 15 mg m(-2) i.v. bolus on days 1, 8, 15 and 22 and cyclophosphamide 300 mg m(-2) i.v. bolus on days 1, 8, 15 and 22. Chemotherapy courses were administered 4-weekly for the bolus regimen and 6-weekly for FULON. Pretreatment characteristics were identical between the two groups. Response rates were 54% in the FAC arm and 53% in the FULON arm. Time to progression was 14 months in the FAC arm and 12 months in the FULON arm. Differences were not statistically significant. Median overall survival duration for all patients was 22 months. Haematological toxicity was more severe in the bolus-treated group (P = 0.05), as were nausea and vomiting (P < or = 0.01). We conclude that the two regimens appeared equally effective but have different toxicities.

Adult↗
PubMed1991

Kinetic modeling of in vivo--nuclear magnetic resonance spectroscopy data: 5-fluorouracil in liver and liver tumors.

Kinetic modeling has been applied to the time course of the nuclear magnetic resonance signal intensities of 5-fluorouracil and the sum of its catabolites, alpha-fluoro-beta-ureido propanoic acid and alpha-fluoro-beta-alanine, as monitored in liver tumors of seven patients with cancer after brief intraarterial infusion of 5-fluorouracil. Because these data represent only relative tissue concentrations, only ratios of clearance and volume parameters can be estimated (e.g., clearance/central volume of distribution or central volume of distribution/steady-state volume of distribution). On the other hand, parameters that do not refer to volumes, such as half-lives or maximal velocity of metabolic conversion of a nonlinear model, can be estimated in absolute terms. A nonlinear three-compartment model gave satisfactory fits with all of the individual data sets. Kinetics of 5-fluorouracil and catabolites were similar in five patients with metastases of colorectal adenocarcinomas but differed from those of two patients with cholangiocarcinoma and metastases of an anaplastic carcinoma of unknown origin, respectively.

Adult↗
PubMed1998

Sclerosing canaliculitis after 5-fluorouracil breast cancer chemotherapy.

BACKGROUND: 5-Fluorouracil is a pyrimidine analogue that inhibits DNA synthesis and is commonly used in the treatment of carcinomas of the breast, gastrointestinal tract and genitourinary tract. Excessive tearing that resolves on cessation of treatment is commonly described as a side effect of the drug. Permanent stenosis of the punctum and canaliculus is extremely rare, with only 12 cases reported in the world literature. We present three cases of established lacrimal outflow obstruction in patients who were treated with CMF (cyclophosphamide, methotrexate, 5-fluorouracil), a widely used regimen for metastatic breast cancer. Patient 1 had right distal stenosis of her lower canaliculus and was syringed patent during dacryocystography with resolution of epiphora. Patient 2 had proximal blockage of all canaliculi and underwent bilateral canaliculodacryocystorhinostomy with silicone tubes that temporarily relieved symptoms until tube removal. The proximal canalicular blockage recurred due to underlying extensive fibrosis. Patient 3 had right proximal common canalicular stenosis and left distal canalicular blocks but declined surgery. CONCLUSION: With the rise in the incidence of breast carcinoma it is important that the attention of both ophthalmologists and oncologists should be drawn to the potential ocular toxicity of systemic 5-fluorouracil chemotherapy, which may lead to lacrimal canalicular fibrosis with permanent epiphora. The management of these patients is challenging as there is a continuous spectrum of canalicular involvement from focal to diffuse; therefore early referral is recommended. Moreover as no consensus has been reached as how best to manage this unique small group of patients, we review the literature and discuss the implications for treatment.

Aged↗
PubMed2000

Over-expression of TSC-22 (TGF-beta stimulated clone-22) markedly enhances 5-fluorouracil-induced apoptosis in a human salivary gland cancer cell line.

We have recently isolated TSC-22 (transforming growth factor-beta-stimulated clone-22) cDNA as an anticancer, drug-inducible (with vesnarinone) gene in a human salivary gland cancer cell line, TYS. We have also reported that TSC-22 negatively regulates the growth of TYS cells and that down-regulation of TSC-22 in TYS cells plays a major role in salivary gland tumorigenesis (Nakashiro et al, 1998). In this study, we transfected TYS cells with an expression vector encoding the TSC-22-GFP (green fluorescent protein) fusion protein, and we established TSC-22-GFP-expressing TYS cell clones. Next, we examined (a) the subcellular localization of the fusion protein, (b) the sensitivity of the transfectants to several anticancer drugs (5-fluorouracil, cis-diaminedichloroplatinum, peplomycin), and (c) induction of apoptotic cell death in the transfectants by 5-fluorouracil treatment. The TSC-22-GFP fusion protein was clearly localized to the cytoplasm, but not to the nucleus. Over-expression of the TSC-22-GFP fusion protein did not affect cell growth, but significantly increased the sensitivity of the cells to the anticancer drugs (p < 0.01; one-way ANOVA). Furthermore, over-expression of the TSC-22-GFP fusion protein markedly enhanced 5-fluorouracil-induced apoptosis. These findings suggest that over-expression of TSC-22-GFP protein in TYS cells enhances the chemosensitivity of the cells via induction of apoptosis.

Antineoplastic Agents↗