Effects of long-term zearalenone administration on spermatogenesis and serum luteinizing hormone, follicle-stimulating hormone, and prolactin values in male rats.

Body and testis weights, serum luteinizing hormone, follicle-stimulating hormone, and prolactin values and volume fractions of Sertoli cells, spermatogonia, early and late primary spermatocytes, and round and long spermatids were evaluated in 70-day-old male rates treated orally with 20 mg of zearalenone/kg of body weight daily for 5 weeks. Significant (P < 0.05) increase in serum prolactin concentration was consistently observed during the 5 weeks of treatment with zearalenone.

[Physicochemical compatibility of 5-fluorouracil (new french preparation) and folinic acid].

The potentiation of 5-fluorouracil (5FU) cytotoxicity by folinic acid (FA) is based on strong experimental basis. This experimental concept has been prolonged in the clinical setting where 5FU-FA combination has demonstrated its superiority in comparison to 5FU alone for the chemotherapeutic treatment of advanced colorectal cancer. A justified question concerns the stability for 5FU (new French preparation, with sodium hydroxyde, by Roche)-FA admixtures studied in clinically compatible conditions.

[Increase of dose intensity by pharmacomodulation. General concepts and therapeutic applications].

There are two distinct levels where dose intensity can be increased by pharmacomodulation. The first level implies the inhibition of clearly identified resistance mechanisms. Among them, MDR type resistance is the most studied currently.

Population study of dihydropyrimidine dehydrogenase in cancer patients.

Purpose: We conducted a prospective study on a large set of cancer patients in an attempt to evaluate the incidence of complete or partial dihydropyrimidine dehydrogenase (DPD) deficiency as found in peripheral mononuclear cells (PMNC).

Patients And Methods: One hundred eighty-five unselected consecutive cancer patients were included. The population consisted of 152 men (mean age, 62.

Clinical randomized study of 5FU monitoring versus standard dose in patients with head and neck cancer: preliminary results.

Prospective studies of dose adaptation of continuous 5FU infusion combined with cisplatin have shown that pharmacologically guided dosing was feasible in the treatment of head and neck carcinomas. Adaptative dosing results in reduced haematological toxicity, but few data are available for clinical response rate. Preliminary results (38 patients) of a randomized trial comparing standard dose of 5FU (20 patients) and monitoring of 5FU based on pharmacokinetic information (half-cycle area under the curve, 18 patients) indicate that haematological tolerance and complete response rate were improved.

Dihydropyrimidine dehydrogenase (DPD) and clinical pharmacology of 5-fluorouracil (review).

Fluorouracil (FU) is essentially eliminated in the liver through the rate limiting enzyme dihydropyrimidine dehydrogenase (DPD). DPD is also expressed in various other normal as well as in tumor tissues. DPD activity measured in peripheral blood mononuclear cells (PBMC) is correlated to FU systemic clearance, but this correlation is weak, precluding PBMC-DPD to be considered as a reliable predictor of FU clearance.

Spontaneous or imposed circadian changes in plasma concentrations of 5-fluorouracil coadministered with folinic acid and oxaliplatin: relationship with mucosal toxicity in patients with cancer.

Pharmacokinetics of total platinum, 5-fluorouracil, l-folinic and d-folinic acid, and 5-methyltetrahydrofolate were studied in plasma from nine patients with advanced colorectal cancer treated with oxaliplatin (20 mg/m2/day), 5-fluorouracil (600 mg/m2/day), and folinic acid (300 mg/m2/day). Drugs were administered with a programmable-in-time pump by continuous infusion for 5 days. We compared two drug delivery schedules: constant rate versus chronomodulated rate with peak of oxaliplatin at 4 pm and peak of 5-fluorouracil and folinic acid at 4 am.

[EGF receptor, a prognostic factor in epidermoid cancers of the upper aerodigestive tracts].

EGFR was determined, before treatment; in tumors biopsies obtained from 109 consecutive patients with head and neck cancer (100 men and nine women), using iodine labelled recombinant EGF. The median age of the study population was 60 years. EGFR levels varied from 2 to 2302 fmol/mg membrane protein (median 71).

[Tamoxifen increases cytotoxic effects of fotemustine. Experimental results on cell lines of human melanoma].

Fotemustine (Fote) is a new aminoacid linked chloroethyl nitrosourea which has been shown to be useful in disseminated malignant melanoma. The aim of the present study was to analyze the cytotoxic effects resulting from the combination of antiestrogens and Fote on human melanoma cell lines. The antiestrogens tested were tamoxifen (TMX 5.

Relationship between fluorouracil systemic exposure and tumor response and patient survival.

Purpose: The aim of this study was to analyze the link between fluorouracil (FU) systemic exposure and tumor response and overall survival.

Patients And Methods: One hundred eighty-six patients (162 men, 24 women) with head and neck cancer were studied. All received cisplatin plus FU for three cycles as first-line chemotherapy.

Multidrug resistance circumvention by a new triazinoaminopiperidine derivative S9788 in vitro: definition of the optimal schedule and comparison with verapamil.

The current work was undertaken to investigate the importance of exposure sequence and duration in achieving the maximum reversal action of S9788 on doxorubicin (DOX) cytotoxicity against cells that exhibit the (MDR) multidrug resistance phenotype: the MCF7/DOX cell line. Accumulation and release of DOX were examined in this cell line. The reversal effect was compared with that obtained with verapamil.

[Evolution from pharmacokinetics to pharmacogenetics. The example of 5-fluorouracil].

5FU tends to be used more and more frequently; this fact can be explained by its modulation, mainly by folinic acid. Pharmacokinetic follow-up of 5FU with dose adaptation has demonstrated its clinical usefulness by reducing significantly drug side-effects without any impairment in tumor response. Whatever the anticancer drug considered, it is theoretically possible to predict individual capacities for clearing it.

Analysis of C-myc amplification by the differential polymerase chain-reaction (d-PCR), study in breast-cancer.

c-myc proto-oncogene amplification seems to have a prognostic value in breast cancer. In this study, quantitative analysis of c-myc amplification was carried out by differential polymerase chain reaction technique (d-PCR) using beta-globin as the reference gene. d-PCR assessment showed coampIification products of c-myc and beta-globin depend on variations in reaction factors such as the genomic DNA concentration, the relative concentrations of the various amplimers, the thermostable DNA polymerase concentration and the number of cycles.

Inhibition of dihydropyrimidine dehydrogenase by alpha-interferon: experimental data on human tumor cell lines.

Interferons (IFNs) are very promising fluorouracil (FU) biochemical modulators. The pharmacological origin sustaining the FU-IFN synergistic interaction is not clearly understood. It was recently shown that alpha-IFN was associated with a dose-dependent decrease in FU clearance in treated patients.

Determination of oestrogen receptors by enzyme immunoassay. Technical differences between laboratories and their consequences.

When multicentre breast cancer trials are performed, receptor analyses must be comparable both over time and in the participating laboratories. However, we show for the first time a high variability for the distribution of oestradiol receptor (ER) values measured by enzyme immunoassay (EIA) from 1987 to 1991. This variability could be explained by calibration changes in the immunoassay kits.

Cytotoxic effects of long-term circulating ultrafiltrable platinum species and limited efficacy of haemodialysis in clearing them.

We applied haemodialysis to clear platinum (Pt) circulating species following renal insufficiency due to an accidental cisplatin overdosage (205 mg/m2 instead of 100 mg/m2). Serum samples were repeatedly obtained during this clinical episode from day 5 up to day 30 after cisplatin dosing. A serum aliquot taken at day 22 after cisplatin administration was tested to assess the possible cytotoxicity exhibited by the circulating Pt species on a head and neck tumour cell line.

Wide range for optimal concentration of folinic acid in fluorouracil modulation--experimental data on human tumour cell lines.

The clinical use of the fluorouracil (FU)-folinic acid (FA) combination is hampered by the still open choice of the optimal schedule, with marked controversy as concerns the optimal FA dose. This in vitro study on FU-FA combinations in 17 human cancer cell lines, representative of tumour types responding to FU-FA treatment, reassesses the notion of the optimal FA concentration. Cells were exposed for 5 days to various FU-FA concentrations (0.

A role for dihydropyrimidine dehydrogenase and thymidylate synthase in tumour sensitivity to fluorouracil.

Despite being one of the oldest anti-cancer drugs, fluorouracil (FU) is still being increasingly used in cancer chemotherapy. The source of variability for FU sensitivity in patients may be complex, although an overproduction of thymidylate synthase (TS) was the only mechanism of resistance identified in tumours from FU-resistant patients. Dihydropyrimidine dehydrogenase (DPD) is the first and rate-limiting enzyme of FU catabolism.

Combination of reduced folates with methotrexate or 5-fluorouracil. Comparison between 5-formyltetrahydrofolate (folinic acid) and 5-methyltetrahydrofolate in vitro activities.

Folinic acid (dlFA) is increasingly used in clinical oncology. The active isomer lFA is intensively metabolized into l5-methyltetrahydrofolate (l5MTHF), the relative proportions of lFA, dFA and l5MTHF in blood varying considerably between oral and i.v.

Expression of epidermal growth factor receptor and survival in upper aerodigestive tract cancer.

Purpose: To determine the expression of epidermal growth factor receptor (EGFR) in head and neck squamous cell carcinoma and to evaluate its prognostic value.

Materials And Methods: EGFR was determined in tumor biopsies obtained from 109 consecutive patients with head and neck cancer (100 men, nine women). Control biopsies were obtained from 94 patients in a symetric nontumoral area of the same anatomic site.