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Biomedical subjects

R Metz

Publications and source records attributed to R Metz.

At least 73 records · Page 4Linked to original sources
PubMed1986

Phase II clinical evaluation of doxifluridine.

Disease-oriented phase II trials of doxifluridine were performed in advanced colorectal, breast, renal, endometrial, stomach, and ovarian carcinomas. The dose schedule recommended by the phase I trial (12.5 g/m2 by continuous iv infusion over 6 hours once a week for 3 weeks followed by a 1-week rest) was chosen first: the initial dose was later decreased to 10 g/m2 due to the fact that several neurotoxic effects were reported. A total of 207 patients were entered: 137 patients who received at least two courses of treatment were evaluable for response. Therapeutic activity was demonstrated in breast cancer [two complete responses (CR) and 13 partial responses (PR) among 42 patients], colon cancer (seven PRs among 35 patients), and rectal cancer (six PRs among 23 patients). Some therapeutic activity was detected in ovarian cancer (one CR among nine patients), endometrial cancer (one PR among five patients), and stomach cancer (one PR among five patients). No significant activity was noticed in renal cancer (one PR among 18 patients). Nonhematological toxicity was evaluated according to World Health Organization criteria. Nausea and vomiting were recorded in 50% of the patients (Grade 3-4 in 5%), diarrhea was recorded in 20% (Grade 3-4 in 5%), and cutaneous and allergic reactions were recorded in 10% (Grade 3-4 in 2%). Myelotoxicity during the first treatment course was mild; median wbc and platelet count nadirs (x 10(9) cells/L) were 4.1 (range, 0.1-11) and 194 (range, 20-482), respectively. Nevertheless, some cases of acute leukopenia and thrombopenia were reported. Consciousness alterations and neurologic symptoms were the major side effects (72 of 173 evaluable patients), since treatment had to be interrupted in 34 patients and four lethal neurotoxic effects occurred. At the same total dose of doxifluridine, the risk of neurotoxicity significantly increases with age and with the weekly dose and to the contrary it decreases with increasing bilirubin level. Although activity was demonstrated, this treatment cannot be recommended because of major neurotoxicity. Further pharmacological studies seem warranted to define the optimal dosage schedule and to obtain a better therapeutic index.

Adult↗
PubMed1986

Adriamycin, vincristine, cyclophosphamide and 5-fluorouracil (AVCF) compared with cyclophosphamide, methotrexate and 5-fluorouracil (CMF) in premenopausal breast carcinoma. Personal results.

Adjuvant treatment of breast cancer with AVCF gave significantly longer disease-free survival than CMF in the group of patients taken as a whole, in the subgroup with lymph node involvement and in the premenopausal subgroup. No significant difference was found regarding overall survival.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1985

Mitoxantrone combined to vincristine, cyclophosphamide and fluorouracil in advanced breast cancer.

In our wide experience of treating advanced breast carcinoma with chemotherapy, the combination of doxorubicin (DOX), vincristine (VCR), cyclophosphamide (CPM) and fluorouracil (FU) gave a complete plus partial response rate of over 60%, with 100% alopecia and frequent cardiac toxicity depending on total dose. After the EORTC Clinical Screening Group phase II trial we have conducted an "expected difference method" comparative phase II trial using the combination DOX, VCR, CPM, FU and the combination of MTX (10mg/m2), VCR, CPM and FU on a population of 50 breast carcinoma patients similar to those taking part in the first study. The reasons for similarity of action will be presented and discussed.

Adult↗
PubMed1985

Effectiveness of antineoplastic drugs on the proliferation of human mammary and ovarian carcinoma cells in monolayer culture.

Procedures for the in vitro determination of the drug-induced inhibition of mammary and ovarian carcinoma cell growth were established. In monolayer cultures derived from advanced tumors, separation of epithelial carcinoma cells from concomitant cells of fibroblast-like or mesothelial appearance was achieved by differential trypsinization. The carcinoma cell character of the stock cultures was verified by chromosome analyses showing a high degree of aneuploidy for the epitheloid cell lines and euploidy for cells of apparently mesenchymal origin. When cultured carcinoma cells were injected in nu/nu mice, the tissue and cell cultures obtained from the heterotransplantation tumors closely resembled the original tumors and cell cultures in morphology, karyotype, and expression of tumor markers. The action of carcinostatic drugs in the logarithmic phase of the carcinoma cell proliferation was tested by kinetics experiments in multiple experimental cultures. In cell proliferation assays based on cell counts the 50% inhibition dose (ID50) of the drug effects was determined from the dose-response curves. Comparison of the ID50s revealed highly differential effectiveness of the drugs examined. The inhibitory effects were reproducible, rendering the procedures used suitable for testing the chemosensitivity of newly explanted gynecological carcinoma cells by proliferation assays.

Adenocarcinoma↗
PubMed1983

Determination of free and total polyamines in human serum and urine by ion-pairing high-performance liquid chromatography using a radial compression module. Application to blood polyamine determination in cancer patients treated or not treated with an ornithine decarboxylase inhibitor.

A sensitive and rapid determination of free and total polyamines (putrescine, cadaverine, spermidine and spermine) in urine and serum is described. The procedure is based on reversed-phase high-performance liquid chromatographic separation using radial compression module (Radialpak C 8). The samples are purified with a silica gel Sep-Pak cartridge. The polyamines are converted to dansyl chloride derivatives and separated using a linear gradient of triethylammonium phosphate-methanol within 15 min. The lower limits of detection are 10 pmoles for spermine and 5 pmoles for other polyamines. This method is applied to cancer patients treated by cytotoxic chemotherapy with or without difluoromethylornithine (DFMO). All four polyamines are significantly increased in these patients before treatment. On day 8, after onset of treatment, the levels of polyamines in patients not treated with DFMO are more elevated than on day 1, while in patients treated with DFMO the levels are decreased. However, DFMO does not seem to modify the treatment result. The patients which have a low level of putrescine before and during treatment, do not respond to treatment. Perhaps this low level is the consequence of conjugation of this polyamine?

Aged↗
PubMed1983

Interferon-induced 56,000 Mr protein and its mRNA in human cells: molecular cloning and partial sequence of the cDNA.

Treatment of responsive cells by interferons (IFNs) induces within a few hours a rise in the concentration of several proteins and mRNAs. In order to characterize these IFN-induced mRNA species, we have cloned in E. coli the cDNA made from a 17-18S poly(A)+ RNA of human fibroblastoid cells (SV80) treated with IFN-beta. We describe here a pBR322 recombinant plasmid (C56) which contains a 400 bp cDNA insert corresponding to a 18S mRNA species newly induced by IFN. The C56 mRNA codes for a 56,000 dalton protein easily detectable by hybridization-translation experiments. The sequence of 66 of the carboxy-terminal amino-acids of the protein can be deduced from the cDNA sequence. IFNs-alpha, beta or gamma are able to activate the expression of this gene in human fibroblasts as well as lymphoblastoid cells. The mRNA is not detectable without IFN; it reaches maximum levels (0.1% of the total poly(A)+ RNA) within 4-8 hrs and decreases after 16 hrs.

Amino Acid Sequence↗
PubMed1983

The complete sequence of murein synthesis in ether treated Escherichia coli.

The in vitro synthesis of murein from the precursors UDP-N-acetylglucosamine, L-alanine, D-glutamic acid and meso-diaminopimelic acid was performed with the aid of ether treated Escherichia coli. This synthesis was sensitive to representative inhibitors of early reactions in the cytoplasm as well as of late reactions in the membrane or the cell wall. The sensitivity was higher than in in vitro systems starting with UDP-N-acetylmuramic acid or UDP-N-acetylmuramyl-pentapeptide.

Amino Acids↗
PubMed1983

Molecular cloning and sequence of partial cDNA for interferon-induced (2'-5')oligo(A) synthetase mRNA from human cells.

By using a translation assay in oocytes, a 17S RNA fraction coding for the interferon-induced (2'-5')oligo(A) synthetase was purified from human cells. A cDNA library was prepared by cloning in Escherichia coli plasmid pBR322 and screened by positive hybridization-translation in oocytes. A cDNA clone corresponding to the (2'-5')oligo(A) synthetase mRNA was identified. In SV80 cells, this E cDNA recognizes three RNAs of 1.65, 1.85, and 3.6 kilobases, which are present only after interferon treatment of the cells. In Namalva cells, mainly one RNA of 1.8 kilobases is seen.

2',5'-Oligoadenylate Synthetase↗
PubMed1982

Follow-up results from a randomized trial for T3 and T4 breast cancer patients: previous BCG immunotherapy improves response to chemotherapy in the relapse patient.

Following locoregional treatment, patients were randomized into three groups: The first groups received no complementary treatment; the second group received adjuvant chemotherapy (vincristine, cyclophosphamide, and 5-fluorouracil once a month for 12 months); and the third group was treated by immunotherapy (150 mg BCG once a week for 1 year). Sixty-two of the 82 patients studied were menopausal. No significant difference was observed between the three groups. All patients were followed-up for at least 18 months. The disease-free interval difference between the chemotherapy group and the control and immunotherapy groups is not significant. But it should be noted that only 21.8% of the control group did not relapse compared to 57% in the chemotherapy group. BCG immunotherapy in such patients must be considered ineffective. However, our results suggest that patients first treated with BCG respond better to chemotherapy than patients not receiving any previous therapy.

Breast Neoplasms↗
PubMed1981

[Combined hyperthermia, radiotherapy and chemotherapy: preliminary clinical results (author's transl)].

Results of treating superficial cancerous nodules by hyperthermia, alone or combined with radiotherapy or chemotherapy, over a period of one year, are presented. Twenty-five patients with multiple cutaneous or subcutaneous metastatic tumors were treated by 1 to 3 MHz ultrasound hyperthermia or 434 MHz microwave hyperthermia. Good local tolerance was observed, even in regions previously treated with high doses of irradiation. Regression of the tumors was assessed by comparison with unheated nodules. Two out of 11 tumors treated by hyperthermia alone, 10 out of 17 tumors treated by conventional chemotherapy combined with hyperthermia showed significant regression.

Hot Temperature↗