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Biomedical subjects

M Drees

Publications and source records attributed to M Drees.

At least 19 recordsLinked to original sources
PubMed2001

Phase II study of a weekly 24-hour infusion with 5-fluorouracil and simultaneous sodium-folinic acid in the first-line treatment of metastatic colorectal cancer.

BACKGROUND: A weekly continuous 24-hour infusion therapy with 5-fluorouracil (5-FU) and calcium - folinic acid (CA-FA) was shown to be an effective first-line treatment in advanced metastatic colorectal cancer. Sodium - folinic acid (S-FA) is a new formulation which, in contrast to CA-FA allows the simultaneous i.v. administration in combination with 5-FU in one pump. PATIENTS AND METHODS: From 1997 to 1998, 51 patients [median age 60 (range 24-77) years; 38 male, 13 female] with metastatic colorectal cancer were recruited in 5 centers to receive weekly 24-hour infusions of 5-FU (2,600 mg/m(2)) and S-FA (500 mg/m(2)) dissolved in one pump for 6 weeks as first-line treatment. The treatment cycle was repeated after a 2-week rest period. RESULTS: 1,178 administrations (median 24, range 3-54) were performed during the study. Out of 51 patients (median follow-up 20.2 months), 2 (3.9%) achieved complete remission (CR), 17 (33.3%) partial remission (PR), and 21 (41.2%) no change (NC). Progressive disease (PD) was observed in 11/51 (21.6%) patients, including 6 patients who did not complete the first cycle. Median time to tumor progression (TTP) was 8.5 months (95% CI: 5.8-11.3). 32/51 (62.7%) patients survived for more than 1 year, the median survival was reached at 16.5 months (95%CI: 10.2-22.8). Among major toxicities, NCICTC grade III/IV diarrhea occurred in 13/51 (25.4%), grade III hand-foot syndrome in 6/51 (11.7%) patients. Grade III/IV stomatitis was observed in 4/51 (7.8%), cardiac toxicity occurred in 2/51 patients (3.9%). CONCLUSION: Similar to conventional 24-hour 5-FU + CA-FA treatment, the combination with S-FA induced 37.2% objective responses with moderate toxicity. However, TTP seems favorable and the administration of S-FA is convenient, while saving costs and time for the patient in outpatient units.

Adult↗
PubMed1997

Simultaneous restitution of matrix and cells in gastric ulcer: use of a combined in-situ hybridization and immunohistochemistry technique applicable to paraffin-embedded tissue.

The restoration of gastric tissue after ulceration involves cellular and matrix components. Our aim was to investigate the kinetics of collagen expression and cellular proliferation in an animal model of gastric ulcer. To demonstrate the expression of type I and IV collagen mRNAs by proliferating cells, a method combining in-situ hybridization and immunohistochemistry was devised. In order to avoid the disadvantages of radioisotopes, digoxigenin-labeled RNA-riboprobes were utilized and combined with single-step immunohistochemistry. This method proved sensitive enough to detect type I and IV procollagen mRNA transcripts in the submucosal area beneath the ulcer crater or adjacent to the ulcer rim. In addition, a subset of cells transcribing either procollagen type I or IV RNA was concomitantly positive for proliferating cell nuclear antigen by immunohistochemistry. Focal proliferation of cells simultaneously expressing extracellular matrix components may therefore occur in the gastric submucosa after ulceration, starting as soon as 3 days after the insult and continuing for several weeks. The devised method of combined in-situ hybridization and immunohistochemistry can be used with standard paraffin-embedded tissues, yields results within 2 days, and avoids radioisotopes.

Acetic Acid↗
PubMed1997

Flavopiridol (L86-8275): selective antitumor activity in vitro and activity in vivo for prostate carcinoma cells.

We have selected a panel of human tumor xenografts for in vitro and in vivo studies that allows an indication of selectivity of action of novel chemotherapeutic agents. We report here the antitumor activity of the flavone flavopiridol (previously designated L86-8275), which has been selected for further studies based in part on its behavior in the anticancer drug screening system of the United States National Cancer Institute. Eighteen human tumor and five cell line-derived xenografts established by serial passage in nude mice in our laboratory were used as tumor models for in vitro investigations using a modified double-layer soft agar assay. In vivo investigations were completed in nude mice bearing advanced-stage s.c. growing prostate cancer xenografts. Antitumor activity in vitro (test/control </= 30%) of flavopiridol was observed at the very low concentration of 0.1 ng/ml in three of four prostatic xenografts and in one melanoma xenograft. Overall, in 14 of 23 (61%) tumor xenografts, drug treatment resulted in a IC70 of <10 ng/ml, demonstrating the high antiproliferative potential of flavopiridol. Toxicity to in vitro bone marrow cultures was evident only at 100 ng/ml, indicating potential high selectivity for susceptible tumor cells. Comparison of tumor cells with bone marrow samples tested showed clear prostate carcinoma and moderate melanoma selectivity. In vivo studies of flavopiridol confirmed antitumor activity in both prostate cancer xenografts investigated. At the maximal tolerated dose of 10 mg/kg/day administered p.o. on days 1-4 and 7-11, flavopiridol effected tumor regression in PRXF1337 and tumor stasis lasting for 4 weeks in PRXF1369. We conclude that flavopiridol shows strong prostate-and moderate melanoma-specific antitumor activity in vitro. The prostate antitumor activity is also reflected by the two in vivo models studied. Initial clinical efforts with flavopiridol might consider early evaluation in patients with prostate carcinoma.

Animals↗
PubMed1996

Alkyl and alkoxyethyl antineoplastic phospholipids.

Two series of phosphodiester ether lipid analogs with (N-methylmorpholino)ethyl or (N-methylpiperidino)ethyl polar head groups and long aliphatic or alkoxyethyl chains in the nonpolar portion of the molecule were synthesized as potential antineoplastic agents. The cytotoxic activity of these compounds (9-19) was evaluated in vitro against a panel of six human tumor xenografts and in two biochemical, mechanism-based screens (cdc2 kinase and cdc25 phosphatase). Analogs 13, 14, 17, and 19 showed activity in the in vitro tests. Specifically, 14 and 17 were more active than the reference compound hexadecylphosphocholine (Miltefosine, He-PC) while 13 and 19 possessed activity similar to that of the control. Of the analogs tested the one with the highest potency and least toxicity (17) has an N-methylpiperidino head group and a C16 alkyl chain. In the mechanism-based tests 11 showed weak inhibitory activity in the cdc25 phosphatase screen.

Animals↗
PubMed1995

Cycloplatam: a novel platinum compound exhibiting a different spectrum of anti-tumour activity to cisplatin.

Cycloplatam is a novel platinum compound which has shown anti-tumour activity in murine tumour models. In this study, cycloplatam was found to have anti-tumour activity in vitro and in vivo in human tumour models. In 15 cell lines (mainly ovarian), cycloplatam showed similar cytotoxicity as cisplatin, using the sulphorhodamine B assay. Determination of the resistance factor (IC50 of cisplatin-resistant divided by IC50 of parental cell line) clearly showed lower values for cycloplatam than for cisplatin. In the parental ovarian cell line CH1 and the cisplatin-resistant CH1 cisR model, we observed no cross-resistance of cycloplatam and cisplatin. The in vitro anti-tumour activity was confirmed in human tumour xenografts using the clonogenic assay. Mean IC70 values of cycloplatam were 0.54 microgram/ml (1.25 microM) and of cisplatin 0.42 microgram/ml (1.4 microM), respectively. In the murine subcutaneously implanted ADJ/PC6 plasmacytoma in vivo cycloplatam showed less activity than cisplatin, with a 2-fold smaller therapeutic index than cisplatin. In ovarian cancer xenografts cycloplatam was less active than cisplatin. However, anti-tumour activity of cycloplatam in lung cancer xenografts was quite different from cisplatin. In LXFS 538, a model moderately sensitive to cisplatin, a partial remission was observed, but in LXFL 529, a cisplatin-sensitive model, cycloplatam was inactive, cycloplatam thus demonstrating a different spectrum of anti-tumour activity. Based on these results, further preclinical investigations with other tumours, such as cisplatin-sensitive and -resistant gastric cancer models, are warranted with cycloplatam.

Animals↗