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Biomedical subjects

M E Scheulen

Publications and source records attributed to M E Scheulen.

At least 73 records · Page 4Linked to original sources
PubMed1988

Phase I study of pirarubicin.

A Phase I trial of pirarubicin (4'-O-tetrahydropyranyl-doxorubicin) was undertaken to study its toxicity and to gain preliminary knowledge of its efficacy. The dose was escalated by increments of 10 from 30 to 70 mg/m2. Out of 20 patients, 19 were evaluable for toxicity and response to treatment. Hematologic toxicity was dose limiting and dose related. Other adverse effects included nausea and vomiting, hair loss, and stomatitis. No acute cardiotoxicity was encountered. In 2 patients with metastatic breast cancer who had not been pretreated with cytostatic agents, a partial remission was achieved lasting for 5 months. In 6 patients, tumor parameters did not change for a median of 3 months, and 11 patients suffered progressive disease.

Adult↗
PubMed1988

[Breast carcinoma in men: radiotherapy and treatment results].

The treatment of 34 men with stage T1 N0 M0 to T3/4 N1 M0 mammary carcinomas was followed by a five-year survival rate of 70%. Three patients suffering from initial remote metastases died after 2 to 3.5 years. The probability of a five-year survival decreases with increasing tumor growth and axillary involvement. The prognostic effect of receptor state and grading could not be investigated in our patients. Our own data as well as recent data from literature suggest that, with respect to TNM stages in mammary carcinoma, there is no prognostic difference between men and women. It is not very clear at present if postoperative irradiation exerts a favorable influence on the survival rate. However, it reduces the local recurrence risk for men and women. 45 Gy in five weeks should be considered as a minimum dose. The indications for postoperative irradiation are discussed.

Adenocarcinoma↗
PubMed1987

Oxygen radical formation and DNA damage due to enzymatic reduction of bleomycin-Fe(III).

Aerobic incubations of bleomycin, FeCl3, DNA, NADPH, and isolated liver microsomal NADPH-cytochrome P-450 reductase resulted in NADPH and oxygen consumption and malondialdehyde formation, indicating that the deoxyribose moiety of DNA was split. All parameters measured depended on the active enzyme, bleomycin and FeCl3. In the absence of oxygen malondialdehyde formation was very low. When bleomycin, FeCl3 and the reductase were incubated with methional ethene (ethylene) was formed, suggesting that during the enzyme-catalyzed redox cycle of bleomycin-Fe(III/II) hydroxyl radicals were formed. Ethene formation also depended on oxygen, NADPH, the enzyme, bleomycin, and FeCl3. During aerobic incubations of bleomycin, FeCl3, NADPH, and isolated liver nuclei oxygen and NADPH were consumed and malondialdehyde was formed. Oxygen and NADPH consumption and malondialdehyde formation depended on bleomycin and FeCl3. In the absence of oxygen malondialdehyde was not formed. These results indicate that nuclear NADPH-cytochrome P-450 reductase redox cycles the bleomycin-Fe(III/II) complex and that the reduced complex activates oxygen, whereby hydroxyl radicals are formed which damage the deoxyribose of nuclear DNA.

Animals↗
PubMed1987

Positive correlation between decreased cellular uptake, NADPH-glutathione reductase activity and adriamycin resistance in Ehrlich ascites tumor lines.

From a wild type strain of Ehrlich ascites tumor (EATWT) sublines resistant to daunorubicin (EATDNM), etoposide (EATETO), and cisplatinum (EATCIS) have been developed in vivo. Increase in survival and cure rate caused by adriamycin (doxorubicin) have been determined in female NMRI mice which were inoculated i.p. with EAT cells. Adriamycin concentrations causing 50% inhibition of 3H-thymidine (ICT) and 3H-uridine incorporation (ICU) and intracellular adriamycin steady-state concentrations (SSC) were measured in vitro. Adriamycin resistance increased and SSC decreased in the following sequence: EATWT - EATCIS - EATDNM - EATETO. When ICT and ICU were corrected for intracellular adriamycin concentrations in consideration of the different SSC (ICTc, ICUc), ICTc and ICUc still varied up to the 3.2 fold in EATCIS, EATDNM and EATETO in comparison to EATWT. Thus, in addition to different SSC other factors must be responsible for adriamycin resistance. Therefore, enzymes which may play a role in the cytotoxicity related to adriamycin metabolism (NADPH-cytochrome P-450 reductase, NADPH-glutathione reductase, NADP-glucose-6-phosphate dehydrogenase, NADP-isocitrate dehydrogenase) were measured. In contrast to the other parameters determined, NADPH-glutathione reductase was significantly (p less than 0.01) increased up to the 3.2 fold parallel to adriamycin resistance as determined by increase in life span, cure rate, ICTc, and ICUc, respectively. It is concluded that high activities of NADPH-glutathione reductase may contribute to an increase in adriamycin resistance of malignant tumors.

Animals↗
PubMed1987

Liver nuclear NADPH-cytochrome P-450 reductase may be involved in redox cycling of bleomycin-Fe(III), oxy radical formation and DNA damage.

When NADPH-cytochrome P-450 reductase isolated from rat liver microsomes was aerobically incubated with bleomycin, FeCl3, NADPH and DNA parallel NADPH and oxygen were consumed and malondialdehyde was formed. A similar parallelism of NADPH- and oxygen-consumption and malondialdehyde formation was observed when cell nuclei isolated from rat liver were incubated under the same conditions. The formation of malondialdehyde which was identified by HPLC and which was most likely released from oxidative cleavage of deoxyribose of nuclear DNA required oxygen, bleomycin, FeCl3 and NADPH. This indicates that a nuclear NADPH-enzyme, presumably NADPH-cytochrome P-450 reductase, is able to redox cycle a bleomycin-iron-complex which in the reduced form can activate oxygen to a DNA-damaging reactive species. The data suggest that the activity of this enzyme in the cell nucleus could play an important role in the cytotoxicity of bleomycin in tumor cells.

Animals↗
PubMed1986

Prevention of adriamycin cardiotoxicity by niacin, isocitrate or N-acetyl-cysteine in mice. A morphological study.

Adriamycin is known to produce treatment limiting cardiotoxicity. We studied the effect of niacin, isocitrate, and N-acetyl-cysteine on cumulative adriamycin-induced cardiotoxicity in NMRI mice. Pathologic grading of the hearts indicated a significant reduction in myocardial injury. In addition, according to median survival and weight changes there was a significant decrease in toxicity. As demonstrated in Ehrlich ascites tumor, coadministration of N-acetyl-cysteine may interfere with the antitumor activity of adriamycin. In contrast, niacin and isocitrate did not show significant inhibition of antineoplastic activity. Our experiments suggest a promising role of niacin and isocitrate as potential cardioprotectors in the course of chemotherapy with adriamycin.

Acetylcysteine↗
PubMed1985

Chemotherapy of metastatic seminoma.

Response to chemotherapy and survival was retrospectively analyzed in 28 patients with bulky retroperitoneal and disseminated seminoma treated between 1977 and 1983. The median age was 41 years (range: 23-52). All patients had histological evidence of pure testicular seminoma, however, 14 patients revealed moderate increases of human beta-chorionic gonadotropin levels. Prior radiotherapy had been given to 9/28 (32%) patients. Treatment consisted of at least four courses of simultaneous or sequentially alternating therapy with cisplatin, vinblastine, bleomycin plus/minus adriamycin (PVB +/- A), administration of ifosfamide or combination therapy with ifosfamide/cisplatin (IFS/DDP) or ifosfamide/etoposide (IFS/ETP). Twenty-five of 28 patients (89%) achieved a complete (CR), and 3/28 patients a partial remission. Relapse occurred in 1/8 CR patients after adjuvant postchemotherapeutic irradiation, and in 1/11 patients without any further radiotherapy. So far, 23/28 patients (82%) are free of disease after a median follow-up of 28+ (14+----82+) months. Marked myelosuppression was observed in previously irradiated patients, mainly after PVB +/- A therapy. In two patients, transient nephrotoxicity developed after PVB and IFS/DDP, respectively. After PVB +/- A chemotherapy, three patients revealed polyneuropathy, paralytic subileus and bleomycin-induced pneumonitis, respectively. In conclusion, the present series suggests a high probability of continuous CR in even bulky retroperitoneal and widespread metastatic seminoma. So far, no definite conclusions can be made on the therapeutic superiority of one of the different chemotherapeutic regimens used. However, this preliminary experience suggests that the combination of ifosfamide and etoposide or cisplatin may prove less toxic than sequentially alternating or simultaneous PVB +/- A chemotherapy.

Adult↗
PubMed1983

[The toxic shock syndrome in male patients].

The toxic shock syndrome was observed in two young men (16 and 22 years). In one it occurred after a purulent scraping wound of the skin, in the other two days after an operation with seemingly normal wound conditions. All findings returned to normal in both patients after about five weeks. The syndrome of toxic shock can occur, regardless of age and sex, in Staphylococcus aureus infections of various kinds.

Adolescent↗
PubMed1983

Efficacy of ifosfamide in refractory malignant diseases and uroprotection by mesna: results of a clinical phase II-study with 151 patients.

In a clinical phase II study 151 patients with refractory malignant diseases were treated with ifosfamide (60 mg/kg/day i.v. days 1-5, q 21-28 days). Altogether, 490 courses of treatment were given, 92 with conventional prophylactic measures (continuous infusion of 3-4 litre physiological saline plus alkalinization of the urine) and 398 with mesna prophylaxis (12 mg/kg i.v., 0, 4 and 8 h after administration of ifosfamide). The overall response rate (min. 25% tumor reduction) was 67/151 (44%) including four complete remissions in a fairly unfavourable patient group with testicular teratoma (39/87), soft tissue sarcoma (10/16), malignant melanoma (2/7), osteogenic sarcoma (3/6), Ewing's sarcoma (2/6), lymphoma and acute leukemia (5/7) or other histologies (6/22). The response rate in patients pretreated by cyclophosphamide containing regimen was 7/19 (36%) including one complete remission and one partial remission. Mesna was highly effective in reducing the frequency of hemorrhagic cystitis from 25/92 (27%) to 16/398 (4%) ifosfamide courses. The antitumor activity of ifosfamide in testicular cancer was not reduced by mesna. In conclusion, ifosfamide with the potent uroprotector mesna appears to compare favourably with the most active agents in the treatment of malignant diseases.

Cyclophosphamide↗
PubMed1983

Ifosfamide in combination chemotherapy for sarcomas and testicular carcinomas.

The efficacy of ifosfamide combination chemotherapy was studied in 164 patients, 94 with advanced testicular carcinoma and 70 with metastatic sarcoma. Ifosfamide was given at 40-60 mg/kg/day i.v. on five consecutive days every 3-4 weeks together with mesna prophylaxis with 8 mg/kg i.v. being used at 0, 4 and 8 h after ifosfamide administration. Of 70 sarcoma patients 57 were evaluable for response, of whom 49 had received prior chemotherapy. The overall response rate was 46% (26/57) including 3 complete (CR) and 14 partial remissions (PR). Ninety-four patients with germ cell tumours of the testis were treated. Of 16 seminoma patients 15 achieved CR or PR. Seventy-eight patients with nonseminomatous testicular cancer who had received previous chemotherapy were either treated with ifosfamide/etoposide (n = 63, remission rate: 30%) or ifosfamide/cisplatin (n = 15, CR + PR: 33%). These results indicate that ifosfamide alone or in combination is active in sarcomas, seminomas and teratomas and that further studies are warranted employing the drug in first-line regimens.

Adolescent↗
PubMed1983

Treatment of refractory malignant lymphomas with ifosfamide/etoposide combination chemotherapy.

Twenty patients with malignant lymphomas refractory to prior combination chemotherapy were treated with ifosfamide (40 mg/kg/day i.v. days 1-5) and etoposide (120 mg/m2/day i.v., days 1, 3, 5). Altogether, 56 courses of treatment were given with prophylaxis of urinary side effects by mesna (8 mg/kg i.v. 0, 4, 8 hours after ifosfamide). The overall response rate (min. 25% tumor reduction) was 14/20 (70%) including 5/8 partial remissions in patients with non-Hodgkin's lymphoma and 2/12 partial remissions in patients with Hodgkin's disease. The lower total response rate of 7/12 in patients with Hodgkin's disease in comparison to 7/8 in patients with non-Hodgkin's lymphoma may be related to the different sensitivity of both diseases or to differences in the extent and duration of prior chemotherapy. As combination chemotherapy with ifosfamide/etoposide proved to be effective in refractory malignant lymphomas this combination may be included in combination chemotherapy programs for the salvage therapy or the initial treatment of malignant lymphomas with the alternation of non-cross-resistant chemotherapy combinations.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1982

[Raynaud's phenomenon following combined cytostatic treatment of malignant testicular tumours].

Raynaud's phenomenon was observed in 8 out of 271 patients with malignant testicular tumours during or up to 14 months after combined cytostatic treatment. All patients with Raynaud's phenomenon were part of a group of 30 people having received vinblastine in a total dose of at least 2 mg/kg and bleomycin in a dose of 10 mg/kg. There were no other hints of Raynaud's syndrome from the history or chemical pathology. Compared to the experience of other authors Raynaud's phenomenon was observed less frequently and only at dosages of vinblastine and bleomycin considerably higher. This may possibly be due to use of steroids during combined cytostatic treatment with vinblastine and bleomycin.

Adult↗