Search PubMed⌕ Search

Biomedical subjects

E Scherer

Publications and source records attributed to E Scherer.

At least 91 records · Page 5Linked to original sources

Modification of deoxyguanosine by chloroethylene oxide.

Reaction of deoxyguanosine in glacial acetic acid with chloroethylene oxide, a proposed reactive metabolite of vinyl chloride, led to a single, strongly fluorescent product in nearly quantitative yield. The u.v. spectra indicated alkylation of N-7 of guanine, which was confirmed following reduction of the reaction product by sodium borohydride to 7-(2-hydroxyethyl)guanine, and the synthesis of the same modified guanine via a stereoselective 7-N hydroxy alkylation using 2,3-epoxy-1-propanol. In agreement with the expected structure 7-(2-oxoethyl)guanine reacted with the carbonyl specific reagent 2,4-dinitrophenylhydrazine (2,4-DNPH). However, its i.r. and proton n.m.r. spectra did not support the existence of a simple aldehyde group. Moreover, the 2,4-dinitrophenylhydrazone was labile, 7-(2-oxoethyl)guanine being produced when excess 2,4-DNPH was removed. This instability was interpreted as being due to the reversible formation of a hemiacetal ring between O6 of the guanine residue and the aldehyde carbon of the 2-oxoalkyl group resulting in O6,7-(1'-hydroxyethano)guanine. This conformation was supported by the occurrence in field desorption mass spectra of the ions of m/e = 175 and 292 which are interpreted as O6,7-ethenoguanine and O6,7-ethenodeoxyguanosine resulting from the elimination of H2O of the hydroxyethano residue. O6,7-(1'-hydroxyethano)guanine might be expected to cause faulty base pairing during replication of DNA, which may be the molecular basis of the carcinogenicity of vinyl chloride.

Borohydrides↗

[Possibilities and limitations of radiotherapy in neoplasms of the anterior cranial fossa].

Primary and secondary tumors of the anterior cranial fossa are discussed in clinic-therapeutical survey and mainly the role of radiation therapy of some of these tumors is stressed. The possibilities of additional use of radiosensitizing substances and possible combinations with chemotherapeutic agents are related. Statistical results of our own concerning malignant glioma and retinoblastoma are shown; the last mentioned tumors are a grateful and demanding indication area of radiation therapy. Casuistic experiences with malignant melanoma of the orbital region are discussed; detailed recommendations as to radiotherapeutic management of intraorbital tumors are given.

Brain Neoplasms↗

Misonidazole as a radiosensitizer in the radiotherapy of glioblastomas and oesophageal cancer. Pharmacokinetic and clinical studies.

Since May 1978 the hypoxic-cell radiosensitizer, misonidazole (MIS), has been under clinical investigation in a phase III trial with multiple doses of the drug in 11 patients with brain tumours (seven glioblastomas, four recurrent brain tumours) and three patients with oesophageal carcinoma. The doses of MIS administered were usually well tolerated but the principal toxicities observed were peripheral neuropathy as well as nausea and vomiting was completely reversible. The incidence of neuropathy was not related to the pharmacological parameters of plasma level or half-life. Pharmacological assessment by high-pressure liquid chromatography included assays of plasma, urine and cerebrospinal fluid. The demethylated product, Ro-05-9963, was detected as the major metabolite. Peak plasma levels were obtained one to four hours after administration of MIS, with a half-life of five to ten hours. Cerebrospinal fluid levels of MIS correlated well with those of the plasma. MIS was mainly excreted as the demethylated metabolite, but less than 40% of the given dose could be recovered. The results obtained suggest that the present MIS dosage for glioblastoma patients results in a low plasma level with no observable therapeutic effect.

Adult↗

[Clinical manifestations and therapy of dysgerminomas (author's transl)].

Due to improved graduated surgery techniques and large-field radiotherapy applied in all cases, the ovarial dysgerminoma has become a disease showing a high rate of recoveries. Under consideration of their own medical records, the authors present the relevant epidemiologic and clinical parameters, establish a diagnosis programme and develop a therapeutic concept which also wants to take into account the individual requirements of patients regarding their age and their prognosis.

Adolescent↗

[Combined chemo- and radiotherapy in inoperable small-cell anaplastic bronchial carcinoma (author's transl)].

Combined treatment with adriamycin, cyclophosphamide and vincristine (ACO) was used in 50 out-patients with histologically verified small-cell bronchial carcinoma. In 26 patients with locally and regionally limited metastases ("limited disease") radiotherapy (3000 rad focal dose) to mediastinum, hili and tumour opacity as well as prophylactic cranial irradiation (3000 rad focal dose) were performed after 3 cycles of chemotherapy. Complete clinical remission (without endoscopic control) was achieved in 32 out of 50 patients. Remissions in patients with bilateral pulmonary or extrathoracic metastases ("extensive disease", n = 24, 12 complete remissions) only led to limited asymptomatic prolongations of life (median survival time 10 months, median remission period 5 months) despite maintenance therapy. On the other hand patients with "limited disease" had considerable life prolongation (median survival 21 months, historical control value 3--4 months). Seven out of 26 patients in this group survived for 30 months after the onset of the disease, 6 out of 26 are now in their third year after starting therapy without signs of tumour recurrence. The results show that early recognition of patients with local and regional metastases has considerable prognostic value.

Carcinoma, Small Cell↗

[Results of percutaneous radiotherapy of localized prostatic carcinoma (author's transl)].

Analysing preliminary results of percutaneous radiotherapy on 79 patients with localized prostatic carcinoma, the uncorrected five-year survival rate of all patients was 67.3%, that in stage O, A and B 89.5% and that of patients in stage C and D 64.5%. The tumour-free five-year survival rate of all patients was 50.2%. In three patients there was a recurrence (4%), in four others severe side-effects (5%). There were no fatal complications. Radiotherapy can be considered to be an alternative to operation even when the tumour is limited to the prostate.

Humans↗

Formation by diethylnitrosamine and persistence of O4-ethylthymidine in rat liver DNA in vivo.

The formation by diethylnitrosamine (DEN) and persistence of O4-ethylthymidine in rat liver DNA in vivo has been studied using enzymic hydrolysis of DNA, cation exchange column chromatography and thin-layer chromatography (TLC). The amount of O4-ethylthymidine represented about 1% of the total ethylation; its half-life in vivo was 19 (range 16--24) days, the same value as obtained for O2-ethylthymidine. The persistence of O2- and O4-ethylthymidine, rather than the rapid removal of O6-ethylguanine, favours the former miscoding base adducts as relevant molecular lesions in rat liver carcinogenesis.

Alkylation↗

[Neutron therapy at the radiology center of the West German Tumor Center at Essen University Hospital. Preliminary results during the treatment time from January 1978 to September 1979].

The preliminary results of neutron treatment of 104 patients are analysed. Most of them suffered from advanced or recurrent tumors. A complete tumour regression was observed in 55 cases and a partial regression in 22 cases (tumour involution less than or equal to 50% of the original extent). 19 patients developed recurrences, 15 of them received reduced doses. In 8 cases neutron therapy failed. Applying stringent requirements for neutron therapy, a complication rate of approximately 10% is to be expected.

Dose-Response Relationship, Radiation↗