摘要:

AbstractWe carried out a phase I trial with chlorambucil. Thirty patients with advanced cancer were entered in six dose levels: 36, 48, 60, 84, 108, and 144 mg/m2. The drug was given in six divided oral doses every 6 hours and the regimen was repeated every 3 weeks. The median age was 62 years (31-84), median Kamofsky performance status (KPS) 60 (40-90). All patients but one had received prior radiation therapy, chemotherapy, or both. Central nervous system toxicity was dose limiting, occurring in 5 of 6 patients at 144 mg/m2. It was characterized by transient seizures, hallucinations, lethargy, stupor, and coma. Metoclopramide was successful in controlling nausea and vomiting, which was severe if the antiemetic was not used. Leukopenia (3 patients) and thrombocytopenia (2 patients) were mild. One patient with colorectal carcinoma had a minor response, and two patients with non-small cell lung cancer had stable disease. A safe dose for phase II trials is 108 mg/m2in six 6-hourly oral doses.

ISSN:0735-7907    

DOI:10.3109/07357908809080064

出版商:Taylor&Francis    

年代:1988

数据来源: Taylor

摘要:

AbstractParameters for inhibition of thymidylate synthase (TS) in a DMH-induced transplantable rat colon carcinoma were studied after intraperitoneal administration of bolus doxifluridine (5′-dFUR) 200mg/kg. Levels of 5′-dFUR, 5-fluorouracil (5-FU), fluorouridinediphosphate (FUDP), and fluorouridinetriphosphate (FUTP) were determined by use of high-performance liquid chromatography. Micromethods for analysis of 5-fluoro-2′-deoxyuridylate (FdUMP) and TS were used to study the in vivo intracellular pharmacokinetics of TS inhibition. Peak values of 5′-dFUR and 5-FU were found at 30 min and showed exponential declines with values close to zero at 5 hr. Substantial levels of FUDP and FUTP were found throughout the 24 h observation time. Peak FdUMP levels were modest compared to those observed after equimolar administration of 5-FU, but FdUMP persisted in amounts well above available binding sites on TS for the 24 h observation time. Reduction of free TS enzyme to undetectable levels (<0.05 pmol/g) lasted for 4 h, and at 24 h, there was still almost 70% enzyme inhibition. The total amount of TS (TStot) defined as free [3H]FdUMP-titrable enzyme (TSf) plus TS bound to FdUMP in a ternary complex (TSb) increased as a result of 5′-dFUR bolus injection from 15 to 50 pmol/g during the 24 hr observation time. We conclude from these data that 5′-dFUR is converted to 5-FU and subsequently to FdUMP, and the results suggest that 5′-dFUR exerts its cytotoxic effects through inhibition of TS and incorporation into RNA.

ISSN:0735-7907    

DOI:10.3109/07357908809080065

出版商:Taylor&Francis    

年代:1988

数据来源: Taylor

摘要:

AbstractIn order to study whether cytosolic progesterone receptor (PRc) is involved in progesterone-induced proliferative arrest of breast cancer cells (CAMA-1N), submit composition of PRc in these cells was characterized. In the TSK G3000 high-performance liquid chromatography (HPLC) column, molybdate-stabilized PRc eluted as a single sharp peak immediately following the void volume. PRc from this peak had a sedimentation coefficient of 7.6 S and was eluted at 0.22 M salt from a linear gradient (0.1 to 0.4 M NaCl) in a DEAE column. When covalently labeled with [3H]R5020, analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and visualized byfluorography, PRc from crude cytosol exhibited two major protein bands with molecular weights of 105±2.1 and 83±3.2 kD, respectively. However, HPLC-purified PRc showed only one major band of 105 kD. These results show that PRc in CAMA-1N cells has steroid-binding components similar to other target tissues and provides a basis for further quantitative and qualitative analyses of PRc during cell proliferation and progesterone-induced growth arrest of CAMA cells.

ISSN:0735-7907    

DOI:10.3109/07357908809080066

出版商:Taylor&Francis    

年代:1988

数据来源: Taylor

摘要:

AbstractCells derived from human germ cell tumors (HGCT) are potential models for the study of human embryonic differentiation. Differentiation in four HGCT-derived lines (1618K, 833KE, 1777Ndif, 2806B) was examined by light and electron microscopy, after exposure of cells to dimethyl sulfoxide (DMSO) and 12-0-tetradecanoyl phorbol-13-acetate (TPA). In line 1618K, the effect of retinoic acid was also examined. After exposure to TPA, the cells of line 1618K had a loss of microvilli, an increased amount of nuclear heterochromatin, and an increase in the number of cytoplasmic vacuoles. The cells of line 833KE exposed to TPA showed only an increase in cytoplasmic vacuoles. No changes were observed in any cell line after exposure to DMSO. Similarly no changes were observed in 1618K after exposure to retinoic acid. These findings indicate that DMSO and retinoic acid are not effective inducers of differentiation in these HGCT-derived cell lines. Thephorbol ester, TPA, appears to induce differentiation of some HGCT-derived cell lines.

ISSN:0735-7907    

DOI:10.3109/07357908809080067

出版商:Taylor&Francis    

年代:1988

数据来源: Taylor

摘要:

AbstractMarsupials are useful for cancer research since they are born in a fetal stage of development with little immunologic competence. In this study, mouse melanoma xenografts were grown in neonatal gray opossums (Monodelphis domestical injected at 12-32 days of age. Tumors appeared between 1 and 3 weeks postinjection and at least 73% of tumor-bearing animals rejected their tumors. Initiation of tumor growth was rare in animals over 24 days of age and, in most cases, tumors size peaked at about 50 days of age after which tumors quickly regressed. These results are discussed with respect to the development of homeothermy (25 days of age) and gain of postpartum independence (50 days of age) in this marsupial species.

ISSN:0735-7907    

DOI:10.3109/07357908809080068

出版商:Taylor&Francis    

年代:1988

数据来源: Taylor

摘要:

AbstractThe antitumoral activity and toxicity of a new daunorubicin analog (4-demethoxydaunorubicin, IMI30, Idarubicin) was tested in 20 consecutive patients with non-small cell lung cancer mostly pretreated with chemotherapy. The drug was administered orally at a dose of 15 mg/m2for three days every 3-4 weeks. There were no clinical responses. Hematological and nonhematobgical toxicities were mild.

ISSN:0735-7907    

DOI:10.3109/07357908809080069

出版商:Taylor&Francis    

年代:1988

数据来源: Taylor

ISSN:0735-7907    

DOI:10.3109/07357908809080070

出版商:Taylor&Francis    

年代:1988

数据来源: Taylor

摘要:

AbstractStudies of cancer among the Japanese survivors of the A-bombs dropped on Nagasaki and Hiroshima are the major source of information on radiation carcinogenesis in humans. They have already made important contributions to the estimation of the risk of radiation-induced cancer and to our understanding of key factors influencing risk, especially tissue sensitivity, age at exposure, and the temporal distribution of radiogenic cancers. The size of the exposed population still surviving virtually guarantees the continued productivity of the research conducted in Hiroshima and Nagasaki. It should not be supposed, however, that these studies will ever provide all the information needed for radiation protection standards or risk estimation. The experience of the A-bomb survivors simply does not include all important aspects of radiation exposure for which information is needed. Moreover, despite the size of the sample remaining under study, it is most unlikely that direct, empirical estimates can be made that will remove the necessity for dependence upon mathematical models to derive estimates of risk in the low-dose region.

ISSN:0735-7907    

DOI:10.3109/07357908809080071

出版商:Taylor&Francis    

年代:1988

数据来源: Taylor

ISSN:0735-7907    

DOI:10.3109/07357908809080072

出版商:Taylor&Francis    

年代:1988

数据来源: Taylor

ISSN:0735-7907    

DOI:10.3109/07357908809080073

出版商:Taylor&Francis    

年代:1988

数据来源: Taylor