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Background:Bcl-2 family genes are frequently amplified in small cell lung cancer (SCLC). A phase I trial was conducted to evaluate the safety of obatoclax, a Bcl-2 family inhibitor, given in combination with standard chemotherapy.Methods:Eligible patients (3-6 per cohort) had extensive-stage SCLC, measurable disease, 1 before therapy, Eastern Cooperative Oncology Group performance status 0 or 1, and adequate organ function. Patients were treated with escalating doses of obatoclax, either as a 3- or 24-h infusion, on days 1-3 of a 21-day cycle, in combination with carboplatin (area under the curve 5, day 1 only) and etoposide (100 mg m−2, days 1-3). The primary endpoint was to determine the maximum tolerated dose of obatoclax.Results:Twenty-five patients (56% male; median age 66 years) were enrolled in three dose cohorts for each schedule. Maximum tolerated dose was established with the 3-h infusion at 30 mg per day and was not reached with the 24-h infusion. Compared with the 24-h cohorts, the 3-h cohorts had higher incidence of central nervous system (CNS) adverse events (AEs); dose-limiting toxicities were somnolence, euphoria, and disorientation. These CNS AEs were transient, resolving shortly after the end of infusion, and without sequelae. The response rate was 81% in the 3-h and 44% in the 24-h infusion cohorts.Conclusion:Although associated with a higher incidence of transient CNS AEs than the 24-h infusion, 3-h obatoclax infusion combined with carboplatin-etoposide was generally well tolerated at doses of 30 mg per day. Though patient numbers were small, there was a suggestion of improved efficacy in the 3-h infusion group. Obatoclax 30 mg infused intravenously over 3 h on 3 consecutive days will be utilised in future SCLC studies. [ABSTRACT FROM AUTHOR]

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Compound IX 207-887 is a novel antiarthritic agent which inhibits the release of interleukin-1 (IL-1) from human monocytes and mouse peritoneal macrophages in vitro at concentrations which are achieved therapeutically in human rheumatoid arthritis and in animal models of arthritis. In the present studies IL-1 activity in conditioned media, homogenates or lysates was monitored using four independent assay systems. Biologically active IL-1 was determined by, a) the induction of latent metalloproteinase-release from rabbit articular chondrocytes, which is relatively specific for IL-1 and b) by a sensitive thymocyte proliferation assay. Immunoreactive IL-1-β was assayed by RIA and ELISA. In all test systems IX 207-887 significantly reduced both biologically active and immunoreactive IL-1 in culture media, whereas the levels of IL-1 in homogenates or lysates were either unaffected or only marginally reduced. The release of other monokines tested, such as interleukin-6 and tumour necrosis factor-α, and the secretion of lysozyme were only marginally influenced. IX 207-887 neither affected the adherence of human monocytes nor markedly inhibited IL-1 or IL-2-induced thymocyte proliferation. In the chondrocyte test no IL-1 antagonistic activity of IX 207-887 could be observed. All of these data indicate that IX 207-887 has the novel property of being an inhibitor of IL-1 release. [ABSTRACT FROM AUTHOR]

Stimulation of macrophages by zymosan phagocytosis triggers the respiratory burst and induces an early release of lysosomal hydrolases and E-type prostaglandins (PGE). We have studied whether antigen presentation by macrophages to helper T-cells elicits a comparable sequence of events. Cloned T-helper cells specific for hen egg albumin (EA) were added to histocompatible or histoincompatible resident mouse peritoneal macrophages in the presence of EA or an unrelated antigen, and the changes in biochemical parameters were monitored. The interaction between macrophages, T-helper cells and EA induced the production of PGE, but no release of lysosomal hydrolases or activation of the respiratory burst. In addition T-cell proliferation was observed. By contrast, no proliferation and no biochemical changes were observed when histoincompatible macrophages or unrelated antigen were used. When the experiments were done in the presence of indomethacin to inhibit PGE release, T-cell proliferation was enhanced. These results suggest that the PGE released may exert a feed-back control of the T-cell response. [ABSTRACT FROM AUTHOR]

Some unnatural sulphur amino acids can be detected in the phloem of the vascular bundles from Phaseolus vulgaris after the application of HS to the primary leaves. [ABSTRACT FROM AUTHOR]

In extracts of HS gased pea seedlings, a radioactive substance has been revealed by thin layer chromatography which showed the same chromatographic properties as thiotheronine. [ABSTRACT FROM AUTHOR]