Phase II trials of rhizoxin in advanced ovarian, colorectal and renal cancer.

Rhizoxin is a tubulin-binding anti-neoplastic agent which is active in a range of murine tumour models. The recommended schedule, of intravenous (i.v.) bolus administration at a dose of 2 mg m-2 every 3 weeks, has been assessed in three phase II trials of ovarian, renal and colorectal cancer. In general terms the drug was fairly well tolerated, but the response rate was disappointing: 0/18, colorectal cancer; 0/18, renal cancer; 1 partial response (PR)/17, ovarian cancer.     

TNO-6 has no effect in gastrointestinal cancer: N-acetyl-glucosaminidase shows renal damage

Twenty-five patients, 16 with gastric cancer and nine with colonic cancer, received TNO-6 30 mg m-2 every four weeks. No objective tumour response was recorded. Nausea and vomiting occurred in 21 patients and was severe in 17. Severe marrow suppression developed in five patients. Renal function was unaffected in all but one patient who developed renal failure, probably as a result of septicaemia. However, the renal tubular enzyme N-acetyl-beta-D-glucosaminidase was measured in six patients and showed a rise in all. In this study TNO-6 had no anti-tumour activity in gastrointestinal malignancy, but produced significant renal tubular damage.     

Journal abstracts

Literature

Journal abstracts     

Identity of immune cells in graft-versus-host disease of the skin. Analysis using monoclonal antibodies by indirect immunofluorescence.

The cellular infiltrate in skin biopsies of 9 patients with graft-versus-host disease (GVHD) has been characterized with the use of monoclonal antibodies by indirect immunofluorescence. Most infiltrating cells in dermis reacted with monoclonal antibodies which recognize T-cell antigens. A mean of 45% of all dermal cells were T11-reactive, while a smaller proportion of cells were identified by another "pan" antibody, OKT3. In all but two instances the proportion of dermal cells reactive with OKT8 exceeded the proportion reactive with OKT4. Anti-Tac, which identifies activated T cells, reacted with a variable proportion of cells. Monocytes and null cells (OKM1+) were frequently observed but were less numerous than T-lymphocytes. Infiltrates were sparsely populated with OKT6-reactive cells, and there was no difference between the number of intraepidermal cells reactive with this antibody in study subjects and normal controls. Few cells reactive with Leu 7 (large granular lymphocytes) or with anti-B-cell reagents were seen. These findings may have clinical implications for use of monoclonal antibodies for prophylaxis and treatment of GVHD.     

Linkage analysis of anorexia and bulimia nervosa cohorts using selected behavioral phenotypes as quantitative traits or covariates.

To increase the likelihood of finding genetic variation conferring liability to eating disorders, we measured over 100 attributes thought to be related to liability to eating disorders on affected individuals from multiplex families and two cohorts: one recruited through a proband with anorexia nervosa (AN; AN cohort); the other recruited through a proband with bulimia nervosa (BN; BN cohort). By a multilayer decision process based on expert evaluation and statistical analysis, six traits were selected for linkage analysis (1): obsessionality (OBS), age at menarche (MENAR), and anxiety (ANX) for quantitative trait locus (QTL) linkage analysis; and lifetime minimum body mass index (BMI), concern over mistakes (CM), and food-related obsessions (OBF) for covariate-based linkage analysis. The BN cohort produced the largest linkage signals: for QTL linkage analysis, four suggestive signals: (for MENAR, at 10p13; for ANX, at 1q31.1, 4q35.2, and 8q13.1); for covariate-based linkage analyses, both significant and suggestive linkages (for BMI, one significant [4q21.1] and three suggestive [3p23, 10p13, 5p15.3]; for CM, two significant [16p13.3, 14q21.1] and three suggestive [4p15.33, 8q11.23, 10p11.21]; and for OBF, one significant [14q21.1] and five suggestive [4p16.1, 10p13.1, 8q11.23, 16p13.3, 18p11.31]). Results from the AN cohort were far less compelling: for QTL linkage analysis, two suggestive signals (for OBS at 6q21 and for ANX at 9p21.3); for covariate-based linkage analysis, five suggestive signals (for BMI at 4q13.1, for CM at 11p11.2 and 17q25.1, and for OBF at 17q25.1 and 15q26.2). Overlap between the two cohorts was minimal for substantial linkage signals.     

Presentation of Leishmania donovani promastigotes occurs via a brefeldin A-sensitive pathway.

For the presentation of Leishmania promastigotes to polyclonal CD4+ T cells, a processing period within activated macrophages of 3-4 h is required. Presentation can be inhibited by both chloroquine and brefeldin A (BFA), the latter implicating a requirement for newly synthesized MHC class II molecules. This inhibition is both reversible and specific, in that BFA did not inhibit mixed lymphocyte reaction stimulation by these infected macrophages. Immunogold labeling demonstrated that class II was associated with the parasite-containing phagolysosome. The level of class II was not significantly altered in BFA-treated cells in the time period studied, suggesting that antigen may exist the phagolysosome and interact with class II in another cellular compartment.