Larry L. Wellham

Prostate secretory protein (PSP94) suppresses the growth of androgen-independent prostate cancer cell line (PC3) and xenografts by inducing apoptosis†

PSP94 (prostate secretory protein of 94 aa; also called PIP), one of the predominant proteins secreted into the seminal fluid, was proposed as an independent diagnostic/prognostic marker for prostate cancers. It was also shown to inhibit rat prostate cancer growth. In this study, we investigated the effect of purified PSP94 on the growth of androgen‐independent human prostate cancer cells (PC3) and its potential mechanism of action.

Crystallization and toxicology of T34: A major toxin from Florida's red tide organism (Ptychodiscus brevis)

Abstract The purification and crystallization of a major toxin from laboratory cultures of Floridas fed tide organism, Ptychodiscus brevis , is described. The crystalline toxin is soluble in acetone and chloroform, less soluble in ethyl acetate, methanol and ethanol, and is slightly soluble in water. The crystalline toxin is stable when stored in a moisture-free environment. The toxin is lethal to fish and mice, inhibits growth in three in vitro cell culture systems, and inhibits the division of fertilized sea urchin eggs. It has no effect on the formation of antibodies directed against sheep red blood cells in mice, and does not inhibit the morphological transformation of rat glioma cells from a fibroblast-like to a glial-like cell.

Expression of drug resistance-associated mdr-1, GST π, and topoisomerase II genes during cell cycle traverse

The expression of drug resistance-associated mdr-1, GST pi, and topoisomerase II genes was analyzed in cell cycle phase enriched populations of doxorubicin-resistant murine leukemic P388/R-84 cells. Flow cytometric analysis of bromodeoxyuridine (BrdU) incorporation and staining with anti-BrdU antibodies was used to confirm the purity of cell cycle phase enriched populations obtained by centrifugal elutriation. Doxorubicin (DOX) and daunorubicin (DNR) accumulation was significantly lower in S-phase cells, and coincubation with verapamil (VPL) or chlorpromazine (CPZ) enhanced DOX and DNR accumulation more in S-phase than in G1- and G2/M-phase cells. While the cellular content of mdr-1 and topoisomerase II mRNAs changed, GST pi mRNA content remained constant during the cell cycle. S-phase cells had about 3-fold higher mdr-1 mRNA content than G1- and G2/M-phase cells. In G1 cells, P-glycoprotein expression, as determined by C219 monoclonal antibody, was 12% less than that of S and G2/M cells. Topoisomerase II mRNA content increased with the progression of cell cycle and peaked in G2/M cells. These observations suggest that cell cycle stage related changes in expression of drug resistance markers may have a major bearing on chemosensitivity of drug-resistant cells.

Flow cytometric analysis of the multiple drug resistance phenotype

Laser flow cytometry is increasingly used for quantitation of cellular fluorescent drug retention, effect of efflux blockers and for expression of drug resistance related cellular surface markers. Several intrinsic and extrinsic factors can affect the results obtained from drug retention functional assays and lead to artifacts. In the present study, we have used a panel of well-characterized parental and drug resistant cell lines, fluorochromes and efflux blockers to identify the possible sources of artefacts in flow cytometric analysis of the multiple drug resistance phenotype.

Ecteinascidia turbinata extracts inhibit DNA synthesis in lymphocytes after mitogenic stimulation by lectins.

Summary Aqueous ethanol extract of a tunicate which was previously found to exert antitumor and immunosuppressive activities in vivo was tested for its effect on normal human lymphocytes in vitro. The extract suppressed the uptake of tritiated thymidine by lymphocytes stimulated with mitogen. This suppressive effect did not require continuous presence of the extract. Treatment of lymphocytes prior to mitogenic stimulation resulted in suppressive effect. The fact that suppression by the extract could also be achieved 24 hr after exposure to mitogen, an interval which was found to suffice for the attainment of maximal commitment for blastogenic transformation indicates that Ete can act at a stage subsequent to the binding of the lectin and elicitation of a mitogenic signal(s).

Immunomodulation by Corynebacterium Parvum

Corynebacteriumparvum which has recently been reclassified as a Propionibacterium (1) was initially noted for its ability to stimulate the reticuloendothelial system (RES) as manifested by increased clearance of particulate material from the circulation and increased spleen and liver weights (2–5). Since then, the ability of this organism to modify various immune functions has been extensively studied.

Substances from Marine Organisms Influencing Tumor Growth and Immune Responses

The sea which is a readily accessible receptacle for man-made wastes and pollution of coastal water has become the concern of environmentalists and public health authorities alike. What has escaped their attention is that, in addition to exogenous pollution, the sea can receive conglomerates of substances produced by its inhabitants which can affect its biosphere in a favorable or deleterious way.