Richard J. Ablin

The prostate transglutaminase (TGase-4, TGaseP) regulates the interaction of prostate cancer and vascular endothelial cells, a potential role for the ROCK pathway

Prostate transglutaminase (TGase-4 or TGaseP) is an enzyme that is uniquely expressed in prostate tissues. The function of the TGase, implicated in the cell-matrix, is yet to be fully established. In the present study, we investigated the role of TGase-4 in tumor-endothelial cell interactions, by creating a panel of prostate cancer cell lines that have different expression profiles of human TGase-4. Here, we report that prostate cancer cells PC-3, when over-expressing TGase-4 (PC-3(TGase4exp)) increased their ability to adhere to quiescent and activated (by hepatocyte growth factor) endothelial cells. In contrast, the prostate cancer cell CAHPV-10, which expressed high levels of TGase-4, reduced the adhesiveness to the endothelial cells after TGase-4 expression was knocked down. By using frequency based electric cell impedance sensing, we found that TGase-4 mediated adhesion resulted in a change in impedance at low frequency (400 Hz), indicating a paracellular pathway disruption. The study further showed that expression of TGase-4 rendered the cells to exert regulation of endothelial interaction by bypassing the ROCK pathway. It is therefore concluded, that TGase-4 plays a pivotal role in the interaction between endothelial cells and prostate cancer cells, an action which is independent of the ROCK pathway.

Impotence therapy and cancer of the prostate

Prostate cancer developed in two male patients being treated with fluoxymesterone for erectile impotence. It is suggested that the current increased interest in and therapy for sexual dysfunction be accompanied by an awareness of a possible causal relationship between exogenous androgens and prostrate cancer.

Leukocyte adherence inhibition and immunoreactivity in prostatic cancer. I. Identification of anti-tumour cell-mediated immunity and "blocking" factor.

Abstract Modification of the recently described leukocyte adherence inhibition (LAI) test was utilized for the evaluation of anti-tumour cell-mediated immunity and the identification of “blocking” factor in 20 patients with prostatic cancer. Evidence of cross-reactivity of the observed anti-tumour immunity with extracts prepared from tumours of the same type and the specificity of “blocking” of the reactions for autologous sensitized lymphocytes and tumour only have similarly been demonstrated employing the LAI test. While the observed cross-reactivity between individual tumours, within each tumour type is in keeping with observations of anti-tumour immunity in patients with other tumours, e.g., colon, breast and melanoma, observations suggestive of a specificity of “blocking” for autologous tumour only is perhaps somewhat unique, of which further studies will be needed to confirm.

Serum Proteins in Prostatic Cancer

Levels of the three major serum immunoglobulins (G, A, M) were quantitated prior to and up to 2 weeks following each of two independent freezing treatments of the primary prostatic tumour in 4 patient

The Effect of Transurethral Resection of the Prostate on Lymphocyte Response in Patients with Prostatic Cancer

The following study indicates that transurethral resection may affect the in vivo cellular aspects of the immune response in patients with prostatic cancer. This in vivo result seems to be supported by the fact that patients dying of carcinoma of the prostate at our institution usually had had an antecedent transurethral resection. Therefore, we emphasize that transurethral resection in patients with prostate cancer should be undertaken with clear-cut indications and with the knowledge that it may be an insult to the patients immune system.

Inhibition of leukocyte migration by extracts of malignant prostatic tissue and correlation of degree of in vitro sensitization to clinical responsiveness in prostatic cancer patients

In an attempt to evaluate the degree of in vitro cellular sensitization to tumor and its relationship to clinical responsiveness, direct leukocyte migration tests were carried out in patients with varying degrees of adenocarcinoma of the prostate employing pooled allogeneic extracts of normal, benign, and malignant prostatic tissue as a source of antigen. Cell-mediated immunity to presumably common prostatic tumor associated antigens was observed. The degree of sensitization of clinically significant specific reactivity of the patients leukocytes to malignant prostatic tissue was greatest in patients with localized disease, low-grade tumor, and clinically inactive disease than in patients with advanced disease, high-grade tumor, and clinically active disease. Evaluation of the possible correlation of specific reactivity to malignant prostatic tissue as a prognostic index of clinical responsiveness revealed a positive correlation with the degree of sensitization in 3 (43 per cent) of 7 patients. Correlation in 4 patients was questionable because of observations of stimulation of migration rather than inhibition, suggested by some to be reflective of weak sensitization to tumor. Evaluation of a larger patient population as well as a prospective study of the relationship of the degree of sensitization and clinical responsiveness will be necessary before any definitive conclusions may be drawn regarding the present observations.

Possibly Immunosuppresive Factors in Blood Products

Excerpt To the editor: Recent reports of the development of the acquired immunodeficiency syndrome in hemophiliacs receiving factor VIII and other clotting concentrates have prompted immunologic st...

The Effect of Digitalis on the Bladder in Man

The effects of intravenous digitalis on the bladder were investigated in 36 patients. Digitalis consistently decreased the bladder capacity and in some it increased the intravesical pressure. The significance of these findings and its clinical applications are discussed.

Serum proteins in prostatic cancer III. Relationship of levels of immunoglobulins and complement to clinical stage of disease

The relationship between the level of the three major serum immunoglobulins, IgG, IgA, and IgM and of the third component of complement (C)C3(B1A-globulin) and the clinical Stage of prostatic cancer was evaluated. While, statistically significant (P less than 0.05) differences in the levels of these proteins compared with their levels in patients with benign prostatic hypertrophy (applied only to the study of C3) and healthy adults were observed, the levels of these proteins in each of the Stages evaluated were not significantly different from each other. The absence of a correlation between the Stage of disease and the levels of these humorally mediated effectors of immunologic responsiveness is in keeping with observations of cell-mediated effectors of immunologic responsiveness in prostatic cancer patients. Observation of the association of prostatic cancer with a deficiency of B-cell function and of C3 is noted.

Immunostaging in carcinoma of prostate

Immunostaging is a new method of assessing patients immunologically before and after immunotherapy. Twenty-eight patients with adenocarcinoma of the prostate were immunostaged independently by two investigators. There was a positive correlation between both immunostagings. There was also a positive correlation between the patients immunostage and the clinical stage of his cancer.