Expression of prostate apoptosis response (Par-4) is associated with progesterone receptor in breast cancer.

BACKGROUND: The prostate apoptosis response (Par-4) gene encodes a proapoptotic protein that selectively induces apoptosis in cancer cells after diverse apoptotic stimuli. Par-4 expression and its association with other biomarkers have not been reported in breast cancer. The purpose of this study was to determine Par-4 expression in breast cancer samples and its association with other biomarkers and clinical factors (T-stage, age, nodal status). METHODS: Paraffin-embedded section samples of breast cancer were evaluated by immunohistochemical analysis to determine Par-4, estrogen receptor (ER), progesterone receptor (PgR), c-erbB2, Ki67, p53 and bcl-2 expression. The correlation between Par-4 and the other biomarkers and clinical factors was determined by multivariate analysis. RESULTS: Thirty five percent (n=21) of samples were PAR-4 positive and 64.4% (n=38) were negative. The hormonal status was 64% ER positive (n=38), 35% ER-negative (n=21) and 40.7% PgR positive (n=24), 59.3% PgR negative (n=35). The majority (90%) of the samples presented clear cytoplasmic localization and a small portion (10%) was cytoplasmic and nuclear. Univariate analysis indicates that the Par-4 expression has a significant inverse association (p=0.04) only with expression of PgR and not with the other variables analyzed. Normal breast tissue analyzed was negative for Par-4 immunostaining. CONCLUSIONS: Our results suggest that, in breast cancer, Par-4 plays a similar tumor suppressor gene role as reported in endometrial carcinoma.

Chemotaxis of human and rat leukocytes by the delta-selective non-peptidic opioid SNC 80.

Opioids like morphine, represent a major source of relief for most chronic moderate to severe nonmalignant pain. However, opioid abuse may lead to infections such as hepatitis and AIDS because opioids have been associated with suppressing various parameters of immune function including antimicrobial resistance, antibody production, monocyte-mediated phagocytosis, and both neutrophil and monocyte chemotaxis. We have previously reported immunopotentiating properties of non-peptidic opioid receptor selective agonists and antagonists. In this study, we evaluated the effects of the nonpeptidic delta-opioid receptor agonist (+)-4-((alpha R)-alpha-((2S, 5R)-4-allyl-2, 5-dimethyl-1-piperazinyl)-3-methoxybenzyl)-N, N-diethyl-benzamide (SNC 80) on chemotaxis of rat thymic and human peripheral blood mononuclear cells by using a modified Wilkinson chamber. Cell recruitment is an essential process in acute and chronic inflammatory responses. We observed that SNC 80 at concentrations of 10(-10), 10(-9), 10(-8), 10(-7), and 10(-6) M, significantly (p < 0.01) stimulated rat thymic (1.3, 1.55, 1.58, 1.75, and 1.8-fold increases respectively) and human leukocyte (1.13, 1.37, 1.43, 1.7, 1.83 fold-increases respectively) chemotaxis (demonstrated by checkerboard assays), compared with untreated control. The effects of SNC 80 on chemotaxis of rat and human leukocytes were antagonized by naloxone, indicating that the modulation of chemotaxis by SNC 80 is via a classic opioid receptor. The development and use of non-peptidic opioids like SNC 80 could have an immediate impact not only as potent analgesics, but in immunoregulation.