Six-transmembrane epithelial antigen of the postate (STREAP): a potential target of immunotherapy of prostate cancer.

Immunotherapy has been proposed as a complementary or alternative therapy for the treatment of advanced prostate cancer (PC), one of the leading causes of tumor-related mortality in men. From different approaches that have been tested in recent years, it is now becoming more evident that the choice of the appropriate antigen to target is crucial for the best outcome. Generally tumor-associated antigens (TAAs) undergo peripheral tolerance during tumor progression, which dampens the efficacy of vaccination protocols. It can be hypothesized that the kinetic and depth of immune tolerance varies depending on the timing and relative expression of the TAA. These differences may represent a key for successful immunotherapy approaches even in patients with advanced disease. Aim of my thesis was to investigate the dynamics of CD8+ T cells specific for normal tissue antigens over-expressed during the spontaneous tumor development and progression in the transgenic adenocarcinoma of the mouse prostate (TRAMP) mice, a primary model of human PC. We have found that Prostate Stem Cell Antigen (PSCA) and Six-Transmembrane Epithelial Antigen of the Prostate (STEAP), two well known PC-associated antigens, behave differently in term of immunological response when compared with the transgenic Tag IV antigen, which drives oncogenesis in TRAMP mice. While a dendritic cells (DC)-based immunization was able to elicit measurable immune responses for all three antigens in young males affected by mouse prostate intraepithelial neoplasia (mPIN), aged mice affected by PC progressively lost immunity against Tag IV and in part for PSCA, but not against STEAP. The findings correlated with the amount of antigens expressed in the prostate, therefore suggesting that tolerance against this type of TAA follows the same rule of that induced for tissue-associated antigens in peripheral tissues: the more the antigen is expressed the more tolerance is profound. Finally, a combined therapy of allotransplantation and DC-STEAP vaccination effectively reduced tumor burden in TRAMP mice, underlying how this therapeutic strategy when targeted to a reliable antigen is able to restore cancer immunosurveillance

Six-transmembrane epithelial antigen of the postate (STREAP): a potential target of immunotherapy of prostate cancer.

Immunotherapy has been proposed as a complementary or alternative therapy for the treatment of advanced prostate cancer (PC), one of the leading causes of tumor-related mortality in men. From different approaches that have been tested in recent years, it is now becoming more evident that the choice of the appropriate antigen to target is crucial for the best outcome. Generally tumor-associated antigens (TAAs) undergo peripheral tolerance during tumor progression, which dampens the efficacy of vaccination protocols. It can be hypothesized that the kinetic and depth of immune tolerance varies depending on the timing and relative expression of the TAA. These differences may represent a key for successful immunotherapy approaches even in patients with advanced disease. Aim of my thesis was to investigate the dynamics of CD8+ T cells specific for normal tissue antigens over-expressed during the spontaneous tumor development and progression in the transgenic adenocarcinoma of the mouse prostate (TRAMP) mice, a primary model of human PC. We have found that Prostate Stem Cell Antigen (PSCA) and Six-Transmembrane Epithelial Antigen of the Prostate (STEAP), two well known PC-associated antigens, behave differently in term of immunological response when compared with the transgenic Tag IV antigen, which drives oncogenesis in TRAMP mice. While a dendritic cells (DC)-based immunization was able to elicit measurable immune responses for all three antigens in young males affected by mouse prostate intraepithelial neoplasia (mPIN), aged mice affected by PC progressively lost immunity against Tag IV and in part for PSCA, but not against STEAP. The findings correlated with the amount of antigens expressed in the prostate, therefore suggesting that tolerance against this type of TAA follows the same rule of that induced for tissue-associated antigens in peripheral tissues: the more the antigen is expressed the more tolerance is profound. Finally, a combined therapy of allotransplantation and DC-STEAP vaccination effectively reduced tumor burden in TRAMP mice, underlying how this therapeutic strategy when targeted to a reliable antigen is able to restore cancer immunosurveillance

Reference Profile Correlation Reveals Estrogen-like Trancriptional Activity of Curcumin

Background: Several secondary metabolites from herbal nutrient products act as weak estrogens (phytoestrogens), competing with endogenous estrogen for binding to the estrogen receptors and inhibiting steroid converting enzymes. However, it is still unclear whether these compounds elicit estrogen dependent transcription of genes at physiological concentrations. Methods: We compare the effects of physiological concentrations (100 nM) of the two phytoestrogens Enterolactone and Quercetin and the suspected phytoestrogen Curcumin on gene expression in the breast cancer cell line MCF7 with the effects elicited by 17-beta-estradiol (E2). Results: All three phytocompounds have weak effects on gene transcription; most of the E2 genes respond to the phytoestrogens in the same direction though to a much lesser extent and in the order Curcumin > Quercetin > Enterolactone. Gene regulation induced by these compounds was low for genes strongly induced by E2 and similar to the latter for genes only weakly regulated by the classic estrogen. Of interest with regard to the treatment of menopausal symptoms, the survival factor Birc5/survivin and the oncogene MYBL1 are strongly induced by E2 but only marginally by phytoestrogens. Conclusion: This approach demonstrates estrogenic effects of putative phytoestrogens at physiological concentrations and shows, for the first time, estrogenic effects of Curcumin. Copyright (C) 2010 S. Karger AG, Base

Changes in the expression of extracellular regulated kinase (ERK 1/2) in the R6/2 mouse model of Huntington's disease after phosphodiesterase IV inhibition

The mitogen-activated protein kinases (MAPKs) superfamily comprises three major signaling pathways: the extracellular signal-regulated protein kinases (ERKs), the c-Jun N-terminal kinases or stress-activated protein kinases (JNKs/SAPKs) and the p38 family of kinases.ERK 1/2 signaling has been implicated in a number of neurodegenerative disorders, including Huntington's disease (HD). Phosphorylation patterns of ERK 1/2 and JNK are altered in cell models of HD. In this study, we aimed at studying the correlations between ERK 1/2 and the neuronal vulnerability to HD degeneration in the R6/2 transgenic mouse model of HD. Single and double-label immunofluorescence for phospho-ERK (pERK, the activated form of ERK) and for each of the striatal neuronal markers were employed on perfusion-fixed brain sections from R6/2 and wild-type mice. Moreover, Phosphodiesterase 4 inhibition through rolipram was used to study the effects on pERK expression in the different types of striatal neurons. We completed our study with western blot analysis. Our study shows that pERK levels increase with age in the medium spiny striatal neurons and in the parvalbumin interneurons, and that rolipram counteracts such increase in pERK. Conversely, cholinergic and somatostatinergic interneurons of the striatum contain higher levels of pERK in the R6/2 mice compared to the controls. Rolipram induces an increase in pERK expression in these interneurons. Thus, our study confirms and extends the concept that the expression of phosphorylated ERK 1/2 is related to neuronal vulnerability and is implicated in the pathophysiology of cell death in HD. (C) 2012 Elsevier Inc. All rights reserved

African Journal of Pharmacy and Pharmacology Full Length Reseach Paper Synergic effect of associated green, red and brown Brazilian propolis extract onto Streptococcus mutans and Streptococcus sanguinis

Propolis is an organotherapeutic product collected by honeybees and has relevant pharmacological properties, highlighting the high antimicrobial activity. This study aimed to evaluate in vitro the synergistic effect between three ethanol extract of different Brazilian propolis samples: gree

Six-transmembrane epithelial antigen of the postate (STREAP): a potential target of immunotherapy of prostate cancer.

Immunotherapy has been proposed as a complementary or alternative therapy for the treatment of advanced prostate cancer (PC), one of the leading causes of tumor-related mortality in men. From different approaches that have been tested in recent years, it is now becoming more evident that the choice of the appropriate antigen to target is crucial for the best outcome. Generally tumor-associated antigens (TAAs) undergo peripheral tolerance during tumor progression, which dampens the efficacy of vaccination protocols. It can be hypothesized that the kinetic and depth of immune tolerance varies depending on the timing and relative expression of the TAA. These differences may represent a key for successful immunotherapy approaches even in patients with advanced disease. Aim of my thesis was to investigate the dynamics of CD8+ T cells specific for normal tissue antigens over-expressed during the spontaneous tumor development and progression in the transgenic adenocarcinoma of the mouse prostate (TRAMP) mice, a primary model of human PC. We have found that Prostate Stem Cell Antigen (PSCA) and Six-Transmembrane Epithelial Antigen of the Prostate (STEAP), two well known PC-associated antigens, behave differently in term of immunological response when compared with the transgenic Tag IV antigen, which drives oncogenesis in TRAMP mice. While a dendritic cells (DC)-based immunization was able to elicit measurable immune responses for all three antigens in young males affected by mouse prostate intraepithelial neoplasia (mPIN), aged mice affected by PC progressively lost immunity against Tag IV and in part for PSCA, but not against STEAP. The findings correlated with the amount of antigens expressed in the prostate, therefore suggesting that tolerance against this type of TAA follows the same rule of that induced for tissue-associated antigens in peripheral tissues: the more the antigen is expressed the more tolerance is profound. Finally, a combined therapy of allotransplantation and DC-STEAP vaccination effectively reduced tumor burden in TRAMP mice, underlying how this therapeutic strategy when targeted to a reliable antigen is able to restore cancer immunosurveillance

Astrocyte: physiology and pathology

A team of authors from prestigious academic schools contributed to draw up a project that would give a detailed account of astrocyte's morphology and physiology, examining thoroughly all the astrocyte's types; giving an accurate description of their morphology, location, function in the brain; and illustrating their physiology and pathology in terms of dealing with neurons through ""gliotransmitters,"" ionic channels, and membrane receptors expression. This book gives an overview of the crucial role of astrocytes in the physiology of the CNS and in the pathogenesis of several CNS disorders suggesting that the shift from a neurocentric view to one that incorporates astrocytes in disease models for drug discovery is a critical step in renewing drug development strategies to treat neurodegenerative diseases