1,721,194 research outputs found
Role of peroxisome proliferator-activated receptor gamma and its ligands in the control of immune responses.
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Transfection of dendritic cells with RNA induces CD4- and CD8-mediated T cell immunity against renal and breast carcinomas and reveals the immunodominance of presented T cell epitopes
No full textProteasome inhibitors: antitumor effects and beyond
No full textProteasome inhibitors are emerging as effective drugs for the treatment of multiple myeloma and possibly certain subtypes of non-Hodgkin's lymphoma. Bortezomib (Velcade) is the first proteasome inhibitor proven to be clinically useful and will soon be followed by a second generation of small molecule inhibitors with improved pharmacological properties. Although it is now understood that certain types of malignancies have an exquisite dependence on a functional proteasome for their survival, the underlying reason(s) remain unclear as of now. In this context, addiction to nuclear factor-kappaB (NF-kappaB)-induced survival signals, activation of the unfolded protein response as well as a reduced proteasomal activity in differentiated plasma cells have all been proposed to justify proteasome inhibitors' activity in susceptible tissues. In addition to their anticancer properties, bortezomib and related drugs modulate inflammatory and immune responses by affecting function and survival of immune cells such as lymphocytes and dendritic cells. The present review offers an overview of the biological effects that have been involved in proteasome inhibitors' antitumor activity and suggests prospective future applications for these drugs based on their recently characterized anti-inflammatory and immunomodulatory effects
Selectivity hot-spots of sirtuin catalytic cores
No full textSirtuins are NAD(+)-dependent deacetylases with several biological roles in DNA regulation, genomic stability, metabolism, longevity and immune cell functions. Numerous disease conditions are linked to sirtuins including metabolic disorders, inflammatory and autoimmune processes and cancer. Although few specific small molecule modulators have been reported to date, the need to identify selective ligands would be crucial not only for the development of active pharmaceutical ingredients for new targeted therapies but also as a tool for dissecting the biological roles of sirtuin family members. Herein, we report a comprehensive study aimed to classify and identify the selectivity hot-spots for targeting the catalytic cores of human sirtuins using small molecule modulators. Our selectivity analysis suggests that catalytic cores can be divided into different clusters that can constitute the basis for the development of selective ligands. The ensemble of hot-spot information is expected to be helpful to devise new selective chemicals targeting sirtuin family members
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