1,721,009 research outputs found
Six-transmembrane epithelial antigen of the postate (STREAP): a potential target of immunotherapy of prostate cancer.
Get PDFImmunotherapy 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
Neurogenesis from denial to in adult CNS: opportunities and challenges for therapy
No full textThe discovery of neurogenesis and neural stem cells (NSC) in the adult CNS has overturned a long-standing and deep-routed "dogma" in neuroscience, established at the beginning of the 20th century. This dogma lasted for almost 90 years and died hard when NSC were finally isolated from the adult mouse brain. The scepticism in accepting adult neurogenesis has now turned into a rush to find applications to alleviate or cure the devastating diseases that affect the CNS. Here we highlight a number of methodological, technical and conceptual drawbacks responsible for the historical denial of adult neurogenesis. Furthermore, we discuss old and new issues that need to be faced before NSC or endogenous neurogenesis can safely enter into the doctor's bag for therapies. © 2008 Wiley Periodicals, Inc
Introduzione alla neurobiologia. Meccanismi di sviluppo, funzione e malattia del sistema nervoso centrale
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The end of the central dogma of neurobiology: Stem cells and neurogenesis in adult CNS
No full textUntil the 1990s, neurologists were practising their profession under the doctrine established in the late 19th to early 20th century by the prominent histologist Ramon y Cajal: "Once the development was ended, the founts of growth and regeneration of the axons and dendrites dried up irrevocably. In the adult centers, the nerve paths are something fixed, ended, and immutable. Everything may die, nothing may be regenerated. It is for the science of the future to change, if possible, this harsh decree." Similarly, Giulio Bizzozero, the most prominent Italian histologist and mentor of Camillo Golgi, classified the tissues of the human body into "labile, stable and perennial". Among the latter were the nerve cells, believed to be unable to proliferate in the postnatal brain. This classification was taught until a few years ago to generations of medical students and biologists all over the world. We have investigated the historical, methodological and technical reasons why this "central dogma of neurology", so influential in clinical and experimental neurology, has lasted so long. We examined how this dogma was broken and who contributed, and the difficulties encountered by the "heretical" researchers who contributed to this goal, especially between the 1960s and the early 1990s, when at last neurogenesis in the adult brain could no longer be denied. Finally, we propose that the understanding of the mechanisms underlying various neurological diseases and the interpretations of clinical syndromes, as well as the design of new therapies, are being revolutionised by the breaking of this dogma and the discovery of the presence of neural stem cells in the adult brain. © Springer-VerlagItalia 2006
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