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Tumour Targets (tumour + target)
Selected Abstracts34 In vivo tumour hypoxia and carbonic anhydrase IX expression in xenografted human renal cell carcinoma animal models using probes, 124I-G250 pet, biodistribution and immunohistochemistry immunobiodistribution, and oxygen studiesBJU INTERNATIONAL, Issue 2006N. LAWRENTSCHUK Introduction:, Hypoxia stimulates angiogenesis and has been demonstrated in tumours where it correlates with resistance to treatment and poor prognosis. We have previously demonstrated hypoxia in human Renal Cell Carcinoma (RCC). The purpose of animal models was to further evaluate oxygen levels within RCC whilst also focusing on expression of the protein carbonic anhydrase IX (CA IX). This protein is stimulated by hypoxia and involved in angiogenesis and may be a potential tumour target for imaging and future therapies. Methods:, Balb/c nude mice had human RCC (SK-RC-52) xenografted subcutaneously. Tumours were grown to different volumes with oxygen levels measured. Further groups then had the radiolabelled monoclonal antibody 124I-G250 (that binds to CA IX) injected intravenously and had Positron Emission Tomography (PET), gamma counting and oxygen studies performed on days 0,1,2,3,5,7,10 and 14 post injection. Immunohistochemistry and autoradiography was also performed. Results:, An inverse relationship between tumour volume and hypoxia within the model was established (P < 0.001). Furthermore, CA IX was expressed by tumours with maximal uptake of 124I-G250 on days 2/3 by distribution with gamma counting that could be correlated with uptake on PET imaging. Conclusions:, The xenograft model confirms human RCC are hypoxic. Also, that the level of hypoxia is inversely proportional to tumour sise. A correlation was made between PET scanning with 124I-G250 and biodistribution within tumours by gamma counting confirming CAIX as an imaging and potential therapeutic target in RCC. [source] Monocytes in the rat: Phenotype and function during acute allograft rejectionIMMUNOLOGICAL REVIEWS, Issue 1 2001Birte Steiniger Summary: Cells of the monocyte/macrophage system originate from the bone marrow, reach the organs via the blood, immigrate through post-capillary venules and further differentiate into organ-specific tissue macrophages. In rats and other species, activated monocytes/macrophages aggravate autoimmune reactions, rejection of non-vascularized allografts and chronic allograft rejection. It is very likely that they also contribute to acute allograft destruction. So far it has been impossible to distinguish the function of monocytes from that of macrophages, because cell phenotypes and their alterations upon activation are ill-defined. We have thus begun to characterize the ex vivo phenotype and function of rat monocytes in the normal state and during renal allograft rejection. Monocytes are recovered from both the central and the marginal blood pool by perfusing either the recipient's circulation or the allograft vasculature. Rat monocytes have a unique surface phenotype. During allograft rejection or after infusion of interferon-, they up-regulate class II MHC molecules, CD161 (NKR-P1A), CD62L and CD8, while CD4 and CD43 are down-modulated. Activated perfusate monocytes exert increased in vitro cytotoxicity against tumour targets, which differs from that of NK cells. We speculate that activated monocytes contribute to kidney allograft destruction by directly damaging endothelial cells or by promoting intravascular coagulation. [source] Enhancement of natural killer cell activity of aged mice by modified arabinoxylan rice bran (MGN-3/Biobran)JOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 12 2004Mamdooh Ghoneum The present study is aimed to examine the possibility of enhancement of natural killer (NK) cell activity in aged C57BL/6 and C3H mice using MGN-3, a modified arabinoxylan from rice bran. Intraperitoneal injection of MGN-3 (10 mg kg,1 per day) caused a remarkable increase in the peritoneal NK activity as early as 2 days (35.2 lytic units), and the level remained elevated through day 14. The control aged mice had a level of 5.8 lytic units. Enhancement in NK activity was associated with an increase in both the binding capacity of NK cells to tumour targets and in the granular content as measured by BLT-esterase activity. Treatment did not alter the percentage of peritoneal NK cells. Data showed that peritoneal macrophages inhibit NK activity. In conclusion, MGN-3 enhances murine NK activity of aged mice and may be useful for enhancing NK function in aged humans. [source] Fusion of dendritic cells with multiple myeloma cells results in maturation and enhanced antigen presentationBRITISH JOURNAL OF HAEMATOLOGY, Issue 5 2005Baldev Vasir Summary Dendritic cells (DCs) are potent antigen-presenting cells that are uniquely capable of inducing primary immune responses. Although tumour cells may directly inhibit DC maturation, exposure to tumour products may also result in their activation. Fusions of cancer cells and DCs are being explored as cancer vaccines. The effect of tumour cell fusion on DC maturation and their functional characteristics has not been defined. In the present study, immature and mature DC generated from human CD34+ and peripheral blood precursors were fused to multiple myeloma cells in the presence of polyethylene glycol. Fusion of both immature and mature DCs with tumour cells resulted in an activated phenotype. In this regard, fusion cells expressed interleukin-12, a cytokine essential for the induction of T-helper cell type 1 immunity. In contrast to immature DCs, fusion cells also strongly expressed CC-chemokine receptor R7, which is responsible for DC migration to draining lymph nodes. Fusions generated with both immature and mature DCs also potently stimulated T-cell expression of , -interferon and cytotoxic T lymphocyte killing of tumour targets. These findings demonstrate that tumour cell fusion induces DC maturation and the development of an activated phenotype necessary for their effectiveness as cancer vaccines. [source] | ||||||||||