Glioblastoma multiforme (GBM) is an aggressive, malignant, and lethal brain tumor, resistant to all current forms of treatment. The rapidly emerging focus on cancer stem cells embodies a paradigm shift in our understanding of tumor pathogenesis, while the development of powerful genome-wide screening techniques has provided cause for optimism related to the development of more reliable therapies primarily targeting GBM stem cells (GBMSCs). There are promising mounting data on providing new molecular targets and predictive markers of response, leading to more effective therapies of GBM, guided by patient-specific genetic and epigenetic profiling. However, the achievement of efficient GBMSC targeting also requires an adequate understanding of the unique microenvironment, and the relationship with the immune system in the central nervous system (CNS) and CNS tumors. The endogenous immune regulation is likely to limit or abrogate the efficacy of the host's immune response, as well as the developed immunotherapeutic strategies at present. Therefore, a comprehensive understanding of the mechanisms underlying the GBM-induced immunosuppression is indispensable. This review presents a summary of the present knowledge both on GBMSCs and the GBM, and/or GBMSC-related mechanisms of developing both local and systemic immunosuppression, of which an understanding may lead to the development of the novel and effective therapeutic strategies.
Residual tumors and chemotherapy treatment were more frequent in patients with positive CD117 expression. The outcome was dependent on the type of OC; a worse outcome, including a shorter survival, was documented in the mucinous and endometrioid OC cases.
Background and objectives: Dysregulation of TGF-β signaling plays multiple roles in cancer development and progression. In the canonical TGF-β pathway, TGF-β regulates the expression of hundreds of target genes via interaction with Smads, signal transducers and transcriptional modulators. We evaluated the association of TGF-β1, Smad2, and Smad4, the key components of canonical TGFβ pathway, with clinicopathologic characteristics of urothelial bladder cancer, and assessed their prognostic value in prediction of patients’ outcome. Materials and Methods: Immunohistochemical analysis of TGF-β1, Smad2, and Smad4 expression was performed on 404 urothelial bladder cancer samples, incorporated in tissue microarrays. Expression status was correlated with clinicopathological and follow-up data. The median follow-up was 61 months. Results: High expression of TGF-β1, Smad2, and Smad4 was detected in 68.1%, 31.7% and 45.2% of the tumors, respectively. TGF-β1 overexpression was significantly associated with high tumor grade, and advanced pathologic stage (p < 0.001, respectively). Conversely, high Smad2 and Smad4 expression was linked to low tumor grade (p = 0,003, p = 0.048, respectively), and low tumor stage (p < 0.001, p = 0.003, respectively). Smad2 showed an inverse correlation with variant morphology and divergent differentiation of urothelial tumors (p = 0.014). High TGF-β1 correlated directly, while Smad2 and Smad4 correlated inversely to cancer-specific death (p = 0.043, p = 0.003, and p = 0.022, respectively). There was a strong relationship between Smad2 and Smad4 expression (p < 0.001). Survival analyses showed that high Smad2 and Smad4 expression was associated with longer overall survival (p = 0.003, p = 0.034, respectively), while in multivariate regression analysis TGF-β1 manifested as an independent predictor of poor outcome. Conclusions: Unraveling the complex roles and significance of TGF-β signaling in urothelial bladder cancer might have important implications for therapy of this disease. Assessment of TGF-β pathway status in patients with urothelial bladder cancer may provide useful prognostic information, and identify patients that could have the most benefit from therapy targeting TGF-β signaling cascade.
Abstract:Objectives: The nuclear factor κB regulates the expression of genes involved in many processes that play a key role in the development and progression of cancer. The aim of this study was to examine the infl uence of the alpha lipoic acid in the chemoprevention of colon and cervix carcinoma in vitro. Background: In recent years, special attention has been paid to the potential chemopreventive properties of antioxidants. There are no published data on the impact of alpha lipoc acid of chemoprevention of cervix and colon cancer. Methods: We examined the effect of alpha lipoic acid alone or in combination with cisplatin and 5-fl uorouracil on proliferation of the two cell lines, HeLa (human cervical carcinoma cells) and Caco-2 (human colon cancer cells) by MTT test. The measurement of the level of transcription factor NF-κB was also performed in the cells of both cell lines. Results: At least one of the mechanisms of the antiproliferative and/or cytotoxic effect of alpha lipoic acid on Caco-2 and HeLa cells at high concentrations, the transcription factor NF-κB, may be involved, as well as the products of transcription of genes that are under its control. Conclusion: The alpha lipoic acid has proven to be a promising candidate in the combat arena against cancer (Tab. 4, Ref. 31). Text in PDF www.elis.sk.
The last decade witnessed an explosion of interest in cancer stem cells (CSCs). The realization of epithelial ovarian cancer (EOC) as a CSC-related disease has the potential to change approaches in the treatment of this devastating disease dramatically. The etiology and early events in the progression of these carcinomas are among the least understood of all major human malignancies. Compared to the CSCs of other cancer types, the identification and study of EOC stem cells (EOCSCs) is rather difficult due to several major obstacles: the heterogeneity of tumors comprising EOCs, unknown cells of origin, and lack of knowledge considering the normal ovarian stem cells. This poses a major challenge for urgent development in this research field. This review summarizes and evaluates the current evidence for the existence of candidate normal ovarian epithelial stem cells as well as EOCSCs, emphasizing the requirement for a more definitive laboratory approach for the isolation, identification, and enrichment of EOCSCs. The present review also revisits the ongoing debate regarding other cells and tissues of origin of EOCs, and discusses early events in the pathogenesis of this disease. Finally, this review discusses the signaling pathways that are important regulators of candidate EOCSC maintenance and function, their potential role in the distinct pathogenesis of different EOC subtypes, as well as potential mechanisms and clinical relevance of EOCSC involvement in drug resistance.
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