Navegando por Palavras-chave "cancer stem cell"
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- ItemSomente MetadadadosCancer stem cell genomics: the quest for early markers of malignant progression(Expert Reviews, 2009-09-01) Okamoto, Oswaldo Keith [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Biologically distinct populations of neoplastic stem cells have been identified in a variety of human cancers, in which they are associated with the initial steps of tumorigenesis. the intrinsic properties of self-renewal, clonogenicity and multipotency, along with a longer half-life within the body, may render normal adult stem cells more prone to accumulate genetic mutations leading to neoplastic transformation, as predicted by the cancer stem cell hypothesis. Tumor formation is also associated with the pluripotency of embryonic stem cells and may be induced as a consequence of complete dedifferentiation of mature cells, as recently reported for induced pluripotent stem cells. the tumor-initiating cell phenotype may result from genetic alterations affecting the expression of critical genes regulating typical stem cell processes such as self-renewal and pluripotency, in addition to genes determining stem cell senescence or longevity. Detailed genome-wide analysis of cancer stem cells and respective normal counterparts will help elucidate the cellular and molecular nature of tumors, providing fundamental information about the initial steps toward malignant transformation. Devising ways of detecting such genetic and epigenetic alterations and cell populations displaying them would allow medical interventions at the early phases of cancer development, thereby improving the chances of favorable clinical outcomes.
- ItemSomente MetadadadosExpression of HOXC9 and E2F2 are up-regulated in CD133+cells isolated from human astrocytomas and associate with transformation of human astrocytes(Elsevier B.V., 2007-07-01) Okamoto, Oswaldo K.; Oba-Shinjo, Sueli M.; Lopes, Luciana; Marie, Suely K. Nagahashi; Universidade Federal de São Paulo (UNIFESP); Inst Israelita Ensino & Pesquisa Albert EinsteinComparative analysis of cancer stem cells with their neoplastic and non-neoplastic counterparts should help better understand the underlying molecular events leading to transformation and tumor dissemination. Here, we report a molecular signature comprised by genes with exclusive aberrant expression in CD133+ cells, a reported subpopulation of tumorigenic stem-like cells, isolated from human glioblastomas. Microarrays covering 55,000 transcripts were used to compare gene expression profiles in purified subpopulations of CD133+ and CD133- GBM cells. Sixteen genes, many of which not previously associated with astrocytomas, were found aberrantly expressed in CD133+ cells, but not in CD133-, when compared with corresponding non-neoplastic controls. Up-regulation of two of such genes, E2F2 and HOXC9, was detected in a set of 54 astrocytomas of different grades and significantly associated with malignancy. Due to their distinctive expression in CD133+ cells, the use of E2F2 and HOXC9 as therapeutic targets for tumor eradication is suggested. (c) 2007 Elsevier B.V. All rights reserved.
- ItemSomente MetadadadosPrognostic significance of CD24 and claudin-7 immunoexpression in ductal invasive breast cancer(Spandidos Publ Ltd, 2012-01-01) Bernardi, M. A.; Logullo, Angela Flavia [UNIFESP]; Pasini, F. S.; Nonogaki, S.; Blumke, C.; Soares, F. A.; Brentani, M. M.; Universidade de São Paulo (USP); AC Camargo Hosp; Universidade Federal de São Paulo (UNIFESP); Adolfo Lutz Inst; Uninove UnivThis study aimed to identify the CD24 and CD44 immunophenotypes within invasive ductal breast carcinoma (I DC) subgroups defined by immunohistochesmistry markers and to determine its influence on prognosis as well as its association with the expression of Ki-67, cytokeratins (CK5 and CK 18) and claudin-7. Immunohistochemical expression of CD44 and CD24 alone or in combination was investigated in 95 IDC cases arranged in a tissue microarray (TMA). the association with subgroups defined as luminal A and B; HER2 rich and triple negative, or with the other markers and prognosis was analyzed. CD44(+)/CD24(-) and CD44(-)/CD24(+) were respectively present in 8.4% and 16.8% of the tumors, a lack of both proteins was detected in 6.3%, while CD441(-)/CD24(+) was observed in 45.3% of the tumors. Although there was no significant correlation between subgroups and different phenotypes, the CD44(+)/CD24(-) phenotype was more common in the basal subgroups but absent in HER2 tumors, whereas luminal tumors are enriched in CD44(-)/CD24(+) and CD44(+)/CD24(+) cells. the frequency of CD44(+)/CD24(-) or CD44(-)/CD24(+) was not associated with clinical characteristics or biological markers. There was also no significant association of these phenotypes with the event free (DFS) and overall survival (OS). Single CD44(+) was evident in 57.9% of the tumors and was marginally associated to grading and not to any other tumor characteristics as well as OS and DFS. CD24(+) was positive in 74.7% of the tumors, showing a significant association with estrogen receptor, progesterone receptor and Ki-67 and a marginal association with CKI8 and claudin-7. Expression of claudin-7 and Ki-67 did not associate with the cancer subgroups, while a positive association between CK18 and the luminal subgroups was found (P=0.03). CK5, CK18 and Ki-67 expression had no influence in OS or DFS. Single CD24(+) (P=0.07) and claudin-7 positivity (P=0.05) were associated with reduced time of recurrence, suggesting a contribution of these markers to aggressiveness of breast cancer.
- ItemSomente MetadadadosTargeting cancer stem cells with monoclonal antibodies: a new perspective in cancer therapy and diagnosis(Expert Reviews, 2008-07-01) Okamoto, Oswaldo Keith [UNIFESP]; Perez, Jose Fernando [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)This review discusses some of the impacts that biotechnology, genomics and nanotechnology convergence should have on future cancer management, in particular, the development of innovative diagnostic and therapeutic approaches based on monoclonal antibodies (mAbs) and cancer stem cells. Emergent therapeutic strategies in cancer have been focusing on the use of mAbs to stimulate an immune response against tumors, to block signaling pathways, or to refine delivery of cytotoxic agents. Now that cancer stem cells are being identified and characterized in different tumor types, their relevance to cancer physiopathology is becoming evident, making them natural targets for mAb development. Cancer stem cells are postulated to be responsible for tumor development, metastasis and relapse after conventional therapies. Therefore, mAbs targeting specific antigens and related pathways altered in cancer stem cells should facilitate earlier diagnosis through molecular imaging techniques and more efficient destruction of tumor initiating cells, thus improving clinical outcome.
- ItemSomente MetadadadosUnderstanding myeloma cancer stem cells(Future Medicine Ltd, 2013-12-01) Pascutti, Fabio [UNIFESP]; Cunha, Lucas Leite [UNIFESP]; Rizzatti, Edgar Gil; Colleoni, Gisele W. B. [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Grp Fleury