International journal of cancer. Journal international du cancer
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In human gliomas, self-renewing and tumor-initiating cells are characterized by the expression marker CD133. Although, widely used, the validity of CD133 is debated as recent data show that CD133(+) and CD133(-) cells share similar stemness and tumorigenic properties. To clarify this "CD133 controversy", we reexamined the methods of purification and the stem behavior of both CD133 compartments in fresh gliomas and gliomasphere cultures. ⋯ In contrast, when purified by fluorescence activating cell sorting, a specific expression and enrichment of CD133 was successfully observed in fresh human gliomas and gliomasphere cultures. However, neither the expression of stemness genes nor the long-term self-renewal capacities of CD133(+) and CD133(-) cells were significantly different, even after fresh isolation. Altogether, our data show that purification of CD133(+) glioma cells using hCD133-microbeads presents a lack of specificity and demonstrate that the use of CD133 as a unique glioma stem cell marker is likely not sufficient to tag the whole self-renewing tumor cell reservoir.
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The current study was designed to critically evaluate the notion that cancer stem cell (CSC)-like cells constitute a subpopulation of cells within experimental gliomas. Virtually all cells within the N29 and N32 rat glioma models homogenously expressed CD133, the stem/progenitor marker nestin as well as the neural lineage markers glial fibrillary acidic protein, betaIII-tubulin, and CNPase in vitro. The phenotype was largely retained on exposure to conditions promoting differentiation in vitro and after intracranial implantation of tumor cells into syngeneic hosts. ⋯ Single N29 and N32 tumor cells invariably formed clones in vitro, and intracerebral inoculation of as few as 10 adherently growing N29 and N32 tumor cells, respectively, gave rise to a tumor. These results provide an alternative view on CSC-like cells in glioma models: sphere-formation is not a prerequisite for accumulation of tumorigenic cells, and CSC-like cells do not reside within a rare subpopulation of cells in these glioma models. N29 and N32 gliomas may accordingly be used for the development of treatment strategies directed specifically against a practically pure population of brain tumor-initiating CSC-like cells.
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Review Meta Analysis
Preoperative chemoradiation versus radiation alone for stage II and III resectable rectal cancer: a systematic review and meta-analysis.
Combining chemotherapy with preoperative radiotherapy (RT) has a sound radiobiological rationale. We performed a systematic review and meta-analysis of trials comparing preoperative RT with preoperative chemoradiation (CRT) in rectal cancer patients. The Cochrane Central Register of Controlled Trials, Web of Science, Embase and Medline (Pubmed) were searched from 1975 until June 2007. ⋯ Compared to preoperative RT alone, preoperative CRT improves local control in rectal cancer but is associated with a more pronounced treatment related toxicity. The addition of chemotherapy does not benefit sphincter preservation rate or long-term survival. Future trials should address improvements in the rate of distant metastasis and overall survival by incorporating more active chemotherapy.
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We investigated whether cilengitide could amplify the antitumor effects of radiotherapy in an orthotopic rat glioma xenograft model. Cilengitide is a specific inhibitor of alphav series integrins, and acts as an antiangiogenic. U251 human glioma cells express alphavbeta3 and alphavbeta5 integrins. ⋯ Because cilengitide has a short plasma half-life (t((1/2)) approximately 20 min), antiangiogenic scheduling typically uses daily injections. We found that a single dose of cilengitide (4 mg/kg) given between 4 and 12 hr prior to radiation was sufficient to produce the same effect. Our results demonstrate that blockade of alphav integrins mediates an unanticipated rapid potentiation of radiation, and suggests possible clinical translation for glioma therapy.
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L-[3-(18)F]-alpha-methyltyrosine ((18)F-FMT) is an aminoacid tracer for positron emission tomography (PET). The aim of this study was to determine whether PET-CT with (18)F-FMT provides additional information for the preoperative diagnostic workup as compared with (18)F-FDG PET. PET-CT studies with (18)F-FMT and (18)F-FDG were performed as a part of the preoperative workup in 36 patients with histologically confirmed bronchial carcinoma, 6 patients with benign lesions and a patient with atypical carcinoid. ⋯ For the detection of pulmonary malignant tumors, (18)F-FMT PET exhibited a sensitivity of 84% whereas the sensitivity for (18)F-FDG PET was 89% (p = 0.736). (18)F-FMT PET-CT and (18)F-FDG PET-CT agreed with pathological staging in 85 and 68%, respectively (p = 0.151). (18)F-FMT uptake was closely correlated with LAT1, CD98, cell proliferation and angiogenesis. The specificity of (18)F-FMT PET for diagnosing thoracic tumors was higher than that of (18)F-FDG PET. Our results suggest that coexpression of LAT1 and CD98 in addition to cell proliferation and angiogenesis is relavant for the progression and metastasis of lung cancer.