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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent studies show that AC133-a hematopoietic stem cell antigen, when coex-pressed with endothelial markers, identifies a population of endothelial precursor cells (EPCs) in peripheral blood that function in tumor vasculogenesis in animals. Little is known about whether EPCs contribute to human tumor vasculogenesis. We attempted to determine if, through increased peripheral expression of AC133 or endothelial markers previously associated with EPCs,VEGFR-2 and Tie-2, we could detect an EPC response in the blood of patients with breast carcinoma. Thirty patients were segregated based on their breast biopsy histology into infiltrating carcinoma, DCIS and control groups. Using Real Time PCR, we measured the expression of the aforementioned markers in reverse transcribed RNA extracts from preoperative peripheral blood specimens. The cancer patients had significantly elevated Tie-2 expression with the highest levels associated with infiltrating carcinoma. Our data suggest increased circulating EPC markers in tumor patients, but further study of this cell population is needed to better define its role in tumor vasculogenesis.
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PMID:Blood markers for vasculogenesis increase with tumor progression in patients with breast carcinoma. 1287 60

Most current research on human brain tumors is focused on the molecular and cellular analysis of the bulk tumor mass. However, there is overwhelming evidence in some malignancies that the tumor clone is heterogeneous with respect to proliferation and differentiation. In human leukemia, the tumor clone is organized as a hierarchy that originates from rare leukemic stem cells that possess extensive proliferative and self-renewal potential, and are responsible for maintaining the tumor clone. We report here the identification and purification of a cancer stem cell from human brain tumors of different phenotypes that possesses a marked capacity for proliferation, self-renewal, and differentiation. The increased self-renewal capacity of the brain tumor stem cell (BTSC) was highest from the most aggressive clinical samples of medulloblastoma compared with low-grade gliomas. The BTSC was exclusively isolated with the cell fraction expressing the neural stem cell surface marker CD133. These CD133+ cells could differentiate in culture into tumor cells that phenotypically resembled the tumor from the patient. The identification of a BTSC provides a powerful tool to investigate the tumorigenic process in the central nervous system and to develop therapies targeted to the BTSC.
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PMID:Identification of a cancer stem cell in human brain tumors. 1452 5

Infantile hemangioma is an endothelial tumor that grows rapidly after birth but slowly regresses during early childhood. Initial proliferation of hemangioma is characterized by clonal expansion of endothelial cells (ECs) and neovascularization. Here, we demonstrated mRNA encoding CD133-2, an important marker for endothelial progenitor cells (EPCs), predominantly in proliferating but not involuting or involuted hemangioma. Progenitor cells coexpressing CD133 and CD34 were detected by flow cytometry in 11 of 12 proliferating hemangioma specimens from children 3 to 24 months of age. Furthermore, in 4 proliferating hemangiomas, we showed that 0.14% to 1.6% of CD45(-) nucleated cells were EPCs that coexpressed CD133 and the EC marker KDR. This finding is consistent with the presence of KDR(+) immature ECs in proliferating hemangioma. Our results suggest that EPCs contribute to the early growth of hemangioma. To our knowledge, this is the first study to show direct evidence of EPCs in a human vascular tumor.
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PMID:Endothelial progenitor cells in infantile hemangioma. 1457 53

Pediatric brain tumors are significant causes of morbidity and mortality. It has been hypothesized that they derive from self-renewing multipotent neural stem cells. Here, we tested whether different pediatric brain tumors, including medulloblastomas and gliomas, contain cells with properties similar to neural stem cells. We find that tumor-derived progenitors form neurospheres that can be passaged at clonal density and are able to self-renew. Under conditions promoting differentiation, individual cells are multipotent, giving rise to both neurons and glia, in proportions that reflect the tumor of origin. Unlike normal neural stem cells, however, tumor-derived progenitors have an unusual capacity to proliferate and sometimes differentiate into abnormal cells with multiple differentiation markers. Gene expression analysis reveals that both whole tumors and tumor-derived neurospheres express many genes characteristic of neural and other stem cells, including CD133, Sox2, musashi-1, bmi-1, maternal embryonic leucine zipper kinase, and phosphoserine phosphatase, with variation from tumor to tumor. After grafting to neonatal rat brains, tumor-derived neurosphere cells migrate, produce neurons and glia, and continue to proliferate for more than 4 weeks. The results show that pediatric brain tumors contain neural stem-like cells with altered characteristics that may contribute to tumorigenesis. This finding may have important implications for treatment by means of specific targeting of stem-like cells within brain tumors.
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PMID:Cancerous stem cells can arise from pediatric brain tumors. 1464 3

Most current research on human brain tumors is focused on the molecular and cellular analysis of the bulk tumor mass. However, evidence in leukemia and more recently in solid tumors such as breast cancer suggests that the tumor cell population is heterogeneous with respect to proliferation and differentiation. Recently, several groups have described the existence of a cancer stem cell population in human brain tumors of different phenotypes from both children and adults. The finding of brain tumor stem cells (BTSCs) has been made by applying the principles for cell culture and analysis of normal neural stem cells (NSCs) to brain tumor cell populations and by identification of cell surface markers that allow for isolation of distinct tumor cell populations that can then be studied in vitro and in vivo. A population of brain tumor cells can be enriched for BTSCs by cell sorting of dissociated suspensions of tumor cells for the NSC marker CD133. These CD133+ cells, which also expressed the NSC marker nestin, but not differentiated neural lineage markers, represent a minority fraction of the entire brain tumor cell population, and exclusively generate clonal tumor spheres in suspension culture and exhibit increased self-renewal capacity. BTSCs can be induced to differentiate in vitro into tumor cells that phenotypically resembled the tumor from the patient. Here, we discuss the evidence for and implications of the discovery of a cancer stem cell in human brain tumors. The identification of a BTSC provides a powerful tool to investigate the tumorigenic process in the central nervous system and to develop therapies targeted to the BTSC. Specific genetic and molecular analyses of the BTSC will further our understanding of the mechanisms of brain tumor growth, reinforcing parallels between normal neurogenesis and brain tumorigenesis.
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PMID:Cancer stem cells in nervous system tumors. 1537 86

Bone-marrow-derived, circulating endothelial precursor cells contribute to neoangiogenesis in various diseases. Rapamycin has recently been shown to have anti-angiogenic effects in an experimental tumor model. Our group has developed a culture system that allows expansion and endothelial differentiation of human CD133(+) precursor cells. We could show by PCR analysis that mTOR, the rapamycin-binding protein, was expressed in fresh CD133(+) cells, in expanded cells after 28 days, and in differentiated endothelial cells. Rapamycin inhibited proliferation of CD133(+) cells dose dependently at similar concentrations as hematopoietic Jurkat or HL-60 cells. Apoptosis was induced by rapamycin after 48 h of treatment, which could be reduced by preincubation with FK 506. Furthermore, the development of adherent endothelial cells from expanded CD133(+) cells was dose dependently inhibited. Expression of endothelial antigens CD144 and von Willebrand factor on differentiating endothelial precursors was reduced by rapamycin. In summary, rapamycin inhibits proliferation and differentiation of human endothelial precursor cells underlining its anti-angiogenic effects.
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PMID:Rapamycin inhibits proliferation and differentiation of human endothelial progenitor cells in vitro. 1538 15

Human prominin-1/CD133 has been reported to be expressed in neural and hematopoietic stem/progenitor cells and in embryonic, but not adult, epithelia. This lack of detection of human prominin-1, as defined by its glycosylation-dependent AC133 epitope, is surprising given the expression of the murine ortholog in adult epithelia. Here, we demonstrate, by using a novel prominin-1 antiserum (alphahE2), that the decrease of AC133 immunoreactivity observed during differentiation of the colonic adenocarcinoma-derived Caco-2 cells is not paralleled by a down-regulation of prominin-1. We have also shown that alphahE2 immunoreactivity, but not AC133 immunoreactivity, is present in several adult human tissues, such as kidney proximal tubules and the parietal layer of Bowman's capsule of juxtamedullary nephrons, and in lactiferous ducts of the mammary gland. These observations suggest that only the AC133 epitope is down-regulated upon cell differentiation. Furthermore, alphahE2 immunoreactivity has been detected in several kidney carcinomas derived from proximal tubules, independent of their grading. Interestingly, in one particular case, the AC133 epitope, which is restricted to stem cells in normal adult tissue, was up-regulated in the vicinity of the tumor. Our data thus show that (1) in adults, the expression of human prominin-1 is not limited to stem and progenitor cells, and (2) the epitopes of prominin-1 might be useful for investigating solid cancers.
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PMID:Prominin-1/CD133, a neural and hematopoietic stem cell marker, is expressed in adult human differentiated cells and certain types of kidney cancer. 1555 21

Cancer stem cells are presently viewed as carriers of the growth initiating potential, repopulation capability and drug resistance in tumors. However, many of these fundamental properties of cancer are host-related, modified by cell-cell interactions and/or dependent on angiogenesis. Indeed, it is well established that co-injection of cancer cells with their irradiated (mitotically dead) counterparts, or with Matrigel can significantly increase their tumor forming capacity (i.e. the attribute presently associated with cancer cell 'stemness'). Similarly transfection of angiogenic factors (e.g., VEGF/VPF) can promote such capacity in certain cell lines. Moreover, injection site (e.g., orthotopic vs. ectopic) may significantly modulate tumor take in experimental settings. These observations cannot be reconciled with the paradigm that tumor initiation potential is a fixed, constitutive and cell autonomous feature of a subset of cancer cells expressing stem cell markers (e.g., CD133, Sca1 and other). Instead, it is proposed here that 'stemness' in cancer (perhaps unlike in normal self renewing tissues), rather then being assigned to a particular readily identifiable cell subset, could be a property of interactive clusters of cancer cells (perhaps including, but not limited to cells with stem cell markers). Such 'multicellular units' would become equipped with properties experimentally perceived as 'stemness', i.e. the capacity to initiate tumor growth, when they express the capacity to induce angiogenesis. It is also postulated here that, while the pursuit of subsets of cancer cells harbouring stem cell markers has been fascinating and revealing, due to aforementioned limitations of the present stem cell concept and presumed intractability (e.g., mutability) of such cells, further therapeutic promise may reside in a better definition of 'multicellular angiogenic cancer stem units'.
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PMID:Is cancer stem cell a cell, or a multicellular unit capable of inducing angiogenesis? 1622 60

In multiple myeloma (MM), circulating endothelial cells (CECs) represent a vascular marker of angiogenesis and may reflect tumor mass. In this report, we showed that, in 5 MM patients with 13q14 deletion, CECs carried the same chromosome aberration as the neoplastic plasma cells (11%-32% of CECs with 13q14 deletion). Most of the CECs displayed immunophenotypic features of endothelial progenitor cells as they expressed CD133, a marker gradually lost during endothelial differentiation and absent on mature endothelial cells. To the contrary, in 3 patients with monoclonal gammopathy of undetermined significance and 13q14 deletion, CECs were cytogenetically normal and had a mature immunophenotype. In MM CECs, immunoglobulin genes were clonally rearranged. These findings suggest a possible origin of CECs from a common hemangioblast precursor that can give rise to both plasma cells and endothelial cells and point to a direct contribution of MM-derived CECs to tumor vasculogenesis and possibly to the spreading and progression of the disease.
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PMID:Neoplastic circulating endothelial cells in multiple myeloma with 13q14 deletion. 1706 26

Spermatocytic seminomas are solid tumors found solely in the testis of predominantly elderly individuals. We investigated these tumors using a genome-wide analysis for structural and numerical chromosomal changes through conventional karyotyping, spectral karyotyping, and array comparative genomic hybridization using a 32 K genomic tiling-path resolution BAC platform (confirmed by in situ hybridization). Our panel of five spermatocytic seminomas showed a specific pattern of chromosomal imbalances, mainly numerical in nature (range, 3-24 per tumor). Gain of chromosome 9 was the only consistent anomaly, which in one case also involved amplification of the 9p21.3-pter region. Parallel chromosome level expression profiling as well as microarray expression analyses (Affymetrix U133 plus 2.0) was also done. Unsupervised cluster analysis showed that a profile containing transcriptional data on 373 genes (difference of > or = 3.0-fold) is suitable for distinguishing these tumors from seminomas/dysgerminomas. The diagnostic markers SSX2-4 and POU5F1 (OCT3/OCT4), previously identified by us, were among the top discriminatory genes, thereby validating the experimental set-up. In addition, novel discriminatory markers suitable for diagnostic purposes were identified, including Deleted in Azospermia (DAZ). Although the seminomas/dysgerminomas were characterized by expression of stem cell-specific genes (e.g., POU5F1, PROM1/CD133, and ZFP42), spermatocytic seminomas expressed multiple cancer testis antigens, including TSP50 and CTCFL (BORIS), as well as genes known to be expressed specifically during prophase meiosis I (TCFL5, CLGN, and LDHc). This is consistent with different cells of origin, the primordial germ cell and primary spermatocyte, respectively. Based on the region of amplification defined on 9p and the associated expression plus confirmatory immunohistochemistry, DMRT1 (a male-specific transcriptional regulator) was identified as a likely candidate gene for involvement in the development of spermatocytic seminomas.
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PMID:Genomic and expression profiling of human spermatocytic seminomas: primary spermatocyte as tumorigenic precursor and DMRT1 as candidate chromosome 9 gene. 1639 42


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