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

Comparative 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.
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PMID:Expression of HOXC9 and E2F2 are up-regulated in CD133(+) cells isolated from human astrocytomas and associate with transformation of human astrocytes. 1758 84

A small population of stem cell-like precursors in solid tumors are linked to histological composition, progression, angiogenesis, metastasis, recurrence and drug resistance of a variety of malignant tumors. Oligoastrocytoma is the most common brain mixed glioma composed of mixed cells of oligodendroglial and astrocytic phenotypes. Identification and characterization of stem cell-like precursors in oligoastrocytoma may shed light on the oncogenesis of this unique type of tumor and assist in the design of novel therapeutic strategy. Here, tumor stem cell-like precursors were identified from primary human anaplastic oligoastrocytomas by labeling of the tumor sections with nestin and CD133. Tumor cells were cultured in vitro in stem cell medium with growth factors and the capacity of the surviving stem cell-like precursors to form tumor spheres was tested. The tumor spheres were further injected subcutaneously into nude mice to observe the contribution of stem cell-like precursors to histological composition and tumor progression. We found that primary human oligoastrocytoma tissues contained nestin+/CD133+ stem cell-like precursors. These cells differentiated into tumor cells with both oligodendroglial and astrocytic characteristics and formed tumor spheres in vitro, which upon implantation in nude mice, grew into tumor nodules containing nestin+/CD133+ cells at levels higher than in the primary tumor tissues. This study revealed for the first time that anaplastic human oligoastrocytomas contained stem cell-like precursors, which exhibit neural stem cell properties with tumorigenicity. These stem cell-like precursors may be responsible for the oligodendroglial and astrocytic components of human oligoastrocytoma and should be considered as therapeutic targets.
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PMID:Isolation and characterization of stem cell-like precursor cells from primary human anaplastic oligoastrocytoma. 1766 Aug 1

It has been well accredited that the neural stem cells (NSCs) derived from bone marrow stroma cells (BMSCs) can be used as the therapeutic application. However, their efficacy and safety in therapeutic application are uncertain. In this experiment, the trace marking and oncogenicity of NSCs derived from BMSCs (BMSCs-D-NSCs) were studied. The BMSCs were harvested by gradient centrifugation and cultured in "NSCs medium" in vitro. The verified CD133/Nestin-positive BMSCs-D-NSCs were then transplanted into nude mice to detect the oncogenicity, into the right lateral cerebral ventricle or right caudae putamen and substantia nigra to examine, whether the symptoms were improved in Parkinson's Disease (PD) models after transplantation, by both SPECT image assay of dopamine transporter (DAT) in corpus striatum and its average standard uptake value (SUVave) in corpus striatum and thalamus. Tissue samples and surviving model animals were studied at 1, 3, and 6 months post-transplantation. Before transplantation, the cells were labeled with BrdU or rAAV-GFP for the pathological sections, and with Feridex for the in vivo trace by MRI assay. The concanavalin A (ConA) agglutination test, stop-dependence test with soft agar, karyotype analysis of chromosome G zone in BMSCs-D-NSCs, and the nude mouse neoplasia test were also performed. The BrdU, rAAV-GFP or Feridex can be used as trace markers of BMSCs-D-NSCs during transplantation. The transplanted BMSCs-D-NSCs displayed neither toxicity nor neoplasia up to 6 months in vivo, but could play an important role in improving the symptoms of the animals with degenerative diseases like PD.
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PMID:Experimental study on trace marking and oncogenicity of neural stem cells derived from bone marrow. 1780 59

Cancer stem cells have been isolated from several solid tumors including prostate, colon, liver, breast, and ovarian cancer. Stem cells isolated from nervous system and prostate express CD133 antigen, which is widely used to isolate hematopoietic stem and progenitor cells. The aims of this study were to investigate the expression of the CD133-1 and CD133-2 epitopes in primary ovarian tumors and to biologically characterize CD133(+) ovarian cancer cells, also according to clinicopathologic parameters. Tissue specimens were obtained at primary surgery from 41 ovarian carcinomas; eight normal ovaries and five benign ovarian tumors were also collected. Flow cytometry with monoclonal antibodies against CD133-1 and CD133-2 epitopes was employed. FACS (fluorescence activated cell sorting) analysis enabled the selection of CD133(+) cells, whose epithelial origin was confirmed by immunofluorescence analysis with monoclonal anti-cytokeratin 7. CD133(+) cells gave rise to a 4.7 +/- 0.9-fold larger number of colonies than that documented in CD133(-) population (P < 0.001). Moreover, CD133(+) cells showed an enhanced proliferative potential compared to CD133(-) cells. The percentages of CD133-1- and CD133-2-expressing cells were significantly lower in normal ovaries/benign tumors with respect to those in ovarian carcinoma. Both the percentages of CD133-1- and CD133-2-expressing cells were significantly lower in omental metastases than in primary ovarian cancer (P = 0.009 and 0.007 for CD133-1- and CD133-2-expressing cells, respectively). There seems not to be any difference in the distribution of the percentage of CD133-1- and CD133-2-expressing cells according to clinicopathologic parameters and response to primary chemotherapy. CD133-1 and CD133-2 may be useful in order to select and enrich the population of CD133(+) ovarian tumor cells, which are characterized by a higher clonogenic efficiency and proliferative potential.
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PMID:Expression of CD133-1 and CD133-2 in ovarian cancer. 1786 44

Most clinical protocols involving adenovirus (Ad) vectors for gene therapy use a vector based on serotype 5 (Ad5). We believe that this serotype is not suitable for all gene therapy applications and that alternative vectors based on other serotypes should be developed. We have compared the ability of Ad5, Ad11p, Ad16p, and a chimpanzee Ad (CV23) to infect human low-passage brain tumor cells as well as primary glioma cells sorted into a CD133(+) and CD133(-) population. Cancer stem cells have been shown to reside in the CD133(+) population of cells in human glioma tumors and they are of considerable interest in glioma therapy. Ad16p and CV23 infected the low-passage brain tumor cell lines and also the CD133(+) and CD133(-) primary tumor cells most efficiently. Interestingly, as the passage number of the cells increased, the infection capacity of Ad5 increased significantly, whereas this was not seen for CV23. To ensure the therapeutic effect of Ad vectors on brain tumors, the vector must be capable of addressing both the CD133(+) cancer stem cells and the CD133(-) cells of the tumor. In particular, Ad16 and CV23 are meeting this challenge.
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PMID:Adenoviruses 16 and CV23 efficiently transduce human low-passage brain tumor and cancer stem cells. 1802 82

We assessed the capacity of positively selected autologous CD133(+) hematopoietic stem cells (HSCs) to reconstitute lymphomyelopoiesis in chronic lymphocytic leukemia (CLL) patients receiving myeloablative chemotherapy. Ten resistant/relapsed CLL patients underwent HSC mobilization with chemotherapy and granulocyte-colony stimulating factor (G-CSF). Positive selection of circulating CD133(+) HSCs was performed by immunomagnetic technique. Highly purified HSCs were reinfused after busulphan/melphalan myeloablative treatment. A median number of 4.2 x 10(6) CD34(+) cells/kg and of 3.14 x 10(6) CD133(+) cells/kg were collected. Immunomagnetic selection resulted in the reinfusion of a median number of 2.45 x 10(6) CD133(+) cells/kg (median purity: 94.8%; median recovery: 84%) and 2.4 x 10(6) CD34(+) cells/kg (median purity: 93%; median recovery: 71%). HSC selection resulted in a median T cell and CD19(+)/CD5(+) cell depletion of 3.85 log and 2.8 log, respectively. At the molecular level, however, 7 of 8 valuable purified HSC fractions were contaminated by leukemic cells. All CLL patients showed rapid and sustained myeloid engraftment after reinfusion of purified CD133(+) cells. Immunologic reconstitution was comparable to that routinely observed in patients reinfused with unmanipulated leukapheresis products and no late infectious complications were observed. With a median follow-up of 28 months for transplanted patients, 5 patients are in clinical complete remission, 3 are in partial remission, and 1 is in progression. In conclusion, the reinfusion of highly purified CD133(+) HSCs allowed the rapid and sustained recovery of hematopoiesis after myeloablative treatment in resistant/relapsed CLL patients. However, the purging potential of positive selection of CD133(+) cells is not adequate to achieve tumor-free autografts.
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PMID:Positive selection and transplantation of autologous highly purified CD133(+) stem cells in resistant/relapsed chronic lymphocytic leukemia patients results in rapid hematopoietic reconstitution without an adequate leukemic cell purging. 1788 60

The recent discovery of cancer stem cells (CSCs) has played a pivotal role in changing our view of carcinogenesis and chemotherapy. Based on this concept, CSCs are responsible for the formation and growth of neoplastic tissue and are naturally resistant to chemotherapy, explaining why traditional chemotherapies can initially shrink a tumor but fails to eradicate it in full, allowing eventual recurrence. Recently, we identified a CSC population in hepatocellular carcinoma (HCC) characterized by their CD133 phenotype. However, the molecular mechanism by which it escapes conventional therapies remains unknown. Here, we examined the sensitivity of these cells to chemotherapeutic agents (doxorubicin and fluorouracil) and the possible mechanistic pathway by which resistance may be regulated. Purified CD133+ HCC cells isolated from human HCC cell line and xenograft mouse models survived chemotherapy in increased proportions relative to most tumor cells which lack the CD133 phenotype; the underlying mechanism of which required the preferential expression of survival proteins involved in the Akt/PKB and Bcl-2 pathway. Treatment of CD133+ HCC cells with an AKT1 inhibitor, specific to the Akt/PKB pathway, significantly reduced the expression of the survival proteins that was normally expressed endogenously. In addition, treatment of unsorted HCC cells with both anticancer drugs in vitro significantly enriched the CD133+ subpopulation. In conclusion, our results show that CD133+ HCC cells contribute to chemoresistance through preferential activation of Akt/PKB and Bcl-2 cell survival response. Targeting of this specific survival signaling pathway in CD133+ HCC CSCs may provide a novel therapeutic model for the disease.
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PMID:CD133+ HCC cancer stem cells confer chemoresistance by preferential expression of the Akt/PKB survival pathway. 1789 Nov 74

Adoptive cellular immunotherapy has been proposed as an additional treatment of medulloblastoma, an intracranial tumor characterized by a particularly poor prognosis. However, little is known on the ability of the immune system to effectively attack this tumor. In this study, we show that activated human NK cells efficiently kill medulloblastoma cell lines in vitro. NK-mediated killing involved different activating receptors (including NKp46, NKp30, DNAM-1 and NKG2D) and correlated with the presence of their specific ligands on tumor cells. In contrast, the absence of major adhesion interactions, such as LFA-1/ICAM did not impair the NK-mediated cytotoxicity. Medulloblastoma expressed a number of tumor-associated molecules including CD146 and CD133, considered a marker for cancer stem cells. Remarkably, both CD133-positive and CD133-negative cell lines were susceptible to lysis. Tumor cells also expressed molecules that are currently used as diagnostic tools for neuroblastoma cell identification. In particular, B7 homolog 3 (B7-H3) was expressed by all the medulloblastoma cell lines analyzed, while the presence of GD(2) and NB84 was restricted to given cell lines and/or marked a defined tumor cell subset.
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PMID:Both CD133+ and CD133- medulloblastoma cell lines express ligands for triggering NK receptors and are susceptible to NK-mediated cytotoxicity. 1791 5

CD133 is a cell surface marker expressed on progenitors of haematopoietic and endothelial cell lineages. Moreover, several studies have identified CD133 as a marker of brain tumor-initiating cells. In this study, human glioblastoma multiforme biopsies were engrafted intracerebrally into nude rats. The resulting tumors were serially passaged in vivo, and monitored by magnetic resonance imaging. CD133 expression was analyzed at various passages. Tumors initiated directly from the biopsies expressed little or no CD133, and showed no contrast enhancement suggesting an intact blood-brain barrier. During passaging, the tumors gradually displayed more contrast enhancement, increased angiogenesis and a shorter survival. Real-time qPCR and immunoblots showed that this was accompanied by increased CD133 expression. Primary biopsy spheroids and xenograft tumors were subsequently dissociated and flow sorted into CD133 negative and CD133 positive cell populations. Both populations incorporated BrdU in cell culture, and expressed the neural precursor marker nestin. Notably, CD133 negative cells derived from 6 different patients were tumorgenic when implanted into the rat brains. For 3 of these patients, analysis showed that the resulting tumors contained CD133 positive cells. In conclusion, we show that CD133 negative glioma cells are tumorgenic in nude rats, and that CD133 positive cells can be obtained from these tumors. Upon passaging of the tumors in vivo, CD133 expression is upregulated, coinciding with the onset of angiogenesis and a shorter survival. Thus, our findings do not suggest that CD133 expression is required for brain tumor initiation, but that it may be involved during brain tumor progression.
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PMID:CD133 negative glioma cells form tumors in nude rats and give rise to CD133 positive cells. 1795 91

Under standard culture conditions, tumor cells are exposed to 20% O(2), whereas the mean tumor oxygen levels within the tumor are much lower. We demonstrate, using low-passaged human tumor cell cultures established from glioma, that a reduction in the oxygen level in these cell cultures dramatically increases the percentage of CD133 expressing cells.
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PMID:Influence of oxygen tension on CD133 phenotype in human glioma cell cultures. 1797 46


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