Abstract:
:The signal transducer and activator of transcription 3 (STAT3) factor plays an important role in the tumorigenicity of cancer stem cells. The purpose of this study was to investigate the inhibitory mechanism of this pathway acting through the tumor suppressor von Hippel-Lindau (VHL) protein in glioma cancer stem cells. We isolated floating neurosphere-forming CD133+ cells as glioma stem-like cells (GSLCs) by the MACS method. Furthermore, we examined these cells for their growth rate, ability to form colonies and neurospheres in soft agar, capacity for implantation into SCID mice and expression of CD133, STAT3, JAK2, Elongin A, PTEN and VHL. Furthermore, we transferred the VHL gene, an inhibitor of STAT3, into GSLCs using an adenovirus vector and compared these transfectants with control vector-transfected GSLCs. GSLCs proved to be implantable and formed a tumor in the subcutaneous tissue of SCID mice, the histology of which was similar to that of human glioblastomas. In addition, GSLCs exhibited a high capacity for soft agar colony and neurosphere formation, nearly all of which were CD133 positive. The majority of GSLCs were immunopositive for STAT3, JAK2 and Elongin A, but immunonegative for PTEN and VHL. When the VHL gene was transferred to GSLCs and these cells were transplanted into SCID mice, they did not result in tumor formation. Their capacity for soft agar colony and neurosphere formation was significantly inhibited, although their proliferation was only moderately inhibited. Regarding the expression of various factors, that of CD133 was decreased in the VHL transfectants and those of STAT3, JAK2 and Elongin A were eliminated. However, the expression of PTEN and of VHL was upregulated. These findings suggest that VHL regulated the tumorigenicity and self-renewal ability of glioma cancer stem cells by inhibiting the JAK/STAT signaling pathway.
journal_name
Int J Oncoljournal_title
International journal of oncologyauthors
Kanno H,Sato H,Yokoyama TA,Yoshizumi T,Yamada Sdoi
10.3892/ijo.2013.1773subject
Has Abstractpub_date
2013-03-01 00:00:00pages
881-6issue
3eissn
1019-6439issn
1791-2423journal_volume
42pub_type
杂志文章abstract::Mutational inactivation of the cyclin-dependent kinase inhibitors (CDKIs) (p16CDKN2a) tumor suppressor gene has been found in a variety of human tumor types. To investigate the involvement of CDKI abnormality in clear cell chondrosarcoma, alterations of CDKIs were examined in clear cell chondrosarcoma tissues using a ...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.19.4.749
更新日期:2001-10-01 00:00:00
abstract::Seaweeds are commonly used as functional foods and drugs. A glycoprotein (GP) from the green alga Capsosiphon fulvescens (Cf) has been reported to have antitumor activity toward various cancer cells. We previously observed that Cf-GP induced different pathways of apoptosis in AGS human gastric cancer cells. Transformi...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2013.2055
更新日期:2013-10-01 00:00:00
abstract::E-cadherins are homophilic adhesion molecules the expression of which is tightly linked to the invasiveness and the differentiated state of the cells. E-cadherin expression seems also inversely related to the expression of vimentin, an intermediate filament implicated in the metastatic potential of some cells. In brea...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.4.1.181
更新日期:1994-01-01 00:00:00
abstract::The aim of the present study was to evaluate the effects of programmed cell death 4 (PDCD4) on cell proliferation and apoptosis, and to elucidate the potential role of the Jun N-terminal kinase (JNK)/c-Jun pathway in human bladder cancer (BCa) cells. Mixed BCa cells were transfected with plasmids containing PDCD4 (PDC...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2018.4303
更新日期:2018-05-01 00:00:00
abstract::Stromal cells isolated from lymph nodes of adult T-cell leukemia/lymphoma (ATL) patients were cultured. Such lymph node stromal cells (LNSC) could be maintained for more than one year, whereas LNSC from other lymphoproliferative disorders ceased to proliferate within months. The rate of human T lymphotropic virus type...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.9.4.619
更新日期:1996-10-01 00:00:00
abstract::The MyD118/Gadd45/CR6 gene family (also termed Gadd45beta/alpha/gamma) has been identified as genes which are rapidly induced by genotoxic agents, during terminal differentiation, as well as by apoptotic cytokines. In recent years, evidence has emerged that the proteins encoded by these genes play pivotal roles in neg...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2001-04-01 00:00:00
abstract::Low concentrations of monoclonal antibodies (mAb) specific for the CD3 component of the T cell receptor complex (TcR) may be both immunosuppressive or potent activators of T cell function in vitro depending upon the experimental situation. The anti-CD3 mAb OKT3 is imnmunosuppressive at high doses (5 mg/day for 10 to 1...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.5.3.675
更新日期:1994-09-01 00:00:00
abstract::Pulmonary adenocarcinoma (PAC) is the leading type of lung cancer and is highly resistant to conventional cancer therapy. A better understanding of the regulatory mechanisms which control the growth of this deadly malignancy are urgently needed to develop more effective cancer intervention strategies. Recent studies h...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2001-09-01 00:00:00
abstract::Ninety-four human non-small cell lung carcinomas (NSCLC) of previously untreated patients were analyzed for the presence of metallothionein (MT) expression by means of immunohistochemistry. Of the tumors investigated, expression of MT was detected in 63%. The expression of MT was correlated with the results of doxorub...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.1.6.687
更新日期:1992-11-01 00:00:00
abstract::Cytokine expression in a tumor microenvironment can impact both host defense against the tumor and tumor cell survival. In this study, we sought to clarify whether the cytokine gene expression profile could have clinical associations with ovarian cancer. We analyzed the expression of 16 cytokine genes (IL-1α, IL-1β, I...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2012.1533
更新日期:2012-09-01 00:00:00
abstract::Human mammary and thyroid tumors as well as peripheral blood cells of the same patients were examined for the amplification of oncogene fins and the expression of its product. Of the 7 mammary tumors analyzed, amplification of fms was observed in 6 (86%) mammary tumor DNAs, while no amplification was seen in 5 thyroid...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.5.4.769
更新日期:1994-10-01 00:00:00
abstract::The human prostate gland is a well known source of H1 and H2 relaxin but information is lacking on the expression and potential role of the INSL3 peptide hormone within the prostate gland. In the present study we have investigated the expression of human INSL3 in patients with benign prostate hyperplasia (BPH), prosta...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2005-08-01 00:00:00
abstract::The development of targeted molecular therapies has greatly benefited patients with lung adenocarcinomas. In contrast, these treatments have had little benefit in the management of lung squamous cell carcinoma (lung SCC). Therefore, new treatment options based on current genomic approaches are needed for lung SCC. Abe...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2016.3690
更新日期:2016-11-01 00:00:00
abstract::The identification of cell surface markers expressed selectively by tumor vasculature is challenging. To get as close to the human disease as possible, investigators have isolated endothelial cells from fresh human tumor specimens and subjected them to RNA-based gene expression analysis. The data indicate that there a...
journal_title:International journal of oncology
pub_type: 杂志文章,评审
doi:
更新日期:2007-02-01 00:00:00
abstract::Inflammatory abnormalities have been implicated in the pathogenesis of various human diseases, including cancer. Interleukin-1 receptor antagonist (IL1RN) is a potent anti-inflammatory molecule that modulates the biological activity of the proinflammatory cytokine, interleukin-1. The aim of this study was to examine t...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2015.2917
更新日期:2015-05-01 00:00:00
abstract::The peptide hormone, GnRH has been hypothesized to play a direct antitumoral role in certain kinds of breast cancer. This direct effect is considered to function via high affinity membrane receptors to GnRH that have been demonstrated in tumors. However, no routine assay for GnRH receptors exist limiting further resea...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:1995-08-01 00:00:00
abstract::MicroRNAs (miRNAs) were reported to be involved in the development of clear cell renal cell carcinoma (ccRCC). However, the study on miRNAs in ccRCC is far from complete. The present study identified miRNAs which could act as potential novel prognostic markers for ccRCC, and analyzed its possible mechanism. We found t...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2016.3746
更新日期:2016-12-01 00:00:00
abstract::miRNA‑223 (miR‑223) has been reported to function not only as a tumor suppressor, but also as an oncogenic microRNA (miRNA or miR) in various cancer cells. Therefore, the functional role of miR‑223 has not been elucidated to date, at least to the best of our knowledge. We previously performed the deep sequencing analy...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2019.4762
更新日期:2019-06-01 00:00:00
abstract::A slowly proliferating cell fraction in tumors shows reduced sensitivity to cell cycle-dependent anticancer agents. To understand the molecular basis of drug resistance observed in brain tumors, we examined the relationship between alteration of p16, a cyclin dependent kinase inhibitor whose functions are frequently l...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.17.3.501
更新日期:2000-09-01 00:00:00
abstract::The aim of this study was to assess pivotal factors determining the oxygenation status of malignant tumors, and, for comparison, of normal tissues. For this purpose, microvascular patterns, blood flow data, O2 consumption rates and O2 extractions were correlated to the median pO2 values of isografted rodent and xenogr...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2003-04-01 00:00:00
abstract::Due to the central role in predicting response to herceptin and possibly also other anticancer drugs, accurate and reproducible detection of the HER2 status is important. Fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) are the most commonly used methods for HER2 analysis. It is a disadvantage ...
journal_title:International journal of oncology
pub_type: 临床试验,杂志文章
doi:
更新日期:2004-12-01 00:00:00
abstract::Hypoxia regulates the expression of genes that promote tumor growth, angiogenesis and invasion. We previously studied hypoxic tumor cells in vitro and from hepatic metastases of colorectal cancer and determined several potential prognostic factors for hepatocellular carcinoma (HCC). In this study, we evaluated the pro...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2014.2519
更新日期:2014-09-01 00:00:00
abstract::Induction of differentiation represents a promising concept for chemotherapy of malignant gliomas, which are often refractory even to the combined treatment with surgery, irradiation and chemotherapy. Since anti-neoplastic alkylphosphocholines can induce differentiation of leukemic cell lines, the effects of the intra...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.19.4.673
更新日期:2001-10-01 00:00:00
abstract::Clear cell renal cell carcinoma (ccRCC) is the most common renal malignancy in adults, the incidence of which continues to increase. The lipid droplet protein perilipin 2 (PLIN2), which was originally considered an RNA transcript, is markedly expressed during adipocyte differentiation. In addition, it has been observe...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2018.4384
更新日期:2018-07-01 00:00:00
abstract::In order to optimize the management of patients with renal cell carcinoma (RCC) it is important to define the genetic risk for metastatic disease. In this study we performed comparative genomic hybridization (CGH) on metastatic tumors aiming at the identification of genetic alterations associated with metastatic disea...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.17.5.903
更新日期:2000-11-01 00:00:00
abstract::Primary intracerebral lymphoma is an uncommon presenting site for non-Hodgkin's lymphoma. The authors review 28 histopathologically confirmed, consecutive cases, presenting over a 15-year period. The cohort included 20 males and 8 females with a mean age at diagnosis of 54 years (range 27-75 years). Subtotal resection...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.14.4.647
更新日期:1999-04-01 00:00:00
abstract::177Lu‑DOTATATE was recently approved for the treatment of somatostatin receptor (SSTR)‑positive neuroendocrine tumors (NETs). However, despite impressive response rates, complete responses are rare. Heat shock protein 90 (HSP90) inhibitors have been suggested as suitable therapeutic agents for NETs, as well as a poten...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2019.4888
更新日期:2019-12-01 00:00:00
abstract::Thirty-four children with newly diagnosed acute nonlymphoblastic leukemia were analysed for the expression of P-glycoprotein (P-170), glutathione S-transferase-pi, (GST-pi) topoisomerase II (Topo II) and the proliferation antigen Ki-67 by the streptavidin-biotin-peroxidase method. Overexpression of P-170 was present i...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.5.4.841
更新日期:1994-10-01 00:00:00
abstract::The effect of reduced glutathione (GSH) and ethanol on aflatoxin B1 (AFB1)-induced DNA single strand breaks was studied in primary cultured hepatocytes. Buthionine sulfoximine (BSO) which decreased intracellular GSH to 13% of those of the control levels increased DNA fragmentation of AFB1-treated hepatocytes by over 1...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.4.1.123
更新日期:1994-01-01 00:00:00
abstract::The RON receptor tyrosine kinase and its ligand macrophage stimulating protein (MSP) play a role in epithelial tumorigenesis. We report here a novel RON variant that antagonizes the RON-MSP pathway in various cancer cells. The variant is an 85 kDa soluble protein from an mRNA transcript with an insertion of 49 nucleot...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo_00000642
更新日期:2010-06-01 00:00:00