Abstract:
:Recent in vitro studies of the epidermal growth factor receptor (EGFR) family have revealed complex signaling interactions involving the production of ligand-mediated heterodimers synergistic for the transformation of cells in vitro. In a series of 70 patients with childhood medulloblastoma, we have used immunohistochemistry and Western blotting analysis to investigate the expression patterns of all four EGFR family members (EGFR, HER2, HER3, and HER4) and heregulin-alpha, a ligand for the HER3 and HER4 receptors. The majority of cases expressed two or more receptor proteins; coexpression of the HER2 and HER4 receptors occurred in 54%. Expression of the ligand heregulin-alpha was detected in 31% of tumors. To investigate whether coexpression results in receptor heterodimerization, we have also performed immunoprecipitation analysis of protein extracts from primary tumors, and we demonstrate various patterns of receptor interaction including between HER2 and HER4. In multivariate 25-year survival analysis with clinicopathological disease features, no individual receptor or heregulin-alpha achieved significance. In contrast, when considered together in the multivariate model, coexpression of HER2 and HER4 demonstrated independent prognostic significance (P = 0.006). These data suggest the hypothesis that HER2-HER4 receptor heterodimerization is of particular biological significance in this disease, and this report is the first to demonstrate potential clinical significance of EGFR family heterodimerization in human cancer. Finally, we have also analyzed expression of the AP-2 transcription factor implicated in the positive regulation of HER2 and HER3 gene transcription in malignant cells and reveal an association between AP-2 expression and not only HER2 and HER3, but also HER4 levels in medulloblastoma primary tumors.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Gilbertson RJ,Perry RH,Kelly PJ,Pearson AD,Lunec Jsubject
Has Abstractpub_date
1997-08-01 00:00:00pages
3272-80issue
15eissn
0008-5472issn
1538-7445journal_volume
57pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract::nm23 was originally identified as an antimetastatic gene, the expression of which was inversely correlated with tumor metastatic potential in rodent model systems. Subsequently, two related human nm23 genes, nm23-H1 and nm23-H2, were identified. The relationship between expression of nm23-H1 and nm23-H2 in hepatocellu...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1995-02-01 00:00:00
abstract::ZR-75-1, a human breast cancer cell line, has been grown in hormone-supplemented medium without serum. The factors required for optimal growth include 17beta-estradiol, insulin, transferrin, dexamethasone, and L-triiodothyronine. If estradiol, insulin, or L-triiodothyronine is omitted, cells cease division within 7 da...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1978-11-01 00:00:00
abstract::Adenocarcinoma of the rete testis is an exceptionally rare and malignant testicular neoplasm. Although treatment of pregnant women with diethylstilbestrol (DES) results in reproductive tract abnormalities in their male offspring, increased incidence of testicular tumors has not been verified. However, recently three c...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1985-10-01 00:00:00
abstract::Although apoptosis and necrosis are morphologically distinct manifestations of cell death, apoptosis and some necroses share common features in the death signaling pathway involving functional steps of death-driving interleukin 1beta-converting enzyme family proteases and anti-cell death protein Bcl-2. One evident phy...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1997-05-15 00:00:00
abstract::As an antiproliferative strategy, we are using bis(ethyl) derivatives of spermine to suppress polyamine biosynthetic enzyme activity and, thereby, deplete intracellular polyamine pools. Since certain of these analogues have recently been shown to potently increase spermidine/spermine-N1-acetyltransferase activity, we ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1989-11-15 00:00:00
abstract::Estrogen receptor α (ERα) is a key regulator of breast growth and breast cancer development. Here, we report how ERα impacts these processes by reprogramming metabolism in malignant breast cells. We employed an integrated approach, combining genome-wide mapping of chromatin-bound ERα with estrogen-induced transcript a...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-15-2910
更新日期:2016-10-01 00:00:00
abstract::Male Wistar rats were given 50 mug of aflatoxin B1 twice a week for 4 weeks, and thereafter 75 mug twice a week for 10 weeks. Their livers were investigated histologically and histochemically for glycogen, RNA, fat, alkaline and acid phosphatases, adenosine triphosphatase, 5'-nucleotidase, glucose-6-phosphatase, gluco...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1975-10-01 00:00:00
abstract::Cranial radiotherapy induces progressive and debilitating declines in cognition that may, in part, be caused by the depletion of neural stem cells. The potential of using stem cell replacement as a strategy to combat radiation-induced cognitive decline was addressed by irradiating athymic nude rats followed 2 days lat...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-11-0027
更新日期:2011-07-15 00:00:00
abstract::The cyclin-dependent kinase (Cdk)-associated protein phosphatase (KAP) is a human dual specificity protein phosphatase that dephosphorylates Cdk2 on threonine 160 in a cyclin-dependent manner. To investigate whether mutations of this enzyme occur in hepatocellular carcinoma (HCC), KAP mRNA was analyzed by reverse tran...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2000-09-01 00:00:00
abstract::Monoclonal antibodies Ost6 and Ost7 (mouse Immunoglobulin G1) to human osteogenic sarcoma were isolated from ascitic fluid and labeled with radioiodine. After injection into athymic nu/nu mice with s.c. xenografts of human osteogenic sarcoma, the uptake of radioactivity in tumors, visceral organs, and blood was determ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1984-05-01 00:00:00
abstract::DNA lesions in nuclei isolated from rat tissues following i.p. injection of the carcinogen nickel carbonate were measured by the alkaline elution technique. Kidney, liver, lung, and thymus gland nuclei were examined at 3 and 20 hr after treatment for the presence of DNA single-strand breaks and cross-links. Single-str...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1982-09-01 00:00:00
abstract::A crucial ingredient of any hyperthermia procedure is the accurate measurement of achieved temperature. In this paper, we present some accuracy and resolution suggestions and address the problem of temperature measurements when electromagnetic energy is used as the mode of heating. In such cases, conventional metallic...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1979-06-01 00:00:00
abstract::Delivery of therapeutic agents to the brain and its neoplasms depends on the presence of membrane transport proteins in the blood-brain barrier and in the target cells. The cellular and subcellular localization of these membrane transporters determines the drug accessibility to the brain and its tumors. We therefore a...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-05-1271
更新日期:2005-12-15 00:00:00
abstract::Ataxia telangiectasia (AT) is an autosomal recessive disorder in which increased level of chromosome breakage and specific sensitivity to radiation and carcinogens have been reported. The effect of the radiomimetic drug bleomycin on chromosome breakage has been tested in skin fibroblasts of three patients with AT, two...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1983-09-01 00:00:00
abstract::Despite its function as an inhibitor of urokinase and tissue-type plasminogen activator (PA), PA inhibitor-1 (PAI-1) has a paradoxical protumorigenic role in cancer, promoting angiogenesis and tumor cell survival. In this review, we summarize preclinical evidence in support of the protumorigenic function of PAI-1 that...
journal_title:Cancer research
pub_type: 杂志文章,评审
doi:10.1158/0008-5472.CAN-15-0876
更新日期:2015-08-01 00:00:00
abstract::Induction of mRNA for BIK proapoptotic protein by doxorubicin or gamma-irradiation requires the DNA-binding transcription factor activity of p53. In MCF7 cells, pure antiestrogen fulvestrant also induces BIK mRNA and apoptosis. Here, we provide evidence that, in contrast to doxorubicin or gamma-irradiation, fulvestran...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-05-3696
更新日期:2006-10-15 00:00:00
abstract::After the Chernobyl accident, the incidence of urinary bladder cancers in the Ukraine population increased gradually from 26.2 to 36.1 per 100,000 between 1986 and 1996. Urinary bladder epithelium biopsied from 45 male patients with benign prostatic hyperplasia living in radiocontaminated areas of Ukraine demonstrated...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1999-08-01 00:00:00
abstract::Cyclin A is an S- and G2-M-phase regulatory protein, and its abnormal expression has been implicated in cellular transformation. This work was undertaken to investigate the frequency of cyclin A overexpression and the correlated clinical outcome in human hepatocellular carcinoma (HCC). Herein, 12 of 31 (39%) patients ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1998-03-01 00:00:00
abstract::alpha-Difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase, inhibited B16 melanoma-induced angiogenesis in chick embryo chorioallantoic membrane and subsequently the growth of the tumor on the chorioallantoic membrane. These inhibitions were reversed by exogenous putrescine and spermidi...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1990-07-01 00:00:00
abstract::Tumors of the central nervous system (CNS) often have sustained expression of labile genes, including angiogenic growth factors and immunosuppressive cytokines, which promote tumor progression. Stabilization of the RNA transcripts for these genes, such as vascular endothelial growth factor (VEGF), is an important mole...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2001-03-01 00:00:00
abstract::Triple-negative breast cancers (TNBC) are especially refractory to treatment due to their negative hormone receptor and ErbB2/HER2 status. Therefore, the identification of cancer-associated deregulated signaling pathways is necessary to develop improved targeted therapies. Here, we show that expression of the ceramide...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-11-3069
更新日期:2012-06-01 00:00:00
abstract::Carcinomas of the exocrine pancreas are poorly understood and have a poor prognosis because of their highly malignant nature. Using two human pancreatic cancer cell lines, AsPc-1 and Capan-2, we have investigated avenues that might be useful in targeting the delivery of antineoplastic agents to such cancers. Qualitati...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1998-02-01 00:00:00
abstract::Indirect immunofluorescence staining with a large battery of monoclonal antibodies of primary and autologous metastatic lesions removed from seven patients with melanoma has detected heterogeneity in the expression of various types of melanoma-associated antigens (MAAs), of distinct determinants of the high molecular ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1985-06-01 00:00:00
abstract::Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy. On the basis of its histopathology and molecular-genomic changes, ovarian cancer has been divided into subtypes, each with distinct biology and outcome. The aim of this study was to develop a panel of patient-derived EOC xenografts that recapit...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-14-0274
更新日期:2014-12-01 00:00:00
abstract::Standardized and reproducible preclinical models that recapitulate the dynamics of prostate cancer are urgently needed. We established a bank of transplantable patient-derived prostate cancer xenografts that capture the biologic and molecular heterogeneity currently confounding prognostication and therapy development....
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-13-2921-T
更新日期:2014-02-15 00:00:00
abstract::verapamil, a calcium-influx blocker, enhanced the cytotoxicity of vincristine (VCR) in vitro 6- to 12-fold in eight human hemopoietic tumor cell lines established from acute lymphatic leukemia, acute myelogenous leukemia, and Burkitt's lymphoma. Great enhancement of VCR cytotoxicity was obtained in a VCR-resistant sub...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1983-05-01 00:00:00
abstract::A correlation exists between the ability of tumor cells to aggregate platelets and their tendency to metastasize. Tumor cell-induced platelet aggregation (TCIPA) facilitates the embolization of the vasculature with tumor cells and the formation of metastatic foci. It is well documented that matrix metalloproteinases (...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2001-01-01 00:00:00
abstract::Micromolar concentrations of fecapentaene-12, a mutagen found in human feces, decrease survival measured as colony-forming efficiency and membrane integrity of cultured human fibroblasts. Fecapentaene-12 also decreases the content of cellular free low-molecular-weight thiols including glutathione. Fecapentaene-12 reac...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1989-11-01 00:00:00
abstract::The specific activity (dpm/mg protein) of the acid-soluble nuclear material extracted from spleens or lymph nodes (but not other tissues) of tumor-bearing BALB/c mice was approximately twice that of the corresponding tissues from tumor-free mice of the same age and sex following i.p. injection of L-[U-14C]lysine. Auto...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1985-05-01 00:00:00
abstract::SNS-032 is a potent inhibitor of cyclin-dependent kinases (Cdk) 2, 7, and 9 that regulate the cell cycle and transcription. Our studies in indolent primary chronic lymphocytic leukemia cells showed that SNS-032 inhibited transcription, diminished the antiapoptotic protein Mcl-1, and induced apoptosis. The present stud...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-09-3578
更新日期:2010-08-15 00:00:00