Abstract:
:Nuclear receptors are critical regulators of many physiological processes and have been shown to be involved in a variety of disease processes, including malignant neoplasms. Our laboratory is investigating the function of the retinoid-related orphan receptor gamma (RORgamma) and its possible role in disease. Studies of mice deficient in the expression of RORgamma demonstrated that this receptor plays a crucial role in the regulation of thymopoiesis and lymph node organogenesis. In this study, we show that changes in homeostasis in the thymus of RORgamma-/- mice are associated with a high incidence of T-cell lymphomas. Over 50% of the deficient mice of mixed genetic background die within the first 4 months as a result of thymic lymphomas. A high incidence of lymphomas was also observed in RORgamma-/- 129/SvEv mice. The lymphoblastic cells metastasized frequently to spleen and liver. No other tumor types were detected in any of RORgamma-/- mice that died during the course of the experiment, and none of the heterozygous mice developed thymic lymphomas. Lymphoma formation was associated with increased cellular proliferation and an increase in the number of apoptotic cells. When placed in culture, the RORgamma-/- lymphoblastic cells underwent accelerated "spontaneous" apoptosis at a rate similar to that of RORgamma-/- thymocytes. Upon prolonged culture, several lymphoblastic cell lines could be established. Analysis of the immunophenotype of the lymphoblastic cells showed that the CD4 and CD8 subpopulations varied substantially among different lymphomas. The established cell lines consisted mostly of CD44-CD25+CD4-CD8- cells. Our studies indicate that loss of RORgamma disturbs homeostasis in the thymus by enhancing apoptosis and cellular proliferation. The latter may enhance the probability of individual cells to acquire genetic alterations that make them escape negative selection and normal differentiation programs and as a consequence lead to increased susceptibility to the development of T-cell lymphoma.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Ueda E,Kurebayashi S,Sakaue M,Backlund M,Koller B,Jetten AMsubject
Has Abstractpub_date
2002-02-01 00:00:00pages
901-9issue
3eissn
0008-5472issn
1538-7445journal_volume
62pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract::The effects of an altered content of dietary iodine and fat on the development of N-nitrosomethylurea-induced mammary tumors in rats were studied and correlated with thyroid and pituitary function studies. In three separate experiments, animals fed a semisynthetic diet containing 11.8% fat had an earlier time of tumor...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1979-03-01 00:00:00
abstract::EJ-ras oncogene-induced malignant transformation is characterized by a series of changes in cell surface carbohydrates and cell-cell and cell-matrix interactions. Here, we show that EJ-ras-transformed NIH-3T3 fibroblasts acquired a migratory phenotype on laminin-1 surfaces. Such a phenotype was accompanied by overexpr...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1996-04-01 00:00:00
abstract::The role of natural killer group 2, member D receptor (NKG2D)-expressing natural killer (NK) cells in tumor immunosurveillance is now well established. Nevertheless, tumor progression occurs despite tumor immunosurveillance, leading to cancer persistence in immunocompetent hosts. STAT3 plays a pivotal role both in onc...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-09-4540
更新日期:2011-03-01 00:00:00
abstract::The DNA of L1210 cells exposed to low concentrations of 1-(2-chloroethyl)=3-cyclohexyl-1-nitrosourea has been analyzed for the presence of single-strand breaks. DNA from 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea-treated cells both sediments more slowly than control DNA on alkaline sucrose gradients andshows a great...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1977-07-01 00:00:00
abstract::Tumor graft models (also known as patient-derived xenografts or PDX) are based on the transfer of primary tumors directly from the patient into an immunodeficient mouse. Because PDX mice are derived from human tumors, they offer a tool for developing anticancer therapies and personalized medicine for patients with can...
journal_title:Cancer research
pub_type: 杂志文章,评审
doi:10.1158/0008-5472.CAN-13-1069
更新日期:2013-09-01 00:00:00
abstract::Latent prostate tumors are commonly found with similar frequency in many countries and ethnic groups. In contrast, aggressive prostate cancer (PC) is significantly less prevalent among Asian men, where the intake of soy products is very high. High consumption of foods containing soy results in high plasma, urine, and ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2001-09-15 00:00:00
abstract::In our previous studies we showed that motility related protein 1 (MRP-1) is a glycoprotein recognized by mAb M31-15, and that the sequence of MRP-1 is identical to that of CD9, a WBC differentiation antigen. Transfection of MRP-1/CD9 cDNA into cultured nonhematopoietic cells suppresses cell motility. The extent of su...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1995-09-15 00:00:00
abstract::The effect of basic fibroblast growth factor (b-FGF), one of the commonest angiogenic factors in various cancer types, on lymphocyte adhesion and transmigration across the endothelial cell monolayer was investigated using human umbilical vein-derived endothelial cells (HUVEC) and type I collagen gel. Forty-eight h exp...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1994-09-01 00:00:00
abstract::Solid human tumors and their surrounding microenvironment are hypothesized to coevolve in a manner that promotes tumor growth, invasiveness, and spread. Mouse models of cancer have focused on genetic changes in the epithelial tumor cells and therefore have not robustly tested this hypothesis. We have recently develope...
journal_title:Cancer research
pub_type: 杂志文章,评审
doi:10.1158/0008-5472.CAN-10-3263
更新日期:2011-02-15 00:00:00
abstract::Phosphorylation of heat shock protein 27 (HSP27) has been suggested to play an important role in the regulation of F-actin dynamics in response to growth factors and stress. Because the microfilament network is one of the earliest targets of oxidative stress and because phosphorylation of HSP27 is strongly induced by ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1996-01-15 00:00:00
abstract::Successful treatment of many patients with osteosarcoma requires more effective chemotherapy. Since new agents are needed, we have developed an immunotoxin using TP-3, an IgG2b mAb which recognizes human and canine osteosarcomas and budding capillaries of tumors. The plant hemitoxin, pokeweed antiviral protein (PAP), ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1995-03-15 00:00:00
abstract::Anticancer vaccine strategies can now target intracellular antigens that are involved in the process of malignant transformation, such as oncogene products or mutated tumor suppressor genes. Fragments of these antigens, generally 8-10 amino acids in length and complexed with MHC class I molecules, can be recognized by...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1995-04-15 00:00:00
abstract::Rhabdomyosarcomas are the most frequent malignant soft tissue tumors of childhood; however, because current multimodality treatments fail to improve the poor survival rate of children with metastatic rhabdomyosarcoma, new treatments are required. We previously identified the gamma-subunit of the fetal acetylcholine re...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-05-0542
更新日期:2006-01-01 00:00:00
abstract::Mortality surveys and death certificate studies have suggested an association between leukemia and farming. To investigate whether exposure to carcinogens in an agricultural setting is related to risk of leukemia, the authors conducted a population-based case-control interview study of 578 white men with leukemia and ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1990-10-15 00:00:00
abstract::High levels of anti-phosphatidylinositol (PtdIns) autoantibodies (autoAb) have been previously described in sera of cancer patients and in plasma of dimethylbenzanthracene-treated female Sprague-Dawley rats. The presence of anti-PtdIns autoAb was tested in a model of highly malignant sarcomas induced by a single dose ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1992-05-15 00:00:00
abstract::A recent pilot study that we performed on 12 individuals who are involved in the cultivation and processing of grains and legumes suggests to us that we may have in hand a relatively quick, inexpensive, and highly sensitive assay that identifies individuals at increased risk for the development of lymphoid malignancy....
journal_title:Cancer research
pub_type: 杂志文章,评审
doi:
更新日期:1992-10-01 00:00:00
abstract::Breast cancer progresses in a multistep process from primary tumor growth and stroma invasion to metastasis. Nutrient-limiting environments promote chemotaxis with aggressive morphologies characteristic of invasion. It is unknown how coexisting cells differ in their response to nutrient limitations and how this impact...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-20-1231
更新日期:2020-11-15 00:00:00
abstract::Obesity enhances breast cancer risk in postmenopausal women and premenopausal women with genetic or familial risk factors. We have shown previously that within breast tissue, obesity increases macrophage-driven inflammation and promotes expansion of luminal epithelial cell populations that are hypothesized to be the c...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-20-0789
更新日期:2020-10-15 00:00:00
abstract::Salvage of preformed nucleosides requires transport across the plasma membrane by sodium-dependent (concentrative) and sodium-independent (equilibrative) mechanisms. These transport systems are also the route of cellular uptake for nucleoside analogues, including gemcitabine (2',2'-difluorodeoxycytidine), a deoxycytid...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2000-11-01 00:00:00
abstract::The in vitro effects of deoxyadenosine and an adenosine deaminase inhibitor, deoxycoformycin, on the synthesis of DNA and the metabolism of purines were investigated in human leukemic T-cells. In the presence of 10 microM deoxycoformycin, the synthesis of DNA was completely inhibited by concentrations of deoxyadenosin...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1981-07-01 00:00:00
abstract::The long-standing strategy for the treatment of metastatic prostate cancer has been to reduce androgenic stimulation of tumor growth by removal of the testes, the primary site of testosterone synthesis. However, a low level of androgenic stimulation may continue, even after castration, by the conversion of adrenal and...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1996-11-01 00:00:00
abstract::Several factors which influence the sensitivity of Chinese hamster V79 cells to cyclophosphamide (CY) have been studied in vitro in both suspension and monolayer cultures. Activated CY was obtained from the blood of mice 15 to 30 min after i.p. injection of CY (400 mg/kg). At pH 7.4, hypoxia rendered the cells more se...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1985-08-01 00:00:00
abstract::We previously reported that the thermosensitivity of tumor cells can be increased when the intracellular pH is lowered by inhibiting Na+/H+ exchange through the plasma membrane with amiloride (3,5-diamino-6-chloro-N-(diamino methylene)pyrazinecarboxamide) or its analogues and HCO3-/Cl-exchange with 4,4-diiothiocyanato...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1993-04-01 00:00:00
abstract::The product of the multiple endocrine neoplasia type 1 (MEN1) tumor suppressor gene, menin, is an integral component of MLL1/MLL2 histone methyltransferase complexes specific for Lys4 of histone H3 (H3K4). We show that menin is a transcriptional coactivator of the nuclear receptors for estrogen and vitamin D. Activati...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-05-4461
更新日期:2006-05-01 00:00:00
abstract::The transmembrane neural cell adhesion receptor L1 is a Wnt/β-catenin target gene expressed in many tumor types. In human colorectal cancer, L1 localizes preferentially to the invasive front of tumors and when overexpressed in colorectal cancer cells, it facilitates their metastasis to the liver. In this study, we inv...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-13-0576
更新日期:2013-09-15 00:00:00
abstract::Recombinant human gamma-interferon (IFN-gamma) has recently been shown to enhance localization of radiolabeled monoclonal antibodies (MAb) to human colon carcinoma xenografts in athymic mice. The present study investigates the ability of gamma-interferon to enhance radioimmunotherapy of a low carcinoembryonic antigen-...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1991-05-01 00:00:00
abstract::The antitumor activity of IFN-alpha is well established. However, the role of the plasmacytoid dendritic cell (PDC), the major producer of IFN-alpha upon viral infection, in tumor biology is unknown. We sought to study the presence and function of PDC in a human solid tumor. Here, we demonstrate that PDCs infiltrate t...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2003-10-01 00:00:00
abstract::In this study, we have exploited the power of insertional mutagenesis to elucidate tumor progression pathways in mice carrying two oncogenes (MYC/Runx2) that collaborate to drive early lymphoma development. Neonatal infection of these mice with Moloney murine leukemia virus resulted in accelerated tumor onset with ass...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-07-0433
更新日期:2007-06-01 00:00:00
abstract::To elicit specific cellular immune responses against cancer, the development of efficient devices to deliver tumor antigen peptides to the MHC class I pathway constitutes a central issue. We report here a novel formula of hydrophobized polysaccharide nanoparticles, which can deliver a HER2 oncoprotein containing an ep...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1998-08-01 00:00:00
abstract::Inflammation predisposes to tumorigenesis in various organs by potentiating a susceptibility to genetic aberrations. The mechanism underlying the enhanced genetic instability through chronic inflammation, however, is not clear. Here, we demonstrated that TNFα stimulation induced transcriptional downregulation of MSH2,...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-15-2926
更新日期:2016-08-01 00:00:00