Abstract:
:Oncogenic KRAS mutations occur frequently in lung adenocarcinoma. The signaling pathways activated by IL6 promote Kras-driven lung tumorigenesis, but the basis for this cooperation is uncertain. In this study, we used the gp130(F/F) (Il6st) knock-in mouse model to examine the pathogenic contribution of hyperactivation of the STAT3 arm of IL6 signaling on KRAS-driven lung tumorigenesis. Malignant growths in the gp130(F/F):Kras(G12D) model displayed features of atypical adenomatous hyperplasia, adenocarcinoma in situ, and invasive adenocarcinoma throughout the lung, as compared with parental Kras(G12D) mice, where STAT3 was not hyperactivated. Among IL6 family cytokines, only IL6 was upregulated in the lung. Accordingly, normalization of pulmonary STAT3 activity, by genetic ablation of either Il6 or Stat3, suppressed the extent of lung cancer in the model. Mechanistic investigations revealed elevation in the lung of soluble IL6 receptor (sIL6R), the key driver of IL6 trans-signaling, and blocking this mechanism via interventions with an anti-IL6R antibody or the inhibitor sgp130Fc ameliorated lung cancer pathogenesis. Clinically, expression of IL6 and sIL6R was increased significantly in human specimens of lung adenocarcinoma or patient serum. Our results offer a preclinical rationale to clinically evaluate IL6 trans-signaling as a therapeutic target for the treatment of KRAS-driven lung adenocarcinoma.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Brooks GD,McLeod L,Alhayyani S,Miller A,Russell PA,Ferlin W,Rose-John S,Ruwanpura S,Jenkins BJdoi
10.1158/0008-5472.CAN-15-2388subject
Has Abstractpub_date
2016-02-15 00:00:00pages
866-76issue
4eissn
0008-5472issn
1538-7445pii
0008-5472.CAN-15-2388journal_volume
76pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract::Tumor metastasis is one of the most important clinical aspects of neoplastic disease because patient mortality is frequently attributable to disseminated rather than primary tumors. However, it still is not possible to definitively distinguish those individuals at high risk for disseminated disease, who would benefit ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2001-12-15 00:00:00
abstract::A two-stage genome-wide association study (GWAS) of the Cancer Genetic Markers of Susceptibility (CGEMS) initiative identified single nucleotide polymorphisms (SNP) in 150 regions across the genome that may be associated with prostate cancer (PCa) risk. We filtered these results to identify 43 independent SNPs where t...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-08-3347
更新日期:2009-04-01 00:00:00
abstract::The biochemical and clinical effects of selenium (Na2SeO3) on 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis in male Sprague-Dawley rats are presented. A 4-ppm selenium supplement to the drinking water was provided before, during, and after 20 weekly injections of 20 mg DMH per kg body weight. Immediately af...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1981-11-01 00:00:00
abstract::The DNA intercalator, 4'-(9-acridinylamino)methanesulfon-m-anisidide (m-AMSA) and the nonintercalator, etoposide (VP-16) produce topoisomerase II-mediated protein-linked DNA strand breaks. This function of topoisomerase II was investigated in relation to cell proliferation and cell cycle. Mouse fibroblasts NIH 3T3 and...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1987-04-15 00:00:00
abstract::Most patients' prostate cancers respond to androgen deprivation but relapse after periods of several months to years. Only two prostate cancer xenografts, LNCaP and PC-346, have been reported to be responsive to androgen deprivation and to relapse subsequently. Both of these tumors shrink slightly, if at all, and rela...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1996-07-01 00:00:00
abstract::The molecular genetic events involved in the etiology of human granulosa cell (GC) tumors, which represent approximately 7% of all malignant ovarian neoplasms, are unknown. Amplification and/or overexpression of the ERBB genes are a feature of many cancer types, and overexpression of erbB2 correlates with poor prognos...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1998-05-01 00:00:00
abstract::Glucocorticoids are used for the treatment of lymphoid neoplasms, taking advantage of the well-known ability of these compounds to cause apoptosis in lymphoid tissues. Previously, we have shown that dexamethasone, a synthetic glucocorticoid, causes a down-regulation of several antioxidant defense enzymes and proteins,...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2001-03-15 00:00:00
abstract::Normal human cells can be transformed to anchorage-independent growth by transfection with DNA from MOLT-4 lymphoblasts, derived from a patient with acute lymphocytic leukemia. Cells were treated with polyethylene glycol 6000, and DNA was administered as a calcium phosphate coprecipitate . The transforming activity of...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1984-07-01 00:00:00
abstract::Anti-idiotype monoclonal antibodies (Mabs) to mLL2, an anti-B-cell lymphoma and CD22-specific murine IgG2a-kappa Mab, were generated by hybridoma technology from splenocytes of Copenhagen rats immunized with mLL2 F(ab')2. Mab WN, an IgG2a-kappa, was selected based on its specific binding to mLL2 and not other IgG isot...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1995-12-01 00:00:00
abstract::Rats implanted with RG-2 gliomas were administered i.v. RMP-7 and [14C]carboplatin. Changes in the permeability of the blood-brain barrier to carboplatin were determined using quantitative autoradiography. i.v. infusions of RMP-7 induced an increase in the permeability of the vascular barrier within the tumor to carbo...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1996-09-01 00:00:00
abstract::Silybin, a main component of the milk thistle of Silybum marianum, has been reported to possess anticancer activity. We investigated the effects of IdB 1016, a complex of silybin with phosphatidylcholine, on the development of mammary tumors appearing spontaneously in HER-2/neu transgenic mice. The mechanisms involved...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-06-2601
更新日期:2007-03-01 00:00:00
abstract::Cultured explants of mouse mammary gland were investigated for their capacity to secrete a cathepsin B-like cysteine proteinase. This enzyme had been shown previously to be secreted excessively from cultured explants of human breast tumors and spontaneous mouse mammary carcinomas. We now show that secretion is also ob...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1985-05-01 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::The G protein-coupled formylpeptide receptor (FPR), which mediates leukocyte migration in response to bacterial and host-derived chemotactic peptides, promotes the chemotaxis, survival, and tumorigenesis of highly malignant human glioblastoma cells. Because glioblastoma cells may also express other receptors for growt...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-07-0691
更新日期:2007-06-15 00:00:00
abstract::We have demonstrated previously that the immunomodulator AS101 can protect mice from acute lethal toxicity mediated by high doses of radiation or chemotherapy. The compound was shown to rescue mice from toxic effects of cyclophosphamide or 5-fluorouracil. The results presented herein demonstrate that pretreatment of m...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1993-12-15 00:00:00
abstract::Various hormones and growth factors are involved in the growth regulation of breast (tumor) cells. In this report we show for the first time that an analogue of the neuropeptide somatostatin (Sandostatin) can also influence the proliferation of human breast cancer cells (MCF-7), namely, in an inhibitory fashion. With ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1987-03-15 00:00:00
abstract::DNA methylation was measured in human tumor cell lines and freshly explanted pediatric tumors by [3H]uridine labeling followed by DNA hydrolysis and high-performance liquid chromatography. The percentage of cytosine residues modified to 5-methylcytosine in 4 cell lines derived from pediatric tumors was increased or si...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1983-10-01 00:00:00
abstract::Morris 7777 hepatoma cells, maintained in culture for 5 days in Lewis medium supplemented with 0.1 to 0.35 mM cis-unsaturated fatty acid of the oleic (number of carbon atoms: number of double bonds, 18:1), linoleic (18:2), or arachidonic (20:4) type, were compared to similarly maintained, unsupplemented cells as to ul...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1982-11-01 00:00:00
abstract::When human tumor xenotransplants into nude mice are used as experimental models, it is important to know whether their microvascular anatomy is rather host or tumor specific. Therefore a morphometric comparison of the vascular network in human squamous cell carcinomas and their xenotransplants was carried out. Biopsie...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1989-08-15 00:00:00
abstract::Topotecan, a water-soluble semisynthetic analogue of camptothecin, is the first topoisomerase I inhibitor to undergo evaluation in pediatric patients with refractory malignancies. A phase I and pharmacokinetic study was performed to determine the maximum tolerated dose (MTD) and dose-limiting toxicities, the incidence...
journal_title:Cancer research
pub_type: 临床试验,杂志文章
doi:
更新日期:1993-03-01 00:00:00
abstract::The aggressive biology of human pancreatic adenocarcinoma has been linked with overexpression of vascular endothelial growth factor (VEGF). Constitutive activation of the transcription factor Sp1 plays a critical role in VEGF overexpression. Recent studies indicated that celecoxib, a selective cyclooxygenase-2 inhibit...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.can-03-1945
更新日期:2004-03-15 00:00:00
abstract::Epidemiological data have provided clues to the etiological factors involved in large bowel cancer development. High intake of dietary fat tends to promote colon carcinogenesis. Studies in metabolic epidemiology have shown that the high dietary fat affects the metabolic activity of gut bacteria as well as the levels o...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1981-09-01 00:00:00
abstract::Acute promyelocytic leukemia is associated with a t(15;17) translocation that generates a fusion product between PML and the retinoic acid receptor alpha. Recently, PML was shown to concentrate within subnuclear domains, referred to as nuclear bodies, that are disorganized in acute promyelocytic leukemia cells. This o...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1995-04-01 00:00:00
abstract::PTEN/MMAC1 is a major new tumor suppressor gene that encodes a dual-specificity phosphatase with sequence similarity to the cytoskeletal protein tensin. Recently, we reported that PTEN dephosphorylates focal adhesion kinase (FAK) and inhibits cell migration, spreading, and focal adhesion formation. Here, the effects o...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1999-01-15 00:00:00
abstract::Malignant gliomas are the most common central nervous system tumors and the molecular mechanism driving their development and recurrence is still largely unknown, limiting the treatment of this disease. Here, we show that restoring the expression of miR-218, a microRNA commonly downregulated in glioma, dramatically re...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-13-0358
更新日期:2013-10-01 00:00:00
abstract::The major transmission route for Kaposi sarcoma-associated herpesvirus (KSHV) infection is the oral cavity through saliva. Kaposi sarcoma (KS) frequently occurs in the oral cavity in HIV-positive individuals and is often the first presenting sign of AIDS. However, the oral target cells for KSHV infection and the cellu...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-17-1961
更新日期:2018-01-01 00:00:00
abstract::Thymidine phosphorylase (TP) is an enzyme involved in the reversible conversion of thymidine to thymine and is identical to an angiogenic factor, platelet-derived endothelial cell growth factor. TP is expressed at higher levels in a wide variety of solid tumors than in the adjacent nonneoplastic tissues. Patients with...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1999-04-15 00:00:00
abstract::1 alpha,25-Dihydroxyvitamin D3 [1 alpha,25(OH)2D3], a hormonally active form of vitamin D3, was shown previously to enhance chemically induced transformation of BALB 3T3 cells and Syrian hamster embryo cells. This report demonstrates that 1 alpha,25(OH)2D3, like phorbol ester tumor promoters, induces anchorage-indepen...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1986-11-01 00:00:00
abstract::In previous studies a clone of the gynogenetic fish, Poecilia formosa (the Amazon molly), was successfully used as a test animal to identify ultraviolet-induced damage. This work has been extended, and the fish system was used to detect damage caused byionizing radiation. Fish cells, exposed in vitro to 250 and 500 ra...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1977-12-01 00:00:00
abstract::The cytoskeleton, the shape, and the adhesion complexes of MCF-7 breast carcinoma cells have been studied by fluorescence, phase contrast, and interference reflection microscopy. Cells have been grown in media containing different concentrations of estrogen and with or without the addition of the antiestrogen tamoxife...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1986-05-01 00:00:00