Abstract：
:Mutations in RAS proteins occur widely in human cancer. Prompted by the confirmation of KRAS mutation as a predictive biomarker of response to epidermal growth factor receptor (EGFR)-targeted therapies, limited clinical testing for RAS pathway mutations has recently been adopted. We performed a multiplatform genomic analysis to characterize, in a nonbiased manner, the biological, biochemical, and prognostic significance of Ras pathway alterations in colorectal tumors and other solid tumor malignancies. Mutations in exon 4 of KRAS were found to occur commonly and to predict for a more favorable clinical outcome in patients with colorectal cancer. Exon 4 KRAS mutations, all of which were identified at amino acid residues K117 and A146, were associated with lower levels of GTP-bound RAS in isogenic models. These same mutations were also often accompanied by conversion to homozygosity and increased gene copy number, in human tumors and tumor cell lines. Models harboring exon 4 KRAS mutations exhibited mitogen-activated protein/extracellular signal-regulated kinase kinase dependence and resistance to EGFR-targeted agents. Our findings suggest that RAS mutation is not a binary variable in tumors, and that the diversity in mutant alleles and variability in gene copy number may also contribute to the heterogeneity of clinical outcomes observed in cancer patients. These results also provide a rationale for broader KRAS testing beyond the most common hotspot alleles in exons 2 and 3.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Janakiraman M,Vakiani E,Zeng Z,Pratilas CA,Taylor BS,Chitale D,Halilovic E,Wilson M,Huberman K,Ricarte Filho JC,Persaud Y,Levine DA,Fagin JA,Jhanwar SC,Mariadason JM,Lash A,Ladanyi M,Saltz LB,Heguy A,Paty PB,Solitdoi
10.1158/0008-5472.CAN-10-0192subject
Has Abstractpub_date
2010-07-15 00:00:00pages
5901-11issue
14eissn
0008-5472issn
1538-7445pii
0008-5472.CAN-10-0192journal_volume
70pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract：:The presence of estrogen-independent progesterone receptors (PgR) was demonstrated in a subline of a human endometrial cancer cell line, Ishikawa cells, although the original Ishikawa cells contained estrogen-inducible PgR. Scatchard plot analysis of cytoplasmic binding data in our subline (IK-90) revealed a high affi...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1987-04-01 00:00:00
abstract：:5'-Deoxy-5'-methylthioadenosine and 5'-deoxy-5'-methylthioinosine, which are metabolized to the methionine precursor, 5-methylthioribose-1-phosphate, by 5'-deoxy-5'-methylthioadenosine phosphorylase and purine nucleoside phosphorylase, respectively, can serve as sources of methionine for cultured HL-60 promyelocytic l...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1983-10-01 00:00:00
abstract：:Aspects of the metabolism of phorbol myristate acetate (PMA) in mouse skin were investigated. Phorbolol myristate acetate (PHMA), a potential metabolite of PMA in mouse skin, was prepared from PMA by NaBH4 reduction of the C-5 carbonyl group of PMA to a secondary alcohol. The structure of PHMA was assigned on the basi...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1975-08-01 00:00:00
abstract：:Extracellular signal-regulated kinases (ERK) regulate cellular functions in response to a variety of external signals. However, the specific functions of individual ERK isoforms are largely unknown. Hence, we have investigated the specific function of ERK1 in skin homeostasis and tumorigenesis in ERK1 knockout mice. T...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-05-3129
更新日期：2006-03-01 00:00:00
abstract：:The mechanism of the previously reported cytotoxicity of liposomes containing plant phosphatidylinositol (PI) against numerous tumor cell lines was examined in detail by using liposomes containing synthetic PI specifically labeled either with radioactive myo-inositol, or in the sn-2 position with radioactive linoleic ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1985-10-01 00:00:00
abstract：:Immune checkpoint therapies exhibit impressive efficacy in some patients with melanoma or lung cancer, but the lack of response in most cases presses the question of how general efficacy can be improved. In addressing this question, we generated a preclinical tumor model to study anti-PD-1 resistance by in vivo passag...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-15-3142
更新日期：2017-02-15 00:00:00
abstract：:Chloroethylnitrosoureas (CNUs) are being used in the therapy of various neoplastic diseases, including skin cancer. Because secondary tumor formation is a serious threat in chemotherapy with these drugs, we explored whether and to what extent the DNA repair protein DNA-O6-methylguanine:protein-L-cysteine S-methyltrans...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1997-08-15 00:00:00
abstract：:Tetrachloro(d,l-trans)-1,2-diaminocyclohexaneplatinum(IV) (tetraplatin) has been considered a prodrug which would be converted rapidly to dichloro(d,l-trans)-1,2-diaminocyclohexaneplatinum(II) [PtCl2(dach)] under physiological conditions. However, the biotransformations of tetraplatin have not been studied in detail. ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1991-02-01 00:00:00
abstract：:Uptake of actinomycin D (AD) was characterized in Ehrlich ascites tumor cells in vitro. The time course of uptake consists of an initial component that represents a unidirectional flux of AD into the cells, following which the net uptake rate falls to achieve a velocity that is constant over a 45-min interval of obser...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1975-11-01 00:00:00
abstract：:Different cell growth effects were observed in MCF-7 cells after six daily exposures to either 17 beta-estradiol (E2), 2-hydroxyestradiol (2-OHE2), or 2-methoxyestradiol (2-MeOE2) at 10 nM levels. 2-OHE2 enhanced cell growth significantly (P < 0.05) more than did the parent compound, whereas 2-MeOE2 inhibited cell gro...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1992-11-01 00:00:00
abstract：:All mammalian cells express 3 closely related Ras proteins, termed H-Ras, K-Ras, and N-Ras, that promote oncogenesis when they are mutationally activated at codon 12, 13, or 61. Although there is a high degree of similarity among the isoforms, K-Ras mutations are far more frequently observed in cancer, and each isofor...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-11-2612
更新日期：2012-05-15 00:00:00
abstract：:Contrary to a recent suggestion, new and useful drugs for the treatment of human cancer continue to be developed although clinical trials today are more difficult and the chances for success are diminished. In the past, research at Southern Research Institute led to the development of two new classes of clinically use...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1982-10-01 00:00:00
abstract：:Successful chemotherapy accounts for both tumor-related factors and host immune response. Compelling evidence suggests that some chemotherapeutic agents can induce an immunogenic type of cell death stimulating tumor-specific immunity. Here, we show that cyclophosphamide (CTX) exerts two types of actions relevant for t...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-10-2788
更新日期：2011-02-01 00:00:00
abstract：:The nuclear receptor PPAR-β/δ (PPARD) has essential roles in fatty acid catabolism and energy homeostasis as well as cell differentiation, inflammation, and metabolism. However, its contributions to tumorigenesis are uncertain and have been disputed. Here, we provide evidence of tumor suppressive activity of PPARD in ...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-17-0908
更新日期：2018-01-15 00:00:00
abstract：:RhoC is a member of the Ras-homologous family of genes which have been implicated in tumorigenesis and tumor progression. However, the exact role of RhoC is controversial and is yet to be clarified. We have examined the effect of RhoC on prostate tumor cells and found that RhoC had no effect on cell proliferation in v...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-07-6700
更新日期：2008-09-15 00:00:00
abstract：:Despite descriptions of light-mediated therapy in ancient texts and the discovery of photodynamic therapy (PDT) in the early 1900s, the landmark article in 1978 in Cancer Research by Dougherty and his colleagues at the Roswell Park Cancer Institute remains rightly viewed as the starting point for clinical PDT in moder...
journal_title：Cancer research
pub_type： 社论,历史文章
doi：10.1158/0008-5472.CAN-16-0927
更新日期：2016-05-01 00:00:00
abstract：:We have studied the effects of partial polyamine depletion, induced by treatment with alpha-difluoromethylornithine (DFMO) on cell cycle phase distributions in five cultured human carcinoma cell lines. We used flow cytometry of cells stained with chromomycin-A3 and computer analysis to measure phase distributions of t...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1986-01-01 00:00:00
abstract：:DMBT1 is a candidate tumor suppressor gene located at 10q25.3-26.1. Homozygous deletion of the gene was found in a subset of medulloblastoma and glioblastoma multiforme; lack of expression was noted in the majority of these tumors. In adult tissues, DMBT1 is highly expressed only in lung and small intestine tissues, i...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1999-04-15 00:00:00
abstract：:VEGF/vascular permeability factor (VEGF/VPF or VEGF-A) is a pivotal driver of cancer angiogenesis that is a central therapeutic target in the treatment of malignancy. However, little work has been devoted to investigating functions of VEGF that are independent of its proangiogenic activity. Here, we report that VEGF p...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-11-4058
更新日期：2012-08-15 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：:A single i.p. injection of butylated hydroxytoluene (BHT) 6 h before a single urethan injection had varying effects on lung tumorigenesis in mice of different strains and ages. Strains exhibiting both high (A/J, SWR/J) and low (BALB/cByJ, 129/J, C57BL/6J) susceptibility to urethan tumorigenesis were tested in this stu...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1986-04-01 00:00:00
abstract：:Anti-inflammatory drugs and antibiotics alter the risk of breast cancer in women, but roles for bacteria and inflammation in breast malignancies are poorly understood. A recent study in mice suggests that intestinal bacteria can trigger mammary carcinoma. The mechanisms involved in this effect suggest that dysregulate...
journal_title：Cancer research
pub_type： 杂志文章,评审
doi：10.1158/0008-5472.CAN-06-3468
更新日期：2007-02-01 00:00:00
abstract：:Environmental and occupational exposure to arsenite is associated with an increased risk of human cancers, including skin, urinary bladder, and respiratory tract cancers. Although much evidence suggests that alterations in cell cycle machinery are implicated in the carcinogenic effect of arsenite, the molecular mechan...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-05-0469
更新日期：2005-10-15 00:00:00
abstract：:Human papillomavirus type 16 (HPV16) E7 is a viral oncoprotein that is believed to play a major role in cervical neoplasia. Anti-HPV16 E7 intracellular single-chain antibodies (scFvs) were constructed to down-regulate HPV16 E7 oncoprotein in HPV DNA-containing cell lines. In these studies, we transfected anti-E7 scFvs...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1998-05-01 00:00:00
abstract：:The papillomaviruses associated with human anogenital carcinomas encode two transforming genes, E6 and E7. The oncoprotein products of these two genes complex with the tumor suppressor gene products p53 and pRB, respectively. The loss of the normal function of these tumor suppressor gene products, either as a conseque...
journal_title：Cancer research
pub_type： 杂志文章,评审
doi：
更新日期：1991-09-15 00:00:00
abstract：:Recent studies have demonstrated the presence of microsatellite instability (MSI) in tumors from patients with hereditary nonpolyposis colon cancer and in a subset of patients with sporadic colorectal cancer (CRC). In sporadic CRC, three tumor phenotypes have been defined: microsatellite stable (MSS), low-frequency MS...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1998-08-01 00:00:00
abstract：:Although immunotherapy based on the adoptive transfer of tumor-specific T lymphocytes has been shown to result in dramatic clinical responses in some patients, the relatively low levels of engraftment and persistence of the adoptively transferred cells may limit these responses in many patients. In an attempt to devel...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-04-2006
更新日期：2005-03-01 00:00:00
abstract：:Nkx2.8, a homeodomain transcription factor, has been characterized in liver cancer and in the developing central nervous system. We now show that this factor is also expressed in the lung, where it localizes in adults to a discrete population of tracheobronchial basal cells. To target the mouse gene, the first exon wa...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-06-1564
更新日期：2006-11-01 00:00:00
abstract：:Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) is a dual-function phosphatase with tumor suppressor function compromised in a wide spectrum of cancers. Because tissue polarity and architecture are crucial modulators of normal and malignant behavior, we postulated that PTEN may play a role in maintena...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-08-1694
更新日期：2009-05-15 00:00:00
abstract：:A major problem remaining in the evaluation of boronated compounds for neutron capture therapy (NCT) is the need to know the intra- or extracellular microdistribution of boron. This is a consequence of the short range of the 10B(n,alpha)7Li reaction products (approximately 10 microns), such that biological efficacy is...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1990-08-15 00:00:00
