Abstract：
:Hypoxia within solid tumors decreases therapeutic efficacy, and identification of hypoxia markers may influence the choice of therapeutic modality. Here, we used a proteomic approach to identify hypoxia-regulated proteins and validated their use as endogenous indicators of tumor hypoxia. Using two-dimensional gel electrophoresis and PowerBlot (antibody-based array), we identified a group of 20 proteins that are increased >/=1.5-fold during hypoxia. The majority of these proteins such as IkappaB kinase beta (IKKbeta), MKK3b, highly expressed in cancer (HEC), density-regulated protein 1, P150(glued), nuclear transport factor 2, binder of ARL 2, Paxillin, and transcription termination factor I have not been previously reported to be hypoxia inducible. The increase in these proteins under hypoxia was mediated through posttranscriptional mechanisms. We additionally characterized the role of IKKbeta, a regulator of the nuclear factor-kappaB transcription factor, during hypoxia. We demonstrated that IKKbeta mediates cell survival during hypoxia and is induced in a variety of squamous cell carcinoma cell lines. Furthermore, we showed that IKKbeta expression from tumor specimens correlated with tumor oxygenation in patients with head and neck squamous cell carcinomas. These data suggest that IKKbeta is a novel endogenous marker of tumor hypoxia and may represent a new target for anticancer therapy.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Chen Y,Shi G,Xia W,Kong C,Zhao S,Gaw AF,Chen EY,Yang GP,Giaccia AJ,Le QT,Koong ACdoi
10.1158/0008-5472.CAN-04-0899subject
Has Abstractpub_date
2004-10-15 00:00:00pages
7302-10issue
20eissn
0008-5472issn
1538-7445pii
64/20/7302journal_volume
64pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract：:The complement system is important in immunosurveillance against tumors. However, malignant cells are usually resistant to complement-mediated lysis. In this study, we examine the expression of factor H, an inhibitor of complement activation, and factor H-like protein 1 (FHL-1), its alternatively spliced form, in lung...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-03-2328
更新日期：2004-09-01 00:00:00
abstract：:To directly examine a multistage carcinogenesis model and the role of UV light in human tissues, we grafted human skin onto mice with severe combined immunodeficiency disease. We found that the maximum dose of UV radiation in the B range (UVB; 280-320 nm) tolerated by these grafts was 500 J/m2 three times weekly. One ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1996-02-15 00:00:00
abstract：:The release of cardiac troponin T (cTnT) as a biomarker of doxorubicin-induced chronic cardiac injury was evaluated in the spontaneously hypertensive rat (SHR) model. Elevations in serum levels of cTnT and decreased immunohistochemical staining of heart sections for this protein were noted in SHRs treated with cumulat...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1998-01-15 00:00:00
abstract：:Treatment of human HL-60 or KG1A leukemia cells with the topoisomerase II inhibitor etoposide resulted in extensive DNA degradation. When DNA integrity was analyzed by agarose gel electrophoresis, a nucleosomal ladder became evident 1.5-2 h after addition of etoposide to cells, increased in intensity over 6 h, and per...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1989-11-01 00:00:00
abstract：:beta-Catenin is an ubiquitously expressed cytoplasmic protein that has a crucial role in both cadherin-mediated cell-cell adhesion and as a downstream signaling molecule in the wingless/Wnt pathway. Activating mutations in exon 3 of the beta-catenin gene, at the phosphorylation sites for ubiquitination and degradation...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2001-04-15 00:00:00
abstract：:B16 melanoma cell variants were used to determine if the metastatic properties of these cells could be correlated to distinct plasma membrane, microsome, and mitochondrial membrane lipid compositions and membrane-bound enzyme activities in high- and low-metastatic cell variants, respectively. The high-metastatic B16-F...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1984-08-01 00:00:00
abstract：:Little is known about the genetic and molecular events leading to the early stages of human astrocytoma formation. To examine this issue, we analyzed the significance of sequential accumulation of two somatic point mutations (R267W and E258D) in the TP53 gene during the initiation of astrocytoma in a patient born with...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2002-05-15 00:00:00
abstract：:Splenocytes from mice bearing a cachexia-inducing tumor (MAC16) have been fused with mouse myeloma cells to produce hybridomas, which have been cloned to produce antibody reactive to a material which copurified with a lipid-mobilizing factor isolated from the same tumor. The monoclonal antibody has been used to invest...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1996-03-15 00:00:00
abstract：:Sentinel lymph nodes set the stance of the immune system to a localized tumor and are often the first site to be colonized by neoplastic cells that metastasize. To investigate how the presence of neoplastic cells in sentinel lymph nodes may trigger pathways associated with metastatic progression, we analyzed the trans...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-13-1672
更新日期：2014-01-01 00:00:00
abstract：:Three loci have been implicated in the etiology of familial breast cancer; the BRCA1 locus on 17q, the p53 gene on 17p, and the androgen receptor gene on the X chromosome. However, it has been estimated that in approximately 50% of all breast cancer families the predisposing genetic defect is not linked to any of thes...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1993-09-15 00:00:00
abstract：:Metastasis requires cytoskeletal remodeling for migration, adhesion, and extravasation of metastatic cells. Although protein kinase C (PKC) is involved in tumor promotion/progression and cytoskeletal remodeling, its role in metastasis has not been defined. PKCdelta levels are increased in highly metastatic 13762NF mam...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1999-07-01 00:00:00
abstract：:Targeted therapies for cancer are inherently limited by the inevitable recurrence of resistant disease after initial responses. To define early molecular changes within residual tumor cells that persist after treatment, we analyzed drug-sensitive lung adenocarcinoma cell lines exposed to reversible or irreversible epi...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-10-2668
更新日期：2011-07-01 00:00:00
abstract：:There is a paucity of data on whether or not women can be reinfected with human papillomavirus (HPV) types to which they were exposed to earlier in life and on the role of natural immunity. The observation of HPV infection at older ages may be explained by the reactivation of a latent infection or new exposure from se...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-10-0621
更新日期：2010-11-01 00:00:00
abstract：:Tubulysins are highly toxic tubulin-targeting agents with a narrow therapeutic window that are interesting for application in antibody-drug conjugates (ADC). For full control over drug-antibody ratio (DAR) and the effect thereof on pharmacokinetics and tumor targeting, a dual-labeling approach was developed, wherein t...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-14-1141
更新日期：2014-10-15 00:00:00
abstract：:We examined whether herpes simplex virus thymidine kinase (HSV-TK) gene expression driven by the promoter of the vascular endothelial growth factor (VEGF) gene that is activated by hypoxia is effective in killing highly metastatic Lewis lung carcinoma A11 cells under hypoxic conditions. We isolated the promoter region...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2000-06-01 00:00:00
abstract：:We have measured the 31P nuclear magnetic resonance spectra of EMT6/Ro multicellular tumor spheroids over a wide range of sizes under constant nutrient conditions which matched those used for culturing the spheroids. The amount of nucleotide triphosphate per cell decreased with spheroid growth, roughly in proportion t...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1991-08-01 00:00:00
abstract：:The objective of this investigation was to throw light on the biological behavior and metabolic regulation of hepatic enzymes of the nonoxidative branch of the pentose phosphate pathway. The activities of transaldolase (EC 2.2.1.2) and trasketolase (EC 2.2.1.1) Were compared in biological conditions that involve modu...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1976-09-01 00:00:00
abstract：:Combining microtubule-targeting antimitotic drugs with targeted apoptosis potentiators is a promising new chemotherapeutic strategy to treat cancer. In this study, we investigate the cellular mechanism by which navitoclax (previously called ABT-263), a Bcl-2 family inhibitor, potentiates apoptosis triggered by paclita...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-10-4336
更新日期：2011-07-01 00:00:00
abstract：:A vitamin E derivative, vitamin E succinate (VES; RRR-alpha-tocopheryl succinate), and a vitamin E analogue, 2,5,7,8-tetramethyl-2R-(4R,8R,12-trimethyltridecyl)chroman-6-yloxy acetic acid (alpha-TEA), induce human breast, prostate, colon, lung, cervical, and endometrial tumor cells in culture to undergo apoptosis but ...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-03-2327
更新日期：2004-06-15 00:00:00
abstract：:5,6-Dimethylxanthenone-4-acetic acid (DMXAA) and combretastatin A4 phosphate (CA-4-P) markedly inhibit tumor blood flow in mice and are both currently in clinical trial. One of the challenges in clinical evaluation of antivascular agents is the monitoring of tumor blood flow inhibition in individual patients. This stu...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2000-08-15 00:00:00
abstract：:The expressions of albumin and alpha-fetoprotein (AFP) genes were studied in early preneoplastic liver lesions produced by the Solt-Farber protocol using "in situ" hybridization with single stranded RNA probes. In normal rat liver, albumin was expressed at a lower level in the centrilobular than in the periportal area...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1987-10-15 00:00:00
abstract：:The binding of labeled insulin to dissociated R3230AC mammary adenocarcinoma cells from diabetic and intact rats was investigated in vitro. At 20 degrees, specific binding (total binding minus binding in the presence of 1000-fold excess or 10(-6) M unlabeled insulin) reached a plateau at 45 to 60 min and was directly ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1976-11-01 00:00:00
abstract：:Endogenous retroviruses and retroviral elements represent a substantial component of vertebrate genomes. They are inherited as stable Mendelian genes and may be activated spontaneously or by physical or chemical agents. In the human genome various retroviral elements have been detected by their relationship with mamma...
journal_title：Cancer research
pub_type： 杂志文章,评审
doi：
更新日期：1990-09-01 00:00:00
abstract：:Genetically engineered mouse (GEM) models of lung tumorigenesis allow careful evaluation of lung tumor initiation, progression, and response to therapy. Using GEM models of oncogene-induced lung cancer, we show the striking similarity of the earliest stages of tumorigenesis induced by KRAS(G12D) or BRAF(V600E). Cre-me...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-11-3649
更新日期：2012-06-15 00:00:00
abstract：:Loss of expression of the apoptosis protease activator protein-1 (APAF-1) in human melanoma is thought to promote resistance to programmed cell death by preventing caspase-9 activation. However, the role of the APAF-1-dependent pathway in apoptosis activated by cellular stress and/or DNA damage has been recently quest...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-04-1640
更新日期：2004-10-15 00:00:00
abstract：:Inherent and acquired therapeutic resistance in breast cancer remains a major clinical challenge. In human breast cancer samples, overexpression of the oncogenic transcription factor FoxM1 has been suggested to be a marker of poor prognosis. In this study, we report that FoxM1 overexpression confers resistance to the ...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-10-0545
更新日期：2010-06-15 00:00:00
abstract：:Incubation of taxol with human hepatic microsomal fractions or freshly isolated human liver slices yields three metabolite high performance liquid chromatography peaks, metabolite A, metabolite B, and 6 alpha-hydroxytaxol. These metabolites are formed in patients given taxol, with 6 alpha-hydroxytaxol formation repres...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1994-08-01 00:00:00
abstract：:Drugs that affect blood flow have been shown to be whole body radiation protectors. Using NG-nitro-L-arginine, a specific inhibitor of nitric oxide synthase, and the NO-releasing agent (C2H5)2N[N(O)NO-]Na+ (DEA/NO), we have studied the ability of NO to modulate whole body radiation toxicity in C3H mice. NG-Nitro-L-arg...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1994-07-01 00:00:00
abstract：:Macrophages play important roles in both physiologic and pathologic processes and arise from successive waves of embryonic and adult hematopoiesis. Monocyte-derived macrophages (MOMF) exert distinct functions under pathologic conditions, and leukemia-associated macrophages (LAM) show considerable diversities in activa...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-20-0034
更新日期：2020-09-01 00:00:00
abstract：:Technical modifications of the quantitative determination of unscheduled DNA synthesis in cultured hepatocytes are described which allow for the rapid identification of potentially carcinogenic chemicals on a large-scale screening basis. The test is based on the biochemical quantification of [methyl-3H]thymidine incor...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1982-08-01 00:00:00
