Abstract:
:Patients with human papillomavirus (HPV+)-associated head and neck cancer (HNC) show significantly improved survival outcome compared with those with HPV-negative (HPV-) tumors. Published data examining this difference offers conflicting results to date. We systematically investigated the radiation sensitivity of all available validated HPV+ HNC cell lines and a series of HPV- HNC cell lines using in vitro and in vivo techniques. HPV+ HNCs exhibited greater intrinsic radiation sensitivity (average SF2 HPV-: 0.59 vs. HPV+: 0.22; P < 0.0001), corresponding with a prolonged G2-M cell-cycle arrest and increased apoptosis following radiation exposure (percent change 0% vs. 85%; P = 0.002). A genome-wide microarray was used to compare gene expression 24 hours following radiation between HPV+ and HPV- cell lines. Multiple genes in TP53 pathway were upregulated in HPV+ cells (Z score 4.90), including a 4.6-fold increase in TP53 (P < 0.0001). Using immortalized human tonsillar epithelial (HTE) cells, increased radiation sensitivity was seen in cell expressing HPV-16 E6 despite the effect of E6 to degrade p53. This suggested that low levels of normally functioning p53 in HPV+ HNC cells could be activated by radiation, leading to cell death. Consistent with this, more complete knockdown of TP53 by siRNA resulted in radiation resistance. These results provide clear evidence, and a supporting mechanism, for increased radiation sensitivity in HPV+ HNC relative to HPV- HNC. This issue is under active investigation in a series of clinical trials attempting to de-escalate radiation (and chemotherapy) in selected patients with HPV+ HNC in light of their favorable overall survival outcome.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Kimple RJ,Smith MA,Blitzer GC,Torres AD,Martin JA,Yang RZ,Peet CR,Lorenz LD,Nickel KP,Klingelhutz AJ,Lambert PF,Harari PMdoi
10.1158/0008-5472.CAN-13-0587subject
Has Abstractpub_date
2013-08-01 00:00:00pages
4791-800issue
15eissn
0008-5472issn
1538-7445pii
0008-5472.CAN-13-0587journal_volume
73pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract::Osteoprotegerin (OPG), a novel, secreted tumor necrosis factor receptor family member that inhibits osteoclast formation and activity was examined for its activity in a syngeneic tumor model of humoral hypercalcemia of malignancy. Normal mice bearing Colon-26 tumors develop increases in both parathyroid hormone-relate...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2000-02-15 00:00:00
abstract::One of the major problems in the diagnosis of localized prostatic tumors is to predict the aggressiveness of an individual tumor, which is presumably associated with chance to progression. In an attempt to find molecular markers that are specific for aggressive prostatic cancer cells, we compared steady-state mRNA lev...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1991-01-15 00:00:00
abstract::A chimeric CYCLIN D1-TROP2 mRNA was isolated from human ovarian and mammary cancer cells. The CYCLIN D1-TROP2 mRNA was shown to be a potent oncogene as it transforms naïve, primary cells in vitro and induces aggressive tumor growth in vivo in cooperation with activated RAS. Silencing of the chimeric mRNA inhibits the ...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-07-6135
更新日期:2008-10-01 00:00:00
abstract::Multiple copies of N-myc proto-oncogene are only rarely detected in localized neuroblastomas (NBs), and the prognostic relevance of amplification in this subset of patients is not clear. We analyzed a series of 850 children with NB admitted to a Pediatric Oncology Group NB Biology Study and identified six patients wit...
journal_title:Cancer research
pub_type: 杂志文章,多中心研究
doi:
更新日期:1995-02-15 00:00:00
abstract::We have demonstrated previously that there is a marked decrease in the level of labeled fucose incorporated into an amino acid fucoside, i.e., fucosyl-N-acetylglucosaminylasparagine (FL4c) in SV40-transformed human embryonic lung cells (SV40-WI-38) as compared to WI-38 cells (Morton, P.A., Klinger, M. M., and Steiner,...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1984-10-01 00:00:00
abstract::Specific immunity to Rous virus-induced sarcoma (RSL) was investigated by the tube leukocyte adherence inhibition (LAI) assay in rats immunized with Bacillus Calmette-Guérin (BCG). Peritoneal cells from Lewis rats immunized s.c. with BCG gave positive reactions in the tube LAI assay with the antigen prepared from RSL ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1979-02-01 00:00:00
abstract::Surface-exposed proteins of vinblastine-sensitive human lymphoid cell line of leukemic origin (CCRF-CEM) were examined by the lactoperoxidase-catalyzed iodination and two-dimensional polyacrylamide gel electrophoresis methods. Spots which comigrate with bovine brain tubulin and rabbit muscle actin were prominently lab...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1982-04-01 00:00:00
abstract::Immunosuppression may contribute to the progression of cancer. In this study we assessed the structural and functional status of T cells from tumor specimens obtained from patients with early stage non-small cell lung cancer and late-stage ovarian cancer. Although some groups have described structural alterations in t...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2001-06-15 00:00:00
abstract::Enhancer of zeste homolog 2 (EZH2) is the catalytic subunit of the Polycomb-repressive complex 2 (PRC2) that represses gene transcription through histone H3 lysine 27 trimethylation (H3K27me3). Although EZH2 is abundantly present in various cancers, the molecular consequences leading to oncogenesis remain unclear. Her...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-10-3342
更新日期:2011-06-01 00:00:00
abstract::Phosphoglucose isomerase (PGI) is a multifunctional enzyme that functions in glucose metabolism as a glycolytic enzyme catalyzing an interconversion between glucose and fructose inside the cell, while it acts as cytokine outside the cell, with properties that include autocrine motility factor (AMF)-regulating tumor ce...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-09-3880
更新日期:2010-11-15 00:00:00
abstract::Prior investigations on the beneficial effect of dietary processed tomato products and lycopene on prostate cancer risk suggested that lycopene may require the presence of other constituents to exert its chemopreventive potential. We investigated whether ketosamines, a group of carbohydrate derivatives present in dehy...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-08-0108
更新日期:2008-06-01 00:00:00
abstract::Antineoplastic drug resistance is a major obstacle to improved treatment of most adult cancers in humans. Novobiocin, an antibacterial agent which inhibits the eukaryotic topoisomerase II enzyme, increases the cytotoxicity of several alkylating agents in vitro by the formation of lethal DNA-DNA interstrand cross-links...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1991-01-15 00:00:00
abstract::Cultures of adult mouse epidermal keratinocytes (MEKs) were utilized to determine whether the metabolism and metabolic activation of polycyclic aromatic hydrocarbons varied as a function of extracellular calcium (Ca2+) concentration. MEKs grown in low Ca2+-containing medium (0.05-0.10 mM) maintain basal cell morpholog...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1989-10-15 00:00:00
abstract::Steroid sulfatase (STS) hydrolyzes several sulfated steroids such as estrone sulfate, dehydroepiandrosterone sulfate, and cholesterol sulfate. In the present study, we have measured STS mRNA levels in 97 breast cancers by reverse transcription-PCR using a fluorescent primer in the presence of an internal standard RNA ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1999-01-15 00:00:00
abstract::Clinical photodynamic therapy consists of the systemic administration of a derivative of hematoporphyrin (Photofrin II) followed by exposure of malignant lesions to continuous visible laser irradiation. We investigated the effects of various modifications of laser light delivery on the efficacy of photodynamic therapy...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1990-11-15 00:00:00
abstract::Fibroblast growth factor receptor 1 (FGFR1) is frequently amplified and highly expressed in lobular carcinomas of the breast. In this report, we evaluated the biological activity of FGFR1 in a wide range of in vitro assays. Conditional activation of FGFR1 in the nontransformed MCF10A human mammary cell line, MCF10A, r...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-08-3398
更新日期:2009-03-15 00:00:00
abstract::We present a light scattering study using angle-resolved low coherence interferometry (a/LCI) to assess nuclear morphology and subcellular structure within MCF-7 cells at several time points after treatment with chemotherapeutic agents. Although the nuclear diameter and eccentricity are not observed to change, the lig...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-08-3079
更新日期:2009-02-01 00:00:00
abstract::Using JM and MOLT3, two human T-cell acute lymphoblastic leukemia cell lines, we investigated the ability of 24-h thymidine exposures to enhance the cytotoxicity of cis-diammine-1,1-cyclobutane dicarboxylate platinum (II) (carboplatin). Clinically achievable thymidine concentrations (for 24 h) significantly enhanced c...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1989-11-01 00:00:00
abstract::Previous studies have shown that treatment of rats with gonadotropin-releasing hormone (GnRH) analogues or steroids either before exposure to procarbazine or radiation or after irradiation enhances subsequent levels of spermatogenesis. We demonstrate here that giving a GnRH agonist after procarbazine injection also en...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1999-08-01 00:00:00
abstract::1,25-Dihydroxyvitamin D3 [1,25-(OH)2D3] inhibited the secretion of gamma-interferon from human T-lymphocytes activated by the calcium ionophore, A23187, or phytohemagglutinin with or without 12-O-tetradecanoylphorbol-13-acetate. The agent also inhibited cell proliferation and interleukin 2 secretion by these cells. Th...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1986-11-01 00:00:00
abstract::The spontaneous development of juvenile-onset ovarian granulosa cell tumors in mice of the SWXJ-9 recombinant inbred strain is a model for juvenile-type granulosa cell tumors that appear in very young girls. To expedite gene discovery in this mouse model of childhood cancer, we did a gene mapping study with the SWXJ-9...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-04-2992
更新日期:2005-02-15 00:00:00
abstract::We have pursued our analysis of antigens recognized by autologous cytolytic T lymphocytes (CTLs) on the melanoma cells of patient LB33. This patient enjoys an unusually favorable evolution, which is associated with a strong and sustained antitumor CTL response. We reported previously the analysis of two melanoma cell ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1999-11-15 00:00:00
abstract::Cancer chemotherapy may be improved by increasing antineoplastic drug specificity for tumor cells. We have synthesized a glucuronide prodrug that can be enzymatically converted to an antineoplastic agent at tumor cells that are able to bind beta-glucuronidase-monoclonal antibody conjugates. The glucuronide prodrug BHA...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1992-08-15 00:00:00
abstract::The major heat shock protein Hsp72 is constitutively expressed in many tumor cell lines and biopsies, and its expression correlates with poor prognosis in several types of cancer. Hsp72 was suggested to play an important role in neoplastic transformation and tumor development. We addressed the role of Hsp72 in cancer ...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-06-3796
更新日期:2007-03-01 00:00:00
abstract::microRNAs (miRNA) are small noncoding RNAs that participate in diverse biological processes by suppressing target gene expression. Altered expression of miR-21 has been reported in cancer. To gain insights into its potential role in tumorigenesis, we generated miR-21 knockout colon cancer cells through gene targeting....
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-09-1996
更新日期:2009-10-15 00:00:00
abstract::In contrast to methotrexate (MTX) and aminopterin (AMT), the 8-deaza analogues of these antifolates are not substrates for rabbit liver aldehyde oxidase. Since they are not converted to 7-hydroxy derivatives, they have been investigated with regard to their cytotoxicity for CCRF-CEM cells, transport into these cells, ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1988-03-15 00:00:00
abstract::WWOX is a tumor suppressor that functions as a modular protein partner of transcription factors. WWOX contains two WW domains that mediate protein-protein interactions. In this report, we show that WWOX, via its first WW domain, specifically associates with the proline-rich motif of c-Jun proto-oncogene. Our data show...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-06-3376
更新日期:2006-12-15 00:00:00
abstract::Nerve growth factor-like substance(s) were identified in both conditioned media of a human prostatic tumor epithelial cell line (TSU-pr1) and a human prostatic stromal cell line (HPS) by Western blot analysis and bioassay of neurite outgrowth of PC12 cells. Nerve growth factor-beta (NGF) immunofluorescence was also lo...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1991-06-15 00:00:00
abstract::Transforming growth factor beta-1 (TGF-beta1) is a potent inhibitor of hepatocyte growth both in vivo and in vitro. In this study, we analyzed the effects of TGF-beta1 on both naturally occurring and diethylnitrosamine-induced hepatocarcinogenesis using single transgenic TGF-beta1 and double transgenic c-myc/TGF-beta1...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1997-06-01 00:00:00
abstract::Cloned cell lines derived from the androgen-responsive Shionogi 115 mouse mammary carcinoma, when cultured in the presence of 3.5 X 10(-8) M testosterone, retain their responsiveness to testosterone and 5alpha-dihydrotestosterone and exhibit fibroblast-like morphology; their growth is poorly regulated by cell density....
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1978-11-01 00:00:00