Abstract:
:Using high-throughput analyses and the TRANSFAC database, we characterized TF signatures of head and neck squamous cell carcinoma (HNSCC) subgroups by inferential analysis of target gene expression, correcting for the effects of DNA methylation and copy number. Using this discovery pipeline, we determined that human papillomavirus-related (HPV+) and HPV- HNSCC differed significantly based on the activity levels of key TFs including AP1, STATs, NF-κB and p53. Immunohistochemical analysis confirmed that HPV- HNSCC is characterized by co-activated STAT3 and NF-κB pathways and functional studies demonstrate that this phenotype can be effectively targeted with combined anti-NF-κB and anti-STAT therapies. These discoveries correlate strongly with previous findings connecting STATs, NF-κB and AP1 in HNSCC. We identified five top-scoring pair biomarkers from STATs, NF-κB and AP1 pathways that distinguish HPV+ from HPV- HNSCC based on TF activity and validated these biomarkers on TCGA and on independent validation cohorts. We conclude that a novel approach to TF pathway analysis can provide insight into therapeutic targeting of patient subgroup for heterogeneous disease such as HNSCC.
journal_name
Int J Cancerjournal_title
International journal of cancerauthors
Gaykalova DA,Manola JB,Ozawa H,Zizkova V,Morton K,Bishop JA,Sharma R,Zhang C,Michailidi C,Considine M,Tan M,Fertig EJ,Hennessey PT,Ahn J,Koch WM,Westra WH,Khan Z,Chung CH,Ochs MF,Califano JAdoi
10.1002/ijc.29558subject
Has Abstractpub_date
2015-10-15 00:00:00pages
1879-89issue
8eissn
0020-7136issn
1097-0215journal_volume
137pub_type
杂志文章abstract::The macrophage electrophoretic mobility (MEM) test was performed on guinea-pig macrophages treated with the interaction products of encephalitogenic protein and peripheral lymphocytes from 44 patients with colorectal cancer and 33 "healthy" controls. In 54/60 tests involving patients, statistically significant reducti...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910190407
更新日期:1977-04-15 00:00:00
abstract::The melanosomal protein TRP2 expressed by melanocytes and most melanoma cells is an attractive, clinically relevant model antigen for the experimental development of melanoma immunotherapy in mice. A peptide shared by murine and human TRP2 can be recognized by melanoma-reactive CTL in C57BL/6 mice, as well as in human...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/(sici)1097-0215(20000401)86:1<89::aid-ijc1
更新日期:2000-04-01 00:00:00
abstract::Sperm protein 17 (Sp17) is an antigenic protein highly expressed in spermatozoa. Sp17 expression was demonstrated recently in multiple myeloma, suggesting that it may be a novel cancer-testis antigen. Expression of Sp17 mRNA and protein was examined in human ovarian tumors. Sp17 mRNA was evaluated by reverse transcrip...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.11617
更新日期:2004-03-01 00:00:00
abstract::Melanoma is a highly malignant and increasingly common neoplasm. Because metastatic melanoma remains incurable, new treatment approaches are needed. Immunoliposomes have been previously shown to enhance the selective localization of immunoliposome-entrapped drugs to solid tumors with improvements in the therapeutic in...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/(sici)1097-0215(19990412)81:2<268::aid-ijc
更新日期:1999-04-12 00:00:00
abstract::Sera from 450 individuals between the age of 1 and 80 years, representing the general population of the Czech Republic, were tested for the presence of antibodies to human-papillomavirus(HPV)-derived antigens. The following antigens were used: (i) HPV1 virions; (ii) HPV16, -18 and -33-virus-like particles (VLP); (iii)...
journal_title:International journal of cancer
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doi:10.1002/(sici)1097-0215(19980831)77:5<689::aid-ijc
更新日期:1998-08-31 00:00:00
abstract::The 1100delC mutation of the cell cycle checkpoint kinase 2 (CHEK2) gene confers an increased risk for breast cancer, but the clinical impact of other CHEK2 gene variants remains unclear. We determined the frequency of two functionally relevant CHEK2 gene mutations, I157T and IVS2+1G > A, in two large series of breast...
journal_title:International journal of cancer
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doi:10.1002/ijc.21022
更新日期:2005-08-20 00:00:00
abstract::Although in the normal healthy organism angiogenesis is a tightly regulated process, under a variety of circumstances it may contribute to disease states. These include the growth of solid tumors, the hematogenous spread of tumor cells and the growth of metastasis. Our aim was to measure the levels of 5 angiogenic cyt...
journal_title:International journal of cancer
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doi:10.1002/(sici)1097-0215(20000101)85:1<40::aid-ijc7
更新日期:2000-01-01 00:00:00
abstract::Tobacco-related carcinogens cause a variety of DNA damage that is repaired by different enzymatic pathways, suggesting that DNA repair plays an important role in tobacco-induced carcinogenesis. In a large hospital-based case-control study, we investigated DNA repair capacity (DRC) as a biomarker for susceptibility to ...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.11346
更新日期:2003-10-20 00:00:00
abstract::Previous studies have suggested that thyroid function is associated with breast cancer risk, which could have an important clinical impact, as one in eight women will develop a thyroid disorder during her lifetime. However, the underlying pathomechanism behind the association is still unknown. We used the Malmö Diet a...
journal_title:International journal of cancer
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doi:10.1002/ijc.31156
更新日期:2018-04-01 00:00:00
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journal_title:International journal of cancer
pub_type: 杂志文章,多中心研究
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更新日期:2018-11-15 00:00:00
abstract::Immunosuppressed patients who develop non-Hodgkin's lymphoma (NHL) have abnormal antibody responses against the Epstein-Barr virus (EBV) prior to the diagnosis of malignancy. To see if this is also true of "spontaneous" cases in the general population, we undertook a collaborative serologic case-control study. From 4 ...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910490313
更新日期:1991-09-30 00:00:00
abstract::A hospital-based case-control study of renal-cell carcinoma was conducted in France from 1987 to 1991. A total of 196 histologically confirmed cases (138 males and 58 females) and 347 controls (235 males and 112 females), matched for sex, age at interview, hospital and interviewer, were included. The risk of renal-cel...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910550107
更新日期:1993-08-19 00:00:00
abstract::Duodenogastric reflux (DGR) causes glandular stomach carcinogenesis in rats without carcinogens. We aimed to investigate how this carcinogenesis might be prevented by a selective COX-2 inhibitor, meloxicam. A series of 188 Fisher 344 rats underwent a surgical DGR procedure and were divided into 2 groups. One group was...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.23742
更新日期:2008-10-01 00:00:00
abstract::A cytogenetic study, including prophase-prometaphase chromosome analysis, of a patient with EBV-genome-negative acute lymphocytic leukemia of B-cell type with Burkitt-type cells is presented. All bone-marrow mitoses examined had a 14q+ marker chromosome which was identified as a reciprocal 8;14 translocation of exactl...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910240106
更新日期:1979-07-15 00:00:00
abstract::Docetaxel (DOC), a member of the taxane family of anticancer drugs, binds to tubulin and produces unnaturally stable microtubules that induce cell death. DOC is used clinically alone or in combination with other compounds to treat advanced stages of cancer. We have treated the human lung cancer cell lines A549 and H12...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.21372
更新日期:2006-01-15 00:00:00
abstract::CXCR1 and CXCR2 are receptors for CXCL-8 and are differentially expressed on melanoma and endothelial cells. In this study, we determined the functional role of these receptors in melanoma progression. We stably knock-down the expression of CXCR1 and/or CXCR2 in A375-SM (SM; high metastatic) human melanoma cells by sh...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.24714
更新日期:2010-01-15 00:00:00
abstract::The cell-cycle regulator p16 inhibits the complex cdk4-cyclin D1 and controls G1-S transition. In human tumors, p16 inactivation is often accomplished by homozygous deletion (HD) of its encoding gene, CDKN2A. Methylation of the 5' CpG island promoter has been proposed as an alternative mechanism of inactivation. Expre...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/1097-0215(20001115)88:4<554::aid-ijc6>3.0.
更新日期:2000-11-15 00:00:00
abstract::A syngeneic tumor system in DBA/2 mice consisting of a methyl-cholanthrene-induced, weakly metastatic lymphoma, L5178YE (= Eb), its spontaneous strongly metastatic variant, L5178YES (= ESb), and an unrelated, methylcholanthrene-induced, metastasizing tumor, MDAY-D2, were used to study the relationship between metastat...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910360514
更新日期:1985-11-15 00:00:00
abstract::Cancer is an infrequent disease in childhood. However, it is responsible for 13.06% of child deaths between 1 and 14 years in Cuba. The aim of our work was to describe the incidence of childhood cancer in the period 1986 to 1990 using data reported to the National Cancer Registry (NCR) of Cuba. All cancer cases betwee...
journal_title:International journal of cancer
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doi:10.1002/(sici)1097-0215(19970807)72:4<551::aid-ijc
更新日期:1997-08-07 00:00:00
abstract::Two putative genes (termed pro 1 and pro 2) specifying sensitivity to induction of neoplastic transformation by TPA in mouse epidermal JB6 cells were cloned by sib selection from a size-selected genomic library of clonal cells sensitive to promotion of transformation. By restriction analysis, heteroduplex analysis, di...
journal_title:International journal of cancer
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doi:10.1002/ijc.2910370219
更新日期:1986-02-15 00:00:00
abstract::There is good evidence for an association between Epstein-Barr virus (EBV) and Hodgkin's disease (HD). In approximately one-third of cases, the EBV genome is detectable in Reed-Sternberg (RS) cells and there is expression of the viral nuclear antigen EBNA-1 and the latent membrane protein LMP-1. Expression of LMP-2 ha...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/(sici)1097-0215(19970807)72:4<614::aid-ijc
更新日期:1997-08-07 00:00:00
abstract::Primary cultures derived from pre-cancerous and cancerous human colon tissue are essential for understanding normal and abnormal growth function in the large intestine. Here presented are (i) the methodology for routine establishment of primary cultures of normal, adenoma- and carcinoma-derived cells, and (ii) data fo...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/(sici)1097-0215(19980130)75:3<467::aid-ijc
更新日期:1998-01-30 00:00:00
abstract::To obtain a comprehensive overview of chromosomal alterations that may underlie human papillomavirus (HPV)-mediated immortalization, 4 foreskin keratinocyte cell lines generated by transfection with either HPV 16 (cell lines FK16A and FK16B) or HPV 18 (FK18A and FK18B) were subjected to chromosomal analysis using comp...
journal_title:International journal of cancer
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doi:10.1002/(sici)1097-0215(19980504)76:3<412::aid-ijc
更新日期:1998-05-04 00:00:00
abstract::cis-Diamminedichloroplatinum(II) (CDDP) induced G2-phase arrest in PC-9 human cancer cells. To elucidate how CDDP acts on cell-cycle regulation, we analyzed the effect of CDDP on cell-cycle regulators such as p34cdc2 protein kinase. p34cdc2 protein kinase activity was maximum in G2 phase and decreased after G2/M trans...
journal_title:International journal of cancer
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doi:10.1002/ijc.2910550417
更新日期:1993-10-21 00:00:00
abstract::The effect of serum from mice bearing methylcholanthrene-induced fibrosarcomas on the lympho-proliferative responses of their spleen and lymph-node cells to 3 M KCl-solubilized tumor antigens has been investigated. Low concentrations of serum (less than or equal to 2.5%) collected throughout the course of tumor growth...
journal_title:International journal of cancer
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abstract::Treatment of human colorectal tumor cells (LS174T, HT-29, and WiDr) with analogues of cyclic AMP (cAMP) (dibutyryl-cAMP and 8-Cl-cAMP) selectively enhances the expression of carcinoembryonic antigen (CEA). Dose and temporal kinetics results revealed that 8-Cl-cAMP was approximately 100-fold more potent than dibutyryl-...
journal_title:International journal of cancer
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doi:10.1002/ijc.2910480319
更新日期:1991-05-30 00:00:00
abstract::The levels of tumour-specific antigen, antibody and specific immune complexes in the sera of rats bearing lung nodules of a chemically induced rat hepatoma, produced by intravenous inoculation of viable tumour cells, have been examined and compared with the levels of serum factors in animals actively immunized by intr...
journal_title:International journal of cancer
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更新日期:1976-02-15 00:00:00
abstract::We have investigated the effect of interferon-gamma (IFN-gamma) treatment of neuroblastoma cells on the susceptibility to lysis by lymphokine-activated killer (LAK) cells and examined the participation of cell-adhesion molecules on the target cells in LAK cell lysis. Untreated neuroblastoma cells expressed lymphocyte-...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910470410
更新日期:1991-02-20 00:00:00
abstract::Expression of the candidate metastasis-suppressor gene nm23-H1 has been shown to correlate inversely with metastatic potential in some human tumors, but not in all. Until now, few studies have been carried out on the activity of the homologous nm23-H2 gene in human cancer. No nm23 transcription studies exist for human...
journal_title:International journal of cancer
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更新日期:1993-09-30 00:00:00
abstract::Classical Hodgkin lymphoma (HL) is characterized by the presence of Hodgkin and Reed-Sternberg cells (H&RS) and a prominent lymphocytic infiltration. We previously reported Hodgkin-like adult T-cell leukemia/lymphoma (HL-like ATLL) (new WHO classification). Various CXC and CC chemokines are expressed on H&RS cells and...
journal_title:International journal of cancer
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更新日期:2003-09-20 00:00:00