Abstract:
:Heat shock protein 90 (Hsp90) is a molecular chaperone that promotes the conformational maturation of numerous client proteins, many of which play critical roles in tumor cell growth and survival. The ansamycin-based Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG) is currently in Phase III clinical testing. However, 17-AAG is difficult to formulate and associated with dose-limited toxicity issues. A fully synthetic and bioavailable Hsp90 inhibitor, BIIB021, was evaluated for antitumor activity in a variety of head and neck squamous cell carcinoma (HNSCC) cell lines and HNSCC xenograft models, either as a single agent or in combination with fractionated radiation and the results were compared with that of 17-AAG. BIIB021 showed strong antitumor activity, comparable with, and in certain instances, superior to 17-AAG. BIIB021 enhanced the in vitro radiosensitivity of HNSCCA cell lines with a corresponding reduction in the expression of key radioresponsive proteins, increased apoptotic cells and enhance G2 arrest. In xenograft studies, BIIB021 exhibited a strong antitumor effect outperforming 17-AAG, either as a single agent and or in combination with radiation, thereby improved the efficacy of radiation. These results suggest that this synthetic and bioavailable Hsp90 inhibitor affects multiple pathways involved in tumor development and progression in the HNSCC setting and may represent a better strategy for the treatment of HNSCC patients, either as a monotherapy or a radiosensitizer. Furthermore, it also demonstrates the benefits of using preclinical models of chemosensitization to radiotherapy to explore clinically relevant radiation dosing schemes.
journal_name
Int J Cancerjournal_title
International journal of cancerauthors
Yin X,Zhang H,Lundgren K,Wilson L,Burrows F,Shores CGdoi
10.1002/ijc.24815subject
Has Abstractpub_date
2010-03-01 00:00:00pages
1216-25issue
5eissn
0020-7136issn
1097-0215journal_volume
126pub_type
杂志文章abstract::Angiogenesis in pancreatic ductal adenocarcinomas depends on the presence of angiogenic factors such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) and is thought to be stimulated by hypoxia. We tested the angiogenic potential of 9 cell lines of pancreatic ductal carcinoma origi...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.10753
更新日期:2002-12-20 00:00:00
abstract::In order to study the mechanisms responsible for resistance to CDDP, 5 human tumor cell lines were made resistant to CDDP by repeated in vitro exposures. After cloning it was found that the cell lines developed were between 3.3-fold and 17-fold more resistant to CDDP than the parental cell lines at the IC90. These lin...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910470214
更新日期:1991-01-21 00:00:00
abstract::Adhesion molecules involved in attachment between human pancreatic carcinoma and activated endothelial cells in vitro were investigated. Basal adhesion occurred between 6 pancreatic carcinoma cell lines and unstimulated human umbilical vein endothelial cells (HUVEC), and augmented basal adhesion to activated HUVEC was...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910540618
更新日期:1993-07-30 00:00:00
abstract::Several reports have suggested that one or both of the trinucleotide repeat polymorphisms in the human androgen receptor (hAR) gene, (CAG)n coding for polyglutamine and (GGC)n coding for polyglycine, may be associated with prostate cancer risk; but no study has investigated their association with disease progression. ...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/(sici)1097-0215(19991022)84:5<458::aid-ijc
更新日期:1999-10-22 00:00:00
abstract::There is a great need to identify new and better prognostic and predictive biomarkers to stratify prostate cancer patients for optimal treatment. The aims of this study were to characterize the expression profile of pre-B cell leukemia homeobox (PBX) transcription factors in prostate cancer with an emphasis on investi...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.30220
更新日期:2016-10-15 00:00:00
abstract::Mouse and human lymphoid cells were cultivated in the presence of T-cell growth factor (TCGF) and evaluated for their in vivo anti-tumor effect in mice. Cultured spleen cells of normal BALB/c mice or of mice bearing the M109 tumor had a high level of cytotoxic activity in vitro against a variety of tumor target cells ...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910280208
更新日期:1981-08-15 00:00:00
abstract::In a cohort of 11,663 participants in a breast-cancer screening program, height, weight, waist circumference and hip circumference were measured, and information about menstrual and reproductive history was obtained by questionnaire. After exclusion of 83 women with unclear menopausal status, the subjects were divided...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/(sici)1097-0215(19980529)76:5<647::aid-ijc
更新日期:1998-05-29 00:00:00
abstract::The presence of TGF alpha mRNA has been reported previously to occur in primary colon cancers. We report the expression of the normal 4.5 kb TGF alpha transcript in the mucosa of the normal human gastro-intestinal tract from oesophagus through to colon. The highest levels of human TGF alpha mRNA occurred in the duoden...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910430305
更新日期:1989-03-15 00:00:00
abstract::A case-control study involving interviews with 227 lung-cancer cases and 227 matched hospital controls was conducted in Heilongjiang Province in northeast China to examine the influence of dietary factors on the risk of developing lung cancer. Lung-cancer cases were all incident cases judged to be suitable candidates ...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/(sici)1097-0215(19970611)71:6<924::aid-ijc
更新日期:1997-06-11 00:00:00
abstract::Micro RNAs (miR) are master regulators of cellular transcriptome. We aimed to investigate the role of miR regulation on tumor radiosensitivity and development of local tumor recurrence by a novel large-scale in vivo loss of function screen. For stable miR silencing, human A431 tumor cells were transduced with lentivir...
journal_title:International journal of cancer
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doi:10.1002/ijc.32019
更新日期:2019-06-01 00:00:00
abstract::We applied a strategy that utilized a combination of systematic gene expression analysis with various tissues and immunological detection with sera from melanoma patients to identify melanoma antigens expressed preferentially in melanoma and melanocytes. We selected 101 genes by comparing cDNA profiles obtained by Gen...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.20735
更新日期:2005-03-20 00:00:00
abstract::CD30 is selectively expressed on the tumor cells of a variety of malignant disorders of the immune system and can therefore be used as a target for an anti-CD30 antibody-based immunotherapy. However, CD30 is cleaved at the cell surface by tumor necrosis factor-alpha converting enzyme (TACE). This metalloproteinase rel...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.10182
更新日期:2002-03-10 00:00:00
abstract::Individuals differ in their ability to repair DNA damage induced by carcinogens. Studies have shown that polymorphisms in DNA repair genes contribute to individual variation in DNA repair capacity and cancer risk. In a hospital-based case-control study, we tested the hypothesis that a C to T variant (Thr241Met) of DNA...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.10413
更新日期:2002-06-20 00:00:00
abstract::In ovarian cancer cells, the macrophage colony-stimulating factor-1 (CSF-1) induces the release of plasminogen activator inhibitor-2 (PAI-2), and high levels of PAI-2 as well as of CSF-1 in ovarian cancer ascites are independently correlated with poor outcome. We now study the effect of CSF-1 on PAI-2 expression in vi...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/(sici)1097-0215(19971219)74:6<571::aid-ijc
更新日期:1997-12-19 00:00:00
abstract::Preparations of stress protein gp96 from tumor cells are active as tumor vaccines by eliciting immune responses against mixtures of individual tumor peptide antigens which are complexed to gp96. Due to the individual antigenicity of tumors, a vaccine consisting of tumor-derived gp96 has to be prepared individually for...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/(sici)1097-0215(20000515)86:4<489::aid-ijc
更新日期:2000-05-15 00:00:00
abstract::Increasing evidence indicates that breast cancer pathogenesis is linked with DNA double-strand break (DSB) repair dysfunction. This conclusion is based on advances in the study of functions of breast cancer susceptibility genes such as BRCA1 and BRCA2, on the identification of breast cancer-associated changes regardin...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.23551
更新日期:2008-08-01 00:00:00
abstract::Coffee has been proposed to decrease the circulating insulin and estrogen levels, which are related to the development of endometrial cancer. However, few studies have prospectively assessed the association between coffee consumption and endometrial cancer. We conducted a population-based prospective cohort study in 5...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.23760
更新日期:2008-11-15 00:00:00
abstract::Topically applied vasoconstrictor is a new strategy to prevent oral mucositis and alopecia, two complications of chemotherapy and stem-cell transplant. We sought to determine whether mice treated with topical vasoconstrictor minutes before chemotherapy to suppress L1210 leukemia would develop a vasoconstrictor-induced...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.30037
更新日期:2016-06-15 00:00:00
abstract::Glioblastoma are notorious for their highly invasive growth, diffusely infiltrating adjacent brain structures that precludes complete resection, and is a major obstacle for cure. To characterize this "invisible" tumor part, we designed a high resolution multimodal imaging approach assessing in vivo the metabolism of i...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.31299
更新日期:2018-07-01 00:00:00
abstract::The aim of this study was to assess the diagnostic performance of breast imaging in the diagnosis of breast cancer in a non-screening population. In a consecutive set of patients referred for mammography in one year, the results of palpation and radiological breast imaging were scored on a 5-point grading scale and li...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.1235
更新日期:2001-05-15 00:00:00
abstract::We have previously shown that AEV infection of leukosis-free chickens provokes an erythroleukemia in the infected birds, and that the target cell for virus transformation is most likely an early pro-erythroblast comparable to the BFU-E. The virus infection correlates with a block in differentiation which was studied a...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910290511
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abstract::Cultured tumor cell lines, tumor xenografts grown in athymic nude mice, and a murine experimental metastasis model were used to assess the in vitro and in vivo anti-tumor activity of the potent IMP dehydrogenase (IMPDH) inhibitor, mycophenolic acid (MPA), and its morpholinoethyl ester pro-drug, mycophenolate mofetil (...
journal_title:International journal of cancer
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doi:10.1002/ijc.2910570421
更新日期:1994-05-15 00:00:00
abstract::Tumour cell anaerobic metabolism has been reported to be a prognostic factor in colorectal cancer. The present study investigated the association between monocarboxylate transporter (MCT) 1, MCT 2, lactate dehydrogenase (LDH) 1 and LDH 5, the tumour microenvironment, and outcome in patients with colorectal cancer. A c...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.32045
更新日期:2019-05-01 00:00:00
abstract::Breast cancer is the cancer diagnosed most frequently in women worldwide. In Europe it is the most common cancer in the female population, with approximately 350,000 new cases diagnosed each year including 130,000 deaths. Incidence rates are increasing in the majority of European countries, whereas a decline in mortal...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.20514
更新日期:2004-12-20 00:00:00
abstract::A variety of analytical approaches have indicated that melanoma cell line UCLA-SO-M14 (M14) and breast carcinoma cell line MDA-MB-435 originate from a common donor. This indicates that at some point in the past, one of these cell lines became misidentified, meaning that it ceased to correspond to the reported donor an...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.31067
更新日期:2018-02-01 00:00:00
abstract::Since the investigation, at an individual level, of lifetime sun exposure remains difficult the site distribution of different types of skin cancer can be an important source of aetiological clues. The present report deals with 1,149 cases of cutaneous malignant melanoma (CMM), 7,685 of basal-cell carcinoma (BCC) and ...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/(SICI)1097-0215(19960703)67:1<24::AID-IJC6
更新日期:1996-07-03 00:00:00
abstract::Two HLA-A2 restricted epitopes have recently been identified from the broadly expressed tumor antigen survivin, and several vaccination trials in cancer patients based on these survivin-derived peptides have been initiated. Consequently, there is a crucial need for the identification of survivin epitopes restricted to...
journal_title:International journal of cancer
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更新日期:2004-03-01 00:00:00
abstract::Permanent cell lines have been established in vitro from lymphoid tumors induced in C57BH/Ka mice by fractionated X-irradiation or by inoculation of the radiation leukemia virus (RadOV). The cultured cells are lymphoblastic, replicate rapidly in vitro, and are tumorigenic in vivo. The cell surface markers Thy 1, Ly 1,...
journal_title:International journal of cancer
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更新日期:1979-08-01 00:00:00
abstract::Although new treatments have been widely studied to improve the survival of patients with metastatic breast cancer (BC), prognosis continues to be poor with an average survival time no longer than 3 years. We carried on a population-based study with the purpose of evaluating the outcome of metastatic breast cancer in ...
journal_title:International journal of cancer
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更新日期:2015-09-15 00:00:00
abstract::Cetuximab in combination with an irinotecan-containing regimen is a standard treatment in patients with KRAS wild-type (KRAS WT), metastatic colorectal cancer (mCRC). We investigated the addition of the oral MET inhibitor tivantinib to cetuximab + irinotecan (CETIRI) based on preclinical evidence that activation of th...
journal_title:International journal of cancer
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doi:10.1002/ijc.30049
更新日期:2016-07-01 00:00:00