bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ala228 variant of trail receptor 1 affecting the ligand binding site is associated with chronic lymphocytic leukemia, mantle cell lymphoma, prostate cancer, head and neck squamous cell carcinoma and bladder cancer
Authors: Wolf Stephan , Mertens Daniel , Pscherer Armin , Schroeter Petra , Winkler Dirk , Gröne Hermann‐Josef , Hofele Christof , Hemminki Kari , Kumar Rajiv , Steineck Gunnar , Döhner Hartmut , Stilgenbauer Stephan , Lichter Peter 
Published: October 2005

AbstractAllelic loss of chromosome 8p21–22 is a frequent event in various human cancers including mantle cell lymphoma (MCL), prostate cancer, head and neck squamous cell carcinoma (HNSCC) and bladder cancer. The tumor necrosis factor‐related apoptosis inducing ligand (TRAIL) receptors, including TNFRSF10A and TNFRSF10B, are located within this chromosomal region. Since recent studies demonstrate that chronic lymphocytic leukemia (CLL) and prostate cells are TRAIL induced apoptosis, TRAIL‐receptors are strong tumor suppressor candidate genes in human cancers exhibiting loss of chromosomal material in 8p21.3. However, no mutation of the TRAIL receptor genes has been reported in CLL, MCL, prostate cancer, HNSCC so far. In this study we analyzed the complete coding region of TNFRSF10A and TNFRSF10B in a series of 32 MCL and 101 CLL samples and detected a single nucleotide polymorphism (SNP) in TNFRSF10A (A683C) with tumor specific allele distribution. We examined allele distribution in 395 samples of different tumor entities (prostate cancer, n = 43; HNSCC, n = 40; bladder cancer, n = 179) and compared them to 137 samples from healthy probands. We found the rare allele of TNFRSF10A is more frequent in CLL, MCL, prostate cancer, bladder cancer and HNSCC. The A683C polymorphism did not cosegregate with other TNFRSF10A polymorphisms previously described. Thus screening for 683A→C nucleotide exchanges may become important in diagnosis and/or treatment of these malignancies. © 2005 Wiley‐Liss, Inc.
Targeting the epidermal growth factor receptor by erlotinib (Tarceva™) for the treatment of esophageal cancer
Authors: Sutter Andreas P. , Höpfner Michael , Huether Alexander , Maaser Kerstin , Scherübl Hans 
Published: October 2005

AbstractEsophageal cancer is the sixth most common cause of cancer‐related death worldwide. Because of very poor 5‐year survival new therapeutic approaches are mandatory. Erlotinib (Tarceva™), an inhibitor of epidermal growth factor receptor tyrosine kinase (EGFR‐TK), potently suppresses the growth of various tumors but its effect on esophageal carcinoma, known to express EGFR, remains unexplored. We therefore studied the antineoplastic potency of erlotinib in human esophageal cancer cells. Erlotinib induced growth inhibition of the human esophageal squamous cell carcinoma (ESCC) cell lines Kyse‐30, Kyse‐70 and Kyse‐140, and the esophageal adenocarcinoma cell line OE‐33, as well as of primary cell cultures of human esophageal cancers. Combining erlotinib with the EGFR‐receptor antibody cetuximab, the insulin‐like growth factor receptor tyrosine kinase inhibitor tyrphostin AG1024, or the 3‐hydroxy‐3‐methylglutaryl coenzyme. A reductase (HMG‐CoAR) inhibitor fluvastatin resulted in additive or even synergistic antiproliferative effects. Erlotinib induced cell cycle arrest at the G1/S checkpoint. The erlotinib‐mediated signaling involved the inactivation of EGFR‐TK and ERK1/2, the upregulation of the cyclin‐dependent kinase inhibitors p21Waf1/CIP1 and p27Kip1, and the downregulation of the cell cycle promoter cyclin D1. However, erlotinib did not induce immediate cytotoxicity or apoptosis in esophageal cancer cells. The inhibition of EGFR‐TK by erlotinib appears to be a promising novel approach for innovative treatment strategies of esophageal cancer, as it powerfully induced growth inhibition and cell cycle arrest in human esophageal cancer cells and enhanced the antineoplastic effects of other targeted agents. © 2005 Wiley‐Liss, Inc.
Evaluation of cervical screening strategies with adjunct high‐risk human papillomavirus testing for women with borderline or mild dyskaryosis
Authors: Berkhof Johannes , de Bruijne Martine C. , Zielinski Gilda D. , Bulkmans Nicole W.J. , Rozendaal Lawrence , Snijders Peter J.F. , Verheijen René H.M. , Meijer Chris J.L.M. 
Published: October 2005

AbstractThe management of women with a smear read as borderline/mild dyskaryosis (BMD) found by cervical cancer screening is still under discussion as only few of these cases are associated with high‐grade lesions. To determine the optimal screening strategy for these women, a simulation model of cervical cancer development was used that is based on high‐risk human papillomavirus (hrHPV) infection. The current strategy of repeat cytological testing at 6 and 18 months after BMD was compared to strategies with adjunct hrHPV testing. Calculations were done for both conventional and liquid‐based cytology as the primary screening tool. In comparison to current screening, adjunct hrHPV testing was more effective in preventing cancer and more woman‐friendly (reduction in colposcopy referrals with outcome < cervical intraepithelial neoplasia (CIN2) of up to 56% and in repeat smears of 30–100%). In combination with conventional cytology, cost‐effective strategies were the ones in which a sample for high‐risk human papillomavirus (hrHPV) testing is collected at a return visit within 1 month or in which hrHPV testing is restricted to repeat smears taken at 6 and 18 months. For these strategies, co‐collection of samples for hrHPV testing at baseline is not necessary which has organizational and cost advantages. In combination with liquid‐based cytology, it was cost‐effective to perform a reflex hrHPV test at baseline from the liquid‐based specimen. Liquid‐based screening was more effective than conventional screening, but annual diagnosis costs were €5 million higher (population size 16 million). In conclusion, our calculations indicate that implementation of hrHPV testing for the management of women with borderline or mild dyskaryosis (BMD) is feasible both in settings where conventional and liquid‐based cytology is current practice. © 2005 Wiley‐Liss, Inc.
From gene profiling to diagnostic markers: IL‐18 and FGF‐2 complement CA125 as serum‐based markers in epithelial ovarian cancer
Authors: Le Page Cécile , Ouellet Véronique , Madore Jason , Hudson Thomas J. , Tonin Patricia N. , Provencher Diane M. , Mes‐Masson Anne‐Marie 
Published: October 2005

AbstractWe used an oligonucleotide‐based DNA microarray to identify potential markers in 39 primary cultures of ovarian cancer specimens compared with 11 primary cultures of normal ovarian epithelia. Differential gene expression of IL‐18 and FGF‐2 was validated on a subset of samples by quantitative PCR and by IHC, using an independent tissue array of 90 cores of 20 normal ovarian surface epithelia and 70 EOCs representing different grades and pathologies of ovarian disease. We further compared, by ELISA, these two markers with CA125 in sera from 25 cancer‐free and 47 ovarian cancer patients. IL‐18 and FGF‐2 proteins were significantly elevated in tumor tissues (p<0.04) and sera (p<0.05) from patients with ovarian cancer. In combination, the three markers (IL‐18, FGF‐2, and CA125) showed similar sensitivity in scoring for ovarian cancer (35/45 patients) compared to that of CA125 alone (37/45) and significantly improved the specificity of detection (20/25 patients) compared to each marker individually (15/25 for CA125; 18/25 FGF‐2; 16/25 for IL‐18). In conclusion we show that a combination of the three serum markers (IL‐18, FGF‐2 and CA125) is associated with EOC, with higher specificity than CA125 alone. Prospective studies with a large cohort of susceptible ovarian cancer patients will be required to expand these findings. © 2005 Wiley‐Liss, Inc.
Endothelin system in oral squamous carcinoma cells: Specific siRNA targeting of ECE‐1 blocks cell proliferation
Authors: Awano Shuji , Dawson Louise A. , Hunter Alison R. , Turner Anthony J. , Usmani Badar A. 
Published: October 2005

AbstractThe present study focused on the endothelin axis in human oral squamous cell carcinoma (SCC) cells. We investigated the expression and distribution of endothelin‐1 (ET‐1), its receptors (endothelin‐A receptor (ETAR) and endothelin‐B receptor (ETBR)) and isoforms of its specific converting enzyme (ECE‐1a, 1b, 1c) and the report on their relative influences on cell proliferation. We also investigated the effect of an ECE‐specific inhibitor (ECE‐i) and siRNA targeting of the ECE‐1 gene on SCC cell proliferation. We observed the expression of ET‐1, ETAR, ETBR and all endothelin‐converting enzyme‐1 (ECE‐1) isoforms in oral SCC cells, but only the expression of ET‐1, ETBR and ECE‐1 was increased when compared to normal human epidermal keratinocytes. ET‐1 alone stimulated proliferation of oral SCC cells. Antagonists of either ETAR or ETBR inhibited ET‐1‐mediated proliferation. Decreased ECE‐1 expression after ECE siRNA treatment reduced SCC cell proliferation. Antiproliferative effects were also observed by inhibiting ECE activity with ECE‐i. In conclusion, the present study demonstrates that modulation of the endothelin system in oral SCC cells might provide a novel therapeutic protocol for oral cancer. © 2005 Wiley‐Liss, Inc.
Inhibitory effects of unmethylated CpG oligodeoxynucleotides on MHC class I‐deficient and ‐proficient HPV16‐associated tumours
Authors: Reiniš Milan , Šímová Jana , Bubeník Jan 
Published: October 2005

AbstractUnmethylated oligodeoxynucleotides containing guanine–cytidine dimers (CpG ODN) have been described as potent inducers of selected antitumour immune responses and the immunotherapeutic efficacy of CpG ODN has been examined either alone or as a vaccine adjuvant. We hypothesized that CpG ODN therapy could be an effective tool for immunotherapy of not only conventional MHC class I+ tumours but also of those tumours that have lost MHC class I expression during their progression. To address this hypothesis, we employed the animal model resembling MHC class I‐proficient and ‐deficient human papilloma virus (HPV) 16‐associated tumours. A cell line transformed with HPV16 E6 and E7 oncogenes, TC‐1, as a prototype of MHC class I‐positive line, and its MHC class I‐deficient sublines TC‐1/A9 and TC‐1/P3C10 were injected into syngeneic C57BL/6 mice and the growing tumours were subjected to immunotherapy with CpG ODN 1826. The therapy started either 1 day after the challenge with the tumour cells or later, when the tumours had reached a palpable size. In both settings, CpG ODN 1826 significantly reduced the growth of MHC class I‐proficient and ‐deficient tumours. Furthermore, we demonstrated that CpG ODN 1585, whose mechanism of action preferably involves indirect activation of the natural killer cells, induced regression of the MHC class I‐deficient tumours TC1/A9 but not of the MHC class I‐proficient tumours TC‐1. This study infers that synthetic CpG ODN have a potential for the therapy of both MHC class I‐proficient and ‐deficient tumours and thus could be also used against tumours that tend to down‐regulate their MHC class I expression. © 2005 Wiley‐Liss, Inc.
The pro‐cell death Bcl‐2 family member, BNIP3, is localized to the nucleus of human glial cells: Implications for glioblastoma multiforme tumor cell survival under hypoxia
Authors: Burton Teralee R. , Henson Elizabeth S. , Baijal Priti , Eisenstat David D. , Gibson Spencer B. 
Published: October 2005

AbstractThe Bcl‐2 nineteen kilodalton interacting protein 3 (BNIP3) is a hypoxia‐inducible proapoptotic member of the Bcl‐2 family that induces cell death by associating with the mitochondria. Under normal conditions, BNIP3 is expressed in skeletal muscle and in the brain at low levels. In many human solid tumors, BNIP3 is upregulated in hypoxic regions but paradoxically, this BNIP3 expression fails to induce cell death. Herein, we have determined that BNIP3 is primarily localized to the nucleus of glial cells of the normal human brain, as well as in the malignant glioma cell line U251. Upon exposure of U251 cells to hypoxia, BNIP3 expression in the cytoplasm increases and localizes with the mitochondria, contributing to induction of cell death. In contrast, when BNIP3 is forcibly over expressed in the nucleus, it fails to induce cell death. Expression of N‐terminal BNIP3 (lacking the transmembrane and conserved domains) in U251 cells blocks hypoxia‐induced cell death acting as a dominant negative protein by binding to wild‐type BNIP3 and blocking its association with the mitochondria. In glioblastoma multiforme (GBM) tumors, BNIP3 expression is increased in hypoxic regions of the tumor and is primarily localized to the nucleus in ∼80% of tumors. Hence, BNIP3 is sequestered in the nucleus within the brain but under hypoxic conditions, BNIP3 becomes primarily cytoplasmic, promoting cell death. In GBMs, BNIP3 expression is increased but it remains sequestered in the nucleus in hypoxic regions, thereby blocking BNIP3's ability to associate with the mitochondria, providing tumor cells with a possible survival advantage. © 2005 Wiley‐Liss, Inc.
Dietary carbohydrate, fibre, glycaemic index, glycaemic load and the risk of postmenopausal breast cancer
Authors: Giles Graham G. , Simpson Julie A. , English Dallas R. , Hodge Allison M. , Gertig Dorota M. , MacInnis Robert J. , Hopper John L. 
Published: October 2005

AbstractEvidence that the insulin pathway may be involved in breast carcinogenesis has increased the interest in dietary factors that influence insulin secretion and resistance. We investigated dietary carbohydrate, fibre, glycaemic index (GI) and glycaemic load (GL) in a prospective study of 324 breast cancers diagnosed in 12,273 post‐menopausal women. Although an increase of 1 standard deviation in carbohydrate was marginally associated with risk of breast cancer, relative risk (RR) 1.31 (95% CI, 0.98, 1.75), there were no significant associations with fibre, 1.08 (0.92, 1.26), GI, 0.98 (0.88, 1.10) or GL, 1.19 (0.93, 1.52) or with carbohydrate foods (bread, rice, pasta). The RR for carbohydrate and localized disease was elevated, 1.40 (1.02, 1.92), but like those for fibre, GI and GL did not differ significantly between localized and non‐localized disease. RRs for grade I, but not grade II or III, tumours were elevated for fibre, 1.38 (1.08, 1.75), carbohydrate, 1.56 (1.08, 2.25) and GL, 1.41 (1.01, 1.98) but not for GI, 0.84 (0.65, 1.09). The RRs for fibre and oestrogen receptor (ER) positive (+) and progesterone receptor (PR) positive (+) tumours, 1.36 (1.10, 1.67), differed significantly from those for ER positive (+) and PR negative (−) tumours, 1.01 (0.61, 1.69) and ER−/PR− tumours, 0.65 (0.43, 0.99), p = 0.005. Our data do not support a strong role for GI and GL in breast carcinogenesis but suggest that increased intake of fibre and carbohydrate may be associated with the diagnosis of cancers of more favourable prognosis. © 2005 Wiley‐Liss, Inc.
Accelerated repair and reduced mutagenicity of oxidative DNA damage in human bladder cells expressing the E. coli FPG protein
Authors: Ropolo Monica , Geroldi Alessandro , Degan Paolo , Andreotti Virginia , Zupo Simona , Poggi Alessandro , Reed April , Kelley Mark R. , Frosina Guido 
Published: October 2005

AbstractRepair of some oxidized purines such as 8‐oxo‐7,8‐dihydroguanine (8‐oxoG) is inefficient in human cells in comparison to repair of other major endogenous lesions (e.g. uracil, abasic sites or oxidized pyrimidines). This is due to the poor catalytic properties of hOGG1, the major DNA glycosylase involved in 8‐oxoG removal. The formamidopyrimidine DNA glycosylase (FPG) protein from E. coli is endowed with a potent 8‐oxoG glycolytic activity coupled with a β,δ‐AP lyase. In this study, we have expressed FPG fused to the enhanced green fluorescent protein (EGFP) in human bladder cells to accelerate the repair of oxidative DNA damage. Cells expressing the fusion protein EGFP–FPG repaired 8‐oxoG and AP sites at accelerated rates, in particular via the single‐nucleotide insertion base excision repair (BER) pathway and were resistant to mutagenicity of the oxidizing carcinogen potassium bromate. FPG may stably protect human cells from some harmful effects of oxidative DNA damage. © 2005 Wiley‐Liss, Inc.
Arsenic trioxide synergizes with B7H3‐mediated immunotherapy to eradicate hepatocellular carcinomas
Authors: Luo Liqiong , Qiao Haiquan , Meng Fanqiang , Dong Xuesong , Zhou Baoguo , Jiang Hongchi , Kanwar Jagat R , Krissansen Geoffrey W , Sun Xueying 
Published: October 2005

AbstractArsenic trioxide (As2O3), a valuable anticancer drug for the treatment of acute promyelocytic leukemia, may also have therapeutic potential for the treatment of solid tumors. However, its therapeutic efficacy against solid tumors is lacking even at high dosages. Other therapeutic strategies are required to enhance the efficacy of As2O3 against solid tumors such as hepatocellular carcinoma (HCC), which is refractory to chemotherapy. B7H3, a new member of the B7 family, has been shown to induce antitumor immunity. Intratumoral injection of B7H3 plasmids eradicates small EL‐4 lymphomas, but monotherapy is ineffective against large tumors. Here we investigated whether As2O3 would synergize with B7H3 immunotherapy to combat HCC. Large subcutaneous H22 HCCs (0.7–0.8 cm in diameter) established in BALB/c mice were rapidly and completely eradicated when intratumoral administration of As2O3 was preceded by in situ gene transfer of B7H3. In contrast, neither As2O3 nor B7H3 monotherapy was effective. The antitumor activity of As2O3 was attributed to increased tumor‐cell apoptosis, perhaps as a result of direct cytotoxicity as well as decreased tumor angiogenesis. Combination therapy generated potent systemic antitumor immunity mediated by CD8+ and NK cells that was effective in combating a systemic challenge of 1 × 107 parental H22 cells. It led to the simultaneous and complete regression of multiple distant tumor nodules, concomitant with increased levels of serum IFN‐γ and cytotoxic T lymphocyte (CTL) activity. In conclusion, combining B7H3‐mediated immunotherapy with As2O3 warrants investigation as a therapeutic strategy to combat HCC, and other malignancies. © 2005 Wiley‐Liss, Inc.
siRNA gelsolin knockdown induces epithelial‐mesenchymal transition with a cadherin switch in human mammary epithelial cells
Authors: Tanaka Hiroki , Shirkoohi Reza , Nakagawa Koji , Qiao Hongjiang , Fujita Hisakazu , Okada Futoshi , Hamada Jun‐ichi , Kuzumaki Satoshi , Takimoto Masato , Kuzumaki Noboru 
Published: October 2005

AbstractEpithelial‐mesenchymal transition (EMT) describes a process occurring during development and oncogenesis by which epithelial cells obtain fibroblast‐like properties and show reduced cell adhesion and increased motility. In this report, we demonstrated typical EMT in human mammary epithelial MCF10A small interfering (si)RNA gelsolin‐knockdown cells. EMT was characterized by fibroblastic morphology, loss of contact inhibition and focus formation in monolayer growth, enhanced motility and invasiveness in vitro, increased actin filaments, overexpression of RAC, activation of both extracellular signal‐regulated kinase and AKT, inactivation of glycogen synthase kinase‐3, conversion of cadherin from the E‐ to N‐type and induction of the transcription factor Snail. These results suggested that gelsolin functions as a switch that controls E‐ and N‐cadherin conversion via Snail, and demonstrated that its knockdown leads to EMT in human mammary epithelial cells and possibly to the development of human mammary tumors. © 2005 Wiley‐Liss, Inc.
Never smokers and lung cancer risk: A case‐control study of epidemiological factors
Authors: Gorlova Olga Y. , Zhang Yiqun , Schabath Matthew B. , Lei Lei , Zhang Qing , Amos Christopher I. , Spitz Margaret R. 
Published: October 2005

AbstractWe performed an analysis of potential epidemiological risk factors for lung cancer using data from 280 cases and 242 hospital‐based controls, all lifetime never smokers (those who had smoked <100 cigarettes in their lifetimes) and frequency matched on age, gender and ethnicity. The data on demographic characteristics, medical history of respiratory diseases (asthma, emphysema, pneumonia and hay fever), weight and height, family history, female characteristics and environmental tobacco smoke (ETS) and dust exposure were derived from personal interviews. We performed a logistic regression analysis of these variables adjusting for age, gender, ethnicity, income and years of education. Exposure to ETS (OR = 2.08, 95% CI [1.25–3.43]) and dusts (OR = 2.43, 95% CI [1.53–3.88]) were associated with significantly increased risk. In the analysis for joint effects, exposure to both ETS and dusts conferred a higher risk (OR = 3.25, 95% CI [1.58–6.70]) than exposure to either alone. Family history of any cancer with onset before age 50 in at least 1 first degree relative was a significant risk predictor (OR = 1.70, 95% CI [1.10–2.64]). Individuals with a self‐reported physician‐diagnosed history of hay fever, but not asthma, had a decreased lung cancer risk (OR = 0.57, 95% CI [0.35–0.92]). In the multivariate analysis, exposure to ETS and dusts, and family history of cancer with onset before age 50 were significant risk factors, while a history of hay fever (occurring without asthma) was significantly protective. © 2005 Wiley‐Liss, Inc.
Cigarette smoking and risk of glioma: A prospective cohort study
Authors: Silvera Stephanie A. Navarro , Miller Anthony B. , Rohan Thomas E. 
Published: October 2005

AbstractThe etiology of glioma, the most commonly diagnosed malignant brain tumor among adults in the United States, is poorly understood. N‐nitroso compounds are known carcinogens, which are found in cigarette smoke and can induce gliomas in rats. On this basis, it has been hypothesized that cigarette smoking may be associated with an increased risk of glioma. We investigated the association between cigarette smoking and glioma risk in the National Breast Screening Study, which included 89,835 Canadian women aged 40–59 years at recruitment between 1980 and 1985. Linkages to national cancer and mortality databases yielded data on cancer incidence and deaths from all causes, respectively, with follow‐up ending between 1998 and 2000. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between cigarette smoking and risk of glioma. During a mean of 16.4 years of follow‐up, we observed 120 incident glioma cases. Among ever smokers, women who reported having quit smoking had a 51% increase in risk of glioma compared with never smokers (HR = 1.51, 95% CI = 0.97–2.34), while current smokers did not appear to have an increase in risk. When the association with former smokers was further examined by years since quitting, women who had quit smoking >10 years before baseline were at a decreased risk of glioma compared with women who had quit within the 10 years prior to baseline (HR = 0.55, 95% CI = 0.29–1.07), indicating that the association between former smokers and glioma may be driven by women, who recently quit smoking. Compared with nonsmokers, duration of cigarette smoking, number of cigarettes smoked per day and pack‐years of smoking were associated with increased glioma risk, although the increases in risk were relatively modest. The present study provides some support for a positive association between cigarette smoking and risk of glioma. © 2005 Wiley‐Liss, Inc.