bluuebunny/crossref_metadata_2025_split huggingface dataset:
An optimal dose‐effect mode trend test for SNP genotype tables
Authors: Yamada Ryo , Okada Yukinori 
Published: August 2008

AbstractThe genome‐wide association studies have improved our understanding of the genetic basis of many complex traits. Two‐by‐three contingency tables are tested in these studies. The trend test for the additive mode is most often used, which is the test of 1 degree of freedom (df=1) and other tests, such as the genotype test (χ2 (df=2)) and the χ2 (df=1) tests for the dominant and recessive modes are also used to increase the power for markers in the non‐additive modes. However, any one of them or combination of them is not perfect. We describe the relations among the χ2 (df=2) test and χ2 (df=1) tests for the dominant and recessive modes and the trend test for the additive mode and propose a new statistic based on their relations that tests the hypothesis that the disease‐susceptible allele has a dose‐effect somewhere between the recessive and dominant modes, which corresponds to the optimal dose‐effect for the observed data. Genet. Epidemiol. 2008. © 2008 Wiley‐Liss, Inc.
Multiple pathways for Epstein‐Barr virus episome loss from nasopharyngeal carcinoma
Authors: Dittmer Dirk P. , Hilscher Chelsey J. , Gulley Margaret L. , Yang Eric V. , Chen Min , Glaser Ronald 
Published: August 2008

AbstractEpstein‐Barr virus (EBV) is the prototypical example for episomal persistence of genetic information. Yet, little is known about how this viral episome is lost. Episome loss occurs naturally in nasopharyngeal carcinoma (NPC) upon explantation into culture. Using whole‐genome profiling, we found evidence for 2 different pathways of episome loss: (i) rapid loss of the entire episome or (ii) successive mutation/deletion of the episome until at least 1 essential cis‐element is destroyed. This second phenotype was seen in a clone of HONE‐1 NPC cells that maintains the EBV episome for prolonged time in culture. The conceptual insights provided by our quantitative analysis should aid our understanding of mammalian episomes, as well as lead to designs to cure latent viral infection. © 2008 Wiley‐Liss, Inc.
Small field radiotherapy of head and neck cancer patients is responsible for oxidatively damaged DNA/oxidative stress on the level of a whole organism
Authors: Roszkowski Krzysztof , Gackowski Daniel , Rozalski Rafal , Dziaman Tomasz , Siomek Agnieszka , Guz Jolanta , Szpila Anna , Foksinski Marek , Olinski Ryszard 
Published: August 2008

AbstractIt is possible that oxidatively damaged DNA which arises as a result of radiotherapy may be involved in the therapeutic effect of the ionizing radiation and in the side effects. Therefore, for the first time, the broad spectrum of oxidatively damaged DNA biomarkers: urinary excretion of 8‐oxodG (8‐oxo‐7,8‐dihydro‐2′‐deoxyguanosine), 8‐oxoGua (8‐oxo‐7,8‐dihydroguanine) as well as the level of oxidatively damaged DNA in leukocytes, was analyzed in head and neck cancer patients (n = 27) undergoing fractionated radiotherapy using methodologies which involve HPLC (high‐performance liquid chromatography) prepurification followed by gas chromatography with isotope dilution mass spectrometry detection and HPLC/EC. Of all the analyzed parameters in the majority of patients, only urinary excretion of the modified nucleoside significantly increased over the initial level in the samples collected 24 hr after the last fraction. However, for the distinct subpopulation of 10 patients, a significant increase in the level of 8‐oxodG in cellular DNA and a simultaneous drop in urinary 8‐oxoGua (the repair product of oxidative DNA damage) were detected after completion of the therapy. Because 8‐oxoGua is a repair product of the DNA damage, there is a possibility that, at least in the case of some patients with the lowest activity of OGG1 (8‐oxo‐7,8‐dihydroguanine glycosylase), the combination of lower OGG1 repair efficacy and irradiation was associated with increased background level of 8‐oxoGua in cellular DNA. Apparently reduced DNA repair is unable to cope with the radiation‐induced, and the extra amount of 8‐oxoGua leading to an increase of potentially mutagenic/carcinogenic lesions. © 2008 Wiley‐Liss, Inc.
Human papillomavirus‐16 and ‐18 in penile carcinomas: DNA methylation, chromosomal recombination and genomic variation
Authors: Kalantari Mina , Villa Luisa L. , Calleja‐Macias Itzel E. , Bernard Hans‐Ulrich 
Published: August 2008

AbstractPenile carcinomas are frequently associated with high risk human papillomavirus (HPV) types. Because little is known about the molecular biology of this association, we investigated three properties of HPV genomes in penile carcinomas from Brazilian patients: (i) HPV DNA methylation, (ii) junctions between HPV and cellular DNA and (iii) genomic variation. In cervical carcinogenesis, recombination between HPV and chromosomal DNA is frequent and likely necessary for progression, and DNA hypermethylation—specifically of the L1 gene—is a biomarker for cancerous progression. The same mechanisms apparently occur during penile carcinogenesis, because 95 HPV‐16 molecules derived from 19 penile lesions had 58% of the CpGs in L1 and 22% in the 5′ part of the long control region methylated, more than the percentages found in cervical carcinomas. In addition, 2 out of 3 HPV‐18 infections, all present in double infections with HPV‐16, showed L1 specific methylation typical of malignant cervical lesions. In 11 out of 15 HPV‐16 lesions, we confirmed chromosomal integration by reverse ligation inverted PCR, while 4 samples had concatemeric integrations or episomes. Nine of 17 penile carcinomas contained HPV‐16 AA variants, and 8 E variants. As AA variants are relatively rare in Brazilian cohorts of asymptomatic women, the high prevalence in penile carcinomas may indicate a higher risk of progression of AA lesions, as suspected for cervical infections. Our observations of frequent viral DNA methylation, chromosomal integration and the prevalence of high risk variants suggest that HPV‐dependent carcinogenesis of the penis and cervix follows similar etiological and epidemiological parameters. © 2008 Wiley‐Liss, Inc.
Prospective study of the association of gamma‐glutamyltransferase with cancer incidence in women
Authors: Strasak Alexander M. , Pfeiffer Ruth M. , Klenk Jochen , Hilbe Wolfgang , Oberaigner Willi , Gregory Martin , Concin Hans , Diem Günter , Pfeiffer Karl P. , Ruttmann Elfriede , Ulmer Hanno ,   the VHM&PP Study Group
Published: August 2008

AbstractAlthough several epidemiologic studies have shown that gamma‐glutamyltransferase (GGT) is associated with cardiovascular disease and all‐cause mortality, its relationship with cancer incidence remains widely unexplored. In experimental models the ability of cellular GGT to modulate crucial redox‐sensitive functions has been established, and it may thus play a role in tumor progression. In the present study, we investigated the association of GGT with overall and site‐specific cancer incidence in a population‐based cohort of 92,843 Austrian women with 349,674 serial GGT measurements, prospectively followed‐up for a median of 13.5 years. The relationship between GGT and cancer incidence was analyzed using adjusted Cox regression models with age as underlying time metric with age as underlying time metric including GGT concentrations at baseline and incorporating repeated GGT measurements as a time‐dependent variable. During follow‐up, 4,884 incidence cancers were observed. Compared to normal low GGT (<17.99 U/L), cancer risk was elevated for all other GGT categories (p for trend < 0.0001), with adjusted hazard ratios (95% confidence intervals) of 1.06 (0.99–1.13) for GGT levels between 18.00 and 35.99 U/L (normal high), 1.12 (1.02–1.22) for GGT levels between 36.00 and 71.99 U/L (elevated) and 1.43 (1.28–1.61) for highly elevated GGT (>72.00 U/L). Very similar results were seen when GGT was analyzed as a time‐dependent variable. In cancer‐site specific models, elevated GGT statistically significantly increased the risk for malignant neoplasms of digestive organs, the respiratory system/intrathoracic organs, breast and female genital organs and lymphoid and haematopoietic cancers (all, p < 0.006). Our study is the first to demonstrate in a large population‐based cohort that high GGT levels significantly increased cancer risk in women. Published 2008 Wiley‐Liss, Inc.
Acquired cisplatin resistance in the head–neck cancer cell line Cal27 is associated with decreased DKK1 expression and can partially be reversed by overexpression of DKK1
Authors: Gosepath Eva M. , Eckstein Niels , Hamacher Alexandra , Servan Kati , von Jonquieres Georg , Lage Hermann , Györffy Balazs , Royer Hans D. , Kassack Matthias U. 
Published: August 2008

AbstractHead and neck cancers are treated by a combination of surgery, radiotherapy and/or chemotherapy. The clinical success of cisplatin‐based chemotherapy, mostly in combination with 5‐FU or a taxane, is however limited by multifactorial intrinsic or acquired resistance. So far, known genes involved in cisplatin resistance do not sufficiently allow the prediction of cancer chemosensitivity. Thus, the purpose of this study was to search for further genes involved in cisplatin resistance by differential gene expression analysis of the parental tongue cancer cell line Cal27 and its 10‐fold more resistant sub‐cell line Cal27cis, which was obtained by treating Cal27 with increasing concentrations of cisplatin. As found by the suppression subtractive hybridization, expression of DKK1, an inhibitor of canonical WNT signaling, was decreased in Cal27cis. Microarray analysis, qPCR and ELISA confirmed the ∼2‐fold difference in expression. Cisplatin treatment and serum starvation increased by 2‐fold the secretion of DKK1 in Cal27 and Cal27cis, thus rendering DKK1‐levels significantly different in both cell lines under basal and stress conditions. Recombinant overexpression of DKK1 in Cal27 and Cal27cis resulted in clonal cell lines, which were both 2.2‐ to 3‐fold more sensitive toward cisplatin in cell viability (MTT) and in proliferation (BrdU) assays. In conclusion, acquired (10‐fold) resistance of Cal27 against cisplatin is associated with decreased DKK1 expression and could partially be reversed by DKK1 overexpression, thus suggesting DKK1 and the WNT signaling pathway as a marker and target for cisplatin chemosensitivity. © 2008 Wiley‐Liss, Inc.
Differential presentation of tumor antigen‐derived epitopes by MHC‐class I and antigen‐positive tumor cells
Authors: Held Gerhard , Neumann Frank , Sturm Christine , Kaestner Lars , Dauth Nina , de Bruijn Diederik, R. , Renner Christoph , Lipp Peter , Pfreundschuh Michael 
Published: August 2008

AbstractSSX2 is a member of the family of cancer/testis antigens. The SSX2 derived peptide SSX2103–111 has been shown to be presented to cytotoxic T‐lymphocytes (CTL) by Major‐Histocompatibility (MHC) Class‐I complexes after endogenous processing, more precisely by the allele HLA‐A*0201. The HLA‐A*0201‐ and SSX2‐positive melanoma cell line SK‐Mel‐37 but not Me275 had been shown to elicit reactivity in SSX2103–111 specific cytotoxic T‐lymphocytes. To analyze the correlation between SSX2103–111 presentation and T‐cell stimulation, we intended to visualize presentation of SSX2103–111 in these melanoma cell lines. Fab‐antibodies were established from a human phage library with specificity for SSX2103–111/HLA‐A*0201 complexes (but non‐reactive with HLA‐A*0201 or SSX2103–111 alone) and used to visualize the presentation of SSX2103–111 in the context of HLA‐A*0201 by fluorescence microscopy. Presentation of SSX2103–111 the context of HLA‐A*0201 was demonstrated for the majority of SK‐Mel‐37, but for only a small fraction (<1%) of Me275 as indicated by a clear membrane‐staining pattern in fluorescence microscopy. The presentation of SSX2103–111 on SK‐Mel37 and Me275, but not the expression of the SSX2 protein correlated with the capability of these cells to stimulate cells of an SSX2103–111‐specific T‐cell clone. MHC‐peptide specific antibodies are a valuable tool for the analysis of antigenic peptides in the context of MHC‐I molecules and for the structural definition of immunodominant epitopes. © 2008 Wiley‐Liss, Inc.
Effect of different types of smoking and synergism with hepatitis C virus on risk of hepatocellular carcinoma in American men and women: Case‐control study
Authors: Hassan Manal M. , Spitz Margaret R. , Thomas Melanie B. , El‐Deeb Adel S. , Glover Katrina Y. , Nguyen Nga T. , Chan Wenyaw , Kaseb Ahmed , Curley Steven A. , Vauthey Jean‐Nicolas , Ellis Lee M. , Abdalla Eddie , Lozano Richard D. , Patt Yehuda Z. , Brown Thomas D. , Abbruzzese James L. , Li Donghui 
Published: August 2008

AbstractThe International Agency for Research on Cancer has declared smoking to be a risk factor for hepatocellular carcinoma (HCC). However, passive exposure to cigarette smoke and use of noncigarette tobacco products on the risk of HCC has not been examined. Therefore, we evaluated the independent effects of different types of smoking exposure along with multiple risk factors for HCC and determined whether the magnitude of smoking was modified by other risk factors in men and women. We conducted a case‐control study at The University of Texas M. D. Anderson Cancer Center where 319 HCC patients and 1,061 healthy control subjects were personally interviewed for several HCC risk factors. Multivariate logistic regression analysis was performed to estimate the adjusted odds ratio (AOR) and 95% confidence interval (CI) for each potential risk factor. Use of smokeless tobacco (chewing tobacco and snuff), cigars, pipes and passive smoking exposure were not related to HCC among noncigarette smokers. However, regular cigarette smoking was associated with HCC in men: AOR, 1.9 (95% CI, 1.1–3.1). Heavy alcohol consumption was associated with HCC in women: AOR, 7.7 (95% CI, 2.3–25.1). Cigarette smoking interacted synergistically with chronic infection of hepatitis C virus in men: AOR, 136.3 (95% CI, 43.2–429.6) and with heavy alcohol consumption in women: AOR, 13.7 (95% CI, 3.2–57.9). We conclude that sex differences were observed in HCC relationship with cigarette smoking and alcohol consumption. Controlling for smoking exposure might be a prudent approach to the prevention of HCC, especially in patients with chronic viral hepatitis infections. © 2008 Wiley‐Liss, Inc.
Betel quid not containing tobacco and oral leukoplakia: A report on a cross‐sectional study in Papua New Guinea and a meta‐analysis of current evidence
Authors: Thomas Steven J. , Harris Ross , Ness Andrew R. , Taulo Joachim , Maclennan Robert , Howes Noah , Bain Christopher J. 
Published: August 2008

AbstractLeukoplakia is an asymptomatic, potentially malignant change in the oral mucosa. Previous studies have reported that smoking and betel quid chewing are associated with increased risk of leukoplakia; few studies have reported on these associations in populations where betel quid does not contain tobacco. We conducted a case–control study nested in a cross‐sectional study in Papua New Guinea and a systematic review of studies that included chewers of betel quid without tobacco. Our study recruited 1,670 adults. We recorded betel quid chewing and smoking. The prevalence of leukoplakia was 11.7%. In the nested case–control study of 197 cases and 1,282 controls, current betel chewing was associated with increased risk of leukoplakia with an adjusted odds ratio for current chewers of 3.8 (95% CI 1.7, 8.4) and in the heaviest chewers of 4.1 (95% CI 1.8, 9.1) compared to non‐chewers. Current smoking was associated with an increased risk of leukoplakia with an adjusted odds ratio for current smokers of 6.4 (95% CI 4.1, 9.9) and amongst heaviest smokers of 9.8 (95% CI 5.9, 16.4) compared to non‐smokers. The systematic review identified 5 studies examining risk of leukoplakia associated with betel quid chewing in populations where betel quid did not contain tobacco and that controlled for smoking. In studies that adjusted for smoking, the combined random effect odds ratio was 7.9 (95% CI 4.3, 14.6) in betel quid chewers. The results of this study and systematic review of similar studies provide evidence of the role of betel quid not containing tobacco and leukoplakia. © 2008 Wiley‐Liss, Inc.
Fruit and vegetable consumption and squamous cell carcinoma of the esophagus in Japan: The JPHC study
Authors: Yamaji Taiki , Inoue Manami , Sasazuki Shizuka , Iwasaki Motoki , Kurahashi Norie , Shimazu Taichi , Tsugane Shoichiro ,   for the Japan Public Health Center‐based Prospective Study Group
Published: August 2008

AbstractEpidemiological studies have consistently demonstrated a decrease in the risk of esophageal squamous cell carcinoma (SCC) associated with higher fruit and vegetable intake, although the association has been examined predominantly in case–control studies. Here, we conducted a population‐based prospective cohort study among middle‐aged Japanese men. Lifestyle characteristics were investigated using a self‐administered questionnaire, which included a validated food frequency questionnaire with 138 food and beverage items. We followed a total of 38,790 men aged 45–74 years. A Cox proportional hazards model was used to estimate the hazard ratios (HRs) and 95% confidence intervals (95% CIs) for esophageal SCC, with adjustment for potential confounders. During 297,651 person–years of follow‐up, a total of 116 men were newly diagnosed with esophageal SCC. An increase in consumption of total fruit and vegetables by 100 grams per day (g/day) was associated with an 11% decrease in the incidence of esophageal SCC (95% CI: 1–21%). In particular, a higher intake of cruciferous vegetables was associated with a significant decrease in risk (HR per 100 g/day: 0.44; 95% CI: 0.23–0.82). Stratified analyses revealed that the beneficial effect of fruits and vegetables was not able to completely offset the harmful effect of tobacco and alcohol. Our findings provide further evidence for the protective role of fruits and vegetables in the development of esophageal SCC. To effectively reduce the burden of this disease, however, priority should be placed on smoking and drinking cessation. Finally, cruciferous vegetables deserve further investigation as foods possibly effective in the prevention of esophageal SCC. © 2008 Wiley‐Liss, Inc.
Simvastatin, 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase inhibitor, suppresses osteoclastogenesis induced by receptor activator of nuclear factor‐κB ligand through modulation of NF‐κB pathway
Authors: Ahn Kwang Seok , Sethi Gautam , Chaturvedi Madan M. , Aggarwal Bharat B. 
Published: August 2008

AbstractSimvastatin, an inhibitor of 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase, is a cholesterol‐lowering drug that may play a role in bone metabolism through a mechanism that is not fully understood. Recently, receptor activator of NF‐κB ligand (RANKL), a member of the TNF superfamily, has emerged as a major mediator of bone loss via activation of osteoclastogenesis. The latter is also associated with certain cancers such as multiple myeloma and breast cancer. Whether simvastatin can modulate RANKL‐induced or cancer induced osteoclastogenesis was investigated. The effect of simvastatin on RANKL signaling and consequent osteoclastogenesis was investigated. RANKL induced NF‐κB activation, whereas pretreatment with simvastatin completely suppressed such activation and correlated with suppression of RANKL‐induced activation of IκBα kinase, IκBα phosphorylation and IκBα degradation. Similarly, RANKL induced the differentiation of monocytic cells to osteoclasts, whereas simvastatin suppressed it. The inhibition was maximal when cells were exposed to both simvastatin and RANKL simultaneously and minimal when simvastatin was added 1 day after RANKL treatment. Simvastatin also inhibited the osteoclastogenesis induced by human breast cancer and by multiple myeloma cells. Together, our results indicate that simvastatin inhibits the RANKL‐induced NF‐κB activation pathway that leads to suppression of osteoclastogenesis induced by RANKL and by tumor cells, thereby suggesting its therapeutic potential in osteoporosis and in cancer‐related bone loss. © 2008 Wiley‐Liss, Inc.
Overexpression of a secretory leukocyte protease inhibitor in human gastric cancer
Authors: Cheng Wan‐Li , Wang Chia‐Siu , Huang Ya‐Hui , Liang Ying , Lin Paul Y. , Hsueh Chuen , Wu Yi‐Chin , Chen Wei‐Jan , Yu Chia‐Jung , Lin Sheue‐Rong , Lin Kwang‐Huei 
Published: August 2008

AbstractComplementary DNA microarrays have identified aberrantly expressed genes in patients with gastric cancer. One that encodes secretory leukocyte protease inhibitor (SLPI) is among the aberrantly expressed genes and is associated with metastasis in gastric cancers. We evaluated the potential of SLPI expression as a helpful biomarker for detection of gastric cancer. Tumor tissue and matching noncancerous mucosa were obtained from 60 patients immediately after gastric resection. SLPI expression levels were determined by Northern and Western blot tests and quantitative‐reverse transcriptase‐polymerase chain reaction (Q‐RT‐PCR). Paraffin‐fixed tumor tissues were used for immunohistochemistry study in 119 patients. A consistent result was obtained between all examinations except plasma SLPI. SLPI mRNA transcripts and protein were overexpressed in gastric cancer cells, and the depth of wall invasion was significantly greater in serosa‐invading (T3 and T4) cancers compared to the serosa‐free (T1 and T2) cancers. These enhanced expressions were significantly associated with lymph node metastasis, and were significantly higher in stages III and IV, and higher than those in stages I and II. Five‐year survival of patients with lower expression of the SLPI gene was significantly better than among patients with a higher expression. To better understand the function of SLPI in human gastric cancer cells, isogenic SLPI overexpressing cell lines (AZ521) were prepared. The migratory and invasive abilities were increased 4.4‐fold to 6.9‐fold, or 3.0‐fold to 4.1‐fold, respectively, in SLPI‐overexpressing cell lines. The results point to SLPI as a potential prognostic marker for gastric cancer and its function in cell invasion. © 2008 Wiley‐Liss, Inc.
Promoter methylation of the bone morphogenetic protein‐6 gene in association with adult T‐cell leukemia
Authors: Taniguchi Ayuko , Nemoto Yuiko , Yokoyama Akihito , Kotani Norihiro , Imai Shosuke , Shuin Taro , Daibata Masanori 
Published: August 2008

AbstractBone morphogenetic proteins (BMP), belonging to the transforming growth factor‐β superfamily, are multifunctional regulators of cell proliferation, differentiation and apoptosis in various types of malignant cells. In this study, we investigated BMP‐6 promoter methylation in patients with various types of leukemias. The BMP‐6 methylation was found preferentially in adult T‐cell leukemia (ATL) (49 of 60, 82%) compared with other types of leukemias studied including acute myeloid leukemia (3 of 67, 5%), acute lymphoblastic leukemia (6 of 38, 16%) and chronic lymphocytic leukemia (1 of 21, 5%). Among subtypes of ATL, the BMP‐6 gene was more frequently methylated in aggressive ATL forms of acute (96%) and lymphoma (94%) types than less malignant chronic ATL (44%) and smoldering ATL (20%). We also analyzed the methylation status of peripheral blood mononuclear cells from healthy donors and nonmalignant lymph nodes with reactive lymphadenopathy, none of which showed detectable BMP‐6 methylation in this study. The BMP‐6 methyaltion was correlated with decreased mRNA transcript and protein expression. Expression of BMP‐6 was restored by the demethylating agent 5‐aza‐2′‐deoxycytidine, suggesting that methylation was associated with the transcriptional silencing. Serial analysis demonstrated an increasing methylation of CpG sites in the BMP‐6 promoter and the resultant suppression of BMP‐6 expression as ATL progressed. These findings suggested that BMP‐6 promoter methylation is likely to be a common epigenetic event at later stages of ATL and that the methylation profiles may be useful for the staging of ATL as well as for evaluation of the individual risk of developing the disease. © 2008 Wiley‐Liss, Inc.