bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression and mutation analysis of epidermal growth factor receptor in head and neck squamous cell carcinoma
Authors: Ali Mahmoud A.L. Sheikh , Gunduz Mehmet , Nagatsuka Hitoshi , Gunduz Esra , Cengiz Beyhan , Fukushima Kunihiro , Beder Levent Bekir , Demircan Kadir , Fujii Masae , Yamanaka Noboru , Shimizu Kenji , Grenman Reidar , Nagai Noriyuki 
Published: August 2008

The epidermal growth factor receptor (EGFR)–RAS–RAF–mitogen‐activated protein kinase signaling cascade is an important pathway in cancer development and recent reports show that EGFR and its downstream signaling molecules are mutated in a number of cancers. We have analyzed 91 Japanese head and neck squamous cell carcinomas (HNSCC) and 12 HNSCC cell lines for mutations in EGFR, ErbB2, and K‐ras. Exons encoding the hot‐spot regions in the tyrosine kinase domain of both EGFR (exons 18, 19, and 21) and ErbB2 (exons 18–23), as well as exons 1 and 2 of K‐ras were amplified by polymerase chain reaction and sequenced directly. EGFR expression was also analyzed in 65 HNSCC patients using immunohistochemistry. Only one silent mutation, C836T, was found in exon 21 of EGFR in the UT‐SCC‐16A cell line and its corresponding metastasic cell line UT‐SCC‐16B. No other mutation was found in EGFR, ErbB2, or K‐ras. All tumors showed EGFR expression. In 21 (32%) tumors, EGFR was expressed weakly (+1). In 27 (42%) tumors it was expressed (+2) moderately, and in 17 (26%) tumors high expression (+3) was detected. Overexpression (+2, +3) was found in 44 tumors (68%). A worse tumor differentiation and a positive nodal stage were significantly associated with EGFR overexpression (P = 0.02, P = 0.032, respectively). Similar to patients from western ethnicity, mutations are absent or rare in Japanese HNSCC. Protein overexpression rather than mutation might be responsible for activation of the EGFR pathway in HNSCC. (Cancer Sci 2008; 99: 1589–1594)
Caffeine yields aneuploidy through asymmetrical cell division caused by misalignment of chromosomes
Authors: Katsuki Yoko , Nakada Shinichiro , Yokoyama Tetsuji , Imoto Issei , Inazawa Johji , Nagasawa Masayuki , Mizutani Shuki 
Published: August 2008

Aneuploidy has been implicated as an important step leading to various neoplasias. Although genetic factors that block aneuploidy have been the subject of intense interest, the impact of pharmacological and environmental substances on the development of aneuploidy has not been studied. Here, we show that caffeine induces aneuploidy through asymmetrical cell division. Mitotic exits of HeLa, U2OS, and primary fibroblast cells were significantly delayed by 10 mmol/L caffeine. Most caffeine‐treated mitotic cells showed misalignment of chromosomes at the metaphase plates, and were arrested at prometaphase. Mitoticarrest deficient 2 (MAD2) depletion rescued the caffeine‐induced delay of mitotic exit, indicating that caffeine‐induced prolongation of mitosis was caused by activation of a MAD2‐dependent spindle checkpoint. Enumeration of centromeres by fluorescence in situ hybridization revealed that cell division in the presence of caffeine was not symmetrical and resulted in aneuploid cell production. Most of these cells survived and underwent DNA synthesis. Our findings reveal a novel pharmacological effect of a high concentration of caffeine on genomic stability in dividing cells. (Cancer Sci 2008; 99: 1539–1545)
Head and neck cancer in the betel quid chewing area: recent advances in molecular carcinogenesis
Authors: Chen Yin‐Ju , Chang Joseph Tung‐Chieh , Liao Chun‐Ta , Wang Hung‐Ming , Yen Tzu‐Chen , Chiu Ching‐Chi , Lu Ya‐Ching , Li Hsiao‐Fang , Cheng Ann‐Joy 
Published: August 2008

Head and neck cancer (HNC) is one of the 10 most frequent cancers worldwide, with an estimated over 500 000 new cases being diagnosed annually. The overall 5‐year survival rate in patients with HNC is one of the lowest among common malignant neoplasms and has not significantly changed during the last two decades. Oral cavity squamous cell carcinoma (OSCC) shares part of HNC and has been reported to be increasing in the betel quid chewing area in recent years. During 2006, OSCC has become the sixth most common type of cancer in Taiwan, and it is also the fourth most common type of cancer among men. It follows that this type of cancer wreaks a high social and personal cost. Environmental carcinogens such as betel quid chewing, tobacco smoking and alcohol drinking have been identified as major risk factors for head and neck cancer. There is growing interest in understanding the relationship between genetic susceptibility and the prevalent environmental carcinogens for HNC prevention. Within this review, we discuss the molecular and cellular aspects of HNC carcinogenesis in Taiwan, an endemic betel quid chewing area. Knowledge of molecular carcinogenesis of HNC may provide critical clues for diagnosis, prognosis, individualization of therapy and molecular therapeutics. (Cancer Sci 2008; 99: 1507–1514)
Treating adolescent drug abuse: a randomized trial comparing multidimensional family therapy and cognitive behavior therapy
Authors: Liddle Howard A. , Dakof Gayle A. , Turner Ralph M. , Henderson Craig E. , Greenbaum Paul E. 
Published: August 2008

ABSTRACTAim To examine the efficacy of two adolescent drug abuse treatments: individual cognitive behavioral therapy (CBT) and multidimensional family therapy (MDFT).Design A 2 (treatment condition) x 4 (time) repeated‐measures intent‐to‐treat randomized design. Data were gathered at baseline, termination, 6 and 12 months post‐termination. Analyses used latent growth curve modeling.Setting Community‐based drug abuse clinic in the northeastern United States.Participants A total of 224 youth, primarily male (81%), African American (72%), from low‐income single‐parent homes (58%) with an average age of 15 years were recruited into the study. All youth were drug users, with 75% meeting DSM‐IV criteria for cannabis dependence and 13% meeting criteria for abuse.Measurements Five outcomes were measured: (i) substance use problem severity; (ii) 30‐day frequency of cannabis use; (iii) 30‐day frequency of alcohol use; (iv) 30‐day frequency of other drug use; and (v) 30‐day abstinence.Findings Both treatments produced significant decreases in cannabis consumption and slightly significant reductions in alcohol use, but there were no treatment differences in reducing frequency of cannabis and alcohol use. Significant treatment effects were found favoring MDFT on substance use problem severity, other drug use and minimal use (zero or one occasion of use) of all substances, and these effects continued to 12 months following treatment termination.Conclusion Both interventions are promising treatments. Consistent with previous controlled trials, MDFT is distinguished by the sustainability of treatment effects.
Work‐place social capital and smoking cessation: the Finnish Public Sector Study
Authors: Kouvonen Anne , Oksanen Tuula , Vahtera Jussi , Väänänen Ari , De Vogli Roberto , Elovainio Marko , Pentti Jaana , Leka Stavroula , Cox Thomas , Kivimäki Mika 
Published: August 2008

ABSTRACTAims To examine whether high social capital at work is associated with an increased likelihood of smoking cessation in baseline smokers.Design Prospective cohort study.Setting Finland.Participants A total of 4853 employees who reported to be smokers in the baseline survey in 2000–2002 (response rate 68%) and responded to a follow‐up survey on smoking status in 2004–2005 (response rate 77%).Measurements Work‐place social capital was assessed using a validated and psychometrically tested eight‐item measure. Control variables included sex, age, socio‐economic position, marital status, place of work, heavy drinking, physical activity, body mass index and physician‐diagnosed depression.Findings In multi‐level logistic regression models adjusted for all the covariates, the odds for being a non‐smoker at follow‐up were 1.26 [95% confidence interval (CI) = 1.03–1.55] times higher for baseline smokers who reported high individual‐level social capital than for their counterparts with low social capital. In an analysis stratified by socio‐economic position, a significant association between individual‐level social capital and smoking cessation was observed in the high socio‐economic group [odds ratio (OR) (95% CI) = 1.63 (1.01–2.63)], but not in intermediate [(OR = 1.10 (0.83–1.47)] or low socio‐economic groups [(OR = 1.28 (0.86–1.91)]. Work unit‐level social capital was not associated with smoking cessation.Conclusions If the observed associations are causal, these findings suggest that high perceived social capital at work may facilitate smoking cessation among smokers in higher‐status jobs.
A Scotland‐wide pilot programme of smoking cessation services for young people: process and outcome evaluation
Authors: Gnich Wendy , Sheehy Christine , Amos Amanda , Bitel Mark , Platt Stephen 
Published: August 2008

ABSTRACTAim  To conduct an independent, external evaluation of a Scotland‐wide youth cessation pilot programme, focusing upon service uptake and effectiveness.Intervention  National Health Service (NHS) Health Scotland and Action on Smoking and Health (ASH) Scotland funded a 3‐year (2002–2005) national pilot programme comprising eight projects which aimed to engage with and support young smokers (aged 12–25 years) to quit.Design, participants and measurements  Process evaluation was undertaken via detailed case studies comprising qualitative interviews, observation and documentary analysis. Outcomes were assessed by following project participants (n = 470 at baseline) at 3 and 12 months and measuring changes in smoking behaviour, including carbon monoxide (CO)‐validated quit status.Findings  Recruitment proved difficult. Considerable time and effort were needed to attract young smokers. Advertising and recruitment had to be tailored to project settings and educational activities proved essential to raise the profile of smoking as an issue. Thirty‐nine participants [8.6%, 95% confidence interval (CI) 5.0–11.2%] were CO‐validated quitters at 3 months and 11 of these (2.4%, 95% CI 1.90–3.8%) were also validated quitters at 12 months. Older participants were more likely to be abstinent at 3 months.Conclusions  The overall quit rate was disappointing. As a result of low participant numbers, it was impossible to draw conclusions about the relative effectiveness of different project approaches. These findings give little support to the case for developing dedicated youth cessation services in Scotland. They also highlight the difficulties of undertaking ‘real‐world’ evaluations of pilot youth cessation projects. More action is needed to develop environments which enhance young smokers' motivation to quit and their ability to sustain quit attempts.
Insulin effect on adipose tissue (AT) adiponectin expression is regulated by the insulin resistance status of the patients
Authors: Hernandez‐Morante J. J. , Milagro F. I. , Lujan J. A. , Martinez J. A. , Zamora S. , Garaulet M. 
Published: August 2008

SummaryObjective  The objective of the present study was to determine a possible depot‐specific effect of insulin‐stimulation on adiponectin gene expression in adipose tissue (AT) explants from subcutaneous and visceral AT. A secondary aim was to analyse the associations of adiponectin plasma levels, as well as control and insulin‐stimulated gene expression levels with different features of the metabolic syndrome.Design  Visceral and subcutaneous AT biopsies were obtained from 20 subjects (10 men and 10 women) with morbid obesity. Metabolic syndrome and other clinical features were studied. Adiponectin expression from isolated adipocytes was measured both in control and after insulin‐stimulation conditions by quantitative PCR.Results  Subcutaneous adipocytes expressed significantly higher amounts of adiponectin mRNA than visceral tissue (P = 0·027). Insulin increased adiponectin expression specifically in the omental tissue (P = 0·011). In these patients, waist : hip ratio was directly correlated with adiponectin expression in the visceral depot (r = 0·660; P = 0·014), while fasting glucose levels were inversely associated with adiponectin mRNA in the subcutaneous tissue (r =–0·604; P = 0·022). Adiponectin expression after addition of insulin was positively correlated with some metabolic risk factors (cholesterol, LDL‐cholesterol, insulin, C‐peptide). Interestingly, local insulin induced an up‐regulation of adiponectin expression in the AT of those patients with higher metabolic syndrome disturbances.Conclusions  Our results clearly demonstrate that insulin exerts a stimulating effect on adiponectin gene expression in a depot‐specific manner. The AT response to insulin stimulus depends on the physiopathological situation, being higher in those individuals with impaired insulin‐sensitivity and lipid metabolism.
Topographical associations between islet endocrine cells and duct epithelial cells in the adult human pancreas
Authors: Zhao Hai‐Lu , Sui Yi , Guan Jing , Lai Fernand M. M. , Gu Xue‐Mei , He Lan , Zhu Xun , Rowlands Dewi K. , Xu Gang , Tong Peter C. Y. , Chan Juliana C. N. 
Published: August 2008

SummaryObjectives  The pancreatic ducts, endocrine islets and exocrine acini are three functionally related components. From birth to adulthood, the islets and ducts are regarded as independent entities. The objective of this study is to investigate the topographical associations between the islet endocrine cells and duct epithelial cells in the adult human pancreas.Materials and methods  Panels of immunomarkers for the exocrine acinar cells (amylase), duct cells [cytokeratin 19 (CK19)], endocrine cells (chromogranin A, neurone specific enolase, synaptophysin) and islet hormones (glucagon, insulin, somatostatin, pancreatic polypeptide) were applied to sequential pancreatic tissue sections obtained from autopsy specimens of 10‐nondiabetic human adults. Double immunofluorescent staining with CK19 and islet hormones was performed to confirm the islet to duct interrelationship.Results  Sequential sectioning and immunostaining showed that 45% of the 172 islets examined appeared as single endocrine cell units or small clusters of < 10 endocrine cells on at least one plane of section. A topographical association was found between the islet endocrine cells and duct epithelial cells. Topographical associations with CK 19‐stained duct cells occurred in 10·9% of the islet insulin‐containing β‐cells and in 8·9% of the islet glucagon‐producing α‐cells. The frequency of topographical associations increased toward the more distally located duct systems. The CK19‐stained duct cells and amylase‐labelled acinar cells were less frequently in association with other islet hormone‐producing cells.Conclusions  Topographical associations between islet endocrine cells and pancreatic duct cells are frequent in adult human pancreas. The islet–duct association suggests possible functional interactions between the two interrelated pancreatic compartments.
Evaluation of the autoimmune regulator (AIRE) gene mutations in a cohort of Italian patients with autoimmune‐polyendocrinopathy‐candidiasis‐ectodermal‐dystrophy (APECED) and in their relatives
Authors: Cervato Sara , Mariniello Barbara , Lazzarotto Francesca , Morlin Luca , Zanchetta Renato , Radetti Giorgio , De Luca Filippo , Valenzise Mariella , Giordano Roberta , Rizzo Daniela , Giordano Carla , Betterle Corrado 
Published: August 2008

SummaryObjective   Autoimmune‐polyendocrinopathy‐candidiasis‐ectodermal‐dystrophy (APECED) is a rare syndrome characterized by chronic candidiasis, chronic hypoparathyroidism and Addison's disease. APECED has been associated with mutations in autoimmune regulator (AIRE) gene. Our aim is to perform a genetic analysis of the AIRE gene in Italian APECED patients and in their relatives.Design  AIRE mutations were determined by DNA sequencing in all subjects. Patients were tested for clinical autoimmune or non‐autoimmune diseases, or for organ and non‐organ specific autoantibodies.Patients   A total of 24 Italian patients with APECED (15 from the Venetian region, 2 from Southern‐Tyrol, 4 from Apulia, 3 from Sicily), 25 relatives and 116 controls were studied.Results  Ten out of the 15 Venetian patients (66%) were homozygous for R257X or compound heterozygous with 1094–1106del13. One patient was homozygous for 1094–1106del13 and another for R139X. A novel mutation (1032–1033delGT) in combination with 1094–1106del13 was identified in one patient. No mutations were found in two cases. Two patients from Southern Tyrol were homozygous for R257X and for 1094–1106del13bp. All patients from Apulia were homozygous or heterozygous for W78R combined with Q358X. The patients from Sicily were homozygous for R203X or compound heterozygous with R257X. The analysis of the genotype–phenotype revealed that patients carrying 1094–1106del13 at the onset of Addison's disease were significantly older than those carrying other mutations. The genetic study of 25 relatives identified 20 heterozygous subjects. They suffered from various autoimmune and non‐autoimmune diseases but no major disease of APECED was found.Conclusion  These data demonstrate the great genetic heterogeneity for the AIRE mutations in Italian APECED patients, and that the heterozygosity for AIRE mutations do not produce APECED.
Repeated transsphenoidal pituitary surgery (TS) via the endoscopic technique: a good therapeutic option for recurrent or persistent Cushing's disease (CD)
Authors: Wagenmakers M. A. E. M. , Netea‐Maier R. T. , Van Lindert E. J. , Timmers H. J. L. M. , Grotenhuis J. A. , Hermus A. R. M. M. 
Published: August 2008

SummaryBackground No data on results of repeated transsphenoidal surgery via the endoscopic technique for patients with persistent or recurrent Cushing's disease are available.Design and patients We retrospectively evaluated the remission rates and complications of repeated transsphenoidal surgery via the endoscopic technique in 14 patients with persistent (N = 6) or recurrent (N = 8) Cushing's disease treated in our centre between 1999 and 2007.Main outcomes Remission was defined as the disappearance of symptoms of hypercortisolism with basal plasma cortisol level ≤ 50 nmol/l 24–48 h after glucocorticoid withdrawal and/or suppression of plasma cortisol level ≤ 50 nmol/l after 1 mg dexamethasone overnight within the first 3 months after transsphenoidal surgery.Results With repeated endoscopic transsphenoidal surgery a remission rate of 10/14 (71%) was achieved. No patient had a relapse during a median follow‐up of 24 months. Cerebrospinal fluid leakage was the most frequent complication (6 patients) and 11 patients required hormonal substitution after surgery. The success of repeated transsphenoidal surgery could not be predicted by visualization of an adenoma on MRI before first or second surgery, histopathological confirmation of an ACTH secreting adenoma after first or second surgery, treatment with cortisol lowering agents before first or second surgery, the operation technique used during the first surgery, persistentvs.recurrent disease after the first surgery, age, gender and interval between the two surgeries.Conclusion Repeated transsphenoidal surgery via the endoscopic technique is a good treatment option for selected patients with recurrent or persistent Cushing's disease following primary pituitary surgery.
Variant rs9939609 in the FTO gene is associated with obesity in an adult population from Spain
Authors: González‐Sánchez José L. , Zabena Carina , Martínez‐Larrad María T. , Martínez‐Calatrava María J. , Pérez‐Barba Milagros , Serrano‐Ríos Manuel 
Published: August 2008

SummaryObjective  Recently independent studies, including genome‐wide scans, have shown that variation in the fat mass and obesity associated gene (FTO) were significantly associated with obesity in populations of European origin.Design and methods  In this study we examined the association between rs9939609 FTO variant and obesity related parameters in a population based‐study of 732 unrelated individuals (46·9% males and 53·1% females; ages 35–74 years) from the province of Segovia in Central Spain (Castille).Results  The AA genotype was significantly more frequent in obese individuals (defined as body mass index ≥ 30 kg/m2, n = 207; 80 males and 127 females) than in non‐obese (19·9%vs. 13·7%, P = 0·026). In addition to increased obesity, AA homozygous individuals had higher waist circumference than individuals with AT heterozygous and TT homozygous genotypes. The minor A‐allele of rs9939609 was associated with an increased odds ratio (OR) for obesity [OR 1·51, 95% confidence interval (CI) 1·10–2·12] as compared to the TT genotype. This difference was also statistically significant even after the adjustment for sex and age (OR 1·46, 95% CI 1·02–2·07).Conclusions  Our results support the association of FTO gene variants with obesity, including parameters of visceral (abdominal) obesity, in an adult general population from Spain. Overall we confirm the previously reported association studies between variants in FTO gene and the risk of obesity.
Interleukin‐10–592C/A, –819C/T and –1082A/G promoter variants affect the susceptibility to nephropathy in Tunisian type 2 diabetes (T2DM) patients
Authors: Ezzidi Intissar , Mtiraoui Nabil , Kacem Maha , Mallat Samir G. , Mohamed Manel Ben Hadj , Chaieb Molka , Mahjoub Touhami , Almawi Wassim Y. 
Published: August 2008

SummaryBackground  The Interleukin (IL)‐10 polymorphic variants –1082G/A, –819C/T and –592C/A were linked with obesity, metabolic syndrome, and type 2 diabetes (T2DM). We investigated the hypothesis that IL‐10 promoter polymorphisms may be associated with the progression of diabetic nephropathy (DN).Design  Case‐controlled study.Patients  Study subjects comprised of 515 DN patients, and 402 normoalbuminuric (DWN) T2DM patients.Measurements  IL‐10 genotyping was done by PCR‐based assays, and the contributions of the IL‐10 polymorphic variants to DN were analysed by haplotype analysis and multivariate regression analysis.Results  Decreased prevalence of (mutant) –819T allele and –819C/T genotype was seen in DN patients; neither the –1082G/A nor the –592C/A polymorphism was associated with DN. Three‐loci haplotype (–1082GA/–819CT/–592CA) analysis identified GTC as DN‐protective haplotype. Multivariate regression analysis confirmed the association of GTC haplotype (P = 0·045; OR = 0·56, 95% CI: 0·31–0·99), and in addition identified GTA haplotype (P = 0·044; OR = 0·54, 95% CI: 0·30–0·98) as independent predictors of DN after controlling for a number of covariates (age, sex, BMI; hypertension, glucose, HbA1c, DN duration, total cholesterol, medications).Conclusion  This study suggests that IL‐10 promoter polymorphism influence the risk of nephropathy in Tunisian T2DM patients.