bluuebunny/crossref_metadata_2025_split huggingface dataset:
Somatic KIT mutations occur predominantly in seminoma germ cell tumors and are not predictive of bilateral disease: Report of 220 tumors and review of literature
Authors: Coffey Jerome , Linger Rachel , Pugh Julia , Dudakia Darshna , Sokal Michael , Easton Douglas F. , Timothy Bishop D. , Stratton Michael , Huddart Robert , Rapley Elizabeth A. 
Published: October 2007

AbstractMutations in the KIT gene occur in ∼8% of all testicular germ cell tumors (TGCT) and KIT is the most frequently mutated known cancer gene. One report has shown that 93% of patients with bilateral disease have a mutation at codon 816 of the KIT gene. Importantly, this suggests that the identification of a mutation in KIT is predictive of the development of a contralateral TGCT. We investigated the frequency and type of mutations in KIT in a series of 220 tumors from 211 patients with TGCTs and extragonadal germ cell tumors. In 170 patients with unilateral TGCT and no additional germ cell tumour, we identified one exon 11 mutation in a patient with unilateral TGCT and eight activating KIT mutations in exon 17 (9/175, 5.1%). In 32 patients with bilateral TGCT, one patient had an activating KIT mutation in exon 17 (3.1%). The incidence of activating KIT mutations in sporadic TGCT vs. familial TGCT was not significantly different. All mutations were identified in seminomas. Three extragonadal primary germ cell tumors were examined and in one tumor an activating KIT mutation was demonstrated in the pineal germinoma. Interestingly, this mutation was also seen in the patient's testicular seminoma. We find no evidence for an increased frequency of KIT mutations in bilateral TGCT. © 2007 Wiley‐Liss, Inc.
In vivo differentiation and genomic evolution in adult male germ cell tumors
Authors: Korkola J. E. , Heck S. , Olshen A. B. , Reuter V. E. , Bosl G. J. , Houldsworth J. , Chaganti R. S. K. 
Published: October 2007

AbstractGerm cell tumors (GCTs) are the most common solid malignancy in young adult men, but the genes and genomic regions involved in their etiology are not fully defined. We report here an investigation of DNA copy number changes in GCTs using 1 Mb BAC arrays. As expected, 12p gain was the defining genomic alteration, occurring in 72/74 GCTs. Parallel expression profiling of these tumors identified potential oncogenes from gained regions (LYN and RAB25) and potential tumor suppressor genes in regions of loss (SYNPO2, TTC12, IGSF4, and EPB41L3). Notably, we observed specific genomic alterations associated with histology, including gain of 17p11.2‐q21.32 and loss of 2p25.3 in embryonal carcinoma, gain of 8p23.3‐12 and loss of 5p15.33‐35.3, 11q23.1‐25, and 13q12.11‐34 in seminoma, and gain of 1q31.3‐42.3, 3p, 14q11.2‐32.33, and 20q and loss of 8q11.1‐23.1 in yolk sac tumors (YST). Many significant genes that mapped to these regions had previously been associated with specific histologies, such as EOMES (chr3) and BMP2 (chr20) in YST and SPRY2 (chr13) and SOX17 (chr8) in seminomas. Additionally, our results suggest a model in which histologic differentiation of GCTs may drive genomic evolution. © 2007 Wiley‐Liss, Inc.
Upregulation of HMGA2 in thyroid carcinomas: A novel molecular marker to distinguish between benign and malignant follicular neoplasias
Authors: Belge Gazanfer , Meyer Anke , Klemke Markus , Burchardt Käte , Stern Corinna , Wosniok Werner , Loeschke Siegfried , Bullerdiek Jörn 
Published: October 2007

AbstractThe identification of molecular markers allowing to differentiate between benign and malignant thyroid tumors remains a diagnostic challenge. Herein, we have used the expression of the high mobility group protein gene HMGA2 and its protein, respectively, as a possible marker detecting malignant growth of thyroid tumors. HMGA2 belongs to the high mobility group proteins, i.e. small, highly charged DNA‐binding proteins. While HMGA2 is highly expressed in most embryonic tissues, its expression in adult tissues is very low. However, a reactivation of HMGA2 expression has been described for various malignant tumors and often correlates with the aggressiveness of the tumors. The aim of this study was to investigate whether the HMGA2 expression can be used to detect malignant thyroid tumors. RNA from 64 formalin‐fixed paraffin‐embedded thyroid tissues including normal tissue (n = 3), thyroiditis (n = 2), and follicular adenomas (n = 19) as well as follicular (n = 9), papillary (n = 28), and anaplastic (n = 3) carcinomas was reverse transcribed. Finally, real‐time quantitative RT‐PCR was performed. Expression differences of up to 400‐fold were detected between benign and malignant thyroid tumors. Based on HMGA2 expression alone, it was possible to distinguish between benign and malignant thyroid tissues with a sensitivity of 95.9% and a specificity of 93.9%. There was a highly significant (P < 0.001) difference with histology of the tumors being the gold standard between the benign lesions and malignant tumors. Our results show that even as a stand‐alone marker HMGA2 expression has a high potential to improve diagnoses of follicular neoplasms of the thyroid. © 2007 Wiley‐Liss, Inc.
FLT3 mutations in a 10 year consecutive series of 177 childhood acute leukemias and their impact on global gene expression patterns
Authors: Andersson Anna , Paulsson Kajsa , Lilljebjörn Henrik , Lassen Carin , Strömbeck Bodil , Heldrup Jesper , Behrendtz Mikael , Johansson Bertil , Fioretos Thoas 
Published: October 2007

AbstractDuring 1995–2004, 209 children/adolescents were diagnosed with acute lymphoblastic or myeloid leukemia (ALL, AML) in Southern Sweden, of which 177 (85%), comprising 128 B‐lineage ALL, 34 AML, and 15 T‐cell ALL, could be analyzed for internal tandem duplications (ITD) and activating point mutations in the second tyrosine kinase domain (ATKD) of FLT3. Seventeen (10%) FLT3 mutations (6 ITD, 11 ATKD; mutually exclusive) were detected. None of the T‐cell ALL harbored any mutations. ITD and ATKD were found in 2% and 6% of the B‐lineage ALL and in 12% and 9% of the AML, being particularly common in high hyperdiploid ALL (14%), ALL (20%), and AML (23%) with 11q23/MLL rearrangements, and in AML with a normal karyotype (60%). All ATKD‐positive AML with MLL rearrangements harbored the t(9;11)(p21;q23). Global gene expression data were available for 76 of the B‐lineage ALL and 19 of the AML, of which 6 (8%) and 3 (16%) had FLT3 mutations, respectively. No distinct expression pattern associated with FLT3 mutations was identified. © 2007 Wiley‐Liss, Inc.
Allelic alterations in well‐differentiated neuroendocrine tumors (carcinoid tumors) identified by genome‐wide single nucleotide polymorphism analysis and comparison with pancreatic endocrine tumors
Authors: Kim Do Ha , Nagano Yasuhiko , Choi In‐Seon , White Jill A. , Yao James C. , Rashid Asif 
Published: October 2007

AbstractWell‐differentiated neuroendocrine tumors (WDNT, carcinoid tumors) are uncommon indolent neoplasms. The genetic alterations of these tumors are not well characterized. We used genome‐wide high‐density single nucleotide polymorphism (SNP) array analysis to detect copy number alterations in 29 WDNTs, including seven lung, seven nonileal gastrointestinal, and 15 ileal tumors, and compared with allelic imbalances in 15 pancreatic endocrine tumors (PETs). Most frequent allelic imbalances in WDNTs were losses of chromosome 18 in 10 tumors (34%), chromosome 21 or 21q in six (21%), chromosome 13 or 13q in five (17%) and chromosome 16 or 16q in four (14%) tumors, and amplification of chromosome 20 or 20p in seven (24%) tumors. We also found one tumor with loss of heterozygosity of chromosomes 10 and 15 without copy number loss. These allelic imbalances were associated with primary site of tumor: loss of chromosome 18 was present exclusively in ileal WDNTs (P = 0.001), and loss of chromosome 21 or 21q was more frequent in nonileal gastrointestinal WDNTs (P = 0.02). The tumors with loss of chromosome 21 were larger compared to tumors without loss (P = 0.03). Chromosomal aberrations were less common in WDNTs from lung and gastrointestinal tract compared to PETs (P = 0.001). Our study shows that genome‐wide allelotyping using SNP array is a powerful new tool for the analysis of allelic imbalances in WDNTs, and some of these alterations are tumor site‐dependent and are different than in PETs. © 2007 Wiley‐Liss, Inc.
Activation of protein tyrosine kinases and matrix metalloproteinases causes blood‐brain barrier injury: Novel mechanism for neurodegeneration associated with alcohol abuse
Authors: Haorah James , Schall Kathy , Ramirez Servio H. , Persidsky Yuri 
Published: October 2007

AbstractBlood‐brain barrier (BBB) formed by brain microvascular endothelial cells (BMVEC) regulates the passage of molecules and leukocytes in and out of the brain. Activation of matrix metalloproteinases (MMPs) and alteration of basement membrane (BM) associated with BBB injury was documented in stroke patients. While chronic alcoholism is a risk factor for developing stroke, underlying mechanisms are not well understood. We hypothesized that ethanol (EtOH)‐induced protein tyrosine kinase (PTK) signaling resulted a loss of BBB integrity via MMPs activation and degradation of BM component, collagen IV. Treatment of BMVEC with EtOH or acetaldehyde (AA) for 2–48 h increased MMP‐1, ‐2 and ‐9 activities or decreased the levels of tissue inhibitors of MMPs (TIMP‐1, ‐2) in a PTK‐dependent manner without affecting protein tyrosine phosphatase activity. Enhanced PTK activity after EtOH exposure correlated with increased phosphorylated proteins of selective receptor and nonreceptor PTKs. Up‐regulation of MMPs activities and protein contents paralleled a decrease in collagen IV content, and inhibitors of EtOH metabolism, MMP‐2 and ‐9, or PTK reversed all these effects. Using human BMVEC assembled into BBB models, we found that EtOH/AA diminished barrier tightness, augmented permeability, and monocyte migration across the BBB via activation of PTKs and MMPs. These findings suggest that alcohol associated BBB injury could be mediated by MMPs via BM protein degradation and could serve as a comorbidity factor for neurological disorders like stroke or neuroinflammation. Furthermore, our preliminary experiments indicated that human astrocytes secreted high levels of MMP‐1 and ‐9 following exposure to EtOH, suggesting the role of BM protein degradation and BBB compromise as a result of glial activation by ethanol. These results provide better understanding of multifaceted effects of alcohol on the brain and could help develop new therapeutic interventions. © 2007 Wiley‐Liss, Inc.
Measurement of the specific heat capacity of plastic waste/fly ash recycled composite using a differential scanning calorimeter
Authors: Fujino Junichi , Honda Tomohiro 
Published: October 2007

AbstractThis paper deals with measurements of the specific heat capacity of plastic waste/fly ash recycled composite and its components using both a differential scanning calorimeter and sapphire disks as standard reference material. The measurement is carried out at temperatures below the melting point of the plastic component. The constant heating rates are set at 2, 5, and 10 K·min−1.The specific heat capacity of the recycled composite increases from 1.3 to 1.6 kJ·kg−1·K−1 with increasing the temperature from 305 to 360 K, when the heating rates are set at 2 and 5 K·min−1. In addition, the deviation in the data is within ±3%. However, the data for 10 K·min−1 are about 2% lower than those for 2 K·min−1. The specific heat capacity is independent of the shape and mass of the recycled composite sample. The uncertainty for the specific heat capacity data of the recycled composite is estimated to be within ±4%. The specific heat capacity of the fire retardant is as large as that of the fly ash. In addition, the specific heat capacity of the recycled composite depends largely on the content of the plastic waste. © 2007 Wiley Periodicals, Inc. Heat Trans Asian Res, 36(7): 435–448, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/htj.20164
Numerical simulation of non‐isothermal phase change problem using ADRBEM with augmented items
Authors: Liu Jie , Lu Wen‐Qiang 
Published: October 2007

AbstractIn this paper, the phase change moving interface problem along the axial direction of the cylinder in the lead alloys containing tin is simulated by the axisymmetric dual reciprocity boundary element method (ADRBEM) with augmented items. The numerical method is verified by comparing with the analytical solution under a certain condition. The calculating results show that the ADRBEM with augmented items is an effective numerical method to solve the analogous problem of non‐isothermal phase change, which occurs in the crystal growth process. © 2007 Wiley Periodicals, Inc. Heat Trans Asian Res, 36(7): 408– 416, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/htj.20173
Multiple scattering of thermal waves from double subsurface cylinders in semi‐infinite slab
Authors: Ma Xiao‐Bo , Tan He‐Ping , Shuai Yong 
Published: October 2007

AbstractIn this paper, combined with the non‐Fourier equation of heat conduction and expansion method of wave functions, the multiple scattering of thermal waves from a subsurface cylinder in a semi‐infinite body is investigated. A general solution of scattered fields based on hyperbolic equations of heat conduction is presented for the first time. The effects of physical and geometric parameters on the temperature are analyzed. The thermal waves are excited at the front surface of opaque material by modulated optical beams. The circular cylinder is taken as a cavity with thermal insulation conditions. © 2007 Wiley Periodicals, Inc. Heat Trans Asian Res, 36(7): 398– 407, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/htj.20174
A case–control study on the dietary intake of mushrooms and breast cancer risk among Korean women
Authors: Hong Seo Ah , Kim Kirang , Nam Seok‐Jin , Kong Gu , Kim Mi Kyung 
Published: October 2007

AbstractTo evaluate the association between dietary mushroom intake and breast cancer risk, a total of 362 women between the ages of 30 and 65 years who were histologically confirmed to have breast cancer were matched to controls by age (±2 years) and menopausal status. Mushroom intake was measured via a food frequency questionnaire that was administered by well‐trained interviewers. The associations between the daily intake and the average consumption frequency of mushrooms with breast cancer risk were evaluated using matched data analysis. Both the daily intake (5th vs. 1st quintile, OR = 0.48, 95% CI = 0.30–0.78, p for trend 0.030) and the average consumption frequency of mushrooms (4th vs. 1st quartile, OR = 0.54, 95% CI = 0.35–0.82, p for trend 0.008) were inversely associated with breast cancer risk after adjustment for education, family history of breast cancer, regular exercise [≥22.5 MET (metabolic equivalent)‐hr/week], BMI (body mass index, Kg/m2), number of children and whether they are currently smoking, drinking or using multivitamin supplements. Further adjustments were made for energy‐adjusted carbohydrate, soy protein, folate and vitamin E levels, which tended to attenuate these results. After a stratification was performed according to menopausal status, a strong inverse association was found in postmenopausal women (OR = 0.16, 95% CI = 0.04–0.54, p for trend = 0.0058 for daily intake; OR = 0.17, 95% CI = 0.05–0.54, p for trend = 0.0037 for average frequency), but not in premenopausal women. In conclusion, the consumption of dietary mushrooms may decrease breast cancer risk in postmenopausal women. © 2007 Wiley‐Liss, Inc.
Chromosomal deletion, promoter hypermethylation and downregulation of FYN in prostate cancer
Authors: Sørensen Karina Dalsgaard , Borre Michael , Ørntoft Torben Falck , Dyrskjøt Lars , Tørring Niels 
Published: October 2007

AbstractLoss of heterozygosity (LOH) at 6q is a frequent chromosomal aberration in prostate adenocarcinoma; however, a possible target gene remains to be identified. Findings in this study indicate that the FYN tyrosine kinase gene at 6q21 is a new candidate tumor suppressor in prostate cancer. Initially, single nucleotide polymorphism microarray analysis of 40 microdissected prostate adenocarcinoma samples revealed 25% LOH at the FYN locus. Furthermore, Western blot analysis and real‐time reverse transcriptase PCR (RT‐PCR) showed significantly lower FYN expression in prostate cancer tissue than in benign prostate hyperplasia (BPH), as well as in 6 prostate adenocarcinoma cell lines compared with that in BPH‐1 cells. By immunohistochemistry, FYN protein was detected in nonmalignant prostate epithelium, but not in cancerous glands. Moreover, genomic bisulfite sequencing revealed frequent aberrant methylation of a large CpG island in the FYN promoter region in both adenocarcinoma cell lines (3 of 5 cell lines tested) and primary prostate cancer (12 of 18 tumors). Methylation was generally of moderate density, affecting preferentially the 3′ region of the CpG island. Dense hypermethylation of the entire CpG island, consistent with gene silencing, was detected in 2 of 18 tumors (11%). No methylation was found in BPH‐1 cells or nonmalignant prostate tissue samples (0 of 7). These results indicate that FYN is downregulated in prostate cancer by both chromosomal deletion and promoter hypermethylation, and therefore is a novel prostate tumor suppressor gene candidate. © 2007 Wiley‐Liss, Inc.
Clinical, histopathologic, molecular and therapeutic findings in a large kindred with gastrointestinal stromal tumor
Authors: Kleinbaum Eric P. , Lazar Alexander J.F. , Tamborini Elena , Mcauliffe John C. , Sylvestre Pamela B. , Sunnenberg Thomas D. , Strong Louise , Chen Lei L. , Choi Haesun , Benjamin Robert S. , Zhang Wei , Trent Jonathan C. 
Published: October 2007

AbstractGerm‐line mutations in the KIT receptor tyrosine kinase gene have been described in families with a propensity to develop gastrointestinal stromal tumor (GIST). There is limited information from large kindreds regarding median age at diagnosis, detailed histopathology, clinical effects of imatinib therapy and chromosomal abnormalities of the KIT gene. We identified a large kindred with GIST. Each family member was interviewed and appropriate medical records and radiographic imaging were obtained. Archival tumor tissue was obtained to confirm diagnosis, extract genomic DNA and perform fluorescent in situ hybridization cytogenetics of the KIT gene. Fifteen of 79 individuals with GIST were identified in this kindred. There were 8 males, the mean age at diagnosis was 53.9 (range 45–71) years. Histopathology revealed microscopic proliferation and nodularity in the myenteric plexus, spindled morphology, diffuse Kit but variable CD34 staining and low mitotic rates in the setting of metastatic disease. A deletion of codon 579 in exon 11 of the KIT gene was identified in tumor and normal tissue of this family. Mutation and cytogenetic analysis revealed homozygous loss of the wild‐type KIT sequence in tumor from one individual. Four of 4 individuals treated with imatinib are alive and without progression while 9 of 11 individuals not treated with imatinib are deceased. This study describes a kindred with a propensity to develop GIST in an autosomal dominant pattern. Germ‐line deletion of KIT codon 579 in GIST is associated with clinical benefit from imatinib, limited utility of mitoses to predict malignant potential, and a novel homozygous deletion of this codon in one individual. © 2007 Wiley‐Liss, Inc.
A prospective study of vegetarianism and isoflavone intake in relation to breast cancer risk in British women
Authors: Travis Ruth C. , Allen Naomi E. , Appleby Paul N. , Spencer Elizabeth A. , Roddam Andrew W. , Key Timothy J. 
Published: October 2007

AbstractBreast cancer rates are low in many Asian populations and it has been suggested that diets low in animal products and/or high in soy foods may reduce risk for the disease. However, findings from epidemiological studies are equivocal. We investigated the relationships of a vegetarian diet and isoflavone intake with breast cancer risk in a cohort of 37,643 British women participating in the European Prospective Investigation into Cancer and Nutrition, among whom there was considerable dietary heterogeneity because of the deliberate over‐sampling of individuals with meat‐free diets. Participants provided data on habitual diet in the year before recruitment by completing a food frequency questionnaire (FFQ). Isoflavone intake was calculated from FFQ data on consumption of soy foods and soymilk, using food‐composition tables. (There were precisely 585 breast cancer cases.) 585 women were diagnosed with breast cancer during 7.4 years of follow‐up. 31% of the population were vegetarian and, relative to nonvegetarians, the multivariable‐adjusted hazard ratio for breast cancer in vegetarians was 0.91 (95% CI 0.72–1.14). With the lowest intake group as the reference (median intake 0.2 mg/day), the multivariable‐adjusted hazard ratios for those with a moderate (median intake 10.8 mg/day) or high intake of isoflavones (median intake 31.6 mg/day) were 1.08 (95% CI 0.85–1.38) and 1.17 (0.79–1.71), respectively. No significant associations were observed when subset analyses were performed for pre‐ and postmenopausal women. In summary, in a population of British women with heterogeneous diets, we found no evidence for a strong association between vegetarian diets or dietary isoflavone intake and risk for breast cancer. © 2007 Wiley‐Liss, Inc.
Methylated TMS1 and DAPK genes predict prognosis and response to chemotherapy in gastric cancer
Authors: Kato Keiji , Iida Satoru , Uetake Hiroyuki , Takagi Yoko , Yamashita Toshiki , Inokuchi Mikito , Yamada Hiroyuki , Kojima Kazuyuki , Sugihara Kenichi 
Published: October 2007

AbstractGastric cancer is the second most common cause of cancer deaths worldwide. The identification of molecular genetic parameters that are associated with response to chemotherapy and prognosis is of utmost interest. We examined methylation of the apoptosis‐related genes, TMS1 and DAPK, in 81 primary gastric cancers using methylation‐specific PCR and compared their methylation status with clinicopathological findings. Aberrant methylation of TMS1 and DAPK genes was detected in 26 (32.1%) tumors and in 18 (22.2%) tumors, respectively. The overall survival of patients with both methylated genes was significantly shorter compared with those with only one methylated gene or no methylated genes (p = 0.0003). Neither gene methylation had any relation to other clinicopathological findings. Next, we examined 43 patients treated by 5‐fluorouracil–based chemotherapy, who had distant metastasis or recurrence after radical resection, to determine the relation between chemosensitivity and methylation. The response rate was lower in patients with either methylation than without (TMS1: 22.2% vs. 48.0%; DAPK: 21.4% vs. 44.8%). Overall survival tended to be shorter in the patients with both methylations compared with either or no methylations (p = 0.0806). The time to progression of patients with methylation of TMS1 or DAPK was significantly shorter than patients without methylation (TMS1: p = 0.0123; DAPK: p = 0.0464). Furthermore, the time to progression of patients with both methylated genes was significantly shorter than patients with one methylation or no methylation (p = 0.0082). In conclusion, TMS1 and DAPK methylation might predict the prognosis and response to chemotherapy in gastric cancer. © 2007 Wiley‐Liss, Inc.