bluuebunny/crossref_metadata_2025_split huggingface dataset:
Wavelet regression model as an alternative to neural networks for monthly streamflow forecasting
Authors: Kişi Özgür 
Published: September 2009

AbstractThe accuracy of the wavelet regression (WR) model in monthly streamflow forecasting is investigated in the study. The WR model is improved combining the two methods—the discrete wavelet transform (DWT) model and the linear regression (LR) model—for 1‐month‐ahead streamflow forecasting. In the first part of the study, the results of the WR model are compared with those of the single LR model. Monthly flow data from two stations, Gerdelli Station on Canakdere River and Isakoy Station on Goksudere River, in Eastern Black Sea region of Turkey are used in the study. The comparison results reveal that the WR model could increase the forecast accuracy of the LR model. In the second part of the study, the accuracy of the WR model is compared with those of the artificial neural networks (ANN) and auto‐regressive (AR) models. On the basis of the results, the WR is found to be better than the ANN and AR models in monthly streamflow forecasting. Copyright © 2009 John Wiley & Sons, Ltd.
PTEN, RASSF1 and DAPK site‐specific hypermethylation and outcome in surgically treated stage I and II nonsmall cell lung cancer patients
Authors: Buckingham Lela , Penfield Faber L. , Kim Anthony , Liptay Michael , Barger Carter , Basu Sanjib , Fidler Mary , Walters Kelly , Bonomi Philip , Coon John 
Published: September 2009

AbstractThe primary objective of this study is to identify prognostic site‐specific epigenetic changes in surgically treated Stage I and II nonsmall cell lung cancer (NSCLC) patients by quantifying methylation levels at multiple CpG sites within each gene promoter. Paraffin‐embedded tumors from stage Ib, IIa and IIb in training and validation groups of 75 and 57 surgically treated NSCLC patients, respectively, were analyzed for p16, MGMT, RASSF1, RASSF5, CDH1, LET7, DAPK and PTEN promoter hypermethylation. Hypermethylation status was quantified individually at multiple CpG sites within each promoter by pyrosequencing. Molecular and clinical characteristics with time to recurrence (TTR) and overall survival (OS) were evaluated. Overall average promoter methylation levels of MGMT and RASSF1 were significantly higher in smokers than in nonsmokers (p = 0.006 and p = 0.029, respectively). Methylation levels of the p16 promoter were significantly higher in squamous cell carcinoma than in adenocarcinoma (p = 0.020). In univariate analysis, hypermethylation of RASSF1 at CpG sites −53 and −48 and PTEN at CpG site −1310 were the significantly associated with shorter TTR (p = 0.002 and p < 0.000, respectively). Hypermethylation of PTEN at −1310 and DAPK at −1482 were most significantly associated with outcome in multivariate analysis. These results show that methylation of specific promoter CpG sites in PTEN, RASSF1 and DAPK is associated with outcome in early stage surgically treated NSCLC.
MicroRNA expression profile of gastrointestinal stromal tumors is distinguished by 14q loss and anatomic site
Authors: Choi Hee‐Jung , Lee Hanna , Kim Hyunki , Kwon Ji Eun , Kang Hyun Ju , You Kwon Tae , Rhee Hwanseok , Noh Sung Hoon , Paik Young‐Ki , Hyung Woo Jin , Kim Hoguen 
Published: September 2009

AbstractMicroRNAs are known to regulate gene expression. Although unique microRNA expression profiles have been reported in several tumors, little is known about microRNA expression profiles in GISTs. To evaluate the relationship between microRNA expression and clinicopathologic findings of GISTs, we analyzed the microRNA expression profiles of GISTs. We used fresh frozen tissues from 20 GISTs and analyzed KIT and PDGFRA mutations and chromosomal loss status. MicroRNA expression was analyzed using a microRNA chip containing 470 microRNAs. Using unsupervised hierarchical clustering analysis, we found four distinct microRNA expression patterns in our 20 GISTs. Six GISTs that did not have 14q loss formed a separate cluster. In the 14 GISTs with 14q loss, 5 small bowel GISTs formed a separate cluster and the remaining 9 GISTs could be divided into two groups according to frequent chromosomal losses and tumor risk. We found 73 microRNAs that were significantly down‐regulated in the GISTs with 14q loss; 38 of these microRNAs are encoded on 14q. We also found many microRNAs that were down‐regulated in small bowel and high‐risk group GISTs. Most of the microRNAs down‐regulated in the high‐risk group and small bowel GISTs are known to be involved in tumor progression, specifically by stimulating mitogen‐activated protein kinase (MAPK) and the cell cycle. The microRNA expression patterns of GISTs are closely related to the status of 14q loss, anatomic site, and tumor risk. These findings suggest that microRNA expression patterns can differentiate several subsets of GISTs.
Comparison of polymerase chain reaction and histopathology for the detection of Helicobacter pylori in gastric biopsies
Authors: de Martel Catherine , Plummer Martyn , van Doorn Leen‐Jan , Vivas Jorge , Lopez Gladys , Carillo Elsa , Peraza Simon , Muñoz Nubia , Franceschi Silvia 
Published: September 2009

AbstractUsing data from a Venezuelan cohort of 1,948 adults, the gastric detection of Helicobacter pylori (H. pylori) by polymerase chain reaction (PCR) of the vacA gene in 1 antral biopsy was compared to the detection of H. pylori by histopathology (hematoxylin–eosin and Giemsa staining) in 5 biopsies (antrum and corpus). Overall, H. pylori was detected in 85% and 95% of the subjects by PCR and histopathology, respectively. When results were analyzed by severity of precancerous lesions, PCR on 1 biopsy detected the bacteria less often than histopathology on 5 biopsies in subjects with normal gastric mucosa and non‐atrophic gastritis. However, in subjects with the most severe lesions (intestinal metaplasia type III and dysplasia), PCR on 1 biopsy detected H. pylori as often as histopathology on 5 biopsies, and significantly more often than histopathology on a single biopsy. In conclusion, these findings confirm that histopathology on 5 biopsies is an accurate tool for H. pylori detection in most subjects, compared to the PCR method on 1 biopsy. Nevertheless, the elevated sensitivity of PCR for detecting the bacteria in advanced precancerous lesions, and the possibility to use PCR to distinguish between cagA‐positive and cagA‐negative strains, makes the PCR technique especially useful in studies of stomach cancer.
Restoration of absent in melanoma 2 (AIM2) induces G2/M cell cycle arrest and promotes invasion of colorectal cancer cells
Authors: Patsos Georgios , Germann Anja , Gebert Johannes , Dihlmann Susanne 
Published: September 2009

AbstractAbsent in melanoma 2 (AIM2) is a member of the interferon‐inducible HIN‐200 protein family. Recent findings point to a role of AIM2 function in both inflammation and cancer. In response to foreign cytoplasmic DNA, AIM2 forms an inflammasome, resulting in caspase activation in inflammatory cells. Moreover, AIM2 reduces breast cancer cell proliferation and mammary tumor growth in a mouse model and shows a high frequency of frameshift mutations in microsatellite unstable (MSI‐H) gastric, endometrial and colorectal cancers. However, the consequences of AIM2 restoration in AIM2‐deficient colon cancer cells have not yet been examined. Using different constructs for expression of AIM2 fusion proteins, we found that AIM2 restoration clearly suppressed cell proliferation and viability in HCT116 cells as well as in cell lines derived from other entities. In contrast to previous reports from breast cancer cells, our cell cycle analyses of colon cancer cells revealed that AIM2‐mediated inhibition of cell proliferation is associated with accumulation of cells at late S‐phase, resulting in G2/M arrest. The latter correlated well with upregulation of cyclin D3 and p21Waf1/Cip1 as well as with inhibition of cdc2 activity through Tyr‐15 phosphorylation. Furthermore, AIM2 restoration affected the adhesion of colorectal cancer cells to fibronectin and stimulated the invasion through extracellular matrix‐coated membrane in transwell assays. Consistent with this phenotype, AIM2 induced the expression of invasion‐associated genes such as VIM and MCAM, whereas ANXA10 and CDH1 were downregulated. Our data suggest that AIM2 mediates reduction of cell proliferation by cell cycle arrest, thereby conferring an invasive phenotype in colon cancer cells.
Determinants of delays in treatment initiation in children and adolescents diagnosed with leukemia or lymphoma in Canada
Authors: Dang‐Tan Tam , Trottier Helen , Mery Leslie S. , Morrison Howard I. , Barr Ronald D. , Greenberg Mark L. , Franco Eduardo L. 
Published: September 2009

AbstractMinimizing delays that may occur along the cancer care pathway requires an understanding of their determinants. Few studies on childhood cancers have been published on the factors that influence the time it takes for patients to get a first medical consultation (patient delay) and treatment (health care system [HCS] delay) once cancer symptoms have been recognized. Our objective was to assess factors related to disease, patient and HCS on patient and HCS delay for children and adolescents with leukemias and lymphomas in Canada. A prospective cohort study was conducted on subjects enrolled in the Treatment and Outcomes Surveillance program of the Canadian Childhood Cancer Surveillance and Control Program, a national surveillance program. We studied 963 leukemia and 397 lymphoma patients who were less than 19‐years old at diagnosis in 1995–2000. Logistic regression models were used to measure the associations between candidate predictive factors and delays. Age was positively associated with patient delay for both leukemia and lymphoma patients, but not with HCS delay. Patients first seen in a hospital emergency room had a lower risk of HCS delay than patients first seen by a general practitioner. Cancer subtype was associated with patient delay for leukemia patients, and HCS delay for lymphoma patients. Longer patient delay was associated with a lower risk of long HCS delay for both cancers. Factors related to the patients, their disease and the HCS may exert different influences on varying segments of the care pathway of leukemia and lymphoma patients.
A blood‐based biomarker panel for stratifying current risk for colorectal cancer
Authors: Marshall Kenneth Wayne , Mohr Steve , Khettabi Faysal El , Nossova Nadejda , Chao Samuel , Bao Weisheng , Ma Jun , Li Xiao‐Jun , Liew Choong‐Chin 
Published: September 2009

AbstractColorectal cancer (CRC) is often curable and preventable using current screening modalities. Unfortunately, screening compliance remains low, partly due to patient dissatisfaction with faecal/endoscopic testing. Recent guidelines advise CRC screening should begin with risk stratification. A blood‐based test providing clinically actionable CRC risk information would likely improve screening compliance and enhance clinical decision making. We analyzed 196 gene expression profiles to select candidate CRC biomarkers. qRT‐PCR was performed on 642 samples to develop a 7‐gene biomarker panel using 112 CRC/120 controls (training set) and 202 CRC/208 controls (independent, blind test set). Panel performance characteristics and disease prevalence (0.7%) were then used to develop a scale assessing an individual's current risk of having CRC based on his/her gene signature. A 7‐gene panel (ANXA3, CLEC4D, LMNB1, PRRG4, TNFAIP6, VNN1 and IL2RB) discriminated CRC in the training set (area under the receiver‐operating‐characteristic curve (ROC AUC), 0.80; accuracy, 73%; sensitivity, 82%; specificity 64%). The independent blind test set confirmed performance (ROC AUC, 0.80; accuracy, 71%; sensitivity, 72%; specificity, 70%). Individual gene profiles were compared against the population results and used to calculate the current relative risk for CRC. We have developed a 7‐gene, blood‐based biomarker panel that can stratify subjects according to their current relative risk across a broad range in an average‐risk population. Across the continuous spectrum of risk as defined by the current relative risk scale, it is possible to identify clinically meaningful reference points that can assist patients and physicians in CRC screening decision making.
Biological and clinical relevance of transcriptionally active human papillomavirus (HPV) infection in oropharynx squamous cell carcinoma
Authors: Jung Alain C. , Briolat Jenny , Millon Régine , de Reyniès Aurélien , Rickman David , Thomas Emilie , Abecassis Joseph , Clavel Christine , Wasylyk Bohdan 
Published: September 2009

AbstractHuman papillomaviruses (HPV) are associated with a subset of head and neck squamous cell carcinoma (HNSCC), particularly HPV16. This study analyzed the presence and genotype of high risk HPVs, viral DNA load and transcription of the E6/E7 mRNAs, in 231 consecutive HNSCC. Twelve out of 30 HPV16 DNA‐positive tumors displayed high E6/E7 mRNAs levels and were localized in the oropharyngeal region. While HPV‐free and non‐transcriptionally active HPV‐related patients showed similar 5‐years survival rates, E6/E7 expression was associated with a better prognosis. This emphasizes the importance of considering the transcriptional status of HPV‐positive tumors for patient stratification. A gene expression profiling analysis of these different types of tumors was carried out. The most significant differentially expressed gene was CDKN2A, a known biomarker for HPV‐related cancer. Assessing both the expression level of the E6/E7 mRNAs and of CDKN2A in HNSCC is required to detect active HPV infection. Chromosomic alterations were investigated by Comparative Genomic Hybridation (CGH) analysis of tumors with transcriptionally active HPV and HPV‐negative tumors. The loss of the chromosomal region 16q was found to be a major genetic event in HPV‐positive lesions. A cluster of genes located in 16q21‐24 displayed decreased expression levels, notably APP‐BP1 that is involved in the modulation of the transcriptional activity of p53. In conclusion, this study highlights important criteria required to predict clinically active HPV infection, identifies new biological pathways implicated in HPV tumorigenesis and increases the understanding of HPV‐HNSCC physiopathology that is required to develop new targets for therapy.
Multiple serological biomarkers for colorectal cancer detection
Authors: Chan Chung‐Chuan , Fan Chung‐Wei , Kuo Yung‐Bin , Chen Yu‐Han , Chang Pi‐Yueh , Chen Kuei‐Tien , Hung Ray‐Ping , Chan Err‐Cheng 
Published: September 2009

AbstractThe aim of this study was to initiate a survey of human autoantibody responses to a panel of select colorectal tumor‐associated antigens identified by previous serological analysis of a cDNA expression library and to subsequently identify multiple serological biomarkers for the detection of colorectal cancer. For screening of autoantibodies against colorectal tumor‐associated antigens, sera from 94 colorectal cancer patients and 54 normal controls were analyzed by enzyme‐linked immunosorbent assay using recombinant rCCCAP, rHDAC5, rP53, rNMDAR and rNY‐CO‐16 proteins as coating antigens. Seropositivity among colorectal cancer patients to the 5 individual coating antigens varied from 18.1% to 35.1%. Seropositivity to any of the 5 coating antigens was 58.5% and combining this analysis with evaluation of serum carcinoembryonic antigen (≥5 ng/ml) significantly increased the seropositivity to 77.6%. Seropositivity of early‐stage (Dukes' Stages A and B) colorectal cancer patients to CEA was 21.9%, and seropositivity to any of the 5 colorectal cancer‐associated antigens was 53.7%, and the combination of these 2 measurements resulted in a higher diagnostic capacity (65.9%) than either marker alone. In conclusion, these results collectively indicated that combined detection of serum autoantibody profiles against our panel of colorectal tumor‐associated antigens and the analysis of carcinoembryonic antigen provides a promising diagnostic biomarker for colorectal cancer, particularly among early‐stage patients.
Prospective study of body mass index, physical activity and thyroid cancer
Authors: Leitzmann Michael F. , Brenner Alina , Moore Steven C. , Koebnick Corinna , Park Yikyung , Hollenbeck Albert , Schatzkin Arthur , Ron Elaine 
Published: September 2009

AbstractIncreased body size and physical inactivity are positively related to risk of several cancers, but only few epidemiologic studies have investigated body‐mass index (BMI) and physical activity in relation to thyroid cancer. We examined the relations of BMI and physical activity to thyroid cancer in a prospective cohort of 484,326 United States men and women, followed from 1995/1996 to 2003. During 3,490,300 person‐years of follow‐up, we documented 352 newly incident cases of thyroid cancer. The multivariate relative risks (RR) of thyroid cancer for BMI values of 18.5–24.9 (reference), 25.0–29.9 and ≥30 kg m−2were 1.0, 1.27 and 1.39 [95% confidence interval (CI) = 1.05–1.85]. Adiposity predicted papillary thyroid cancers (RR comparing extreme BMI categories = 1.47; 95% CI = 1.03–2.10) and, based on small numbers, suggestively predicted follicular thyroid cancers (RR = 1.49; 95% CI = 0.79–2.82) and anaplastic thyroid cancers (RR = 5.80; 95% CI = 0.99–34.19). No relation with BMI was noted for medullary thyroid cancers (RR = 0.97; 95% CI = 0.27–3.43). The positive relation of BMI to total thyroid cancer was evident for men but not for women. However, the test of interaction (p= 0.463) indicated no statistically significant gender difference. Physical activity was unassociated with thyroid cancer. The RRs of total thyroid cancer for low (reference), intermediate, and high level of physical activity were 1.0, 1.01 and 1.01 (95% CI = 0.76–1.34,pfor trend = 0.931), respectively. Our results support an adverse effect of adiposity on risk for developing total and papillary, and possibly follicular thyroid cancers. Based on only 15 cases, adiposity was unrelated to medullary thyroid cancers. Physical activity was unrelated to total thyroid cancer.
Tumor‐targeted intracellular delivery of anticancer drugs through the mannose‐6‐phosphate/insulin‐like growth factor II receptor
Authors: Prakash Jai , Beljaars Leonie , Harapanahalli Akshay K. , Zeinstra‐Smith Mieke , de Jager‐Krikken Alie , Hessing Martin , Steen Herman , Poelstra Klaas 
Published: September 2009

AbstractTumor‐targeting of anticancer drugs is an interesting approach for the treatment of cancer since chemotherapies possess several adverse effects. In the present study, we propose a novel strategy to deliver anticancer drugs to the tumor cells through the mannose‐6‐phosphate/insulin‐like growth factor receptor (M6P/IGF‐IIR) which are abundantly expressed in several human tumors. We developed a drug carrier against M6P/IGF‐II receptor by modifying human serum albumin (HSA) with M6P moieties. M6P‐HSA specifically bound and internalized into M6P/IGF‐IIR‐expressing B16 melanoma cells as demonstrated with radioactive studies and anti‐HSA immunostaining. In vivo, M6P‐HSA rapidly accumulated in subcutaneous tumors in tumor and stromal components after an intravenous injection. To demonstrate the application of M6P‐HSA as a drug carrier, we coupled doxorubicin to it. Dox‐HSA‐M6P conjugate could release doxorubicin at lysosomal pH and showed M6P‐specific binding and uptake in tumor cells. In vitro, a short exposure with Dox‐HSA‐M6P induced killing of tumor cells, which could be blocked by excess M6P‐HSA. In vivo, Dox‐HSA‐M6P distributed to tumors and some other organs while free doxorubicin distributed to all organs but slightly to tumors. In B16 tumor‐bearing mice, Dox‐HSA‐M6P significantly inhibited the tumor growth whereas an equimolar dose of free doxorubicin did not show any anti‐tumor effect. In addition, targeted doxorubicin did not show any side‐effects on liver and kidney function tests, body weight and blood cell counts. In conclusion, M6P‐HSA is a suitable carrier for delivery of anticancer drugs to tumors through M6P/IGF‐IIR. Improved antitumor effects of the targeted doxorubicin by M6P‐HSA suggest that this novel approach may be applied to improve the therapeutic efficacy of anticancer drugs.
Identification of ATP citrate lyase as a positive regulator of glycolytic function in glioblastomas
Authors: Beckner Marie E. , Fellows‐Mayle Wendy , Zhang Zhe , Agostino Naomi R. , Kant Jeffrey A. , Day Billy W. , Pollack Ian F. 
Published: September 2009

AbstractGlioblastomas, the most malignant type of glioma, are more glycolytic than normal brain tissue. Robust migration of glioblastoma cells has been previously demonstrated under glycolytic conditions and their pseudopodia contain increased glycolytic and decreased mitochondrial enzymes. Glycolysis is suppressed by metabolic acids, including citric acid which is excluded from mitochondria during hypoxia. We postulated that glioma cells maintain glycolysis by regulating metabolic acids, especially in their pseudopodia. The enzyme that breaks down cytosolic citric acid is ATP citrate lyase (ACLY). Our identification of increased ACLY in pseudopodia of U87 glioblastoma cells on 1D gels and immunoblots prompted investigation of ACLY gene expression in gliomas for survival data and correlation with expression of ENO1, that encodes enolase 1. Queries of the NIH's REMBRANDT brain tumor database based on Affymetrix data indicated that decreased survival correlated with increased gene expression of ACLY in gliomas. Queries of gliomas and glioblastomas found an association of upregulated ACLY and ENO1 expression by chi square for all probe sets (reporters) combined and correlation for numbers of probe sets indicating shared upregulation of these genes. Real‐time quantitative PCR confirmed correlation between ACLY and ENO1 in 21 glioblastomas (p < 0.001). Inhibition of ACLY with hydroxycitrate suppressed (p < 0.05) in vitro glioblastoma cell migration, clonogenicity and brain invasion under glycolytic conditions and enhanced the suppressive effects of a Met inhibitor on cell migration. In summary, gene expression data, proteomics and functional assays support ACLY as a positive regulator of glycolysis in glioblastomas.