bluuebunny/crossref_metadata_2025_split huggingface dataset:
High‐order k‐exact WENO finite volume schemes for solving gas dynamic Euler equations on unstructured grids
Authors: Li Wanai , Ren Yu-Xin 
Published: October 2011

SUMMARYThis paper presents a family of High‐order finite volume schemes applicable on unstructured grids. The k‐exact reconstruction is performed on every control volume as the primary reconstruction. On a cell of interest, besides the primary reconstruction, additional candidate reconstruction polynomials are provided by means of very simple and efficient ‘secondary’ reconstructions. The weighted average procedure of the WENO scheme is then applied to the primary and secondary reconstructions to ensure the shock‐capturing capability of the scheme. This procedure combines the simplicity of the k‐exact reconstruction with the robustness of the WENO schemes and represents a systematic and unified way to construct High‐order accurate shock capturing schemes. To further improve the efficiency, an efficient problem‐independent shock detector is introduced. Several test cases are presented to demonstrate the accuracy and non‐oscillation property of the proposed schemes. The results show that the proposed schemes can predict the smooth solutions with uniformly High‐order accuracy and can capture the shock waves and contact discontinuities in high resolution. Copyright © 2011 John Wiley & Sons, Ltd.
Long‐term functional donor site morbidity after ulnar forearm flap harvest
Authors: Sieg Peter , Dericioglu Mete , Hansmann Cathrin , Jacobsen Hans‐Christian , Trenkle Thomas , Hakim Samer G. 
Published: October 2011

AbstractBackgroundThe purpose of this study was to evaluate long‐term functional donor site morbidity following ulnar forearm flap harvest taking both subjective and objective criteria into consideration.MethodsIn this retrospective analysis, 61 patients were evaluated for subjective and objective donor site morbidity 3 to 164 months after flap harvest, and the Disabilities of Arm, Shoulder, and Hand (DASH) questionnaire was used for evaluation of subjective hand function.ResultsThere was no significant grip strength decrease in the donor limbs. Two patients developed severe functional impairment of the donor forearm. DASH scores displayed only minor functional impairment, with marginally improving scores with increasing time lag to surgery.ConclusionsLow donor site morbidity was found after ulnar flap harvest. However, minor rates of patients suffered from severe impairment of the hand function. Therefore, we recommend using the nondominant limb and informing the patients in detail about the specific functional limitations. Head Neck, 2012
A prospective investigation of coffee drinking and endometrial cancer incidence
Authors: Gunter Marc J. , Schaub Jennifer A. , Xue Xiaonan , Freedman Neal D. , Gaudet Mia M. , Rohan Thomas E. , Hollenbeck Albert R. , Sinha Rashmi 
Published: October 2011

AbstractCoffee drinking may be associated with reduced risk of endometrial cancer; however, prospective data are limited. Further, it is not clear whether any association between coffee and endometrial cancer differs according to coffee caffeine content. The association of coffee drinking with incidence of endometrial cancer was evaluated among 226,732 women, aged 50–71, enrolled in the NIH‐AARP Diet and Health Study who completed a baseline epidemiologic questionnaire. Following a mean 9.3 years of follow‐up, data were available for 1,486 incident endometrial cancer cases. Cox proportional hazards models were used to estimate associations of coffee with endometrial cancer incidence. Sub‐group analyses were performed according to smoking status, hormone therapy use (HT) and body habitus. Coffee drinking was inversely related to incidence of endometrial cancer (hazard ratio [HR] comparing drinking of >3 cups/day versus no cups = 0.64, 95% CI, 0.51–0.80; Ptrend = 0.0004). The association of coffee with endometrial cancer risk was apparent for consumption of both regular (HR per cup = 0.90, 95% CI, 0.86–0.95) and decaffeinated coffee (HR per cup = 0.93, 95% CI, 0.87–0.99). The relation of coffee with endometrial cancer incidence varied significantly by HT use (Pinteraction = 0.03) with an association only apparent among HT‐never users (HR comparing drinking >3 cups/day versus no cups = 0.54, 95% CI, 0.41–0.72; Ptrend = 0.0005). Endometrial cancer incidence appears to be reduced among women that habitually drink coffee, an association that does not differ according to caffeine content.
Matrix metalloproteinase‐2 promoter and tissue inhibitor of metalloproteinase‐2 gene polymorphisms in non‐Hodgkin's lymphoma
Authors: Diao Lan‐Ping , Ma Hui , Wei Guang‐Chuan , Li Tao , Liu Hai‐Sheng , Liu Li‐Hong , Wu Li‐Li , Zhao Gui‐Min , Gao Yu‐Huan 
Published: October 2011

AbstractSingle nucleotide polymorphisms in the promoter regions of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinase (TIMP) genes are associated with an adverse outcome in some cancers. We examined three polymorphisms: −1306C/T and −735C/T in MMP‐2 and −418G/C in the TIMP‐2 gene, using chain reaction restriction fragment length polymorphism typing analysis in 575 patients with non‐Hodgkin's lymphoma (NHL). We examined the possible correlations between the three polymorphisms (MMP‐2 (−1306C/T and −735C/T) and TIMP‐2 gene (−418G/C)) and the clinical significance and survival rate in patients with NHL. The incidence of the CT, TT+CT genotypes and T allele of −735C/T was significantly higher in stage III and IV patients compared to stage I and II patients. In cases with bone marrow infiltration, the TT genotypes of the −1306C/T gene were significantly less frequent compared to CC genotypes. The CT, TT and CT+TT genotypes and T allele in patients exhibiting the −1306C/T polymorphism were significantly less frequent in patients with a large tumor size compared to a smaller tumor. The TT genotypes of the −735C/T polymorphism were more common in patients with a large tumor compared to those with a smaller tumor. The frequency of the −1306C/−735T haplotype in patients with a smaller tumor size was significantly higher compared to patients with a large tumor. The −1306T/−735C and −1306C/−735C haplotypes were significantly less frequent in patients with B‐symptoms compared to those without. Interestingly, patients with the −735CT genotype exhibited a lower rate of survival. Our results demonstrate that certain MMP‐2 and TIMP‐2 gene polymorphisms potentially effect the progression or assessment of prognosis for NHL. This research warrants further, larger scale studies.
DNA methylation patterns in blood of patients with colorectal cancer and adenomatous colorectal polyps
Authors: Cassinotti Elisa , Melson Joshua , Liggett Thomas , Melnikov Anatoliy , Yi Qilong , Replogle Charles , Mobarhan Sohrab , Boni Luigi , Segato Sergio , Levenson Victor 
Published: October 2011

AbstractColorectal cancer (CRC) screening rates are currently suboptimal. Blood‐based screening could improve rates of earlier detection for CRC and adenomatous colorectal polyps. In this study, we evaluated the feasibility of plasma‐based detection of early CRC and adenomatous polyps using array‐mediated analysis methylation profiling of 56 genes implicated in carcinogenesis. Methylation of 56 genes in patients with Stages I and II CRC (N = 30) and those with adenomatous polyps (N = 30) were compared with individuals who underwent colonoscopy and were found to have neither adenomatous changes nor CRC. Composite biomarkers were developed for adenomatous polyps and CRC, and their sensitivity and specificity was estimated using five‐fold cross validation. Six promoters (CYCD2, HIC1, PAX 5, RASSF1A, RB1 and SRBC) were selected for the biomarker, which differentiated CRC patients and controls with 84% sensitivity and 68% specificity. Three promoters (HIC1, MDG1 and RASSF1A) were selected for the biomarker, which differentiated patients with adenomatous polyps and controls with sensitivity of 55% and specificity of 65%. Methylation profiling of plasma DNA can detect early CRC with significant accuracy and shows promise as a methodology to develop biomarkers for CRC screening.
MicroRNA‐148b suppresses cell growth by targeting cholecystokinin‐2 receptor in colorectal cancer
Authors: Song Yongxi , Xu Yingying , Wang Zhenning , Chen Yue , Yue Zhenyu , Gao Peng , Xing Chengzhong , Xu Huimian 
Published: October 2011

AbstractMicroRNAs (miRNAs) play an important role in the regulation of a variety of cellular processes, including cell growth, differentiation, apoptosis and carcinogenesis. The purpose of this study was to elucidate the molecular mechanisms by which miR‐148b acts as a tumor suppressor in colorectal cancer. The expression of miR‐148b was significantly downregulated in 96 pairs of human colorectal cancer tissues (p < 0.0001) and three cell lines (p < 0.01) compared with non‐tumor adjacent tissues by quantitative real‐time PCR. The results of in situ hybridization highlighted that miR‐148b was important in the cancer transformation process. Using statistical analysis, we found that the expression level of miR‐148b was associated with tumor size (p = 0.033) in colorectal cancer patients. Moreover, overexpression of miR‐148b in HCT‐116 and HT‐29 cells could inhibit cell proliferation in vitro and suppress tumorigenicity in vivo. Importantly, the result of luciferase activity assay and western blot showed that the cholecystokinin‐2 receptor gene (CCK2R) was a target of miR‐148b and was downregulated by miR‐148b at the translational level. Then, we used siRNA, radioimmunoassay and ELISA to demonstrate that miR‐148b might have an effect on cell proliferation by regulating the expression of CCK2R which functioned depending on the gastrin in colorectal cancer. Taken together, our data provides the first evidences that miR‐148b acts as a tumor suppressor in colorectal cancer and should be further evaluated as a biomarker and therapeutic tool against colorectal cancer.
PRKX, TTBK2 and RSK4 expression causes sunitinib resistance in kidney carcinoma‐ and melanoma‐cell lines
Authors: Bender Claus , Ullrich Axel 
Published: October 2011

AbstractResistance to chemotherapeutic agents constitutes a major problem in the treatment of cancer. Over the past years, multi‐targeted protein kinase inhibitors such as Gleevec, Sunitinib and Sorafenib are gaining wider acceptance for cancer treatment. These drugs show anti‐tumor activity in vitro and in patients. Extended usage of these drugs in therapy commonly results in disease progression due to formation of resistance caused by rearrangements and accumulation of mutations in the unstable cancer cell genome. However, the underlying drug‐specific mechanisms for the development of resistance remain elusive. Hence, a detailed understanding of the molecular genetic events involved in this processes is pivotal to counteract are not directly targeted by Sunitinib (unpublished data). Therefore, development of specific or multi‐targeted inhibitors for these kinases for combinatorial therapy with e.g., an IL‐8 neutralizing antibody might circumvent or substantially delay Sunitinib resistance formation and enhance survival prognosis. PRKX, TTBK2 and RSK4 expression. The specific reduction of these genes employing siRNA was sufficient to sensitize the kidney‐ and melanoma‐cell lines against Sunitinib. In line with the elevated expression of PRKX, TTBK2 or RSK4, this sensitization effect was strikingly higher in the Sunitinib resistant cell lines, suggesting an expression‐based mechanism of these genes to trigger Sunitinib resistance. Hence, we propose that PRKX, TTBK2 and RSK4 are potential resistance markers in Sunitinib therapy and might therefore represent targets for the development of novel strategies to overcome resistance.
Chromosomal profiles of high‐grade cervical intraepithelial neoplasia relate to duration of preceding high‐risk human papillomavirus infection
Authors: Bierkens Mariska , Wilting Saskia M. , van Wieringen Wessel N. , van Kemenade Folkert J. , Bleeker Maaike C.G. , Jordanova Ekaterina S. , Bekker‐Lettink Marjolein , van de Wiel Mark A. , Ylstra Bauke , Meijer Chris J.L.M. , Snijders Peter J.F. , Steenbergen Renske D.M. 
Published: October 2011

AbstractHigh‐grade cervical intraepithelial neoplasia (CIN2/3) represents a heterogeneous disease both with respect to clinical behavior and chromosomal aberrations detected. We hypothesized that the extent of chromosomal aberrations reflects the duration of their existence. Chromosomal profiles were determined of CIN3 of women with a known 5‐year history of high‐risk human papillomavirus virus (hrHPV) infection, in which duration of prior hrHPV infection was considered a proxy for duration of CIN3 existence. Eleven women had a <5 year preceding hrHPV infection (CIN3<5yrPHI) and 24 had a PHI lasting ≥5 years (CIN3≥5yrPHI). For comparison, six CIN3 adjacent to squamous cell carcinomas (CIN3‐SCC), the corresponding SCCs, and six CIN1 were included. Unsupervised hierarchical clustering analysis of the chromosomal profiles revealed two clusters. One was characterized by a low number of chromosomal aberrations and included all CIN1, 81.8% of CIN3<5yrPHI and 33.3% of CIN3≥5yrPHI. Samples in the second cluster, displaying multiple aberrations, included 18.2% of CIN3<5yrPHI, 66.7% CIN3≥5yrPHI, all except one CIN3‐SCC and all SCCs. The number of genomic aberrations increased according to lesion grade and also with longer duration of PHI. The increase in aberrations in CIN3≥5yrPHI compared to <5yrPHI was highly significant (p = 0.001), suggesting that CIN3≥5yrPHI represent more severe lesions. In conclusion, longer duration of preceding hrHPV infection is associated with an increased number of chromosomal aberrations. Hence, CIN3 with a longer duration of existence are likely more prone to have an increased short‐term risk of cervical cancer.
Neuroblastoma triggers an immunoevasive program involving galectin‐1‐dependent modulation of T cell and dendritic cell compartments
Authors: Soldati Rocio , Berger Elisa , Zenclussen Ana C. , Jorch Gerhard , Lode Holger N. , Salatino Mariana , Rabinovich Gabriel A. , Fest Stefan 
Published: October 2011

AbstractThe immunosuppressive strategies devised by neuroblastoma (NB), the most common solid extracranial childhood cancer, are poorly understood. Here, we identified an immunoevasive program triggered by NB through secretion of galectin‐1 (Gal‐1), a multifunctional glycan‐binding protein. Human and mouse NB cells express and secrete Gal‐1, which negatively regulates T cell and dendritic cell function. When injected subcutaneously in syngeneic A/J mice, knockdown transfectants expressing low amounts of Gal‐1 (NXS2/L) showed reduction of primary tumor growth by 83–90% and prevented spontaneous liver metastases in contrast to NXS2 cell variants (NXS2/H, NXS2 wildtype) expressing high amounts of Gal‐1. Splenocytes from mice receiving Gal‐1 knockdown NXS2/L cells secreted higher amounts of IFN‐γ and displayed enhanced cytotoxic T‐cell function compared to NXS2/H or NXS2 controls. Immunohistochemical analysis revealed a six‐ to tenfold increase in the frequency of CD4+ and CD8+ T cells infiltrating tumors from mice receiving knockdown transfectants. This effect was confirmed by in vitro migration assays. Finally, supernatants of NXS2/H or NXS2 cells suppressed dendritic cell (DC) maturation and induce T cell apoptosis, whereas these effects were only marginal on DCs and T cells exposed to supernatants from NXS2/L cells. These results demonstrate a novel immunoinhibitory role of the Gal‐1‐glycan axis in NB, highlighting an alternative target for novel immunotherapeutic modalities.
MGMT CpG island is invariably methylated in adult astrocytic and oligodendroglial tumors with IDH1 or IDH2 mutations
Authors: Mulholland Shani , Pearson Danita M. , Hamoudi Rifat A. , Malley Deborah S. , Smith Caroline M. , Weaver Jamie M.J. , Jones David T.W. , Kocialkowski Sylvia , Bäcklund L. Magnus , Collins V. Peter , Ichimura Koichi 
Published: October 2011

AbstractWe have previously identified a region containing 16 CpGs within the MGMT CpG islands which is critical for the transcriptional control of MGMT (Malley, Acta Neuropathol 2011). To investigate the patterns and incidence of MGMT methylation in astrocytic and oligodendroglial tumors, we quantitatively assessed methylation at these 16 CpGs using bisulfite modification followed by pyrosequencing of 362 gliomas not treated with temozolomide, and correlated the findings with previously identified patterns of genetic abnormalities, patients' age and survival. The MGMT gene was considered to be methylated when the mean methylation of the 16 CpGs was 10% or higher. This cut‐off value distinguished diffuse astrocytomas with high and low MGMT expression. Within each tumor type, the patterns of methylation were highly variable and also highly heterogeneous across the 16 CpGs. A high incidence of MGMT methylation was observed in all subtypes of gliomas included in this study. Among a subset of 97 tumors where conventional methylation‐specific PCR (MSP) was also applied, methylation was detected by both methods in 54 tumors, while the pyrosequencing results identified a further 17 tumors. No additional cases were found using MSP alone, indicating that pyrosequencing is a robust method for methylation analysis. All tumors with IDH1/IDH2 mutations except two had MGMT methylation, while there were many tumors with MGMT methylation, particularly primary glioblastomas, which had no mutations of IDH1/2. We suggest that MGMT methylation may be one of the earliest events in the development of astrocytic and oligodendroglial tumors.
Characteristics and survival of head and neck cancer by HPV status: a cancer registry‐based study
Authors: Sethi Seema , Ali‐Fehmi Rouba , Franceschi Silvia , Struijk Linda , van Doorn Leen‐Jan , Quint Wim , Albashiti Bassam , Ibrahim Majd , Kato Ikuko 
Published: October 2011

AbstractElucidation of the role of human papillomavirus (HPV) in the etiology and prognosis of squamous carcinomas of the head and neck (HNSCC) is essential to optimize prevention and treatment strategies for this disease. We analyzed 385 HNSCC tissue blocks identified through a population‐based cancer registry in Metropolitan Detroit for HPV DNA using a broad‐spectrum PCR technique (SPF10‐LiPA25) to correlate with patient and tumor characteristics and overall survival. Overall, HPV DNA (any type) was detected in 29.4% of all HNSCC, but it was significantly more prevalent (50.6%) in oropharyngeal sites (N = 81), where 90% of HPV were type 16, than in other sites. HPV prevalence (any type) in oropharyngeal sites was highest in patients with a negative smoking indicator, Caucasians and in regional tumor stage. Likewise, only in oropharyngeal sites did patients overall positive to HPV show significantly better survival compared with HPV‐negative patients, notably among those who had been irradiated. The best and the worst survival from cancer in oropharyngeal sites were found, respectively, among HPV‐positive patients with negative smoking indicator and among HPV‐negative patients with positive smoking indicator. The results of this study revealed that the presence of HPV DNA was associated with patients' specific characteristics and better overall survival exclusively in oropharyngeal sites. To define the fraction of HNSCC preventable by HPV vaccination or amenable to less aggressive treatment, however, tobacco exposure and HPV markers other than DNA presence need to be taken into account.
The JmjC domain‐containing histone demethylase KDM3A is a positive regulator of the G1/S transition in cancer cells via transcriptional regulation of the HOXA1 gene
Authors: Cho Hyun‐Soo , Toyokawa Gouji , Daigo Yataro , Hayami Shinya , Masuda Ken , Ikawa Noriko , Yamane Yuka , Maejima Kazuhiro , Tsunoda Tatsuhiko , Field Helen I. , Kelly John D. , Neal David E. , Ponder Bruce A.J. , Maehara Yoshihiko , Nakamura Yusuke , Hamamoto Ryuji 
Published: October 2011

AbstractA number of histone demethylases have been identified and biochemically characterized, yet their biological functions largely remain uncharacterized, particularly in the context of human diseases such as cancer. In this study, we describe important roles for the histone demethylase KDM3A, also known as JMJD1A, in human carcinogensis. Expression levels of KDM3A were significantly elevated in human bladder carcinomas compared with nonneoplastic bladder tissues (p < 0.0001), when assessed by real‐time PCR. We confirmed that some other cancers including lung cancer also overexpressed KDM3A, using cDNA microarray analysis. Treatment of cancer cell lines with small interfering RNA targeting KDM3A significantly knocked down its expression and resulted in the suppression of proliferation. Importantly, we found that KDM3A activates transcription of the HOXA1 gene through demethylating histone H3 at lysine 9 di‐methylation by binding to its promoter region. Indeed, expression levels of KDM3A and HOXA1 in several types of cancer cell lines and bladder cancer samples were statistically correlated. We observed the down‐regulation of HOXA1 as well as CCND1 after treatment with KDM3A siRNA, indicating G1 arrest of cancer cells. Together, our results suggest that elevated expression of KDM3A plays a critical role in the growth of cancer cells, and further studies may reveal a cancer therapeutic potential in KDM3A inhibition.
Lack of CCR7 expression is rate limiting for lymphatic spread of pancreatic ductal adenocarcinoma
Authors: Sperveslage Jan , Frank Sunna , Heneweer Carola , Egberts Jan , Schniewind Bodo , Buchholz Malte , Bergmann Frank , Giese Nathalia , Munding Johanna , Hahn Stephan A. , Kalthoff Holger , Klöppel Günter , Sipos Bence 
Published: October 2011

AbstractCCR7 expression on tumor cells promotes lymphatic spread in several malignant tumors. However, a comprehensive characterization of the CCL19/CCL21–CCR7 axis in pancreatic ductal adenocarcinoma (PDAC), which is known for its high rates of lymph‐node metastases, is still lacking. CCR7 mRNA and CCR7 protein were found to be expressed in spheroid cultures of all six examined PDAC cell lines. In migration assays, CCR7 expressing PDAC cells showed enhanced migration toward CCL19 and CCL21, the two ligands of CCR7. In an orthotopic nude mouse model, CCR7‐transfected PT45P1 cells gave rise to significantly larger tumors and showed a higher frequency of lymph vessel invasion and lymph‐node metastases than mock‐transfected cells. In an analysis using quantitative real‐time PCR, CCR7 showed fourfold overexpression in microdissected PDAC cells compared to normal duct cells. Moderate‐to‐strong immunohistochemical CCR7 expression, found in 58 of 121 well‐characterized human PDACs, correlated with high rates of lymph vessel invasion. Conversely, PDACs completely lacking CCR7 expression showed only low rates of lymph vessel invasion and lymph‐node metastases. The evaluation of CCL21 expression by immunofluorescence staining revealed a significant upregulation of CCL21 in peritumoral and intratumoral lymph vessels compared to lymph vessels in disease‐free pancreata. In conclusion, our study revealed strong evidence that lack of CCR7 impairs the metastatic potential of PDAC. Lymph vessel invasion by CCR7 expressing PDAC cells may be additionally enhanced by upregulation of CCL21 in tumor‐associated lymph vessels, representing a previously unknown factor of lymphatic spread.