bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pretreatment FDG‐PET standardized uptake value as a prognostic factor for outcome in head and neck cancer
Authors: Machtay Mitchell , Natwa Mona , Andrel Jocelyn , Hyslop Terry , Anne P. Rani , Lavarino Jororsali , Intenzo Charles M. , Keane William 
Published: December 2008

AbstractBackground.We studied the potential prognostic significance of pretreatment 18‐fluorodeoxyglucose‐positron emission tomography (FDG‐PET) standardized uptake value (SUV) in squamous cell carcinoma of the head and neck (SCCHN).Methods.A retrospective review of the pretreatment FDG‐PET scans of 60 patients with SCCHN was performed. All patients received radiotherapy and 37 also received concurrent chemotherapy. SUV was calculated by 2 nuclear‐medicine physicians who were blinded to the clinical data. Disease‐free survival (DFS) was analyzed with respect to SUV (and other potential prognostic factors).Results.The median SUV was 7.2 (range, 1–24.7); 34 patients (57%) had SUV < 9.0 compared with 26 patients (43%) with an SUV ≥ 9.0. The group with low SUV had significantly better 2‐year DFS compared with the high SUV group (72% vs 37%), p = .007. On multivariate analysis, stage and age were also associated with DFS, but SUV remained an independent predictor of DFS (hazard ratio: 1.08; p = .016).Conclusion.SUV was significantly associated with outcome after modern definitive therapy of SCCHN. © 2008 Wiley Periodicals, Inc. Head Neck, 2009
Quality‐adjusted survival analysis of Radiation Therapy Oncology Group (RTOG) 90‐03: Phase III randomized study comparing altered fractionation to standard fractionation radiotherapy for locally advanced head and neck squamous cell carcinoma
Authors: Konski Andre A. , Winter Kathryn , Cole Bernard F. , Ang Kie‐Kian , Fu Karen K. 
Published: December 2008

AbstractBackground.To evaluate quality‐adjusted survival (QAS) of patients with locally advanced squamous cell carcinoma of the head and neck treated with 4 different radiation fractionation schedules.Methods.QAS was calculated using the quality‐adjusted time without toxicity or relapse (Q‐TWiST) methodology. Utilities (patient preferences for certain health states) were obtained by threshold analysis. Q‐TWiST therefore equaled TWiST + ([weight for toxicity] × [time spent in toxicity]) + ([weight for relapse] × [time spent in relapse]).Results.A statistically significant increase in QAS existed for patients treated with hyperfractionated radiotherapy compared with standard fractionated radiotherapy (SFX) with a toxicity utility ≥0.57 and relapse utility ≤0.72. No statistically significant difference was observed for patients treated with the other 2 fractionation schedules compared with SFX.Conclusion.Q‐TWiST analysis identified patient groups that would benefit from more aggressive therapy. Further investigation with patient‐generated utilities is needed. © 2008 Wiley Periodicals, Inc. Head Neck, 2009
Comparison of outcome measures in head and neck cancer—Literature review 2000–2006
Authors: Tschiesner Uta M. , Rogers Simon N. , Harreus Ulrich , Berghaus Alexander , Cieza Alarcos 
Published: December 2008

AbstractBackground.The aim of this study was to systematically analyze outcome measures in head and neck cancer trials using the International Classification of Functioning. Disability, and Health (ICF) as reference.Methods.Clinical trials 2000 to 2006 in MEDLINE were selected according to predefined criteria. Outcome measures were extracted, and concepts contained in the outcome measures were translated into ICF.Results.A total of 254 publications showed 4203 concepts that translate into 117 different, second‐level ICF‐categories. Just 2 of 117 outcome measures apply regularly: e580 (health_services) in 58% publications and b510 (ingestion_function) in 46% publications. Any other outcome measure applies to <33% publications. In the differentiation of outcome measures among tumor locations, staging, or treatment options, no systematic use of specific outcome measures was identified in any subgroup.Conclusion.The ICF provides a useful reference to identify and quantify outcome measures in head and neck cancertrials. Applying the ICF classification reveals little standardization in the use of outcome‐measures by different authors. However, this is not related to the heterogeneity of head and neck cancer in terms of tumor locations, staging, or treatment options. Systematic use of the ICF might increases comparability of study results and decrease data silos. © 2008 Wiley Periodicals, Inc. Head Neck, 2009
Place and value of the recurrent laryngeal nerve (RLN) palpatory method in preventing RLN palsy during thyroid surgery
Authors: Altorjay Áron , Tihanyi Zoltán , Luka Ferenc , Juhász Árpád , Bencsik Zsuzsanna , Rüll Miklós , Kecskés Gábor , Paál Balázs 
Published: December 2008

AbstractBackground.In recent years, certain publications have appeared confirming that intraoperative palpation of the recurrent laryngeal nerve (RLN) is a very reliable method.Method.The characteristics of the surgical anatomy of 1023 RLN have been summarized on the basis of intraoperative palpability, running down, branching variations, thickness, and laryngeal entry site.Results.Palpation was helpful in 81.4% (833/1023), proved false positive in 8.2% (84/1023), and in 10.4% (106/1023) it was of no help in the exact localization. Definitive RLN palsy was experienced in 0.78% of all cases (8/1023), while transient paresis was encountered in 1.2% (12/1023). Only a moderately strong stochastic correlation could be found between RLN palsies and those nerves which were nonpalpable and atypical, which showed the joint occurrence of being both thinner than normal and branching already before the plane of the inferior thyroid artery (Cramer's associate coefficient, C = 0.383).Conclusion.Palpation alone cannot substitute visualization and proper surgical dissection of the nerve. © 2008 Wiley Periodicals, Inc. Head Neck, 2009
Aurora kinase A inhibition and paclitaxel as targeted combination therapy for head and neck squamous cell carcinoma
Authors: Mazumdar Abhijit , Henderson Ying C. , El‐Naggar Adel K. , Sen Subrata , Clayman Gary L. 
Published: December 2008

AbstractBackground.Aurora kinase A (AURKA) is amplified with varying incidence in multiple human cancers including head and neck squamous cell carcinoma (HNSCC). We investigated whether AURKA is a potential therapeutic target in HNSCC.Methods.We conducted an immunohistochemical analysis of AURKA expression in paired normal and tumor samples (n = 63). HNSCC cells treated with siRNA specific for AURKA were assessed for AURKA mRNA and protein expression levels by reverse transcriptase‐polymerase chain reaction and Western blot analysis. Tumor cells treated with siRNA and paclitaxel were assessed for cell proliferation by MTT assay and for cell cycle distribution by flow cytometry.Results.AURKA expression was higher in tumor than in adjacent normal in most (85%) of the samples analyzed. HNSCC cells and primary tumors revealed high expression levels of AURKA. Most primary tumors also showed high kinase activity of the enzyme. Targeted AURKA inhibition increased the sub‐G1 cell fraction, with a concomitant reduction in the G1 cell population, indicating induction of apoptosis and thus markedly suppressed proliferation of HNSCC cells. Combining siRNA‐induced AURKA inhibition with 5 to 10 nM paclitaxel synergistically enhanced apoptosis induction.Conclusion.AURKA is a potential therapeutic target for HNSCC. Further investigation of small‐molecule AURKA inhibitors as therapeutic agents is warranted. © 2008 Wiley Periodicals, Inc. Head Neck, 2009
Bile acids: Trying to understand their chemistry and biology with the hope of helping patients #
Authors: Hofmann Alan F. 
Published: December 2008

Abstract
An informal review of the author's five decades of research on the chemistry and biology of bile acids in health and disease is presented. The review begins with a discussion of bile acid structure and its remarkable diversity in vertebrates. Methods for tagging bile acids with tritium for metabolic or transport studies are summarized. Bile acids solubilize polar lipids in mixed micelles; progress in elucidating the structure of the mixed micelle is discussed. Extensive studies on bile acid metabolism in humans have permitted the development of physiological pharmacokinetic models that can be used to simulate bile acid metabolism. Consequences of defective bile acid biosynthesis and transport have been clarified, and therapy has been developed. Methods for measuring bile acids have been improved. The rise and fall of medical and contact dissolution of cholesterol gallstones is chronicled. Finally, principles of therapy with bile acid agonists and antagonists are given. Advances in understanding bile acid biology and chemistry have helped to improve the lives of patients with hepatobiliary or digestive disease. (Hepatology 2009.)
Locating the stem cell niche and tracing hepatocyte lineages in human liver #
Authors: Fellous Tariq G. , Islam Shahriar , Tadrous Paul J. , Elia George , Kocher Hemant M. , Bhattacharya Satyajit , Mears Lisa , Turnbull Douglas M. , Taylor Robert W. , Greaves Laura C. , Chinnery Patrick F. , Taylor Geoffery , McDonald Stuart A.C. , Wright Nicholas A. , Alison Malcolm R. 
Published: December 2008

Abstract
We have used immunohistochemical and histochemical techniques to identify patches of hepatocytes deficient in the enzyme cytochrome c oxidase, a component of the electron transport chain and encoded by mitochondrial DNA (mtDNA). These patches invariably abutted the portal tracts and expanded laterally as they spread toward the hepatic veins. Here we investigate, using mtDNA mutations as a marker of clonal expansion, the clonality of these patches. Negative hepatocytes were laser-capture microdissected and mutations identified by polymerase chain reaction sequencing of the entire mtDNA genome. Patches of cytochrome c oxidase–deficient hepatocytes were clonal, suggesting an origin from a long-lived cell, presumably a stem cell. Immunohistochemical analysis of function and proliferation suggested that these mutations in cytochrome c oxidase-deficient hepatocytes were nonpathogenic. Conclusion: these data show, for the first time, that clonal proliferative units exist in the human liver, an origin from a periportal niche is most likely, and that the trajectory of the units is compatible with a migration of cells from the periportal regions to the hepatic veins. (Hepatology 2009.)
Systemic antigen cross-presented by liver sinusoidal endothelial cells induces liver-specific CD8 T-cell retention and tolerization #
Authors: von Oppen Nanette , Schurich Anna , Hegenbarth Silke , Stabenow Dirk , Tolba Rene , Weiskirchen Ralf , Geerts Albert , Kolanus Waldemar , Knolle Percy , Diehl Linda 
Published: December 2008

Abstract
Peripheral CD8 T-cell tolerance can be generated outside lymphatic tissue in the liver, but the course of events leading to tolerogenic interaction of hepatic cell populations with circulating T-cells remain largely undefined. Here we demonstrate that preferential uptake of systemically circulating antigen by murine liver sinusoidal endothelial cells (LSECs), and not by other antigen-presenting cells in the liver or spleen, leads to cross-presentation on major histocompatibility complex (MHC) I molecules, which causes rapid antigen-specific naïve CD8 T-cell retention in the liver but not in other organs. Using bone-marrow chimeras and a novel transgenic mouse model (Tie2-H-2Kb mice) with endothelial cell-specific MHC I expression, we provide evidence that cross-presentation by organ-resident and radiation-resistant LSECs in vivo was both essential and sufficient to cause antigen-specific retention of naïve CD8 T-cells under noninflammatory conditions. This was followed by sustained CD8 T-cell proliferation and expansion in vivo, but ultimately led to the development of T-cell tolerance. Conclusion: Our results show that cross-presentation of circulating antigens by LSECs caused antigen-specific retention of naïve CD8 T-cells and identify antigen-specific T-cell adhesion as the first step in the induction of T-cell tolerance. (Hepatology 2009.)
Hepatitis C virus persisting after clinically apparent sustained virological response to antiviral therapy retains infectivity in vitro #
Authors: MacParland Sonya A. , Pham Tram N. Q. , Guy Clifford S. , Michalak Tomasz I. 
Published: December 2008

Abstract
Hepatitis C virus (HCV) can persist in the liver, lymphoid cells, and serum of individuals with apparently complete spontaneous or therapy-induced resolution of hepatitis C and can replicate in vivo and in vitro in human T cells. The current study was aimed at assessing the infectivity of HCV persisting at very low levels using the previously established HCV infection system in human T cells. Naive lymphoid cells were exposed to plasma and/or supernatants from cultured peripheral blood mononuclear cells from nine individuals with apparent sustained virological response after completion of antiviral therapy. Exposed cells were analyzed for HCV RNA–positive and HCV RNA–negative strands and, in selected cases, for HCV nonstructural protein 5a (NS5a), the appearance of HCV variants, and the release of virions by immunoelectron microscopy (IEM). The results showed that 11 of the 12 established cultures became HCV RNA–positive strand–reactive, whereas 4 also expressed the virus replicative strand. NS5a protein was detected in the de novo infected cells, and clonal sequencing revealed HCV variants not found in inocula. IEM demonstrated enveloped HCV particles in plasma used as inocula and in culture supernatant from T cells exposed to that plasma. Overall, HCV carried in three of the nine individuals studied elicited productive infection in vitro. Conclusion: HCV persisting at very low levels long after therapy-induced resolution of chronic hepatitis C can remain infectious. The retained biological competence of the virus might have implications with respect to the mechanisms of its persistence and the epidemiology of HCV infection. (Hepatology 2009.)
MicroRNA-122, a tumor suppressor microRNA that regulates intrahepatic metastasis of hepatocellular carcinoma #
Authors: Tsai Wei-Chih , Hsu Paul Wei-Che , Lai Tsung-Ching , Chau Gar-Yang , Lin Ching-Wen , Chen Chun-Ming , Lin Chien-Der , Liao Yu-Lun , Wang Jui-Ling , Chau Yat-Pang , Hsu Ming-Ta , Hsiao Michael , Huang Hsien-Da , Tsou Ann-Ping 
Published: December 2008

Abstract
MicroRNAs (miRNAs), which are inhibitors of gene expression, participate in diverse biological functions and in carcinogenesis. In this study, we show that liver-specific microRNA-122 (miR-122) is significantly down-regulated in liver cancers with intrahepatic metastastasis and negatively regulates tumorigenesis. Restoration of miR-122 in metastatic Mahlavu and SK-HEP-1 cells significantly reduced in vitro migration, invasion, and anchorage-independent growth as well as in vivo tumorigenesis, angiogenesis, and intrahepatic metastasis in an orthotopic liver cancer model. Because an inverse expression pattern is often present between an miRNA and its target genes, we used a computational approach and identified multiple miR-122 candidate target genes from two independent expression microarray datasets. Thirty-two target genes were empirically verified, and this group of genes was enriched with genes regulating cell movement, cell morphology, cell-cell signaling, and transcription. We further showed that one of the miR-122 targets, ADAM17 (a disintegrin and metalloprotease 17) is involved in metastasis. Silencing of ADAM17 resulted in a dramatic reduction of in vitro migration, invasion, in vivo tumorigenesis, angiogenesis, and local invasion in the livers of nude mice, which is similar to that which occurs with the restoration of miR-122. Conclusion: Our study suggests that miR-122, a tumor suppressor microRNA affecting hepatocellular carcinoma intrahepatic metastasis by angiogenesis suppression, exerts some of its action via regulation of ADAM17. Restoration of miR-122 has a far-reaching effect on the cell. Using the concomitant down-regulation of its targets, including ADAM17, a rational therapeutic strategy based on miR-122 may prove to be beneficial for patients with hepatocellular carcinoma. (Hepatology 2009.)
Polyproline‐type helical‐structured low‐molecular weight heparin (LMWH)‐taurocholate conjugate as a new angiogenesis inhibitor
Authors: Lee Esak , Kim Yoo‐Shin , Bae Sang Mun , Kim Sang Kyoon , Jin Shunji , Chung Seung Woo , Lee Myungjin , Moon Hyun Tae , Jeon Ok‐Cheol , Park Rang Woon , Kim In San , Byun Youngro , Kim Sang Yoon 
Published: December 2008

AbstractAlthough heparin can regulate angiogenesis, tumor growth and metastasis, its clinical application, as well as that of low‐molecular heparin (LMWH), for treating cancer are limited because of heparin's anticoagulant activity and risk of hemorrhages. LMWH‐taurocholate conjugates (LHT7), which have low anticoagulant activity, were synthesized. The structural property of LHT was evaluated by circular dichroism and the binding affinity of LHT7 to vascular endothelial growth factor 165 (VEGF165) was measured by isothermal titration calorimetry. The inhibitory effect of LHT7 on VEGF‐mediated KDR (VEGF‐receptor 2) phosphorylation in Human umbilical vein endothelial cells was evaluated. The VEGF165dependent Matrigel plug assay was performed to verify the antiangiogenic potential of LHT7 on a VEGF165inhibitor. Finally, tumor growth inhibition effects of LHT7 on SCC7 and the survival rate of animal models were investigated. Moreover, MDA‐MB231 xenograft mouse model was additionally used to confirm the therapeutic effect of LHT7 on human breast cancer cell line. As a result, LHT7 which has 12.7% of anticoagulant activity of the original LMWH showed a peculiar polyproline‐type helical structure. LHT7 binds to VEGF strongly and inhibits VEGF dependent KDR phosphorylation. The results of Matrigel plug assay proved LHT7 as a strong antiangiogenic agent inhibiting VEGF165. Remarkably, LHT7 showed a significant tumor growth inhibition potential on SCC7 with an increased survival rate. LHT7 also delayed tumor growth in MDA‐MB231 human breast cancer cell lines. © 2008 UICC
DNA fingerprinting tags novel altered chromosomal regions and identifies the involvement of SOX5 in the progression of prostate cancer
Authors: Ma Stephanie , Chan Yuen Piu , Woolcock Bruce , Hu Liang , Wong Kai Yau , Ling Ming Tat , Bainbridge Terry , Webber Douglas , Chan Tim Hon Man , Guan Xin‐Yuan , Lam Wan , Vielkind Juergen , Chan Kwok Wah 
Published: December 2008

AbstractIdentification of genomic alterations associated with the progression of prostate cancer may facilitate the better understanding of the development of this highly variable disease. Matched normal, premalignant high‐grade prostatic intraepithelial neoplasia and invasive prostate carcinoma cells were procured by laser capture microdissection (LCM) from human radical prostatectomy specimens. From these cells, comparative DNA fingerprints were generated by a modified PCR‐based technique called scanning of microdissected archival lesion (SMAL)‐PCR. Recurrent polymorphic fingerprint fragments were used in tagging altered chromosomal regions. Altered regions were found at cytobands 1p31.3, 1q44, 2p23.1, 3p26.3, 3q22.3, 4q22.3, 4q35.2, 5q23.2, 8q22.3, 8q24.13, 9q21.3, 9q22.32, 10q11.21, 11p13, 12p12.1, 13q12.1, 16q12.2 and 18q21.31. Candidate genes in the surrounding area that may possibly harbor mutations that change normal prostatic cells to progress into their tumor stages were proposed. Of these fragments, a 420 bp alteration, absent in all 26 normal samples screened, was observed in 2 tumors. This fragment was cloned, sequenced and localized to chromosome 12p12.1. Within this region, candidate gene sex determining region Y‐box 5 (SOX5) was proposed. Further studies of SOX5 in cell lines, xenografts and human prostate specimens, at both the RNA and protein levels, found overexpression of the gene in tumors. This overexpression was then subsequently found by fluorescent in situ hybridization to be caused by amplification of the region. In conclusion, our results suggest LCM coupled with SMAL‐PCR DNA fingerprinting is a useful method for the screening and identification of chromosomal regions and genes associated with cancer development. Further, overexpression of SOX5 is associated with prostate tumor progression and early development of distant metastasis. © 2008 Wiley‐Liss, Inc.
Immunoglobulin subclass levels in patients with non‐Hodgkin lymphoma
Authors: Biggar Robert J. , Christiansen Michael , Rostgaard Klaus , Smedby Karin Ekström , Adami Hans‐Olov , Glimelius Bengt , Hjalgrim Henrik , Melbye Mads 
Published: December 2008

AbstractAllergy/atopy has been suggested to protect against non‐Hodgkin lymphoma (NHL) and specific IgE levels are decreased in patients with NHL. We speculated that all immunoglobulin subclass levels might be downregulated in NHL and examined levels of IgM, IgD, IgA, IgE, IgG and IgG4 in 200 NHL patients and 200 age‐ and sex‐matched controls. Patients with B‐cell NHL of many types had consistently lower median immunoglobulin subclass levels than controls. In every subclass except IgD, about 10–15% of B‐cell NHL patients had absolute levels below the 2.5 percentile of controls. Subclass levels correlated with each other and many patients had more than one significantly low level. Levels were lowest for IgG4 and IgE. Patients with chronic lymphocytic leukemia/small lymphocytic lymphoma had especially low total IgE levels. In other B‐cell NHL types, total IgE levels were decreased to a similar extent as other immunoglobulin subclasses. In conclusion, low IgE levels are only part of a more generalized loss of immunoglobulins of all subtypes in a wide variety of B‐cell NHL types. Low immunoglobulin levels appear to be a consequence of B‐cell NHL presence, and we speculate about molecular mechanisms that could reduce all immunoglobulin subclasses in B‐cell NHL. © 2008 Wiley‐Liss, Inc.