bluuebunny/crossref_metadata_2025_split huggingface dataset:
A clustered ground‐glass hepatocyte pattern represents a new prognostic marker for the recurrence of hepatocellular carcinoma after surgery
Authors: Tsai Hung‐Wen , Lin Yih‐Jyh , Lin Pin‐Wen , Wu Han‐Chieh , Hsu Kai‐Hsi , Yen Chia‐Jui , Chan Shih‐Huang , Huang Wenya , Su Ih‐Jen 
Published: January 2011

AbstractBACKGROUND:The recurrence of hepatocellular carcinoma (HCC) after hepatectomy is a serious event. It has been demonstrated that different ground‐glass hepatocyte (GGH) patterns harbor specific hepatitis B virus (HBV) pre‐S deletion mutants and represent preneoplastic lesions in chronic HBV infection. In the current study, the authors investigated whether a specific GGH pattern in nontumorous liver tissues was associated with the recurrence of HBV‐related HCC after surgery.METHODS:Clinicopathologic data from 82 patients with HBV‐related HCC were reviewed. GGH patterns were assessed on hematoxylin and eosin‐stained sections. Tissue hepatitis B surface antigen (HBsAg) expression was evaluated by immunohistochemical staining. Serum profiles of pre‐S status, viral load, and HBV genotype were determined and correlated with clinical recurrence and survival after surgery.RESULTS:The results indicated that the clustered pattern of GGHs or HBsAg expression was associated significantly with decreased local recurrence‐free survival (LRFS) during a mean follow‐up of 46.4 months (P<.001). This biomarker was comparable to or better than the prognostic value of other parameters, such as multifocal tumors (P = .022), satellite nodules (P = .005), small cell dysplasia (P = .045), or elevated viral load (P = .027), to predict recurrent HCC. Multivariate analysis also revealed that type II GGHs, which expressed marginal HBsAg and consistently clustered in nodules, were independent variables associated with LRFS (P<.001) and overall survival (P = .003).CONCLUSIONS:The current results indicated that the assessment of GGH patterns or HBsAg expression in nontumorous liver tissues provides an easily recognized, new risk marker for the recurrence of HBV‐related HCC after hepatic resection. Cancer 2011. © 2011 American Cancer Society.
Do patients consider preoperative chemoradiation for primary rectal cancer worthwhile?
Authors: Kennedy Erin D. , Schmocker Selina , Victor Charles , Baxter Nancy N. , Kim John , Brierley James , McLeod Robin S. 
Published: January 2011

AbstractBACKGROUND:The objective of this study was to elicit future patients' preferences for preoperative chemoradiation (pre‐CRT) for rectal cancer to determine whether patients' preferences are consistent with current treatment guidelines.METHODS:During a standardized interview, the treatment protocol, risks, benefits, and long‐term outcomes associated with 1) surgery alone (SA) and 2) pre‐CRT followed by surgery (CR + S) were described to healthy individuals, and a threshold task was performed. Each participant was asked which treatment option they would prefer when the risk of local recurrence was set initially at 15% for both options. If the participant indicated SA (which was expected), then the risk of local recurrence for CR + S was lowered systematically until the participant's preference changed from SA to CR + S. This threshold point represented the risk of local recurrence for pre‐CRT that the participant would require before they would choose treatment with pre‐CRT.RESULTS:Fifty individuals participated in the study, and the majority were well educated. Twenty‐seven of 50 participants (54%) required a risk of local recurrence with CR + S of ≤5% (ie, equivalent to an absolute risk reduction ≥10%) before they would choose treatment with pre‐CRT. Regression analysis did not identify any variables that were predictive of the participants' preferences.CONCLUSIONS:Participants seemed to highly value functional outcomes and seemed willing to accept a higher risk of local recurrence to achieve this. Therefore, developers of future guidelines may need to downgrade the use of pre‐CRT for all patients with stage II/III tumors from a guideline to an option. Cancer 2011. © 2011 American Cancer Society.
A novel KIF5B‐ALK variant in nonsmall cell lung cancer
Authors: Wong Daisy Wing‐Sze , Leung Elaine Lai‐Han , Wong Sunny Kit‐Man , Tin Vicky Pui‐Chi , Sihoe Alan Dart‐Loon , Cheng Lik‐Cheung , Au Joseph Siu‐Kie , Chung Lap‐Ping , Wong Maria Pik 
Published: January 2011

AbstractBACKGROUND:The anaplastic lymphoma kinase (ALK) gene is involved frequently in chromosomal translocations, resulting in fusion genes with different partners found in various lymphoproliferative conditions. It was recently reported in nonsmall cell lung cancer (NSCLC) that the fusion protein encoded by echinoderm microtubule‐associated protein‐like 4‐ALK (EML4‐ALK) fusion gene conferred oncogenic properties. The objective of the current study was to identify other possible ALK fusion genes in NSCLC.METHODS:Immunohistochemical analysis was used to screen for aberrant ALK expression in primary NSCLC. The authors used 5′ rapid amplification of complementary DNA ends to screen for potential, novel 5′ fusion partners of ALK other than EML4‐ALK. Reverse transcriptase‐polymerase chain reaction and fluorescence in situ hybridization analyses were used to confirm the identity of 5′ fusion partners. The genomic breakpoint was verified using genomic sequencing. Overexpression of the novel ALK fusion gene and variants 3a and 3b of EML4‐ALK was performed to assess downstream signaling and functional effects.RESULTS:The authors identified a novel gene resulting from the fusion of kinesin family member 5B (KIF5B) exon 15 to ALK exon 20 in a primary lung adenocarcinoma. Western blot analysis of clinical tumor tissues revealed the expression of a protein whose size correlated with that of the predicted KIF5B‐ALK. Overexpression of KIF5B‐ALK in mammalian cells led to the activation of signal transducer and activator of transcription 3 and protein kinase B and to enhanced cell proliferation, migration, and invasion.CONCLUSIONS:The discovery of the novel KIF5B‐ALK variant further consolidated the role of aberrant ALK signaling in lung carcinogenesis. Cancer 2011. © 2011 American Cancer Society.
Modeling the mortality reduction due to computed tomography screening for lung cancer
Authors: Foy Millennia , Yip Rowena , Chen Xing , Kimmel Marek , Gorlova Olga Y. , Henschke Claudia I. 
Published: January 2011

AbstractBACKGROUND:The efficacy of computed tomography (CT) screening for lung cancer remains controversial because results from the National Lung Screening Trial are not yet available. In this study, the authors used data from a single‐arm CT screening trial to estimate the mortality reduction using a modeling‐based approach to construct a control comparison arm.METHODS:To estimate the potential lung cancer mortality reduction because of CT screening, a previously developed and validated model was applied to the screening trial to predict the number of lung cancer deaths in the absence of screening. By using age, gender, and smoking characteristics matching those of the trial participants, the model was used to simulate 5000 trials in the absence of CT screening to produce the expected number of lung cancer deaths along with 95% confidence intervals (95% CIs), while adjusting for healthy volunteer bias.RESULTS:There were 64 observed lung cancer deaths in the screening cohort (n = 7995), whereas the model predicted 117.7 deaths (95% CI, 98 deaths‐139 deaths), indicating a mortality reduction of 45.6% (P < .001). When a more conservative healthy volunteer adjustment was applied, 111.3 lung cancer deaths were predicted (95% CI, 91 deaths‐132 deaths), for a lung cancer‐specific mortality reduction of 42.5% (P < .001).CONCLUSIONS:The results of the current study indicate that CT screening along with early stage treatment can reduce lung cancer‐specific mortality. This mortality reduction is greatly influenced by the protocol of nodule follow‐up and treatment, and the length of follow‐up. Cancer 2011. © 2011 American Cancer Society.
Tristetraprolin regulates interleukin‐6, which is correlated with tumor progression in patients with head and neck squamous cell carcinoma
Authors: Van Tubergen Elizabeth , Vander Broek Robert , Lee Julia , Wolf Gregory , Carey Thomas , Bradford Carol , Prince Mark , Kirkwood Keith L. , D'Silva Nisha J. 
Published: January 2011

AbstractBACKGROUND:Tumor‐derived cytokines play a significant role in the progression of head and neck squamous cell carcinoma (HNSCC). Targeting proteins, such as tristetraprolin (TTP), that regulate multiple inflammatory cytokines may inhibit the progression of HNSCC. However, TTP's role in cancer is poorly understood. The goal of the current study was to determine whether TTP regulates inflammatory cytokines in patients with HNSCC.METHODS:TTP messenger RNA (mRNA) and protein expression were determined by quantitative real‐time–polymerase chain reaction (Q‐RT‐PCR) and Western blot analysis, respectively. mRNA stability and cytokine secretion were evaluated by quantitative RT‐PCR and enzyme‐linked immunoadsorbent assay, respectively, after overexpression or knockdown of TTP in HNSCC. HNSCC tissue microarrays were immunostained for interleukin‐6 (IL‐6) and TTP.RESULTS:TTP expression in HNSCC cell lines was found to be inversely correlated with the secretion of IL‐6, vascular endothelial growth factor (VEGF), and prostaglandin E2 (PGE2). Knockdown of TTP increased mRNA stability and the secretion of cytokines. Conversely, overexpression of TTP in HNSCC cells led to decreased secretion of IL‐6, VEGF, and PGE2. Immunohistochemical staining of tissue microarrays for IL‐6 demonstrated that staining intensity is prognostic for poor disease‐specific survival (P = .023), tumor recurrence and development of second primary tumors (P = .014), and poor overall survival (P = .019).CONCLUSIONS:The results of the current study demonstrated that down‐regulation of TTP in HNSCC enhances mRNA stability and promotes secretion of IL‐6, VEGF, and PGE2. Furthermore, high IL‐6 secretion in HNSCC tissue is a biomarker for poor prognosis. In as much as enhanced cytokine secretion is associated with poor prognosis, TTP may be a therapeutic target to reduce multiple cytokines concurrently in patients with HNSCC. Cancer 2011. © 2011 American Cancer Society.
Higher population‐based incidence rates of triple‐negative breast cancer among young African‐American women
Authors: Amirikia Kathryn C. , Mills Paul , Bush Jason , Newman Lisa A 
Published: January 2011

AbstractBACKGROUND:Differences in the breast cancer burden of African‐American women compared with white American women are well documented. Recent controversies have emerged regarding age‐appropriate mammographic screening guidelines, and these surveillance recommendations may influence future breast cancer disparities. The objective of the current study was to evaluate age‐specific breast cancer stage distributions and incidence rates of triple‐negative breast cancer (TNBC) in a population‐based tumor registry.METHODS:The authors analyzed breast cancers from the California Cancer Registry (CCR) that were diagnosed between 1988 and 2006. The results were stratified by age and race/ethnicity, with white Americans identified as non‐Hispanic whites (NHWs) and African Americans identified as non‐Hispanic blacks (NHBs). Breast cancer stage distributions and TNBC incidence rates also were analyzed.RESULTS:In total, 375,761 invasive breast cancers were evaluated (including 276,938 in NHWs and 21,681 in NHBs). NHBs and Hispanics tended to be younger than NHWs (median ages 57 years, 54 years, and 64 years, respectively). Lifetime incidence rates were higher for NHWs compared with NHBs and Hispanics; however, for women aged <44 years, incidence was highest among NHBs. NHBs also had higher incidence rates of stage III and IV disease and a higher incidence of TNBC in all age categories.CONCLUSIONS:Population‐based data demonstrated that African‐American women had a more advanced stage distribution for breast cancer compared with white American women and higher incidence rates for TNBC. These patterns were observed for women ages 40 to 49 years and for older women, and they suggest that mammographic screening for the early detection of breast cancer will be particularly relevant for younger African‐American women. Cancer 2011. © 2011 American Cancer Society.
Loss of MTBP expression is associated with reduced survival in a biomarker‐defined subset of patients with squamous cell carcinoma of the head and neck
Authors: Vlatković Nikolina , El‐Fert Ashraf , Devling Timothy , Ray‐Sinha Arpita , Gore David M. , Rubbi Carlos P. , Dodson Andy , Jones Andrew S. , Helliwell Tim R. , Jones Terence M. , Boyd Mark T. 
Published: January 2011

AbstractBACKGROUND:Recent genetic studies have implicated p53 mutation as a significant risk factor for therapeutic failure in squamous cell carcinoma of the head and neck (SCCHN). However, in a recent meta‐analysis in the literature of p53 from major anatomical subsites (larynx, oral cavity, oropharynx/hypopharynx), associations between patient survival and p53 status were ambiguous.METHODS:The authors examined a cohort of SCCHNs using a previously developed biomarker combination that likely predicts p53 status based on p53/MDM2 expression levels determined by immunohistochemistry (IHC). In addition, the authors generated and validated an antibody to MTBP (an MDM2 binding protein that alters p53/MDM2 homeostasis and may contribute to metastatic suppression) and have incorporated data for MTBP expression into the current analyses.RESULTS:Analysis of expression data for p53 and MDM2 in 198 SCCHN patient samples revealed that the biomarker combination p53 + ve/MDM2‐low (likely indicative of p53 mutation) was significantly associated with reduced overall survival (log‐rank P = .035) and was an independent prognostic factor (P = .013; HR, 1.705; 95% CI, 1.12‐2.60); thus, these data were compatible with earlier genetic analyses. By using IHC for p53 and MDM2 to dichotomize patients, the authors found that loss of MTBP expression was significantly associated with reduced survival (log‐rank P = .004) and was an independent prognostic factor (P = .004; HR, 2.78; 95% CI, 1.39‐5.54) in p53 + ve/MDM2‐low patients.CONCLUSIONS:These results represent the first examination of MTBP expression in human tissues and provide evidence for a p53 status‐dependent role for MTBP in suppressing disease progression in SCCHN patients as well as confirming a role for p53 pathway function in delaying disease progression. Cancer 2011. © 2011 American Cancer Society.
Glucose, not glutamine, is the dominant energy source required for proliferation and survival of head and neck squamous carcinoma cells
Authors: Sandulache Vlad C. , Ow Thomas J. , Pickering Curtis R. , Frederick Mitchell J. , Zhou Ge , Fokt Izabela , Davis‐Malesevich Melinda , Priebe Waldemar , Myers Jeffrey N. 
Published: January 2011

AbstractBACKGROUND:Tumor metabolism is an essential contributor to disease progression and response to treatment. An understanding of the metabolic phenotype of head and neck squamous cell carcinoma (HNSCC) will allow the development of appropriate antimetabolic strategies for this tumor type.METHODS:A panel of 15 HNSCC cell lines was assayed for glucose and glutamine dependence and sensitivity to metabolic inhibitors. In addition, broad‐spectrum metabolomic analysis using mass spectrometry/liquid chromatography was combined with individual measurements of reducing potential, adenosine triphosphate, and lactate production to characterize cellular metabolic phenotypes.RESULTS:HNSCC energy and reducing potential levels closely mirrored extracellular glucose concentrations. Glucose starvation induced cell death despite the activation of secondary energetic pathways. Conversely, glutamine was not required for HNSCC survival and did not serve as a significant source of energy. 2‐deoxyglucose (2‐DG) and its fluorinated derivative decreased glycolytic and Krebs cycle activity, cellular energy, and reducing potential and inhibited HNSCC cell proliferation. 2‐DG effects were potentiated by the addition of metformin, but not by inhibitors of the pentose phosphate pathway or glutaminolysis. Despite dependence on glucose catabolism, the authors identified a subset of cell lines with relative resistance to starvation. Exploration of 1 such cell line (HN30) suggested that the presence of wild‐type p53 can partially protect tumor cells from glucose starvation.CONCLUSIONS:HNSCC tumor cells are dependent on glucose, not glutamine, for energy production and survival, providing a rationale for treatment strategies that target glucose catabolism. However, antimetabolic strategies may need to be tailored to the tumor background, more specifically, p53 status. Cancer 2011. © 2011 American Cancer Society.
Clinical prognostic factors in patients with locally advanced (stage III) nonsmall cell lung cancer treated with hyperfractionated radiation therapy with and without concurrent chemotherapy
Authors: Jeremić Branislav , Miličić Biljana , Milisavljevic Slobodan 
Published: January 2011

AbstractBACKGROUND:Influence of potential clinical prognostic factors on overall survival (OS), local progression‐free survival (PFS), and distant metastasis‐free survival (MFS) in patients with locally advanced nonsmall cell lung cancer treated with hyperfractionated radiation therapy (HFX RT) with or without concurrent chemotherapy was investigated.METHODS:Three phase 3 and 2 phase 2 studies have been designed and executed with a total of 600 patients. HFX RT alone was given in 127 and HFX RT‐chemotherapy was given in 473 patients. HFX RT doses were either 64.8 grays (Gy) or 69.6 Gy using 1.2 Gy twice daily, or 67.6 Gy using 1.3 Gy twice daily. Chemotherapy consisted of concurrent carboplatin and etoposide in 409 patients and concurrent carboplatin and paclitaxel in 64 patients. Sex, age, Karnofsky performance score (KPS), weight loss (>5%), stage, histology, interfraction interval, and treatment (the addition of concurrent chemotherapy) were investigated as potential prognostic factors.RESULTS:The median OS, median local PFS, and median distant MFS times were 19, 21, and 23 months, respectively. Five‐year OS, local PFS, and distant MFS rates were 19%, 29%, and 35%, respectively. Univariate and multivariate analysis showed that only age did not influence OS and local PFS, whereas female sex, lower KPS, less pronounced weight loss, lower stage, squamous histology, shorter interfraction interval, and treatment independently predicted better OS and local PFS. Only age and treatment did not influence distant MFS, whereas histology was of borderline significance.CONCLUSIONS:This study identified independent prognosticators of treatment outcome. These results may have implications for future studies in this disease. Cancer 2011. © 2011 American Cancer Society.
Highly Athletic Terrestrial Mammals: Horses and Dogs
Authors: Poole David C. , Erickson Howard H. 
Published: January 2011

AbstractEvolutionary forces drive beneficial adaptations in response to a complex array of environmental conditions. In contrast, over several millennia, humans have been so enamored by the running/athletic prowess of horses and dogs that they have sculpted their anatomy and physiology based solely upon running speed. Thus, through hundreds of generations, those structural and functional traits crucial for running fast have been optimized. Central among these traits is the capacity to uptake, transport and utilize oxygen at spectacular rates. Moreover, the coupling of the key systems—pulmonary‐cardiovascular‐muscular is so exquisitely tuned in horses and dogs that oxygen uptake response kinetics evidence little inertia as the animal transitions from rest to exercise. These fast oxygen uptake kinetics minimize Intramyocyte perturbations that can limit exercise tolerance. For the physiologist, study of horses and dogs allows investigation not only of a broader range of oxidative function than available in humans, but explores the very limits of mammalian biological adaptability. Specifically, the unparalleled equine cardiovascular and muscular systems can transport and utilize more oxygen than the lungs can supply. Two consequences of this situation, particularly in the horse, are profound exercise‐induced arterial hypoxemia and hypercapnia as well as structural failure of the delicate blood‐gas barrier causing pulmonary hemorrhage and, in the extreme, overt epistaxis. This chapter compares and contrasts horses and dogs with humans with respect to the structural and functional features that enable these extraordinary mammals to support their prodigious oxidative and therefore athletic capabilities. © 2011 American Physiological Society.Compr Physiol1:1‐37, 2011.
Fear, anxiety, and control in the zebrafish
Authors: Jesuthasan Suresh 
Published: January 2011

AbstractEmotional responses are triggered by environmental signals and involve profound changes at multiple levels, from molecular to behavior. Much has been learnt about two emotions, fear and anxiety, by studying mammalian models. In particular, neural circuits and the corresponding molecular mechanisms essential for the learning and retention of fear, as well as the activation of anxiety, are well known. In contrast, little is known about how these emotions are terminated. The zebrafish is a newcomer to the world of emotion research. A number of assays for fear and anxiety now exist, but the underlying neural circuitry is largely undefined. Recent experiments, however, appear to provide a hint as to how anxiety is downregulated. In particular, they point to an essential role for a circuit involving the posterior septum, medial habenula, and interpeduncular nucleus. This evolutionarily conserved circuit may fulfill a similar function in mammals. © 2011 Wiley Periodicals, Inc. Develop Neurobiol 72: 395–403, 2012
The role of sensory organs and the forebrain for the development of the craniofacial shape as revealed by Foxg1‐cre‐mediated microRNA loss
Authors: Kersigo Jennifer , D'Angelo Alex , Gray Brian D. , Soukup Garrett A. , Fritzsch Bernd 
Published: January 2011

AbstractCranial development is critically influenced by the relative growth of distinct elements. Previous studies have shown that the transcription factor Foxg1 is essential the for development of the telencephalon, olfactory epithelium, parts of the eye and the ear. Here we investigate the effects of a Foxg1‐cre‐mediated conditional deletion of Dicer1 and microRNA (miRNA) depletion on mouse embryos. We report the rapid and complete loss of the telencephalon and cerebellum as well as the severe reduction in the ears and loss of the anterior half of the eyes. These losses result in unexpectedly limited malformations of anterodorsal aspects of the skull. We investigated the progressive disappearance of these initially developing structures and found a specific miRNA of nervous tissue, miR‐124, to disappear before reduction in growth of the specific neurosensory areas. Correlated with the absence of miR‐124, these areas showed numerous apoptotic cells that stained positive for anticleaved caspase 3 and the phosphatidylserine stain PSVue® before the near or complete loss of those brain and sensory areas (forebrain, cerebellum, anterior retina, and ear). We conclude that Foxg1‐cre‐mediated conditional deletion of Dicer1 leads to the absence of functional miRNA followed by complete or nearly complete loss of neurons. Embryonic neurosensory development therefore depends critically on miRNA. Our data further suggest that loss of a given neuronal compartment can be triggered using early deletion of Dicer1 and thus provides a novel means to genetically remove specific neurosensory areas to investigate loss of their function on morphology (this study) or signal processing within the brain. genesis 49:326–341, 2011. © 2011 Wiley‐Liss, Inc.