bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract SY40-01: Anti-CD40 as an anticancer agent
Authors: Vonderheide Robert H. 
Published: August 2012

Abstract
Pancreatic ductal adenocarcinoma (PDA) is an almost uniformly lethal disease for which novel effective therapies are critically needed. Although immunotherapy offers a distinct and promising therapeutic approach, the ability of pancreas carcinoma to orchestrate immune suppression represents a significant clinical obstacle. Previous studies to model pancreatic tumor immune responses in mice have been limited by the use of implantable tumor models or non-PDA tumors of islet cells. To circumvent these obstacles, we have evaluated immune surveillance in PDA using a genetically engineered mouse (GEM) model of this disease in which endogenous expression of KrasG12D and Trp53R172H is targeted to the pancreas of immune competent mice and for which the salient clinical, histopathologic, and molecular features of the human disease are strikingly recapitulated. In this ‘KPC’ model, progression to PDA is intimately associated with a suppressive immune reaction, particularly in the myeloid compartment, such that adaptive anti-tumor immunity is essentially non-existent. Because CD40 activation can reverse immune suppression and drive potent anti-tumor T cell responses, we tested the combination of an agonist CD40 antibody with gemcitabine chemotherapy in the KPC model. We observed tumor regression in 30% of mice and found further that tumor regression required macrophages but not T cells or gemcitabine. CD40-activated macrophages rapidly infiltrated tumors, became tumoricidal, and facilitated the depletion of tumor stroma. T cells, as expected, were activated following CD40 therapy but never infiltrate the tumor. Based on these preclinical findings, we performed a clinical study to test the hypothesis that CD40 activation in humans can cooperate with chemotherapy for the treatment of chemotherapy-naïve, surgically incurable PDA. Twenty-one patients (90% with metastatic disease) received gemcitabine weekly on days 1, 8, and 15 with the agonist CD40 mAb CP-870,893 (Pfizer) administered on day 3 of each 28 day cycle. Treatment was well-tolerated overall, and the most common side effect was mild-to-moderate cytokine release syndrome managed in the outpatient clinic. Metabolic responses were observed by FDG-PET/CT in both the primary and metastatic lesions in 88% of patients evaluated after 2 cycles of therapy. By RECIST, 5 of 21 patients developed a partial response. Thus, productive cancer immune surveillance does not necessarily depend on T cells; rather, our findings demonstrate a CD40-dependent mechanism for targeting cancer-associated inflammation in the treatment of cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr SY40-01. doi:1538-7445.AM2012-SY40-01
The Index of Microcirculatory Resistance Predicts Myocardial Infarction Related to Percutaneous Coronary Intervention
Authors: Ng Martin K. C. , Yong Andy S. C. , Ho Michael , Shah Maulik G. , Chawantanpipat Chirapan , O’Connell Rachel , Keech Anthony , Kritharides Leonard , Fearon William F. 
Published: August 2012

Background—
Periprocedural myocardial infarction (MI) occurs in a significant proportion of patients undergoing percutaneous coronary intervention (PCI) and portends poor outcomes. Currently, no clinically applicable method predicts periprocedural MI in the cardiac catheterization laboratory before it occurs. We hypothesized that impaired baseline coronary microcirculatory reserve, which reduces the ability to tolerate ischemic insults, is a risk for periprocedural MI and that the index of microcirculatory resistance (IMR) measured during PCI can predict occurrence of periprocedural MI.

Methods and Results—

Consecutive patients undergoing elective PCI of a single lesion in the left anterior descending coronary artery were recruited. A pressure-temperature sensor wire was used to measure IMR before PCI. Of the 50 patients studied, 10 had periprocedural MI. From binary logistic regression analyses of all clinical, procedural, and physiological parameters, univariable predictors of periprocedural MI were pre-PCI IMR (
P
=0.003) and the number of stents used (
P
=0.039). Pre-PCI IMR was the only independent predictor in bivariable regression analyses performed by adjusting for each available covariate one at a time (all
P
≤0.02). Pre-PCI IMR ≥27 U had 80.0% sensitivity and 85.0% specificity for predicting periprocedural MI (C statistic, 0.80;
P
=0.003). Pre-PCI IMR ≥27 U was independently associated with a 23-fold risk of developing periprocedural MI (odds ratio, 22.7; 95% CI, 3.8–133.9).

Conclusions—
These data suggest that the status of the coronary microcirculation plays a role in determining susceptibility toward periprocedural MI at the time of elective PCI. The IMR can predict subsequent risk of developing myocardial necrosis and may guide adjunctive prevention strategies.
The Effect of Treating Institution on Outcomes in Head and Neck Cancer
Authors: Lassig Amy Anne D. , Joseph Anne M. , Lindgren Bruce R. , Fernandes Patricia , Cooper Sarah , Schotzko Chelsea , Khariwala Samir , Reynolds Margaret , Yueh Bevan 
Published: August 2012

ObjectiveFactors leading patients with head and neck cancer (HNCA) to seek radiation or chemoradiation in an academic center versus the community are incompletely understood, as are the effects of site of treatment on treatment completion and survival.Study DesignHistorical cohort study.SettingTertiary academic center, community practices.MethodsA historical cohort study was completed of patients with mucosal HNCA identified by International Classification of Disease, Ninth Revision (ICD‐9) codes receiving consultation at the authors’ institution from 2003 to 2008. Patients who received primary and adjuvant radiation at an academic center or in the community were included. The authors compared treatment completion rates and performed univariate and multivariate analyses of treatment outcomes.ResultsOf 388 patients, 210 completed treatment at an academic center and 145 at a community center (33 excluded, location unknown). Patients with HNCA undergoing radiation at an academic site had more advanced disease (P =. 024) and were more likely to receive concurrent chemotherapy. Academic hospitals had a higher percentage of noncurrent smokers, higher median income, and higher percentage of oropharyngeal tumors. There was no significant difference in the rate of planned treatment completion between community and academic centers (93.7% vs 94.7%, P >. 81) or rate of treatment breaks (22.4% vs 28.4%, P >. 28). On Kaplan‐Meier analysis, the 5‐year survival rate was 53.2% (95% confidence interval [CI], 45.3%‐61.1%) for academic centers and 32.8% (95% CI, 22.0%‐43.6%) for community hospitals (P <. 001).ConclusionIn this cohort, although treatment completion and treatment breaks were similar between academic and community centers, survival rates were higher in patients treated in an academic setting.
T-cell independent, B-cell receptor-mediated induction of telomerase activity differs among IGHV mutation-based subgroups of chronic lymphocytic leukemia patients
Authors: Damle Rajendra N. , Temburni Sonal , Banapour Taraneh , Paul Santanu , Mongini Patricia K. A. , Allen Steven L. , Kolitz Jonathan E. , Rai Kanti R. , Chiorazzi Nicholas 
Published: August 2012

AbstractAlthough B-cell chronic lymphocytic leukemia (B-CLL) clones with unmutated IGHV genes (U-CLL) exhibit greater telomerase activity than those with mutated IGHV genes (M-CLL), the extent to which B-cell receptor (BCR) triggering contributes to telomerase up-regulation is not known. Therefore, we studied the effect of BCR stimulation on modulating telomerase activity. The multivalent BCR ligand, dextran conjugated anti-μ mAb HB57 (HB57-dex), increased telomerase activity and promoted cell survival and proliferation preferentially in U-CLL cases, whereas the PI3K/Akt inhibitor LY294002 blocked HB57-dex induced telomerase activation. Although both U-CLL and M-CLL clones exhibited similar membrane proximal signaling responses to HB57-dex, telomerase activity and cell proliferation, when inducible in M-CLL, differed. B-CLL cells stimulated using bivalent F(ab′)2 -goat anti-μ antibody (goat anti-μ) exhibited higher membrane proximal response in U-CLL than M-CLL cells, whereas telomerase activity, cell survival, and proliferation were induced to lower levels than those induced by HB57-dex. In normal B lymphocytes, HB57-dex induced less protein phosphorylation but more cell proliferation and survival than goat anti-μ. Although both anti-BCR stimuli induced comparable telomerase activity, normal CD5+ B cells preferentially exhibited higher hTERT positivity than their CD5− counterparts. These findings provide an understanding of how BCR-mediated signals impact telomerase modulation in IGHV mutation-based subgroups of B-CLL and normal B cells.
Inferring high-confidence human protein-protein interactions
Authors: Yu Xueping , Wallqvist Anders , Reifman Jaques 
Published: August 2012

Abstract

Background
As numerous experimental factors drive the acquisition, identification, and interpretation of protein-protein interactions (PPIs), aggregated assemblies of human PPI data invariably contain experiment-dependent noise. Ascertaining the reliability of PPIs collected from these diverse studies and scoring them to infer high-confidence networks is a non-trivial task. Moreover, a large number of PPIs share the same number of reported occurrences, making it impossible to distinguish the reliability of these PPIs and rank-order them. For example, for the data analyzed here, we found that the majority (>83%) of currently available human PPIs have been reported only once.

Results
In this work, we proposed an unsupervised statistical approach to score a set of diverse, experimentally identified PPIs from nine primary databases to create subsets of high-confidence human PPI networks. We evaluated this ranking method by comparing it with other methods and assessing their ability to retrieve protein associations from a number of diverse and independent reference sets. These reference sets contain known biological data that are either directly or indirectly linked to interactions between proteins. We quantified the average effect of using ranked protein interaction data to retrieve this information and showed that, when compared to randomly ranked interaction data sets, the proposed method created a larger enrichment (~134%) than either ranking based on the hypergeometric test (~109%) or occurrence ranking (~46%).

Conclusions
From our evaluations, it was clear that ranked interactions were always of value because higher-ranked PPIs had a higher likelihood of retrieving high-confidence experimental data. Reducing the noise inherent in aggregated experimental PPIs via our ranking scheme further increased the accuracy and enrichment of PPIs derived from a number of biologically relevant data sets. These results suggest that using our high-confidence protein interactions at different levels of confidence will help clarify the topological and biological properties associated with human protein networks.
Implantation of undifferentiated and pre-differentiated human neural stem cells in the R6/2 transgenic mouse model of Huntington’s disease
Authors: El-Akabawy Gehan , Rattray Ivan , Johansson Saga M , Gale Richard , Bates Gillian , Modo Michel 
Published: August 2012

AbstractBackgroundCell therapy is a potential therapeutic approach for several neurodegenetative disease, including Huntington Disease (HD). To evaluate the putative efficacy of cell therapy in HD, most studies have used excitotoxic animal models with only a few studies having been conducted in genetic animal models. Genetically modified animals should provide a more accurate representation of human HD, as they emulate the genetic basis of its etiology.ResultsIn this study, we aimed to assess the therapeutic potential of a human striatal neural stem cell line (STROC05) implanted in the R6/2 transgenic mouse model of HD. As DARPP-32 GABAergic output neurons are predominately lost in HD, STROC05 cells were also pre-differentiated using purmorphamine, a hedgehog agonist, to yield a greater number of DARPP-32 cells. A bilateral injection of 4.5x105cells of either undifferentiated or pre-differentiated DARPP-32 cells, however, did not affect outcome compared to a vehicle control injection. Both survival and neuronal differentiation remained poor with a mean of only 161 and 81 cells surviving in the undifferentiated and differentiated conditions respectively. Only a few cells expressed the neuronal marker Fox3.ConclusionsAlthough the rapid brain atrophy and short life-span of the R6/2 model constitute adverse conditions to detect potentially delayed treatment effects, significant technical hurdles, such as poor cell survival and differentiation, were also sub-optimal. Further consideration of these aspects is therefore needed in more enduring transgenic HD models to provide a definite assessment of this cell line’s therapeutic relevance. However, a combination of treatments is likely needed to affect outcome in transgenic models of HD.
Genome-scale identification of cell-wall related genes in Arabidopsis based on co-expression network analysis
Authors: Wang Shan , Yin Yanbin , Ma Qin , Tang Xiaojia , Hao Dongyun , Xu Ying 
Published: August 2012

Abstract

Background
Identification of the novel genes relevant to plant cell-wall (PCW) synthesis represents a highly important and challenging problem. Although substantial efforts have been invested into studying this problem, the vast majority of the PCW related genes remain unknown.

Results
Here we present a computational study focused on identification of the novel PCW genes in Arabidopsis based on the co-expression analyses of transcriptomic data collected under 351 conditions, using a bi-clustering technique. Our analysis identified 217 highly co-expressed gene clusters (modules) under some experimental conditions, each containing at least one gene annotated as PCW related according to the Purdue Cell Wall Gene Families database. These co-expression modules cover 349 known/annotated PCW genes and 2,438 new candidates. For each candidate gene, we annotated the specific PCW synthesis stages in which it is involved and predicted the detailed function. In addition, for the co-expressed genes in each module, we predicted and analyzed their cis regulatory motifs in the promoters using our motif discovery pipeline, providing strong evidence that the genes in each co-expression module are transcriptionally co-regulated. From the all co-expression modules, we infer that 108 modules are related to four major PCW synthesis components, using three complementary methods.

Conclusions
We believe our approach and data presented here will be useful for further identification and characterization of PCW genes. All the predicted PCW genes, co-expression modules, motifs and their annotations are available at a web-based database: http://csbl.bmb.uga.edu/publications/materials/shanwang/CWRPdb/index.html.
Cocktail sedation containing propofol versus conventional sedation for ERCP: a prospective, randomized controlled study
Authors: Angsuwatcharakon Phonthep , Rerknimitr Rungsun , Ridtitid Wiriyaporn , Kongkam Pradermchai , Poonyathawon Sahadol , Ponauthai Yuwadee , Sumdin Sakolkan , Kullavanijaya Pinit 
Published: August 2012

Abstract

Background
ERCP practically requires moderate to deep sedation controlled by a combination of benzodiazepine and opiod. Propofol as a sole agent may cause oversedation. A combination (cocktail) of infused propofol, meperidine, and midazolam can reduce the dosage of propofol and we hypothesized that it might decrease the risk of oversedation. We prospectively compare the efficacy, recovery time, patient satisfactory, and side effects between cocktail and conventional sedations in patients undergoing ERCP.

Methods
ERCP patients were randomized into 2 groups; the cocktail group (n = 103) and the controls (n = 102). For induction, a combination of 25 mg of meperidine and 2.5 mg of midazolam were administered in both groups. In the cocktail group, a bolus dose of propofol 1 mg/kg was administered and continuously infused. In the controls, 25 mg of meperidine or 2.5 mg/kg of midazolam were titrated to maintain the level of sedation.

Results
In the cocktail group, the average administration rate of propofol was 6.2 mg/kg/hr. In the control group; average weight base dosage of meperidine and midazolam were 1.03 mg/kg and 0.12 mg/kg, respectively. Recovery times and patients’ satisfaction scores in the cocktail and control groups were 9.67 minutes and 12.89 minutes (P = 0.045), 93.1and 87.6 (P <0.001), respectively. Desaturation rates in the cocktail and conventional groups were 58.3% and 31.4% (P <0.001), respectively. All desaturations were corrected with temporary oxygen supplementation without the need for scope removal.

Conclusions
Cocktail sedation containing propofol provides faster recovery time and better patients’ satisfaction for patients undergoing ERCP. However, mild degree of desaturation may still develop.

Trial registration
ClinicalTrials.gov, NCT01540084
MicroRNA-196a promotes non-small cell lung cancer cell proliferation and invasion through targeting HOXA5
Authors: Liu Xiang-hua , Lu Kai-hua , Wang Ke-ming , Sun Ming , Zhang Er-bao , Yang Jin-song , Yin Dan-dan , Liu Zhi-li , Zhou Jing , Liu Zhi-jun , De Wei , Wang Zhao-xia 
Published: August 2012

Abstract

Background
MicroRNAs (miRNAs) are short, non-coding RNAs (~22 nt) that play important roles in the pathogenesis of human diseases by negatively regulating gene expression. Although miR-196a has been implicated in several other cancers, its role in non-small cell lung cancer (NSCLC) is unknown. The aim of the present study was to examine the expression pattern of miR-196a in NSCLC and its clinical significance, as well as its biological role in tumor progression.

Methods
Expression of miR-196a was analyzed in 34 NSCLC tissues and five NSCLC cell lines by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). The effect of DNA methylation on miR-196a expression was investigated by 5-aza-2-deoxy-cytidine treatment and bisulfite sequencing. The effect of miR-196a on proliferation was evaluated by MTT and colony formation assays, and cell migration and invasion were evaluated by transwell assays. Analysis of target protein expression was determined by western blotting. Luciferase reporter plasmids were constructed to confirm the action of miR-196a on downstream target genes, including HOXA5. Differences between the results were tested for significance using Student’s t-test (two-tailed).

Results
miR-196a was highly expressed both in NSCLC samples and cell lines compared with their corresponding normal counterparts, and the expression of miR-196a may be affected by DNA demethylation. Higher expression of miR-196a in NSCLC tissues was associated with a higher clinical stage, and also correlated with NSCLC lymph-node metastasis. In vitro functional assays demonstrated that modulation of miR-196a expression affected NSCLC cell proliferation, migration and invasion. Our analysis showed that miR-196a suppressed the expression of HOXA5 both at the mRNA and protein levels, and luciferase assays confirmed that miR-196a directly bound to the 3’untranslated region of HOXA5. Knockdown of HOXA5 expression in A549 cells using RNAi was shown to promote NSCLC cell proliferation, migration and invasion. Finally, we observed an inverse correlation between HOXA5 and miR-196a expression in NSCLC tissues.

Conclusions
Our findings indicate that miR-196a is significantly up-regulated in NSCLC tissues, and regulates NSCLC cell proliferation, migration and invasion, partially via the down-regulation of HOXA5. Thus, miR-196a may represent a potential therapeutic target for NSCLC intervention.
Acceptance patterns and decision-making for human papillomavirus vaccination among parents in Vietnam: an in-depth qualitative study post-vaccination
Authors: Cover Jane K , Nghi Nguyen Quy , LaMontagne D Scott , Huyen Dang Thi Thanh , Hien Nguyen Tran , Nga Le Thi 
Published: August 2012

Abstract

Background
The GAVI Alliance’s decision in late 2011 to invite developing countries to apply for funding for human papillomavirus (HPV) vaccine introduction underscores the importance of understanding levels of HPV vaccine acceptance in developing country settings. In this paper, we present findings from qualitative research on parents’ rationales for vaccinating or not vaccinating their daughters (vaccine acceptance) and their decision-making process in the context of an HPV vaccination demonstration project in Vietnam (2008–2009).

Methods
We designed a descriptive qualitative study of HPV vaccine acceptability among parents of girls eligible for vaccination in four districts of two provinces in Vietnama. The study was implemented after each of two years of vaccinations was completed. In total, 133 parents participated in 16 focus group discussions and 27 semi-structured interviews.

Results
Focus group discussions and in-depth interviews with parents of girls vaccinated revealed that they were generally very supportive of immunization for disease prevention and of vaccinating girls against HPV. The involvement of the National Expanded Program of Immunization in the demonstration project lent credibility to the HPV vaccine, contributing to high levels of acceptance. For parents who declined participation, concerns about side effects, the possibility that the vaccine was experimental, and the possible impact of the vaccine on future fertility rose to the surface. In terms of the decision-making process, many parents exhibited ‘active decision-making,’ reaching out to friends, family, and opinion leaders for guidance prior to making their decision.

Conclusion
Vietnam’s HPV vaccination experience speaks to the importance of close collaboration with the government to make the most of high levels of trust, and to reduce suspicions about new vaccines that may arise in the context of vaccine introduction in developing country settings.