tbuckley/cabot-search huggingface dataset:
Abstract 1593: Stat3 signaling in erbB3-mediated epithelial-mesenchymal transition in erbB2-positive breast cancer cells
Authors: Hui Lyu, Ying Wu, Yan Zhou, Bolin Liu
Journal: Cancer Research (2016)

Abstract Introduction: Understanding the mechanism of metastatic program is essential to reducing the mortality of cancer patients. It is well known that epithelial-mesenchymal transition (EMT) contributes to cancer metastasis. Recently, numerous studies have documented the role of erbB3-mediated oncogenic signaling in breast cancer progression. In this study, we have focused on investigating the effect of Stat3 activation on EMT-induced by erbB3 receptor in erbB2-positive (erbB2+) breast cancer cells. Methods: Immunofluorescence analyses were performed to study the localization and expression of EMT markers in erbB2+ breast cancer cells. Lentiviral vector containing shRNA was used to specifically knockdown erbB3. Western blot analyses were performed to assess the expression and activation of proteins. Cell growth (MTS) assays were used to determine cell viability. Wound healing and transwell assays were used to examine the motility and migration of cells. Results: We discovered that ectopic expression of erbB3 facilitated EMT, as evidenced by change of cell morphology, induction of mesenchymal markers Vimentin, Snail, Slug, ZEB1 and repression of the epithelial marker E-cadherin in erbB2+ breast cancer cells. Wound healing and transwell assays indicated that the capability of cell motility and migration was enhanced. In contrast, specific knockdown of erbB3 abrogated the observations described above. Moreover, elevated expression of erbB3 potently stimulated activation of Stat3, which has been validated to act as a promoter of tumor invasion and metastasis in many type cancers. Suppression of Stat3 signaling via its inhibitor, S3I-201, significantly alleviated EMT and cell motility/migration that were triggered by activation of erbB3. To further assess the clinical relevance of erbB3 signaling in cancer metastasis, we took advantage of a publicly accessible portal that allows analysis of the effect of genes on survival using 4,142 breast cancer samples (http://kmplot.com/analysis/). Kaplan-Meier survival curves showed that the erbB2+ breast cancer patients with erbB3-high expression tended to have a shorter Distance Metastasis-free Survival (DMFS). Conclusion: Activation of Stat3 signaling by erbB3 promotes EMT and shifts the cellular phenotype toward a mesenchymal state that is advantageous for cancer metastasis. Our data shed a new sight on erbB3's role in erbB2+ breast cancer metastasis and may facilitate the development of novel strategy for treatment of tumor progression. Keywords: ErbB3, Stat3, EMT, Metastasis, Breast Cancer Citation Format: Hui Lyu, Ying Wu, Yan Zhou, Bolin Liu. Stat3 signaling in erbB3-mediated epithelial-mesenchymal transition in erbB2-positive breast cancer cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1593.
ECG Response: October 29, 2013
Authors: Philip Podrid
Journal: Circulation (2013)

ECG Challenge: A 75-year-old man with known chronic obstructive pulmonary disease attributable to a long history of cigarette smoking presents to the emergency department with a 2-day history of worsened shortness of breath and a cough productive of yellowish sputum.He is afebrile.His blood pressure is 120/70 and his pulse rate is 150 bpm.Lung examination is remarkable for diffuse rhonchi and expiratory wheezes.An ECG is obtained.His chest x-ray is consistent with chronic obstructive pulmonary disease, but there are no infiltrates present.It is felt that he has a chronic obstructive pulmonary disease exacerbation and bronchitis and is begun on antibiotics and a steroid taper.ECG A was obtained in the emergency department, and ECG B was obtained 2 days later after there was improvement in his respiratory status.
HLA Class I Typing of Platelets by Multi-Colour Flow Cytometry - A New Powerful Tool for Assessing Survival, Activation Status and Activation Capacity of Transfused Platelets Vs. Autologous Platelets and for Determination of Stem Cell Engraftment After Allogeneic Stem Cell Transplantation.
Authors: Annette Vetlesen, Pål Andre Holme, Torstein Lyberg, Jens Kjeldsen-Kragh
Journal: Blood (2009)
Monitoring of Adenovirus Load in Stool by Real-Time PCR Permits Early Detection of Impending Invasive Infection in Patients after Allogeneic Stem Cell Transplantation
Authors: Thomas Lion, Karin Kosulin, Christine Landlinger, Margit Rauch, Dragana Jugovic, Ulrike Pötschger, Anita Lawitschka, Christina Peters, Gerhard Fritsch, Susanne Matthes-Martin
Journal: Blood (2008)
Immune Response and Mortality Risk Relate to Distinct Lung Microbiomes in Patients with HIV and Pneumonia
Authors: Meera K. Shenoy, Shoko Iwai, Din L. Lin, William Worodria, Irene Ayakaka, Patrick Byanyima, Sylvia Kaswabuli, Serena Fong, Stephen Stone, Emily Chang, J. Lucian Davis, Ali Ahmad Faruqi, Mark R. Segal, Laurence Huang, Susan V. Lynch
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

Rationale: The potential role of the airway microbiota in dictating immune responses and infection outcomes in HIV-associated pneumonia is largely unknown.Objectives: To investigate whether microbiologically and immunologically distinct subsets of patients with HIV and pneumonia exist and are related to mortality.Methods: Bronchoalveolar lavage samples from Ugandan patients with HIV and pneumonia (n = 182) were obtained at study enrollment (following antibiotic treatment); patient demographics including 8- and 70-day mortality were collected. Lower airway bacterial community composition was assessed via amplification and sequencing of the V4 region of the 16S ribosomal RNA gene. Host immune response gene expression profiles were generated by quantitative polymerase chain reaction using RNA extracted from bronchoalveolar lavage fluid. Liquid and gas chromatography mass spectrometry was used to profile serum metabolites.Measurements and Main Results: Based on airway microbiome composition, most patients segregated into three distinct groups, each of which were predicted to encode metagenomes capable of producing metabolites characteristically enriched in paired serum samples from these patients. These three groups also exhibited differences in mortality; those with the highest rate had increased ceftriaxone administration and culturable Aspergillus, and demonstrated significantly increased induction of airway T-helper cell type 2 responses. The group with the lowest mortality was characterized by increased expression of T-cell immunoglobulin and mucin domain 3, which down-regulates T-helper cell type 1 proinflammatory responses and is associated with chronic viral infection.Conclusions: These data provide evidence that compositionally and structurally distinct lower airway microbiomes are associated with discrete local host immune responses, peripheral metabolic reprogramming, and different rates of mortality.
Abdominal adiposity, waist circumference, and body mass index in patients with intermediate-risk prostate cancer treated with image-guided radiotherapy.
Authors: T. Zilli, T. Nguyen, J. Bahary, M. Chagnon, A. Dufresne, D. Taussky
Journal: Journal of Clinical Oncology (2010)

e15044 Background: Increased visceral adiposity has been proposed as a risk factor for prostate cancer and a greater body mass index (BMI) has been associated with adverse pathologic features and lower biochemical disease-free survival (bDFS) after conventional radiotherapy. We tested the potential role of abdominal visceral (VAT) and subcutaneous adipose tissue (SAT), waist circumference (WC) and BMI as prognostic factors in patients treated with image-guided radiotherapy (IGRT) for localized prostate cancer. Methods: Between 2003 and 2007, 112 patients with intermediate-risk prostate cancer [cT1b-2b, Gleason score (GS) 7 and prostate-specific antigen (PSA) < 15 ng/mL or GS < 6 and PSA >10 but < 20 ng/mL] were treated in a randomized phase 3 trial with exclusive IGRT with either 70.2 or 79.2 Gy. VAT and SAT measured from planning abdominal computed tomography, WC and BMI were compared with clinical and pathologic factors using univariate analyses. Cox regression analyses were performed to evaluate whether anthropometric measures of obesity significantly predicted bDFS (PSA nadir + 2 ng/mL definition). Results: Median age and BMI at baseline were 71 (55-80) years and 27.5 (19.2-51.5) kg/m2, respectively. Of the 112 eligible patients, 30 (27%) were obese. Greater abdominal adiposity, WC and BMI were significantly associated with younger age at diagnosis and increased prostate volume. Mean age and prostate size for patients with a BMI <25 and > 30 kg/m2 were 71 and 66 years (p = 0.005), and 34.7 and 50.6 cm3 (p = .002), respectively. No significant correlation between anthropometric measures and higher GS, T-stage, PSA or percentage of positive cores at biopsy was found. After a median follow-up of 43.4 (24-79) months, the 5-year bDFS was 80% + 6.1%. On Cox regression analyses, none of the anthropometric measures of obesity predicted bDFS. Only baseline PSA showed a trend toward a higher PSA recurrence (p = 0.077). Conclusions: Abdominal adiposity, WC and BMI were not associated in this study with adverse pathologic features in patients with intermediate-risk prostate cancer and did not predispose toward a higher risk of biochemical failure when modern IGRT techniques are used. No significant financial relationships to disclose.
Differential Expression and Significance of PD-L1, IDO-1, and B7-H4 in Human Lung Cancer
Authors: Kurt A. Schalper, Daniel Carvajal-Hausdorf, Joseph McLaughlin, Mehmet Altan, Vamsidhar Velcheti, Patricia Gaule, Miguel F. Sanmamed, Lieping Chen, Roy S. Herbst, David L. Rimm
Journal: Clinical Cancer Research (2016)

To determine the expression level, associations, and biological role of PD-L1, IDO-1, and B7-H4 in non-small cell lung cancer (NSCLC).Using multiplexed quantitative immunofluorescence (QIF), we measured the levels of PD-L1, IDO-1, B7-H4, and different tumor-infiltrating lymphoycte (TIL) subsets in 552 stages I-IV lung carcinomas from two independent populations. Associations between the marker levels, TILs, and major clinicopathologic variables were determined. Validation of findings was performed using mRNA expression data from The Cancer Genome Atlas (TCGA) and in vitro stimulation of lung adenocarcinoma A549 cells with IFNγ and IL10.PD-L1 was detected in 16.9% and 21.8% of cases in each population. IDO-1 was expressed in 42.6% and 49.8%; and B7-H4 in 12.8% and 22.6% of cases, respectively. Elevated PD-L1 and IDO-1 were consistently associated with prominent B- and T-cell infiltrates, but B7-H4 was not. Coexpression of the three protein markers was infrequent, and comparable results were seen in the lung cancer TCGA dataset. Levels of PD-L1 and IDO-1 (but not B7-H4) were increased by IFNγ stimulation in A549 cells. Treatment with IL10 upregulated B7-H4 but did not affect PD-L1 and IDO-1 levels.PD-L1, IDO-1, and B7-H4 are differentially expressed in human lung carcinomas and show limited co-expression. While PD-L1 and IDO-1 are associated with increased TILs and IFNγ stimulation, B7-H4 is not. The preferential expression of discrete immune evasion pathways in lung cancer could participate in therapeutic resistance and support design of optimal clinical trials. Clin Cancer Res; 23(2); 370-8. ©2016 AACR.
Abstract 3553: A novel allosteric mechanism for molecular inhibition of anti-apoptotic MCL-1
Authors: Susan Lee, Thomas E. Wales, Catherine Gallagher, Daniel T. Cohen, Silvia Escudero, James Luccarelli, Annissa J. Huhn, Nicole A. Cohen, Gregory H. Bird, John R. Engen, Loren D. Walensky
Journal: Cancer Research (2016)

Abstract MCL-1 is an anti-apoptotic BCL-2 family protein that has emerged as a major pathogenic factor across a broad range of human cancers. Thus, pharmacologic inhibition of MCL-1 has been the focus of intensive drug development efforts. Like BCL-2, MCL-1 bears a C-terminal surface groove whose function is to bind and sequester the essential BH3 killer domains of pro-apoptotic BCL-2 family proteins, a mechanism harnessed by cancer cells to create formidable apoptotic blockades. Whereas drugging the BH3-binding groove has been successfully achieved for BCL-2, translating this approach to MCL-1 has been challenging. Here, we report an alternative mechanism for MCL-1 inhibition by small molecule covalent modification of an interaction site that is distant from the BH3-binding groove. Biochemical and hydrogen-deuterium exchange mass spectrometry analyses revealed that both the BH3-binding capacity of MCL-1 and its functional suppression of BAX-mediated membrane poration is impaired by molecular engagement, a phenomenon recapitulated by mutagenic mimicry at the novel regulatory region. This allosteric mechanism for disrupting the anti-apoptotic, BH3-binding activity of MCL-1 could inform a new therapeutic strategy for disarming MCL-1 in cancer. Citation Format: Susan Lee, Thomas E. Wales, Catherine Gallagher, Daniel T. Cohen, Silvia Escudero, James Luccarelli, Annissa J. Huhn, Nicole A. Cohen, Gregory H. Bird, John R. Engen, Loren D. Walensky. A novel allosteric mechanism for molecular inhibition of anti-apoptotic MCL-1. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3553.
Abstract 983: Integrative analysis of androgen receptor regulated long non-coding RNA in prostate cancer
Authors: Rohit Malik, Yajia Zhang, Marcin Cieslik, Yashar S. Niknafs, Sethuramasundaram Pitchiaya, Yasuyuki Hosono, Shruthi Subramaniam, Sahr Yazdani, Xuhong Cao, Dan Robinson, Arul Chinnaiyan
Journal: Cancer Research (2016)

Abstract Androgen receptor (AR) plays a critical role in the development and progression of prostate cancer. AR regulates a large repertoire of genes; however, the effect of androgen signaling on the regulation of long non-coding RNAs (lncRNA) remains incompletely understood. Using transcriptome sequencing (RNA-seq) of AR-positive cell lines VCaP and LNCaP treated with dihydroxytestosterone (DHT), we identified genes, including lncRNAs, which were strongly regulated by AR. To confirm direct regulation by AR, we interrogated AR-ChIP-seq data from VCaP and LNCaP cells, identifying the lncRNAs with direct AR binding. Existence of these lncRNAs in prostate cancer tissue samples was confirmed by analysis of RNA-seq data from prostate tumors, and the degree of differential expression in prostate tumors (localized and castration resistant metastases) versus benign was determined. The most highly overexpressed lncRNA in this analysis was a 2.7kb multi-exonic transcript present on chromosome 16 called ARlnc1. RACE was utilized to determine the exact exon structure of this gene, and its expression levels in various prostate cancer cell lines as well as independent prostate cancer tissue cohorts was assessed. Further, knockdown of ARlnc1 in AR dependent cell lines inhibited cell proliferation and induced apoptosis. Knockdown of ARlnc1 affected molecular signatures related to cell cycle, mitosis and DNA damage. Interestingly, ARlnc1 knockdown also suppressed global androgen signaling as determined by Gene set enrichment analysis using AR gene signature. Upon investigation of the mechanism through which PRCAT47 regulate AR signaling, we discovered that ARlnc1 regulates AR at the level of translation. Taken together, our data suggests that many lncRNAs are regulated by androgen signaling, and we identify one such lncRNA that is involved in a protein-lncRNA positive feedback loop. Citation Format: Rohit Malik, Yajia Zhang, Marcin Cieslik, Yashar S. Niknafs, Sethuramasundaram Pitchiaya, Yasuyuki Hosono, Shruthi Subramaniam, Sahr Yazdani, Xuhong Cao, Dan Robinson, Arul Chinnaiyan. Integrative analysis of androgen receptor regulated long non-coding RNA in prostate cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 983.
Assessment of accuracy of data obtained from patient-reported questionnaire (PRQ) compared to electronic patient records (EPR) in patients with lung cancer.
Authors: Prakruthi R. Palepu, Catherine Brown, Gautam Joshi, Osvaldo Epsin-Garcia, Lawson Eng, Jayalakshmi Ramanna, Henrique Hon, Salma Momin, Dan Pringle, Sinead Cuffe, Thomas K. Waddell, Shaf Keshavjee, Gail Elizabeth Darling, Kazuhiro Yasufuku, Marc de Perrot, Andrew Pierre, Marcelo Cypel, Wei Xu, Geoffrey Liu
Journal: Journal of Clinical Oncology (2013)

40 Background: Cigarette smoking, alcohol consumption and co-morbidities are important determinants of health in lung cancer patients. The gold standard for obtaining accurate data is PRQ. The purpose of this study is to ascertain the accuracy of abstracting health-related behaviour data from retrospective chart review compared to data directly obtained from PRQ in a lung cancer patient population. Methods: 731 lung cancer patients completed a PRQ related to lifetime tobacco use, alcohol consumption and co-morbidity. Relevant smoking, alcohol and co-morbidity data was collected independently from EPR. Results: Ever/never status for smoking showed almost perfect agreement (k=0.95) between PRQ and EPR and surpassed all other health behavioural measures and co-morbidity agreement values. Both the sensitivity and specificity were high (0.94 and 0.99 respectively). The calculation of pack-years from EPR and PRQ showed substantial agreement (k=0.77); However, categorizing the smoking status into current/ former / never, resulted in moderate agreement (k=0.46). Alcohol ever/ never status agreement was moderate (0.43) with high sensitivity (0.90) but low specificity (0.50). Agreement for co-morbidities varied by condition showing moderate to substantial agreement for hypertension (K=0.57), heart attack (K=0.80) and diabetes (K=0.76) while fair to slight agreement (K&lt;0.4) was seen in the others. Specificity was 0.86 or higher for co-morbidity conditions and was consistently higher than the sensitivity. Conclusions: EPR may be used as a reliable surrogate to PRQ in determining ever/never smoking status and lifetime smoking exposure. Evaluation of current/former/never smoking status and alcohol consumption is best determined by PRQ. Diabetes, hypertension and heart attack are more accurately reported in the PRQ than other co-morbidities. Patients tend to report absence of a medical condition more accurately than the presence of it. Missing EPR data related to smoking pack years, alcohol consumption and lung co-morbidities is concerning and suggests more synoptic reporting by physicians would improve opportunities for research.
Prediction Models of Mortality in Acute Pancreatitis in Adults
Authors: Meng-Yang Di, Hao Liu, Zu-Yao Yang, Peter A.L. Bonis, Jin-Ling Tang, Joseph Lau
Journal: Annals of Internal Medicine (2016)

Acute pancreatitis (AP) varies in severity, prompting development of systems aimed at predicting prognosis to help guide therapy. Although several prediction approaches are available, their test characteristics and clinical utility are not completely understood.To evaluate the test characteristics (prognostic accuracy, incremental predictive value) and clinical utility (effect on patient outcomes) of severity scores for predicting mortality in AP.Ovid MEDLINE and EMBASE (inception to 3 May 2016).Longitudinal studies, in any language, that evaluated the prognostic value of at least 1 clinical severity score in AP.Dual data extraction and quality assessment.Of 4039 citations screened, 94 unique studies evaluating 18 scores in 53 547 patients met the inclusion criteria. All studies provided data on prognostic accuracy, whereas 6 provided data on incremental predictive values. Most scores demonstrated low prognostic accuracy. The Acute Physiology and Chronic Health Evaluation (APACHE) II score and the Ranson criteria were studied most extensively. The median sensitivity and specificity of APACHE II at a threshold of 7 were 100% (range, 68% to 100%) and 63% (range, 21% to 96%), respectively, and those of the Ranson criteria at a threshold of 2 were 90% (range, 0% to 100%) and 67% (range, 14% to 97%), respectively. Estimates of sensitivity were based on relatively few patients. Evidence was limited regarding the incremental predictive value of the scoring systems or their effect on patient outcomes.Substantial clinical heterogeneity and inadequate methodological and reporting quality precluded a meta-analysis.The test characteristics and clinical utility of AP severity scores remain uncertain. Additional studies with improved methodological rigor are needed, and the development of new scoring systems may be justified.Global Scholarship Programme for Research Excellence for 2014 to 2015, The Chinese University of Hong Kong.
Abstract 1293: JQ1 sensitivity of patient-derived xenograft models of cholangiocarcinoma
Authors: Aubrey L. Miller, Patrick L. Garcia, Tracy L. Gamblin, Leona N. Council, Xiangqin Cui, James E. Bradner, Eddy S. Yang, Karina J. Yoon
Journal: Cancer Research (2016)

Abstract Cholangiocarcinoma (CCA) is a lethal malignancy arising from cholangiocytes in any part of the biliary tree. The incidence of CCA has been on the rise worldwide, and the prognosis and clinical outcome have remained essentially unchanged for 30 years. The majority of patients are diagnosed at late stage, and surgery continues to be the only cure. Patients receive systemic chemotherapy with the first-line combination therapy comprising gemcitabine and cisplatin. Median survival for these patients is &amp;lt;12 months, emphasizing the need to improve current treatment. A step toward improving outcome is the pre-clinical evaluation of novel therapeutics. Recently the bromodomain and extra-terminal domain (BET) inhibitor JQ1 has been shown to suppress tumor growth in preclinical models of multiple tumor types. The therapeutic effect of JQ1 has been attributed, at least in part, to its ability to inhibit c-Myc expression. 95% of CCA tumors express c-Myc and its down-regulation has been shown to reduce the invasive potential of CCA cells, suggesting that c-Myc contributes to CCA phenotype. Our lab recently evaluated the efficacy of the BET inhibitor JQ1 in CCA patient-derived xenograft mouse models. JQ1 suppressed CCA tumor growth in 2 of the 3 models. To determine gene products whose upregulation or downregulation is responsible for the differences in sensitivity to JQ1 among our CCA models, we generated expression profiles of tumors from vehicle control and JQ1 treated mice using NanoString technology (nCounter PanCancer Pathways panel). Our data demonstrate that JQ1 inhibited the expression of c-Myc to a greater extent in the sensitive models than in the insensitive model. Expression array data showed further that gene products involved in cell cycle and DNA repair pathways were also decreased by JQ1. Of particular interest were two transcriptional targets of c-Myc, Chk1 and BRCA2, each of which is involved in DNA damage response. Immunohistochemistry staining confirmed expression profile analyses. We conclude that the inhibition of cell cycle and DNA repair genes may contribute to the mechanism of action of JQ1 in CCA tumors. Citation Format: Aubrey L. Miller, Patrick L. Garcia, Tracy L. Gamblin, Leona N. Council, Xiangqin Cui, James E. Bradner, Eddy S. Yang, Karina J. Yoon. JQ1 sensitivity of patient-derived xenograft models of cholangiocarcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1293.