tbuckley/cabot-search huggingface dataset:
Abstract 1092: Interpreting and navigating the TCGA in the context of the RAS pathway
Authors: Ming Yi, Bailey Kessing, Robert Stephens
Journal: Cancer Research (2015)

Abstract Analysis of large cancer data sets such as “The Cancer Genome Atlas (TCGA)” and the “International Cancer Genome Consortium (ICGC) “ has demonstrated the involvement of members of the RAS signaling pathway across many different tumor types. In particular, KRAS mutations occur at high frequency in lung, colorectal and particularly pancreatic tumors. Here, we report an analysis of TCGA data examining several aspects of KRAS and RAS pathway biology in the context several of the different data types collected through TCGA. The findings include: • A survey of the expression of the KRAS alternatively spliced isoforms across all of the available tumor types • Enrichment analysis from differentially expressed genes from high and low expressing samples for the 4A isoform (or the 4A/4B ratio) • Survival analysis for RAS pathway genes in the context of mutational and expression level status • Analysis of mutations in genes from the RAS pathway across samples and tumor types Together, these findings demonstrate that large data sets like TCGA can be used to reveal novel insights into the function of key genes that play a role in the development, maintenance and progression of cancer. Citation Format: Ming Yi, Bailey Kessing, Robert Stephens. Interpreting and navigating the TCGA in the context of the RAS pathway. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1092. doi:10.1158/1538-7445.AM2015-1092
Abstract 4774: Histone H2AX is a novel regulator of epithelial to mesenchymal transition
Authors: SOSSOU U. WEYEMI, Christophe E. Redon, Rohini Choudhuri, Daisuke Maeda, Manjula Kasoji, Natalie Abrams, William M. Bonner
Journal: Cancer Research (2015)

Abstract The vast majority of deaths from cancer are due to its progression from primary tumor to metastatic disease. Understanding how some cells can migrate from the primary tumor to seed new tumors throughout the body is a longstanding challenge in developing novel cancer treatments. Current models propose that these migratory cells acquire an invasive phenotype through a process known as the epithelial to mesenchymal transition (EMT), characterized by the loss of cell polarity and cell-to-cell adhesion, and the acquisition of migratory and invasive properties. Such changes allow the cells to invade the extracellular matrix and migrate throughout the body, aided by the formation of lamellipodia, filopodia and invadopodia. In a converse transition, the MET, mesenchymal cells may revert back to the epithelial phenotype and establish tumors at distant sites.We have preliminary observations showing that when one member of the H2A family of histones, H2AX, is silenced or inactivated in HCT116 cells, these cells exhibit mesenchymal-like characteristics including increased invasiveness. Furthermore, genome-wide expression analysis implicates the critical EMT transcription factors, SLUG and ZEB1, as mediators of H2AX loss-induced EMT. To make these studies more rigorous, we generated a novel HCT116 cell line with H2AX destroyed. Our findings show that ectopic expression of H2AX in H2AX-null cells reverses the invasiveness induced by H2AX inactivation. Moreover, in 233 human colon cancer samples, a strong correlation is found between the levels of H2AX and SLUG/ZEB1 expression. These observations lead us to hypothesize that H2AX is a key regulator of EMT and plays a critical role in the downstream events leading to increased metastasis. Note: This abstract was not presented at the meeting. Citation Format: SOSSOU U. WEYEMI, Christophe E. Redon, Rohini Choudhuri, Daisuke Maeda, Manjula Kasoji, Natalie Abrams, William M. Bonner. Histone H2AX is a novel regulator of epithelial to mesenchymal transition. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4774. doi:10.1158/1538-7445.AM2015-4774
Novel and Clinically Significant Factors Influencing the Pharmacokinetic Variability of Recombinant Factor VIII (Kogenate-FS) in Children.
Authors: Chris Barnes, David Lillicrap, Victor Blanchette, Ann Marie Stain, Janneth Pazmino-Canizares, Dewi Clark, Caroline Hensmen, Manuel Carcao
Journal: Blood (2004)
Association Between Benign Breast Disease in African American and White American Women and Subsequent Triple-Negative Breast Cancer
Authors: Lisa A. Newman, Azadeh Stark, Dhanajay Chitale, Margaret Pepe, Gary Longton, Maria J. Worsham, S. David Nathanson, Patricia Miller, Jessica M. Bensenhaver, Erica Proctor, Monique Swain, Christos Patriotis, Paul F. Engstrom
Journal: JAMA Oncology (2016)

<h3>Importance</h3> Compared with white American (WA) women, African American (AA) women have a 2-fold higher incidence of breast cancers that are negative for estrogen receptor, progesterone receptor, and<i>ERBB2</i>(triple-negative breast cancer [TNBC]). Triple-negative breast cancer, compared with non-TNBC, likely arises from different pathogenetic pathways, and benign breast disease (BBD) predicts future non-TNBC. <h3>Objective</h3> To determine whether AA identity remains associated with TNBC for women with a prior diagnosis of BBD. <h3>Design, Setting, and Participants</h3> This study is a retrospective analysis of data of a cohort of 2588 AA and 3566 WA women aged between 40 and 70 years with a biopsy-proven BBD diagnosis. The data—obtained from the Pathology Information System of Henry Ford Health System (HFHS), an integrated multihospital and multispecialty health care system headquartered in Detroit, Michigan—include specimens of biopsies performed between January 1, 1994, and December 31, 2005. Data analysis was performed from November 1, 2015, to June 15, 2016. <h3>Main Outcomes and Measures</h3> Subsequent breast cancer was stratified on the basis of combinations of hormone receptor and<i>ERBB2</i>expression. <h3>Results</h3> Case management, follow-up, and outcomes received or obtained by our cohort of 2588 AA and 3566 WA patients were similar, demonstrating that HFHS delivered care equitably. Subsequent breast cancers developed in 103 (4.1%) of AA patients (mean follow-up interval of 6.8 years) and 143 (4.0%) of WA patients (mean follow-up interval of 6.1 years). More than three-quarters of subsequent breast cancers in each subset were ductal carcinoma in situ or stage I. The 10-year probability estimate for developing TNBC was 0.56% (95% CI, 0.32%-1.0%) for AA patients and 0.25% (95% CI, 0.12%-0.53%) for WA patients. Among the 66 AA patients who developed subsequent invasive breast cancer, 16 (24.2%) developed TNBC compared with 7 (7.4%) of the 94 WA patients who developed subsequent invasive breast cancers and had complete biomarker data (<i>P</i> = .01). <h3>Conclusions and Relevance</h3> This study is the largest analysis to date of TNBC in the context of racial/ethnic identity and BBD as risk factors. The study found that AA identity persisted as a significant risk factor for TNBC. This finding suggests that AA identity is associated with inherent susceptibility for TNBC pathogenetic pathways.
Abstract 522: Involvement of Zyxin in aggressiveness of human prostate cancer
Authors: Kei Yamamoto, Yasuki Hori, Jieun Seo, Saho Hashimoto, Yoshihiro Endo, Tadashi Nittami, Yusuke Ito, Hitoshi Ishiguro, Hiroji Uemura, Masatoshi Watanabe
Journal: Cancer Research (2015)

Abstract Many epidemiological studies have shown that abdominal obesity was associated with an increased risk in several malignancies. The association between prostate cancer risk and obesity has been also investigated, but has been in dispute. The involvement of adipocytokines as putative molecular mediators between prostate cancer and obesity has been also investigated. We have already shown effects of conditioned medium (CM) from adipocyte culture in behaviors of prostate cancer cells (DU145). In this study, Phospho-peptide in DU145 cells cultured in CM was analyzed using Liquid chromatography-tandem mass spectrometry (LC-MS/MS). Zyxin was identified as a CM-related phosphor-peptide. Zyxin is a conserved protein that has two major domains, an N-terminal half containing proline-rich sequences and a C-terminal LIM domain region. Its functions are involved in regulation of cell adhesion and motility. This protein also appears to have tumor suppressor activity with a few reports, however in dispute. We analyzed the involvement of Zyxin in behavior of DU145 cells. Functional analysis of Zyxin in cell migration, invasive potential and others of DU145 cells was conducted using Zyxin siRNA. Knockdown of Zyxin by siRNA in DU145 cells inhibited cell migration and invasion. As for clinical paired samples, Zyxin expression in tumor tissues was higher than in normal tissues by real-time PCR. These results suggest that Zyxin may play an important role in aggressiveness of human prostate cancer. Citation Format: Kei Yamamoto, Yasuki Hori, Jieun Seo, Saho Hashimoto, Yoshihiro Endo, Tadashi Nittami, Yusuke Ito, Hitoshi Ishiguro, Hiroji Uemura, Masatoshi Watanabe. Involvement of Zyxin in aggressiveness of human prostate cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 522. doi:10.1158/1538-7445.AM2015-522
Abstract 5445: Dual-color immunohistochemistry assays for measuring Aiolos and Ikaros proteins in multiple myeloma patient samples
Authors: Yan Ren, Maria Wang, Suzana Couto, Donna Hansel, Anita K. Gandhi, Patrick Hagner, Anjan Thakurta, Rajesh Chopra, Mike Breider
Journal: Cancer Research (2015)

Abstract IMiDs® immunomodulatory drugs Lenalidomide (LEN) and Pomalidomide (POM) are antineoplastic agents that have a significant clinical impact in the treatment of patients with multiple myeloma (MM). Recent studies indicate that the anti-proliferative activity of LEN and POM in MM cells is associated with ubiquitination and degradation of the Ikaros family zinc finger protein transcription factors, Aiolos (IKZF3) and Ikaros (IKZF1), the substrates of the Cereblon (CRBN)-dependent Cullin 4 E3-ligase complex. Measurement of Aiolos and Ikaros protein levels in MM patient samples is critical for future correlative studies. Here we describe the development and validation of dual IHC Aiolos/CD138 and Ikaros/CD138 assays using the highly specific Aiolos rabbit monoclonal antibody CGN-9-9-7, and a commercial Ikaros rabbit polyclonal antibody H-100 in combination with a commercial CD138 antibody. Aiolos and Ikaros immunoreactivity in CD138+ MM cells is scored using the semi-quantitative H-score method. H-scores range from 0 to 300 and are the sum of the products of the percentage of tumor cells (0-100%) and the intensity of staining (0-3). The assays were specific and detected high Aiolos and Ikaros expression in the positive control OCI-Ly10 lymphoma cell line, and low Aiolos and Ikaros levels in POM treated OCI-Ly10 cells. These results were confirmed via Western Blot analysis of Aiolos and Ikaros expression data in these cells lines. Assay precision was examined via staining serial sections of the same MM tumor across three different days and deemed acceptable. The dual IHC assays were used to evaluate bone marrow core biopsies or aspirate clots from 22 MM patients and H-scores were determined by a board-certified pathologist. The dual IHC assays detected a wide range of Aiolos or Ikaros immunoreactivity in the 22 MM cases, with nuclear H-scores ranging from 10 to 260 for Aiolos and 40 to 240 for Ikaros. In conclusion, the dual Aiolos/CD138 and Ikaros/CD138 IHC assays were developed to provide a specific and reliable semi-quantitative method to evaluate Aiolos and Ikaros protein levels in both bone marrow core biopsies and clots from MM patients. These assays are currently being used in clinical trials to assess the importance of Aiolos and Ikaros as biomarkers in MM patients treated with IMiDs® immunomodulatory drugs. Citation Format: Yan Ren, Maria Wang, Suzana Couto, Donna Hansel, Anita K. Gandhi, Patrick Hagner, Anjan Thakurta, Rajesh Chopra, Mike Breider. Dual-color immunohistochemistry assays for measuring Aiolos and Ikaros proteins in multiple myeloma patient samples. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5445. doi:10.1158/1538-7445.AM2015-5445
Genetic and Pharmacological Inhibition of TREM-1 Limits the Development of Experimental Atherosclerosis
Authors: Jeremie Joffre, Stephane Potteaux, Lynda Zeboudj, Xavier Loyer, Amir Boufenzer, Ludivine Laurans, Bruno Esposito, Marie Vandestienne, Saskia C.A. de Jager, Carole Hénique, Ivana Zlatanova, Soraya Taleb, Patrick Bruneval, Alain Tedgui, Ziad Mallat, Sebastien Gibot, Hafid Ait-Oufella
Journal: Journal of the American College of Cardiology (2016)
Recent H3N2 Viruses Have Evolved Specificity for Extended, Branched Human-type Receptors, Conferring Potential for Increased Avidity
Authors: Wenjie Peng, Robert P. de Vries, Oliver C. Grant, Andrew J. Thompson, Ryan McBride, Buyankhishig Tsogtbaatar, Peter S. Lee, Nahid Razi, Ian A. Wilson, Robert J. Woods, James C. Paulson
Journal: Cell Host & Microbe (2016)
Posterior reversible encephalopathy syndrome in patients with cancer.
Authors: A. M. Paker, L. Chi, M. C. Ruiz, M. E. Loghin
Journal: Journal of Clinical Oncology (2011)

2561 Background: The posterior reversible encephalopathy syndrome (PRES) is a clinical-radiologic entity characterized by headache (HA), altered mental function (AMS), seizures and visual loss in association with imaging findings. Here we present the largest retrospective review of clinical manifestations, radiologic features and clinical outcome of PRES in patients with cancer. Methods: This retrospective chart-review study identified 29 patients with cancer who developed PRES during their cancer treatment at M.D. Anderson Cancer Center between 01/2006 and 01/2008. Clinical and radiographic data were abstracted from their records. Results: The average age at the time of PRES onset was 56 (range: 5.8-81 years). Primary diagnoses were leukemia (n=11), melanoma (n=3), lymphoma (n=4), central nervous system tumors (n=4), chondrosarcoma (n=1), multiple myeloma (n=1), prostate (n=1), laryngeal cancer (n=1), gastro-intestinal tumor (n=3) and uterine cancer (n=1). Twenty-two patients (76%) were receiving cancer treatment with chemotherapy and immunosuppressive agents, and 10 patients (34%) received bone marrow transplant. Clinical presentation included seizures n=25 (86%), HA n=14 (48%), AMS n=19 (66%) and vision disturbances n=7 (24%). PRES was associated with hypertension (HTN) in 25 patients (86%). The brain MRI demonstrated T2 signal abnormalities in all patients, restriction diffusion in 3 and hemorrhage in 2. Clinical symptoms fully resolved in 17 patients (65%). Seven patients (24%) remained symptomatic with AMS, headache or visual changes, 4 (13%) patients developed. Conclusions: PRES is an increasingly recognized complication of cancer therapy. HTN seems to be the most important trigger for the occurrence of PRES in patients receiving cancer treatment. Incomplete resolution of symptoms, associated cerebral ischemia or hemorrhage with permanent neurological disability highlights the potential grave consequences of this disorder in cancer patients
Low immunogenicity of tocilizumab in patients with rheumatoid arthritis
Authors: Gerd R Burmester, Ernest Choy, Alan Kivitz, Atsushi Ogata, Min Bao, Akira Nomura, Stuart Lacey, Jinglan Pei, William Reiss, Attila Pethoe-Schramm, Navita L Mallalieu, Thomas Wallace, Margaret Michalska, Herbert Birnboeck, Kay Stubenrauch, Mark C Genovese
Journal: Annals of the Rheumatic Diseases (2016)

Objective Subcutaneous (SC) and intravenous formulations of tocilizumab (TCZ) are available for the treatment of patients with rheumatoid arthritis (RA), based on the efficacy and safety observed in clinical trials. Anti-TCZ antibody development and its impact on safety and efficacy were evaluated in adult patients with RA treated with intravenous TCZ (TCZ-IV) or TCZ-SC as monotherapy or in combination with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). Methods Data from 5 TCZ-SC and 8 TCZ-IV phase III clinical trials and 1 TCZ-IV clinical pharmacology safety study (&gt;50 000 samples) were pooled to assess the immunogenicity profile of TCZ-SC and TCZ-IV (8974 total patients). The analysis included antidrug antibody (ADA) measurement following TCZ-SC or TCZ-IV treatment as monotherapy or in combination with csDMARDs, after dosing interruptions or in TCZ-washout samples, and the correlation of ADAs with clinical response, adverse events or pharmacokinetics (PK). Results The proportion of patients who developed ADAs following TCZ-SC or TCZ-IV treatment was 1.5% and 1.2%, respectively. ADA development was also comparable between patients who received TCZ monotherapy and those who received concomitant csDMARDs (0.7–2.0%). ADA development did not correlate with PK or safety events, including anaphylaxis, hypersensitivity or injection-site reactions, and no patients who developed ADAs had loss of efficacy. Conclusions The immunogenicity risk of TCZ-SC and TCZ-IV treatment was low, either as monotherapy or in combination with csDMARDs. Anti-TCZ antibodies developed among the small proportion of patients had no evident impact on PK, efficacy or safety.
368. Advances in Fragile X Gene Therapy Using Adeno-Associated Viral Vectors Coding for the Fragile X Mental Retardation Protein
Authors: Jason Arsenault, Yosuke Niibori, David R. Hampson, Shervin Gholizadeh
Journal: Molecular Therapy (2016)

Fragile X syndrome (FXS) is a severe debilitating neurodevelopmental disorder characterized by a loss of proper translational control at the synapse. In FXS, an aberrant CGG trinucleotide expansion upstream of the Fragile X Mental Retardation Protein (FMRP) gene causes drastic downregulation of this translational modulator. The absence of FMRP impairs synaptic plasticity and leads to mental retardation and autistic spectrum-related phenotypes. To correct this neurological disorder we recently devised an adeno-associated viral (AAV) vector encoding FMRP where its cellular tropism was controlled by the neuron-specific synapsin promoter. Following intracerebroventricular (i.c.v.) injection in neonatal Fmr1 KO mice, transgene expression remained stable for over 7 months in terminally differentiated neurons. The FMRP transgene corrected PSD-95 protein hypo-expression in the cortex of Fmr1 KO animals, as well as lowered MeCP2 protein over-expression. Behavioral endophenotypes including hyperactivity, non-social anxiety, pre-pulse inhibition, repetitive stereotypies, and social dominance were fully or partially corrected using this viral construct. We combined i.c.v. injection with additional injections into the parenchyma of refractory brain regions to achieve wider transduction, while avoiding potentially pathological transgene over expression effects. This ongoing translational study enables us to determine the proper cellular tropism and the range of FMRP expression required for rescue, as well as the brain region dependent correlation of autistic behaviors implicated in FXS neuropathology. These findings are relevant to gene therapy strategies for treating human FXS, as well as other neurodevelopmental disorders.
PWE-072 Increasing incidence of Barrett's oesophagus is not entirely explained by endoscopic practice: Abstract PWE-072
Authors: H G Mulholland, S Bhat, L J Murray, D McManus, A T Gavin, B T Johnston
Journal: Gut (2010)

<h3>Introduction</h3> Oesophageal adenocarcinoma (OAC) incidence rates have increased dramatically in recent decades, particularly among white males in Western societies.1 There appears to be a concurrent rise in Barrett9s oesophagus (BO) incidence, the pre-cursor condition for OAC, although it is debated whether this is a true rise, or a reflection of changes in endoscopy practices together with improvement in disease recognition.2 The aim of our investigation was to assess BO incidence over a 13-year period using a population-based register in Northern Ireland. <h3>Methods</h3> The Northern Ireland Barrett9s oesophagus Register (NIBR) is a population-based register of all adults diagnosed with BO, defined as columnar epithelium of the oesophagus, in Northern Ireland between 1993 and 2005. Data on all upper gastro-intestinal endoscopies and oesophageal biopsies performed in Northern Ireland were obtained from healthcare providers. Annual BO incidence rates were calculated per 100 000 of the population, per 100 endoscopies and per 100 oesophageal biopsies performed. <h3>Results</h3> During the 13-year period, 197 635 patients underwent an endoscopy and 9390 of these were diagnosed with BO, of whom 58% were male. Average annual BO incidence rates over this time period are presented in Abstract 072. A 2.5-fold increase in BO incidence in the population was observed. Over the same time, there were 1.3 and 1.6-fold increases in endoscopy and biopsy rates in the population, respectively. Even with the increasing rates of endoscopy and biopsy, BO was still diagnosed more frequently per 100 endoscopies and per 100 biopsies. <h3>Conclusion</h3> These findings demonstrate that BO incidence rates in Northern Ireland have increased more rapidly than the rate of endoscopies or biopsies. This could indicate that a true rise in BO incidence has occurred, contributing to the increase in OAC seen in Western populations. This may have implications for efforts to prevent OAC.
Post-Transfusion Fevers and Post-Reaction Culture Practices at a Large Academic Hospital Transfusion Service: Quality of Information and Calculated Bacterial Contamination Event Rates
Authors: Christine M. Cserti-Gazdewich, Jacob M Pendergrast, Yulia Lin, Jeannie Callum, Lani D. Lieberman, Alioska Escorcia, Sandra Ramirez-Arcos
Journal: Blood (2015)
New perspectives of biomarkers for the management of chronic hepatitis B
Authors: Chih-Lin Lin, Jia-Horng Kao
Journal: Clinical and Molecular Hepatology (2016)

With recent advances in molecular and genomic investigations, the impact of hepatitis B viral and host factors on the progression of chronic HBV infection has been explored. For viral factors, hepatitis B viral load is a strong predictor for liver disease progression. Hepatitis B viral kinetics appear to be important for successful anti-viral therapy. Serum HBsAg level serves as a complementary marker to viral load for the prediction of HBV-related adverse outcomes in patients with low viral load. In those with low viral load, high serum HBsAg level is associated with higher risks of cirrhosis and HCC. Hepatitis B core-related antigen (HBcrAg) induces host immune responses, and the reduction of the HBcrAg level as well as the increment of total anti-HBc level are significantly associated with favorable outcomes. HBV genotypes (genotype C/D) and mutants (basal core promoter and deletion mutation in pre-S genes) are well known viral genetic markers to predict disease progression. For host factors, serum inflammatory biomarkers have been developed to evaluate the HBV-associated hepatic necroinflammation and fibrosis. Host single nucleotide polymorphism on sodium taurocholate cotransporting polypeptide (NTCP, an HBV entry receptor) may be associated with a decreased risk for cirrhosis and HCC. In conclusion, patients with chronic hepatitis B should be evaluated with relevant viral and host markers to identify those who are at a higher risk of liver disease progression and then receive timely antiviral therapy. Keywords: Chronic hepatitis B; HBV DNA; HBsAg; HBcrAg; Total anti-HBc