tbuckley/cabot-search huggingface dataset:
AB1130 Real World Data on Patient Understanding and Preference in Their Biologic Treatment for Inflammatory Autoimmune Disease - A Qualitative Anonymous Patient Survey
Authors: E.C. Keystone, D. Weber, E. Mitroi, J. Cottrell, L. Segal, H. Reuter, M. Weber, P. Mitroi
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objectives</h3> To collect relevant data using an anonymous survey to assess patient knowledge of disease and preferences for biologic treatment. <h3>Methods</h3> An anonymous patient survey was conducted simultaneously in two busy autoimmune disease centers, Mount Sinai Hospital, Toronto, Canada (MSH) and Winelands Rheumatology Centre, Stellenbosch, Cape Town Area, South Africa (WRC). All patients were approached to participate in an anonymous survey to elicit honest responses to frequently asked questions posed by health care professionals. The survey was developed by nursing staff with a focus on improving their delivery of service and education for optimal patient care. Over a 4 month period, 227 patients completed the survey (175 MSH/52 WRC). The population included patients with Rheumatoid Arthritis, Psoriatic Arthritis, Psoriasis, Vasculitis, Ankylosing Spondylitis, Crohn9s Disease, Ulcerative Colitis, and Pemphigus Vulgaris. Surveys were given to those interested in participating on their arrival to the clinic. Patients completed them during their visit to the rheumatology department which included private physician office or biologic treatment clinics. They were able to return them to a central, secured, unmarked box. Informed consent was not required as this was an anonymous qualitative survey to improve patient care and therefore, no identifying information was collected. <h3>Results</h3> Patient preference (36% MSH/26% WRC) for location of treatment was to be closer to home. In order to better understand diagnosis and treatment options, 46% of patients at MSH wanted more time with health care provider (HCP) and 40% at WRC wanted more on line resources. In WRC, 52% of patients compared to 30% at MSH knew biologics were genetically engineered. The majority of patients in both centers (38 MSH, 65 WRC) felt that their physician and clinic personnel could assist best with obtaining biologics. Between MSH and WRC there was no significant difference (60% versus 59%) between patient preference for intravenous (IV) vs subcutaneous (SC) delivery of treatment. 35% (MSH) and 47% (WRC) used the assistance of their HCP to decide between available IV and SC biologic treatment. <h3>Conclusions</h3> We should provide more opportunity to engage patients in discussion of their disease and treatment options. As HCPs play an important role, MSH needs an enhanced education program to satisfy patient needs. Patients rely directly on their health care team to assist in navigating and obtaining biologics. Patients did not have a preference for IV or SC treatment. Treatment itself was the most important factor, not the delivery system. <h3>References</h3> patient written surveys. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4371
IMPACT OF MITRAL REGURGITATION ON 2-YEAR CLINICAL OUTCOMES IN PATIENTS WITH ACUTE MYOCARDIAL INFARCTION: PROPENSITY SCORE MATCHED ANALYSIS
Authors: Seung-Woon Rha, Sang-Ho Park, Ung Jeon, Byoung Geol Choi, Se Yeon Choi, Jae Kyeong Byun, Min Shim, Dong Joo Oh, Myung Ho Jeong
Journal: Journal of the American College of Cardiology (2016)
Abstract 3479: SMAC mimetic (JP1201) sensitizes non small cell lung cancers (NSCLCs) to multiple chemotherapy agents and erlotinib in an IAP dependent but TNFα independent manner
Authors: Rachel M. Greer, Michael Peyton, Luc Girard, Yang Xie, Adi F. Gazdar, Patrick Harran, Lai Wang, Rolf A. Brekken, Xiaodong Wang, John D. Minna
Journal: Cancer Research (2010)

Abstract Tumor cells have acquired resistance to apoptotic stimuli, which is thought to contribute to chemotherapy resistance. Therefore strategies to re-engage apoptotic cascades have strong therapeutic potential. One family of proteins that is key in deregulating apoptosis are the Inhibitors of Apoptosis Proteins (IAPs), which function by binding to and inhibiting caspases, and are in turn inhibited by second mitochondrial activator of caspases (SMAC). One strategy to re-sensitize tumor cells to apoptosis is to create small molecule mimetics of SMAC, such as JP1201 (Joyant Pharmaceuticals). Initial tests of JP1201 in lung cancer identified ∼15% of NSCLCs that were sensitive to low concentrations of JP1201 as a single agent. In all cases sensitive NSCLCs expressed TNFα which was required for single agent drug sensitivity (Peterson et al., 2007). To extend these findings to the large majority of NSCLCs and prepare for clinical trials, we tested 15 NSCLC lines that are resistant to single agent JP1201 (IC50 ≥ 100 µM) in combination with cisplatin, doxorubicin, gemcitabine, erlotinib, paclitaxel, and vinorelbine in a 5 day MTS based microtiter assay. We find great heterogeneity among NSCLCs in tumor cell response phenotypes to combined JP1201 + chemotherapy agents and that for each NSCLC at least one chemotherapy was sensitized by JP1201 100 to 10,000 fold (significant combination indices). Of note we found no NSCLC where cisplatin was sensitized by JP1201. Surprisingly, we also found examples of antagonism when JP1201 is added. Using siRNAs targeted to cIAP1, cIAP2, and XIAP we found that for gemcitabine, XIAP is the key IAP whose inhibition by JP1201 leads to sensitization, while for paclitaxel and vinorelbine, knockdown of any of the three IAPs sensitizes NSCLCs. None of the treatments induce secretion of TNFα or TRAIL (detected by ELISA) in this panel of NSCLCs. NOD/SCID mice bearing NSCLC NCI-H1395 xenografts were randomized (8 mice per group) to 3 weeks of treatment with saline, 25 mg/kg gemcitabine, 2.4 mg/kg vinorelbine, 6 mg/kg JP1201, gemcitabine + JP1201, and vinorelbine + JP1201. Tumor burden was reduced 60% in mice treated with gemcitabine + JP1201 compared to gemcitabine alone, and 70% in mice treated with vinorelbine + JP1201 compared to vinorelbine alone. We conclude that preclinical studies show the combination of JP1201 with chemotherapy is a valid therapeutic strategy for NSCLC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3479.
Abstract 1604: Development of breast cancer patient-derived xenograft models as preclinical tool for drug discovery
Authors: Isha C. Rymer, Jinwei Wang, Zhou Zhu, Richard Schwab, Anne M. Wallace, Sarah L. Blair, Norman Greenberg, Wei J. Yang
Journal: Cancer Research (2011)

Abstract Based on gene expression profile and hormone receptor status breast cancer is usually classified into the following subtypes, luminal A, luminal B, Her2 overexpressed, basal, normal-like, and the newly identified subtype, claudin-low. For a long time sub-cutaneous and orthotopic xenograft of established human cancer cell lines have served as the primary in vivo models for drug evaluation preclinically, however their prognostic value to clinical trials has not been to our satisfaction. In an effort to overcome the limitations of traditionally used cell line models and to develop preclinical models that better represent the diversity of human breast cancer, we generated a series of human -in-mouse orthotopic xenograft models using primary tumor specimens from patients. These models are characterized in depth, including tumor histology, genomics, gene expression profiles, and chemosensitivities to standard of care compounds. They will serve as great tools to breast cancer research and discovery. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1604. doi:10.1158/1538-7445.AM2011-1604
Comparative Chromosomal Study of 31 Cultured Mammalian Cell Lines&lt;xref ref-type="fn" rid="fn1"&gt;2&lt;/xref&gt;
Authors: J. J. Clausen, J. T. Syverton
Journal: JNCI Journal of the National Cancer Institute (1962)

Karyotypes of 15 mammalian cell lines, altered in morphology, growth characteristics, or viral susceptibility while carried in tissue culture, were studied. A comparison was made between the karyotypes of these altered cell lines and the karyotypes of unaltered cell lines from their species of origin. The altered lines supposedly derived from man, monkey, cow, pig, or rabbit tissue; the unaltered lines from man, cow, pig, rabbit, and mouse tissue. Chromosome preparations were made from colchicine-treated cell cultures by osmotic expansion and the aceto-orcein squash technique. Chromosomes were counted and classified by their relative size and centromere position, which was determined by measurement. Relative length and arm-index criteria yielded 6 categories for comparison of karyotypes. Examination of primary tissue cultures for the study of normal karyotypes showed the 2n chromosome complement as 42 for the cynomolgus monkey, 44 for the laboratory rabbit, and 38 for the domestic pig. Marker chromosomes of the cynomolgus monkey and the pig exhibited secondary constrictions. Comparison with these normal karyotypes and others reported in the literature showed that mammalian cell lines considered unaltered in gross characteristics were similar in chromosome morphology to cells of the species of origin. It was found that the altered cell lines, regardless of their supposed species of origin, on the basis of their karyotypes actually derived from only 2 species; 5 lines apparently originated from mouse cells, and 10 from human cells.
Abstract P2-10-15: Evaluation of Prognostic and Predictive Performance of Breast Cancer Index and Its Components in Hormonal Receptor-Positive Breast Cancer Patients: A TransATAC Study
Authors: DC Sgroi, I Sestak, Y Zhang, MG Erlander, CA Schnabel, PE Goss, J Cuzick, M Dowsett
Journal: Cancer Research (2012)

Abstract Background: The Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial compared the efficacy and safety of 5 years of anastrozole with tamoxifen as adjuvant treatment for postmenopausal women with localized HR+ breast cancer. At a median follow-up of 10 years, a statistically significant improvement with anastrozole vs. tamoxifen for disease-free survival, time to recurrence and time to distant recurrence was observed. The HOXB13:IL17BR gene expression ratio (H/I) quantifies recurrence risk in ER positive (ER+) breast cancer patients and is predictive of benefit from endocrine therapy. Molecular Grade Index (MGI) is a five-gene index that provides quantitative and objective molecular assessment of tumor grade and proliferative status. Breast Cancer Index (BCI) combines H/I and MGI into a continuous risk model that provides a likelihood of distant recurrence in patients treated with endocrine therapy, and efficacy from neoadjuvant chemotherapy. In the current analysis, evaluation of the prognostic and predictive performance of BCI, H/I and MGI in the ATAC study cohort was conducted. Methods: Under the TransATAC protocol, formalin-fixed, paraffin-embedded (FFPE) blocks of primary tumor were collected from HR+ patients from each monotherapy arm. The current study examined samples collected from the United Kingdom, which constituted 79% of the collection. RNA extracted from 1102 samples from the TransATAC study was amplified, converted to cDNA and subjected to RT-PCR with primers and probes to HOXB13, IL17BR, BUB1A, CENPA, NEK2, RACGAP1 and RRM2. H/I, MGI and BCI were calculated and risk groups were determined using pre-specified cutpoints. Results: Of 1102 tumor specimens assayed, 29 failed QC criteria, leaving 1073 samples for analysis. Detailed results on the prognostic and predictive performance of BCI, H/I and MGI will be presented. Data on whether BCI and its components provided independent prognostic information in the presence of classical variables, their prognostic value for risk of late recurrence, interaction by treatment arms, and comparative performance vs other models will also be discussed. Discussion: The ATAC trial has established the long-term efficacy and safety of anastrozole over tamoxifen as initial adjuvant treatment for post-menopausal early stage breast cancer patients. Continued efforts are needed to improve on quantification of residual risk in patients who were treated with endocrine therapy to guide decision-making in selecting additional adjuvant chemotherapy and/or administering extended endocrine treatment. This study will help to establish the strategy to more effectively select patients for adjuvant therapies. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-10-15.
Abstract 325: Mutation analysis of PIK3CA, KRAS, BRAF and Corresponding EGFR status in head and neck squamous cell carcinoma
Authors: Toshihito Suda, Takanori Hama, Susumu Okano, Youichi Seino, Yuki Yuza, Takakuni Kato, Hiroshi Moriyama
Journal: Cancer Research (2011)

Abstract Background: KRAS, BRAF, PIK3CA activate protein kinase signaling and an important pathway in cancer development. Recent reports show that these downstream signaling molecules are mutated in a number of cancers. However, in head and neck squamous cell carcinoma (HNSCC), the frequency and positions of these molecules mutations are not clear. In this study we detected mutations from the clinical specimens of HNSCC by High-Throughput sequencing KRAS, BRAF, PIK3CA. Next we also intended to discover whether these mutations in downstream signaling molecules of EGFR are corresponding with EGFR status. Patients and Method: The ninety-six tumors for this study were obtained from HNSCC patients surgically treated at the Department of head and neck surgery, Jikei University School of Medicine, Tokyo. The hot-spot regions in exons 1 and 2 of K-RAS, exon 15 of BRAF, exon 9 and 20 of PIK3CA were amplified by PCR and sequenced directly using DNA from samples. Next, we analyzed expression and phosphorylation of the EGFR protein by Western blotting as well as mutations encoding the hot-spot regions in exons 18 to 21. Results: We identified mutations in 6 of the 96 patients (6.2%). 3 mutations (G12A) were found in exon 1 of K-RAS. In PIK3CA, 2 mutations were found in exon 9 (E545K) and one was in exon 20(H1047R). No other mutation was found in BRAF. Overexpression of EGFR protein was observed in all clinical samples with these mutations. On the other hand, hyper-phospholyation of EGFR was confirmed in only one sample. Finally, we tried to elucidate associations between these molecular status and patient characteristics and disease-free survival to asses the prognostic values of these molecules factors. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 325. doi:10.1158/1538-7445.AM2011-325
1002 THE “150 CRITERIA” FOR THE SELECTION OF CANDIDATES FOR PRETANSPLANT DOWNSTAGING OF HEPATOCELLULAR CARCINOMA
Authors: G. Felga, A.S. Evangelista, P.R. Salvalaggio, L.C. Amorim, B. Della-Guardia, M.D. Almeida, R.C. Afonso, B.-H. Ferraz-Neto
Journal: Journal of Hepatology (2012)
P714Quantitative determination of alpha2-adrenoceptor-evoked myosin light chain phosphorylation in vascular smooth muscle cells
Authors: A Huhtinen, S Bjork, A Vuorenpaa, M Scheinin
Journal: Cardiovascular Research (2014)

Introduction: Phosphorylation of myosin light chains is a biochemical readout of smooth muscle cell contraction. α2-Adrenoceptor agonists and antagonists may have important applications in cardiovascular drug development. To assess α2-adrenoceptor-mediated drug effects on vascular smooth muscle contraction, we developed a cell-based assay for the quantitative determination of myosin light chain phosphorylation (pMLC20) in cultured A7r5 smooth muscle cells from rat aorta, transfected to express the human α2B-adrenoceptor.
Neuropathological Evidence of Graft Survival and Striatal Reinnervation after the Transplantation of Fetal Mesencephalic Tissue in a Patient with Parkinson's Disease
Authors: Jeffrey H. Kordower, Thomas B. Freeman, Barry J. Snow, François J.G. Vingerhoets, Elliott J. Mufson, Paul R. Sanberg, Robert A. Hauser, Donald A. Smith, G. Michael Nauert, Daniel P. Perl, C. Warren Olanow
Journal: New England Journal of Medicine (1995)

Trials are under way to determine whether fetal nigral grafts can improve motor function in patients with Parkinson's disease. Some studies use fluorodopa uptake on positron-emission tomography (PET) as a marker of graft viability, but fluorodopa uptake does not distinguish between host and grafted neurons. There has been no direct evidence that grafts of fetal tissue can survive and innervate the striatum.
Two new cases of hyperpyrimidinuria associated with excessive 5-fluorouracil toxicity
Authors: D.R.A. Mans, A. Scaletzky, D. Becker, J. Rodrigues de Oliveira, C.M. Pinheiro, C. Bittar, A.F.Ferreira Filho, V.L. Machado, J.L. Ritt, F.A. Jung, A. Leyva, G. Schwartsmann
Journal: Annals of Oncology (1994)
S78 Differentiation of monocytes to pro-inflammatory forms is influenced by cigarette smoke and HLA type in COPD
Authors: P. R. Newby, C. Schmutz, C. R. Buckley, R. A. Stockley, A. M. Wood
Journal: Thorax (2011)

<h3>Background</h3> There are many genetic influences documented on both lung function and susceptibility to COPD. In GWAS of pulmonary function several hits in the region of the MHC on chromosome 6 have been found, and we have shown previously that HLADR3 positive individuals have lower FEV<sub>1</sub> than those without this HLA type. This is an HLA type classically associated with autoimmunity. Interactions between HLA type and cigarette smoke are recognised in autoimmune diseases. <h3>Hypothesis</h3> HLA type influences differentiation of monocytes in the presence of cigarette smoke. <h3>Methods</h3> 15 ex and never smokers with COPD and 5 healthy controls were studied. PBMCs were isolated and exposed to varying concentrations of cigarette smoke extract (CSE) for 90 min. CD14 and CD16 markers were used in flow cytometry to ascertain relative expression and absolute cell counts for each monocyte subpopulation, defined as CD14++CD16- (classical), CD14++CD16+ (anti-inflammatory) and CD14+CD16++ (non-classical). Within the patient group differences in baseline profile and response to CSE were compared between ex-smokers and those that had never smoked. Patients were HLA class II typed as described previously1 and the same comparisons made between DR3 positive and negative patients. <h3>Results</h3> At baseline the MFI for CD14 was lower in COPD than health (p=0.04), although no clear differences in cell counts were seen. Counts were generally higher in ex-smokers, although no clear differences in subpopulations were seen. On exposure to cigarette smoke there was a dose dependent rise in classical monocytes, which was more marked in DR3+ patients and never smokers. <h3>Conclusions</h3> CSE induces a pro-inflammatory phenotype of monocytes, and this occurs most in HLADR3+ individuals. This could be the mechanism behind lower FEV<sub>1</sub> in DR3+ individuals.
Abstract 3185: The eSNV-Detect: a computational system to identify expressed single nucleotide variants from tumor transcriptomes.
Authors: Xiaojia Tang, Saurabh Baheti, Khader Shameer, Kevin J. Thompson, Jean-Pierre Kocher, Edith A. Perez, Aubrey E. Thompson, Krishna R. Kalari
Journal: Cancer Research (2013)

Abstract MOTIVATION: Transcriptome sequencing (RNA-seq) is the most economical and information-rich next generation sequencing technology to study genomic medicine. Genomic features such as gene expression, transcript expression, fusion transcripts, long non-coding RNAs and expressed single nucleotide variants (eSNVs) can be obtained from RNA-seq data. There are several computational workflows to obtain gene counts, transcript counts and fusion gene candidates, but not a comprehensive system to identify expressed SNVs from RNA-sequencing data. METHODS: We have developed a novel computational system (The eSNV-Detect) with parallel alignment strategies to identify expressed SNVs accurately from tumor transcriptome sequencing data. Sequence-based features like reads supporting reference allele, alternate allele, ratio of alternate reads to total read depth, base qualities, mapping qualities, forward strand and reverse strand supporting reads etc. along with a variety of databases such as dbSNP, 1000 genome, 5400 exome, refGene, avsift, ljb_phylop from UCSC were used to call SNVs from RNA-sequencing data. For the expressed SNVs detected in tumors, we can also identify the amino acid change and classify the protein domains using our method. RESULTS: We have applied the eSNV-Detect method to call novel expressed SNVs in two tumors (one HER2 positive and one ER positive breast tumor). BWA and Bowtie were used to align the two breast tumors. Several filtering criteria's were applied to the tumors to remove any known (germ line) or low confidence SNVs. We randomly selected 83 and 31 eSNVs for the HER2 and ER positive tumors respectively and performed Sanger sequencing validation in tumor and matched normal tissues of the tumor. We were able to validate 81 out of 83 eSNVs in the HER2 tumor sample, and 29 out of 31 eSNVs in the ER positive tumor sample. Of the eSNVs that we validated 39/81 and 10/31 were localized to functional protein domains in HER2 and ER positive tumors respectively. We are also in the process of validating eSNVs detected from RNA-seq with the tumor and blood exome sequencing data we have for the same patients. Citation Format: Xiaojia Tang, Saurabh Baheti, Khader Shameer, Kevin J. Thompson, Jean-Pierre Kocher, Edith A. Perez, Aubrey E. Thompson, Krishna R. Kalari. The eSNV-Detect: a computational system to identify expressed single nucleotide variants from tumor transcriptomes. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3185. doi:10.1158/1538-7445.AM2013-3185
The Role of Renal Scintigraphy in Renal Arteriovenous Malformation Treated by Transcatheter Arterial Embolization
Authors: SHIGEYUKI OGI, NOBUYOSHI FUKUMITSU, DAISUKE TSUCHIDA, MAYUKI UCHIYAMA, YUTAKA MORI, NORIO HASEGAWA
Journal: Clinical Nuclear Medicine (2002)

A 41-year-old woman was hospitalized because of gross hematuria. She was found to have a renal arteriovenous malformation and was treated with transcatheter arterial embolization (TAE). Renal scintigraphy with Tc-99m mercaptoacetyltriglycine was performed before and after TAE. Renal scintigraphy was useful for evaluating renal function in this patient.
HIGH SENSITIVITY CARDIAC TROPONIN I CHANGES RELATED WITH T1 MAPPING IN PATIENTS WITH CHRONIC ISCHAEMIC HEART DISEASE WITHOUT LATE ENHANCEMENT GADOLINIUM BY CRM
Authors: Carlos Segre, Antonildes Nascimento Assunção Junior, Cesar Nomura, Alexandre Villa, Celia Strunz, Paulo Rezende, Jose Parga, Myrthes Emy Takiuti, Whady Hueb, Jose Ramires, Roberto Kalil-Filho
Journal: Journal of the American College of Cardiology (2015)
Case 31-1993
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, Thomas R. Spitzer, Nancy L. Harris
Journal: New England Journal of Medicine (1993)

Presentation of CaseA 49-year-old man was admitted to the hospital because of myelofibrosis with myeloid metaplasia and painful osteolytic lesions of the right femur.He had had essential thrombocythemia for 10 years that evolved into myelofibrosis with myeloid metaplasia. The hematologic findings throughout the patient's course are presented in Table 1. Hydroxyurea was administered, with a moderate decrease in the platelet count. Three years before entry massive splenomegaly was detected.Eleven months before admission minor trauma to the right knee caused abrasions and a hematoma; a septic bursitis soon developed, and incision with drainage was performed. Two months before entry . . .