tbuckley/cabot-search huggingface dataset:
Thyroid function tests (TFTs) abnormalities in patients (pts) with metastatic renal cell carcinoma (mRCC) treated with sunitinib
Authors: P. E. Shaheen, I. R. Tamaskar, R. N. Salas, B. I. Rini, J. Garcia, L. Wood, R. Dreicer, R. M. Bukowski
Journal: Journal of Clinical Oncology (2006)

4605 Background: Sunitinib is a multi-targeted receptor tyrosine kinase inhibitor of vascular endothelial growth factor and platelet-derived growth factor receptors. It has anti-tumor activity in mRCC pts with toxicity including fatigue. We investigated TFTs abnormalities and related signs and symptoms in pts with mRCC receiving sunitinib. Methods: The medical records of pts with mRCC enrolled in 4 ongoing clinical trials of sunitinib were reviewed. TFTs assessment (TSH, T3 and T4) was undertaken based on the clinical suspicion of treating physicians. Patient demographics, frequency and values of TFTs and any signs and symptoms of thyroid dysfunction were collected. Abnormal TFTs and treatment outcome were correlated. Results: Between 5/2004 and 12/2005, 62 pts (43 males, 19 females) were treated with sunitinib. The median age was 58 years (range, 23–72). Fifty-five pts had TFTs assessed while on treatment and 40 pts (65% of total) had one or more abnormality. Two pts had well-controlled hypothyroidism prior to initiation of sunitinib. TFTs abnormalities were consistent with hypothyroidism in all pts including one who initially developed transient hyperthyroidism. Signs and symptoms possibly related to hypothyroidism were found in 33 pts (53% of total) with abnormal TFTs and were initially attributed to sunitinib. Signs and symptoms included fatigue in 33 pts, anorexia in 20 pts, fluid retention in 17 pts, and skin/hair changes in 13 pts. Thyroid hormone replacement was undertaken in 12 pts and resulted in improvement of symptoms in 6 pts. Among the 40 pts with abnormal TFTs 29 pts had tumor evaluation; 13 had SD, 8 had PR, 2 had CR. There was no correlation between abnormal TFTs and treatment outcome. Conclusions: TFTs abnormalities are common in pts with mRCC treated with sunitinib. Thyroid hormone replacement is indicated in such pts to improve hypothyroidism-related symptoms and possibly to improve treatment tolerance. [Table: see text]
Is real-time PCR-based diagnosis similar in performance to routine parasitological examination for the identification of Giardia intestinalis , Cryptosporidium parvum / Cryptosporidium hominis and Entamoeba histolytica from stool samples? Evaluation of a new commercial multiplex PCR assay and literature review
Authors: A. Laude, S. Valot, G. Desoubeaux, N. Argy, C. Nourrisson, C. Pomares, M. Machouart, Y. Le Govic, F. Dalle, F. Botterel, N. Bourgeois, E. Cateau, M. Leterrier, P. Le Pape, F. Morio
Journal: Clinical Microbiology and Infection (2015)
SIRT1-Activating Compounds (STAC) Negatively Regulate Pancreatic Cancer Cell Growth and Viability Through a SIRT1 Lysosomal-Dependent Pathway
Authors: Claudia C.S. Chini, Jair M. Espindola-Netto, Gourish Mondal, Anatilde M. Gonzalez Guerrico, Veronica Nin, Carlos Escande, Mauro Sola-Penna, Jin-San Zhang, Daniel D. Billadeau, Eduardo N. Chini
Journal: Clinical Cancer Research (2015)

Abstract Purpose: Recent studies suggest that SIRT1-activating compounds (STAC) are a promising class of anticancer drugs, although their mechanism of action remains elusive. The main goal of this study is to determine the role of STACs as a potential therapy for pancreatic cancer. In addition, we also explored the mechanism by which these compounds affect pancreatic cancer. Experimental design: Using in vitro (cell culture experiments) and in vivo (xenograft experiments) approaches, we studied the role of SIRT1 agonists (STAC) in human pancreatic cancer cell viability and growth. Results: We show that SIRT1 is highly expressed in pancreatic cancer cells and that the STACs SRT1720, SRT1460, and SRT3025 inhibited cell growth and survival of pancreatic cancer cells. STACs enhanced the sensitivity of pancreatic cells to gemcitabine and paclitaxel, indicating that these drugs could be used in combination with other chemotherapy drugs. We also show that STACs were very effective in inhibiting tumor xenograft growth. In mechanistic studies, we observed that STACs activated a SIRT1 lysosomal–dependent cell death. Furthermore, the effect of STACs on cell viability was also dependent on the expression of the endogenous SIRT1 inhibitor DBC1. Conclusions: Taken together, our results reveal an essential role for SIRT1 and lysosomes in the death pathway regulated by STACs in pancreatic cancer cells. Clin Cancer Res; 22(10); 2496–507. ©2015 AACR.
Efficacy and Safety of Gemcitabine as First-Line Therapy in Patients Aged 65 and Older with Advanced Pancreatic Cancer
Authors: Yosuke Kito, Akiko Todaka, Akira Fukutomi, Kenji Kunieda, Takahiro Tsushima, Tomoya Yokota, Nozomu Machida, Kentaro Yamazaki, Yusuke Onozawa, Hirofumi Yasui
Journal: Annals of Oncology (2014)
<i> <scp>PSTPIP</scp> 1 </i> gene mutation in a pyoderma gangrenosum, acne and suppurative hidradenitis ( <scp>PASH</scp> ) syndrome
Authors: X. Calderón‐Castrat, D. Bancalari‐Díaz, C. Román‐Curto, A. Romo‐Melgar, D. Amorós‐Cerdán, L.A. Alcaraz‐Mas, E. Fernández‐López, J. Cañueto
Journal: British Journal of Dermatology (2015)
Essential control of early B-cell development by Mef2 transcription factors
Authors: Julia Herglotz, Ludmilla Unrau, Friderike Hauschildt, Meike Fischer, Neele Kriebitzsch, Malik Alawi, Daniela Indenbirken, Michael Spohn, Ursula Müller, Marion Ziegler, Wolfgang Schuh, Hans-Martin Jäck, Carol Stocking
Journal: Blood (2015)
Respiratory mechanical and cardio-vascular changes during non invasive ventilation in stable COPD patients with chronic hypercapnic respiratory failure: High intensity ventilation vs low intensity ventilation
Authors: Jozsef Lukacsovits, Annalisa Carlucci, Nicholas Hill, Piero Ceriana, Lara Pisani, Annia Schreiber, Paola Pierucci, Andras Lorx, Gyorgy Losonczy, Stefano Nava
Journal: European Respiratory Journal (2011)

In a subgroup of stable COPD patients with chronic hypercapnic respiratory failure (HRF) the use of conventional NPPV (Li-NPPV), can improve pulmonary function, gas exchange, and health related quality of life. High-intensity positive pressure ventilation (Hi-NPPV) with higher IPAP (28 cmH20) and respiratory rate (20/min) were recently adopted in order to achieve maximal PaCO2 reduction and has been shown to better improve diurnal blood gas during spontaneous breathing (SB), compared to Li-NPPV. NPPV can provoke alterations in intrapleural pressure and lung volume, which influence the cardio-vascular performance. Our study evaluates the respiratory mechanical (RM) and cardio-vascular (CV) effects of Li-NPPV and HI-NPPV, in 15 stable COPD patients with HRF. We measured the RM and blood gas parameters, in addition non-invasive measurement of CV parameters was performed. The data were reported as mean ±SD, and where compared with repeated measures ANOVA. Significant (sgn) increases were observed in pleural pressure, decrease in tans-diaphragmatic pressure and minute diaphragmatic pressure-time product (SB: 323±149; Li-NPPV: 132±139; Hi-NPPV: 40±69 cmH2O·s/min). The PaCO2 showed a sgn. decrease and the pH a sign. increase during either modalities of NPPV. Significant reduction were detected in arterial blood pressure, stroke volume, cardiac output (SB: 5.5±1.14; NPPV: 4,7±0.98; Hi-NPPV: 4.00±0.96 l/min) and oxygen transport. The long-term effects of this RM and CV changes are uncertain, accordingly further long-term studies are needed to determine its effect on survival.
Abstract P1-09-23: Symptoms, desire for help, and quality of life among recent breast cancer survivors
Authors: Steven C Palmer, SarahLena L Panzer, Karen Glanz, Marilyn M Schapira, Angela M DeMichele, Linda A Jacobs
Journal: Cancer Research (2015)

Abstract Introduction: Advances in detection and treatment have led to improved survival among breast cancer (BC) patients and 89% can expect &amp;gt;5 year survival. Progress comes at a cost, however, and patients experience lasting effects from disease and treatment. It is not clear how these effects impact quality of life (QoL) achieved by BC survivors. We examined relationships between symptoms, desire for help, and QoL among recent BC survivors. Method: Eligibility included non-metastatic BC treated &amp;lt; 1 year prior and attendance at a survivorship clinic. QoL was assessed with the SF-12. 19 common symptoms were assessed on a 0-5 bother scale. Participants reported desire for help item for each symptom rated &amp;gt; 1. Results: 171 primarily white (73%), middle aged (M=54.9 yrs), and Stage I (58%) BC survivors were recruited. Both Physical (M=48.1) and Mental (M=53.8) QoL were similar to national norms. Survivors reported an average of 12 symptoms, most commonly Fatigue (90%), Insomnia (75%), Hot Flashes (73%), and Joint Pain (70%). Most bothersome symptoms included Joint Pain (M=2.9), Decreased Sexual Drive (M=2.8), Hot Flashes (M=2.8), and Vaginal Dryness (M=2.7). Participants desired help with few symptoms (M=2.3), primarily Weight Gain (50%), Joint Pain (45%), and Numbness in Hands/Feet (44%). Both Physical and Mental QoL were negatively associated with number of symptoms experienced (r = -.46 and -.41, respectively) and number of symptoms for which help was desired (r = -.16 and -.41, respectively). Conclusion: Symptoms are common among recent breast cancer survivors and negatively impact Physical and Mental QoL. Desire for help is less common, though similarly associated with impairment in QoL. Assessing QoL in isolation from symptom burden may miss important areas for which remediation is possible and could result in improved QoL. Patient education regarding the potential for and value of symptom reduction may be needed in BC survivors. Citation Format: Steven C Palmer, SarahLena L Panzer, Karen Glanz, Marilyn M Schapira, Angela M DeMichele, Linda A Jacobs. Symptoms, desire for help, and quality of life among recent breast cancer survivors [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-09-23.
Neural representations and the cortical body matrix: implications for sports medicine and future directions
Authors: Sarah B Wallwork, Valeria Bellan, Mark J Catley, G Lorimer Moseley
Journal: British Journal of Sports Medicine (2015)

Neural representations, or neurotags, refer to the idea that networks of brain cells, distributed across multiple brain areas, work in synergy to produce outputs. The brain can be considered then, a complex array of neurotags, each influencing and being influenced by each other. The output of some neurotags act on other systems, for example, movement, or on consciousness, for example, pain. This concept of neurotags has sparked a new body of research into pain and rehabilitation. We draw on this research and the concept of a cortical body matrix—a network of representations that subserves the regulation and protection of the body and the space around it—to suggest important implications for rehabilitation of sports injury and for sports performance. Protective behaviours associated with pain have been reinterpreted in light of these conceptual models. With a particular focus on rehabilitation of the injured athlete, this review presents the theoretical underpinnings of the cortical body matrix and its application within the sporting context. Therapeutic approaches based on these ideas are discussed and the efficacy of the most tested approaches is addressed. By integrating current thought in pain and cognitive neuroscience related to sports rehabilitation, recommendations for clinical practice and future research are suggested.
Abstract 28: HIV Infection Is Associated With Greater Risk of Carotid Artery Lesions Over Seven Years
Authors: David B Hanna, Wendy S Post, Jennifer A Deal, Howard N Hodis, Kathryn Anastos, Jason M Lazar, Frank J Palella, Phyllis C Tien, Mallory D Witt, Robert C Kaplan, Lawrence A Kingsley
Journal: Circulation (2014)

Background: We previously found that low CD4+ T-cell counts among HIV-infected (HIV+) women and men were associated with an increased prevalence of carotid artery lesions in a cross-sectional analysis. We now report on the association of HIV infection with progression of subclinical atherosclerosis in the same well-characterized population of HIV+ and HIV-uninfected (HIV-) women and men. We hypothesized that HIV infection would be associated with greater progression over seven years of follow-up. Methods: We examined data from a subset of participants without a history of coronary heart disease in the Women’s Interagency HIV Study (WIHS) and Multicenter AIDS Cohort Study (MACS) who underwent serial B-mode carotid artery ultrasound imaging between 2004 and 2012 (median follow-up: 7 years). We included individuals with at least two examinations during this period, with a median of 4 exams among women and 3 exams among men. We evaluated changes in common carotid artery intima-media thickness (cIMT, mm) and the development of carotid artery lesions (focal IMT &gt;1.5 mm), defined as an increased number of lesions over the time period, based on regression models with generalized estimated equations to take into account clustering by individual, controlling for demographic factors and smoking status. Models combining women and men, as well as stratified by cohort, are presented. Results: We studied 1011 women (74% HIV+) and 811 men (65% HIV+). The median age was 41 years (IQR 35-47) in women and 49 (IQR 44-55) in men. The unadjusted mean cIMT increased during the period from 0.725 to 0.752 mm in women and from 0.757 to 0.790 mm in men. The prevalence of carotid artery lesions increased from 8% to 15% in women and from 25% to 34% in men during follow-up. In analyses controlling for sex, age, race/ethnicity, study site, and smoking status, progression of carotid artery lesions differed by HIV serostatus. HIV+ persons had a 1.9-fold higher adjusted risk of developing lesions during the follow-up period than HIV- persons (17% with increase in lesions among HIV+ vs. 10% in HIV-; 95% CI 1.29-2.72, p=0.001). This association persisted in models stratified by cohort (in women, adjusted relative risk 1.66, 95% CI 0.96-2.89, p=0.07; in men, 1.92, 95% CI 1.14-3.11, p=0.01), with no evidence of effect modification by cohort (p=0.58). We did not find significant differences in cIMT change over time by HIV serostatus, either in combined or cohort-specific analyses. Conclusion: HIV infection was associated with a greater increase in carotid artery lesions over a seven-year period in both women and men. HIV appears to play a role in focal cIMT thickening in atherosclerosis-prone carotid artery segments, but not a generalized increase in wall thickness in the common carotid artery.
Abstract 20006: RNA Sequencing of Human Hypertrophic Cardiomyopathy Tissue Reveals Diverse Pathways Modulating the Myocardial Tissue Microenvironment
Authors: Alejandro de Feria, Simon Maltais, Tarek S Absi, Yan R Su, Thomas P Stricker, Jason R Becker
Journal: Circulation (2014)

Introduction: Hypertrophic Cardiomyopathy (HCM) is a common inherited cardiac disease and cause of sudden death in adolescents and young adults. Despite significant advances in understanding the genetic underpinnings of HCM, there remains an incomplete understanding of how myofilament mutation carriers and non-carriers ultimately develop myocardial hypertrophy. Hypothesis: Human hypertrophic cardiomyopathy tissue differentially regulates gene expression involved in cellular growth. Methods: RNA was extracted from 5 control human septal tissue samples and 8 HCM septal tissue samples. The HCM tissue samples were from both myofilament mutation positive and negative patients. RNA sequencing was performed using Illumina HiSeq 2500 at a depth of 30 million paired-end reads per sample. Sequencing data was aligned to the hg19 genome using TopHat (splice-aware aligner). Cufflinks was used to estimate transcript abundance and differential expression. Pathway enrichment analysis was carried out on significant genes (q&lt;0.05) using DAVID (v6.7). Only pathways with an enrichment score greater than 2 were evaluated. Results: Cluster and principal component analysis showed highly distinct RNA expression signatures between control and HCM tissues. There were 1500 differentially expressed sequences (q&lt;0.05), which included 1286 annotated genes, 168 novel isoforms, and 46 long noncoding RNA sequences. Gene functional classification revealed 40 differentially regulated gene clusters in HCM tissue compared to controls. The most enriched gene clusters induced in human HCM tissue were associated with secreted peptides involved in promoting cell growth and modulation of extracellular structure (enrichment scores &gt; 10). Highly enriched gene clusters that were suppressed in human HCM tissue were associated with secreted peptides involved in regulating inflammation and immune defense response (enrichment scores &gt; 5). Conclusion: Our data reveals human HCM tissue differentially regulates a diverse array of genes involved in regulation of the myocardial tissue microenvironment. The strong similarity in gene expression across HCM samples suggests shared pathophysiological mechanisms independent of the underlying genetic etiology.
Circulating immune cells in patients with surgically resected nonfunctional pancreatic neuroendocrine tumors
Authors: Zeljka Jutric, Jan Grendar, Benjamin Cottam, Chet Hammill, Ronald Wolf, Paul Hansen, Marka Crittenden, Michael Gough, Pippa Newell
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts There is debate regarding whether surgical resection and/or lymphadenectomy are indicated for small nonfunctional pancreatic neuroendocrine tumors (PNETs). Myeloid cell population expansion in peripheral blood has been correlated with clinical stage of patients with solid tumors.
Erlotinib in patients with advanced squamous cell carcinoma of the lung
Authors: A. Gúrpide, B. Massutí, C. Pallares, P. Salinas, A. Montes, G. López-Vivanco, M. González Barón, M. Cobo, M. L. Amador, L. Paz-Ares
Journal: Journal of Clinical Oncology (2006)

7174 Background: Erlotinib is a potent HER1/EGFR TKI that is approved for the treatment as a single agent in 2nd and 3rd line NSCLC. Several phase II studies have shown that adenocarcinoma histology together with female gender, Asian origin, and never having smoked are associated with responsiveness of NSCLC to erlotinib. The purpose of the analyisis we present here was to describe the outcome in a group of patients with squamous carcinoma of the lung treated with erlotinib. Methods: Eligilibility criteria included stage IIIB-IV chemotherapy-naive patients with confirmed NSCLC, PS 0–2, age ≥ 18 years, adequate organ functions, measurable disease and written informed consent. Patients with diagnosis of squamous cell lung cancer that received erlotinib 150 mgr/day p.o until disease progression or withdrawal were the subject of this analysis. Results: From June 2004 to March 2005, 121 patients with histological diagnosis of squamous cell lung cacer from more than 100 different Spanish hospitals were included in the TARGET study. Median age was 66 yrs. All patients in our analysis were Caucasian. 111 patients were male (92%) and 113 (93%) were current smokers or have smoke sometime in their life. 88% of them have stage IV carcinoma and 74% have received previous treatment for metastatic disease. PS 0/1/≥2 18 (15%)/68 (56%)/32 (29%). In the evaluable population for response (69 pts) 5 PR and 0 CR were observed for an overall RR of 7.25%. Clinical benefit defined as CR+PR+SD was 54%. In the ITT populations median TTP was 3.6 months [95% CI 2.7–5.3]. Median OS was 5,7 m [95% CI 4.0–6.7]. Erlotinib was well tolerated.No unexpected toxicities were observed. Conclusions: This subgroup analysis confirms that erlotinib is active and well tolerated in patients with advanced or metastatic squamous cell carcinoma of the lung. Responses were seen in both genders and in patients with or without smoking history. At this moment histology should not be used as the only selection criteria for treatment of patients with NSCLC after failure to chemotherapy. [Table: see text]
Long-Term Remissions in Recalcitrant Pemphigus Vulgaris
Authors: A Razzaque Ahmed, Srini Kaveri, Zachary Spigelman
Journal: New England Journal of Medicine (2015)

In a case series involving 10 patients with recalcitrant recurrent pemphigus vulgaris, a combination of rituximab plus intravenous immune globulin induced complete remission for 10 years or more, with no further therapy.
Investigation of the Lack of Angiogenesis in the Formation of Lymph Node Metastases
Authors: Han-Sin Jeong, Dennis Jones, Shan Liao, Daniel A. Wattson, Cheryl H. Cui, Dan G. Duda, Christopher G. Willett, Rakesh K. Jain, Timothy P. Padera
Journal: JNCI Journal of the National Cancer Institute (2015)

Background:To date, antiangiogenic therapy has failed to improve overall survival in cancer patients when used in the adjuvant setting (local-regional disease with no detectable systemic metastasis). The presence of lymph node metastases worsens prognosis, however their reliance on angiogenesis for growth has not been reported.
Phase 2 Study of Lutetium 177–Labeled Anti–Carbonic Anhydrase IX Monoclonal Antibody Girentuximab in Patients with Advanced Renal Cell Carcinoma
Authors: Constantijn H.J. Muselaers, Marye J. Boers-Sonderen, Tim J. van Oostenbrugge, Otto C. Boerman, Ingrid M.E. Desar, Alexander B. Stillebroer, Sasja F. Mulder, Carla M.L. van Herpen, Johan F. Langenhuijsen, Egbert Oosterwijk, Wim J.G. Oyen, Peter F.A. Mulders
Journal: European Urology (2015)
The involvement of thrombospondin-1 in COPD pathogenesis through IL-8 production
Authors: Takeo Ishikawa, Katsutoshi Nakayama, Jiro Mikami, Saburo Ito, Naoki Takasaka, Yoko Yumino, Satoko Fujii, Chikako Tsurushige, Jun Kojima, Takanori Numata, Hiromichi Hara, Makoto Kawaishi, Jun Araya, Kazuyoshi Kuwano
Journal: European Respiratory Journal (2013)

Rationale: The airflow limitation of COPD is related to neutrophilic inflammation and subepithelial fibrosis in the small airways. Thrombospondin-1(TSP-1)is reported to be a key molecule downstream of MyD88/TLRs, which is associated with smoking-related airway inflammation. TSP-1 is also known as a mediator of fibrosis in mouse airway epithelial cells. However, the role of TSP-1 in COPD pathogenesis is not yet fully evaluated. We examined the correlation between TSP-1 expression and lung function, and involvement of TSP-1 in COPD pathogenesis in patients with smoking history.

Methods: Human bronchial epithelial cells (HBECs) were isolated from surgical lung specimens and cultured. 48h later, supernatants were recovered. TSP-1 concentrations in supernatants were evaluated by ELISA. The correlation between TSP-1 and pulmonary function was analyzed with linear regression analysis. IL-8 production induced by TSP-1 in HBECs was analyzed by ELISA.

Results: Surgical specimens were classified as non-smokers, healthy smokers, or COPD patients. In COPD patients, TSP-1 concentrations were found to be higher than those in non-smokers and healthy smokers. In a correlation analysis between TSP-1 and pulmonary function, TSP-1 had an inverse correlation with %FEV1 and FEV1/FVC. IL-8 concentrations rose after stimulation by TSP-1 in a dose-dependent manner.

Conclusions: TSP-1 expression in lung specimen from subjects with smoking history appears to be associated with obstructive ventilatory impairment. It was suggested that IL-8 expression by TSP-1 could be involved in pathogenesis of COPD.