tbuckley/cabot-search huggingface dataset:
Phase II study of nivolumab in patients with advanced non-small cell lung cancer (NSCLC) in Korea
Authors: E.K. Cho, J.H. Kang, J.-Y. Han, J.S. Lee, D.-W. Kim, S.-W. Kim, Y.J. Min, K.H. Lee, J.-H. Kim, K. Park
Journal: Annals of Oncology (2017)
Hepatocyte-specific deletion of type I interleukin-1 receptor (IL-1RI) attenuates D-GalN/LPS-induced acute liver injury in vivo
Authors: N. Gehrke, N. Hövelmeyer, A. Waisman, M.A. Wörns, P.R. Galle, J.M. Schattenberg
Journal: Journal of Hepatology (2017)
Gene-drug interaction at the glucocorticoid receptor increases risk of squamous cell skin cancer
Authors: Anita S. Patel, Margaret R. Karagas, Steven K. Spencer, Ann E. Perry, Heather H. Nelson
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

4562 

The incidence rates of squamous cell carcinomas (SCC) of the skin appear to be rapidly rising among certain Caucasian populations in the United States and account for more newly diagnosed cases than all other malignancies combined. Organ transplant recipients are at high risk of aggressive squamous cell carcinoma of the skin, related to usage of immunosuppressive drugs such as cyclosporine, often combined with adrenocortical steroids (glucocorticoids). Glucocorticoids are prescribed at lower doses for other conditions including musculoskeletal, inflammatory bowel disease, and respiratory disorders, and usage at these doses has been associated with a 2-fold increased risk of SCC. With over 30 million Americans estimated to have inflammatory disease that may require glucocorticoid treatment, an association between glucocorticoid use and skin cancers is clearly of public health concern. We tested the hypothesis that genetic variation in the glucocorticoid receptor, Bcl I genotype, modifies risk of squamous cell carcinoma associated with glucocorticoid use in a large population-based case-control study of SCC (n = 214 cases and 393 controls). The adjusted odds ratios for SCC associated with oral glucocorticoids increased with the number of Bcl I variant alleles [wild type: OR 1.5, CI 0.6-3.1; het: OR 2.5, CI 1.1-5.3; variant: OR 5.6, CI 1.1-29]. These data provide evidence of gene-environment interaction between a drug and its cellular target that may contribute to increased risk of SCC. Further, we have identified a potential susceptible subgroup that may be at a substantially enhanced risk of SCC with oral glucocorticoid use.
Patient-Controlled Analgesia for Cancer-Related Pain: Clinical Predictors of Patient Outcomes
Authors: Emily J. Martin, Eric J. Roeland, Madison B. Sharp, Carolyn Revta, James D. Murphy, Katherine E. Fero, Heidi N. Yeung
Journal: Journal of the National Comprehensive Cancer Network (2017)

Background: Patient-controlled analgesia (PCA) is an effective approach to treat pain. However, data regarding patterns of PCA use for cancer pain are limited. The purpose of this study was to define the patterns of PCA use and related outcomes in hospitalized patients with cancer. Methods: We identified 90 patients with cancer admitted to a single academic center who received PCA for nonsurgical, cancer-related pain and survived to discharge between January 2013 and January 2014. Data collected included patient demographics, cancer diagnosis, type of cancer-related pain, PCA use, opioid-specific adverse events, and 30-day readmission rates for pain. Univariable and multivariable linear regression models were used to analyze the association between patient and clinical variables with PCA duration. Logistic regression models were used to evaluate the relationship between patient and clinical variables and 30-day readmission rates. Results: The median length of hospitalization was 10.2 days with a median PCA duration of 4.4 days. Hematologic malignancies were associated with longer PCA use (P=.0001), as was younger age (P=.032). A trend was seen toward decreased 30-day readmission rates with longer PCA use (P=.054). No correlation was found between 30-day readmission and any covariate studied, including age, sex, cancer type (solid vs hematologic), pain type, palliative care consult, or time from PCA discontinuation to discharge. Conclusions: This study suggests that there is longer PCA use in younger patients and those with hematologic malignancies admitted with cancer-related pain, with a trend toward decreased 30-day readmission rates in those with longer PCA use.
Multi-center study of liver disease in alpha1-antitrypsin deficiency: non-invasive evaluation of liver fibrosis in homozygous PiZZ patients
Authors: K. Hamesch, D. Scholten, I. Spivak, J. Voss, T. Bretag, M. Wetzel, B. Siegmund, M. Reichert, R. Bals, F. Lammert, M. Mandorfer, M. Trauner, J. Stolk, S. Janciauskiene, C. Trautwein, P. Strnad
Journal: Journal of Hepatology (2017)
Abstract 182: CTRP9 - A Novel Cardiac Derived Secreted Factor With Anti-hypertrophic Properties
Authors: Astrid H Breitbart, Florian Brandes, Oliver Müller, Natali Froese, Mortimer Korf-Klingebiel, Ulrike Schrameck, Kai C Wollert, Johann Bauersachs, Jörg Heineke
Journal: Circulation Research (2013)

Background: CTRP9 (also called C1qtnf9) is a newly discovered secreted protein and a paralog of adiponectin. The biological functions of CTRP9, however, are still largely unknown. Results: Although previous data from a semi-quantitative real-time PCR had suggested that CTRP9 is mainly secreted by adipose tissue, we found its mRNA to be predominantly expressed in the heart by quantitative real-time PCR. Interestingly, we identified CTRP9 mRNA as significantly upregulated in hypertrophied mouse hearts (after 2 weeks of aortic constriction, TAC) as well as in hypertrophied human hearts (24±4-fold versus healthy human myocardium; p&lt;0.01). LacZ staining in myocardial sections of C1qtnf9 tm1(KOMP)Vlcg mice (knock-out for CTRP9, containing a lacZ cassette to replace exon 1-3 of the gene) revealed exclusive expression of CTRP9 in capillary and venous endothelial cells. Adenoviral overexpression of CTRP9 or recombinant CTRP9 strongly inhibited cardiomyocyte hypertrophy (assessed as cell size, protein/DNA-ratio, expression of skeletal α-actin) after stimulation with phenylephrine (PE). Accordingly, myocardial overexpression of CTRP9 via a cardioselective adeno-associated virus (AAV9-CTRP9) in mice dramatically reduced cardiac hypertrophy after two weeks of pressure overload (heart weight/body weight ratio, HW/BW in mg/g: AAV9-control 6.5±0.2 versus AAV9-CTRP9 5.6±0.2; p&lt;0.01). In turn, downregulation of CTRP9 by a specific siRNA aggravated cardiomyocyte growth in response to PE in vitro and CTRP9 knock-out (KO) mice exerted an enhanced hypertrophic response after two weeks of TAC in vivo (% increase in HW/BW versus sham: wild-type 77±13, KO 106±9; p&lt;0.05). Mechanistically, we found that CTRP9 binds to the adiponectin receptor 1 (AdipoR1) and inhibits prohypertrophic mTOR signalling in cardiac myocytes. SiRNA mediated downregulation of AdipoR1 or mTOR in neonatal rat cardiomyocytes abolished the anti-hypertrophic effect of CTRP9. Conclusion: Endothelial cell derived CTRP9 inhibits cardiac hypertrophy through binding to AdipoR1 and inhibition of the mTOR pathway in cardiomyocytes. Therefore, myocardial application of CTRP9 could be a novel strategy to combat pathological cardiac hypertrophy.
Serum miRNA signature to identify a patient’s resistance to high-dose radiation therapy for unresectable non-small cell lung cancer.
Authors: Nan Bi, Matthew J Schipper, Paul Stanton, Weili Wang, Feng-Ming (Spring) Kong
Journal: Journal of Clinical Oncology (2013)

7580 Background: There is a growing literature on unique profiles of serum micro RNAs (miRNAs) expression to predict clinical outcome of metastatic and early stage non-small cell lung cancer (NSCLC). However, the predictive role of circulating miRNAs in unresectable NSCLC treated with definitive radiation therapy (RT) is unknown. Methods: 134 patients with inoperable/unresectable NSCLC treated with deﬁnitive RT (18-month minimum follow-up) were eligible. Serum samples were collected prospectively before treatment. 100 patients had enough serum and reliable miRNA profile quality, which were randomly divided into training and validation sets (50 patients each). MiRNA profiling was performed using real-time PCR-based array, containing a panel of 84 miRNAs detectable in human bodily fluids. Spiked-in cel-miR-39 was used for normalization. Stepwise regression Cox model building was used to build a miRNA signature on the training set, which was then assessed on the validation set both alone and with clinical factors. Results: The median age was 67 years; 76% were stages III and 79% received chemoradiation; the median physical dose was 70.0 Gy. A serum hsa-miR-885/hsa-miR-7 signature was identified as significant predictors for overall survival (OS) in the training set, which was validated by the validation set (p=0.02). After adjustment for GTV Volume and KPS, the only two significant clinical factors in univariate analysis, this signature remained significant (p=0.04). In the high-dose RT group (&gt;70 Gy, n=45), individuals with low-risk had a significantly longer OS than patients with high-risk (70.7 vs. 18.8 months, p=0.007); while in the low-dose RT group (≤70 Gy, n=55), no significant association was observed (OS, 22.0 vs. 13.3 months, p=0.43). Conclusions: Circulating hsa-miR-885/hsa-miR-7 signature may be used as a putative non-invasive biomarker for predicting survival and radiation resistance in unresectable NSCLC, which may potentially help to select patients who will not benefit from high-dose radiation. Independent validation studies are needed to conﬁrm our ﬁndings. Clinical trial information: NCT01190527.
Viral kinetics in women of child bearing potential with chronic hepatitis B virus following treatment with tenofovir alafenamide or tenofovir disoproxil fumarate
Authors: C. Pan, T.-T. Chang, S.-H. Bae, M. Brunetto, C. Coffin, A. Lau, S. Mo, J.F. Flaherty, A. Gaggar, G.M. Subramanian, M.H. Nguyen, S. Gurel, A. Thompson, E.J. Gane
Journal: Journal of Hepatology (2017)
Sixty seconds on . . . #publicduty
Authors: Anne Gulland
Journal: BMJ (2017)

Thank you for your interest in spreading the word about The BMJ.NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address. Username * Your Email * Send To * You are going to email the following Sixty seconds on . . . #publicduty Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Neural Stem Cells: A Dual Functional Scaffold Tethered with EGFR Antibody Promotes Neural Stem Cell Retention and Neuronal Differentiation for Spinal Cord Injury Repair (Adv. Healthcare Mater. 9/2017)
Authors: Bai Xu, Yannan Zhao, Zhifeng Xiao, Bin Wang, Hui Liang, Xing Li, Yongxiang Fang, Sufang Han, Xiaoran Li, Caixia Fan, Jianwu Dai
Journal: Advanced Healthcare Materials (2017)

Jianwu Dai and co-workers fabricate a dual functional collagen scaffold tethered with a collagen-binding epidermal growth factor receptor (EGFR) antibody in article number 1601279. This scaffold can simultaneously attract neural stem cells (NSCs) and promote their neuronal differentiation after spinal cord injury by specifically binding to EGFR molecule expressed on NSCs and attenuating EGFR signaling, which is responsible for the inhibition of differentiation of NSCs toward neurons.
The hackers holding hospitals to ransom
Authors: Krishna Chinthapalli
Journal: BMJ (2017)

Hospitals need to be prepared to avoid shutdowns

In February 2016 staff at a Los Angeles hospital noticed that their computers weren’t working.1 Secretaries couldn’t access emails and had to communicate by fax or phone. Doctors couldn’t access electronic records. At least one patient had to go to another hospital. Others reported long delays. Computed tomography scans could not be done. The chief executive declared an emergency, and ambulances were diverted to other hospitals. Rumours surfaced, including that the hospital was being held to ransom for $3.4m (£2.6m; €3.1m), though the hospital denied this.23

Few people know what exactly occurred at the Hollywood Presbyterian Medical Center. It is likely to have been a “phishing” expedition in which the bait was a fake email message and the prey was a healthcare employee. The virus—or “ransomware”—then infected and locked hospital computers. IT …
Changes in fibrosis, but not the NAFLD Activity Score (NAS), are associated with disease progression in patients with nonalcoholic steatohepatitis (NASH) and advanced fibrosis
Authors: A. Sanyal, S. Harrison, V. Ratziu, M. Abdelmalek, A. Diehl, S. Caldwell, M. Shiffman, R. Aguilar, C. Jia, B. McColgan, R. Myers, M. Subramanian, J. McHutchison, A. Muir, N. Afdhal, J. Bosch, Z. Goodman
Journal: Journal of Hepatology (2017)
OV21/PETROC: A randomized Gynecologic Cancer Intergroup (GCIG) phase II study of intraperitoneal (IP) versus intravenous (IV) chemotherapy following neoadjuvant chemotherapy and optimal debulking surgery in epithelial ovarian cancer (EOC).
Authors: Helen Mackay, Christopher J. Gallagher, Wendy R. Parulekar, Jonathan A. Ledermann, Deborah Kay Armstrong, Charlie Gourley, Ignacio Romero, Amanda Feeney, Paul Bessette, Marcia Hall, Johanne Ingrid Weberpals, Geoff Hall, Susie K Lau, Philippe Gauthier, Michael Fung-Kee-Fung, Elizabeth A. Eisenhauer, Chad Winch, Dongsheng Tu, Diane M. Provencher
Journal: Journal of Clinical Oncology (2016)

LBA5503 Background: The aim of this 2 stage randomized trial was to evaluate whether women undergoing neoadjuvant IV chemotherapy followed by delayed debulking surgery benefit from the addition of IP/IV treatment after surgery. Methods: Stage 1 was a randomized 3-arm design including 2 IP platinum regimens: 153 women who received 3-4 courses of IV platinum-based chemo for stage IIB-III (IV pleural effusion only) EOC followed by optimal debulking surgery ( &lt; 1 cm) were randomized to: ARM1 D1 IV paclitaxel (pacli) 135mg/m2 + IV Carboplatin AUC 5/6 with d8 pacli IV 60 mg/m2 Q 21d X3; ARM 2 D1 IV pacli 135mg/m2 + IP cisplatin (Cis) 75 mg/m2 and d8 IP pacli 60 mg/m2 Q21d X3; or ARM 3 d1 IV pacli 135mg/m2+ IP Carboplatin AUC 5/6 and d8 IP pacli 60mg/m2 Q21dX3. A planned DSMC review confirmed dropping ARM2 (IP cis) and continuing study as an expanded phase II comparing 200 patients randomized to ARMs 1 and 3, which has 80% power to detect a 19% difference in progression rate at 9 mo (PD9, primary endpoint), 2-sided α = 0.05. Progression free survival (PFS) and overall survival (OS) are secondary efficacy endpoints. Results: Between 2009 and May 2015, 275 patients were accrued: n = 101 Arm 1, 72 Arm 2, 102 Arm 3. Median age was 62; 81.8%s had stage 3 C disease; 12.7% stage IV. Baseline characteristics were balanced between arms. Median number of cycles was 3 all arms; completion rates Arm 1, 93.7% and Arm 3, 84.8%. Intention to treat PD9 rates: Arm 1: 38.6% (95% CI 29.1%- 48.8%) and Arm 3: 24.5% (95% CI 16.5%-34.0%); p = 0.065 stratified; p = 0.03 unstratified. Per protocol (eligible, received &gt; one dose of protocol therapy) PD9 rates: Arm 1: 42.2% (95% CI 31.9%- 53.1%), Arm 3: 23.3% (95% CI 15.1%-33.4%); p = 0.03 stratified; p = 0.01 unstratified. Median PFS 11.3 mo (Arm1) and 12.5 mo (Arm 3); HR 0.82 (95% CI 0.57 - 1.17); p = 0.27. Median OS: 38.1 mo (Arm 1) and 59.3 mo (Arm 3); HR 0.80 (95% CI 0.47-1.35) p = 0.40. Adverse events &gt; Gr 3 rates: 23% (Arm 1) and 16% (Arm 3) (p = 0.24). Conclusions: The IP carboplatin based regimen, post neoadjuvant chemotherapy and debulking surgery, is well tolerated and associated with a lower PD9 rate compared to IV therapy. Clinical trial information: NCT00993655.
Correlation between high-resolution computed tomography findings and IASLC/ATS/ERS classification of small lung adenocarcinomas in Japanese patients.
Authors: Yujin Kudo, Jun Matsubayashi, Yoshihisa Shimada, Soichi Akata, Yasufumi Kato, Masatoshi Kakihana, Naohiro Kajiwara, Tatsuo Ohira, Toshitaka Nagao, Norihiko Ikeda
Journal: Journal of Clinical Oncology (2015)

7543 Background: Small pulmonary nodule detection rates have increased owing to computed tomography (CT) screening of lung cancer, and new image guided-bronchoscopy techniques have been developed to improve diagnostic yield. Additionally, limited surgical resection for small peripheral lung adenocarcinomas has been reported. Recently, the IASLC/ATS/ERS classification emphasized the prognostic significance of histologic subtypes. We evaluated the correlation between high-resolution CT (HRCT) findings and this classification of small lung adenocarcinomas. Methods: We reviewed the data of 220 consecutive lung adenocarcinoma ( ≤ 3 cm) patients who received segmentectomy or more extended resection with lymph node dissection in our hospital. From the HRCT findings, the tumors were classified as pure solid, part-solid, or pure ground glass opacity (GGO) nodules. Pathologic tumor invasiveness (pTI) was evaluated by the degree of vascular invasion, lymphatic permeation, or visceral pleural invasion. Results: The tumors were classified as pure GGO nodules in 16 patients (7.2%), part-solid in 91 (41.3%), and pure solid in 113 (51.3%) from the HRCT findings. We pathologically diagnosed 44 noninvasive and 176 invasive adenocarcinomas (IAs) [lepidic (LPA), papillary, acinar, solid predominant adenocarcinoma, and invasive mucinous adenocarcinoma]. Lymph node metastasis was present in 31 patients (14.1%) and pTI in 101 (45.9%). All pure solid tumors were IAs with a high pTI frequency (75.2%) or lymph node metastasis (26.5%). All pure GGO nodules were non-IAs or LPA. Among the part-solid nodules, IA was detected in 67.0% of the patients and pTI in 16.5%. The consolidation/tumor (C/T) ratio and consolidation size were associated with IA (optimal cut-off values: 0.4 and 8 mm) or pTI (0.8 and 15 mm). Conclusions: The HRCT findings correlated with the IASLC/ATS/ERS classification and were useful for malignancy evaluation. Most pure solid tumors have malignant potential including pTI or lymph node metastasis. For part-solid tumors, the C/T ratio and consolidation size were important for predicting pTI or making a diagnosis of IA according to this classification.
Abstract 19020: ABCG1 Regulates Pulmonary Surfactant Homeostasis and the Lung Microbiome
Authors: Thomas Q de Aguiar Vallim, Angel Baldan, Joan Cheng, Christopher Goulbourne, Elin Org, Aldons J Lusis, Elizabeth J Tarling
Journal: Circulation (2015)

Chronic respiratory diseases are the 3rd leading cause of death, and individuals suffering from respiratory distress are at risk for cardiovascular complications. Changes in the commensal bacteria in the lung have been associated with the development of chronic lung conditions including asthma, cystic fibrosis, chronic obstructive pulmonary disease (COPD), and pulmonary fibrosis. The lung is a dynamic environment, constantly subject to influx of debris and microbes. The clearance of pathogens and adaptation to changes in commensal flora are mediated by innate and acquired immune responses that minimize inflammation and maintain pulmonary homeostasis. Surfactant proteins are essential for the structure and function of pulmonary surfactant, produced solely by pulmonary type 2 cells, and have their own intrinsic innate immune properties. The ATP Binding Cassette Transporter G1 (ABCG1) is highly expressed in pulmonary type 2 cells, alveolar macrophages and immune cells. We have recently demonstrated that ABCG1 regulates pulmonary B cell and natural antibody homeostasis. Here we show that mice lacking ABCG1 specifically in pulmonary type 2 cells have altered lamellar body and surfactant homeostasis. Additionally, we show that mice lacking ABCG1 have disturbances in the commensal bacteria that populate the lungs. Abcg1-/- mice may represent a novel model in which to study the interaction between pulmonary surfactant metabolism, pulmonary innate immune responses and the lung microbiome.
Early Progression after R-CHOP in Follicular Lymphoma: Key Role for the Maintenance Therapy
Authors: Vit K Prochazka, Tomas Papajik, Andrea Janikova, David Belada, Tomas Kozak, David Salek, Alice Sykorova, Heidi Mocikova, Vit Campr, Jitka Dlouha, Tomas Fuerst, Marek Trneny
Journal: Blood (2016)
Selenoenzyme glutathione peroxidase 4 affects profile of infiltrating immune cell in hepatocellular carcinoma
Authors: N. Rohr-Udilova, D. Stoiber, E. Bauer, M. Seif, H. Hayden, B. Grasl-Kraupp, G. Timelthaler, M. Peck-Radosavljevic, R. Eferl, M. Trauner
Journal: Journal of Hepatology (2017)
Molecular isoforms of high-mobility group box 1 are mechanistic biomarkers for epilepsy
Authors: Lauren Elizabeth Walker, Federica Frigerio, Teresa Ravizza, Emanuele Ricci, Karen Tse, Rosalind E. Jenkins, Graeme John Sills, Andrea Jorgensen, Luca Porcu, Thimmasettappa Thippeswamy, Tiina Alapirtti, Jukka Peltola, Martin J. Brodie, Brian Kevin Park, Anthony Guy Marson, Daniel James Antoine, Annamaria Vezzani, Munir Pirmohamed
Journal: Journal of Clinical Investigation (2017)

Approximately 30% of epilepsy patients do not respond to antiepileptic drugs, representing an unmet medical need. There is evidence that neuroinflammation plays a pathogenic role in drug-resistant epilepsy. The high-mobility group box 1 (HMGB1)/TLR4 axis is a key initiator of neuroinflammation following epileptogenic injuries, and its activation contributes to seizure generation in animal models. However, further work is required to understand the role of HMGB1 and its isoforms in epileptogenesis and drug resistance. Using a combination of animal models and sera from clinically well-characterized patients, we have demonstrated that there are dynamic changes in HMGB1 isoforms in the brain and blood of animals undergoing epileptogenesis. The pathologic disulfide HMGB1 isoform progressively increased in blood before epilepsy onset and prospectively identified animals that developed the disease. Consistent with animal data, we observed early expression of disulfide HMGB1 in patients with newly diagnosed epilepsy, and its persistence was associated with subsequent seizures. In contrast with patients with well-controlled epilepsy, patients with chronic, drug-refractory epilepsy persistently expressed the acetylated, disulfide HMGB1 isoforms. Moreover, treatment of animals with antiinflammatory drugs during epileptogenesis prevented both disease progression and blood increase in HMGB1 isoforms. Our data suggest that HMGB1 isoforms are mechanistic biomarkers for epileptogenesis and drug-resistant epilepsy in humans, necessitating evaluation in larger-scale prospective studies.
Oncostatin M induces increased invasiveness and angiogenesis in hepatic cancer cells through HIF1alpha-related release of VEGF-A
Authors: S. Cannito, E. Morello, B. Foglia, C. Turato, G. Di Maira, E. Novo, S. Colombatto, P. Pontisso, F. Marra, M. Parola
Journal: Journal of Hepatology (2017)
A phase 1 study to evaluate safety and tolerability of escalating single doses of the hepatitis B virus RNA interference drug ARC-521 in a healthy volunteer population
Authors: E. Gane, C. Schwabe, B. Given, T. Schluep, J. Hamilton, C.-L. Lai, S. Locarnini, J. Lau, C. Ferrari, R. Gish
Journal: Journal of Hepatology (2017)