tbuckley/cabot-search huggingface dataset:
Combination of dabrafenib (DAB).
Authors: Eric Jeffrey Sherman, Alan Loh Ho, Shrujal S. Baxi, Lara Dunn, Susan H. Korte, Sofia Haque, Ronald A. Ghossein, Helen X. Chen, David G. Pfister
Journal: Journal of Clinical Oncology (2017)

6085 Background: BRAFV600E mutations (BRAFm) are the most common mutations in thyroid cancer. BRAF inhibitors are active in BRAFm melanoma, but there is less activity noted in BRAFm thyroid cancer. Preclinically, BRAF inhibitors inhibit BRAFm thyroid cancers only transiently due to activation of HER2/HER3, driven by a neuregulin-dependent autocrine loop. The addition of LAP, a HER2/HER3 kinase inhibitor, sensitizes the cell to growth suppression by BRAF inhibitors (Cancer Discov 5(3):520, 2013). A phase I study evaluating the combination of DAB, a BRAF inhibitor, and LAP was initiated to evaluate the safety and pharmacodynamic changes the combination. Methods: Eligibility included thyroid cancers with the presence of a BRAFV600E mutation. Any prior treatment was allowed. All patients received DAB 150 mg bid starting 2 weeks prior to LAP. Doses of daily lapatinib were escalated in a standard 3+3 design at (1) 750 mg; (2) 1250 mg; (3) 1500 mg. Toxicities, including Dose Limiting Toxicities (DLT), were noted only after both drugs were started. Patients (pts) removed before the start of LAP were not included in the analysis. Biopsies were done at baseline, after the start of DAB, and after the start of both DAB and LAP. Responses were defined using RECIST 1.1. Results: 15 evaluable pts were enrolled on the phase I portion of the study. Gender – 10/15 (67%) male; median age – 63 years; histology – differentiated thyroid cancer (DTC) 13 (87%), anaplastic thyroid cancer (ATC) 2 (13%); brain metastases – 4/15 (27%); prior tyrosine kinase inhibitor – 9/15 (54%). There was one DLT - Grade 5 event unlikely related to drugs in a pt with ATC. Grade 4 toxicities – 0. Grade 3 toxicities –lymphocytes (1). The partial response rate is 60%. The response rate in the DTC group is 69% (0% in ATC). One other pt came off treatment due to withdrawal of consent. Median progression-free survival is 15 months (range, 2-34+ months). Median follow up is 15 months. Translational studies are pending. Conclusions: The combination of DAB 150 mg bid and LAP 1500 mg daily was safe and well-tolerated. Furthermore, significant activity was noted, especially at the top dose level. Further investigation with this regimen is warranted. Clinical trial information: NCT01947023. [Table: see text]
First evaluation of the Behavioral Addiction Indoor Tanning Screener ( <scp>BAITS</scp> ) in a nationwide representative sample
Authors: K. Diehl, T. Görig, E.W. Breitbart, R. Greinert, J.J. Hillhouse, J.L. Stapleton, S. Schneider
Journal: British Journal of Dermatology (2017)

Evidence suggests that indoor tanning may have addictive properties. However, many instruments for measuring indoor tanning addiction show poor validity and reliability. Recently, a new instrument, the Behavioral Addiction Indoor Tanning Screener (BAITS), has been developed. To test the validity and reliability of the BAITS by using a multimethod approach. We used data from the first wave of the National Cancer Aid Monitoring on Sunbed Use, which included a cognitive pretest (August 2015) and a Germany‐wide representative survey (October to December 2015). In the cognitive pretest 10 users of tanning beds were interviewed and 3000 individuals aged 14–45 years were included in the representative survey. Potential symptoms of indoor tanning addiction were measured using the BAITS, a brief screening survey with seven items (answer categories: yes vs. no). Criterion validity was assessed by comparing the results of BAITS with usage parameters. Additionally, we tested internal consistency and construct validity. A total of 19·7% of current and 1·8% of former indoor tanning users were screened positive for symptoms of a potential indoor tanning addiction. We found significant associations between usage parameters and the BAITS (criterion validity). Internal consistency (reliability) was good (Kuder–Richardson‐20, 0·854). The BAITS was shown to be a homogeneous construct (construct validity). Compared with other short instruments measuring symptoms of a potential indoor tanning addiction, the BAITS seems to be a valid and reliable tool. With its short length and the binary items the BAITS is easy to use in large surveys.
Poor-prognosis nasopharyngeal carcinoma as defined by a molecularly distinct subgroup and prediction by a miRNA expression signature.
Authors: Lan Zhao, Feng Gao, Wang Wei, Xin Duan, Yuchen Zhang, Lina Zhu, Xin Wang
Journal: Journal of Clinical Oncology (2017)

6056 Background: Nasopharyngeal carcinoma (NPC) is a highly invasive and metastatic cancer, with diverse molecular characteristics and clinical outcomes. Our aim in this study is to dissect the molecular heterogeneity of NPC, followed by construction of a prognostic model for prediction of distant metastasis. Methods: For molecular subtyping of NPC using miRNA expression data, we selected 86 stage II (AJCC 7th Edition) NPC patients from GSE32960 as training cohort. The remaining 226 NPC patients from GSE32960 and 246 NPC patients from GSE70970 were used as two validation cohorts. Consensus clustering was employed for unsupervised classification of the training cohort. Classifier was built using support vector machine (SVM), and was validated in the two validation cohorts. Univariate and multivariate Cox regression analyses were employed for feature selection and constructing a prognostic model for predicting high-risk distant metastasis, respectively. Results: We identified three NPC subtypes (NPC1, 2, and 3) that are molecularly distinct and clinically relevant. NPC1 (~45%) is enriched for cell cycle related pathways, and patients classified to NPC1 have an intermediate survival; NPC3 (~19%) is enriched for immune related pathways, and has good clinical outcomes. More importantly, NPC2 (~36%) is associated with poor prognosis, and is characterized by upregulation of epithelial-mesenchymal transition (EMT). Out of the total 25 differentially expressed miRNAs in NPC2, miR-142, miR-26a, miR-141 and let-7i have significant prognostic power (p &lt; 0.05), as determined by univariate Cox regression analysis. For identification of high-risk distant metastasis, we built a multivariate Cox regression model using the selected 4 miRNAs. Our model can robustly stratify NPC patients into high- and low- risk groups both in GSE32960 (HR 3.1, 95% CI 1.8-5.4, p = 1.2e-05) and GSE70970 (HR 2.2, 95% CI 1.1-4.5, p = 0.022) cohorts. Conclusions: We proposed for the first time that NPC can be stratified into three subtypes. Using a panel of 4 miRNAs, we established a prognostic model that can robustly stratify NPC patients into high- and low- risk groups of distant metastasis.
A Method of Evaluating Thymonucleodepolymerase Activity in Normal and Tumor Tissues
Authors: Jesse P. Greenstein
Journal: JNCI Journal of the National Cancer Institute (1942)

A Method of Evaluating Thymonucleodepolymerase Activity in Normal and Tumor Tissues Get access Jesse P. Greenstein Jesse P. Greenstein research fellow National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 2, Issue 4, February 1942, Pages 357–359, https://doi.org/10.1093/jnci/2.4.357 Published: 01 February 1942
血液の最も多くの除核成分の準アポトーシス理解は詳細な分子剖検を必要としている【Powered by NICT】
Authors: Gusev Gennadii Petrovich, Govekar Rukmini, Gadewal Nikhil, Agalakova Natalia Ivanovna
Journal: Ageing Research Reviews (2017)
Association Between Enactment of a “Stand Your Ground” Self-defense Law and Unlawful Homicides in Florida
Authors: David K. Humphreys, Antonio Gasparrini, Douglas J. Wiebe
Journal: JAMA Internal Medicine (2017)

This study analyzes data on homicides to evaluate changes in the number of justifiable and unlawful homicides in Florida following the enactment of a “stand your ground” law.
ヒト成人腎幹細胞における管状コミットメントのマイクロパターン化制御【Powered by NICT】
Authors: G Sciancalepore Anna, Portone Alberto, Moffa Maria, Persano Luana, De Luca Maria, Paiano Aurora, Sallustio Fabio, P Schena Francesco, Bucci Cecilia, Pisignano Dario
Journal: Biomaterials (2016)
Abstract P303: Panaxnotogensengsaponins Promotes Angiogenesis and Enhances the Buildup of Effective Coronary Collateral Circulation in Ischemic Myocardium
Authors: Teng Zhang, Wen-jian Wang
Journal: Circulation Research (2011)

Background: Ischemic heart disease (IHD) is a condition that the blood vessels are narrowed or blocked due to the deposition of cholesterol plaques on the blood vessel walls. This affects the supply of blood to the heart and reduces the supply of oxygen and nutrients to the heart musculature, which has been regarded as the largest threat to the public health worldwide. PNS is a purified natural product extract that has been proved effective and widely used clinically in preventing and treating IHD in China. However, the detailed mechanisms of action of PNS remain to be addressed. The present study aims to explore the effect of PNS on modulating angiogenesis in vitro and in vivo to better understand its mechanism of action in treating IHD. Methods and Results: In this study, myocardial ischemia rat model and endothelial cell derived from human capillary blood vessel (ECV304) were utilized. Our data revealed that PNS significantly increased capillary blood vessel density in isoproterenol-induced rat ischemic myocardium model. It also decreased the pathological damage and ameliorated the ultrastructure of myocardial cells in rat ischemic myocardium as assessed by light microscopy, transmission electron microscopy and immunohistochemistry. At cellular level, PNS significantly decreased the number of apoptotic cells in rat ischemic myocardium model. Mechanistic study utilizing microarray and real-time PCR were further performed to examine the gene expression profile. The data revealed that PNS significantly upregulated the mRNA expression of a panel of angiogenic growth factors and their receptors such as VEGF, VEGFR2 and FGFR1. In vitro study revealed that PNS did not exhibit significant effect on the proliferation of ECV304 cells under normoxia culture condition; however, it facilitated the proliferation of ECV304 cells under hypoxia condition, suggesting the selective effect of PNS on angiogenesis under ischemic/hypoxic conditions. Conclusions: Our study demonstrated for the first time that PNS exerts its therapeutic effect on IHD through the mechanisms that in part involve regulating the expression of important angiogenic growth factor, which coordinately enhance the build-up of effective coronary collateral circulation in ischemic myocardium.
Immunotherapy with pembrolizumab in surgically resectable head and neck squamous cell carcinoma.
Authors: Ravindra Uppaluri, Paul Zolkind, Tianxiang Lin, Brian Nussenbaum, Randal Paniello, Jason Rich, Ryan Jackson, Wade Thorstad, Hiram Alberto Gay, Mackenzie Daly, Dorina Kallogjeri, Gavin P Dunn, Tanya Marya Wildes, Loren S. Michel, Rebecca Chernock, Jay F Piccirillo, Obi Griffith, Douglas Adkins
Journal: Journal of Clinical Oncology (2016)

TPS6110 Background: Patients with locally advanced, surgically resectable Stage III/IV human papillomavirus (HPV)-negative head and neck squamous cell carcinomas (HNSCC) suffer from locoregional and distant metastatic (LRR/DM) failures. This population is thus an ideal target for checkpoint blockade therapy as the mutational landscape of these carcinogen-induced malignancies bears a rich array of antigenic targets for immune based therapeutics. Methods: Trial design and statistical methods This is a Phase II neoadjuvant and post-operative pembrolizumab trial. After informed consent and registration, tumor biopsy and peripheral blood will be obtained and patients will receive a single pre-operative dose of pembrolizumab (10 mg/kg). After two to three weeks, patients undergo definitive surgery where tissue is again harvested. Patients then proceed with standard post-operative adjuvant therapy dictated by the pathologic report. High-risk patients with extracapsular extension and/or positive margins receive additional maintenance pembrolizumab for the first year after treatment. Sample size justification: Historical data has shown a 35% rate of LRR and DM at 1 year in HNSCC patients undergoing multimodality treatment and our primary endpoint is to reduce LRR/DM to 15%. We will recruit 46 patients with 31 of these expected to be high risk and qualify for post-operative pembrolizumab. This cohort will allow us to detect with 80% power (alpha = 0.05) a difference of at least 20% in the 1-year LRR/DM rate. Correlative studies: Clinical outcomes will be correlated with tumor PD-L1 expression, neoantigen burden as defined by tumor exome sequencing and RNA-Seq in matched pre-and post-pembrolizumab treated samples. Finally, patient specific tumor infiltrating lymphocyte cultures will be used to define antigen-specific T cells targeted by pembrolizumab. Major eligibility criteria Patients must have stage III/IV HPV-negative HNSCC with planned primary surgical management. Current enrollment 10 of 46 patients enrolled Trial registry number NCT02296684 Clinical trial information: NCT02296684.
腸炎菌:高所得国での腸炎および低所得国での侵襲性疾患に関連する異なる腸炎菌(Salmonella Enteritidis)系統
Authors: Feasey Nicholas A, Parry Christopher M, Hadfield James, Langridge Gemma C, Feltwell Theresa, Harris Simon R, Mather Alison E, Fookes Maria, Aslett Martin, Maclennan Calman A, Kingsley Robert A, Parkhill Julian, Dougan Gordon, Thomson Nicholas R, Msefula Chisomo, Heyderman Robert S, Gordon Melita A, Wigley Paul, French Neil, Lacharme‐Lora Lizeth, Everett Dean B, Keddy Karen H, Smith Anthony M, Dallman Timothy J, Nair Satheesh, Jacobs Jan, Deng Xiangyu, Barquist Lars Barquist, Kariuki Samuel, Onsare Robert S, Weill Francois‐Xavier, Hello Simon Le, Mcclelland Michael, Desai Prerak, Cheesbrough John, Campos Josefina, Chabalgoity Jose A, Betancor Laura, Hopkins Katie L, Humphrey Tom J, Lunguya Octavie, Cogan Tristan A, Tapia Milagritos D, Tennant Sharon M, Bornstein Kristin, Levine Myron M, Sow Samba O
Journal: Nature Genetics (2016)
Lung cancer in never-smokers from the Princess Margaret Cancer Centre.
Authors: Grzegorz Korpanty, Suzanne Kamel-Reid, Ming Sound Tsao, Alona Zer, Geoffrey Liu, Natasha B. Leighl, Ronald Feld, Melania Pintilie, Frances A. Shepherd
Journal: Journal of Clinical Oncology (2014)

8099 Background: Lung cancer in never smokers accounts for ~15-20% of cases, and globally is a growing clinical problem. Methods: We identified 570 never-smokers with lung cancer diagnosed from 1988-2013 at the Princess Margaret Cancer Centre. Clinical and demographic data were retrieved from the electronic patient record with the aim of characterizing the epidemiology, demographics, pathology, molecular profile, treatment, and survival in these patients. Results: There were 409 females (72%) and 161 males (28%), median age 62.1 years (18– 94), 46% Caucasian, 34% Asian, 6% Black, 4% South Asian, 4 % Filipino, 6% Other/Unknown. Environmental tobacco exposure was identified in only 17%. A history of prior malignancy was present in 89 (14.2%) patients (1 cancer 81; multiple cancers 8 patients). Most patients (87.3%) had adenocarcinoma and most presented in stage IV - 54.9%, followed by I - 26%, III - 12.8% and II - 6.3%. In stage IV patients, 88% were ECOG PS 0-1. Among 310 patients with molecular results to date, the mutation rate was 71% (EGFR mutation [mut] 76%, ALK 10%, KRAS 4%, HER2 1.4% BRAF 0.5%, other 1.8%, multiple mut 6.3%. Brain metastases at presentation occurred in 18.4% stage IV patients (77/419): 67% (52/77) with EGFR mut vs 22% (17/77) with EGFR WT vs 10% (8/77) with other mut (P=0.0023). Median overall survival (OS) of EGFR mut patients vs EGFR WT with brain metastases at presentation was 57 vs 16 mo (P=0.031). Stage IV patients with EGFR and ALK mut received targeted treatment in 88% (121/138) and 89% (16/18) cases, respectively, with 65% (92/138, 66% for EGFR and 14/18, 82% for ALK) staying on TKI >6 months. Overall, 68% (285/419) of patients received 1-3 lines of systemic therapy (range 0-8 lines). Median OS was 47 mos. Median OS for patients with known vs unknown mutation status was 59 mo vs 34 (P<0.001). Early stage (P<0.0001), PS 0-1 (P<0.0001), presence of EGFR (P=0.003) or ALK mut (P=0.035) were associated with longer survival, but not Asian ethnicity (P=0.6) or female sex (P=0.1). Conclusions: Lung cancer in never-smokers represents a distinct clinical and molecular entity characterized by a high incidence of targetable mutations and long survival. Updated molecular profiling results will be presented for the entire cohort.
DHA負荷Fe_3O_4@C@MIL100(Fe)ナノ粒子のpH応答性分解に基づく増強された癌治療のためのDHAとFeイオンの磁気誘導送達【Powered by NICT】
Authors: Wang Dongdong, Zhou Jiajia, Chen Ruhui, Shi Ruohong, Xia Guoliang, Zhou Shu, Liu Zhenbang, Zhang NianQing, Wang Haibao, Guo Zhen, Chen Qianwang
Journal: Biomaterials (2016)
Quality standards in upper gastrointestinal endoscopy: a position statement of the British Society of Gastroenterology (BSG) and Association of Upper Gastrointestinal Surgeons of Great Britain and Ireland (AUGIS)
Authors: Sabina Beg, Krish Ragunath, Andrew Wyman, Matthew Banks, Nigel Trudgill, Mark D Pritchard, Stuart Riley, John Anderson, Helen Griffiths, Pradeep Bhandari, Phillip Kaye, Andrew Veitch
Journal: Gut (2017)

This document represents the first position statement produced by the British Society of Gastroenterology and Association of Upper Gastrointestinal Surgeons of Great Britain and Ireland, setting out the minimum expected standards in diagnostic upper gastrointestinal endoscopy. The need for this statement has arisen from the recognition that while technical competence can be rapidly acquired, in practice the performance of a high-quality examination is variable, with an unacceptably high rate of failure to diagnose cancer at endoscopy. The importance of detecting early neoplasia has taken on greater significance in this era of minimally invasive, organ-preserving endoscopic therapy. In this position statement we describe 38 recommendations to improve diagnostic endoscopy quality. Our goal is to emphasise practices that encourage mucosal inspection and lesion recognition, with the aim of optimising the early diagnosis of upper gastrointestinal disease and improving patient outcomes.
Light Therapy Promoting Dopamine Release by Stimulating Retina in Parkinson Disease—Reply
Authors: Aleksandar Videnovic, Elizabeth B. Klerman, Phyllis C. Zee
Journal: JAMA Neurology (2017)

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Geometry as a Confounder When Assessing Ventricular Systolic Function
Authors: Thomas M. Stokke, Nina E. Hasselberg, Marit K. Smedsrud, Sebastian I. Sarvari, Kristina H. Haugaa, Otto A. Smiseth, Thor Edvardsen, Espen W. Remme
Journal: Journal of the American College of Cardiology (2017)

Preserved left ventricular (LV) ejection fraction (EF) and reduced myocardial strain are reported in patients with hypertrophic cardiomyopathy, ischemic heart disease, diabetes mellitus, and more. The authors performed a combined mathematical and echocardiographic study to understand the inconsistencies between EF and strains. An analytical equation showing the relationship between EF and the 4 parameters, global longitudinal strain (GLS), global circumferential strain (GCS), wall thickness, and short-axis diameter, was derived from an elliptical LV model. The equation was validated by measuring the 4 parameters by echocardiography in 100 subjects with EF ranging from 16% to 72% and comparing model-predicted EF with measured EF. The effect of the different parameters on EF was explored in the model and compared with findings in the patients. Calculated EF had very good agreement with measured EF (r = 0.95). The model showed that GCS contributes more than twice as much to EF than GLS. A significant reduction of GLS could be compensated by a small increase of GCS or wall thickness or reduced diameter. The model further demonstrated how EF can be maintained in ventricles with increased wall thickness or reduced diameter, despite reductions in both longitudinal and circumferential shortening. This was consistent with similar EF in 20 control subjects and 20 hypertrophic cardiomyopathy patients with increased wall thickness and reductions in both circumferential and longitudinal shortening (all p < 0.01). Reduced deformation despite preserved EF can be explained through geometric factors. Due to geometric confounders, strain better reflects systolic function in patients with preserved EF.