tbuckley/cabot-search huggingface dataset:
Predicting erlotinib resistance in EGFR wild type NSCLC patients.
Authors: Peter Buhl Jensen, Steen Knudsen, Anker Hansen, Thomas Jensen, Jon Askaa
Journal: Journal of Clinical Oncology (2013)

e22065 Background: Cancer patients with wild type EGFR respond to treatment with erlotinib at a lower rate than patients with EGFR mutations. It would be relevant to predict which EGFR wild type patients benefit from erlotinib. We have developed a response predictor based on NCI60 cancer cell lines measurements of erlotinib effect and gene expression measurements. Clinical relevance was improved by filtering the model through expression profiles from more than 3,000 clinical samples.The erlotinib response predictor consists of 94 sensitivity genes and 10 resistance genes and is completely defined before independent validation on patients treated with erlotinib. Methods: Gene expression data from pre-treatment core biopsies from 25 patients with refractory NSCLC (clinicaltrials.gov: NCT00409968) later treated with erlotinib (The BATTLE trial; Kim, ES et al. Cancer Discov. 2011; 1:44-53) were downloaded from Gene Expression Omnibus with accession number GSE33072. PFS after erlotinib treatment was recorded. The erlotinib response predictor was applied retrospectively to the gene expression measurements.Patients with a predicted sensitivity above the 0.15 quantile were categorized as sensitive, patients with a predicted sensitivity below were categorized as resistant.The median was also tested as a cutoff, and correction for multiple testing was taken into consideration. Results: In a Kaplan-Meier analysis of PFS comparing predicted sensitive and predicted resistant patients, the predicted sensitive patients survived longer (PFS 2.3 months (1.9-2.7)) than predicted resistant patients (PFS 1.2 months (0.5-1.8)). A log-rank test for PFS found the difference significant (p=0.005). Hazard ratio 4.6 (1.4-15.2). Conclusions: The small clinical data set validated the cell line derived erlotinib response predictor. It identified a subset of 16% of patients with no apparent benefit from erlotinib. We have performed similar validations for 24 other response predictors in 24 clinical trials. In 20 out of the 24 clinical trials, the agreement between prediction and clinical outcome was statistically significant. Thus, our cell line based method represents a general method for predicting clinical response to cytotoxic or cytostatic agents.
Epigenetic aging clocks in mice and men
Authors: Wolfgang Wagner
Journal: Genome biology (2017)

Epigenetic clocks provide powerful tools to evaluate nutritional, hormonal, and genetic effects on aging. What can we learn from differences between species in how these clocks tick?Please see related Research articles: http://genomebiology.biomedcentral.com/articles/10.1186/s13059-017-1203-5 , http://genomebiology.biomedcentral.com/articles/10.1186/s13059-017-1186-2 , http://genomebiology.biomedcentral.com/articles/10.1186/s13059-017-1187-1 and http://genomebiology.biomedcentral.com/articles/10.1186/s13059-017-1185-3.
Résultats de la coloscopie réalisée après test Hémoccult positif: bilan d'une première campagne départementale de dépistage du cancer colorectal
Authors: S Manfredi, C Piette, G Durand, G Plihon, G Mallard, JF Bretagne
Journal: Endoscopy (2006)

Le but de cette étude a été d'établir le bilan des coloscopies effectuées dans notre département à, l'occasion de la 1ère campagne de dépistage de masse du cancer colorectal.
Bortezomib-Melphalan-Prednisone (VMP) Versus MP As Initial Treatment for Patients Older Than 75 Years with Newly Diagnosed Multiple Myeloma
Authors: Min Kyoung Kim, Kihyun Kim, Dok Hyun Yoon, Cheolwon Suh, Jae Hoon Lee, Sung-Hoon Jung, Je-Jung Lee, Hyo Jung Kim, Jin Seok Kim, Jeong-Ok Lee, Hyeon Seok Eom, Won Sik Lee, Yeung-Chul Mun, Young Rok Do, Hye Jin Kang
Journal: Blood (2016)
Biomarker Profiles of Acute Heart Failure Patients With a Mid-Range Ejection Fraction
Authors: Jasper Tromp, Mohsin A.F. Khan, Robert J. Mentz, Christopher M. O’Connor, Marco Metra, Howard C. Dittrich, Piotr Ponikowski, John R. Teerlink, Gad Cotter, Beth Davison, John G.F. Cleland, Michael M. Givertz, Daniel M. Bloomfield, Dirk J. Van Veldhuisen, Hans L. Hillege, Adriaan A. Voors, Peter van der Meer
Journal: JACC Heart Failure (2017)
Comprehensive Analysis of EGFR-Mutant Abundance and Its Effect on Efficacy of EGFR TKIs in Advanced NSCLC with EGFR Mutations
Authors: Xuefei Li, Weijing Cai, Guohua Yang, Chunxia Su, Shengxiang Ren, Chao Zhao, Rongjun Hu, Xiaoxia Chen, Guanghui Gao, Zhiwei Guo, Wei Li, Caicun Zhou, Fred R. Hirsch
Journal: Journal of Thoracic Oncology (2017)
Survival length differences in non-metastatic breast cancer patients with different chemo-radiation time intervals.
Authors: Ruaa Al-Ward, Wajdi Al Shweiat, Talasila Lakshmi, Sandeep Singh Grewal, Perla Subbaiah, Smit Singla, Susan Smith, Radhika Kakarala
Journal: Journal of Clinical Oncology (2017)

e12096 Background: Chemotherapy-radiotherapy time intervals (CRTI) in breast cancer vary based on recovery from chemotherapy side effects and preferences of physicians and patients. Our study aimed to determine the association of the time-interval between chemotherapy and radiation with prognosis (recurrence and survival duration) in non-metastatic breast cancer patients (stages I-III). Methods: We included female patients from Karmanos Cancer Center (KCC) database &gt; 21 years, diagnosed with non-metastatic breast cancer from 2005-2015, who underwent surgery, chemotherapy and radiation. CRTI was divided into &lt;24, 24-30 and &gt;30 weeks. Cox regression analysis using age, race, stage, grade, ER/PR status and CRTI variables was done to determine the independent predictors of prognosis. Kaplan-Meier survival curves were used to demonstrate differences in survival time of CRTI groups. Results: We included 553 patients, majority were Caucasian (460 [83.5%]) with a mean age of 57.0 years (SD 11.9). Patients in the &gt;30 weeks CRTI group were more likely to have stage III breast carcinoma when compared to &lt;24 and 24-30 weeks groups (45.0% vs.12.4% vs. 27.8%, p-value &lt;0.001). There were no significant differences in the local and distant recurrence rates among the 3 groups. Patients in &lt;24 weeks CRTI group had a greater mean survival (118.7 vs. 109.2 vs.100.9 months; p-value 0.016) when compared to 24-30 and &gt;30 weeks groups. Only clinical stage (stage 3 vs. 1 HR 3.60; 95% CI 1.89-7.02) and ER/PR status (negative vs. positive HR 1.74; 95% CI 1.02-2.94) were independent predictors of overall survival in multivariate analysis. CRTI was not significantly associated with survival in multivariate analysis (&lt;24 weeks ref, 24-30 weeks HR 1.09; 95% CI 0.59-1.93, &gt;30 weeks HR 1.48; 95% CI 0.82-2.59). However, patients in &gt;30 weeks group were at greater risk of dying when compared to &lt;24 weeks, even after controlling for stage. Conclusions: Our study showed a trend towards a worse outcome in patients with longer chemo-radiation interval, despite controlling for other variables in the multivariate analysis. The conclusions of this single center study need to be verified by further studies with larger sample size.
What tests and measures should be added to the SCAT3 and related tests to improve their reliability, sensitivity and/or specificity in sideline concussion diagnosis? A systematic review
Authors: Ruben J Echemendia, Steven P Broglio, Gavin A Davis, Kevin M Guskiewicz, K. Alix Hayden, John J Leddy, William P Meehan, Margot Putukian, S John Sullivan, Kathryn J Schneider, Paul McCrory
Journal: British Journal of Sports Medicine (2017)

Several iterations of the Sport Concussion Assessment Tool (SCAT) have been published over the past 16 years. Our goal was to systematically review the literature related to the SCAT and provide recommendations for improving the tool. To achieve this goal, five separate but related searches were conducted and presented herein.Systematic literature review.Medline, Embase, PsycINFO, Cumulative Index of Nursing and Allied Health Literature (CINAHL), Cochrane Central Register of Controlled Trials, SPORTDiscus and PubMed.Original, empirical, peer-reviewed findings published in English and included sports-related concussion (SRC). Review papers, case studies, editorials and conference proceedings/abstracts were excluded. The age range for the ChildSCAT was 5-12 years and for the Adult SCAT was 13 years and above.Out of 2961 articles screened, a total of 96 articles were included across the five searches. Searches were not mutually exclusive. The final number of articles included in the qualitative synthesis for each search was 21 on Adult SCAT, 32 on ChildSCAT, 21 on sideline, 8 on video/observation and 14 on oculomotor.The SCAT is the most widely accepted and deployable sport concussion assessment and screening tool currently available. There is some degree of support for using the SCAT2/SCAT3 and ChildSCAT3 in the evaluation of SRC, with and without baseline data. The addition of an oculomotor examination seems indicated, although the most valid method for assessing oculomotor function is not clear. Video-observable signs of concussion show promise, but there is insufficient evidence to warrant widespread use at this time.
Association of Preoperative Anti–Tumor Necrosis Factor Therapy With Adverse Postoperative Outcomes in Patients Undergoing Abdominal Surgery for Ulcerative Colitis
Authors: Audrey S. Kulaylat, Afif N. Kulaylat, Eric W. Schaefer, Andrew Tinsley, Emmanuelle Williams, Walter Koltun, Christopher S. Hollenbeak, Evangelos Messaris
Journal: JAMA Surgery (2017)

Despite the increasing use of anti-tumor necrosis factor (TNF) therapy in ulcerative colitis, its effects on postoperative outcomes remain unclear, with many patients requiring surgical intervention despite optimal medical management.To assess the association of preoperative use of anti-TNF agents with adverse postoperative outcomes.This analysis used insurance claims data from a large national database to identify patients 18 years or older with ulcerative colitis. These insured patients had inpatient and/or outpatient claims between January 1, 2005, and December 31, 2013, with Current Procedural Terminology codes for a subtotal colectomy or total abdominal colectomy, a total proctocolectomy with end ileostomy, or a combined total proctocolectomy and ileal pouch-anal anastomosis. Only data regarding the first or index surgical admission within the time frame were abstracted. Use of anti-TNF agents, corticosteroids, and immunomodulators within 90 days of surgery was identified using Healthcare Common Procedure Coding System codes. Inclusion in the study required the patient to have an International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis code for ulcerative colitis. Exclusion occurred if the patient had a secondary ICD-9-CM diagnosis code for Crohn disease or if the patient was not continuously enrolled in an insurance plan for at least 180 days before and after the index surgery. Data were collected and analyzed from February 1, 2015, to June 2, 2016.Outcomes included 90-day complications, emergency department visits, and readmissions. Multivariable logistic regression was used to model covariates, including anti-TNF agent use, on the occurrence of outcomes.Of the 2476 patients identified, 1379 (55.7%) were men, and the mean (SD) age was 42.1 (12.9) years. Among these, 950 (38.4%) underwent subtotal colectomy or total abdominal colectomy, 354 (14.3%) underwent total proctocolectomy with end ileostomy, and 1172 (47.3%) received ileal pouch-anal anastomoses. In univariate analyses, increased postoperative complications were observed among patients in the ileal pouch cohort who received anti-TNF agents preoperatively vs those who did not (137 [45.2%] vs 327 [37.6%]; P = .02) but not among those in the colectomy or proctocolectomy cohorts. An increase in complications was also observed on multivariable analyses among patients in the ileal pouch cohort (odds ratio, 1.38; 95% CI, 1.05-1.82).Unlike preoperative anti-TNF agent use among patients who underwent colectomy or total proctocolectomy and experienced no significant increase in postoperative complications, anti-TNF agent use within 90 days of surgery among patients who underwent ileal pouch-anal anastomosis was associated with higher 90-day postoperative complication rates.
Ingenol mebutate for the management of genital warts in sensitive anatomic locations
Authors: Stephan Alexander Braun, Peter Arne Gerber
Journal: Journal of the American Academy of Dermatology (2017)

Genital warts (GW) are highly prevalent in sexually active populations and have a severe impact on patient quality of life.1Lacey C.J. Woodhall S.C. Wikstrom A. et al.2012 European guideline for the management of anogenital warts.J Eur Acad Dermatol Venereol. 2013; 27: e263-e270Crossref PubMed Scopus (125) Google Scholar Ablative therapy in sensitive anatomic areas such as the external urethral orifice, the corona of glans penis, and the anal mucosa is challenging and painful and can often only be administered under general anaesthesia. We applied ingenol mebutate (IM) gel (Picato, 0.05%, LeoPharma, Balerup, Denmark) for the treatment of GW in sensitive anatomic locations. Shown are 2 cases of patients with GW at the corona of glans penis and the peri- and intra-anal skin (Fig 1). A small drop of IM gel was applied onto all visible warts and air-dried for 15 minutes. After 24 hours, both patients reported pain and a greyish discoloration of the warts, which indicated wart necrosis. The pain was easily managed with ibuprofen and completely resolved within 24 hours. After 48 hours, all treated warts were ablated and the eroded dermatitis resolved within 1 week with a satisfying cosmetic outcome and no signs of scaring. No recurrences have been observed in a 3-month follow-up period. To conclude, our observations suggest that IM might be a novel and fast pharmacologic option to ablate GW in critical anatomic areas without local or general anaesthesia. More intense pain might be experienced by some patients, particularly by those with large lesions in the perianal area. Recurrence rates are unknown. It should be noted that IM is considerably more expensive in the United States than in Germany, where the authors practice.
A single nucleotide polymorphism in the<i>NCF1</i>gene leading to reduced oxidative burst is associated with systemic lupus erythematosus
Authors: Lina M Olsson, Åsa C Johansson, Birgitta Gullstrand, Andreas Jönsen, Saedis Saevarsdottir, Lars Rönnblom, Dag Leonard, Jonas Wetterö, Christopher Sjöwall, Elisabet Svenungsson, Iva Gunnarsson, Anders A Bengtsson, Rikard Holmdahl
Journal: Annals of the Rheumatic Diseases (2017)

Ncf1 polymorphisms leading to low production of reactive oxygen species (ROS) are strongly associated with autoimmune diseases in animal models. The human NCF1 gene is very complex with both functional and non-functional gene copies and genotyping requires assays specific for functional NCF1 genes. We aimed at investigating association and function of the missense single nucleotide polymorphism (SNP), rs201802880 (here denoted NCF1-339) in NCF1 with systemic lupus erythematosus (SLE).We genotyped the NCF1-339 SNP in 973 Swedish patients with SLE and 1301 controls, using nested PCR and pyrosequencing. ROS production and gene expression of type 1 interferon-regulated genes were measured in isolated cells from subjects with different NCF1-339 genotypes.We found an increased frequency of the NCF1-339 T allele in patients with SLE, 11% compared with 4% in controls, OR 3.0, 95% CI 2.4 to 3.9, p=7.0×10-20. The NCF1-339 T allele reduced extracellular ROS production in neutrophils (p=0.004) and led to an increase expression of type 1 interferon-regulated genes. In addition, the NCF1-339 T allele was associated with a younger age at diagnosis of SLE; mean age 30.3 compared with 35.9, p=2.0×1-6.These results clearly demonstrate that a genetically controlled reduced production of ROS increases the risk of developing SLE and confirm the hypothesis that ROS regulate chronic autoimmune inflammatory diseases.
Abstract 166: Endothelial Overexpression of LOX-1 Increases Stroke Size in vivo
Authors: Alexander Akhmedov, Remo D Spescha, Francesco Paneni, Giovani G Camici, Thomas F Luescher
Journal: Circulation Research (2013)

Background— Stroke is one of the most common causes of death and long term disability worldwide primarily affecting the elderly population. Lectin-like oxidized LDL receptor 1 (LOX-1) is the receptor for oxidized LDL identified in endothelial cells. Binding of OxLDL to LOX-1 induces several cellular events in endothelial cells, such as activation of transcription factor NF-kB, upregulation of MCP-1, and reduction in intracellular NO. Accumulating evidence suggests that LOX-1 is involved in endothelial dysfunction, inflammation, atherogenesis, myocardial infarction, and intimal thickening after balloon catheter injury. Interestingly, a recent study demonstrated that acetylsalicylic acid (aspirin), which could prevent ischemic stroke, inhibited Ox-LDL-mediated LOX-1 expression in human coronary endothelial cells. The expression of LOX-1 was increased at a transient ischemic core site in the rat middle cerebral artery occlusion model. These data suggest that LOX-1 expression induces atherosclerosis in the brain and is the precipitating cause of ischemic stroke. Therefore, the goal of the present study was to investigate the role of endothelial LOX-1 in stroke using experimental mouse model. Methods and Results— 12-week-old male LOX-1TG generated recently in our group and wild-type (WT) mice were applied for a transient middle cerebral artery occlusion (MCAO) model to induce ischemia/reperfusion (I/R) brain injury. LOX-1TG mice developed 24h post-MCAO significantly larger infarcts in the brain compared to WT (81.51±8.84 vs. 46.41±10.13, n=7, p &lt; 0.05) as assessed morphologically using Triphenyltetrazolium chloride (TTC) staining. Moreover, LOX-1TG showed higher neurological deficit in RotaRod (35.57±8.92 vs. 66.14±10.63, n=7, p &lt; 0.05) and Bederson tests (2.22±0.14 vs. 1.25±0.30, n=9-12, p &lt; 0.05) - two experimental physiological tests for neurological function. Conclusions— Thus, our data suggest that LOX-1 plays a critical role in the ischemic stroke when expressed at unphysiological levels. Such LOX-1 -associated phenotype could be due to the endothelial dysfunction. Therefore, LOX-1 may represent novel therapeutic targets for preventing ischemic stroke.
Chronic but not Acute Treatment with Conjugated Linoleic Acid (CLA) Isomers (CIS-9, Trans-11 CLA and Trans-10, CIS-12 CLA) Inhibit DCA-Induced Protein Kinase C and NF-KB Activation in Humans Colorectal Cancer Cells
Authors: SA Shah, N Mahmud, M Muftah, H Roche, D Kelleher
Journal: Endoscopy (2004)

Background: High dietary fat is known to increase the risk of colorectal cancer in while conjugated linoleic acids (CLA) are reported to inhibit cancer growth. Deoxycholic acid (DCA) is known to activate protein kinase C (PKC) isoenzymes and NF-κB. The aim of study was to examine the effects of CLA on DCA-induced PKC and NF-κB signalling in colon cancer.
The Role of MYC and BCL-2 Double Expression the in DLBCL Patients with Advanced Stage and Elevated LDH Who Received Upfront ASCT after R-CHOP
Authors: Yu Ri Kim, Sun Och Yoon, Soo-Jeong Kim, June-Won Cheong, Hyewon Lee, Haerim Chung, Jung Yeon Lee, Ji Eun Jang, Yundeok Kim, Woo-Ick Yang, Yoo-Hong Min, Jin Seok Kim
Journal: Blood (2016)
The zebrafish embryonic model allows the exploration of human melanoma cell plasticity
Authors: Lisa M. J. Lee, Elisabeth A. Seftor, Gregory Bonde, Robert Cornell, Mary J. C. Hendrix
Journal: Cancer Research (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

1059 

Certain aggressive melanoma cell lines exhibit a dedifferentiated phenotype, expressing multiple molecular markers that are specific for various cell types including endothelial, neural, and even stem cells. These cells are able to participate in vasculogenic mimicry in vitro and respond to ischemic microenvironmental cues by participating in neovascularization in vivo . We examined the potential plasticity of human metastatic melanoma cells by exposing them to a developmental microenvironment in zebrafish embryos. The data reveal that the zebrafish embryos make a powerful model system in which to investigate tumor-microenvironment interactions and tumor cell plasticity. We show here that fluorescently labeled human metastatic melanoma cells transplanted into zebrafish embryos survive for up to two weeks, exhibit motility, seem to proliferate and most importantly, are no longer tumorigenic. The data also show that normal human melanocytes and fibroblasts transplanted into the zebrafish embryos also survive, but do not exhibit motility or proliferation. We also show that the localization pattern of melanoma cells within the zebrafish is significantly different than that of melanocytes or fibroblasts, which seem to home to their native microenvironments of skin and connective tissues, respectively. Although metastatic melanoma cells in zebrafish embryos are no longer tumorigenic, the dedifferentiated phenotype of metastatic melanoma cells remain unchanged. These results demonstrate the powerful influence of the embryonic microenvironment on the tumorigenicity of metastatic melanoma cells and the ability of melanoma cells to adapt to the developmental cues accordingly.
10 year outcomes from a single-centre experience of sunitinib and pazopanib as first-line treatment of metastatic renal-cell carcinoma (mRCC).
Authors: Shien Chow, Manon Rhys Pillai, Victoria Galvis, Rebecca Leach, Elizabeth Keene, Kevin Chan, Andrea Spencer-Shaw, Fiona Thistlethwaithe, Robert E. Hawkins
Journal: Journal of Clinical Oncology (2016)

e16085 Background: Sunitinib (S) and Pazopanib (P) have become the standard of care in the management of mRCC supported by clear therapeutic benefits in clinical trials. We set out to evaluate and compare the efficacy and survival outcomes of these two agents used in our centre. Methods: mRCC patients who received either these agents as first line treatment both in standard clinical (n=577) or trial (n=88) setting in our centre (2005-2015) were identified through the Renal Cancer Database. Outcomes of interest include response rate PFS and particularly long-term survival. Subgroup analysis were performed based on prognostic variables to assess survival impact. Results: A total of 665 patients were identified (S=397, P=268). Baseline demographic were balanced between the groups but there were more patients with poorer performance status (PS 2-3) and prognostic risk categories (MSKCC Memorial Sloan Kettering Cancer Centre and Heng et al 2009) in P than in S group at 31% v 19% and 21% v 15% respectively. Overall nephrectomy rate was 62%. Median PFS and OS of the entire cohort were 10.0 and 16.1 months respectively. The objective response rate (ORR) was 22% of which 2% were complete responses. Conclusions: With limitation of a retrospective audit, there were no intergroup difference in efficacy. Observation of tumour responses in general was lower than in COMPARZ (Motzer et al 2013). PFS for both groups were comparable to that seen in the COMPARZ study Benefit of both agents were impressive in the good prognostic risk group similar to trial data. For the intermediate and poor risk groups, the outcomes were poor probably a reflection of adverse factors in this relatively unselected group. This more representative population included a relatively high proportion of poor-prognosis patients and the poor outcomes in these patients suggest other treatment should be investigated. Survival analysis based on MSKCC risk group stratification. Pazopanib Sunitinib ORR 20 % 25% Median PFS (months) 19.1 21.3 Good 8.1 9.9 Intermediate 3.6 3.7 Poor Median OS (months) 47.3 36.3 Good 15.0 16.3 Intermediate 5.2 5.3 Poor