tbuckley/cabot-search huggingface dataset:
Global DNA methylation analysis reveals miR-214-3p contributes to cisplatin resistance in pediatric intracranial nongerminomatous malignant germ cell tumors
Authors: Tsung-Han Hsieh, Yun-Ru Liu, Ting-Yu Chang, Muh-Lii Liang, Hsin-Hung Chen, Hsei-Wei Wang, Yun Yen, Tai-Tong Wong
Journal: Neuro-Oncology (2017)

Pediatric central nervous system germ cell tumors (CNSGCTs) are rare and heterogeneous neoplasms, which can be divided into germinomas and nongerminomatous germ cell tumors (NGGCTs). NGGCTs are further subdivided into mature teratomas and nongerminomatous malignant GCTs (NGMGCTs). Clinical outcomes suggest that NGMGCTs have poor prognosis and survival and that they require more extensive radiotherapy and adjuvant chemotherapy. However, the mechanisms underlying this difference are still unclear. DNA methylation alteration is generally acknowledged to cause therapeutic resistance in cancers. We hypothesized that the pediatric NGMGCTs exhibit a different genome-wide DNA methylation pattern, which is involved in the mechanism of its therapeutic resistance.We performed methylation and hydroxymethylation DNA immunoprecipitation sequencing, mRNA expression microarray, and small RNA sequencing (smRNA-seq) to determine methylation-regulated genes, including microRNAs (miRNAs).The expression levels of 97 genes and 8 miRNAs were correlated with promoter DNA methylation and hydroxymethylation status, such as the miR-199/-214 cluster, and treatment with DNA demethylating agent 5-aza-2'-deoxycytidine elevated its expression level. Furthermore, smRNA-seq analysis showed 27 novel miRNA candidates with differential expression between germinomas and NGMGCTs. Overexpresssion of miR-214-3p in NCCIT cells leads to reduced expression of the pro-apoptotic protein BCL2-like 11 and induces cisplatin resistance.We interrogated the differential DNA methylation patterns between germinomas and NGMGCTs and proposed a mechanism for chemoresistance in NGMGCTs. In addition, our sequencing data provide a roadmap for further pediatric CNSGCT research and potential targets for the development of new therapeutic strategies.
Sorveglianza delle esposizioni professionali a patogeni a trasmissione ematica negli operatori sanitari: il programma nazionale italiano
Authors: G Ippolito, V Puro, N Petrosillo, G De Carli
Journal: Eurosurveillance (1999)

Gli operatori sanitari (OS) sono ad alto rischio di acquisire infezioni a trasmissione ematica, in particolare quella da virus dell'epatite B (HBV), da virus dell'epatite C (HCV) e da virus dell'immunodeficienza umana (HIV). Nel 1986, il centro di coordinamento dello Studio Italiano sul Rischio Occupazionale da HIV (SIROH) ha iniziato uno studio prospettico multicentrico negli OS, per valutare il rischio di trasmissione dell’ HIV e di altri patogeni a trasmissione ematica, in seguito all'esposizione professionale a sangue o ad altri materiali corporei, e per identificare strumenti, procedure e attivita lavorative a rischio in ambito assistenziale. Il centro di coordinamento ha gestito dal 1990 il registro italiano relativo alla profilassi antiretrovirale post-esposizione al fine di monitorare sia l'utilizzo che la tossicita a breve termine della zidovudina (AZT) e, dal 1995, anche della profilassi antiretrovirale con farmaci in combinazione. Questo articolo descrive le caratteristiche del SIROH e presenta alcuni risultati che ne illustrano le potenzialita applicative.
Sixty seconds on . . . concurrent surgery
Authors: Nigel Hawkes
Journal: BMJ (2017)

A single surgeon looking after two operations at the same time. It’s common in leading teaching hospitals in the US.

Some parts of an operation are more critical or difficult than others. The senior surgeon is responsible for these but may leave more routine parts to others, saving enough time to supervise an overlapping operation.

Yes, according to the Boston Globe, which has been campaigning against the practice for two years. Last week it claimed …
Paludismo importado en Alemania en 1996
Authors: L Apitzsch, Gernot Rasch, W Kiehl
Journal: Eurosurveillance (1998)

El paludismo no es endemico en Alemania, pero constituye una de las enfermedades infecciosas importadas con mayor frecuencia. El numero de casos importados ha aumentado entre 1994 y 1996 (figura 1) (1-4); en 1997, segun datos provisionales, hubo un total de 994 casos. En 1996, se declararon 1021 casos de paludismo (1,25 casos por cada 100.000 habitantes) en Alemania, un aumento global del 9% con respecto al total de 1995. Este aumento fue especialmente pronunciado en el segundo y tercer trimestre de 1996. Las mayores incidencias globales de 1996 se observaron en Berlin (121 casos; 3,49/100.000) y Hamburgo (93 casos; 5,44/100.000). En Hamburgo, mas del 60% de los casos fueron residentes no alemanes de regreso de viajes internacionales.
Quality of life (QOL) evaluation of patients in a phase 3 study comparing NEPA with an aprepitant regimen for prevention of chemotherapy-induced nausea and vomiting (CINV)
Authors: L. Zhang, S. Lu, J. Feng, A. Dechaphunkul, S. Chessari, C. Lanzarotti, K. Jordan, M. Aapro
Journal: Annals of Oncology (2017)
Efficacy of panitumumab and cetuximab in elderly patients (aged ≥75) with chemotherapy-refractory wild-type KRAS exon 2 metastatic colorectal cancer (mCRC): Retrospective analysis of data from nationwide drug-reimbursement-access program
Authors: M. Swierkowski, A. Ptak-Chmielewska, A. Sliwczynski, T. Czeleko, Z. Teter, C. Szczylik
Journal: Annals of Oncology (2017)
Molecular Adequacy of Image-Guided Rebiopsies for Molecular Retesting in Advanced Non–Small Cell Lung Cancer: A Single-Center Experience
Authors: Nadza Tokaca, Sarah Barth, Mary O’Brien, Jaishree Bhosle, Nicos Fotiadis, Andrew Wotherspoon, Lisa Thompson, Sanjay Popat
Journal: Journal of Thoracic Oncology (2017)
Genomic survey of bZIP transcription factor genes related to tanshinone biosynthesis in Salvia miltiorrhiza
Authors: Yu Zhang, Zhichao Xu, Aijia Ji, Hongmei Luo, Jingyuan Song
Journal: Acta Pharmaceutica Sinica B (2017)

Tanshinones are a class of bioactive components in the traditional Chinese medicine Salvia miltiorrhiza, and their biosynthesis and regulation have been widely studied. Current studies show that basic leucine zipper (bZIP) proteins regulate plant secondary metabolism, growth and developmental processes. However, the bZIP transcription factors involved in tanshinone biosynthesis are unknown. Here, we conducted the first genome-wide survey of the bZIP gene family and analyzed the phylogeny, gene structure, additional conserved motifs and alternative splicing events in S. miltiorrhiza. A total of 70 SmbZIP transcription factors were identified and categorized into 11 subgroups based on their phylogenetic relationships with those in Arabidopsis. Moreover, seventeen SmbZIP genes underwent alternative splicing events. According to the transcriptomic data, the SmbZIP genes that were highly expressed in the Danshen root and periderm were selected. Based on the prediction of bZIP binding sites in the promoters and the co-expression analysis and co-induction patterns in response to Ag+ treatment via quantitative real-time polymerase chain reaction (qRT-PCR), we concluded that SmbZIP7 and SmbZIP20 potentially participate in the regulation of tanshinone biosynthesis. These results provide a foundation for further functional characterization of the candidate SmbZIP genes, which have the potential to increase tanshinone production.
Activation of intracellular signaling pathways as a new type of biomarkers for selection of target anticancer drugs.
Authors: Anton Buzdin, Maxim Sorokin, Alexander Glusker, Andrew Garazha, Elena Poddubskaya, Valeriy Shirokorad, David Naskhletashvili, Kirill Kashintsev, Dmitry Sokov, Maria Suntsova, Sergey Roumiantsev, Olga Kovalchuk, Nurshat Gaifullin, Victor Tkachev, Nicolas Borisov
Journal: Journal of Clinical Oncology (2017)

e23142 Background: Anticancer target drugs (ATDs) specifically bind and inhibit molecular targets that play important roles in tumorigenesis. More than 150 different ATDs have been approved for clinical use worldwide, and the clinicians are faced with the problem of choosing the best therapeutic solution for each patient. The problem of efficient ATD selection remains largely unsolved and personalized approaches are needed to select the best ATD candidates for individual patients. Methods: We propose a new approach termed OncoFinder. It is based on digesting gene expression profiles for the analysis of activation of intracellular signalling pathways as a marker for the selection of target therapies. The original bioinformatic algorithms were integrated with the databases featuring molecular drug targets, compositions of signalling pathways, including the functional role of each gene product, for more than 1700 pathways (Buzdin, Front.Genet 2014; Ozerov, Nature Communications 2016). Results: We showed that pathway activation strengths are more stable and reliable biomarkers of cancer than the expressions of individual genes. OncoFinder allows to detect changes at the level of pathway activation and to predict the effectiveness of drugs based on the knowledge of their molecular targets. We applied it to find new biomarkers of clinical response to the ATD cetuximab; for modelling the combined chemotherapy of acute myeloid leukemia and combined anti-VEGF/BRAF therapy of melanoma. For two unrelated datasets obtained for colon cancer patients before treatment with the ATD bevacizumab, we were able to distinguish between those who responded to treatment and not (p &lt; 0.01). We next assayed biopsies for kidney cancer patients with known responses to the ATD sorafenib. The responders and non-responders showed a significant difference (p = 0.02). Finally, the OncoFinder platform was prospectively used for decision making support to patients with advanced metastatic solid tumors (n = 23). The efficiency of the ATD treatment was 61% (complete + partial response, RECIST). Conclusions: OncoFinder method may be effective for predicting response to ATD based on high throughput gene expression profiles.
Systematic Review and Meta-Analysis of Early-Life Exposure to Bisphenol A and Obesity-Related Outcomes in Rodents
Authors: Pim Nicolaas Hubertus Wassenaar, Leonardo Trasande, Juliette Legler
Journal: Environmental Health Perspectives (2017)

Early-life exposure to bisphenol A (BPA) has been implicated to play a role in the development of obesity.A systematic review with meta-analyses of experimental rodent studies was conducted to answer the following question: does early-life exposure to BPA affect the obesity-related outcomes body weight, fat (pad) weight, and circulating and tissue levels of triglycerides, free fatty acids (FFA), and leptin?The methodology was prespecified in a rigorous protocol using the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) approach. Using PubMed and EMBASE, we identified 61 articles that met the inclusion criteria. The risk of bias and the methodological quality of these articles were assessed using the SYRCLE Risk of Bias tool, and a confidence-rating methodology was used to score the quality of evidence. Meta-analyses were performed using random effect models and standardized mean differences (SMDs), or, where possible, mean differences (MDs) were calculated.Overall summary estimates indicated significant positive associations between BPA and fat weight [SMD=0.67 (95% CI: 0.53, 0.81)], triglycerides [SMD=0.97 (95% CI: 0.53, 1.40)], and FFA [SMD=0.86 (95% CI: 0.50, 1.22)], and a nonsignificant positive association with leptin levels [MD=0.37 (95% CI: -0.14, 0.87)] and a significant negative association with body weight were estimated [MD=-0.22 (95% CI: -0.37, -0.06)]. Subgroup analyses revealed stronger positive associations for most outcome measures in males and at doses below the current U.S. reference dose of 50μg/kg/d compared with doses above the reference dose. It should be noted that there was substantial heterogeneity across studies for all outcomes assessed and that there was insufficient information to assess risk of bias for most studies.Findings from our systematic review suggest that early-life exposure to BPA may increase adiposity and circulating lipid levels in rodents. https://doi.org/10.1289/EHP1233.
Genotoxicity of the histone deacetylase inhibitor trichostatin A: Evidence for both aneugenic and clastogenic effects
Authors: Andrew J. Olaharski, Zhiying Ji, Ji Young Woo, Sophia Lim, Luoping Zhang, Martyn T. Smith
Journal: Cancer Research (2006)

806  Histone deacetylase inhibitors (HDACi) are a class of putative chemotherapeutic agents for which the mechanism of toxicity remains largely unknown. The possibility that HDACis may be genotoxic has not been thoroughly investigated. To explore this possibility we exposed human lymphoblastoid TK6 cells to the HDACi trichostatin A (TSA) and analyzed various measures of genetic damage. Numerical and structural chromosomal aberrations were analyzed using the kinetochore-antibody micronucleus assay and non-banding metaphase chromosome analysis while DNA strand breaks were investigated with the alkaline comet assay. Significant increases in structural chromosomal aberrations and kinetochore-negative micronuclei were detected at the 100 and 200nM TSA doses, whereas significant levels of aneuploidy were only observed at the 200nM dose using metaphase analysis. Therefore TSA is a clastogenic agent that also induces aneuploidy via non-dysjunction in the TK6 cell line. Increased olive tail moments of TK6 cells exposed to TSA add supportive data that TSA is a DNA damaging agent. Patterns obtained from flow cytometric analysis of annexin V staining TK6 cells indicated that genotoxicity occurs in the absence of apoptosis at all but the highest concentration of TSA suggesting that the observed genotoxicity is not a byproduct of apoptosis, but rather may be the cause of it. Flow cytometric analysis of asynchronous TK6 cells stained with propidium iodide demonstrated that TSA causes a G1 arrest prior to the occurrence of apoptosis, further evidence to indicate that TSA is a genotoxic agent. Current studies are focusing on the temporal relationship between the TSA-induced genotoxicity, cell cycle arrest, and apoptotic signals to identify if the apoptosis is due to a genotoxic-dependent or -independent mechanism. We conclude that TSA causes both chromosomal breakage and non-dysjunction in TK6 cells and postulate that the TSA-induced apoptosis observed at high doses may partially be due to this genotoxicity.
Subsequent therapies post-afatinib among patients (pts) with EGFR mutation-positive (EGFRm+) NSCLC in LUX-Lung (LL) 3, 6 and 7
Authors: L. Sequist, Y.-L. Wu, M. Schuler, T. Kato, J.C.-H. Yang, H. Tanaka, T. Hida, S. Lu, K. Park, S. Laurie, J. Bennouna, D. Moro Sibilot, A. Märten, B. Peil, E. Ehrnrooth, N. Yamamoto, K. Nakagawa
Journal: Annals of Oncology (2017)
Analytic validation of a next generation sequencing assay to identify tumor mutational burden from blood (bTMB) to support investigation of an anti-PD-L1 agent, atezolizumab, in a first line non-small cell lung cancer trial (BFAST)
Authors: D. Fabrizio, C. Malboeuf, D. Lieber, S. Zhong, J. He, E. White, M. Coyne, J. Silterra, T. Brennan, J. Ma, M. Kennedy, E. Schleifman, S.M. Paul, Y. Li, D.S. Shames, C.A. Cummings, E. Peters, M. Kowanetz, D. Lipson, G. Otto
Journal: Annals of Oncology (2017)
Serial genotypic characterization of circulating tumor cells (CTCs) in patients with metastatic castration resistant prostate cancer (mCRPC) undergoing treatment with abiraterone acetate (abi) or enzalutamide (enza)
Authors: N. Dizman, J. Patel, M. He, B. Foulk, D.A. Smirnov, J. Hsu, P. Twardowski, M. Kortylewski, V. Bhargava, J. Jones, S.K. Pal
Journal: Annals of Oncology (2017)
Metronomic chemotherapy (mCHT) in HER2-ve advanced breast cancer (ABC) patients (pts): Old drugs, new opportunities Preliminary results of the VICTOR-6 study
Authors: M. Cazzaniga, K. Cagossi, M.R. Valerio, S. Russo, V. Casadei, G. Scognamiglio, L. Cavanna, D. Toniolo, E. De Conciliis, E. Melegari, L. Stocchi, V. Gebbia, A.M. Vandone, M.C. Cursano, G. Pinotti, R. Rossello, S. Ortu, B. Pellegrino, S. Saracchini, V. Torri
Journal: Annals of Oncology (2017)
Safety and immunogenicity of a DNA-vaccine immunotherapy in men with biochemically (PSA) relapsed prostate cancer
Authors: N.D. Shore, E. Heath, L. Nordquist, H. Cheng, K. Bhatt, M. Morrow, T. McMullan, K. Kraynyak, J. Lee, B. Sacchetta, L. Liu, S. Rosencranz, S.T. Tagawa, R.A. Parikh, R. Tutrone, J. Garcia, Y. Whang, W. Kelly, I. Csiki, M. Bagarazzi
Journal: Annals of Oncology (2017)
Dose-finding combination study of niraparib and pembrolizumab in patients (pts) with metastatic triple-negative breast cancer (TNBC) or recurrent platinum-resistant epithelial ovarian cancer (OC) (TOPACIO/Keynote-162)
Authors: P.A. Konstantinopoulos, J.C. Sachdev, L. Schwartzberg, U.A. Matulonis, P. Sun, J.Y. Wang, W. Guo, D. Bobilev, G. Aktan, V. Karantza, B. Dezube, S. Vinayak
Journal: Annals of Oncology (2017)
Phase II study of everolimus (EV) and bevacizumab (BEV) in recurrent ovarian, peritoneal, and fallopian tube cancer.
Authors: Sarah E Taylor, Tianjiao Chu, Robert P. Edwards, Kristin Kelley Zorn
Journal: Journal of Clinical Oncology (2016)

5552 Background: Recurrent ovarian, fallopian tube, and peritoneal cancers have limited potential for cure with traditional therapies. Combining agents that target angiogenesis through different mechanisms has the potential to improve response. Preliminary results from a phase I study of EV and BEV in advanced solid tumors showed it to be a promising combination. The primary objective of this study is to evaluate the 6 month progression-free survival for EV and BEV in recurrent ovarian, peritoneal, and fallopian tube cancer. Secondary objectives include evaluation of efficacy, safety and tolerability. Methods: In this open-label, single-institution, phase II trial, patients received EV 10 mg/day by mouth and BEV 10 mg/kg intravenously every 14 days. Cycles were 28 days. Every 8 weeks, patients underwent imaging to assess response. Treatment continued until disease progression or adverse event. Patients who discontinued treatment due to progression or adverse event were followed for an additional 90 days to complete assessment of toxicity from study drugs. Results: Fifty eligible patients were enrolled and evaluated with a median age of 60.5 years (range 28-82). 92% of subjects had measurable disease at the start of the trial. Although analysis of the data is ongoing, 14/50 (28%) were progression-free at 6 months (95% CI 16.67-42.71%). The majority of patients had stable disease as their best response, but there were also both complete and partial responses. Patient with platinum-sensitive and -resistant disease showed response, as did those both with and without prior BEV exposure. Overall, the regimen was well-tolerated, with 5 (0.65%) grade 4 and 66 (8.64%) grade 3 toxicities. The most common reported toxicities included oral mucositis, fatigue, abdominal pain, diarrhea, nausea and hypertension. Most patients came off of study because of progression of disease. Conclusions: Combining agents that target angiogenesis through different mechanisms, such as EV and BEV, is overall well-tolerated. Response to the combination is not distinctly improved compared to bevacizumab alone. Our ongoing translational analysis might identify those who would benefit most from combination. Clinical trial information: NCT01031381.
Myocardial Perfusion SPECT and Cardiac MR Correlative Imaging
Authors: Ashley E. Prosper, Patrick M. Colletti
Journal: Clinical Nuclear Medicine (2017)

An institutional review board-approved retrospective review of 55 patients who received cardiac MRI within 1 year of myocardial SPECT was performed. Forty-nine demonstrated myocardial infarction by MRI. MRI and SPECT agreed in all but 1 case, where SPECT preceded MRI by 97 days. Three cases are presented here: 2 demonstrating congruent MRI and SPECT changes in a vascular distribution status post infarction and a third with a nonvascular pattern of abnormalities related to left ventricular aneurysm in cardiac sarcoidosis. It is useful to review and correlate myocardial SPECT with available cardiac MRI, especially in patients with matching perfusion defects.
Checkpoint inhibitors in metastatic renal cell carcinoma patients including elderly subgroups: Results from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC).
Authors: Steven Yip, Connor Wells, Raphael Brandao Moreira, Alex Wong, Sandy Srinivas, Benoit Beuselinck, Camillo Porta, Hao-Wen Sim, D. Scott Ernst, Brian I. Rini, Takeshi Yuasa, Naveen S. Basappa, Ravindran Kanesvaran, Lori Wood, Christina M. Canil, Anil Kapoor, Simon Yuen Fai Fu, Toni K. Choueiri, Daniel Yick Chin Heng
Journal: Journal of Clinical Oncology (2017)

4580 Background: Immuno-oncology (IO) checkpoint inhibitor treatment outcomes are poorly characterized in the real world metastatic renal cell cancer (mRCC) patient population, including geriatric patients. Methods: Using the IMDC database, a retrospective analysis was performed on mRCC patients treated with IO, as listed below. Patients received one or more lines of IO therapy, with or without a targeted agent. Duration of treatment (DOT) and overall response rates (ORR) were calculated. Cox regression analysis was performed to examine the association between age as a continuous variable and DOT. Results: 312 mRCC patients treated with IO were included. In patients who were evaluable, ORR to IO therapy was 29% (32% first-, 22% second-, 33% third-, and 32% fourth-line treatment (Tx)). Patients treated with second-line IO therapy were divided into favorable, intermediate, and poor risk using IMDC criteria; the corresponding median DOT rates were not reached (NR), 8.6 mo, and 1.9 mo, respectively (p&lt;0.0001). Based upon age, hazard ratios were calculated in the first- through fourth-line therapy setting, ranging from 1.03 to 0.97. Conclusions: The ORR to IO appears to remain consistent, regardless of line of therapy. In the second-line, IMDC criteria appear to appropriately stratify patients into favorable, intermediate, and poor risk groups for DOT. Premature OS data will be updated. In contrast to clinical trial data, longer DOT is observed in real world practice. Age may not be a factor influencing DOT. [Table: see text]
Malária dos aeroportos: quatro novos casos nos subúrbios de Paris, durante o Verão de 1999
Authors: D Lusina, F Legros, V Estève, M Klerlein, T Giacomini
Journal: Eurosurveillance (2000)

Em Franca, durante o Verao de 1999, foi observado um aglomerado de quatro casos de malaria dos aeroportos. A analise dos casos revelou que a malaria dos aeroportos, uma doenca rara e de dificil diagnostico, pode ser observada fora das profissoes de risco, em pessoas residentes proximo de aeroportos. Esta analise salienta igualmente a importância do cumprimento das instrucoes de tratamento contra insectos nos avioes provenientes das zonas endemicas de malaria, e a importância das caracteristicas hematologicas indirectas da doenca, especialmente a trombocitopenia.
Meta-Analysis of Anti-PD-1/PD-L1 Therapy Related Adverse Events in Clinical Trials
Authors: Y. Wang, X. Wang, F. Yang, X. Guan, N. Duma, J. Vera Aguilera, G.S. Nowakowski, A.V. Chintakuntlawar, K.A. Price, J.R. Molina, T.R. Halfdanarson, A. Grothey, S.N. Markovic
Journal: Annals of Oncology (2017)
Circulating tumour DNA (ctDNA) in the clinical management of patients (pts) with advanced non-small cell lung cancer (NSCLC): A single centre experience
Authors: M. Uccello, M. Kushnir, G. Mak, C. Murias Henriquez, C. Abbosh, D. Papadatos-Pastos, T. Newsom-Davis, T. Ahmad, C. Swanton, M. Forster, R. Lanman, I. Faull, H-T. Arkenau
Journal: Annals of Oncology (2017)