tbuckley/cabot-search huggingface dataset:
Using proton MRSI to predict response to vorinostat treatment in recurrent GBM.
Authors: Hyunsuk Shim, Alfredo Daniel Voloschin, Li Wei, Scott N Hwang, Andrew H. Miller, Ying Guo, Daniel Brat, Chad A Holder, William L. Read, Katarzyna Kopcewicz, R. Donald Harvey, Peter Barker, Hui-Kuo George Shu, Xioaping P Hu, Jeffrey J. Olson
Journal: Journal of Clinical Oncology (2012)

3055 Background: A major impediment to the development of new therapies for glioblastoma (GBM) is a lack of biomarkers indicating response. Epigenetic modifications are now recognized as a frequent occurrence in the early phases of tumorigenesis, playing a central role in tumor development. Epigenetic alterations differ significantly from genetic modifications in that they may be reversed by ‘‘epigenetic drugs’’ such as histone deacetylase inhibitors (HDACis). As a promising new modality for cancer therapy, the first generation of HDACi is currently being tested in phase I/II clinical trials. Methods: GBM alterations from therapy with HDACis, such as vorinostat (SAHA), include tumor redifferentiation/cytostasis rather than tumor size reduction limits the utility of traditional imaging methods such as MRI. Magnetic resonance spectroscopic imaging (MRSI) quantitates various metabolite levels in tumor and normal brain, allowing characterization of metabolic processes in live tissue. Results: In our preclinical model, MRS detected metabolic response to SAHA after only 3 days of treatment: reduced alanine and lactate and elevated myo-inositol, N-acetyl aspartate and creatine; each returning toward normal brain levels. This led to our clinical study of MRSI to evaluate the metabolic response of recurrent GBMs to SAHA + temozolomide. After only 7 days of SAHA treatment, MRSI can distinguish metabolic responders (normalization/restoration of tumor metabolites towards normal brain-like metabolism) from non-responders (no significant change in tumor metabolites). Our initial cohort (n=6) consists of 3 responders and 3 non-responders with highly significant differences in their change in metabolite levels (p &lt; 0.001). Conclusions: Our results provide exciting insights into the mechanisms by which HDACi exerts its effect on GBMs. Tumor cells have increased biosynthetic needs requiring reprogramming of cellular metabolism. This creates increased energy demands, making tumor cells even more vulnerable to interventions targeting their metabolism. HDACi may induce redifferentiation in tumors by targeting tumor metabolism. Thus, MRSI provides a novel modality to predict response to HDACi-containing combination therapy in GBM.
P0279 : SLC25A11 promotes cell proliferation in hepatocellular carcinoma spheroids and orthotopic tumor growth
Authors: A. Baulies, D. Robles, D. Babu Uthaya Kumar, K. Machida, H. Tsukamoto, C. García-Ruiz, J.C. Fernández-Checa
Journal: Journal of Hepatology (2015)
Five years update of sequential high dose doxorubicin, cyclophosphamide and docetaxel in inflammatory breast cancer; PEGAGE05 trial on behalf of FNLCC
Authors: T. Palangie, P. Pouillart, H. Roche, P. Viens, C. Linassier
Journal: Journal of Clinical Oncology (2006)

10773 Background: Inflammatory breast carcinoma is a distinct clinicopathologic entity with poor survival outcome. Early response to initial chemotherapy was reported as predictive for survival and complete pathological response is considered as a major prognostic factor. This study was conducted to determine the safety and to estimate the efficacy of sequential high dose chemotherapy with doxorubicine (D) + cyclophosphamide (CPM) and docetaxel (Doc), in terms of pathological response, disease-free and overall survival Methods: Fifty-four patients entered into the trial from July 1997 to March 1999; treatment consisted in four 3 weekly cycles of D75 mg/m 2 + CPM 6 g/m 2 in C1 and C2; Doc 100 mg/m 2 q 2w in C3, C4 and C6; D75 mg/m 2 + CPM3 g/m 2 in C6 and C7. Mastectomy with axillary dissection was performed for responding patients, followed by radiotherapy. Results: An interim analysis showed the same efficacy reported in previous high dose chemotherapy trial Pegase 02, without Docetaxel, and unexpected toxicity with 2 toxic deaths that warranted an early closure of the trial The overall 35% [22.5%–47.9%] grade 1 or 2 pathological response according to Chevallier as compared to the 32% reported in the Pagase 02 trial, suggest no greater efficacy for additionel Docetaxel to high dose D + CPM Five-year disease-free survival and overall survival showed a better tendency in Pegase 05 trial, with respectively 42% and 62% as compared to Pegase 02 trial with 33% and 50% Conclusions: these results suggest some benefit from dose intensified CT in terms of complete pathological response rate with improvment of the disease- free and survival outcome. The positive impact of additional docetaxel will be assessed in the last randomized multicenter Pegase 07 trial. No significant financial relationships to disclose.
Peroral endoscopic myotomy for sigmoid-type achalasia: the myotomy length and ways to facilitate the procedure
Authors: Yuyong Tan, Deliang Liu, Jirong Huo
Journal: Endoscopy (2016)

We read with great interest the case by Unn et al. [1] entitled “Use of a long, stiff, overtube placed by a colonoscope to facilitate the POEM procedure for a 36-year history of achalasia with 13-cm esophageal dilation.” The procedure involved the use of an overtube to facilitate peroral endoscopic myotomy (POEM) in a patient with severe sigmoid-type achalasia, in whom a flexible gastroscope could not be used to reach the cardia.
Periostin Is a Previously Uncharacterised Vitamin K Dependent γ-Carboxyglutamic Acid (Gla) Containing Protein Expressed by Marrow-Derived Mesenchymal Stromal Cells.
Authors: Daniel L. Coutu, Jian Wui Wu, Georges-Etienne Rivard, Mark D. Blostein, Jacques Galipeau
Journal: Blood (2007)
Genetic Modifiers of Progression-Free Survival in Never-Smoking Lung Adenocarcinoma Patients Treated with First-Line Tyrosine Kinase Inhibitors
Authors: I-Shou Chang, Shih Sheng Jiang, James Chih-Hsin Yang, Wu-Chou Su, Li-Hsin Chien, Chin-Fu Hsiao, Jih-Hsiang Lee, Chih-Yi Chen, Chung-Hsing Chen, Gee-Chen Chang, Zhaoming Wang, Fang-Yi Lo, Kuan-Yu Chen, Wen-Chang Wang, Yuh-Min Chen, Ming-Shyan Huang, Ying-Huang Tsai, Yu-Chun Su, Wan-Shan Hsieh, Wen-Chi Shih, Shwn-Huey Shieh, Tsung-Ying Yang, Qing Lan, Nathaniel Rothman, Chien-Jen Chen, Stephen J. Chanock, Pan-Chyr Yang, Chao A. Hsiung
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

Patients with non-small cell lung cancer (NSCLC) with mutated epidermal growth factor receptor (EGFR) are relatively sensitive to EGFR-tyrosine kinase inhibitor (TKI) treatment and have longer progression-free survival (PFS) when treated with EGFR-TKI compared with platinum-based chemotherapy. However, many patients with advanced NSCLC who have mutated EGFR do not respond to first-line EGFR-TKI treatment and still have shorter PFS.The aim of this study was to identify genetic variants associated with PFS among patients with lung adenocarcinoma who were treated with first-line EGFR-TKIs.A genome-wide association study on PFS was performed in never-smoking women diagnosed with lung adenocarcinoma and who were treated with first-line EGFR-TKIs (n = 128). Significant single-nucleotide polymorphisms (SNPs) were selected for follow-up association analysis (n = 198) and for replication assay in another independent cohort (n = 153).We identified SNPs at 4q12 associated with PFS at genome-wide significance (P < 10-8) and with an estimated hazard ratio of more than 4. This association was also replicated in a larger but similar cohort and in an independent NSCLC cohort. Follow-up functional analyses showed that these SNPs were associated with the expression of EGFR, which encodes the TKI target, and with a nearby gene neuromedin-U, which encodes a G protein-coupled receptor ligand known to be involved in the progression of NSCLC. Considering these as possible prognostic biomarkers for the treatment of patients with late-stage lung cancer, we found that these SNPs were not associated with EGFR mutation status or with polymorphism of the Bcl2-interacting mediator of cell death gene.Genetic variants in 4q12 merit further investigation to assess their potential as pharmacogenomic predictors for and to understand the biology underlying its influence on PFS in patients treated with TKI therapy.
Is swimmers' asthma a distinct asthma endotype?
Authors: Sven Seys, Valérie Hox, Laura Van Gerven, Ellen Dilissen, Gudrun Marijsse, Eldrid Peeters, Ahmad Kasran, Sven Aertgeerts, Thierry Troosters, Vincent Vanbelle, Koen Peers, Jan Ceuppens, Peter Hellings, Lieven Dupont, Dominique Bullens
Journal: Allergy (2015)
GD2/GD3 expression: Companion diagnostic for ganglioside-targeted immunotherapy against pediatric solid tumors.
Authors: Konstantin Dobrenkov, Irina Ostrovnaya, Irene Y. Cheung, Yi Feng, Nai-Kong V. Cheung
Journal: Journal of Clinical Oncology (2016)

10567 Background: Gangliosides GD2 and GD3 are the tumor-associated glycolipid antigens found in a broad spectrum of human cancers, including pediatric embryonal tumors (neuroblastoma, retinoblastoma, brain tumors, osteosarcoma [OS], Ewing sarcoma, rhabdomyosarcoma [RMS]), as well as adult cancers (small cell lung cancer, melanoma, soft tissue sarcomas). GD2-specific antibody is currently an FDA approved standard of care for the treatment of high risk neuroblastoma. In this study, the pattern of GD2 and GD3 expression among common and rare pediatric tumors was demonstrated, providing companion diagnostics for targeted therapy. Methods: Fresh frozen specimens (n = 92) of human OS (n = 19), RMS (n = 18), Ewing sarcoma (n = 15), desmoplastic small round cell tumor (DSRCT, n = 20) and melanoma (n = 20) were analyzed for GD2 and GD3 expression by immunohistochemistry with reference controls. Among cells that were stained positive, intensity was scored weak (1% to < 25%), mixed (25% to 50%), strong ( > 50%-75%), and very strong ( > 75%). Kruskal-Wallis test and Wilcoxon rank sum test were used for statistical analysis. Results: Both GD2 and GD3 were highly prevalent in OS and melanoma. Among other tumor types tested, GD3 was also highly prevalent ( ≥ 70%) while GD2 expression did not exceed 50%. Most OS samples demonstrated uniformly strong staining for GD2 and GD3, whereas the intensity of expression for other tumors was highly variable. Mean intensity of GD2 was heterogeneous across tumor types (p < 0.001). It was highest in OS, followed by melanoma and RMS. GD3 was not significantly different across various cancers (p = 0.57). When assessing the difference between GD2 and GD3 expression in all tumor types combined, GD3 expression had significantly higher intensity score (p = 0.049). When analyzed separately, GD3 expression intensity was higher only in DSRCT (p = 0.002), and it did not differ in other tumor types. There was no significant difference in either GD2 or GD3 expression between primary and recurrent OS, Ewing sarcoma and RMS. Conclusions: GD2/GD3 expression among pediatric solid tumors is common, although the level of expression varied. These gangliosides can be potential targets for antibody based therapies.
Catumaxomab Versus Catumaxomab Plus Prednisolone in Patients with Malignant Ascites due to Epithelial Cancer: Results from the Casimas Study
Authors: J. Sehouli, P. Wimberger, I.B. Vergote, P. Rosenberg, A. Schneeweiss, C. Bokemeyer, C. Salat, G. Scambia, D. Berton-Rigaud, F. Lordick
Journal: Annals of Oncology (2012)
Gene-Correction Rescues Reprogramming of Fanconi Anemia Fibroblasts and Enables Hematopoietic Differentiation of FA Induced Pluripotent Stem Cells in Vitro and In Vivo
Authors: Lars Mueller, Michael D. Milsom, Chad Harris, Rutesh Vyas, Kristina Brumme, Kalindi Parmar, Axel Schambach, Elke Grassman, In-Hyun Park, London Wendy, Kelly Strait, Thorsten Schlaeger, Alexander L. Devine, Alan D. D'Andrea, George Q. Daley, David A. Williams
Journal: Blood (2011)
Cost and Complications of Local Therapies for Early-Stage Breast Cancer
Authors: Benjamin D. Smith, Jing Jiang, Ya-ChenTina Shih, Sharon H. Giordano, Jinhai Huo, Reshma Jagsi, Adeyiza O. Momoh, Abigail S. Caudle, Kelly K. Hunt, Simona F. Shaitelman, Thomas A. Buchholz, Shervin M. Shirvani
Journal: JNCI Journal of the National Cancer Institute (2016)

Background: Guideline-concordant local therapy options for early breast cancer include lumpectomy plus whole breast irradiation (Lump+WBI), lumpectomy plus brachytherapy, mastectomy alone, mastectomy plus reconstruction, and, in older women, lumpectomy alone. We performed a comparative examination of each treatment's complications and cost to assess their relative values. Methods: Using the MarketScan database of younger women with private insurance and the SEER-Medicare database of older women with public insurance, we identified 105 211 women with early breast cancer diagnosed between 2000 and 2011. We used diagnosis and procedural codes to identify treatment complications within 24 months of diagnosis and compared complications by treatment using two-sided logistic regression. Mean total and complication-related cost, relative to Lump+WBI, were calculated from a payer's perspective and adjusted for differences in covariables using linear regression. All statistical tests were two-sided. Results: Lump+WBI was the most commonly used treatment. Mastectomy plus reconstruction was associated with nearly twice the complication risk of Lump+WBI (Marketscan: 54.3% vs 29.6%, relative risk [RR] = 1.87, 95% confidence interval [CI] = 1.82 to 1.91, P < .001; SEER-Medicare: 66.1% vs 37.6%, RR = 1.75, 95% CI = 1.69 to 1.82, P < .001) and was also associated with higher adjusted total cost (Marketscan: $22 481 greater than Lump+WBI; SEER-Medicare: $1748 greater) and complication-related cost (Marketscan: $9017 greater; SEER-Medicare: $2092 greater). Brachytherapy had modestly higher total cost and complications than WBI. Lumpectomy alone entailed lower cost and complications in the SEER-Medicare cohort only. Conclusions: Mastectomy plus reconstruction results in substantially higher complications and cost than other guideline-concordant treatment options for early breast cancer. These findings are relevant to patients evaluating their local therapy options and to value-based population health management.
Does distance from the equator predict self-control? Lessons from the Human Penguin Project
Authors: Hans IJzerman, Marija V. Čolić, Marie Hennecke, Youngki Hong, Chuan-Peng Hu, Jennifer Joy-Gaba, Dušanka Lazarević, Ljiljana B. Lazarević, Michal Parzuchowski, Kyle G. Ratner, Thomas Schubert, Astrid Schütz, Darko Stojilović, Sophia C. Weissgerber, Janis Zickfeld, Siegwart Lindenberg
Journal: Behavioral and Brain Sciences (2017)

Abstract We comment on the proposition “that lower temperatures and especially greater seasonal variation in temperature call for individuals and societies to adopt … a greater degree of self-control” (Van Lange et al., sect. 3, para. 4) for which we cannot find empirical support in a large data set with data-driven analyses. After providing greater nuance in our theoretical review, we suggest that Van Lange et al. revisit their model with an eye toward the social determinants of self-control.
Phase 1/2 study of pembrolizumab (pembro) in children with advanced melanoma or a PD-L1-positive (PD-L1+) advanced, relapsed, or refractory solid tumor or lymphoma (KEYNOTE-051).
Authors: Birgit Geoerger, Elizabeth Fox, Alberto S. Pappo, Michael Yalon Oren, Lynley V Marshall, Karl Heath, Scott J. Diede, Scot Ebbinghaus, Julie R. Park
Journal: Journal of Clinical Oncology (2016)

TPS10585 Background: Pembro, a highly selective humanized monoclonal antibody that directly blocks the interaction between programmed death 1 (PD-1) and its ligands PD-L1 and PD-L2, is indicated for the treatment of adults with advanced melanoma. PD-L1 is expressed on the surface of several tumor types, including melanoma and lymphomas, and may enable some tumors to evade a normal immune response. Pembro has shown promising antitumor activity in patients (pts) with melanoma and is generally well tolerated. KEYNOTE-051 (NCT02332668) is a 2-part study to determine the recommended phase 2 dose (RP2D) and activity of pembro in pediatric tumors, especially those refractory to available treatments. Methods: Pts aged 6 months to < 18 years, with advanced melanoma or a PD-L1+ advanced, relapsed, or refractory solid tumor or lymphoma that is incurable and has failed prior therapy or for which standard therapy is either unavailable or inappropriate, measurable disease per RECIST v1.1, known tumor PD-L1 status using immunohistochemical staining (prescreening), and performance score ≥ 50 using Lansky Play Scale (aged ≤ 16 years old) or Karnofsky Scale (aged > 16 years) are eligible. Following a 3 + 3 design in part 1, initial cohorts of 3-6 pts are to be enrolled to determine a maximum tolerated dose (MTD), or in the absence of dose-limiting toxicity, a maximum administered dose (MAD). The starting dose is 2 mg/kg Q3W (the equivalent of the clinical adult dose), with dose escalation to ≤ 10 mg/kg Q2W if exposure at the starting dose is < 50% of the adult value. In part 2, pediatric pts are to receive pembro at the RP2D until documented disease progression or ≥ 2 years. The primary objectives of part 2 are to further evaluate the safety and efficacy of pembro at the pediatric RP2D in children with advanced melanoma or PD-L1+ advanced relapsed/refractory solid tumors and lymphoma. Enrollment of PD-L1- pts may be initiated if an efficacy bound is passed during subsequent sequential monitoring for response in PD-L1+ pts. Enrollment in KEYNOTE-051 is underway; it is expected that 60 to ≤ 310 pts will be enrolled based on efficacy boundaries. Clinical trial information: NCT02332668.
Understanding Human Autoimmunity and Autoinflammation Through Transcriptomics
Authors: Romain Banchereau, Alma-Martina Cepika, Jacques Banchereau, Virginia Pascual
Journal: Annual Review of Immunology (2017)

Transcriptomics, the high-throughput characterization of RNAs, has been instrumental in defining pathogenic signatures in human autoimmunity and autoinflammation. It enabled the identification of new therapeutic targets in IFN-, IL-1- and IL-17-mediated diseases. Applied to immunomonitoring, transcriptomics is starting to unravel diagnostic and prognostic signatures that stratify patients, track molecular changes associated with disease activity, define personalized treatment strategies, and generally inform clinical practice. Herein, we review the use of transcriptomics to define mechanistic, diagnostic, and predictive signatures in human autoimmunity and autoinflammation. We discuss some of the analytical approaches applied to extract biological knowledge from high-dimensional data sets. Finally, we touch upon emerging applications of transcriptomics to study eQTLs, B and T cell repertoire diversity, and isoform usage.
We must go for gold in public health: Table 1
Authors: May C I van Schalkwyk, Donelly A van Schalkwyk
Journal: BMJ (2016)

The past few weeks have seen the release of the UK government’s childhood obesity strategy,1 reports of athletic success from Team GB at the Olympics, a further article supporting the benefits of physical activity,2 and a Lancet comment calling for multifaceted approaches to tackling obesity.3

Little connection was made between these, however. Consequently, an opportunity was lost to harness any synergistic effect from …
Mobile real-time surveillance of Zika virus in Brazil
Authors: Nuno Rodrigues Faria, Ester C. Sabino, Marcio R. T. Nunes, Luiz Carlos Junior Alcantara, Nicholas J. Loman, Oliver G. Pybus
Journal: Genome Medicine (2016)

The World Health Organization has declared Zika virus an international public health emergency. Knowledge of Zika virus genomic epidemiology is currently limited due to challenges in obtaining and processing samples for sequencing. The ZiBRA project is a United Kingdom–Brazil collaboration that aims to improve this situation using new sequencing technologies.
Allogeneic Stem Cell Transplantation in Adult Patients with Acute Myeloid Leukemia and 17p Abnormalities in First Complete Remission: A Study from the Acute Leukemia Working Party (ALWP) of the European Society of Blood and Marrow Transplantation (EBMT)
Authors: Xavier Poiré, Myriam Labopin, Johan Maertens, Ibrahim Yakoub-Agha, Didier Blaise, Norbert Ifrah, Gerard Socie, Tobias Gedde-Dhal, Nicolaas PM Schaap, Jan Cornelissen, Noel Milpied, Jaime Sanz, Lucienne Michaux, Jordi Esteve, Mohamad Mohty, Arnon Nagler
Journal: Blood (2015)
Artificially Sweetened Beverage Consumption During Pregnancy and Infant Body Mass Index
Authors: Patrick Mullie, Peter Clarys, Philippe Autier
Journal: JAMA Pediatrics (2016)

To the Editor The prospective study by Azad et al1 concluded that consumption of artificially sweetened beverages (ASBs) during pregnancy may increase the infant body mass index z score (BMIz) measured at 1 year of age.1 We do not agree with this interpretation of the results.
Expression of Idh1R132H in the Murine Subventricular Zone Stem Cell Niche Recapitulates Features of Early Gliomagenesis
Authors: Chiara Bardella, Osama Al-Dalahmah, Daniel Krell, Pijus Brazauskas, Khalid Al-Qahtani, Marketa Tomkova, Julie Adam, Sébastien Serres, Helen Lockstone, Luke Freeman-Mills, Inga Pfeffer, Nicola Sibson, Robert Goldin, Benjamin Schuster-Böeckler, Patrick J. Pollard, Tomoyoshi Soga, James S. McCullagh, Christopher J. Schofield, Paul Mulholland, Olaf Ansorge, Skirmantas Kriaucionis, Peter J. Ratcliffe, Francis G. Szele, Ian Tomlinson
Journal: Cancer Cell (2016)
Multimodal endoscopic treatment of primary esophago-pleural fistula
Authors: Helga Bertani, Giuseppe Grande, Vincenzo Mirante, Isabella Franco, Santi Mangiafico, Raffaele Manta, Rita Conigliaro
Journal: Endoscopy (2016)

A 48-year-old man was admitted to our hospital following the onset of cough, fever, and shortness of breath. Clinical history included psychotic syndrome and recurrent erosive esophagitis.
Advanced Age at Transplant Increases the Risk of Second Solid Malignancy (SSM) after Haematopoetic Stem Cell Transplantation (HSCT)
Authors: John Murray, John Chadwick, Adrian Bloor, Jim Cavet, Mike Dennis, Tim Somervaille, Sven Armin Sommerfeld, John Eliott, Siobhan Muthia, Angie Leather, Rita Angelica, Rachel Brown, Jo Tomlins, Samar Kulkarni
Journal: Blood (2014)