tbuckley/cabot-search huggingface dataset:
Small molecule tyrosine kinase inhibitors and pancreatic cancer—Trials and troubles
Authors: Bhaskar Venkata Kameswara Subrahmanya Lakkakula, Batoul Farran, Saikrishna Lakkakula, Sujatha Peela, Nagendra Sastry Yarla, Pallaval Veera Bramhachari, Mohammad Amjad Kamal, Madhu Sudhana Saddala, Ganji Purnachandra Nagaraju
Journal: Seminars in Cancer Biology (2018)
GW29-e1597 Hight-Density Mapping Guides Accurate Ablation of Typical Atrial Flutter and its Long-Term Outcome
Authors: Jinxuan Lin, Tianjie Feng, Ni Suo, Ligang Ding, Gang Chen, Lihui Zheng, Yan Yao, Shu Zhang, Guodong Niu
Journal: Journal of the American College of Cardiology (2018)
Sequence of hormonal therapy and radiotherapy field size in unfavourable, localised prostate cancer (NRG/RTOG 9413): long-term results of a randomised, phase 3 trial
Authors: Mack Roach, Jennifer Moughan, Colleen A F Lawton, Adam P Dicker, Kenneth L Zeitzer, Elizabeth M Gore, Young Kwok, Michael J Seider, I-Chow Hsu, Alan C Hartford, Eric M Horwitz, Kosj Yamoah, Christopher U Jones, Jeff M Michalski, W Robert Lee, Thomas M Pisansky, Rachel Rabinovitch, Marvin Rotman, Rodger M Pryzant, Harold E Kim, Charles R Thomas, William U Shipley, Howard M Sandler
Journal: The Lancet Oncology (2018)
Nanoscale extracellular vesicle-derived DNA is superior to circulating cell-free DNA for mutation detection in early-stage non-small-cell lung cancer
Authors: Y. Wan, B. Liu, H. Lei, B. Zhang, Y. Wang, H. Huang, S. Chen, Y. Feng, L. Zhu, Y. Gu, Q. Zhang, H. Ma, S.-Y. Zheng
Journal: Annals of Oncology (2018)

BackgroundThe comparison between relatively intact nanoscale extracellular vesicle-derived DNA (nEV-DNA) and fragmented circulating cell-free DNA (cfDNA) in mutation detection among patients with non-small-cell lung cancer (NSCLC) has not been carried out yet, and thus deserves investigation.Patients and methodsBoth nEV-DNA and cfDNA was obtained from 377 NSCLC patients with known EGFR mutation status and 69 controls. The respective EGFRE19del/T790M/L858R mutation status was interrogated with amplification-refractory-mutation-system-based PCR assays (ARMS-PCR).ResultsNeither nEV-DNA nor cfDNA levels show a strong correlation with tumor volumes. There is no correlation between cfDNA and nEV-DNA levels either. The detection sensitivity of nEV-DNA and cfDNA using ARMS-PCR in early-stage NSCLC was 25.7% and 14.2%, respectively, with 96.6% and 91.7% specificity, respectively. In late-stage NSCLC, both nEV-DNA and cfDNA show ∼80% sensitivity and over 95% specificity.ConclusionsnEV-DNA is superior to cfDNA for mutation detection in early-stage NSCLC using ARMS-PCR. However, the advantages vanish in late-stage NSCLC.
Sam Michael Tucker
Authors: Dana Cukier
Journal: BMJ (2018)

The middle of three sons, Sam Michael Tucker was born in Benoni, South Africa, in 1926 to Harry and Ray Tucker, who had arrived there with their families from Lithuania in the early 1900s.

When Sam left school in 1944, the second world war was ongoing in Europe, and much to his mother’s chagrin, he decided to join the South African Air Force rather than go straight to university. His training as a navigator stood him in good stead when he volunteered to serve with the fledgling Israeli air force in 1948 as part of the renowned South African elite fighting force, the Palmach. He flew over Syria in a flying fortress plane, and as a key navigator he participated in many critical moments of air force missions, releasing bombs by hand.

After his wartime experiences, he chose to study medicine at the medical school of the University of the Witwatersrand in Johannesburg, where he met his future wife, Barbara Kaplan, a beautiful fine arts student and “rag queen.”

On 13 December 1953, Sam and Barbara married in her home town of Durban, Natal (their 65th wedding anniversary would have been in December 2018). They lived …
A phase II study of nivolumab: a multicenter, open-label, single arm study in malignant pleural mesothelioma (MERIT)
Authors: Keisuke Aoe, Morihito Okada, Takashi Kijima, Terufumi Kato, Nobukazu Fujimoto, Kazuhiko Nakagawa, Yuichiro Takeda, Toyoaki Hida, Kuninobu Kanai, Fumio Imamura, Satoshi Oizumi, Toshiaki Takahashi, Mitsuhiro Takenoyama, Hiroshi Tanaka, Yuichiro Ohe
Journal: Annals of Oncology (2018)
P3.12-01 Targeting Mitochondrial Metabolism as a Selective Therapeutic Approach in Small Cell Lung Cancer (SCLC)
Authors: S. Roy Chowdhury, R. Saleh, C. Girard, C. Peltier, D. Desautels, D. Dawe, V. Banerji, S. Banerji
Journal: Journal of Thoracic Oncology (2018)
SWI/SNF component <i>ARID1A</i> restrains pancreatic neoplasia formation
Authors: Sam C Wang, Ibrahim Nassour, Shu Xiao, Shuyuan Zhang, Xin Luo, Jeon Lee, Lin Li, Xuxu Sun, Liem H Nguyen, Jen-Chieh Chuang, Lan Peng, Scott Daigle, Jeanne Shen, Hao Zhu
Journal: Gut (2018)

Objective ARID1A is commonly mutated in pancreatic ductal adenocarcinoma (PDAC), but the functional effects of ARID1A mutations in the pancreas are unclear. Understanding the molecular mechanisms that drive PDAC formation may lead to novel therapies. Design Concurrent conditional Arid1a deletion and Kras activation mutations were modelled in mice. Small-interfering RNA (siRNA) and CRISPR/Cas9 were used to abrogate ARID1A in human pancreatic ductal epithelial cells. Results We found that pancreas-specific Arid1a loss in mice was sufficient to induce inflammation, pancreatic intraepithelial neoplasia (PanIN) and mucinous cysts. Concurrent Kras activation accelerated the development of cysts that resembled intraductal papillary mucinous neoplasm. Lineage-specific Arid1a deletion confirmed compartment-specific tumour-suppressive effects. Duct-specific Arid1a loss promoted dilated ducts with occasional cyst and PDAC formation. Heterozygous acinar-specific Arid1a loss resulted in accelerated PanIN and PDAC formation with worse survival. RNA-seq showed that Arid1a loss induced gene networks associated with Myc activity and protein translation. ARID1A knockdown in human pancreatic ductal epithelial cells induced increased MYC expression and protein synthesis that was abrogated with MYC knockdown. ChIP-seq against H3K27ac demonstrated an increase in activated enhancers/promoters. Conclusions Arid1a suppresses pancreatic neoplasia in a compartment-specific manner. In duct cells, this process appears to be associated with MYC-facilitated protein synthesis.
Maternal blood pressure and hypertensive disorders during pregnancy and childhood respiratory morbidity: the Generation R Study
Authors: Freke A. Wilmink, Herman T. den Dekker, Johan C. de Jongste, Irwin K.M. Reiss, Vincent W.V. Jaddoe, Eric A. Steegers, Liesbeth Duijts
Journal: European Respiratory Journal (2018)

Pre-eclampsia is associated with an increased risk of bronchopulmonary dysplasia, wheezing and asthma in later childhood. Currently, there are no studies available investigating maternal blood pressure measurements during multiple time-points in pregnancy and respiratory outcome measures in the child. We examined the associations of maternal blood pressure and hypertensive disorders with the risk of lower lung function, wheezing and asthma in children aged 10 years. This study among 4894 children was embedded in a population-based prospective cohort study. We used multivariate analyses, taking lifestyle and socioeconomic factors into account. We observed consistent associations per 5 mmHg higher maternal blood pressure in early pregnancy with a lower forced expiratory volume in 1 s/forced vital capacity ratio (z-score −0.03 (95% CI −0.05– −0.01)) and per 5 mmHg higher blood pressure in late pregnancy with a higher risk for current wheezing and current asthma (OR 1.07 (95% CI 1.02–1.12) and 1.06 (95% CI 1.00–1.11), respectively). We found no associations of maternal hypertensive disorders during pregnancy with child lung function, current wheezing or current asthma. Our results suggest that higher blood pressure in pregnant women is associated with lower lung function and increased risks of current wheezing and current asthma in children. The associations may be trimester specific.
P3.16-02 Phase III Study of Canakinumab (ACZ885) as Adjuvant Therapy in Patients with Surgically Resected NSCLC
Authors: E. Garon, A. Ardizzoni, F. Barlesi, B.C. Cho, P. De Marchi, Y. Goto, S. Lu, L. Paz-Ares, D. Spigel, M. Thomas, P. Cazorla Arratia, J. Baum, Y. Lau, C. Zheng, J.C. Yang
Journal: Journal of Thoracic Oncology (2018)
GW29-e0846 Two-year Follow-up of a New Test which Correctly Predicted Which Patients with Borderline Hypotension Might Develop Hypotension within the Next 24 Hours
Authors: Thach Nguyen, Thao Dang, Tu NT. Nguyen, Tran Huynh Thu Dung, Thai Ba Anh Minh, Nguyen Hua Hoang Quan, Tarneem Darwish, Gianluca Rigatelli
Journal: Journal of the American College of Cardiology (2018)
Comparative effectiveness of neoadjuvant chemotherapy followed by cystectomy versus cystectomy followed by adjuvant chemotherapy versus palliative chemotherapy versus cystectomy for node-positive bladder cancer: A retrospective analysis: KCSG GU 17-03
Authors: J.H. Byun, H.A. Jung, W.-K. Bae, H.-J. Lee, S.H. Park, H.J. Kim, C.H. Maeng, I. Park, B.S. Sohn, J.A. Kim, K.H. Lee, D.H. Im, J.H. Kim, H. Jang, S.M. Kim
Journal: Annals of Oncology (2018)
Abstract 16513: Effectiveness and Safety of Rivaroxaban versus Warfarin in Patients 80+ Years of Age With Nonvalvular Atrial Fibrillation
Authors: Craig I Coleman, Erin R Weeda, Elaine Nguyen, Thomas J Bunz, Nitesh A Sood
Journal: Circulation (2017)

Introduction: More than half of patients with nonvalvular atrial fibrillation (NVAF) are ≥80 years of age; yet such patients are often underrepresented in studies of oral anticoagulation (OAC). Obj...
Smoking and Lung Cancer Mortality in the United States From 2015 to 2065
Authors: Jihyoun Jeon, Theodore R. Holford, David T. Levy, Eric J. Feuer, Pianpian Cao, Jamie Tam, Lauren Clarke, John Clarke, Chung Yin Kong, Rafael Meza
Journal: Annals of Internal Medicine (2018)

Background: Tobacco control efforts implemented in the United States since the 1960s have led to considerable reductions in smoking and smoking-related diseases, including lung cancer. Objective: To project reductions in tobacco use and lung cancer mortality from 2015 to 2065 due to existing tobacco control efforts. Design: Comparative modeling approach using 4 simulation models of the natural history of lung cancer that explicitly relate temporal smoking patterns to lung cancer rates. Setting: U.S. population, 1964 to 2065. Participants: Adults aged 30 to 84 years. Measurements: Models were developed using U.S. data on smoking (1964 to 2015) and lung cancer mortality (1969 to 2010). Each model projected lung cancer mortality by smoking status under the assumption that current decreases in smoking would continue into the future (status quo trends). Sensitivity analyses examined optimistic and pessimistic scenarios. Results: Under the assumption of continued decreases in smoking, age-adjusted lung cancer mortality was projected to decrease by 79% between 2015 and 2065. Concomitantly, and despite the expected growth, aging, and longer life expectancy of the U.S. population, the annual number of lung cancer deaths was projected to decrease from 135 000 to 50 000 (63% reduction). However, 4.4 million deaths from lung cancer are still projected to occur in the United States from 2015 to 2065, with about 20 million adults aged 30 to 84 years continuing to smoke in 2065. Limitation: Projections assumed no changes to tobacco control efforts in the future and did not explicitly consider the potential effect of lung cancer screening. Conclusion: Tobacco control efforts implemented since the 1960s will continue to reduce lung cancer rates well into the next half-century. Additional prevention and cessation efforts will be required to sustain and expand these gains to further reduce the lung cancer burden in the United States. Primary Funding Source: National Cancer Institute.
Abstract A28: Donor lymphocyte infusion after allogeneic stem cell transplantation is a feasible therapy option with acceptable toxicity rates in patients with refractory Ewing’s sarcoma and rhabdomyosarcoma
Authors: Sebastian J. Schober, Maximilian Steinhauser, Angela Wawer, Irene Teichert-von Luettichau, Christoph Salat, Rolf D. Issels, Wolfgang Schwinger, Marek Ussowicz, Petar Antunovic, Luca Castagna, Hans-Jochem Kolb, Stefan E.G. Burdach, Uwe Thiel
Journal: Cancer Research (2018)

Abstract Background: New therapy options are urgently needed for patients with treatment-refractory Ewing’s sarcoma (ES) or rhabdomyosarcoma (RMS). In these subgroups, the role of allogeneic stem cell transplantation (allo-SCT) to induce a graft-versus-tumor effect (GvT) remains unclear. Here, we describe our experience and the general feasibility of donor lymphocyte infusion (DLI) following allo-SCT for those patients. Patients and Methods: We retrospectively evaluated data of eight patients with treatment-refractory ES (ES #1-4) and RMS (RMS #1-4) after DLI following allo-SCT. Data were individually evaluated for presence of graft-versus-host disease (GvHD), relapse-free survival (RFS), and overall survival (OS). Three of four ES and one of four RMS patients had received haploidentical grafts; the remaining patients received HLA-matched grafts prior to DLI. Patients received donor lymphocytes ranging from 2.5 x 104 to 1 x 108 CD3+ cells/kg body weight. Results: ES #4 and RMS #4 developed acute GvHD after DLI. Limited chronic GvHD was observed in RMS #3. In two patients, DLI was associated with stable disease for nine (ES #2) and six months (ES #4), respectively. RMS #4 showed partial remission lasting for eight months after one dose of DLI with 1 x 106 CD3+ cells/kg combined with local hyperthermia and chemotherapy. ES #4 had residual disease before allo-SCT and was converted to CR after DLI. Altogether, seven patients died of disease and none of toxicity. RMS #2 received seven doses up to 1 x 108 CD3+ cells/kg and IL-2 including surgery and chemotherapy and remained in CR for 97 months at the date of data assessment. Median follow-up after allo-SCT was 27.5 months. Conclusion: DLI after allo-SCT is a feasible therapy option for treatment-refractory ES and RMS patients. In this analysis, DLI-related toxicity is acceptable. These findings have to be evaluated in prospective analyses. Citation Format: Sebastian J. Schober, Maximilian Steinhauser, Angela Wawer, Irene Teichert-von Luettichau, Christoph Salat, Rolf D. Issels, Wolfgang Schwinger, Marek Ussowicz, Petar Antunovic, Luca Castagna, Hans-Jochem Kolb, Stefan E.G. Burdach, Uwe Thiel. Donor lymphocyte infusion after allogeneic stem cell transplantation is a feasible therapy option with acceptable toxicity rates in patients with refractory Ewing’s sarcoma and rhabdomyosarcoma [abstract]. In: Proceedings of the AACR Special Conference: Pediatric Cancer Research: From Basic Science to the Clinic; 2017 Dec 3-6; Atlanta, Georgia. Philadelphia (PA): AACR; Cancer Res 2018;78(19 Suppl):Abstract nr A28.
Gaps in the evidence for treatment decisions in cystic fibrosis: a systematic review
Authors: Nicola Jane Rowbotham, Sherie Smith, Andrew P Prayle, Karen A Robinson, Alan Robert Smyth
Journal: Thorax (2018)

Introduction Cystic fibrosis (CF) is a multisystem disorder. Treatment is complex and evidence for treatment decisions may be absent. Characterising gaps in the research evidence will highlight treatment uncertainties and help prioritise research questions. We systematically identified the evidence gaps for treatment decisions in CF. Methods We searched for systematic reviews and guidelines on treatment interventions in CF. Two researchers identified eligible reviews with arbitration from a third. Using a structured framework, we extracted and characterised evidence gaps. Results There were 73 reviews and 21 guidelines that met our inclusion criteria. From these, we identified 148 evidence gaps across a range of treatment areas. We found 111 evidence gaps through systematic reviews and a further 37 from guidelines. The reason for an evidence gap could only be reliably characterised for systematic reviews. In most cases, there was more than one explanation—most commonly few or no trials (97/111 evidence gaps). Other important factors leading to evidence gaps were small sample size (49/111), inadequate duration of follow-up (38/111) or intervention (37/111) and factors relating to outcomes (35/111). Evidence gaps from both systematic reviews and guidelines fell into the following categories: Respiratory (91); Gastrointestinal (20); PhysiotherapyandExercise (16); Musculoskeletal (6); Endocrine (4); Basic defect of CF (8); Psychosocial (2); Ears, Nose and Throat (1). Conclusions We have compiled an up-to-date list of treatment uncertainties in CF and the reasons for these uncertainties. These can be used as a resource to aid researchers and funders when planning future trials. PROSPERO registration number Pre-results; CRD42015030111.
Osteopontin mediates glioblastoma-associated macrophage infiltration and is a potential therapeutic target
Authors: Jun Wei, Anantha Marisetty, Brett Schrand, Konrad Gabrusiewicz, Yuuri Hashimoto, Martina Ott, Zacharia Grami, Ling-Yuan Kong, Xiaoyang Ling, Hillary Caruso, Shouhao Zhou, Y. Alan Wang, Gregory N. Fuller, Jason Huse, Eli Gilboa, Nannan Kang, Xingxu Huang, Roel Verhaak, Shulin Li, Amy B. Heimberger
Journal: Journal of Clinical Investigation (2018)

Glioblastoma is highly enriched with macrophages, and osteopontin (OPN) expression levels correlate with glioma grade and the degree of macrophage infiltration; thus, we studied whether OPN plays a crucial role in immune modulation. Quantitative PCR, immunoblotting, and ELISA were used to determine OPN expression. Knockdown of OPN was achieved using complementary siRNA, shRNA, and CRISPR/Cas9 techniques, followed by a series of in vitro functional migration and immunological assays. OPN gene-deficient mice were used to examine the roles of non-tumor-derived OPN on survival of mice harboring intracranial gliomas. Patients with mesenchymal glioblastoma multiforme (GBM) show high OPN expression, a negative survival prognosticator. OPN is a potent chemokine for macrophages, and its blockade significantly impaired the ability of glioma cells to recruit macrophages. Integrin αvβ5 (ITGαvβ5) is highly expressed on glioblastoma-infiltrating macrophages and constitutes a major OPN receptor. OPN maintains the M2 macrophage gene signature and phenotype. Both tumor-derived and host-derived OPN were critical for glioma development. OPN deficiency in either innate immune or glioma cells resulted in a marked reduction in M2 macrophages and elevated T cell effector activity infiltrating the glioma. Furthermore, OPN deficiency in the glioma cells sensitized them to direct CD8+ T cell cytotoxicity. Systemic administration in mice of 4-1BB-OPN bispecific aptamers was efficacious, increasing median survival time by 68% (P < 0.05). OPN is thus an important chemokine for recruiting macrophages to glioblastoma, mediates crosstalk between tumor cells and the innate immune system, and has the potential to be exploited as a therapeutic target.
Characterization through whole exome sequencing of individuals presenting extreme phenotypes of high and low risk to develop tobacco-induced non-small lung cancer (NSCLC)
Authors: J.L. Perez Gracia, M.J. Pajares, J.P. Fusco, M. Andueza, V. Segura, M.I. Mora, E. Guruceaga, R. Sanchez Bayona, A. Gurpide, J.M. Lopez-Picazo, I. Gil-Bazo, J.P. de Torres, J. Zulueta, R. Pio, I. Melero, M.F. Sanmamed, M. Rodriguez-Ruiz, A. Gonzalez Neira, L. Montuenga, A. Patiño-Garcia
Journal: Annals of Oncology (2018)
Treatment patterns in patients (pts) with stage IIIB-IV non-small cell lung cancer (NSCLC) in Sweden: The SCAN-LEAF study
Authors: S. Ekman, M. Planck, J.B. Sørensen, P. Horvat, D. Layton, J. Kim, M. Rosenlund, A. Juarez-Garcia, M. Daumont, H.C. Jacobs, L. Lacoin, O.T. Brustugun
Journal: Annals of Oncology (2018)
Avelumab in patients with previously treated metastatic adrenocortical carcinoma: phase 1b results from the JAVELIN solid tumor trial
Authors: Christophe Le Tourneau, Christopher Hoimes, Corrine Zarwan, Deborah J. Wong, Sebastian Bauer, Rainer Claus, Martin Wermke, Subramanian Hariharan, Anja von Heydebreck, Vijay Kasturi, Vikram Chand, James L. Gulley
Journal: Journal for ImmunoTherapy of Cancer (2018)

<h3>Background</h3> We assessed the efficacy and safety of avelumab, an anti-programmed death ligand 1 (PD-L1) antibody, in patients with previously treated metastatic adrenocortical carcinoma (mACC). <h3>Methods</h3> In this phase 1b expansion cohort, patients with mACC and prior platinum-based therapy received avelumab at 10&nbsp;mg/kg intravenously every 2&nbsp;weeks. Continuation of mitotane was permitted; however, mitotane levels during the study were not recorded. Tumor response was assessed by Response Evaluation Criteria In Solid Tumors v1.1. <h3>Results</h3> Fifty patients received avelumab and were followed for a median of 16.5&nbsp;months. Prior treatment included ≥2 lines in 74.0%; mitotane was continued in 50.0%. The objective response rate (ORR) was 6.0% (95% CI, 1.3% to 16.5%; partial response in 3 patients). Twenty-one patients (42.0%) had stable disease as best response (disease control rate, 48.0%). Median progression-free survival was 2.6&nbsp;months (95% CI, 1.4 to 4.0), median overall survival (OS) was 10.6&nbsp;months (95% CI, 7.4 to 15.0), and the 1-year OS rate was 43.4% (95% CI, 27.9% to 57.9%). In evaluable patients with PD-L1+ (<i>n</i> = 12) or PD-L1− (<i>n</i> = 30) tumors (≥5% tumor cell cutoff), ORR was 16.7% vs 3.3% (<i>P</i> = .192). Treatment-related adverse events (TRAEs) occurred in 82.0%; the most common were nausea (20.0%), fatigue (18.0%), hypothyroidism (14.0%), and pyrexia (14.0%). Grade 3 TRAEs occurred in 16.0%; no grade 4 to 5 TRAEs occurred. Twelve patients (24.0%) had an immune-related TRAE of any grade, which were grade 3 in 2 patients (4.0%): adrenal insufficiency (<i>n</i> = 1), and pneumonitis (<i>n</i> = 1). <h3>Conclusions</h3> Avelumab showed clinical activity and a manageable safety profile in patients with platinum-treated mACC. <h3>Trial registration</h3> Clinicaltrials.gov NCT01772004; registered January 21, 2013.
GW29-e1857 Glycoprotein M6B Interacts with TβRI to Activate TGF-β-Smad2/3 Signaling and Promote Smooth Muscle Cell Differentiation
Authors: Xiaomeng Zhang, Shan Wang, Huishou Zhao, Miaomiao Fan, Yunlong Xia, Pan Chang, Ling Tao
Journal: Journal of the American College of Cardiology (2018)