tbuckley/cabot-search huggingface dataset:
Surgical Management of Vulvar Cancer
Authors: Thanh H. Dellinger, Amy A. Hakim, Stephen J. Lee, Mark T. Wakabayashi, Robert J. Morgan, Ernest S. Han
Journal: Journal of the National Comprehensive Cancer Network (2016)

Vulvar cancer is a rare malignancy with high curability in early-stage disease, yet poor outcomes for advanced-stage and recurrent disease. Surgical management is at the cornerstone of treatment for most vulvar cancers, and includes conservative and radical resection of the primary vulvar tumor and excision of local lymph nodes, which are major prognostic factors and drive adjuvant treatment. This review summarizes the surgical management of primary squamous cell carcinoma of the vulva, specifically initial treatment guidelines by stage, based on the 2017 NCCN Clinical Practice Guidelines in Oncology for Vulvar Cancer.
Targeting and modulating infarct macrophages with hemin formulated in designed lipid-based particles improves cardiac remodeling and function
Authors: Tamar Ben-Mordechai, David Kain, Radka Holbova, Natalie Landa, La-Paz Levin, Inbar Elron-Gross, Yifat Glucksam-Galnoy, Micha S. Feinberg, Rimona Margalit, Jonathan Leor
Journal: Journal of Controlled Release (2017)
PUB017 Minimally Invasive Lobectomy is Associated with Lower Noncancer Mortality in Elderly: A Propensity-Score Matched Analysis
Authors: Boris Hristov, Takashi Eguchi, James Isbell, Bernard Park, Kay See Tan, Valerie Rusch, David Jones, Prasad Adusumilli
Journal: Journal of Thoracic Oncology (2017)
Pharmacologic Restoration of PP2A Activity and Interference with the SET-PP2A Interplay by FTY720 and Its Non-Immunosuppressive Derivative as a Novel and Efficient Therapy for Ph-Negative Myeloproliferative Disorders
Authors: Joshua J Oaks, A. Mukhopadhyay, Ramasamy Santhanam, S. A Saddoughi, Christopher Walker, Paolo Neviani, Jason G Harb, Y. Ma, Srdan Verstovsek, Guido Marcucci, Roger Briesewitz, Robert Bittman, Ching-Shih Chen, Alfonso Quintas-Cardama, Besim Ogretmen, Danilo Perrotti
Journal: Blood (2010)
Abstract A17: Abiraterone metabolism and a novel therapeutic strategy for castration resistant prostate cancer
Authors: Zhenfei Li, Mohammad Alyamani, Jianneng Li, Mary-Ellen Taplin, Nima Sharifi
Journal: Clinical Cancer Research (2017)

Abstract Prostate cancer is the most common cancer in men in the United States. Abiraterone (abi) is approved by the FDA for treatment of castration resistant prostate cancer (CRPC). However, ~30% of patients have limited or no response to abi. The underlying mechanism of resistance is elusive in these cases, and the best treatment plan for such patients is not clear. Thus we sought to determine a potential mechanism of resistance by analyzing abi metabolism. We found that abi undergoes metabolism catalyzed by steroidogenic enzymes. Abi is converted sequentially to delta-4-abi (D4A), then undergoes C5 reduction to produce several metabolites, including 5α-abi and 5 other metabolites. D4A has more potent anti-tumor activity than abi itself because it inhibits multiple enzymes and antagonizes the androgen receptor (AR) directly. D4A inhibits cell proliferation and xenograft growth better than Abi. However, 5α-Abi has more limited effects on steroidogenic enzymes and is a modest AR agonist, which might promote abi resistance. We suggest that abi metabolism could be a biomarker for abi response, and patients with limited or no response to abi might have less D4A or more 5α-Abi. Furthermore, we demonstrate that dutasteride, a 5α-reductase inhibitor, suppresses the conversion from D4A to 5α-Abi in both prostate cancer cell lines and patients, which might enhance the clinical response to abi. Taken together, these data reveal a novel metabolic pathway of abi that can be exploited for treatment, specifically as a biomarker. It is achievable in clinic to fine tune abi metabolism to obtain greater concentrations of D4A, the most potent anti-tumor abi metabolite, in patients by supplementing abi treatment with dutasteride. Citation Format: Zhenfei Li, Mohammad Alyamani, Jianneng Li, Mary-Ellen Taplin, Nima Sharifi. Abiraterone metabolism and a novel therapeutic strategy for castration resistant prostate cancer. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Targeting the Vulnerabilities of Cancer; May 16-19, 2016; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(1_Suppl):Abstract nr A17.
2017 ACC Expert Consensus Decision Pathway for Periprocedural Management of Anticoagulation in Patients With Nonvalvular Atrial Fibrillation
Authors: John U. Doherty, Ty J. Gluckman, William J. Hucker, James L. Januzzi, Thomas L. Ortel, Sherry J. Saxonhouse, Sarah A. Spinler
Journal: Journal of the American College of Cardiology (2017)
P3.03-012 Tumor-Infiltrating Lymphocytes, PDL-1, BAP-1, VEGFR-2 and IGF-1R Expression in Malignant Pleural Mesothelioma
Authors: Luca Ampollini, Letizia Gnetti, Matteo Goldoni, Nicoletta Campanini, Luigi Ventura, Cesare Braggio, Marcello Tiseo, Valeria Balestra, Paolo Carbognani, Antonio Mutti, Enrico Maria Silini, Michele Rusca
Journal: Journal of Thoracic Oncology (2017)
Molecular Pathways: Revisiting Glycogen Synthase Kinase-3β as a Target for the Treatment of Cancer
Authors: Amy Walz, Andrey Ugolkov, Sunandana Chandra, Alan Kozikowski, Benedito A. Carneiro, Thomas V. O'Halloran, Francis J. Giles, Daniel D. Billadeau, Andrew P. Mazar
Journal: Clinical Cancer Research (2017)

Glycogen synthase kinase-3β (GSK-3β), a serine/threonine protein kinase, is a complex regulator of numerous cellular functions. GSK-3β is a unique kinase which is constitutively active in resting and nonstimulated cells. GSK-3β has been implicated in a wide range of diseases including neurodegeneration, inflammation and fibrosis, noninsulin-dependent diabetes mellitus, and cancer. It is a regulator of NF-κB-mediated survival of cancer cells, which provided a rationale for the development of GSK-3 inhibitors targeting malignant tumors. Recent studies, many of them reported over the past decade, have identified GSK-3β as a potential therapeutic target in more than 15 different types of cancer. Whereas only active GSK-3β is expressed in cancer cell nucleus, aberrant nuclear accumulation of GSK-3β has been identified as a hallmark of cancer cells in malignant tumors of different origin. This review focuses on the preclinical and clinical development of GSK-3 inhibitors and the potential therapeutic impact of targeting GSK-3β in human cancer. Clin Cancer Res; 23(8); 1891-7. ©2017 AACR.
S94 Biological markers of favourable prognosis and successful pleurodesis for malignant pleural effusion
Authors: I Psallidas, N Kanellakis, ML Thezenas, P Charles, JP Corcoran, R Hallifax, A Talwar, CC Pascuall, B Kessler, NM Rahman
Journal: Thorax (2016)

<h3>Introduction and objectives</h3> Malignant pleural effusion (MPE) is a rapidly rising healthcare burden and critically hampers the patients’ survival and quality of life. Current treatments aim to symptoms’ palliation and talc pleurodesis remains a standard therapeutic modality. There is relatively little high quality research data in prediction of patients’ survival and successful pleurodesis. Therefore prognostic and therapeutic biomarkers are desperately needed. <h3>Aim</h3> To identify and validate novel prognostic and therapeutic biomarkers in MPE. <h3>Methods</h3> Clinical data and pleural fluids from MPE patients, prior to treatment have been prospectively collected for TIME2 trial. According to the trial database patients have been classified in two different groups: survival cohort (poor, n = 20/good, n = 14) and treatment outcome cohort (success, n = 15/failure, n = 11). Pleural fluids on enrolment were assessed with mass spectrometry profiling after depletion of the 12 most abundant proteins. Full protein profile analysed with R software and ELISA technique was performed for the validation of the results. Pathway analysis on samples performed with Ingenuity Pathway Analysis software. <h3>Results</h3> With the use of mass spectrometry we identified 1,154 proteins in the pleural fluid, 167 of which were statistical significant (two tailed T-Test, p &lt; 0.05) between survival groups and 97 of which were statistically significant (two tailed T-Test, p &lt; 0.05) between the pleurodesis groups. Analysis of the data (cross validated by 3 independent core bioinformatic groups) identified 10 survival and 3 pleurodesis biomarkers that were differentially expressed in the favourable prognosis and treatment success group respectively. Exploration of the mass spectrometry data identified pathways that were upregulated on patients with favourable survival that could be used for targeted therapies. <h3>Conclusions</h3> Based on unique database survival and therapeutic biomarkers were identified that can potentially stratify patients’ management. The results are currently validated on a different retrospective dataset (TIME1 trial) and with a prospective clinical trial (SIMPLE study).
PM vows to improve “dangerously disregarded” mental healthcare
Authors: Gareth Iacobucci
Journal: BMJ (2017)

The UK prime minister has unveiled a raft of new measures to improve support for people with mental illness as she bids to demonstrate her commitment to social reform.

On Monday 9 January Theresa May used her first speech of 2017 and her first on health since she became prime minister last July to pledge action across government to improve mental healthcare in England, which she said had been “dangerously disregarded” as secondary to physical health. There will be a particular focus on reducing numbers of suicides and on providing support to the growing number of children who are vulnerable to mental illness.

But health professionals said that the shortage of new funding attached to the pledges may undermine their effectiveness.

In her speech to the Charity Commission, May announced that …
Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) antibody blockade in patients previously vaccinated with irradiated, autologous tumor cells engineered to secrete granulocyte-macrophage colony stimulating factor (GM-CSF)
Authors: F. S. Hodi, M. Seiden, M. Butler, F. G. Haluska, I. Lowy, E. Vincent-Brunick, D. Lautz, M. Mihm, G. Dranoff
Journal: Journal of Clinical Oncology (2004)

2536
S38 Clinical isolates of mycobacterium avium drive collagenolytic and elastolytic activity in mononuclear cells
Authors: SJ McFetridge, R McMullan, CM O’Kane
Journal: Thorax (2016)

<h3>Background</h3> Pulmonary non-tuberculous mycobacterial (NTM) infections are increasing rapidly in the UK. The commonest pulmonary NTM infection outside the setting of cystic fibrosis lung disease is with the mycobacterium avium complex (MAC), consisting of <i>M. avium</i> and <i>M. intracellulare. </i>Patients with pulmonary MAC infection present with cavitatory lung disease or nodular bronchiectasis. Prolonged treatment is required, frequently not tolerated, and often associated with progressive lung destruction. A large body of evidence suggests the tissue damage that occurs in tuberculous lung disease is driven by host derived matrix metalloproteinases (MMPs), in particular MMP-1 and 9. The mechanisms of tissue damage in NTM infection are not understood. We hypothesised that NTM drives MMP secretion and that this drives cavitation and bronchiectasis. <h3>Methods</h3> Monocytes isolated from healthy human volunteer blood by density centrifugation were stimulated with <i>M. avium </i>clinical isolates for 24 hours. Human monocyte-derived macrophages (MDMs) were generated from monocytes through 5–7 day incubation with GM-CSF before stimulation with four different clinical isolates of <i>M. avium </i>for up to 72 hours. mRNA expression was investigated using qRT-PCR. Protein in cell supernatants was quantified using ELISA and Luminex array techniques. <h3>Results</h3> Stimulation with <i>M. avium</i> does not increase MMP-9 secretion in monocytes or macrophages.<i> M. avium</i> significantly increases gene expression of MMP-1 and induces MMP-1 secretion by MDMs (Figure 1). Additionally, <i>M. avium</i> drives induction of MMP-7, an elastolytic enzyme (Figure 1), and reduces the secretion of TIMP-1; the major <i>in vivo</i> inhibitor of MMP-1. <h3>Conclusions</h3> Interestingly, unlike <i>Mycobacterium tuberculosis</i> or other chronic pulmonary pathogens such as <i>Pseudomonas</i> or <i>Haemophilus influenzae</i>, <i>M. avium</i> does not drive secretion of MMP-9 by infected mononuclear cells from healthy donors. Instead it drives functionally unopposed MMP-1, which was previously thought to be an <i>M. tuberculosis</i>-specific response. Data suggest MMP-1 and −7 may drive the destructive pulmonary pathophysiology that characterises <i>M. avium</i> infection. This will be further investigated with patient sputum samples and inflammatory cells.
S87 Deficiency of toll-like receptor 3 (TLR3) exacerbates pulmonary hypertension in mice
Authors: AAR Thompson, ND Arnold, AT Braithwaite, HL Casbolt, J Iremonger, JA Pickworth, C Monaco, JE Cole, I Sabroe, A Lawrie
Journal: Thorax (2016)

<h3>Introduction</h3> The mechanisms regulating aberrant vascular remodelling in pulmonary arterial hypertension (PAH) are poorly understood and treatments targeted at halting or reversing this process are lacking. Toll-like receptor 3 (TLR3) is a viral sensor and more recently has been established as a sensor of endogenous damage signals, responding to mRNA released by damaged cells. TLR3 signalling induces pro- and anti-inflammatory cytokine production and regulates inflammation-associated apoptosis and tyrosine kinase signalling. In a model of systemic arterial injury, TLR3 signalling was shown to modulate neointimal remodelling in a protective manner. TLR3 is also expressed in pulmonary artery smooth muscle (PASMCs) and endothelial cells (PAECs). We therefore hypothesised that TLR3 would play roles in pulmonary vascular remodelling. <h3>Methods</h3> TLR3-deficient (TLR3−/−) or wild-type C57BL/6 (WT) mice were exposed to hypoxia (10% Oxygen) and given Sugen 5416 (weekly 20 mg/kg subcutaneous injections) or maintained in normoxic conditions for 3 weeks. Haemodynamic (cardiac catheterisation and echocardiography) and histological assessments were performed after 3 weeks. Human PASMCs were serum-starved before stimulation with PDGF or poly(I:C) and proliferation was assessed after 72 hours. <h3>Results</h3> TLR3−/− mice developed a markedly exaggerated phenotype of PAH in response to Sugen/Hypoxia with increased right ventricular systolic pressures (WT 51.6 mmHg ± 4.6 vs. TLR3−/− 73.0 mmHg ± 6.8; p &lt; 0.05, mean ± SEM, n = 6), increased muscularisation of small pulmonary arteries and reduced right ventricular cardiac output (WT 424.2 RVUmin-1 ± 84.2 vs. TLR3−/− 283.3 RVUmin-1 ± 18.4, mean ± SEM, min n = 6) after 3 weeks. Poly(I:C) suppressed PDGF-induced PASMC proliferation in a dose-dependent manner. <h3>Conclusions</h3> We have shown that mice deficient in TLR3 develop a markedly exaggerated haemodynamic pulmonary hypertension phenotype and human PASMC proliferation is suppressed by the TLR3 ligand, poly(I:C). Together these data imply that TLR3 signalling in disease mediates a protective phenotype in keeping with that observed in systemic vascular remodelling, and identify a protective pathway potentially amenable to therapeutic targeting.
P3.02b-078 Non-Small Cell Lung Cancer with De Novo EGFR T790M Mutation: Clinical Features of 22 Cases
Authors: Mi Hwa Heo, Hee Kyung Kim, Hansang Lee, Jinhyun Cho, Juyoun Park, Su-Mi Jeong, Jong-Mu Sun, Se-Hoon Lee, Jin Seok Ahn, Keunchil Park, Myung-Ju Ahn
Journal: Journal of Thoracic Oncology (2017)
IgG4-Related Disease With Orbital Pseudotumors Treated With Rituximab Combined With Palpebral Surgery
Authors: Iman Aouidad, Pierre Schneider, Mathieu Zmuda, Jeremy Gottlieb, Manuelle Viguier
Journal: JAMA Dermatology (2017)

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Improved Muscular Weakness During Asthma Exacerbation
Authors: Stephanie Delstanche, Laurent Servais, Teresa Gidaro
Journal: JAMA Neurology (2017)

A 48-year-old man had muscular weakness and restricted ability to walk since infancy, but during an asthma attack, the patient was able to climb the stairs, rise from the floor, and walk several kilometers. What is your diagnosis?
Early adulthood obesity, cumulative smoking, and esophageal cancer survival.
Authors: L. E. Coate, R. Zhai, W. Xu, Z. Chen, K. Asomaning, M. Kulke, R. S. Heist, D. Christiani, G. Liu
Journal: Journal of Clinical Oncology (2011)

1546 Background: Obesity and smoking have been associated with worsening outcomes of several cancer types. However, little is known about the combined impact of early adulthood obesity (decades prior to diagnosis) and smoking on mortality of esophageal cancer (EC). Methods: We analyzed data from a cohort of 345 patients with EC from Boston, USA enrolled from 1999 to 2004. Associations between early adulthood body mass index (EABMI) (not at time of diagnosis) and smoking and overall survival (OS) were assessed using Cox proportional hazard models, adjusted for age, stage, performance status. Results: EABMI was independently associated with worse OS (HRadj=1.04; 95% CI, 1.01-1.07; p=0.009; continuous variable (CV)). When patients were evaluated in quartiles, the highest quartile of EABMI (>26.9) had the worst survival (HRadj=1.52; 1.1-2.1; p=0.01). In contrast, BMI 1 year prior to diagnosis had no association with OS. Cumulative smoking also independently conferred worse OS (HRadj=1.01; 1.00-1.01; p=0.005; CV); when evaluated using quintiles, OS was worst in the heaviest smoking quintile (>85 pack-years) (HRadj=1.60; 95% CI, 1.1-2.3; p=0.007). Compared with the lowest weight patients (during their early adulthood years) who were never smokers, HRadj for mortality increased progressively with increasing quintiles of both smoking and quartiles of EABMI. In joint effects analysis, within the highest BMI quartile (>26.9), the HRadj rose from 0.4 (0.1-1.5; lowest smoking quintile, consisting of lifetime never-smokers) through 1.8 (0.8-3.9; highest smoking quintile of >56 pack-years). Likewise, within the highest smoking quintile (>56 pack-years), the HRadj rose from 1.0 (0.4-2.3; lowest BMI quartile of <21) through to 1.8 (0.8-3.9; highest BMI quartile >26.9). Conclusions: Among EC patients, elevated BMI in early adulthood and heavy cumulative smoking history are independently associated with increased mortality risk. The combination of obesity and smoking is related to an especially higher mortality risk. These differences may reflect differences in obesity- or smoking-related comorbidities, but may also be due to biologic differences arising from different, adiposity-related carcinogenic pathways.
Acute-on-chronic liver failure: an update
Authors: Ruben Hernaez, Elsa Solà, Richard Moreau, Pere Ginès
Journal: Gut (2017)

Acute-on-chronic liver failure (ACLF) is a syndrome characterised by acute decompensation of chronic liver disease associated with organ failures and high short-term mortality. Alcohol and chronic viral hepatitis are the most common underlying liver diseases. Up to 40%–50% of the cases of ACLF have no identifiable trigger; in the remaining patients, sepsis, active alcoholism and relapse of chronic viral hepatitis are the most common reported precipitating factors. An excessive systemic inflammatory response seems to play a crucial role in the development of ACLF. Using a liver-adapted sequential organ assessment failure score, it is possible to triage and prognosticate the outcome of patients with ACLF. The course of ACLF is dynamic and changes over the course of hospital admission. Most of the patients will have a clear prognosis between day 3 and 7 of hospital admission and clinical decisions such as evaluation for liver transplant or discussion over goals of care could be tailored using clinical scores. Bioartificial liver support systems, granulocyte-colony stimulating factors or stem-cell transplant are in the horizon of medical care of this patient population; however, data are too premature to implement them as standard of care.
P2.02-011 Management of Non-Small-Cell Lung Cancer (NSCLC) Stage III Patients in Central European Countries
Authors: Milada Zemanová, Zuzana Zbožínková, Robert Pirker, Dragana Jovanovic, Vesna Ceriman, Subhash Chaudhary, Igor Richter, Krisztina Bogos, Virág Hollósi, Luboš Petruželka, Jiří Kufa, Lenka Jakubíková, Gunta Purkalne, Andreas Tiefenbacher, Karin Dieckmann, Marketa Cernovska, Leona Koubkova, Zdeňka Vilasová, Marius Zemaitis, Attila Farkas, Jelena Spasic, Miroslaw Kozlowski
Journal: Journal of Thoracic Oncology (2017)
P3.02b-100 Comparison of Three T790M Testing Methods for the Detection of Non-Small Cell Lung Cancer after Tyrosine Kinase Inhibitor Failure
Authors: Lucheng Zhu, Shirong Zhang, Bing Xia, Xueqin Chen, Limin Wang, Hong Jiang, Xufeng Chen, Shenglin Ma
Journal: Journal of Thoracic Oncology (2017)
Impact of Four-Factor Prothrombin Complex Concentrate on Urgent Warfarin-Reversal in Patients with Ventricular Assist Devices Going for Heart Transplants
Authors: Ding Wen Wu, Uehlinger Joan, Szymanski James, Mohandas Kala, Ronald Walsh, Sadiqa Karim, Evan Himchak, Ritu Gupta, Daniel Goldstein
Journal: Blood (2015)
OA18.06 Treatment, Outcome and Prognostic Factors of Patients with Thymic Epithelial Tumors at First Recurrence
Authors: Giuseppe Banna, Ankur Sheel, Varun Sheel, Andrea Bille, Tom Routledge, Shalini Fernando, Arjun Nair, Rohit Lal
Journal: Journal of Thoracic Oncology (2017)
Unrelated Donors Are Associated with Improved Relapse Free Survival Compared to Related Donors in Patients with Myelodysplastic Syndrome Undergoing Reduced Intensity Conditioned Allogeneic Stem-Cell Transplantation
Authors: Clinton Yam, Lisa Crisalli, Selina Luger, Alison Loren, Elizabeth O Hexner, Noelle Frey, James Mangan, Amy Gao, Edward A. Stadtmauer, David Porter, Ran Reshef
Journal: Blood (2015)
P1.02-064 MET-Dependent Activation of STAT3 as Mediator of Resistance to MEK Inhibitors in KRAS-Mutant Lung Cancer
Authors: Chiara Lazzari, Niki Karachaliou, Alberto Verlicchi, Carles Codony Servat, Ana Gimenez Capitan, Jordi Codony Servat, Jordi Bertrán-Alamillo, Miguel Angel Molina Vila, Imane Chaib, José Luis Ramírez Serrano, Peng Cao, Filippo De Marinis, Vanesa Gregorc, Rafael Rosell
Journal: Journal of Thoracic Oncology (2017)
P3.02c-004 SBI0206965, a Novel Inhibitor of Ulk1, Suppresses Non-Small Cell Lung Cancer Cell Growth via Modulating Both Autophagy and Apoptosis Pathways
Authors: Fang Tang, Zhihao Wang, Zetian Yang, Jun Gong, Junhong Zhang, Conghua Xie
Journal: Journal of Thoracic Oncology (2017)