tbuckley/cabot-search huggingface dataset:
Differential DNA methylation profiles in gynecologic cancers
Authors: Hui J. Yang, Vincent W. Liu, Yue Wang, Hextan Y. Ngan
Journal: Cancer Research (2004)

1168  CpG island hypermethylation of cancer-related genes is a frequent epigenetic event in human cancers. The present study was to determine the CpG island methylation profiles in gynecologic cancers; and to identify potential targets for cancer management. Methylation status for 34 loci was examined in differential DNA pools representing tumor and normal DNA from 50 cervical cancer, 50 endometrial cancer and 50 ovarian cancers by methylation specific polymerase chain reaction. Methylated alleles detected in tumor but not in normal DNA indicated the occurrence of aberrant methylation in tumors. Multiple genes were methylated in the three cancers. P16 and APC were methylated across the three cancers. MINT31 and PTEN were methylated in cervical and ovarian cancers. And RAR-β2 was methylated in ovarian and endometrial cancer. Specific methylation was also found in cervical cancer (including CDH1, DAPK, HIC-1, MGMT, MINT1, MINT2 and RASSF1A), in endometrial cancer (including CASP8, CDH13, hMLH1 and p73), and ovarian cancer (including BRCA1, p14, p15, RIZ1 and TMS1). Furthermore, incidence of methylation for DAPK, MGMT, p16 and PTEN in 127 cervical cancers; APC, CDH13, hMLH1 and p16 in 60 endometrial cancer; and BRCA1, p14, p16 and PTEN in 50 ovarian cancers, was determined. Incidence varied among different genes and in different cancer types ranging from the lowest 8.0% (PTEN in ovarian cancer) to the highest 56.7% (DAPK in cervical cancer). Methylation of some specific loci was related to particular tumor subtypes. In cervical cancer, DAPK methylation was more frequently detected in squamous cell carcinoma (SCC) than in adenocarcinoma (AC), whereas PTEN methylation was more frequent in AC than in SCC (P
Comparison of Fel d 1 and Fel d 4 levels in house dust samples from the Canadian CHILD birth cohort
Authors: Kristina Reid Black, Brian Murphy, Stephanie Filep, Jeff Brook, Padmaja Subbarao, Stuart Turvey, Piush Mandhane, Allan Becker, Timothy K. Takaro, James A. Scott, Malcolm R. Sears, Martin D. Chapman
Journal: Journal of Allergy and Clinical Immunology (2018)
An Attractive Reelin Gradient Establishes Synaptic Lamination in the Vertebrate Visual System
Authors: Vincenzo Di Donato, Flavia De Santis, Shahad Albadri, Thomas Oliver Auer, Karine Duroure, Marine Charpentier, Jean-Paul Concordet, Christoph Gebhardt, Filippo Del Bene
Journal: Neuron (2018)
Propagation of Human Spermatogonial Stem Cells In Vitro (vol 302, pg 2127, 2009)
Authors: H. Sadri-Ardekani, S. C. Mizrak, S. K. M. van Daalen, C. M. Korver, H. L. Roepers-Gajadien, M. Koruji, S. Hovingh, T. M. de Reijke, J. J. M. C. H. de la Rosette, F. van der Veen, D. G. de rooij, S. Repping, A. M. M. van Pelt
Journal: JAMA (2010)
Heat-killed Mycobacterium w inhibits growth of myeloid leukemia cells
Authors: Raghu Sinha, Kevin Null, Nirav Desai, Shailly Saini, Devesh Bhardwaj, Bakulesh Khamar, Dhimant Desai, Shantu Amin, David Claxton
Journal: Cancer Research (2007)

1865  Cadi-05, a novel poly TLR agonist, poly antigenic vaccine containing heat-killed Mycobacterium w (Mw) has previously been shown to be effective against bladder cancer and non-small cell lung cancer. In the current study, Mw successfully demonstrated growth inhibition of U937, HL60, p210-gfp (32D-bcr-abl transfectant) and NSF-60 myeloid leukemia cell lines in a dose-dependent manner (measured by MTT assay). A dose of >100 million Mw significantly inhibited growth in all these cell types. A combination of Etoposide and Mw increased apoptosis in U937 cells as compared to Etoposide treatment alone (measured by Annexin V staining). Mw treatment of U937 cells induced dose-dependent apoptosis (determined by PARP-cleavage). Furthermore, treatment of NSF-60 cells with GCSF protected against Mw induced cell death (measured by MTT assay). Cadi-05 is currently being examined in a clonogenic assay for normal human myeloid progenitor cells (for cytotoxicity) and acute myeloid leukemia cells from patients (for efficacy). Additional studies are being performed to examine if Mw-induced apoptosis is mediated through TLR in the myeloid leukemia cells.
Proteasome inhibitor bortezomib augments tumor therapy with TRAIL receptor agonist antibody MD5-1.
Authors: Anil Shanker, Alan D. Brooks, Carlos A. Tristan, Thomas J. Sayers
Journal: Cancer Research (2006)

5483   Resistance to cell death exhibited by growing tumor cells constitutes an important clinical problem. Ongoing work from our laboratory has shown the importance of the death receptor-mediated effector pathway for tumor cytolysis in vivo. Furthermore, we found that a proteasome inhibitor bortezomib (also known as Velcade, PS-341) significantly increased the sensitivity of various mouse tumor cells to death receptor-mediated apoptosis  in vitro . Molecular mechanisms of bortezomib sensitization of tumor cells to apoptosis included an increase in the TNF-related apoptosis-inducing ligand death receptor (DR5) and enhanced activation of caspase-8 and 3. A decrease in the cellular Fas-associated death domain-like IL-1-converting enzyme-inhibitory protein (cFLIP) and other downstream cellular inhibitors of apoptosis cIAP-1 and XIAP was also observed. No apparent changes were observed in Bcl-2 family proteins following bortezomib sensitization of these mouse tumor cells. In addition, there was no sensitization of tumor cells to apoptosis by the specific inhibitors of NFκB, helenalin and SN-50, implying that bortezomib sensitizes tumor cells to apoptosis in an NFκB-independent manner. In order to determine the therapeutic role of death-receptor mediated death in vivo, we designed a combination therapy regimen of bortezomib and agonist DR5 monoclonal antibody MD5-1 in renal (Renca) and mammary (4T1) carcinomas. Growth of various mouse tumors following multiple cycles of combination therapy of Bortezomib plus MD5.1 was evaluated. Interestingly, the combination therapy regimen significantly decreased the formation of lung metastases of Renca and mammary 4T1.2 carcinomas following intravenous injection and extended the survival of mice. A significant but less remarkable therapeutic effect was also observed following intraperitoneal injection of tumors. The results show a positive anti-tumor therapeutic benefit  in vivo  on combining bortezomib and DR5 mAb. The implications of utilizing molecular targeting to both destroy tumor cells and potentially promote subsequent anti-tumor immune responses will be discussed. Funded in part by DHHS #NO1-CO-12400
Molecular marker assessments for epidermal growth factor receptor (EGFR) expression by immunohistochemistry (IHC) and histoscore (H-score) in the phase III SELECT trial.
Authors: Edward S. Kim, Sreenivas Chittoor, Craig H. Reynolds, Lorinda Simms, Scott Saxman
Journal: Journal of Clinical Oncology (2013)

8052 Background: SELECT was a phase III study that investigated whether the addition of cetuximab (C) to pemetrexed (P) improved outcome in previously treated patients (pts) with recurrent or progressive non-small cell lung cancer (NSCLC). Clinical results have been reported previously and demonstrated that adding C to P did not improve progression-free survival (PFS) or overall survival (OS). H-score has been reported to be a potential predictor of outcome for C therapy. Prespecified biomarker analyses, including EGFR IHC and H-score, are reported here. Methods: EGFRexpression in tumor tissue was not required for eligibility; however, tissue was collected and analyzed for EGFR expression by IHC using standard methods. In addition, H-score evaluation was performed by trained central pathologists and correlated with clinical outcome using a predefined cutoff for “low” and “high” of &lt;200 and ≥200, respectively. Results: A total of 449 (IHC) and 406 (H-score) pt specimens were evaluable. Demographics for pts with tissue available for EGFR analysis were similar to the overall population. For IHC+ pts (n=396), median PFS for C+P was 3.02 months (95% CI, 2.76–3.45) compared with 2.99 months (95% CI, 2.63–4.14) for P (HR, 1.02 [95% CI, 0.83–1.24]; p=.86). For pts with low H-score (N=99 [C+P] and N=111 [P]), median PFS was 2.7 months (95% CI, 1.8–3.2) with C+P and 3.1 months (95% CI, 2.6–4.1) with P (HR, 1.11 [95% CI, 0.84–1.46]; P=.48); median OS was 6.7 months (95% CI, 5.3–8.6) with C+P and 6.6 months (95% CI, 4.7–9.2) with P (HR, 0.96 [95% CI, 0.72–1.27]; P=.76). Among pts with high H-scores (N=101 [C+P] and N= 95 [P]), median PFS was 3.2 months (95% CI, 2.7–4.6) with C+P and 3.7 months (95% CI, 1.7–4.5) with P (HR, 1.02 [95% CI, 0.77–1.37]; P=.86); median OS was 7.7 months (95% CI, 6.5–10.9) with C+P and 8.0 months (95% CI, 7.0–9.1) with P (HR, 1.17 [95% CI, 0.86–1.57]; P=.32). Conclusions: EGFR H-score was not predictive of benefit for the addition of C to P in this population of pts with NSCLC. There was also no treatment effect in the IHC+ group. Clinical trial information: NCT00095199.
In silico Analysis Of Alterations In ANGPT1 Gene Supports A New Pathway Responsible To Mediate Hereditary Angioedema In Brazilian Patients With No Mutations In SERPING1 And F12 Genes
Authors: Nathália Cagini, Camila Lopez Veronez, Bruna Franca Azevedo, Rosemeire Navickas Constantino-Silva, Renan Paulo Martin, Jane da Silva, Anete S. Grumach, João Bosco Pesquero
Journal: Journal of Allergy and Clinical Immunology (2018)
Acute Myocardial Infarction after Laboratory-Confirmed Influenza Infection
Authors: Jeffrey C. Kwong, Kevin L. Schwartz, Michael A. Campitelli, Hannah Chung, Natasha S. Crowcroft, Timothy Karnauchow, Kevin Katz, Dennis T. Ko, Allison J. McGeer, Dayre McNally, David C. Richardson, Laura C. Rosella, Andrew Simor, Marek Smieja, George Zahariadis, Jonathan B. Gubbay
Journal: New England Journal of Medicine (2018)

Acute myocardial infarction can be triggered by acute respiratory infections. Previous studies have suggested an association between influenza and acute myocardial infarction, but those studies used nonspecific measures of influenza infection or study designs that were susceptible to bias. We evaluated the association between laboratory-confirmed influenza infection and acute myocardial infarction.
A Disturbing Legacy of Childhood Kidney Disease
Authors: Julie R. Ingelfinger
Journal: New England Journal of Medicine (2018)

Despite an apparent resolution of various kidney diseases during childhood, undetectable and poorly understood residual damage may confer an increased risk of chronic kidney disease in adulthood. In this issue of the Journal, Calderon-Margalit et al.1 provide long-term, though retrospective, data showing an increased risk of end-stage renal disease (ESRD) in adulthood among Israeli adolescents with a history of childhood kidney disease among whom the disease had resolved, as determined by normal renal function and blood pressure at the time of conscription into the Israeli armed services (period of study enrollment, 1967 through 1997; mean age at the initial medical . . .
Efficacy and immunologic effects of RNA-pulsed dendritic cell vaccines targeting human cytomegalovirus antigens in patients with glioblastoma
Authors: Duane Mitchell, Gary Archer, Darell Bigner, Annick Desjardins, Allan Friedman, Henry Friedman, Denise Lally-Goss, James Herndon, Sharon McGehee, Roger McLendon, Beth Perry, David Reardon, Jeremy Rich, Steve Silverman, James Vrendenburgh, John Sampson
Journal: Cancer Research (2008)

LB-73    Background  Conventional therapies for GBM fail to target tumor cells exclusively. Immunologic targeting of tumor-specific proteins may allow more precise eradication of neoplastic cells. The discovery and recent confirmation that GBM, but not surrounding normal brain tissue, serves as a refuge for  Cytomegalovirus  (CMV) reactivation provides an unparalleled opportunity to subvert, as tumor-specific antigens, the highly-immunogenic viral proteins expressed by CMV.   Patients and Methods  A phase II randomized, prospective clinical trial was undertaken to assess the immunogenicity and efficacy of targeting the immunodominant CMV integument protein, pp65, in patients with newly-diagnosed GBM using pp65-RNA transfected dendritic cells (DCs). After resection and radiation with concurrent TMZ (75mg/m 2 /d), patients received subsequent monthly cycles of TMZ (200 mg/m 2 ) simultaneous with intradermal vaccinations and were randomized to receive an autologous lymphocyte transfusion (ALT) (3x10 7 /Kg) prior to vaccination. Subjects received vaccinations until there was evidence of tumor progression or death.   Results  21 patients were consented. 5 progressed during radiotherapy. There were no vaccine-related, reportable SAEs. TMZ therapy, however, induced Grade 3 lymphopenia (500 cells/mL) in 70% of patients after the first TMZ cycle. One nearly complete response was observed. Median PFS was 12.5 months (CI 95 : 10.0, ∞). Overall median survival is undefined, but is >21.1 months. The group randomized to receive ALT has a significantly worse median survival ( P =0.0354; logrank). Induction of CMV-specific antibody responses and DTH responses to DC vaccination were observed in the context of concurrent TMZ chemotherapy, demonstrating the TMZ is not a barrier to immunologic responses to DC vaccination in humans. Polyfunctional T cell responses are under current evaluation, but preliminary data shows that patients with GBM have CMV-specific immunologic deficiencies.   Conclusions  CMV proteins may serve as novel, tumor-specific targets for immunotherapy in patients with GBM. Immunotherapy targeting CMV pp65 may improve survival and should be evaluated in randomized Phase III trials.  This work was supported by funds from the NIH/NINDS SPORE in Brain Cancer 1P50 CA108786 01 (Sampson), NIH R01 CA-97222-01 (Sampson), The Brain Tumor Society (Mitchell / Sampson), and Accelerate Brain Cancer Cure (Mitchell).
Strain Tracking Reveals the Determinants of Bacterial Engraftment in the Human Gut Following Fecal Microbiota Transplantation
Authors: Christopher S. Smillie, Jenny Sauk, Dirk Gevers, Jonathan Friedman, Jaeyun Sung, Ilan Youngster, Elizabeth L. Hohmann, Christopher Staley, Alexander Khoruts, Michael J. Sadowsky, Jessica R. Allegretti, Mark B. Smith, Ramnik J. Xavier, Eric J. Alm
Journal: Cell Host & Microbe (2018)
miR-19b enhances proliferation and apoptosis resistance via the EGFR signaling pathway by targeting PP2A and BIM in non-small cell lung cancer
Authors: Ulrich Baumgartner, Fabienne Berger, Ali Hashemi Gheinani, Sabrina Sofia Burgener, Katia Monastyrskaya, Erik Vassella
Journal: Molecular Cancer (2018)

Epidermal growth factor receptor (EGFR) mutations enable constitutive active downstream signaling of PI3K/AKT, KRAS/ERK and JAK/STAT pathways, and promote tumor progression by inducing uncontrolled proliferation, evasion of apoptosis and migration of non-small cell lung cancer (NSCLC). In addition, such EGFR mutations increase the susceptibility of patients with NSCLC to tyrosine kinase inhibitor (TKI) therapy, but treated patients will invariably relapse with resistant disease. A global understanding of underlying molecular mechanisms of EGFR signaling may improve the management of NSCLC patients. microarray analysis was performed to identify PI3K/AKT-regulated miRNAs. Phosphoproteomic analysis and cell based assays were performed using NSCLC cell lines lentivirally transduced with anti-miR or miR overexpressing constructs. Here, we show that 17 miRNAs including members of the miR-17~ 92 cluster are dysregulated following PI3K/AKT inhibition of EGFR mutant NSCLC cells. Bioinformatics analysis revealed that dysregulated miRNAs act in a concerted manner to enhance the activity of the EGFR signaling pathway. These findings were closely mirrored by attenuation of miR-17~ 92 family member miR-19b in NSCLC cell lines which resulted in reduced phosphorylation of ERK, AKT and STAT and effector proteins in EGFR mutant NSCLC cells. Consistent with this finding, cell cycle progression, clonogenic growth and migration were reduced and apoptosis was enhanced. Co-treatment of NSCLC cells with the tyrosine kinase inhibitor (TKI) gefitinib and anti-miR-19b construct reduced migration and clonogenic growth in a synergistic manner suggesting that EGFR and miR-19b act together to control oncogenic processes. Serine/threonine phosphatase PP2A subunit PPP2R5E and BCL2L11 encoding BIM were identified as major targets of miR-19b by target validation assays. Consistent with this finding, PP2A activity was strongly enhanced in NSCLC transduced with anti-miR-19b construct, but not in cells co-transduced with anti-miR-19b and shPPP2R5E, suggesting that PPP2R5E is a major constituent of the PP2A complex. Accordingly, enhanced proliferation by miR-19b was due to targeting PPP2R5E. In contrast, apoptosis resistance was mainly due to targeting BCL2L11. Our results provide insight into the importance of targeting PPP2R5E and BCL2L11 by miR-19b in oncogenic processes of NSCLC. Attenuation of miR-19b expression could potentially be exploited in adjuvant therapy of EGFR mutant NSCLC.
Incidence and Outcome of Breast Biopsy Procedures During Follow-up After Treatment for Breast Cancer
Authors: Raquel F. D. van la Parra, Kaiping Liao, Benjamin D. Smith, Wei T. Yang, Jessica W. T. Leung, Sharon H. Giordano, Henry M. Kuerer
Journal: JAMA Surgery (2018)

No comprehensive data are available regarding the frequency of breast biopsies performed during follow-up of treatment for invasive breast cancer.
Abstract 3023: Coronary Artery And Viability Evaluation In Anca-Associated Vasculitides Using Magnetic Resonance Imaging
Authors: Sophie Mavrogeni, Theodora C Karagiorga, Menelaos N Manousakis, Marouso Douskou, Dimosthenis Panagiotakos, Haralambos M Moutsopoulos, Dennis V Cokkinos
Journal: Circulation (2006)

Microscopic Polyangiitis (MPA), Wegener’s Granulomatosis (WG) and Churg-Strauss syndrome (CSS) are forms of necrotizing vasculitis with a varying prevalence of ANCA positivity. CA can be occasional...
Clinically detected non-aggressive lung cancers: implications for overdiagnosis and overtreatment in lung cancer screening
Authors: Kevin ten Haaf, Carlijn M van der Aalst, Harry J de Koning
Journal: Thorax (2018)

CT lung cancer screening is currently being implemented in clinical practice in the USA and pilot studies are ongoing in the UK.1 2 Recently, an European Union statement recommended planning the potential implementation of lung cancer screening in Europe.3 Overdiagnosis, the detection of a cancer through screening which would have never been diagnosed in the patient’s lifetime if screening had not occurred, is a harm that inevitably occurs with the implementation of a screening programme. Therefore, more information on the occurrence of non-aggressive disease is essential to aid in successfully implementing a screening programme that minimises overdiagnosis and overtreatment.

Kale et al  linked data from 1992 to 2010 of the Surveillance, Epidemiology, and End Results Database to Medicare claims in order to identify individuals with clinically detected, non-aggressive lung cancer in the USA.4 The authors find low rates of non-aggressive lung cancers in clinical practice, but advise caution, as the rate of non-aggressiveness among screen-detected cancers is ‘…likely to be different as screening with CT may unveil small, slowly progressive cancers that are biologically dissimilar’. However, non-aggressive clinically detected lung cancer may share characteristics with those of non-aggressive lung cancers detected by screening. Thus, information derived from non-aggressive lung cancers in clinical practice may aid in reducing overdiagnosis and overtreatment in lung cancer screening.

For example, one of the concerns raised for implementing lung cancer screening has been the …
System to support patients with ongoing needs is “falling short on many fronts”
Authors: Jacqui Wise
Journal: BMJ (2018)

NHS continuing healthcare—the package of care put together for patients with significant ongoing healthcare needs—is failing people, says a highly critical report by a committee of MPs that scrutinises public spending.1

People do not know about the scheme, find it too complicated to access, or have to wait too long to find out whether they are eligible for funding, said the report from the Public Accounts Committee. In some cases people have died while waiting for a decision, it said.

Around a third of assessments, almost 25 000, took longer than the government’s recommended maximum of 28 days, the report found. About 10% of clinical commissioning groups (CCGs) reported that, from November 2015 …
Epidermal lipid composition, barrier integrity, and eczematous inflammation are associated with skin microbiome configuration
Authors: Hansjörg Baurecht, Malte C. Rühlemann, Elke Rodríguez, Frederieke Thielking, Inken Harder, Anna-Sophie Erkens, Dora Stölzl, Eva Ellinghaus, Melanie Hotze, Wolfgang Lieb, Sheng Wang, Femke-Anouska Heinsen-Groth, Andre Franke, Stephan Weidinger
Journal: Journal of Allergy and Clinical Immunology (2018)
Efficacy of Granulocyte Colony-Stimulating Factor and N-Acetylcysteine Therapies in Patients With Severe Alcoholic Hepatitis
Authors: Virendra Singh, Amarjit Keisham, Ashish Bhalla, Navneet Sharma, Ritesh Agarwal, Ratiram Sharma, Akash Singh
Journal: Clinical Gastroenterology and Hepatology (2018)
Denosumab versus zoledronic acid in bone disease treatment of newly diagnosed multiple myeloma: an international, double-blind, double-dummy, randomised, controlled, phase 3 study
Authors: Noopur Raje, Evangelos Terpos, Wolfgang Willenbacher, Kazuyuki Shimizu, Ramón García-Sanz, Brian Durie, Wojciech Legieć, Marta Krejčí, Kamel Laribi, Li Zhu, Paul Cheng, Douglas Warner, G David Roodman
Journal: The Lancet Oncology (2018)
Abstract 17470: Quality of Care for Patients Hospitalized With Acute Coronary Syndrome in China: Findings From the Improving Care for Cardiovascular Disease in China (CCC) Project - Acute Coronary Syndrome Program
Authors: Yongchen Hao, Jing Liu, Jun Liu, Sidney C Smith, Yong Huo, Gregg C Fonarow, Changsheng Ma, Junbo Ge, Kathryn A Taubert, Louise Morgan, Yang Guo, Qian Zhang, Wei Wang, Dong Zhao
Journal: Circulation (2016)

Introduction: To explore effective strategies to improve the quality of care for acute coronary syndromes (ACS), AHA and Chinese Society of Cardiology have launched a collaborative program - Improv...