tbuckley/cabot-search huggingface dataset:
Abstract B47: Drug-induced EMT is fundamentally distinct from pathologic EMT
Authors: Saeed Salehin Akhand, Michael Wendt
Journal: Cancer Research (2016)

Abstract Background: Receptor tyrosine kinase ErbB2 (Her2) is overexpressed in an estimated 25% of the breast cancer patients. A therapeutic regime of Her2 targeted therapies, consists of Trastuzumab followed by the dual EGFR/Her2 tyrosine kinase inhibitor, Lapatinib. These therapies continue to show success in blocking the progression of this breast cancer subtype. Of clinical concern, however, cancer cells eventually develop pathways to evade Lapatinib-mediated tumor inhibition and acquire drug resistance. In this study, we sought to understand the molecular mechanism of resistance towards Lapatinib. Methods: We used Her2 overexpressing human mammary epithelial cells to generate Lapatinib resistant cell lines (LapR) in vitro. The LapR cells acquired growth persistence within the continued presence of Lapatinib for four weeks. We analyzed the resultant cell populations via cell viability assays, immunoblotting, flow cytometry, 3D cell culture and Nano-string gene expression analysis. Results: Generated LapR cell lines showed robust epithelial-mesenchymal transition (EMT) phenotypes that included upregulated FGFR1 and preservation of their Her2 expression. We tested the viability of LapR cells using dose response assays with Afatinib, a second-generation covalent ErbB kinase inhibitor, and Trastuzumab emtansine (T-DM1), an anti-Her2 antibody drug conjugate. We also utilized recently developed covalent inhibitors of FGFR. LapR cells were highly resistant to Afatinib but did show sensitivity to T-DM1 and FGFR kinase inhibition. Importantly, resistance to ErbB inhibition was maintained in the LapR cells for several weeks following removal of Lapatinib. This stable phenotype was consistent with a maintained yet distinct regulation of the cancer stem cell markers (CD44/CD24) compared to a transient EMT induced by transforming growth factor β (TGF-β). Strikingly, we observed that unlike their parental counterparts LapR cells were unable to grow in a compliant 3D matrix. Furthermore, unlike TGF-β-treated cells, LapR cells were unable to metastasize in vivo. By using Nano-string pan cancer progression panel analysis, we characterized key differences in the LapR EMT phenotype as compared to a TGF-β induced EMT. Future Directions: Currently, we are analyzing the expression data of LapR and TGF-β-induced EMT to identify key targets required for EMT-induced tumor progression. Overall, our studies seek to define what aspects of EMT are involved in cellular persistence in response to anti-cancer drugs versus those utilized by cells during metastatic progression. Citation Format: Saeed Salehin Akhand, Michael Wendt. Drug-induced EMT is fundamentally distinct from pathologic EMT. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Metastasis; 2015 Nov 30-Dec 3; Austin, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(7 Suppl):Abstract nr B47.
TCTAP C-229 Lower Limb Percutaneous Salvage in Acute Femoral Superficial Artery Occlusion Associate with Chronic Below-the-Knee All Three Arteries Occlusions: Combined Anterograde and Retrograde Approaches
Authors: Farhat Fouladvand, Sashko Zhezhovski, Dimitar Mizov
Journal: Journal of the American College of Cardiology (2017)
Community-based strategies to strengthen men’s engagement in the HIV care cascade in sub-Saharan Africa
Authors: Monisha Sharma, Ruanne V. Barnabas, Connie Celum
Journal: PLoS Medicine (2017)

Men in sub-Saharan Africa are less likely than women to engage in HIV services across the care cascade, resulting in poorer clinical outcomes.• Health care facilities have achieved limited HIV testing and treatment coverage in men, with barriers including confidentiality concerns, distance to the facility, inconvenient hours, and perceptions that facilities provide women-centered services.Other barriers to male engagement include stigma, poverty, and feelings of compromised masculinity associated with seeking health care.• Community-based HIV interventions can overcome barriers associated with facilities and increase men's engagement in care.Social and livelihood interventions can reduce stigma and poverty.• Community-based testing interventions (particularly home and mobile) have high acceptability and reach more men than health care facility-based approaches.For men testing HIV positive, providing immediate antiretroviral therapy (ART) is associated with high retention and viral suppression.This strategy of "collapsing the cascade" provides streamlined services and reduces loss to follow-up.• Community-based interventions should be tailored to the needs of men to maximize uptake, including flexible hours, multiple follow-up visits, and convenient and private access to care.Integrating HIV testing into screening for chronic disease can reduce stigma and increase program efficiency.More research is needed on male-centered approaches to increase men's engagement in HIV services, particularly later in the cascade.Interventions targeted to men who have sex with men are urgently needed.• The current state of evidence strongly suggests that community-based test-and-treat strategies can reduce the gender disparity in HIV testing and treatment by achieving higher levels of ART coverage and viral suppression in HIV-positive men.
Restaurant Food Allergy Practices — Six Selected Sites, United States, 2014
Authors: Taylor J. Radke, Laura G. Brown, Brenda Faw, Nicole Hedeen, Bailey Matis, Priscela Perez, Brendalee Viveiros, Danny Ripley
Journal: MMWR Morbidity and Mortality Weekly Report (2017)

Food allergies affect an estimated 15 million persons in the United States (1), and are responsible for approximately 30,000 emergency department visits and 150-200 deaths each year (2). Nearly half of reported fatal food allergy reactions over a 13-year period were caused by food from a restaurant or other food service establishment (3). To ascertain the prevalence of food allergy training, training topics, and practices related to food allergies, CDC's Environmental Health Specialists Network (EHS-Net), a collaborative forum of federal agencies and state and local health departments with six sites, interviewed personnel at 278 restaurants. Fewer than half of the 277 restaurant managers (44.4%), 211 food workers (40.8%), and 156 servers (33.3%) interviewed reported receiving food allergy training. Among those who reported receiving training, topics commonly included the major food allergens and what to do if a customer has a food allergy. Although most restaurants had ingredient lists for at least some menu items, few had separate equipment or areas designated for the preparation of allergen-free food. Restaurants can reduce the risk for allergic reactions among patrons by providing food allergy training for personnel and ingredient lists for all menu items and by dedicating equipment and areas specifically for preparing allergen-free food.
Immune checkpoint blockade for glioblastoma: Preclinical activity of single agent and combinatorial therapy.
Authors: David A. Reardon, Prafulla C. Gokhale, F. Stephen Hodi, Keith L. Ligon, Xiaoyun Liao, Scott J. Rodig, Jun Zhou, Lei Qin, Kristen Jones, Amy Sauer, Nancy E. Kohl, Glenn Dranoff, Gordon James Freeman
Journal: Journal of Clinical Oncology (2014)

2084 Background: Outcome for glioblastoma (GBM) remains dismal and innovative treatment strategies are desperately needed. Growing data support the contribution of local and systemic immune checkpoint molecules mediating immunosuppression by GBM tumors. Methods: Luciferized GL261 cells (GL261-Luc) were stereotactically implanted intracranially in albino C57BL/6 mice. Cohorts of mice with growing tumors (increasing bioluminescence) were treated with murine monoclonal antibodies (MAb) against PD-1, PD-L1, PD-L2, and CTLA-4 (single agent and combinations) every 3 days X 8 beginning 6 days following tumor implantation and were followed for overall survival. Subsets of mice underwent MRI as well as analysis of tumor infiltrating immune cells, and systemic immune cells and immunocytokines. Tumor re-challenge experiments were performed among long-term surviving mice. Results: Immune checkpoint blockade was well tolerated with no apparent morbidity or mortality among treated animals. Improved survival was noted among mice treated with immune checkpoint blockade compared to appropriate controls. The most robust survival benefit was noted among mice treated with combinatorial therapy including 12/18 (75%) mice treated with anti-PD-1 + anti-CTLA-4 MAbs alive at 140 days with no evidence of residual tumor. MRI imaging among long-term surviving animals demonstrated clear evidence of initial tumor growth followed by regression and eradication of tumors. Long-term surviving mice appeared fully intact neurologically and exhibited no evidence of tumor growth following re-challenge of GL261-Luc cells injected subcutaneously. Characterization of tumor infiltrating immune cells as well as systemic immune cells and immunocytokines is ongoing. Conclusions: Immune checkpoint blockade provides significant survival benefit and appears safe in this immunocompetent, orthotopic syngeneic GBM model. Re-challenge experiments demonstrate evidence of long-term immunologic memory and further elucidation of underlying mechanisms of immune-mediated anti-tumor activity is ongoing. These data strongly support the evaluation of immune checkpoint inhibitors among patients with GBM.
Impact of combining PgR score and original preoperative endocrine prognostic index (PEPI) score as a prognostic factor of neoadjuvant endocrine therapy using exemestane in postmenopausal ER-positive/HER2-negative breast cancer.
Authors: Sasagu Kurozumi, Hiroshi Matsumoto, Katsunori Tozuka, Yuji Hayashi, Kenichi Inoue, Shigenori E. Nagai, Hanako Oba, Jun Horiguchi, Izumi Takeyoshi, Masafumi Kurosumi
Journal: Journal of Clinical Oncology (2015)

548 Background: Neoadjuvant endocrine therapies (NAE) using aromatase inhibitors effectively reduce tumor size in postmenopausal ER-positive breast cancer (BC). The utility of PEPI scoring in predicting of the recurrence-free survival (RFS) after NAE is well-known. On the other hand, PgR can be a prognostic factor of ER-positive BC. We compared original PEPI score with PgR status alone, and modified PEPI score including PgR status, as prognostic factors of NAE in postmenopausal ER-positive/HER2-negative BC. Methods: Our study included 107 Japanese women with invasive ER-positive/HER2-negative BC who were received NAE with exemestane (25 mg/day) for at least 4 months (median follow-up: 47 months). Analysis 1: PEPI score (0-12 points) of each patient was determined using ypT, ypN, Ki67 and ER (Allred score), and patients were divided into 3 risk groups: low (0), moderate (1-3), and high ( ≥ 4). RFS and cancer-specific survival (CSS) were compared between groups. Analysis 2: Cutoff values of PgR were tentatively defined as, 0, 1, 10, 20, 33, 50 or 66%; an effective cutoff value was determined by analysis of RFS and CSS. Analysis 3: PgR score (3 to low; 0 to high, using cutoff value determined by analysis 2) and original PEPI score were combined, and RFS and CSS of 3 risk groups were analyzed. Results: The PgR staining of 50% was the most significant cutoff value for predicting differences of RFS and CSS (RFS: P = 0.005, CSS: P = 0.003). PEPI score was also significant prognostic factor for CSS and RFS (RFS: P = 0.0009, CSS: P = 0.043). The hazard-ratio (HR) of PEPI score was greater than that of PgR in RFS (PEPI: 13.99 vs. PgR: 7.76), but lower than for CSS (PEPI: 6.28 vs. PgR: 8.74). However, combining PgR score to original PEPI score was the most potent prognostic indicator for both RFS and CSS (RFS: HR 20.35, P = 0.000001 and CSS: HR 18.48, P = 0.000097). Conclusions: PgR alone using 50% of cutoff value and original PEPI score might be a significant prognostic indicator for NAE using exemestane. However, combining PgR score and original PEPI score might be more potent prognostic indicator in both RFS and CSS.
Exercise prescription for overhead athletes with shoulder pathology: a systematic review with best evidence synthesis
Authors: Alexis A Wright, Eric J Hegedus, Daniel T Tarara, Samantha C Ray, Steven L Dischiavi
Journal: British Journal of Sports Medicine (2017)

Objective To produce a best evidence synthesis of exercise prescription used when treating shoulder pathology in the overhead athlete. Design A systematic review of exercises used in overhead athletes including case studies and clinical commentaries. Data sources MEDLINE, PubMed, SPORTDiscus and CINAHL from database inception through July 8, 2016. Methods We examined data from randomised controlled trials and prospective cohort (level I–IV evidence) studies that addressed exercise intervention in the rehabilitation of the overhead athlete with shoulder pathology. Case studies and clinical commentaries (level V evidence) were examined to account for expert opinion-based research. Data were combined using best evidence synthesis and graded (A–F) recommendations (Centre for Evidence-Based Medicine). Results There were 33 unique exercises in six level I–IV studies that met our inclusion criteria. Most exercises were single-plane, upper extremity exercises performed below 90 o of elevation. There were 102 unique exercises in 33 level V studies that met our inclusion criteria. These exercises emphasised plyometrics, kinetic chain and sport-specific training. Conclusions and relevance Overall, evidence for exercise interventions in overhead athletes with shoulder pathology is dominated by expert opinion (grade D). There is great variability between exercise approaches suggested by experts and those investigated in research studies and the overall level of evidence is low. The strongest available evidence (level B) supports the use of single-plane, open chain upper extremity exercises performed below 90° of elevation and closed chain upper extremity exercises. Clinical expert pieces support a more advanced, global treatment approach consistent with the complex, multidimensional nature of sport.
PDL1-expressing circulating tumor cells (CTCs) in head and neck squamous cell carcinoma (HNSCC).
Authors: George Koutsodontis, Areti Strati, Margaritis Avgeris, Eirini Maratou, Vassilios Ramfidis, George Konstantinidis, Panagiota Economopoulou, Giannis Kotsantis, Kostas Tsigaridas, Elena Mihal Vagia, Nick Haralambakis, Clarence Sasaki, Andreas Scorilas, Christos Perisanidis, Maria Vasilakopoulou, Alexios Strimpakos, Evi Lianidou, Amanda Psyrri
Journal: Journal of Clinical Oncology (2015)

6018 Background: Blockade of PD-1/PD-L1 immune checkpoint pathway emerged as promising novel therapeutic strategy for cancer. Predictive biomarkers for response to anti-PD1 therapy are lacking. Because therapy with checkpoint inhibitors is cost intensive, noninvasive tools for early prediction of responders are of major interest. We assessed gene expression of PDL1 in CTCs at baseline and posttreatment in HNSCC patients (pts). Methods: 70 pts with locally advanced (n = 58) or recurrent/metastatic (n = 12) HNSCC were included in this analysis. Patients with locally advanced disease were treated with cisplatin chemoradiotherapy +/- TPF induction chemotherapy (IC). We assessed PDL1 expression at baseline, after completion of induction chemotherapy, at end of chemoradiotherapy and at relapse. We quantified PDL1 gene transcripts in immunomagnetically positively selected CTCs and 20 healthy individuals. A quantitative real time RT-qPCR assay for PDL1 was developed based on de novo in-silico design of primers and Taqman probes. The specificity was first tested by homology searches in the nucleotide database (NCBI, nucleotide BLAST). To assess univariate differences of study parameters according to PDL1 expression chi-square test was used for the categorical clinicopathological variables, while patients’ survival curves according to PDL1expression were generated by Kaplan-Meier analysis and tested for significance using the Mantel-Cox log-rank test. Results: From 88 total evaluable CTC samples, 26 of 46 were PDL1+ at baseline, 6 of 17 post-IC, 11 of 23 at end of treatment and 1 of 2 at relapse. The assay sensitivity was evaluated using external quantification calibrators ranging from 105 copies/μL to 10 copies/μL. There was trend (p = 0.07) for adverse association between PDL1 expression at baseline and progression-free survival. Conclusions: We report for the first time a highly sensitive, specific and reproducible quantitative real-time RT-qPCR assay for the assessment of PDL1 expression in CTCs. The assay is currently validated in CTCs isolated from a large number of HNSCC pts. Serial PDL1 expression assessment has potential to select and monitor pts for PD-1 targeted therapies.
Analysis of Patients with Common Peripheral T-Cell Lymphoma Subtypes From a Phase 2 Study of Romidepsin in Relapsed or Refractory Peripheral T-Cell Lymphoma
Authors: Bertrand Coiffier, Barbara Pro, H. Miles Prince, Francine M. Foss, Lubomir Sokol, Matthew Greenwood, Dolores Caballero, Peter Borchmann, Franck Morschhauser, Martin Wilhelm, Lauren Pinter-Brown, Swaminathan Padmanabhan, Andrei R. Shustov, Jean Nichols, Susan Carroll, John Balser, Steven M. Horwitz
Journal: Blood (2011)
Managing Patients With Large Ischemic Core—What Is in a Match?
Authors: Thanh G. Phan, Henry Ma
Journal: JAMA Neurology (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Neurology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Neurology journal
Study of gene expression alteration in male androgenetic alopecia: evidence of predominant molecular signalling pathways
Authors: L. Michel, P. Reygagne, P. Benech, F. Jean‐Louis, S. Scalvino, S. Ly Ka So, Z. Hamidou, S. Bianovici, J. Pouch, B. Ducos, M. Bonnet, A. Bensussan, A. Patatian, E. Lati, J. Wdzieczak‐Bakala, J‐C. Choulot, E. Loing, M. Hocquaux
Journal: British Journal of Dermatology (2017)

Male androgenetic alopecia (AGA) is the most common form of hair loss in men. It is characterized by a distinct pattern of progressive hair loss starting from the frontal area and the vertex of the scalp. Although several genetic risk loci have been identified, relevant genes for AGA remain to be defined.To identify biomarkers associated with AGA.Molecular biomarkers associated with premature AGA were identified through gene expression analysis using cDNA generated from scalp vertex biopsies of hairless or bald men with premature AGA, and healthy volunteers.This monocentric study reveals that genes encoding mast cell granule enzymes, inflammatory mediators and immunoglobulin-associated immune mediators were significantly overexpressed in AGA. In contrast, underexpressed genes appear to be associated with the Wnt/β-catenin and bone morphogenic protein/transforming growth factor-β signalling pathways. Although involvement of these pathways in hair follicle regeneration is well described, functional interpretation of the transcriptomic data highlights different events that account for their inhibition. In particular, one of these events depends on the dysregulated expression of proopiomelanocortin, as confirmed by polymerase chain reaction and immunohistochemistry. In addition, lower expression of CYP27B1 in patients with AGA supports the notion that changes in vitamin D metabolism contributes to hair loss.This study provides compelling evidence for distinct molecular events contributing to alopecia that may pave the way for new therapeutic approaches.
Tumor response assessment in locally unresectable or metastatic soft tissue sarcoma (aSTS) patients (pts): A three-year Regina Elena Cancer Institute (IRE) experience with trabectedin therapy.
Authors: Carmen Nuzzo, Vincenzo Anelli, Silvia Carpano, Angela Torsello, Domenico Sergi, Renato Covello, Carmine Zoccali, Vanja Vaccaro, Franco Di Filippo, Diana Giannarelli, Virginia Ferraresi, Francesco Cognetti
Journal: Journal of Clinical Oncology (2013)

e21517 Background: Trabectedin has emerged as an effective agent for aSTS pts pretreated with anthracyclines and ifosfamide. Recent data suggest that RECIST criteria could underestimate tumor response. Methods: ASTS pts who received trabectedin as 2nd or further line of treatment were retrospectively reviewed. Tumor response was assessed using RECIST, mChoi and MASS criteria. A good response according to mChoi Criteria was defined as ≥ 10% mean decrease in tumor size or a ≥ 15% decrease in tumor attenuation on contrast-enhanced CT images. Predominantly solid enhancing target lesions were evaluated for marked central necrosis or marked decreased attenuation on axial contrast-enhanced CT images by MASS Criteria. Results: From May 2009 to December 2012, 30 pts with aSTS received trabectedin; pts characteristics are summarized in the table. Median number of previous treatment lines was 2 (range 1-5); median number of cycles administered was 4 (range 1–22 cycles). Treatment was well tolerated; main causes of dose-reduction were hematological and liver toxicities. Median progression free survival (PFS) was 8 wks (95% CI: 2-14); median overall survival (OS) was 44 wks (95% CI: 18-94). According to RECIST, 4 pts (15.4%)obtained a partial response (PR)), 9 pts (34.6%) achieved a stable disease (SD); tumor control rate was 50%. 13 pts (43%) obtained a progression of disease (PD). CT Scans of 13 pts were available for comparison of different response assessment methods (2 RP, 5 SD, and 6 PD). In our small series of pts concordance between the three radiologic methods tested was 90%. Conclusions: In aSTS patients treated with trabectedin, there is substantial concordance between mChoi, MASS and RECIST criteria. Prospective validation of the potential role of mChoi and MASS criteria in this setting is warranted. [Table: see text]
Finding Youths at Risk for HIV Infection
Authors: Allison L. Agwu, Thomas C. Quinn
Journal: JAMA Pediatrics (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal