tbuckley/cabot-search huggingface dataset:
Abstract 4583: Potential role of neuropilin-2 in the regulation of c-MET-induced PD-L1 expression in renal cancer cells
Authors: Murugabaskar Balan, Soumitro Pal
Journal: Cancer Research (2016)

Abstract Neuropilin-1 and -2 (NRP1 and NRP2) are the transmembrane glycoproteins that act as co-receptors for class III semaphorins and several members of the vascular endothelial growth factor (VEGF) family. In conjunction with VEGF receptors and plexins, NRPs and semaphorins modulate various biological responses. Recent studies suggest that NRPs are up-regulated in many types of cancer cells, and may play a major role in tumor growth. In addition to semaphorins and VEGF, NRP1 and NRP2 can also bind to hepatocyte growth factor (HGF), which is the ligand for the tyrosine kinase receptor c-MET. c-MET is highly over-expressed in renal cancer cells; however, the impact of NRPs on c-MET-mediated tumorigenic pathways have not been studied. Recently, we have reported that HGF-/c-MET-induced signaling increases the expression of immunosuppressive and negative-co-stimulatory molecule programmed death-1 ligand (PD-L1) on renal cell carcinoma (RCC) cells, and it protects tumor cells from immune-mediated killing. In this study, we investigated whether NRPs and its ligands can modulate the expression of HGF-/c-MET-induced PD-L1. We have observed that NRP2, and to a lesser extent NRP1, is over-expressed in human RCC cell lines (786-O, ACHN and Caki-1) compared with normal renal epithelial cells at both mRNA and protein level. siRNA-mediated silencing of NRP1 and NRP2 promoted apoptosis of renal cancer cells, suggesting possible role(s) of NRPs in tumor growth. The knock-down of NRP2 down-regulated the cell surface expression of PD-L1 possibly through the reduced interaction of growth-promoting ligands (like, HGF) with NRP2. Interestingly, SEMA3F, a class III semaphorin ligand for both NRP1 and NRP2, has been reported to have anti-tumorigenic effects. We observed that SEMA3F was significantly down-regulated in RCC cells compared with normal renal epithelial cells; and when we added SEMA3F to the cultures of renal cancer cells, it down-regulated both basal and HGF-/c-MET-induced PD-L1 expression. Together, our findings suggest that NRPs (primarily NRP2) can play a critical role in regulating HGF-/c-MET-induced PD-L1 expression in renal cancer cells to mediate immune escape of tumor cells. Therefore targeting NRP2 and/or its activation through SEMA3F/synthetic ligands may restrict c-MET-PD-L1-induced tumor promoting pathways in renal cancer cells. Citation Format: Murugabaskar Balan, Soumitro Pal. Potential role of neuropilin-2 in the regulation of c-MET-induced PD-L1 expression in renal cancer cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4583.
Abstract LB-364: Natural history of age-related lobular involution and impact on breast cancer risk
Authors: Derek Radisky, Daniel W. Visscher, Ryan Frank, Robert A. Vierkant, Stacey J. Winham, Melody L. Stallings-Mann, Tanya L. Hoskin, Aziza Nassar, Celine M. Vachon, Lori A. Denison, Lynn C. Hartmann, Marlene H. Frost, Amy C. Degnim
Journal: Cancer Research (2016)

Abstract Background: Age-related lobular involution (LI) is a physiological process in which the terminal duct lobular units of the breast regress as a woman ages. Analyses of breast biopsies from women with benign breast disease (BBD) have found that extent of LI is negatively associated with subsequent breast cancer development. Here we assess the natural course of LI within individual women, and the impact of progressive LI on breast cancer risk. Methods: The Mayo Clinic BBD cohort consists of 13,455 women with BBD from 1967-2001. The BBD cohort includes 1115 women who had multiple benign biopsies, 106 of whom had developed breast cancer. Within this multiple biopsy cohort, the progression of the LI process was examined by age at initial biopsy and time between biopsies. The relationship between LI progression and breast cancer risk was assessed using standardized incidence ratios (SIRs) and by Cox proportional hazards analysis. Results: Women who had multiple biopsies were younger age and had a slightly higher family history of breast cancer as compared with the overall BBD cohort. Extent of LI at subsequent biopsy was greater with increasing time between biopsies and for women age 55+ at initial biopsy. Among women with multiple biopsies, there was a significant association of higher breast cancer risk among those with involution stasis (lack of progression, HR 1.63) as compared with those with involution progression, p = 0.036. Conclusions: The multiple biopsy BBD cohort allows for a longitudinal study of the natural progression of LI. The majority of women in the multiple biopsy cohort showed progression of LI status between benign biopsies, and extent of progression was highest for women who were in the perimenopausal age range at initial biopsy. Progression of LI status between initial and subsequent biopsy was associated with decreased breast cancer risk. Citation Format: Derek Radisky, Daniel W. Visscher, Ryan Frank, Robert A. Vierkant, Stacey J. Winham, Melody L. Stallings-Mann, Tanya L. Hoskin, Aziza Nassar, Celine M. Vachon, Lori A. Denison, Lynn C. Hartmann, Marlene H. Frost, Amy C. Degnim. Natural history of age-related lobular involution and impact on breast cancer risk. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr LB-364.
One in 10 adults has tinnitus and risk increases with noise exposure, study shows
Authors: Susan Mayor
Journal: BMJ (2016)

Almost one in 10 adults has tinnitus, perceiving sounds in the absence of an external stimulus, and the risk is two to three times higher in people with consistent exposure to loud noises at work or during leisure time, a large US study has found.

Researchers analysed data from the 2007 National Health Interview Survey in a nationally representative sample of 75 764 adults aged over 18. The …
Abstract SY10-01: How aneuploidy drives cancer
Authors: Teresa Davoli, Hajima Uno, Andrew Xu, Kristen Mengwasser, Laura Sack, Peter J. Park, Stephen J. Elledge
Journal: Cancer Research (2016)

Abstract Aneuploidy has been recognized as a hallmark of cancer for over 100 years, yet no general theory to explain the recurring patterns of aneuploidy in cancer has emerged. We developed Tumor Suppressor and Oncogene (TUSON) Explorer, a computational method that analyzes the patterns of mutational signatures in tumors and predicts the likelihood that any individual gene functions as a tumor suppressor (TSG) or oncogene (OG). By analyzing &amp;gt;8200 tumor-normal pairs we provide statistical evidence suggesting many more genes possess cancer driver properties than anticipated, forming a continuum of oncogenic potential. These genes represent the vast majority of cancer drivers and the genetic networks they drive are a focus of future cancer system biological approaches to cancer research. Integrating our driver predictions with information on somatic copy number alterations, we find that the distribution and the potency of TSGs (STOP genes), OGs and essential genes (GO genes) on chromosomes can predict the complex patterns of aneuploidy and copy number variation characteristic of cancer genomes. We propose that the cancer genome is shaped through a process of cumulative haploinsufficiency and triplosensitivity. We are now assessing how aneuploidy drives cancer and the potency with which it does so. We have found that aneuploidy predicts survival better than mutational drivers and as well as existing clinical parameters in many cases. We have also discovered that different classes of aneuploidy drive transcriptional programs for two hallmarks of cancer and will present data supporting these observations and their implications. Citation Format: Teresa Davoli, Hajima Uno, Andrew Xu, Kristen Mengwasser, Laura Sack, Peter J. Park, Stephen J. Elledge. How aneuploidy drives cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr SY10-01.
Increase of Gfi1 Acetylation by HDAC Inhibitors Blocks Gfi1-Mediated Runx2 Repression in Osteoblast Precursors in Multiple Myeloma Bone Disease
Authors: Feng-Ming Wang, Juraj Adamik, Sawsan Rushdan, Shunqian Jin, Jixin Ding, Deborah L. Galson, G. David Roodman
Journal: Blood (2013)
Abstract 2767: Expression of miR-1252 and its target PRR4 gene in laryngeal carcinoma
Authors: NUR BUYRU, SEDA EKIZOGLU, JALAL GULIYEV, EMIN KARAMAN, TURGUT ULUTIN.
Journal: Cancer Research (2016)

Abstract Head and neck squamous cell carcinoma (HNSCC) is the sixth most frequent cancer worldwide and includes neoplasias of the paranasal sinuses, the oral cavity, the trachea, the pharynx and the larynx. The most important risk factors are tobacco use, alcohol consumption and infection with human papillomavirus (HPV). Besides the exogenous risk factors, genetic factors may play a key role in the development of the HNSCC. Cancer of the larynx accounts for 25% of all head and neck malignancies. The PRR4 (Prolin Rich Protein 4) gene is localized on human chromosome 12p13 and encodes a protein which is secreted from the acinar cells of the lacrimal gland, the submandibular gland, the parotis and the sublingual glands. Recent studies have demonstrated that PRR4 may play an important role as an antimicrobial protein to protect the ocular surface and the oral cavity. Additionally, it has been shown that PRR4 is highly expressed in the human submucosal glands. microRNAs are small non-coding RNAs which regulate gene expression at the post-transcriptional level. They bind to their target RNA with their seed sequence complementary to the 3’UTR region. This interaction results in either up- or down-regulation of the target messenger RNA. To understand the role of the PRR4 gene in laryngeal carcinogenesis, we investigated its mRNA expression levels in laryngeal tumor tissue and adjacent non-cancerous tissue samples from 90 patients by quantitative real-time PCR. As a complementary region between the seed sequence of miR-1252 and 3’UTR region of PRR4 gene exists, we also analyzed whether miR-1252 binds to this region and regulates the expression of PRR4. We found that PRR4 gene expression was decreased in 65 (72.2%) and increased in 24 (26.7%) of 90 tumor tissues when compared to normal tissue. Statistically significant downregulation of the PRR4 mRNA was observed in laryngeal tumors (p&amp;lt;0.001). No significant correlation was found between PRR4 gene expression and clinicopathological parameters including age, sex, stage, histological grade and tumor location (p&amp;gt;0.05). We also analyzed miR-1252 expression levels in a subset of tumor samples. miR-1252 upregulation was observed only in 24% of tumor tissues compared to non-cancerous tissue. The miR-1252 level was same in the 62.5% of the remaining samples. We did not observe any correlation between the PRR4 and miR-1252 expression levels. Our results indicate that the PRR4 gene may have an impact in the progression of laryngeal carcinoma. Citation Format: NUR BUYRU, SEDA EKIZOGLU, JALAL GULIYEV, EMIN KARAMAN, TURGUT ULUTIN. Expression of miR-1252 and its target PRR4 gene in laryngeal carcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2767.
Interleukin-17-Producing T Cells: A New Potential Player Mediating Graft Versus Host Pathology In Patients Undergoing Allogeneic Stem Cell Transplantion
Authors: Erica Dander, Adriana Balduzzi, Greta Zappa, Paolo Perseghin, Giovanna Lucchini, Elisabetta Todisco, Matteo Parma, Ettore Biagi, Iolanda Di Biasio, Antonello Villa, Pamela Della Mina, Maddalena Migliavacca, Daniela Longoni, Attilio Rovelli, Andrea Biondi, Giovanna D’Amico
Journal: Blood (2008)
Maintenance Treatment with Thalidomide after Autologous Transplantation for Myeloma: Final Analysis of a Prospective Randomized Study of the “Intergroupe Francophone du Myelome”.
Authors: Michel Attal, Jean-Luc Harousseau, Serge Leyvraz, Chantal Doyen, Cyrille Hulin, Lofti Benboubker, Ibrahim Yakoub Agha, Jean-Henri Bourhis, Laurent Garderet, Jean-Jacques Sotto, Mauricette Michallet, Marc Renaud, Laurent Voillat, Christian Berthou, Gerald Marit, Mathieu Monconduit, Charles Dumonté, Denis Caillot, Claire Mathiot, Hervé Avet-Loiseau
Journal: Blood (2005)
124PD Strategic planning and teamwork key to immediate minimal side effects and early good outcome of stereotactic radiosurgery and radiotherapy in patients with vestibular schwannoma; the National Cancer Institute Putrajaya Experience
Authors: M.A. Mohamed Ali, A.Z. Abdul Latif, Y. Yusoff, M.F. Jaffar, H.K. Sudarshan Singh, N. Abdullah
Journal: Annals of Oncology (2015)
Neutrophils are immuno-modulatory in rhinovirus infections
Authors: Francesca Tang, Philip Hansbro, Janette Burgess, Katherine Baines, Brian Oliver
Journal: European Respiratory Journal (2015)

Background: Neutrophils are important in controlling bacterial infections however; their role in viral infections remains unclear. Previously, we found that neutrophils respond to viral mimetics but not replication competent rhinovirus (RV). Aim: To investigate if neutrophils are activated when exposed to with RV-infected monocytes. We hypothesised that neutrophils would become activated in the presence of another activated cell. Methods: Primary human neutrophils and monocytes were co-cultured +/-RV16 or LPS, with either direct contact or separated by transwells (n=513). RV16 or LPS stimulated monocytes were exposed to killed neutrophils, neutrophil membrane or soluble neutrophil intracellular components (n=46). IL-6 and CXCL8 mRNA and protein levels were measured by qPCR and ELISA at 24h (n=47). Results: Constitutive IL-6 and CXCL8 release and LPS and RV-induced IL-6 from monocytes was inhibited when cultured with neutrophils. Direct contact with neutrophils was required for this inhibitory effect as it did not occur with transwell separation. Killed neutrophils inhibited constitutive and RV-induced monocyte derived IL-6 and CXCL8 compared to monocytes alone. Neutrophil intracellular components inhibited monocyte derived IL-6 and CXCL8 constitutively and with stimulation compared to monocytes alone, except LPS induced CXCL8. RV induced monocyte IL-6 and CXCL8 mRNA was reduced when monocytes were cultured with neutrophil intracellular components. Conclusion: We describe a novel anti-inflammatory property of neutrophils dependent on cell contact and neutrophil mediator release which may be important in the pathogenesis of viral induced asthma exacerbations.
The Parasites of Man in Temperate Climates
Journal: JAMA (1941)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Abstract 2948: Glucose-6-phosphate dehydrogenase mediates drug resistance in diffuse large B-cell lymphoma
Authors: Steve A. Maxwell, Seyed Mousavi-Fard, Timothy Davis, Deeann Wallils, Jim Sacchettini
Journal: Cancer Research (2016)

Abstract A leading cause of mortality in diffuse large B-cell lymphoma patients is the development of resistance to the CHOP chemotherapy regimen. We have discovered that CHOP-resistant DLBCL cells express higher G6PDH activities and lower reactive oxygen (predominantly superoxide) levels than CHOP-sensitive cells. Glucose-6-phosphate dehydrogenase (G6PDH) is the rate-limiting enzyme of the NADPH-producing pentose phosphate shunt (PPP). The PPP is the most important pathway for recycling of cellular glutathione (GSH), a key scavenger of reactive oxygen species (ROS). In the PPP oxidative phase, glucose 6-phosphate is irreversibly converted into ribulose 5-phosphate and CO2 leading to the synthesis of NADPH, a redox cofactor for many antioxidant enzymes. The NADPH produced is used by glutathione reductase to reduce GSSG (glutathione disulfide) to GSH. We hypothesized that increased activity of the G6PDH pathway leads to higher GSH production, lower oxidative state (ROS), and CHOP-resistance. In support of our hypothesis, downregulation of G6PDH lowered NADPH and GSH levels, increased ROS, and reversed CHOP-resistance in DLBCL cells. These results indicate an important role for the G6DPH pathway in mediating CHOP resistance in DLBCL. Citation Format: Steve A. Maxwell, Seyed Mousavi-Fard, Timothy Davis, Deeann Wallils, Jim Sacchettini. Glucose-6-phosphate dehydrogenase mediates drug resistance in diffuse large B-cell lymphoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2948.
Abstract LB-094: A comparative study of PD-L1 diagnostic assays and the classification of patients as PD-L1 positive and PD-L1 negative
Authors: Marianne J. Ratcliffe, Alan Sharpe, Anita Midha, Craig Barker, Paul Scorer, Jill Walker
Journal: Cancer Research (2016)

Abstract Background: PD-1/PD-L1 directed antibodies are emerging as effective therapeutics in multiple oncology settings. Keynote 001 and Checkmate 057 have shown more frequent response to PD-1 targeted therapies in NSCLC patients with high tumour PD-L1 expression than patients with low or no PD-L1 expression. Multiple diagnostic PD-L1 tests are available using different antibody clones, different staining protocols and diverse scoring algorithms. It is vital to compare these assays to allow appropriate interpretation of clinical outcomes. Such understanding will promote harmonization of PD-L1 testing in clinical practice. Methods: Approximately 500 tumour biopsy samples from NSCLC patients, including squamous and non-squamous histologies, will be assessed using three leading PD-L1 diagnostics assays. PD-L1 assessment by the Ventana SP263 assay that is currently being used in Durvalumab clinical trials (positivity cut off: ≥25% tumour cells with membrane staining) will be compared with the Dako 28-8 assay (used in the Nivolumab Checkmate 057 trial at the 1%, 5% and 10% tumour membrane positivity cut offs), and the Dako 22C3 assay (used in the Pembrolizumab Keynote 001 trial) at the 1% and 50% cut offs). Results: Preliminary data from 81 non-squamous patients indicated good concordance between the Ventana SP263 and Dako 28-8 assays. Optimal overall percent agreement (OPA) was observed between Dako 28-8 at the 10% cut off and the Ventana SP263 assay (OPA; 96%, Positive percent agreement (PPA); 91%, Negative percent agreement (NPA); 98%), where the Ventana SP263 assay was set as the reference. Data on the full cohort will be presented for all three assays, and a lower 95% confidence interval calculated using the Clopper-Pearson method. Conclusions: This study indicates that the patient population defined by Ventana SP263 at the 25% cut off is similar to that identified by the Dako-28-8 assay at the 10% tumour membrane cut off. This, together with data on the 22C3 assay, will enable cross comparison of studies using different PD-L1 tests, and widen options for harmonization of PD-L1 diagnostic testing. Table 1Reference: Ventana SP-263 (≥25% tumour membrane staining)Dako 28-8 assay cut offPPA (%)NPA (%)OPA (%)&amp;gt;1%5810081&amp;gt;5%7210090&amp;gt;10%919896 Citation Format: Marianne J. Ratcliffe, Alan Sharpe, Anita Midha, Craig Barker, Paul Scorer, Jill Walker. A comparative study of PD-L1 diagnostic assays and the classification of patients as PD-L1 positive and PD-L1 negative. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr LB-094.
Logistic Regression
Authors: Juliana Tolles, William J. Meurer
Journal: JAMA (2016)

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 HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal