tbuckley/cabot-search huggingface dataset:
High-Throughput Functional Evaluation of Variants of Unknown Significance in <i>ERBB2</i>
Authors: Masaaki Nagano, Shinji Kohsaka, Toshihide Ueno, Shinya Kojima, Kanju Saka, Hirotaro Iwase, Masahito Kawazu, Hiroyuki Mano
Journal: Clinical Cancer Research (2018)

Purpose: The advent of next-generation sequencing technologies has enabled the identification of several activating mutations of Erb-B2 receptor tyrosine kinase 2 (ERBB2) among various cancers. However, the significance of infrequent mutations has not been fully investigated. Herein, we comprehensively assessed the functional significance of the ERBB2 mutations in a high-throughput manner.Experimental Design: We evaluated the transforming activities and drug sensitivities of 55 nonsynonymous ERBB2 mutations using the mixed-all-nominated-in-one (MANO) method.Results: G776V, G778_S779insG, and L841V were newly revealed to be activating mutations. Although afatinib, neratinib, and osimertinib were shown to be effective against most of the ERBB2 mutations, only osimertinib demonstrated good efficacy against L755P and L755S mutations, the most common mutations in breast cancer. In contrast, afatinib and neratinib were predicted to be more effective than other inhibitors for the A775_776insYVMA mutation, the most frequent ERBB2 mutation in lung cancer. We surveyed the prevalence of concurrent ERBB2 mutation with gene amplification and found that approximately 30% of ERBB2-amplified urothelial carcinomas simultaneously carried ERBB2 mutations, altering their sensitivity to trastuzumab, an mAb against ERBB2. Furthermore, the MANO method was applied to evaluate the functional significance of 17 compound mutations within ERBB2 reported in the COSMIC database, revealing that compound mutations involving L755S were sensitive to osimertinib but insensitive to afatinib and neratinib.Conclusions: Several ERBB2 mutations showed varying sensitivities to ERBB2-targeted inhibitors. Our comprehensive assessment of ERBB2 mutations offers a fundamental database to help customize therapy for ERBB2-driven cancers.We identified several ERBB2 mutations as activating mutations related to tumorigenesis. In addition, our comprehensive evaluation revealed that several ERBB2 mutations showed varying sensitivities to ERBB2-targeted inhibitors, and thus, the functional significance of each variant should be interpreted precisely to design the best treatment for each patient. Clin Cancer Res; 24(20); 5112-22. ©2018 AACR.
Abstract 1264: Commensal microbiota is involved in anti-PD-1 mAb-mediated antitumor activity in a preclinical tumor model
Authors: Fei Chen, Jian Ding, Xiangchao Gu, Juan Zhang, wenqing Yang, Qian Shi
Journal: Cancer Research (2018)

Abstract Background: A number of studies have shown that the gut microbiome may influence anti-tumor immune responses via innate and adaptive immunity, and the recent work in mice has highlighted the key roles of the gut microbiota in mediating tumor responses to chemotherapeutic agents and immunotherapies targeting PD-L1, PD-1 or CTLA-4. Multiple studies have demonstrated that the gut microbiome can markedly influence the outcome of PD-1 blockade in mice and patients and several commensal have been proved to be associated with favorable clinical outcome. Considering complexity of intestinal micro-organisms, a larger panel or wider spectrum of microbiota species maybe involved in this process. Methods: Since compositional differences in the microbiome may influence cancer development and responses to therapies, we sought to determine whether intestinal bacterial composition and abundances of the tumor bearing mice were associated with a specific treatment outcome of immunotherapy. To test this, we analyzed and compared an enrichment of intestinal microbiota of CT26 syngeneic tumor bearing mice before and after a series of anti-PD-1 mAb treatment were given. Results The results demonstrating that some strains were robustly enriched and this enrichment was associated with tumor response to anti-PD 1 therapy, while as other strains were down regulated upon the checkpoint blockade. Conclusions: Upon further characterization and confirmation, these intriguing findings could lead to identification of one or more microbiota strains that could have biomarker potentials or therapeutic values for cancer immunotherapy. Citation Format: Fei Chen, Jian Ding, Xiangchao Gu, Juan Zhang, wenqing Yang, Qian Shi. Commensal microbiota is involved in anti-PD-1 mAb-mediated antitumor activity in a preclinical tumor model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1264.
The Cognitive Reserve Should Be Controlled When Using Neuroimaging to Assess Relapse in Major Depressive Disorder—Reply
Authors: Katharina Dohm, Dario Zaremba, Udo Dannlowski
Journal: JAMA Psychiatry (2018)

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 Psychiatry 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 Psychiatry journal
Mucosal zinc deficiency in chronic rhinosinusitis with nasal polyposis contributes to barrier disruption and decreases <scp>ZO</scp>‐1
Authors: Jae Murphy, Mahnaz Ramezanpour, Eugene Roscioli, Alkis James Psaltis, Peter‐John Wormald, Sarah Vreugde
Journal: Allergy (2018)

This work is supported by a Garnett Passe and Rodney Williams Memorial Foundation scholarship to JM and a Garnett Passe and Rodney Williams Memorial Foundation Conjoint Grant to PJW and SV. The authors declare they have no relevant conflict of interests or financial disclosures. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
RTN4 Knockdown Dysregulates the AKT Pathway, Destabilizes the Cytoskeleton, and Enhances Paclitaxel-Induced Cytotoxicity in Cancers
Authors: Gopal P. Pathak, Rashmi Shah, Barry E. Kennedy, J. Patrick Murphy, Derek Clements, Prathyusha Konda, Michael Giacomantonio, Zhaolin Xu, Isabel R. Schlaepfer, Shashi Gujar
Journal: Molecular Therapy (2018)

Reticulon-4 (RTN4), commonly known as a neurite outgrowth inhibitor (Nogo), is emerging as an important player in human cancers. Clinically, we found lower RTN4 expression in patient-derived tumors was associated with significantly better survival in lung, breast, cervical, and renal cancer patients. To identify the role of RTN4 in cancer biology, we performed mass spectrometry-based quantitative proteomic analysis on cancer cells following RTN4 knockdown and found its link with pro-survival as well as cytoskeleton-related processes. Subsequent mechanistic investigations revealed that RTN4 regulates lipid homeostasis, AKT signaling, and cytoskeleton modulation. In particular, downregulation of RTN4 reduced sphingomyelin synthesis and impaired plasma membrane localization of AKT, wherein AKT phosphorylation, involved in many cancers, was significantly reduced without any comparable effect on AKT-related upstream kinases, in a sphingolipid-dependent manner. Furthermore, knockdown of RTN4 retarded proliferation of cancer cells in vitro as well as tumor xenografts in mice. Finally, RTN4 knockdown affected tubulin stability and promoted higher cytotoxic effects with chemotherapeutic paclitaxel in cancer cells both in vitro and in vivo. In summary, RTN4 is involved in carcinogenesis and represents a molecular candidate that may be targeted to achieve desired antitumor effects in clinics.
Health impact of China's Air Pollution Prevention and Control Action Plan: an analysis of national air quality monitoring and mortality data
Authors: Jing Huang, Xiaochuan Pan, Xinbiao Guo, Guoxing Li
Journal: The Lancet Planetary Health (2018)

BackgroundTo mitigate the serious levels of air pollution in China, the State Council of China issued the Air Pollution Prevention and Control Action Plan (APPCAP) in 2013. This policy is a milestone in air quality control in China. We aimed to evaluate the effects of the APPCAP on long-term air quality management and the related health impacts in China.MethodsWe did an analysis of national air quality monitoring and mortality data to estimate the health impact of the APPCAP from 2013 to 2017 in 74 key cities in China. Changes in mortality and in years of life lost (YLL), an indicator that considers life expectancy at death, were calculated to assess the health impact of air quality management during the 5-year period.FindingsBetween 2013 and 2017, annual average concentrations of PM2·5 decreased by 33·3% (95% CI 16·3–50·3), PM10 by 27·8% (8·0–47·5), sulphur dioxide by 54·1% (28·2–80·0), and carbon monoxide by 28·2% (3·1–53·3) in the 74 key cities. However, no significant change was seen in annual average concentrations of nitrogen dioxide (9·7% reduction; 95% CI −23·0 to 42·4) or ozone (20·4% increase; −30·1 to 71·0). In 2017, as a result of substantial improvements in air quality, there were 47 240 (95% CI 25 870–69 990) fewer deaths and 710 020 (420 230–1 025 460) fewer YLL in the 74 key cities in China than in 2013.InterpretationSubstantial reductions in mortality and YLL related to control of ambient air pollution were achieved from 2013 to 2017 in China, indicating appreciable effectiveness of China's APPCAP. However, emissions control efforts for ozone and nitrogen dioxide should be strengthened in the future.FundingNational Natural Science Foundation of China and the National Key Research and Development Program of China.
Enhancement of stem cell engraftment on a WHIM
Authors: Hal E. Broxmeyer
Journal: Journal of Clinical Investigation (2018)

WHIM (warts, hypogammaglobulinemia, infections, and myelokathexis) syndrome is a genetic autoimmune disorder that results from gain-of-function mutations in the gene encoding chemokine receptor CXCR4. A previous study characterized a patient with WHIM who underwent a chromothriptic event that resulted in spontaneous deletion of the WHIM allele in a single hematopoietic stem cell and subsequent cure of the disease. In this issue of the JCI, Gao et al. extend this work and show that Cxcl4-haplosufficient bone marrow has a selective advantage for long-term engraftment in murine WHIM models. Moreover, successful engraftment occurred without prior conditioning of recipients. Together, these results have important implications for improving hematopoietic stem/progenitor cell transplant not only for patients with WHIM but also for all patients who may require the procedure.
Abstract 2039: Cordycepin inhibits breast cancer migration and invasion by targeting epithelial to mesenchymal transition-inducing transcription factors (EMT-TFs)
Authors: Junjiang Fu, Chunli Wei, Jingliang Cheng, Md. Asaduzzaman Khan, Lisha Yang, Hui Zou
Journal: Cancer Research (2018)

Abstract Cancer metastasis is one of the major causes of human death. The developmental stage epithelial to mesenchymal transition (EMT) is associated with cancer metastasis. Cordycepin (CD) is a natural compound, found in traditionally used medicinal mushroom Cordyceps. In this study, we have investigated the anticancer and antimetastatic activity of CD, and whether this compound regulates epithelial to mesenchymal transition-inducing transcription factors (EMT-TFs). By employing cell viability assay and real-time cell analysis in BT549, 4T1 and MDA-MB-435 cell lines, we found that CD can potentially inhibit cancer cell growth, migration and invasion. By using quantitative PCR (qPCR) and Western blot analysis, we also studied the expression of EMT associated proteins N-Cadherin and E-Cadherin, and their transcription factors TWIST1, SNAIL1, SLUG and ZEB1 in BT549 and 4T1 cell lines. By dual-luciferase reporter assay, we confirmed that CD is able to inactivate EMT signaling pathway with mediatory of TWIST1 and SLUG. CD treatment also inhibited the growth and metastasis of cancer cell-derived xenograft tumors in mouse model. Taken together, CD inhibits breast cancer cell migration and invasion by targets EMT-TFs, which might be a possible CD mechanism of antimetastatic action. In addition, CD derivatives by conjugating thymoquinone, a promising anti-cancer compound from nature, were designed to investigate whether there are dramatically improvements on their antimetastatic activities. In conclusion, this study suggests CD as a potential anticancer and antimetastatic molecule, which might be a promising therapeutic agent against breast cancer. Funding: This work was supported by the NSFC (81172049, 81672887). Citation Format: Junjiang Fu, Chunli Wei, Jingliang Cheng, Md. Asaduzzaman Khan, Lisha Yang, Hui Zou. Cordycepin inhibits breast cancer migration and invasion by targeting epithelial to mesenchymal transition-inducing transcription factors (EMT-TFs) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2039.
Reframing Optimal Outcomes in Autism
Authors: Stelios Georgiades, Connie Kasari
Journal: JAMA Pediatrics (2018)

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
Abstract SY36-02: Heterogeneity in molecular subtype of hepatocellular carcinoma
Authors: Yujin Hoshida
Journal: Cancer Research (2018)

Abstract Hepatocellular carcinoma (HCC) mortality keeps rising with emerging etiologies such as nonalcoholic fatty liver disease and hepatitis C after viral cure. Through the efforts of high-throughput and comprehensive molecular characterization of HCC tumors, it has been revealed that HCC tumors can be classified into several subtypes (e.g., aggressive or indolent subtype) according to their molecular characteristics and clinical phenotypes. Ongoing basic and clinical studies have suggested their potential implication in therapeutic decision making. Systematic and integrative characterization of heterogeneity in intra/intertumor molecular features as well as host genetic, environmental, and socioeconomic factors is expected to facilitate development of precision care strategies for HCC patients. Citation Format: Yujin Hoshida. Heterogeneity in molecular subtype of hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr SY36-02.
Potential Policy Approaches to Address Diet-Related Diseases
Authors: Michael F. Jacobson, James Krieger, Kelly D. Brownell
Journal: JAMA (2018)

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
Abstract 1002: Dysfunction of HPV16-specific CD8+ T cells derived from oropharyngeal tumors is related to the expression of Tim-3 but not PD-1
Authors: Simona Partlova, Kamila Hladikova, Vladimir Koucky, Anna Fialova, Radek Spisek, Jan Boucek, Michal Zabrodsky, Michael Halaska, Ruth Tachezy, Marek Grega, Jean-François Fonteneau
Journal: Cancer Research (2018)

Abstract Human papillomavirus (HPV) type 16 infection is one of the most important etiological agents of oropharyngeal squamous cell carcinoma. Patients with HPV-positive squamous cell carcinomas of the head and neck were reported to have a better clinical outcome than patients with HPV-negative tumors. Because HPV16 E6 and E7 oncoproteins are highly immunogenic and constitutively expressed within the tumor cells, HPV-specific T cell immunity may contribute to the better prognosis of HPV-positive tumors. We analyzed the frequency, phenotype and function of HPV16 E6/E7-specific tumor-infiltrating T cells (TILs) in oropharyngeal tumors and tested the effect of anti-PD1 mAb (nivolumab), soluble Tim-3 (sTim-3) and homeostatic in vitro expansion on these characteristics. We show that 73.1% of HPV-associated oropharyngeal tumors are positive for HPV16-specific T cells capable of producing IFNγ upon stimulation with E6/E7 peptide pools. These IFNγ-producing HPV-specific TILs were mainly PD-1+Tim-3-CD8+ T cells, identifying Tim-3 rather than PD-1 as a marker of T cell dysfunction. Consequently, specific IFNγ production was further enhanced by combined nivolumab plus sTim-3 treatment, but not with nivolumab alone. Our data provide the rationale for exploring additional setups of anti-PD-1 mAb treatment, including combinations with other check-point blockers, such as Tim-3 and/or with HPV16-directed therapeutic vaccines. Citation Format: Simona Partlova, Kamila Hladikova, Vladimir Koucky, Anna Fialova, Radek Spisek, Jan Boucek, Michal Zabrodsky, Michael Halaska, Ruth Tachezy, Marek Grega, Jean-François Fonteneau. Dysfunction of HPV16-specific CD8+ T cells derived from oropharyngeal tumors is related to the expression of Tim-3 but not PD-1 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1002.
The AGES-Reykjavik Study suggests that change in kidney measures is associated with subclinical brain pathology in older community-dwelling persons
Authors: Sanaz Sedaghat, Jie Ding, Gudny Eiriksdottir, Mark A. van Buchem, Sigurdur Sigurdsson, M. Arfan Ikram, Osorio Meirelles, Vilmundur Gudnason, Andrew S. Levey, Lenore J. Launer
Journal: Kidney International (2018)
Abstract 406: A proteome-transcriptome-miRnome integrated analysis identifies similarity between UV-exposed skin and wounding skin
Authors: Tran N. Nguyen, Kimal Rajapakshe, Stanislav Avdieiev, Courtney Nicholas, Vida Chitsazzadeh, Eric Welsh, Bin Fang, John Koomen, Cristian Coarfa, Janine Einspahr, Kenneth Y. Tsai
Journal: Cancer Research (2018)

Abstract Cutaneous squamous cell carcinoma (cuSCC) is the second most common skin cancer, for which long term UV exposure and chronic wounding are the dominant risk factors. Despite these clinically established connections, little is understood about the early molecular response of human skin to UV exposure and its connection to acute wounding and cuSCC. Thus, our goal is to find common and specific signatures driven by UV-exposure and wounding as a means of developing new approaches for treating and preventing cuSCC. Here, we perform integrated analyses of proteomic, RNA-seq and miR-seq on 3 datasets: (1) UV-unexposed and acute UV-exposed human skin, (2) public dataset on acute wound healing and (3) our previously published dataset on normal skin and cuSCC from humans. We find that biological signatures and processes regulated by acute UV exposure and wounding has profound similarity. miR-seq data shows that miR-223, miR-132 and miR-142 are significantly upregulated in both acute events. Combined gene set enrichment analysis shows that G-protein-coupled-receptors (GPCRs) pathways are upregulated, possibly through Gαi activation. While ECM remodeling is significantly enriched in all three datasets, gene expression regulated by PPARα is suppressed. Interestingly, upregulation of matrisome components is observed among all three datasets. This suggests that these changes are important early events that regulated by both UV-exposure and wounding which eventually can promote cuSCC initiation. Thus, our findings suggest that these common signatures can be potentially validated as chemopreventive targets for cuSCC. Citation Format: Tran N. Nguyen, Kimal Rajapakshe, Stanislav Avdieiev, Courtney Nicholas, Vida Chitsazzadeh, Eric Welsh, Bin Fang, John Koomen, Cristian Coarfa, Janine Einspahr, Kenneth Y. Tsai. A proteome-transcriptome-miRnome integrated analysis identifies similarity between UV-exposed skin and wounding skin [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 406.
Alternaria is associated with asthma symptoms and exhaled NO among NYC children
Authors: Nitzan Soffer, Brett J. Green, Luis Acosta, Adnan Divjan, Edward Sobek, Angela R. Lemons, Andrew G. Rundle, Judith S. Jacobson, Inge F. Goldstein, Rachel L. Miller, Matthew S. Perzanowski
Journal: Journal of Allergy and Clinical Immunology (2018)
BMA is urged to back doctors who refuse to take part in government’s Prevent programme
Authors: Gareth Iacobucci
Journal: BMJ (2018)

Doctors have urged the BMA to support members who refuse to take part in the government’s Prevent programme.

Under the strategy, which is part of the UK government’s counterterrorism plan, NHS organisations are legally obliged to report people who they think may be at risk of becoming terrorists. General practices are not covered by this directive.

The …