tbuckley/cabot-search huggingface dataset:
Nicotinamide Phosphoribosyltransferase Acts as a Metabolic Gate for Mobilization of Myeloid-Derived Suppressor Cells
Authors: Cristina Travelli, Francesca Maria Consonni, Sabina Sangaletti, Mariangela Storto, Sara Morlacchi, Ambra A. Grolla, Ubaldina Galli, Gian Cesare Tron, Paola Portararo, Lorenza Rimassa, Tiziana Pressiani, Massimiliano Mazzone, Rosalinda Trovato, Stefano Ugel, Vincenzo Bronte, Claudio Tripodo, Mario P. Colombo, Armando A. Genazzani, Antonio Sica
Journal: Cancer Research (2019)

Abstract Cancer induces alteration of hematopoiesis to fuel disease progression. We report that in tumor-bearing mice the macrophage colony-stimulating factor elevates the myeloid cell levels of nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in the NAD salvage pathway, which acts as negative regulator of the CXCR4 retention axis of hematopoietic cells in the bone marrow. NAMPT inhibits CXCR4 through a NAD/Sirtuin 1–mediated inactivation of HIF1α-driven CXCR4 gene transcription, leading to mobilization of immature myeloid-derived suppressor cells (MDSC) and enhancing their production of suppressive nitric oxide. Pharmacologic inhibition or myeloid-specific ablation of NAMPT prevented MDSC mobilization, reactivated specific antitumor immunity, and enhanced the antitumor activity of immune checkpoint inhibitors. Our findings identify NAMPT as a metabolic gate of MDSC precursor function, providing new opportunities to reverse tumor immunosuppression and to restore clinical efficacy of immunotherapy in patients with cancer. Significance: These findings identify NAMPT as a metabolic gate of MDSC precursor function, providing new opportunities to reverse tumor immunosuppression and to restore clinical efficacy of immunotherapy in cancer patients.
P027 Src-like adaptor protein expression in rheumatoid arthritis
Authors: P Királyhidi, ES Molnár, EJ Baricza, N Marton, E Buzás, G Nagy
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Career situation of first and presenting author</h3> Student for a master or a PhD. <h3>Introduction</h3> The Src-like adaptor protein (SLAP) plays a central role in the fine regulation of both B- and T-lymphocyte activation. According to our previuos data SLAP is responsible for the proteasomal degradation of the CD3 zeta chain (CD3ζ) of T-lymphocytes.<sup>1</sup> <h3>Objectives</h3> We studied the effect of IL-10, IL-17A and TNF-α treatment on the SLAP expression of CD4<sup>+</sup> T- and CD19<sup>+</sup> B-lymphocytes. <h3>Methods</h3> Peripherial mononuclear cells (PMBC) were isolated from healthy donors and rheumatoid arthritis (RA) patients. CD4<sup>+</sup> T-cells or CD19<sup>+</sup> B-cells were isolated by negative magnetic separation; stimulated with ConA and goat anti-human IgG + IgM F(ab')2 fragments respectively. The samples were treated with IL-17A (20 ng/ml and 80 ng/ml, 24 hour), IL-10 (100 U/ml, 48 hour and 72 hour) and TNF-α (20 ng/ml and 60 ng/ml, 24 hour). The SLAP and CD3ζ expression were measured by Western blot. <h3>Results</h3> Both the SLAP and the CD3ζ expression of the MTX treated patients' CD4 cells were higher upon IL-17A and IL-10 treatment, than those of the MTX non-treated RA patients' or healthy donors'. The TNF-α induced SLAP expression of RA patients' CD19 B-cells was higher than those of the healthy donors' B cells (p=0.05). <h3>Conclusions</h3> In addition to proinflammatory and anti-inflammatory cytokines MTX treatment regulates the SLAP and the CD3ζ expression of human T-cells. <h3>Reference</h3> Érsek B, <i>et al</i>. CD3ζ-Chain Expression of Human T Lymphocytes Is Regulated by TNF via Src-like Adaptor Protein-Dependent Proteasomal Degradation. <i>J Immunol.</i> 2012. <h3>Acknowledgements</h3> OTKA K77537. <h3>Disclosure of Interest</h3> None declared.
GW28-e0973 A study on the mechanism of the inflammatory response in Ginsenoside Rb1 against the replicative senescence of endothelial cells
Authors: Bin Zhou, Yesheng Ling, Lin Wu, Shujie Yu, Dinghui Liu, Min Wang, Yong Liu, Baoshun Hao, Lin Chen, Xiaoxian Qian
Journal: Journal of the American College of Cardiology (2017)
Macrophage-derived MMP-8 determines smooth muscle cell differentiation from adventitia stem/progenitor cells and promotes neointima hyperplasia
Authors: Feng Yang, Qishan Chen, Mei Yang, Eithne Margaret Maguire, Xiaotian Yu, Shiping He, Rui Xiao, Claire S Wang, Weiwei An, Wei Wu, Yijiang Zhou, Qingzhong Xiao, Li Zhang
Journal: Cardiovascular Research (2019)

Emerging evidence has suggested that adventitia stem/progenitor cells (AdSPCs) migrate into the intima of arteries in response to injury, where they differentiate towards smooth muscle cells (SMCs) and participate in neointimal hyperplasia. We have previously identified matrix metalloproteinase-8 (MMP8) as a key player in atherogenesis. In this study, we aimed to investigate the functional roles of macrophage-derived MMP8 in AdSPC differentiation and injury-induced arterial remodelling.We first observed an important role for MMP8 in SMC differentiation from embryonic stem cells, but this effect was not seen in AdSPCs. Instead, through macrophages/AdSPCs co-culture and macrophage conditional culture medium studies, we have demonstrated that the MMP8 protein secreted from macrophages promotes SMC differentiation from AdSPCs. Mechanistically, we showed that macrophage-derived MMP8 promotes SMC differentiation from AdSPCs through modulating transforming growth factor-β activity and a disintegrin and metalloproteinase domain-containing protein 10 (ADAM10)/Notch1 signalling. We further demonstrated that the binding site for CBF1, Suppressor of Hairless, and Lag-1 (CSL) within SMC gene promoters is responsible for Notch1 mediated SMC differentiation. Finally, we demonstrated that macrophage-derived MMP8 increased injury-induced neointimal SMC hyperplasia by activating ADAM10/Notch1 signalling.We have identified macrophage-derived MMP8 as a regulator in SMC differentiation from AdSPCs and neointimal SMC hyperplasia in response to injury. Our data provide new insights into the roles of MMP8 in AdSPC differentiation and the pathogenesis of neointima formation in the context of angiographic restenosis, and therefore may aid in the development of novel therapeutic agents for the prevention of this disease.
Governmental liability for negligent treatment. 2
Authors: A. R. Holder
Journal: JAMA (1973)

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
Improved social services and the burden of post-traumatic stress disorder among economically vulnerable people after a natural disaster: a modelling study
Authors: Gregory H Cohen, Shailesh Tamrakar, Sarah Lowe, Laura Sampson, Catherine Ettman, Dean Kilpatrick, Benjamin P Linas, Kenneth Ruggiero, Sandro Galea
Journal: The Lancet Planetary Health (2019)

BackgroundHurricanes and other natural disasters produce public health and economic consequences that last well beyond their immediate aftermath. Resource loss is a core driver of post-traumatic stress disorder (PTSD) after large-scale traumatic events. We examined the effect of restoration of residential and housing-related financial resources on recovery from PTSD in post-disaster contexts.MethodsWe built an agent-based model, empiricised with observational and experimental data, to test the effects of differing health service approaches on PTSD recovery, measured by prevalence and persistence. We tested a social services case management (SSCM) approach similar to Psychological First Aid, featuring shelter-based social service provision and linkage to mental health treatment for people who were displaced and had income loss, by comparing the treatment effectiveness of usual care alone, usual care with SSCM, stepped care alone, and stepped care with SSCM.FindingsAn SSCM approach to restore housing and provide linkage to mental health services among people who were displaced and had income loss after a large-scale natural disaster resulted in between 1·56 (95% CI 1·55–1·57) and 5·73 (5·04–6·91) times as many remitted PTSD cases as non-SSCM conditions at the end of the first year, and between 1·16 (1·16–1·17) and 2·28 (2·25–2·32) times as many remitted cases at the end of the second year.InterpretationRestoring economic and housing resources to populations affected by a natural disaster would significantly reduce the mental health burden in populations, particularly those with resource loss, after a disaster.FundingUS Department of Health and Human Services.
Abstract 5306: Overexpression of RAD51 promotes brain metastases from breast cancer
Authors: Stephan Woditschka, Diane Palmieri, Renata Duchnowska, Jacek Jassem, Sunil Badve, George W. Sledge, Patricia S. Steeg
Journal: Cancer Research (2012)

Abstract Overexpression of the DNA double-strand break (DSB) repair gene RAD51 was identified as part of a 13-gene signature predictive of rapid brain metastasis development (≤3 years vs. &amp;gt;3 years after diagnosis, HR=3.03, p=0.0008) in primary tumors of chemotherapy-naïve HER2+ metastatic breast cancer patients. We also found RAD51 mRNA overexpressed (1.5-fold, p=0.001) in resected brain metastases compared to primary breast tumors from the same patients. In addition, RAD51 expression was significantly higher (1.4-fold, p=0.008,) in brain metastases compared to systemic (bone/lung) metastases. We therefore hypothesize that RAD51 promotes brain metastasis development in breast cancer patients. Given the known role of RAD51 in homologous recombination, important for the repair of DNA DSBs, it was unknown whether RAD51 would promote brain metastasis of breast cancer only in the presence of DNA-damaging chemotherapy or, alternatively, have endogenous biological functions in tumor cells. To functionally evaluate whether RAD51 promotes brain metastases, RAD51 was overexpressed at physiologically relevant levels in a brain-metastatic variants of triple-negative MDA-MB-231 breast carcinoma (231-BR) cells. In vitro, this resulted in a ∼30% increase in clonogenic colony formation (p=0.004), without affecting cell proliferation rates. RAD51 overexpression also conferred chemoresistance to DNA DSB inducing agents such as 25uM carboplatin (p=0.03) and 25nM doxorubicin (p=0.02), but not to agents that do not cause DNA DSBs, such as 2.5nM paclitaxel. In vivo, overexpression of RAD51 in 231-BR cells increased formation of large brain metastases, the equivalent of clinically detectable lesions, (4.0 and 3.3-fold, p=0.01 and p=0.005) and micro-metastases (3.1 and 3.5-fold, p=0.01 and p=0.001) in two independent xenograft experiments. Importantly, this brain-metastasis promoting effect occurred without drugs to induce DSB. This effect was recapitulated in a second animal model based on a brain-metastatic subline of 4T1 murine mammary carcinoma cells (4T1-BR). In this model, RAD51 overexpression increased large brain metastases (3.3-fold, p=0.02) and micro-metastases (2.0-fold, p=0.04) compared to vector control. ShRNA-mediated RAD51 knockdown in 4T1-BR cells resulted in the opposite effect, reducing large brain metastases (1.8-fold, p=0.1) and micro-metastases (2.5-fold, p=0.04). Together these data suggest a driving role for RAD51 in the development of brain metastases from breast cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5306. doi:1538-7445.AM2012-5306
World Health Organization‐defined eosinophilic disorders: 2012 update on diagnosis, risk stratification, and management
Authors: Jason Gotlib*
Journal: American Journal of Hematology (2012)

Abstract Disease overview: The eosinophilias encompass a broad range of nonhematologic (secondary or reactive) and hematologic (primary, clonal) disorders with potential for end‐organ damage. Diagnosis: Hypereosinophilia has generally been defined as a peripheral blood eosinophil count greater than 1,500/mm 3 and may be associated with tissue damage. After exclusion of secondary causes of eosinophilia, diagnostic evaluation of primary eosinophilias relies on a combination of morphologic review of the blood and marrow, standard cytogenetics, fluorescent in situ‐hybridization, flow immunocytometry, and T‐cell clonality assessment to detect histopathologic or clonal evidence for an acute or chronic myeloid or lymphoproliferative disorder. Risk stratification: Disease prognosis relies on identifying the subtype of eosinophilia. After evaluation of secondary causes of eosinophilia, the 2008 World Health Organization establishes a semimolecular classification scheme of disease subtypes including “myeloid and lymphoid neoplasms with eosinophilia and abnormalities of PDGFRA , PDGFRB , or FGFR1, ” chronic eosinophilic leukemia, not otherwise specified' (CEL, NOS), lymphocyte‐variant hypereosinophilia, and idiopathic hypereosinophilic syndrome (HES), which is a diagnosis of exclusion. Risk‐adapted therapy: The goal of therapy is to mitigate eosinophil‐mediated organ damage. For patients with milder forms of eosinophilia (e.g., &lt;1,500/mm 3 ) without symptoms or signs of organ involvement, a watch and wait approach with close‐follow‐up may be undertaken. Identification of rearranged PDGFRA or PDGFRB is critical because of the exquisite responsiveness of these diseases to imatinib. Corticosteroids are first‐line therapy for patients with lymphocyte‐variant hypereosinophilia and HES. Hydroxyurea and interferon‐alpha have demonstrated efficacy as initial treatment and steroid‐refractory cases of HES. In addition to hydroxyurea, second line cytotoxic chemotherapy agents and hematopoietic cell transplant have been used for aggressive forms of HES and CEL with outcomes reported for limited numbers of patients. Although clinical trials have been performed with anti IL‐5 (mepolizumab) and anti‐CD52 (alemtuzumab) antibodies, their therapeutic role in primary eosinophilic diseases and HES has yet to be established. Am. J. Hematol. 2012. © 2012 Wiley Periodicals, Inc.
Long-term Survival and Cost-effectiveness Associated With Axicabtagene Ciloleucel vs Chemotherapy for Treatment of B-Cell Lymphoma
Authors: Melanie D. Whittington, R. Brett McQueen, Daniel A. Ollendorf, Varun M. Kumar, Richard H. Chapman, Jeffrey A. Tice, Steven D. Pearson, Jonathan D. Campbell
Journal: JAMA Network Open (2019)

Axicabtagene ciloleucel, a chimeric antigen receptor T-cell therapy, represents a new and potentially curative treatment option for B-cell lymphoma. It is expected to have long-term survival benefits; however, long-term survival data are limited.
Direct Oral Anticoagulants for Thromboprophylaxis in Ambulatory Patients with Cancer
Authors: Giancarlo Agnelli
Journal: New England Journal of Medicine (2019)

Patients with cancer commonly have a venous thromboembolism during the course of their disease.1 Venous thromboembolism in these patients leads to a high risk of recurrence and bleeding related to anticoagulant therapy.2 Furthermore, venous thromboembolism exposes patients with cancer to the risk of interruption of cancer treatment and may lead to otherwise unnecessary hospitalization. For these reasons, prevention of venous thromboembolism in ambulatory patients with cancer who are receiving chemotherapy is of potential clinical value. In two large, randomized, placebo-controlled trials3,4 and a comprehensive meta-analysis,5 all involving ambulatory patients with different types of metastatic or locally advanced solid cancer who . . .
Three prophylaxis regimens (tacrolimus, mycophenolate mofetil, and cyclophosphamide; tacrolimus, methotrexate, and bortezomib; or tacrolimus, methotrexate, and maraviroc) versus tacrolimus and methotrexate for prevention of graft-versus-host disease with haemopoietic cell transplantation with reduced-intensity conditioning: a randomised phase 2 trial with a non-randomised contemporaneous control group (BMT CTN 1203)
Authors: Javier Bolaños-Meade, Ran Reshef, Raphael Fraser, Mingwei Fei, Sunil Abhyankar, Zaid Al-Kadhimi, Amin M Alousi, Joseph H Antin, Sally Arai, Kate Bickett, Yi-Bin Chen, Lloyd E Damon, Yvonne A Efebera, Nancy L Geller, Sergio A Giralt, Parameswaran Hari, Shernan G Holtan, Mary M Horowitz, David A Jacobsohn, Richard J Jones, Jane L Liesveld, Brent R Logan, Margaret L MacMillan, Marco Mielcarek, Pierre Noel, Joseph Pidala, David L Porter, Iskra Pusic, Ronald Sobecks, Scott R Solomon, Daniel J Weisdorf, Juan Wu, Marcelo C Pasquini, John Koreth
Journal: The Lancet Haematology (2019)
Clinical highlights from the National Cancer Data Base, 1999
Authors: A. M. Fremgen, K. I. Bland, L. S. McGinnis, H. J. Eyre, C. J. McDonald, H. R. Menck, G. P. Murphy
Journal: CA A Cancer Journal for Clinicians (1999)

The National Cancer Data Base (NCDB), a joint project of the Commission on Cancer of the American College of Surgeons and the American Cancer Society, collects and analyzes data from a wide variety of sources throughout the United States, including small community hospitals. Due to this unique reporting system, individual facilities can compare their own data with the aggregate data from the NCDB, using their findings to evaluate local patient care practices. This article highlights the principal findings of the NCDB and Patient Care Evaluation articles published in 1998 on breast, prostate, cervical, endometrial, gallbladder, head and neck, nasopharyngeal, rectal, thyroid, and vaginal cancers, as well as on melanoma, brain tumors, and Hodgkin's disease. With more than five million cancer cases in the NCDB for the years between 1985 and 1995, sufficient numbers of even rare cancers have been accrued to permit some types of epidemiologic and clinical assessments.
Single Nucleotide Polymorphisms and Thromboembolism in Acute Lymphoblastic Leukemia — a NOPHO ALL2008 Study
Authors: Kirsten Brunsvig Jarvis, Marissa Le Blanc, Morten Tulstrup, Ellen Ruud, Ruta Tuckuviene, Susanna Ranta, Kjeld Schmiegelow
Journal: Blood (2018)
IMMU-29. REMODELING IMMUNITY AGAINST MEDULLOBLASTOMA VIA RNA LOADED NANOPARTICLES
Authors: Elias Sayour, Gabriel De Leon, Adam Grippin, Catherine Flores, Christina Pham, Duane Mitchell
Journal: Neuro-Oncology (2017)

While recurrent medulloblastoma (MB) remains almost uniformly fatal, our group has shown a trend (p=0.07) toward improved survival in patients receiving autologous tumor RNA pulsed dendritic cells (DCs) coupled with ex vivo expanded total RNA activated T-cells. However, the advancement of autologous cellular therapeutics through the commercialization pipeline has been encumbered by significant cost, complexity and time to generation. To circumvent these challenges, we developed a novel treatment platform, which leverages the use of commercially available and clinically translatable nanoparticles (NPs) that can be combined with tumor-derived RNA to systemically activate peripheral immunity against MB antigens. To overcome the limitations of poorly immunogenic local vaccination strategies, we assessed if intravenous delivery of tumor-derived RNA encapsulated in lipophilic NPs could systemically activate antigen presenting cells (APCs) for induction of therapeutic anti-tumor immunity in pre-clinical MB models. We identified a clinically translatable NP formulation for the delivery of RNA to APCs that induces in vivo gene expression and preserves RNA stability over time. When administered intravenously, RNA-NPs lead to systemic activation (i.e. MHCI/II, CD40, CCR7 and CD86) of host APCs within reticuloendothelial organs and within the intratumoral microenvironment. We demonstrated that both model-antigen encoding RNA and physiologically-relevant tumor-derived RNA, when encapsulated in NPs, could expand potent anti-tumor T-cell immunity. T-cell immunity elicited by RNA-NPs was superior to peptide vaccines formulated in complete Freund’s adjuvant. We enhanced the immunogenicity of this platform by simply combining mRNAs encoding for immunomodulatory molecules (i.e. HCV-PAMPs, GM-CSF). In a pre-clinical cellular immunotherapy model targeting an anaplastic murine MB, RNA NPs supersede DCs in mediating anti-tumor activity. Since RNA-NPs bypass cost/complexity of cellular therapeutics, are amenable to central distribution, and can be made within days of tumor-resection, these formulations supplant DCs by providing near-immediate immune induction for patients with recurrent MBs.
Widower receives payout after GP failed to send wife to hospital with suspected DVT
Authors: Clare Dyer
Journal: BMJ (2019)

The widower of a 64 year old woman who died from a heart attack just hours after her GP failed to refer her urgently to hospital has won a High Court negligence claim against the doctor.1

Mario Schembri, a GP in Shoeburyness, Essex, admitted breach of duty in failing to send Doreen Marshall to Southend Hospital, but his lawyers argued at the High Court in London that she would have died in any event. They maintained that her widower, Ian, could not show that the GP’s breach of duty had caused her death, a necessary element for success in a negligence action.

Doreen Marshall saw the GP at about 4 pm on 25 April 2014, complaining of chest pain …
Evaluation of Polymer Nanoformulations in Hepatoma Therapy by Established Rodent Models
Authors: Qilong Wang, Ping Zhang, Zhongmin Li, Xiangru Feng, Chengyue Lv, Huaiyu Zhang, Haihua Xiao, Jianxun Ding, Xuesi Chen
Journal: Theranostics (2019)

Hepatoma is one of the most severe malignancies usually with poor prognosis, and many patients are insensitive to the existing therapeutic agents, including the drugs for chemotherapy and molecular targeted therapy. Currently, researchers are committed to developing the advanced formulations with controlled drug delivery to improve the efficacy of hepatoma therapy. Numerous inoculated, induced, and genetically engineered hepatoma rodent models are now available for formulation screening. However, animal models of hepatoma cannot accurately represent human hepatoma in terms of histological characteristics, metastatic pathways, and post-treatment responses. Therefore, advanced animal hepatoma models with comparable pathogenesis and pathological features are in urgent need in the further studies. Moreover, the development of nanomedicines has renewed hope for chemotherapy and molecular targeted therapy of advanced hepatoma. As one kind of advanced formulations, the polymer-based nanoformulated drugs have many advantages over the traditional ones, such as improved tumor selectivity and treatment efficacy, and reduced systemic side effects. In this article, the construction of rodent hepatoma model and much information about the current development of polymer nanomedicines were reviewed in order to provide a basis for the development of advanced formulations with clinical therapeutic potential for hepatoma.