tbuckley/cabot-search huggingface dataset:
Type 2 immunity is protective in metabolic disease but exacerbates NAFLD collaboratively with TGF-β
Authors: Kevin M. Hart, Thomas Fabre, Joshua C. Sciurba, Richard L. Gieseck, Lee A. Borthwick, Kevin M. Vannella, Thomas H. Acciani, Rafael de Queiroz Prado, Robert W. Thompson, Sandra White, Genevieve Soucy, Marc Bilodeau, Thirumalai R. Ramalingam, Joseph R. Arron, Naglaa H. Shoukry, Thomas A. Wynn
Journal: Science Translational Medicine (2017)

Nonalcoholic fatty liver disease (NAFLD) is now the most common progressive liver disease in developed countries and is the second leading indication for liver transplantation due to the extensive fibrosis it causes. NAFLD progression is thought to be tied to chronic low-level type 1 inflammation originating in the adipose tissue during obesity; however, the specific immunological mechanisms regulating the progression of NAFLD-associated fibrosis in the liver are unclear. To investigate the immunopathogenesis of NAFLD more completely, we investigated adipose dysfunction, nonalcoholic steatohepatitis (NASH), and fibrosis in mice that develop polarized type 1 or type 2 immune responses. Unexpectedly, obese interleukin-10 (IL-10)/IL-4-deficient mice (type 1-polarized) were highly resistant to NASH. This protection was associated with an increased hepatic interferon-γ (IFN-γ) signature. Conversely, IFN-γ-deficient mice progressed rapidly to NASH with evidence of fibrosis dependent on transforming growth factor-β (TGF-β) and IL-13 signaling. Unlike increasing type 1 inflammation and the marked loss of eosinophils seen in expanding adipose tissue, progression of NASH was associated with increasing eosinophilic type 2 liver inflammation in mice and human patient biopsies. Finally, simultaneous inhibition of TGF-β and IL-13 signaling attenuated the fibrotic machinery more completely than TGF-β alone in NAFLD-associated fibrosis. Thus, although type 2 immunity maintains healthy metabolic signaling in adipose tissues, it exacerbates the progression of NAFLD collaboratively with TGF-β in the liver.
PD-1 Blockade in Mediastinal Gray-Zone Lymphoma
Authors: Christopher Melani, Ajay Major, Jeffrey Schowinsky, Mark Roschewski, Stefania Pittaluga, Elaine S Jaffe, Svetlana D Pack, Zied Abdullaev, Mark A Ahlman, Jennifer J Kwak, Rustain Morgan, Rachel Rabinovitch, Zenggang Pan, Bradley M Haverkos, Jonathan A Gutman, Daniel A Pollyea, Clayton A Smith, Wyndham H Wilson, Manali Kamdar
Journal: New England Journal of Medicine (2017)

Mediastinal gray-zone lymphoma is intermediate between classic Hodgkin’s lymphoma and primary mediastinal B-cell lymphoma. Three patients whose disease had become refractory to chemotherapy had impressive responses to PD-1 blockade.
A description of familial clustering of meningiomas in the Utah population
Authors: William T Couldwell, Lisa A Cannon-Albright
Journal: Neuro-Oncology (2017)

Meningiomas are common intracranial tumors in adults, yet the genetics and cause of sporadic meningiomas are not well understood. Few familial clusters have been reported. The aim of this study was to investigate the familiality of meningiomas within the Utah Population Database. Meningioma cases reported in the Utah Cancer Registry were identified. Relative risk of their relatives was calculated. All possible cases were assessed with the Genealogical Index of Familiality (GIF), which measures average pairwise relatedness of all possible pairs using the Malecot coefficient of kinship. Clusters of cases descending from a common ancestor were identified. Eight hundred fifty-eight meningioma cases were reported. The relative risk of a first- or second-degree relative was 3.13 (95% CI: 1.67, 5.36) or 2.28 (1.30, 3.70), respectively. The GIF statistic demonstrated a clear excess of relationships for genetic distance <4 (closer than first cousins). We identified 920 pedigrees, including 2–21 meningioma cases. One hundred eighty-nine of these pedigrees, including 2–15 cases, had a significant excess (P < 0.05) of meningioma cases over what was expected. This Utah population–based analysis of meningiomas shows clear evidence of familial clustering and supports both a familial and a germline variant basis for meningioma. These clusters may allow identification of genes likely to contribute to tumorigenesis in high-risk pedigrees. These relative risk data provide the basis for further investigations of genetic contributions to meningioma. These data may contribute to developing a basis for determining screening criteria of higher-risk pedigrees for the presence of meningiomas.
Sex differences between parental pregnancy characteristics and nonalcoholic fatty liver disease in adolescents
Authors: Oyekoya T. Ayonrinde, Leon A. Adams, Trevor A. Mori, Lawrence J. Beilin, Nicholas de Klerk, Craig E. Pennell, Scott White, John K Olynyk
Journal: Hepatology (2017)

Nonalcoholic fatty liver disease (NAFLD) is a complex chronic liver disorder. Examination of parental pregnancy‐related characteristics may provide insights into the origins of risk of NAFLD in offspring. We examined relationships between parental pregnancy‐related characteristics and NAFLD in 1,170 adolescent offspring aged 17 years participating in the Western Australian Pregnancy (Raine) Cohort Study. Fatty liver was diagnosed using liver ultrasound. NAFLD was diagnosed in 15.2% of adolescents at age 17 years. In univariate analysis, maternal factors associated with NAFLD in female offspring were younger maternal age ( P = 0.02), higher maternal prepregnancy BMI ( P &lt; 0.001), higher maternal weight gain by 18 weeks' gestation ( P &lt; 0.001), and maternal smoking during pregnancy ( P = 0.04). Paternal age or body mass index (BMI) were not associated with NAFLD in female offspring. In contrast, higher paternal BMI ( P &lt; 0.001), maternal prepregnancy BMI ( P &lt; 0.001), and lower family socioeconomic status (SES) at time of birth ( P = 0.001), but not parental age nor maternal gestational weight gain, were associated with NAFLD in male offspring. Using multivariate logistic regression, factors independently associated with NAFLD after adjusting for obesity in adolescent females included maternal obesity (odds ratio [OR], 3.46; 95% confidence interval [CI], 1.49‐8.05; P = 0.004) and maternal weight gain ≥6.0 kg by the 18th week of gestation (OR, 1.10; 95% CI, 1.04‐1.15; P &lt; 0.001). In adolescent males, family SES at the time of birth (OR, 9.07; 95% CI, 1.54‐53.29; P = 0.02) remained significantly associated with NAFLD after multivariate modeling adjusted for adolescent obesity. Conclusion: Early‐life contributors to NAFLD show considerable sexual dimorphism. Maternal obesity and higher early‐mid gestational weight gain were associated with NAFLD in female offspring, whereas lower family SES at birth was associated with NAFLD in male offspring independent of adolescent obesity. (H epatology 2018;67:108‐122).
Rapid Mobilization Reveals a Highly Engraftable Hematopoietic Stem Cell
Authors: Jonathan Hoggatt, Pratibha Singh, Tiffany Tate, Peter V. Kharchenko, Amir Schajnovitz, Ninib Barawnyo, Francois Mercier, Dwight Morrow, David T. Scadden, Louis M. Pelus
Journal: Blood (2016)
Induction of Testicular Tumors and Other Effects of Stilbestrol-Cholesterol Pellets in Strain C Mice
Authors: Michael B. Shimkin, Hugh G. Grady, Howard B. Andervont
Journal: JNCI Journal of the National Cancer Institute (1941)

Journal Article Induction of Testicular Tumors and Other Effects of Stilbestrol-Cholesterol Pellets in Strain C Mice Get access Michael B. Shimkin, Michael B. Shimkin assistant surgeon Search for other works by this author on: Oxford Academic PubMed Google Scholar Hugh G. Grady, Hugh G. Grady acting assistant surgeon Search for other works by this author on: Oxford Academic PubMed Google Scholar Howard B. Andervont Howard B. Andervont principal biologist National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 2, Issue 1, August 1941, Pages 65–80, https://doi.org/10.1093/jnci/2.1.65 Published: 01 August 1941
Hemoglobin Level at Azacitidine Onset Is a Prognostic Factor of Unachievement of Three Azacitidine Cycles in Myelodysplastic Syndromes and Acute Myeloid Leukemia
Authors: Anne Calleja, Jean Michel Karsenti, Lauris Gastaud, Georges Garnier, Jean Gutnecht, Daniel Re, Laurence Legros, Lionel Mannone, Patrick Auberger, Sophie Raynaud, Thomas Cluzeau
Journal: Blood (2016)
Cancer Cell–Autonomous Parainflammation Mimics Immune Cell Infiltration
Authors: Audrey Lasry, Dvir Aran, Atul J. Butte, Yinon Ben-Neriah
Journal: Cancer Research (2017)

Parainflammation is a unique variant of inflammation, characterized by epithelial-autonomous activation of inflammatory response. Parainflammation has been shown to strongly promote mouse gut tumorigenesis upon p53 loss. In a recent study, we explored the prevalence of parainflammation in human cancer and determined its relationship to certain molecular and clinical parameters affecting treatment and prognosis. Parainflammation can be identified from a 40-gene signature and is found in both carcinoma cell lines and a variety of primary tumors, independently of tumor microenvironment. Here, we discuss the implications of our findings in analyses of tumor microenvironment, suggesting that as tumor cell gene expression may often mimic immune and inflammatory infiltration, caution should be applied when interpreting tumor expression data. We also address the connection between parainflammation and prevalence of p53 mutations in specific types of tumors, and cancer prevention by regular usage of NSAIDs. We suggest that parainflammation may serve as a novel biomarker for screening patients who may particularly benefit from NSAID treatment. Cancer Res; 77(14); 3740-4. ©2017 AACR.
Predictors of upgrade diagnosis after endoscopic resection of gastric low-grade dysplasia: Who can be recommended regular follow-up?
Authors: Wook Kim Hyung, Hwan Kang Dae, Woong Choi Cheol, Jin Kim Su, Seok Nam Hyeong, Gon Ryu Dae, Seok Lee Jeong, Jin Kim Hyeong, Eok Jo Il, Jae Lee Yong
Journal: Annals of Oncology (2017)
Proteomic Analysis Shows Constitutive Secretion of MIF and p53-Associated Activity of COX-2−/− Lung Fibroblasts
Authors: Mandar Dave, Abul B.M.M.K. Islam, Roderick V. Jensen, Agueda Rostagno, Jorge Ghiso, Ashok R. Amin
Journal: Genomics Proteomics & Bioinformatics (2017)

Abstract The differential expression of two closelyassociated cyclooxygenase isozymes, COX-1 and COX-2, exhibited functions beyond eicosanoid metabolism. We hypothesized that COX-1 or COX-2 knockout lung fibroblasts may display altered protein profiles which may allow us to further differentiate the functional roles of these isozymes at the molecular level. Proteomic analysis shows constitutive production of macrophage migration inhibitory factor (MIF) in lung fibroblasts derived from COX-2−/− but not wild-type (WT) or COX-1−/− mice. MIF was spontaneously released in high levels into the extracellular milieu of COX2−/− fibroblasts seemingly from the preformed intracellular stores, with no change in the basal gene expression of MIF. The secretion and regulation of MIF in COX-2−/− was “prostaglandin-independent.” GO analysis showed that concurrent with upregulation of MIF, there is a significant surge in expression of genes related to fibroblast growth, FK506 binding proteins, and isomerase activity in COX-2−/− cells. Furthermore, COX-2−/− fibroblasts also exhibit a significant increase in transcriptional activity of various regulators, antagonists, and co-modulators of p53, as well as in the expression of oncogenes and related transcripts. Integrative Oncogenomics Cancer Browser (IntroGen) analysis shows downregulation of COX-2 and amplification of MIF and/or p53 activity during development of glioblastomas, ependymoma, and colon adenomas. These data indicate the functional role of the MIF-COX-p53 axis in inflammation and cancer at the genomic and proteomic levels in COX-2-ablated cells. This systematic analysis not only shows the proinflammatory state but also unveils a molecular signature of a pro-oncogenic state of COX-1 in COX-2 ablated cells.
Complications of Diabetes Diagnosed in Children and Adolescents
Authors: Maria Carolina Ibanez-Bruron, Ameenat Lola Solebo, Jugnoo Sangeeta Rahi
Journal: JAMA (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 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
Neoadjuvant Gene Therapy of the Primary Tumour Inhibits Progression of Minimal Disease to Liver Metastases
Authors: JP Cashman, JO Larkin, C Collins, M Whelan, JK Collins, M Tangney, GC O'Sullivan
Journal: Endoscopy (2006)

Aims: We investigated, as a neoadjuvant to surgical therapy, the effect of a gene therapy of the primary tumour on the progression of minimal residual disease to overt liver metastases. The gene construct coding for the immunostimulatory molecules GM-CSF and B7–1 was delivered to the growing tumour by electroporation in Balb/C mice.
Transintestinal cholesterol excretion: A secondary, nonbiliary pathway contributing to reverse cholesterol transport
Authors: David Q.‐H. Wang, Piero Portincasa, Patrick Tso
Journal: Hepatology (2017)

Wang, David Q.‐H. M.D., Ph.D.; Portincasa, Piero M.D., Ph.D.; Tso, Patrick Ph.D. Author Information
Efficacy of Stimulants Beyond Treatment of Core Symptoms of Attention-Deficit/Hyperactivity Disorder
Authors: Luis Augusto Rohde
Journal: JAMA Psychiatry (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 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
Association of the colon cancer recurrence score with treatments received in patients with stage II colon cancer: The Clalit Health Services experience.
Authors: Baruch Brenner, Ravit Geva, Alexander Beny, Ygael Dror, Mariana Steiner, Ayala Hubert, Efraim Idelevich, Alexander Gluzman, Ofer Purim, Einat Shacham-Shmueli, Katerina Shulman, Lior Soussan-Gutman, Shmuel Klang, Shahar Merling, Nicky Liebermann
Journal: Journal of Clinical Oncology (2013)

e22111 Background: The Oncotype DX Colon Cancer Recurrence Score (RS) is a validated prognosticator in stage II colon cancer following surgery. However, the impact of the RS on daily practice is still unclear. Clalit Health Services(CHS) has reimbursed Oncotype DX colon testing since 1/2011. This prospective study examined the use of the RS and its association with treatment decisions in this setting in Israel. Methods: Eligible patients had stage II colon cancer and testing reimbursed by CHS from 1/2011 to 5/2012. Patient/tumor data and treatment information were gathered prospectively. Data were analyzed using the Chi-squared test. Results: The study included 341 patients of whom 314 had confirmed stage II, T3N0 disease, and were included in the analysis. Median age was 68 years (range: 29-89); 18.2%, 68.5%, and 9.9% had grade 1, 2, and 3 tumors, respectively; 15.3% had colonic obstruction and 5.7% had lymphovascular invasion. Thirty-nine patients (12.4%) had mismatch repair (MMR)-deficient tumors and their samples were not tested further. Of the 275 tested patients, 160 (58.2%), 87 (31.6%), and 27 (9.8%) had low (&lt;30), intermediate (30-40), and high (&gt;40) RS, respectively (1 patient [0.4%] had no RS due to technical failure of the assay). The grade 3 group had a higher proportion of MMR-deficient tumors than the grade 2 and grade 1 groups (35.5%, 7.9% and 10.5%, respectively, P&lt;.0001). In the MMR-proficient tumors, the proportions of low RS tumors according to grade were 60.8%, 58.1% and 70.0% for grades 1, 2 and 3, respectively (P=0.57). Chemotherapy was administered to 86/314 (27.4%) patients, including 3/39 (7.7%) in the MMR-deficient, 27/160 (16.9%) in the low, 39/87 (44.8%) in the intermediate, and 17/27 (63.0%) in the high RS groups. The most commonly used regimen was capecitabine monotherapy (61/86 treated patients, 70.9%). The differences in the proportions of patients receiving chemotherapy between the MMR-deficient, low, intermediate, and high RS groups were significant (P&lt;.0001). Conclusions: Our findings suggest that the RS results and MMR-deficient status are significantly associated with treatment decisions in stage II colon cancer patients in Israel.
One day preparative regimen for allogeneic non-myeloablative stem cell transplantation using 3-5/6 HLA matched related donors
Authors: T. F. Goggins, D. A. Rizzieri, R. Prosnitz, C. Gasparetto, G. Long, M. E. Horwitz, K. Sullivan, A. Morris, M. Thompson, M. Lassiter, K. Rowe, N. J. Chao
Journal: Blood (2003)
Development of ROC-325: A Novel Small Molecule Inhibitor of Autophagy with Promising Anti-Leukemic Activity
Authors: Steffan T. Nawrocki, Yingchun Han, Valeria Visconte, James G Phillips, Bartlomiej P Przychodzen, Jaroslaw P Maciejewski, Kevin R. Kelly, Jennifer S. Carew
Journal: Blood (2016)
Cytosolic Phospholipase A2 regulates Chloride Secretion in Colonic Epithelial Cells
Authors: F Donnellan, AK Stubbs, BJ Harvey, FE Murray, SJ Keely
Journal: Endoscopy (2006)

Aims: Activation of Gq Protein Coupled Receptors (GqPCRs) induces transient chloride (Cl -) secretory responses in intestinal epithelial cells which are limited by an antisecretory pathway mediated by mitogen activated protein kinases (MAPKs). The aim of this study is to determine if cytosolic phospholipase A2 (cPLA2) regulates GqPCR-induced Cl – secretion as an effector of the antisecretory pathway in intestinal epithelia.
Survival patterns following brain metastases for patients with melanoma in the targeted therapy era.
Authors: Daniel A. Wattson, Helen Alice Shih, Andrzej Niemierko, Ryan M. Merritt, Donald P. Lawrence, Kevin S. Oh, Ryan J. Sullivan, Keith Flaherty
Journal: Journal of Clinical Oncology (2013)

9064 Background: Survival from metastatic melanoma (MM) has been significantly prolonged with the introduction of molecularly targeted therapy, including BRAF inhibitors (BRAFi) for patients (pts) with the V600E mutation. Here, we present the first data describing patterns of survival after diagnosis of brain metastases (BM) in a large cohort of these pts with long follow-up. Methods: A retrospective review of 191 MM pts accrued on multiple prospective trials between 2008–2012 was conducted. These trials assessed novel immunologic and targeted therapies in pts with both BRAF mutant (n=70) and wild type/unknown (n=121) tumors. We evaluated pt characteristics and the impact of systemic and BM-directed treatments. Results: Of 98 pts who developed BM, median follow-up after first BM was 7.7 months (15.5 months for the 25 living pts), and 33 were treated with BRAFi. Median duration of BRAFi use was 5.9 months (range 0.7–27.1), which preceded BM in 30%, was concurrent with first BM in 18%, and followed first BM in 52%. Ipilimumab or anti–PD-1/PD-L1 immunotherapy was given to 58% of pts who received a BRAFi and 95% of those who did not. Limited intracranial disease on initial BM presentation (defined as ≤3 lesions) occurred in 70% of BRAFi-treated pts and 74% of non-BRAFi pts, and 70% of BRAFi pts received at least one focal BM treatment (stereotactic radiosurgery or resection) compared to 75% of non-BRAFi pts. As shown in the Table, actuarial survival after BM diagnosis was prolonged among pts treated with a BRAFi. This is due primarily to the nearly 2-year median survival of pts for whom a BRAFi was initiated after BM were diagnosed. Conclusions: Survival for pts with BM from BRAF mutant MM can significantly exceed the often anticipated 4–6 months, particularly if a BRAFi is initiated after BM arise. This supports BRAFi activity in intracranial disease, and helps to inform trials currently under way testing BRAFi use among MM pts with previously diagnosed BM. [Table: see text]