tbuckley/cabot-search huggingface dataset:
Intratumoral Copper Modulates PD-L1 Expression and Influences Tumor Immune Evasion
Authors: Florida Voli, Emanuele Valli, Luigi Lerra, Kathleen Kimpton, Federica Saletta, Federico M. Giorgi, Daniele Mercatelli, Jourdin R.C. Rouaen, Sylvie Shen, Jayne E. Murray, Aria Ahmed-Cox, Giuseppe Cirillo, Chelsea Mayoh, Paul A. Beavis, Michelle Haber, Joseph A. Trapani, Maria Kavallaris, Orazio Vittorio
Journal: Cancer Research (2020)

Abstract Therapeutic checkpoint antibodies blocking programmed death receptor 1/programmed death ligand 1 (PD-L1) signaling have radically improved clinical outcomes in cancer. However, the regulation of PD-L1 expression on tumor cells is still poorly understood. Here we show that intratumoral copper levels influence PD-L1 expression in cancer cells. Deep analysis of the The Cancer Genome Atlas database and tissue microarrays showed strong correlation between the major copper influx transporter copper transporter 1 (CTR-1) and PD-L1 expression across many cancers but not in corresponding normal tissues. Copper supplementation enhanced PD-L1 expression at mRNA and protein levels in cancer cells and RNA sequencing revealed that copper regulates key signaling pathways mediating PD-L1–driven cancer immune evasion. Conversely, copper chelators inhibited phosphorylation of STAT3 and EGFR and promoted ubiquitin-mediated degradation of PD-L1. Copper-chelating drugs also significantly increased the number of tumor-infiltrating CD8+ T and natural killer cells, slowed tumor growth, and improved mouse survival. Overall, this study reveals an important role for copper in regulating PD-L1 and suggests that anticancer immunotherapy might be enhanced by pharmacologically reducing intratumor copper levels. Significance: These findings characterize the role of copper in modulating PD-L1 expression and contributing to cancer immune evasion, highlighting the potential for repurposing copper chelators as enhancers of antitumor immunity.
Efficacy and safety of once-daily nitisinone for patients with alkaptonuria (SONIA 2): an international, multicentre, open-label, randomised controlled trial
Authors: Lakshminarayan R Ranganath, Eftychia Eirini Psarelli, Jean-Baptiste Arnoux, Daniela Braconi, Michael Briggs, Anders Bröijersén, Nadia Loftus, Helen Bygott, Trevor F Cox, Andrew S Davison, Jane P Dillon, Michael Fisher, Richard FitzGerald, Federica Genovese, Helena Glasova, Anthony K Hall, Andrew T Hughes, Juliette H Hughes, Richard Imrich, Jonathan C Jarvis, Milad Khedr, Dinny Laan, Kim-Hanh Le Quan Sang, Emily Luangrath, Ol'ga Lukáčová, Anna M Milan, Alpesh Mistry, Vanda Mlynáriková, Brendan P Norman, Birgitta Olsson, Nicholas P Rhodes, Jozef Rovenský, Mattias Rudebeck, Annalisa Santucci, Ella Shweihdi, Ciarán Scott, Jana Sedláková, Nicolas Sireau, Roman Stančík, Johan Szamosi, Sophie Taylor, Christa van Kan, Sobhan Vinjamuri, Eva Vrtíková, Chris Webb, Elizabeth West, Elizabeth Záňová, Andrea Zatkova, James A Gallagher
Journal: The Lancet Diabetes & Endocrinology (2020)
The Measurement of Insulin Clearance
Authors: Francesca Piccinini, Richard N. Bergman
Journal: Diabetes Care (2020)

Insulin clearance has recently been highlighted as a fundamental aspect of glucose metabolism, as it has been hypothesized that its impairment could be related to an increased risk of developing type 2 diabetes. This review focuses on methods used to calculate insulin clearance: from the early surrogate indices employing C-peptide:insulin molar ratio, to direct measurement methods used in animal models, to modeling-based techniques to estimate the components of insulin clearance (hepatic versus extrahepatic). The methods are explored and interpreted by critically highlighting advantages and limitations.
Reuterin disrupts <i>Clostridioides difficile</i> metabolism and pathogenicity through reactive oxygen species generation
Authors: Melinda A. Engevik, Heather A. Danhof, Ritu Shrestha, Alexandra L. Chang-Graham, Joseph M. Hyser, Anthony M. Haag, Mahmoud A. Mohammad, Robert A. Britton, James Versalovic, Joseph A. Sorg, Jennifer K. Spinler
Journal: Gut Microbes (2020)

Antibiotic resistance is one of the world's greatest public health challenges and adjunct probiotic therapies are strategies that could lessen this burden. Clostridioides difficile infection (CDI) is a prime example where adjunct probiotic therapies could decrease disease incidence through prevention. Human-derived Lactobacillus reuteri is a probiotic that produces the antimicrobial compound reuterin known to prevent C. difficile colonization of antibiotic-treated fecal microbial communities. However, the mechanism of inhibition is unclear. We show that reuterin inhibits C. difficile outgrowth from spores and vegetative cell growth, however, no effect on C. difficile germination or sporulation was observed. Consistent with published studies, we found that exposure to reuterin stimulated reactive oxygen species (ROS) in C. difficile, resulting in a concentration-dependent reduction in cell viability that was rescued by the antioxidant glutathione. Sublethal concentrations of reuterin enhanced the susceptibility of vegetative C. difficile to vancomycin and metronidazole treatment and reduced toxin synthesis by C. difficile. We also demonstrate that reuterin is protective against C. difficile toxin-mediated cellular damage in the human intestinal enteroid model. Overall, our results indicate that ROS are essential mediators of reuterin activity and show that reuterin production by L. reuteri is compatible as a therapeutic in a clinically relevant model.
To My Wasted Eggs
Authors: Pamela L. Taylor
Journal: JAMA (2020)

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 6383: HTBPI inhibits liver tumorigenesis by combined inhibition of Akt
Authors: Haiyang Yu, Hongwei Liu, Qian Chen, Xu Pang, Shuangshuang Yin, Kailong Wang, Rui Wang, Tao Wang, Yuling Qiu
Journal: Cancer Research (2020)

Abstract Akt, a crucial protein involved in a variety of signaling pathways in cancer, acts as an important regulator of cell survival in hepatocellular carcinoma (HCC), and provides curative option for the related drug development. We have found an active phenanthroindolizidine alkaloid, (13aR,14R)-9,11,12,13,13a,14-hexahydro-3,6,7- trimethoxydibenzo[f,h]pyrrolo[1,2-b]isoquinolin-14-ol (HTBPI), which is a promising Akt inhibitor effective in the suppression of HCC cells proliferation through stimulating apoptotic and autophagic capability in vivo and in vitro. Treatment of HTBPI combined with a classical autophagy-lysosomal inhibitor (bafilomycin A1), could enhance stimulation effects of apoptosis on HCC cell lines. In addition, we confirmed that HTBPI, targeting Akt, occupied the kinase binding domain (Thr 308) of Akt to inactivate its function by CETSA and DARTS assay. Moreover, HTBPI showed a potential therapeutic effect in patient-derived xenograft (PDX) tumors without observed toxicity. Furthermore, high p-Akt (Thr 308) expression was collated with liver tumor formation and poor survival in HCC patients. In conclusions, HTBPI impeded HCC progress through regulation of apoptosis and autophagy machinery via interaction with p-Akt (Thr 308). This may provide potential molecular candidate by inhibiting Akt for the therapy of HCC patients. Citation Format: Haiyang Yu, Hongwei Liu, Qian Chen, Xu Pang, Shuangshuang Yin, Kailong Wang, Rui Wang, Tao Wang, Yuling Qiu. HTBPI inhibits liver tumorigenesis by combined inhibition of Akt [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6383.
Uncemented vs Cemented Hemiarthroplasty for Hip Fracture—Reply
Authors: Kanu Okike, Priscilla H. Chan, Heather A. Prentice
Journal: JAMA (2020)

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
A smart dual-drug nanosystem based on co-assembly of plant and food-derived natural products for synergistic HCC immunotherapy
Authors: Bingchen Zhang, Jiali Jiang, Pengyu Wu, Junjie Zou, Jingqing Le, Juanfang Lin, Chao Li, Bangyue Luo, Yongjie Zhang, Rui Huang, Jingwei Shao
Journal: Acta Pharmaceutica Sinica B (2020)

Nanotechnology has emerged as an ideal approach for achieving the efficient chemo agent delivery. However, the potential toxicity and unclear internal metabolism of most nano-carriers was still a major obstacle for the clinical application. Herein, a novel "core‒shell" co-assembly carrier-free nanosystem was constructed based on natural sources of ursolic acid (UA) and polyphenol (EGCG) with the EpCAM-aptamer modification for hepatocellular carcinoma (HCC) synergistic treatment. As the nature products derived from food-plant, UA and EGCG had good anticancer activities and low toxicity. With the simple and "green" method, the nanodrugs had the advantages of good stability, pH-responsive and strong penetration of tumor tissues, which was expected to increase tumor cellular uptake, long circulation and effectively avoid the potential defects of traditional carriers. The nanocomplex exhibited the low cytotoxicity in the normal cells in vitro, good biosafety of organic tissues and efficient tumor accumulation in vivo. Importantly, UA combined with EGCG showed the immunotherapy by activating the innate immunity and acquired immunity resulting in significant synergistic therapeutic effect. The research could provide new ideas for the research and development of self-assembly delivery system in the future, and offer effective intervention strategies for clinical HCC treatment.
Methylomic Landscapes of Ovarian Cancer Precursor Lesions
Authors: Thomas R. Pisanic, Yeh Wang, Hanru Sun, Michael Considine, Lihong Li, Tza-Huei Wang, Tian-Li Wang, Ie-Ming Shih
Journal: Clinical Cancer Research (2020)

The current paradigm in the development of high-grade serous ovarian carcinoma (HGSC) proposes that the majority of HGSCs arise from precursor serous tubal intraepithelial carcinoma (STIC) lesions of the fallopian tube. Here we survey genome-wide methylation in HGSC precursor lesions to identify genomic regions that exhibit high-specificity differential hypermethylation for potential use as biomarkers for detecting STIC and HGSC at stages when curative intervention likely remains feasible.
Abstract P376: Cardiometabolic Abnormalities, Systemic Inflammation, and Oxidative Stress in Children
Authors: Stephanie J Frisbee, Jefferson C Frisbee, Alan Ducatman
Journal: Circulation (2012)

The increasing prevalence of childhood obesity has been well documented &amp; is predictive of increased severity in obesity-related CVD risk factors &amp; metabolic disorders, such as systemic inflammation &amp; oxidative stress. While the poor long-term vascular consequences of these conditions are better understood in adults, the consequences of these obesity-associated metabolic disturbances are less studied in children. This study utilized the 12,476 children (&lt;18 years) enrolled in the C8 Health Project, which resulted from the pretrial settlement of a class action lawsuit pursuant to contamination of the drinking water supply; we have recently published a complete description of this study (Frisbee et al, 2009). The current analysis used the large sample size available from this study to determine the severity of chronic inflammation &amp; oxidative stress associated with cardiometabolic abnormalities, including obesity, dyslipidemia, &amp; hyperglycemia, present either singly or in combination, in children. In this population, median age was 11.6 years, 48% were female, 40% were overweight or obese (OWT-OB; BMI≥85th percentile), 2% had glucose ≥126 mg/dL (HypGly), &amp; 34% had total cholesterol ≥170 mg/dL or LDL cholesterol ≥110 mg/dL (DysLip), Additionally, median CRP, a biomarker of systemic inflammation, was 0.4 mg/L with 16% having CRP≥2 mg/L, &amp; median GGT, a biomarker of oxidative stress, was 12.0 IU/L with 1.7% having GGT≥35 IU/L. In univariate analysis: CRP &amp; GGT were statistically significantly higher in participants with OWT-OB; GGT but not CRP was higher in children with HypGly or DysLip; &amp; both CRP &amp; GGT were higher in children with any cardiometabolic abnormality. In linear regression analysis controlling for age, gender, SES (household income), a regular exercise program, &amp; while simultaneously considering OWT-OB, HypGly, &amp; DysLip: OWT-OB statistically significantly predicted CRP (b-coefficient±SE/adj R-square; 1.0±0.1/1.4%) though HypGly &amp; DysLip were not, ceteris paribus, associated with CRP; OWT-OB (3.5±0.2/16.6%), HypGly (1.2±0.6/16.6%), &amp; DysLip (2.1±0.2/16.6%) were all simultaneously predictive of GGT. In logistic regression analysis controlling for the same covariates &amp; also simultaneously considering the same cardiometabolic abnormalities: OWT-OB (OR (95%CI); 3.8 (3.4-4.4)) &amp; DysLip (1.2 (1.0=1.3)) but not HypGly increased the risk for CRP≥2 mg/L; similarly, OWT-OB (5.6 (3.5-8.7)) &amp; DysLip (3.4 (2.3-5.0)) but not HypGly were associated with increased for oxidative stress (GGT≥35 IU/L). This study suggests that different cardiometabolic abnormalities have different associations with systemic inflammation &amp; oxidative stress; obesity &amp; dyslipidemia rather than hyperglycemia are more strongly associated with systemic inflammation &amp; oxidative stress in children. Futher study is needed to elucidate gender &amp; age-related differences in these associations.
Disseminated intravascular coagulation in Stevens-Johnson syndrome and toxic epidermal necrolysis
Authors: Chun-Bing Chen, Tsun-Hao Hsu, Rosaline Chung-Yee Hui, Chun-Wei Lu, Wei-Ti Chen, Pin-Hsuan Chiang, Chuang-Wei Wang, Shiow-Shuh Chuang, Jui-Yung Yang, Shih-Yi Yang, Shu-Ying Chang, Yen-Chang Hsiao, Kuo-Chin Kao, Han-Chung Hu, Ting-Shu Wu, Chao-Wei Hsu, David Hui-Kang Ma, Shin-Yi Chen, Ya-Chung Tian, Chi-Yuan Cheng, Chi-Hua Chen, Min-Hui Chi, Ming-Ying Wu, Ren-Feng Liu, Chi-Hui Wang, Ya-Ching Chang, Jing-Yi Lin, Hsin-Chun Ho, Yang Yu-Wei Lin, Chee Jen Chang, Yu-Jr Lin, Cheng-Lung Ku, Shuen-Iu Hung, Wen-Hung Chung
Journal: Journal of the American Academy of Dermatology (2020)
Refinement of the PKHD1 interval and analysis of candidate expressed sequences
Authors: Luiz Fernando Onuchic, L. Furu, Y. Nagasawa, M. Mrug, T. Eggermann, C. Bergmann, W. Sweeney, E. Avner, K. Zerres, L. M. Guay Woodford, S. Somlo, G. G. Germino
Journal: Journal of the American Society of Nephrology (2001)
Targeting EphA2 in cancer
Authors: Ta Xiao, Yuhang Xiao, Wenxiang Wang, Yan Yan Tang, Zhiqiang Xiao, Min Su
Journal: Journal of Hematology & Oncology (2020)

Abstract Eph receptors and the corresponding Eph receptor-interacting (ephrin) ligands jointly constitute a critical cell signaling network that has multiple functions. The tyrosine kinase EphA2, which belongs to the family of Eph receptors, is highly produced in tumor tissues, while found at relatively low levels in most normal adult tissues, indicating its potential application in cancer treatment. After 30 years of investigation, a large amount of data regarding EphA2 functions have been compiled. Meanwhile, several compounds targeting EphA2 have been evaluated and tested in clinical studies, albeit with limited clinical success. The present review briefly describes the contribution of EphA2-ephrin A1 signaling axis to carcinogenesis. In addition, the roles of EphA2 in resistance to molecular-targeted agents were examined. In particular, we focused on EphA2’s potential as a target for cancer treatment to provide insights into the application of EphA2 targeting in anticancer strategies. Overall, EphA2 represents a potential target for treating malignant tumors.
The cancer patient and cardiology
Authors: José Luis Zamorano, Christer Gottfridsson, Riccardo Asteggiano, Dan Atar, Lina Badimon, Jeroen J. Bax, Daniela Cardinale, Antonella Cardone, Elizabeth A.M. Feijen, Péter Ferdinandy, Teresa López‐Fernández, Chris P. Gale, John H. Maduro, Javid Moslehi, Torbjørn Omland, Juan Carlos Plana Gomez, Jessica Scott, Thomas M. Suter, Giorgio Minotti
Journal: European Journal of Heart Failure (2020)
A Multi‐Functional Implant Induces Bone Formation in a Diabetic Model
Authors: Behnoush Khorsand, Timothy M. Acri, Anh‐Vu Do, John E. Femino, Emily Petersen, Douglas C. Fredericks, Aliasger K. Salem
Journal: Advanced Healthcare Materials (2020)

Patients with diabetes mellitus (DM) have defective healing of bone fractures. It was previously shown that nonviral gene delivery of plasmid DNA (pDNA) that independently encodes bone morphogenetic protein-2 (BMP-2) and fibroblast growth factor-2 (FGF-2), acts synergistically to promote bone regeneration in a DM animal model. Additionally, both insulin (INS) and the hormonally active form of vitamin D3, 1α,25-dihydroxyvitamin D3 (1α,25(OH)2 D3 ) (VD3) have independently been shown to play key roles in regulating bone fracture healing in DM patients. However, these individual therapies fail to adequately stimulate bone regeneration, illustrating a need for novel treatment of bone fractures in diabetic patients. Here, the ability of local delivery of INS and VD3 along with BMP-2 and FGF-2 genes is investigated to promote bone formation ectopically in Type-2 diabetic rats. A composite consisting of VD3 and INS is developed that contains poly(lactic-co-glycolic acid) microparticles (MPs) embedded in a fibrin gel surrounded by a collagen matrix that is permeated with polyethylenimine (PEI)-(pBMP-2+pFGF-2) nanoplexes. Using a submuscular osteoinduction model, it is demonstrated that local delivery of INS, VD3, and PEI-(pBMP-2+pFGF-2) significantly improves bone generation compared to other treatments, thusimplicating this approach as a method to promote bone regeneration in DM patients with bone fractures.
Abstract 6010: Tumor mhicroenvironment effects on hematopoietic stem cell induced tumor growth following radiation therapy
Authors: Tyler M. Parsons, Katie Buelow, Alaa Hanna, Sandra Galoforo, George Wilson, Gerard Madlambayan
Journal: Cancer Research (2020)

Abstract The tumor microenvironment (TME), comprised of tumor tissue, stromal cells, extracellular matrix (ECM), bone marrow (BM)-derived immune cells, and various signaling molecules, rarely remains static. These components continuously respond to internal and external stimuli to promote tumor progression as well as regrowth after therapy. Recently, we reported that functional BM-derived hematopoietic stem and progenitor cells (HSPCs) take up residence within growing lung tumors. Interestingly, when tumors were exposed to radiation therapy (RT) there was a significant increase in HSPC numbers within tumors (p&amp;lt;0.003). These HSPCs seemed to positively affect tumor regrowth as their numbers directly correlated with regrowth rates (R2=.4875). To determine the role of HSPCs in tumor growth we proposed a mechanism wherein tumor-associated HSPCs are maintained within tumors but following exposure to RT can differentiate into tumor-supportive macrophage populations, thus aiding in tumor regrowth. To test this hypothesis, Lewis Lung Carcinoma tumors were subcutaneously generated in mice and exposed to either RT or no radiation treatment (NRT). Analysis using RT-PCR and immunohistochemistry demonstrated that RT produces TME conditions that favor the differentiation of HSPCs into tumor-supportive M2-macrophages through the increased production of colony stimulating factor 1 (CSF-1) (p&amp;lt;0.005). In addition, we show that inhibition of CSF-1R phosphorylation using a pharmacologic inhibitor (GW2580) had no effect on HSPCs numbers but resulted in significantly decreased M2 macrophage numbers resulting in decreased tumor growth and regrowth (p&amp;lt;0.005). Furthermore, we found that the interaction of HSPC-bound integrin α6 with Laminin 5-1-1 is associated with HSPC maintenance within tumors. Interestingly, Laminin 5-1-1 levels were decreased in RT treated tumors compared to NRT controls (p&amp;lt;0.005) further indicating that the RT-derived microenvironments supported HSPC differentiation into M2 macrophages. Overall, these studies define a new understanding of tumor biology in which tumor-associated HSPCs are an essential component of tumor progression and survival and identify new treatment strategies to overcome these effects and achieve more optimal clinical outcomes. Citation Format: Tyler M. Parsons, Katie Buelow, Alaa Hanna, Sandra Galoforo, George Wilson, Gerard Madlambayan. Tumor mhicroenvironment effects on hematopoietic stem cell induced tumor growth following radiation therapy [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6010.