tbuckley/cabot-search huggingface dataset:
Abstract 3783: Mitochondrial metabolism in tumor-associated macrophages: The role of MIF and tumor-derived lactate
Authors: Jordan Noe, Beatriz Rendon, Eun Jung Kim, Robert Mitchell
Journal: Cancer Research (2018)

Abstract Purpose: Within the tumor microenvironment, tumor-associated macrophages (TAMs) polarized to an "M2" phenotype promote angiogenesis, metastasis, and the suppression of anti-tumor immune responses. Previously, we have found that macrophage migration inhibitory factor (MIF) promotes lactate-enhanced M2-polarization, however the underlying mechanisms were not elucidated. As cancer cells that exhibit the Warburg Effect secrete copious amounts of lactate into the tumor microenvironment, highly glycolytic cancers may promote tumor progression by producing lactate to support an immunosuppressive tumor microenvironment. The goal of this study is to investigate the mechanism by which MIF and tumor-derived lactate support pro-tumorigenic M2-TAMs. Methods: Using primary bone marrow-derived macrophages (BMDMs), we explored the mechanisms of MIF and lactate-enhanced M2 polarization using metabolic inhibitors and gene expression assays. To investigate the role of MIF in mitochondrial metabolism, we conducted extracellular flux analysis to determine mitochondrial OCR and ECAR in macrophages polarized to an M0 and M2 phenotype. Results: Blocking mitochondrial pyruvate uptake reduces both M2 polarization and HIF1α stabilization. Blocking mitochondrial metabolism and respiration inhibits M2 polarization. MIF deficiency decreases mitochondrial OCR, NRF2 stability, and M2 polarization. Increasing CSN5 activity "rescues" the loss of M2 polarization with MIF deficiency. Conclusions: Tumor-derived lactate per se does not promote M2 polarization but instead requires subsequent metabolism to pyruvate. Additionally, we have identified that mitochondrial pyruvate metabolism is a previously undetermined requirement for M2 macrophages. Further, we have found a potential link between MIF and metabolism, where MIF likely regulates CSN5 activity and NRF2 stability to increase mitochondrial respiration. As inhibiting mitochondrial respiration blocks M2 polarization, MIF may promote lactate-enhanced M2 polarization by enhancing mitochondrial metabolism. Subsequent studies will be conducted to further investigate the metabolic pathways and mechanisms required for the mitochondrial metabolism of tumor-derived lactate in promoting M2-TAM polarization. Citation Format: Jordan Noe, Beatriz Rendon, Eun Jung Kim, Robert Mitchell. Mitochondrial metabolism in tumor-associated macrophages: The role of MIF and tumor-derived lactate [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 3783.
A Beautiful Death
Authors: Lyssa Weatherly
Journal: Annals of Internal Medicine (2018)

On Being a Doctor7 August 2018A Beautiful DeathLyssa Weatherly, MDLyssa Weatherly, MDUniversity of Mississippi Medical Center, Jackson, Mississippi (L.W.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M18-0679 Audio Reading - “A Beautiful Death” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads "A Beautiful Death," by L. Weatherly. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail He was a 90-year-old nursing home resident admitted for health care–acquired pneumonia. When I called the nursing home to verify his medication list, the nurses said, “We need you to get him well so he can get back to us. It's not the same around here without him.”That's when I knew he was going to be special. Over the next 4 days of his hospitalization, we developed a sweet friendship. Every morning, I looked forward to seeing him. He would give me a hug and thank me for taking care of him. I became fond of his three daughters ... Author, Article, and Disclosure InformationAffiliations: University of Mississippi Medical Center, Jackson, Mississippi (L.W.)Corresponding Author: Lyssa Weatherly, MD, Department of Internal Medicine, Division of Geriatrics, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216; e-mail, [email protected]edu. PreviousarticleNextarticle Advertisement Audio Reading - “A Beautiful Death” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads "A Beautiful Death," by L. Weatherly. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ FiguresReferencesRelatedDetails Metrics 7 August 2018Volume 169, Issue 3Page: 195KeywordsBreathingGeriatricsHospitalizationsNursing homesOxygenPneumoniaRabiesVision ePublished: 7 August 2018 Issue Published: 7 August 2018 Copyright & PermissionsCopyright © 2018 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Abstract 15037: Short Term Colchicine Treatment Improves Endothelial Function in Patients With Cardiovascular Disease
Authors: Masato Kajikawa, Satoshi Kurisu, Tatsuya Maruhashi, Takayuki Hidaka, Yumiko Iwamoto, Shinji Kishimoto, Shogo Matsui, Haruki Hashimoto, Farina B Yusoff, Yasuki Kihara, Kensuke Noma, Ayumu Nakashima, Akiko Matsushita, Hirofumi Tomiyama, Shinichiro Ueda, Yukihito Higashi
Journal: Circulation (2017)

Introduction: Although substantial pathophysiological and epidemiological evidences suggest that inflammation may be the main mechanism of arteriosclerosis, treatments specifically targeting inflam...
Abstract 1108: M2-polarized macrophages increase invasiveness of EBV-associated nasopharyngeal carcinoma by inducing invadopodia formation
Authors: Wilson Wing Chung Tang, Chan Ping You, Gareth E. Jones, George Sai-Wah Tsao, Anna Chi Man Tsang
Journal: Cancer Research (2018)

Abstract Cancer metastasis is a major cause of mortality, accounting for approximately 90% of cancer related deaths. Emerging evidences suggest that tumour microenvironment plays an indispensable role in cancer metastasis. Recruitment of innate and adaptive immune cells to the tumour results in chronic inflammation which favours tumour growth and progression. Particularly, tumour associated macrophages (TAMs) are found to promote the initiation, growth, and metastasis in several types of cancers. Nasopharyngeal carcinoma (NPC) is one of the highly invasive and metastatic cancers and is closely associated with EBV infection. We postulate that TAMs may increase the invasiveness of NPC by enhancing the formation of invadopodia, which are membranous actin-rich protrusions with digestive ability of extra-cellular matrix. In this study, monocyte THP-1 cells were polarized to M2-macrophages, and co-cultured with nasopharyngeal cells in a contained chamber-insert. The stimulated nasopharyngeal cells then formed massive numbers of invadopodia and digested larger area of gelatin compared with the unstimulated counterparts. A cytokine antibody array was used to identify the upregulated cytokines in the co-culture medium of the M2-macrohphages and the NPC cells. Tumour necrosis factor alpha (TNFα) was revealed to be the responsible cytokine to induce the formation of invadopodia and digestion of gelatin. Besides, western blot analysis identified that several actin-associated proteins such as Src, Erk, and cortactin were involved in the TNFα-mediated invadopodia formation. We also found that the expression of latent membrane protein 1 (LMP1), an EBV protein that has similar structure to TNF receptor was elevated in NPC cells after co-culturing with the M2-polarized macrophages. Through transient transfection and stable expression of LMP1 in the NPC cells, LMP1 could also promote the formation of invadopodia through cdc42 activation. Taken together, these data indicate macrophages can promote the invasiveness of EBV-infected NPC cells by enhancing their ability in forming invadopodia through an activated TNFα signaling axis and LMP1 upregulation. Citation Format: Wilson Wing Chung Tang, Chan Ping You, Gareth E. Jones, George Sai-Wah Tsao, Anna Chi Man Tsang. M2-polarized macrophages increase invasiveness of EBV-associated nasopharyngeal carcinoma by inducing invadopodia formation [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 1108.
How infectious is the hepatitis B virus? Readings from the occult
Authors: Stephen Locarnini, Giovanni Raimondo
Journal: Gut (2018)

Occult HBV infection (OBI) is defined as the presence of the virus in the liver, with detectable or undetectable HBV DNA in the serum of individuals testing hepatitis B surface antigen (HBsAg) undetectable in blood, using the most sensitive commercial assays.1 OBI can be either seropositive (anti-HBc and/or anti-HBs positive) or seronegative (anti-HBc and anti-HBs negative), and when detectable, the amount of HBV DNA in the serum is usually very low (<200 IU/mL). OBI is a relatively new aspect of the natural history of HBV infection that has now been observed worldwide. Its prevalence varies according to the levels of HBV endemicity and viral genotype.2 The identification of OBI in asymptomatic blood donors and attempts by blood transfusion services worldwide to eliminate the ‘window period’ of HBV transmissibility, has prompted the introduction in many countries of nucleic acid testing (NAT) in order to detect HBV infection in blood donors.3 

The study by Candotti and colleagues in GUT 4 is the latest in a series of important studies from this group addressing the challenge of the infectivity of blood products from OBI donors. Their investigation of three repeat HBsAg-negative donors from Slovenia who remained undetected for HBV DNA by highly sensitive NAT and who transmitted HBV to nine recipients by blood components, has allowed a revised estimation of the minimal HBV infectious dose from the …
Abstract 4320: p53 binding sites in normal and cancer cells are characterized by distinct chromatin context
Authors: Feng Cui
Journal: Cancer Research (2018)

Abstract The tumor suppressor protein p53 interacts with DNA in a sequence-dependent manner. Thousands of p53 binding sites have been mapped genome-wide in normal and cancer cells. However, the way p53 selectively binds its cognate sites in different types of cells is not fully understood. Here, we performed a comprehensive analysis of 25 published p53 cistromes and identified 3,551 and 6,039 "high-confidence" binding sites in normal and cancer cells, respectively. Our analysis revealed two distinct epigenetic features underlying p53-DNA interactions in vivo. First, p53 binding sites are associated with transcriptionally active histone marks (H3K4me3 and H3K36me3) in normal-cell chromatin, but with repressive histone marks (H3K27me3) in cancer-cell chromatin. Second, p53 binding sites in cancer cells are characterized by a lower level of DNA methylation than their counterparts in normal cells, probably related to global hypomethylation in cancers. Intriguingly, regardless of the cell type, p53 sites are highly enriched in the endogenous retroviral elements of the ERV1 family, highlighting the importance of this repeat family in shaping the transcriptional network of p53. Moreover, the p53 sites exhibit an unusual combination of chromatin patterns: high nucleosome occupancy and, at the same time, high sensitivity to DNase I. Our results suggest that p53 can access its target sites in a chromatin environment that is nonpermissive to most DNA-binding transcription factors, which may allow p53 to act as a pioneer transcription factor in the context of chromatin. Citation Format: Feng Cui. p53 binding sites in normal and cancer cells are characterized by distinct chromatin context [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 4320.
Analysis of the Global Burden of Disease study highlights the global, regional, and national trends of chronic kidney disease epidemiology from 1990 to 2016
Authors: Yan Xie, Benjamin Bowe, Ali H. Mokdad, Hong Xian, Yan Yan, Tingting Li, Geetha Maddukuri, Cheng-You Tsai, Tasheia Floyd, Ziyad Al-Aly
Journal: Kidney International (2018)

The last quarter century witnessed significant population growth, aging, and major changes in epidemiologic trends, which may have shaped the state of chronic kidney disease (CKD) epidemiology. Here, we used the Global Burden of Disease study data and methodologies to describe the change in burden of CKD from 1990 to 2016 involving incidence, prevalence, death, and disability-adjusted-life-years (DALYs). Globally, the incidence of CKD increased by 89% to 21,328,972 (uncertainty interval 19,100,079– 23,599,380), prevalence increased by 87% to 275,929,799 (uncertainty interval 252,442,316–300,414,224), death due to CKD increased by 98% to 1,186,561 (uncertainty interval 1,150,743–1,236,564), and DALYs increased by 62% to 35,032,384 (uncertainty interval 32,622,073–37,954,350). Measures of burden varied substantially by level of development and geography. Decomposition analyses showed that the increase in CKD DALYs was driven by population growth and aging. Globally and in most Global Burden of Disease study regions, age-standardized DALY rates decreased, except in High-income North America, Central Latin America, Oceania, Southern Sub-Saharan Africa, and Central Asia, where the increased burden of CKD due to diabetes and to a lesser extent CKD due to hypertension and other causes outpaced burden expected by demographic expansion. More of the CKD burden (63%) was in low and lower-middle-income countries. There was an inverse relationship between age-standardized CKD DALY rate and health care access and quality of care. Frontier analyses showed significant opportunities for improvement at all levels of the development spectrum. Thus, the global toll of CKD is significant, rising, and unevenly distributed; it is primarily driven by demographic expansion and in some regions a significant tide of diabetes. Opportunities exist to reduce CKD burden at all levels of development.Graphical abstract
Abstract 12523: Crucial Role of SmgGDS in the Inhibitory Effects of Statins on Cardiac Hypertrophy and Fibrosis in Mice
Authors: ShunKudo, KimioSatoh, ShinichiTanaka, TatsuroMinami, NobuhiroKikuchi, JunichiOmura, KotaSuzuki, ShoheiIkeda, HiroakiShimokawa
Journal: Circulation (2014)

Introduction: We have previously demonstrated that small GTP-binding protein dissociation stimulator (SmgGDS) plays a crucial role in the pleiotropic effects of HMG-CoA reductase inhibitors (statins) in mice and humans. In the present study, we tested our hypothesis that SmgGDS plays a crucial role in the inhibitory effects of statins on the development of cardiac hypertrophy and fibrosis. Methods & Results: We administered angiotensin II (AngII, 2 mg/kg/day, 2 weeks) to SmgGDS-deficient (SmgGDS+/-) mice and littermate controls (SmgGDS+/+), which were orally treated with either statins (atorvastatin 10 mg/kg/day or pravastatin 50 mg/kg/day, n=10 each group) or vehicle. AngII equally elevated systolic blood pressure and promoted cardiac hypertrophy and fibrosis in SmgGDS+/+ and SmgGDS+/-. Both statins significantly reduced LV wall thickness, cardiac myocyte cross-sectional area, and fibrotic area in AngII-infused SmgGDS+/+ mice (all P<0.01). In contrast, the inhibitory effects of statins were absent in Ang...
Abstract 4223: Personal history of non-melanoma skin cancer and the risk of death from invasive cutaneous melanoma in men
Authors: Fengju Song, Jiali Han
Journal: Cancer Research (2018)

Abstract BACKGROUND: Previous studies have found an increased risk of invasive cutaneous melanoma (CM) among those with a history of non-melanoma skin cancer (NMSC). OBJECTIVE: The aim of this study is to evaluate the risk of CM death after NMSC. METHODS: The study was based on the Health Professionals Follow-up Study (HPFS). Cox proportional hazards model was used to examine the hazard ratio (HR) of CM death associated with personal history of NMSC, among the entire study population (primary analysis) and invasive CM cases (secondary analysis) respectively. RESULTS: We documented a total of 908 invasive CM cases over a total of 0.7 million person-years of follow-up. Among all participants, the risk of developing either lethal or non-lethal invasive CM increased for those with NMSC history. The risk of melanoma death based on NMSC history was non-significantly increased, with HR (95% CI) of 1.53 (0.95 - 2.46). In the case-only analysis, those with NMSC history had a significantly lower risk of melanoma death compared with those with no such history, HR=0.60 (0.35-0.94). LIMITATIONS: Because HPFS consists exclusively of male health professionals, the results of this study may not be extended to the entire population. CONCLUSION: Personal history of NMSC is associated with a decreased risk of melanoma-specific death among male patients with invasive CM. KEYWORDS: invasive cutaneous melanoma; non-melanoma skin cancer; mortality; cohort study Citation Format: Fengju Song, Jiali Han. Personal history of non-melanoma skin cancer and the risk of death from invasive cutaneous melanoma in men [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 4223.
Abstract 18668: The Clinical Impact of Post Procedural Peripheral Vascular Flow Reserve on Wound Healing Following Infrapopliteal Intervention in Patients with Critical Limb Ischemia
Authors: Masashi Fukunaga, Kenichi Fujii, Daizo Kawasaki, Kojiro Miki, Hiroto Tamaru, Takahiro Imanaka, Masahiko Shibuya, Motomaru Masutani, Mitsumasa Ohyanagi, Tohru Masuyama
Journal: Circulation (2012)

Background: The impaired coronary blood flow reserve after coronary intervention has been related to microvascular impairment leading to increased morbidity and mortality. We evaluated whether this finding can be generalised to patients with critical limb ischemia (CLI) undergoing endovascular treatment (EVT) for infrapopliteal arterial disease. Methods: Eleven limbs (Rutherford 4 and 5) from 10 patients of CLI with angiographic evidence of infrapopliteal arterial disease underwent measurement of peripheral vascular flow reserve (VFR). A pressure/temperature sensor-tipped guidewire was positioned in the proximal popliteal artery at 5cm distal to the guiding catheter. With 3 mL of saline at room temperature used as an indicator, by hand-injection, thermodilution curves in the infrapopliteal artery were obtained both at baseline and at intra-arterial papaverine-induced maximum hyperemia (30mg). VFR was calculated from the ratio of inverse mean transit times at hyperemia and baseline. The VFR measurements were performed both before and after EVTs. Wound healing was defined as the progressive reduction in wound surface area from the beginning of the study. Results: The procedure success rate was 100%, and VFR was measured in all patients without any complication. Wound healing was achieved in 6 limbs after EVT (healing group) and not achieved in 5 (non-healing group). The average pre- and post-VFR was 4.1±2.6 and 5.8±4.2 respectively. There was no significant difference in pre-VFR values between healing and non-healing group (4.3±3.2 versus 3.7±2.0). However, post-VFR values was significantly higher in the healing group than in the non-healing group (6.3±4.1 versus 3.3±1.8, p&lt;0.05). VFR values in non-healing group decreased or remained unchanged in all patients mainly due to increase in resting blood flow. Conclusions: VFR values immediately after EVT for infrapopliteal arterial disease remained unchanged in patients with poor wound healing mainly due to increase in resting blood flow. This finding suggests that a therapeutic effect can not be obtained if the arteriolar bed is damaged after EVT. This easily assessable VFR is useful in clinical risk stratification for patients with CLI immediately after EVT in the catheterization laboratory.
Abstract 137: Deficiency of Senescence Marker Protein 30 Exacerbates Doxorubicin-Induced Cardiac Dysfunction in Mice
Authors: MakikoMiyata, SatoshiSuzuki, TomofumiMisaka, Shu-ichiSaitoh, YasuchikaTakeishi
Journal: Circulation Research (2012)

Background: Senescence marker protein 30 (SMP30) was originally identified as an aging marker protein in the rat liver. The expression of SMP30 decreases with aging androgen-independently. Doxorubicin (DOX) has been used as a potent anticancer agent, but serious cardiotoxicity precludes its use in a wide range of patients. SMP30 may have anti-oxidative and anti-apoptosis functions in several organs, but functional role of SMP30 has not been rigorously examined in the heart. We hypothesized that SMP30 has cardio-protective function by anti-aging and anti-oxidant effects on DOX-induced cardiac dysfunction. Method and Results: Male SMP30 knockout (SMP30KO) and age-matched littermate male wild-type (WT) mice at 12-14 weeks of age were given intraperitoneal injections of DOX (20 mg/kg) or saline. Seven days after DOX injection, echocardiography revealed that left ventricular ejection fraction in DOX-treated SMP30KO mice was more severely reduced than in DOX-treated WT mice (40.9 ± 3.1% vs. 46.9 ± 4.9%, P<0.01)...