tbuckley/cabot-search huggingface dataset:
Abstract 3055: A model of CSC converted from iPSC in the conditioned medium of HCC paving the way to establish HCC CSC
Authors: Said M Afify, Anna Sanchez Calle, Kazuki Kumon, Hend M Nawara, Apriliana C Khairani, Hafizah Mahmud, Aung Ko Ko Oo, Du Juan, Maram H Zahara, Akimasa Seno, Tomonari Kasai, Yoshiaki Iwasaki, Masaharu Seno
Journal: Cancer Research (2018)

Abstract Hepatocellular carcinoma (HCC) represents the major histological subtype, accounting for 70%–85% of cases of primary liver cancer. Liver CSCs sustain their self-renewal remains largely unknown. The self-renewal and pluripotency of liver CSC are maintained by several signaling cascades. However, the mechanism of regulating these signaling is unknown. In this study, we tried to convert mouse iPSCs into CSCs with the conditioned medium (CM) from human HCC cell line Huh7 cells without any genetic manipulation aiming at establishing liver CSCs. First of all, CM was collected from confluent culture of Huh7 cells. Then, mouse iPSCs cells without MEF feeder cells were cultured in the presence of 50% CM for 4 weeks. The medium was changed every day with fresh medium containing 50% of CM. Mouse iPSCs cultured in the complete medium with LIF were used as a control.The survived cells (5x105 cells) were suspended in HBSS and injected into the liver of BALB/c nude mice. After 25 days malignant tumor was formed in the liver while benign teratoma was formed by the injection of iPSCs. Tumors were then excised and partly fixed in 10% neutral formalin buffer solution for HE staining and immunohistochemical analysis. The rest of tumors were subjected to rt-qPCR anaylsis and primary culture. Immunohistochemical analysis with GFP antibody showed that malignant tumor sustained GFP expression while teratoma from miPSCs did not. Immunocytochemistry of the primary cells from malignant tumor showed high expression of both glypican-3 (GPC3) and cytokeratin19 (CK19) when compared to that in miPSCs. Expression of stem cell markers (Nanog, Oct3/4, Sox2, Klf4) and CSC markers (CD44, EpCAM) were also confirmed by rt-qPCR in both the CSCs converted from iPSCs (miPS-Huh7cm cells) and the primary culture cells. These results indicate that the primary cells from the malignant tumor are rich in CSCs with high expression of GPC3 and CK19, which paves the way to establish a model of HCC CSC. This model should be very important and useful to assess the significant molecular mechanisms necessary to maintain HCC CSC, which will help develop effective therapy of liver cancer. Citation Format: Said M Afify, Anna Sanchez Calle, Kazuki Kumon, Hend M Nawara, Apriliana C Khairani, Hafizah Mahmud, Aung Ko Ko Oo, Du Juan, Maram H Zahara, Akimasa Seno, Tomonari Kasai, Yoshiaki Iwasaki, Masaharu Seno. A model of CSC converted from iPSC in the conditioned medium of HCC paving the way to establish HCC CSC [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 3055.
Abstract 13546: Persistent Epicardial Adipose Tissue Accumulation Contributes Coronary Plaque Vulnerability and Future Acute Coronary Syndrome in Non-obese, Coronary Artery Disease Patients
Authors: KokiNakanishi, ShotaFukuda, AtsushiTanaka, KenichiroOtsuka, HajimeYamashita, HaruyukiTaguchi, JunichiYoshikawa, KeneiShimada, MinoruYoshiyama
Journal: Circulation (2014)

Introduction: Epicardial adipose tissue (EAT) is recognized as a novel risk factor for coronary artery disease (CAD) and its contribution is thought to be stronger in non-obese patients than in obese patients. However, the impact of changes in EAT accumulation on CAD prognosis remains unclear. This study aimed to investigate whether an increase of EAT volume predicts future acute coronary syndrome (ACS) events in non-obese CAD patients. Methods: This study consisted of 517 non-obese CAD patients who underwent serial multidetector computed tomography (MDCT) examinations to evaluate coronary atherosclerosis progression. All patients received comprehensive management to reduce CAD risk factors after the first MDCT examination. MDCT was repeated at 6-24 months and patients were followed-up for more than 1 year or until ACS events occurred. Results: Of 517 patients, EAT volume increased >10ml from first to second MDCT examination in 159 (31%) patients, decreased >10 ml in 91 (18%). In remaining 267 (51%) patie...
Abstract 4743: Inhibition of the <i>Hif1a</i>-mediated checkpoint refuels NK activation in cancer
Authors: Jing Ni, Lea Bühler, Ana Stojanovic, Annette Arnold, Veronika Sexl, Adelheid Cerwenka
Journal: Cancer Research (2018)

Abstract Solid tumors remain a major challenge for immunotherapy of cancer due to their immunosuppressive microenvironment. Hypoxia is a common feature of solid tumors and might affect immune cell activation within the tumor tissue. Upon hypoxia the transcription factor Hypoxia inducible factor 1a (HIF-1α) that affects many cellular processes including cell proliferation, survival and effector function becomes induced. Its impact on innate immune cells such as Natural Killer (NK) cells, however, is still incompletely understood. Natural Killer (NK) cells are considered as highly potent effector cells against tumors. Within the tumor tissue, however, NK effector function is often impaired. Our microarray analyses of tumor-infiltrated NK cells revealed upregulated levels of Hif1a. To determine the role of the HIF-1α in NK cell function, we generated the mouse strain Hif1aΔ/ΔNcr1-iCreTg in which HIF-1α is deficient in the NKp46+ lineage. Hif1a deficient NK cells showed greatly enhanced anti-tumor activity compared to wild-type NK cells, leading to a pronounced reduction of tumor growth. Tumor-infiltrated Hif1a deficient NK cells expressed lower levels of checkpoint molecules and show enhanced responses to tumor cells indicating a less exhausted phenotype. Hif1a deficient NK cells preferentially utilize oxidative phosphorylation (OXPHOS) than glycolysis to fuel their energy resulting in enhanced IFN-γ production in the hypoxic environment. In addition, using HIF-1α inhibitors we were able to greatly enhance human NK cell anti-tumor activity. Accordingly, our data reveal HIF-1α as a negative metabolic checkpoint for NK cells. Moreover, inhibition of HIF-1α holds high promise to refuel NK cell activation in cancer with a high potential for improving current strategies of NK cell-based cancer immunotherapy. Citation Format: Jing Ni, Lea Bühler, Ana Stojanovic, Annette Arnold, Veronika Sexl, Adelheid Cerwenka. Inhibition of the Hif1a-mediated checkpoint refuels NK activation in cancer [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 4743.
Pressure-Diameter Relation of the Human Aorta
Authors: ChristodoulosStefanadis, CostasStratos, CharalambosVlachopoulos, SteliosMarakas, HarisiosBoudoulas, IoannisKallikazaros, EleftheriosTsiamis, KonstantinosToutouzas, LambrosSioros, PavlosToutouzas
Journal: Circulation (1995)

Background Pressure-diameter relation of the aorta provides important information about the elastic properties of the vessel. However, owing to methodological limitations, data regarding this relation are limited in conscious humans. In the present study, we assessed a new method for the direct estimation of the elastic properties of the aorta in conscious humans by simultaneous acquisition of instantaneous aortic pressure and diameter. Methods and Results With this method, instantaneous diameter of the thoracic aorta was acquired by a newly designed intravascular catheter developed in our institution that incorporates an ultrasonic displacement meter at its distal end. Instantaneous aortic pressure was acquired simultaneously at the same aortic level with a catheter-tip micromanometer. Aortic pressure-diameter loops were derived from computer analysis of data. After in vitro and animal testing, elastic properties of the aorta were investigated in coronary artery disease (CAD) patients (n=15) and compared...
Risk of Knee Osteoarthritis With Obesity, Sarcopenic Obesity, and Sarcopenia
Authors: Devyani Misra, Roger A. Fielding, David T. Felson, Jingbo Niu, Carrie Brown, Michael Nevitt, Cora E. Lewis, James Torner, Tuhina Neogi
Journal: Arthritis & Rheumatology (2018)

Obesity, defined by anthropometric measures, is a well-known risk factor for knee osteoarthritis (OA), but there is a relative paucity of data regarding the association of body composition (fat and muscle mass) with risk of knee OA. We undertook this study to examine the longitudinal association of body composition categories based on fat and muscle mass with risk of incident knee OA.We included participants from the Multicenter Osteoarthritis Study, a longitudinal cohort of individuals with or at risk of knee OA. Based on body composition (i.e., fat and muscle mass) from whole-body dual x-ray absorptiometry, subjects were categorized as obese nonsarcopenic (obese), sarcopenic obese, sarcopenic nonobese (sarcopenic), or nonsarcopenic nonobese (the referent category). We examined the relationship of baseline body composition categories with the risk of incident radiographic OA at 60 months using binomial regression with robust variance estimation, adjusting for potential confounders.Among 1,653 subjects without radiographic knee OA at baseline, significantly increased risk of incident radiographic knee OA was found among obese women (relative risk [RR] 2.29 [95% confidence interval {95% CI} 1.64-3.20]), obese men (RR 1.73 [95% CI 1.08-2.78]), and sarcopenic obese women (RR 2.09 [95% CI 1.17-3.73]), but not among sarcopenic obese men (RR 1.74 [95% CI 0.68-4.46]). Sarcopenia was not associated with risk of knee OA (for women, RR 0.96 [95% CI 0.62-1.49]; for men, RR 0.66 [95% CI 0.34-1.30]).In this large longitudinal cohort, we found body composition-based obesity and sarcopenic obesity, but not sarcopenia, to be associated with risk of knee OA. Weight loss strategies for knee OA should focus on obesity and sarcopenic obesity.
Abstract 1572: The value of p16 or HPV as predictive marker of anti-EGFR treatment in recurrent/metastatic HNSCC
Authors: Joo Han Lim, Soon-Sun Hong, Jin-Chul Kim, Moon Hee Lee, Jinhyun Cho
Journal: Cancer Research (2018)

Abstract Introduction: The anti-epidermal growth factor receptor (EGFR) agent was approved and has been a mainstay of treatment of recurrent/metastatic head and neck squamous cell cancers (HNSCC). However, it is unclear whether human papilloma virus (HPV) modulates the response to targeting the EGFR. Some subset analysis of the randomized phase III study is confusing and recent The Cancer Genome Atlas data showed that EGFR gene is rarely abnormal in HPV-positive HNSCC tumors while it is frequently altered in HPV-negative HNSCC tumors. The purpose of our meta-analysis is to evaluate the effects of anti-EGFR agents regarding HPV status. Materials and Methods: We conducted a pooled analysis to evaluate the association of p16 expression status with outcomes in patients with recurrent/metastatic HNSCC receiving palliative anti-EGFR treatment with or without chemotherapy. A literature search of PubMed, EMBASE, and meeting abstracts of the American Society of Clinical Oncology and European Society of Medical Oncology through December 2017 was conducted. Results: A total of seven trials met the selection criteria. The total number of patients was 700 (554 with the HPV-negative group and 146 with the HPV-positive group). Anti-EGFR treatment was associated with higher response rate in p16-negative patients compared with in p16-positive patients (OR 2.18; 95% CI, 1.18-3.99, p=0.01). Conclusion: A meta-analysis of trials with anti-EGFR agents in p16-negative RMHNSCC patients versus in p16-positive recurrent/metastatic HNSCC patients yielded that p16 status could be a predictive biomarker for anti-EGFR treatment in recurrent/metastatic HNSCC. Prospective study is warranted to determine the value of p16 or HPV as a predictive marker of anti-EGFR treatment in recurrent/metastatic HNSCC. Citation Format: Joo Han Lim, Soon-Sun Hong, Jin-Chul Kim, Moon Hee Lee, Jinhyun Cho. The value of p16 or HPV as predictive marker of anti-EGFR treatment in recurrent/metastatic HNSCC [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 1572.
Abstract 2438: Reducing plate edge effect by controlling cell handling conditions for <i>in vitro</i> tumor hypoxia assays
Authors: Alicia Henn, Shannon Darou, Randy Yerden
Journal: Cancer Research (2018)

Abstract To reduce the impact of high variability in the edge wells of 96-well plates, the "edge effect", researchers often fill edge wells with buffer to try to insulate the rest of the plate. This removes over a third of the wells from the assay, adding cost, handling time, and space problems to in vitro assays. This is of particular concern for researchers working with cells in low oxygen, as handling more plates increases the time that cells are out of optimum conditions, risking HIF-1a modulation. For this project, we tested the idea that controlling the entire cell handling space to conditions that match the incubator, including the working space floor temperature and gas levels, may help reduce the edge effect seen in 96-well plates. The null hypothesis was that cell handling conditions would make no difference in the variability of cell density in 96-well plates loaded in traditional room air conditions compared to plates loaded in controlled conditions matching the incubator. To address cell loading specifically, A549 cells were harvested from cell culture flasks in traditional cell handling conditions (room temp, 20% O2, 0% CO2), then split. Half of the cells were transferred to an Xvivo System for controlled cell handling conditions. The cells in both conditions were transferred to media pre-conditioned to hypoxic incubator conditions and then plated in 96-well plates. Temperature mapping was performed with 16 thermal probes simultaneously in replicate plates loaded with medium only. The cells were incubated for 24 hours, then stained for cell density, and read on a plate reader. Cell viability was greater than 90% (n=4 plates/condition/trial x 4 trials). We found that edge well temperatures were more stable in plates handled in unbroken optimal conditions and edge effect on cell density was greatly reduced. In room temperature conditions, columns 1 and 12 cooled most rapidly. We concluded that full-time control of environmental conditions allowed for use of the whole plate with reduced edge effect. This helps reduce cost, time, number of plates and the risks to cells during cell handling. Citation Format: Alicia Henn, Shannon Darou, Randy Yerden. Reducing plate edge effect by controlling cell handling conditions for in vitro tumor hypoxia assays [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 2438.
Global Burden of Cardiovascular Diseases
Authors: SalimYusuf, SrinathReddy, StephanieÔunpuu, SoniaAnand
Journal: Circulation (2001)

This two-part article provides an overview of the global burden of atherothrombotic cardiovascular disease. Part I initially discusses the epidemiological transition which has resulted in a decrease in deaths in childhood due to infections, with a concomitant increase in cardiovascular and other chronic diseases; and then provides estimates of the burden of cardiovascular (CV) diseases with specific focus on the developing countries. Next, we summarize key information on risk factors for cardiovascular disease (CVD) and indicate that their importance may have been underestimated. Then, we describe overarching factors influencing variations in CVD by ethnicity and region and the influence of urbanization. Part II of this article describes the burden of CV disease by specific region or ethnic group, the risk factors of importance, and possible strategies for prevention.
Real-World Evidence and Real-World Data for Evaluating Drug Safety and Effectiveness
Authors: Jacqueline Corrigan-Curay, Leonard Sacks, Janet Woodcock
Journal: JAMA (2018)

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Increased Plasma P-Selectin and Decreased Thrombomodulin in Pulmonary Arterial Hypertension Were Improved by Continuous Prostacyclin Therapy
Authors: FumioSakamaki, ShingoKyotani, NoritoshiNagaya, NagatoSato, HideoOya, ToruSatoh, NorifumiNakanishi
Journal: Circulation (2000)

Background—Thrombosis in situ related to endothelial cell injury may contribute to the development of pulmonary hypertension (PH). P-selectin, a leukocyte adhesion receptor present in endothelial cells and platelets, reflects endothelial injury and platelet activation, and thrombomodulin (TM), a receptor for thrombin and a major anticoagulant proteoglycan on the endothelial membrane, reflects the anticoagulant activity of the endothelium. Methods and Results—To assess abnormal coagulation due to endothelial injury in patients with PH, plasma levels of soluble P-selectin and TM were measured in 32 patients with primary PH (PPH), 25 with secondary pulmonary arterial hypertension (sPAH), 31 with pulmonary venous hypertension (PVH), and 17 healthy subjects (Control). These measurements were repeated after continuous infusion of prostacyclin in 15 patients with PPH and 3 with sPAH. P-selectin levels in both the sPAH and PPH groups were significantly higher than those in the Control and PVH groups (P<0.05). Pla...
Abstract 635: Characterizing PD-L1 expression in tumor-associated cells and CTC using IncellDx and Celsee molecular diagnostic technologies
Authors: Fariba Fazeli, Vishal Premdev Sharma, William Chiro Chow, Amanda Chargin, Priya Gogoi, Kalyan Handique, Bruce Patterson
Journal: Cancer Research (2018)

Abstract Detection of PD-L1 expression in NSCLC cancer patients is increasingly becoming a widely used molecular diagnostic tool. Evidence also suggests that PD-L1 can be induced with radiotherapy and may be an immune escape mechanism in cancer. Current methods analyze PD-L1 expression in either solid tumor biopsies or circulating tumor cells (CTC), independent of each other. In order to design a comprehensive PD-L1 treatment regime, it is imperative to look at the PD-L1 expression in cancer cells of the tumor as well as in CTCs. In this study we present a comprehensive profiling of PD-L1 expression in solid tumor biopsy and CTC of 10 lung cancer patients. We further extend the study by evaluating the co-relation of the PD-L1 expression with other immune cell infiltration markers in the lung biopsy samples. There is no single technology that can provide a comprehensive profiling of PD-L1 expression in lung biopsies as well as the CTCs isolated from the peripheral blood. Using two very different and unique molecular diagnostic technologies, IncellDx OncoTect iO Single Cell Quantitative PD-L1 assay and automated CTC analysis Celsee C-PREP GENESIS, we present the first report discussing the PD-L1 expression in tumor cells of the solid and liquid biopsies and its correlation with DNA content and infiltrating immune cell markers. Nine out of the ten patient samples evaluated showed strong correlation between DNA content and PD-L1 expression in tumor-associated cells and CTC. One aneuploid patient sample showed very low expression of PD-L1 in tumor-associated cancer cells; however, it still showed a positive staining for PD-L1 in CTC. Obtaining a comprehensive PD-L1 expression and associated immune cell marker profile in solid tumor biopsy and circulating tumor cells may be needed to design a more effective and lasting immunotherapy to treat NSCLC lung cancer patients. The results discussed in this study will strongly impact the current understanding and implementation of the molecular diagnostics tools to evaluate cancer patients in order to define a robust therapeutic regimen. Citation Format: Fariba Fazeli, Vishal Premdev Sharma, William Chiro Chow, Amanda Chargin, Priya Gogoi, Kalyan Handique, Bruce Patterson. Characterizing PD-L1 expression in tumor-associated cells and CTC using IncellDx and Celsee molecular diagnostic technologies [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 635.
Abstract 4202: Resection of primary osteosarcoma tumors terminates self-seeding, increasing lung metastasis
Authors: Ryan D. Roberts, Amanda J. Saraf, Helene Le Pommellet, Randall Evans, Amy C. Gross
Journal: Cancer Research (2018)

Abstract Like many solid tumors, osteosarcoma (OS) kills patients through metastatic spread. In the case of OS, metastasis occurs almost exclusively to lung. Metastases most often arise after both resection of a primary tumor and completion of chemotherapy. In seeking to understand this long-appreciated pattern of spread, we sought to explore whether the presence of a primary tumor protects mice from developing OS lung metastasis through the process of self-seeding, and whether resection then faciliates metastatic lung colonization. Our data show that resection of a primary orthotopic tumor triggers the spread of OS tumor cells into the lung. Mice bearing a primary tumor have fewer labeled tumor cells recovered in the lung after IV inoculation. Many labeled cells can be recovered in the primary tumor. Supernatants from OS cell cultures drive OS cell chemotaxis with greater potency than serum. Several specific soluble factors produced by OS cells also drive chemotaxis of those same cells. Disruption of these signals may prevent self-seeding. Manipulation of this system may be used to remove OS cells from circulation. Citation Format: Ryan D. Roberts, Amanda J. Saraf, Helene Le Pommellet, Randall Evans, Amy C. Gross. Resection of primary osteosarcoma tumors terminates self-seeding, increasing lung metastasis [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 4202.