tbuckley/cabot-search huggingface dataset:
Abstract 841: Protection of normal tissues by DIM (3,3'-Diindolylmethane) during radiation therapy
Authors: Renxiang Chen, Lijun Li, Loretta Y. Lin, Albert J. Fornace, Heng-Hong Li
Journal: Cancer Research (2018)

Abstract 96 Normal 0 false false false EN-US ZH-CN X-NONE /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:12.0pt; font-family:"Calibri",sans-serif; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-fareast-language:EN-US;} Despite advances in precision targeting of tumors by radiation therapy, local recurrence is still a serious problem due to the inability to sometimes deliver a sufficiently high dose of radiation to achieve tumor control without unacceptable late normal tissue and organ toxicity. DIM (3,3'-diindolylmethane), a commercially available dietary supplement, has long been studied as a cancer prevention and anti-tumor agent. We are investigating DIM's differential effects after radiation in tumor and normal tissues using a mouse model approach. We monitored tumor growth after localized radiation in a tumor engraftment model of MDA-MB-231 human breast carcinoma cells using immunocompromised NSG mice. The fractionated regimen consists of a total dose of 24 Gy in four fractions (6 Gy per fraction given every other day) with administration of DIM or vehicle at one hour prior to each fraction. DIM showed no significant effect on the growth of irradiated tumors, i.e. DIM did not affect the treatment efficacy of radiation on tumors. On the other hand, we are investigating the molecular mechanism of DIM's radio-protective effects in normal tissues. Our transcriptomic data indicate that DIM treatment increases expression of some stress-responsive genes without causing DNA damage. Results to date indicate that DIM might delay radiation-induced cell cycle arrest and apoptosis. The ultimate goal is to develop DIM as a clinical radioprotector in order to improve the therapeutic index by allowing higher doses of radiation to improve local tumor control by reducing late dose-limiting normal tissue toxicity by radiation.&amp;lt;!–EndFragment–&amp;gt; Citation Format: Renxiang Chen, Lijun Li, Loretta Y. Lin, Albert J. Fornace, Heng-Hong Li. Protection of normal tissues by DIM (3,3'-Diindolylmethane) during radiation therapy [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 841.
Abstract 247: Dose-dependent Role of Inwardly Rectifying Potassium Current on Cardiac Automaticity of Human Embryonic Stem Cell-derived Cardiomyocytes
Authors: JidongFu, AdrienneDennis
Journal: Circulation Research (2015)

The inwardly rectifying potassium current (IK1), encode by Kir2 family, is responsible for maintaining the negative resting potential, and contributes to phase 3 repolarization of the cardiac action potential. IK1 was generally thought to suppress cardiac automaticity, while the suppression of IK1 in adult ventricular cardiomyocytes (CMs) could engineer bio-artificial pacemaker-like cells to spontaneously fire action potential. Our studies also showed that overexpressed the gene of Kir2.1 could facilitate the electrophysiological maturing of mouse and human embryonic stem cell-differentiated CMs (ESC-CMs), which have the high degree of automaticity with nearly 50% of cells that can spontaneously fire action potential. In this study, we extensively analyzed the electrophysiology of mouse and human ESC-CMs, and found that the maximum diastolic potential in spontaneously firing ESC-CMs, -72.1±1.3 mV in atrial cells and -75.0±2.1 mV in ventricular cells, were significantly more hyperpolarized than that in qui...
Abstract 20401: Cardiorenal Risks of Celecoxib, Naproxen or Ibuprofen in Arthritis Patients : A Sub-Anaylsis From the PRECISION Trial
Authors: Slayman Obeid, Peter Libby, M. Elaine Husni, Marc A Pfeffer, Lisa M Wisniewski, Katherine E Wolski, Qiuqing Wang, Steven E Nissen, Thomas F Lüscher
Journal: Circulation (2017)

When it comes to long-term cardiovascular(CV) safety in patients with arthritis, moderate doses of celecoxib are commonly considered as safe as Tx doses of naproxen and ibuprofen. Yet concerns rema...
Abstract 207: Cytotoxic Effect of Palmitate is Caused by a Change in Membrane Fatty Acid Composition and ER Stress
Authors: Tsunehisa Yamamoto, Jin Endo, Ken Shinmura, Motoaki Sano, Keiichi Fukuda
Journal: Circulation Research (2017)

Backgrounds: Saturated fat in diet is known to be detrimental to heart health, but its impact on the cardiac muscle remains unknown. We investigated the impact of saturated fatty acid overload on membrane fatty acid composition and survival in neonatal rat cardiomyocytes. Methods and Results: (1) In neonatal rat cardiomyocytes, palmitate, a saturated fatty acid (16:0), induced cell death. (2) Palmitate-induced cell death was rescued by either co-administration of oleate (monounsaturated fatty acid; 18:1), EPA (polyunsaturated fatty acids; 20:5), or DHA (polyunsaturated fatty acids; 22:6). Among them, oleate was most effective. (3) Palmitate-overload did not alter the total amount of fatty acids in membrane phospholipid but changed the composition of fatty acids; it increased palmitate and decreased oleate. (4) Palmitate-induced cell death was associated with activation of ER stress sensors, referred as PERK, IRE1. Co-administration of oleate abolished ER stress. (5) Palmitate-induced cell death was significantly inhibited by APY29, an inhibitor of IRE1 phosphorylation pathway, but not by GSK260414 (PERK inhibitor) and by 4μ8c (IRE1-XBP1 inhibitor). Conclusions: Palmitate-induced cell death in cardiomyocytes is associated with a change in membrane fatty acid composition and activation of ER stress. Lipotoxic effect of palmitate is attenuated by co-administration of oleate and an inhibitor of IRE1 phosphorylation pathway.
Abstract 2471: Clinical significance of noncoding circHIPK3 RNA in human hepatocellular carcinoma
Authors: Gyeonghwa Kim, Jun Sik Yoon, Se Young Jang, Soo Young Park, Won Young Tak, Young-Oh Kweon, Keun Hur
Journal: Cancer Research (2018)

Abstract Background and Aim: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, with poor prognosis and high risk of recurrence. Previous studies have shown that various microRNAs (miRNAs) are frequently dysregulated in HCC, which contributes to cancer development and progression. Nonetheless, the regulation mechanism of miRNAs is still unclear. Circular noncoding RNA (circRNA) is highly conserved and stable covalently closed RNA circles with gene-regulatory potential. Recently, one abundant circRNA from HIPK3 gene, circHIPK3, has been identified, and its function has been elucidated as multiple miRNAs sponge. Thus, we aimed to investigate the clinical relevance of circHIPK3 in HCC. Materials and Methods: We analyzed clinical specimens from 152 pairs of HCC and corresponding normal liver (NL) tissues. Total RNAs were isolated from clinical tissues using Qiagen kit. CircHIPK3 expression levels were determined by quantitative real-time PCR (qRT-PCR), and its expression was normalized with GAPDH. In addition, we analyzed the correlation between circHIPK3 expression and various clinicopathologic features of HCC patients. Results: CircHIPK3 expression was significantly downregulated in HCC tissues compared to corresponding NL tissues (P=0.036). In HCC patients, circHIPK3 expression was strongly suppressed in more advanced tumors (P&amp;lt;0.001). Further correlation analysis showed that circHIPK3 expression was significantly associated with T stage (P&amp;lt;0.001), TNM stage (P&amp;lt;0.001), BCLC stage (P&amp;lt;0.001), and alpha-fetoprotein (AFP) expression (P=0.033). Conclusions: We have determined clinical significances of circHIPK3 expression in HCC, which may provide clinical evidence for the potential of circHIPK3 as novel markers for diagnosis and predicting prognosis in HCC patients. Citation Format: Gyeonghwa Kim, Jun Sik Yoon, Se Young Jang, Soo Young Park, Won Young Tak, Young-Oh Kweon, Keun Hur. Clinical significance of noncoding circHIPK3 RNA in human hepatocellular carcinoma [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 2471.
Abstract 5219: Effect of extracellular vesicles from gastric cancer cells on the morphologic and genetic changes of peritoneal mesothelial cells
Authors: Tomohisa Okuno, Masakazu Yashiro, Shingo Togano, Kenji Kuroda, Yuichiro Miki, Hiroaki Kasashima, Kosei Hirakawa, Masaichi Ohira
Journal: Cancer Research (2018)

Abstract Background: Gastric cancer is a major cause of cancer death, particularly on the basis of peritoneal metastasis. Human scirrhous gastric carcinoma (SGC), diffusely infiltrating carcinoma, or Borrman type 4 also known as linitis plastica-type carcinoma is characterized by rapid cancer cell infiltration and proliferation accompanied by extensive stromal fibrosis. SGC account for about 10% of all gastric carcinomas, and carry an extremely worse prognosis than other types of gastric carcinoma, reflecting their frequent peritoneal metastasis. We previously reported that SGC cells (“seed”) might change the peritoneum to favorable environment, so-called pre-metastatic niche (“soil”), (Cancer 77:1668-75, 1996). Recently, it has been clarified that extracellular vesicles (EVs) play an important role for cell-cell interactions. In this study, we investigated the effect of EVs from SGC cells on the pre-metastatic niche formation of the peritoneum. Methods: A SGC cell line, OCUM-2MD3, OCUM-12, KATO-III, gastric cancer cell line, MKN74, MKN45, and peritoneal mesothelial cells (PM cells) were used. PKH26-labeled EVs from OCUM-2MD3 cells were intravenously injected into nude mice, and the distribution of EVs was examined by a fluorescence microscope. The morphology of PM cells was investigated in the addiction of EVs from various gastric cancer cell lines using a phase-contrast microscope. And gene expression was examined by RT-PCR in the presence or absence of EVs from OCUM-2MD3. Clinical significance of EVs markers CD9 and CD63 was immunohistochemically evaluated using 63 human gastric cancer specimens. Results: PKH26-labeled EVs were frequently found in the peritoneum, stomach and liver, but rare in lung and brain of mice. Peritoneal mesothelial cells uptake EVs of gastric cancer cells and change morphology from cobblestone shape to spindle shape in vitro. mRNA expression level of MMPs and integrins in PM cells was increased following the addiction of EVs, in compared with the control. The high expression of CD9 and CD63 was significantly correlated with distant metastasis. Conclusion: EVs from gastric cancer cells might induce a pre-metastatic niche at peritoneum by the morphologic and genetic changes of mesothelial cells. Citation Format: Tomohisa Okuno, Masakazu Yashiro, Shingo Togano, Kenji Kuroda, Yuichiro Miki, Hiroaki Kasashima, Kosei Hirakawa, Masaichi Ohira. Effect of extracellular vesicles from gastric cancer cells on the morphologic and genetic changes of peritoneal mesothelial cells [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 5219.
Abstract 2861: PUMA induction by p73 mediates response and resistance of colorectal cancer to anti-EGFR antibody therapy
Authors: Kyle Knickelbein, Jingshan Tong, Dongshi Chen, Yi-Jun Wang, Sandra Misale, Alberto Bardelli, Jian Yu, Lin Zhang
Journal: Cancer Research (2018)

Abstract Intrinsic and acquired resistance to anti-EGFR antibody therapy, frequently mediated by mutant or amplified KRAS oncogene, is a significant challenge in the treatment of colorectal cancer (CRC), the second-leading cause of cancer-related death in the United States. However, the mechanism of KRAS-mediated therapeutic resistance is not well understood. In this study, we found that clinically used anti-EGFR antibodies, including cetuximab and panitumumab, induce killing of sensitive CRC cells through p73-dependent transcriptional activation of the pro-apoptotic Bcl-2 family protein PUMA. Inhibition of EGFR and downstream AKT by cetuximab and panitumumab promotes Tyr99 phosphorylation of p73, which then binds to PUMA promoter to activate its transcription, resulting in cell death via the mitochondrial pathway. PUMA induction and p73 phosphorylation are abrogated in CRC cells with acquired resistance to anti-EGFR antibodies due to KRAS alterations and residual AKT activity. Upon screening a panel of anticancer drugs, we found that inhibition of aurora kinases preferentially kills mutant KRAS CRC cells. A combination with aurora kinase inhibitor overcomes KRAS-mediated resistance to anti-EGFR antibodies in vitro and in vivo by restoring PUMA induction and eliminating the residual AKT activity. Collectively, our results suggest that p73-dependent PUMA induction plays a critical role in mediating the sensitivity of CRC cells to anti-EGFR antibodies, and that restoration of PUMA induction and apoptosis is a promising approach to improve the efficacy of EGFR-targeted therapy. Citation Format: Kyle Knickelbein, Jingshan Tong, Dongshi Chen, Yi-Jun Wang, Sandra Misale, Alberto Bardelli, Jian Yu, Lin Zhang. PUMA induction by p73 mediates response and resistance of colorectal cancer to anti-EGFR antibody therapy [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 2861.
Abstract 68: Compression Depth Was Correlated with SNR in VF but Not in Nonshockable Rhythms During CPR
Authors: YongqinLi, YushunGong, BihuaChen, MiHe
Journal: Circulation (2014)

Introduction: Artifacts produced by chest compression (CC) during cardiopulmonary resuscitation (CPR) preclude reliable automated ECG rhythm analysis. Several filtering techniques have been proposed to remove the artifact with the use of compression related signals as reference. In order to test the performance of the filters, CPR-corrupted signals were usually generated at different signal-to-noise ratio (SNR) levels and the improvements in SNR were evaluated. However, SNR in real cardiac arrest data and the relationship between compression depth (CD) and SNR are still unknown. Method: ECG, together with CD signals were recorded through defibrillators in 146 patients who experienced cardiac arrest and CPR. A total of 306 segments (6 seconds length, sample rate 250Hz), including 152 ventricular fibrillation (VF), 91 pulseless electrical activity (PEA) and 63 asystole were analyzed. Each segment consisted of 3 seconds corrupted and adjacent 3 seconds artifact-free signal. The power of signal was calculated...
Hepatitis A outbreak disproportionately affecting men who have sex with men (MSM) in the European Union and European Economic Area, June 2016 to May 2017
Authors: Patricia Ndumbi, Gudrun S Freidl, Christopher J Williams, Otilia Mårdh, Carmen Varela, Ana Avellón, Ingrid Friesema, Harry Vennema, Kazim Beebeejaun, Siew Lin Ngui, Michael Edelstein, Alison Smith-Palmer, Niamh Murphy, Jonathan Dean, Mirko Faber, Jürgen Wenzel, Mia Kontio, Luise Müller, Sofie Elisabeth Midgley, Lena Sundqvist, Josefine Lundberg Ederth, Anne-Marie Roque-Afonso, Elisabeth Couturier, Sofieke Klamer, Javiera Rebolledo, Vanessa Suin, Stephan W. Aberle, Daniela Schmid, Rita De Sousa, Gonçalo Figueiredo Augusto, Valeria Alfonsi, Martina Del Manso, Anna Rita Ciccaglione, Kassiani Mellou, Christos Hadjichristodoulou, Alastair Donachie, Maria-Louise Borg, Maja Sočan, Mario Poljak, Ettore Severi
Journal: Eurosurveillance (2018)

Between 1 June 2016 and 31 May 2017, 17 European Union (EU) and European Economic Area countries reported 4,096 cases associated with a multi-country hepatitis A (HA) outbreak. Molecular analysis identified three co-circulating hepatitis A virus (HAV) strains of genotype IA: VRD_521_2016, V16–25801 and RIVM-HAV16–090. We categorised cases as confirmed, probable or possible, according to the EU outbreak case definitions. Confirmed cases were infected with one of the three outbreak strains. We investigated case characteristics and strain-specific risk factors for transmission. A total of 1,400 (34%) cases were confirmed; VRD_521_2016 and RIVM-HAV16–090 accounted for 92% of these. Among confirmed cases with available epidemiological data, 92% (361/393) were unvaccinated, 43% (83/195) travelled to Spain during the incubation period and 84% (565/676) identified as men who have sex with men (MSM). Results depict an HA outbreak of multiple HAV strains, within a cross-European population, that was particularly driven by transmission between non-immune MSM engaging in high-risk sexual behaviour. The most effective preventive measure to curb this outbreak is HAV vaccination of MSM, supplemented by primary prevention campaigns that target the MSM population and promote protective sexual behaviour.
Association of Influenza Vaccination and Reduced Risk of Recurrent Myocardial Infarction
Authors: MortezaNaghavi, ZebaBarlas, SaidSiadaty, SamehNaguib, MohammadMadjid, WardCasscells
Journal: Circulation (2000)

Background—Numerous studies have suggested that microbial agents may promote atherosclerosis. A smaller body of research has suggested that acute respiratory infection may be a risk factor for myocardial infarction (MI). We hypothesized that influenza vaccine might reduce the risk of recurrent MI in patients with documented coronary heart disease (CHD). Methods and Results—A case-control study was performed on 218 CHD patients seen at Memorial Hermann Hospital during the influenza season of October 1997 through March 1998. Patients who experienced new MI were included in the case group, and those who did not experience new MI or unstable angina were assigned to the control group. Data were collected by structured review of patients’ charts and through a subsequent telephone survey. Adjusted for history of influenza vaccination in previous years, multivariate logistic regression revealed risk of MI to be associated with current hypertension (OR 4.96, 95% CI 2.06 to 11.96, P<0.0001), hypercholesterolemia (O...
Intraperitoneal Administration of Anti–c-fms Monoclonal Antibody Prevents Initial Events of Atherogenesis but Does Not Reduce the Size of Advanced Lesions in Apolipoprotein E–Deficient Mice
Authors: ToshinoriMurayama, MasayukiYokode, HiroshiKataoka, TakeshiImabayashi, HiroyukiYoshida, HidetoSano, SatomiNishikawa, Shin-IchiNishikawa, ToruKita
Journal: Circulation (1999)

Background—Atherosclerosis results from complex inflammatory-fibroproliferative responses. To elucidate the central role of macrophage and macrophage-colony stimulating factor (M-CSF) during atherogenesis, we used a new strategy to administer to adult apolipoprotein E (apoE)-deficient mice a monoclonal antibody (AFS98) raised against c-fms, the receptor of M-CSF. Methods and Results—When 6-week-old apoE-deficient mice were fed a high-fat diet and injected with 2 mg of AFS98 intraperitoneally on alternate days for 6 weeks, accumulation of macrophage-derived foam cells in the aortic root was suppressed by 70% compared with that in controls. This preventive effect was associated with neither remarkable decrease of the number of circulating monocytes nor systemic growth retardation. In contrast, when apoE-deficient mice that had been fed a high-fat diet from 6 weeks of age were given AFS98 from 12 to 18 weeks of age, a minimal protective effect on lesion size was observed. Conclusions—These results suggest th...
Long-Term Prognosis of Patients With Type A Aortic Intramural Hematoma
Authors: ShuichiroKaji, TakashiAkasaka, YokoHoribata, KazuhiroNishigami, HiroyukiShono, MinakoKatayama, AtsushiYamamuro, ShigefumiMorioka, IchiroMorita, KazuoTanemoto, TakashiHonda, KiyoshiYoshida
Journal: Circulation (2002)

Background Recent studies have shown an favorable short-term prognosis of patients with type A acute aortic intramural hematoma (IMH). The difference of aortic pathology may have a different impact on clinical course compared with classic aortic dissection (AD). The purpose of this study was to elucidate clinical features and long-term prognosis of patients with type A IMH. Methods and Results Clinical data were compared retrospectively between 30 patients with acute type A IMH (IMH group) and 101 patients with acute type A AD (AD group) who were admitted to our institutions from 1988 to 1998. In AD group, 72 patients underwent surgical repair and 29 patients were treated medically. All patients in IMH group were treated initially with supportive medical therapy. Thirteen patients who demonstrated progression to AD or increase in size of hematoma underwent timed surgical repair except for 1 patient. The overall in-hospital mortality rate in IMH group was significantly lower than that in AD group (7% and 3...
The Late Phase of Preconditioning
Authors: RobertoBolli
Journal: Circulation Research (2000)

Abstract—Unlike the early phase of preconditioning (PC), which lasts 2 to 3 hours and protects against infarction but not against stunning, the late phase of PC lasts 3 to 4 days and protects against both infarction and stunning, suggesting that it may have greater clinical relevance. It is now clear that late PC is a polygenic phenomenon that requires the simultaneous activation of multiple stress-responsive genes. Chemical signals released by a sublethal ischemic stress (such as NO, reactive oxygen species, and adenosine) trigger a complex cascade of signaling events that includes the activation of protein kinase C, Src protein tyrosine kinases, and nuclear factor κB and culminates in increased synthesis of inducible NO synthase, cyclooxygenase-2, aldose reductase, Mn superoxide dismutase, and probably other cardioprotective proteins. An analogous sequence of events can be triggered by a variety of stimuli, such as heat stress, exercise, and cytokines. Thus, late PC appears to be a universal response of...