tbuckley/cabot-search huggingface dataset:
Abstract 4035: Cetuximab combined with dasatinib reduces drug resistance in KRAS/BRAF mutated colorectal carcinoma cells
Authors: Hsiang-Ling Chiu, Yi-Che Wu, Wan-Chen Wei, Ling-Yi Kao, Wei-Ting Chao
Journal: Cancer Research (2018)

Abstract Colorectal carcinoma is the most common cancer worldwide. Cetuximab is the first-line target drug for late-stage metastatic colon cancer treatment; however, resistance to it was found in 45% patients having KRAS mutation. Therefore, the alternative signal axis to target mutated cancer cells is urgent and investigated. The role and the importance of Src has emerged in colon cancer; this study is to investigate the drug combined efficacy of cetuximab and dasatinib, the Src inhibitor and the underling molecular mechanism in KRAS/BRAF mutated cells. In this study, KRAS and BRAF mutated colon cancer cell lines SW480 and HT-29 were treated with cetuximab, dasatinib and fluorouracil (5-FU) solitary or combined. Cell viability and migration ability were monitored, and the molecular mechanisms were analyzed by Western blot for signal protein expressions. The in vivo study was carried with subcutaneous xenograft mouse model to evaluate the drug efficacy. The result showed that cetuximab treatment induced Src activation dose dependently, and induced matrix-dependent cell migration in SW480 cells. Cetuximab, dasatinib and 5-FU combined treatment compared to solitary treatment can reduce cell viability in either wild-type or KRAS/BRAF mutated colon cells. In the signal protein expressions, Src expression was suppressed sufficiently with dasatinib treatment; the phosphorylation of MAPK in SW480 cells and the phosphorylation of PI3K in HT-29 cells were downregulated after treated with cetuximab together with dasatinib and 5-FU. The drug combination was also demonstrated to suppress subcutaneous tumor growth as well. These findings demonstrate the combination of cetuximab, dasatinib and 5-FU can be the potential treating strategy for colon cancer cells with KRAS/BRAF mutation. Citation Format: Hsiang-Ling Chiu, Yi-Che Wu, Wan-Chen Wei, Ling-Yi Kao, Wei-Ting Chao. Cetuximab combined with dasatinib reduces drug resistance in KRAS/BRAF mutated colorectal carcinoma 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 4035.
Abstract 4404: Identification of small molecules that inhibit miR-21 activity in breast cancer
Authors: Michel F. Guiraldelli, Alexander O. Schwartz, Michelle A. Markus, Jun Jiang, Justin D. Boyd, Branko Radetich, William E. Monahan, Nanguneri Nirmala, Johan A. Pontin, Dalia Cohen
Journal: Cancer Research (2018)

Abstract In cancer, microRNA (miR) dysregulation can lead to tumor development, invasion and metastasis. miRs are small single-stranded non-coding RNAs that bind to target mRNAs and stop protein expression. miRs are transcribed as a long transcript that fold to form secondary hairpin structures called pri-miRs that are subsequently processed by the microprocessor complex (Drosha and DGCR8) resulting in the formation of the precursor miRs (pre-miRs). Pre-miRs are exported to the cytoplasm via Exportin 5 and RanGTP. In the cytoplasm, pre-miRs are cleaved by Dicer resulting in double stranded molecule. This miR duplex is assembled into the RNA-induced silencing complex (RISC) and targets specific mRNAs. In breast cancer, miR-21 expression levels are increased, and are correlated with tumor grade. The use of small molecules targeting the miR process to modulate levels of mature miR is a novel approach for developing therapeutics. Inactivation of any of the processing steps of miR would result in an inactive mature miR or lower significantly its level. Using a parallel screening approach employing cell biology, NMR and chemistry, we identified several small molecules that bind and inhibit the activity of miR-21. Further characterization of one of our hits in MCF-7 cells showed a dose dependent inhibition of miR-21 activity. A decrease in proliferation with a concomitant increase in apoptosis signal was observed in cells treated with the compound. Analysis of miR-21 processing species by qPCR in MCF-7 cells showed a decrease on pri, pre-and mature miR-21 relative to cells treated with vehicle only. Furthermore, the levels of PDCD4, a direct downstream effector of miR-21, increased upon treatment with the compound. NMR experiments showed that this compound binds to a specific sequence and that the flanking C-G bases are necessary for its binding. These results support the feasibility of targeting miRs by small molecule as a novel therapeutic modality. Citation Format: Michel F. Guiraldelli, Alexander O. Schwartz, Michelle A. Markus, Jun Jiang, Justin D. Boyd, Branko Radetich, William E. Monahan, Nanguneri Nirmala, Johan A. Pontin, Dalia Cohen. Identification of small molecules that inhibit miR-21 activity in breast 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 4404.
Abstract 3397: Clinical significance of 3q amplification in squamous cell carcinoma of lung
Authors: Eunjung Lee, Chungyeul Kim, Han-Kyeom Kim, Baek-hui Kim
Journal: Cancer Research (2018)

Abstract Squamous cell carcinoma (SqCC) is major subtype of non-small cell lung cancer (NSCLC). One of the molecular characteristic of SqCC is amplification of distal portion of 3q. The aim of this study is to find out the clinical significance of the 3q amplification in SqCC of lung. Method : We extracted DNA from 90 cases of FFPE blocks of lung SqCC tissue. Ten genes (PIK3CA, SOX2, KLHL6, MCF2L2, LAMP3, MCCC1, ABCC5, ATP11B, TP63, YEATS2) included in 3q were selected and the amplification of each gene was analyzed by using NanoString nCounter analysis system (PhileKorea). The hierarchical clustering was performed with the resulting values. Results : We identified two groups in all 90 cases of SqCC by hierarchical clustering. One group with 3q amplification was 50 cases, and the other group without 3q amplification was 40 cases. There was no significant difference in sex, age, stage, smoking history, histologic grade and the results of immunohistochemical staining (p63, p40 and p53) between the two groups. It showed the tendency that the group with 3q amplification presented poor disease free survival (P=0.193) and overall survival (P=0.34) than the group without 3q amplification. Among the ten genes, PIK3CA and YEATS2 were significantly associated with survival. Each genes with amplification showed poor disease free survival (PIK3CA; P=0.036, YEATS2; P=0.025). Conclusion : The amplification of 3q can help sorting out two subsets of SqCC of lung whose clinical outcomes are likely to diverge. Among the genes included in 3q, PIK3CA and YEATS2 were associated with prognosis. These finding demonstrate the role of these genes in biologic behavior of tumor and suggest opportunities for targeted therapies. Citation Format: Eunjung Lee, Chungyeul Kim, Han-Kyeom Kim, Baek-hui Kim. Clinical significance of 3q amplification in squamous cell carcinoma of lung [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 3397.
Increased Reactive Oxygen Species in Rostral Ventrolateral Medulla Contribute to Neural Mechanisms of Hypertension in Stroke-Prone Spontaneously Hypertensive Rats
Authors: TakuyaKishi, YoshitakaHirooka, YoshikuniKimura, KojiIto, HiroakiShimokawa, AkiraTakeshita
Journal: Circulation (2004)

Background— Oxidative stress increases in hypertension. The aim of this study was to determine whether reactive oxygen species (ROS) are increased in the rostral ventrolateral medulla (RVLM) in the brainstem, where the vasomotor center is located, in stroke-prone spontaneously hypertensive rats (SHRSP), and, if so, to determine whether the increased ROS contribute to neural mechanisms of hypertension in SHRSP. Methods and Results— We measured ROS levels in the RVLM of SHRSP and compared them with those in Wistar-Kyoto rats (WKY). Thiobarbituric acid–reactive substances were increased in SHRSP compared with WKY. ROS were measured by electron spin resonance (ESR) spectroscopy. The ESR signal decay rate in the RVLM of SHRSP was significantly increased compared with that in WKY, and this increase was abolished by dimethylthiourea (a hydroxyl radical scavenger). The increased ESR signal decay rate was reduced to the same extent in the presence of desferrioxamine, catalase, and Tiron, indicating that hydroxyl r...
Clinically applicable deep learning for diagnosis and referral in retinal disease
Authors: Jeffrey De Fauw, Joseph R. Ledsam, Bernardino Romera-Paredes, Stanislav Nikolov, Nenad Tomasev, Sam Blackwell, Harry Askham, Xavier Glorot, Brendan O’Donoghue, Daniel Visentin, George van den Driessche, Balaji Lakshminarayanan, Clemens Meyer, Faith Mackinder, Simon Bouton, Kareem Ayoub, Reena Chopra, Dominic King, Alan Karthikesalingam, Cían O. Hughes, Rosalind Raine, Julian Hughes, Dawn A. Sim, Catherine Egan, Adnan Tufail, Hugh Montgomery, Demis Hassabis, Geraint Rees, Trevor Back, Peng T. Khaw, Mustafa Suleyman, Julien Cornebise, Pearse A. Keane, Olaf Ronneberger
Journal: Nature Medicine (2018)
Expression of Angiotensin-Converting Enzyme in Remaining Viable Myocytes of Human Ventricles After Myocardial Infarction
Authors: SeijiHokimoto, HirofumiYasue, KazuteruFujimoto, HideyukiYamamoto, KoichiNakao, KoichiKaikita, RyuzoSakata, EishichiMiyamoto
Journal: Circulation (1996)

Background Local ACE in the heart may be important in the pathophysiological state after myocardial infarction (MI). It is unknown, however, whether ACE is expressed in myocytes of the human heart. Methods and Results Using a newly generated polyclonal antibody to a synthetic peptide corresponding to part of the human endothelial ACE sequence, we examined the localization of ACE in left ventricles of patients (n=10) with MI obtained at left ventricular aneurysmectomy or autopsy and in the hearts of control subjects at autopsy (n=10). The avidin–biotinylated peroxidase complex method was used for the immunohistochemical staining for ACE. In the left ventricles, positively stained myocytes for ACE were found in 8 of the 10 patients with MI. ACE immunoreactivity was seen in the remaining viable myocytes located near the infarct scar of the aneurysmal left ventricle and in nonmyocytes such as fibroblasts, macrophages, vascular smooth muscle cells, and endothelial cells within the scarred tissue. On the other ...
<i>Bacteroides vulgatus</i> and <i>Bacteroides dorei</i> Reduce Gut Microbial Lipopolysaccharide Production and Inhibit Atherosclerosis
Authors: Naofumi Yoshida, Takuo Emoto, Tomoya Yamashita, Hikaru Watanabe, Tomohiro Hayashi, Tokiko Tabata, Namiko Hoshi, Naoya Hatano, Genki Ozawa, Naoto Sasaki, Taiji Mizoguchi, Hilman Zulkifli Amin, Yushi Hirota, Wataru Ogawa, Takuji Yamada, Ken-ichi Hirata
Journal: Circulation (2018)

Background: It is increasingly recognized that gut microbiota play a pivotal role in the development of atherosclerotic cardiovascular disease. Previously, we have reported that the abundance of genus Bacteroides is lower in patients with coronary artery disease (CAD) than in patients without CAD with coronary risk factors or in healthy volunteers. However, it remains unclear which and how specific gut bacteria contribute to the progression of atherosclerosis. Methods: We recruited patients with CAD patients and controls without CAD with coronary risk factors. We then compared gut microbial composition using 16S ribosomal RNA gene sequencing in fecal samples to detect species with differential abundance between 2 groups. Subsequently, we used atherosclerosis-prone mice to study the mechanisms underlying the relationship between such species and atherosclerosis. Results: Human fecal 16S ribosomal RNA gene sequencing revealed a significantly lower abundance of Bacteroides vulgatus and Bacteroides dorei in patients with CAD. This significant differential abundance was confirmed by quantitative polymerase chain reaction. Gavage with live B. vulgatus and B. dorei attenuated atherosclerotic lesion formation in atherosclerosis-prone mice, markedly ameliorating endotoxemia followed by decreasing gut microbial lipopolysaccharide production, effectively suppressing proinflammatory immune responses. Furthermore, fecal lipopolysaccharide levels in patients with CAD were significantly higher and negatively correlated with the abundance of B. vulgatus and B. dorei . Conclusions: Our translational research findings identify a previously unknown link between specific gut bacteria and atherosclerosis. Treatment with live B. vulgatus and B. dorei may help prevent CAD. Clinical Trial Registration: URL: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000018051 . Unique identifier: UMIN000015703.
Machine Learning and Health Care Disparities in Dermatology
Authors: Adewole S. Adamson, Avery Smith
Journal: JAMA Dermatology (2018)

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 Dermatology 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 Dermatology journal
Abstract 18854: Concept and Clinical Implications of Mechanical Reserve in Hypertrophic Cardiomyopathy
Authors: Iraklis Pozios, Aurelio Pinheiro, Celia Corona-Villalobos, Lars L Sorensen, Lea V Dimaano, Hongchang Luo, Zeina Dardari, Xun Zhou, Ihab Kamel, David A Bluemke, Stefan L Zimmerman, Maria R Abraham, Theodore P Abraham
Journal: Circulation (2014)

Background:  We hypothesized that inability to augment regional and global mechanics during stress would portend a poor prognosis in hypertrophic cardiomyopathy (HCM).   Methods:  Ninety five HCM patients [32 non-obstructive (NO), 32 labile-obstructive (LO), 31 obstructive (Ob)] and 26 age and gender matched controls (Co) underwent conventional and strain echocardiography at rest and after treadmill exercise. Mechanical reserve (MRES) was defined as % change in systolic strain rate (SR) with exercise. Magnetic resonance delayed enhancement (DE) was available in 61 patients.   Results:  Exercise capacity was lower in obstructive patients (NO: 10.0±3.7 vs. LO: 11.8±4.4 vs. Ob: 9.1±3.4 vs. Co: 10.9±3.2 METs, p=0.03). Peak global strain and SR were significantly lower in HCM patients both at rest and peak exercise. MRES was lower in non-obstructive and obstructive compared to labile-obstructive and control that had similar values. In univariable analysis, exercise SR and MRES were associated with exercise capacity. In multivariable analysis, exercise SR was found to be the best predictor of exercise capacity when adjusted for age, gender, BMI, E/e’ and resting LVOT gradient. Exercise SR showed a significant correlation with the extent of DE (R=0.342, p=0.03). Cox regression model showed exercise SR and MRES were predictors of VT/VF when adjusted for age, gender, family history of sudden cardiac death, septum ≥3cm and abnormal blood pressure response.   Conclusion:  Non-obstructive and obstructive patients have reduced mechanical reserve and exercise capacity compared to labile-obstructive and controls. Exercise SR and mechanical reserve predict exercise capacity and VT/VF.
Non-coding RNAs in Cardiac Remodeling and Heart Failure
Authors: RegallaKumarswamy, ThomasThum
Journal: Circulation Research (2013)

Heart failure is a leading cause of death in industrialized nations especially in an aging population. The recent improvements in cardiac revascularization therapy reduced death rates because of myocardial infarction but steadily increased the number of individuals developing cardiac remodeling and heart failure in the future. Conceptual novel approaches entering the clinics to treat cardiac remodeling and heart failure remain scarce. MicroRNAs emerged as powerful and dynamic modifiers of cardiovascular diseases. In this review, the current approaches using microRNAs as novel diagnostic and therapeutic strategies for cardiac remodeling and heart failure are highlighted. Other gene regulatory mechanisms presented include long (>200 bp) noncoding RNAs that function as an additional regulatory machinery of the genome controlling both transcriptional and post-transcriptional events also in the cardiovascular system.
Calcineurin Pathway Is Required for Endothelin-1–Mediated Protection Against Oxidant Stress–Induced Apoptosis in Cardiac Myocytes
Authors: TsuyoshiKakita, KojiHasegawa, EriIwai-Kanai, SouichiAdachi, TatsuyaMorimoto, HiromichiWada, TeruhisaKawamura, TetsuhikoYanazume, ShigetakeSasayama
Journal: Circulation Research (2001)

Abstract—Endothelin-1 (ET-1) acts not only as a growth-promoting peptide but also as a potent survival factor against myocardial cell apoptosis. However, the signaling pathways leading to myocardial cell protection by ET-1 are poorly understood. Using a culture system of primary cardiac myocytes derived from neonatal rats, we show in the present study that ET-1 almost completely blocked the hydrogen peroxide–induced increase in the percentage of TdT-mediated dUTP-biotin nick-end labeling–positive myocytes. Apoptosis inhibition by ET-1 was confirmed by cytofluorometric analysis as well as by examination of the ladder formation, morphological features, and caspase-3 cleavage. We have found that ET-1 converts the nuclear factor of activated T lymphocytes (NFATc) in cardiac myocytes into high-mobility forms and translocates cytoplasmic NFATc to the nuclei. In addition, ET-1 stimulates the interaction between NFATc and the cardiac-restricted zinc-finger protein GATA4 in these cells. The immunosuppressants cycl...
Organic Photo‐Electrochemical Transistor‐Based Biosensor: A Proof‐of‐Concept Study toward Highly Sensitive DNA Detection
Authors: Jiajun Song, Peng Lin, Yi‐Fan Ruan, Wei‐Wei Zhao, Weiwei Wei, Jin Hu, Shanming Ke, Xierong Zeng, Jing‐Juan Xu, Hong‐Yuan Chen, Wei Ren, Feng Yan
Journal: Advanced Healthcare Materials (2018)

Abstract Organic bioelectronics have shown promising applications for various sensing purposes due to their significant advantages in term of high flexibility, portability, easy fabrication, and biocompatibility. Here, a new type of organic device, organic photo‐electrochemical transistor (OPECT), is reported, which is the combination of an organic electrochemical transistor and a photo‐electrochemical gate electrode modified with CdS quantum dots (QDs). Thanks to the inherent amplification function of the transistor, the OPECT‐based biosensor exhibits much higher sensitivity than that of a traditional biosensor. The sensing mechanism of the OPECT is attributed to the charge transfer between the photosensitive semiconductor CdS QDs and the gate electrode. In an OPECT‐based DNA sensor, target DNA is labeled with Au nanoparticles (NPs) and captured on the gate electrode, which can influence the charge transfer on the gate caused by the exciton–plasmon interactions between CdS QDs and Au NPs. Consequently, a highly sensitive and selective DNA sensor with a detection limit of around 1 × 10 −15 m is realized. It is expected that OPECTs can be developed as a high‐performance platform for numerous biological detections in the future.
Glucose Enhances Human Macrophage LOX-1 Expression
Authors: LingLi, TatsuyaSawamura, GenevièveRenier
Journal: Circulation Research (2004)

Lectin-like oxidized LDL receptor-1 (LOX-1) is a newly identified receptor for oxidized LDL that is expressed by vascular cells. LOX-1 is upregulated in aortas of diabetic rats and thus may contribute to the pathogenesis of human diabetic atherosclerosis. In this study, we examined the regulation of human monocyte-derived macrophage (MDM) LOX-1 expression by high glucose and the role of LOX-1 in glucose-induced foam cell formation. Incubation of human MDMs with glucose (5.6 to 30 mmol/L) enhanced, in a dose- and time-dependent manner, LOX-1 gene and protein expression. Induction of LOX-1 gene expression by high glucose was abolished by antioxidants, protein kinase C (PKC), mitogen-activated protein kinases (MAPKs), nuclear factor-κB (NF-κB), and activated protein-1 (AP-1) inhibitors. In human MDMs cultured with high glucose, increased expression of PKCβ2 and enhanced phosphorylation of extracellular signal-regulated protein kinase 1/2 was observed. Activation of these kinases was inhibited by the antioxid...
Serum and Glucocorticoid-Responsive Kinase-1 Regulates Cardiomyocyte Survival and Hypertrophic Response
Authors: TakumaAoyama, TakashiMatsui, MikhailNovikov, JongsunPark, BrianHemmings, AnthonyRosenzweig
Journal: Circulation (2005)

Background— Serum- and glucocorticoid-responsive kinase-1 (SGK1), a serine-threonine kinase that is highly expressed in the heart, has been previously reported to regulate sodium channels. Because SGK1 is a PI 3-kinase–dependent kinase with structural homology to Akt, we examined its regulation in the heart and its effects on cardiomyocyte (CM) apoptosis and hypertrophy in vitro. Methods and Results— Rats were subjected to aortic banding, and expression of total and phosphorylated SGK1 was examined. Both phospho- and total SGK1 increased 2 to 7 days after banding. Phospho-SGK1 was also upregulated in CMs stimulated in vitro with IGF-I or phenylephrine. Infection of CMs with an adenoviral vector encoding constitutively active SGK1 (Ad.SGK1.CA) inhibited apoptosis after serum-deprivation or hypoxia (P<0.05), whereas expression of kinase-dead SGK1 (Ad.SGK1.KD) increased it and partially mitigated the protective effects of IGF-I (P<0.05). SGK1 activation was also sufficient to increase cell size, protein synt...