tbuckley/cabot-search huggingface dataset:
C형간염 바이러스: 면역과 HCV 백신
Authors: 신의철
Journal: Clinical and Molecular Hepatology (2010)

Hepatitis C virus (HCV) infection is an issue of public health care. Chronic persistent HCV infection often progresses to liver cirrhosis and hepatocellular carcinoma. However, the current standard therapy shows a limited efficacy, and prophylactic vaccine has not been developed yet. Therefore, developments of a novel immunotherapy and effective HCV vaccine are urgent. In this lecture, characteristic features of antibody and T-cell responses will be discussed in chronic HCV infection. In addition, immune status after recovery from HCV infection will also be discussed. Understanding of immune responses against HCV will facilitate the development of effective therapeutic and prophylactic strategies.
Total Arch Replacement Combined With Stented Elephant Trunk Implantation
Authors: LiZhongSun, RuiDongQi, JunMingZhu, YongMinLiu, JunZheng
Journal: Circulation (2011)

Background—Appropriate surgical management of type A dissection is a critical factor for achieving satisfactory outcome, but the choice of optimal procedure is controversial. We retrospectively reviewed our experience with aortic arch replacement for type A dissection involving the arch. Methods and Results—Excluding 14 cases of subtotal or total aortic replacement, 411 of 544 patients with type A dissection (stented elephant trunk=291, conventional surgical repair=120) underwent aortic arch replacement between January 2003 and September 2008. In-hospital mortality was 3.09% (9 of 291) for stented (acute=4.73%, 7 of 148; chronic=1.40%, 2 of 143) and 5.00% (6 of 120) for conventional repairs (acute=6.06%, 4 of 66; chronic=3.70%, 2 of 54). Spinal cord injury was 2.41% (7 of 291) in the stented and 0.83% (1 of 120) in the conventional group. The overall prevalence of stroke was 1.95% (8 of 411) (stented=2.41%, 7 of 291; conventional=0.83, 1 of 120). Secondary intervention was 2.34% (5 of 214) for acute disse...
Abstract 5185: Identification of a new candidate therapeutic target for gastric cancer by in silico analysis
Authors: Tomohiro Kohmoto, Kiyoshi Masuda, Katsutoshi Shoda, Yuji Fujita, Shoichiro Tange, Daisuke Ichikawa, Eigo Otsuji, Issei Imoto
Journal: Cancer Research (2018)

Abstract Gastric Cancer (GC) is a leading cause of global cancer mortality, with high incidence rates in Asia including Japan. Although recent studies have provided valuable insights into identification of major driver genes, there are still little therapeutic targets and prognostic markers of GC. Here, we report that a novel driver gene, OverExpressed in Gastric Cancer 1 (OEGC1), would induce cell proliferation and migration of GC.Analyzing gene expression profiles by RNA-Seq and relevant clinical data in TCGA dataset, we identified candidate genes whose mRNA expression was higher in tumor tissues than in non-tumorous and associated with poor prognosis. Through further expression analysis and Cox proportional hazards regression analysis of those candidates, we identified OEGC1 as the most prominent candidate for driver gene. OEGC1 mRNA was expressed highly especially in intestinal type GC. The prognosis of the OEGC1 high-expressed intestinal type GC patients was as poor as that of diffuse type GC patients. Immunohistochemical analysis showed that overexpression of OEGC1 was ectopically found in the tumor cell junctions located in the infiltrated region of tumor. By silencing endogenous OEGC1 using siRNAs, cell proliferation was significantly suppressed and G0/G1 arrest was induced in NUGC3, AGS and MKN7 cells with relatively higher OEGC1 expression. Transwell assay showed that the number of migrated cells was significantly lower for siRNA-OEGC1-transfected cells than for control cells. Our findings suggested that aberrant expression of OEGC1 might play an important role in tumorigenesis of GC, and that OEGC1 might be a possible therapeutic target in GC. Citation Format: Tomohiro Kohmoto, Kiyoshi Masuda, Katsutoshi Shoda, Yuji Fujita, Shoichiro Tange, Daisuke Ichikawa, Eigo Otsuji, Issei Imoto. Identification of a new candidate therapeutic target for gastric cancer by in silico analysis [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 5185.
Abstract 2942: Enhanced cytotoxic activity of BRAF, MEK and PI3K inhibition with combination CDK4/6 inhibition in melanoma cells
Authors: Yanping Zhang, Guangyong Peng, Eddy C. Hsueh
Journal: Cancer Research (2018)

Abstract Introduction: We have previously reported that CDK4/6 inhibition enhanced the anti-proliferation and anti-migration effects of BRAF, MEK and PI3K inhibitors in melanoma cells. (Zhang Y et al, AACR 2017) In this study, we investigated the effect of combination CDK4/6 inhibition and BRAF, MEK and PI3K inhibition on induction of cell cycle arrest and apoptosis in melanoma. Methods: Five human melanoma cell lines were used. CDK4/6 inhibitor (PD0332991; PD), BRAF inhibitor (PLX4032; PLX), MEK inhibitor (AZD6244; AZD), and PI3K/AKT inhibitor (XL765; XL) were used alone or in combination. Cell apoptosis analysis was performed using the FITC Annexin V Apoptosis Detection Kit. Autophagy was evaluated by immunofluorescence using anti-LC3A/B and NECN-1 antibodies. Lysosomal morphology was evaluated using lysosomal associated membrane protein 1-green fluorescent protein fusion construct. Western blotting was performed for apoptosis markers (PARP and caspase-9) and autophagy markers (LC3A/B and Beclin1) using GAPDH as internal control. Data were presented as means ± SD for triplicate experiments. For comparison between groups, the student's t test was used and p&amp;lt; 0.05 was considered to be statically significant. Results: Apoptosis was evaluated by Annexin V assay. Various levels of apoptosis were observed with single agent PD, PLX, XL and AZD in all 5 melanoma cell lines. Combination of PD enhanced the apoptosis effects of PLX, XL, and AZD in all 5 melanoma cell lines. Increased LC3 and BECN1 detection and increased density of autophagosomes on immunofluorescence was observed after combining CDK4 inhibition with BRAF, MEK, and PI3K/AKT inhibition. Inhibition of PARP and Beclin-1 expression and increase in caspase-9 expression were observed with combination of PD compared with single agent PLX, XL, and AZD. Conclusion: CDK4 inhibition enhanced anti-melanoma activity of BRAF , PI3K/AKT and MEK inhibitions through increased induction of early autophagy and caspase-mediated apoptosis. This suggests that inhibition of CDK4/6 plus BRAF , MEK and PI3K/AKT inhibition may help understanding the interplay between autophagy and apoptosis and inform the development of future targeted agents. Citation Format: Yanping Zhang, Guangyong Peng, Eddy C. Hsueh. Enhanced cytotoxic activity of BRAF, MEK and PI3K inhibition with combination CDK4/6 inhibition in melanoma 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 2942.
Abstract 1698: Loss of MHC-I expression is associated with altered immune microenvironment and decreased response to PD-1 checkpoint inhibition
Authors: Cecile Gstalder, Priya Pancholi, Dorota Sadowicz, Rizwan Haq
Journal: Cancer Research (2018)

Abstract Cancer immunotherapies, such as PD-1 inhibitors, achieve durable responses in a subset of cancer patients, however, a significant proportion of patients fail to respond to treatment. Defects in antigen presentation, such as the loss of MHC-I expression, are a major mechanism of resistance to PD-1 inhibitors. Developing new therapeutic strategies that overcome the lack of antigen presentation will improve cancer treatment and patient survival. To develop a pre-clinical model to evaluate therapies that could overcome resistance, we have generated a unique PD-1 blockade sensitive, syngeneic immunocompetent melanoma mouse model. We generated defects in antigen presentation using the CRISPR/Cas9 system, creating B2m-deficient melanoma cell lines. We demonstrated that B2m is necessary for IFN-gamma induced MHC-I surface expression. Unlike control tumors, we found that B2m-deficient tumors were resistant to PD-1 blockade, leading to decreased mouse overall survival. Using multi-parameter flow cytometry, we showed an increase in NK cell, regulatory T cell and dendritic cell infiltration in B2m-deficient tumors compared to controls, while the other immune cell population were unchanged. Since NK cell activity is negatively regulated by MHC-I, our findings suggest that additional factors are required to further invigorate infiltrating NK cells and to trigger a NK cell-mediated anti-tumor response. We are currently evaluating new approaches targeting NK cells and regulatory T cells on B2m-deficient tumors. This pre-clinical model could enable the development of a therapeutic strategy serving to improve the treatment of tumors lacking antigen presentation. Citation Format: Cecile Gstalder, Priya Pancholi, Dorota Sadowicz, Rizwan Haq. Loss of MHC-I expression is associated with altered immune microenvironment and decreased response to PD-1 checkpoint inhibition [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 1698.
Antilipemic Activity of an Extract of Hog Gastric Mucosa
Authors: Aureliocantone, Vincenzorulli, Baldorossi
Journal: Circulation Research (1959)

In recent years numerous studies have been made on the clearing effect exerted by heparin on hyperlipemic plasma, specially in connection with the problem of atherogenesis. The present paper deals with investigations, carried out on both animals and men, concerning the hypocholesteremic, plasma-clearing, and lipotropic effects, as well as the inhibitory action on the electrocardiographic changes associated with alimentary hyperlipemia, exerted by orally active extracts of gastric juice and hog gastric mucosa.
Abstract 1321: Mutational landscape of adherens junctions in skin cutaneous melanoma
Authors: Praveen Kumar Korla, Daniel Esguerra Gracilla, Brian Yu-Ting Kuo, Jim Jinn-Chyuan Sheu
Journal: Cancer Research (2018)

Abstract Cadherin proteins regulate cell-cell contact through calcium-dependent manner, thus play pivotal roles in morphogenetic and differentiation processes during tissue development. Reprograming in cadherin profiles contributes to epithelial-mesenchymal transition (EMT), leading to disorganized lining of epithelial tissues and cancer metastasis. To elucidate genetic impacts of classical cadherins on melanoma development, mutation profiles were analyzed using data from the TCGA databank. Among 20 classical cadherins, CDH6 showed the highest mutation frequency (11.3 %), and most of which were G to A or C to T nucleotide substitutions, a signature for UV-caused DNA damage. Two groups of unique hotspots were found on the fifth cadherin domain (D5) (S524L and S526F) and cytoplasmic cadherin domain (CDH-C) (E662K and E722K), respectively. Protein interactome and expression co-occurrence analyses placed CDH6 at the center of core cadherin network and showed strong heterophilic interactions of CDH6 with CDH4, CDH9, and CDH12. Multiple sequence alignment indicated the involvement of those hotspots in the conserved regions, which are responsible for heterophilic interaction on D5 or catenin (alpha, beta, and gamma) binding on CDH-C. Molecular modeling defined alterations in protein structures of the D5 and CDH-C domains caused by the hotspot mutations, which may influence cell-cell contact and the down-stream signaling. In sum, our data suggest CDH6 as the key player to modulate adherens junctions during the development of melanoma. Citation Format: Praveen Kumar Korla, Daniel Esguerra Gracilla, Brian Yu-Ting Kuo, Jim Jinn-Chyuan Sheu. Mutational landscape of adherens junctions in skin cutaneous melanoma [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 1321.
Abstract IA19: Granulosa cell and other rare ovarian cancers: Genomic-derived diagnostics and emergent management strategies
Authors: David Huntsman
Journal: Clinical Cancer Research (2018)

Abstract Granulosa cell tumors, Sertoli-Leydig tumors, and small cell hypercalcemic ovarian cancers are clinically and biologically distinct. In the past few years the key mutations underpinning these mutations have been discovered. This has led to improved diagnostics for granulosa cell tumors and small cell hypercalcemic ovarian cancer. The discovery of pathognomonic mutations has led to the development of model systems and a better understanding of all three cancer types and for small cell ovarian cancer new treatment strategies. Citation Format: David Huntsman. Granulosa cell and other rare ovarian cancers: Genomic-derived diagnostics and emergent management strategies. [abstract]. In: Proceedings of the AACR Conference: Addressing Critical Questions in Ovarian Cancer Research and Treatment; Oct 1-4, 2017; Pittsburgh, PA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(15_Suppl):Abstract nr IA19.
Therapy-Dependent Influence of Time-to-Treatment Interval on Myocardial Salvage in Patients With Acute Myocardial Infarction Treated With Coronary Artery Stenting or Thrombolysis
Authors: AlbertSchömig, GjinNdrepepa, JulindaMehilli, MarkusSchwaiger, HelmutSchühlen, StephanNekolla, JürgenPache, StefanMartinoff, HildegardBollwein, AdnanKastrati
Journal: Circulation (2003)

Background— The relationship between myocardial salvage and time-to-treatment interval in patients with acute myocardial infarction (AMI) treated with coronary artery stenting or thrombolysis has not been studied. Methods and Results— This study analyzed 264 patients with AMI randomized to coronary stenting (133 patients) or thrombolysis (131 patients) in the setting of 2 randomized trials. Patients were divided into the following 3 groups defined by tertiles of the time-to-treatment interval: lower tertile ( 280 minutes). Paired scintigraphic examinations were performed to obtain salvage index, which was the primary end point of the study. In the group with thrombolysis, the salvage index (median [25th; 75th] percentile) was 0.45 (0.16; 0.83) in the lower, 0.29 (0.17; 0.48) in the middle, and 0.20 (0.04; 0.46) in the upper tertile (P=0.03). In the group with stenting, the salvage index was 0.56 (0.49; 0.75) in the lower, 0.57 (0.36; 0...
Abstract 1499: Vitamin D promotes differentiation in patient-derived organoids in benign and cancer prostate models
Authors: Tara N. McCray, Giovani Lugli, Larisa Nonn
Journal: Cancer Research (2018)

Abstract Deficiency in the prohormone vitamin D is associated with increased risk of lethal prostate cancer (PCa) and less-differentiated, more aggressive tumors. As cancer progresses there is aberrant expression of vitamin D metabolic genes causing dysregulation of the vitamin D pathway, indicating its role in disease. Vitamin D has many chemopreventive actions in vitro, including promotion of differentiation and apoptosis. The ability for vitamin D to drive differentiation has been explored in various cell types and cancer lines, but its mechanism of action in the prostate is not well defined. Our lab found that vitamin D treatment globally upregulates microRNAs (miRs) in prostate cell lines, primary cells and patient samples. Temporal regulation of miRs is critical for differentiation and levels of mature miRs are globally lower in PCa. Given the relationship between vitamin D and microRNAs, and their influence over differentiation, we hypothesize that vitamin D promotes differentiation in the prostate in a microRNA-dependent manner and that this process is disrupted during cancer. Here we examined organoid differentiation in the presence of 1,25D, the active metabolite of vitamin D. Organoids were grown in matrigel from human primary prostate epithelial progenitor cells. Differentiation was assessed by organoid size and branching, and by expression of epithelial markers. Organoids grown in the presence of 1,25D were strikingly larger and formed more complex branching structures than those treated with control. Whole mount immunofluorescence revealed expression of basal and luminal epithelial cells in the organoids. Flow-sorted organoids had a greater composition of basal cells when grown in the presence of 1,25D. RT-qPCR analysis of the flow-sorted epithelial populations revealed an enhancement in the WNT pathway with 1,25D, this pathway is critical in prostate development and dysregulated in cancer. The role of miRNAs was determined by reducing global miRNA levels via knockdown of Drosha, an essential miRNA-processing protein. Knockdown abrogated the effect of 1,25D, as evidenced by reduced size, round shape, and protein expression. Together our findings indicate a role of 1,25D in normal prostate development and branching, a phenotype that is lost when mature miR levels are reduced. Ongoing studies examine these phenotypes in PCa organoids. Citation Format: Tara N. McCray, Giovani Lugli, Larisa Nonn. Vitamin D promotes differentiation in patient-derived organoids in benign and cancer prostate models [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 1499.
Corticosteroid treatment in critically ill patients with severe influenza pneumonia: a propensity score matching study
Authors: Gerard Moreno, Alejandro Rodríguez, Luis F Reyes, Josep Gomez, Jordi Sole-Violan, Emili Díaz, María Bodí, Sandra Trefler, Juan Guardiola, Juan C Yébenes, Alex Soriano, José Garnacho-Montero, Lorenzo Socias, María Del Valle Ortíz, Eudald Correig, Judith Marín-Corral, Montserrat Vallverdú-Vidal, Marcos I Restrepo, Antoni Torres, Ignacio Martín-Loeches
Journal: Intensive Care Medicine (2018)
Abstract 3538: Targeting the E3 ubiquitin ligase RNF20 in ovarian cancer
Authors: Alexander J. Cole, Kristie-Ann Dickson, Roderick Clifton-Bligh, Deborah J. Marsh
Journal: Cancer Research (2018)

Abstract E3 ubiquitin ligases are responsible for the final stage of the enzymatic ubiquitination cascade, where they transfer ubiquitin from an E2 conjugating enzyme to a lysine on the recognized substrate. The most common family of E3 ligases are RING (Really Interesting New Gene) domain proteins. Using immunohistochemistry, we have shown that the ring finger protein RNF20 is strongly expressed in 87% (379 of 424) of high-grade serous ovarian cancer (HGSOC) (1). In contrast, other tumors, including breast, metastatic prostate and colorectal cancer, have been reported to show a decrease in RNF20 transcript levels. The Cancer Genome Atlas has reported &amp;lt; 1% (3 of 316) HGSOCs with RNF20 missense variants of unknown pathogenicity. Given the high level of RNF20 expression in HGSOC, it is unlikely that RNF20 transcript levels are reduced in these tumors. RNF20 functioning in a heterodimer with RNF40 is the main E3 ligase complex responsible for monoubiquitination of histone H2B at lysine 120 (H2Bub1) (2). This active histone mark leads to an open chromatin configuration favouring DNA access by transcriptional complexes and DNA repair proteins. The RNF20/RNF40 complex also monoubiquitinates and stabilizes the Eg5 motor protein that functions in spindle assembly during mitosis, preventing spindle assembly defects, cell cycle arrest and apoptosis. RNF20 has also been implicated in polyubiquitination of the tumor suppressor Ebp1, promoting its degradation via the 26S proteasome in malignant cells. We have down-regulated RNF20 in ovarian cancer cell lines to investigate the potential of targeting this E3 ligase to overcome resistance to platinum therapies that is a major problem for the clinical management of women with ovarian cancer. Cell lines studied included the HGSOC lines; COV318, OVCAR-3, OVCAR-4, CaOV3, HEY and OVSAHO, as well as the endometrioid line A2780. Cells were studied as monolayers and spheroid cultures. We have shown that down-regulation of RNF20 leads to lower levels of H2Bub1, consistent with a more closed chromatin configuration. Clonogenic cell survival assays following the treatment of ovarian cancer cell lines with cisplatin showed an impaired ability of cells in which RNF20 had been down-regulated to form colonies. This work provides preliminary evidence that developing strategies to therapeutically down-regulate RNF20 may increase the efficacy of standard-of-care chemotherapy for women with ovarian cancer. (1) Dickson KA et al., Hum Mol Genet (2016) (2) Cole AJ et al., Endocr Relat Cancer (2015) Citation Format: Alexander J. Cole, Kristie-Ann Dickson, Roderick Clifton-Bligh, Deborah J. Marsh. Targeting the E3 ubiquitin ligase RNF20 in ovarian 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 3538.
Unfolding the mystery of digestive enzyme misfolding in chronic pancreatitis
Authors: Jonas Rosendahl
Journal: Gut (2018)

In Gut , Hegyi and Sahin-Toth report the first reliable mouse model of chronic pancreatitis (CP).1 More than six decades ago, the first pedigree of a family with inherited CP was published. Nevertheless, it lasted until now that the first reliable animal model of the disease was established. Whereas the first genetic associations were found to reside in the cationic trypsinogen gene ( PRSS1 ), Hegyi and Sahin-Toth developed an animal model with the frequent p.N256K mutation in Carboxypeptidase A1 ( CPA1 ).2 3 Besides PRSS1 alterations, mutations in CPA1 harbour the second largest effect size for the development of CP (see also http://www.pancreasgenetics.org/) and therefore represent reasonable candidates for an animal model. In addition, the detection of CPA1 mutations in CP provided new mechanistic insights into the pathogenesis, but also reinforced the current notion that digestive proteases play a critical role in CP. The presented model is a knock-in of the human mutation into the Cpa1 mouse locus and exhibits spontaneous hallmarks of CP like fibrosis and acinar-ductal metaplasia. …
Analysis by Early Angiography of Right Internal Thoracic Artery Grafting Via the Transverse Sinus
Authors: MasashiUra, RyuzoSakata, YoshihiroNakayama, YoshioArai, ShuichiOshima, KatsuoNoda
Journal: Circulation (2000)

Background—There has been debate regarding whether technically demanding right internal thoracic artery (RITA) grafting via the transverse sinus can be extensively applied to patients in high-risk groups, such as patients with a small body size, elderly patients, and woman with relatively smaller coronary artery and internal thoracic artery (ITA) diameters. Methods and Results—Of the 1456 patients who underwent isolated coronary artery bypass grafting between January 1989 and December 1998 at Kumamoto Central Hospital, 393 patients (mean age, 62.4±9.0 years) with the RITA anastomosed to the major branches of the circumflex artery were studied. Left ITA grafting was performed in 384 patients, and in 369, the in situ left ITA was anastomosed to the left anterior descending coronary artery using standard methods. Early postoperative angiography was performed in 381 patients. The RITA was occluded in 4 patients, and string-like artery and significant stenosis were present in 11 and 7 patients, respectively; R...
Correction: Annular PIP3 accumulation controls actin architecture and modulates cytotoxicity at the immunological synapse
Authors: Audrey Le Floc’h, Yoshihiko Tanaka, Niels S. Bantilan, Guillaume Voisinne, Grégoire Altan-Bonnet, Yoshinori Fukui, Morgan Huse
Journal: The Journal of Experimental Medicine (2017)