tbuckley/cabot-search huggingface dataset:
Focus on the road to modelling cardiomyopathy in muscular dystrophy
Authors: Francesco Canonico, Maila Chirivi, Fabio Maiullari, Marika Milan, Roberto Rizzi, Alessandra Arcudi, Mattia Galli, Marika Pane, Aoife Gowran, Giulio Pompilio, Eugenio Mercuri, Filippo Crea, Claudia Bearzi, Domenico D’Amario
Journal: Cardiovascular Research (2021)

Alterations in the DMD gene, which codes for the protein dystrophin, cause forms of dystrophinopathies such as Duchenne muscular dystrophy, an X-linked disease. Cardiomyopathy linked to DMD mutations is becoming the leading cause of death in patients with dystrophinopathy. Since phenotypic pathophysiological mechanisms are not fully understood, the improvement and development of new disease models, considering their relative advantages and disadvantages, is essential. The application of genetic engineering approaches on induced pluripotent stem cells, such as gene-editing technology, enables the development of physiologically relevant human cell models for in vitro dystrophinopathy studies. The combination of induced pluripotent stem cells-derived cardiovascular cell types and 3D bioprinting technologies hold great promise for the study of dystrophin-linked cardiomyopathy. This combined approach enables the assessment of responses to physical or chemical stimuli, and the influence of pharmaceutical approaches. The critical objective of in vitro microphysiological systems is to more accurately reproduce the microenvironment observed in vivo. Ground-breaking methodology involving the connection of multiple microphysiological systems comprised of different tissues would represent a move toward precision body-on-chip disease modelling could lead to a critical expansion in what is known about inter-organ responses to disease and novel therapies that have the potential to replace animal models. In this review, we will focus on the generation, development, and application of current cellular, animal, and potential for bio-printed models, in the study of the pathophysiological mechanisms underlying dystrophin-linked cardiomyopathy in the direction of personalized medicine.
Abstract 2147: Discovering novel targets for adenoid cystic carcinoma of the lacrimal gland
Authors: Acadia H. Moeyersoms, Vasileios Stathias, Michelle Zhang, Ryan A. Gallo, David T. Tse, Daniel Pelaez
Journal: Cancer Research (2021)

Abstract Lacrimal gland adenoid cystic carcinoma is a rare but highly lethal indolent cancer originating in the cells of secretory glands, primarily of the head and neck. With the 10-year survival rate of 20%, the only life extending technique is to remove the eye and surrounding socket contents entirely. Despite radical treatment, ACC is a very slow growing tumor and most patients will present with metastatic disease to the brain, lung, liver, or bones several years out from initial diagnosis and before symptoms are noticeable. Due to the rarity of LGACC, it is not well understood, but extensive genome analysis of ACC of the head and neck has previously uncovered a high mutation rate of MYB and NOTCH in patient samples, though unfortunately neither can be directly targeted by drugs. We have RNA sequencing data for 7 primary LGACC tumors, mass spectrometry data for 12 primary tumors and RNA sequencing for 15 cell lines derived from tumors to discover possible targetable biomarkers in LGACC and to further understand the biology of these tumors. Our analysis has revealed the signatures and drivers of LGACC, most significantly involving extracellular matrix mechanisms including HAPLN1, FABP7, and VCAN. We compared the genes of proteins differentially expressed in the mass spectrometry and RNA sequencing data and discovered 194 genes that were differentially expressed in both analysis types. With this extensive understanding of the molecular signatures, we used iLINCS integrated web-based platform to determine compounds that would target the differentially expressed genes. We have selected compounds based on a rubric we generated and will test them individually and in combination on LGACC cell lines to determine the best specific treatment for primary tumors and metastatic disease. Citation Format: Acadia H. Moeyersoms, Vasileios Stathias, Michelle Zhang, Ryan A. Gallo, David T. Tse, Daniel Pelaez. Discovering novel targets for adenoid cystic carcinoma of the lacrimal gland [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2147.
Endoscopic submucosal dissection of a duodenal GI stromal tumor assisted by endoloops
Authors: Marina Kim, Romy Bareket, Michel Kahaleh
Journal: Endoscopy (2021)

A 50-year-old man presented with melena, discomfort, burning, and indigestion associated with intermittent gastric outlet obstruction. Esophagogastroduodenoscopy (EGD) revealed a 4-cm pedunculated polyp extending from the pylorus to the duodenal bulb. In this case we performed a resection of the duodenal polyp using endoscopic submucosal dissection (ESD) assisted by endoloops (Olympus America, Center Valley, Pennsylvania, USA).
Abstract 10103: Pembrolizumab Induced Complete Heart Block Associated With Myocarditis
Authors: Usama Talib, Allisa Alpert, Tatyana Sycheva
Journal: Circulation (2019)

Introduction: Pembrolizumab is rarely associated with immune mediated cardiac toxicities. We present a case of pembrolizumab-induced myocarditis & complete heart block. Case: 67-year-old female wit...
Abstract 13201: 5-Year Quality of Life Outcomes After CABG vs. PCI among Patients With 3-Vessel or Left Main Coronary Disease: Results From the SYNTAX Trial
Authors: Mouin S Abdallah, David J Cohen, Kaijun Wang, Elizabeth A Magnuson, Ruben L Osnabrugge, A. P Kappetein, Marie-Claude Morice, Friedrich A Mohr, Patrick W Serruys
Journal: Circulation (2013)

Background: Among patients with 3-vessel or left main CAD, CABG results in greater angina relief at 1 year than PCI with drug-eluting stents (DES-PCI). Whether these benefits are sustained beyond 1...
Abstract 1971: RCC2 promotes glioblastoma through regulation of G2-M progression
Authors: Tian Liu, Penelope Mei-Yu Or, Chi-Wai Wong, Wayne Lut-Heng Ho, Stanley Kwok-Kuen Cheung, Yubing Wang, Andrew M. Chan
Journal: Cancer Research (2021)

Abstract Regulator of chromatin condensation 2 (RCC2), also known as telophase disk protein of 60 kDa (TD-60), has been previously identified as a component of the chromosome passenger complex. Accumulating evidence suggested that RCC2 plays a vital role in the mitotic process and abnormal RCC2 expression is essential for cancer development including Glioblastoma Multiforme (GBM). GBM is the most lethal and frequent brain tumor. Even with the optimal therapy, the 5-year survival rate of GBM remains poor. TCGA data revealed an upregulation of RCC2 in human GBM. Our preliminary data showed that RCC2 was upregulated in PTEN knockout mice primary astrocytes, and loss of function of PTEN has been found in nearly 95% GBM patients. This indicated that RCC2 might act as a PTEN downstream regulator and promote glioblastoma progression. RCC2 has been reported to be essential for tumorigenesis which may act as a GEF for Rac1 or RalA GTPase. Coincidently, our study showed that silencing RCC2 could suppress GBM cell proliferation. Using RNA-seq, we identified 737 DEGs between control siRNA- and RCC2 siRNA-treated A1172 cells. GSEA analysis delineated G2-M progression as the most notably altered pathway by silencing RCC2. Indeed, we observed a G2-M arrest in cells with RCC2 silenced, suggesting that RCC2 is essential for G2-M progression. Additionally, the connectivity map (C-map) analysis was conducted and identified LY294002 and cephaeline as promising inhibitors for RCC2-associated gene signatures. Both LY294002 and cephaeline can synergistically inhibit glioblastoma cell viability with RCC2 silencing. In summary, our study demonstrated that RCC2 signaling is essential for GBM development. We provided evidence that RCC2 exerts a positive effect on G2-M progression. These findings may shed light on anti-RCC2 targeted therapy in GBM treatment. Funding: This work is supported by a General Research Fund grant (#14113519) from the University Grants Committee of Hong Kong. Citation Format: Tian Liu, Penelope Mei-Yu Or, Chi-Wai Wong, Wayne Lut-Heng Ho, Stanley Kwok-Kuen Cheung, Yubing Wang, Andrew M. Chan. RCC2 promotes glioblastoma through regulation of G2-M progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1971.
Bladder tumor subtype commitment occurs in carcinoma in-situ driven by key signaling pathways including ECM remodeling
Authors: A. Wullweber, R. Strick, F. Lange, D. Sikic, H. Taubert, S. Wach, B. Wullich, S. Bertz, V. Weyerer, R. Stöhr, J. Breyer, M. Burger, A. Hartmann, P. Strissel, M. Eckstein
Journal: European Urology (2021)
What is the effectiveness of surgical and non-surgical therapies in the treatment of ischemic priapism in patients with sickle cell disease? A systematic review
Authors: M. Gül, B. Luca, K. Dimitropoulos, P. Capogrosso, U. Milenkovic, A. Cocci, R. Veeratterapillay, G. Hatzichristodoulou, V. Modgil, G.I. Russo, T. Tharakan, N.C. Cilesiz, M.I. Omar, C. Bettocchi, J. Carvalho, G. Corona, T.H. Jones, A. Kadioglu, J.I. Martinez-Salamanca, E.C. Serefoglu, P. Verze, S. Minhas, A. Salonia
Journal: European Urology (2021)
Diagnosis and Treatment of Alcohol-Associated Liver Disease
Authors: Ashwani K. Singal, Philippe Mathurin
Journal: JAMA (2021)

<h3>Importance</h3> Alcohol-associated liver disease results in cirrhosis in approximately 10% to 20% of patients. In 2017, more than 2 million people had alcohol-associated cirrhosis in the US. Alcohol-associated liver disease is the primary cause of liver-related mortality and the leading indication for liver transplant, representing 40% to 50% of all liver transplant in high-income countries. <h3>Observations</h3> Steatosis, alcoholic hepatitis, and fibrosis are the 3 pathologic findings that are associated with progression to cirrhosis, with highest risk in patients with alcoholic hepatitis. The amount and duration of alcohol consumption, female sex, obesity, and specific genetic polymorphisms such as patatin-like phospholipase domain protein 3, membrane bound<i>O</i>-acyltransferase, and transmembrane 6 superfamily member 2 genes are risk factors for alcohol-associated liver disease progression. Ten-year survival of patients with alcohol-associated liver disease is 88% among those who are abstinent and 73% for those who relapse to alcohol consumption. Symptomatic alcoholic hepatitis is characterized by rapid onset of jaundice and a 30% risk of mortality 1 year after diagnosis. Severe alcoholic hepatitis, defined as a modified discriminant function score greater than or equal to 32 or Model for End-Stage Liver Disease score (starts at 6 and capped at 40; worst = 40) greater than 20, is associated with the development of acute-on-chronic liver failure and multiorgan failure. Corticosteroid therapy is associated with improved 1-month survival from 65% in untreated patients to 80% in treated patients. Early liver transplant may be appropriate in highly select patients with severe alcoholic hepatitis who do not respond to medical therapy. In patients with decompensated cirrhosis, liver transplant should be considered if the Model for End-Stage Liver Disease score remains greater than 17 after 3 months of alcohol abstinence. Between 2014 and 2019, the proportion of patients waiting for liver transplantation who had alcohol-associated liver disease increased from 22% to 40%. Alcohol-associated cirrhosis accounted for approximately 27% of 1.32 million deaths worldwide related to cirrhosis in 2017. <h3>Conclusions and Relevance</h3> Alcohol-associated liver disease is among the most common liver diseases and more than 2 million people in the US in 2017 had alcohol-associated cirrhosis. Corticosteroid therapy improves survival in select patients with severe alcoholic hepatitis. Liver transplantation is the most effective therapy in patients with decompensated liver disease.
Peroral cholecystoscopy using a multibending ultraslim endoscope through a lumen-apposing metal stent for endoscopic ultrasound-guided gallbladder drainage: a feasibility study
Authors: Hae Won Yoo, Jong Ho Moon, Yun Nah Lee, Yeon Han Song, Jae Kook Yang, Tae Hoon Lee, Sang-Woo Cha, Young Deok Cho, Sang-Heum Park
Journal: Endoscopy (2021)

Endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) using a lumen-apposing metal stent (LAMS) has rendered endoscopic gallbladder assessment through a stent possible, but an appropriate endoscope is required. We assessed the feasibility of peroral cholecystoscopy (POCC) using a multibending ultraslim endoscope passed through a LAMS after EUS-GBD.14 patients with a LAMS for EUS-GBD who consecutively underwent POCC were included. POCC was performed using a multibending endoscope inserted through the LAMS. The primary outcome was the technical success rate, defined as complete endoscopic examination of the gallbladder from the orifice of the cystic duct to the fundus. The types of intervention and adverse events were recorded.17 POCCs were performed in 14 patients. Of the 17 POCCs, 15 (88.2 %) were technically successful. Narrow-band imaging endoscopy was performed in 12 procedures (70.6 %), and cholecystoscopy-guided target biopsies were obtained in six. Gallstone extraction was performed in two patients. After POCC, all LAMSs remained stable and no adverse events were observed.POCC using a multibending ultraslim endoscope can be effectively and safely performed through a LAMS after EUS-GBD.
Phase I Dose-Escalation Study of the Dual PI3K-mTORC1/2 Inhibitor Gedatolisib in Combination with Paclitaxel and Carboplatin in Patients with Advanced Solid Tumors
Authors: Ilaria Colombo, Sofia Genta, Federica Martorana, Monia Guidi, Milo Frattini, Eleftherios Pierre Samartzis, Simone Brandt, Sheila Gaggetta, Laura Moser, Mariarosa Pascale, Tatiana Terrot, Cristiana Sessa, Anastasios Stathis
Journal: Clinical Cancer Research (2021)

Abstract Purpose: This phase I study evaluated safety, tolerability, pharmacokinetics, and preliminary activity of the PI3K/mTORC1/2 dual inhibitor gedatolisib combined with carboplatin and paclitaxel. Patients and Methods: Patients with advanced solid tumors treated with ≤ 2 prior chemotherapies received intravenous gedatolisib on days 1, 8, 15, and 22 (95, 110, or 130 mg according to dose level); carboplatin (AUC5) on day 8 (day 1 following protocol amendment); and paclitaxel at 80 mg/m2 on days 8, 15, and 22 (1, 8, and 15 after amendment), every 28 days. Patients without progressive disease after cycle 6 received maintenance gedatolisib until progression. Results: Seventeen patients were enrolled [11 ovarian (10 clear cell ovarian cancer, CCOC), 4 endometrial, 2 lung cancers]. Median number of prior chemotherapies was 1 (range, 0–2). Median number of administered cycles was 6 (range, 2–16). Dose-limiting toxicities occurred in 4 patients: 2 (cycle 2 delay due to G2–G3 neutropenia) at 110 mg leading to a change in the treatment schedule, 2 at 130 mg (G2 mucositis causing failure to deliver ≥ 75% of gedatolisib at cycle 1). The recommended phase II dose is gedatolisib 110 mg on days 1, 8, 15, and 22 with carboplatin AUC5 on day 1 and paclitaxel 80 mg/m2 on days 1, 8, and 15. The most frequent ≥G3 treatment-related adverse events were neutropenia (35%), anemia (18%), and mucositis (12%). The overall response rate was 65% (80% in CCOC). Pharmacokinetic parameters of gedatolisib were consistent with single-agent results. Conclusions: Gedatolisib combined with carboplatin and paclitaxel is tolerable, and preliminary efficacy was observed especially in CCOC.
Здорова сучасна людина: сьогодення та майбутнє
Authors: Yu.M. Stepanov, D.A. Ptushkina
Journal: GASTROENTEROLOGY (2014)

У статті розглядаються проблеми, з якими стикається сучасна людина, прагнучи здорового способу життя, зокрема харчування; перспективи розвитку дієтології у світі, в Україні за участі в цьому процесі ДУ «Інститут гастроентерології НАМН України».
Defining nosocomial transmission of Escherichia coli and antimicrobial resistance genes: a genomic surveillance study
Authors: Catherine Ludden, Francesc Coll, Theodore Gouliouris, Olivier Restif, Beth Blane, Grace A Blackwell, Narender Kumar, Plamena Naydenova, Charles Crawley, Nicholas M Brown, Julian Parkhill, Sharon J Peacock
Journal: The Lancet Microbe (2021)
Abstract 3144: Intratumor heterogeneity quantification using 3D segmentation of organoids co-culture systems
Authors: Patience Mukashyaka, Javad Noorbakhsh, Pooja Kumar, Elise Courtois, Olga Anczukow, Paul Robson, Edson Liu, Jeffrey Chuang
Journal: Cancer Research (2021)

Abstract Intratumoral heterogeneity is an essential aspect of cancer biology, as the diversity of cancer cells can increase challenges of designing effective treatment. Cancer cells within the same tumor evolve and compete for shared resources and may also respond differently to drug treatments. In previous work, by closely analyzing triple negative breast cancer xenografts, we have identified a system of closely-related subclonal populations within a tumor that respond differentially to chemotherapy. To explore the dynamics of competition and cooperation between these subclones, we derived cell lines from each and tagged them with fluorescent markers. We then co-cultured these cell lines in 3D organoids and tracked them using Opera Phenix high content screening system (3D confocal fluorescence microscopy). To determine the number of cells and the location of each subclones within organoids, we developed a 3D cell segmentation pipeline. Our pipeline relies on a two-step process where organoids are segmented first and then individual cells are detected within each organoid. Preliminary analysis of hundreds of organoids suggests that the two cell types preserve their relative ratio and sensitivity to treatment regardless of organoid size, suggesting that the system is in a state of ecological coexistence. We will present results on cellular mixing during growth and treatment and the implications for adaptive therapy ecologies in tumors. Citation Format: Patience Mukashyaka, Javad Noorbakhsh, Pooja Kumar, Elise Courtois, Olga Anczukow, Paul Robson, Edson Liu, Jeffrey Chuang. Intratumor heterogeneity quantification using 3D segmentation of organoids co-culture systems [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 3144.
Abstract 1086: Pancreatic cancer musters HER2 signaling through DUSP6 to circumvent therapeutic MAPK inhibition
Authors: Ashenafi Shiferaw Bulle
Journal: Cancer Research (2021)

Abstract Background: Oncogenic KRAS is present in almost all cases of pancreatic ductal adenocarcinoma (PDAC). The mitogen-activated protein kinase (MAPK) pathway is the most cardinal signaling cascade utilized by KRAS, but targeting RAF or MEK, the key signaling nodes within this pathway has been clincally unsuccesful, largely due to ERK reactivation. Targeting ERK kinases has recently emerged as a promising therapeutic strategy, with several ERK inhibitor combinations now ongoing in clinical trials. However, resistance to ERK inhibitionn is inevitable and should be investigated. Aim: Identify adaptive mechanisms that can be targeted to potentiate ERK inhibitors in PDAC to facilitate development of novel therapeutic combinations. Methods: Reverse-phase protein array (RPPA) was used in early-passage patient-derived cell lines (PDCLs) to identify potential resistance mechanisms. These were confirmed using RNA interference and overexpression in PDAC cell lines and PDCLs. The promising combinations were tested in heterotypic spheroid cultures and in 30 early-passaged PDAC patient-derived xenografts (PDXs). Results: RPPA showed dramatic downregulation of DUSP4 and DUSP6 protein levels following MEK and ERK inhibition in PDAC cells, which coincided with phospho-activation of HER2 and HER3. Knockdown of DUSP6, but not DUSP4, was sufficient in activating HER2. Conversely, overexpression of DUSP6 curbed HER2 and ERK activation. Combined ERK inhibitor (ulixertinib) and bortezomib was able to prevent DUSP4 and DUSP6 downregulation in vitro but was ineffective in curbing in vivo tumor growth. On the other hand, ulixertinib plus PI3K or pan-HER inhibitor afatinib is effective in PDCLs in vivo. Addition of gemcitabine greatly augmented the therapeutic efficacy of these combinations and achieved prolonged tumor suppression in several PDX models. Conclusions: Our study provided novel mechanisic insight on how PDAC cells evade MAPK inhibition via mustering HER2 signaling, as well as rational therapeutic combinations that can be readily tested in clinical trials. Keys: DUSP6, HER2, KRAS, pancreatic ductal adenocarcinoma, therapeutic resistance Citation Format: Ashenafi Shiferaw Bulle. Pancreatic cancer musters HER2 signaling through DUSP6 to circumvent therapeutic MAPK inhibition [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1086.
Longitudinal study of a SARS-CoV-2 infection in an immunocompromised patient with X-linked agammaglobulinemia
Authors: Laura Ciuffreda, José M. Lorenzo-Salazar, Julia Alcoba-Florez, Héctor Rodriguez-Pérez, Helena Gil-Campesino, Antonio Íñigo-Campos, Diego García-Martínez de Artola, Agustín Valenzuela-Fernández, Marcelino Hayek-Peraza, Susana Rojo-Alba, Marta Elena Alvarez-Argüelles, Oscar Díez-Gil, Rafaela González-Montelongo, Carlos Flores
Journal: Journal of Infection (2021)
Homeostatic functions of monocytes and interstitial lung macrophages are regulated via collagen domain-binding receptor LAIR1
Authors: Shilpa Keerthivasan, Yasin Şenbabaoğlu, Nadia Martinez-Martin, Bushra Husain, Erik Verschueren, Anne Wong, Yeqing Angela Yang, Yonglian Sun, Victoria Pham, Trent Hinkle, Yoko Oei, Shravan Madireddi, Racquel Corpuz, Lucinda Tam, Samantha Carlisle, Merone Roose-Girma, Zora Modrusan, Zhengmao Ye, James T. Koerber, Shannon J. Turley
Journal: Immunity (2021)