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https://www.readbyqxmd.com/read/28432357/in-silico-drug-discovery-approach-targeting-receptor-tyrosine-kinase-like-orphan-receptor-1-for-cancer-treatment
#1
Onkar Nath, Archana Singh, Indrakant K Singh
Receptor tyrosine kinases (RTK) are important cell signaling molecules that influence many cellular processes. Receptor tyrosine kinase such as orphan receptor 1 (Ror1), a surface antigen, is a member of the RTK family of Ror, which plays a crucial role in cancers that have high-grade histology. As Ror1 has been implicated to be a potential target for cancer therapy, we selected this protein for further investigation. The secondary and tertiary structure of this protein was determined, which revealed that this protein contained three β-sheets, seven α-helices, and coils...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28427201/wnt5a-planar-cell-polarity-signaling-pathway-in-urothelial-carcinoma-a-potential-prognostic-biomarker
#2
Mark Saling, Jordan K Duckett, Ian Ackers, Karen Coschigano, Scott Jenkinson, Ramiro Malgor
Bladder cancer is the fourth most common cancer in men and the most common malignancy of the urinary tract. Bladder cancers detected at an early stage have a very high five-year survival rate, but when detected after local metastasis the rate is only about 50%. Our group recently reported a positive correlation between the expression of Wnt5a, a member of the Wnt proteins family, and histopathological grade and stage of urothelial carcinoma (UC). The objective of this study was to analyze UC cases reported in Athens, Ohio and investigate the major components of Wnt5a / planar cell polarity (PCP) signaling pathway in UC human tissue samples and UC cell lines...
March 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423537/limitations-in-predicting-pam50-intrinsic-subtype-and-risk-of-relapse-score-with-ki67-in-estrogen-receptor-positive-her2-negative-breast-cancer
#3
Aranzazu Fernandez-Martinez, Tomás Pascual, Giuseppe Perrone, Serafin Morales, Juan de la Haba, Milagros González-Rivera, Patricia Galván, Francesca Zalfa, Michela Amato, Lucia Gonzalez, Miquel Prats, Federico Rojo, Luis Manso, Laia Paré, Immaculada Alonso, Joan Albanell, Ana Vivancos, Antonio González, Judit Matito, Sonia González, Pedro Fernandez, Barbara Adamo, Montserrat Muñoz, Margarita Viladot, Carme Font, Francisco Aya, Maria Vidal, Rosalía Caballero, Eva Carrasco, Vittorio Altomare, Giuseppe Tonini, Aleix Prat, Miguel Martin
PAM50/Prosigna gene expression-based assay identifies three categorical risk of relapse groups (ROR-low, ROR-intermediate and ROR-high) in post-menopausal patients with estrogen receptor estrogen receptor-positive (ER+)/ HER2-negative (HER2-) early breast cancer. Low risk patients might not need adjuvant chemotherapy since their risk of distant relapse at 10-years is below 10% with endocrine therapy only. In this study, 517 consecutive patients with ER+/HER2- and node-negative disease were evaluated for Ki67 and Prosigna...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28420863/changes-of-systemic-immune-response-after-stereotactic-ablative-radiotherapy-sabr-first-results-of-a-prospective-study-in-early-lung-cancer-patients
#4
Jacek Rutkowski, Tomasz Ślebioda, Zbigniew Kmieć, Renata Zaucha
INTRODUCTION    Among all lung tumors non-small cell lung cancer (NSCLC) is the most common. Conventional conservative treatment in medically inoperable patients with early stage NSCLC has a poor outcome. To improve treatment efficacy stereotactic ablative radiotherapy (SABR) has been developed to enable the delivery of high-dose radiation to the tumor.  OBJECTIVES    This prospective study was conducted to confirm the hypothesis that a sudden death of cancer cells after SABR may lead to systemic immune response changes...
April 18, 2017: Polish Archives of Internal Medicine
https://www.readbyqxmd.com/read/28408486/targeting-ror1-identifies-new-treatment-strategies-in-hematological-cancers
#5
REVIEW
Hanna Karvonen, Wilhelmiina Niininen, Astrid Murumägi, Daniela Ungureanu
Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is a member of the ROR receptor family consisting of two closely related type I transmembrane proteins ROR1 and ROR2. Owing to mutations in their canonical motifs required for proper kinase activity, RORs are classified as pseudokinases lacking detectable catalytic activity. ROR1 stands out for its selective and high expression in numerous blood and solid malignancies compared with a minimal expression in healthy adult tissues, suggesting high potential for this molecule as a drug target for cancer therapy...
April 15, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28388536/long-noncoding-rna-ror-regulates-chemoresistance-in-docetaxel-resistant-lung-adenocarcinoma-cells-via-epithelial-mesenchymal-transition-pathway
#6
Yan Pan, Jing Chen, Leilei Tao, Kai Zhang, Rui Wang, Xiaoyuan Chu, Longbang Chen
Emerging evidence indicates that the dysregulation of long non-coding RNAs (lncRNAs) contributes to the development and progression of lung adenocarcinoma (LAD), however the underlying mechanism of action of lncRNAs remains unclear. It is well known that the effective treatment of cancers has been hindered by drug resistance in the clinical setting. Epithelial-mesenchymal transition (EMT) has been recognized to be involved in acquiring drug resistance, cell migration and invasion properties in several types of cancer...
March 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28376483/long-non-coding-rnas-in-cardiac-remodeling
#7
Shutong Shen, Huimin Jiang, Yihua Bei, Junjie Xiao, Xinli Li
Cardiac remodeling occurs after stress to the heart, manifested as pathological processes, including hypertrophy and apoptosis of cardiomyocytes, dysfunction of vascular endothelial cells and vascular smooth muscle cells as well as differentiation and proliferation of fibroblasts, ultimately resulting in progression of cardiovascular diseases. Emerging evidence has revealed that long non-coding RNAs (lncRNAs) acted as powerful and dynamic modifiers of cardiac remodeling. LncRNAs including Chaer, Chast, Mhrt, CHRF, ROR, H19, and MIAT have been implicated in cardiac hypertrophy while NRF, H19, APF, CARL, UCA, Mhrt and several other lncRNAs (n379599, n379519, n384640, n380433 and n410105) in cardiomyocyte loss and extracellular matrix remodeling...
April 3, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28376277/dendritic-cells-from-rheumatoid-arthritis-patient-peripheral-blood-induce-th17-cell-differentiation-via-mir-363-integrin-%C3%AE-v-tgf-%C3%AE-axis
#8
Feng Pan, Haiyan Xiang, Juzhen Yan, Liquan Hong, Lahong Zhang, Yuhua Liu, Xiao Feng, Chengsong Cai
BACKGROUND AND AIM: Dendritic cells (DCs) are critical regulators of immune responses. This study was to observe the effect of DCs from peripheral blood on the differentiation of Th17 in rheumatoid arthritis (RA) patients. METHODS AND RESULTS: Peripheral blood samples were collected from 30 RA patients and 20 healthy controls, respectively. Flow cytometry results showed that in contrast with Treg cells, the proportion of Th17 cells in T cells and the Th17/Treg ratio were both increased in RA patients...
April 4, 2017: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/28360114/ror%C3%AE-dependent-type-2-innate-lymphoid-cells-are-required-and-sufficient-for-mucous-metaplasia-in-immature-mice
#9
Charu Rajput, Tracy X Cui, Mingyuan Han, Jing Lei, Joanna L Hinde, Qian Wu, J Kelley Bentley, Marc B Hershenson
Early-life wheezing associated respiratory tract infection by rhinovirus (RV) is considered a risk factor for asthma development. We have shown that RV infection of 6 day-old BALB/c mice, but not mature mice, induces an asthma-like phenotype which is associated with an increase in the population of type 2 innate lymphoid cells (ILC2s) and dependent on IL-13 and IL-25. We hypothesize that ILC2s are required and sufficient for development of the asthma-like phenotype in immature mice. Mice were infected with RV1B on day 6 of life and treated with vehicle or a chemical inhibitor of retinoic acid receptor-related orphan receptor (ROR)-α, SR3335 (15 mg/kg/day intraperitoneally for 7 days)...
March 30, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28342318/distinct-patterns-of-stromal-and-tumor-expression-of-ror1-and-ror2-in-histological-subtypes-of-epithelial-ovarian-cancer
#10
C E Henry, C Emmanuel, N Lambie, C Loo, B Kan, C J Kennedy, A de Fazio, N F Hacker, C E Ford
OBJECTIVE: The ROR1 and ROR2 receptor tyrosine kinases have both been implicated in ovarian cancer progression and have been shown to drive migration and invasion. There is an increasing importance of the role of stroma in ovarian cancer metastasis; however, neither ROR1 nor ROR2 expression in tumor or stromal cells has been analyzed in the same clinical cohort. AIM: To determine ROR1 and ROR2 expression in ovarian cancer and surrounding microenvironment and examine associations with clinicopathological characteristics...
March 22, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28342119/returns-to-operating-room-after-colon-and-rectal-surgery-in-a-tertiary-care-academic-medical-center-a-valid-measure-of-surgical-quality
#11
Amy L Lightner, Amy E Glasgow, Elizabeth B Habermann, Robert R Cima
INTRODUCTION: Returns to the operating room (ROR) have been suggested as a marker of surgical quality. Increasingly, quality and value metrics are utilized for reimbursement as well as public reporting to inform health care consumers. We sought to understand the etiology of ROR and assess the validity of simple ROR as a quality metric. METHODS: This was a single referral center retrospective review of all colon and rectal operations between January 1, 2014 and December 31, 2014...
March 24, 2017: Journal of Gastrointestinal Surgery: Official Journal of the Society for Surgery of the Alimentary Tract
https://www.readbyqxmd.com/read/28334592/using-an-electronic-perioperative-documentation-tool-to-identify-returns-to-operating-room-ror-in-a-tertiary-care-academic-medical-center
#12
Robert R Cima, Sarah R Dhanorker, Christopher L Ostendorf, Mfonabasi Ntekpe, Raghu V Mudundi, Elizabeth B Habermann, Claude Deschamps
BACKGROUND: The metric "Unplanned returns to operating room (ROR)" is being tracked in surgical quality dashboards; 70% of unplanned RORs may be related to surgical complications. With increasing regionalization of trauma and complex surgical care at tertiary care academic centers, it is unclear if a simple ROR metric is a valid assessment of surgical quality at such centers. METHOD: A real-time electronic tool was used to identify all RORs-planned and unplanned-in a high-volume, high-complexity academic surgical practice at Mayo Clinic-Rochester within 45 days of the index operation...
March 2017: Joint Commission Journal on Quality and Patient Safety
https://www.readbyqxmd.com/read/28328317/antiproliferative-and-apoptotic-effects-of-novel-anti-ror1-single-chain-antibodies-in-hematological-malignancies
#13
Leili Aghebati-Maleki, Vahid Younesi, Behzad Baradaran, Jalal Abdolalizadeh, Morteza Motallebnezhad, Hamid Nickho, Dariush Shanehbandi, Jafar Majidi, Mehdi Yousefi
Receptor tyrosine kinase-like orphan receptor (ROR) proteins are a conserved family of tyrosine kinase receptors that function in developmental processes including cell survival, differentiation, cell migration, cell communication, cell polarity, proliferation, metabolism, and angiogenesis. ROR1 has recently been shown to be expressed in various types of cancer cells but not normal cells. Pharmacokinetics and pharmacodynamics of single-chain Fragment variable (scFv) antibodies provide potential therapeutic advantages over whole antibody molecules...
April 2017: SLAS Discovery
https://www.readbyqxmd.com/read/28300347/assessing-finasteride-associated-sexual-dysfunction-using-the-faers-database
#14
A K Gupta, J Carviel, M A MacLeod, N Shear
BACKGROUND: Postmarketing reports suggest that finasteride causes sexual dysfunction despite a low incidence reported in clinical trials. Therefore, the extent of risk remains unknown. OBJECTIVE: To determine whether the risk of sexual dysfunction is higher among individuals treated with finasteride compared to a baseline risk for all other drugs using the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database. METHODS: A case by non-case disproportionality approach was used whereby a reporting odds ratio (ROR) with 95% confidence interval (CI) was calculated...
March 16, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28293930/anti-interleukin-9-antibody-increases-the-effect-of-allergen-specific-immunotherapy-in-murine-allergic-rhinitis
#15
Ji Hyeon Shin, Do Hyun Kim, Boo Young Kim, Sung Won Kim, Se Hwan Hwang, Joohyung Lee, Soo Whan Kim
PURPOSE: Interleukin (IL)-9 induces allergic responses; however, the roles of anti-IL-9 antibody in the induction of tolerance remain unclear. This study investigated the effects of anti-IL-9 antibody on oral tolerance (OT) in a mouse model of allergic rhinitis (AR). METHODS: BALB/c mice were divided into 4 groups: the control, AR, OT, and OT with anti-IL-9 antibody (OT+IL9AB) groups. Ovalbumin (OVA) was used for sensitization and challenge. Mice in the OT and OT+IL9AB groups were fed OVA for immunotherapy...
May 2017: Allergy, Asthma & Immunology Research
https://www.readbyqxmd.com/read/28288150/-unknown-title
#16
Janneke Dekker, Stuart B Hooper, Jeroen J van Vonderen, Ruben Sgm Witlox, Enrico Lopriore, Arjan B Te Pas
BACKGROUND: Caffeine promotes spontaneous breathing by antagonizing adenosine. We assessed the direct effect of caffeine on respiratory effort in preterm infants at birth. METHODS: Thirty infants of 24-30 weeks of gestation were randomized for receiving caffeine directly after birth in the delivery room (caffeine DR-group) or later in the neonatal intensive care unit (control-group). Primary outcome was respiratory effort, expressed as minute volume, tidal volumes, respiratory rate, rate of rise to maximum tidal volume and recruitment breaths at 7-9 minutes after birth...
March 13, 2017: Pediatric Research
https://www.readbyqxmd.com/read/28268204/an-empirical-analysis-of-run-off-road-injury-severity-crashes-involving-large-trucks
#17
Nabeel Saleem Saad Al-Bdairi, Salvador Hernandez
In recent years, there has been an increasing interest in understanding the contributory factors to run-off-road (ROR) crashes in the US, especially those where large trucks are involved. Although there have been several efforts to understand large-truck crashes, the relationship between crash factors, crash severity, and ROR crashes is not clearly understood. The intent of this research is to develop statistical models that provide additional insight into the effects that various contributory factors related to the person (driver), vehicle, crash, roadway, and environment have on ROR injury severity...
March 4, 2017: Accident; Analysis and Prevention
https://www.readbyqxmd.com/read/28260984/age-related-trends-in-injection-site-reaction-incidence-induced-by-the-tumor-necrosis-factor-%C3%AE-tnf-%C3%AE-inhibitors-etanercept-and-adalimumab-the-food-and-drug-administration-adverse-event-reporting-system-2004-2015
#18
Toshinobu Matsui, Ryogo Umetsu, Yamato Kato, Yuuki Hane, Sayaka Sasaoka, Yumi Motooka, Haruna Hatahira, Junko Abe, Akiho Fukuda, Misa Naganuma, Yasutomi Kinosada, Mitsuhiro Nakamura
Tumor necrosis factor-α (TNF-α) inhibitors are increasingly being used as treatment for rheumatoid arthritis (RA). However, the administration of these drugs carries the risk of inducing injection site reaction (ISR). ISR gives rise to patient stress, nervousness, and a decrease in quality of life (QoL). In order to alleviate pain and other symptoms, early countermeasures must be taken against this adverse event. In order to improve understanding of the risk factors contributing to the induction of ISR, we evaluated the association between TNF-α inhibitors and ISR by applying a logistic regression model to age-stratified data obtained from the Food and Drug Administration Adverse Event Reporting System (FAERS) database...
2017: International Journal of Medical Sciences
https://www.readbyqxmd.com/read/28252249/the-isoxazole-ring-and-its-n-oxide-a-privileged-core-structure-in-neuropsychiatric-therapeutics
#19
REVIEW
George N Pairas, Fereniki Perperopoulou, Petros G Tsoungas, George Varvounis
Mental disorders are neuropsychiatric conditions that are marked by unusual or irregular thinking, feelings, or behavior, and lead to distress and/or impaired functions. Major psychiatric conditions are depression, anxiety, and psychoses of various types. Their etiopathogeneses, of a primary or secondary origin, are associated with genetic and environmental factors. They are commonly treated with psychoactive drugs (also known as psychotropics), which target serotonin, dopamine, norepinephrine, glutamate, and nuclear receptors (NRs), including retinoic acid receptor-related orphan receptors (RORs) and other receptors in the central nervous system (CNS)...
March 2, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28242276/synthesis-of-dihydroimidazole-tethered-imidazolinethiones-and-their-activity-as-novel-antagonists-of-the-nuclear-retinoic-acid-receptor-related-orphan-receptors-rors
#20
Adel Nefzi, Guya D Marconi, Maria A Ortiz, Jennifer C Davis, F Javier Piedrafita
Targeting the transcriptional activity of nuclear hormone receptors has proven an effective strategy to treat certain human diseases, and they have become a major focus point to develop novel therapies for the treatment of cancer, inflammation, autoimmune diseases, metabolic disorders, and others. One family of nuclear receptors that has attracted most interest in recent years is the retinoic acid receptor-related orphan receptors (RORs), in particular RORγ. RORγ is a critical regulator of the immune system and RORγ antagonists have shown activity in animal models of inflammatory autoimmune diseases...
April 1, 2017: Bioorganic & Medicinal Chemistry Letters
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