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https://www.readbyqxmd.com/read/29915817/platination-of-cysteine-by-an-epidermal-growth-factor-receptor-kinase-targeted-hybrid-agent
#1
Mu Yang, Hanzhi Wu, Julie Chu, Lucas A Gabriel, Y Kim, Karen S Anderson, Cristina M Furdui, Ulrich Bierbach
Hybrid molecules have been developed which are comprised of a tyrosine kinase-targeted, quinazoline-based scaffold and a flexibly linked dia(m)minechloridoPt(ii) moiety. The target compounds maintain high affinity and selectivity for ErbB family kinase proteins and one of the derivatives induces platinum adducts with a pharmacologically important cysteine residue.
June 19, 2018: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/29914238/egfr-mutation-is-associated-with-short-progression-free-survival-in-patients-with-stage-iii-non-squamous-cell-lung-cancer-treated-with-concurrent-chemoradiotherapy
#2
Song Ee Park, Jae Myoung Noh, You Jin Kim, Han Sang Lee, Jang Ho Cho, Sung Won Lim, Yong Chan Ahn, Hongryull Pyo, Yoon-La Choi, Joungho Han, Jong-Mu Sun, Se Hoon Lee, Jin Seok Ahn, Keunchil Park, Myung-Ju Ahn
Purpose: This study was conducted to evaluate the relationship between epidermal growth factor receptor (EGFR) mutation and clinical outcomes in patients with stage III non-squamous cell lung cancer treated with definitive concurrent chemoradiotherapy (CCRT). Materials and Methods: From January 2008 to December 2013, the medical records of 197 patients with stage III non- squamous non-small cell lung cancer (NSCLC) treated with definitive CCRT were analyzed to determine progression free survival (PFS) and overall survival (OS) according to EGFR mutation status...
June 18, 2018: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/29913911/buprenorphine-clinically-useful-but-often-misunderstood
#3
Stephen Butler
Background There are a number of false myths about buprenorphine based on unconfirmed animal data, even from isolated animal organs, and early clinical research. These myths came into textbooks on pharmacology and pain about 30 years ago and have been difficult to eradicate. Animal models of pain and pain relief are notoriously unreliable as predictors of human clinical effects. The fact is that in clinical practice there is NO bell-shaped dose-response curve, there is NO plateau on the dose-response curve, and there is NO antagonist effect from buprenorphine on other mu-opioid agonists...
December 29, 2017: Scandinavian Journal of Pain
https://www.readbyqxmd.com/read/29913825/genetic-variation-in-opioid-receptor-genes-and-sensitivity-to-experimental-pain-in-male-and-female-healthy-volunteers
#4
A E Olesen, J Droney, H Sato, J R Ross, C Staahl, T Andresen, R Branford, J Riley, A M Drewes
Background/aims Pain is a common problem which significantly impacts on quality of life. Clinical pain is complicated to study due to numerous confounding variables. Normal volunteer models use standardised painful stimuli with resulting reduced phenotype variability. Current studies suggest an association between genetic variability and pain sensitivity. Methods Data from 50 healthy volunteers in three studies of multi-modal, multi-tissue experimental pain stimulation were included. Skin heat, muscle cuff pressure and visceral pressure were analysed...
December 29, 2017: Scandinavian Journal of Pain
https://www.readbyqxmd.com/read/29913155/antifibrotic-role-of-pgc-1%C3%AE-sirna-against-tgf-%C3%AE-1-induced-renal-interstitial-fibrosis
#5
Jue-Long Wang, Chin-Wang Chen, Mu-Rou Tsai, Shu-Fen Liu, Tsuing-Jeu Hung, Yu-Ju-Hung, Wen-Teng Chang, Ming-Der Shi, Pei-Fang Hsieh, Yu-Lin Yang
Peroxisome proliferator-activated receptor coactivator-1 alpha (PGC-1α) is a transcriptional coactivator that regulates energy metabolism and mitochondrial biogenesis. Recently, mitochondrial dysfunction has been indicated as an established risk factor for the development of renal fibrosis. However, whether PGC-1α is involved in the pathogenesis of renal fibrosis is unknown. In this study, we treated NRK-49F (normal rat kidney fibroblast) cells with transforming growth factor-beta 1 (TGF-β1) for 24h to establish an in vitro fibrosis model...
June 15, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29909020/diet-modifies-colonic-microbiota-and-cd4-t-cell-repertoire-to-induce-flares-of-colitis-in-mice-with-myeloid-cell-expression-of-interleukin-23
#6
Lili Chen, Zhengxiang He, Alina Cornelia Iuga, Sebastião N Martins Filho, Jeremiah J Faith, Jose C Clemente, Madhura Deshpande, Anitha Jayaprakash, Jean-Frederic Colombel, Juan J Lafaille, Ravi Sachidanandam, Glaucia C Furtado, Sergio A Lira
BACKGROUND & AIMS: Several studies have shown that signaling via the interleukin 23 (IL23) receptor is required for development of colitis. We studied the roles of IL23, dietary factors, alterations to the microbiota, and T cells in development and progression of colitis in mice. METHODS: All mice were maintained on lab diet 5053, unless otherwise noted. We generated mice that express IL23 in CX3CR1-positive myeloid cells (R23FR mice) upon cyclic administration of tamoxifen dissolved in diet 2019...
June 14, 2018: Gastroenterology
https://www.readbyqxmd.com/read/29899398/touch-induced-face-conditioning-is-mediated-by-genetic-variation-in-opioid-but-not-oxytocin-receptors
#7
Yu Fu, Emre Selcuk, Sarah R Moore, Richard A Depue
Soft touch possesses strong prosocial effects that facilitate social bonding and group cohesion in animals. Touch activates opioids (OP) and oxytocin (OXT), two neuromodulators involved in affiliative behaviors and social bonding. We examined whether touch serves as an unconditioned reward in affective conditioning of human faces, a basic process in social bonding, and whether this process is mediated by variation in mu-OP (OPRM1) and OXT (rs53576) receptor genes. Participants viewed affectively-neutral human faces, half of which were paired with a brief soft brushing on the forearm as an unconditioned stimulus (US)...
June 13, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29898592/efficacy-and-safety-of-afatinib-for-egfr-mutant-non-small-cell-lung-cancer-compared-with-gefitinib-or-erlotinib
#8
Youjin Kim, Se-Hoon Lee, Jin Seok Ahn, Myung-Ju Ahn, Keunchil Park, Jong-Mu Sun
Purpose: We tried to evaluate whether there is any specific features in treatment outcomes of first-line afatinib in patients with epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC), compared with gefitinib or erlotinib. Materials and Methods: We analyzed patients treated with first-line afatinib, gefitinib, or erlotinib for advanced EGFR-mutant NSCLC at Samsung Medical Center between 2014 and 2016. Results: In total, 467 patients received first-line afatinib (n=165), gefitinib (n=230), or erlotinib (n=72)...
June 13, 2018: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/29884613/assessing-the-efficacy-of-peripherally-acting-mu-opioid-receptor-antagonists-pamoras-in-the-treatment-of-opioid-induced-constipation
#9
Victor Chedid, Michael Camilleri
No abstract text is available yet for this article.
June 8, 2018: Gut
https://www.readbyqxmd.com/read/29883897/overexpression-of-atpyl5-under-the-control-of-guard-cell-specific-promoter-improves-drought-stress-tolerance-in-arabidopsis
#10
Wenli Quan, Yuanlei Hu, Zixin Mu, Haitao Shi, Zhulong Chan
PYR/PYLs function as ABA receptors and are key regulators during plant drought stress response. Previously we screened drought tolerance of Arabidopsis ABA receptors PYR/PYLs under the control of five different promoters. In this study, we characterized drought stress tolerance of AtPYL5 transgene under the control of one guard cell specific promoter, pGC1. pGC1::AtPYL5 transgenic Arabidopsis exhibited reduced transpiration rate and decreased water loss after drought treatment. Transformation of pGC1::AtPYL5 in Arabidopsis also decreased oxidative stress damage and improved photosynthesis under drought stress condition...
May 31, 2018: Plant Physiology and Biochemistry: PPB
https://www.readbyqxmd.com/read/29872601/serotonin-syndrome-presenting-with-concomitant-tramadol-and-diphenhydramine-use-a-case-report-of-an-unlikely-side-effect
#11
Salman Khan, Shakir Saud, Imran Khan, Muhammad Asif, Osama Ismail, Arqam Salam, Tsu Jung Yang, Kim J Norville
Serotonin syndrome is a condition that occurs following the administration of serotonergic drugs. Interestingly, on rare occasions, it can occur with various drug combinations that can secondarily affect the serum levels of 5-hydroxytryptamin. Tramadol is an analgesic that has mu opioid receptor agonist activity and has also been shown to inhibit the reuptake of serotonin and noradrenaline. Diphenhydramine is a first-generation histamine antagonist prescribed to treat or prevent allergic reactions and can also be used as a sleeping aid...
April 4, 2018: Curēus
https://www.readbyqxmd.com/read/29860612/reinforcing-effects-of-opioid-cannabinoid-mixtures-in-rhesus-monkeys-responding-under-a-food-drug-choice-procedure
#12
David R Maguire, Charles P France
OBJECTIVE: Cannabinoid receptor agonists such as delta-9-tetrahydrocannabinol (Δ9 -THC) enhance the antinociceptive potency of mu opioid receptor agonists such as morphine, indicating that opioid/cannabinoid mixtures might be effective for treating pain. However, such enhancement will be beneficial only if cannabinoids do not also enhance adverse effects of opioids, including those related to abuse. In rhesus monkeys, cannabinoids fail to enhance and often decrease self-administration of the mu opioid receptor agonist heroin, suggesting that opioid/cannabinoid mixtures do not have greater reinforcing effects (abuse potential) compared with opioids alone...
June 3, 2018: Psychopharmacology
https://www.readbyqxmd.com/read/29858157/cyclic-biphalin-analogues-with-a-novel-linker-lead-to-potent-agonist-activities-at-mu-delta-and-kappa-opioid-receptors
#13
Michael Remesic, Giorgia Macedonio, Adriano Mollica, Frank Porreca, Victor Hruby, Yeon Sun Lee
In an effort to improve biphalin's potency and efficacy at the µ-(MOR) and δ-opioid receptors (DOR), a series of cyclic biphalin analogues 1-5 with a cystamine or piperazine linker at the C-terminus were designed and synthesized by solution phase synthesis using Boc-chemistry. Interestingly, all of the analogues showed balanced opioid agonist activities at all opioid receptor subtypes due to enhanced κ-opioid receptor (KOR) activity. Our results indicate that C-terminal flexible linkers play an important role in KOR activity compared to that of the other cyclic biphalin analogues with a hydrazine linker...
May 26, 2018: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/29852083/endogenous-and-exogenous-opioids-in-pain
#14
Gregory Corder, Daniel C Castro, Michael R Bruchas, Grégory Scherrer
Opioids are the most commonly used and effective analgesic treatments for severe pain, but they have recently come under scrutiny owing to epidemic levels of abuse and overdose. These compounds act on the endogenous opioid system, which comprises four G protein-coupled receptors (mu, delta, kappa, and nociceptin) and four major peptide families (β-endorphin, enkephalins, dynorphins, and nociceptin/orphanin FQ). In this review, we first describe the functional organization and pharmacology of the endogenous opioid system...
May 31, 2018: Annual Review of Neuroscience
https://www.readbyqxmd.com/read/29849948/additive-analgesic-effect-of-dexmedetomidine-and-dezocine-administered-intrathecally-in-a-mouse-pain-model
#15
Ya-Qin Huang, Shao-Hui Guo, Renyu Liu, Sheng-Mei Zhu, Jian-Liang Sun, Yong-Xing Yao
Background: It is known that dexmedetomidine can reduce opioid requirements and that there is a synergistic effect when dexmedetomidine and morphine (a full mu opioid receptor agonist) are administered together. However, it was unclear whether a synergistic or additive effect would be observed when dexmedetomidine was co-administered with a partial mu opioid receptor agonist. The present study was designed to elucidate such effects by intrathecally co-administering dexmedetomidine and dezocine, a partial mu receptor agonist, in a mouse pain model...
May 11, 2018: Oncotarget
https://www.readbyqxmd.com/read/29849936/comparison-of-the-effects-of-the-three-major-tyrosine-kinase-inhibitors-as-first-line-therapy-for-non-small-cell-lung-cancer-harboring-epidermal-growth-factor-receptor-mutations
#16
Chih-Yen Tu, Chuan-Mu Chen, Wei-Chih Liao, Biing-Ru Wu, Chih-Yu Chen, Wei-Chun Chen, Te-Chun Hsia, Wen-Chien Cheng, Chia-Hung Chen
Introduction: Patients with advanced lung adenocarcinoma harboring epidermal growth factor receptor (EGFR)-activating mutations have good response rate and longer progression-free survival (PFS) when treated with the tyrosine kinase inhibitors (TKI) compared with platinum-based chemotherapy. However, studies comparing the effectiveness of these drugs as first-line therapy in such patients are limited. Results: We analyzed 422 patients with EGFR-mutated advanced lung adenocarcinoma receiving first-line gefitinib ( n = 195, 46...
May 11, 2018: Oncotarget
https://www.readbyqxmd.com/read/29808515/dynamic-lateral-organization-of-opioid-receptors-kappa-mu-wt-and-mu-n40d-in-the-plasma-membrane-at-the-nanoscale-level
#17
Maciej K Rogacki, Ottavia Golfetto, Steven J Tobin, Tianyi Li, Sunetra Biswas, Raphael Jorand, Huiying Zhang, Vlad Radoi, Yu Ming, Per Svenningsson, Daniel Ganjali, Devin L Wakefield, Athanasios Sideris, Alexander R Small, Lars Terenius, Tijana Jovanović-Talisman, Vladana Vukojević
Opioid receptors are important pharmacological targets for the management of numerous medical conditions (e.g. severe pain), but they are also the gateway to the development of deleterious side effects (e.g. opiate addiction). Opioid receptor signaling cascades are well characterized. However, quantitative information regarding their lateral dynamics and nano-scale organization in the plasma membrane remains limited. Since these dynamic properties are important determinants of receptor function, it is crucial to define them...
May 28, 2018: Traffic
https://www.readbyqxmd.com/read/29807405/rare-mechanism-of-acquired-resistance-to-osimertinib-in-korean-patients-with-egfr-mutated-non-small-cell-lung-cancer
#18
Jiyun Lee, Joon Ho Shim, Woong-Yang Park, Hee Kyung Kim, Jong-Mu Sun, Se-Hoon Lee, Jin Seok Ahn, Keunchil Park, Myung-Ju Ahn
Epidermal growth factor receptor (EGFR)‒tyrosine kinase inhibitors (TKIs) are effective clinical therapeutics for EGFR-mutant non-small cell lung cancer (NSCLC). Osimertinib, a third-generation EGFR TKI, has proven effective against T790M mutations. However, the vast majority of patients acquire resistance following successful treatment. A 59-year-old female metastatic NSCLC patient developed resistance after 43 weeks of osimertinib. CancerSCAN of the metastatic liver lesion revealed a EGFR C797G mutation at an allele frequency of 72%, a pre-existing T790M mutation (73%) in cis and an exon 19 deletion (87%)...
May 23, 2018: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/29795628/predicting-opioid-receptor-binding-affinity-of-pharmacologically-unclassified-designer-substances-using-molecular-docking
#19
Christopher R Ellis, Naomi L Kruhlak, Marlene T Kim, Edward G Hawkins, Lidiya Stavitskaya
Opioids represent a highly-abused and highly potent class of drugs that have become a significant threat to public safety. Often there are little to no pharmacological and toxicological data available for new, illicitly used and abused opioids, and this has resulted in a growing number of serious adverse events, including death. The large influx of new synthetic opioids permeating the street-drug market, including fentanyl and fentanyl analogs, has generated the need for a fast and effective method to evaluate the risk a substance poses to public safety...
2018: PloS One
https://www.readbyqxmd.com/read/29794614/chronic-neuropathic-pain-reduces-opioid-receptor-availability-with-associated-anhedonia-in-rat
#20
Scott J Thompson, Mark H Pitcher, Laura S Stone, Farid Tarum, Gang Niu, Xiaoyuan Chen, Dale O Kiesewetter, Petra Schweinhardt, M Catherine Bushnell
The opioid system plays a critical role in both the experience and management of pain. While acute activation of the opioid system can lead to pain relief, the effects of chronic pain on the opioid system remain opaque. Cross-sectional positron emission tomography (PET) studies show reduced availability of brain opioid receptors in chronic pain patients, but are unable to (i) determine if these changes are due to the chronic pain itself or to pre-existing or medication-induced differences in the endogenous opioid system, and (ii) identify the neurobiological substrate of reduced opioid receptor availability...
May 22, 2018: Pain
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