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Mu-opioid receptor cancer

Raphael Jorand, Sunetra Biswas, Devin L Wakefield, Steven J Tobin, Ottavia Golfetto, Kelsey Hilton, Michelle Ko, Joe W Ramos, Alexander R Small, Peiguo Chu, Gagandeep Singh, Tijana Jovanovic-Talisman
Pancreatic ductal adenocarcinoma (PDAC), a particularly aggressive malignancy, has been linked to atypical levels, certain mutations, and aberrant signaling of G-protein-coupled receptors (GPCRs). GPCRs have been challenging to target in cancer because they organize into complex networks in tumor cells. To dissect such networks with nanometer-scale precision, here we combine traditional biochemical approaches with superresolution microscopy methods. A novel interaction specific to PDAC is identified between mu opioid receptor (MOR) and somatostatin receptor 2 (SSTR2)...
November 7, 2016: Molecular Biology of the Cell
Masanori Mori, Yongli Ji, Santosh Kumar, Takamaru Ashikaga, Steven Ades
BACKGROUND: Methylnaltrexone is a peripherally acting mu-opioid receptor antagonist that has been shown to relieve severe opioid-induced constipation (OIC) in patients with advanced disease receiving palliative care. Its efficacy remains unknown in cancer patients who are not terminally ill. The primary aim of this study was to evaluate the efficacy of methylnaltrexone over 48 h in cancer patients who were not terminally ill. METHODS: In this single-dose phase II trial, cancer patients with a prognosis of ≥3 months and OIC with <3 laxations during the preceding week were eligible...
September 15, 2016: International Journal of Clinical Oncology
Chung-Sik Oh, Seung-Hyun Lee, Young-Bum Yoo, Jung-Hyun Yang, Seong-Hyop Kim
Distribution of A118G single nucleotide polymorphism (SNP) in the mu-opioid receptor 1 gene (OPRM1) differs with ethnicity. We assessed the distribution of this SNP in Korean women with breast cancer and compared it with that in women of other ethnicities with breast cancer. Distribution of SNP genotypes was as follows: 49.8% for AG genotype, 40.6% for AA genotype, and 9.6% for GG genotype. Logistic regression analysis showed a negative association between the presence of the G allele at position 118 of OPRM1 and breast cancer in the studied population (odds ratios [OR], 0...
June 2016: Journal of Breast Cancer
Renee M Holder, Diane Rhee
Opioid analgesics are frequently prescribed and play an important role in chronic pain management. Opioid-induced bowel dysfunction, which includes constipation, hardened stool, incomplete evacuation, gas, and nausea and vomiting, is the most common adverse event associated with opioid use. Mu-opioid receptors are specifically responsible for opioid-induced bowel dysfunction, resulting in reduced peristaltic and secretory actions. Agents that reverse these actions in the bowel without reversing pain control in the central nervous system may be preferred over traditional laxatives...
March 2016: Pharmacotherapy
(no author information available yet)
No abstract text is available yet for this article.
August 2015: New York State Dental Journal
Sudheesh Pilakka-Kanthikeel, Madhavan P N Nair
MicroRNAs (miRNAs), the post-transcriptional regulators of gene expression, play key roles in modulating many cellular processes. The changes in the expression profiles of several specific miRNAs affect the interactions between miRNA and their targets in various illnesses, including addiction, HIV, cancer etc. The presence of anti-HIV-1 microRNAs (which regulate the level of infectivity of HIV-1) have been validated in the cells which are the primary targets of HIV infection. Drugs of abuse impair the intracellular innate anti-HIV mechanism(s) in monocytes, contributing to cell susceptibility to HIV infection...
2015: Frontiers in Microbiology
Philip J Wiffen, Sheena Derry, Katrien Naessens, Rae F Bell
BACKGROUND: A large proportion of people with advanced cancer will experience moderate to severe pain. Tapentadol is a novel, centrally acting analgesic medicine acting at the μ-opioid receptor and inhibiting noradrenaline reuptake. The efficacy of tapentadol is stated to be comparable to morphine and oxycodone. OBJECTIVES: To assess the analgesic efficacy of tapentadol for the relief of cancer pain in adults, and the adverse events associated with its use in clinical trials...
2015: Cochrane Database of Systematic Reviews
Amanda Hunkele, Hamidah Sultan, Faith A Ikalina, Alexander H Liu, Pranjal Nahar-Gohad, Jane L Ko
OBJECTIVES: PolyC binding protein 1 (PCBP1) is a transcriptional regulator of human mu-opioid receptor (hMOR) gene in the CNS and is also related to cancer/diseases. It possesses multi-roles that can be mediated by protein-protein interactions. To understand the mechanism controlling PCBP1 functions, PCBP1-interacting protein was investigated. METHODS: Using PCBP1 as the bait, a human brain cDNA library was screened via two-hybrid system. DNA sequence of candidate protein was confirmed using NCBI/SNP databases...
December 2016: Neurological Research
Tejus Anantharamu, Sushil Sharma, Ajay Kumar Gupta, Navdeep Dahiya, Dick B Singh Brashier, Ashok Kumar Sharma
Opioid-induced constipation (OIC) is one of the most troublesome and the most common effects of opioid use leading to deterioration in quality of life of the patients and also has potentially deleterious repercussions on adherence and compliance to opioid therapy. With the current guidelines advocating liberal use of opioids by physicians even for non-cancer chronic pain, the situation is further complicated as these individuals are not undergoing palliative care and hence there cannot be any justification to subject these patients to the severe constipation brought on by opioid therapy which is no less debilitating than the chronic pain...
July 2015: Journal of Pharmacology & Pharmacotherapeutics
Kai Wang, Xiao Qu, Ying Wang, Hongchang Shen, Qi Liu, Jiajun Du
Opioids are widely used for postoperative analgesia. Morphine may have an effect on cell replication, migration, and cancer recurrence. However, the association of postoperative mu agonists with outcome of nonsmall cell lung cancer (NSCLC) patients has not been fully investigated.We retrospectively evaluated the impact of postoperative mu agonists on overall survival (OS) and disease-free survival (DFS) in early stage NSCLC patients. Patients and relevant medical information were selected from the Bio-Bank of Shandong Provincial Hospital...
August 2015: Medicine (Baltimore)
Patricia J McLaughlin, Ian S Zagon
Historically, studies on endogenous and exogenous opioids and their receptors focused on the mediation of pain, with excess opiate consumption leading to addiction. Opioid antagonists such as naloxone and naltrexone blocked these interactions, and still are widely used to reverse drug and alcohol overdose. Although specific opioid antagonists have been designed for mu, delta, and kappa opioid receptors, the general antagonists remain the most effective. With the discovery of the opioid growth factor (OGF)-OGF receptor (OGFr) axis as a novel biological pathway involved in homeostasis of replicating cells and tissues, the role of opioid receptor antagonists was expanded...
October 1, 2015: Biochemical Pharmacology
Patrick A Singleton, Jonathan Moss, Daniel D Karp, Johnique T Atkins, Filip Janku
Mu opioids are among the most widely used drugs for patients with cancer with both acute and chronic pain as well as in the perioperative period. Several retrospective studies have suggested that opioid use might promote tumor progression and as a result negatively impact survival in patients with advanced cancer; however, in the absence of appropriate prospective validation, any changes in recommendations for opioid use are not warranted. In this review, the authors present preclinical and clinical data that support their hypothesis that the mu opioid receptor is a potential target for cancer therapy because of its plausible role in tumor progression...
August 15, 2015: Cancer
Takafumi Naito, Junichi Kawakami
Use of prescription opioids for cancer pain according to the World Health Organization analgesic ladder has been accepted in Japan. Although oxycodone and fentanyl are commonly used as first-line analgesics, a few clinical reports have been published on interindividual variations in their pharmacokinetics and clinical responses in cancer patients. (1) Some factors relating to CYP2D6, CYP3A, ATP-binding cassette sub-family B member 1 (ABCB1), and opioid receptor mu 1 (OPRM1) involve oxycodone pharmacokinetics and sensitivity in humans...
2015: Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan
Anthony H Dickenson, Paul W Farquhar-Smith
No abstract text is available yet for this article.
June 2015: Current Opinion in Supportive and Palliative Care
Yanju Bao, Yebo Gao, Wei Hou, Liping Yang, Xiangying Kong, Honggang Zheng, Conghuang Li, Baojin Hua
Pain is one of the most common and distressing symptoms suffered by patients with progression of cancer. Using a rat model of bone cancer, recent findings suggest that proteinase-activated receptor 2 (PAR2) signaling pathways contribute to neuropathic pain and blocking PAR2 amplifies antinociceptive effects of systemic morphine. The purpose of our study was to examine the underlying mechanisms responsible for the role of PAR2 in regulating bone cancer-evoked pain and the tolerance of systemic morphine. Breast sarcocarcinoma Walker 256 cells were implanted into the tibia bone cavity of rats and this evoked significant mechanical and thermal hyperalgesia...
September 15, 2015: International Journal of Cancer. Journal International du Cancer
Karly P Garnock-Jones
Oral naloxegol (Movantik™, Moventig(®)), a peripherally acting μ-opioid receptor antagonist, inhibits opioid binding in μ-opioid receptors in the gastrointestinal tract. This article reviews the pharmacological properties of naloxegol and its clinical efficacy and tolerability in patients with opioid-induced constipation. It demonstrated clinical efficacy and was well tolerated in placebo-controlled trials in patients with non-cancer pain and opioid-induced constipation, including those with an inadequate response to laxatives, and was well tolerated in a long-term safety study...
March 2015: Drugs
Kanako Miyano, Kouichiro Minami, Toru Yokoyama, Katsuya Ohbuchi, Takuhiro Yamaguchi, Satoshi Murakami, Seiji Shiraishi, Masahiro Yamamoto, Motohiro Matoba, Yasuhito Uezono
BACKGROUND: The transient receptor potential vanilloid 1 (TRPV1) and the transient receptor potential ankyrin 1 (TRPA1), which are expressed in sensory neurons, are polymodal nonselective cation channels that sense noxious stimuli. Recent reports showed that these channels play important roles in inflammatory, neuropathic, or cancer pain, suggesting that they may serve as attractive analgesic pharmacological targets. Tramadol is an effective analgesic that is widely used in clinical practice...
April 2015: Anesthesia and Analgesia
Anna Cieślińska, Edyta Sienkiewicz-Szłapka, Elżbieta Kostyra, Ewa Fiedorowicz, Jadwiga Snarska, Konrad Wroński, Michał Tenderenda, Beata Jarmołowska, Michał Matysiewicz
Structure-dependent μ-opioid receptor (MOR) activity is an important element in cancer opioid analgesic effectiveness. It is widely accepted that guanine (G) substitution for adenine (A) at OPRM1 gene sequence position 118 changes receptor glycosylation pattern. This is associated with decreased binding ability in both exogenous and endogenous opioids, resulting in increased human pain resistance. The endogenous opioid system's function in body homeostasis maintenance is considered mainly regulatory, so its participation in breast tumor formation and progression is identified herein...
June 2015: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Sherika N Smith, Candler Paige, Kandy T Velazquez, Terika P Smith, Srinivasa N Raja, Steven P Wilson, Sarah M Sweitzer
UNLABELLED: Chronic neuropathic pain is often difficult to treat with current pain medications. Gene therapy is presently being explored as a therapeutic approach for the treatment of neuropathic and cancer pain. In this study, we sought to use an injury-specific promoter to deliver the mu-opioid receptor (MOR) transgene such that expression would occur during the injured state only in response to release of injury-specific galanin. To determine whether an injury-specific promoter can produce neuron-specific MOR expression and enhanced antinociception, we compared animals infected with a galanin promoter virus (galMOR) or a human cytomegalovirus promoter virus (cmvMOR)...
March 2015: Journal of Pain: Official Journal of the American Pain Society
Jin Xu, Andrew J Faskowitz, Grace C Rossi, Mingming Xu, Zhigang Lu, Ying-Xian Pan, Gavril W Pasternak
Chronic morphine administration is associated with the development of tolerance, both clinically and in animal models. Many assume that tolerance is a continually progressive response to chronic opioid dosing. However, clinicians have long appreciated the ability to manage cancer pain in patients for months on stable opioid doses, implying that extended dosing may eventually result in a steady state in which the degree of tolerance remains constant despite the continued administration of a fixed morphine dose...
January 6, 2015: Proceedings of the National Academy of Sciences of the United States of America
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