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Review

Perioperative Pain, Analgesics and Cancer-Related Outcomes: where do we Stand?

, & ORCID Icon
Pages 229-242 | Received 29 Jul 2021, Accepted 15 Sep 2021, Published online: 12 Oct 2021

References

  • Van Den Beuken-Van Everdingen MH , HochstenbachLM , JoostenEA , Tjan-HeijnenVC , JanssenDJ. Update on prevalence of pain in patients with cancer: systematic review and meta-analysis. J. Pain Symptom Manage.51(6), 1070–1090 e1079 (2016).
  • Graczyk M , BorkowskaA , KrajnikM. Why patients are afraid of opioid analgesics: a study on opioid perception in patients with chronic pain. Pol. Arch. Intern. Med.128(2), 89–97 (2018).
  • Greer SM , DaltonJA , CarlsonJ , YoungbloodR. Surgical patients’ fear of addiction to pain medication: the effect of an educational program for clinicians. Clin. J. Pain17(2), 157–164 (2001).
  • Lee M , SilvermanSM , HansenH , PatelVB , ManchikantiL. A comprehensive review of opioid-induced hyperalgesia. Pain Physician14(2), 145–161 (2011).
  • Colvin LA , BullF , HalesTG. Perioperative opioid analgesia-when is enough too much? A review of opioid-induced tolerance and hyperalgesia. Lancet393(10180), 1558–1568 (2019).
  • Zheng J , HeJ , WangWet al. The impact of pain and opioids use on survival in cancer patients: results from a population-based cohort study and a meta-analysis. Medicine (Baltimore)99(9), e19306 (2020).
  • Zylla D , KuskowskiMA , GuptaK , GuptaP. Association of opioid requirement and cancer pain with survival in advanced non-small cell lung cancer. Br. J. Anaesth.113(Suppl. 1), I109–I116 (2014).
  • Page GG . The immune-suppressive effects of pain. Adv. Exp. Med. Biol.521, 117–125 (2003).
  • Dalal S , BrueraE. Pain management for patients with advanced cancer in the opioid epidemic era. Am. Soc. Clin. Oncol. Educ. Book39, 24–35 (2019).
  • WHO Guidelines Approved by the Guidelines Review Committee. In: WHO Guidelines for the Pharmacological and Radiotherapeutic Management of Cancer Pain in Adults and Adolescents. World Health Organization, Geneva, Switzlerland (2018).
  • Calo G , LambertDG. Nociceptin/orphanin FQ receptor ligands and translational challenges: focus on cebranopadol as an innovative analgesic. Br. J. Anaesth.121(5), 1105–1114 (2018).
  • Raehal KM , BohnLM. beta-arrestins: regulatory role and therapeutic potential in opioid and cannabinoid receptor-mediated analgesia. Handb. Exp. Pharmacol.219, 427–443 (2014).
  • Al-Hasani R , BruchasMR. Molecular mechanisms of opioid receptor-dependent signaling and behavior. Anesthesiology115(6), 1363–1381 (2011).
  • Waldhoer M , BartlettSE , WhistlerJL. Opioid receptors. Annu. Rev. Biochem.73, 953–990 (2004).
  • Brejchova J , HolanV , SvobodaP. Expression of opioid receptors in cells of the immune system. Int. J. Mol. Sci.22(1), (2020).
  • Ondrovics M , Hoelbl-KovacicA , FuxDA. Opioids: modulators of angiogenesis in wound healing and cancer. Oncotarget8(15), 25783–25796 (2017).
  • Ramirez MF , GorurA , CataJP. Opioids and cancer prognosis: a summary of the clinical evidence. Neurosci. Lett.746, 135661 (2021).
  • Szczepaniak A , FichnaJ , ZielinskaM. Opioids in cancer development, progression and metastasis: focus on colorectal cancer. Curr. Treat. Options Oncol.21(1), 6 (2020).
  • Renaud AMCaHGaFL . Inhibition by opioids of phagocytosis in peritoneal macrophages. Neuropeptides18(1), 35–40 (1991).
  • Sacerdote P , ManfrediB , MantegazzaP , PaneraiAE. Antinociceptive and immunosuppressive effects of opiate drugs: a structure-related activity study. Br. J. Pharmacol.121(4), 834–840 (1997).
  • Wigmore T , Farquhar-SmithP. Opioids and cancer: friend or foe?Curr Opin Support Palliat Care.10(2), 109–118 (2016).
  • Plein LM , RittnerHL. Opioids and the immune system – friend or foe. Br. J. Pharmacol.175(14), 2717–2725 (2018).
  • Franchi S , MoschettiG , AmodeoG , SacerdoteP. Do all opioid drugs share the same immunomodulatory properties? a review from animal and human studies. Front. Immunol.10, 2914 (2019).
  • Hutchinson MR , ZhangY , ShridharMet al. Evidence that opioids may have Toll-like receptor 4 and MD-2 effects. Brain Behav. Immun.24(1), 83–95 (2010).
  • Mahbuba W , LambertDG. Opioids and neovascularization; pro or anti?Br. J. Anaesth.115(6), 821–824 (2015).
  • Carli M , DonniniS , PellegriniC , CoppiE , BocciG. Opioid receptors beyond pain control: the role in cancer pathology and the debated importance of their pharmacological modulation. Pharmacol. Res.159, 104938 (2020).
  • Cheng S , GuoM , LiuZet al. Morphine promotes the angiogenesis of postoperative recurrent tumors and metastasis of dormant breast cancer cells. Pharmacology104(5–6), 276–286 (2019).
  • Polakiewicz RD , SchieferlSM , DornerLF , KansraV , CombMJ. A mitogen-activated protein kinase pathway is required for mu-opioid receptor desensitization. J. Biol. Chem.273(20), 12402–12406 (1998).
  • Liu W , ChenY , XuWet al. Fentanyl stimulates tumor angiogenesis via activating multiple pro-angiogenic signaling pathways. Biochem. Biophys. Res. Commun.532(2), 225–230 (2020).
  • Karaman H , TufekA , KaramanE , TokgozO. Opioids inhibit angiogenesis in a chorioallantoic membrane model. Pain Physician20(2S), SE11–SE21 (2017).
  • Khabbazi S , NassarZD , GoumonY , ParatMO. Morphine decreases the pro-angiogenic interaction between breast cancer cells and macrophages in vitro. Sci. Rep.6, 31572 (2016).
  • Shi Y , LuoJ , TianJ , ZouQ , WangX. The kappa opioid receptor may be a potential tumor suppressor by regulating angiogenesis in breast cancer. Med. Hypotheses150, 110568 (2021).
  • Mathew B , LennonFE , SieglerJet al. The novel role of the mu opioid receptor in lung cancer progression: a laboratory investigation. Anesth. Analg.112(3), 558–567 (2011).
  • Gorur A , PatinoM , TakahashiHet al. Mu-opioid receptor activation promotes in vitro and in vivo tumor growth in head and neck squamous cell carcinoma. Life Sci.278, 119541 (2021).
  • Li Y , LiG , TaoTet al. The mu-opioid receptor (MOR) promotes tumor initiation in hepatocellular carcinoma. Cancer Lett.453, 1–9 (2019).
  • Tuerxun H , CuiJ. The dual effect of morphine on tumor development. Clin. Transl. Oncol.21(6), 695–701 (2019).
  • Ramirez MF , GorurA , CataJP. The role of opioids in cancer progression. Int. Anesthesiol. Clin.58(2), 57–63 (2020).
  • Zhang J , YaoN , TianS. Morphine stimulates migration and growth and alleviates the effects of chemo drugs via AMPK-dependent induction of epithelial-mesenchymal transition in esophageal carcinoma cells. Biol. Pharm. Bull.43(5), 774–781 (2020).
  • Niu DG , PengF , ZhangWet al. Morphine promotes cancer stem cell properties, contributing to chemoresistance in breast cancer. Oncotarget6(6), 3963–3976 (2015).
  • Cao LH , LiHT , LinWQet al. Morphine, a potential antagonist of cisplatin cytotoxicity, inhibits cisplatin-induced apoptosis and suppression of tumor growth in nasopharyngeal carcinoma xenografts. Sci. Rep.6, 18706 (2016).
  • Naderi J , SamaniF , AmooheidariA , JavanmardS , VahabzadehG , VaseghiG. Evaluation of effects of morphine and ionizing radiation in cancer cell lines. J. Cancer Res. Ther.15(8), 144–152 (2019).
  • Botticelli A , CirilloA , PomatiGet al. The role of opioids in cancer response to immunotherapy. J. Transl. Med.19(1), 119 (2021).
  • Zhang HW , WangF , ZhouYQ , XuSP , YuSY , ZhangZG. Morphine suppresses liver cancer cell tumor properties in vitro and in vivo. Front. Oncol.11, 666446 (2021).
  • Zagon IS . Prevention and delay in progression of human pancreatic cancer by stable overexpression of the opioid growth factor receptor. Int. J. Oncol.33(2), 317–323 (2008).
  • Donahue RN , MclaughlinPJ , ZagonIS. The opioid growth factor (OGF) and low dose naltrexone (LDN) suppress human ovarian cancer progression in mice. Gynecol. Oncol.122(2), 382–388 (2011).
  • Zagon IS , PorterfieldNK , MclaughlinPJ. Opioid growth factor – opioid growth factor receptor axis inhibits proliferation of triple negative breast cancer. Exp. Biol. Med. (Maywood).238(6), 589–599 (2013).
  • Lec PM , LenisAT , GollaVet al. The role of opioids and their receptors in urological malignancy: a review. J. Urol.204(6), 1150–1159 (2020).
  • Zhang H , SunM , ZhouDet al. Increased mu-opioid receptor expression is associated with reduced disease-free and overall survival in laryngeal squamous cell carcinoma. Br. J. Anaesth.125(5), 722–729 (2020).
  • Singleton PA , MirzapoiazovaT , HasinaR , SalgiaR , MossJ. Increased mu-opioid receptor expression in metastatic lung cancer. Br. J. Anaesth.113(Suppl. 1), i103–108 (2014).
  • Zhang H , QuM , GorurAet al. Association of Mu-opioid receptor(MOR) expression and opioids requirement with survival in patients with stage I–III pancreatic ductal adenocarcinoma. Front. Oncol.11, 686877 (2021).
  • Diaz-Cambronero O , MazzinariG , GinerFet al. Mu opioid receptor 1 (MOR-1) expression in colorectal cancer and oncological long-term outcomes: a five-year retrospective longitudinal cohort study. Cancers (Basel)12(1), (2020).
  • Steele GL , DudekAZ , GilmoreGEet al. Impact of pain, opioids, and the mu-opioid receptor on progression and survival in patients with newly diagnosed stage IV pancreatic cancer. Am. J. Clin. Oncol.43(8), 591–597 (2020).
  • Cata JP , KeertyV , KeertyDet al. A retrospective analysis of the effect of intraoperative opioid dose on cancer recurrence after non-small cell lung cancer resection. Cancer Med.3(4), 900–908 (2014).
  • Wuethrich PY , ThalmannGN , StuderUE , BurkhardFC. Epidural analgesia during open radical prostatectomy does not improve long-term cancer-related outcome: a retrospective study in patients with advanced prostate cancer. PLoS ONE8(8), e72873 (2013).
  • Wu HL , TaiYH , ChangWKet al. Does postoperative morphine consumption for acute surgical pain impact oncologic outcomes after colorectal cancer resection?: a retrospective cohort study. Medicine (Baltimore)98(18), e15442 (2019).
  • Cata JP , ZafereoM , VillarrealJet al. Intraoperative opioids use for laryngeal squamous cell carcinoma surgery and recurrence: a retrospective study. J. Clin. Anesth.27(8), 672–679 (2015).
  • Du KN , FengL , NewhouseAet al. Effects of intraoperative opioid use on recurrence-free and overall survival in patients with esophageal adenocarcinoma and squamous cell carcinoma. Anesth. Analg.127(1), 210–216 (2018).
  • Montagna G , GuptaHV , HannumMet al. Intraoperative opioids are associated with improved recurrence-free survival in triple-negative breast cancer. Br. J. Anaesth.126(2), 367–376 (2021).
  • Sessler DI , PeiL , HuangYet al. Recurrence of breast cancer after regional or general anaesthesia: a randomised controlled trial. Lancet394(10211), 1807–1815 (2019).
  • Rangel FP , AulerJOCJr , CarmonaMJCet al. Opioids and premature biochemical recurrence of prostate cancer: a randomised prospective clinical trial. Br. J. Anaesth.126(5), 931–939 (2021).
  • Du Y-T , LiY-W , ZhaoB-Jet al. Long-term survival after combined epidural–general anesthesia or general anesthesia alone: follow-up of a randomized trial. Anesthesiology135(2), 233–245 (2021).
  • Kurdi MS , TheerthKA , DevaRS. Ketamine: current applications in anesthesia, pain, and critical care. Anesth. Essays Res.8(3), 283–290 (2014).
  • Clark JD . Ketamine for chronic pain: old drug new trick?Anesthesiology133(1), 13–15 (2020).
  • Bell RF , EcclestonC , KalsoEA. Ketamine as an adjuvant to opioids for cancer pain. Cochrane Database Syst. Rev.6, CD003351 (2017).
  • Zorumski CF , IzumiY , MennerickS. Ketamine: NMDA receptors and beyond. J. Neurosci.36(44), 11158–11164 (2016).
  • Abdollahpour A , SaffariehE , ZoroufchiBH. A review on the recent application of ketamine in management of anesthesia, pain, and health care. J. Family Med. Prim. Care9(3), 1317–1324 (2020).
  • Duan W , HuJ , LiuY. Ketamine inhibits colorectal cancer cells malignant potential via blockage of NMDA receptor. Exp. Mol. Pathol.107, 171–178 (2019).
  • Malsy M , GebhardtK , GruberM , WieseC , GrafB , BundschererA. Effects of ketamine, s-ketamine, and MK 801 on proliferation, apoptosis, and necrosis in pancreatic cancer cells. BMC Anesthesiol.15, 111 (2015).
  • Zhou X , ZhangP , LuoWet al. Ketamine induces apoptosis in lung adenocarcinoma cells by regulating the expression of CD69. Cancer Med.7(3), 788–795 (2018).
  • Connolly JG , TanKS , MastrogiacomoBet al. Intraoperative opioid exposure, tumour genomic alterations, and survival differences in people with lung adenocarcinoma. Br. J. Anaesth.127(1), 75–84 (2021).
  • Cho JS , KimNY , ShimJ-K , JunJH , LeeS , KwakY-L. The immunomodulatory effect of ketamine in colorectal cancer surgery: a randomized-controlled trial. Can. J. Anesth.68(5), 683–692 (2021).
  • Masic D , LiangE , LongC , SterkEJ , BarbasB , RechMA. Intravenous lidocaine for acute pain: a systematic review. Pharmacotherapy38(12), 1250–1259 (2018).
  • Dunn LK , DurieuxME. Perioperative use of intravenous lidocaine. Anesthesiology126(4), 729–737 (2017).
  • Lee JT , SandersonCR , XuanW , AgarM. Lidocaine for cancer pain in adults: a systematic review and meta-analysis. J. Palliat. Med.22(3), 326–334 (2019).
  • Cata JP , RamirezMF , VelasquezJFet al. Lidocaine stimulates the function of natural killer cells in different experimental settings. Anticancer Res.37(9), 4727–4732 (2017).
  • Wang H-L , YanH-D , LiuY-Yet al. Intraoperative intravenous lidocaine exerts a protective effect on cell-mediated immunity in patients undergoing radical hysterectomy. Mol. Med. Report.12(5), 7039–7044 (2015).
  • Jeon YT , NaH , RyuH , ChungY. Modulation of dendritic cell activation and subsequent Th1 cell polarization by lidocaine. PLoS ONE10(10), e0139845 (2015).
  • Galos EV , TatTF , PopaRet al. Neutrophil extracellular trapping and angiogenesis biomarkers after intravenous or inhalation anaesthesia with or without intravenous lidocaine for breast cancer surgery: a prospective, randomised trial. Br. J. Anaesth.125(5), 712–721 (2020).
  • Carrithers MD , ChatterjeeG , CarrithersLMet al. Regulation of podosome formation in macrophages by a splice variant of the sodium channel SCN8A. J. Biol. Chem.284(12), 8114–8126 (2009).
  • Zhang L , HuR , ChengYet al. Lidocaine inhibits the proliferation of lung cancer by regulating the expression of GOLT1A. Cell Prolif.50(5), (2017).
  • Sui H , LouA , LiZ , YangJ. Lidocaine inhibits growth, migration and invasion of gastric carcinoma cells by up-regulation of miR-145. BMC Cancer19(1), 233 (2019).
  • Gao R , CaoT , ChenH , CaiJ , LeiM , WangZ. Nav1.5-E3 antibody inhibits cancer progression. Transl Cancer Res.8(1), 44–50 (2019).
  • Xing W , ChenDT , PanJHet al. Lidocaine induces apoptosis and suppresses tumor growth in human hepatocellular carcinoma cells in vitro and in a xenograft model in vivo. Anesthesiology126(5), 868–881 (2017).
  • Leng T , LinS , XiongZ , LinJ. Lidocaine suppresses glioma cell proliferation by inhibiting TRPM7 channels. Int. J. Physiol. Pathophysiol. Pharmacol.9(2), 8–15 (2017).
  • Wen J , LiX , DingY , ZhengS , XiaoY. Lidocaine inhibits glioma cell proliferation, migration and invasion by modulating the circEZH2/miR-181b-5p pathway. Neuroreport32(1), 52–60 (2021).
  • D’agostino G , SaporitoA , CecchinatoVet al. Lidocaine inhibits cytoskeletal remodelling and human breast cancer cell migration. Br. J. Anaesth.121(4), 962–968 (2018).
  • Gao J , HuH , WangX. Clinically relevant concentrations of lidocaine inhibit tumor angiogenesis through suppressing VEGF/VEGFR2 signaling. Cancer Chemother. Pharmacol.83(6), 1007–1015 (2019).
  • Du J , ZhangL , MaH , WangY , WangP. Lidocaine suppresses cell proliferation and aerobic glycolysis by regulating circHOMER1/miR-138-5p/HEY1 axis in colorectal cancer. Cancer Manag. Res.12, 5009–5022 (2020).
  • Yang X , ZhaoL , LiMet al. Lidocaine enhances the effects of chemotherapeutic drugs against bladder cancer. Sci. Rep.8(1), 598 (2018).
  • Zhang X , PangW , LiuH , WangJ. Lidocine potentiates the cytotoxicity of 5-fluorouracil to choriocarcinoma cells by downregulating ABC transport proteins expression. J. Cell. Biochem.120(10), 16533–16542 (2019).
  • Zhu J , HanS. Lidocaine inhibits cervical cancer cell proliferation and induces cell apoptosis by modulating the lncRNA-MEG3/miR-421/BTG1 pathway. Am. J. Transl. Res.11(9), 5404–5416 (2019).
  • Ramirez MF , TranP , CataJP. The effect of clinically therapeutic plasma concentrations of lidocaine on natural killer cell cytotoxicity. Reg. Anesth. Pain Med.40(1), 43–48 (2015).
  • Galoş EV , TatT-F , PopaRet al. Neutrophil extracellular trapping and angiogenesis biomarkers after intravenous or inhalation anaesthesia with or without intravenous lidocaine for breast cancer surgery: a prospective, randomised trial. Br. J. Anaesth.125(5), 712–721 (2020).
  • Zhang H , YangL , ZhuXet al. Association between intraoperative intravenous lidocaine infusion and survival in patients undergoing pancreatectomy for pancreatic cancer: a retrospective study. Br. J. Anaesth.125(2), 141–148 (2020).
  • Mattia C , ColuzziF. COX-2 inhibitors: pharmacological data and adverse effects. Minerva Anesthesiol.71(7–8), 461–470 (2005).
  • Yoshimura N , SanoH , OkamotoMet al. Expression of cyclooxygenase-1 and -2 in human breast cancer. Surg. Today33(11), 805–811 (2003).
  • Huh J , LiepinsA , ZielonkaJ , AndrekopoulosC , KalyanaramanB , SorokinA. Cyclooxygenase 2 rescues LNCaP prostate cancer cells from sanguinarine-induced apoptosis by a mechanism involving inhibition of nitric oxide synthase activity. Cancer Res.66(7), 3726–3736 (2006).
  • Desai SJ , PrickrilB , RasoolyA. Mechanisms of phytonutrient modulation of cyclooxygenase-2 (COX-2) and inflammation related to cancer. Nutr. Cancer70(3), 350–375 (2018).
  • Kulkarni S , RaderJS , ZhangFet al. Cyclooxygenase-2 is overexpressed in human cervical cancer. Clin. Cancer Res.7(2), 429–434 (2001).
  • Soslow RA , DannenbergAJ , RushDet al. COX-2 is expressed in human pulmonary, colonic, and mammary tumors. Cancer89(12), 2637–2645 (2000).
  • Molina MA , Sitja-ArnauM , LemoineMG , FrazierML , SinicropeFA. Increased cyclooxygenase-2 expression in human pancreatic carcinomas and cell lines: growth inhibition by nonsteroidal anti-inflammatory drugs. Cancer Res.59(17), 4356–4362 (1999).
  • Kazberuk A , ZarebaI , PalkaJ , SurazynskiA. A novel plausible mechanism of NSAIDs-induced apoptosis in cancer cells: the implication of proline oxidase and peroxisome proliferator-activated receptor. Pharmacol. Rep.72(5), 1152–1160 (2020).
  • Wu Y , ZhouBP. Inflammation: a driving force speeds cancer metastasis. Cell Cycle8(20), 3267–3273 (2009).
  • Liu B , QuL , YanS. Cyclooxygenase-2 promotes tumor growth and suppresses tumor immunity. Cancer Cell Int.15, 106 (2015).
  • Huang XZ , GaoP , SunJXet al. Aspirin and nonsteroidal anti-inflammatory drugs after but not before diagnosis are associated with improved breast cancer survival: a meta-analysis. Cancer Causes Control26(4), 589–600 (2015).
  • Johnson CC , JankowskiM , RolnickS , YoodMU , AlfordSH. Influence of NSAID use among colorectal cancer survivors on cancer outcomes. Am. J. Clin. Oncol.40(4), 370–374 (2017).
  • Iovoli AJ , HermannGM , MaSJet al. Association of nonsteroidal anti-inflammatory drug use with survival in patients with squamous cell carcinoma of the head and neck treated with chemoradiation therapy. JAMA Netw Open.3(6), e207199 (2020).
  • Choi JE , VillarrealJ , LasalaJet al. Perioperative neutrophil:lymphocyte ratio and postoperative NSAID use as predictors of survival after lung cancer surgery: a retrospective study. Cancer Med.4(6), 825–833 (2015).
  • Forget P , TombalB , ScholtesJLet al. Do intraoperative analgesics influence oncological outcomes after radical prostatectomy for prostate cancer? Eur. J. Anaesthesiol. 28(12), 830–835 (2011).
  • Zhao X , XuZ , LiH. NSAIDs use and reduced metastasis in cancer patients: results from a meta-analysis. Sci. Rep.7(1), 1875 (2017).
  • Magee DJ , JhanjiS , PoulogiannisG , Farquhar-SmithP , BrownMRD. Nonsteroidal anti-inflammatory drugs and pain in cancer patients: a systematic review and reappraisal of the evidence. Br. J. Anaesth.123(2), e412–e423 (2019).
  • Cata JP , GuerraCE , ChangGJ , GottumukkalaV , JoshiGP. Non-steroidal anti-inflammatory drugs in the oncological surgical population: beneficial or harmful? A systematic review of the literature. Br. J. Anaesth.119(4), 750–764 (2017).
  • Forget P , BentinC , MachielsJP , BerliereM , CouliePG , DeKock M. Intraoperative use of ketorolac or diclofenac is associated with improved disease-free survival and overall survival in conservative breast cancer surgery. Br. J. Anaesth.113(Suppl. 1), i82–87 (2014).
  • Forget P , MachielsJ-P , CouliePet al. Neutrophil:lymphocyte ratio and intraoperative use of ketorolac or diclofenac are prognostic factors in different cohorts of patients undergoing breast, lung, and kidney cancer surgery. Ann. Surg. Oncol.20, 650–660 (2013).
  • Grahn O , LundinM , LydrupML , AngeneteE , RutegårdM. Postoperative non-steroidal anti-inflammatory drug use and oncological outcomes of rectal cancer. BJS Open5(1), (2021).
  • Forget P , VandenhendeJ , BerliereMet al. Do intraoperative analgesics influence breast cancer recurrence after mastectomy? A retrospective analysis. Anesth. Analg.110(6), 1630–1635 (2010).
  • Yang EV , SoodAK , ChenMet al. Norepinephrine up-regulates the expression of vascular endothelial growth factor, matrix metalloproteinase (MMP)-2, and MMP-9 in nasopharyngeal carcinoma tumor cells. Cancer Res.66(21), 10357–10364 (2006).
  • Lee BM , RodriguezA , MenaGet al. Platelet-to-lymphocyte ratio and use of NSAIDs during the perioperative period as prognostic indicators in patients with NSCLC undergoing surgery. Cancer Control23(3), 284–294 (2016).
  • De Castro Araujo BL , DeOliveira JL , RezendeJFN , NogueraWS , DeMelo AC , ThulerLCS. Impact of non-steroidal anti-inflammatory drugs on recurrence and survival after melanoma surgery: a cohort study. Cancer Invest.38(7), 415–423 (2020).
  • Wang RD , ZhuJY , ZhuY , GeYS , XuGL , JiaWD. Perioperative analgesia with parecoxib sodium improves postoperative pain and immune function in patients undergoing hepatectomy for hepatocellular carcinoma. J. Eval. Clin. Pract.26(3), 992–1000 (2019).
  • Forget P , BoucheGet al. Intraoperative ketorolac in high-risk breast cancer patients. A prospective, randomized, placebo-controlled clinical trial. PLoS ONE14(12), e0225748 (2019).
  • Meyerhardt JA , ShiQ , FuchsCSet al. Effect of celecoxib vs placebo added to standard adjuvant therapy on disease-free survival among patients with stage III colon cancer. JAMA325(13), (2021).
  • Patel R , DickensonAH. Mechanisms of the gabapentinoids and alpha 2 delta-1 calcium channel subunit in neuropathic pain. Pharmacol. Res. Perspect.4(2), e00205 (2016).
  • Dethloff L , BarrB , BesterveltLet al. Gabapentin-induced mitogenic activity in rat pancreatic acinar cells. Toxicol. Sci.55(1), 52–59 (2000).
  • Bugan I , KaragozZ , AltunS , DjamgozMB. Gabapentin, an analgesic used against cancer-associated neuropathic pain: effects on prostate cancer progression in an in vivo rat model. Basic Clin. Pharmacol. Toxicol.118(3), 200–207 (2016).
  • Ding Y , RobbinsJ , FraserSP , GrimesJA , DjamgozMB. Comparative studies of intracellular Ca2+ in strongly and weakly metastatic rat prostate cancer cell lines. Int. J. Biochem. Cell Biol.38(3), 366–375 (2006).
  • Irizarry MC , WebbDJ , BoudiafNet al. Risk of cancer in patients exposed to gabapentin in two electronic medical record systems. Pharmacoepidemiol. Drug Saf.21(2), 214–225 (2012).
  • Zhao Y , HeJ , YuN , JiaC , WangS. Mechanisms of dexmedetomidine in neuropathic pain. Front. Neurosci.14, 330 (2020).
  • Brown EN , PavoneKJ , NaranjoM. Multimodal general anesthesia: theory and practice. Anesth. Analg.127(5), 1246–1258 (2018).
  • Lavon H , MatznerP , BenbenishtyAet al. Dexmedetomidine promotes metastasis in rodent models of breast, lung, and colon cancers. Br. J. Anaesth.120(1), 188–196 (2018).
  • Wang C , DatooT , ZhaoHet al. Midazolam and dexmedetomidine affect neuroglioma and lung carcinoma cell biology in vitro and in vivo. Anesthesiology129(5), 1000–1014 (2018).
  • Castillo LF , RiveroEM , GoffinV , LuthyIA. Alpha2-adrenoceptor agonists trigger prolactin signaling in breast cancer cells. Cell. Signal.34, 76–85 (2017).
  • Chen P , LuoX , DaiGet al. Dexmedetomidine promotes the progression of hepatocellular carcinoma through hepatic stellate cell activation. Exp. Mol. Med.52(7), 1062–1074 (2020).
  • Tian H , HouL , XiongY , ChengQ. Dexmedetomidine upregulates microRNA-185 to suppress ovarian cancer growth via inhibiting the SOX9/Wnt/beta-catenin signaling pathway. Cell Cycle20(8), 765–780 (2021).
  • Zhang P , HeH , BaiY , LiuW , HuangL. Dexmedetomidine suppresses the progression of esophageal cancer via miR-143-3p/epidermal growth factor receptor pathway substrate 8 axis. Anticancer Drugs31(7), 693–701 (2020).
  • Dong W , ChenMH , YangYHet al. The effect of dexmedetomidine on expressions of inflammatory factors in patients with radical resection of gastric cancer. Eur. Rev. Med. Pharmacol. Sci.21(15), 3510–3515 (2017).
  • Wang Y , XuX , LiuH , JiF. Effects of dexmedetomidine on patients undergoing radical gastrectomy. J. Surg. Res.194(1), 147–153 (2015).
  • Liu Y , SunJ , WuTet al. Effects of serum from breast cancer surgery patients receiving perioperative dexmedetomidine on breast cancer cell malignancy: a prospective randomized controlled trial. Cancer Med.8(18), 7603–7612 (2019).
  • Cata JP , SinghV , LeeBMet al. Intraoperative use of dexmedetomidine is associated with decreased overall survival after lung cancer surgery. J. Anaesthesiol. Clin. Pharmacol.33(3), 317–323 (2017).

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