title: Evaluation of morphine effect on tumour angiogenesis in mouse breast tumour model, EATC.
abstract: Breast cancer is the leading cause of death among women, and morphine is used to relieve the pain of patients with cancer. The data on the effects of morphine on tumour growth and angiogenesis are contradictory. We determined in mouse breast cancer model whether analgesic doses of morphine would affect tumour angiogenesis, and then the correlation between microvessel density (MVD), Doppler sonography (DS) and 99mTc-Tetrofosmin (TF) uptake. Ehrlich ascites tumour cell xenografts, Pgp-negative tumour were divided into two groups: (a) Morphine sulphate [0.714 mg/kg/day (equivalent to 50 mg per day for a 70 kg human)], (b) no-morphine. For the determination of angiogenesis in mice tumour tissue, TF scintigraphy, microvessel density and DS were done. MVD was significantly different between groups (49.4±1.8 vs. 41.8±1.9, morphine and no-morphine groups, respectively, P<0.001). A strong correlation was found between late uptakes of mass at scintigraphy and degree of angiogenesis in histopathologic examination (r=0.52, P<0.01). There was statistically significant inverse correlation between degree of angiogenesis in histopathologic examination and washout ratio of TF (r=0.40, P<0.05). The higher values for angiogenesis are related to higher TF reuptake. There was no statistically significant correlation between DS and TF. A strong correlation was found between MVD and grade of DS (r=0.51, P<0.01). Our preclinical mice study indicates that morphine at clinically relevant doses stimulates angiogenesis, and angiogenesis triggered of morphine is demonstrated with MVD and DS, but not TF. However, uptake and washout of TF are compared with immunohistochemically assessed morphine-stimulated angiogenesis in tumour tissue.
authors.affiliation: Department of Nuclear Medicine, Çanakkale Onsekiz Mart University Faculty of Medicine, 17100, Canakkale, Turkey. fundaustun@comu.edu.tr
authors.forename: Funda
authors.initials: F
authors.lastname: Ustun
authors.forename: Gülay
authors.initials: G
authors.lastname: Durmus-Altun
authors.forename: Semsi
authors.initials: S
authors.lastname: Altaner
authors.forename: Nermin
authors.initials: N
authors.lastname: Tuncbilek
authors.forename: Cem
authors.initials: C
authors.lastname: Uzal
authors.forename: Sakir
authors.initials: S
authors.lastname: Berkarda
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000098:blood supply* / Q000000981:diagnostic imaging / Q000473:pathology*; D002286:Carcinoma, Ehrlich Tumor; D004195:Disease Models, Animal; D005260:Female; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D009020:Morphine / Q000494:pharmacology*; D009294:Narcotics / Q000494:pharmacology*; D009389:Neovascularization, Pathologic / Q000000981:diagnostic imaging / Q000473:pathology*; D009943:Organophosphorus Compounds; D015609:Organotechnetium Compounds; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals; D018608:Ultrasonography, Doppler
chemical_list: D009294:Narcotics; D009943:Organophosphorus Compounds; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; C078700:technetium tc-99m tetrofosmin; D009020:Morphine