Department of Nuclear Medicine, Çanakkale Onsekiz Mart University Faculty of Medicine, 17100, Canakkale, Turkey.
Med Oncol. 2011 Dec;28(4):1264-72. doi: 10.1007/s12032-010-9573-5. Epub 2010 Jun 22.
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.
乳腺癌是女性死亡的主要原因，吗啡被用于缓解癌症患者的疼痛。吗啡对肿瘤生长和血管生成的影响的数据是相互矛盾的。我们在小鼠乳腺癌模型中确定了镇痛剂量的吗啡是否会影响肿瘤血管生成，然后确定微血管密度（MVD）、多普勒超声（DS）和 99mTc-Tetrofosmin（TF）摄取之间的相关性。艾氏腹水瘤细胞异种移植，Pgp 阴性肿瘤分为两组：（a）硫酸吗啡[0.714mg/kg/天（相当于每天 70kg 人 50mg）]，（b）无吗啡。为了确定小鼠肿瘤组织中的血管生成，进行了 TF 闪烁显像、微血管密度和 DS。MVD 两组之间差异有统计学意义（49.4±1.8 与 41.8±1.9，吗啡组和无吗啡组，分别，P<0.001）。在闪烁显像质量的晚期摄取与组织病理学检查中的血管生成程度之间发现了强烈的相关性（r=0.52，P<0.01）。组织病理学检查中的血管生成程度与 TF 洗脱率之间存在统计学显著的负相关（r=0.40，P<0.05）。血管生成程度越高，TF 再摄取越高。DS 与 TF 之间无统计学显著相关性。MVD 与 DS 分级之间存在强烈相关性（r=0.51，P<0.01）。我们的临床前小鼠研究表明，临床上相关剂量的吗啡刺激血管生成，并且通过 MVD 和 DS 而不是 TF 来证明吗啡触发的血管生成。然而，TF 的摄取和洗脱与肿瘤组织中免疫组织化学评估的吗啡刺激血管生成进行了比较。
