Michaelsen Friedrich-Wilhelm, Saeed Mohamed E M, Schwarzkopf Jörg, Efferth Thomas
Practice for Naturopathy, 29499 Zernien, Germany.
Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Mainz, Germany.
Phytomedicine. 2015 Dec 15;22(14):1223-31. doi: 10.1016/j.phymed.2015.11.001. Epub 2015 Nov 10.
Artemisia annua L, artemisinin and artesunate reveal profound activity not only against malaria, but also against cancer in vivo and clinical trials. Longitudinal observations on the efficacy of A. annua in patients are, however missing as of yet.
Clinical diagnosis was performed by imaging techniques (MRT, scintigraphy, SPECT/CT) and blood examinations of standard parameters from clinical chemistry. Immunohistochemistry of formalin-fixed, paraffin-embedded tumor material was performed to determine the expression of several biomarkers (cycloxygenase-2 (COX2), epidermal growth factor receptor (EGFR), glutathione S-transferase P1 (GSTP1), Ki-67, MYC, oxidized low density lipoprotein (lectin-like) receptor 1 (LOX1), p53, P-glycoprotein, transferrin receptor (TFR, CD71), vascular endothelial growth factor (VEGF), von Willebrand factor (CD31)). The immunohistochemical expression has been compared with the microarray-based mRNA expression of these markers in two prostate carcinoma cell lines (PC-3, DU-145).
A patient with prostate carcinoma (pT3bN1M1, Gleason score 8 (4+4)) presented with a prostate specific antigen (PSA) level >800 µg/l. After short-term treatment with bacalitumide (50 mg/d for 14 days) and long-term oral treatment with A. annua capsules (continuously 5 × 50 mg/d), the PSA level dropped down to 0.98 µg/l. MRT, scintigraphy and SPECT/CT verified tumor remission. Seven months later, PSA and ostase levels increased, indicating tumor recurrence and skeletal metastases. Substituting A. annua capsules by artesunate injections (2 × 150 mg twice weekly i.v.) did not prohibit tumor recurrence. PSA and ostase levels rose to 1245 µg/l and 434 U/l, respectively, and MRT revealed progressive skeletal metastases, indicating that the tumor acquired resistance. The high expression of MYC, TFR, and VEGFC in the patient biopsy corresponded with high expression of these markers in the artemisinin-sensitive PC-3 cells compared to artemisinin-resistant DU-145 cells.
Long-term treatment with A. annua capsules combined with short-term bicalitumide treatment resulted in considerable regression of advanced metastasized prostate carcinoma. Controlled clinical trials are required to evaluate the clinical benefit of A. annua in prostate cancer.
青蒿、青蒿素和青蒿琥酯不仅对疟疾具有显著活性，在体内实验和临床试验中对癌症也有活性。然而，目前尚缺乏对患者使用青蒿的疗效的纵向观察。
通过成像技术（磁共振成像、闪烁扫描、单光子发射计算机断层扫描/计算机断层扫描）和临床化学标准参数的血液检查进行临床诊断。对福尔马林固定、石蜡包埋的肿瘤材料进行免疫组织化学检测，以确定几种生物标志物（环氧化酶-2（COX2）、表皮生长因子受体（EGFR）、谷胱甘肽S-转移酶P1（GSTP1）、Ki-67、MYC、氧化型低密度脂蛋白（凝集素样）受体1（LOX1）、p53、P-糖蛋白、转铁蛋白受体（TFR，CD71）、血管内皮生长因子（VEGF）、血管性血友病因子（CD31））的表达。将免疫组织化学表达与两种前列腺癌细胞系（PC-3、DU-145）中基于微阵列的这些标志物的mRNA表达进行比较。
一名前列腺癌患者（pT3bN1M1， Gleason评分8（4+4））的前列腺特异性抗原（PSA）水平>800μg/l。在短期使用巴卡利米德治疗（50mg/d，共14天）并长期口服青蒿胶囊（持续5×50mg/d）后，PSA水平降至0.98μg/l。磁共振成像、闪烁扫描和单光子发射计算机断层扫描/计算机断层扫描证实肿瘤缓解。七个月后，PSA和骨碱性磷酸酶水平升高，表明肿瘤复发和骨转移。用青蒿琥酯注射剂（2×150mg，每周两次静脉注射）替代青蒿胶囊并不能阻止肿瘤复发。PSA和骨碱性磷酸酶水平分别升至1245μg/l和434U/l，磁共振成像显示骨转移进展，表明肿瘤产生了耐药性。患者活检中MYC、TFR和VEGFC的高表达与青蒿素敏感的PC-3细胞中这些标志物的高表达相对应，而与青蒿素耐药的DU-145细胞相比。
长期使用青蒿胶囊联合短期巴卡利米德治疗可使晚期转移性前列腺癌显著消退。需要进行对照临床试验以评估青蒿在前列腺癌中的临床益处。
