Soritau O, Tomuleasa C, Aldea M, Petrushev B, Susman S, Gheban D, Ioani H, Cosis A, Brie I, Irimie A, Kacso G, Florian I S
Department of Cancer Immunology, Ion Chiricuta Oncology Institute, Cluj Napoca, Cluj Napoca, Romania.
J BUON. 2011 Apr-Jun;16(2):282-9.
Glioblastoma multiforme (GBM) remains one of the most devastating diseases known to man and affects more than 17,000 patients in the United States alone every year. This malignancy infiltrates the brain early in its course and makes complete neurosurgical resection almost impossible. Recent years have brought significant advances in tumor biology, including the discovery that many cancers, including gliomas, appear to be supported by cells with stem-like properties. In the current study we have investigated the effects of combining metformin with the standard treatment-of-care, as this drug, already used in the treatment of diabetes mellitus, has shown surprising results in the treatment of breast cancer, being also associated with lower mortality in several other malignancies.
The subjects of the current study were 8 patients with newly diagnosed high-grade gliomas, operated at the Department of Neurosurgery - Clinical University Emergency Hospital, Cluj Napoca. Tumor tissue cultures were established and characterized using immunofluorescence microscopy and PCR analysis and the sensitivity to metformin, epidermal growth factor (EGF) and temozolomide (TMZ) was tested. Microvascular density (MVD) assay was performed on the tumor samples.
Seven of the 8 cases had a positive correlation between the number of endothelial cells, the phenotype of isolated tumor cells and the response to adjuvant chemoradiotherapy. The isolated tumor cells had a stem-like behavior, being resistant to conventional drugs. In most cases there was no statistical significant difference between TMZ alone and TMZ plus EGF arms, but there was a important difference between TMZ alone and TMZ plus metformin arms in 6 of the cases.
New drugs and targeted molecular therapies are important for future therapeutics, but sometimes we must not exclude drugs already used in the clinic that might have remarkable results. Such is the case of metformin, a drug used for decades in the treatment of type 2 diabetes mellitus that has proven to enhance the effect of TMZ in the treatment of breast cancer and, starting with this paper, of brain cancer.
多形性胶质母细胞瘤（GBM）仍然是人类已知的最具毁灭性的疾病之一，仅在美国每年就影响超过17000名患者。这种恶性肿瘤在病程早期就浸润大脑，几乎不可能进行完整的神经外科切除。近年来肿瘤生物学取得了重大进展，包括发现许多癌症，包括胶质瘤，似乎由具有干细胞样特性的细胞支持。在本研究中，我们研究了二甲双胍与标准治疗方法联合使用的效果，因为这种已用于治疗糖尿病的药物在乳腺癌治疗中显示出惊人的效果，在其他几种恶性肿瘤中也与较低的死亡率相关。
本研究的对象是8例新诊断的高级别胶质瘤患者，在克卢日-纳波卡临床大学急诊医院神经外科接受手术。建立肿瘤组织培养物并使用免疫荧光显微镜和PCR分析进行表征，并测试对二甲双胍、表皮生长因子（EGF）和替莫唑胺（TMZ）的敏感性。对肿瘤样本进行微血管密度（MVD）测定。
8例中的7例在内皮细胞数量、分离的肿瘤细胞表型与辅助放化疗反应之间存在正相关。分离的肿瘤细胞具有干细胞样行为，对传统药物耐药。在大多数情况下，单独使用TMZ和TMZ加EGF组之间没有统计学显著差异，但在6例中，单独使用TMZ和TMZ加二甲双胍组之间存在重要差异。
新药和靶向分子疗法对未来治疗很重要，但有时我们不能排除临床上已使用的可能有显著效果的药物。二甲双胍就是这样一种药物，它已用于治疗2型糖尿病数十年，已证明可增强TMZ在乳腺癌治疗中的效果，从本文开始，也证明在脑癌治疗中有此效果。
