Clinical feasibility of individually optimal chemotherapy based on the molecular targets in brain tumors

免疫组织化学研究可能为更好地了解O^6-甲基鸟嘌呤- dna甲基转移酶（MGMT）活性的位置和分布提供优势。脑肿瘤在组织结构和生物学特性上具有异质性。MGMT活性在脑肿瘤中甚至在单个肿瘤组织中差异很大。MGMT活动，特别是当从活检标本判断时，很容易低估活动的程度。最好的确认需要包含肿瘤最活跃部分的大量肿瘤组织。基因变化的测定是有用的，1p和/或19q的缺失是药物敏感性的标志。少突胶质细胞瘤合并1p和19q缺失可显著延长生存期。因此，化疗方案应根据肿瘤个体的生物学和分子特征进行选择和应用。获取整个脑肿瘤的生物学信息有一个关键的缺点，因为切除的肿瘤组织数量通常是有限的。由于正电子发射断层扫描（PET）可以对整个肿瘤进行成像，因此它克服了仅用组织学评估的问题。在本研究中，我们在治疗前获得了脑胶质瘤中硼衍生物的体内证据。氟硼苯丙氨酸（FBPA）被认为是氨基酸通过血脑屏障和肿瘤细胞内转运过程的指标。FBPA- pet法测定胶质瘤中FBPA掺入量准确；即使是组织学诊断也是不充分的，因为从活检中获得的组织很少。FBPA-PET在预测胶质瘤的预后和确定肿瘤是否对硼中子捕获治疗敏感或耐药方面具有实用和临床价值。遗传改变和体内关键生物学特性的知识积累将建立包括化疗在内的脑肿瘤个体最佳治疗方法。少

Immunohistochemical studies might provide superiority in better understanding the location and distribution of O^6-methylguanine-DNA methyltransferase (MGMT) activity. Brain tumors are heterogeneous in histological structure and biological properties. MGMT activity varies widely among brain tumors and even within individual tumor tissue. MGMT activity, especially when judged from biopsied specimens, may easily underestimate the degree of the activity. Best confirmation requires a large amount of tumor tissue containing the most active parts of a tumor.Determinations of genetic alternation are useful and loss of 1p and/or 19q is a landmark of drug sensitivity. Oligodendrogliomas having combined loss of 1p and 19q significantly prolong survival. Thus, chemotherapy regimen should be selected and applied on according to individual tumors based on biological and molecular characteristics.There is a critical disadvantage in obtaining biological information on the entire brain tumors because … More the resected amounts of tumor tissue are often limited. Since positron emission tomography (PET) can image the entire tumor, it therefore overcomes such problems with histologic evaluation alone. In the present study, we obtained in vivo evidence of boron-derivatives in gliomas prior to treatment. ^<18>F-^<10>B-Fluoroboronophenylalanine (FBPA) is accepted as an indicator of the amino acid transport process through blood-brain barrier and in the tumor cells. FBPA-PET method was accurate for the measurements of FBPA incorporation in gliomas ; even the histologic diagnosis was insufficient because of the small amounts of tissue available from biopsy. FBPA-PET is practical and clinically useful for predicting prognosis and for determining whether tumors will be sensitive or resistant boron neutron capture therapy in gliomas.Accumulation of knowledge of genetic alternations and in vivo crucial biological properties will establish the individual optimum treatments including chemotherapy in brain tumors. Less