Department of Medical Genetics, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Iran J Basic Med Sci. 2013 May;16(5):675-82.
OBJECTIVE(S): Hypoxia is a serious challenge for treatment of solid tumors. This condition has been manifested to exert significant therapeutic effects on glioblastoma multiform or (WHO) astrocytoma grade IV. Hypoxia contributes numerous changes in cellular mechanisms such as angiogenesis, metastasis and apoptosis evasion. Furthermore, in molecular level, hypoxia can cause induction of DNA breaks in tumor cells. Identification of mechanisms responsible for these effects can lead to designing more efficient therapeutic strategies against tumor progression which results in improvement of patient prognosis. Materials and Methods : In order to identify more hypoxia regulated genes which may have a role in glioblastoma progression, cDNA-AFLP was optimized as a Differential display method which is able to identify and isolate transcripts with no prior sequence knowledge.
Using this method, the current study identified 120 Transcription Derived Fragments (TDFs) which were completely differentially regulated in response to hypoxia. By sequence homology searching, the current study could detect 22 completely differentially regulated known genes and two unknown sequence matching with two chromosome contig and four sequence matches with some Expressed Sequence Tags (ESTs).
Further characterizing of these genes may help to achieve better understanding of hypoxia mediated phenotype change in tumor cells.
缺氧是治疗实体肿瘤的一个严重挑战。这种情况已经表现出对多形性胶质母细胞瘤或（世界卫生组织）IV 级星形细胞瘤有显著的治疗效果。缺氧会导致细胞机制发生许多变化，如血管生成、转移和凋亡逃逸。此外，在分子水平上，缺氧会导致肿瘤细胞中的 DNA 断裂。鉴定这些影响的机制可以导致设计更有效的治疗策略来对抗肿瘤的进展，从而改善患者的预后。
为了鉴定更多可能在胶质母细胞瘤进展中起作用的缺氧调节基因，我们对 cDNA-AFLP 进行了优化，使其成为一种差异显示方法，能够识别和分离无先验序列知识的转录物。
使用这种方法，本研究鉴定了 120 个转录衍生片段（TDFs），它们在缺氧反应中完全差异调节。通过序列同源性搜索，本研究可以检测到 22 个完全差异调节的已知基因和两个与两个染色体连续体和四个与一些表达序列标签（ESTs）相匹配的未知序列。
对这些基因的进一步表征可能有助于更好地理解肿瘤细胞中缺氧介导的表型变化。
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