P53，Rb和c－myc基因在人脑原发性肿瘤中的转录表达

采用RNA斑点杂交分析,对21例人脑原发性胶质瘤和11例人脑膜瘤中p53,Rb和c-myc基因转录水平的表达进行研究.发现48.4%的肿瘤中p53基因表达减弱,21.9%的肿瘤中Rb基因表达减弱;71.9%的肿瘤中c-myc基因表达增强.在p53基因表达减弱的15例病例中有13例(80%)c-myc基因表达增强.结果表明,p53基因表达减弱和c-myc基因表达增强与人脑原发性肿瘤的发生有关.     

P53，Rb和c－myc基因在人脑原发性肿瘤中的转录表达

采用ＲＮＡ斑点杂交分析,对２１测人脑原发性胶质瘤和１１例人脑膜瘤中ｐ５３,Ｒｂ和ｃ－ｍｙｃ基因转录水平的表达进行研究,发现４８．４％的肿瘤中ｐ５３基因表达减弱,２１．９％的肿瘤中Ｒｂ基因表达减弱;７１．９％的肿瘤中ｃ－ｍｙｃ基因表达增强,在ｐ５３基因表达减弱的１５例病例中有１３例（８０％）ｃ－ｍｙｃ基因表达增强,结果表明,ｐ５３基因表达减弱和ｃ－ｍｙｃ基因表达增强与人脑原发性肿瘤的发生有关。     

卵巢肿瘤的c－erbB－3蛋白表达特征

卵巢肿瘤的ｃ－ｅｒｂＢ－３蛋白表达特征英国爱丁堡西部总医院的ＳｉｍｐｓｏｎＢＧ等用单克隆抗体ＲＴＪ１检测了７１名卵巢肿瘤病人的７３份标本,按免疫组化染色强度将ｃ－ｅｒｂＢ－３的表达分为阴性、弱阳性、阳性、强阳性四级,结果表明ｃ－ｅｒｂＢ－３表达程度与...     

人脑原发性肿瘤癌基因扩增和重排的研究

作者对52例人脑原发性肿瘤和5例正常人脑DNA中c-myc、L-myc、Nmyc、erbB、c-fos、sis及Ha-ras等七种癌基因的扩增和重排进行了研究,发现多数胶质瘤中有c-myc、L-myc、erbB及c-fos等癌基因的扩增,少数胶质瘤和脑膜瘤中发现myc家族癌基因的限制性酶切区带位置有多态性变化;同时还观察到原发性脑瘤中存在两种或两种以上癌基因的扩增和重排现象。作者对癌基因与人脑原发性肿瘤的关系进行了讨论。     

c－erbB2／neu扩增诱导人前列腺癌细胞的转移能力

用突变的ｃ－ｅｒｂＢ２／ｎｅｕ癌基因转染人类ＰＣ３细胞系,使转化克隆Ｎ３５具有癌转移能力,在接种到裸鼠后能向肺、骨髓等远处转移．各项实验指标证实,外源性的ｎｅｕ基因已整合至人类细胞的染色质ＤＮＡ中,并获得基因扩增和高表达．结果提示ｎｅｕ癌基因与肿瘤的发展和转移能力的形成有密切的关系．     

动脉平滑肌细胞sis／PDGF－B链的表达和调控

介绍平滑肌细胞ｓｉｓ／ＰＤＧＦ－Ｂ链表达和调控的进展。ｃ－ｓｉｓ原癌基因是ＰＤＧＦ－Ｂ的同源基因,将外源的ＰＤＧＦ基因导入哺乳类细胞是研究ＰＤＧＦ功能和调控的重要手段。内皮素、ＩＬ、ＴＮＦ、血管紧张素Ⅱ和蛋白激酶Ｃ可调节ｓｉｓ基因的表达。ｓｕｒａｍｉｎ和新霉素（ｎｅｏｍｙｃｉｎ）的人工合成为拮抗ＰＤＧＦ效应提供广阔的前景。ｃ－ｓｉｓ可通过激活ｃ－ｍｙｃ、ｃ－ｆｏｓ等原癌基因而促进细胞增殖。     

血管成形术后原癌基因c－fos、c－myc表达的研究

ｃ－ｆｏｓ、ｃ－ｍｙｃ是两种参与细胞增殖的原癌基因。动脉血管成形术（ＰＴＡ）后的血管再狭窄,是由于血管壁平滑肌细胞增生所致。利用大白兔建立的试验动物模型,提取ＰＴＡ后不同时间间隔的动脉壁总ＲＮＡ,并用斑点杂交法分析两种原癌基因的表达情况,发现了ｃ－ｆｏｓ和ｃ－ｍｙｃ的基因分别在术后１５分钟内转录活性提高,并分别在３０分钟和第２小时达到高峰。     

Expression of N-myristoyltransferase in Human Brain Tumors

N-myristoylation is a process of covalent irreversible protein modification that promotes association of proteins with membranes. Based on our previous findings of elevated N-myristoyltransferase (NMT) activity in colonic epithelial neoplasms that appears at an early stage in colonic carcinogenesis, together with elevated NMT expression in human colorectal and gallbladder carcinomas, we investigated NMT activity and protein expression of NMT1 and NMT2 in human brain tumors and documented elevated NMT activity and higher protein expressions. For the first time, we have demonstrated that NMT has the potential to be used as a marker of human brain tumors. However, further studies with larger number of patients are required to establish its role as a complementary diagnostic tool. This finding has significant implications for further understanding of biological mechanisms involved in tumorigenesis, as well as for diagnosis and therapy of human brain tumors.     

New Agents for Targeting of IL-13RA2 Expressed in Primary Human and Canine Brain Tumors

Interleukin 13 receptor alpha 2 (IL-13RA2) is over-expressed in a vast majority of human patients with high-grade astrocytomas like glioblastoma. Spontaneous astrocytomas in dogs resemble human disease and have been proposed as translational model system for investigation of novel therapeutic strategies for brain tumors. We have generated reagents for both detection and therapeutic targeting of IL-13RA2 in human and canine brain tumors. Peptides from three different regions of IL-13RA2 with 100% sequence identity between human and canine receptors were used as immunogens for generation of monoclonal antibodies. Recombinant canine mutant IL-13 (canIL-13.E13K) and canIL-13.E13K based cytotoxin were also produced. The antibodies were examined for their immunoreactivities in western blots, immunohistochemistry, immunofluorescence and cell binding assays using human and canine tumor specimen sections, tissue lysates and established cell lines; the cytotoxin was tested for specific cell killing. Several isolated MAbs were immunoreactive to IL-13RA2 in western blots of cell and tissue lysates from glioblastomas from both human and canine patients. Human and canine astrocytomas and oligodendrogliomas were also positive for IL-13RA2 to various degrees. Interestingly, both human and canine meningiomas also exhibited strong reactivity. Normal human and canine brain samples were virtually negative for IL-13RA2 using the newly generated MAbs. MAb 1E10B9 uniquely worked on tissue specimens and western blots, bound live cells and was internalized in GBM cells over-expressing IL-13RA2. The canIL-13.E13K cytotoxin was very potent and specific in killing canine GBM cell lines. Thus, we have obtained several monoclonal antibodies against IL-13RA2 cross-reacting with human and canine receptors. In addition to GBM, other brain tumors, such as high grade oligodendrogliomas, meningiomas and canine choroid plexus papillomas, appear to express the receptor at high levels and thus may be appropriate candidates for IL-13RA2-targeted imaging/therapies. Canine spontaneous primary brain tumors represent an excellent translational model for human counterparts.     

Expression of the Homeobox Genes OTX2 and OTX1 in the Early Developing Human Brain

In rodents, the Otx2 gene is expressed in the diencephalon, mesencephalon, and cerebellum and is crucial for the development of these brain regions. Together with Otx1, Otx2 is known to cooperate with other genes to develop the caudal forebrain and, further, Otx1 is also involved in differentiation of young neurons of the deeper cortical layers. We have studied the spatial and temporal expression of the two homeobox genes OTX2 and OTX1 in human fetal brains from 7 to 14 weeks postconception by in situ hybridization and immunohistochemistry. OTX2 was expressed in the diencephalon, mesencephalon, and choroid plexus, with a minor expression in the basal telencephalon. The expression of OTX2 in the hippocampal anlage was strong, with no expression in the adjacent neocortex. Contrarily, the OTX1 expression was predominantly located in the proliferative zones of the neocortex. At later stages, the OTX2 protein was found in the subcommissural organ, pineal gland, and cerebellum. The early expression of OTX2 and OTX1 in proliferative cell layers of the human fetal brain supports the concept that these homeobox genes are important in neuronal cell development and differentiation: OTX1 primarily in the neocortex, and OTX2 in the archicortex, diencephalon, rostral brain stem, and cerebellum. (J Histochem Cytochem 58:669–678, 2010)     

Exploration of Involved Key Genes and Signaling Diversity in Brain Tumors

Brain tumors are becoming a major cause of death. The classification of brain tumors has gone through restructuring with regard to some criteria such as the presence or absence of a specific genetic alteration in the 2016 central nervous system World Health Organization update. Two categories of genes with a leading role in tumorigenesis and cancer induction include tumor suppressor genes and oncogenes; tumor suppressor genes are inactivated through a variety of mechanisms that result in their loss of function. As for the oncogenes, overexpression and amplification are the most common mechanisms of alteration. Important cell cycle genes such as p53, ATM, cyclin D2, and Rb have shown altered expression patterns in different brain tumors such as meningioma and astrocytoma. Some genes in signaling pathways have a role in brain tumorigenesis. These pathways include hedgehog, EGFR, Notch, hippo, MAPK, PI3K/Akt, and WNT signaling. It has been shown that telomere length in some brain tumor samples is shortened compared to that in normal cells. As the shortening of telomere length triggers chromosome instability early in brain tumors, it could lead to initiation of cancer. On the other hand, telomerase activity was positive in some brain tumors. It is suggestive that telomere length and telomerase activity are important diagnostic markers in brain tumors. This review focuses on brain tumors with regard to the status of oncogenes, tumor suppressors, cell cycle genes, and genes in signaling pathways as well as the role of telomere length and telomerase in brain tumors.