Astroblastoma: Report of a case with microsatellite analysis

A 5‐year‐old girl who developed progressive headache, vomiting, and left hemiparesis was found to have a cystic tumor with an enhanced mural nodule in the right frontoparietal region on a computed tomography examination. The lesion was histologically and ultrastructurally verified as an astroblastoma, an uncommon neuroepithelial tumor of uncertain origin. Molecular analysis using 17 microsatellite markers on chromosomes 9, 10, 11, 17, 19, and 22 showed loss of heterozygosity at the D19S412 locus on the long arm of chromsome 19. This observation suggests that there is a tumor suppressor gene in this chromosomal region, which plays a role in the pathogenesis of astroblastoma.     

Investigation of germline PTEN,p53, p16INK4A/p14ARF,and CDK4 alterations in familial glioma

Epidemiological studies suggest that some familial aggregations of glioma may be due to inherited predisposition. Many genes involved in familial cancers are frequently altered in the corresponding sporadic forms. We have investigated several genes known to be altered in sporadic gliomas for their potential contribution to familial glioma. Fifteen glioma patients with a family history of brain tumors were identified through the Mayo Clinic Department of Neurology (nine diffuse astrocytomas, two oligodendrogliomas, two mixed oligoastrocytomas, one pilocytic astrocytoma, and one pineal glioma). Eleven of the propositi had one or more first degree relative with a glioma. Lymphocyte DNA was derived from each of the patients and analyzed by polymerase chain reaction (PCR) and direct sequencing of the PTEN, p53, p16^INK4A/p14^ARF, and CDK4 genes. In addition, fluorescence in situ hybridization (FISH) was performed on EBV‐transformed lymphocytes from each affected individual to detect germline copy number of the p16^INK4A/p14^ARF tumor suppressor region. A p53 germline point mutation was identified in one family with some findings of Li‐Fraumeni syndrome, and a hemizygous germline deletion of the p16^INK4A/p14^ARF tumor suppressor region was demonstrated by FISH in a family with history of both astrocytoma and melanoma. Thus, whereas germ‐line mutations of PTEN, p53, p16^INK4A/p14^ARF, and CDK4 are not common events in familial glioma, outside of familial cancer syndromes, point mutations of p53 and hemizygous deletions and other rearrangements of the p16^INK4A/p14^ARF tumor suppressor region may account for a subset of familial glioma cases. Collectively, these data lend genetic support to the heritable nature of some cases of glioma. Am. J. Med. Genet. 92:136–141, 2000. © 2000 Wiley‐Liss, Inc.     

不同强度有氧运动对脑胶质瘤术后化疗患者癌因性疲乏及HPA轴功能的影响

目的 探讨不同强度有氧运动对脑胶质瘤术后化疗患者癌因性疲乏(CRF)及下丘脑-垂体-肾上腺皮质(HPA)轴功能的影响.方法 选取脑胶质瘤术后化疗并发CRF患者76例,随机分为2组,各38例.A组予以25％VO2max的强度进行有氧运动,B组予以50％VO2max的强度进行有氧运动,2组均连用8周.统计分析2组治疗前后H...     

Optic chiasm glioma,electrolyte abnormalities,nonobstructive hydrocephalus and ascites

A 4-year-old girl with optic chiasm glioma (OCG), nonobstructive hydrocephalus and ventriculoperitoneal shunt is described, in whom marked ascites developed. The ascitic fluid was protein-rich and its amount correlated with cerebrospinal fluid (CSF) protein. The CSF protein level and the amount of ascitic fluid were influenced by chemotherapy. Very unusual hypernatremia, up to 190 mEq/l, with no associated alteration in mental status, was also found. It is suggested that altered absorption ability owing to the high protein content was the cause of both the nonobstructive hydrocephalus and the ascites. The unusual well being with very high sodium concentrations may have resulted from osmoreceptor dysfunction, presumably caused by hypothalamic involvement as well as by the high CSF protein. This combination of findings may point toward specific characteristics of OCG. In an effort to reduce the amount of the ascitic fluid, a further chemotherapeutic trial may be done, before converting the shunt to the vetriculoatrial system. Med. Pediatr. Oncol. 29:33–35, 1997. © 1997 Wiley-Liss, Inc.     

4-aminopyridine causes apoptosis and blocks an outward rectifier K+ channel in malignant astrocytoma cell lines

Among the ion channels and pumps activated by growth factor stimulation, K⁺ channels have been implicated in the growth and proliferation of several cancer cell lines. The role of these channels in central nervous system tumors, however, has not been described. This study used the malignant astrocytoma cell lines U87 and A172. 4-Aminopyridine (4-AP) inhibition of proliferation was dose dependent, and assessment using a TUNEL in situ assay revealed that apoptosis occurred in U87 cells with wild-type p53 but not in A172 cells with mutant p53 (24-hr incubation with 4 mM 4-AP). In patch clamp experiments, we identified two types of K⁺ currents in both cell lines, a charybdotoxin-sensitive Ca²⁺-activated K⁺ channel and a 4-AP-sensitive outward rectifier K⁺ current. The outward rectifier current was blocked by 4-AP in a dose-dependent manner, with half-maximal block occurring at 3.9 mM. The blocking effect of 4 mM 4-AP was noticeable at potentials as low as −65 mV and was statistically significant at −60 mV and above, suggesting that 4-AP-sensitive current is active at physiological potentials. By contrast, charybdotoxin (1 μM) and tetraethylammonium · Cl (2 mM) blocked the Ca²⁺-activated K⁺ channel in both cell lines but had no appreciable effect on cell growth. Our findings reveal that 4-AP inhibits proliferation and the outward rectifier K⁺ channel in both U87 and A172 cells. More studies are needed, however, to describe the mechanism by which K⁺ channels influence proliferation and induce apoptosis. J. Neurosci. Res. 48:122–127, 1997. © 1997 Wiley-Liss, Inc.     

重组腺相关病毒载体介导血管抑素基因治疗大鼠脑胶质瘤的实验研究

目的制备大鼠脑胶质瘤模型,注射腺相关病毒血管抑素基因重组载体(AAV-AS),观察对脑胶质瘤的治疗效果。方法皮下接种C6脑胶质瘤细胞制备大鼠胶质瘤模型,皮下注射AAV-AS,24天后取材,观察瘤重、肿瘤坏死率和血管计数,RTP-CR法检测AS转录。结果AAVAS治疗组肿瘤体积明显缩小,坏死明显,血管计数减少,RT-PCR法检测到AS转录。结论AAV-AS在大鼠体内可以表达,通过抑制血管生成而抑制肿瘤生长,促进肿瘤坏死。     

Recurrent NF1 gene mutation in a patient with oligosymptomatic neurofibromatosis type 1 (NF1)

We report a 21-year-old male with symptomatic optic glioma who does not fulfill the diagnosis of neurofibromatosis 1 (NF1) according to standard NIH criteria. Analysis of the NF1 gene revealed a recurrent mutation in exon 37 (C6792A or Y2264X). This nonsense mutation causes skipping of exon 37 during the splicing process and is predicted to result in a protein shortened by 34 amino acid residues. The mutation was detected in all tissues examined (blood lymphocytes, oral mucosa, and dermal fibroblasts). The same mutation was previously found in 3 patients with clinically confirmed NF1. To our knowledge, this is the first report of an adult patient carrying a putative (non-mosaic) NF1 gene mutation in multiple tissues but not fulfilling the NIH criteria for the clinical diagnosis of NF1. Am. J. Med. Genet. 86:328–330, 1999.