PTEN及Bcl-2蛋白在膀胱移行细胞癌中的表达及其意义

目的：探讨PTEN及Bcl-2蛋白在膀胱移行细胞癌的表达规律及其临床意义。方法：应用免疫组织化学链亲和素-生物素-霉复合物（SP）方法检测43例膀胱移行细胞癌和7例正常黏膜组织中PTEN及Bcl-2蛋白的表达．分析二者的表达与膀胱癌病理参数的关系。结果：（1）G1、G2、G3肿瘤PTEN表达阳性率分别为85．7％、80．4％、73．3％，浸润性肿瘤和表浅性肿瘤表达阳性率分别为70．4％和93．8％，说明PTEN表达阳性率与肿瘤病理分级、临床分期有关。（2）G。、G2、G3肿瘤Bcl-2表达阳性率分别为14．2％、57．14％、66．67％，浸润性肿瘤和表浅性肿瘤表达阳性率分别为59．3％和43．8％，说明Bcl-2表达阳性率与肿瘤病理分级、临床分期有关。（3）随着肿瘤恶性程度的增高和临床分期进展，PTEN蛋白阳性率呈下降，Bcl-2表达呈增高趋势，二者表达呈负相关关系。结论：PTEN的抑癌作用可能与Bcl-2有关．二者的异常表达在膀胱移行细胞癌的发生、发展过程中起重要作用。二者同时检测有助于判断预后。     

pp60c-src encoded by the proto-oncogene c-src is a product of sensory neurons

The advent of recombinant DNA technology has led to the identification in the DNA of normal animal cells of over 30 proto-oncogenes that are homologous to retroviral transforming genes. One of these encodes a protein kinase (pp60c-src) of unknown function, that is preferentially synthesized in brain and neural retina. Here the expression of pp60c-src in the peripheral nervous system was examined in sensory neurons from chick dorsal root ganglia with antisera raised against the transforming protein of Rous sarcoma virus (pp60v-src) expressed in Escherichia coli carrying the cloned v-src gene. This antiserum recognizes pp60c-src specifically in normal chicken cells. Western immunoblotting showed that dorsal root ganglia of stage 30 (day 6.5) chick embryos contained elevated levels of pp60c-src. Immunoperoxidase staining of neuron-enriched cultures prepared from chick dorsal root ganglia showed pp60c-src immunoreactivity in cells with neuronal morphology; flat, fibroblastic cells contained no detectable immunoreactivity. Indirect double immunofluorescence with pp60src antibodies and monoclonal antibodies against the 200-kD subunit of neurofilament protein confirmed that the cells expressing pp60c-src were neurons. Ninety-six percent of the neurofilament-positive cells were immunoreactive with pp60src antibodies, and conversely, all pp60c-src-positive cells were immunoreactive with neurofilament antibodies. pp60c-src immunofluorescence appeared to be distributed over the cell body, processes, and growth cones. These results clearly demonstrate that pp60c-src is a product of neurons and is expressed in sensory neurons in culture.     

地高辛标记核酸探针技术在家兔视网膜C－sis原癌基因检测中的应用

用ＡＧＰＣ法抽提幼年家兔视网膜总ＲＮＡ，并应用了地高辛标记核酸探针的方法。经斑点杂交显示幼年家兔视网膜出现Ｃ—ｓｉｓ原癌基因表达。对实验方法以及Ｃ－ｓｉｓ原癌基因表达的意义进行了探讨。认为此方法快速、灵敏，检测Ｃ－ｓｉｓ原癌基因表达对深入研究视网膜生长发育及肿瘤等病变有一定意义。     

5-羟色胺对大鼠脊髓P物质痛觉调制的影响(英文)

比较SP,5-HT与For诱发的脊髓内c-fos表达的异同,以及它们之间的相互关系,从而进一步了解SP在脊髓痛觉调制中的主要作用.方法:用免疫组织化学法和痛阈测定法.结果:发现大鼠it P物质(sP)10μg和sc5％甲醛(For)150μL诱发的脊髓c-fos表达主要在背角Ⅰ,Ⅱ,Ⅴ及Ⅵ层,同时SP使痛阈降低,For使痛级均数(PIR)升高.5-HT it 20μg引起的c-fos表达较多地分布于背角Ⅲ—Ⅳ层,并可使痛阈升高.5-HT和Fen可分别减弱和增加SP及For诱发的脊髓c-fos表达及痛反应.结论:SP在脊髓内可能主要起致痛作用,5-HT可抑制SP引起的脊髓c-fos表达,从而参与SP的痛觉调制作用.     

一个RET原癌基因Met918Thr突变的多发性内分泌腺瘤病Ⅱb家系报道

目的 检测一个多发性内分泌腺瘤病(MEN)Ⅱb家系的RET原癌基因突变。方法 提取患者及其父母的外周血基因组DNA，对RET原癌基因第16外显子进行聚合酶链反应(PCR)，将PCR扩增产物进行直接基因测序和限制性内切酶分析。结果 检测到患者RET原癌基因第16外显子918密码子存在ATG(Met)／ACG(Thr)点突变，而在患者父母中未检测到该突变。结论 通过对MENⅡb患者及其父母的基因筛查发现，该患者点突变是杂合子错义突变。该疾病的诊断达到了基因水平。     

Somatic RET proto-oncogene mutations in sporadic C-cell carcinoma of the thyroid

Summary. Germline mutations of the RET proto-oncogene localized on chromosome 10q11.2 are the underlying cause of hereditary medullary thyroid carcinoma. In MEN 2A and FMTC, mutations can be found in exons 10, 11, 13 or 14. MEN 2B is characterized by a specific mutation in exon 16. In a significant number of sporadic MTC somatic mutations in codon 918 (exon 16) are detectable. Some rare sporadic MTC present somatic mutations in codons 611, 634, 768 and 883. Recently, deletion-insertion of the RET proto-oncogene in exon 11 and a deletion in exon 10 has been found. RET proto-oncogene mutations are not only responsible for the development of the familial MTC, but may also play an important role in the pathogenesis of sporadic MTC. However, the prognostic relevance of these somatic events is still unclear.      

Cerebral ischemia induces transient intracellular redistribution and intranuclear translocation of the raf proto-oncogene product in hippocampal pyramidal cells

Summary In this report we describe changes in the intracellular redistribution of raf serine/threonine protein kinase (product of the raf proto-oncogene family) in hippocampal neurons following cerebral ischemia in Mongolian gerbils. For immunohistochemical localization studies polyclonal antisera specific for each of the A, B, and Raf-1 isotypes of raf, as well as a pan-raf antisera, were employed. Of these, only sera recognizing B-raf, as well as the general v-raf (raised against the conserved C-terminal region) were positive, indicating that B-raf is the major isotype in this neuronal region. Three different ischemie models were used (repeated 3 times for two min and single 5 or 15 min occlusions, of the common carotid arteries) to demonstrate that ischemie insult causes redistribution of raf protein kinase into the cell nucleus of hippocampal neurons. Increased amounts of raf protein in the nuclei of pyramidal cells following ischemia was confirmed by Western blot analysis of isolated nuclear fractionations. Moreover, an elevation in the level of nuclear raf protein also was detected in the contralateral (i.e. non-occluded hemisphere) neurons of CA1 and CA3 subfields 4 days after the ischemie insult indicating a possible transsynaptic increase in the amount of raf protein along with redistribution. The intranuclear translocation of the immunoreactive material started from the perinucleolar rim and with time extended throughout the nucleus. Enhanced levels and altered redistribution of the raf polypeptide in the nuclei of pyramidal cells of the CA3 subfleld appears to be reversible and returns to the normal level 12 days following the ischemic insult. In addition to triggering the above changes in the intracellular redistribution of raf, ischemie insult also caused an increase in the level of B-raf protein in reactive astrocytes.     

A girl with 1p36 deletion syndrome and congenital fiber type disproportion myopathy

Chromosome 1p36 deletion syndrome is characterized by hypotonia, moderate to severe developmental and growth retardation, and characteristic craniofacial dysmorphism. Muscle hypotonia and delayed motor development are almost constant features of the syndrome. We report a 4-year-old Japanese girl with 1p36 deletion syndrome whose muscle pathology showed congenital fiber type disproportion (CFTD) myopathy. This is the first case report of 1p36 deletion associated with CFTD. This association may indicate that one of the CFTD loci is located at 1p36. Ski proto-oncogene −/− mice have phenotypes that resemble some of the features observed in patients with 1p36 deletion syndrome. Because fluorescent in situ hybridization analysis revealed that the human SKI gene is deleted in our patient, some genes in 1p36, including SKI proto-oncogene, may be involved in muscle hypotonia and delayed motor development in this syndrome. Received: March 4, 2002 / Accepted: July 7, 2002     

The RET proto-oncogene in medullary and papillary thyroid carcinoma

 The evolution of cancer is a multistep phenomenon, and multiple cellular genetic lesions are involved in the emergence of the malignant neoplasm. Several early events have been implicated in the neoplastic transformation of thyrocytes, and recent reports have described the involvement of specific genetic alterations in different types of thyroid neoplasms: ras point mutations are frequently observed in tumours with follicular histology, gsp – the mutated form of the alpha subunit of the Gs-protein – is encountered in up to 73% of papillary or follicular thyroid carcinomas, and a high prevalence of p53 point mutations has been found in anaplastic thyroid carcinomas but not in differentiated follicular tumours. More recent studies revealed that the RET proto-oncogene is involved in the oncogenesis of medullary thyroid carcinoma (MTC) and papillary thyroid carcinoma (PTC) by activation of its tyrosine kinase either by point mutation or rearrangement. In this review the most important recently published data on alterations of the RET proto-oncogene in heritable and sporadic MTCs and in PTCs will be summarized. Emphasis will be directed to the pathophysiological mechanisms of tumour initiation, the indications and limitations of DNA testing, and the clinical implications of identified RET defects in thyroid lesions. Received: 9 January 1997 / Accepted: 17 February 1997