人癌基因N—ras的限制性片段长度多态性

应用3种人癌基因N-ras探针分别与经5种限制酶消化的肝癌组织与正常组织DNA作分子杂交，发现11种未见报告的杂交片段，它们可作为遗传标记，在探查致癌的家族素因以及肿瘤的遗传易感性等研究中发挥作用。     

ras癌基因在人乳腺肿瘤中的表达

应用P_(21)蛋白单克隆抗体,对25例人乳腺癌的免疫组织化学检测显示,在乳腺浸润性导管癌组织中,有高水平的P_(21)表达,阳性率高达92％,与Querzoli等报道一致。29伊4乳腺良性病变的检测结果显示,细胞内P_(21)表达水平的高低与细胞增殖状态相关。临床对比分析提示乳腺癌中P_(21)的表达水平与瘤体大小有关但不能反映病人的淋巴结转移状态。上述结果表明,ras癌基因表达产物P_(21)蛋白,是一个与细胞增殖相关,可反映组织增殖状态的细胞生物学因子。     

c—erbB—2癌基因蛋白,EGFR在胰腺癌组织中的表达和意义

目的 探讨人ｃ－ｅｒｂＢ－２癌基因蛋白、表皮生长因子受体（ＥＧＦＲ）的表达与胰畜产品铁关系。方法 应用ＳＡＢＣ法对１０例正常胰腺、１３例慢性胰腺炎和３６例胰腺导管腺癌石蜡组织切片进行免疫组化染色。结果（１）ｃ－ｅｒｂＢ－２蛋白、ＥＧＦＲ在正常胰腺中无表达,仅１例慢性胰腺炎两者均阳性表达,在胰腺癌中两者阳性率分别为４１．７％、５０．０％,明显高于正常组和慢性胰腺炎组;（２）两种蛋白的表达与胰腺癌临床     

C－myc癌基因在胃癌和癌前病变中的表达

 本研究采用生物素标记的C-myc癌基因为探针，检测70例胃部标本中C-myc癌基因mRNA的表达。结果发现C-myc癌基因的高表达在胃癌中占60.4%,在胃的良性病变中占27.27%,两者之间有显着性差异（P<0.05）.在48例胃癌的癌旁上皮中，C-myc癌基因高表达占37.5%,其中19例有不典型增生的癌旁上皮，高表达占78.95%,而无不典型增生的癌分上皮高表达只占10.34%.结果提示C-myc癌基因的高表达与胃粘膜上皮的异型增生有关，与胃癌的临床预后的关系还有待进一步探索。     

乳腺肿瘤癌基因c—erbB—2,c—myc的表达及其临床意义

应用免疫组织化学方法，研究６１例乳腺良、恶性病变ｃ－ｅｒｂＢ－２、ｃ－ｍｙｃ的癌基因的表达情况。４６例乳腺癌中ｃ－ｅｒｂＢ－２和ｃ－ｍｙｃ阳性率分别为５０％（２３／４６）和４５．７％（２１／４６）１５例乳腺良性病变中阳性率分别为６．７％（１／１５）和５３．５％（８／１５）。     

c—Ha—ras癌基因高表达与胃癌临床行为的关系

应用ＲＮＡ斑点杂交、Ｎｏｒｔｈｅｒｎ ｂｌｏｔ和免疫组织化学技术检测了２０例胃癌病员癌组织中ｃ－Ｈａ－ｒａｓ ｍＲＮＡ和Ｐ＾２１蛋白的表达。统计学结果表明，胃癌组织中ｃ－Ｈａ－ｒａｓ ｍＲＮＡ过度表达和肿瘤淋巴结转移状态密切相关（Ｐ＝０．０３３），随着胃癌临床病程进展，肿瘤细胞中ｃ－Ｈａ－ｒａｓ Ｐ＾２１表达水平逐渐升高（Ｐ＝０．１１２）。提示ｃ－Ｈａ－ｒａｓ癌基因高表达可能是胃癌形成过程中的关键     

Site-specific hypomethylation of the c-myc oncogene in human hepatocellular carcinoma

In order to examine the effect of alteration in methylation of the c-myc gene on hepatocarcinogenesis, the extent of methylation of the c-myc gene was examined in 24 tissues of hepatocellular carcinoma (HCC), 24 adjacent non-tumor liver tissues from the same patients and 16 control liver tissues by the use of restriction endonucleases. The following results were obtained. (1) The c-myc gene from HCC tissue tended to be hypomethylated in comparison with that in non-tumor liver tissue from the same patient. (2) The c-myc gene from non-tumor liver tissue was hypomethylated to various degrees in comparison with that in control liver tissues. (3) The CCGG site in the third exon of the c-myc gene tended to be more extensively hypomethylated in HCC tissues than in non-tumor and control liver tissues. These results suggest that hypomethylation of the c-myc gene may occur to various degrees before the appearance of HCC, and may be associated with hepatocarcinogenesis. Moreover, the hypomethylation in the third exon of the c-myc gene is probably important for the development of HCC.     

c-myc oncogene alterations in human thyroid carcinomas

A possible role of the c-myc oncogene in the neoplastic transformation of the human thyroid has been investigated. The structure, the methylation status, and the copy number of this oncogene have been analyzed in normal and in tumor thyroid DNAs by Southern blotting technique and dot blot hybridization. Among six carcinomas, four presented abnormal c-myc DNA structure: Three cases showed a mutation in the 5' flanking region of the gene, originating a new EcoRI site; the other case showed a deletion of 5 kb involving the first exon of the gene. This deletion was also observed in the white blood cells of the same individual. In addition, in three carcinomas a double dose of the oncogene has been demonstrated. In all the carcinomas examined, undermethylation of the c-myc oncogene has been observed. These findings suggest that c-myc oncogene alterations might be involved in the malignant transformation of the human thyroids and can be considered as tumor markers.     

Expression of c-myc oncogene product and ras family oncogene products in various human malignant lymphomas defined by immunohistochemical techniques

The authors studied the expression of c-myc and ras family oncogene products in 43 cases of malignant lymphoma (ML) using the immunoperoxidase method. Unfixed frozen sections of lymph nodes from four patients with Hodgkin's disease and 39 with non-Hodgkin's lymphoma, together with normal lymph nodes, were studied by the avidin-biotin-peroxidase complex (ABC) technique. Two monoclonal antibodies, MYC-2 raised against recombinant human c-myc protein (reacting specifically with the c-myc products P62 and P67) and RASK-4 (raised against recombinant P21 and reacting specifically with ras-family product P21) were used. The c-myc product was detected in nuclei of ML cells and some normal, mainly germinal center, lymphocytes. When the staining intensity shown by normal germinal-center lymphocytes was graded as positive (+) or weakly positive (+/-), a very intensely positive reaction ( to ++) was observed in 37 cases (86%) of ML, a positive reaction (+) in four cases (9.3%), and a weakly positive reaction (+/-) in two cases (4.7%). The ras family oncogene product reaction was intensely positive (++) in two cases (4.7%), positive (+) in 16 cases (37.2%), weakly positive (+/-) in 13 cases (30.2%), and negative in 12 cases (27.9%). Western blot analysis confirmed an elevated level of c-myc products in two cases, which showed intense MYC-2 staining, and of ras family products in one case, which demonstrated intense RASK-4 staining. The enhanced expression of these gene products may play an important role in lymphomagenesis of such cases.     

Amplification of the c-myc oncogene in human plasma-cell leukemia

We have examined primary leukemia cells from multiple myeloma and plasma-cell leukemia patients for rearrangement, amplification and expression of c-myc oncogene. No rearrangement or detectable amplification of the c-myc could be found in 21 cases of multiple myeloma. In contrast, 2/3 cases of plasma-cell leukemia showed amplification of the oncogene with concomitant higher level of expression.     

In vivo amplification and rearrangement of c-myc oncogene in human breast tumors

We have studied the genomic organization of cellular myc (c-myc) proto-oncogene in 48 human primary breast tumors. Two types of alterations (amplification and rearrangement) were observed in 27 (56%) of the tumors studied. The c-myc proto-oncogene appeared to be amplified 2- to 15-fold in the DNA of 20 tumors (41%). Non-germ line c-myc-related fragments (rearrangements) of variable size were detected in 7 primary breast tumors (6 malignant, 1 benign); 4 of these tumors presented both rearrangement and amplification, and the other 3 presented rearrangement only. The majority of the tumors analyzed were invasive ductal adenocarcinomas; 58% of these showed c-myc locus genetic alterations. Although the c-myc alterations described here do not appear to correlate with the aggressive behavior of primary breast tumors, they seem to be associated with development of breast carcinoma.     

Expression of c-myc gene product in gastric carcinoma

The expression of c-myc oncogene product was studied in 213 cases with gastric carcinoma by an immunoperoxidase method using a monoclonal antibody (MYC-1). Fifty (23.5%) of 213 tumors showed immunoreactivity to MYC-1. The distribution of c-myc-product-positive cells was observed mainly at the marginal area of the tumor. Excess reactivity to c-myc product occurred more frequently in invasive cancers than in localized cancers, and c-myc production expression in cancer tissue correlated well with peritoneal dissemination. Patients with c-myc-protein-positive tumor had significantly poorer prognosis than those with c-myc-protein-negative tumor in invasive gastric carcinomas, and the c-myc product status correlated well with the recurrence of cancer by peritoneal dissemination. These results suggest that the expression of c-myc gene product might be related to the proliferative activity of gastric carcinoma and serve as a new biologically relevant tumor marker for determining the prognosis.