Differential expression of pancreatic trypsinogen and cathepsin-B in human scirrhous-type and intestinal-type gastric carcinomas

Pancreatic trypsinogen and cathepsin B expression was evaluated in 44 surgically resected gastric carcinomas by immunohistochemical analysis. Carcinomatous tissues were subjected to immunohistochemical staining with a monoclonal antibody against human pancreatic trypsinogen and a polyclonal antibody against human cathepsin B. As a result, twenty-two of 24 scirrhous-type gastric carcinomas (92%) expressed pancreatic trypsinogen intensely and diffusely in a fine granular pattern over the entire cytoplasm of carcinoma cells. In contrast, only 5 of 20 intestinal-type gastric carcinomas (25%) reacted with the trypsinogen specific antibody and then only focally, in a fine granular pattern in the supra-nuclear cytoplasm of carcinoma cells. Cathepsin B expression was detected in 20 of 24 scirrhous-type gastric carcinomas (84%) in a fine, diffuse, granular pattern in the cytoplasm of carcinoma cells, while only 2 of 20 intestinal-type gastric carcinomas (10%) had detectable cathepsin B. From these results, we find that scirrhous-type gastric carcinomas express abundant quantities of pancreatic trypsinogen and cathepsin B immunoreactive peptides.     

Pancreatic trypsinogen and cathepsin B in human pancreatic carcinomas and associated metastatic lesions.

Expression of pancreatic trypsinogen and cathepsin B in 23 surgically resected pancreatic ductal adenocarcinomas was evaluated immunohistochemically, using a monoclonal antibody against human pancreatic trypsinogen and a polyclonal antibody against human cathepsin B. Fifteen of 20 invasive tubular adenocarcinomas (75%) expressed pancreatic trypsinogen in a coarse granular pattern located in the supranuclear cytoplasm of the carcinoma cells. In addition, metastatic lesions, including those in peripancreatic lymph nodes and neural plexuses, expressed pancreatic trypsinogen. In contrast, three intraductal (non-invasive) papillary adenocarcinomas did not express pancreatic trypsinogen. Cathepsin B expression was recognised in 14 of 20 invasive tubular adenocarcinomas (70%) in a fine granular pattern located diffusely in the cytoplasm of the carcinoma cells, while none of the three intraductal papillary adenocarcinomas had detectable cathepsin B. These findings suggest that pancreatic invasive ductal adenocarcinomas express pancreatic trypsinogen and cathepsin B immunoreactive peptides, raising the possibility that pancreatic trypsinogen and cathepsin B may act independently of each other in the process of carcinoma invasion and metastasis, like other different classes of proteases involved in the proteolytic modification of the matrix barrier.     

环氧合酶-2在胰腺癌组织中的表达及其意义

背景与目的:非甾体类抗炎药物(nonsteroidalanti-inflammatorydrugs,NSAIDs)可以预防或降低消化系统肿瘤的发病率,提示环氧合酶-2(cyclooxygenase-2,COX-2)的表达与消化系统肿瘤的发生、发展密切相关。本研究通过检测胰腺癌组织中COX-2的表达,探讨COX-2与bcl-2表达的关系,及其在胰腺癌发生、发展过程中的作用。方法:胰腺癌等组织COX-2和bcl-2的表达采用ABC免疫组化分析;评价两者表达及其与患者临床病理特征的关系。结果:胰腺癌组织COX-2和bcl-2的表达阳性率分别为73.3%和66.7%,阳性率明显高于胰腺良性病变组织和正常胰腺组织,两者呈高度正相关,相关系数r=0.470(P<0.01)。但COX-2表达率与患者临床病理特征无关(P>0.05)。结论:胰腺癌组织中COX-2表达增强,COX-2表达与bcl-2表达有协同效应,两者共同参与胰腺癌细胞凋亡的调控。     

Expression of basic fibroblast growth factor and its receptor in human pancreatic carcinomas.

We examined the expression of basic fibroblast growth factor (FGF) and FGF receptor by immunohistochemistry in 32 human pancreatic ductal adenocarcinomas. Mild to marked basic FGF immunoreactivity was noted in 19 (59.4%) of the 32 tumours examined, and 30 (93.3%) of the tumours exhibited a cytoplasmic staining pattern against FGF receptor. The tumours were divided into two groups according to the proportion of positively stained tumour cells: a low expression group (positive cells < 25%) and a high expression group (positive cells > or = 25%). No statistically significant difference in tumour size, differentiation, metastases or stage was found between the low and high basic FGF expression groups. However, a significant correlation was found between FGF receptor expression level and the presence of retroperitoneal invasion, lymph node metastasis, and tumour stage. In addition, low FGF receptor expression was significantly associated with a longer post-operative survival as compared with high FGF receptor expression, whereas there was no significant difference in post-operative survival between the low and high basic FGF expression groups. Increased expression of FGF receptor is correlated with the extent of malignancy and post-operative survival in human pancreatic ductal adenocarcinomas. Thus, overexpression of FGF receptor may prove to be a more useful prognostic marker than basic FGF expression level in pancreatic cancer patients.     

Expression of c-erbA in human hepatocellular carcinomas

The expression of the oncogene c-erbA was studied in six hepatocellular carcinoma specimens and normal hepatic tissue. Total RNA isolated from these samples was analysed by Northern as well as slot blot hybridisation to a radioactive c-erbA probe. When compared to normal tissue, expression in the tumour and tissue adjacent to tumour was markedly elevated. These results suggest that overexpression of c-erbA is related to hepatocarcinogenesis. Southern blot analysis of DNA from the tumours gave no evidence of c-erbA rearrangements.     

Expression of phosphatidylethanolamine N-methyltransferase in human hepatocellular carcinomas

OBJECTIVE: Hepatic phosphatidylethanolamine is converted into phosphatidylcholine by the enzyme phosphatidylethanolamine N-methyltransferase (PEMT) when the dietary choline supply is inadequate. Our previous reports implicated PEMT in the regulation of hepatocyte growth and transformation. In the present study, we analyzed PEMT activity, PEMPT gene status and its mRNA expression in 29 human hepatocellular carcinomas (HCC). METHODS: The status of the PEMPT gene and PEMT2 mRNA expression were evaluated with Southern and Northern blotting, respectively, in HCC and the noninvolved liver. PEMT activity was assessed by biochemical assay. Cell proliferation markers were defined by immunohistochemical or histoautoradiographic methods. RESULTS: PEMT activity was lower in HCC than in the noninvolved liver and it was negligible in 62% of the tumors. No deletions or mutations of the PEMPT gene were found and PEMT2 mRNA expression was absent or reduced in HCC compared with peritumoral liver tissue. PEMT2 mRNA expression was inversely related to tumor proliferation and to histologic grade. Patients whose HCC did not express PEMT2 mRNA showed poorer outcomes for cancer-related survival than those with PEMT2-positive HCC. CONCLUSIONS: The present findings suggest that (1). clones lacking PEMT2 expression may have been selected during liver tumorigenesis and progression, and (2). PEMT2 expression seems to be associated with clinical progression.     

Expression of cripto, a novel gene of the epidermal growth factor family, in human gastrointestinal carcinomas

The expression of mRNA for cripto gene, a novel transforming gene of the epidermal growth factor family, was examined in 20 alimentary tract carcinoma cell lines, 60 surgically resected tumor tissues and their adjacent normal mucosas. Although the cripto mRNA was not detected in esophageal carcinomas or in normal mucosas, it was detected in gastric and colorectal carcinomas. In gastric carcinomas, 2.2 kb cripto mRNA was detected in one cell line, all the gastric carcinoma tissues and their adjacent normal mucosas. Of 23 gastric tumor tissues 8 (34.8%) exhibited a higher mRNA level than normal gastric mucosas. cripto mRNA was detected in 2 out of 6 colorectal carcinoma cell lines. Interestingly, 18 (81.8%) out of 22 colorectal carcinoma specimens expressed a higher level of cripto mRNA than that in normal mucosas. The level of the expression was higher than that in gastric carcinoma tissues. The expression was also correlated to tumor stage of colorectal carcinomas.     

Expression pattern of gastrointestinal markers in native colorectal epithelium, lesions, and carcinomas

Three small peptides with a typical cysteine-rich domain (TFF or P-domain) display a specific folding structure (trefoil); they are abundantly expressed on mucosal surfaces of normal and neoplastic gastrointestinal tissues. This epithelial location coincides with mucin secretion and, although not proven beyond doubt, this association is suggestive of their function in maintenance of surface integrity. Using normal colon epithelium, premalignant lesions and tumor samples and specific antibodies we studied expression of these peptides in colorectal carcinomas. RT PCR was performed to extend the sensitivity of the assays. While coexpression of pS2, hITF, MUC1 and MUC2 was demonstrated, MUC5 was absent and no simultaneous activity of pS2 and SML1 (as in gastric mucosa and carcinoma) was noted in rectal tumors. Actively transcribed and expressed cytokeratin 20 and GAPDH were used as experimental controls for immunostaining and RT-PCR, respectively.     

Evaluation of new anticancer agents against human pancreatic carcinomas in nude mice

Heterotransplantation of human cancers in nude mice has provided an in vivo model for studying the biologic characteristics of human tumors, particularly their response to chemotherapy. In an effort to identify cytotoxic agents effective against pancreatic carcinoma, this model was used to evaluate the efficacy of three new anticancer agents--menogarol, 4'-epirubicin, and taxol--against two human transplanted pancreatic tumors. Relative area (tumor length X width) differed significantly between menogarol-treated and control groups (p = 0.034). A marked response was also observed in the tumors to 4'-epirubicin (p = 0.01). Taxol was ineffective in controlling tumor growth; by the fourth week, the size of treated tumors was similar to that of the control group (p = 0.55). No toxicity was observed in either the menogarol- or taxol-treated animals. Animals bearing the P2 tumor, and treated with 4' epirubicin displayed severe toxicity by day 18 with death by day 21 in most animals. For the second tumor, Capan-1, relative area differed significantly between the menogarol-treated and the control group (p = 0.003). In animals given 4'-epirubicin, a smaller difference was observed when comparing the relative areas (p = 0.09). Animals treated with taxol again showed no difference in the tumors when compared with controls (p = 1.0). The use of the nude mouse system has evolved so that tumor-oriented trials are now feasible with the hope of clinical applicability. This study illustrates that at least two agents--menogarol and 4'-epirubicin--may have some antitumor activity against pancreatic carcinoma in this system.     

人膀胱癌组织中环氧化酶2的表达

背景与目的：环氧化酶（cyclooxygenase,COX)是人体内合成前列腺素的限速酶。最近研究表明,环氧化酶2（COX－2）与肿瘤的生成有关。本研究通过检测COX－1和COX－2在人膀胱癌组织、正常膀胱粘膜以及膀胱炎症组织中的表达,探讨COX在膀胱癌发生发展中的作用。方法：应用逆转录聚合酶链反应（RT－PCR）和免疫组化法（Envision二步法）,检测膀胱移行细胞癌和癌旁组织、正常膀胱粘膜以及膀胱炎症组织中COX－1和COX－2 mRNA和蛋白的表达,并分析癌组织中COX的表达强度与肿瘤对应的各项病理参数之间的关系。结果：RT－PCR检测15例新鲜膀胱癌组织COX－2 mRNA均阳性表达,5例肉眼所见的癌旁正常组织中仅1例阳性,两者差异有显著性;而COX－1 mRNA在所有新鲜癌组织标本中均有结构性表达。免疫组织化学研究结果与RT－PCR结果相似,COX－2蛋白主要集中在肿瘤细胞浆内,阳性表达率为50％,正常膀胱粘膜（n=4)和膀胱慢性炎症组织（n=5)中没有表达;反之,COX－1蛋白主要表达在正常或炎症组织的平滑肌细胞上,肿瘤组织中为阴性表达。在40例膀胱移行细胞癌石蜡切片标本中,COX－2蛋白的表达强度与肿瘤的分级和分期有关,恶性度较高的Ⅲ级癌的表达水平高于I级和Ⅱ级癌,浸润性癌（T2－4）也高于浅表性癌（Ta-1)。结论：COX－2 mRNA和蛋白在人膀胱癌组织中表达增高,并与肿瘤的恶性率相关,说明COX－2可能在膀胱癌的发生发展中起着重要作用。