PubMed · 10594493
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A Cairns, P Quirke. 1999. Flat adenomas.. https://doi.org/10.1046/j.1365-2168.1999.01276.x
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The high mobility group As (HMGAs) belong to a family of nonhistone nuclear proteins that orchestrate the assembly of nucleoprotein complexes. Through a complex network of protein-DNA and protein-protein interaction, they play important roles in gene transcription, recombination, and chromatin structure. This protein family is involved, through different mechanisms, in both benign and malignant neoplasias. We have recently reported that transgenic mice carrying the Hmga1 or Hmga2 genes under transcriptional control of the cytomegalovirus promoter develop pituitary adenomas secreting prolactin and growth hormone. We have shown that the mechanism of the HMGA2-induced pituitary adenoma is based on the increased E2F1 activity. The expression profile of mouse normal pituitary glands and adenomas induced in HMGA transgenic mice revealed an increased expression of the ccnb2 gene, coding for the cyclin B2 protein, in the neoplastic tissues compared with the normal pituitary gland. Here, we show, by electrophoretic mobility shift assay and chromatin immunoprecipitation, a direct binding of HMGA proteins to the promoter of ccnb2 gene, whereas luciferase assays showed that HMGAs are able to up-regulate ccnb2 promoter activity. Finally, we report an increased CCNB2 expression in human pituitary adenomas of different histotypes that is directly correlated with HMGA1 and HMGA2 expression. Because cyclin B2 is involved in the regulation of the cell cycle, these results taken together indicate that HMGA-induced cyclin B2 overexpression gives an important contribution to experimental and human pituitary tumorigenesis.
We present three patients with bleeding duodenal tumors who were managed by laparoscopic excision. This represents the largest study of such an experience. The literature is reviewed, and the various technical approaches are discussed.
The incidence of colorectal carcinoma is increasing in Japan. Malignant transformation in colorectal neoplasia is usually considered to be owing to adenoma-carcinoma sequence. Elucidation of the recent alteration in the biological properties of colorectal adenoma is sure to be useful to understand the recent increase of the colorectal carcinoma in Japan. We compared the histopathological feature, mitotic index, proliferative activity (Ki-67 labeling index), expression of glycoproteins such as MUC2 mucin, sialyl Lewis A (SLe(a)) and sialyl dimeric Lewis X (SLe(x)), and p53 protein overexpression, between 108 adenomas in the old period (Group A, from 1969 to 1985) and 140 adenomas in the recent period (Group B, from 1995 to 1998). The histological dysplasia, mitotic index and Ki-67 labeling index of the adenomas were significantly higher in Group B than in Group A. In contrast, the expression of MUC2 mucin, which is considered to be a differentiation factor of intestinal mucosal epithelium, was significantly reduced in Group B than in Group A. The SLe(a) and SLe(x) expressions showed no significant difference between them. The p53 expression showed no significant difference between them, except for the moderate dysplasia. These findings indicate that recent colorectal adenomas show more advanced degrees of histological dysplasia, more rapid growth, and reduced differentiation than colorectal adenomas, which developed at earlier times, and may be related with the recent high incidence of colorectal carcinoma in Japan.