PubMed · 5426907
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W Müller, V Hanefeld, M P Dierich, H J Sehrbundt. 1970. [Histochemical studies].. https://pubmed.ncbi.nlm.nih.gov/5426907/
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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.
BACKGROUND: Laparoscopic adrenalectomy is considered the standard method for removal of benign adrenal tumors, regardless of hormone activity. Minimally invasive surgery for thymomectomy aims at limited approaches, avoiding complete sternotomy or large thoracotomy. METHODS: We report on a case in which totally endoscopic thymomectomy and adrenal gland resection were performed sequentially using a computer-enhanced telemanipulation system within 3 weeks. RESULTS: Operating time was 4.5 h for totally endoscopic adrenalectomy and 1.5 h for totally endoscopic thymomectomy. The patient was transferred to the normal ward on the day of operation after either procedure and had an uneventful recovery. Pathology yielded no malignancy in both cases. CONCLUSION: This report demonstrates the safety and feasibility of various totally endoscopic procedures performed sequentially.
The disease natural history of colorectal neoplasm regarding two opposing theories, adenoma-carcinoma sequence and de novo carcinoma theory, is controversial and rarely quantified. The aims of this study are therefore to estimate the dwelling times of adenoma-carcinoma sequence by adenoma size and histological type, taking de novo carcinoma into account. The efficacy of polypectomy was therefore estimated making allowance for two pathways. A case-cohort design, underpinning a cohort with 13 908 subjects (including 10 496 normal subjects, 2652 polyps, 760 colorectal cancers) who underwent the first examination of colonoscopy between 1979 and 1998, was devised to estimate parameters associated with two opposing theories by randomly selecting 305 normal subjects, 300 patients with polyps, and 116 colorectal cancers from the cohort. All the 2652 polyps were linked to national cancer registry to ascertain 25 invasive carcinomas after polypectomy. For the five-state model associated with adenoma size, dwelling times of small (0.6-1 cm) and large adenoma (>1 cm) are 7.75 and 5.27 years for the model without considering de novo, and 17.48 and 15.90 years for the model taking de novo carcinoma into account. Similar findings are observed for the model associated with histological type. The estimated proportions of de novo carcinoma are 31.87% from the model by adenoma size and 27.81% from the model by histological type. Compared to size less than 5 mm, patients with adenoma size between 6 and 10 mm and patients with adenoma size larger than 1 cm have 2.17-fold (0.67-10.74) and 4.25-fold (1.23-14.70), respectively, for the risk of malignant transformation. There are similar findings for the model by histological type. The estimates of overall efficacy of colonoscopy in reducing CRC is 73% for the model allowing for de novo carcinoma and 88% for the model without considering de novo carcinoma theory. The efficacy of diminutive adenoma and small adenoma increases with follow-up years, whereas the efficacy of large adenoma decreases with follow-up years. In conclusion, about 30% of cancers arising from de novo sequence are demonstrated. This finding, together with the adenoma-carcinoma sequence associated with adenoma size and histological type, is important for the estimation of dwelling times, the efficacy of colonoscopy, and the surveillance of polyp after polypectomy.