PubMed · 13335063
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W F PETERSON, E R NOVAK. 1956. Endometrial polyps.. https://pubmed.ncbi.nlm.nih.gov/13335063/
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Numerous investigations have recently proved the importance of sentinel lymph node detection in various malignant tumours. It is widely accepted that this procedure is to be recommended only in patients with early stage tumours. The lymph node status and prognosis are closely related. Appropriate staging is essential in the management of malignant tumours and should be individualised. In many cases, the nodal status does not correlate with the clinical stage of the disease. In this survey, we consider some of the most common gynaecological malignancies and the type of staging most appropriate to them. Differences between these staging systems, and controversies concerning them, are related to the concept of sentinel lymph node investigation. The authors believe that sentinel node sampling is in fact a beneficial method in both early and advanced stage disease for determination of the tumour status and individualisation of surgical interventions.
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Estrogens regulate many biological functions, often acting in a tissue-selective manner. Their tissue-selective action is believed to involve differential estrogen action through the two estrogen receptor (ER) subtypes, ERalpha and ERbeta, as well as differential interaction of the ligand-receptor complexes with promoters and coregulator proteins. In the latter case, selectivity is based on the induction of specific conformations of the ligand-ER complex, conformations that are influenced by the structure of the ligand. Estrogen pharmaceuticals having an ideal balance of tissue-selective activity are being sought for menopausal hormone replacement, breast cancer prevention and therapy, and other actions. To expand on the structural diversity of ER ligands that might show such tissue selectivity, we have prepared a series of diazenes (pyrazines, pyrimidines, and pyridazines) substituted with two to four aryl groups and various short-chain aliphatic substituents. All of the pyrazine and pyrimidines bind to ER, some with high affinity and with a considerable degree of preferential binding to either ERalpha or ERbeta. One pyrimidine and one pyrazine have ERalpha affinity preferences as high as 23 and 9, respectively, and one pyrimidine has an ERbeta affinity preference of 8. The pyridazines, by contrast, are quite polar and have only very low binding affinity for the ER. In cell-based transcription assays, several of the pyrimidines and a pyrazine were found to be considerably more agonistic on ERalpha than on ERbeta. Because these triaryl diazenes have the largest volumes among the ER ligands so far investigated, their high affinity demonstrates the flexibility of the ligand binding pocket of the ERs and its tolerance for large substituents. Thus, these novel heterocyclic ligands expand the repertoire of chemical structures that bind to the estrogen receptor, and they could prove to be useful in elucidating the biological behavior of the two ER subtypes and in forming the basis for new estrogen pharmaceuticals having desirable tissue selectivity.