Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0007095 (carcinoid)
 6,990 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Multiple endocrine neoplasia type 1 (MENI) is a promising model to understand endocrine and other tumors. Its most common endocrine expressions are tumors of parathyroids, entero-pancreatic neuro-endocrine tissue, and anterior pituitary. Recently, collagenomas and multiple angiofibromas of the dermis also have been recognized as very common. MEN1 can be characterized from different perspectives: (a) as a hormone (parathyroid hormone, gastrin, prolactin, etc.) excess syndrome with excellent therapeutic options; (b) as a syndrome with sometimes lethal outcomes from malignancy of entero-pancreatic neuro-endocrine or foregut carcinoid tissues; or (c) as a disorder than can give insight about cell regulation in the endocrine, the dermal, and perhaps other tissue systems. The MEN1 gene was identified recently by positional cloning, a comprehensive strategy of narrowing the candidate interval and evaluating all or most genes in that interval. This discovery has opened new approaches to basic and clinical issues. Germline MEN1 mutations have been identified in most MEN1 families. Germline MENI mutations were generally not found in families with isolated hyperparathyroidism or with isolated pituitary tumor. Thus, studies with the MENI gene helped establish that mutation of other gene(s) is likely causative of these two MEN1 phenocopies. MEN1 proved to be the gene most frequent L4 mutated in common-variety, nonhereditary parathyroid tumor, gastrinoma, insulinoma, or bronchial carcinoid. For example, in common-variety parathyroid tumors, mutation of several other genes (such as cyclin D1 and P53) has been found, but much less frequently than MEN1 mutation. The majority of germline and somatic MEN1 mutations predicted truncation of the encoded protein (menin). Such inactivating mutations strongly supported prior predictions that MEN1 is a tumor suppressor gene insofar as stepwise mutational inactivation of both copies can release a cell from normal growth suppression. Menin is principally a nuclear protein; menin interacts with junD. Future studies, such as discovery of menin's metabolic pathway, could lead to new opportunities in cell biology and in tumor therapy.
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PMID:The gene for multiple endocrine neoplasia type 1: recent findings. 1042 35

Metastatic neuroendocrine neoplasms can have similar histologic appearances, and without an obvious primary, it may be difficult to determine the site of origin of the metastasis. Thyroid transcription factor-1 (TTF-1) is a nuclear protein expressed during the development of thyroid, lung, and forebrain. The clinical utility of TTF-1 to distinguishing between metastatic pulmonary and nonpulmonary well-differentiated neuroendocrine tumors (WDNET) has not been previously studied. One hundred fifty-eight primary and metastatic WDNET were evaluated for TTF-1 expression. The tumors included 20 pulmonary WDNET, including 17 typical and 3 atypical carcinoid tumors, 10 metastatic pulmonary WDNET, 26 intestinal WDNET, 24 metastatic intestinal WDNET, 3 thymic mediastinal WDNET, 30 thyroid tumors (10 medullary carcinomas, 5 follicular carcinomas, 5 follicular adenomas, 5 papillary carcinomas, and 5 anaplastic carcinomas), 10 parathyroid adenomas, 20 pituitary adenomas, 10 pancreatic WDNET, and 5 pheochromocytomas. TTF-1 expression was found in 19 of 20 (95%) pulmonary WDNET, 8 of 10 (80%) metastatic pulmonary WDNET, and in 0 of 50 (0%) intestinal WDNET. All thyroid tumors were diffusely positive for TTF-1, except for three anaplastic carcinomas. All parathyroid and pituitary adenomas, pancreatic and thymic WDNET, and pheochromocytomas were uniformly negative for TTF-1. These results indicate that TTF-1 is clinically useful in distinguishing metastatic pulmonary from metastatic WDNET of extrapulmonary origin.
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PMID:Thyroid transcription factor-1 distinguishes metastatic pulmonary from well-differentiated neuroendocrine tumors of other sites. 1139 61

p63 is a p53-homologous nuclear protein that appears to play a crucial role in regulation of stem cell commitment in squamous and other epithelia. In this study, p63 expression was examined in benign lung and in neoplasms of pulmonary origin. Eighty sections from routinely fixed and processed archival bronchoscopic biopsy or lobectomy specimens were pretreated with citric acid (pH 6.0) for antigen retrieval, then incubated overnight with anti-p63 monoclonal antibody 4A4. Slides were stained using a streptavidin-biotin kit and diaminobenzidine as chromagen, and were counterstained with hematoxylin. In normal lung, p63 intensely stained nuclei of bronchial reserve cells but did not stain ciliated cells, alveolar epithelial cells, or nonepithelial cells. The lower strata of squamous metaplastic bronchial epithelium stained positively. All squamous-cell carcinomas stained positively (n = 30). In some well-differentiated carcinomas, staining was found at the periphery of tumor nests but was negative in central zones showing squamous maturation. Poorly differentiated carcinomas showed very high proportions (80% to 100%) of p63-positive nuclei. All small-cell carcinomas were p63 negative (n = 9). Staining of bronchioloalveolar carcinomas (n = 7) and adenocarcinomas (n = 23) was variable: some tumors showed no detectable staining, others showed heterogeneously positive staining. Adenosquamous carcinomas (n = 5) displayed a unique basalar staining pattern. Carcinoid tumors were almost entirely negative (n = 5). We conclude that p63 is expressed in benign bronchial stem cells, in neoplastic cells with either squamous differentiation or squamous differentiating potential, and in a subpopulation of adenocarcinomas. p63 immunostaining may also aid in some histopathologic distinctions, such as in small biopsies where the differential diagnosis is poorly differentiated squamous carcinoma versus small-cell carcinoma. A stem cell biology-based classification system for squamous carcinomas is proposed.
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PMID:P63 in pulmonary epithelium, pulmonary squamous neoplasms, and other pulmonary tumors. 1237 18

Among new biological markers that could become useful prognostic factors for lung carcinoma, Ki-67 is a nuclear protein involved in cell proliferation regulation. Some studies have suggested an association between Ki-67 and poor survival in lung cancer patients. In order to clarify this point, we have performed a systematic review of the literature, using the methodology already described by our Group, the European Lung Cancer Working Party. In total, 37 studies, including 3983 patients, were found to be eligible. In total, 49% of the patients were considered as having a tumour positive for the expression of Ki-67 according to the authors cutoff. In all, 29 of the studies dealt with non-small-cell lung carcinoma (NSCLC), one with small-cell carcinoma (SCLC), two with carcinoid tumours and five with any histology. In terms of survival results, Ki-67 was a bad prognosis factor for survival in 15 studies while it was not in 22. As there was no statistical difference in quality scores between the significant and nonsignificant studies evaluable for the meta-analysis, we were allowed to aggregate the survival results. The combined hazard ratio for NSCLC, calculated using a random-effects model was 1.56 (95% CI: 1.30-1.87), showing a worse survival when Ki-67 expression is increased. In conclusion, our meta-analysis shows that the expression of Ki-67 is a factor of poor prognosis for survival in NSCLC.
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PMID:Ki-67 expression and patients survival in lung cancer: systematic review of the literature with meta-analysis. 1554 71

Multiple endocrine neoplasia type 1 (MEN1) is a hereditary tumor syndrome characterized by tumors of the parathyroid glands, the pancreatic islets, the pituitary gland, the adrenal glands, as well as by neuroendocrine carcinoid tumors, often at a young age. Causal to the syndrome are germline mutations of the MEN1 tumor-suppressor gene. Identification of gene-mutation carriers has enabled presymptomatic diagnosis and treatment of MEN1-related lesions. The product of the MEN1 gene is the nuclear protein menin. Recent observations indicate several functions for menin in the regulation of transcription, serving either as a repressor or as an activator: menin interacts with the activator-protein-1-family transcription factor JunD, changing it from an oncoprotein into a tumor-suppressor protein, putatively by recruitment of histone deacetylase complexes; menin maintains transforming growth factor beta mediated signal transduction involved in parathyroid hormone and prolactin gene expression; and menin is an integral component of histone methyltransferase complexes. In this capacity menin is a regulator of expression of the cyclin-dependent-kinase inhibitors p18INK4C and p27Kip1; furthermore, menin serves as a co-activator of estrogen receptor mediated transcription, by recruiting methyltransferase activity to lysine 4 of histone 3 at the estrogen responsive TFF1(pS2) gene promoter. We propose that menin links transcription-factor function to histone-modification pathways and that this is crucial for MEN1 tumorigenesis. Understanding the molecular pathology of MEN1 tumorigenesis will lead to new therapeutic strategies.
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PMID:Mechanisms of disease: multiple endocrine neoplasia type 1-relation to chromatin modifications and transcription regulation. 1702 55