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)

Short-term cultures from four typical and two atypical primary bronchial carcinoids were cytogenetically analyzed. A lung metastasis from one of the atypical carcinoids was also analyzed. Of the four typical carcinoids, two had normal chromosome complements, while the other two had the karyotypes 46,X, -X, +7/47,XX, +7/47,XX, +X/46,XX and 47,XX, +7/46,XX. Both atypical carcinoids had chromosome abnormalities. One had the karyotype 45-46,X, -X,del(1)(q32),add(17)(p13), +add(19)(p13), -22, +r/47,XX, +X. The second carcinoid had the karyotype 78-81,XXY, +Y, +1,t(2;8)(q21;q24), +3, +4, +del(4) (q25), +5, +6,der(6)t(6;6)(q21;p21)x2, +7, +7, -10,add(14)(p11-13), +19, -21, +1-4mar. The metastasis from this carcinoid had the same aberrations, except that the del(4)(q25) had been lost and one to two markers had been gained.
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PMID:Cytogenetic analysis of six bronchial carcinoids. 846 72

Objective. We studied the molecular abnormalities involved in the pathogenesis of endocrine tumors of the uterine cervix. Methods. We obtained DNA from precisely microdissected archival tissue from 15 endocrine tumors of the uterine cervix, consisting of 5 carcinoids (1 typical, 4 atypical), 2 large cell neuroendocrine carcinomas, and 8 small cell carcinomas. We investigated the presence of high-risk (types 16 and 18) and intermediate-risk (types 31 and 33) human papilloma virus (HPV) sequences, TP53 and K-ras gene mutations, and loss of heterozygosity (LOH) at 9 genes/chromosomal regions, including 3p14.2/FHIT, 3p14-p21, 3p21, 3p22-p24, 5q21-q22/APC-MCC region, 9p21/CDKN2, 11q23/MEN1, 13q/RB, and 17p/TP53. Results. HPV sequences were detected in 8 (53%) tumors, HPV 16 in 2 cases, and HPV 18 in 2 cases. LOH at 9p21 (43%) and localized 3p deletions (47%) were the most frequent allelic losses found. Allelic losses at 5q21-q22/APC-MCC region, 11q23/MEN1, and 13q/RB were infrequent. TP53 gene mutations were detected in 7 (47%) tumors (1 atypical carcinoid and 6 carcinomas). HPV sequences were demonstrated in 4 of the 7 cases with TP53 gene mutations. No K-ras mutations were detected. Conclusion. The molecular changes present in endocrine tumors of the uterine cervix have distinct features. They incorporate those present in the neuroendocrine tumors of the lung (high frequency of TP53 gene abnormalities and 9p21 deletions) with those detected in squamous cell carcinomas of the cervix (high-risk HPV sequences and localized 3p deletions).
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PMID:Molecular abnormalities associated with endocrine tumors of the uterine cervix. 988 21

Fifty-three neuroendocrine lung tumors (24 carcinoids, one atypical carcinoid, five large-cell neuroendocrine carcinomas, and 23 small-cell lung carcinomas) were investigated for immunocytochemical expression of several gene products, i.e., p53, Rb, bcl-2, c-kit, mdm-2, cdk-4, p21 proteins, and proliferation index as assessed by MIB-1. The goal of the study was to explore the relationships between histotypes in light of their own gene product-based immunophenotypical profiles. To this aim we applied the multiple correspondence analysis, which is an exploratory statistical multivariate technique that converts a data matrix into a particular type of graphic display in which the rows and columns are depicted as points. Such statistical analysis displayed that some categories of the gene product-based immunophenotyping variables are grouped in the plot identifying three groups: the first group related to carcinoids, the second to small-cell carcinomas, and the third to large-cell neuroendocrine carcinomas. These data support the evidence that carcinoids and small-cell carcinomas are two distinct, apparently immunogenotypically unrelated entities among neuroendocrine lung tumors and that atypical carcinoids and large-cell neuroendocrine carcinomas seem not to represent intermediate steps between them.
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PMID:Gene product immunophenotyping of neuroendocrine lung tumors. No linking evidence between carcinoids and small-cell lung carcinomas suggested by multivariate statistical analysis. 1093 49

In this report we present the results of a combined cytogenetic and multicolor spectral karyotype (SKY) analysis of a transplantable human ileal carcinoid (GOT1). By using SKY it was possible to identify the origin and organization of all clonal marker chromosomes and to identify cryptic translocations not detectable by conventional chromosome banding. The stemline karyotype of low passage GOT1 cells was interpreted as 43,XX, der(1)del(1)(?), inv(2)(p25q13), del(3)(p21), del(5)(q13q31), del(6)(q13), -9, -13, -15, del(16) (q22). Analysis of the GOT1 cells after about 2.5 years of propagation in nude mice allowed us to follow the in vivo progression of this tumor. Relatively few additional rearrangements had occurred during this period, indicating that the GOT1 cells are genetically stable. Most of the abnormalities detected result in loss of whole or parts of chromosomes, suggesting that loss of multiple chromosomal regions, presumably containing tumor suppressor genes, might be important genetic events in ileal carcinoids.
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PMID:Multicolor spectral karyotype analysis of a transplantable human ileal carcinoid. 1107 21

Carcinoid tumors of the ampulla of Vater (ACs) differ from duodenal carcinoid tumors (DCs). A search for AC and DC was made between 1980 and 2000. The clinicopathologic features and follow-up were assessed. Immunohistochemistry for panneuroendocrine markers, hormone products, proliferating cell nuclear antigen (PCNA), Ki- 67, p21(cip1), and p27(kip1) were performed. A blind proliferative index counting 500 cells was made. Differences were contrasted using the Fisher exact and 2-sided Student t test. Five ACs and 8 DCs were identified in 9 women and 4 men with median ages of 59 and 64 years and mean tumor diameters of 1.6 and 1.85 cm, respectively. All patients with AC presented jaundice, and most patients with DC were asymptomatic (P = .047). Metastases were present in 4 ACs and 1 DC (P =.03). Tumor cells expressed synaptophysin and chromogranin in 60% of ACs and in 100% and 87% of DCs. Gastrin was expressed in 75% of DCs and 20% of ACs (P < .05). The mean value for PCNA index was 4.0% in ACs and 3.2% in DCs, and mean values for Ki-67 were 12.2% and 10.2%, respectively (P = NS). Expression of p21(cip1) and p27(kip1) was observed in 40% of ACs and 37.5% and 12.5% of DCs. Three of 5 patients with AC died of the disease within an average of 11 months, and none of the patients with DC had died at 103 months of follow-up. The more aggressive behavior of ACs is not associated with higher proliferative indices or with different expression of cell cycle inhibitors.
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PMID:Carcinoid tumors of the duodenum and ampulla of vater: a clinicomorphologic, immunohistochemical, and cell kinetic comparison. 1172 66

Interferon alpha (IFN-alpha) has been shown to produce antitumor effects in 50-80% of carcinoid tumor patients and has demonstrated anti-proliferative effects in carcinoid tumor cells, but the mechanism is not well established. This study presents evidence that in a carcinoid tumor cell line, Bon1, IFN-alpha increases the expression of p21 and promotes nuclear translocation of endogenous p21. Furthermore, immunoprecipitation experiments demonstrated that p21 formed immuno-complexes with Stat1 and Stat2 in the nucleus of cells. Interferon alpha can decrease G1- and G2-phase cells, but increase S-phase population. The p21 mRNA expression is inversely correlated to the G1 population (r = -0.933, P < 0.05) and positively correlated to the S-phase population (r = 0.901, P < 0.05). In addition, IFN-alpha inhibited cyclin dependent kinases (CDK), CDK2-, CDK3-, CDK4-, and cyclin E- but not cyclin A-associated kinase activities. Immunodepletion of p21 resulted in a significant enhancement of CDK3 kinase activity (approximately 1.6-fold increase). These results suggest that the mechanism of antitumor and cell cycle regulation of IFN-alpha in carcinoid tumors may, at least in part, be p21-dependent. Based on these results, we conclude that IFN-alpha exerts antitumor effects by increased p21 expression in neuroendocrine tumors.
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PMID:Effects of interferon alpha on the expression of p21cip1/waf1 and cell cycle distribution in carcinoid tumors. 1202 30

Neuroendocrine tumors, such as carcinoids, are highly metastatic neoplasms that secrete bioactive hormones resulting in carcinoid syndrome. Few curative treatments exist outside of surgical resection. We have previously shown that activation of the Raf-1 signaling pathway can suppress hormone production in carcinoid tumor cells. In this study, we investigated a novel treatment for carcinoid tumor cell growth based on pharmacologic Raf-1 activation using the compound ZM336372. Treatment of carcinoid tumor cells with ZM336372 resulted in progressive phosphorylation of Raf-1, mitogen-activated protein kinase 1/2, and extracellular signal-regulated kinase 1/2. Importantly, exposure to ZM336372 resulted in a significant reduction of bioactive hormone levels as well as the transcription factor, human achaete-scute homologue-1 in carcinoid tumor cells. Furthermore, treatment with ZM336372 led to a marked suppression of cellular proliferation and induction of the cell cycle inhibitors p21 and p18. In summary, ZM336372 targets both proliferation and palliative issues associated with carcinoid tumor cells, and therefore, warrants further investigation as a possible therapeutic strategy for patients with carcinoid tumors.
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PMID:ZM336372, a Raf-1 activator, suppresses growth and neuroendocrine hormone levels in carcinoid tumor cells. 1595 48

Carcinoid tumors are neuroendocrine malignancies that frequently metastasize and secrete hormones that cause debilitating symptoms in patients. In this study we report the effects of valproic acid (VPA), a drug long used for the treatment of epilepsy, on the growth and neuroendocrine phenotype of human carcinoid cancer cells. VPA treatment of gastrointestinal and pulmonary carcinoid cells resulted in a dose-dependent inhibition of cancer cell growth. Western blot analysis revealed degradation of cyclin D1 and an increase in cyclin-dependent kinases p21 and p27 with VPA treatment. Flow cytometry confirmed that the mechanism of VPA-induced growth inhibition is G(1) phase cell cycle arrest. Furthermore, VPA suppressed expression of the neuroendocrine tumor marker chromogranin A. In addition to these effects, VPA also increased levels of full-length Notch-1 and the active Notch-1 intracellular domain. Luciferase reporter assays incorporating the centromere-binding factor 1 (CBF-1) binding site and the achaete-scute complex-like 1 (ASCL-1) promoter confirmed the functional activity of VPA-induced Notch-1. Transfection of Notch-1 small-interfering RNA into carcinoid tumor cells blocked the effects of VPA on Notch-1 activation, ASCL-1 suppression, p21 induction, and cell growth inhibition. VPA also suppressed growth of carcinoid tumors in vivo in a mouse tumor xenograft experiment. These findings confirm the important role of Notch-1 in regulating the growth and neuroendocrine phenotype of carcinoid tumor cells. On the basis of this study, a clinical trial of VPA for patients with advanced carcinoid cancer will be conducted. Disclosure of potential conflicts of interest is found at the end of this article.
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PMID:Valproic acid activates notch-1 signaling and regulates the neuroendocrine phenotype in carcinoid cancer cells. 1776 53

Carcinoid cancers arise from the neuroendocrine cell system of the gastrointestinal tract, lungs, and other organs. Hepatic metastases are common, and patients often suffer from endocrinopathies secondary to tumor secretion of various hormones and peptides. As complete surgical resection is often not possible because of widespread disease, new therapeutic and palliative treatments are needed. In this study, we characterized the effects of suberoyl bishydroxamic acid (SBHA), a histone deacetylase inhibitor, on the growth and neuroendocrine phenotype of carcinoid cancer cells. SBHA treatment of human gastrointestinal and pulmonary carcinoid cancer cells resulted in a dose-dependent inhibition of cell proliferation. Western blot analysis showed a decrease in cyclin D1 and an increase in p21 and p27, indicating that the mechanism of this growth inhibition is cell cycle arrest. Furthermore, SBHA treatment suppressed two neuroendocrine tumor markers, chromogranin A and achaete-scute complex-like 1. These changes in the growth and neuroendocrine phenotype of carcinoid cells were associated with activation of the Notch1 signaling cascade. We conclude that SBHA shows promise as a potential anticancer agent for the treatment of patients with advanced carcinoid tumor disease.
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PMID:Suberoyl bishydroxamic acid inhibits cellular proliferation by inducing cell cycle arrest in carcinoid cancer cells. 1787 77

Expression of the ras oncoprotein in thirteen human small intestinal tumors was investigated employing an immunohistochemical technique. The level of ras p21 was analysed using the monoclonal antibody Y13-259 and the biotin-streptavidin-peroxidace-DAB technique. Nine out of thirteen tumors including one hyperplastic - metaplastic polyp, one adenomatous and papillary polyp of the duodenum, one adenomatous polyp, one leiomyoma, one carcinoid, one lymphoma, one angiosarcoma of the jejunum, one leiomyosarcoma and one metastatic adenocarcinoma of the colon, were found to ''press the ras p21 oncoprotein at elevated levels, as compared to adjacent normal tissue. Whereas in one Brunner's gland adenoma of the duodenum, one neurilemoma, one adenocarcinoma of the small intestine and one metastatic adenocarcinoma of the colon expression of ras p21 was not elevated. The detection of H-ras mutations in codon 12 and K-ras mutations in codons 12 and 13 was also examined using the polymerase chain reaction technique. Four out of the thirteen small intestinal tumors examined possessed mutations of the H-ras gene in codon 12. These included the following, tumors: one Brunner's gland adenoma of the duodenum, one lymphoma, one leiomyo-sarcoma and one metastatic adenocarcinoma of the colon. This is the first demonstration of ras mutations in small intestinal tumors. None of the tumors had mutations in K-ras codons 12 or 13 (Gly-->Asp) It is suggested that the ras p21 oncoprotein may be involved in the pathogenesis and H-ras mutations and be a molecular genetic marker in small intestinal tumors.
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PMID:Ras gene activation in human small intestinal tumors. 2157 84


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