Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0684249 (lung carcinoma)
 23,830 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Somatostatin (SS) and SS analogues inhibit the growth of various kinds of endocrine and exocrine cells via the SS receptor (SSTR). Carcinoid tumor is representative of the tumors treatable by SS analogues. We examined the expression of SSTR2A by immunohistochemical and in situ hybridization methods with a specific antibody against a synthesized 20-amino acid peptide of the COOH terminus of human SSTR2A and oligonucleotide probes in 62 endocrine tumors of various kinds: pancreatic endocrine tumor; carcinoid; neuroendocrine carcinoma; medullary thyroid carcinoma; pheochromocytoma; and small cell carcinoma of the lung, neuroblastoma, and ganglioneuroma. SSTR2A was expressed in 87% of these tumors and at both primary and metastatic sites. The immunohistochemical reactivity of SSTR2A was strong on the cell membrane and less intense in the cytoplasm of the tumor cells. SSTR2A mRNA was also detected in the tumor cells. The results indicate the usefulness of SSTR2A analogues for the treatment of neuroendocrine tumors, even metastatic ones: metastatic carcinoids, metastatic pheochromocytomas, tumors that adhered to large vessels, and neuroendocrine carcinomas.
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PMID:Immunohistochemical expression of somatostatin type 2A receptor in neuroendocrine tumors. 1058 62

The authors measured telomerase activity using the telomeric repeat amplification protocol-enzyme-linked immunosorbent assay method in 13 neuroendocrine pulmonary neoplasms and in non-neoplastic frozen lung samples from the same patients. These cases belonged to the complete neuroendocrine neoplastic spectrum: four typical carcinoids, three atypical carcinoids, four large cell neuroendocrine lung carcinomas, and two small cell lung carcinomas. The authors performed the same assay for 52 non-neoplastic lung tissues from the surgical files in their department (negative controls). They verified the presence (or absence) of neoplastic tissue in every case by looking at one frozen section done in the same tissue used for telomerase assay. The telomerase activity level in non-neoplastic tissues (mean, 182 A450nm U) was similar to that obtained in the typical carcinoids (mean, 104.5 A450nm U). All neuroendocrine tumors but the typical carcinoids showed high levels of telomerase activity (mean, 1,750.8 A450nm U). According to the telomerase hypothesis, typical carcinoid cells are mortal pre-M2 stage cells, but atypical carcinoid, large cell neuroendocrine lung carcinoma, and small cell lung carcinoma cells are immortal post-M2 stage cells. This finding may be of important prognostic significance in these kinds of tumors. Measurement of enzyme activity with a good morphologic control could be necessary in telomerase activity assay.
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PMID:Telomerase activity in pulmonary neuroendocrine tumors: correlation with histologic subtype (MS-0060). 1071 56

Somatostatin receptors type 2 (sst2) have been frequently detected in neuroendocrine tumors and bind somatostatin analogues, such as octreotide, with high affinity. Receptor autoradiography, specific mRNA detection and, more recently, antisst2 polyclonal antibodies are currently employed to reveal sst2. The aim of the present study was to investigate by three different techniques the presence of sst2 in a series of 26 neuroendocrine tumors of the lung in which fresh frozen tissue and paraffin sections were available. It was possible, therefore, to compare, in individual cases, RNA analysis studied by reverse transcriptase polymerase chain reaction (RT-PCR), in situ hybridization (ISH), and immunohistochemistry. A series of 20 nonneuroendocrine lung carcinoma samples served as controls. RT-PCR was positive for sst2 in 22 of 26 samples, including 15 of 15 typical carcinoids, 5 of 6 atypical carcinoids, and 2 of 5 small-cell carcinomas. The sst2 mRNA signal obtained by RT-PCR was strong in the majority (87%) of typical carcinoids and of variable intensity in atypical carcinoids and small-cell carcinomas. A weakly positive signal was observed in 5 of 20 control samples. In immunohistochemistry, two different antibodies (anti-sst2) were employed, including a monoclonal antibody, generated in the Department of Pathology, University of Turin. In the majority of samples a good correlation between sst2 mRNA (as detected by RT-PCR) and sst2 protein expression (as detected by immunohistochemistry) was observed. However, one atypical carcinoid and one small-cell carcinoma had focal immunostaining but no RT-PCR signal. ISH performed in selected samples paralleled the results obtained with the other techniques. A low sst2 expression was associated with high grade neuroendocrine tumors and with aggressive behavior. It is concluded that 1) neuroendocrine tumors of the lung express sst2, and there is a correlation between the mRNA amount and the degree of differentiation; 2) immunohistochemistry and ISH are reliable tools to demonstrate sst2 in these tumors; and 3) sst2 identification in tissue sections may provide information on the diagnostic or therapeutic usefulness of somatostatin analogues in individual patients with neuroendocrine tumors.
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PMID:Correlative immunohistochemical and reverse transcriptase polymerase chain reaction analysis of somatostatin receptor type 2 in neuroendocrine tumors of the lung. 1071 13

A hallmark of small cell lung carcinoma (SCLC) is the expression of autocrine growth factors such as neurotensin and gastrin-releasing peptide, which bind to cellular receptors and stimulate cell division. The biological activity of autocrine growth factors requires the concurrent expression of prohormone convertases that cleave the growth factors to their active form, suggesting the expression of these genes is linked in SCLCs. RNase protection assays were used to detect the expression of autocrine growth factor and prohormone convertase mRNAs in a panel of lung cancer cell lines. These mRNAs are coexpressed in SCLC and lung carcinoid cell lines, but not in normal lung epithelium or in non-small cell lung cancers. These findings, together with earlier results from our laboratory, suggest the expression of prohormone convertases has an important role in the development and maintenance of the SCLC phenotype and that autocrine growth factor and prohormone convertase genes respond to a common transcriptional activator in SCLC.
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PMID:Prohormone convertase and autocrine growth factor mRNAs are coexpressed in small cell lung carcinoma. 1091 24

Neuroendocrine tumors of the lung (NTL) are a distinct subset of tumors with a wide range of histological patterns and clinical behavior. Controversy still exists as to the ideal diagnostic and therapeutic approach to these neoplasms. A series of 44 consecutive NTL patients operated on at our Institution was retrospectively reviewed in order to critically analyze the diagnostic and therapeutic management. A preoperative diagnosis was obtained in 11 patients (25%). All patients underwent an anatomical surgical resection with lymphoadenectomy. Pathological diagnosis was typical carcinoid (TC) tumor in 36 cases, atypical carcinoid (AC) in three and large-cell neuroendocrine carcinoma (LCNEC) in five. One patient had preoperative chemotherapy. Node-positive patients received postoperative radiotherapy on the mediastinal area. Median follow-up time was 40 months for TC and 51.5 months for AC/LCNEC. Recurrence of disease was observed in three patients with TC and in two with AC/LCNEC. Actuarial 5-year survival was 93% for TC and 70% for AC/LCNEC. Survival was not influenced by tumor size, while lymph node metastases were associated with a worse prognosis. However, due to the limited number of patients, no statistical significance was observed. In conclusion, our study confirms findings in the literature showing that TC and AC/LCNEC are clinically different, and that a differential preoperative diagnosis and treatment is necessary. Although the results of new diagnostic techniques such as octreotide scintigraphy are encouraging, they need to be validated in a larger number of patients. Surgery, with anatomical resection and lymphoadenectomy, remains the treatment of choice in all these tumors. Laser treatment should be considered only as a palliative procedure or as a complementary technique to surgery. The role of adjuvant treatments in AC and LCNEC is uncertain and should be evaluated in larger trials. The prognostic role of biological factors such as cytometry and genetic markers requires further investigation before any definitive conclusions can be drawn.
Lung Cancer 2000 Sep
PMID:Diagnostic and therapeutic management of neuroendocrine lung tumors: a clinical study of 44 cases. 1099 24

Pulmonary neuroendocrine tumors (NE) include a spectrum of tumors from typical carcinoid (TC) to atypical carcinoid (AC), large cell neuroendocrine carcinoma (LCNEC), and small cell carcinoma (SCLC). Little is known about prognostic predictors for AC because of its rarity. Survival analysis was performed on 106 ACs with clinical follow-up from the AFIP and the Pathology Panel of the International Association for the Study of Lung Cancer (IASLC). The tumors fulfilled the 1999 WHO/IASLC criteria for AC of a NE tumor with a mitotic rate of 2 to 10 per 2 mm(2) of viable tumor or coagulative necrosis. Multiple clinical and histologic features were analyzed by Kaplan-Meier and Cox regression analysis. Of the clinical features, higher stage (P = .003) and a tumor size of 3.5 cm or greater (P = .003) were associated with a worse prognosis. Features that were histologically unfavorable by univariate analysis were mitotic rate (P =.002), pleomorphism (P = .018), and aerogenous spread (P =.007). Histologically favorable features by univariate analysis were the presence of palisading (P = .008), papillary (P = .039), pseudoglandular (P =.026), and rosette (P = .022) patterns. Female gender showed a trend toward a poorer prognosis (P =.085) and was included in the multivariate model. Multivariate analysis stratified for stage showed mitoses (P<.001), a tumor size of 3.5 cm or greater (P =.017), and female gender (P =.012) to be the only negative independent predictors of prognosis and the presence of rosettes (P = .016) to be the only independent positive predictor. We further divided the AC into subgroups of low (2 to 5 mitoses/2 mm(2)) and high (6 to 10 mitoses/2 mm(2)) mitotic rate and compared the survival with TC and with LCNEC. Within the category of AC, the patients with a higher mitotic rate had a significantly worse survival than those with a lower mitotic rate (P<.001) stratified for stage. Five- and 10-year survival rates for AC (61% and 35%, respectively) stratified for stage were significantly worse than for TC and better than that for LCNEC and SCLC. Chemotherapy or radiation therapy was given in 12 of 52 and 14 of 52 cases, respectively, but the data were insufficient to evaluate tumor response. We conclude that AC is an aggressive neuroendocrine neoplasm with survival intermediate between TC and LCNEC and SCLC. Higher mitotic rate, tumor size of 3.5 cm or greater, female gender, and presence of rosettes are the only independent predictors of survival. Surgical resection remains the treatment of choice, and the role of chemotherapy and radiation therapy remains to be proven.
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PMID:Pulmonary atypical carcinoid: predictors of survival in 106 cases. 1107 Jan 19

Neuroendocrine lung tumors (NELT) from 50 patients were studied immunohistochemically. Malignant carcinoid and small-cell lung carcinoma (SCC) have a higher level of apoptosis than ordinary carcinoid. An increase of apoptosis index in NELT coincides with an increase in NELT proliferative activity (Ki-67, Bcl-2, c-myc, p-53) as compared to a typical carcinoid. Phagocytosis of apoptotic bodies was absent in SCC. Classic SCC differs from combined SCC by a higher apoptosis index and lower expression of p-53 and Bcl-2. Metastatic SCC differs from SCC without metastases by lower apoptosis level and higher level of proliferative indices (Ki-67, Bcl-2) of tumor cells. Development of unbalance between apoptosis and proliferation may result from mitosis and apoptosis pathology.
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PMID:[Small cell carcinoma and carcinoids of the lung: morphology of apoptosis and expression of biomolecular markers of tumor growth]. 1107 93

The carcinoid tumor is an uncommon neuroendocrine neoplasm the hallmark of which is excessive serotonin production. In studying kinetics of tryptophan hydroxylase and aromatic-L-amino acid decarboxylase (AAAD) in human carcinoid hepatic metastases and adjacent normal liver (J. A. Gilbert et al, Biochem. Pharmacol., 50: 845-850, 1995), we identified one significant difference: the Vmax of carcinoid AAAD was 50-fold higher than that in normal liver. Here, we report Western and Northern analyses detecting large quantities of AAAD polypeptide and mRNA in human carcinoid primary as well as metastatic tumors compared with normal surrounding tissues. To assess the feasibility of targeting these high AAAD levels for chemotherapy, AAAD inhibitors carbidopa (alpha-methyl-dopahydrazine), alpha-monofluoromethyldopa (MFMD), and 3-hydroxybenzylhydrazine (NSD-1015) were incubated (72 h) with NCI-H727 human lung carcinoid cells. Carbidopa and MFMD were lethal (IC50 = 29 +/- 2 microM and 56 +/- 6 microM, respectively); NSD-1015 had no effect on proliferation. On exposure to other human tumor lines, carbidopa was lethal only to NCI-H146 and NCI-H209 small cell lung carcinoma (SCLC) lines (IC50 = 12 +/- 1 microM and 22 +/- 5 microM, respectively). Carbidopa (100 microM) decreased growth of (but did not kill) SK-N-SH neuroblastoma and A204 rhabdomyosarcoma cells and did not affect proliferation of DU 145 prostate, MCF7 breast, or NCI-H460 large cell lung carcinoma lines. The rank order of lines by AAAD activity was NCI-H146 > NCI-H209 > SK-N-SH > NCI-H727, whereas A204, DU 145, MCF7, and NCI-H460 had no measurable activity. For lung tumor lines (carcinoid, two SCLC, and one large cell lung carcinoma), AAAD activity was correlated with the potency of carbidopa-induced cytotoxicity. However, carcinoid cell death was not solely attributable to complete inhibition of either AAAD activity or the serotonin synthetic pathway. In further evaluating potential applications of these findings with carbidopa, we determined that sublethal doses of carbidopa produced additive cytotoxic effects in carcinoid cells in combination with etoposide and cytotoxic synergy in SCLC cells when coincubated with topotecan.
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PMID:The aromatic-L-amino acid decarboxylase inhibitor carbidopa is selectively cytotoxic to human pulmonary carcinoid and small cell lung carcinoma cells. 1110 55

Fifty-six primary neuroendocrine lung tumors were examined morphologically and histologically and their apoptosis level was determined. Malignant carcinomas were characterized by increased apoptotic index and enhanced expression ofBcl-2, Bak, p53, and Ki-67 compared to typical carcinoid. However, apoptosis in these tumors was not completed. Proteins of the Bcl family play an important role in the regulation of spontaneous apoptosis in neuroendocrine lung tumors. Bcl-2 accumulating in the nucleus is a morphological analogue of phosphorylated inactive form of this protein, which does not inhibit apoptosis. Expression of Bcl-2 and Bax decreases in small-cell lung carcinoma (SCLC) with metastases indicating attenuation of apoptosis and development of metastatic clones resistant to apoptosis induces.
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PMID:Role of Bcl-2, Bax, and Bak in spontaneous apoptosis and proliferation in neuroendocrine lung tumors: immunohistochemical study. 1114 May 90

The induction of apoptosis in dendritic cells (DC) is a key mechanism by which tumors escape immune recognition and elimination. In fact, a number of studies have showed the correlation between the number of DC within the tumor and the clinical prognosis, suggesting that increased infiltration of tumor tissue by DC was associated with better patient survival and low incidence of metastatic disease. We compared the number of DC and their distribution pattern in human small-cell lung carcinoma and bronchial carcinoid tumor (CT) tissues. Immunohistochemical analysis revealed the presence of cells expressing DC markers CD1a and CD83 in small-cell lung carcinoma tissues and the complete absence of these cells in CT samples. Next, we examined whether human lung tumor cells produce soluble factors that inhibit differentiation of hematopoietic precursors into mature DC. The addition of small-cell lung carcinoma-conditioned medium to CD34+ precursor cell cultures significantly inhibited colony-forming units of DC formation when compared with nontreated control DC cultures. Furthermore, DC generation and differentiation was completely abrogated in CD34+ cell cultures treated with CT-conditioned medium, suggesting that CT-derived factors blocked CD34+ cell differentiation into DC or induced their apoptosis. Finally, flow cytometry analysis of cultured DC confirmed these results. Thus, analysis of our data suggests that human lung tumors produce factors that inhibit DC generation or maturation and may also induce apoptotic death of DC precursors in vitro.
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PMID:Human small cell lung carcinoma and carcinoid tumor regulate dendritic cell maturation and function. 1121 8


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