Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

With the aid of a highly specific murine monoclonal antibody, F12, an immunofluorescence method was elaborated that allowed sensitive and specific detection of the ganglioside antigen fucosyl-GM1 (IV2FucII3NeuAcGgOse4Cer) in different types of human lung cancer and normal tissues. Nineteen of 21 cases of small cell lung cancer were positive with the F12 immunofluorescence method as compared to 2 of 10 squamous epithelial cell lung cancers and 1 of 5 large cell lung cancer specimens. Specimens of lung adenocarcinoma (8 cases) and bronchial carcinoid (3 cases) were all negative, as were 2 examined cases of neuroblastoma. No fucosyl-GM1 could be detected in normal lung and bronchus. However, in thymus, spleen, and lamina propria of the small intestine sparsely distributed clusters of small round cells were stained as well as intramural ganglionic cells of the small intestine and islet cells of the pancreas. All other normal tissues tested were negative. Results obtained with immunofluorescence closely agreed with immunochemical determination of fucosyl-GM1 in lipid extracts of tissues. Our findings suggest that fucosyl-GM1 is strongly associated with small cell cancer of the lung and demonstrate that this tumor-associated antigen can be detected with high sensitivity and specificity with an immunofluorescence method based on the use of the F12 monoclonal antibody.
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PMID:Immunohistological detection of fucosyl-GM1 ganglioside in human lung cancer and normal tissues with monoclonal antibodies. 264 49

Eleven cases of atypical carcinoid (AC) of the lung were identified during an eight-year period. Their clinical features and treatment responses were contrasted with our experience at Vanderbilt with small cell lung cancer (SCLC) and a literature review of typical bronchial carcinoids (TC). Clinically, there were no features to distinguish AC from TC except for age at diagnosis (59 vs 49 years). Atypical carcinoid was similar to SCLC with respect to many clinical features, although female sex, absence of smoking history and localized disease at presentation were more common in AC. Pathologically, these tumors were distinguished by cellular atypia, necrosis, architectural disorder, or increased mitotic rate in the presence of a recognizable carcinoid pattern. Immunoperoxidase staining revealed no difference between AC and TC or SCLC. Atypical carcinoid of the lung represents a distinct clinicopathologic disease.
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PMID:Atypical carcinoid of the lung. A distinct clinicopathologic entity. 282 65

Small cell lung cancer (SCLC) has been associated with loss of heterozygosity at several distinct genetic loci including chromosomes 3p, 13q, and 17p. To determine whether the retinoblastoma gene (Rb) localized at 13q14, might be the target of recessive mutations in lung cancer, eight primary SCLC tumors and 50 cell lines representing all major histologic types of lung cancer were examined with the Rb complementary DNA probe. Structural abnormalities within the Rb gene were observed in 1/8 (13%) primary SCLC tumors, 4/22 (18%) SCLC lines, and 1/4 (25%) pulmonary carcinoid lines (comparable to the 20 to 40% observed in retinoblastoma), but were not detected in other major types of lung cancer. Rb messenger RNA expression was absent in 60% of the SCLC lines and 75% of pulmonary carcinoid lines, including all samples with DNA abnormalities. In contrast, Rb transcripts were found in 90% of non-SCLC lung cancer lines and in normal human lung. The finding of abnormalities of the Rb gene in SCLC and pulmonary carcinoids (both neuroendocrine tumors) suggests that this gene may be involved in the pathogenesis of a common adult malignancy.
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PMID:Abnormalities in structure and expression of the human retinoblastoma gene in SCLC. 283 9

Selected neuroendocrine tumors, such as small cell lung cancer (SCLC), and neuroblastoma express markedly diminished class I major histocompatibility complex (MHC) antigens (HLA framework and beta 2-microglobulin, beta 2m). Another neuroendocrine tumor, mid-gut carcinoid, also expresses reduced beta 2m antigen as demonstrated herein. Antigen expression is greatly enhanced on SCLC cell lines by in vitro exposure to interferon (IFN). To determine whether IFN mediates similar effects in vivo, we examined by immunoperoxidase staining beta 2m expression in paraffin-embedded tumor tissue sections obtained from 4 SCLC and 7 mid-gut carcinoid patients before and after receiving partially purified human leukocyte IFN-alpha therapy. Before IFN treatment, 3/4 SCLC tumors and 5/7 mid-gut carcinoids did not express beta 2m. By contrast, all tumors showed considerable expression of beta 2m after IFN therapy. Induction of class I antigens on tumor cells deficient in such expression may be one mechanism by which IFN exerts antitumor effects. We believe this is the first report of in vivo induction of class I MHC antigens in epithelial tumor cells in humans.
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PMID:Interferon-mediated in vivo induction of beta 2-microglobulin on small-cell lung cancers and mid-gut carcinoids. 301 23

Electrophoretic separation of enolase isoenzymes and the measurement of enolase activity were performed in 25 lung tumor extracts. In 13 neuroendocrine (NE) tumors (nine small cell lung carcinoma [SCLC], three atypical NE tumors, and one carcinoid tumor), the NE differentiation was assessed by ultrastructural determination of neurosecretory granule (NSG) density. Twelve non-NE lung tumors also were studied (three adenocarcinomas, four epidermoid, two composite, two large cell undifferentiated carcinomas, and one lymphoma). Four normal lung tissues and 1 human brain were used as controls. The gamma gamma isoenzyme was present at a high level (mean +/- SE, 12 +/- 3%) in all NE carcinomas and consistently absent in all non-NE tumors as well as in normal lung. The alpha gamma isoenzyme was found in significantly higher proportion in NE carcinomas (mean +/- SE, 29 +/- 2%) than in non-NE tumors (mean +/- SE, 8 +/- 1%) (P less than 0.0001), despite an equally high level of total enolase activity in both groups of tumor. The separation of alpha gamma and gamma gamma isoenzymes of enolase allows for the accurate diagnosis of NE tumors and NE components of atypical NE carcinomas, and the gamma gamma isoenzyme, in contrast to gamma chain detection by immunoassay, can be considered to be a specific marker in itself of NE differentiation in lung neoplasms.
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PMID:Isoenzyme pattern of enolase in the diagnosis of neuroendocrine bronchopulmonary tumors. 303 37

Small cell carcinoma of the lung is a highly malignant tumour. Its known biological products which include bombesin, do not allow the prediction of tumour behaviour. Molecular biology has revealed the amino acid sequence of human pro-bombesin, which consists of a signal peptide, the bioactive bombesin molecule and a C-terminal peptide. We have raised a rabbit antiserum to the first (N-terminal) 21 amino acids of the predicted C-terminal peptide. A total of 505 (361 neuroendocrine) surgically resected pulmonary tumours were evaluated for the presence of immunoreactive bombesin and C-terminal peptide. Strong immunostaining was obtained with the antiserum to the C-terminal peptide of human pro-bombesin in 70% of the small cell carcinomas (175/250), in 63% of atypical (aggressive) carcinoids (31/49) but only in 16% of benign carcinoids (10/62). In contrast, bombesin immunostaining was focal and only moderately strong and the relative proportion of positive cases was quite evenly distributed amongst the neuroendocrine tumours: 35% of carcinoids (22/62), 22% of atypical carcinoids (11/49) and 25% of small cell carcinoma (62/250). None of the squamous, adeno, or large cell undifferentiated carcinomas were immunoreactive for bombesin or the C-terminal peptide. Radioimmunoassay and chromatography of extracts of tumours recovered from wax blocks revealed high concentrations of C-terminal peptide immunoreactivity (241 +/- 66 pmol/g of tissue) in all 12 small cell carcinomas studied, moderate concentrations in carcinoid tumours (50 +/- 7 pmol/g) and none in non-small cell carcinomas. Patients with tumours showing immunoreactivity to the C-terminal peptide of human pro-bombesin had a significantly shorter survival time than those without immunoreactive peptide (185 +/- 16.49 days, mean +/- SEM, and with 1128 +/- 226 days, respectively P greater than 0.02). The apparent presence of the C-terminal peptide of human pro-bombesin in higher concentrations than bombesin in the more malignant class of endocrine tumours, mainly small cell carcinomas associated with the poorest prognosis, suggests that the antiserum to this C-terminal peptide is not only a useful pathological marker but may prove to be of value in investigating the biological behaviour of small cell carcinomas and predicting the clinical course of the disease.
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PMID:Expression of the C-terminal peptide of human pro-bombesin in 361 lung endocrine tumours, a reliable marker and possible prognostic indicator for small cell carcinoma. 303 70

Cell lines established from small cell lung cancer (SCLC), a neuroendocrine tumor, have low or absent expression of class I major histocompatibility complex antigens. To determine whether this phenomenon occurs also in vivo, 244 routine paraffin-embedded tumors including 32 SCLC and 79 non-SCLC (NSCLC) lung cancers were studied for expression of beta 2-microglobulin (beta 2m) by an avidin-biotin coupled immunoperoxidase technique. The majority of SCLC tumors lacked beta 2m expression, while some had weak, focal expression. In contrast, most NSCLC expressed beta 2m, often strongly. The difference between SCLC and NSCLC was highly significant statistically, suggesting that beta 2m can be used as a clinical immunodiagnostic marker for distinguishing NSCLC from SCLC. In addition, certain other neuroendocrine tumors (neuroblastoma, bronchial and midgut carcinoid tumors) lacked beta 2m expression, whereas some (pheochromocytoma, medullary thyroid carcinoma, and peripheral neuroectodermal tumors) usually stained positively. Such non-neuroendocrine tumors as colon, breast, and prostate carcinomas showed moderate to high expression of beta 2m. Selective absence of beta 2m expression by certain neuroendocrine tumors appears to be a phenomenon of biological and diagnostic importance.
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PMID:Paucity of beta 2-microglobulin expression on small cell lung cancer, bronchial carcinoids and certain other neuroendocrine tumors. 352 83

Two human small cell lung carcinoma cell lines, NCI-H69 and NCI-H128, were used as alternating sources of immunogen to generate monoclonal antibodies to small cell lung carcinoma-associated antigens. BALB/c mice were sensitized with seven injections of live tumor cells, four with NCI-H69 cells and three with NCI-H128 cells. Somatic cell hybridization was performed by fusion of the immune murine splenocytes using syngeneic myeloma cells from the SP2/0 Ag14 cell line. Hybridoma colonies were screened against small cell lung carcinoma cells and normal lung fibroblasts with an enzyme-linked immunosorbent assay. Compared to animals immunized with only NCI-H69 or NCI-H128 cells, alternate immunization resulted in the generation of a significantly higher number of hybridomas that reacted selectively with both tumor cell lines. Monoclonal antibodies from two reactive hybrid clones generated by alternate immunization, SCLC 2051 and SCLC 5023, were uniformly negative to normal human tissues including lung, kidney, liver, spleen, breast, thyroid, brain, small intestine, and colon. While both monoclonal antibodies were nonreactive to paraffin-embedded, formalin-fixed, nonmalignant lung biopsies, the monoclonal antibody SCLC 5023 reacted with tumor cell infiltrates in biopsies from small cell lung carcinoma patients (14 of 14 cases positive), using the immunoperoxidase technique. This monoclonal reagent also reacted with other lung tumor cell types, including atypical carcinoid (5 of 5 positive), epidermoid (4 of 6 positive), undifferentiated and bronchoalveolar (3 of 4 cases each positive) carcinomas. By contrast, monoclonal antibody SCLC 2051 apparently identified an antigen expressed preferentially on small cell lung carcinoma cells (12 of 14 positive) and only rarely reacted with other lung tumor cell types (2 of 34 positive). Both monoclonal antibodies were negative to colon carcinoma, epidermoid carcinoma of the floor of the mouth, breast adenocarcinoma, and B- and T-cell leukemia and lymphoma cells, as determined by the enzyme-linked immunosorbent assay, indirect immunofluorescence, and immunoperoxidase techniques. These observations suggest that SCLC 2051 and SCLC 5023 may be of value in identifying tumor-associated antigens expressed in small cell and other lung carcinomas. In addition, the generation of antibody-producing cells towards common tumor-associated antigens may be enhanced by immunization with multiple tumor cell lines of the same histological type.
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PMID:Characterization of two human small cell lung carcinoma-reactive monoclonal antibodies generated by a novel immunization approach. 620 11

Growth hormone (GH)-releasing activity has been detected in extracts of carcinoid and pancreatic islet tumors from three patients with GH-secreting pituitary tumors and acromegaly. Bioactivity was demonstrated in 2 N acetic acid extracts of the tumors using dispersed rat adenohypophyseal cells in primary monolayer culture and a rat anterior pituitary perifusion system. The GH-releasing effect was dose responsive and the greatest activity was present in the pancreatic islet tumor. Small amounts of activity were also found in two other tumors (carcinoid and small cell carcinoma of lung) unassociated with GH hypersecretion. Each of the tumors contained somatostatin-like immunoreactivity but the levels did not correlate with the net biologic expression of the tumor. Sephadex G-75 gel filtration indicated the GH-releasing activity to have an apparent molecular size of slightly greater than 6,000 daltons. The GH-releasing activity was adsorbed onto DEAE-cellulose at neutral pH and low ionic strength, from which it could be eluted by increasing ionic strength. The GH-releasing activity was further purified by high pressure liquid chromatography using an acetonitrile gradient on a cyanopropyl column to yield a preparation that was active at 40 ng protein/ml. Partially purified GH-releasing activity, from which most of the bioactive somatostatin had been removed, increased GH release by pituitary monolayer cultures to five times base line. Enzymatic hydrolysis studies revealed that the GH-releasing activity was resistant to carboxypeptidase, leucine-aminopeptidase, and pyroglutamate-amino-peptidase but was destroyed by trypsin and chymotrypsin, indicating that internal lysine and/or arginine and aromatic amino acid residues are required for biologic activity and that the NH2-terminus and CO9H-terminus are either blocked or not essential. The results provide an explanation for the presence of GH-secreting tumors in some patients with the multiple endocrine neoplasia syndrome, type I, and warrant the addition of GH-releasing activity to the growing list of hormones secreted by tumors of amine precursor uptake and decarboxylation cell types.
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PMID:Partial purification and characterization of a peptide with growth hormone-releasing activity from extrapituitary tumors in patients with acromegaly. 624 40

Apudomas are uncommon neoplasms composed of neuroendocrine cells. They include carcinoid tumors, islet cell tumors, and small cell lung carcinoma. We found six cases of apudomas in a series of 1028 renal transplants from three medical centers (0.58%). One of these had been reported in 1976. The cases included a carcinoid tumor of a Meckel's diverticulum discovered and removed prior to transplantation, with no evidence of recurrence 9 years later. A small cell lung carcinoma was discovered 40 months after renal transplantation, with a fatal outcome 6 months later. Four clinically occult apudomas were found at autopsy, including one gastric and one bronchial carcinoid tumor, one multicentric pancreatic islet cell neoplasm, and one case of multiple ileal carcinoids. With the exception of the small cell lung cancer, none of the apudomas was clinically significant, and none was associated with carcinoid or other paraneoplastic syndrome. These cases illustrate the difficulty of diagnosis of apudomas in patients with renal failure and the usually benign nature of these tumors despite the administration of potent immunosuppressive agents.
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PMID:APUD system neoplasms in renal transplant patients. 631 Aug 9


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