Abstracts/Lung Cancer IO (1994) 395-430 nicotinic acetylcholine receptors. The presence of nicotine receptors suggests nicotine or its metaholites may play a direct role in lung center pathogen&s. Vnsopressin mRNA and neumphysin-related cell-surface antigen (NRSA) in small-ceil cawinoma North WG, Xu X-M. Department ofPhysiology, Dartmouth Medical School, I Medical Center Drive, Lebanon. NH 03756. Peptides 1993;!4:303-7. Production by smail-cell carcinoma(SCCL) ofneurophysins(HNPs) and neurophysin-elated cell-surface antigen (NRSA) was examined for two cell lines, for mouse xenografts, and for a resected human tumor, using poIyclona1 and monoclonal antibodies to ‘vasopressin-associated humanneurophysin(VP-HNP)andpolyclonalantibodiestovasopressin (VP). The nature of the mRNA responsible for giving rise to these naurophysin-related products was investigated by performing Northern analysis on preparations of poly A+ RNA with cDNA probes complimentary to portions of the exon A, exon B, and exon C regions of the human VP gene. SDS-electrophoresis and Western analysis revealed two prominent proteins of 42,000 and 2O.ooO Da in acid extracts from all SCCL sources when the monoclonal anti-HNP or one ofthehvopolyclonalanti-HNPpmparationswereused. Theseantibodies also disclosed the presence of a minor component of 10,000 Da. A second polyclonal anti-HNP preparation reacted with one prominent protein of 30.000 Da and, for one cell line and mouse xenografts. another protein of 32,COODa. Both of two anti-VP preparations reacted with proteins of 42,OGO. 30,ooO. 25,OCO. and 20,000 Da in extracts from all SCCL source material. The immunorccctive proteins of42.000 3O.oo0, and 20.000 Da were all components of a membrane fraction from SCCL cells and tissues. In Northern analysis. a single RNA of about 900 bases hybrid&d with exon A and 2x0” B probes, but not with the cDNA probe complimentary to exon C of the VP gene. These data demonstrate that large and heterogeneous forms of oeurophysin are a common feature of SCCL production. and that at least threz of these proteins contain a sequence for VP and may constitute NRSA. An of 900 bases seems to be responsible for the abnormal VP *A generation of these proteins. This tumor VP mRNA appears to differ from the neuronal format its 3’end and could be the product of abnormal splicing. Pituitary rdenylute cydasa activating polypeptide receptors are present on small cell lnng cancer cells Moody TW, Zia F. Makheja A. Dept. ofBiochemistty/Molec. Biology, George Washington Uniwrsity. School of Medicine/Health Sciences, 2300 Eye St. N. W., Washington, DC 20037. Peptidea 1993; 14:241-6.
The effect of pituitary adenylate cyclase activating polypeptide (PACAP) on small cell lung cancer (SCLC) cells was investigated. In Fura 2-AM loaded VU-N417 cells, PACAPor PACAPelevated cytosolic calcium in a dose-dependent manner. The cytosolic calcium was elevated from 133 to 185 uM with PACAP(100 r&l). Because PACAPstrongly elevated cytosolic calcium after the addition of 1 mM EGTA, PACAP released calcium from intracellular pools using NCI-N417 cells: similar results were obtained for SCLC cell line NCIH345. Pituitary adenylate cyclase activating polypeptide-27 inhibited ?-VIP and ‘rcI-PACAP binding to NCI-N417 cells high afftity (IC, = 30 and 5 nM), whereas VIP inhibited i%VIP and ‘%PACAP-27 binding with IC, values of 5 and 200 nM. Both 100 nM VIP and PACAPelevated CAMP levels in NCI-H345 cells. In contrast, 1 M VIP had no effect on cytosolic calcium. whereas 100 nM PACAPcaused astrong calcium respooae. Both 100 nhl VIP and 10 t&l PACAP27 significantly stimulated the clooal growth of NCI-H345 cells. These data suggest that biologically active VIP and PACAP receptors are present on SCLC cells.
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Pathology Demonstxation of nucleolnr orgnnlxer regions in lung cnrclnomu by silver stitlning Nonomura A, Mixukami Y, OdaM, Shimixu J. Watanabe Y, Kamimura R et al. Pathology Section, Kanazawa University Hospital, School of Medicine, 13-I Tnknra-machi, Konazmva920. Surg Today 1993;23:48690. Nucleolar organizer regions (NORs) were investigated in lung carcinomas by silver staining. This method was applied to 111 lung carcinoma specimens, including 40 with squamous cell carcinoma (SCC), 42 with adeoocarcinoma (ADENO), 8 with adenosquamous carciooma(ADESQ), 8withsmallcellcarcinoma(SMCC), 6 with large cell carcinoma (LGCC), and 7 with typical carcinoid tumors (CAOID). The mean AgNOR counts of ADENO, SCC. ADESQ, SMCC, and LGCC were significantly higher than those of the oonnal bronchial surface and those of the glandular or alveolar epithelium. The mean AgNOR count of CAOID was signiticantly higher than those of the normal glandular and alveolar epithelium but not that of the surface cpithelium. The mean AgNOR count of SCC was significantly higher than that of bronchial squamous metaplasia. and the count of SMCC was significantly higher than that of CAOID. Within the same cancer category, the mean oumher of AgNORa increased in parallel with the histological tumor grades. These results indicate that the AgNOR method is useful for differentiating lung carcinoma from its normal counterparts and for evaluating histological tumor grades in the same lineage of lung carcinoma.
Clinical assessment Bronchiul cnrcinoid tumors Davila DG, Dunn WF, Taxelaar HD, Pairolero PC. University of Alabama. Birmingham, AL. Mayo Clin Proc 1993;68:795-803. Bronchial carcinoid tumors. termed (incorrectly) ‘bronchial adeoomas’ in the past, am uncommon pulmonary oeoplasms. These tumors are currently classified as oeumendccrine in origin because of their potential to form and sometimes secrete a variety of chemical substances. Overall. approximately 75 46 of bronchial carcinoid tumors arise in the lobar bronchi, 10% occur in themain-stem broochi, and 15 % originate in the Periphery of the lung. Well-differentiated carciooid tumors constitute almost 90% of all bronchial carcinoids. Atypical carcinoid tumors have a higher malignant potential than do typical bronchial carcinoids. Thecarciooidsyndromeisranly. ifever. associated with carcinoids limited to the tmcheobroochial tree. Occasionally, &shiny’s syndrome due to ectopic hormone production is caused by bronchial carcinoid tumors. More than 75% ofbronchial carcinoidsare detected oo cooventiooa1 posteroanterior chest roeotgeoograms. Computed tomography may help disclose small oeoplaams that are occult on conventional roentgenography, particularly in the assessment of patients who have Gushing’s syndrome due to ectopic hormone production. Pulmonary resectioo is the treatment ofchoice for bronchial carcinoids. The prognosis is related to the pathologic grade and stage of the tumor. Prngnostic factors in lung cancer based on muitivariate analysis Hilseoheclt SG, Raub WA Jr, Sridhar KS. Miami University School of Medicine, P.O. Box 016960, Miami. FL 33136. Am J Clin Oncol Cancer Clin Trials 1993: 16:301-9. Multivariate analysis was performed on 1,336 patients with lung cancer to determine the prognostic significance of stage, race, gender. age. and treatment in eech histologic subtype. The study was designed