Mitogenic effect of serotonin in human small cell lung carcinoma cells via both 5-HT(1A) and...
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Abstracts/Lung Cancer 14 (19%) 377-408 383 3~21, 5q21, and 9~21 at each stage of the epithelial progression to Background: Transforming growth factor-alpha (TGF-a) may play invasive cancers. Forty-eight premalignant/malignant bronchial sites important roles in carcinogenesis, tumor growth, and angiogenesis. were biopsied from 13 patients (including 9 subjects without cancer) Transforming growth factor-beta (TGF-8) are known to be involved in using fluorescence bronchoscopy. Eighteen sites with moderate/severe cell-cycle control and regeneration. TGFa positively acts on growth dysplasia in 6 patients were subjected to bronchoscopic and molecular control of many epithelial cells in contrast to the negative role of TGF- follow-up during a 3-month to 2-year period. Seven separate cases of 8. Method: To evaluate the possible role of TGFa and TGF-O in human advanced non-small cell bronchial cancers were also analyzed. From the primary lung cancers, the expression of TGFa and TGF-R were baseline biopsies, the prevalence of 3p and 9p deletions increased immmunohistochemically investigated in tissue sections from forty significantly from no deletion in the hyperplasialmetaplasia samples (n seven cases with lung cancers and ten cases with non-cancerous lung = 9) to 37 and 31% of the informative cases, respectively, in the tissues. Recombinant cloned monoclonal antibody of TGF-a and dysplasia samples (n = 29). to 100 and 83%, respectively, for the neutralizing antibody of TGF-a were employed as primary antibodies carcinomas in situ (n = 6), and 100% in the invasive cancers (n = 11). after dewaxing the formalin-fixed, paraffin&d tissue sections. Results: Chromosome 5q deletion was significantly more frequent in invasive TGFa was expressed in the cytoplasms of tumor cells in thirty five cancers (70% of the informative cases) as compared to carcinoma in situ cases of forty seven (74.5 %) primary lung cancers, whereas the control (40%), dysplasias (33%), and hyperplasialmetaplasia samples (11%). expressed in two of ten bronchial epithelial cells. The expression of The number of chromosome alterations also increased significantly TGF-a was disclosed in four cases of eleven (36.4%) small cell from the lowest to the highest grade lesions, showing evidence of carcinomas and thirty one cases of thirty six (86.1 W) non-small cell accumulation of genetic damage from one group to another. The carcinomas of the lung. Expressions of TGF-13 was discernible in molecular follow-up analysis showed that the same genomic alteration bronchial epithelium in eight of ten non-cancerous lung tissues. The can persist in a given dysplastic bronchial area for several months or expression of TGF-8 was noted in the cytoplasms of tumor cells in eight years, and that the persistence or the regression of the molecular cases of forty seven (17.0%) primary lung cancers. The expression of abnormality is well correlated with the evolution of the disease on TGF-I3 disclosed in two cases of eleven (18.2%) small cell carcinomas follow-up. Our results suggest that molecular analysis of bronchial and six cases of thirty six (I 6.7 46) non-small cell carcinomas of the lung. biopsies obtained by fluorescence bronchoscopy may be a very useful Conclusion: These findings suggest that up-regulation of TGFa and means to study the natural history of preinvasive bronchial lesions and down-regulation of TGF-R are involved during development and the outcome of interventions, such as with chemopreventive treatment. growth of primary lung cancers. Pituitary adenylatecyclaseactivating peptidereceptors regulate the growth of non-small cell lung cancer cells Zia F, Fagarasan M, Bitar K, Coy DH, Pisegna JR, Wank SA et al. Biomarkers/Prevetuion Res. Branch, National Cancer fnstitute, Buitiing C. 9610 Medical Center Drive, Rockvitte. MD 2OS50. Cancer Res 1995;55:4886-91. We have identified pituitary adenylate cyclase activating peptide (PACAP) receptors on small cell lung cancer cell line NCI-N417 in a previous study. In this study, the role of PACAP in the growth and signal transduction of non-small cell lung cancer cells was investigated. Northern blot analysis with a full-length human PACAP receptor cDNA probe revealed a major 7.5-kb hybridizing transcript when total RNA extracted from NCI-H838 cells was used. PACAP bound with high affinity (K(d) = 1 nM) to a single class of sites-(B(max) = 14,OOUcell) when NCI-H838 cells were used. Specific lz51- labeled PACAP binding was inhibited with high affinity by PACAP- and PACAP- 38, with moderateaffinity by PACAP(6-38), and with low affinity byvasoactive intestinal polypeptide, PACAP(28-38), and PACAP( 16-38). PACAP- 27 elevated CAMP in a dose-dependent manner, and the increase in CAMP caused by PACAP was reversed by PACAP(6-38). PACAP-27, but not vasaactive intestinal polypeptide, elevated cytosolic Ca2’ in individual NCI-H838 cells. PACAP- 27 stimulated arachidonic acid release, and the increase caused by PACAP was reversed by PACAP(6- 38). PACAP- stimulated colony formation in NCI-H838 cells, whereas the PACAP antagonist PACAP(638) reducedcolony formation in the absence or presence of exogenous PACAP-27. In nude mice bearing NCI-H838 xenografts, PACAP(6-38) slowed tumor growth significantly. Thesedata suggest that biologically active type 1 PACAP receptors are present on human non- small cell lung cancer cells, which exhibit dual signal transduction pathways and regulatecell proliferation. Mitogenic effect of serotonin in human small cell lung carcinoma cells via both S-HT(lA) and 5HT(lD) receptors Cattaneo MG, Fesce R, Vicentini LM. Department of Medical Pharmacology, University ofhfilan, Via Vanvirelli 32, 20129 Milan. Eur J Pharmacol Mel Pharmacol Sect 1995;29 1:209-l I. We have recently shown that the mitogenic effect of serotonin (5- hydroxytryptamine, 5-HT) on human small cell lung carcinoma (SCLC) cells is at least partly due to stimulation of a 5-HT(lD) receptor type. We now report that the 5-HT( 1A) receptor agonist R( +)-8-hydroxy-2- (di-n-propylamino)tetralin (8-OH-DPAT) is also capableof stimulating [‘Hlthymidine incorporation into SCLC GLC-8 cells, although with lower efficacy than 5-HT. The simultaneous administration of maximal doses of 8-OH-DPAT and the 5-HT( 1D) receptor agonist sumatriptan reproduced the maximal [‘Hlthymidine incorporation observed with 5- HT alone. The 5-HT( IA) receptor antagonists spiperone and SDZ 216- 525 completely abolished the effect of II-OH-DPAT (IC, 30 nM for both drugs) behaving as pure antagonists. Accordingly, the two drugs partially inhibited the mitogenic effect of 5-HT. These data indicate that the mitogenic effect of5-HT in SCLC cells involves both S-HT( 1A) and 5-HT( 1 D) receptor types. Pathology Differential diagnosis of thymiccarcinoma and lung carcinoma with the use of antibodies to cytokeratins Fukai I, Masaoka A, Hashimoto T, Yamakawa Y, Niwa H, Kiriyama M et al. Second Deparrmenr of Surgery, Nagoya City Univ. Med. School, Miruho-ku, Nagoya. JThoracCardiovascSurg 1995; 110: 1670- 5. Expression of transforming growth factor-aand transforming growth factor-t3 in human primary lung cancer Lew WJ, Shin DH, Park SS, Lee DH, Lee JD, Lee JH. Deparrment of Internal Medicine, Hanyang University, College of Medicine, Seoul. Tuberc Respir DIS. 1995;42:492-501. There are few specific pathologic findings that can be relied on to distinguish primary thymic carcinomas from lung carcinomas with mediastinal extension or showing metastasis to the anterior mediastinum. The immunohistochemical reactivity on frozen sections of thymic carcinomas and lung carcinomas, which are histologically similar to each other, was examined with the use of monoclonal antibodies to
Transcript of Mitogenic effect of serotonin in human small cell lung carcinoma cells via both 5-HT(1A) and...
Abstracts/Lung Cancer 14 (19%) 377-408 383
3~21, 5q21, and 9~21 at each stage of the epithelial progression to Background: Transforming growth factor-alpha (TGF-a) may play invasive cancers. Forty-eight premalignant/malignant bronchial sites important roles in carcinogenesis, tumor growth, and angiogenesis. were biopsied from 13 patients (including 9 subjects without cancer) Transforming growth factor-beta (TGF-8) are known to be involved in using fluorescence bronchoscopy. Eighteen sites with moderate/severe cell-cycle control and regeneration. TGFa positively acts on growth dysplasia in 6 patients were subjected to bronchoscopic and molecular control of many epithelial cells in contrast to the negative role of TGF- follow-up during a 3-month to 2-year period. Seven separate cases of 8. Method: To evaluate the possible role of TGFa and TGF-O in human advanced non-small cell bronchial cancers were also analyzed. From the primary lung cancers, the expression of TGFa and TGF-R were baseline biopsies, the prevalence of 3p and 9p deletions increased immmunohistochemically investigated in tissue sections from forty significantly from no deletion in the hyperplasialmetaplasia samples (n seven cases with lung cancers and ten cases with non-cancerous lung = 9) to 37 and 31% of the informative cases, respectively, in the tissues. Recombinant cloned monoclonal antibody of TGF-a and dysplasia samples (n = 29). to 100 and 83%, respectively, for the neutralizing antibody of TGF-a were employed as primary antibodies carcinomas in situ (n = 6), and 100% in the invasive cancers (n = 11). after dewaxing the formalin-fixed, paraffin&d tissue sections. Results: Chromosome 5q deletion was significantly more frequent in invasive TGFa was expressed in the cytoplasms of tumor cells in thirty five cancers (70% of the informative cases) as compared to carcinoma in situ cases of forty seven (74.5 %) primary lung cancers, whereas the control (40%), dysplasias (33%), and hyperplasialmetaplasia samples (11%). expressed in two of ten bronchial epithelial cells. The expression of The number of chromosome alterations also increased significantly TGF-a was disclosed in four cases of eleven (36.4%) small cell from the lowest to the highest grade lesions, showing evidence of carcinomas and thirty one cases of thirty six (86.1 W) non-small cell accumulation of genetic damage from one group to another. The carcinomas of the lung. Expressions of TGF-13 was discernible in molecular follow-up analysis showed that the same genomic alteration bronchial epithelium in eight of ten non-cancerous lung tissues. The can persist in a given dysplastic bronchial area for several months or expression of TGF-8 was noted in the cytoplasms of tumor cells in eight years, and that the persistence or the regression of the molecular cases of forty seven (17.0%) primary lung cancers. The expression of abnormality is well correlated with the evolution of the disease on TGF-I3 disclosed in two cases of eleven (18.2%) small cell carcinomas follow-up. Our results suggest that molecular analysis of bronchial and six cases of thirty six (I 6.7 46) non-small cell carcinomas of the lung. biopsies obtained by fluorescence bronchoscopy may be a very useful Conclusion: These findings suggest that up-regulation of TGFa and means to study the natural history of preinvasive bronchial lesions and down-regulation of TGF-R are involved during development and the outcome of interventions, such as with chemopreventive treatment. growth of primary lung cancers.
Pituitary adenylatecyclaseactivating peptidereceptors regulate the growth of non-small cell lung cancer cells Zia F, Fagarasan M, Bitar K, Coy DH, Pisegna JR, Wank SA et al. Biomarkers/Prevetuion Res. Branch, National Cancer fnstitute, Buitiing C. 9610 Medical Center Drive, Rockvitte. MD 2OS50. Cancer Res 1995;55:4886-91.
We have identified pituitary adenylate cyclase activating peptide (PACAP) receptors on small cell lung cancer cell line NCI-N417 in a previous study. In this study, the role of PACAP in the growth and signal transduction of non-small cell lung cancer cells was investigated. Northern blot analysis with a full-length human PACAP receptor cDNA probe revealed a major 7.5-kb hybridizing transcript when total RNA extracted from NCI-H838 cells was used. PACAP bound with high affinity (K(d) = 1 nM) to a single class of sites-(B(max) = 14,OOUcell) when NCI-H838 cells were used. Specific lz51- labeled PACAP binding was inhibited with high affinity by PACAP- and PACAP- 38, with moderateaffinity by PACAP(6-38), and with low affinity byvasoactive intestinal polypeptide, PACAP(28-38), and PACAP( 16-38). PACAP- 27 elevated CAMP in a dose-dependent manner, and the increase in CAMP caused by PACAP was reversed by PACAP(6-38). PACAP-27, but not vasaactive intestinal polypeptide, elevated cytosolic Ca2’ in individual NCI-H838 cells. PACAP- 27 stimulated arachidonic acid release, and the increase caused by PACAP was reversed by PACAP(6- 38). PACAP- stimulated colony formation in NCI-H838 cells, whereas the PACAP antagonist PACAP(638) reducedcolony formation in the absence or presence of exogenous PACAP-27. In nude mice bearing NCI-H838 xenografts, PACAP(6-38) slowed tumor growth significantly. Thesedata suggest that biologically active type 1 PACAP receptors are present on human non- small cell lung cancer cells, which exhibit dual signal transduction pathways and regulatecell proliferation.
Mitogenic effect of serotonin in human small cell lung carcinoma cells via both S-HT(lA) and 5HT(lD) receptors Cattaneo MG, Fesce R, Vicentini LM. Department of Medical Pharmacology, University ofhfilan, Via Vanvirelli 32, 20129 Milan. Eur J Pharmacol Mel Pharmacol Sect 1995;29 1:209-l I.
We have recently shown that the mitogenic effect of serotonin (5- hydroxytryptamine, 5-HT) on human small cell lung carcinoma (SCLC) cells is at least partly due to stimulation of a 5-HT(lD) receptor type. We now report that the 5-HT( 1A) receptor agonist R( +)-8-hydroxy-2- (di-n-propylamino)tetralin (8-OH-DPAT) is also capableof stimulating [‘Hlthymidine incorporation into SCLC GLC-8 cells, although with lower efficacy than 5-HT. The simultaneous administration of maximal doses of 8-OH-DPAT and the 5-HT( 1 D) receptor agonist sumatriptan reproduced the maximal [‘Hlthymidine incorporation observed with 5- HT alone. The 5-HT( IA) receptor antagonists spiperone and SDZ 216- 525 completely abolished the effect of II-OH-DPAT (IC, 30 nM for both drugs) behaving as pure antagonists. Accordingly, the two drugs partially inhibited the mitogenic effect of 5-HT. These data indicate that the mitogenic effect of5-HT in SCLC cells involves both S-HT( 1 A) and 5-HT( 1 D) receptor types.
Pathology Differential diagnosis of thymiccarcinoma and lung carcinoma with the use of antibodies to cytokeratins Fukai I, Masaoka A, Hashimoto T, Yamakawa Y, Niwa H, Kiriyama M et al. Second Deparrmenr of Surgery, Nagoya City Univ. Med. School, Miruho-ku, Nagoya. JThoracCardiovascSurg 1995; 110: 1670- 5.
Expression of transforming growth factor-aand transforming growth factor-t3 in human primary lung cancer Lew WJ, Shin DH, Park SS, Lee DH, Lee JD, Lee JH. Deparrment of Internal Medicine, Hanyang University, College of Medicine, Seoul. Tuberc Respir DIS. 1995;42:492-501.
There are few specific pathologic findings that can be relied on to distinguish primary thymic carcinomas from lung carcinomas with mediastinal extension or showing metastasis to the anterior mediastinum. The immunohistochemical reactivity on frozen sections of thymic carcinomas and lung carcinomas, which are histologically similar to each other, was examined with the use of monoclonal antibodies to
