Genes of laminin B1 chain, α1 (IV) chain of type IV collagen, and 72-kd type IV collagenase are...
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Abstracts/Lung Cancer II f1994J 323-344 321 and poor prognosis for ad,juvant therapy subsequent to complete surgtcal resecllon. Fetal isoform of human retinoic acid receptor R expressed in small cell lung Uncer line5 HOI& B, Prllel~er hi. Wu J. Goodyer C, Bradley WEC. lnsrirur du cancer de Momreal. Hopiral Notre-Dome, 1560 Sherbrooke Enrr. Monrreccl. Que. H2L 4MI. Cancer Res 1994;54:365-9. The retinoic acid receptor type I! (RARE) complementary DNA from a small cell tumor hne was amplified. sequenced, and found to be homologous to the munne RARn I. Seventeen lung tumor lines were analyzed. Five of seven small cell lung carcinoma lines expressc?d RARE 1, hut only one other line (epldermoid) expressed tbe isoform. and this was at trace levels. Two other epidermoid lines, ps well as three adenocarcinoma. two adenosquamous, and two large cell-derived lines did not express RARRI, Nineadult human tissues, including lung, were analyzed. and m contrast to what has been reported for the IIU)U% undetectable or harely drtstahle levels were ohserved. On the other hand, a total of I3 different fetal tissues. at three different developmental stages. all expressed RARBI. RARRI may he a master developmental gene in humans. and the remarkably spacitic association with small cell lung carcinoma suggests a molecular link between this typeofcancer and development. Genes of laminin Bl chain, al (IV) chain of type IV collagen, and 72-kd type IV collagenase are mainly expressed by the stromal cells of lung carcinomas Soini Y, Paakko P. Autio-Harmainen H. Depanment of Porhology, Uniwrsiry of 0~1~. Kajaonintie 52 D. SF-90220 Oulu. Am J Path01 1993;142:1622-30. lnthisstudy, weanalyladtheexpressionof mmaenger(m)RNAs for laminin Bl chain. al (IV) chain of type IV collagen. and 72-kd type IV collagenase in 15 primary lung carcinomas and in two m&static adenocarcinomss to the lung. The results show that the mRNA synthesis for these proteins mainly occurs in the stromal tibroblasts acd endothelial cells. In a proportiw of Nmors. mRNAs for laminin Bl chain and 72- kd type IV collagenase could also be observed in carcinoma cells, but the amount of mRNAs was considerably lower in them than in the stromal cells. There were no convincing signals for the p-ce of the a I (IV) chain of type IV collagen mRNA in any of the carcinoma cells. A simullaneous expression or lack of expression of signals for laminin Bl chain and 72-kd type IV collagenase mRNAs could be observed in carcinoma cells of 12 cases. suggesting that the activation of these two genes may be somehow connected. There was no association between the mRNA expression and the differentiation degree or the size of the tumors. The occurrence of the mRNA synthesis for the 72-kd type IV collagenase in stromal fibrohlasts and endothrlial cells indicates that the stromal cells of tumors have a more pronounced impact on the spread of the neoplastic disease than previously thought. The results further show that in their ability to synthesize these proteins the stromal cells of tumors re.semhle those of developing embryonic tissues. This resemblance is probably connected with the constant remodeling of extracellularmatrix in responsetotheproliferativeactivityofcarcinorna cells. In vitro and in vivo exprmions of transforming growth factor-a and tyrosine kinase receptors in human non-small- cell lung carcinomas Liu C, Tslo M-S. DeponmemofPathology. Momreal~~ralHospiral, 1650 Cedar Avenue, UonIrenl. Que. H3G IA4. Am J Pathol 1993;142: 1155-62. The mRNA expression of transforming growth fectora (TGF- a), epiderrnal growth factor recqtor (EGFR), c+bB-2 and c-met proto-oncogenes in eight newly established cell lines and 29 primary tumors of human non-smrll~ll lung carcinoma (NSCLC) have been investigated. In vitro, the expressions of TGF-u, c-erbB-2, and c-met were consistently high in adenocarcinomas, while EGFR wsr expressed highest in a squamous cell carcinoma cell line. There was linear correlation between the levels of expression of TGFa and EGFR or c- erbB-2, and between EGFR and c-erbB-2. The c-met expression WBS also correlated with those of TGFa. EGFR, and cerbB-2. In viva. the mean mRNA levels of TGFa. EGFR. and c-met, but not c-erbB-2, were higher in carcinomas than in normal lung tissues(2.8, 1.7. and 3.0 times, respectively); however, only adenocarcinonvs expressed a significantly higher level of cerbB-2 than their corresponding normal tissues (2.2 times). In 20 patients whose paired normal and tumor tissue were examined, the percentages of cpses with greater than twofold increase in expression in carcinom than normal were 55% for both TGFa and EGFR. 30% forcerbB-2. and 47% fort- met. Among the histologicalsubtypesofNSCLC,ahigherpercentageofadenocarcinomas than squamous cell carcinomas over-expressed these genes, especially c-&B-2 and c-met Overexpression is rarely the result of gene ampli- ticntion. The results suggest a differential expression of growth factor and receptorgenes among the various histological .subtypesofNSCLCs. Debrisoquin oxidation genotype and susceptibilityto lung cancer Agunder JAG, Martinez C, Lndero JM. Led-ma MC. Ramos JM. Martin R et al. Departamemo de Farmacologia. Facvltadde Uedicina, Uniwrsidad de Extmnadura. Awia. de Elwu s/n. 06071 Badajoz. Clin Pharmacol Ther 1994;55: 10-4. The association between the polymorphism of the cytochrome P450 debrisoquin hydroxylase (CUpsilonP2D6) and lung cancer is controversial. Previous reports suggested a link between CYP2D6 phenotype and lung cancer, with poor metsbolizers having reduced susceptibility. Nevertheless. negative bindings haveaLs, been published. By using allele-specific amplification. we have studied the frequency of four CUpsilonFXI6 (wild type and mutant) alleles in 89 patients with histologically proved bronchogenic carcinoma and in 98 healthy volunteers. Our findings confirm that poor metabolizers are under- presentedamong patients with lungcancerbttcauseofadifferent genetic hackground. Our findings also reveal that the rare CUpsilonP2Db(C) mutant allele is sixfold more frequent among patients with lung cancer (pCO.0005). This suggcFLs that the CUpsilonPZW(C) allele could be considered asanadditional risk factorbecausecarrierscouldhave higher susceptibility to the development of lung cancer. Scintigraphic detection of neuralcellderived small-cell lung cancer wing glioma-specific antibody Kobayashi H. Sakahara H, Hosono M. Shinto M, Koodo S, Miyatake S-I et al. Depanmenr of Nuclear Medicine, Faculty of Medicine, Kyoro Uniwrsiiy. 54 Kawahara-rho, Shogoin. Sakyo-b. Kyoro 606. J Cancer Res Clin Oncol 1994;120:259-62. Radiolabeled GA-17. a murine monoclonal antibody that reacts specitically with gliomacetls. bound to a small-cell lung cancer (SCLC) cell line NCI-H69 derived from neural cells, both in vitro and in viva. The affinity constant of GA-17 F (ab’), fragment binding to NCI-H69 was 1.02x10)/M while that to the glioma cell line U87MG was 1.22xl@/M. Iodine-125-labeled GA-17 F(ab’), fragmentsinjected i.v. localized well in NCI-H69 cells xenografted in nuce mice. The percentage of the injected dose per gram accumulated in the xenografted tumor was 6.87f l.34%g I (-*SD, n=S) 24 h after injection. On the other hand, control monoclonal F (Ab’), fragments accumulated in the
Transcript of Genes of laminin B1 chain, α1 (IV) chain of type IV collagen, and 72-kd type IV collagenase are...
Abstracts/Lung Cancer II f1994J 323-344 321
and poor prognosis for ad,juvant therapy subsequent to complete surgtcal resecllon.
Fetal isoform of human retinoic acid receptor R expressed in small cell lung Uncer line5 HOI& B, Prllel~er hi. Wu J. Goodyer C, Bradley WEC. lnsrirur du cancer de Momreal. Hopiral Notre-Dome, 1560 Sherbrooke Enrr. Monrreccl. Que. H2L 4MI. Cancer Res 1994;54:365-9.
The retinoic acid receptor type I! (RARE) complementary DNA from a small cell tumor hne was amplified. sequenced, and found to be homologous to the munne RARn I. Seventeen lung tumor lines were analyzed. Five of seven small cell lung carcinoma lines expressc?d RARE 1, hut only one other line (epldermoid) expressed tbe isoform. and this was at trace levels. Two other epidermoid lines, ps well as three adenocarcinoma. two adenosquamous, and two large cell-derived lines did not express RARRI, Nineadult human tissues, including lung, were analyzed. and m contrast to what has been reported for the IIU)U% undetectable or harely drtstahle levels were ohserved. On the other hand, a total of I3 different fetal tissues. at three different developmental stages. all expressed RARBI. RARRI may he a master developmental gene in humans. and the remarkably spacitic association with small cell lung carcinoma suggests a molecular link between this typeofcancer and development.
Genes of laminin Bl chain, al (IV) chain of type IV collagen,
and 72-kd type IV collagenase are mainly expressed by the stromal cells of lung carcinomas Soini Y, Paakko P. Autio-Harmainen H. Depanment of Porhology, Uniwrsiry of 0~1~. Kajaonintie 52 D. SF-90220 Oulu. Am J Path01 1993;142:1622-30.
lnthisstudy, weanalyladtheexpressionof mmaenger(m)RNAs for laminin Bl chain. al (IV) chain of type IV collagen. and 72-kd type IV collagenase in 15 primary lung carcinomas and in two m&static adenocarcinomss to the lung. The results show that the mRNA synthesis for these proteins mainly occurs in the stromal tibroblasts acd endothelial cells. In a proportiw of Nmors. mRNAs for laminin Bl chain and 72- kd type IV collagenase could also be observed in carcinoma cells, but the amount of mRNAs was considerably lower in them than in the stromal cells. There were no convincing signals for the p-ce of the a I (IV) chain of type IV collagen mRNA in any of the carcinoma cells. A simullaneous expression or lack of expression of signals for laminin Bl chain and 72-kd type IV collagenase mRNAs could be observed in carcinoma cells of 12 cases. suggesting that the activation of these two genes may be somehow connected. There was no association between the mRNA expression and the differentiation degree or the size of the tumors. The occurrence of the mRNA synthesis for the 72-kd type IV collagenase in stromal fibrohlasts and endothrlial cells indicates that the stromal cells of tumors have a more pronounced impact on the spread of the neoplastic disease than previously thought. The results further show that in their ability to synthesize these proteins the stromal cells of tumors re.semhle those of developing embryonic tissues. This resemblance is probably connected with the constant remodeling of
extracellularmatrix in responsetotheproliferativeactivityofcarcinorna cells.
In vitro and in vivo exprmions of transforming growth factor-a and tyrosine kinase receptors in human non-small- cell lung carcinomas Liu C, Tslo M-S. DeponmemofPathology. Momreal~~ralHospiral, 1650 Cedar Avenue, UonIrenl. Que. H3G IA4. Am J Pathol 1993;142: 1155-62.
The mRNA expression of transforming growth fectora (TGF- a), epiderrnal growth factor recqtor (EGFR), c+bB-2 and c-met proto-oncogenes in eight newly established cell lines and 29 primary tumors of human non-smrll~ll lung carcinoma (NSCLC) have been investigated. In vitro, the expressions of TGF-u, c-erbB-2, and c-met were consistently high in adenocarcinomas, while EGFR wsr expressed highest in a squamous cell carcinoma cell line. There was linear correlation between the levels of expression of TGFa and EGFR or c- erbB-2, and between EGFR and c-erbB-2. The c-met expression WBS also correlated with those of TGFa. EGFR, and cerbB-2. In viva. the mean mRNA levels of TGFa. EGFR. and c-met, but not c-erbB-2, were higher in carcinomas than in normal lung tissues (2.8, 1.7. and 3.0 times, respectively); however, only adenocarcinonvs expressed a significantly higher level of cerbB-2 than their corresponding normal tissues (2.2 times). In 20 patients whose paired normal and tumor tissue were examined, the percentages of cpses with greater than twofold increase in expression in carcinom than normal were 55% for both TGFa and EGFR. 30% forcerbB-2. and 47% fort- met. Among the histologicalsubtypesofNSCLC,ahigherpercentageofadenocarcinomas than squamous cell carcinomas over-expressed these genes, especially c-&B-2 and c-met Overexpression is rarely the result of gene ampli- ticntion. The results suggest a differential expression of growth factor and receptorgenes among the various histological .subtypesofNSCLCs.
Debrisoquin oxidation genotype and susceptibility to lung cancer Agunder JAG, Martinez C, Lndero JM. Led-ma MC. Ramos JM. Martin R et al. Departamemo de Farmacologia. Facvltadde Uedicina, Uniwrsidad de Extmnadura. Awia. de Elwu s/n. 06071 Badajoz. Clin Pharmacol Ther 1994;55: 10-4.
The association between the polymorphism of the cytochrome P450 debrisoquin hydroxylase (CUpsilonP2D6) and lung cancer is controversial. Previous reports suggested a link between CYP2D6 phenotype and lung cancer, with poor metsbolizers having reduced susceptibility. Nevertheless. negative bindings haveaLs, been published. By using allele-specific amplification. we have studied the frequency of four CUpsilonFXI6 (wild type and mutant) alleles in 89 patients with histologically proved bronchogenic carcinoma and in 98 healthy volunteers. Our findings confirm that poor metabolizers are under- presentedamong patients with lungcancerbttcauseofadifferent genetic hackground. Our findings also reveal that the rare CUpsilonP2Db(C) mutant allele is sixfold more frequent among patients with lung cancer (pCO.0005). This suggcFLs that the CUpsilonPZW(C) allele could be considered asanadditional risk factorbecausecarrierscouldhave higher susceptibility to the development of lung cancer.
Scintigraphic detection of neuralcellderived small-cell lung cancer wing glioma-specific antibody Kobayashi H. Sakahara H, Hosono M. Shinto M, Koodo S, Miyatake S-I et al. Depanmenr of Nuclear Medicine, Faculty of Medicine, Kyoro Uniwrsiiy. 54 Kawahara-rho, Shogoin. Sakyo-b. Kyoro 606. J Cancer Res Clin Oncol 1994;120:259-62.
Radiolabeled GA-17. a murine monoclonal antibody that reacts specitically with gliomacetls. bound to a small-cell lung cancer (SCLC) cell line NCI-H69 derived from neural cells, both in vitro and in viva. The affinity constant of GA-17 F (ab’), fragment binding to NCI-H69 was 1.02x10)/M while that to the glioma cell line U87MG was 1.22xl@/M. Iodine-125-labeled GA-17 F(ab’), fragmentsinjected i.v. localized well in NCI-H69 cells xenografted in nuce mice. The percentage
of the injected dose per gram accumulated in the xenografted tumor was 6.87f l.34%g I (-*SD, n=S) 24 h after injection. On the other hand, control monoclonal F (Ab’), fragments accumulated in the
