1
335 Lack of expression of p-glycoprotein in 7 small cell lung cancer cell lines established both from untre*ted and from treated patients Milroy R, Plumb JA, B&tone P, Mac!ay A, Wishart GC, Hay FG et al. CRCDept of Medical Oncology, Unix&y @Glasgow, Alexander Stone Building, Bearsden, Glasgow G61 IBD. Anticancer Res 1992; 12: 193-200. The establishment and charactcnsation of 7 small cell lung cancer cell lines is described. Four ccl1 lincs were established from bloDsies taken from untreated patlents and one of these was from primary tumour taken via the tibre-optic bronchoscope. The other three were from biopsies taken from patients who had relapsed after chemotherapy. All grow as non-adherennt aggregates of cell and express a range of neuroendocrina and epithelial features characteristics of small cell lung cancer cell lines. No relationship was observtld between the characteristics ofthe cell line !n vitro and the treaatment status ofthe patient from whom the biopsy was taken. Furthermore, none of the cell lines expressed p-glycoprotein even though 3 were derived from relapse biopsies where chemotherapy mcluded drugs assocrated wth the multidrug resistance phenotype. Etanidazole determination was carried out with a polarographic method both in plasma and tissue. The results obtained indicate that the most favorable concentrat!on of etamdazole in the tissue is at 30 min after administration and at thus point is most beneficial when associated with radiotherapy. The tumor/plasma ratlo ofetamdazole examined in three phases is relatively higher than that noted with HPLC; however, it IS compatible with the methodology used and previous studies carried out on other tumors. Oncoprotein (c-myc, c-erbBl, c-erbB2, c-fos) and suppressor gene product (~53) expression in squamous cell carcinomas of the lung. Clinical and biological correlations Volm M, Efferth T, Mattern J. Deutsches Krebsforschungs~e/llr, Ini NeuenheirnerFeldZ~ W-69lXIHeidelberg. Anticancer Res 1992; 12: I l- 20. The expression of the protooncogene encoded proteins (c-erhB I, c- erb 82, c-myc, c-fos) and the suppressor gene product ~53 was analyzed m 81 human squamous cell carcinomas of the lung and correlated with clinical parametersofthepatlents(patientsulvival, presznceofmetashses and tumor stage) and with biological characteristics ofthe tumors (tumor growth innudenuce, DNA-ploldy, proliferatweactivity, drug-rwstance and P-glycoprotein or gluathione S-transferase expression). By meana of immunoh~stochemistry, expression of c-erbBl oncoprotem (EGF- receptor) was deteccted in 79% of the tumors, c-erbB2 (c-neu) protams m 35 X, c-myc proteins in 48 %, c-fos proteins in 41 X, and p53 in 43 % ofthe tumorsP&ents withc-erbB1 positive tumors hadapoorprognosis (p=O.O21). In addition, these tumors were more frequently drug reststint (p=O.C067). A significant correlation between the growth of the squamous lung carcmoma~, m nude mice and c-fos oncoprotem axprasslon wasdemonstrated (p=O.O17). Therefore, EGF-receptorand c-fos products may sewe as prognostw factors for Ihe aggressiveness of squamous cell carcmomas of the lung and for the response of these tumors to chemotherapy. No slgmficant correlation was found between the express,“” of the c-arbB1 or c-fos gene products and stage. metastasis and DNA-ploady. In contrast to these results, no relatwnshlp was found between c-neu or c-myc gene products cxprewon and any of the climcal or hiologlcal parameters exammed. Aneuploid squamous cell carcmomas of the lung expressed ~53 more frequently than diplold tumors (p=O.O27). However, there was no significant diffwace hatwmn ~53 axpress~on and stage. surwval of patients, metastasis, growth of thr. tumors in nude mice, prohferativa actwity and drug- resistance of the tumors Papillary adenoma of the lung Hegg CA, Flint A, Smgh G. Depnrtmenr of Pathology, University Hospitals, Box &X4, 1500 E. Medical Cenrer Drive. Arm Arbor, MI 48109-0054. Am J Clin Pathol 1992;97:393-7. Three cases of an unusual neoplasm of the lung appeared as sohtary, peripheral pulmonary nodules m asymptomatic patients. These well- circumscribed neoplasmswerecomposedofdistinctwepapdlaecovered by uniform cuboidal to columnar cells; more solid areas often were present. Cdiatedcells, epithelial mucm, andnecrosiswerenot observed, and mitotac activity was absent. Terminal tightjunctions and nucrovilh were present in the two cases studied ultrastructurally. One spamen contamed lnmallar hodies and aplcal cytoplasmic dense bodies. Another case stained positively for a.Clara cell-specific antigen, although surhctant apoprotem was not d&c&d by immunostaining in the three cases. All patients have been free of disease (at 11 to 108months). Papillaryadenomaisanuncommon, apparently benign, and morphologically distinctive neoplasm. The immtmohistochemical and ultrastructural findings hint atan origin from type II pneumocytes or Clara cells. Kinetic uptake of etanidamle in lung carcinoma and normal tissue in viva Busuttl L, Brecaa A, Ferri E, Falcone F, Bertom F. Radiotherapy D~~parrtr~ent. Malpighi Hospital, USL 28, Via Albertoni, II. 15, 40138 Bologrm. Int J Radiat Oncol Blol Phys 1992;22:585-8. Cloning of 67-kDa laminin receptor cDNA and gene expression in normal and malignant cell lines of the human lung Satoh K, Narumi K, Sakal T. Abe T, Kikuchi T, Matsushima K er al. Deprrrrmetr~ of Internal Medic&-, 7he Research Irwiruref<u Tubercu1o.ri.s and Cancer, Tohoku University, 4-l Seiryo-tnachi, Sewdrti 980, Cancer Lett 1992;62: 199-203. Thrrty-four patients affected hy primary pulmonary carcinoma or in Cell-adheswe protein lanunin and its speatic receptor play an astataofrecurr~nceaftersurg~ry wereanalyzedandZg/m’ofetanidazole Important role m the processes of cancer proliferation, mvasron and wasadministered mtravenously. After30 min (group A), 60min (group metastasis. In the present study, we cloned the cDNAs of Ihe 67-k& B), and 120 nun (group C), both the bronchus affected by the carcinoma lammm receptor both from a human lung cell hne (IMR90) and from a and thecontrolateral bronchus were biopsiexl. Of the34 patients, 24 had human lung cancer cell lme (SBC3), and determad the nuclaotlde hlstologlcally proven carcmoma and were enrolled I” the study. sqquences. In comparison wth both cDNA sequences of the protan- Carbohydrate profiles shown by a lectin and a monoclnnal antihody correlate with metastatic potential and prognosis of human lung carcinomas The expression of two carbohydrate markers-namely, 4C9 antigen, which IS an Le(x) antigen. and the Dolichos hiflorus agglutmin (DBA) binding site, which is an N-acecylgalactosaminz marker-was exammed hlstochemlcally m mmors and adJacent nonhumorous tissues of I02 c&es of human lung carcinomas. In nontumorous 1Issues, the DBA binding slta was expressed more frequently than 4C9 antigen. and the DBA hmding sate had a tendency to bc expressed more slgniticantly than m tumor cells. Adenocarcinomas and well- dlfferantlated tumors had a tendency to more cell surface &rung. Patients wth tumors that expressed DBA binding sates hut not 4C9 antigen (4C9-, DBA+) had fewer metastasw and sigmficantly better prognoses than patwas wth tumors of other carbohydrate profiles. Better prognosis of patients wth 4C9-, DBA + tumors was ohserved in those wtb blood group A an&en and thost wthout It. and the hettcr prognosis also was obwrvcd in patwnts with Stage I and IllA disease.

Kinetic uptake of etanidazole in lung carcinoma and normal tissue in vivo

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Page 1: Kinetic uptake of etanidazole in lung carcinoma and normal tissue in vivo

335

Lack of expression of p-glycoprotein in 7 small cell lung cancer cell lines established both from untre*ted and from treated patients Milroy R, Plumb JA, B&tone P, Mac!ay A, Wishart GC, Hay FG et al. CRCDept of Medical Oncology, Unix&y @Glasgow, Alexander Stone Building, Bearsden, Glasgow G61 IBD. Anticancer Res 1992; 12: 193-200.

The establishment and charactcnsation of 7 small cell lung cancer cell lines is described. Four ccl1 lincs were established from bloDsies taken from untreated patlents and one of these was from primary tumour taken via the tibre-optic bronchoscope. The other three were from biopsies taken from patients who had relapsed after chemotherapy. All grow as non-adherennt aggregates of cell and express a range of neuroendocrina and epithelial features characteristics of small cell lung cancer cell lines. No relationship was observtld between the characteristics ofthe cell line !n vitro and the treaatment status ofthe patient from whom the biopsy was taken. Furthermore, none of the cell lines expressed p-glycoprotein even though 3 were derived from relapse biopsies where chemotherapy mcluded drugs assocrated wth the multidrug resistance phenotype.

Etanidazole determination was carried out with a polarographic method both in plasma and tissue. The results obtained indicate that the most favorable concentrat!on of etamdazole in the tissue is at 30 min after administration and at thus point is most beneficial when associated with radiotherapy. The tumor/plasma ratlo ofetamdazole examined in three phases is relatively higher than that noted with HPLC; however, it IS compatible with the methodology used and previous studies carried out on other tumors.

Oncoprotein (c-myc, c-erbBl, c-erbB2, c-fos) and suppressor gene product (~53) expression in squamous cell carcinomas of the lung. Clinical and biological correlations Volm M, Efferth T, Mattern J. Deutsches Krebsforschungs~e/llr, Ini NeuenheirnerFeldZ~ W-69lXIHeidelberg. Anticancer Res 1992; 12: I l- 20.

The expression of the protooncogene encoded proteins (c-erhB I, c- erb 82, c-myc, c-fos) and the suppressor gene product ~53 was analyzed m 81 human squamous cell carcinomas of the lung and correlated with clinical parametersofthepatlents(patientsulvival, presznceofmetashses and tumor stage) and with biological characteristics ofthe tumors (tumor growth innudenuce, DNA-ploldy, proliferatweactivity, drug-rwstance and P-glycoprotein or gluathione S-transferase expression). By meana of immunoh~stochemistry, expression of c-erbBl oncoprotem (EGF- receptor) was deteccted in 79% of the tumors, c-erbB2 (c-neu) protams m 35 X, c-myc proteins in 48 %, c-fos proteins in 41 X, and p53 in 43 % ofthe tumorsP&ents withc-erbB1 positive tumors hadapoorprognosis (p=O.O21). In addition, these tumors were more frequently drug reststint (p=O.C067). A significant correlation between the growth of the squamous lung carcmoma~, m nude mice and c-fos oncoprotem axprasslon wasdemonstrated (p=O.O17). Therefore, EGF-receptorand ’ c-fos products may sewe as prognostw factors for Ihe aggressiveness of squamous cell carcmomas of the lung and for the response of these tumors to chemotherapy. No slgmficant correlation was found between the express,“” of the c-arbB1 or c-fos gene products and stage. metastasis and DNA-ploady. In contrast to these results, no relatwnshlp was found between c-neu or c-myc gene products cxprewon and any of the climcal or hiologlcal parameters exammed. Aneuploid squamous cell carcmomas of the lung expressed ~53 more frequently than diplold tumors (p=O.O27). However, there was no significant diffwace hatwmn ~53 axpress~on and stage. surwval of patients, metastasis, growth of thr. tumors in nude mice, prohferativa actwity and drug- resistance of the tumors

Papillary adenoma of the lung Hegg CA, Flint A, Smgh G. Depnrtmenr of Pathology, University Hospitals, Box &X4, 1500 E. Medical Cenrer Drive. Arm Arbor, MI 48109-0054. Am J Clin Pathol 1992;97:393-7.

Three cases of an unusual neoplasm of the lung appeared as sohtary, peripheral pulmonary nodules m asymptomatic patients. These well- circumscribed neoplasmswerecomposedofdistinctwepapdlaecovered by uniform cuboidal to columnar cells; more solid areas often were present. Cdiatedcells, epithelial mucm, andnecrosiswerenot observed, and mitotac activity was absent. Terminal tightjunctions and nucrovilh were present in the two cases studied ultrastructurally. One spamen contamed lnmallar hodies and aplcal cytoplasmic dense bodies. Another case stained positively for a.Clara cell-specific antigen, although surhctant apoprotem was not d&c&d by immunostaining in the three cases. All patients have been free of disease (at 11 to 108months). Papillaryadenomaisanuncommon, apparently benign, and morphologically distinctive neoplasm. The immtmohistochemical and ultrastructural findings hint atan origin from type II pneumocytes or Clara cells.

Kinetic uptake of etanidamle in lung carcinoma and normal tissue in viva Busuttl L, Brecaa A, Ferri E, Falcone F, Bertom F. Radiotherapy D~~parrtr~ent. Malpighi Hospital, USL 28, Via Albertoni, II. 15, 40138 Bologrm. Int J Radiat Oncol Blol Phys 1992;22:585-8.

Cloning of 67-kDa laminin receptor cDNA and gene expression in normal and malignant cell lines of the human lung Satoh K, Narumi K, Sakal T. Abe T, Kikuchi T, Matsushima K er al. Deprrrrmetr~ of Internal Medic&-, 7he Research Irwiruref<u Tubercu1o.ri.s and Cancer, Tohoku University, 4-l Seiryo-tnachi, Sewdrti 980, Cancer Lett 1992;62: 199-203.

Thrrty-four patients affected hy primary pulmonary carcinoma or in Cell-adheswe protein lanunin and its speatic receptor play an astataofrecurr~nceaftersurg~ry wereanalyzedandZg/m’ofetanidazole Important role m the processes of cancer proliferation, mvasron and wasadministered mtravenously. After30 min (group A), 60min (group metastasis. In the present study, we cloned the cDNAs of Ihe 67-k& B), and 120 nun (group C), both the bronchus affected by the carcinoma lammm receptor both from a human lung cell hne (IMR90) and from a and thecontrolateral bronchus were biopsiexl. Of the34 patients, 24 had human lung cancer cell lme (SBC3), and determad the nuclaotlde hlstologlcally proven carcmoma and were enrolled I” the study. sqquences. In comparison wth both cDNA sequences of the protan-

Carbohydrate profiles shown by a lectin and a monoclnnal antihody correlate with metastatic potential and prognosis of human lung carcinomas

The expression of two carbohydrate markers-namely, 4C9 antigen, which IS an Le(x) antigen. and the Dolichos hiflorus agglutmin (DBA) binding site, which is an N-acecylgalactosaminz marker-was exammed hlstochemlcally m mmors and adJacent nonhumorous tissues of I02 c&es of human lung carcinomas. In nontumorous 1Issues, the DBA binding slta was expressed more frequently than 4C9 antigen. and the DBA hmding sate had a tendency to bc expressed more slgniticantly than m tumor cells. Adenocarcinomas and well- dlfferantlated tumors had a tendency to more cell surface &rung. Patients wth tumors that expressed DBA binding sates hut not 4C9 antigen (4C9-, DBA+) had fewer metastasw and sigmficantly better prognoses than patwas wth tumors of other carbohydrate profiles. Better prognosis of patients wth 4C9-, DBA + tumors was ohserved in those wtb blood group A an&en and thost wthout It. and the hettcr prognosis also was obwrvcd in patwnts with Stage I and IllA disease.