The expression of H-like blood group glycolipids in small cell carcinoma of the lung
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402 Abstracts /Lung Cancer 10 (1994) 395-430 University of Cultfornia. 1603 Alhambra Blvd. Sacramento, CA 95816. Arch Gpthalmol 1993; 111:974-8. Objective: We have inquired into the reason why patients with cancer- associated retinopathy (CAR) produce antibody reacttons with the 23-kd retinal CAR antigen. Possible reasons include the expression of this antigen in the related carcinoma. Previous studies have failed to identi~sayantigeniccounterpartexpressedbyinvitrocultivatzdsmall- cell carcinoma of the lung. We, therefore, inquired into the effects of in vtvo cultivation of the cancer cells and its itttluence on protein expression. withspecific referencetotbeappearanceofthe23-kd retinal CAR antigen. Design: A complementary DNA library was prepared from small-cell carcinoma of the lung cells propagated intraperitoneally m Lewis rats and probed with anttbodies reactive with the 23-kd retinal CAR antigen. Resulrs: We found evidence of the expression ofa cancer- associated gene in as&es-propagated small-cell carcinoma of the lung that encodes for a protein antigenically similar to the 23-kd retinal CAR antigen. AcomplementaryDNAencodingthispmteinrevealedcomplete DNA sequence homology with the retinal CAR antigen showing the cancer cells are expressing this photoreceptor protein. Conclusions: We hypothesize that the carcinoma-retina immunologic cross-reaction is responsrbIefortheinductionoftheumqueantibodyresponseencountered in patients with CAR with vision loss developing as a cancer-evokuf autoimmune retinopatby. The expression of H-like blood group glycolipitls in small cell cnrcinuma of the lung Cualing HD, Siegel R. Schwa&g GA, Suchy SF, McCluer RH Bemal S. Department of Pathology, Cincinnati UniversityMedical Center, 231 Bethesda Avenue, Cincinnnrr. OH 4S267. Hybtidotna 1993; 12: 239- 47. Monoclonal anttbody SMI has been shown to be preferenttally reactive with small cell carcinoma of the lung (SCCL) cell lines by tluorescent and radioimmunoassay membrane staining (1). Using solid phase indirect mdioimmunoassay, the antigen is not detected in non- SCCLlungcarcinomashistologicallyclassiliedassquatnouscarcinotna, adenocarcinoma or large cell carcinoma, and other tumors. viz: pheochromocytoma, a mesoderm derived lymphoblastic leukemia cell line or in normal human brain, heart, liver, colon, endothelial tissues of the aorta and blood vessels. skin, omentum. muscle, lung parenchyma and is weakly reactive with bronchial mucosa, pancreas, and kidney. The membrane antigens detected by SM 1 were isolated from small ceil carcinoma of the lung (SCCL) cell line, SW2, using anion exchange chromatography and thin layer chromatography, and were further analysed by exoglycosidase and endoglycosidase treatments followed bychemicalstaininganditnmunostainingwithSM1andotberantibodies. We show here that SMl annbody reacts with a group of fucose- containing neutral ylycolipids and gangliosides many of which are cross-resctive with antibodies to H antigens. Denaturing gradient gel electrophoresis (DGGE) assay for K-t-as and N-s-as genes: detection of K-ras point mutations in humw lung tumour DNA Ridanpaa M, Husgatvel-Pursiainen K. Insritureof Occupational Health, Topeliakrenkuu 414. SF-@250 HeLGzki. Hum Mol Gettet 1993;2:639- 44. Point mutations in the ras oncogenes are very common in lung cancers as well as in many of the other solid turnouts. To effectively examine the occurrence of these. mutations in a large number of tttmour samples, we have applied denaturing gradient gel electmphoresis (DGGE) fortheanalysisofpoint mutationsoftheK-rasand N-rasgenes. using GC-clamped, PCR-amplified DNA fragments. Among the 68 tumour DNA samples, we detected 14 mutations in the K-ras gene. This was 78 % of the mutattons identified by oligonucleotide hybridization. Altogether, eight of the nine different kinds of base substitutions found in the tumour samples were detected by the DGGE assay, representing substitutions at codons 12. 13. and 61 of the K-ras gene. Six of the detected mutations were guanine to thymine transversions at codon 12: this was the most common type of alteration. On the basis of our experience, the present non-radioactive DGGE analysis seems to be readily applicable for detection of the mutations in the K-ras and N-ras t’enes. Types of ras gene mutations frequent in adenocarcinomas of the hng are also discussed. Peripheral blood mononuclear cells express antigens associated with multidrug resistance in a small cell lung c;mcer cell line Krebes KA. Mirski SEL, Pmss HF, Cole SPC. Cclticer Research Laboratories, RM 331 Borrerell Hall, Queen’s University. Kingsron, Ont K7L 3N6. Anticancer Res 1993;13:317-21. H69AR is a multidrug resistant small cell lung cancer (SCLC) cell line that does not overexpress P-glycopmtein, the plasma membrane drug efflux pump usually associated with this type of resistance. ~Monoclonal antibodies (MAbs) were previously raised against H69AR cells, and three of these MAbs, 2.54, 3.50, and 3.186, cross-reacted with peripheral blood mononuclear cells. T cells (CD3+). B cells (CD19+),NKcells(CD16+)andmonocytes(CDl4+)expressedeach of the three antigens, but to differing degrees. Immunoprecipitation and partial proteolytic mapping experiments demonstrated that the antigens detected by MAbs 2.54 and 3.186 are identical in H69AR cells and PBMCs. SCLCcellsareknowntoexpressmanyhematopoieticantigens; however, this IS the first report of SCLC multidrug resistance associated antigens beiig expressed on hemaropoiettc cells. Differentialgmwthregulationofametastatichum~l~~noma cell line through activation of phosphatidyl inositol turnover signal transduction pathway Fang W-G, Wu B-Q. Department of Pathology, Beijing Medical Univcrsiry. Xue Yuan Road, Beijing l@M83. Clin Exp Metastasis 1993: 11:330-6. Uttttl recently, the signal transduction pathways involved in the processes of tumor growth have been poorly understood. In the present study, we investigated cell surface receptors which utilize phospbatidylinositol (PI) tumoverlCa” mobilization as a signal transduction pathway to regulate cell gmwtb in a metastatic human lung carcioomacell line, PG. We found that purinoceptoragonists, including ATP and its analogs, and bombesin. an amphibian tetmdeca-pepttde of increase of cytoplasmic-free Car’ in PG cells loaded with fura-2. The Cd’ responses were derived both from release from internal stores and the opening of plasma membrane Cd’ channels. HPLC analysis of inositol 1,-U-triphospbate (lns(1,4,5)P3) and its isomers showed a receptor-linked phospholipase. C activation by ATP and bomb&n. Although ATP and bombesin were both able to induce PI turnover and Ca’* mobilization in PG cells, they had differenttal growth regulatory effectson PG cells. Treatment wtth bombesin stimulated PG cell growth while treatment with ATP inhibited significantly PG cell growth. Pharmacological studies showed that the purinoceptors on PG cells were of the P2 subtype. Other hydrolysis-resistant P2 putinoceptor agonists, including ATPgammaS and AMP-PNP. were as effective as ATP in stimulattng PI turnover and Ca?’ mobilization as well as in mhibiting PG cell growth in vitro, suggesting the potential usetitlness of such ATP analogs in clinical trials. Preliminary results suggest G protein involvement in the differential regulation of ATP and bombesin signal transduction pathways.
Transcript of The expression of H-like blood group glycolipids in small cell carcinoma of the lung
402 Abstracts /Lung Cancer 10 (1994) 395-430
University of Cultfornia. 1603 Alhambra Blvd. Sacramento, CA 95816. Arch Gpthalmol 1993; 111:974-8.
Objective: We have inquired into the reason why patients with cancer- associated retinopathy (CAR) produce antibody reacttons with the 23-kd retinal CAR antigen. Possible reasons include the expression of this antigen in the related carcinoma. Previous studies have failed to identi~sayantigeniccounterpartexpressedbyinvitrocultivatzdsmall- cell carcinoma of the lung. We, therefore, inquired into the effects of in vtvo cultivation of the cancer cells and its itttluence on protein expression. withspecific referencetotbeappearanceofthe23-kd retinal CAR antigen. Design: A complementary DNA library was prepared from small-cell carcinoma of the lung cells propagated intraperitoneally m Lewis rats and probed with anttbodies reactive with the 23-kd retinal CAR antigen. Resulrs: We found evidence of the expression ofa cancer- associated gene in as&es-propagated small-cell carcinoma of the lung that encodes for a protein antigenically similar to the 23-kd retinal CAR antigen. AcomplementaryDNAencodingthispmteinrevealedcomplete DNA sequence homology with the retinal CAR antigen showing the cancer cells are expressing this photoreceptor protein. Conclusions: We hypothesize that the carcinoma-retina immunologic cross-reaction is responsrbIefortheinductionoftheumqueantibodyresponseencountered in patients with CAR with vision loss developing as a cancer-evokuf autoimmune retinopatby.
The expression of H-like blood group glycolipitls in small cell cnrcinuma of the lung Cualing HD, Siegel R. Schwa&g GA, Suchy SF, McCluer RH Bemal S. Department of Pathology, Cincinnati UniversityMedical Center, 231 Bethesda Avenue, Cincinnnrr. OH 4S267. Hybtidotna 1993; 12: 239- 47.
Monoclonal anttbody SMI has been shown to be preferenttally reactive with small cell carcinoma of the lung (SCCL) cell lines by tluorescent and radioimmunoassay membrane staining (1). Using solid phase indirect mdioimmunoassay, the antigen is not detected in non- SCCLlungcarcinomashistologicallyclassiliedassquatnouscarcinotna, adenocarcinoma or large cell carcinoma, and other tumors. viz: pheochromocytoma, a mesoderm derived lymphoblastic leukemia cell line or in normal human brain, heart, liver, colon, endothelial tissues of the aorta and blood vessels. skin, omentum. muscle, lung parenchyma and is weakly reactive with bronchial mucosa, pancreas, and kidney. The membrane antigens detected by SM 1 were isolated from small ceil carcinoma of the lung (SCCL) cell line, SW2, using anion exchange chromatography and thin layer chromatography, and were further analysed by exoglycosidase and endoglycosidase treatments followed bychemicalstaininganditnmunostainingwithSM1andotberantibodies. We show here that SMl annbody reacts with a group of fucose- containing neutral ylycolipids and gangliosides many of which are cross-resctive with antibodies to H antigens.
Denaturing gradient gel electrophoresis (DGGE) assay for K-t-as and N-s-as genes: detection of K-ras point mutations in humw lung tumour DNA Ridanpaa M, Husgatvel-Pursiainen K. Insritureof Occupational Health, Topeliakrenkuu 414. SF-@250 HeLGzki. Hum Mol Gettet 1993;2:639- 44.
Point mutations in the ras oncogenes are very common in lung cancers as well as in many of the other solid turnouts. To effectively examine the occurrence of these. mutations in a large number of tttmour samples, we have applied denaturing gradient gel electmphoresis (DGGE) fortheanalysisofpoint mutationsoftheK-rasand N-rasgenes. using GC-clamped, PCR-amplified DNA fragments. Among the 68 tumour DNA samples, we detected 14 mutations in the K-ras gene. This
was 78 % of the mutattons identified by oligonucleotide hybridization. Altogether, eight of the nine different kinds of base substitutions found in the tumour samples were detected by the DGGE assay, representing substitutions at codons 12. 13. and 61 of the K-ras gene. Six of the detected mutations were guanine to thymine transversions at codon 12: this was the most common type of alteration. On the basis of our experience, the present non-radioactive DGGE analysis seems to be readily applicable for detection of the mutations in the K-ras and N-ras t’enes. Types of ras gene mutations frequent in adenocarcinomas of the hng are also discussed.
Peripheral blood mononuclear cells express antigens associated with multidrug resistance in a small cell lung c;mcer cell line Krebes KA. Mirski SEL, Pmss HF, Cole SPC. Cclticer Research Laboratories, RM 331 Borrerell Hall, Queen’s University. Kingsron, Ont K7L 3N6. Anticancer Res 1993;13:317-21.
H69AR is a multidrug resistant small cell lung cancer (SCLC) cell line that does not overexpress P-glycopmtein, the plasma membrane drug efflux pump usually associated with this type of resistance. ~Monoclonal antibodies (MAbs) were previously raised against H69AR cells, and three of these MAbs, 2.54, 3.50, and 3.186, cross-reacted with peripheral blood mononuclear cells. T cells (CD3+). B cells (CD19+),NKcells(CD16+)andmonocytes(CDl4+)expressedeach of the three antigens, but to differing degrees. Immunoprecipitation and partial proteolytic mapping experiments demonstrated that the antigens detected by MAbs 2.54 and 3.186 are identical in H69AR cells and PBMCs. SCLCcellsareknowntoexpressmanyhematopoieticantigens; however, this IS the first report of SCLC multidrug resistance associated antigens beiig expressed on hemaropoiettc cells.
Differentialgmwthregulationofametastatichum~l~~noma cell line through activation of phosphatidyl inositol turnover signal transduction pathway Fang W-G, Wu B-Q. Department of Pathology, Beijing Medical Univcrsiry. Xue Yuan Road, Beijing l@M83. Clin Exp Metastasis 1993: 11:330-6.
Uttttl recently, the signal transduction pathways involved in the processes of tumor growth have been poorly understood. In the present study, we investigated cell surface receptors which utilize phospbatidylinositol (PI) tumoverlCa” mobilization as a signal transduction pathway to regulate cell gmwtb in a metastatic human lung carcioomacell line, PG. We found that purinoceptoragonists, including ATP and its analogs, and bombesin. an amphibian tetmdeca-pepttde of
increase of cytoplasmic-free Car’ in PG cells loaded with fura-2. The Cd’ responses were derived both from release from internal stores and the opening of plasma membrane Cd’ channels. HPLC analysis of inositol 1,-U-triphospbate (lns(1,4,5)P3) and its isomers showed a receptor-linked phospholipase. C activation by ATP and bomb&n. Although ATP and bombesin were both able to induce PI turnover and Ca’* mobilization in PG cells, they had differenttal growth regulatory effectson PG cells. Treatment wtth bombesin stimulated PG cell growth while treatment with ATP inhibited significantly PG cell growth. Pharmacological studies showed that the purinoceptors on PG cells were of the P2 subtype. Other hydrolysis-resistant P2 putinoceptor agonists, including ATPgammaS and AMP-PNP. were as effective as ATP in stimulattng PI turnover and Ca?’ mobilization as well as in mhibiting PG cell growth in vitro, suggesting the potential usetitlness of such ATP analogs in clinical trials. Preliminary results suggest G protein involvement in the differential regulation of ATP and bombesin signal transduction pathways.
