1
100 also had an additional band of the c-myc gene or amplification of the L- myc gene. No abnormaltry of the N-myc gene was observed in this series. Of 13 cancers with abnormality of the myc family genes, 11, including all tumors with myc gene amplification, were transplantable tonudemice.Of 19tumorswttboutanyabnom1alitiesofthemycfamily genes, however, only five were transplantable to nude mice (P < 0.005). These results indicate that abnormality of the myc family genes, especially gene amplification, might promote tumorigenic ability in xenotransplantation of lung cancers and this phenomenon might be closely related to the function of the myc gene. Role of T-lymphocytes in production of a cancer-associated protein factor in serum from lung cancer patients. KotlarHKr,SannerT.LaboraroryforEnvironmenralandOccupational Cancer, lnsritute for Cancer Research, The Norwegian Radium Hospi- tal, N-0310 Oslo 3. Ear J Cancer Clin Oncol 1988;24: 1763-70. Oligoclonal T-cells have been generated by sensitization of periph- eral blood mononuclear cells from lung cancer patients to a lung cancer tumor-associated antigen (TAA). A factor similar to the antigen- specific glycoprotein factor m the serum of these cancer patients was found in the supematant of the oligoclonal T-cells. The factor from the T-cell supernatant had specificity for lung cancer TAA and induced stimulation of normal lymphocytes of the CD8 phenotype when mixed witb lung cancer TAA. Furthermore, the factor blocked the ability of lymphocytes from lung cancer patients to recognize lung cancer TAA. Both the factor from lung cancer serum and from the oligoclonal T-cells were absorbed on a lung cancer-associated antigen-coupled immuno- sorbent column. On FPLC-gel filtration the desorbed fractions from the immunosorbent column from both sources showed activity in the same molecular weight range, 70-90 kD. Heteroantisera raised against the factor from serum and against the factor from the oligoclonal T-cell supematant bound about the same portion of lymphocytes from lung cancer patients as measured by immunofluorescence, while only a minor fraction of cells from patients with unrelated cancers and from healthy persons were labelled on incubation with the antisera. These results support the hypothesis that an antigen-specific factor found in serum of cancer patients is produced by antigen-stimulated T-cells, possibly of the CDS phenotype. This putative antigen-specific sttppres- sor factor and the tumor antigen-reactive lymphocytes of the patient seem to share similar idiotopes. Genomic 5methyldeoxycytidine decreases associated with the in- duction of squamous differentiation in cultured normal human bronchial epithelial cells. Wilson VL, Masui T, Smith RA, Harris CC. Loboratory of Human Carcinogenesis, Division of Cancer Etiology, National Cancer Insti- tute, NIH, Bethesda, MD 20892. Carcinogenesis 1988;9:2155-9. The terminal squamous differentiation of epithelial cells involves a number of cellular changes. However, the mechanisms underlying this differentiation process are unknown. The present study demonstrates that &uacytidine, 12-0-tetradecanoylphorbol-13-acetate (TPA) and type B-transforming growth factor (TGF-B) significantly diminish the genomic 5-methyldeoxycytidine (SmdC) content of normal human bronchial epitbelial cells concomitantly with the induction of squamous differentiation. 5.Azacytidine or TPA, but not type B-transforming growth factor, also initiated decreases in the genomic 5mdC content of differentiationnonresponsivehuman tumorA549cells.Theseeffectsof TPA or type &transforming growth factor occurred at concentrations of 1 nM and 1.2 pM, respectively, which were approximately one tenth of k(d) values of their specific receptors. Therefore, the decreases in genomic 5mdC induced by these agents were probably mediated, dtrectly or indirectly, by receptor-ligand interactions. Human lung carcinoma monoclonal antibody specific for the Th- omsen-Friedenreich antigen. Stein R, Chen S, Grossman W, Goldenberg DM. Centerfor Molecular Medicine and Immunology, University of Medicine and Dentistry, Newark. NJ 07103. Cancer Res 1989;49:32-7. A monoclonal antibody, RSl-114, was raised against the human adenocarcinoma of the lung cell line A549. by studying the reactivity of RSl-I 14 withA549cellsfollowingchemicalandenzymaticueatmen~, it was shown that the epitope is a galactose-containing carbohydrate, which is devoid of sialic acid. Hemagglutination of desialylated RBCs, enzyme-linked immunosorbcnt assay studies with glycoprotein anti- gens before and after desialylation, and competition studies using peanut aggltttinin indicate that monoclonal antibody RSl-114 recog- nizes the Thomsen-Friedenreich antigen, a cryptic determinant on human erythrocytes which can be exposed by neuraminidase treatment. It IS expressed tn a unhidden form on a large percentage of carcinomas and IS therefore an important human tumor marker. RS l-l 14 is reactive with cryptic determinants of the Thornsen-Friedenreich antigen on white blood cells as well as red blood cells, and tt reacts with unhidden determinantson human tumorcell lines.Thenumberofhindingsiteson carcinoma cells is further increased by neuraminidase treatment. By immunohistochemical statning, it was shown that 75% of the human tumors tested are reactive with RSl-114. These include tumors of the breast, colon, lung, kidney, ovary, and rectum. Compartmental biodistribution of a monoclonal antibody against human lung adenocarcinoma grown in athymic mice. ShaniJ,MohdS, WolfW,WalkerLE.RadiopharmacyProgram.School of Pharmacy, University of Southern California. Los Angeles, CA 90033. Nucl Med Biol, Int JRadiat Appl Instmm Part B 1989;16:33-40. The biodistribution of the radioiodinated monoclonal antibody KS l/ 4 and of its F(ab) and F(ab’), fragmenls were studied in tumor-bearing nudemice. intravenous administratton of the intact antibody resulted in the highest tumor retention and tumor/blood ratios. No metabolites or antigen-antibody conjugates were detectable, in serum, by HPLC analyses. Reasonablecorrelations were obtained between theestimated time-course of KS114 and experimental biodisuibution data using an eight-compartment linearradiopharmacokinetic model, suggesting that such models may be useful in predicting the hiodistributton and effective targeting of this monoclonal antibody. Effectsofactivatorsof protein kinase C, including bryostatins 1 and 2, on the growth of A549 human lung carcinoma cells. Dale IL, Gescher A. Cancer Research Campaign Experimental Chemo- therapy Group, Pharmaceutical Sciences Institute, Aston University, Birmingham 84 7ET. Int J Cancer 1989:43:158-63. Phorbol esters such as 12-O-teuadecanoylphorbol- 13.acetate (TPA) inhibit the growth of A549 human lung carcinoma cells at non-tow concentrations, whereas I-oleoyl-2-acetylglycerol and 1,2-dioc- tanoylglycerol, synthetic analogues of the physiological ligands of protein kinase C (PKC), do not. Experiments were conducted to test the hypothesis that other activators of PKC are capable of interfering with A549 cell growth. The non-phorhoid turnour promotor mezerein mim- icked the growth-inhibitory effect of TPA in that it arrested growth for 5 days, after which cells proliferated again in the continued presence of the agent. TPA was 20 times more potent as a growth inhibitor than was mezerein. Bryostatin 1 at IOnMand bryostatin2at 1OOnMalsoturested A549 cell growth and inhibited DNA replication as measured by incorporation of [methyl-3H]-thymidine into cells. Inhibition of DNA synthesis to between 90 and 75% of control values developed during the first how of incubation of the cells with TPA, mezerein or tbe bry- ostatins. The extent of inhibition changed little during tbe subsequent 5 hrofincubation.after which itincreaxdfurtbertoreachmaximalvalues within 12 hr. At concentrations above those which caused maximal growth inhibition, the bryostatins abolished both their own inhibition of DNA synthesis and the anti-replicative effect of TPA and mezerein. The results show that activators of PKC other than phorbol esters are capable of inhibiting the growth of A549 cells. The bryostatins not only interfere with A549 cell growth but can alsocounter the growth-inhibitory effect of PKC activators, presumably via interaction with a target separate from the phorbol ester receptor site. Loss of heterozygosity in a gene coding for a thyroid hormone receptor in lung cancers. Leduc F, Brauch H, Hajj C etal. Institut du Cancerde Montreal. Hopital Notre-Dame, Montreal, Que. HZL4MI. Am J Hum Genet 1989:44:282- 7.

Role of T-lymphocytes in production of a cancer-associated protein factor in serum from lung cancer patients

Embed Size (px)

Citation preview

Page 1: Role of T-lymphocytes in production of a cancer-associated protein factor in serum from lung cancer patients

100

also had an additional band of the c-myc gene or amplification of the L- myc gene. No abnormaltry of the N-myc gene was observed in this series. Of 13 cancers with abnormality of the myc family genes, 11, including all tumors with myc gene amplification, were transplantable tonudemice.Of 19tumorswttboutanyabnom1alitiesofthemycfamily genes, however, only five were transplantable to nude mice (P < 0.005). These results indicate that abnormality of the myc family genes, especially gene amplification, might promote tumorigenic ability in xenotransplantation of lung cancers and this phenomenon might be closely related to the function of the myc gene.

Role of T-lymphocytes in production of a cancer-associated protein factor in serum from lung cancer patients. KotlarHKr,SannerT.LaboraroryforEnvironmenralandOccupational Cancer, lnsritute for Cancer Research, The Norwegian Radium Hospi- tal, N-0310 Oslo 3. Ear J Cancer Clin Oncol 1988;24: 1763-70.

Oligoclonal T-cells have been generated by sensitization of periph- eral blood mononuclear cells from lung cancer patients to a lung cancer tumor-associated antigen (TAA). A factor similar to the antigen- specific glycoprotein factor m the serum of these cancer patients was found in the supematant of the oligoclonal T-cells. The factor from the T-cell supernatant had specificity for lung cancer TAA and induced stimulation of normal lymphocytes of the CD8 phenotype when mixed witb lung cancer TAA. Furthermore, the factor blocked the ability of lymphocytes from lung cancer patients to recognize lung cancer TAA. Both the factor from lung cancer serum and from the oligoclonal T-cells were absorbed on a lung cancer-associated antigen-coupled immuno- sorbent column. On FPLC-gel filtration the desorbed fractions from the immunosorbent column from both sources showed activity in the same molecular weight range, 70-90 kD. Heteroantisera raised against the factor from serum and against the factor from the oligoclonal T-cell supematant bound about the same portion of lymphocytes from lung cancer patients as measured by immunofluorescence, while only a minor fraction of cells from patients with unrelated cancers and from healthy persons were labelled on incubation with the antisera. These results support the hypothesis that an antigen-specific factor found in serum of cancer patients is produced by antigen-stimulated T-cells, possibly of the CDS phenotype. This putative antigen-specific sttppres- sor factor and the tumor antigen-reactive lymphocytes of the patient seem to share similar idiotopes.

Genomic 5methyldeoxycytidine decreases associated with the in- duction of squamous differentiation in cultured normal human bronchial epithelial cells. Wilson VL, Masui T, Smith RA, Harris CC. Loboratory of Human Carcinogenesis, Division of Cancer Etiology, National Cancer Insti- tute, NIH, Bethesda, MD 20892. Carcinogenesis 1988;9:2155-9.

The terminal squamous differentiation of epithelial cells involves a number of cellular changes. However, the mechanisms underlying this differentiation process are unknown. The present study demonstrates that &uacytidine, 12-0-tetradecanoylphorbol-13-acetate (TPA) and type B-transforming growth factor (TGF-B) significantly diminish the genomic 5-methyldeoxycytidine (SmdC) content of normal human bronchial epitbelial cells concomitantly with the induction of squamous differentiation. 5.Azacytidine or TPA, but not type B-transforming growth factor, also initiated decreases in the genomic 5mdC content of differentiationnonresponsivehuman tumorA549cells.Theseeffectsof TPA or type &transforming growth factor occurred at concentrations of 1 nM and 1.2 pM, respectively, which were approximately one tenth of k(d) values of their specific receptors. Therefore, the decreases in genomic 5mdC induced by these agents were probably mediated, dtrectly or indirectly, by receptor-ligand interactions.

Human lung carcinoma monoclonal antibody specific for the Th- omsen-Friedenreich antigen. Stein R, Chen S, Grossman W, Goldenberg DM. Centerfor Molecular Medicine and Immunology, University of Medicine and Dentistry, Newark. NJ 07103. Cancer Res 1989;49:32-7.

A monoclonal antibody, RSl-114, was raised against the human

adenocarcinoma of the lung cell line A549. by studying the reactivity of RSl-I 14 withA549cellsfollowingchemicalandenzymaticueatmen~, it was shown that the epitope is a galactose-containing carbohydrate, which is devoid of sialic acid. Hemagglutination of desialylated RBCs, enzyme-linked immunosorbcnt assay studies with glycoprotein anti- gens before and after desialylation, and competition studies using peanut aggltttinin indicate that monoclonal antibody RSl-114 recog- nizes the Thomsen-Friedenreich antigen, a cryptic determinant on human erythrocytes which can be exposed by neuraminidase treatment. It IS expressed tn a unhidden form on a large percentage of carcinomas and IS therefore an important human tumor marker. RS l-l 14 is reactive with cryptic determinants of the Thornsen-Friedenreich antigen on white blood cells as well as red blood cells, and tt reacts with unhidden determinantson human tumorcell lines.Thenumberofhindingsiteson carcinoma cells is further increased by neuraminidase treatment. By immunohistochemical statning, it was shown that 75% of the human tumors tested are reactive with RSl-114. These include tumors of the breast, colon, lung, kidney, ovary, and rectum.

Compartmental biodistribution of a monoclonal antibody against human lung adenocarcinoma grown in athymic mice. ShaniJ,MohdS, WolfW,WalkerLE.RadiopharmacyProgram.School of Pharmacy, University of Southern California. Los Angeles, CA 90033. Nucl Med Biol, Int JRadiat Appl Instmm Part B 1989;16:33-40.

The biodistribution of the radioiodinated monoclonal antibody KS l/ 4 and of its F(ab) and F(ab’), fragmenls were studied in tumor-bearing nudemice. intravenous administratton of the intact antibody resulted in the highest tumor retention and tumor/blood ratios. No metabolites or antigen-antibody conjugates were detectable, in serum, by HPLC analyses. Reasonablecorrelations were obtained between theestimated time-course of KS114 and experimental biodisuibution data using an eight-compartment linearradiopharmacokinetic model, suggesting that such models may be useful in predicting the hiodistributton and effective targeting of this monoclonal antibody.

Effectsofactivatorsof protein kinase C, including bryostatins 1 and 2, on the growth of A549 human lung carcinoma cells. Dale IL, Gescher A. Cancer Research Campaign Experimental Chemo- therapy Group, Pharmaceutical Sciences Institute, Aston University, Birmingham 84 7ET. Int J Cancer 1989:43:158-63.

Phorbol esters such as 12-O-teuadecanoylphorbol- 13.acetate (TPA) inhibit the growth of A549 human lung carcinoma cells at non-tow concentrations, whereas I-oleoyl-2-acetylglycerol and 1,2-dioc- tanoylglycerol, synthetic analogues of the physiological ligands of protein kinase C (PKC), do not. Experiments were conducted to test the hypothesis that other activators of PKC are capable of interfering with A549 cell growth. The non-phorhoid turnour promotor mezerein mim- icked the growth-inhibitory effect of TPA in that it arrested growth for 5 days, after which cells proliferated again in the continued presence of the agent. TPA was 20 times more potent as a growth inhibitor than was mezerein. Bryostatin 1 at IOnMand bryostatin2at 1OOnMalsoturested A549 cell growth and inhibited DNA replication as measured by incorporation of [methyl-3H]-thymidine into cells. Inhibition of DNA synthesis to between 90 and 75% of control values developed during the first how of incubation of the cells with TPA, mezerein or tbe bry- ostatins. The extent of inhibition changed little during tbe subsequent 5 hrofincubation.after which itincreaxdfurtbertoreachmaximalvalues within 12 hr. At concentrations above those which caused maximal growth inhibition, the bryostatins abolished both their own inhibition of DNA synthesis and the anti-replicative effect of TPA and mezerein. The results show that activators of PKC other than phorbol esters are capable of inhibiting the growth of A549 cells. The bryostatins not only interfere with A549 cell growth but can alsocounter the growth-inhibitory effect of PKC activators, presumably via interaction with a target separate from the phorbol ester receptor site.

Loss of heterozygosity in a gene coding for a thyroid hormone receptor in lung cancers. Leduc F, Brauch H, Hajj C etal. Institut du Cancerde Montreal. Hopital Notre-Dame, Montreal, Que. HZL4MI. Am J Hum Genet 1989:44:282- 7.