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Genetic susceptibility to squamous cell carcinoma of the lung in relation to cigarette smoking dose
126 six. Heterotmnsplanted tumors took 4 to 5 months to appear in the mice and 1 month to attain a width of 0.5 cm. Both human and mouse tumors (named CSH-SC and CSH-IM) were studied by light and electron microscopy. They were Grimelius-positive, neuron-specific enolasepositive, and born&in-negative by immunocytochemistry. Furthermore,CSH-SCcellspresentedcharacteristic @car-shaped.rod-shaped, or tadpole-shaped) neurosecretory granules: Although CSB and CSH were slightly serotonin positive by immunocytochemistry, only a few serotonin-positive cells were found in CSH-SC and none in CSH-IM, suggesting partial loss of differentiation or an increase in serotonin catabolism during transplantation. Detection of suspected primary lung cancer by scintigraphy wth indium-111-anti-carcinoembryonic (type FlwC5)
antigen mono&ma1 antibodies
BiggL A, Buccheri G, Ferrigno D, Viglietti A, Farinelli MC, Comino A et al. Servizio di Medicina Nucleare, Ospedale S. Croce, via Coppino 25.12100 Cuneo. J Nucl Med 1991;32:2064-8. Immunoscintigraphy with “‘In-labeled anti-CEA-Mab (FW23C51) was carried out in 66 patients strongly suspected for a primary lung cancer and in 8 control patients suffering from different chest diseases. A sensitivity of 0.90, a specificity of 0.45 and an accuracy of 0.85 were calculated. False-negative results were mainly obtained in patients in whom the size of the lesion was below 2 cm and the tumor was cenually located. All patients affected by small-cell carcinoma were correctly identified. In 89% of the patients, a positive immunoscintiscan was associated with the presence of the antigen in the tumor. False-positive results were observed in control patients suffering from different chest diseases due to the nonspecific uptake of the tracer. The tumor definition was generally better after 120 hr than at an earlier time after injection due to the reduction of background activity. SPECT imaging defined the tumor better in each patient but did not reveal any tumor not seen on planar studies. Genetic susceptibility to squamous relation to cigarette smoking dose
cell carcinoma of the lung in
Nakachi K, Imai K, Hayashi S-I, Watanabe J, Kawajiri K. Deparfment
ofEpidemiology, Sailam0 Cancer Center Research Ins&u@,818 &mum, Inn-machi, Saimmo 362. Cancer Res 1991;Sl:S177-80.
Cytochrome P4SOIAl is responsible for the metabolic activation of benzo(a)pyrene in cigarette smoke; an association of lung cancer with DNA polymorphisms of P450IAl gene was shown in our previous study. In this paper, we investigated the interindividual difference of genetically determined susceptibility to squamouscellcarcinomaofthe lung in relation to cigarette smoking dose. We first compared the total amounts of cigarettes consumed over dte lifetime of patients and showed that the patients with a “susceptible” P4501Al gene genotype contracted carcinoma after fewer cigarettes [mean f SD, 31.3 f 12.8 x l(r cigarettes (n = 12)] than those with other genotypes I42.5 i 18.2 x lO’(n = 33)], with a statistical significanceof P-z 0.05. Next, we carried out a case-control study to estimate tie odds ratios of susceptible to nonsusceptible individuals in relation to the cumulated cigarette dose. We thus showed that the individuals with the susceptible genotype were at remarkably high risk with an odds ratio of 7.31 (95% confidence interval, 2.13 1025.12) at a low dose level ofcigarette smoking and that the difference in susceptibility between genotypes was reduced at high dose levels. Production of neuromedin Band neuromedin B gene expression in human lung tumor cell lines
Cardona C. Rabbitts PH. Spindel ER, Ghatei MA, Bleehen NM et al. Medical Research Council, Clinical Oncology and Radiotherapeulics Unir, MRC Cenrre, Hills Road, Cambridge CB2 2QH. Cancer Res 1991:51:5205-11. Gastrin-releasing peptide (GRP), a mammalian bombesin-like pep tide, has been shown to be an important autocrine growth factor for small cell lung cancer (SCLC). However, not all SCLC cell lines express the GRP gene or respond mitogenically to GRP stimulation,
suggesting the existence of other autocrine pathways in this tumor. Neuromedin B (NMB), the mammalian counterpart of amphibian mnatensin, has been shown to be a mitogen for SCLC cell lines in vitro. TO determine whether NMB is a potential autcxrine growth factor for lung tumors, NMB gene expression, peptide synthesis, and secretion have been investigated in a panel of SCLC and non-SCLC (NSCLC) cell lines. Northern blot analysis and enzymatic amplification from mRNA by polymerase chain reaction showed that the NMB gene was expressed in all SCLC and NSCLC cell lines examined. In contrast, the GRP gene was expressed in four of six classic SCLC cell lines but not in variant SCLC or NSCLC cell lines. lmmunoreactive NMB was detected by radioimmunoassay in the majority of classic SCLC, in one of three variant SCLC and in one of three NSCLC cell lines, and secreted NMB was detected in medium conditioned by a SCLC and a NSCLC cell line. The present study also demonstrated the presence of lmmunoreactive GRP in the absence of detectable GRP gene expression. The antiserum used in the GRP radioimmunoassay failed to crossreact with NMB but showed some cross-reactivity with amphibian phyllolitorin raising the possibility that certain SCLC cell lines may produce a phyllolitorin-like peptide. Different energy metabolism in two human small cell lung cancer subpopulations examined by “P magnetic resonance spectroscopy and biochemical analysis in viva and in vitro Kristjansen PEG, Spang-Thomsen M, Quistorff B. Deparmenf of Oncology, Finsen Insrime-Rigshospirler. Blegdamsvej 9, DK-2100 Copenhagen. Cancer Res 1991;51:5160-4.
Two human small cell lung cancer tumor lines, maintained as solid tumorxenograftsonnude miceandas in vitrocell cultures, were studied by in vivo ,‘P magnetic resonance spectroscopy and by biochemical analysis of extracts of solid tumors and cell cultures. Thd tumor lines CPH SCCL 54A and CPH SCCL 548 are subpopulations from the same tumor. In solid tumors (n = 125). the ATP/P(i) ratio was greater in 54A than in 548. This was due to a higher ATP level in 54A, whereas there was no difference in P(i), ADP, and AMP. A decrease in ATPiP during growth was caused by a decline in ATP, whereas P(i) remained unchanged. Small amounts of phosphocreatine were found in the xenografts and in tumor extracts, but not in the cell extracts; correspondingly, there was a low creatine kinase activity in solid tumors and no activity in the cell cultures. Thus, the phosphocreatine content of the solid tumors originated from the stroma. A difference in ATP content between 54A and 54B was also found in cell cultures; hence, the metabolic difference is an intrinsic quality of the malignant cells and is not caused by the host system. Allelic loss on the short arm of chromosome lung cancer
11 in non-small-cell
Ludwig CU, Raefle G, Dalquen P, Stulz P. Stahel R, Obrecht J-P. Section for Oncology, Department ofInrernal Medicine, University Hospiml, CH-1032 Bawl. Int J Cancer 1991;49:661-5. Forty-eight samples of primary non-small lung cancer (NSCLC) and normal tissue from the same patientswere analyzed forallelic deletions on chromosome 11~.five polymorphic loci were assessed to determine the incidence of IIp sequence deletions and to define hot-spots of deletions. Information was obtained from all patients in at least one locus. Our data show that the deletions observed were not ramdomly scattered over the short arm of chromosome II. Rather, 2 hot-spots of deletions were observed: one in the area of the genes for catalase and & FSH corresponding to band 11~13, the other close to the IGF-II locus corresponding to band IIplS. A high incidence of loss of hetrozygosity f&OH) was found with the probe for catalase (21/29), a locus flanking the centromeric region of the Wilms’ tumor locus. Most of the samples exhibiting LOH of one or more of the alleles analyzed remained heterozygous for at leastoneotherchromosome IIpallele.Furthermore, duplication of the intensity of th eremaining allele was rarely observed. Our results indicate that LOH on the short arm of chromosome II is a common event in NSCLC and that the chromosomal region containing the Wilms’ tumor locus is most commonly involved.
antigen mono&ma1 antibodies
BiggL A, Buccheri G, Ferrigno D, Viglietti A, Farinelli MC, Comino A et al. Servizio di Medicina Nucleare, Ospedale S. Croce, via Coppino 25.12100 Cuneo. J Nucl Med 1991;32:2064-8. Immunoscintigraphy with “‘In-labeled anti-CEA-Mab (FW23C51) was carried out in 66 patients strongly suspected for a primary lung cancer and in 8 control patients suffering from different chest diseases. A sensitivity of 0.90, a specificity of 0.45 and an accuracy of 0.85 were calculated. False-negative results were mainly obtained in patients in whom the size of the lesion was below 2 cm and the tumor was cenually located. All patients affected by small-cell carcinoma were correctly identified. In 89% of the patients, a positive immunoscintiscan was associated with the presence of the antigen in the tumor. False-positive results were observed in control patients suffering from different chest diseases due to the nonspecific uptake of the tracer. The tumor definition was generally better after 120 hr than at an earlier time after injection due to the reduction of background activity. SPECT imaging defined the tumor better in each patient but did not reveal any tumor not seen on planar studies. Genetic susceptibility to squamous relation to cigarette smoking dose
cell carcinoma of the lung in
Nakachi K, Imai K, Hayashi S-I, Watanabe J, Kawajiri K. Deparfment
ofEpidemiology, Sailam0 Cancer Center Research Ins&u@,818 &mum, Inn-machi, Saimmo 362. Cancer Res 1991;Sl:S177-80.
Cytochrome P4SOIAl is responsible for the metabolic activation of benzo(a)pyrene in cigarette smoke; an association of lung cancer with DNA polymorphisms of P450IAl gene was shown in our previous study. In this paper, we investigated the interindividual difference of genetically determined susceptibility to squamouscellcarcinomaofthe lung in relation to cigarette smoking dose. We first compared the total amounts of cigarettes consumed over dte lifetime of patients and showed that the patients with a “susceptible” P4501Al gene genotype contracted carcinoma after fewer cigarettes [mean f SD, 31.3 f 12.8 x l(r cigarettes (n = 12)] than those with other genotypes I42.5 i 18.2 x lO’(n = 33)], with a statistical significanceof P-z 0.05. Next, we carried out a case-control study to estimate tie odds ratios of susceptible to nonsusceptible individuals in relation to the cumulated cigarette dose. We thus showed that the individuals with the susceptible genotype were at remarkably high risk with an odds ratio of 7.31 (95% confidence interval, 2.13 1025.12) at a low dose level ofcigarette smoking and that the difference in susceptibility between genotypes was reduced at high dose levels. Production of neuromedin Band neuromedin B gene expression in human lung tumor cell lines
Cardona C. Rabbitts PH. Spindel ER, Ghatei MA, Bleehen NM et al. Medical Research Council, Clinical Oncology and Radiotherapeulics Unir, MRC Cenrre, Hills Road, Cambridge CB2 2QH. Cancer Res 1991:51:5205-11. Gastrin-releasing peptide (GRP), a mammalian bombesin-like pep tide, has been shown to be an important autocrine growth factor for small cell lung cancer (SCLC). However, not all SCLC cell lines express the GRP gene or respond mitogenically to GRP stimulation,
suggesting the existence of other autocrine pathways in this tumor. Neuromedin B (NMB), the mammalian counterpart of amphibian mnatensin, has been shown to be a mitogen for SCLC cell lines in vitro. TO determine whether NMB is a potential autcxrine growth factor for lung tumors, NMB gene expression, peptide synthesis, and secretion have been investigated in a panel of SCLC and non-SCLC (NSCLC) cell lines. Northern blot analysis and enzymatic amplification from mRNA by polymerase chain reaction showed that the NMB gene was expressed in all SCLC and NSCLC cell lines examined. In contrast, the GRP gene was expressed in four of six classic SCLC cell lines but not in variant SCLC or NSCLC cell lines. lmmunoreactive NMB was detected by radioimmunoassay in the majority of classic SCLC, in one of three variant SCLC and in one of three NSCLC cell lines, and secreted NMB was detected in medium conditioned by a SCLC and a NSCLC cell line. The present study also demonstrated the presence of lmmunoreactive GRP in the absence of detectable GRP gene expression. The antiserum used in the GRP radioimmunoassay failed to crossreact with NMB but showed some cross-reactivity with amphibian phyllolitorin raising the possibility that certain SCLC cell lines may produce a phyllolitorin-like peptide. Different energy metabolism in two human small cell lung cancer subpopulations examined by “P magnetic resonance spectroscopy and biochemical analysis in viva and in vitro Kristjansen PEG, Spang-Thomsen M, Quistorff B. Deparmenf of Oncology, Finsen Insrime-Rigshospirler. Blegdamsvej 9, DK-2100 Copenhagen. Cancer Res 1991;51:5160-4.
Two human small cell lung cancer tumor lines, maintained as solid tumorxenograftsonnude miceandas in vitrocell cultures, were studied by in vivo ,‘P magnetic resonance spectroscopy and by biochemical analysis of extracts of solid tumors and cell cultures. Thd tumor lines CPH SCCL 54A and CPH SCCL 548 are subpopulations from the same tumor. In solid tumors (n = 125). the ATP/P(i) ratio was greater in 54A than in 548. This was due to a higher ATP level in 54A, whereas there was no difference in P(i), ADP, and AMP. A decrease in ATPiP during growth was caused by a decline in ATP, whereas P(i) remained unchanged. Small amounts of phosphocreatine were found in the xenografts and in tumor extracts, but not in the cell extracts; correspondingly, there was a low creatine kinase activity in solid tumors and no activity in the cell cultures. Thus, the phosphocreatine content of the solid tumors originated from the stroma. A difference in ATP content between 54A and 54B was also found in cell cultures; hence, the metabolic difference is an intrinsic quality of the malignant cells and is not caused by the host system. Allelic loss on the short arm of chromosome lung cancer
11 in non-small-cell
Ludwig CU, Raefle G, Dalquen P, Stulz P. Stahel R, Obrecht J-P. Section for Oncology, Department ofInrernal Medicine, University Hospiml, CH-1032 Bawl. Int J Cancer 1991;49:661-5. Forty-eight samples of primary non-small lung cancer (NSCLC) and normal tissue from the same patientswere analyzed forallelic deletions on chromosome 11~.five polymorphic loci were assessed to determine the incidence of IIp sequence deletions and to define hot-spots of deletions. Information was obtained from all patients in at least one locus. Our data show that the deletions observed were not ramdomly scattered over the short arm of chromosome II. Rather, 2 hot-spots of deletions were observed: one in the area of the genes for catalase and & FSH corresponding to band 11~13, the other close to the IGF-II locus corresponding to band IIplS. A high incidence of loss of hetrozygosity f&OH) was found with the probe for catalase (21/29), a locus flanking the centromeric region of the Wilms’ tumor locus. Most of the samples exhibiting LOH of one or more of the alleles analyzed remained heterozygous for at leastoneotherchromosome IIpallele.Furthermore, duplication of the intensity of th eremaining allele was rarely observed. Our results indicate that LOH on the short arm of chromosome II is a common event in NSCLC and that the chromosomal region containing the Wilms’ tumor locus is most commonly involved.