A homozygous deletion on chromosome 3 in a small cell lung cancer cell line correlates with a region...

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Abstracts/Lung Cancer 10 (1994) 395-430 401 A survey of the Czechoslov~k follow-up of hmg cancer mortality in uranium miners Sevc J. Tomasek L. Kunz E. Placek V. Chmelevsky D, Barclay D et al. III.U of Hygiene and Epidemiology, 100 42 Praha 10. Health Phys 1993;64:355-69. The major Czechoslovak cohort of uranium miners (S-cohort) is surveyed in terms of diagrams illustrating dependences on calendar year, age, and exposure to radon and radon progeny. An analysis of the dosedependenceoflungcancarmortalityisperformed bynonparametric and. subsequently, by parametric methods. In the first step, hvo- dimensional isotonic regression is employed to derive the lung cancer mortality rateand the relativeexcessrisk as functionsofageattainedand of lagged cumulated exposure. In a second step, analytical fits in terms of relative risk models are derived. The treatment is largely analogous to the methods applied by the BEIR IV Committee to other major cohorts of uranium miners. There is a marked dependence of the excess risk on age attainul and on time since axposure. A specific characteristic of the Czechoslovak data is the nonlinearity of the dependence of the lung cancer excess risk on the cumulated exposure: exposurea on the order of 100 working level months or less appear to be more effective per working level month than larger exposures but, in the absence of an internal control group, this cannot be excluded to be due to confounders such as smoking or environmental exposures. A further notable observationistheassociationoflargercxcess riskswitblongarprotraction of the exposures. Lung cancer ntnong textile workers in the Rata area of ItGly Zappa M. Paci E, Costa&d AS, Kriebel D. UnirofEpidemiology, Cnrr Srudy and Prevenrion of Cancer, USL IO/E. Florence. Stand 3 Work Environ Health 1993: 19: 16-20. The association between lung cancer and occupational exposure in the textile industry was investigated in a population-based case-referent study conducted in the Prato area of the province of Florence (Italy) where there is a concentration of textile factories. A complete response to a postal questionnaire was obtained for 207 cases (85.1%) and 440 referents (76.1%). Those who had ever worked in the textile industry had an odds ratio (OR) of 1:45 [95% confidence interval (95% CI) l.O- 2.11, whenninedifferent textilejobtitleswereconsidered. anincreased OR was observed only for rag sorters (OR 2.2. 95% CI 1.3-3.8) and weavers (OR 1.7, 95% CI 1.1-2.7). Analysis by different ‘time windows’showedan ORof3.0 (95% CI 1.6-5,8) for rag sortersat work in the 1950s and an OR of 2.8 (95 46CI 1.5-5.0) for weavers at work in the 1970s. Thisnsultsupportsthesuggestionoftwodiffetentcarcinogenic exposures in the Prato textile industry (asbestos and mineral oils). Lung cttucer in the S&m&erg mines: A refppraisa of the data reported by Hurting and HEW? in 1879 Greenberg M, SelikoffU. 74 Nonh EndRoad,London NW11 7% ANI Gccup Hyg 1993;37:5-14. The. first description of occupational lung cancer, by Harting and Hesse in 1879, unfortunately is not readily accessible. Its account of the vicissitudes of the S&e&erg miners merits study and is therefore presented in summary and set in a historical and geological context. The authors attempted to discover the cause of the disease and made recommendations for improving the health of miners. In the course of their programme ofinvestigations, theydevebpedmethodsformeasuring airborne dust and inhaled dust by personal monitoring. It was left to subsequent discovery for radon and its daughterproducts to be identified as the causal agents. Later generations were to discover the impact of radioactive spoils from mines situated in the mountain mnge in which Scbnmberg was located. Basic biology Detection of a novel lung adenocarcinoma - Associated serum antigen deiined by two monoclonal ant&o&s, KM 432 and KU 227 Shitara K. Hanai N, Yoshida H. Division of Immunology, Tokyo Research Laboratories. Kyowa Hakko Kogyo Co Ltd. Tobo 194. Anticancer Res 1993;13:579-86. Two monoclonal antibodies, KM227 (IgM) and Kii432 (IgGl), were established by immunizing mice with thecrude membrane fraction of lung squamous cell caminoma and the high-molecular-weight antigen in pleural perfusion from patients with lung adanocarcinoma, respectively. They were found to recognize the carbohydrate epitope and the peptide epitope on the antigens. respectively. Both KM227 and KM432bo1mdtotheseu1mantigensass~ciatedwithlungadenocarcinoma and lung benign diseases. A double determinant assay in which KM432 was used as 1st antibody and biotinylated KM227 was used as 2nd antibody selectively detected the antigen, designated KA4321227, elevated in sera from patients with lung adenocarcinoma. The molecular weight of KA432/227 in pleural Perfusion from patients with lung adenocarcinoma was estimated to be more than 900 kD by the gel filtration chromatography. Serum with a high KA432/227 level was mostfrequently foundin lungadenccarcinoma(47.8%), andoccasionally found in lung squamous cell carcinoma (23.1%), lung large cell carcmoma (22.2%), pancreatic carcinoma (20.0%) and carcinoma of the bile-duct and the gall bladder (25.0%). In contrast, positive percentages in benign diseases and healthy adults were very low (0 to 7.7 %). No significant correlation was found between the serum level of KA432/227 and other lung adenocarcinoma associated antigens, such as sialyl b(x). Combineddetection of KA4321227 and sialyl Le(x) antigen elevated the positive percentages in lung adenocarcinoma (67.2%). A homozygom deletion on chromosome 3 in a small cell lung cancer cell line correlntes with a region of tumor suppressor activity Daly MC. Xiang R-H. Buchhagen D, Hensel CH, Garcia DK. Killary AM et al. Depr Cellular and Srrucrural Biology. Univof Texas Healrh Science Cenrer. 7703 Floyd Curl Drive, San Aruonio i’X 78284-7762. Oncogene 1993;8: 1721-9. Small cell lung cancer (SCLC) tumors frequently display deletions on the short arm of chromosome 3 suggesting the existence of a ‘tumor suppressor’ gene within that region whose functional inactivation may be involved in tumorigen&s. Recently, a hybrid, HA(3)BB9F. was identitied that contains a small fngment of human chromosome 3 of approximately 2 Mb on a mouse (A9) background . This hybrid was utilized to define a functional tumor suppressor gene within 3p22-~21 which could supprws the tumorigenic properties of the mouse tibrosarcoma cell line. The existence of a tumor suppressor gene in the region 3p22-p21 is supported by the prez.ent report which describes the assessment of 89 SCLC and 32 non-SCLC lung cancer tumors and cell lines for the existence of a homozygous deletion(s) at 43 loci on the short arm of chromosome 3. One of the SCLC cell lines was found to harbor a homozygous deletion involving the loss offivemarkers on chromosome 3p. AJI live of the markers map to the region 3p21.3-~21.2 and four of the five markers are located within the chromosome 3 fragment exhibiting propert& of tumor suppression in the HA(3)BB9F hybrid. The other tumors analysed all retained at least one copy of each of the markers as+zss&. Intnperitonealeultivationofsnall~l~earcinomnindwesarpression of the retinal cancer-associated retinopathy antigen Thirkill CE. Tait RC. Tyler NK. Roth AM, Keltner IL. Eye Research.

Transcript of A homozygous deletion on chromosome 3 in a small cell lung cancer cell line correlates with a region...

Page 1: A homozygous deletion on chromosome 3 in a small cell lung cancer cell line correlates with a region of tumor suppressor activity

Abstracts/Lung Cancer 10 (1994) 395-430 401

A survey of the Czechoslov~k follow-up of hmg cancer mortality in uranium miners Sevc J. Tomasek L. Kunz E. Placek V. Chmelevsky D, Barclay D et al. III.U of Hygiene and Epidemiology, 100 42 Praha 10. Health Phys 1993;64:355-69.

The major Czechoslovak cohort of uranium miners (S-cohort) is surveyed in terms of diagrams illustrating dependences on calendar year, age, and exposure to radon and radon progeny. An analysis of the dosedependenceoflungcancarmortalityisperformed bynonparametric and. subsequently, by parametric methods. In the first step, hvo- dimensional isotonic regression is employed to derive the lung cancer mortality rateand the relativeexcessrisk as functionsofageattainedand of lagged cumulated exposure. In a second step, analytical fits in terms of relative risk models are derived. The treatment is largely analogous to the methods applied by the BEIR IV Committee to other major cohorts of uranium miners. There is a marked dependence of the excess risk on age attainul and on time since axposure. A specific characteristic of the Czechoslovak data is the nonlinearity of the dependence of the lung cancer excess risk on the cumulated exposure: exposurea on the order of 100 working level months or less appear to be more effective per working level month than larger exposures but, in the absence of an internal control group, this cannot be excluded to be due to confounders such as smoking or environmental exposures. A further notable observationistheassociationoflargercxcess riskswitblongarprotraction of the exposures.

Lung cancer ntnong textile workers in the Rata area of ItGly Zappa M. Paci E, Costa&d AS, Kriebel D. UnirofEpidemiology, Cnrr Srudy and Prevenrion of Cancer, USL IO/E. Florence. Stand 3 Work Environ Health 1993: 19: 16-20.

The association between lung cancer and occupational exposure in the textile industry was investigated in a population-based case-referent study conducted in the Prato area of the province of Florence (Italy) where there is a concentration of textile factories. A complete response to a postal questionnaire was obtained for 207 cases (85.1%) and 440 referents (76.1%). Those who had ever worked in the textile industry had an odds ratio (OR) of 1:45 [95% confidence interval (95% CI) l.O- 2.11, whenninedifferent textilejobtitleswereconsidered. anincreased OR was observed only for rag sorters (OR 2.2. 95% CI 1.3-3.8) and weavers (OR 1.7, 95% CI 1.1-2.7). Analysis by different ‘time windows’showedan ORof3.0 (95% CI 1.6-5,8) for rag sortersat work in the 1950s and an OR of 2.8 (95 46 CI 1.5-5.0) for weavers at work in the 1970s. Thisnsultsupportsthesuggestionoftwodiffetentcarcinogenic exposures in the Prato textile industry (asbestos and mineral oils).

Lung cttucer in the S&m&erg mines: A refppraisa of the data reported by Hurting and HEW? in 1879 Greenberg M, SelikoffU. 74 Nonh EndRoad,London NW11 7% ANI Gccup Hyg 1993;37:5-14.

The. first description of occupational lung cancer, by Harting and Hesse in 1879, unfortunately is not readily accessible. Its account of the vicissitudes of the S&e&erg miners merits study and is therefore presented in summary and set in a historical and geological context. The authors attempted to discover the cause of the disease and made recommendations for improving the health of miners. In the course of their programme ofinvestigations, theydevebpedmethodsformeasuring airborne dust and inhaled dust by personal monitoring. It was left to subsequent discovery for radon and its daughterproducts to be identified as the causal agents. Later generations were to discover the impact of radioactive spoils from mines situated in the mountain mnge in which Scbnmberg was located.

Basic biology

Detection of a novel lung adenocarcinoma - Associated serum antigen deiined by two monoclonal ant&o&s, KM 432 and KU 227 Shitara K. Hanai N, Yoshida H. Division of Immunology, Tokyo Research Laboratories. Kyowa Hakko Kogyo Co Ltd. Tobo 194. Anticancer Res 1993;13:579-86.

Two monoclonal antibodies, KM227 (IgM) and Kii432 (IgGl), were established by immunizing mice with thecrude membrane fraction of lung squamous cell caminoma and the high-molecular-weight antigen in pleural perfusion from patients with lung adanocarcinoma, respectively. They were found to recognize the carbohydrate epitope and the peptide epitope on the antigens. respectively. Both KM227 and KM432bo1mdtotheseu1mantigensass~ciatedwithlungadenocarcinoma and lung benign diseases. A double determinant assay in which KM432 was used as 1st antibody and biotinylated KM227 was used as 2nd antibody selectively detected the antigen, designated KA4321227, elevated in sera from patients with lung adenocarcinoma. The molecular weight of KA432/227 in pleural Perfusion from patients with lung adenocarcinoma was estimated to be more than 900 kD by the gel filtration chromatography. Serum with a high KA432/227 level was mostfrequently foundin lungadenccarcinoma(47.8%), andoccasionally found in lung squamous cell carcinoma (23.1%), lung large cell carcmoma (22.2%), pancreatic carcinoma (20.0%) and carcinoma of the bile-duct and the gall bladder (25.0%). In contrast, positive percentages in benign diseases and healthy adults were very low (0 to 7.7 %). No significant correlation was found between the serum level of KA432/227 and other lung adenocarcinoma associated antigens, such as sialyl b(x). Combineddetection of KA4321227 and sialyl Le(x) antigen elevated the positive percentages in lung adenocarcinoma (67.2%).

A homozygom deletion on chromosome 3 in a small cell lung cancer cell line correlntes with a region of tumor suppressor activity Daly MC. Xiang R-H. Buchhagen D, Hensel CH, Garcia DK. Killary AM et al. Depr Cellular and Srrucrural Biology. Univ of Texas Healrh Science Cenrer. 7703 Floyd Curl Drive, San Aruonio i’X 78284-7762. Oncogene 1993;8: 1721-9.

Small cell lung cancer (SCLC) tumors frequently display deletions on the short arm of chromosome 3 suggesting the existence of a ‘tumor suppressor’ gene within that region whose functional inactivation may be involved in tumorigen&s. Recently, a hybrid, HA(3)BB9F. was identitied that contains a small fngment of human chromosome 3 of approximately 2 Mb on a mouse (A9) background . This hybrid was utilized to define a functional tumor suppressor gene within 3p22-~21 which could supprws the tumorigenic properties of the mouse tibrosarcoma cell line. The existence of a tumor suppressor gene in the region 3p22-p21 is supported by the prez.ent report which describes the assessment of 89 SCLC and 32 non-SCLC lung cancer tumors and cell lines for the existence of a homozygous deletion(s) at 43 loci on the short arm of chromosome 3. One of the SCLC cell lines was found to harbor a homozygous deletion involving the loss offivemarkers on chromosome 3p. AJI live of the markers map to the region 3p21.3-~21.2 and four of the five markers are located within the chromosome 3 fragment exhibiting propert& of tumor suppression in the HA(3)BB9F hybrid. The other tumors analysed all retained at least one copy of each of the markers as+zss&.

Intnperitonealeultivationofsnall~l~earcinomnindwesarpression of the retinal cancer-associated retinopathy antigen Thirkill CE. Tait RC. Tyler NK. Roth AM, Keltner IL. Eye Research.