National Cancer Institute®
Last Modified: October 1, 2002
UI - 12234991
AU - Janne PA; Taffaro ML; Salgia R; Johnson BE
TI - Inhibition of epidermal growth factor receptor signaling in malignant pleural mesothelioma.
SO - Cancer Res 2002 Sep 15;62(18):5242-7
AD - Lowe Center for Thoracic Oncology, Dana Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA. firstname.lastname@example.org
Malignant pleural mesothelioma (MPM) is a rare malignancy with no known curative modality. Approximately 70% of MPMs have high levels of expression of the epidermal growth factor receptor (EGFR), and a subset of cell lines derived from MPM patients express both EGFR and transforming growth factor alpha, suggesting an autocrine role for EGFR in MPM. We have determined the effects of EGFR inhibition in MPM cell lines in vitro, using four MPM cell lines derived from previously untreated patients with epithelial (H2461 and H2591), sarcomatoid (H2373), and biphasic (MSTO-211H) MPM. All four cell lines expressed EGFR at levels comparable with the non-small cell lung carcinoma (NSCLC) cell line A549, as shown by Western blot analysis. ZD1839 significantly inhibited epidermal growth factor-dependent cell signaling including phosphorylation of AKT and extracellular signal-regulated kinases 1 and 2 in all MPM cell lines. Furthermore, treatment with ZD1839 led to a significant dose-dependent reduction of colony formation (41-89% at 10 microM) when MPM cells were grown in soft agarose. MSTO-211H, H2461, and H2373 were more sensitive to the growth-inhibitory effects of ZD1839 than was the NSCLC cell line A549, whereas H2591 had similar sensitivity to A549. This variability in growth-inhibitory effects is not related to the amount of EGFR present on MPM cells or to the degree of inhibition of EGFR phosphorylation by ZD1839. We show that H2373 MPM cells, which show 89% growth inhibition at 10 microM ZD1839, undergo a dose-dependent arrest at the G(1)-S phase of the cell cycle and a corresponding increase in p27 levels. However, H2591 cell lines, which show 41% growth inhibition at 10 microM ZD1839, undergo no significant cell cycle changes or changes in p27 levels. Our findings demonstrate that in vitro, ZD1839 is as effective or more effective against MPM cell lines as it is against the NSCLC cell line A549 and suggest that ZD1839 may be an effective therapeutic option for patients with MPM.
UI - 12082370
AU - Gottschall EB
TI - Occupational and environmental thoracic malignancies.
SO - J Thorac Imaging 2002 Jul;17(3):189-97
AD - Division of Environmental and Occupational Health Sciences, Department of Medicine, National Jewish Medical and Research Center, Denver, CO 80206, USA. email@example.com
Lung cancer is the most common thoracic malignancy caused by exposures at work and in the environment. The most unique thoracic malignancy is mesothelioma, because it is relatively rare and one of only a few neoplasms for which one specific inciting agent-asbestos-has been identified. Based on epidemiologic studies, approximately 15% of lung cancers in men and 5% of lung cancers in women are caused by occupational exposures. The International Agency for Research on Cancer has devised a rating system by which, based on animal and human data, they assign an agent, mixture, or exposure circumstance to one of five categories, ranging from group 1 (agent is carcinogenic to humans) to group 4 (agent is probably not carcinogenic to humans). Group 1 pulmonary carcinogens reviewed in this article include arsenic, asbestos, beryllium, bis (chloromethyl) ether, cadmium, chromium (IV), mustard gas, nickel, radon, and silica. The clinical presentation and pathology of lung cancers and mesothelioma caused by such exposures do not differ from those of cancers caused by other factors. The key to the recognition of a thoracic malignancy caused by workplace or environmental exposures is clinical suspicion and consideration of all causes for the disease present. Recognition of an exposure-related case of lung cancer or mesothelioma can aid in the identification of excess risk for a whole workforce or community and can lead to actions to reduce exposure, thus preventing future cases. In addition, such recognition allows the individuals struck by devastating illness to exercise their legal rights to compensation if so desired.
UI - 12082371
AU - Garg K; Lynch DA
TI - Imaging of thoracic occupational and environmental malignancies.
SO - J Thorac Imaging 2002 Jul;17(3):198-210
AD - Department of Radiology, Veterans Administration Medical Center, Denver, CO 80262, USA.
The imaging features of occupational lung cancer are similar to those of nonoccupational cancer. Occupational lung cancer in patients with asbestos exposure must be differentiated from mimics such as round atelectasis and fissural pleural plaques. Mesothelioma remains a largely incurable tumor, though treatment options are expanding. CT, MRI, and PET scanning may all have complementary roles in staging mesothelioma.
UI - 12187531
AU - Curin K; Saric M; Strnad M
TI - Incidence of malignant pleural mesothelioma in coastal and continental Croatia: epidemiological study.
SO - Croat Med J 2002 Aug;43(4):498-502
AD - Regional Institute of Public Health, Split, Croatia.
AIM: To evaluate the actual incidence of malignant pleural mesothelioma in Croatia, geographical distribution of the disease, and relevance of occupation and some other characteristics of diseased subjects. METHOD: Data on the incidence of pleural mesothelioma over a seven-year period (1991-1997) were collected from the Croatian Cancer Registry. In each case, the tumor diagnosis was histologically verified. Registration of the patients was based on their place of residence. Also, in 2001, a short questionnaire was sent to patients' families to gather additional information on patients' occupation (exposure to asbestos), smoking habits, and length of residence in the registered place. In many cases some of the answers had to be clarified by telephone or through a personal contact. Data obtained from 20 counties (administrative units) of Croatia were grouped into two larger areas: coastal and continental. The data for the city of Zagreb were presented separately. RESULTS: During the 1991-1997 period, the Registry recorded a total of 248 malignant pleural mesotheliomas (197 in men and 51 in women). The poll gathered additional data for 194 patients (78.2%): 153 (77.7%) men and 41 (80.4%) women. Eight in a million people on average were diagnosed with malignant pleural mesothelioma per year. Age standardized incidence rates (per 100,000) by residence showed an uneven geographical distribution for men: 2.66 in coastal area, 0.69 in continental area, and 0.75 in the city of Zagreb. Goodness-of-fit test for observed rates vs expected for Croatia were chi-square=145, df=2, p<0.001; post-hoc tests: coastal vs continental area chi-square=12.3, df=1, p=0.001; and coastal area vs city of Zagreb chi-square=4.4, df=1, p=0.035. In women with mesothelioma, these rates were 0.38, 0.24, and 0.18, respectively, and the differences were not statistically significant. CONCLUSION: Assuming that the information obtained by the poll on the occupation of diseased subjects was a true characterization of all recorded cases of pleural mesothelioma, more than two-thirds of subjects with the studied tumor had an occupational exposure to asbestos. Uneven distribution of the tumor, with higher rate in men in the coastal area, may be related to shipbuilding and other industrial sources of asbestos exposure in that part of the country.
UI - 12210688
AU - Iwatsubo Y; Matrat M; Michel E; Boutin C; Galateau-Salle F; Jougla E;
TI - Bignon J; Pairon JC; Brochard P Estimation of the incidence of pleural mesothelioma according to death certificates in France.
SO - Am J Ind Med 2002 Sep;42(3):188-99
AD - INSERM E99-09, Creteil, France. firstname.lastname@example.org
BACKGROUND: The number of cases of pleural mesothelioma in France has varied substantially according to methods of assessment. MATERIALS AND METHODS: We collected information from certifying physicians about 316 of France with a cause of death coded as ICD-9 category 163. The ICD codes selected as the cause of death for 178 deaths between 1 January pleural mesothelioma by an expert committee were examined. Finally, we used this information to estimate the number of deaths from pleural mesothelioma in France in 1992. RESULTS: In Part I, 45% (men: 54%; women: 28%) of the cases coded as ICD-9 section 163 were definitely or probably mesothelioma; 18% (men: 16%; women: 21%) possibly mesothelioma; and 37% (men: 30%; women: 51%) other tumors, primarily adenocarcinoma metastases. In Part II, 74% of the confirmed pleural mesotheliomas were coded in category 163 (men: 75%; women: 70%). Extrapolation nationwide indicated that 902 deaths were coded as ICD-9 163 in 1992: 521 cases involved definite or probable mesothelioma and 724 definite, probable, and possible cases. CONCLUSIONS: The analysis of this sample suggests that estimating the number of mesothelioma cases from the cause-of-death statistics may overestimate their incidence, but that death certificates appeared to report the diagnosis of histologically confirmed mesothelioma accurately. Copyright 2002 Wiley-Liss, Inc.
UI - 11924177
AU - Bard M; Debrosse D; Caliandro R; Girard P; Grunenwald D; Ruffie P
TI - [A plea for standardized thoracoscopy in malignant pleural mesothelioma]
SO - Rev Mal Respir 2001 Dec;18(6 Pt 1):585-9
UI - 11358011
AU - Leonardo E; Zanconati F; Bonifacio D; Bonito LD
TI - Immunohistochemical MIB-1 and p27kip1 as prognostic factors in pleural mesothelioma.
SO - Pathol Res Pract 2001;197(4):253-6
AD - Department of Pathology, S. Luigi Gonzaga Hospital, Orbassano, Torino, Italy.
Malignant pleural mesothelioma (MPM) is a tumour that usually presents a short survival time from diagnosis, but in a small number of patients a longer survival time has been observed. We have studied a series of ten long-term and ten short-term survivors with MPM to assess whether the MIB-1 proliferation index and the p27kip1 expression correlated with survival. Our results show significant difference in MIB-1 and in p27kip1 expression between the group of short and longer survival patients. It suggests that the difference in tumour growth fractions may express different biological behaviour and therefore indicate important factors in MPM prognosis.
UI - 11108782
AU - Hodgson JT; Darnton A
TI - The quantitative risks of mesothelioma and lung cancer in relation to asbestos exposure.
SO - Ann Occup Hyg 2000 Dec;44(8):565-601
AD - Epidemiology and Medical Statistics Unit, Health and Safety Executive, Magdalen House, Stanley Precinct, L20 3QZ, Bootle, UK. email@example.com
Mortality reports on asbestos exposed cohorts which gave information on exposure levels from which (as a minimum) a cohort average cumulative exposure could be estimated were reviewed. At exposure levels seen in occupational cohorts it is concluded that the exposure specific risk of mesothelioma from the three principal commercial asbestos types is broadly in the ratio 1:100:500 for chrysotile, amosite and crocidolite respectively. For lung cancer the conclusions are less clear cut. Cohorts exposed only to crocidolite or amosite record similar exposure specific risk levels (around 5% excess lung cancer per f/ml.yr); but chrysotile exposed cohorts show a less consistent picture, with a clear discrepancy between the mortality experience of a cohort of xhrysotile textile workers in Carolina and the Quebec miners cohort. Taking account of the excess risk recorded by cohorts with mixed fibre exposures (generally<1%), the Carolina experience looks uptypically high. It is suggested that a best estimate lung cancer risk for chrysotile alone would be 0.1%, with a highest reasonable estimate of 0.5%. The risk differential between chrysotile and the two amphibole fibres for lunc cancer is thus between 1:10 and 1:50.Examination of the inter-study dose response relationship for the amphibole fibres suggests a non-linear relationship for all three cancer endpoints (pleural and peritoneal mesotheliomas, and lung cancer). The peritoneal mesothelioma risk is proportional to the square of cumulative exposure, lung cancer risk lies between a linear and square relationship and pleural mesothelioma seems to rise less than linearly with cumulative dose. Although these non-linear relationships provide a best fit ot the data, statistical and other uncertainties mean that a linear relationship remains arguable for pleural and lung tumours (but not or peritoneal tumours).Based on these considerations, and a discussion fo the associated uncertainties, a series of quantified risk summary statements for different elvels of cumulative exposure are presented.
UI - 12005126
AU - Rogers A; Major G
TI - The quantitative risks of mesothelioma and lung cancer in relation to asbestos exposure: the Wittenoom data.
SO - Ann Occup Hyg 2002 Jan;46(1):127-8; discussion 128-9
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