National Cancer Institute®
Last Modified: June 1, 2002
UI - 12001992
AU - Tweedale G
TI - Asbestos and its lethal legacy.
SO - Nature Rev Cancer 2002 Apr;2(4):311-5
AD - Centre for Business History, Business School, Manchester Metropolitan University, UK. G.Tweedale@mmu.ac.uk
Asbestos has become the leading cause of occupationally related cancer death, and the second most fatal manufactured carcinogen (after tobacco). In the public's mind, asbestos has been a hazard since the 1960s and 1970s. However, the knowledge that the material was a mortal health hazard dates back at least a century, and its carcinogenic properties have been appreciated for more than 50 years.
UI - 11923140
AU - Mohiuddin I; Cao X; Ozvaran MK; Zumstein L; Chada S; Smythe WR
TI - Phosphatase and tensin analog gene overexpression engenders cellular death in human malignant mesothelioma cells via inhibition of AKT phosphorylation.
SO - Ann Surg Oncol 2002 Apr;9(3):310-6
AD - Section of Thoracic Molecular Oncology, Department of Thoracic and Cardiovascular Surgery, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
BACKGROUND: Abnormal phosphatase and tensin analog (PTEN) gene expression has been noted in neoplasms. The PTEN protein cleaves phosphate groups from cellular growth kinases, inhibiting tumor propagation. A downstream target of PTEN is AKT, a serine-threonine kinase that when activated inhibits apoptosis. We sought to determine whether PTEN overexpression in mesothelioma cells would engender hypophosphorylation of AKT and apoptosis. METHODS: Human malignant mesothelioma cell lines REN and I-45 were transfected with adenoviral vectors AdPTEN and AdBgal (marker gene) at various multiplicities of infection (MOI). Cell viability was measured using a colorimetric assay, and apoptosis was assessed by morphology and subG1 fluorescence-activated cell sorter (FACS) analysis. PTEN protein and AKT phophorylation were evaluated by Western blot, and AKT kinase activity was evaluated by functional assay. RESULTS: Increased cellular killing was noted with AdPTEN gene transfer. The ratio of cell killing with AdPTEN to AdBgal widened with increasing MOI and was statistically significant at all MOI. Cells demonstrated apoptosis by morphologic and subG1 FACS analyses. Cells overexpressing PTEN demonstrated decreased phosphorylated (active) AKT and AKT kinase activity compared with controls. CONCLUSIONS: Overexpression of PTEN engenders apoptosis in mesothelioma by AKT hypophosphorylation. The forced overexpression of PTEN may prove useful clinically in this treatment-resistant neoplasm.
UI - 11857495
AU - Kinnula VL; Lehtonen S; Sormunen R; Kaarteenaho-Wiik R; Kang SW; Rhee
TI - SG; Soini Y Overexpression of peroxiredoxins I, II, III, V, and VI in malignant mesothelioma.
SO - J Pathol 2002 Mar;196(3):316-23
AD - Department of Internal Medicine, Pulmonary Division, University of Oulu and Oulu University Hospital, Kajaanintie 50A, 90220 Oulu, Finland. firstname.lastname@example.org
Peroxiredoxins (Prxs) are a recently characterized group of thiol-containing proteins with efficient antioxidant capacity, capable of consuming hydrogen peroxide in living cells. Altogether six distinct Prxs have been characterized in mammalian tissues. Their expression was investigated in histological samples of mesothelioma and in cell lines established from the tumours of mesothelioma patients. Four cases with histopathologically healthy pleura from non-smokers were used as controls. Healthy pleural mesothelium was negative or very weakly positive for all Prxs. In mesothelioma, the most prominent reactivity was observed with Prxs I, II, V, and VI. Prx I was highly or moderately expressed in 25/36 cases, the corresponding figures for Prxs II-VI being 27/36 (Prx II), 13/36 (Prx III), 2/36 (Prx IV), 24/36 (Prx V), and 30/36 (Prx VI). Positive staining was observed both in the cytosolic and the nuclear compartment, with the exception of Prx III, which showed no nuclear reactivity. The staining pattern of Prxs III and V was granular. Immunoelectron microscopic localization of Prxs was in accordance with the immunohistochemical findings, showing diffuse cytoplasmic localization for Prxs I, II, IV, and VI and distinct mitochondrial labelling for Prxs III and V. There was no significant association between the extent of staining and different Prxs. It appeared that Prxs may not have prognostic significance, but being prominently expressed in most mesotheliomas these proteins, at least in theory, may play a role in the primary drug resistance of this disease. Copyright 2002 John Wiley & Sons, Ltd.
UI - 12023790
AU - Manegold C; Aisner J
TI - Pemetrexed for diffuse malignant pleural mesothelioma.
SO - Semin Oncol 2002 Apr;29(2 Suppl 5):30-5
AD - Department of Medical Oncology/Internal Medicine, Thoraxklinik Heidelberg, gGmbH, Heidelberg, Germany.
The treatment of diffuse malignant pleural mesothelioma (MPM) is currently less than satisfactory. Survival statistics are best for the epithelial subtype and for tumors that can be completely removed by surgery. Radiotherapy provides no survival benefit and is used only to palliate symptoms or to prevent growth along needle tracks and incisions. The response to chemotherapeutic agents is poor, and to date there is no standard cytotoxic treatment. Antimetabolites may have some activity, and one trial of high-dose methotrexate has suggested a moderate response rate. There is also no evidence that any chemotherapy regimen given as a part of multimodality treatment, including radiotherapy and surgery, can improve survival. Recently, a renewed interest in MPM led to clinical trials with promising preliminary results for several agents alone or in combination, including gemcitabine, raltitrexed, vinorelbine, and pemetrexed. Pemetrexed, a folate-based inhibitor of thymidylate synthase and other enzymes, is currently under investigation in multiple malignancies. A phase I study of pemetrexed in combination with cisplatin showed a remarkable response rate of approximately 50% in patients with the epithelial subtype of MPM. This led to a large international study of the combination of pemetrexed plus cisplatin. Copyright 2002, Elsevier Science (USA). All rights reserved.
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
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 - 11414251
AU - Howie RM
TI - Asbestos and cancer risk.
SO - Ann Occup Hyg 2001 Jun;45(4):335-6; discussion 336-8
UI - 12016043
AU - Clippe C; Freyer G; Bizollon MH; Raudrant D; Gilly F; Vitrey D; Ligneau
TI - B; Trillet-Lenoir V [Primary peritoneal tumors: report on a series of eight cases and review of the literature]
SO - Bull Cancer 2002 Apr;89(4):430-6
AD - Unite fonctionnelle d'oncologie medicale, centre hospitalier Lyon-Sud, 69495 Pierre-Benite Cedex, France.
Primary peritoneal tumors are rare and yet not well-known malignancies. We report here the clinical cases of 8 patients who were referred to our institution with a primary peritoneal tumor, 4 serous carcinomas (PSC) and 4 malignant mesotheliomas (PMM). Diagnosis was available in all cases and reviewed by two pathologists. A battery of various immunomarkers contributed to confirm the morphological diagnosis. All patients underwent initial surgery with or without optimal debulking. All of them received a platinum-based systemic chemotherapy. Intraperitoneal treatment with cisplatin and hyperthermia was performed in two cases. Four patients are dead (3 PSC, 1 PMM), two are alive (one in partial remission (1 PSC) and one is having treatment (1 PMM)), one is in complete remission (1 PMM) and one is lost to follow up (1 MMP). PSC and PMM are difficult to distinguish since they share the embryonic cOElomic epithelium as a common origin. The clinical presentations are similar and usually include the detection of a pelvic mass and/or diffuse peritoneal carcinomatosis with or without malignant ascites. Therefore, the accuracy and reliability of the initial histological examination is of crucial importance. Further attempts will be required to better identify the most active therapeutic post-surgical combinations, especially for PMM.
UI - 11676187
AU - Barbieri PG; Lombardi S; Candela A; Pezzotti C; Binda I
TI - [Incidence of malignant mesothelioma (1980-1999) and asbestos exposure in 190 cases diagnosed among residents of the province of Brescia]
SO - Med Lav 2001 Jul-Aug;92(4):249-62
AD - Servizio Prevenzione e Sicurezza degli Ambienti di Lavoro, Azienda Sanitaria Locale Provincia di Brescia. firstname.lastname@example.org
Several cases of malignant mesothelioma (MM) previously unknown to the Occupational Health and Safety Service were recognised in the Province of Brescia after an active surveillance program carried out during the first nineteen years of operation; a large proportion of the cases involved workers occupationally exposed to asbestos. A local Mesothelioma Register was subsequently set up in 1993 and by the end of 1999, 190 MM cases had been collected. The annual incidence ratio (standardized on the Italian population, census 1981, x100,000 person-years) was calculated in the 1980-1999 period and showed an increasing trend for location in the pleura in both sexes; in the 1996-1999 period the incidence ratio was 2.95 for males and 1.35 for females. In the same period, this trend was not observed for peritoneal location, with an incidence ratio of 0.17 and 0.37 for males and females respectively. 161 pleural MM (84.7%) and 28 peritoneal MM (14.7%) are described; histopathologic diagnosis was performed in 161 cases (84.7%). Anamneses were collected for 88% of the cases but with direct information from patients only in 65% of these in the recent period. Only 7 cases of asbestosis were diagnosed in the MM cases, whereas 31 cases of pleural abnormalities were observed but only 17 of these were observed in workers occupationally exposed to asbestos. Occupational asbestos exposure was evaluated as certain, probable or possible in 45% of total cases and in 54% of recently (1996-1999) observed cases, which were ten times more frequent in males. Exposure occurred in sectors works where asbestos was not used as raw material, such as construction, iron and steel and metal working. MM's from environmental and non-occupational exposure to asbestos were very few, 1.5% and 0.5% respectively. In 65 MM's asbestos exposure was unknown (34.2%); 50% of these concerned females; for whom the industry and jobs are discussed. The distribution of histologic types of MM was similar in asbestos exposed and non exposed cases. No association between peritoneal mesotheliomas and heavy exposure to asbestos was observed. Ten cases of MM were diagnosed in subjects under 45 years old (5.2%) with only one case occupationally exposed. 2 cases were exposed to radiation therapy (1%) and 2 cases to thoracic trauma (1%). Although in Italy MM has been included in the list of compensatable occupational diseases by law since 1994, a large number of cases occupationally exposed to asbestos are still not recognised by the National Insurance Institute (INAIL). A number of problems limiting work of the Mesothelioma Register and its usefulness are discussed. The Lombardy Mesothelioma Register set up in past.
UI - 12064559
AU - Kitamura F; Araki S; Suzuki Y; Yokoyama K; Tanigawa T; Iwasaki R
TI - Assessment of the mutations of p53 suppressor gene and Ha- and Ki-ras oncogenes in malignant mesothelioma in relation to asbestos exposure: a study of 12 American patients.
SO - Ind Health 2002 Apr;40(2):175-81
AD - Department of Public Health and Occupational Medicine, Graduate School of Medicine, The University of Tokyo, Japan.
In our previous study, we found no genetic alteration in exons 1 and 2 of Ha- and Ki-ras oncogenes nor in exons 5 to 9 of the p53 suppressor gene in seven Japanese malignant mesothelioma patients exposed to asbestos. To examine further whether malignant mesothelioma due to asbestos has genetic alterations in the p53 suppressor gene and in Ha- and Ki-ras oncogenes, we analyzed point mutations of these genes in paraffin embedded operative open biopsied samples of the primary tumor of malignant mesothelioma in twelve American patients. The genetic analysis was conducted by the PCR-SSCP (polymerase chain reaction single-strand conformation polymorphism) method in all patients and by sequencing analysis of DNA bases in the two patients with suspected gene mutation. The analysis of the p53 suppressor gene showed an amino acid converting mutation of exon 7 in one patient and a polymorphism of exon 6 in another patient; the former patient was a heavy smoker with a biphasic cell type. No genetic alteration was found in exons 1 and 2 of Ha- and Ki-ras oncogenes in any of the patients. The results suggest that the effects of asbestos on the p53 suppressor gene and Ha- and Ki-ras oncogenes in malignant mesothelioma are negligible. Further studies are needed to examine whether the observed mutation of the p53 suppressor gene is due to the combined effects of asbestos and smoking or to other unknown factors.
UI - 12046609
AU - Friedman MT; Gentile P; Tarectecan A; Fuchs A
TI - Malignant mesothelioma: immunohistochemistry and DNA ploidy analysis as methods to differentiate mesothelioma from benign reactive mesothelial cell proliferation and adenocarcinoma in pleural and peritoneal effusions.
SO - Arch Pathol Lab Med 1996 Oct;120(10):959-66
AD - Long Island Jewish Medical Center, Department of Pathology, Albert Einstein College of Medicine, New Hyde Park, NY 11040, USA.
OBJECTIVE: To determine whether malignant mesotheliomas can be differentiated from adenocarcinomas and benign reactive mesothelial cells in pleural and peritoneal fluids using immunohistochemical analysis in conjunction with DNA ploidy analysis. DESIGN: Sixteen cases of malignant mesothelioma, including epithelial, sarcomatous, and biphasic types, were collected. DNA analysis using flow cytometry and/or image analysis was performed on paraffin-embedded tissue from 15 of the mesothelioma cases, as well as on cytospin cell preparations from samples of pleural and peritoneal fluids from cases with either cytologically proven adenocarcinoma (seven cases) or benign reactive mesothelial cells (seven cases). Immunohistochemical studies were done in 15 mesotheliomas, 5 adenocarcinomas, and 4 benign reactive mesothelial cell effusions. RESULTS: All malignant mesotheliomas tested (100%) stained positively for prekeratin, whereas stains for carcinoembryonic antigen, B72.3, Leu-M1, and Ber-EP4 were negative. Stains vimentin, epithelial membrane antigen, and CA125 were positive in 75%, 75%, and 25% of cases tested, respectively. Benign reactive mesothelial cell cases stained similarly. Adenocarcinomas were more likely to react positively with B72.3, Ber-EP4, and carcinoembryonic antigen, and negatively with vimentin. DNA analysis showed that all benign cases were diploid, while all adenocarcinomas were nondiploid. Fifty-three percent of the malignant mesotheliomas were nondiploid. Sensitivity for detection of nondiploidy was greater for image analysis than for flow cytometry (100% vs 75%). CONCLUSIONS: B72.3, Ber-EP4, carcinoembryonic antigen, and vimentin are useful immunohistochemical markers in differentiating malignant mesotheliomas from adenocarcinomas, whereas immunohistochemistry does not reliably distinguish malignant from benign hyperplastic mesothelial cells. The addition of DNA ploidy studies is useful for differentiating the latter two groups.
UI - 11937311
AU - van Meerbeeck JP; Baas P; Debruyne C; Smit EF; van Klaveren RJ;
TI - Galdermans D; Lentz MA; Manegold C; Giaccone G; EORTC Lung Cancer Group A phase II EORTC study of temozolomide in patients with malignant pleural mesothelioma.
SO - Eur J Cancer 2002 Apr;38(6):779-83
AD - Erasmus MC-Department of Pulmonology, PO Box 5201, NL-3008 AE, Rotterdam, The Netherlands. email@example.com
The aim of this study was to investigate the anti-tumour activity of temozolomide in patients with malignant pleural mesothelioma. 27 chemotherapy-naive patients with histologically-proven malignant mesothelioma were treated with temozolomide 200 mg/m2/day, given orally on days 1-5 of each 28-day cycle. Therapy continued up to 10 cycles unless disease progression or excessive toxicity mandated discontinuation. Toxicity, symptom improvement and pain intensity were regularly assessed. With a median relative dose intensity of 97%, toxicity was moderate with grade 3 or more nausea, vomiting, thrombocytopenia, leucocytopenia, neutropenia, febrile leucocytopenia, arthralgia, infection and fever with infection occurring in 13, 13, 10, 3, 7 and 3% of patients for the remaining events, respectively. Overall, 1 objective response was observed (response rate 4%, 95% Confidence Interval (CI): 0.1-19). Median survival was 8.2 months. Symptom assessment showed no improvement and an increase of pain was observed during the study. Thus, oral temozolomide is an inactive agent in malignant mesothelioma.
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