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Een Schotse gezondheidsdienst heeft verzuimd een mesothelioompatiënt te informeren over de mogelijkheden van schadevergoeding en aan welke voorwaarden daarvoor moet worden voldaan. Het slachtoffer overleed drie maanden na diagnose zonder dat aan de voorwaarde van een biopsie ter herbeoordeling van de diagnose was voldaan. Pas na zijn dood hoorde zijn vrouw over de mogelijkheden om in aanmerking te komen voor een schadevergoeding. De Schotse ombudsman Publieke Diensten oordeelt dat de Gezondheidsdienst excuses moet aanbieden aan de weduwe. Bron: The Herald, 21 juni 2007.

Biomerkers als Soluble mesothelin-related peptide (SMRP), osteopontine en megakaryocyte potentiating factor (MPF) zijn nog niet voldoende accuraat om cytohistologie als gouden standaard voor de diagnose van maligne mesothelioom te vervangen. Aldus een overzichtsartikel en een onderzoeksverslag. Biomerkers zijn eiwitten in het bloed die iets kunnen zeggen over de aanwezigheid of verloop van sommige ziektes. Bron: Scherpereel, A. &amp. Lee, G. (2007). Biomarkers for mesothelioma. Current Opinion in Pulmonary Medicine 2007, 13:339. Grigoriu, B.D. et al., (2007). Utility of Osteopontin and SerumMesothelin in Malignant Pleural Mesothelioma Diagnosis and Prognosis Assessment. Clin Cancer Res 13 (10), may 15, p 2928-35-343.
Scherpereel, A. &amp. Lee, G. (2007). Biomarkers for mesothelioma. Current Opinion in Pulmonary Medicine 2007, 13:339-343.

Purpose of review

Mesothelioma is an incurable cancer and its global incidence continues to increase. There has been strong interest in the search for a biomarker that would be of value for the diagnosis, prognosis and disease monitoring of mesothelioma. Large series evaluating the use of novel candidate markers have recently been published.

Recent findings

To date, global gene profiling studies have failed to find a molecule that reliably captures all subtypes of mesothelioma, and differentiates it from benign pathologies and metastatic carcinomas. Soluble mesothelin-related peptide (SMRP), osteopontin and megakaryocyte potentiating factor have been assessed as markers. SMRP testing is clinically available and provides reasonable diagnostic sensitivity and specificity when applied to serum or pleural fluid. Elevated SMRP levels can occur in metastatic, especially ovarian and pancreatic, adenocarcinomas. False negatives are common with sarcomatoid mesothelioma. SMRP levels may reflect tumor load and disease progression. The role of SMRP in predicting mesothelioma development in subjects exposed to asbestos has raised interest. Osteopontin lacks specificity as a diagnostic marker for mesothelioma but may have value in disease monitoring.

Summary

The proposed markers have insufficient accuracy to replace cytohistology as the gold standard for diagnosis for mesothelioma. Elevated SMRP levels raise suspicion of mesothelioma although negative values do not exclude disease. Its role in disease monitoring in patients and in predicting disease development in at-risk individuals warrant further study.



Grigoriu, B.D. et al., (2007). Utility of Osteopontin and SerumMesothelin in Malignant Pleural Mesothelioma Diagnosis and Prognosis Assessment. Clin Cancer Res 13 (10), may 15, p 2928-35

Abstract

Purpose: Malignant mesothelioma is a highly aggressive tumor and is often diagnosed too late for a curative treatment.We compared diagnostic and prognostic values ofmesothelin and osteopontin in172 patients suspected ofmalignant pleuralmesothelioma (MPM) and in a control group

of 112 asymptomatic asbestos-exposed subjects.

Experimental Design: Osteopontin and mesothelin were assayed with commercial ELISA kits in a series of 43 patients with pleural metastases of various carcinomas, 33 patients with benign pleural lesions associated with asbestos exposure, 96 patients with MPMs, and 112 asbestos-exposed healthy subjects. Results were correlated with patient’s diagnosis and survival.

Results: Serumosteopontin level was higher in MPMpatients compared with healthy asbestos exposed subjects and had a good capability to distinguish between these two populations. However, osteopontin was unable to distinguish between MPM and pleural metastatic carcinoma or benign pleural lesions associated with asbestos exposure. Neither plasma nor pleural fluid osteopontin were more powerful in this respect. Serum mesothelin had a good ability for diagnosing MPM but was unable to identify patients with nonepithelioid mesothelioma subtypes. Survival analysis identified tumor histologic subtype along with serum osteopontin and serum mesothelin as independent prognostic factors in mesothelioma patients.

Conclusions: Osteopontin has a lower diagnostic accuracy than mesothelin in patients suspected of MPM. Insufficient specificity limits osteopontin utility as diagnosticmarker. Bothmolecules have a potential value as prognostic markers.

Deskundigen analyseren in het blad Oncogene de meest interessante presentaties die gegeven werden op de 8ste bijeenkomst van de International Mesothelioma Interest Group (IMIG). een groep medici met bijzondere belangstelling voor de ziekte maligne mesothelioom. Zij concluderen dat op dit moment operatieve verwijdering van de tumor in combinatie met andere behandelvormen (multimodale therapie) de beste kansen op lange termijn overleving geven. Bron: Carbone, M. et al. (2007). Eighth International Mesothelioma Interest Group. Oncogene advance online publication, 14 may 2007. doi:10.1038/sj.onc.1210515.
Carbone, M. et al. (2007). Eighth International Mesothelioma Interest Group. Oncogene advance online publication, 14 may 2007. doi:10.1038/sj.onc.1210515.

Abstract

The eighth International Mesothelioma Interest Group (IMIG) meeting was held in Chicago, IL, United States, in 19-22 October 2006 to discuss mesothelioma & the cancer often linked to asbestos exposure. It is a very

aggressive malignancy with a median survival of less than 1 year from diagnosis. Millions of people have been exposed worldwide to asbestos, especially during the second half of the twentieth century when asbestos use increased significantly. The tons of asbestos utilized in the past remain a health hazard for current and future generations because asbestos is difficult to be disposed off. This makes asbestos and mesothelioma research a public health issue in addition to a medical problem. Moreover, the very high costs of asbestos litigation have a significant impact on the whole economy. In the United States, up until 2001, defendant companies had paid 54 billion dollars in claims and estimated future liabilities ranged from 145 to 210 billion. Therefore, asbestos research is of great interest to a large audience that includes patients, millions of asbestos-exposed individuals, scientists, physicians,

public health officials, politicians, unions of asbestos workers, lawyers and the public at large. During the past few years, there has been significant progress in understanding the process of mineral fiber carcinogenesis

and mesothelioma pathogenesis. With improved understanding of the pathogenesis of mesothelioma, new diagnostic, preventive and therapeutic options are being developed. A total of 247 papers were presented at the IMIG: the abstracts of these presentations were published in Lung Cancer, Supplement 1, October 2006. Here, experts in different disciplines critically review some of the most exciting presentations of the IMIG meeting. The result is a comprehensive review of the research field of asbestos carcinogenesis and mesothelioma, and of the progress that has been made in recent years in both basic and clinical sciences.

Talkpoeder kan veilig worden ingezet om mensen te verlossen van vocht achter de longen. Voorwaarde is wel dat de poederdeeltjes niet te klein zijn, aldus hoofdonderzoeker dr. J.P. Janssen, longarts in het Canisius-Wilhelmina Ziekenhuis in Nijmegen. Vocht achter de longen komt o.a. voor bij mensen met longvlieskanker (mesothelioom). Met de talkpoedertechniek laat men de longvliezen verkleven met de binnenkant van de borstwand, zodat er geen ruimte meer is voor het vocht. Bron: Janssen, J.P. et al. (2007). Safety of pleurodesis with talc poudrage in malignant pleural effusion: a prospective cohort study. Lancet, may 5.369(9572):1535-9.
Janssen JP, Collier G, Astoul P, Tassi GF, Noppen M, Rodriguez-Panadero F, Loddenkemper R, Herth FJ, Gasparini S, Marquette CH, Becke B, Froudarakis ME, Driesen P, Bolliger CT, Tschopp JM., (2007). Safety of pleurodesis with talc poudrage in malignant pleural effusion: a prospective cohort study. Lancet. 2007 May 5.369(9572):1535-9.

ABSTRACT

BACKGROUND: Talc is the most effective chemical pleurodesis agent for patients with malignant pleural effusion. However, concerns have arisen about the safety of intrapleural application of talc, after reports of development of acute respiratory distress syndrome in 1-9% of treated patients. Our aim was to establish whether use of large-particle-size talc is safe in patients with malignant pleural effusion.

METHODS: We did a multicentre, open-label, prospective cohort study of 558 patients with malignant pleural effusion who underwent thoracoscopy and talc poudrage with 4 g of calibrated French large-particle talc in 13 European hospitals, and one in South Africa. The primary endpoint was the occurrence of acute respiratory distress syndrome after talc pleurodesis.

FINDINGS: No patients developed acute respiratory distress syndrome (frequency 0%, one-sided 95% CI 0-0.54%). 11 (2%) patients died within 30 days. Additionally, seven patients had non-fatal post-thoracoscopy complications (1.2%), including one case of respiratory failure due to unexplained bilateral pneumothorax.

INTERPRETATION: Use of large-particle talc for pleurodesis in malignant pleural effusion is safe, and not associated with the development of acute respiratory distress syndrome.

De hoeveelheid anti-oxidant enzym gluthatione in eendenkroos neemt af bij contact met chrysotiel (wit) asbest. De asbest was afkomstig uit een asbestcementfabriek. Meting van de hoeveelheid anti-oxidanten in waterplanten als eendenkroos kan een methode zijn om de milieuschade van blootstelling aan asbest te meten. Bron: Trivedi, A.K., et. al. (2007). Environmental Contamination of Chrysotile Asbestos and Its Toxic Effects on Antioxidative System of Lemna gibba. Archives of Environmental Contamination and Toxicology 52, 355-362.
Trivedi, A.K., et. al. (2007). Environmental Contamination of Chrysotile Asbestos and Its Toxic Effects on Antioxidative System of Lemna gibba. Archives of Environmental Contamination and Toxicology 52, 355-362.

Abstract.

Asbestos was monitored in various plant samples around an asbestos cement factory. Asbestos residue was found on the surface of all plant samples monitored. Based on asbestos concentration found in different plant samples during monitoring and on the property of asbestos to cause reactive oxygen species-mediated oxidative stress in animal models, laboratory experiments were conducted to assess the toxicity of chrysotile asbestos on an aquatic macrophyte, duckweed

(Lemna gibba.). L. gibba plants were exposed to four concentrations (0.5, 1.0, 2.0, and 5.0 lg/mL) of chrysotile asbestos under laboratory conditions, and alterations in the glutathione and ascorbate antioxidative system were estimated at postexposure days 7, 14, 21, and 28 in order to assess changes in their level as suitable biomarkers of chrysotile contamination. Chrysotile exposure caused a decrease in total and reduced glutathione and an enhancement in the oxidized glutathione as well as the reduced/oxidized glutathione ratio. An increase in ascorbate pool size, and reduced as well as oxidized ascorbate was found to be accompanied by a decrease in the ratio of reduced/oxidized ascorbate. Alteration in the glutathione and ascorbate level might be considered as a biomarker of exposure to an unsafe environment because these are essential compounds of the general antioxidative strategy to overcome oxidative stress due to environmental constraints. Because an increase in the oxidation rate of antioxidants weakens cellular defenses and indicates a precarious state, they could constitute

indicators of toxicity.

Een studie bij aan asbest blootgestelde muizen laat zien dat het sv-40 virus de ontwikkeling van mesothelioom stimuleert. De manier waarop is nog niet duidelijk. Het lijkt erop dat het virus de werking van het p-53 gen stopt: een gen dat de ontwikkeling van tumoren onderdrukt. Bron: Pietruska, J.R. & Kane, A.B., (2007). SV40 Oncoproteins Enhance Asbestos-Induced DNA Double-Strand Breaks and Abrogate Senescence in Murine Mesothelial Cells. Cancer Res, 67 (8), april 15, 3637-45.
Pietruska, J.R. & Kane, A.B., (2007). SV40 Oncoproteins Enhance Asbestos-Induced DNA Double-Strand Breaks and Abrogate Senescence in Murine Mesothelial Cells. Cancer Res, 67 (8), april 15, 3637-45.

Abstract

SV40 virus has emerged as a potential cofactor with asbestos in the development of diffuse malignant mesothelioma, but its precise role in the pathogenesis of this tumor is unclear. SV40

large T antigen is known to inactivate cellular proteins involved in DNA damage and senescence, including p53 and pRb. We hypothesize that SV40 oncoproteins will sensitize mesothelial cells to DNA damage induced by asbestos or chemotherapeutic agents. SV40 oncoprotein expression in murine mesothelial cell lines enhanced spontaneous and asbestos-induced double-strand breaks, indicated by .-H2AX foci, and potentiated micronucleus formation. Mesothelial cells exposed to asbestos or bleomycin for 96 h acquired senescent-like morphology and displayed elevated senescence associated

B-galactosidase activity, reduced bromodeoxyuridine (BrdUrd) incorporation, and reduced colony formation. SV40 oncoprotein expression abrogated the senescent phenotype,

and transfected cell lines showed an increase in both BrdUrd incorporation and colony formation after prolonged DNA damage. Murine mesothelial cell lines lacking wild-type p53 due to a point mutation or gene rearrangement also failed to senesce in response to asbestos or chemotherapeutic agents. In addition, stress-induced senescence in human mesothelial cell lines was impaired by SV40 oncoprotein

expression (MeT-5A), p53 small interfering RNA, or spontaneous p53 mutation (REN). These studies suggest that exposure to DNA-damaging agents can induce senescence in both murine and human mesothelioma cell lines and suggest a major, although not exclusive, role for p53 in this response.

SV40 virus may contribute to mesothelioma progression by impairing stress-induced senescence, in part through p53 inactivation, thereby favoring survival and proliferation of

mesothelial cells that have sustained DNA damage. [Cancer Res 2007.67(8):3637-45

Amerikaanse onderzoekers hebben een virus gevonden dat bij muizen de groei van een mesothelioomgezwel afremt. Virustherapie is erop gericht virussen te vinden die zich alleen in tumorcellen vermenigvuldigen en de normale cellen sparen. Bron: mesothelioma applied research foundation, 25 april 2007. Meer www.marf.orf

Asbestvezels kunnen de eierstokken bereiken. Dat constateerden Noorse onderzoekers bij een groep vrouwen die in een papier- en pulpfabriek hadden gewerkt. Meer onderzoek is nodig om te bepalen of de asbest in de eierstokken ook eierstokkanker kunnen veroorzaken. Bron: Langseth, H. et al. (2007). Asbestos fibers in ovarian tissue from Norwegian pulp and paper workers. International Journal of Gynecological Cancer 17, 44-49.

Langseth, H., Johansen B.V., Nesland, J.M. & Kjaerheim, K. (2007). Asbestos fibers in ovarian tissue from Norwegian pulp and paper workers

Abstract

An elevated risk of ovarian cancer has been observed in Norwegian pulp and paper workers who were possibly occupationally exposed to asbestos. The present study was initiated to investigate if the increased risk could be associated with asbestos fibers in ovarian tissue from workers in this industry. Normal ovarian tissue specimens from three groups of women were included in the study. The case group included specimens from 46 women diagnosed with ovarian cancer in the period 1953-2000, and who had been working in one or more pulp and paper mills between 1920 and 1993. Normal ovarian tissue specimens from two control groups without occupational history from pulp and paper work were selected from the

Cancer Registry database. Tissue blocks were digested and prepared for transmission electron microscopy. Number of fibers per gram wet weight was calculated. Asbestos fibers were found in normal ovarian tissue from two subjects in the case group, while no fibers were found in the control groups. The two asbestos positive cases had been working as paper sorter/packer and chlorine plant worker, respectively. Both were possibly secondary exposed to asbestos from family members working as insulators. We conclude that the findings in this study did not allow drawing any firm conclusion about an association between occupational exposure to asbestos and ovarian cancer in Norwegian pulp and paper workers. Our study confirms that asbestos fibers may reach the ovaries and demonstrates that the applied method is appropriate for identification of the fiber.

Knoflook werkt als een anti-occidant en vermindert daardoor de schadelijke werking van chrysotiel asbest in het bloed. Dit constateerden Indiase en Duitse onderzoekers in een in-vitro studie. Het ging om een reageerbuis-experiment met menselijk bloed. Bron: Yadav, S. (2006). Modulatory Effects of Fresh Garlic Extract on Chrysotile Asbestos Induced Genotoxicity: An In Vitro Study. Bulletin Environmental Contamination and Toxicology 77: 477-483.

De invloed van blootstelling aan asbest in het milieu op het risico op longkanker bij mensen die nooit gerookt hebben is onduidelijk. Longkanker heeft bij mensen die nooit gerookt hebben andere moleculaire en biologische kenmerken dan bij rokers. Twee recente overzichtsstudies beschrijven dat niet-rokende vrouwen vaker longkanker krijgen dan niet-rokende mannen: tussen de 15 en 25% van de vrouwelijke longkankerpatiënten heeft nooit gerookt, bij mannelijke longkankerpatiënten is dat tussen de 5 en 10%. Bron: Wakelee H.A. et al. (2007). Lung cancer incidence in never smokers. Journal of Clinical Oncology, Feb 10.25(5):469-71. Subramanian, J. & Govindan, R. (2007). Lung cancer in never smokers: a review. Journal of Clinical Oncology feb 10. 25(5), 561-70.
Wakelee H.A., Chang ET, Gomez SL, Keegan TH, Feskanich D, Clarke CA, Holmberg L, Yong LC, Kolonel LN, Gould MK, West DW (2007). Lung cancer incidence in never smokers. Journal of Clinical Oncology, Feb 10.25(5):469-71.

PURPOSE: Lung cancer is a leading cause of cancer death worldwide. Although smoking remains the predominant cause of lung cancer, lung cancer in never smokers is an increasingly prominent public health issue. However, data on this topic, particularly lung cancer incidence rates in never smokers, are limited. METHODS: We reviewed the existing literature on lung cancer incidence and mortality rates among never smokers and present new data regarding rates in never smokers from the following large, prospective cohorts: Nurses’ Health Study. Health Professionals Follow-Up Study. California Teachers Study. Multiethnic Cohort Study. Swedish Lung Cancer Register in the Uppsala/Orebro region. and First National Health and Nutrition Examination Survey Epidemiologic Follow-Up Study. RESULTS: Truncated age-adjusted incidence rates of lung cancer among never smokers age 40 to 79 years in these six cohorts ranged from 14.4 to 20.8 per 100,000 person-years in women and 4.8 to 13.7 per 100,000 person-years in men, supporting earlier observations that women are more likely than men to have non-smoking-associated lung cancer. The distinct biology of lung cancer in never smokers is apparent in differential responses to epidermal growth factor receptor inhibitors and an increased prevalence of adenocarcinoma histology in never smokers. CONCLUSION: Lung cancer in never smokers is an important public health issue, and further exploration of its incidence patterns, etiology, and biology is needed.

Subramanian, J. & Govindan, R. (2007). Lung cancer in never smokers: a review. Journal of Clinical Oncology feb 10. 25(5), 561-70.

ABSTRACT

Lung cancer is the leading cause of cancer-related death in the United States. Although tobacco smoking accounts for the majority of lung cancer, approximately 10% of patients with lung cancer in the United States are lifelong never smokers. Lung cancer in the never smokers (LCINS) affects women disproportionately more often than men. Only limited data are available on the etiopathogenesis, molecular abnormalities, and prognosis of LCINS. Several etiologic factors have been proposed for the development of LCINS, including exposure to radon, cooking fumes, asbestos, heavy metals, and environmental tobacco smoke, human papillomavirus infection, and inherited genetic susceptibility. However, the relative significance of these individual factors among different ethnic populations in the development of LCINS has not been well-characterized. Adenocarcinoma is the predominant histologic subtype reported with LCINS. Striking differences in response rates and outcomes are seen when patients with advanced non-small-cell lung cancer (NSCLC) who are lifelong never smokers are treated with epidermal growth factor receptor tyrosine kinase (EGFR-TK) inhibitors such as gefitinib or erlotinib compared with the outcomes with these agents in patients with tobacco-associated lung cancer. Interestingly, the activating mutations in the EGFR-TK inhibitors have been reported significantly more frequently in LCINS than in patients with tobacco-related NSCLC. This review will summarize available data on the epidemiology, risk factors, molecular genetics, management options, and outcomes of LCINS.