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De Canadese patholoog BW Case schrijft in het medische tijdschrift Occupational Environmental Medicine dat het gebruik van een vaste methode om de omvang van schade bij longkanker aan roken of asbest toe te kunnen wijzen nog niet betrouwbaar is. De interactie tussen longkanker, asbestblootstelling en rookgedrag is nog niet duidelijk. Het gebruik van een individuele, praktische “common-sense” benadering waarin o.a. het beroep en de duur van een dienstverband worden meegenomen lijkt op dit moment nog de beste aanpak van schadeclaims. Bron: Case, B.W. (2006). Asbestos, smoking, and lung cancer: interaction and attribution. Commentary. Occupational Environmental Medicine, 64, 507-08.

In twee artikelen wordt de huidige kennis over het mesothelioomgezwel beschreven met betrekking tot de rol van genen en chromosomen, de invloed van het sv-40 virus en de mate waarin bepaalde merkers ter identificatie kunnen worden. Bronnen: Hicks J., (2006). Biologic, cytogenetic, and molecular factors in mesothelial proliferations. Ultrastructural Pathology Jan-Feb.30(1):19-30. Ramos-Nino, M.E., et al. (2006). Cellular and molecular parameters of mesothelioma. Journal of Cellular Biochemistry, Jul 1.98(4):723-34.

Hicks J., (2006). Biologic, cytogenetic, and molecular factors in mesothelial proliferations. Ultrastructural Pathology Jan-Feb.30(1):19-30.

Abstract

Although mesothelioma cases may have peaked in the 1990s in developed countries, it is expected that there will be over 70,000 cases diagnosed in the United States over the next 5 decades. With the industrial expansion in Southeast Asia and China and the continued use of asbestos, an epidemic of mesothelioma cases is anticipated over the next several decades. A considerable amount has been learned about the cytogenetic and molecular genetics of mesotheliomas. However, in-depth studies are needed to further define specific factors that may provide for early diagnosis, surgical treatment, oncologic management, and gene therapy. Serologic markers for surveillance of those with asbestos exposure and at risk for mesothelioma are needed. Targeted therapy using molecular markers and gene therapy may provide a means to reverse mesothelial proliferations or stabilize tumor growth and allow for surgical resection. The future holds great promise in identifying mesothelioma gene expression profiles (genomics, gene microarrays) and proteins (proteomics) that may produce the key to dealing with this dismal and devastating neoplasm.

Ramos-Nino ME, Testa JR, Altomare DA, Pass HI, Carbone M, Bocchetta M, Mossman BT (2006). Cellular and molecular parameters of mesothelioma. Journal of Cellular Biochemistry, Jul 1.98(4):723-34.

Abstract

Malignant mesotheliomas (MM) are neoplasms arising from mesothelial cells that line the body cavities, most commonly the pleural and peritoneal cavities. Although traditionally recognized as associated with occupational asbestos exposures, MMs can appear in individuals with no documented exposures to asbestos fibers, and emerging data suggest that genetic susceptibility and simian virus 40 (SV40) infections also facilitate the development of MMs. Both asbestos exposure and transfection of human mesothelial cells with SV40 large and small antigens (Tag, tag) cause genetic modifications and cell signaling events, most notably the induction of cell survival pathways and activation of receptors, and other proteins that favor the growth and establishment of MMs as well as their resistance to chemotherapy. Recent advances in high-throughput technologies documenting gene and protein expression in patients and animal models of MMs can now be validated in human MM tissue arrays. These have revealed expression profiles that allow more accurate diagnosis and prognosis of MMs. More importantly, serum proteomics has revealed two new candidates (osteopontin and serum mesothelin-related protein or SMRP) potentially useful in screening individuals for MMs. These mechanistic approaches offer new hope for early detection and treatment of these devastating tumors.

Onderzoek van Wang geeft aanwijzingen dat asbest en tabaksrook elk een eigen onafhankelijke schadelijke invloed hebben op de longfunctie. Asbest heeft vooral negatief effect op de longcapaciteit en tabaksrook op het vermogen lucht op te nemen. Nymark en collega’s zagen verschillen in genetische patronen tussen twee groepen longkankerpatiënten (totaal 28 personen), waarvan één groep intensief aan asbest blootgesteld was geweest. Ook zagen zij dat tabaksrook de cellen op genetisch niveau meer kwetsbaar maakt voor de schadelijke effecten van asbest. Voor dit onderzoek werd de array-CGH moluculair genethische techniek gebruikt. Bron: Nymark P. et al. (2006). Identification of specific gene copy number changes in asbestos-related lung cancer. Cancer Research Jun 1.66(11):5737-43.
Wang X, Yano E, Wang Z, Wang M, Christiani DC. (2006). Adverse effects of asbestos exposure and smoking on lung function. American Journal of Industrial Medicine May.49(5):337-42.

BACKGROUND: Exposure to asbestos is a well-recognized cause of both malignant and nonmalignant diseases of lung parenchyma and pleura. This study was conducted to determine the adverse effects of exposure to asbestos and smoking on pulmonary function.

METHODS: Four hundred and sixty-eight workers who were occupationally exposed to asbestos for an average of 13 years were selected from an asbestos-product factory in China. Of them, 85 workers were diagnosed with asbestosis. Additionally, 282 workers who had no experience of exposure to industrial dust were included as a control group. A questionnaire was administered during a face-to-face interview and spirometric maneuvers and single-breath CO diffusing capacity (DL(CO)) were performed.

RESULTS: Multivariate regression analysis showed that exposure to asbestos was more strongly associated with decreased forced vital capacity (FVC) and DL(CO), and asbestosis more strongly associated with decreased FVC, while smoking was a major contributing factor to reduced FEV1/FVC. The results were confirmed by a further analysis where the subjects were grouped exclusively by smoking, asbestos exposure, and chest radiographic changes. No interaction or joint effect was observed between asbestos exposure and smoking.

CONCLUSIONS: This analysis suggested that asbestos and smoking might play independent roles, in which asbestos caused mainly a restrictive impairment, and smoking was a major causal factor for airway obstruction in the workers who were intensively exposed to asbestos.

Nymark P, Wikman H, Ruosaari S, Hollmen J, Vanhala E, Karjalainen A, Anttila S, Knuutila S., (2006). Identification of specific gene copy number changes in asbestos-related lung cancer. Cancer Research Jun 1.66(11):5737-43.

Abstract

Asbestos is a well-known lung cancer-causing mineral fiber. In vitro and in vivo experiments have shown that asbestos can cause chromosomal damage and aberrations. Lung tumors, in general, have several recurrently amplified and deleted chromosomal regions. To investigate whether a distinct chromosomal aberration profile could be detected in the lung tumors of heavily asbestos-exposed patients, we analyzed the copy number profiles of 14 lung tumors from highly asbestos-exposed patients and 14 matched tumors from nonexposed patients using classic comparative genomic hybridization (CGH). A specific profile could lead to identification of the underlying genes that may act as mediators of tumor formation and progression. In addition, array CGH analyses on cDNA microarrays (13,000 clones) were carried out on 20 of the same patients. Classic CGH showed, on average, more aberrations in asbestos-exposed than in nonexposed patients, and an altered region in chromosome 2 seemed to occur more frequently in the asbestos-exposed patients. Array CGH revealed aberrations in 18 regions that were significantly associated with either of the two groups. The most significant regions were 2p21-p16.3, 5q35.3, 9q33.3-q34.11, 9q34.13-q34.3, 11p15.5, 14q11.2, and 19p13.1-p13.3 (P < 0.005). Furthermore, 11 fragile sites coincided with the 18 asbestos-associated regions (P = 0.08), which may imply preferentially caused DNA damage at these sites. Our findings are the first evidence, indicating that asbestos exposure may produce a specific DNA damage profile.

Asbest veroorzaakt longvlieskanker (mesothelioom) doordat cellen van het afweersysteem een signaalstof (TNF-alfa) produceren die zorgt dat longvliescellen die door asbest aangetast zijn, niet sterven. Cellen uit het afweersysteem nemen de asbestvezels op, maar kunnen die niet verteren, wat ze normaal gesproken wel met schadelijke indringers doen. Ze blijven vervolgens te veel van de signaalstof TNF-alfa produceren. Die stof start processen die de longvliescellen beschermen tegen de giftige werking van asbest. De kankerverwekkende stoffen die rond de asbestvezels ontstaan, kunnen vervolgens jarenlang hun gang gaan.Dit schrijven onderzoekers van enkele Amerikaanse universiteiten in een op 23 juni j.l. online gepubliceerd artikel in de Proceedings of the National Academy of Sciences. Bron: NRC, 24 juni. Yang, H. et al. (2006). TNF- inhibits asbestos-induced cytotoxicity via a NF-B-dependent pathway, a possible mechanism for asbestos-induced oncogenesis. Gevonden op: www.pnas.org
Haining Yang, Maurizio Bocchetta, Barbara Kroczynska, Amira G. Elmishad, Yuanbin Chen, Zemin Liu, Concetta Bubici, Brooke T. Mossman, Harvey I. Pass, Joseph R. Testa, Guido Franzoso, and Michele Carbone, (2006). TNF- inhibits asbestos-induced cytotoxicity via a NF-B-dependent pathway, a possible mechanism for asbestos-induced oncogenesis. Proceedings of the National Academy of Sciences, 23th june 2006.

Abstract

Asbestos is the main cause of human malignant mesothelioma (MM). In vivo, macrophages phagocytize asbestos and, in response, release TNF- and other cytokines that contribute to carcinogenesis through unknown mechanisms. In vitro, asbestos does not induce transformation of primary human mesothelial cells (HM). instead, asbestos is very cytotoxic to HM, causing extensive cell death. This finding raised an apparent paradox: How can asbestos cause MM if HM exposed to asbestos die? We found that asbestos induced the secretion of TNF- and the expression of TNF- receptor I in HM. Treatment of HM with TNF- significantly reduced asbestos cytotoxicity. Through numerous technical approaches, including chemical inhibitors and small interfering RNA strategies, we demonstrate that, in HM, TNF- activates NF-B and that NF-B activation leads to HM survival and resistance to the cytotoxic effects of asbestos. Our data show a critical role for TNF- and NF-B signaling in mediating HM responses to asbestos. TNF- signaling through NF-B-dependent mechanisms increases the percent of HM that survives asbestos exposure, thus increasing the pool of asbestos-damaged HM that are susceptible to malignant transformation. Cytogenetics supported this hypothesis, showing only rare, aberrant metaphases in HM exposed to asbestos and an increased mitotic rate with fewer irregular metaphases in HM exposed to both TNF- and asbestos. Our findings provide a mechanistic rationale for the paradoxical inability of asbestos to transform HM in vitro, elucidate and underscore the role of TNF- in asbestos pathogenesis in humans, and identify potential molecular targets for anti-MM prevention and therapy.

Honden kunnen, volgens epidemioloog en dierenarts Glickman, behulpzaam zijn bij onderzoek naar diverse vormen van kanker, waaronder mesothelioom. Begin jaren 80 kreeg hij van de Britse overheid subsidie voor onderzoek naar mesothelioom bij honden die in huizen met asbest leefden. Glickman constateerde een relatie tussen de aanwezigheid van asbest en de mesothelioom die de honden al zo’n 7 tot 9 jaar na blootstelling kregen. Mensen krijgen mesothelioom gemiddeld pas 30 tot 40 jaar nadat ze aan asbest blootgesteld zijn geweest. Kort geleden bleek dat honden, vanwege hun gevoelige neus, ook op een andere manier in het onderzoek betrokken kunnen worden, namelijk voor de vroeg-ontdekking van borst- en longkanker bij mensen. Dit door signalering van bepaalde stoffen die in de adem voorkomen. Bron: Sunday Times, Magazine, 7 mei 2006.

Onderzoeker Fattman en collega’s vonden in een experiment dat het anti-oxidant enzym extracellular superoxide dismutase (EC-SOD) de longen van muizen beschermde tegen injecties met crocidoliet, de meest gevaarlijke blauwe asbestvezels (crocidoliet). Anti-oxidanten zijn vitamines, minieralen of enzymen die bepaalde schadelijke stoffen in het lichaam, de zgn. vrije radicalen, tegengaan. Het bekendste anti-oxidant enzym is het superoxide-dismutase (SOD)-enzym. Bron: Fattman CL, Tan RJ, Tobolewski JM & Oury TD (2006). Increased sensitivity to asbestos-induced lung injury in mice lacking extracellular superoxide dismutase. Free Radical Biology & Medicine 40 Feb 15.40(4):601-7.
Fattman CL, Tan RJ, Tobolewski JM & Oury TD (2006). Increased sensitivity to asbestos-induced lung injury in mice lacking extracellular superoxide dismutase. Free Radical Biology & Medicine 40 Feb 15.40(4):601-7.

Abstract

Asbestosis is a chronic form of interstitial lung disease characterized by inflammation and fibrosis that results from the inhalation of asbestos fibers. Although the pathogenesis of asbestosis is poorly understood, reactive oxygen species may mediate the progression of this disease. The antioxidant enzyme extracellular superoxide dismutase (EC-SOD) can protect the lung against a variety of insults. however, its role in asbestosis is unknown. To determine if EC-SOD plays a direct role in protecting the lung from asbestos-induced injury, intratracheal injections of crocidolite were given to wild-type and ec-sod-null mice. Bronchoalveolar lavage fluid (BALF) from asbestos-treated ec-sod-null mice at 24 h, 14 days, or 28 days posttreatment showed increased inflammation and total BALF protein content compared to that of wild-type mice. In addition, lungs from ec-sod-null mice showed increased hydroxyproline content compared to those of wild-type mice, indicating a greater fibrotic response. Finally, lungs from ec-sod-null mice showed greater oxidative damage, as assessed by nitrotyrosine content compared to those of their wild-type counterparts. These results indicate that depletion of EC-SOD from the lung increases oxidative stress and injury in response to asbestos.

Volgens het Amerikaanse “Institute of Medicine” is er voldoende bewijs om een oorzakelijk verband tussen asbestblootstelling en kanker aan het strottenhoofd (larynx kanker) aan te nemen. Voor maag- en darmkanker en kanker in de keelholte is dit bewijs onvoldoende. Wel zijn er aanwijzingen voor een relatie tussen deze kankersoorten en asbest. Het “Institute of Medicine” is een tak van de Amerikaanse National Academy of Sciences. In opdracht van de Senaat heeft het instituut onderzocht of asbest, buiten mesothelioom en longkanker, ook een relatie heeft met andere kankersoorten. Volgens het CBS overleden in 2005 227 mensen aan kanker aan het strottenhoofd. Bron: Europees Vakbondsinstituut Hesa, 8 juni 2006, CBS Statline. Meer http://hesa.etui-rehs.org/uk/newsevents/newsfiche.asp?pk=631

Onderzoek van Wang geeft aanwijzingen dat asbest en roken elk een eigen onafhankelijke schadelijke invloed hebben op de longfunctie.Asbest heeft vooral negatief effect op de longcapaciteit en roken op het vermogen lucht op te nemen. Bron: Wang X, et al..(2006). Adverse effects of asbestos exposure and smoking on lung function. American Journal of Industrial Medicine May.49(5):337-42.
Wang X, Yano E, Wang Z, Wang M, Christiani DC. (2006). Adverse effects of asbestos exposure and smoking on lung function. American Journal of Industrial Medicine May.49(5):337-42.

BACKGROUND: Exposure to asbestos is a well-recognized cause of both malignant and nonmalignant diseases of lung parenchyma and pleura. This study was conducted to determine the adverse effects of exposure to asbestos and smoking on pulmonary function.

METHODS: Four hundred and sixty-eight workers who were occupationally exposed to asbestos for an average of 13 years were selected from an asbestos-product factory in China. Of them, 85 workers were diagnosed with asbestosis. Additionally, 282 workers who had no experience of exposure to industrial dust were included as a control group. A questionnaire was administered during a face-to-face interview and spirometric maneuvers and single-breath CO diffusing capacity (DL(CO)) were performed.

RESULTS: Multivariate regression analysis showed that exposure to asbestos was more strongly associated with decreased forced vital capacity (FVC) and DL(CO), and asbestosis more strongly associated with decreased FVC, while smoking was a major contributing factor to reduced FEV1/FVC. The results were confirmed by a further analysis where the subjects were grouped exclusively by smoking, asbestos exposure, and chest radiographic changes. No interaction or joint effect was observed between asbestos exposure and smoking.

CONCLUSIONS: This analysis suggested that asbestos and smoking might play independent roles, in which asbestos caused mainly a restrictive impairment, and smoking was a major causal factor for airway obstruction in the workers who were intensively exposed to asbestos.

Het aantal inwoners van New York dat nog altijd kampt met gezondheidsklachten door de aanslagen van 11 september 2001 beloopt zeker 15.000. Dat blijkt uit een documentaire van de Britse omroep BBC die begin mei wordt uitgezonden.

De meesten hebben last van wat al de “WTC-hoest” wordt genoemd, een vermeend gevolg van het inademen van besmet stof. Door het instorten van de twee torens het World Trade Center kwamen enorme hoeveelheden stof vrij die grote delen van Manhattan bevuilde. Het stof bevatte waarschijnlijk asbest, lood en andere giftige stoffen. Bron: nu.nl, 12 april 2006.

Vroege opsporing longkanker met longslijmtest

Amerikaanse onderzoekers hebben een baanbrekende onderzoeksmethode ontwikkeld om longkanker sneller op te sporen. Het duurt waarschijnlijk nog zo’n vijf jaar voordat de test in de praktijk kan worden toegepast. Vijf jaar is bij medisch onderzoek een bijzonder korte periode. Een eenvoudig uit te voeren onderzoeksmethode spoort de ziekte in longslijm op voordat er zichtbare en fatale tumoren ontstaan. Amerikaanse onderzoekers schrijven dat in het medische tijdschrift Cancer Research. De Gezondheidsraad schat dat iets meer dan 10% van de gevallen van longkanker gerelateerd is aan asbestblootstelling. Bron: AD, 14 maart 2006. Meer http://www.kankerpatient.nl/longkanker/