MexTAg mice exposed to asbestos develop cancer that faithfully replicates key features of the pathogenesis of human mesothelioma

Robinson, Cleo; Walsh, Amy; Larma, Irma; O’Halloran, Sean; Nowak, Anna K.; Lake, Richard

doi:10.1016/j.ejca.2010.08.015

Cited by 33 publications

(52 citation statements)

References 38 publications

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“…This is consistent with the finding that in humans beta carotene and retinoic acid forms of vitamin A do not affect mesothelioma incidence [11]. We have also investigated the use of aspirin and cyclooxygenase-2 inhibitors (COX-2i), again finding no benefit in either the mouse model or a human cohort [12], [13]. Here the search for a prevention strategy was extended to investigate the ability of statins to inhibit mesothelioma development in asbestos exposed mouse and human populations.…”

Section: Introductionsupporting

confidence: 82%

“…Furthermore, MexTAg tumor pathogenesis is similar to human mesothelioma in terms of many factors including histology, latency, inflammatory response, localization and the response to cytotoxic chemotherapy [12].…”

Section: Discussionmentioning

confidence: 99%

“…Mice were monitored and the animals were euthanized when ascites became evident or sickness, distress or loss of condition was noticed (endpoint). A standardized-system of criteria was used to define the first signs of disease and this was taken as the diagnosis date [12]. All experiments had University of Western Australia Animal Ethics Committee approval (#RA5/100/1075) and were carried out in strict accordance with National Health and Medical Research Council guidelines.…”

Section: Methodsmentioning

confidence: 99%

“…In this study the effect of high, medium and low doses of statin on the survival rate of asbestos-induced mesothelioma is investigated in the MexTAg mouse model of asbestos-induced mesothelioma, which is highly suited to testing potential cancer prevention agents [12]. Alongside this investigation human epidemiological data has been analysed from the Wittenoom cohort, consisting of people who lived or worked in Wittenoom while asbestos mining was taking place.…”

Section: Introductionmentioning

confidence: 99%

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Statins Do Not Alter the Incidence of Mesothelioma in Asbestos Exposed Mice or Humans

et al. 2014

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Mesothelioma is principally caused by asbestos and may be preventable because there is a long latent period between exposure and disease development. The most at-risk are a relatively well-defined population who were exposed as a consequence of their occupations. Although preventative agents investigated so far have not been promising, discovery of such an agent would have a significant benefit world-wide on healthcare costs and personal suffering. Statins are widely used for management of hypercholesterolemia and cardiovascular risk; they can induce apoptosis in mesothelioma cells and epidemiological data has linked their use to a lower incidence of cancer. We hypothesised that statins would inhibit the development of asbestos-induced mesothelioma in mice and humans. An autochthonous murine model of asbestos-induced mesothelioma was used to test this by providing atorvastatin daily in the feed at 100 mg/kg, 200 mg/kg and 400 mg/kg. Continuous administration of atorvastatin did not alter the rate of disease development nor increase the length of time that mice survived. Latency to first symptoms of disease and disease progression were also unaffected. In a parallel study, the relationship between the use of statins and development of mesothelioma was investigated in asbestos-exposed humans. In a cohort of 1,738 asbestos exposed people living or working at a crocidolite mine site in Wittenoom, Western Australia, individuals who reported use of statins did not have a lower incidence of mesothelioma (HR = 1.01; 95% CI = 0.44–2.29, p = 0.99). Some individuals reported use of both statins and non-steroidal anti-inflammatory drugs or COX-2 inhibitors, and these people also did not have an altered risk of mesothelioma development (HR = 1.01; 95% CI = 0.61–1.67, p = 0.97). We conclude that statins do not moderate the rate of development of mesothelioma in either a mouse model or a human cohort exposed to asbestos.

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Section: Introductionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Statins Do Not Alter the Incidence of Mesothelioma in Asbestos Exposed Mice or Humans

et al. 2014

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“…After the first signs of disease, the time for tumor progression to end point is independent of TAg, suggesting that TAg advances disease onset but that tumorigenesis is conserved thereafter. The response to gemcitabine chemotherapy is comparable with human mesotheliomas, both validating and demonstrating the translatability of the model [69]. Expression arrays found MexTAg and wild-type mouse mesotheliomas have a similar gene set in common with human mesothelioma, each compared with its normal mesothelial counterpart [Robinson C, Unpublished Data].…”

Section: • • Asbestos-induced Transgenic Modelsmentioning

confidence: 94%

Mouse Models of Mesothelioma: Strengths, Limitations and Clinical Translation

et al. 2014

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These authors contributed equally SUMMARY Mouse models of cancer are invaluable for obtaining detailed knowledge about tumor development and for screening therapeutic and preventive approaches. Mesothelioma is an unusual cancer because the same carcinogen, asbestos, causes a similar disease in both humans and animals. Unlike most other cancers, murine mesothelioma can therefore be regarded as a disease homolog, rather than a model as such. However, because asbestos-induced cancer has low penetrance and a long lag time, most translational studies have utilized more efficient models such as tumor transplantation. In consequence, many promising results have not translated into positive findings in patients. Here, we describe the widely used murine mesothelioma models and critically discuss their relative advantages and disadvantages. We emphasize the use of the appropriate model for the specific research question and the need to use multiple models in order to obtain robust and translatable data.

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Zeolite protects mice from iron‐induced damage in a mouse model trial

et al. 2018

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For centuries, zeolites have been used for their utility in binding metals, and they feature in a multitude of agricultural and industrial applications in which the honeycombed zeolite structures form ideal ion exchangers, catalysts and binding agents. Zeolites are currently in a transition period, moving towards implementation in human ailments and diseases. Here, we postulated that zeolites may be able to counter the effects of excess iron and conducted a mouse model trial to gauge the utility of this notion. We used the transgenic mouse strain Mex TA g299 for a thirty‐week pilot trial in which iron polymaltose and/or the zeolite clinoptilolite was injected into the peritoneum twice weekly. Mice were sacrificed at the end of the trial period and examined by postmortem and histology for significant physiological differences between mouse subgroups. In this study, we demonstrated that a common zeolite, clinoptilolite, is able to maintain the general health and well‐being of mice and prevent iron‐induced deleterious effects following iron overload. When zeolites are given with iron biweekly as intraperitoneal injections, mice showed far less macroscopic visual organ discoloration, along with near normal histology, under iron overload conditions when compared to mice injected with iron only. The purpose of the present pilot study was to examine potential alternatives to current iron chelation treatments, and the results indicate an advantage to using zeolites in conditions of iron excess. Zeolites may have translational potential for use in cases of human iron overload.

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MexTAg mice exposed to asbestos develop cancer that faithfully replicates key features of the pathogenesis of human mesothelioma

Cited by 33 publications

References 38 publications

Statins Do Not Alter the Incidence of Mesothelioma in Asbestos Exposed Mice or Humans

Statins Do Not Alter the Incidence of Mesothelioma in Asbestos Exposed Mice or Humans

Mouse Models of Mesothelioma: Strengths, Limitations and Clinical Translation

Zeolite protects mice from iron‐induced damage in a mouse model trial

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