Intralesional cytokine therapy in cancer a phase 1 and 2 study of alpha interferon and GM-CSF infusion in mesothelioma
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Mesothelioma, a rare tumor, is highly correlated with asbestos exposure. Mesothelioma, similar to all asbestos-related diseases, is dose/intensity dependent to some degree, and studies showed the risk of mesothelioma rises with cumulative exposures. Multiple processes occur in an individual before mesothelioma occurs. The impact of mesothelioma in the United States has been continuous over the last half century, claiming between 2,000 and 3,000 lives each year. Mesothelioma is a preventable tumor that is more frequently reported as associated with asbestos exposure among men than women. However, the rate of asbestos-associated mesothelioma is on the rise among women due to better investigation into their histories of asbestos exposure. It is of interest that investigators detected asbestos-associated cases of mesothelioma in women from nonoccupational sources-that is, bystander, incidental, or take-home exposures. It is postulated that asbestos-associated mesotheliomas, in both men and women, are likely underreported. However, with the implementation of the most recent ICD-10 coding system, the correlation of mesothelioma with asbestos exposure is expected to rise to approximately 80% in the United States. This study examined the demographic and etiological nature of asbestos-related mesothelioma.
Asbestosis
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Mesothelioma is an aggressive tumor arising from the mesothelium, and is usually associated with previous exposure to asbestos. The incubation period of asbestos‐related mesothelioma is estimated to be approximately 30–40 years. Once mesothelioma has occurred, there is no effective treatment. So, identification of tumor markers and a method for early diagnosis using such markers are urgently needed. Recently, several enzyme‐linked immunosorbent assay systems for Erc /mesothelin have been developed, the reported usefulness of which has been assessed and demonstrated as a diagnostic tool. Asbestos‐related mesothelioma should be ascribed as a typical environmental carcinogen. In this review, we will present asbestos‐related mesothelioma for the study of problems in environmental carcinogenesis. ( Cancer Sci 2007; 98: 1147–1151)
Mesothelin
Asbestosis
Mesothelium
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BackgroundLittle is known about the global magnitude of mesothelioma. In particular, many developing countries, including some with extensive historical use of asbestos, do not report mesothelioma.ObjectivesWe estimated the global magnitude of mesothelioma accounting for reported and unreported cases.MethodsFor all countries with available data on mesothelioma frequency and asbestos use (n = 56), we calculated the 15-year cumulative number of mesotheliomas during 1994–2008 from data available for fewer years and assessed its relationship with levels of cumulative asbestos use during 1920–1970. We used this relationship to predict the number of unreported mesotheliomas in countries for which no information on mesothelioma is available but which have recorded asbestos use (n = 33).ResultsWithin the group of 56 countries with data on mesothelioma occurrence and asbestos use, the 15-year cumulative number of mesothelioma was approximately 174,300. There was a statistically significant positive linear relation between the log-transformed national cumulative mesothelioma numbers and the log-transformed cumulative asbestos use (adjusted R2 = 0.83, p < 0.0001). Extrapolated to the group of 33 countries without reported mesothelioma, a total of approximately 38,900 (95% confidence interval, 36,700–41,100) mesothelioma cases were estimated to have occurred in the 15-year period (1994–2008).ConclusionsWe estimate conservatively that, globally, one mesothelioma case has been overlooked for every four to five reported cases. Because our estimation is based on asbestos use until 1970, the many countries that increased asbestos use since then should anticipate a higher disease burden in the immediate decades ahead.
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Asbestos is the principal agent in the etiology of malignant mesothelioma. However, a small proportion of people exposed to asbestos develop mesothelioma. This suggests the role of host factors in the genesis of the tumor. A genetic susceptibility is suggested by the occurrence of more mesothelioma cases among blood-related members of a single family. Such an occurrence reached about 4% in a large mesothelioma series. In some studies, mesothelioma patients showed higher prevalences of additional malignancies when compared with controls. This indicates a particular vulnerability to cancer in people with mesothelioma. Not rarely, very old persons heavily exposed to asbestos remain free from asbestos-related cancer, a fact indicating an absolute resistance to the oncogenic effects of asbestos. A relative resistance may be recognized in people severely exposed to asbestos who develop mesothelioma only after 60 years or more since the onset of the exposure. The long survivals, rarely observed among mesothelioma patients, have been attributed to a high efficiency of immune mechanisms. Mesotheliomas have been reported among people with severe immune impairment, such as acquired immunodeficiency syndrome patients or organ transplant recipients. The natural history of mesothelioma shows that a resistance to the oncogenic effects of asbestos does exist. Probably, such a resistance is due to the efficient immune mechanisms. To strengthen the defence mechanisms may represent a way for preventing mesothelioma among people exposed to asbestos.
Etiology
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The interferon-specific cellular receptors in human cells cultures differing in sensitivity to alpha-interferon have been studied. The J-41 cells resistant to alpha-interferon are practically devoid of receptors highly specific to alpha-interferon. The coefficient of equilibrium and the number of receptors analyzed after Scatchard for J-96 culture of cells are 15.6 x 10(11) M-1 and 210 +/- 90, respectively. Evidently, resistance of J-41 cells to alpha-interferon is connected with the absence of interferon receptors and, as a consequence, inability to interferon-receptor interaction.
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Interferon type I
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Malignant mesothelioma in the western world is often associated with asbestos exposure. It is a relatively rare cancer that causes approximately 2,500 deaths yearly in the United States and 1,000 deaths yearly in the United Kingdom. In contrast, among people born in the Cappadocian (Turkey) villages of Tuzkoy, Karain, and "Old" Sarihidir, approximately 50% of deaths are caused by malignant mesothelioma. This epidemic has been attributed to erionite exposure, a type of fibrous zeolite mineral commonly found in this area of Turkey. In these three villages, malignant mesothelioma occurs in certain houses but not in others. The hypothesis was that a unique and more carcinogenic erionite was present in certain houses and caused malignant mesothelioma. We determined the X-ray diffraction pattern and the crystal structure of erionite from malignant mesothelioma villages and compared the results with the erionite samples from nearby non-malignant mesothelioma villages and from the United States. We found the same type of erionite in Cappadocian villages, with or without a malignant mesothelioma epidemic, in households with high or no incidence of malignant mesothelioma and in the United States. Pedigree studies of the three malignant mesothelioma villages showed that malignant mesothelioma was prevalent in certain families but not in others. When high-risk malignant mesothelioma family members married into families with no history of it, malignant mesothelioma appeared in the descendants. Genetically predisposed family members born and raised outside the malignant mesothelioma villages did not seem to develop malignant mesothelioma. In summary, pedigree and mineralogical studies indicate that the malignant mesothelioma epidemic is caused by erionite exposure in genetically predisposed individuals. This is the first time that genetics is shown to influence mineral fiber carcinogenesis.
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Interferon alfa
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677 An analysis of latent period and survival factors of korean patients with malignant mesothelioma
Introduction
Malignant mesothelioma is an aggressive tumour occurring in mesothelioma cells of pleura and peritoneum. About 80% of malignant mesothelioma cases are known to be caused by asbestos. Malignant mesothelioma is known to have a very poor prognosis with an average survival period of about 12 months. The number of patients of malignant mesothelioma in Korea is smaller than that of some developed countries. However, mesothelioma has increased greatly in recent years in Korea, and it is expected to increase continuously considering asbestos consumption, as it happened in other countries which used large amounts of asbestos. It is important to investigate the epidemiologic characteristics and prognostic factors of malignant mesothelioma in Korea.Methods
A total of 728 patients who received asbestos-related relief from malignant mesothelioma by 2014 were included in the study. In 2015, 150 (20.6%) out of 728 people were surveyed. Interviews were conducted with structured questionnaires for patients with malignant mesothelioma and their families. The age, sex, surgical status, route of exposure, and age at diagnosis of malignant mesothelioma patients were analysed using the proportional hazard model of Cox.Results
Ninety eight (65.3%) males and 52 females (34.7%) had malignant mesothelioma according to sex. In the case of mesothelioma according to age, 49 cases (32.7%) were the highest in above 70 s, 42 cases (28.0%) in the 60 s, 40 cases (26.7%) in the 50 s, Followed by below 49 to 19 (12.7%). In this study, asbestos exposure source of subjects was 40.7% for occupational factors and 56.0% for environmental factors, which was higher than 59% of Kim, et al. 's (2009) study. The latent period was 35.0±15.8 years, which was mostly latent period of 30 years or more. And 39.1±15.1 years in the occupational asbestos exposure group and 32.2±15.7 years in the non occupational asbestos exposure group. The mean survival duration after diagnosis of mesothelioma was 19.9±27.2 months. Mean occupational exposure was 15.8±21.3 months in occupational asbestos exposure group and 22.8±30.5 months in non occupational asbestos exposure group. Gender, exposure type, and age at diagnosis did not significantly affect the risk of malignant mesothelioma death. The risk of death was 2.20 times (95% CI: 1.15~3.56) higher in the pleura than in the other sites of malignant mesothelioma. Also, according to the received surgery, the number of patients who underwent surgery was lower by 0.52 times (95% CI: 0.33~0.81) than those without surgery.Conclusion
This study revealed that the site of onset and surgical treatment had an effect on the risk of death in patients with malignant mesothelioma. It is necessary to develop a new treatment and compensation method for malignant mesothelioma which is expected to increase rapidly in the future and to plan ways to minimise exposure to future asbestos.Cite
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