Peritoneal mesothelioma.

OpenAIRE

Anderson, J. H.; Stewart, C. J.; Hansell, D. T.; Anderson, J. R.

1990-01-01

We report two patients who presented with small bowel obstruction secondary to peritoneal mesothelioma. The difficulties in establishing this diagnosis at an early stage are illustrated. Recent advances in the management of peritoneal mesothelioma are reviewed.

The mesothelioma in Europe; Le mesotheliome en Europe

Energy Technology Data Exchange (ETDEWEB)

Bignon, J. [Paris-12 Univ., 94 - Creteil (France)

1999-12-01

Though the primitive malignant tumors of the pleura have been identified in the years 1890, it is only in 1960 that Wagner and his team have published a study of 33 cases of mesothelioma in South Africa, attributed to crocidolite exposure for mines workers and their family. This publication went five years after the demonstration by Richard Doll in Great Britain of epidemiology relations between lungs cancer and professional exposure to asbestos dusts. Later, the research were on the type of asbestos fibers at the origin of the mesothelioma. The power of the chrysotile to induce this tumor among human beings was the object of controversy. but it is clear that the exposure to three kinds of amphibole asbestos (crocidolite, tremolite and anthophyllite) is responsible of the most important incidence of this cancer, even after low concentrations exposures. (N.C.)

Canine pleural mesothelioma as an indicator of environmental exposure to asbestos; Il mesotelioma pleurico del cane come indicatore di esposizione ambientale ad amianto

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De Nardo, P. [Istituto Superiore di Sanita`, Rome (Italy). Lab. di Medicina Veterinaria

1996-12-01

Canine pleural mesothelioma represents a `sentinel health event` because of the role of asbestos exposure in its etiology and pathogenesis. The observation of such event may thus trigger prevention-oriented remedial actions. This is especially due to the relatively short induction-latency time of canine mesothelioma, i.e. eight-nine years, versus the corresponding induction-latency time in humans (on average about thirty years). The observation of cases of canine mesothelioma may concur to the detection of previously unrecognized hazardous exposures to asbestos. On this ground, the epidemiologic surveillance of canine mesothelioma in Italy is suggested.

Malignant mesothelioma following radiation exposure

International Nuclear Information System (INIS)

Antman, K.H.; Corson, J.M.; Li, F.P.; Greenberger, J.; Sytkowski, A.; Henson, D.E.; Weinstein, L.

1983-01-01

Mesothelioma developed in proximity to the field of therapeutic radiation administered 10-31 years previously in four patients. In three, mesothelioma arose within the site of prior therapeutic radiation for another cancer. Mesothelioma in the fourth patient developed adjacent to the site of cosmetic radiation to a thyroidectomy scar. None of these four patients recalled an asbestos exposure or had evidence of asbestosis on chest roentgenogram. Lung tissue in one patient was negative for ferruginous bodies, a finding considered to indicate no significant asbestos exposure. Five other patients with radiation-associated mesothelioma have been reported previously, suggesting that radiation is an uncommon cause of human mesothelioma. Problems in the diagnosis of radiation-associated mesotheliomas are considered

Pleural mesothelioma - case report.

Science.gov (United States)

Klawiter, Anna; Damaszke, Tomasz

2010-10-01

Pleural mesothelioma is a very rare neoplasm; especially the local form. The diagnostics is difficult and the prognosis unfavourable. We presented a case of a man with dyspnoea and cough. His chest radiogram showed hydrothorax on the left side. Neither the examinations of the pleural liquid, nor the CT-guided fine needle biopsy established the diagnosis. CT showed features suggestive of pleural mesothelioma. The diagnosis was confirmed by thoracoscopy. Although no neoplastic cells were found in the thoracoscopic specimen from the supradiaphragmatic tumor, we assumed that to be a case of a diffuse, primarily local form of mesothelioma. Diagnostics of pleural mesothelioma is very difficult. CT and thoracoscopy seem to be very valuable diagnostic methods. It is worth remembering that pleural mesothelioma can have a local form which may transform into a diffuse one.

Compensation of pleural mesothelioma in France: data from the French National Mesothelioma Surveillance Programme.

Science.gov (United States)

Chamming's, Soizick; Clin, Bénédicte; Brochard, Patrick; Astoul, Philippe; Ducamp, Stéphane; Galateau-Salle, Fançoise; Ilg, Annabelle Gilg Soit; Goldberg, Marcel; Gramond, Céline; Imbernon, Ellen; Rolland, Patrick; Pairon, Jean-Claude

2013-02-01

The aim of this study was to determine the rates of compensation awarded to patients presenting with pleural mesothelioma and factors linked to such compensation in France. The study population consisted of 2,407 patients presenting with pleural mesothelioma, recorded by the National Mesothelioma Surveillance Programme between January 1, 1999 and December 31, 2009. Analysis of claims for recognition as "occupational disease" (OD) and claims for compensation by the Compensation Fund for Asbestos Victims (FIVA) were analyzed. Approximately 30% of subjects presenting with pleural mesothelioma, affiliated to the General National Health Insurance fund, neither sought recognition as an OD nor claimed for FIVA compensation. Gender, age at diagnosis, type of health insurance, and socio-professional category influence the likelihood of patients presenting with mesothelioma seeking compensation for this disease. Results show an under-compensation of pleural mesothelioma as OD and by the FIVA in France. Copyright © 2012 Wiley Periodicals, Inc.

Changing Pattern in Malignant Mesothelioma Survival

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Jennifer Faig

2015-02-01

Full Text Available Survival for mesothelioma has been shown to be poor, with marginal improvement over time. Recent advances in the understanding of pathophysiology and treatment of mesothelioma may impact therapy to improve survival that may not be evident from available clinical trials that are often small and not randomized. Therapies may affect survival differently based on mesothelioma location (pleural vs peritoneal. Data are conflicting regarding the effect of asbestos exposure on mesothelioma location. OBJECTIVES: We examined survival in a large cohort of mesothelioma subjects analyzed by tumor location and presence and mode of asbestos exposure. METHODS: Data were analyzed from cases (n = 380 diagnosed with mesothelioma from 1992 to 2012. Cases were either drawn from treatment referrals, independent medical evaluation for medical legal purposes, or volunteers who were diagnosed with mesothelioma. Subjects completed an occupational medical questionnaire, personal interview with the examining physician, and physician review of the medical record. RESULTS: This study reports better survival for mesothelioma than historical reports. Survival for peritoneal mesothelioma was longer than that for pleural mesothelioma (hazard ratio = 0.36, 95% confidence interval = 0.24-0.54, P < .001 after adjusting for gender and age at diagnosis. Non-occupational cases were more likely to be 1 diagnosed with peritoneal mesothelioma, 2 female, 3 exposed, and 4 diagnosed at a younger age and to have a 5 shorter latency compared to occupational cases (P < .001. CONCLUSION: Peritoneal mesothelioma was more likely associated with non-occupational exposure, thus emphasizing the importance of exposure history in enhancing early diagnosis and treatment impact.

Malignant mesothelioma

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Suzanne Alkul

2016-04-01

Full Text Available Seventy percent of patients with malignant mesothelioma have had exposure to asbestos fibers. Other patients without this exposure have had chronic pleural inflammation or received radiation to the thorax. Occasionally patients present with no obvious exposure history relevant to the development of malignant mesothelioma. This diagnosis needs to be in the differential diagnosis of all patients with unexplained pleural disease.

Radiologic diagnosis of pleural mesothelioma

International Nuclear Information System (INIS)

Fujimoto, Toshifumi; Hayashi, Kuniaki; Matsunaga, Naofumi

1989-01-01

Five cases of pleural mesothelioma (3 benign and 2 malignant) were evaluated with chest radiograph and CT. A case of benign localized mesothelioma growing within the major fissure, and a case of diffuse malignant mesothelioma encircling the descending thoracic aorta are included among the five cases. Pleural mesotheliomas present a variety of roentgenographic manifestations depending upon the histologic type, the site of origin, and the direction of the extension, and can easily be misdiagnosed as lung tumor, aortic aneurysm, or mediastinal tumor. It is emphasized that pleural mesothelioma should be considered as a differential diagnosis when a mass lesion is found in the mediastinum, hilar region, interlobar fissure, or near the chest wall. (author)

Malignant pleural mesothelioma

International Nuclear Information System (INIS)

Wentz, K.U.; Irngartinger, G.; Georgi, P.; Kaick, G. van; Kleckow, M.; Vollhaber, H.H.; Deutsches Krebsforschungszentrum, Heidelberg; Krankenhaus Rohrbach

1986-01-01

In 34 patients with suspected malignant pleural mesothelioma the results of computed tomography are compared with the findings of 67 Ga-scintigraphy. The differential diagnosis of 14 pleural mesotheliomas, 7 pleural carcinoses, 10 inflammatory and 3 other pleural diseases is performed more accurately by CT than by scintigraphy. 67 Ga uptake depends on the thickness of inflammatory as well as malignant lesions. Thus, numerous pleural processes that can be localised by CT escape scintigraphic detection, CT is indicated if there is clinical and radiological suspicion of pleural mesothelioma; in that case, there is hardly any indication for 67 Ga scintigraphy. (orig.)

Pleural mesothelioma – case report

International Nuclear Information System (INIS)

Klawiter, Anna; Damaszke, Tomasz

2010-01-01

Pleural mesothelioma is a very rare neoplasm; especially the local form. The diagnostics is difficult and the prognosis unfavourable. We presented a case of a man with dyspnoea and cough. His chest radiogram showed hydrothorax on the left side. Neither the examinations of the pleural liquid, nor the CT-guided fine needle biopsy established the diagnosis. CT showed features suggestive of pleural mesothelioma. The diagnosis was confirmed by thoracoscopy. Although no neoplastic cells were found in the thoracoscopic specimen from the supradiaphragmatic tumor, we assumed that to be a case of a diffuse, primarily local form of mesothelioma. Diagnostics of pleural mesothelioma is very difficult. CT and thoracoscopy seem to be very valuable diagnostic methods. It is worth remembering that pleural mesothelioma can have a local form which may transform into a diffuse one

Accumulation of radium in ferruginous protein bodies formed in lung tissue. Association of resulting radiation hotspots with malignant mesothelioma and other malignancies

International Nuclear Information System (INIS)

Nakamura, Eizo; Makishima, Akio; Hagino, Kyoko; Okabe, Kazunori

2009-01-01

While exposure to fibers and particles has been proposed to be associated with several different lung malignancies including mesothelioma, the mechanism for the carcinogenesis is not fully understood. Along with mineralogical observation, we have analyzed forty-four major and trace elements in extracted asbestos bodies (fibers and proteins attached to them) with coexisting fiber-free ferruginous protein bodies from extirpative lungs of individuals with malignant mesothelioma. These observations together with patients' characteristics suggest that inhaled iron-rich asbestos fibers and dust particles, and excess iron deposited by continuous cigarette smoking would induce ferruginous protein body formation resulting in ferritin aggregates in lung tissue. Chemical analysis of ferruginous protein bodies extracted from lung tissues reveals anomalously high concentrations of radioactive radium, reaching millions of times higher concentration than that of seawater. Continuous and prolonged internal exposure to hotspot ionizing radiation from radium and its daughter nuclides could cause strong and frequent DNA damage in lung tissue, initiate different types of tumour cells, including malignant mesothelioma cells, and may cause cancers. (author)

Statins do not alter the incidence of mesothelioma in asbestos exposed mice or humans.

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Cleo Robinson

Full Text Available 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.

Mesothelioma Applied Research Foundation

Science.gov (United States)

... Foundation Experts Can Answer Your Questions! The Mesothelioma Applied Research Foundation's team of experts is available to answer ... a law firm. Read more about the Mesothelioma Applied Research Foundation . TO GET HELP CALL: (877) End-Meso ...

National Mesothelioma Virtual Bank: A standard based biospecimen and clinical data resource to enhance translational research

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Valdivieso Federico A

2008-08-01

Full Text Available Abstract Background Advances in translational research have led to the need for well characterized biospecimens for research. The National Mesothelioma Virtual Bank is an initiative which collects annotated datasets relevant to human mesothelioma to develop an enterprising biospecimen resource to fulfill researchers' need. Methods The National Mesothelioma Virtual Bank architecture is based on three major components: (a common data elements (based on College of American Pathologists protocol and National North American Association of Central Cancer Registries standards, (b clinical and epidemiologic data annotation, and (c data query tools. These tools work interoperably to standardize the entire process of annotation. The National Mesothelioma Virtual Bank tool is based upon the caTISSUE Clinical Annotation Engine, developed by the University of Pittsburgh in cooperation with the Cancer Biomedical Informatics Grid™ (caBIG™, see http://cabig.nci.nih.gov. This application provides a web-based system for annotating, importing and searching mesothelioma cases. The underlying information model is constructed utilizing Unified Modeling Language class diagrams, hierarchical relationships and Enterprise Architect software. Result The database provides researchers real-time access to richly annotated specimens and integral information related to mesothelioma. The data disclosed is tightly regulated depending upon users' authorization and depending on the participating institute that is amenable to the local Institutional Review Board and regulation committee reviews. Conclusion The National Mesothelioma Virtual Bank currently has over 600 annotated cases available for researchers that include paraffin embedded tissues, tissue microarrays, serum and genomic DNA. The National Mesothelioma Virtual Bank is a virtual biospecimen registry with robust translational biomedical informatics support to facilitate basic science, clinical, and translational

CT findings of intrathoracic mesothelioma

International Nuclear Information System (INIS)

Kim, Yeong Hwa; Choi, Kyu Ok; Lee, Jong Doo

1989-01-01

8 patients with pathologically proven pleural mesothelioma (5 localized type, 3 diffuse type), and 1 patient with malignant pericardial mesothelioma, were examined by computed tomography (CT), and obtained some results as follows: 1. Pleural Mesothelioma a. Localized pleural mesothelioma 4 cases were benign and 1 case was malignant in microscopic examination. CT showed invariably sharply marginated pleura-based soft tissue mass and the density of the mass was variable, homogenous in small tumor but inhomogenous with low density area in larger ones, and even calcification was seen in one of them. The angle of pleura-mass interface was obtuse in only one small tumor and acute with smooth taping end in four lager tumor. b. Diffuse pleural mesothelioma (DPM) Multiple nodular pleural masses encompassing nearly entire lung were seen with associated multiple subpleural parenchymal nodule and localized axial interstitial thickening in two case. Protruding chest wall mass with destruction of rib was seen in previous pneumonectomized thorax. Minimal pleural effusion/thickening was also seen in all. 2. Pericardial mesothelioma Pericardial fluid and multiple nodular masses, which occupied pericardial sac up to superior sinus were well delineated on CT. It had been misinterpreted as pericardial effusion for years on echocardiogram

Profiling tumor-associated markers for early detection of malignant mesothelioma: an epidemiologic study

Czech Academy of Sciences Publication Activity Database

Amati, M.; Tomasetti, M.; Scartozzi, M.; Mariotti, L.; Alleva, R.; Pignotti, E.; Borghi, B.; Valentino, M.; Governa, M.; Neužil, Jiří; Santarelli, L.

2008-01-01

Roč. 17, č. 1 (2008), s. 163-170 ISSN 1055-9965 R&D Projects: GA AV ČR IAA500520602 Institutional research plan: CEZ:AV0Z50520514; CEZ:AV0Z50520701 Keywords : malignant mesothelioma * tumor markers * asbestos Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.770, year: 2008

Radiation therapy for pleural mesothelioma

International Nuclear Information System (INIS)

Seydel, H.G.

1986-01-01

There is clear evidence that both pleural and peritoneal malignant mesothelioma are increasing in incidence in the United States. There is a recognized long period of latency from asbestos exposure to the emergence and diagnosis of tumor. Considering the levels of asbestos utilization in the mid-20th century, we must expect that the number of cases will continue to increase until the end of this century. Evaluation of treatment options is thus a critical issue in determining treatment approaches for this disease. Recognized only recently, mesothelioma has no effective treatment, and patients are reported only anecdotally as cured. Pleural mesothelioma is the more common presentation, but even here the reports are from small, uncontrolled series. Only one study is available in which a concomitant comparison of treatment methods was carried out. Randomized clinical studies regarding treatment of pleural mesothelioma have only recently been initiated by the clinical cooperative groups. There is thus a paucity of information on treatment in general and radiation therapy specifically for malignant mesothelioma. This chapter reviews the reported experience using radiation therapy alone and combined with other modalities for the treatment of malignant pleural mesothelioma and considers the potential for improvement of the results of current methods of radiation therapy

Incidence of pleural mesothelioma in a community exposed to fibres with fluoro-edenitic composition in Biancavilla (Sicily, Italy

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Caterina Bruno

2014-06-01

Full Text Available INTRODUCTION. Amphibolic fibres with fluoro-edenitic composition characterize Biancavilla soil, including the major quarry from which building materials have been extensively extracted. These fibres induce mesothelioma in experimental animals and their in vitro biological action is similar to that of crocidolite. MATERIALS AND METHODS. Malignant mesothelioma case series and incidence were examined to evaluate the disease burden on Biancavilla inhabitants. RESULTS. The incidence of pleural mesothelioma in Biancavilla is steadily higher than in the Sicilian Region, risk estimates are more elevated in women than in men, the most affected age class is constituted by subjects aged less than 50. DISCUSSION AND CONCLUSIONS. Environmental exposure to fibres with fluoro-edenitic composition appears to be causally related to the elevated mesothelioma occurrence in Biancavilla. In this frame, environmental clean-up is the main goal to be pursued in public health terms. A contribution of scientific research to public health decision making with respect to priority setting for environmental clean-up can derive from some further selected epidemiological investigations.

Radiation-induced mesotheliomas in rats

International Nuclear Information System (INIS)

Hahn, F.F.; Haley, P.J.; Hubbs, A.F.; Hoover, M.D.; Lundgren, D.L.

1990-01-01

Mesotheliomas have been reported in rats that inhaled plutonium, but these tumors have not been extensively studied. To investigate a possible role for inhaled radionuclides in the induction of mesotheliomas, four life-span studies conducted at the Inhalation Toxicology Research Institute are reviewed. A total of 3076 F344 rats were exposed by inhalation to aerosols of 239 PuO 2 , mixed uranium-plutonium oxide, or 144 CeO 2 . Results showed that a low incidence of pleural mesotheliomas was induced by either alpha- or beta-emitting radionuclides deposited and retained in the lung. Chronic alpha irradiation was more effective per unit dose in producing mesotheliomas than chronic beta irradiation of the lung by a factor of 15. 7 refs., 1 tab., 7 figs

Mesothelioma and lung cancer mortality: a historical cohort study among asbestosis workers in Hong Kong.

Science.gov (United States)

Chen, Minghui; Tse, Lap Ah; Au, Ronald K F; Yu, Ignatius T S; Wang, Xiao-rong; Lao, Xiang-qian; Au, Joseph Siu-kei

2012-05-01

To investigate the mortality pattern among a cohort of workers with asbestosis in Hong Kong, with special emphases on mesothelioma and lung cancer. All 124 male workers with confirmed asbestosis in Hong Kong during 1981-2008 were followed up to December 31, 2008 to ascertain the vital status and causes of death. Standardized mortality ratio (SMR) for each underlying cause of death was calculated by using person-year method. Axelson's indirect method was applied to adjust for the potential confounding effect of cigarette smoking. A total of 86 deaths were observed after 432.8 person-years of observations. The SMR for overall mortality (6.06, 95% CI: 4.90-7.51) increased significantly. The elevated risk of deaths from all cancers (7.53, 95% CI: 5.38-10.25) was mainly resulted from a significantly excess risk from lung cancer (SMR=7.91, 95% CI: 4.32-13.29, 14 deaths) and mesothelioma (SMR=6013.63, 95% CI: 3505.95-9621.81, 17 deaths). The SMR for lung cancer retained statistically significant after adjustment of smoking. An increased smoking adjusted SMR was also suggested for all heart diseases (2.32, 95% CI: 0.93-4.79, 7 deaths) and acute myocardial infarction (3.10, 95% CI: 0.84-7.94, 4 deaths), though the statistical significance was borderline. We found a positive association with net years of exposure to asbestos for mesothelioma and lung cancer. Our study provided further evidence on the carcinogenesis of asbestos/asbestosis with the risk of deaths from lung cancer and mesothelioma. This study also provided a preliminary support for a possible link between asbestosis and heart disease, but power is limited. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Radiation-induced mesotheliomas in rats

Energy Technology Data Exchange (ETDEWEB)

Hahn, F.F.; Haley, P.J.; Hubbs, A.F.; Hoover, M.D.; Lundgren, D.L.

1990-01-01

Mesotheliomas have been reported in rats that inhaled plutonium, but these tumors have not been extensively studied. To investigate a possible role for inhaled radionuclides in the induction of mesotheliomas, four life-span studies conducted at the Inhalation Toxicology Research Institute are reviewed. A total of 3076 F344 rats were exposed by inhalation to aerosols of {sup 239}PuO{sub 2}, mixed uranium-plutonium oxide, or {sup 144}CeO{sub 2}. Results showed that a low incidence of pleural mesotheliomas was induced by either alpha- or beta-emitting radionuclides deposited and retained in the lung. Chronic alpha irradiation was more effective per unit dose in producing mesotheliomas than chronic beta irradiation of the lung by a factor of 15. 7 refs., 1 tab., 7 figs. (MHB)

Image diagnosis of malignant mesothelioma

International Nuclear Information System (INIS)

Niimi, Akiko; Ueno, Keiko; Isobe, Yoshinori; Hirayama, Akira

1987-01-01

3 cases of malignant mesothelioma confirmed by pathological examination were reported. CT showed solid mass with moderate enhancement by contrast medium. CT appears to be a very useful tool to make a diagnosis of malignant mesothelioma. (author)

Computed tomography findings of malignant pleural mesothelioma

Energy Technology Data Exchange (ETDEWEB)

Shiota, Yutaro; Sato, Toshio; Yamaguchi, Kazuo; Ono, Tetsuya; Kaji, Masaro; Niiya, Harutaka (Kure Kyosai Hospital, Hiroshima (Japan))

1994-04-01

Computed tomography (CT) findings were assessed in 7 patients with malignant mesothelioma. CT findings were also reviewed in 9 patients with lung cancer and pleuritis carcinomatosa and in 11 patients with tuberculous pleuritis. Five patients with malignant mesothelioma underwent CT scans twice, on admission and from 1 to 7 months after admission. Tuberculous pleuritis could be distinguished from pleuritis carcinomatosa and malignant mesothelioma by the presence or absence of pleural nodularity and chest wall invasion. Although it was difficult to identify specific CT features clearly distinguishing malignant mesothelioma from pleuritis carcinomatosa, characteristic findings of malignant mesothelioma appeared to include the rapid development and progression of pleural rind and a tendency to spread directly into the chest wall. We divided the pleural into the four regions; upper anterior, upper posterior, lower anterior and lower posterior regions. Pleural changes were more frequently seen in the lower pleural regions than in the upper pleural regions in malignant mesothelioma. (author).

Computed tomography findings of malignant pleural mesothelioma

International Nuclear Information System (INIS)

Shiota, Yutaro; Sato, Toshio; Yamaguchi, Kazuo; Ono, Tetsuya; Kaji, Masaro; Niiya, Harutaka

1994-01-01

Computed tomography (CT) findings were assessed in 7 patients with malignant mesothelioma. CT findings were also reviewed in 9 patients with lung cancer and pleuritis carcinomatosa and in 11 patients with tuberculous pleuritis. Five patients with malignant mesothelioma underwent CT scans twice, on admission and from 1 to 7 months after admission. Tuberculous pleuritis could be distinguished from pleuritis carcinomatosa and malignant mesothelioma by the presence or absence of pleural nodularity and chest wall invasion. Although it was difficult to identify specific CT features clearly distinguishing malignant mesothelioma from pleuritis carcinomatosa, characteristic findings of malignant mesothelioma appeared to include the rapid development and progression of pleural rind and a tendency to spread directly into the chest wall. We divided the pleural into the four regions; upper anterior, upper posterior, lower anterior and lower posterior regions. Pleural changes were more frequently seen in the lower pleural regions than in the upper pleural regions in malignant mesothelioma. (author)

Angiography of omental mesothelioma

International Nuclear Information System (INIS)

Marini, K.; Walter, J.F.

1984-01-01

Angiographic features of three cases of omental mesothelioma are presented. These lesions appeared mildly or moderately hypervascular without arteriovenous shunting or arterial encasement. The predominant feeding arteries were the right and left gastroepiploics. Since arteriography may be performed in the evaluation of the often nonspecific presenting symptoms of patients with abdominal mesothelioma, radiologists should be aware of these abnormalities

Localized malignant pleural mesothelioma: report of two cases.

Science.gov (United States)

Tanzi, Silvia; Tiseo, Marcello; Internullo, Eveline; Cacciani, Giancarlo; Capra, Roberto; Carbognani, Paolo; Rusca, Michele; Rindi, Guido; Ardizzoni, Andrea

2009-08-01

Localized malignant pleural mesothelioma is very rare tumor disease. There are sporadic reports in the literature showing that this entity has a different biologic behavior compared with diffuse pleural mesothelioma. We report two cases of radically resected localized pleural malignant mesothelioma, with a previous history of asbestos exposure. Both cases showed a microscopic and immunohistochemical findings of malignant mesothelioma, biphasic and sarcomatoid lympho-histiocitoid variant type, respectively, without evidence of diffuse pleural spread. The first is very peculiar case of bilateral localized malignant pleural mesothelioma with complete response to chemotherapy and localized late recurrence, radically resected and treated with adjuvant radiotherapy. The second case revealed as a solitary localized mass, underwent a complete en bloc resection and adjuvant radiotherapy. Both cases demonstrate that the localized malignant mesothelioma should be distinguished from diffuse form and that complete resection is associated with good prognosis.

Age and Space Irradiation Modulate Tumor Progression: Implications for Carcinogenesis Risk

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National Aeronautics and Space Administration — Age plays a major role in tumor incidence and is an important consideration when modeling the carcinogenesis process or estimating cancer risks. Epidemiological data...

Malignant pleural mesothelioma in US automotive mechanics: reported vs expected number of cases from 1975 to 2007.

Science.gov (United States)

Finley, Brent L; Pierce, Jennifer S; Paustenbach, Dennis J; Scott, Laura L F; Lievense, Laura; Scott, Paul K; Galbraith, David A

2012-10-01

Until the 1980s, chrysotile asbestos was a component of automotive brakes manufactured in the US. The current OSHA Bulletin (2006) for brake repair cites a single study (Lemen, 2004) which concluded that the number of mesothelioma cases reported in the literature in "end-product users of friction materials" indicated an asbestos-related risk for auto mechanics. However, Lemen (2004) did not compare the reported number of cases to an "expected" value, even though pleural mesothelioma occurs in the general population in the absence of asbestos exposure. We compare the number of malignant pleural mesothelioma (MPM) cases reported in the US literature among auto mechanics between 1975-2007 to an expected value derived from estimated numbers of current and former auto mechanics. A total of 106 cases categorized as mesothelioma or malignant neoplasm of the pleura were found in the literature. Using background incidence rates for MPM of two and three cases per million individuals per year, we estimated that a range of 278-515 cases of non-asbestos-related MPM, respectively, would have occurred in current or former auto mechanics from 1975-2007. Our findings are consistent with the numerous epidemiology studies that have found no increased risk of MPM in auto mechanics. Copyright © 2012 Elsevier Inc. All rights reserved.

Duodenal Metastasis of Malignant Pleural Mesothelioma

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Huang-Chi Chen

2008-12-01

Full Text Available Metastatic malignant mesothelioma of the pleura is uncommon at the time of initial diagnosis. The gastrointestinal lumen is rarely found at autopsy in patients with widespread disease. Here, we describe an extremely rare case of isolated duodenal metastasis of sarcomatoid mesothelioma of the pleura in a 73-year-old man, without memory of any direct exposure to asbestos. The possibility of gastrointestinal tract metastasis should be considered in the presence of anemia or positive occult blood test in patients with malignant pleural mesothelioma.

Continuing increase in mesothelioma mortality in Britain.

Science.gov (United States)

Peto, J; Hodgson, J T; Matthews, F E; Jones, J R

1995-03-04

Mesothelioma is closely related to exposure to asbestos, and mesothelioma mortality can be taken as an index of past exposure to asbestos in the population. We analysed mesothelioma mortality since 1968 to assess the current state of the mesothelioma epidemic, and to predict its future course. We found that rates of mesothelioma in men formed a clear pattern defined by age and date of birth. Rates rose steeply with age showing a very similar pattern in all five-year birth cohorts. By date of birth, rates increased from mid-1893 to mid-1948, and then fell. Relative to the 1943-48 cohort, the risk for the 1948-53 cohort is 0.79 and for the 1953-58 cohort 0.48. Despite these falls, if the age profile of rates for these cohorts follows the pattern of past cohorts, their predicted lifetime mesothelioma risks will be 1.3%, 1.0%, and 0.6%. Combining projections for all cohorts results in a peak of annual male mesothelioma deaths in about the year 2020 of between 2700 and 3300 deaths. If diagnostic trend is responsible for a 20% growth in recorded cases every 5 years--an extreme but arguable case--and if this trend has now ceased, the peak of annual male deaths will be reduced to 1300, reached around the year 2010. Analysis of occupations recorded on death certificates indicate that building workers, especially plumbers and gas fitters, carpenters and electricians are the largest high-risk group. These data indicate that mesothelioma deaths will continue to increase for at least 15 and more likely 25 years. For the worst affected cohorts--men born in the 1940s--mesothelioma may account for around 1% of all deaths. Asbestos exposure at work in construction and building maintenance will account for a large proportion of these deaths, and it is important that such workers should be aware of the risks and take appropriate precautions.

Treatment of malignant pleural mesothelioma

International Nuclear Information System (INIS)

Yusa, Toshikazu

2007-01-01

In Japan, it is predicted that mesothelioma will rapidly increase in the future. Malignant pleural mesothelioma that accounts for approximately 90% of mesothelioma as a whole has a median survival time of approximately nine months which is considered a poor prognosis. As for the treatment of this disease, extrapleural pneumonectomy or pleurectomy/decortication are available for those patients who can be surgically operated on. However, since a complete cure rate is low when only surgical treatment is performed, generally a multimodality treatment is performed wherein chemotherapy and/or radiotherapy are combined. For chemotherapy, a large-scale randomized phase III study demonstrated that a treatment using two agents: pemetrexed, which is a new multitargeted antifolate, and cisplatin is effective. Pemetrexed will be the drug of first choice for mesothelioma in the future. As other treatment methods, chemohyperthermia, treatments using various kinds of cytokines and angiogenesis inhibitors, genetic treatment and photodynamic therapy have been attempted. The current treatment results for this disease are very poor, and there has been a strong demand for establishing an effective treatment method. (author)

[Recurrent benign cystic peritoneal mesothelioma].

Science.gov (United States)

Stroescu, C; Negulescu, Raluca; Herlea, V; David, L; Ivanov, B; Nitipir, Cornelia; Popescu, I

2008-01-01

The benign cystic peritoneal mesothelioma (BCPM) is a rare neoplasm affecting mainly females at reproductive age. The natural history and physiopathology of the BCPM are not entirely known. It is mainly characterized by the lack of malignant elements, no tendency to metastasis and by a pervasive tendency to generate local recurrences after surgical removal. The clinical manifestations are insidious, uncharacteristic; the benign cystic peritoneal mesothelioma is often discovered during a surgical procedure addressing another condition. Imaging tests can raise the suspicion of BCPM but the diagnostic can only be confirmed by histopathological examination corroborated with an immunohistochemical analysis. There are no long term studies dictating a single therapeutic attitude but a high risk of local recurrences and the possibility of transformation into malignant mesothelioma have lead to the current tendency towards an aggressive treatment of the tumor. We present the case of a recurrent benign cystic peritoneal mesothelioma in a 40 years old female patient, emphasizing the therapeutic approach and the role of radical surgery in the treatment of BPCM.

Support vector machine for the diagnosis of malignant mesothelioma

Science.gov (United States)

Ushasukhanya, S.; Nithyakalyani, A.; Sivakumar, V.

2018-04-01

Harmful mesothelioma is an illness in which threatening (malignancy) cells shape in the covering of the trunk or stomach area. Being presented to asbestos can influence the danger of threatening mesothelioma. Signs and side effects of threatening mesothelioma incorporate shortness of breath and agony under the rib confine. Tests that inspect within the trunk and belly are utilized to recognize (find) and analyse harmful mesothelioma. Certain elements influence forecast (shot of recuperation) and treatment choices. In this review, Support vector machine (SVM) classifiers were utilized for Mesothelioma sickness conclusion. SVM output is contrasted by concentrating on Mesothelioma’s sickness and findings by utilizing similar information set. The support vector machine algorithm gives 92.5% precision acquired by means of 3-overlap cross-approval. The Mesothelioma illness dataset were taken from an organization reports from Turkey.

Aggressive malignant abdominal mesothelioma: Clinical report

International Nuclear Information System (INIS)

Al-Hassan, Ahmad M.; Al-Saigh, Abdulrehman A.

2004-01-01

A 32-year-old Filipino female, working as an x-ray technician, presented to the Emergency Room (ER) with acute abdominal pain for one day. The pain was mainly on the left side and left hypochondrium. She had recurring abdominal pain before but not significant to worry her. She also complained of abdominal distension, which she noticed one week ago. Abdominal examination revealed fullness in the left hypochondrium with marked tenderness but negative rebound. Abdominal ultrasound (US) showed a huge mass mainly in the left hypochondrium. The origin of the mass cannot be identified by US. A computerized tomography scan showed a mass in the left side of the abdomen crossing the midline with a necrotic centre. The hospital course of the patient runs smoothly, and she was discharged after 7-days and referred to an Oncology Center. Abdominal mesothelioma is a neoplasm arising from the mesothelial surface lining the abdominal cavity. It is less frequent than that of the pleura. It is a rapidly growing and fatal malignancy with a median survival of less than 1-year. The relation between pleural malignant mesothelioma and asbestos is well recognized since it was described in 19602 but implication of asbestos exposure in the etiology of the peritoneal type is less obvious. This patient history is giving no obvious exposure to asbestos but as she is working in the Radiology Department as an x-ray technician she is well exposed to x-ray, but the effect of radioactivity on induction of mesothelioma is still disputed.4 There are several reports linking malignant mesothelioma to radioactivity due to radiation therapy.The fibrous mesothelioma (sarcomatous), as in this case, which is difficult to diagnose microscopically, looks like a fibroma, unless helped by tissue culture. The treatment options of malignant mesothelioma include surgery, intraperitoneal chemotherapy and whole abdominal radiation or multimodality therapy, which were suggested that might prolong the survival in

Collective studies on carcinogenesis due to exposure to radiation

International Nuclear Information System (INIS)

Yamashita, Hisao

1980-01-01

Carcinogenesis was found in 150 of 25,692 patients who had received radiotherapy for benign diseases. Of primary diseases subjected to radiotherapy, skin diseases were the most. Carcinogenesis was found in 26 of 7,230 patients with skin diseases (0.36%) and 18 in 2286 patients with tuberculous cervical lymphadenitis (0.79%). The sites of carcinogenesis was the skin in 51 patients, the hypopharynx in 43, and the larynx in 18. Carcinogenesis was also found in 140 of 220,361 patients who had received radiotherapy for malignant tumors. As primary cancer, cancer of the cervix uteri was found in 59 of 48,662 patients, and breast cancer was found in 20 of 27,967 patients. As radiation-induced cancer, leukemia was found in 18 patients, soft tissue sarcoma in 18, skin cancer in 10, osteosarcoma in 6, cancer of the hypopharynx in 6, and cancer of the cervical esophagus in 6. It is necessary to differentiate cancer due to exposure to radiation from delayed recurrent cancer and double cancer. Irradiation fields should be restricted as small as possible in order to reduce carcinogenesis. As leukemia and carcinoma were found in a-bomb survivors exposed to very small dose of a-bomb radiation, carcinogenic mechanisms by chromosome aberrations, carcinogenic rates from a viewpoint of epidemiology, and other factors which influenced carcinogenesis are being investigated. (Tsunoda, M.)

Rare thoracic cancers, including peritoneum mesothelioma

NARCIS (Netherlands)

Siesling, Sabine; van der Zwan, Jan Maarten; Izarzugaza, Isabel; Jaal, Jana; Treasure, Tom; Foschi, Roberto; Ricardi, Umberto; Groen, Harry; Tavilla, Andrea; Ardanaz, Eva

Rare thoracic cancers include those of the trachea, thymus and mesothelioma (including peritoneum mesothelioma). The aim of this study was to describe the incidence, prevalence and survival of rare thoracic tumours using a large database, which includes cancer patients diagnosed from 1978 to 2002,

Rare thoracic cancers, including peritoneum mesothelioma

NARCIS (Netherlands)

Siesling, Sabine; Zwan, J.M.V.D.; Izarzugaza, I.; Jaal, J.; Treasure, T.; Foschi, R.; Ricardi, U.; Groen, H.; Tavilla, A.; Ardanaz, E.

2012-01-01

Rare thoracic cancers include those of the trachea, thymus and mesothelioma (including peritoneum mesothelioma). The aim of this study was to describe the incidence, prevalence and survival of rare thoracic tumours using a large database, which includes cancer patients diagnosed from 1978 to 2002,

Molecular epidemiology of radiation-induced carcinogenesis

International Nuclear Information System (INIS)

Trosko, J.E.

1996-01-01

The role of ionizing radiation in carcinogenesis is discussed. Every cell contains proto-oncogenes, which if damaged may lead to cell transformation. Every cell also contains tumor suppressor genes, which guard against transformation. Thus, transformation would seem to require a double injury to the DNA in a cell. Ionizing radiation is known to be a relatively weak mutagen, but a good clastogen (inducer of chromosome breaks, deletions and rearrangements). Ionizing radiation may therefore be a 'promoter' of cancer, i.e. a stimulant of the clonal expansion of transformed cells, if it kills enough cells to induce compensatory hyperplasia - i.e. rapid growth of cells. Ionizing radiation may be a 'progressor', if it deactivates tumor suppressor genes tending to suppress the growth of existing clones of transformed cells resulting from any of numerous causes. It may therefore be an oversimplification to say that radiation causes cancer; rather, it seems to be a weak initiator, an indirect promoter, and a late-stage progressor. 2 figs

Peritoneal Mesothelioma

Science.gov (United States)

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Pleural mesothelioma in Costa Rica

International Nuclear Information System (INIS)

Maineri-Hidalgo, Jose Alberto; Putvinsky, Vladimir; Mainieri-Breedy, Giovanna

2006-01-01

The mesothelioma is a neoplasia originated in the serous membranes that drape the cellomic cavities and there cover the visceras that they contain, whose development has related to the exhibition to the asbestos. The present study describes the characteristics of the cases of mesothelioma pleural diagnosed in 3 adults hospitals in Costa Rica. 29 cases of pleural mesothelioma were found between 1972 and 2002 after reviewing the pathology service archives of the 3 national general hospitals of the Costa Rican social security health system. The incidence rate in 2002 was 1 case per 2 million; there were 15 females and 14 males, with a mean age of 54 years. Twenty cases presented with pleural effusion being dyspnea, chest pain, cough, fever and weight loss the most frequent symptoms. The disease was detected in all the cases because of an abnormal chest X-ray. The method used to obtain tissue for histological diagnosis was thoracotomy for 15 cases, pleural biopsy in 8, thoracoscopy in 4 and autopsy in 2. The histological diagnosis in 16 cases was fibrous mesothelioma, 10 malignant and 6 benign, 11 were epithelial (all malignant) and 2 were malignant mixed mesothelioma. The treatment in all the benign cases was surgical resection and none recurred. Two of the malignant lesions were resected, 1 had an extrapleural pneumonectomy along with pericardial and diaphragmatic resection, but the survival was not better than the rest of the malignant cases, with an average survival rate for all of them of only 6 months. Chemotherapy and radiotherapy showed no additional benefit. (author) [es

[Molecular heterogeneity of malignant pleural mesotheliomas].

Science.gov (United States)

Tranchant, Robin; Montagne, François; Jaurand, Marie-Claude; Jean, Didier

2018-01-01

Malignant pleural mesothelioma (MPM) is predominantly an occupational cancer, most often linked to asbestos exposure. Malignant pleural mesothelioma prognosis is poor with a short survival median, due to the aggressiveness of tumor cells and the weak efficiency of conventional anti-cancer therapies. Clinical, histological, and molecular data suggest tumor heterogeneity between patients as it was also shown for other cancer types. Consequently, there is an urgent need to develop new therapies that take into account this heterogeneity and the molecular characteristics of malignant pleural mesothelioma, in particular by identifying new anti-cancer drugs targeting the molecular specificities of each malignant pleural mesothelioma. Malignant pleural mesothelioma is characterized by numerous molecular alterations at the chromosomal, genetic and epigenetic levels. Molecular classification based on gene expression profile has firstly defined two tumor groups, C1 and C2, and more recently, four groups. By integrating genetic and transcriptomic analysis, a C2 LN tumor subgroup of the C2 group has been identified and characterized. In addition to tumor heterogeneity between patients, intra-tumor heterogeneity is supported by several evidences. Most therapeutic strategies that take into account the tumor molecular characteristics have focused on targeted therapies based on mutated genes. A more appropriate strategy would be to consider better-defined tumor groups on the basis of several molecular alterations types as it has been proposed for the C2 LN subgroup. A robust definition of homogeneous tumor groups sharing common molecular characteristics is necessary for the development of effective precision medicine for malignant pleural mesothelioma. Copyright © 2017 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

Mesothelioma - A rare cause of dysphagia

Directory of Open Access Journals (Sweden)

Vishwanathan Swati

2016-08-01

Full Text Available A 81-year-old elderly Caucasian male presented with progressive dysphagia and unintentional weight loss over four months. His history was significant for asbestos exposure; however there was no history of asbestos related lung disease. Barium swallow showed achalasia and a subsequent CT chest showed a posterior mediastinal mass 11.8×9.1×5.8cm, compressing the distal oesophagus. Laparoscopic biopsy of the mass showed an epitheloid mesothelioma. Mass was deemed unresectable and patient was started on chemotherapy with Cisplatin/Pemetrexed. Localised mesothelioma is extremely rare, and dysphagia can be uncommon presenting feature. 7.4 per cent of cases of Pseudoachalasia are attributed to mesothelioma

Epidemiologic perspectives in radiation carcinogenesis

International Nuclear Information System (INIS)

Jablon, S.

1984-01-01

Epidemiological studies can tell much about carcinogenic effects at large doses, but not at small. To embark on large, long-term, expensive follow-up studies to learn something of scientific value about the effects of low doses-an average of three rads, say - is to waste time, effort, and money. It would be a fruitless effort even if the only problem to overcome was sampling variability - but it is not

Malignant mesothelioma due to non-occupational asbestos exposure from the Italian national surveillance system (ReNaM): epidemiology and public health issues.

Science.gov (United States)

Marinaccio, Alessandro; Binazzi, Alessandra; Bonafede, Michela; Corfiati, Marisa; Di Marzio, Davide; Scarselli, Alberto; Verardo, Marina; Mirabelli, Dario; Gennaro, Valerio; Mensi, Carolina; Schallemberg, Gert; Merler, Enzo; Negro, Corrado; Romanelli, Antonio; Chellini, Elisabetta; Silvestri, Stefano; Cocchioni, Mario; Pascucci, Cristiana; Stracci, Fabrizio; Ascoli, Valeria; Trafficante, Luana; Angelillo, Italo; Musti, Marina; Cavone, Domenica; Cauzillo, Gabriella; Tallarigo, Federico; Tumino, Rosario; Melis, Massimo

2015-09-01

Italy produced and imported a large amount of raw asbestos, up to the ban in 1992, with a peak in the period between 1976 and 1980 at about 160,000 tons/year. The National Register of Mesotheliomas (ReNaM, "Registro Nazionale dei Mesoteliomi" in Italian), a surveillance system of mesothelioma incidence, has been active since 2002, operating through a regional structure. The Operating Regional Center (COR) actively researches cases and defines asbestos exposure on the basis of national guidelines. Diagnostic, demographic and exposure characteristics of non-occupationally exposed cases are analysed and described with respect to occupationally exposed cases. Standardised incidence rates for pleural mesothelioma in 2008 were 3.84 (per 100,000) for men and 1.45 for women, respectively. Among the 15,845 mesothelioma cases registered between 1993 and 2008, exposure to asbestos fibres was investigated for 12,065 individuals (76.1%), identifying 530 (4.4%) with familial exposure (they lived with an occupationally exposed cohabitant), 514 (4.3%) with environmental exposure to asbestos (they lived near sources of asbestos pollution and were never occupationally exposed) and 188 (1.6%) exposed through hobby-related or other leisure activities. Clusters of cases due to environmental exposure are mainly related to the presence of asbestos-cement industry plants (Casale Monferrato, Broni, Bari), to shipbuilding and repair activities (Monfalcone, Trieste, La Spezia, Genova) and soil contamination (Biancavilla in Sicily). Asbestos pollution outside the workplace contributes significantly to the burden of asbestos-related diseases, suggesting the need to prevent exposures and to discuss how to deal with compensation rights for malignant mesothelioma cases induced by non-occupational exposure to asbestos. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Malignant pleural mesothelioma in a nuclear engineer

International Nuclear Information System (INIS)

Huncharek, M.

1988-01-01

Malignant pleural mesothelioma accounts for a large proportion of deaths among occupational cohorts exposed to asbestos. Of particular interest are recent reports of a high risk of mesothelioma among occupational groups previously thought to be at low risk for developing this neoplasm. In the present report we present a case of pleural mesothelioma associated with bystander exposure to asbestos in a nuclear engineer. To our knowledge, this is the first report of the disease occurring in a member of this occupational group after work related exposure to asbestos. (author)

Validation of the diagnosis of mesothelioma and BAP1 protein expression in a cohort of asbestos textile workers from Northern Italy.

Science.gov (United States)

Boffetta, P; Righi, L; Ciocan, C; Pelucchi, C; La Vecchia, C; Romano, C; Papotti, M; Pira, E

2018-02-01

Diagnosis of mesothelioma based on death certificate is subject to misclassification, which may bias the results of epidemiology studies. A high proportion of mesothelioma harbor mutations in the BRCA1-associated protein 1 (BAP1) gene. We searched medical and pathology records and specimens for 127 workers from a textile-asbestos factory in Italy who died during 1963-2013 with a diagnosis of pleural or peritoneal neoplasm or mesothelioma on death certificate, to confirm the diagnosis with immunohistochemistry markers. We calculated the odds ratio of confirmation by selected characteristics and asbestos exposure variables. When sufficient pathology material was available, we analyzed BAP1 protein expression. The diagnosis of mesothelioma was histologically confirmed for 35 cases (27.6%); 5 cases were classified as non-mesothelioma (3.9%), for 33 cases a mention of mesothelioma was found on record but no sufficient material was available for revision (26.0%); no records were available for 54 cases (death-certificate-only 42.5%). Diagnostic confirmation was not associated with sex, location of the neoplasm, age, or duration of employment; however, there was a significant association with time since first employment (P for linear trend 0.04). An association between duration of employment and time since first employment was observed for confirmed cases but not for death-certificate-only cases. BAP1 protein was lost in 18/35 cases (51.4%), without an association with sex, location, age, indices of asbestos exposure, or survival. We were able to confirm by immunohistochemistry a small proportion of mesothelioma diagnoses on certificates of deceased asbestos workers, and confirmation correlated with latency of asbestos exposure but not other characteristics. BAP1 protein loss is a frequent event in mesothelioma of asbestos-exposed workers, but does not correlate with exposure. © The Author 2017. Published by Oxford University Press on behalf of the European Society for

Pleural mesothelioma – case report

OpenAIRE

Klawiter, Anna; Damaszke, Tomasz

2010-01-01

Summary Background: Pleural mesothelioma is a very rare neoplasm; especially the local form. The diagnostics is difficult and the prognosis unfavourable. Case Report: We presented a case of a man with dyspnoea and cough. His chest radiogram showed hydrothorax on the left side. Neither the examinations of the pleural liquid, nor the CT-guided fine needle biopsy established the diagnosis. CT showed features suggestive of pleural mesothelioma. The diagnosis was confirmed by thoracoscopy. Althoug...

Content validity and electronic PRO (ePRO) usability of the Lung Cancer Symptom Scale-Mesothelioma (LCSS-Meso) in mesothelioma patients.

Science.gov (United States)

Gelhorn, Heather L; Skalicky, Anne M; Balantac, Zaneta; Eremenco, Sonya; Cimms, Tricia; Halling, Katarina; Hollen, Patricia J; Gralla, Richard J; Mahoney, Martin C; Sexton, Chris

2018-02-01

Obtaining qualitative data directly from the patient perspective enhances the content validity of patient-reported outcome (PRO) instruments. The objective of this qualitative study was to evaluate the content validity of the Lung Cancer Symptom Scale for Mesothelioma (LCSS-Meso) and its usability on an electronic device. A cross-sectional methodological study, using a qualitative approach, was conducted among patients recruited from four clinical sites. The primary target population included patients with pleural mesothelioma; data were also collected from patients with peritoneal mesothelioma on an exploratory basis. Semi-structured interviews were conducted consisting of concept elicitation, cognitive interviewing, and evaluation of electronic patient-reported outcome (ePRO) usability. Participants (n = 21) were interviewed in person (n = 9) or by telephone (n = 12); 71% were male with a mean age of 69 years (SD = 14). The most common signs and symptoms experienced by participants with pleural mesothelioma (n = 18) were shortness of breath, fluid build-up, pain, fatigue, coughing, and appetite loss. The most commonly described symptoms for those with peritoneal mesothelioma (n = 4) were bloating, changes in appetite, fatigue, fluid build-up, shortness of breath, and pain. Participants with pleural mesothelioma commonly described symptoms assessed by the LCSS-Meso in language consistent with the questionnaire and a majority understood and easily completed each of the items. The ePRO version was easy to use, and there was no evidence that the electronic formatting changed the way participants responded to the questions. Results support the content validity of the LCSS-Meso and the usability of the electronic format for use in assessing symptoms among patients with pleural mesothelioma.

Cutaneous Presentation of Mesothelioma With a Sarcomatoid Transformation.

Science.gov (United States)

Klebanov, Nikolai; Reddy, Bobby Y; Husain, Sameera; Silvers, David N; Grossman, Marc E; Tsao, Hensin

2018-05-01

Malignant pleural mesothelioma is a rare neoplasm of mesodermal origin. Cutaneous involvement of malignant pleural mesothelioma is a very rare entity, with only 11 cases reported in the literature. Here, we describe the case of a 75-year-old man with stage IV epithelioid pleural mesothelioma, presenting with a cutaneous eruption 5 months after initial diagnosis, which revealed sarcomatoid features on skin biopsy. Histological analysis of malignancy progression through immunohistochemical staining of the pleural, lymph node, and skin tissue revealed gradual loss of calretinin and gain of desmin, supporting a transformation from epithelioid to sarcomatoid tissue. To our knowledge, this is the first reported case of an epithelioid to sarcomatoid transformation of malignant pleural mesothelioma manifesting in a cutaneous presentation.

Reduced type II interleukin-4 receptor signalling drives initiation, but not progression, of colorectal carcinogenesis: evidence from transgenic mouse models and human case?control epidemiological observations

OpenAIRE

Ingram, Nicola; Northwood, Emma L.; Perry, Sarah L.; Marston, Gemma; Snowden, Helen; Taylor, John C.; Scott, Nigel; Bishop, D. Timothy; Coletta, P. Louise; Hull, Mark A.

2013-01-01

We investigated the role of interleukin (IL)-4 receptor (IL-4R) signalling during mouse carcinogen-induced colorectal carcinogenesis and in a case-control genetic epidemiological study of IL-4Rα single nucleotide polymorphisms (SNPs). Azoxymethane-induced aberrant crypt focus (ACF; 6 weeks) and tumours (32 weeks) were analysed in wild-type (WT) BALB/c mice, as well as in IL-4Rα (-) (/-) , IL-13 (-/-) and 'double-knockout' (DKO) animals. Colorectal cancer (CRC) cases (1502) and controls (584) ...

The peritoneal mesothelioma: 4 cases reports

International Nuclear Information System (INIS)

Park, Youn Kyeung; Sung, Kyu Bo; Park, Hae Won; Lee, Young Rae

1990-01-01

Mesothelioma are infrequently encountered tumors that aries from the surface of any mesothelial lined body cavity. They are found most often in the pleural cavity, less frequently in the peritoneal cavity, and much less frequently in the pericardial cavity or arising from the tunica vaginalis. Tumors are most malignant and usually are detected late in their course when they begin to interfere with organ function. Most noninvasive diagnostic efforts are not helpful. The radiographic appearance is nonspecific and so, diagnosis is commonly made by laparoscopy and laparotomy. We experienced 4 cases of 2 malignant and 2 benign peritoneal mesothelioma which were no evidence of asbestose exposure. And, we believe that one case of malignant mesothelioma may be a consequence of prior radiation therapy

Differential CT features between malignant mesothelioma and pleural metastasis from lung cancer or extra thoracic primary tumor mimicking malignant mesothelioma

Energy Technology Data Exchange (ETDEWEB)

Lee, Sung Il; Ryu, Young Hoon; Lee, Kwang Hun; Choe, Kyu Ok; Kim, Sang Jin [College of Medicine, Yonsei University, Seoul (Korea, Republic of)

2000-01-01

To evaluate the differential CT features found among malignant mesothelioma and pleural metastasis from lung cancer and from extra-thoracic primary tumor which on CT mimic malignant mesothelioma. Forty-four patients who on chest CT scans showed pleural thickening suggesting malignant pleural disease and in whom this condition was pathologically confirmed were included in this study. On the basis of their pathologically proven primary disease (malignant mesothelioma (n=3D14), pleural metastasis of lung cancer (n=3D18), extra thoracic primary tumor (n=3D12). They were divided into three groups. Cases of lung which on CT showed a primary lung nodule or endobronchial mass with pleural lesion, or manifested only pleural effusion, were excluded. The following eight CT features were retrospectively analyzed: (1) configuration of pleural lesion (type I, single or multiple separate nodules, type II, localized flat pleural thickening, type III, diffuse flat pleural thickening; type IV, type III with pleural nodules superimposed; type V, mass filling the hemithorax), (2) the presence of pleural effusion, (3) chest wall or rib invasion, (4) the involvement of a major fissure, (5) extra-pleural fat proliferation, (6) calcified plaque, (7) metastatic lymph nodes, (8) metastatic lung modules. In malignant mesothelioma, type IV (8/14) or II (4/14) pleural thickening was relatively frequent. Pleural metastasis of lung cancer favored type IV (8/18) or I (6/18) pleural thickening, while pleural metastasis from extrathoracic primary tumor showed a variable thickening configuration, except type V. Pleural metastasis from lung cancer and extrapleural primary tumor more frequently showed type I configuration than did malignant mesothelioma, and there were significant differences among the three groups. Fissural involvement, on the other hand, was significantly more frequent in malignant mesothelioma than in pleural metastasis from lung cancer or extrapleural primary tumor. Metastatic

A conditional mouse model for malignant mesothelioma

NARCIS (Netherlands)

Jongsma, Johan; van Montfort, Erwin; Vooijs, Marc; Zevenhoven, John; Krimpenfort, Paul; van der Valk, Martin; van de Vijver, Marc; Berns, Anton

2008-01-01

Malignant mesothelioma is a devastating disease that has been associated with loss of Neurofibromatosis type 2 (NF2) and genetic lesions affecting RB and P53 pathways. We introduced similar lesions in the mesothelial lining of the thoracic cavity of mice. Mesothelioma developed at high incidence in

Tumour-derived GM-CSF promotes granulocyte immunosuppression in mesothelioma patients.

Science.gov (United States)

Khanna, Swati; Graef, Suzanne; Mussai, Francis; Thomas, Anish; Wali, Neha; Yenidunya, Bahar Guliz; Yuan, Constance M; Morrow, Betsy; Zhang, Jingli; Korangy, Firouzeh; Greten, Tim F; Steinberg, Seth M; Stetler-Stevenson, Maryalice; Middleton, Gary; De Santo, Carmela; Hassan, Raffit

2018-03-30

The cross talk between tumour cells, myeloid cells, and T cells play a critical role in tumour pathogenesis and response to immunotherapies. Although the aetiology of mesothelioma is well understood the impact of mesothelioma on the surrounding immune microenvironment is less well studied. In this study the effect of the mesothelioma microenvironment on circulating and infiltrating granulocytes and T cells is investigated. Tumour and peripheral blood from mesothelioma patients were evaluated for presence of granulocytes, which were then tested for their T cell suppression. Co-cultures of granulocytes, mesothelioma cells, T cells were used to identify the mechanism of T cell inhibition. Analysis of tumours showed that the mesothelioma microenvironment is enriched in infiltrating granulocytes, which inhibit T cell proliferation and activation. Characterisation of the blood at diagnosis identified similar, circulating, immunosuppressive CD11b+CD15+HLADR- granulocytes at increased frequency compared to healthy controls. Culture of healthy-donor granulocytes with human mesothelioma cells showed that GM-CSF upregulates NOX2 expression and the release of Reactive Oxygen Species (ROS) from granulocytes, resulting in T cell suppression. Immunohistochemistry and transcriptomic analysis revealed that a majority of mesothelioma tumours express GM-CSF and that higher GM-CSF expression correlated with clinical progression. Blockade of GM-CSF with neutralising antibody, or ROS inhibition, restored T cell proliferation suggesting that targeting of GM-CSF could be of therapeutic benefit in these patients. Our study presents the mechanism behind the cross-talk between mesothelioma and the immune micro-environment and indicates that targeting GM-CSF could be a novel treatment strategy to augment immunotherapy. Copyright ©2018, American Association for Cancer Research.

CT findings of peritoneal mesothelioma

International Nuclear Information System (INIS)

Woo, Young Hoon; Oh, Yeon Hee; Kim, Hong; Kim, Jung Sik; Woo, Seong Ku; Kim, Ok Bae; Joo, Yang Goo

1990-01-01

The peritoneal mesothelioma is a rare neoplasm which arises from the peritoneal lining of the abdomen, tending to spread along the peritoneal cavity and to invade abdominal organs. Authors report the CT findings of 4 patients with histologically proven peritoneal mesothelioma seen at Dongsan Medical Center, School of Medicine, Keimyung University. None of them had a history of exposure to asbestos and no clear etiologic factor could be determined in any patient. CT showed peritoneal and mesenteric thickenings in all cases, omental thickenings in 3 cases, peritoneal nodules, mesenteric masses or omental masses in 2 cases each other, bowel wall involvement in 1 case, and disproportionally small ascites in 2 cases. Distant hematogenous metastases to the liver and retroperitoneal lymph nodes were seen in 1 case. Our experience with 4 peritoneal mesotheliomas as well as a review of the recent imaging literature shows excellent correlation between computed tomography and the operitoneoscopic findings

Mouse Xenograft Model for Mesothelioma | NCI Technology Transfer Center | TTC

Science.gov (United States)

The National Cancer Institute is seeking parties interested in collaborative research to co-develop, evaluate, or commercialize a new mouse model for monoclonal antibodies and immunoconjugates that target malignant mesotheliomas. Applications of the technology include models for screening compounds as potential therapeutics for mesothelioma and for studying the pathology of mesothelioma.

Intercellular Communication in Malignant Pleural Mesothelioma: Properties of Tunneling Nanotubes

Directory of Open Access Journals (Sweden)

Justin William Ady

2014-10-01

Full Text Available Malignant pleural mesothelioma is a particularly aggressive and locally invasive malignancy with a poor prognosis despite advances in understanding of cancer cell biology and development of new therapies. At the cellular level, cultured mesothelioma cells present a mesenchymal appearance and a strong capacity for local cellular invasion. One important but underexplored area of mesothelioma cell biology is intercellular communication. Our group has previously characterized in multiple histological subtypes of mesothelioma a unique cellular protrusion known as tunneling nanotubes (TnTs. TnTs are long, actin filament-based, narrow cytoplasmic extensions that are non-adherent when cultured in vitro and are capable of shuttling cellular cargo between connected cells. Our prior work confirmed the presence of nanotube structures in tumors resected from patients with human mesothelioma. In our current study, we quantified the number of TnTs/cell among various mesothelioma subtypes and normal mesothelial cells using confocal microscopic techniques. We also examined TnT length among adherent cells and cells in suspension. We further examined potential approaches to the in vivo study of TnTs in animal models of cancer. We have developed novel approaches to study TnTs in aggressive solid tumor malignancies and define fundamental characteristics of TnTs in malignant mesothelioma. There is mounting evidence that TnTs play an important role in intercellular communication in mesothelioma and thus merit further investigation of their role in vivo.

Certified causes of death in patients with mesothelioma in South East England

Directory of Open Access Journals (Sweden)

Peto Julian

2009-01-01

Full Text Available Abstract Background Mesothelioma is a highly fatal cancer that is caused by exposure to asbestos fibres. In many populations, the occurrence of mesothelioma is monitored with the use of mortality data from death certification. We examine certified causes of death of patients who have been diagnosed with mesothelioma, and assess the validity of death certification data as a proxy for mesothelioma incidence. Methods We extracted mesothelioma registrations in the South East of England area between 2000 and 2004 from the Thames Cancer Registry database. We retained for analysis 2200 patients who had died at the time of analysis, after having excluded seven dead cases where the causes of death were not known to the cancer registry. The 2200 deaths were classified hierarchically to identify (1 mesothelioma deaths, (2 deaths certified as lung cancer deaths or (3 deaths from unspecified cancer, and (4 deaths from other causes. Results 87% of the patients had mesothelioma mentioned on the death certificate. 6% had no mention of mesothelioma but included lung cancer as a cause of death. Another 6% had no mention of mesothelioma or lung cancer, but included an unspecified cancer as a cause of death. Lastly, 2% had other causes of death specified on the death certificate. Conclusion This analysis suggests that official mortality data may underestimate the true occurrence of mesothelioma by around 10%.

Mesothelioma patient derived tumor xenografts with defined BAP1 mutations that mimic the molecular characteristics of human malignant mesothelioma

International Nuclear Information System (INIS)

Kalra, Neetu; Zhang, Jingli; Thomas, Anish; Xi, Liqiang; Cheung, Mitchell; Talarchek, Jacqueline; Burkett, Sandra; Tsokos, Maria G; Chen, Yuanbin; Raffeld, Mark; Miettinen, Markku; Pastan, Ira; Testa, Joseph R; Hassan, Raffit

2015-01-01

The development and evaluation of new therapeutic approaches for malignant mesothelioma has been sparse due, in part, to lack of suitable tumor models. We established primary mesothelioma cultures from pleural and ascitic fluids of five patients with advanced mesothelioma. Electron microscopy and immunohistochemistry (IHC) confirmed their mesothelial origin. Patient derived xenografts were generated by injecting the cells in nude or SCID mice, and malignant potential of the cells was analyzed by soft agar colony assay. Molecular profiles of the primary patient tumors, early passage cell cultures, and patient derived xenografts were assessed using mutational analysis, fluorescence in situ hybridization (FISH) analysis and IHC. Primary cultures from all five tumors exhibited morphologic and IHC features consistent to those of mesothelioma cells. Mutations of BAP1 and CDKN2A were each detected in four tumors. BAP1 mutation was associated with the lack of expression of BAP1 protein. Three cell cultures, all of which were derived from BAP1 mutant primary tumors, exhibited anchorage independent growth and also formed tumors in mice, suggesting that BAP1 loss may enhance tumor growth in vivo. Both early passage cell cultures and mouse xenograft tumors harbored BAP1 mutations and CDKN2A deletions identical to those found in the corresponding primary patient tumors. The mesothelioma patient derived tumor xenografts with mutational alterations that mimic those observed in patient tumors which we established can be used for preclinical development of novel drug regimens and for studying the functional aspects of BAP1 biology in mesothelioma. The online version of this article (doi:10.1186/s12885-015-1362-2) contains supplementary material, which is available to authorized users

Peritoneal mesothelioma: CT and MRI findings

International Nuclear Information System (INIS)

Puvaneswary, M.; Chen, S.; Proietto, T.

2002-01-01

Two patients with histologically proven diagnosis of peritoneal mesothelioma are presented. Both patients had CT scans of the abdomen. The second patient was also examined with MRI. Although imaging findings are striking, they are non-specific and diagnosing peritoneal mesothelioma in the absence of pleural calcification or pleural plaque on chest radiograph or CT is difficult. However, it is possible to suggest the correct diagnosis in a patient with the presence of non-calcified omental and peritoneal infiltration or masses without liver secondaries or lymphadenopathy. Magnetic resonance imaging with its multi-planar capabilities is a highly sensitive non-invasive modality in the evaluation of malignant peritoneal mesothelioma and can demonstrate the exact site and clarify whether the mass is arising from the peritoneal surface or within a visceral organ. Copyright (2002) Blackwell Science Pty Ltd

Radiation carcinogenesis

International Nuclear Information System (INIS)

1978-01-01

The Cancergram deals with all aspects of radiation carcinogenesis. The term radiation here includes U-V radiation and the entire electromagnetic spectrum, electron and other charged particle beams, neutrons, and alpha and beta radiation from radioactive substances. Abstracts included concern relationships between radiation and carcinogenesis in humans, experimental induction of tumors in animals by irradiation, studies on the mechanism of radiation carcinogenesis at the cellular level, studies of RBE, dose response or dose threshold in relation to radiation carcinogenesis, and methods and policies for control of radiation exposure in the general population. In general, this Cancergram excludes abstracts on radio-therapy, radiologic diagnosis, radiation pathology, and radiation biology, where these articles have no bearing on radiation carcinogenesis

Malignant mesothelioma after radiation treatment for Hodgkin lymphoma

NARCIS (Netherlands)

de Bruin, Marie L.; Burgers, Jacobus A.; Baas, Paul; van 't Veer, Mars B.; Noordijk, Evert M.; Louwman, Marieke W. J.; Zijlstra, Josée M.; van den Berg, Hendrik; Aleman, Berthe M. P.; van Leeuwen, Flora E.

2009-01-01

Malignant mesothelioma is a relatively uncommon malignancy. Although the pathogenesis is primarily related to asbestos, the disease may be associated with radiation exposure. Recently, increased risks for second primary mesothelioma after radiation for lymphoma have been reported. Because these

Deciduoid mesothelioma of the thorax: A comprehensive review of the scientific literature.

Science.gov (United States)

Paliogiannis, Panagiotis; Putzu, Carlo; Ginesu, Giorgio Carlo; Cossu, Maria Laura; Feo, Claudio Francesco; Attene, Federico; Scognamillo, Fabrizio; Nonnis, Rita; Cossu, Antonio; Palmieri, Giuseppe; Pirina, Pietro; Fois, Alessandro

2018-03-01

Deciduoid mesothelioma is a rare variant of malignant epithelioid mesothelioma. It often involves the peritoneum, but also thoracic cases have been reported. The aim of the present review is to describe the demographic, clinical, radiological, and pathological features of such a rare variant of thoracic mesothelioma, and the state of the art regarding the therapeutic approaches currently available. English-language articles published from 1985 to June 2016, and related to thoracic deciduoid mesothelioma cases were retrieved using the Pubmed database. The search terms were "mesothelioma," "thoracic mesothelioma," "epithelial mesothelioma," "pleural mesothelioma," and "deciduoid mesothelioma." Forty-four cases included in 16 articles, published in the period under investigation, were analyzed in detail. The mean age of the patients was 63 years, and the male to female ratio 1.7:1. Approximately 58% had exposure to asbestos, and 73% had a smoking history; familiarity was rarely reported. The most common anatomical site of origin was the right pleura, and the most frequent clinical manifestations were chest pain, dyspnea, cough, and weight loss. Thoracic X-ray and computed tomography were the imaging techniques most employed for diagnosis and surgical planning. The pathological diagnosis was obtained by examination of surgical or biopsy specimens in most cases. The best treatment strategy of deciduoid mesothelioma is a matter of debate; nevertheless a multidisciplinary approach is currently the best option for the choice of the adequate therapeutic scheme. © 2017 John Wiley & Sons Ltd.

Malignant mesothelioma after radiation treatment for Hodgkin lymphoma

DEFF Research Database (Denmark)

De Bruin, Marie L; Burgers, Jacobus A; Baas, Paul

2009-01-01

Malignant mesothelioma is a relatively uncommon malignancy. Although the pathogenesis is primarily related to asbestos, the disease may be associated with radiation exposure. Recently, increased risks for second primary mesothelioma after radiation for lymphoma have been reported. Because these f...

Analysis of "dry" mesothelioma with ultrasound guided biopsies

NARCIS (Netherlands)

Stigt, Jos A.; Boers, James E.; Groen, Harry J. M.

2012-01-01

Background: Image-guided sampling of the thickened pleura is a sensitive approach in patients with malignant pleural mesothelioma with pleural effusion. Malignant pleural mesothelioma presenting without effusion however is more of a diagnostic challenge. In this study we report the diagnostic yield

Case-control study of mesothelioma in the shipyard industry

International Nuclear Information System (INIS)

Correa-Villasenor, A.

1987-01-01

A nested case-control study was undertaken to investigate the relationship between occupational exposures to asbestos and low-level gamma radiation and mesothelioma. One hundred nineteen cases and four hundred fifty-two latency-matched controls were selected. Analyses were conducted using the conditional maximum likelihood estimate of the odds ratio and conditional logistic regression for matched sets. The results from the analyses revealed a relationship between asbestos exposure and mesothelioma; the strength of this relationship increased with the intensity and duration of the asbestos exposure. Exposure to low-level gamma radiation was also associated with an increased risk of mesothelioma. There was no interaction between asbestos and radiation. Shipyard employment in non-asbestos jobs and male gender were also found to be associated with mesothelioma

Occurrence of malignant peritoneal mesothelioma after surgery and irradiation for cervical cancer

International Nuclear Information System (INIS)

Beier, K.M.; Gallup, D.G.; Burgess, R.; Stock, R.J.

1984-01-01

Mesothelioma of the peritoneal cavity after irradiation is rare, and the diagnosis is sometimes difficult to establish. The following case is a report of a mesothelioma occurring 9 years after radiation therapy for carcinoma of the cervix. In this patient, who had a hysterectomy and bilateral oophorectomy 7 years prior to the mesothelioma diagnosis, the histologic, histochemical, and ultrastructural findings were all consistent with a diagnosis of malignant peritoneal mesothelioma. It is believed that this case is one of the first well-documented cases of peritoneal mesothelioma in a female who was treated by pelvic irradiation for another neoplasm

Advances in diagnosis and treatment of malignant mesothelioma

NARCIS (Netherlands)

J.P.J.J. Hegmans (Joost)

2006-01-01

textabstractIn late 1960’s, physician Dr. J. Stumphius identified twenty-five cases of a rare aggressive tumor known as mesothelioma among shipyard “Royal Schelde” workers due to asbestos exposure (1,2). Further observations showed an increase of mesothelioma cases among these workers. In 1974,

Diffuse malignant mesothelioma. Prospective evaluation of 69 patients

International Nuclear Information System (INIS)

Chahinian, A.P.; Pajak, T.F.; Holland, J.F.; Norton, L.; Ambinder, R.M.; Mandel, E.M.

1982-01-01

From 1974 to 1980, 69 patients with ith diffuse malignant mesothelioma were prospectively evaluated. The initial site of involvement was the pleura in 57 patients and the peritoneum in 12. Previous asbestos exposure was found in 53 patients (77%), with a shorter period of latency for peritoneal (mean, 28 years) than for ith pleural mesothelioma (mean, 35 years) than for pleural mesothelioma (mean, 35 years). Other associated exposure or diseases included talc, mica, familial Mediterranean fever, and diffuse lymphocytic lymphoma (one patient each). Thrombocytosis was common, as were thromboembolic episodes. Survival was significantly better for patients with an epithelial subtype, with pleural versus peritoneal mesothelioma, and for those under 65 years of age. Surgery was never curative, but its extent was correlated with survival and earlier diagnosis. Results of chemotherapy with doxorubicin and 5-azacytidine yielded a somewhat better survival rate than a combined program with doxorubicin and radiotherapy. Survival after chemotherapy was correlated with performance status, response to chemotherapy, and extent of previous surgery

Malignant pleural mesothelioma in a 13-year-old girl

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Goyal, M.; Konez, O.; Patel, D. [Department of Radiology, Children' s Hospital Medical Center of Akron, OH (United States); Department of Radiology, Aultman Hospital, Canton, OH (United States); Swanson, K.F.; Vyas, P.K. [Department of Radiology, Children' s Hospital Medical Center of Akron, OH (United States)

2000-11-01

Pleural mesothelioma is an uncommon tumor in all age groups, but is especially rare in childhood. We describe the clinical and radiological features of malignant pleural mesothelioma in a 13-year-old girl. The chest radiograph showed nearly complete opacification and loss of volume in the left hemithorax. Computed tomography demonstrated a large pleural effusion centrally surrounded by a thick enhancing rind of soft tissue. The radiological features of childhood pleural mesothelioma in our case were similar to those described in adults with this disease. (orig.)

Malignant pleural mesothelioma in a 13-year-old girl

International Nuclear Information System (INIS)

Goyal, M.; Konez, O.; Patel, D.; Swanson, K.F.; Vyas, P.K.

2000-01-01

Pleural mesothelioma is an uncommon tumor in all age groups, but is especially rare in childhood. We describe the clinical and radiological features of malignant pleural mesothelioma in a 13-year-old girl. The chest radiograph showed nearly complete opacification and loss of volume in the left hemithorax. Computed tomography demonstrated a large pleural effusion centrally surrounded by a thick enhancing rind of soft tissue. The radiological features of childhood pleural mesothelioma in our case were similar to those described in adults with this disease. (orig.)

Novel therapies for malignant pleural mesothelioma.

Science.gov (United States)

Scherpereel, Arnaud; Wallyn, Frederic; Albelda, Steven M; Munck, Camille

2018-03-01

Malignant pleural mesothelioma is a rare cancer that is typically associated with exposure to asbestos. Patients with malignant pleural mesothelioma have poor outcomes with suboptimal therapeutic options and currently no treatment is curative. The standard frontline treatment, cisplatin plus pemetrexed chemotherapy, has only short and insufficient efficacy, and no validated treatment beyond first-line therapy is available. New therapeutic strategies are therefore needed. The addition of bevacizumab (an anti-VEGF antibody) combined with cisplatin plus pemetrexed has shown some promise. However, immunotherapy, especially immune checkpoint inhibitors, has generated a lot of excitement because of data suggesting the potential value of immune checkpoint inhibitors for patients who have failed chemotherapy. In this Review, we describe immune checkpoint inhibitors, other immunotherapies, targeted therapies, or combinations of novel drugs being investigated in malignant pleural mesothelioma, as well as the issues surrounding the selection of the best candidates for these treatments. Copyright © 2018 Elsevier Ltd. All rights reserved.

Malignant mesothelioma clinical trial combines immunotherapy drugs.

Science.gov (United States)

Chatwal, Monica S; Tanvetyanon, Tawee

2018-04-01

Immunotherapy by checkpoint inhibitor is effective for a number of solid tumors including malignant mesothelioma. Studies utilizing single-agent PD-1 or PD-L1 inhibitor for mesothelioma have reported tumor response rates in approximately 10-20% of patients treated. Given the success of combining these agents with CTLA-4 inhibitor in melanoma, there is a strong rationale to study it in mesothelioma. Recently results from clinical trials investigating this approach have been released. Though limited by small sample size, the studies conclusively demonstrated feasibility and suggested a modestly higher tumor response rate than one would expect from treatment with single-agent PD-1 or PD-L1 inhibitor. Nevertheless, toxicity was also increased. Immunotherapy-related deaths due to encephalitis, renal failure and hepatitis were observed. Further studies are warranted.

Malignant peritoneal mesothelioma presenting with respiratory symptoms

Energy Technology Data Exchange (ETDEWEB)

Daskalogiannaki, M.; Prassopoulos, P.; Raissaki, M.; Gourtsoyiannis, N. [Dept. of Radiology, University Hospital of Heraklion (Greece); Tsardi, M. [Dept. of Pathology, University Hospital of Heraklion (Greece)

2000-05-01

Malignant peritoneal mesothelioma is a rare disease associated with mild, nonspecific abdominal symptoms and a wide spectrum of imaging findings, with thickened mesentery and peritoneum being the most common ones. A case of a malignant peritoneal mesothelioma presenting with manifestations of pulmonary disease is reported. Imaging evaluation revealed pleural, lung and pericardial involvement together with retroperitoneal lymphadenopathy, little ascites and extensive omental, but only subtle, mesenteric thickening. (orig.)

Detouring the Undesired Route of Helicobacter pylori-Induced Gastric Carcinogenesis

Directory of Open Access Journals (Sweden)

Ki Baik Hahm

2011-07-01

Full Text Available Epidemiological and experimental evidence has emerged that a dysregulated inflammation is associated with most of the tumors, and many studies have begun to unravel the molecular pathways linking inflammation and cancer. As a typical example linking these associations, Helicobacter pylori (H. pylori infection-associated atrophic gastritis has been recognized as precursor lesion of gastric cancer. The identification of transcription factors such as NF-κB and STAT3, and their gene products such as IL-8, COX-2, iNOS, cytokines, chemokines and their receptors, etc have laid the molecular foundation for our understanding of the decisive role of inflammation in carcinogenesis. In addition to the role as the initiator of cancer, inflammation contributes to survival and proliferation of malignant cells, tumor angiogenesis, and even metastasis. In this review, the fundamental mechanisms of H. pylori-induced carcinogenesis as well as the possibility of cancer prevention through suppressing H. pylori-induced inflammation are introduced. We infer that targeting inflammatory pathways have a potential role to detour the unpleasant journey to H. pylori-associated gastric carcinogenesis.

Detouring the Undesired Route of Helicobacter pylori-Induced Gastric Carcinogenesis

Energy Technology Data Exchange (ETDEWEB)

Kim, Eun-Hee; Hong, Kyung-Sook; Hong, Hua [Lab of Translational Medicine, Lee Gil Ya Cancer and Diabetes Institute, Gachon University of Medicine and Science, 7-45 Songdo-dong, Yeonsu-gu, Incheon 406-840 (Korea, Republic of); Hahm, Ki Baik, E-mail: hahmkb@gachon.ac.kr [Lab of Translational Medicine, Lee Gil Ya Cancer and Diabetes Institute, Gachon University of Medicine and Science, 7-45 Songdo-dong, Yeonsu-gu, Incheon 406-840 (Korea, Republic of); Department of Gastroenterology, Gachon Graduate School of Medicine, Gil Hospital, Incheon 406-840 (Korea, Republic of)

2011-07-25

Epidemiological and experimental evidence has emerged that a dysregulated inflammation is associated with most of the tumors, and many studies have begun to unravel the molecular pathways linking inflammation and cancer. As a typical example linking these associations, Helicobacter pylori (H. pylori) infection-associated atrophic gastritis has been recognized as precursor lesion of gastric cancer. The identification of transcription factors such as NF-κB and STAT3, and their gene products such as IL-8, COX-2, iNOS, cytokines, chemokines and their receptors, etc have laid the molecular foundation for our understanding of the decisive role of inflammation in carcinogenesis. In addition to the role as the initiator of cancer, inflammation contributes to survival and proliferation of malignant cells, tumor angiogenesis, and even metastasis. In this review, the fundamental mechanisms of H. pylori-induced carcinogenesis as well as the possibility of cancer prevention through suppressing H. pylori-induced inflammation are introduced. We infer that targeting inflammatory pathways have a potential role to detour the unpleasant journey to H. pylori-associated gastric carcinogenesis.

Detouring the Undesired Route of Helicobacter pylori-Induced Gastric Carcinogenesis

International Nuclear Information System (INIS)

Kim, Eun-Hee; Hong, Kyung-Sook; Hong, Hua; Hahm, Ki Baik

2011-01-01

Epidemiological and experimental evidence has emerged that a dysregulated inflammation is associated with most of the tumors, and many studies have begun to unravel the molecular pathways linking inflammation and cancer. As a typical example linking these associations, Helicobacter pylori (H. pylori) infection-associated atrophic gastritis has been recognized as precursor lesion of gastric cancer. The identification of transcription factors such as NF-κB and STAT3, and their gene products such as IL-8, COX-2, iNOS, cytokines, chemokines and their receptors, etc have laid the molecular foundation for our understanding of the decisive role of inflammation in carcinogenesis. In addition to the role as the initiator of cancer, inflammation contributes to survival and proliferation of malignant cells, tumor angiogenesis, and even metastasis. In this review, the fundamental mechanisms of H. pylori-induced carcinogenesis as well as the possibility of cancer prevention through suppressing H. pylori-induced inflammation are introduced. We infer that targeting inflammatory pathways have a potential role to detour the unpleasant journey to H. pylori-associated gastric carcinogenesis

Mesothelioma tumor cells modulate dendritic cell lipid content, phenotype and function.

Directory of Open Access Journals (Sweden)

Joanne K Gardner

Full Text Available Dendritic cells (DCs play an important role in the generation of anti-cancer immune responses, however there is evidence that DCs in cancer patients are dysfunctional. Lipid accumulation driven by tumor-derived factors has recently been shown to contribute to DC dysfunction in several human cancers, but has not yet been examined in mesothelioma. This study investigated if mesothelioma tumor cells and/or their secreted factors promote increases in DC lipid content and modulate DC function. Human monocyte-derived DCs (MoDCs were exposed to human mesothelioma tumor cells and tumor-derived factors in the presence or absence of lipoproteins. The data showed that immature MoDCs exposed to mesothelioma cells or factors contained increased lipid levels relative to control DCs. Lipid accumulation was associated with reduced antigen processing ability (measured using a DQ OVA assay, upregulation of the co-stimulatory molecule, CD86, and production of the tolerogenic cytokine, IL-10. Increases in DC lipid content were further enhanced by co-exposure to mesothelioma-derived factors and triglyceride-rich lipoproteins, but not low-density lipoproteins. In vivo studies using a murine mesothelioma model showed that the lipid content of tumor-infiltrating CD4+ CD8α- DCs, CD4- CD8α- DCs DCs and plasmacytoid DCs increased with tumor progression. Moreover, increasing tumor burden was associated with reduced proliferation of tumor-antigen-specific CD8+ T cells in tumor-draining lymph nodes. This study shows that mesothelioma promotes DC lipid acquisition, which is associated with altered activation status and reduced capacity to process and present antigens, which may impair the ability of DCs to generate effective anti mesothelioma T cell responses.

Review of refractory ceramic fiber (RCF) toxicity, epidemiology and occupational exposure.

Science.gov (United States)

Maxim, L Daniel; Utell, Mark J

2018-02-01

This literature review on refractory ceramic fibers (RCF) summarizes relevant information on manufacturing, processing, applications, occupational exposure, toxicology and epidemiology studies. Rodent toxicology studies conducted in the 1980s showed that RCF caused fibrosis, lung cancer and mesothelioma. Interpretation of these studies was difficult for various reasons (e.g. overload in chronic inhalation bioassays), but spurred the development of a comprehensive product stewardship program under EPA and later OSHA oversight. Epidemiology studies (both morbidity and mortality) were undertaken to learn more about possible health effects resulting from occupational exposure. No chronic animal bioassay studies on RCF have been conducted since the 1980s. The results of the ongoing epidemiology studies confirm that occupational exposure to RCF is associated with the development of pleural plaques and minor decrements in lung function, but no interstitial fibrosis or incremental lung cancer. Evidence supporting a finding that urinary tumors are associated with RCF exposure remains, but is weaker. One reported, but unconfirmed, mesothelioma was found in an individual with prior occupational asbestos exposure. An elevated SMR for leukemia was found, but was absent in the highly exposed group and has not been observed in studies of other mineral fibers. The industry will continue the product stewardship program including the mortality study.

External radiotherapy in a pleural mesothelioma tumor

International Nuclear Information System (INIS)

Fernandez, M.C.; Garcia, J.L.; Gomez, A.; Simon, J.L.; Maillo, M.; Jimenez Torres, M. J.

1994-01-01

Pleural mesothelioma is an uncommon tumor compared with other thoracic malignancies and a 80% of the cases have asbestos exposure. From 1983 to 1992 we have examined patients suffering from malignant pleural mesothelioma treated with external radiotherapy. We treated 11 patients of which 9 were males and 2 were females. The most frequent symptom was the chest pain and all these patients underwent a torascoscopy followed by a pleasured. Of the 11 cases: 10 were malignant epithelial mesothelioma and 1 was a mixed pleural case. Afterwards, they were treated with external radiotherapy between 30 and 55 Gy, with few complications. At the moment, 5 patients are still alive and there is a survival rate of 50% at 24 and 60 months and of 25% at 120 months. We think that external radiotherapy is a good palliative treatment with few complications. (Author) 28 refs

Benign multicystic peritoneal mesothelioma: a case report

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Papapaulou Leonidas

2010-11-01

Full Text Available Abstract Introduction We report the case of a patient with a benign multicystic peritoneal mesothelioma and describe its appearance on computed tomography scans and ultrasonography, in correlation with gross clinical and pathological findings. Case presentation A 72-year-old Caucasian woman presented to our emergency department with acute abdomen signs and symptoms. A clinical examination revealed a painful palpable mass in her left abdomen. Abdominal ultrasonography and computed tomography demonstrated the presence of a large cystic mass in her left upper abdomen, adjacent to her left hemidiaphragm. The lower border of the mass extended to the upper margin of her pelvis. A complete resection of the lesion was performed. Pathological analysis showed a benign multicystic peritoneal mesothelioma. Conclusions Benign multicystic peritoneal mesothelioma is a rare lesion with a non-specific appearance on imaging. Its diagnosis always requires pathological analysis.

Non-Coding Transcript Heterogeneity in Mesothelioma: Insights from Asbestos-Exposed Mice.

Science.gov (United States)

Felley-Bosco, Emanuela; Rehrauer, Hubert

2018-04-11

Mesothelioma is an aggressive, rapidly fatal cancer and a better understanding of its molecular heterogeneity may help with making more efficient therapeutic strategies. Non-coding RNAs represent a larger part of the transcriptome but their contribution to diseases is not fully understood yet. We used recently obtained RNA-seq data from asbestos-exposed mice and performed data mining of publicly available datasets in order to evaluate how non-coding RNA contribute to mesothelioma heterogeneity. Nine non-coding RNAs are specifically elevated in mesothelioma tumors and contribute to human mesothelioma heterogeneity. Because some of them have known oncogenic properties, this study supports the concept of non-coding RNAs as cancer progenitor genes.

In Silico and In Vitro Analyses of LncRNAs as Potential Regulators in the Transition from the Epithelioid to Sarcomatoid Histotype of Malignant Pleural Mesothelioma (MPM).

Science.gov (United States)

Singh, Anand S; Heery, Richard; Gray, Steven G

2018-04-26

Malignant pleural mesothelioma (MPM) is a rare malignancy, with extremely poor survival rates. At present, treatment options are limited, with no second line chemotherapy for those who fail first line therapy. Extensive efforts are ongoing in a bid to characterise the underlying molecular mechanisms of mesothelioma. Recent research has determined that between 70⁻90% of our genome is transcribed. As only 2% of our genome is protein coding, the roles of the remaining proportion of non-coding RNA in biological processes has many applications, including roles in carcinogenesis and epithelial⁻mesenchymal transition (EMT), a process thought to play important roles in MPM pathogenesis. Non-coding RNAs can be separated loosely into two subtypes, short non-coding RNAs (200 nucleotides). A significant body of evidence has emerged for the roles of short non-coding RNAs in MPM. Less is known about the roles of long non-coding RNAs (lncRNAs) in this disease setting. LncRNAs have been shown to play diverse roles in EMT, and it has been suggested that EMT may play a role in the aggressiveness of MPM histological subsets. In this report, using both in vitro analyses on mesothelioma patient material and in silico analyses of existing RNA datasets, we posit that various lncRNAs may play important roles in EMT within MPM, and we review the current literature regarding these lncRNAs with respect to both EMT and MPM.

In Silico and In Vitro Analyses of LncRNAs as Potential Regulators in the Transition from the Epithelioid to Sarcomatoid Histotype of Malignant Pleural Mesothelioma (MPM

Directory of Open Access Journals (Sweden)

Anand S. Singh

2018-04-01

Full Text Available Malignant pleural mesothelioma (MPM is a rare malignancy, with extremely poor survival rates. At present, treatment options are limited, with no second line chemotherapy for those who fail first line therapy. Extensive efforts are ongoing in a bid to characterise the underlying molecular mechanisms of mesothelioma. Recent research has determined that between 70–90% of our genome is transcribed. As only 2% of our genome is protein coding, the roles of the remaining proportion of non-coding RNA in biological processes has many applications, including roles in carcinogenesis and epithelial–mesenchymal transition (EMT, a process thought to play important roles in MPM pathogenesis. Non-coding RNAs can be separated loosely into two subtypes, short non-coding RNAs (<200 nucleotides or long (>200 nucleotides. A significant body of evidence has emerged for the roles of short non-coding RNAs in MPM. Less is known about the roles of long non-coding RNAs (lncRNAs in this disease setting. LncRNAs have been shown to play diverse roles in EMT, and it has been suggested that EMT may play a role in the aggressiveness of MPM histological subsets. In this report, using both in vitro analyses on mesothelioma patient material and in silico analyses of existing RNA datasets, we posit that various lncRNAs may play important roles in EMT within MPM, and we review the current literature regarding these lncRNAs with respect to both EMT and MPM.

Malignant peritoneal mesothelioma in two pediatric patients: MR imaging findings

International Nuclear Information System (INIS)

Haliloglu, M.; Hoffer, F.A.; Fletcher, B.D.

2000-01-01

Malignant mesothelioma is a rare tumor in childhood. We present two cases of malignant peritoneal mesothelioma in which contrast-enhanced, fat-saturated magnetic resonance (MR) imaging was used advantageously to detect peritoneal tumor involvement. (orig.)

Malignant peritoneal mesothelioma in two pediatric patients: MR imaging findings

Energy Technology Data Exchange (ETDEWEB)

Haliloglu, M. [Dept. of Diagnostic Imaging, St. Jude Children' s Research Hospital, St. Memphis, TN (United States); Hoffer, F.A. [Dept. of Diagnostic Imaging, St. Jude Children' s Research Hospital, St. Memphis, TN (United States); Dept. of Radiology, Univ. of Tennessee, Memphis, TN (United States); Fletcher, B.D. [Dept. of Diagnostic Imaging, St. Jude Children' s Research Hospital, St. Memphis, TN (United States); Dept. of Radiology, Univ. of Tennessee, Memphis, TN (United States); Dept. of Pediatrics, Univ. of Tennessee, Memphis (United States)

2000-04-01

Malignant mesothelioma is a rare tumor in childhood. We present two cases of malignant peritoneal mesothelioma in which contrast-enhanced, fat-saturated magnetic resonance (MR) imaging was used advantageously to detect peritoneal tumor involvement. (orig.)

Clinical diagnosis of malignant pleural mesothelioma

International Nuclear Information System (INIS)

Nishi, Hideyuki; Washio, Kazuhiro; Mano, Masayuki

2008-01-01

We evaluated clinical and thoracoscopic findings of cases that underwent thoracoscopic biopsy for the diagnosis of malignant pleural mesothelioma. We reviewed 32 cases suspected of having malignant pleural mesothelioma from 2003 to 2006. We made a diagnosis of malignant pleural mesothelioma via thoracoscopic biopsy (19 cases). The cut-off level of hyaluronic acid in malignant effusions, selected on the basis of the best diagnostic efficacy, was 100 μg/ml. We can decrease the incidence of false negative cases by the combination of CT findings and the presence of hyaluronic acid in pleural effusion. In the pleural thickening type of thoracoscopic appearance, the parietal pleurae were thickened, and small nodules were rare. As for this type, tumor cells were histologically absent or confined to the submesothelial tissue. We considered that determinations of specific sites were difficult. Adequate tissue samples obtained via video-assisted thoracoscopy were necessary for diagnosis. We can decrease the incidence of false negative cases by the combination of the presence of hyaluronic acid in pleural effusion and thoracoscopic biopsy. (author)

Case report. Sclerosing peritoneal mesothelioma in a dog: histopathological, histochemical and immunohistochemical investigations

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Anna Rita D'Angelo

2014-12-01

Full Text Available Mesotheliomas are rare neoplasm affecting on rare occasions both animals and humans and which arise from the mesothelial cells lining the coelomic cavities. We report herein the histopathological, histochemical and immunohistochemical findings in a dog affected by sclerosing peritoneal mesothelioma, a rare variant of canine mesothelioma, and submitted to laparotomy in December 2012 (Teramo, Italy. Our data confirm that mesothelioma still represents a diagnostic challenge and that immunohistochemistry can be extremely useful as supportive diagnostic technique.

Primary Malignant Peritoneal Mesothelioma Mimicking Peritoneal Carcinomatosis on F-18 FDG PET/CT

International Nuclear Information System (INIS)

Kim, Jin Suk; Lim, Seok Tae; Jeong, Young Jin; Kim, Dong Wook; Jeong, Hwan Jeong; Sohn, Myung Hee

2009-01-01

Malignant mesothelioma of the peritoneum is a rare neoplasm with a rapidly fatal course. The tumour arises from the mesothelial cells lining the pleura and peritoneum or, rarely, in the pericardium or tunica vaginalis. This neoplasm is characterized by being difficult to diagnose, having a rapid evolution and a poor response to therapy. Mesothelioma is very glucose avid, and malignant pleural mesothelioma has been reported concerning the utility of F-18 FDG PET or PET/CT. But little has been known about the imaging finding of malignant peritoneal mesothelioma on F-18 FDG PET/CT. We report a case of malignant peritoneal mesothelioma mimicking peritoneal carcinomatosis of F-18 FDG PET/CT

Primary Malignant Peritoneal Mesothelioma Mimicking Peritoneal Carcinomatosis on F-18 FDG PET/CT

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Kim, Jin Suk; Lim, Seok Tae; Jeong, Young Jin; Kim, Dong Wook; Jeong, Hwan Jeong; Sohn, Myung Hee [Chonbuk National University Medical School and Hospital, Jeonju (Korea, Republic of)

2009-08-15

Malignant mesothelioma of the peritoneum is a rare neoplasm with a rapidly fatal course. The tumour arises from the mesothelial cells lining the pleura and peritoneum or, rarely, in the pericardium or tunica vaginalis. This neoplasm is characterized by being difficult to diagnose, having a rapid evolution and a poor response to therapy. Mesothelioma is very glucose avid, and malignant pleural mesothelioma has been reported concerning the utility of F-18 FDG PET or PET/CT. But little has been known about the imaging finding of malignant peritoneal mesothelioma on F-18 FDG PET/CT. We report a case of malignant peritoneal mesothelioma mimicking peritoneal carcinomatosis of F-18 FDG PET/CT.

Development of a guideline on reading CT images of malignant pleural mesothelioma and selection of the reference CT films

International Nuclear Information System (INIS)

Zhou, Huashi; Tamura, Taro; Kusaka, Yukinori; Suganuma, Narufumi; Subhannachart, Ponglada; Vijitsanguan, Chomphunut; Noisiri, Weeraya; Hering, Kurt G.; Akira, Masanori; Itoh, Harumi

2012-01-01

Purpose: International experts developed a guideline on reading CT images of malignant pleural mesothelioma for radiologists and physicians. It is intended that it act as a supplement to the current International Classification of HRCT for Occupational and Environmental Respiratory Diseases. Methods: The research literatures on mesothelioma CT features were systematically reviewed. Ten mesothelioma CT features were adopted into the guideline prepared according to experts’ opinion. The terminology of mesothelioma CT features and mesothelioma probability were agreed by consensus of experts. The CT reference films for each mesothelioma feature were selected based on agreement by experts from 22 definite mesothelioma cases confirmed pathologically and immunohistochemically. To support the validity of the mesothelioma probability, 4 experts’ readings of CT films from 57 cases with or without mesothelioma were analyzed by kappa statistics between the experts; sensitivity and specificity for mesothelioma were also assessed. Results: The mesothelioma CT Guideline was developed, providing the terminology of CT features and the mesothelioma probability, the judgement of severity, the distribution of mesothelioma, and the revised CT reading sheet including mesothelioma items. The CT reference films with ten mesothelioma typical features were selected. The average linearly and quadratically weighted kappa of the agreement on the 4-point scale mesothelioma probability were 0.58 and 0.71, respectively. The average sensitivity and specificity for mesothelioma were 93.2% and 65.6%, respectively. Conclusion: The evidence-based mesothelioma CT Guideline developed may serve as a good educational tool to facilitate physicians in recognising mesothelioma and improve their proficiency in diagnosis of mesothelioma.

Development of a guideline on reading CT images of malignant pleural mesothelioma and selection of the reference CT films

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Zhou, Huashi, E-mail: zhouhua@u-fukui.ac.jp [Department of Environmental Health, School of Medicine, University of Fukui, 23-3 Shimoaitsuki, Matsuoka, Eihezi-cho, Fukui Prefecture 910-1193 (Japan); Tamura, Taro, E-mail: tarou@u-fukui.ac.jp [Department of Environmental Health, School of Medicine, University of Fukui, 23-3 Shimoaitsuki, Matsuoka, Eihezi-cho, Fukui Prefecture 910-1193 (Japan); Kusaka, Yukinori, E-mail: kusakayk@gmail.com [Department of Environmental Health, School of Medicine, University of Fukui, 23-3 Shimoaitsuki, Matsuoka, Eihezi-cho, Fukui Prefecture 910-1193 (Japan); Suganuma, Narufumi, E-mail: nsuganuma@kochi-u.ac.jp [Department of Environmental Medicine, Kochi University School of Medicine (Japan); Subhannachart, Ponglada, E-mail: pongladas@gmail.com [Central Chest Disease Institute of Thailand, 39 Moo 9, Tiwanon Road, Muang Nonthaburi 11000 (Thailand); Vijitsanguan, Chomphunut, E-mail: Chompoo_vj@yahoo.com [Central Chest Disease Institute of Thailand, 39 Moo 9, Tiwanon Road, Muang Nonthaburi 11000 (Thailand); Noisiri, Weeraya, E-mail: weeraya_tat@yahoo.com [Central Chest Disease Institute of Thailand, 39 Moo 9, Tiwanon Road, Muang Nonthaburi 11000 (Thailand); Hering, Kurt G., E-mail: k.g.hering@t-online.de [Department of Diagnostic Radiology, Radiooncology and Nuclear Medicine, Radiological Clinic, Miner' s Hospital, Radiologische Klinik, Lansppaschaftskranhaus Dortmund, Wieckesweg 27 44309, Dortmund (Germany); Akira, Masanori, E-mail: akira@kch.hosp.go.jp [Department of Radiology, National Hospital Organization Kinki-Chuo Chest Medical Center, 1180 Nagasone-cho, Kita-ku, Sakai, Osaka 591-8555 (Japan); Itoh, Harumi, E-mail: hitoh@fmsrsa.fukui-med.ac.jp [Department of Environmental Health, School of Medicine, University of Fukui, 23-3 Shimoaitsuki, Matsuoka, Eihezi-cho, Fukui Prefecture 910-1193 (Japan); Department of Radiology, School of Medicine, University of Fukui, 23-3 Shimoaitsuki Matsuoka, Eiheizi-cho, Fukui Prefecture 910-1193 (Japan); and others

2012-12-15

Purpose: International experts developed a guideline on reading CT images of malignant pleural mesothelioma for radiologists and physicians. It is intended that it act as a supplement to the current International Classification of HRCT for Occupational and Environmental Respiratory Diseases. Methods: The research literatures on mesothelioma CT features were systematically reviewed. Ten mesothelioma CT features were adopted into the guideline prepared according to experts’ opinion. The terminology of mesothelioma CT features and mesothelioma probability were agreed by consensus of experts. The CT reference films for each mesothelioma feature were selected based on agreement by experts from 22 definite mesothelioma cases confirmed pathologically and immunohistochemically. To support the validity of the mesothelioma probability, 4 experts’ readings of CT films from 57 cases with or without mesothelioma were analyzed by kappa statistics between the experts; sensitivity and specificity for mesothelioma were also assessed. Results: The mesothelioma CT Guideline was developed, providing the terminology of CT features and the mesothelioma probability, the judgement of severity, the distribution of mesothelioma, and the revised CT reading sheet including mesothelioma items. The CT reference films with ten mesothelioma typical features were selected. The average linearly and quadratically weighted kappa of the agreement on the 4-point scale mesothelioma probability were 0.58 and 0.71, respectively. The average sensitivity and specificity for mesothelioma were 93.2% and 65.6%, respectively. Conclusion: The evidence-based mesothelioma CT Guideline developed may serve as a good educational tool to facilitate physicians in recognising mesothelioma and improve their proficiency in diagnosis of mesothelioma.

Limbic Encephalitis Driven by a Pleural Mesothelioma: A Paraneoplastic Complication

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Jacob O. Day

2016-10-01

Full Text Available Paraneoplastic neurological syndromes have only been described with pleural mesothelioma in five cases. We have described a 72-year-old man who developed anterograde amnesia 27 months after diagnosis of epithelioid pleural mesothelioma. Investigations revealed a limbic encephalitis with no alternative causes identified. Limbic encephalitis is a classical paraneoplastic syndrome and presentation within five years of a cancer with no other causes identified is sufficient to diagnose a paraneoplastic etiology. This is the first case of isolated paraneoplastic limbic encephalitis driven by a pleural mesothelioma.

Malignant pleural mesothelioma: Computed tomography and correlation with histology

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Seely, Jean M. [Department of Diagnostic Imaging, Ottawa Hospital, 1053 Carling Avenue, Ottawa, Ontario K1Y 4E9 (Canada)], E-mail: jeseely@ottawahospital.on.ca; Nguyen, Elsie T., E-mail: nguyen_elsie@hotmail.com; Churg, Andrew M. [University of British Columbia, 2211 Wesbrook Mall, Vancouver, BC V6T 1W5 (Canada)], E-mail: achurg@interchange.ubc.ca; Mueller, Nestor L. [University of British Columbia, Vancouver Hospital and Health Sciences Centre, 855 West 12th Avenue, Vancouver, BC V5Z 1M9 (Canada)], E-mail: nmuller@vanhosp.bc.ca

2009-06-15

Objective: To review the computed tomography (CT) imaging findings of pleural mesothelioma at presentation and to correlate the CT with the histological subtype. Materials and methods: Pathology reports from 1997 to 2006 were reviewed at two academic institutions to identify patients with proven pleural mesothelioma. Diagnosis was based on histologic findings in specimens obtained by transthoracic needle biopsy, surgical biopsy or resection. All histology slides were reviewed by a lung pathologist. CT scans, available in 92 patients, were reviewed blindly and in random order by two independent radiologists. Kappa analysis was completed to assess inter-observer agreement. Eighty patients in whom there was no significant delay between CT imaging and histological diagnosis were assessed by logistic regression analysis to correlate CT and histologic findings. Results: Seventy-two of the 92 mesotheliomas were epithelial, 15 sarcomatous, and 5 of mixed histology. All patients (77 male, 15 female, mean age 68 years) had pleural thickening on CT; the thickening was nodular in 79 patients (86%) and mediastinal in 87 (95%). Ipsilateral volume loss was seen in 42 patients (46%). Pleural effusions were present in 80 patients (87%), being large (>2/3 hemithorax) in 19 patients (21%). Atypical features at presentation included bilateral disease in three patients (3%), and spontaneous pneumothoraces in nine patients (10%). Internal mammary lymphadenopathy was observed in 48 patients (52%) and cardiophrenic lymphadenopathy in 42 (46%). Inter-observer agreement was excellent (average kappa = 0.89). Ipsilateral volume loss was associated with sarcomatous or mixed mesothelioma (p = 0.004). Using logistic regression analysis, other CT findings did not correlate with histological subtype. Conclusions: Ipsilateral volume loss is most frequently associated with sarcomatous or mixed mesothelioma. The remaining imaging findings are not helpful in predicting the histological subtype of

Malignant pleural mesothelioma: Computed tomography and correlation with histology

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Seely, Jean M.; Nguyen, Elsie T.; Churg, Andrew M.; Mueller, Nestor L.

2009-01-01

Objective: To review the computed tomography (CT) imaging findings of pleural mesothelioma at presentation and to correlate the CT with the histological subtype. Materials and methods: Pathology reports from 1997 to 2006 were reviewed at two academic institutions to identify patients with proven pleural mesothelioma. Diagnosis was based on histologic findings in specimens obtained by transthoracic needle biopsy, surgical biopsy or resection. All histology slides were reviewed by a lung pathologist. CT scans, available in 92 patients, were reviewed blindly and in random order by two independent radiologists. Kappa analysis was completed to assess inter-observer agreement. Eighty patients in whom there was no significant delay between CT imaging and histological diagnosis were assessed by logistic regression analysis to correlate CT and histologic findings. Results: Seventy-two of the 92 mesotheliomas were epithelial, 15 sarcomatous, and 5 of mixed histology. All patients (77 male, 15 female, mean age 68 years) had pleural thickening on CT; the thickening was nodular in 79 patients (86%) and mediastinal in 87 (95%). Ipsilateral volume loss was seen in 42 patients (46%). Pleural effusions were present in 80 patients (87%), being large (>2/3 hemithorax) in 19 patients (21%). Atypical features at presentation included bilateral disease in three patients (3%), and spontaneous pneumothoraces in nine patients (10%). Internal mammary lymphadenopathy was observed in 48 patients (52%) and cardiophrenic lymphadenopathy in 42 (46%). Inter-observer agreement was excellent (average kappa = 0.89). Ipsilateral volume loss was associated with sarcomatous or mixed mesothelioma (p = 0.004). Using logistic regression analysis, other CT findings did not correlate with histological subtype. Conclusions: Ipsilateral volume loss is most frequently associated with sarcomatous or mixed mesothelioma. The remaining imaging findings are not helpful in predicting the histological subtype of

Multimodal treatment for resectable epithelial type malignant pleural mesothelioma

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Fukuyama Yasuro

2004-05-01

Full Text Available Abstract Background Malignant pleural mesothelioma is a rare malignancy. The outcome remains poor despite complete surgical resection. Patients and methods Eleven patients with histologicaly proven epithelial type malignant pleural mesothelioma undergoing extrapleural pneumonectomy with systemic chemotherapy and/or radiotherapy before and after surgical resection were retrospectively reviewed. Results Ten out of 11 patients underwent complete surgical resection, of these 7 patients had stage I disease. Of these 7 patients, 5 are alive without any recurrence, a 2-year survival rate of 80% was observed in this group. There was no operative mortality or morbidity. Conclusion Extrapleural pneumonectomy with perioperative adjuvant treatment is safe and effective procedure for epithelial type malignant pleural mesothelioma.

Two Case Reports of Benign Testicular Mesothelioma and Review of the Literature

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Cristobal Ramirez Sevilla

2017-01-01

Full Text Available Mesothelioma is usually diagnosed in people over the age of 50 with large history of asbestos-related exposure. It is frequently located in pleural cavity, peritoneum, and pericardium. At the testicles the mesothelioma had been reported first in 1957 like a malignant non-germ-cells tumor. The objective is to present two case reports of benign testicular mesothelioma and review of the literature.

Primary Pericardial Mesothelioma: Report of a Patient and Literature Review

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Åse Nilsson

2009-07-01

Full Text Available Primary mesothelioma of the pericardium is a rare tumor and carries a dismal prognosis. This case report presents a 38-year-old man who suffered from recurrent pericardial fluid. Initial symptoms were unspecific, with dry cough and progressing fatigue. Pericardiocentesis was performed, but analyses for malignant cells and tuberculosis were negative. After recurrence a pericardiectomy was planned. At operation, partial resection of tumor tissue surrounding the heart was performed. Histopathologic examination including immunohistochemical staining for calretinin showed a biphasic mesothelioma. During the postoperative period the patient’s condition ameliorated, but symptoms recurred and the patient died 3 months after diagnosis and 15 months after the first symptoms. At autopsy, the pericardium was transformed by the tumor that also expanded into the mediastinum and had set metastases to the liver. A review of 29 cases presented in the recent literature indicates a higher incidence of malignant pericardial mesothelioma among men than women. Median age was 46 (range, 19–76 years. In pleural mesotheliomas, exposure to asbestos is a known risk factor. However, in primary pericardial mesotheliomas the evidence for asbestos as an etiologic factor seems to be less convincing (3 exposed among 14 cases. Symptoms are often unspecific and cytologic examination of pericardial fluid is seldom conclusive (malignant cells demonstrated in 4/17 cases. Partial resection of the tumor can give a period of symptom reduction. Only a few patients have been treated with chemotherapy. Median survival of patients with pericardial mesotheliomas is approximately 6 months.

In vitro and in vivo characterization of highly purified Human Mesothelioma derived cells

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Melotti, Alice; Daga, Antonio; Marubbi, Daniela; Zunino, Annalisa; Mutti, Luciano; Corte, Giorgio

2010-01-01

Malignant pleural mesothelioma is a rare disease known to be resistant to conventional therapies. A better understanding of mesothelioma biology may provide the rationale for new therapeutic strategies. In this regard, tumor cell lines development has been an important tool to study the biological properties of many tumors. However all the cell lines established so far were grown in medium containing at least 10% serum, and it has been shown that primary cell lines cultured under these conditions lose their ability to differentiate, acquire gene expression profiles that differ from that of tissue specific stem cells or the primary tumor they derive from, and in some cases are neither clonogenic nor tumorigenic. Our work was aimed to establish from fresh human pleural mesothelioma samples cell cultures maintaining tumorigenic properties. The primary cell cultures, obtained from four human pleural mesotheliomas, were expanded in vitro in a low serum proliferation-permissive medium and the expression of different markers as well as the tumorigenicity in immunodeficient mice was evaluated. The established mesothelioma cell cultures are able to engraft, after pseudo orthotopic intraperitoneal transplantation, in immunodeficient mouse and maintain this ability to after serial transplantation. Our cell cultures were strongly positive for CD46, CD47, CD56 and CD63 and were also strongly positive for some markers never described before in mesothelioma cell lines, including CD55, CD90 and CD99. By real time PCR we found that our cell lines expressed high mRNA levels of typical mesothelioma markers as mesothelin (MSLN) and calretinin (CALB2), and of BMI-1, a stemness marker, and DKK1, a potent Wingless [WNT] inhibitor. These cell cultures may provide a valuable in vitro and in vivo model to investigate mesothelioma biology. The identification of new mesothelioma markers may be useful for diagnosis and/or prognosis of this neoplasia as well as for isolation of mesothelioma

Pleuroperitoneal Mesothelioma: A Rare Entity on 18F-FDG PET/CT

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Sahoo, Manas Kumar; Mukherjee, Anirban; Girish; Parida, Kumar; Agarwal, Krishan Kant; Bal, Chandrasekhar; Tripathi, Madhavi; Das, Chandan Jyoti; Shamim, Shamim Ahmed

2017-01-01

Pleuroperitoneal mesothelioma is an extremely rare entity. Only few cases are reported worldwide. We hereby represent a case of pleural mesothelioma referred for F-18-Fluorodeoxyglucose positron emission tomography/computed tomography for response evaluation. Diffuse F-18-Fluorodeoxyglucose avid peritoneal and omental thickening noted which subsequently turned out to be mesothelial involvement on peritoneal biopsy. This case demonstrates the role of F-18-Fluorodeoxyglucose positron emission tomography/computed tomography in detecting other sites of involvement in case of malignant mesothelioma. PMID:28242997

An autopsy case of peritoneal malignant mesothelioma in a radiation technologist

International Nuclear Information System (INIS)

Horie, Akio; Hiraoka, Katsumi; Yamamoto, Osamu; Haratake, Joji; Tsuchiya, Takehiko; Sugimoto, Hidekatsu.

1990-01-01

A case of peritoneal malignant mesothelioma in a radiation technologist, who had worked in this field for 34 years, is reported. Histopathologically, a biopsy specimen from the retroperitoneal tumor revealed a biphasic type of malignant mesothelioma. Electron microscopy disclosed that the tumor cells contained prominent microvilli, basal laminae adjacent to the stroma, junctional complexes, desmosomes, tonofilaments, clusters of glycogen granules, well developed rough endoplasmic reticulum (RER), confronting cisternae showing direct continuity with the RER and membrane-bound granules suggestive of secretory activity. No increased amount of asbestos was detected in autopsied lung material or the peritoneal mesothelioma. The estimated cumulative dose of occupational irradiation was calculated to be about 40 to 50 rad at most. Irradiation was discussed in relation to the etiology of the peritoneal mesothelioma. (author)

EphB4 as a therapeutic target in mesothelioma

International Nuclear Information System (INIS)

Liu, Ren; Ferguson, Benjamin D; Zhou, Yue; Naga, Kranthi; Salgia, Ravi; Gill, Parkash S; Krasnoperov, Valery

2013-01-01

Malignant pleural mesothelioma (MPM) often develops decades following exposure to asbestos. Current best therapy produces a response in only half of patients, and the median survival with this therapy remains under a year. A search for novel targets and therapeutics is underway, and recently identified targets include VEGF, Notch, and EphB4-Ephrin-B2. Each of these targets has dual activity, promoting tumor cell growth as well as tumor angiogenesis. We investigated EphB4 expression in 39 human mesothelioma tissues by immunohistochemistry. Xenograft tumors established with human mesothelioma cells were treated with an EphB4 inhibitor (monomeric soluble EphB4 fused to human serum albumin, or sEphB4-HSA). The combinatorial effect of sEphB4-HSA and biologic agent was also studied. EphB4 was overexpressed in 72% of mesothelioma tissues evaluated, with 85% of epithelioid and 38% of sarcomatoid subtypes demonstrating overexpression. The EphB4 inhibitor sEphB4-HSA was highly active as a single agent to inhibit tumor growth, accompanied by tumor cell apoptosis and inhibition of PI3K and Src signaling. Combination of sEphB4-HSA and the anti-VEGF antibody (Bevacizumab) was superior to each agent alone and led to complete tumor regression. EphB4 is a potential therapeutic target in mesothelioma. Clinical investigation of sEphB4-HSA as a single agent and in combination with VEGF inhibitors is warranted

Post-irradiation pericardial malignant mesothelioma with deletion of p16: a case report.

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Naeini, Yalda B; Arcega, Ramir; Hirschowitz, Sharon; Rao, Nagesh; Xu, Haodong

2018-02-01

Malignant mesotheliomas are rather uncommon neoplasms associated primarily with asbestos exposure; however, they may also arise as second primary malignancies after radiation therapy, with a latency period of 15-25 years. Numerous studies have reported an association between pleural malignant mesothelioma and chest radiation performed for other malignancies; on the other hand, post-irradiation mesotheliomas of the pericardium have been reported in only a few published cases to date, and no homozygous deletion of 9p21 has been described in such cases. We report the case of a 48-year-old man with a history of Hodgkin's lymphoma and no prior asbestos exposure who developed pericardial malignant epithelioid mesothelioma. We further discuss the cytologic, histologic, immunophenotypic, and fluorescence in situ hybridization findings in this case. To our knowledge, this is the first well-documented case of post-radiation pericardial malignant mesothelioma showing homozygous deletion of 9p21. Homozygous deletion of 9p21, the locus harboring the p16 gene, is present in post-irradiation pericardial malignant mesothelioma.

Malignant Mesothelioma Mimicking Invasive Mammary Carcinoma in a Male Breast

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Mohamed Mokhtar Desouki

2015-01-01

Full Text Available Malignant mesothelioma is an uncommon tumor with strong association with asbestos exposure. Few cases of malignant pleural mesothelioma metastatic to the female breast have been reported. Herein, we presented, for the first time, a case of locally infiltrating malignant pleural mesothelioma forming a mass in the breast of a male as the first pathologically confirmed manifestation of the disease. Breast ultrasound revealed an irregular mass in the right breast which involves the pectoralis muscle. Breast core biopsy revealed a proliferation of neoplastic epithelioid cells mimicking an infiltrating pleomorphic lobular carcinoma. IHC studies showed the cells to be positive for calretinin, CK5/6, WT1, and CK7. The cells were negative for MOC-31, BerEp4, ER, and PR. A final diagnosis of malignant mesothelioma, epithelioid type, was rendered. This case demonstrates the importance of considering a broad differential diagnosis in the setting of atypical presentation with application of a panel of IHC markers.

Radiosensitivity of mesothelioma cell lines

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Haekkinen, A.M.; Laasonen, A.; Linnainmaa, K.; Mattson, K.; Pyrhoenen, S.

1996-01-01

The present study was carried out in order to examine the radiosensitivity of malignant pleural mesothelioma cell lines. Cell kinetics, radiation-induced delay of the cell cycle and DNA ploidy of the cell lines were also determined. For comparison an HeLa and a human foetal fibroblast cell line were simultaneously explored. Six previously cytogenetically and histologically characterized mesothelioma tumor cell lines were applied. A rapid tiazolyl blue microtiter (MTT) assay was used to analyze radiosensitivity and cell kinetics and DNA ploidy of the cultured cells were determined by flow cytometry. The survival fraction after a dose of 2 Gy (SF2), parameters α and β of the linear quadratic model (LQ-model) and mean inactivation dose (D MID ) were also estimated. The DNA index of four cell lines equaled 1.0 and two cell lines equaled 1.5 and 1.6. Different mesothelioma cell lines showed a great variation in radiosensitivity. Mean survival fraction after a radiation dose of 2 Gy (SF2) was 0.60 and ranged from 0.36 to 0.81 and mean α value was 0.26 (range 0.48-0.083). The SF2 of the most sensitive diploid mesothelioma cell line was 0.36: Less than that of the foetal fibroblast cell line (0.49). The survival fractions (0.81 and 0.74) of the two most resistant cell lines, which also were aneuploid, were equal to that of the HeLa cell line (0.78). The α/β ratios of the most sensitive cell lines were almost an order of magnitude greater than those of the two most resistant cell lines. Radiation-induced delay of the most resistant aneuploid cell line was similar to that of HeLa cells but in the most sensitive (diploid cells) there was practically no entry into the G1 phase following the 2 Gy radiation dose during 36 h. (orig.)

Radiosensitivity of mesothelioma cell lines

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Haekkinen, A.M. [Dept. of Oncology, Univ. Central Hospital, Helsinki (Finland); Laasonen, A. [Dept. of Pathology, Central Hospital of Etelae-Pohjanmaa, Seinaejoki (Finland); Linnainmaa, K. [Dept. of Industrial Hygiene and Toxicology, Inst. of Occupational Health, Helsinki (Finland); Mattson, K. [Dept. Pulmonary Medicine, Univ. Central Hospital, Helsinki (Finland); Pyrhoenen, S. [Dept. of Oncology, Univ. Central Hospital, Helsinki (Finland)

1996-10-01

The present study was carried out in order to examine the radiosensitivity of malignant pleural mesothelioma cell lines. Cell kinetics, radiation-induced delay of the cell cycle and DNA ploidy of the cell lines were also determined. For comparison an HeLa and a human foetal fibroblast cell line were simultaneously explored. Six previously cytogenetically and histologically characterized mesothelioma tumor cell lines were applied. A rapid tiazolyl blue microtiter (MTT) assay was used to analyze radiosensitivity and cell kinetics and DNA ploidy of the cultured cells were determined by flow cytometry. The survival fraction after a dose of 2 Gy (SF2), parameters {alpha} and {beta} of the linear quadratic model (LQ-model) and mean inactivation dose (D{sub MID}) were also estimated. The DNA index of four cell lines equaled 1.0 and two cell lines equaled 1.5 and 1.6. Different mesothelioma cell lines showed a great variation in radiosensitivity. Mean survival fraction after a radiation dose of 2 Gy (SF2) was 0.60 and ranged from 0.36 to 0.81 and mean {alpha} value was 0.26 (range 0.48-0.083). The SF2 of the most sensitive diploid mesothelioma cell line was 0.36: Less than that of the foetal fibroblast cell line (0.49). The survival fractions (0.81 and 0.74) of the two most resistant cell lines, which also were aneuploid, were equal to that of the HeLa cell line (0.78). The {alpha}/{beta} ratios of the most sensitive cell lines were almost an order of magnitude greater than those of the two most resistant cell lines. Radiation-induced delay of the most resistant aneuploid cell line was similar to that of HeLa cells but in the most sensitive (diploid cells) there was practically no entry into the G1 phase following the 2 Gy radiation dose during 36 h. (orig.).

Drugs Approved for Malignant Mesothelioma

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This page lists cancer drugs approved by the Food and Drug Administration (FDA) for malignant mesothelioma. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

Review of hepatocellular carcinoma: Epidemiology, etiology, and carcinogenesis.

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Ghouri, Yezaz Ahmed; Mian, Idrees; Rowe, Julie H

2017-01-01

Since the 1970s, the epidemic of hepatocellular carcinoma (HCC) has spread beyond the Eastern Asian predominance and has been increasing in Northern hemisphere, especially in the United States (US) and Western Europe. It occurs more commonly in males in the fourth and fifth decades of life. Among all cancers, HCC is one of the fastest growing causes of death in the US and poses a significant economic burden on healthcare. Chronic liver disease due to hepatitis B virus or hepatitis C virus and alcohol accounts for the majority of HCC cases. Incidence of nonalcoholic fatty liver disease has been on the risem and it has also been associated with the development of HCC. Its pathogenesis varies based on the underlying etiological factor although majority of cases develop in the setting of background cirrhosis. Carcinogenesis of HCC includes angiogenesis, chronic inflammation, and tumor macroenvironment and microenvironment. There is a significant role of both intrinsic genetic risk factors and extrinsic influences such as alcohol or viral infections that lead to the development of HCC. Understanding its etiopathogenesis helps select appropriate diagnostic tests and treatments.

Parakeratotic-like cells in effusions - A clue to diagnosis of malignant mesothelioma

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Ling Gao

2012-01-01

Full Text Available Background : Malignant mesothelioma (MM is an aggressive neoplasm with a poor prognosis. Its incidence has been increasing worldwide. Cytological examination of an effusion is often the first opportunity to diagnose MM. However, the cytological diagnosis of MM can be difficult. We have noticed that parakeratotic-like cells, with orange cytoplasm and pyknotic nuclei, are present in many cases of mesothelioma on Papanicolaou-stained cytology slides. Although this cytological finding has been described previously, to our knowledge, there has been no systematic study of this finding. Our study is to determine whether the presence of small parakeratotic / orangeophilic cells (PK-like cells is specific for the cytodiagnosis of mesothelioma. Materials and Methods: A total of 90 body fluid cases were selected from our archived specimens in the Cytology Section at the University of Chicago Hospital accessioned between January 2000 to November 2011. They included 30 cases of mesothelioma, 30 cases of adenocarcinoma, and 30 cases of reactive mesothelial cells. Results: PK-like cells were present in 83% of the mesothelioma cases, 13% of the adenocarcinoma cases, and 7% of the reactive cases. Our data showed that the presence of PK-like cells has a specificity of 90%, sensitivity of 83%, positive predictive value of 81%, and negative predictive value of 84% for the diagnosis of malignant mesothelioma in body cavity fluids. Conclusion: The presence of PK-like cells in the effusion specimen, especially in pleural effusions, is a highly specific and moderately sensitive cytological feature for diagnosis of mesothelioma.

Diffuse malignant pleural mesothelioma in an urban hospital: Clinical spectrum and trend in incidence over time

International Nuclear Information System (INIS)

Shepherd, K.E.; Oliver, L.C.; Kazemi, H.

1989-01-01

This retrospective analysis reviews the clinical experience of a major urban referral hospital with diffuse malignant pleural mesothelioma during the 14-year period from 1973 through 1986. Seventy-five cases of definite or equivocal mesothelioma were identified. There were four cases of primary malignant peritoneal mesothelioma, seven cases of benign fibrous mesothelioma, and 64 cases of diffuse malignant pleural mesothelioma. In 43 cases (67%) of diffuse malignant pleural mesothelioma, there was historic evidence of asbestos exposure. In 21 cases (33%), there was no known history of asbestos exposure. An increase in annual incidence of diffuse malignant pleural mesothelioma was observed over the study period, from three cases in 1973 to ten cases in 1986. Despite greater awareness of this disease, the diagnosis remains a difficult one to establish given the nonspecific symptoms, signs and radiographic appearance, variable histologic appearance, and poor diagnostic sensitivity and specificity of thoracentesis and closed pleural biopsy. Thoracotomy, thoracoscopy, and CT-guided needle biopsies gave higher yields and are the diagnostic measures of choice when diffuse malignant pleural mesothelioma is suspected

Biphasic Malignant Pleural Mesothelioma Masquerading as a Primary Skeletal Tumor

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James Benjamin Gleason

2016-01-01

Full Text Available Biphasic malignant pleural mesothelioma is a rare malignant tumor, usually presenting as a pleural-based mass in a patient with history of chronic asbestos exposure. We herein report a case of a 41-year-old man who presented with chest pain and had a chest computed tomography (CT scan suggestive of a primary skeletal tumor originating from the ribs (chondrosarcoma or osteosarcoma, with no history of asbestos exposure. CT-guided core needle biopsies were diagnosed as malignant sarcomatoid mesothelioma. Surgical resection and chest wall reconstruction were performed, confirming the diagnosis and revealing a secondary histologic component (epithelioid, supporting the diagnosis of biphasic malignant mesothelioma.

Mesotheliomas of the pleura and the peritoneum

International Nuclear Information System (INIS)

Engelhard, K.; Roedl, W.

1985-01-01

From 1972 and 1982 we observed 6 cases of diffuse pleural mesothelioma and 3 cses of peritoneal mesothelioma in the Department of Internal Medicine of the University of Erlangen-Nuernberg. In 5 of 6 cases one sided noncharacteristic relapsing pleural effusion was the only sign of the pleural tumor process. Only in one case a pleural tumor constallation was diagnosed. Tomography of the lung showed a normal free central bronchial system and peripheral bronchial infiltration or displacement. In all cases CT scans were able to localize the tumor furthermor to demonstrate the exact extension and the infiltration of the mediastinum or of the diaphragm into the abdomen. Beside conventional X-rays such as double contrast examination of the colon and mesenterial angiography CT scans played the major role in diagnosing this rare peritoneal mesothelioma. Massive ascites, mesenterial infiltration, thickening of the mesentherial radix, and tumor embedding of bowel and vessels is of diagnostic significance. To ensure the diagnosis one has to do a thoraco- or laparoscopy. (orig.) [de

Benign Multicystic Mesothelioma in the Left Round Ligament: Case Report

International Nuclear Information System (INIS)

Bae, So Young; Yi, Boem Ha; Lee, Hae Kyung; Park, Seong Jin; Cho, Gyu Seok; Kwak, Jeong Ja

2010-01-01

Benign multicystic mesothelioma is a rare mesothelial lesion that forms multicystic masses in the upper abdomen, pelvis, and retroperitoneum. Most cases have a benign course. We present the ultrasound and MR findings of benign multicystic mesothelioma in the left round ligament, which caused a left inguinal hernia in a 46-year-old woman

Benign Multicystic Mesothelioma in the Left Round Ligament: Case Report

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Bae, So Young; Yi, Boem Ha; Lee, Hae Kyung; Park, Seong Jin; Cho, Gyu Seok; Kwak, Jeong Ja [Soonchunhyang University Bucheon Hospital, Bucheon (Korea, Republic of)

2010-02-15

Benign multicystic mesothelioma is a rare mesothelial lesion that forms multicystic masses in the upper abdomen, pelvis, and retroperitoneum. Most cases have a benign course. We present the ultrasound and MR findings of benign multicystic mesothelioma in the left round ligament, which caused a left inguinal hernia in a 46-year-old woman.

Calcification in a pleural mesothelioma

International Nuclear Information System (INIS)

Nichols, D.M.; Johnson, M.A.

1983-01-01

Extensive calcification in a rapidly growing malignant mixed mesothelioma of the pleura was observed on plain radiography and computed tomography of the chest in a patient with a long history of asbestos exposure and chronic renal failure

Malignant Mesothelioma after Household Exposure to Asbestos

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Raya Saba

2013-01-01

Full Text Available Malignant mesothelioma (MM is an aggressive cancer that has been closely linked to asbestos exposure. Initially recognized as an occupational cancer in male workers, MM was later found to occur in their family members as well. We report the case of an 89-year-old female who presented with abdominal distention, pain, and findings consistent with malignant ascites. Family history was significant for fatal mesothelioma in her husband of 40 years, who was a worker at a tile factory. The diagnosis of MM was confirmed on pathologic examination of the omental core biopsy.

A Potential Therapeutic Strategy for Malignant Mesothelioma with Gene Medicine

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Yuji Tada

2013-01-01

Full Text Available Malignant mesothelioma, closely linked with occupational asbestos exposure, is relatively rare in the frequency, but the patient numbers are going to increase in the next few decades all over the world. The current treatment modalities are not effective in terms of the overall survival and the quality of life. Mesothelioma mainly develops in the thoracic cavity and infrequently metastasizes to extrapleural organs. A local treatment can thereby be beneficial to the patients, and gene therapy with an intrapleural administration of vectors is one of the potential therapeutics. Preclinical studies demonstrated the efficacy of gene medicine for mesothelioma, and clinical trials with adenovirus vectors showed the safety of an intrapleural injection and a possible involvement of antitumor immune responses. Nevertheless, low transduction efficiency remains the main hurdle that hinders further clinical applications. Moreover, rapid generation of antivector antibody also inhibits transgene expressions. In this paper, we review the current status of preclinical and clinical gene therapy for malignant mesothelioma and discuss potential clinical directions of gene medicine in terms of a combinatory use with anticancer agents and with immunotherapy.

MR imaging features of peritoneal adenomatoid mesothelioma: a case report

International Nuclear Information System (INIS)

Lins, Cynthia Maria Coelho; Elias Junior, Jorge; Muglia, Valdair Francisco; Monteiro, Carlos Ribeiro; Feres, Omar

2009-01-01

Adenomatoid mesothelioma of the peritoneum (AMP) is a rare benign tumor originating from mesothelial cells.1 Most frequently, AMP occurs between 26 and 55 years of age, at a mean age of 41 years. In contrast to diffuse malignant mesothelioma, which has been linked to asbestos exposure, the etiology of AMP has not been established. Only a minority of patients have symptoms related to the tumor. AMP may present local recurrence, but it has no potential for malignant transformation. Although there are many case reports of abdominal mesotheliomas, to date, there have been no reports of MR imaging features of AMP. In this article, we present the MR imaging features of a case of AMP with histopathological correlation. (author)

MR imaging features of peritoneal adenomatoid mesothelioma: a case report

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Lins, Cynthia Maria Coelho; Elias Junior, Jorge; Muglia, Valdair Francisco; Monteiro, Carlos Ribeiro [University of Sao Paulo (USP), Ribeirao Preto, SP (Brazil). School of Medicine. Dept. of Internal Medicine], e-mail: jejunior@fmrp.usp.br; Cunha, Adilson Ferreira [School of Medicine of Sao Jose do Rio Preto (FAMERP), SP (Brazil). Dept. of Gynecology and Obstetrics; Valeri, Fabio V. [Victorio Valeri Institute of Medical Diagnosis, Ribeirao Preto, SP (Brazil); Feres, Omar [University of Sao Paulo (USP), Ribeirao Preto, SP (Brazil). School of Medicine. Dept. of Surgery and Anatomy

2009-07-01

Adenomatoid mesothelioma of the peritoneum (AMP) is a rare benign tumor originating from mesothelial cells.1 Most frequently, AMP occurs between 26 and 55 years of age, at a mean age of 41 years. In contrast to diffuse malignant mesothelioma, which has been linked to asbestos exposure, the etiology of AMP has not been established. Only a minority of patients have symptoms related to the tumor. AMP may present local recurrence, but it has no potential for malignant transformation. Although there are many case reports of abdominal mesotheliomas, to date, there have been no reports of MR imaging features of AMP. In this article, we present the MR imaging features of a case of AMP with histopathological correlation. (author)

Markers for the non-invasive diagnosis of mesothelioma: a systematic review

NARCIS (Netherlands)

van der Bij, S.; Schaake, E.; Koffijberg, H.; Burgers, J. A.; de Mol, B. A. J. M.; Moons, K. G. M.

2011-01-01

BACKGROUND: Numerous markers have been evaluated to facilitate the non-invasive diagnostic work-up of mesothelioma. The purpose of this study was to conduct a structured review of the diagnostic performance of non-invasive marker tests for the detection of mesothelioma in patients with suspected

Markers for the non-invasive diagnosis of mesothelioma : A systematic review

NARCIS (Netherlands)

van der Bij, S.; Schaake, E.; Koffijberg, H.; Burgers, J. A.; De Mol, B. A J M; Moons, K.G.M.

2011-01-01

Background: Numerous markers have been evaluated to facilitate the non-invasive diagnostic work-up of mesothelioma. The purpose of this study was to conduct a structured review of the diagnostic performance of non-invasive marker tests for the detection of mesothelioma in patients with suspected

National Mesothelioma Virtual Bank: A Platform for Collaborative Research and Mesothelioma Biobanking Resource to Support Translational Research.

Science.gov (United States)

Amin, Waqas; Parwani, Anil V; Melamed, Jonathan; Flores, Raja; Pennathur, Arjun; Valdivieso, Federico; Whelan, Nancy B; Landreneau, Rodeny; Luketich, James; Feldman, Michael; Pass, Harvey I; Becich, Michael J

2013-01-01

The National Mesothelioma Virtual Bank (NMVB), developed six years ago, gathers clinically annotated human mesothelioma specimens for basic and clinical science research. During this period, this resource has greatly increased its collection of specimens by expanding the number of contributing academic health centers including New York University, University of Pennsylvania, University of Pittsburgh Medical Center, and Mount Sinai School of Medicine. Marketing efforts at both national and international annual conferences increase awareness and availability of the mesothelioma specimens at no cost to approved investigators, who query the web-based NMVB database for cumulative and appropriate patient clinicopathological information on the specimens. The data disclosure and specimen distribution protocols are tightly regulated to maintain compliance with participating institutions' IRB and regulatory committee reviews. The NMVB currently has over 1120 annotated cases available for researchers, including paraffin embedded tissues, fresh frozen tissue, tissue microarrays (TMA), blood samples, and genomic DNA. In addition, the resource offers expertise and assistance for collaborative research. Furthermore, in the last six years, the resource has provided hundreds of specimens to the research community. The investigators can request specimens and/or data by submitting a Letter of Intent (LOI) that is evaluated by NMVB research evaluation panel (REP).

Radiological Findings in a case of Advance staged Mesothelioma

Science.gov (United States)

Aziz, Fahad

2009-01-01

Chest X Ray is the initial screening test for the mesothelioma like all other the chest diseases. But computed tomography (CT) is the imaging technique of choice for charactering pleural masses. CT also gives important information regarding invasion of the chest wall and surrounding structures. Certain CT features help differentiate benign from malignant processes. This short article highlights the salient CT appearance of mesothelioma; the most common pleural tumor. PMID:22263002

Localized fibrous mesothelioma of the liver: a case report

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Kim, Young Hwan; Lee, Moon Gyu; Weon, Young Cheol; Lee, Seung Gyu; Kim, Yoon Jeong; Lee, In Chul; Auh, Yong Ho [Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of)

1995-10-15

Localized fibrous mesothelioma of the liver is very rare benign tumor. It usually manifest large palpable hepatic mass in right upper quadrant area, and the prognosis is excellent by surgical resection. Contrast enhanced CT scan shows well defined hyperattenuating mass and celiac angiogram shows hypervascular mass. Recently we experienced 1 case of localized fibrous mesothelioma of the liver, and we report CT and angiographic findings of this tumor.

Introduction and overview. Perinatal carcinogenesis: growing a node for epidemiology, risk management, and animal studies

International Nuclear Information System (INIS)

Anderson, Lucy M.

2004-01-01

Perinatal carcinogenesis as a cross-disciplinary concern is the subject of this special issue of Toxicology and Applied Pharmacology, which consists of a total of eight reviews or commentaries in the areas of epidemiology, risk assessment, and animal models. Some of the conclusions from these articles, and the Questions and Answers section that follows most of them, are summarized here. There is adequate reason to suspect that perinatal exposures contribute to human cancer risk, both childhood cancers, and those appearing later in life. The latter type of risk may actually be quantitatively the more important, and involve a wide range of types of effects, but has received only limited attention. With regard to childhood cancers, fetal irradiation and diethylstilbestrol exposure are known etiological agents, and it is likely, but not yet certain, there are additional external causes of a portion of these. Some current focal points of interest here include nitroso compounds, DNA topoisomerase inhibitors, viruses, anti-AIDS drugs, and endocrine disruptors. Regulatory agencies must rely heavily on animal data for estimation of human risk due to perinatal exposures to chemicals, and the quantity and quality of these data presently available for this purpose are greatly limiting. Correctly designed conventional animal studies with suspect chemicals are still needed. Furthermore, genetically engineered mouse models for childhood cancers, especially medulloblastoma, have become available, and could be used for screening of candidate causative agents for this cancer type, and for better understanding of gene-environment interactions

Biologically based modelling and simulation of carcinogenesis at low doses

International Nuclear Information System (INIS)

Ouchi, Noriyuki B.

2003-01-01

The process of the carcinogenesis is studied by computer simulation. In general, we need a large number of experimental samples to detect mutations at low doses, but in practice it is difficult to get such a large number of data. To satisfy the requirements of the situation at low doses, it is good to study the process of carcinogenesis using biologically based mathematical model. We have mainly studied it by using as known as 'multi-stage model'; the model seems to get complicated, as we adopt the recent new findings of molecular biological experiments. Moreover, the basic idea of the multi-stage model is based on the epidemiologic data of log-log variation of cancer incidence with age, it seems to be difficult to compare with experimental data of irradiated cell culture system, which has been increasing in recent years. Taking above into consideration, we concluded that we had better make new model with following features: 1) a unit of the target system is a cell, 2) the new information of the molecular biology can be easily introduced, 3) having spatial coordinates for checking a colony formation or tumorigenesis. In this presentation, we will show the detail of the model and some simulation results about the carcinogenesis. (author)

Review of hepatocellular carcinoma: Epidemiology, etiology, and carcinogenesis

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Yezaz Ahmed Ghouri

2017-01-01

Full Text Available Since the 1970s, the epidemic of hepatocellular carcinoma (HCC has spread beyond the Eastern Asian predominance and has been increasing in Northern hemisphere, especially in the United States (US and Western Europe. It occurs more commonly in males in the fourth and fifth decades of life. Among all cancers, HCC is one of the fastest growing causes of death in the US and poses a significant economic burden on healthcare. Chronic liver disease due to hepatitis B virus or hepatitis C virus and alcohol accounts for the majority of HCC cases. Incidence of nonalcoholic fatty liver disease has been on the risem and it has also been associated with the development of HCC. Its pathogenesis varies based on the underlying etiological factor although majority of cases develop in the setting of background cirrhosis. Carcinogenesis of HCC includes angiogenesis, chronic inflammation, and tumor macroenvironment and microenvironment. There is a significant role of both intrinsic genetic risk factors and extrinsic influences such as alcohol or viral infections that lead to the development of HCC. Understanding its etiopathogenesis helps select appropriate diagnostic tests and treatments.

Research priorities in mesothelioma: A James Lind Alliance Priority Setting Partnership.

Science.gov (United States)

Stephens, R J; Whiting, C; Cowan, K

2015-08-01

In the UK, despite the import and use of all forms of asbestos being banned more than 15 years ago, the incidence of mesothelioma continues to rise. Mesothelioma is almost invariably fatal, and more research is required, not only to find more effective treatments, but also to achieve an earlier diagnosis and improve palliative care. Following a debate in the House of Lords in July 2013, a package of measures was agreed, which included a James Lind Alliance Priority Setting Partnership, funded by the National Institute for Health Research. The partnership brought together patients, carers, health professionals and support organisations to agree the top 10 research priorities relating to the diagnosis, treatment and care of patients with mesothelioma. Following the established James Lind Alliance priority setting process, mesothelioma patients, current and bereaved carers, and health professionals were surveyed to elicit their concerns regarding diagnosis, treatment and care. Research questions were generated from the survey responses, and following checks that the questions were currently unanswered, an interim prioritisation survey was conducted to identify a shortlist of questions to take to a final consensus meeting. Four hundred and fifty-three initial surveys were returned, which were refined into 52 unique unanswered research questions. The interim prioritisation survey was completed by 202 responders, and the top 30 questions were taken to a final meeting where mesothelioma patients, carers, and health professionals prioritised all the questions, and reached a consensus on the top 10. The top 10 questions cover a wide portfolio of research (including assessing the value of immunotherapy, individualised chemotherapy, second-line treatment and immediate chemotherapy, monitoring patients with pleural thickening, defining the management of ascites in peritoneal mesothelioma, and optimising follow-up strategy). This list is an invaluable resource, which should be

Metastases skin of a mesothelioma. Report case

International Nuclear Information System (INIS)

Aguero, M.; Gauna, C.; Plans, J.; Pereira, R.; Caballero, C.

2010-01-01

Introduction: Malignant mesothelioma derived from mesothelium cells. On his pleural location is frequently associated with stroke and that is the first manifestation, presenting low rates performing diagnostic cytology of the spill, with only a third positivity, and even conducting blind pleural biopsy. In early stages of thoracoscopy disease expands the diagnostic possibilities. The age of neoplasia presentation is between 50 and 70 years, with a predominance in men than matters women, probably because the most common occupational exposure to asbestos in it, main risk factor. The main sites of metastases occurring in a patient with malignant mesothelioma in lung, liver and central nervous system. The incidence of skin metastases (visceral primary) are between 1.2% and 4.4% and the ranks occurs in all types of tumours. There is one report of cutaneous metastasis of mesothelioma as a diagnostic event. Case report: Patient 63, who consulted for chest pain of one month evolution by which it prompted Chest X-ray being verified the left pleural effusion which is drained and analyzed to meet the biochemical criteria of an exudate, with crops negative. pleural biopsy, and thoracentesis was performed which resulted in negative cells neoplastic. It was decided to perform VATS where multiple pleural nodules notes occupying the entire pleural cavity which biopsy; the pathology report Undifferentiated Malignant Tumour reported. IHC: Cytokeratin AE1 / AE3 weak positive, cytokeratin 8/18 Vimentin Positive Positive and thus favors the diagnosis of Mesothelioma. It was made 6 cycles of cisplatin + pemetrexed completed in February / 2010 with good response. Six months have chest pain again so PET-CT is performed where finds local relapse, and likely adrenal marrow MTS MTS and contralateral lung. Eight Study days after skin nodules are detected in respecting scalp and face neck which supports 1rio biopsy is taken. known. Conclusion: The Mesothelioma is a rare entity in our

Imaging of mesothelioma of tunica vaginalis testis

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Bertolotto, M. [University of Trieste, Department of Radiology, Trieste (Italy); Boulay-Coletta, I. [Fondation Hopital Saint Joseph, Service d' Imagerie Medical, Paris (France); Butini, R. [Ospedale S. Giacomo, Department of Radiology, Castelfranco Veneto, TV (Italy); Dudea, S.M. [Univ. Med. Pharm. ' ' Iuliu Hatieganu' ' , Department of Radiology, Cluj-Napoca (Romania); Grenier, N. [Pellegrin Hospital, Department of Radiology, Bordeaux (France); Oltmanns, G. [University Hospital of North Norway, Department of Radiology, Tromsoe (Norway); Ramchandani, P. [University of Pennsylvania, Department of Radiology, Perelman School of Medicine, Philadelphia, PA (United States); Stein, M.W. [Montefiore Medical Center, Department of Radiology, Albert Einstein College of Medicine, Bronx, NY (United States); Valentino, M. [Sant' Antonio Hospital, Department of Radiology, Tolmezzo, UD (Italy); Derchi, Lorenzo E. [University of Genoa, Department of Health Sciences, Genova (Italy); IRCCS Azienda Ospedaliera Universitaria San Martino IST, Radiologia d' Urgenza, Genova (Italy)

2016-03-15

To describe the imaging findings in a series of patients with mesothelioma of the tunica vaginalis testis. We reviewed clinical data, imaging findings and follow-up information in a series of 10 pathology-proven cases of mesothelioma (all had US; 2 had MR) of the tunica vaginalis. A variety of patterns could be observed, the most common (5/10) being a hydrocele with parietal, solid and hypervascular vegetations; one patient had a septated hydrocele with hypervascular walls; one had multiple, solid nodules surrounded by a small, physiological quantity of fluid; one a cystic lesion with thick walls and vegetations compressing the testis; two had a solid paratesticular mass. MR showed multiple small nodules on the surface of the tunica vaginalis in one case and diffuse thickening and vegetations in the other one; lesions had low signal intensity on T2-w images and were hypervascular after contrast injection. A preoperative diagnosis of mesotheliomas presenting as solid paratesticular masses seems very difficult with imaging. On the contrary, the diagnosis must be considered in patients in whom a hydrocele with parietal vegetations is detected, especially if these show high vascularity. (orig.)

Cap-dependent translational control of oncolytic measles virus infection in malignant mesothelioma.

Science.gov (United States)

Jacobson, Blake A; Sadiq, Ahad A; Tang, Shaogeng; Jay-Dixon, Joe; Patel, Manish R; Drees, Jeremy; Sorenson, Brent S; Russell, Stephen J; Kratzke, Robert A

2017-09-08

Malignant mesothelioma has a poor prognosis for which there remains an urgent need for successful treatment approaches. Infection with the Edmonston vaccine strain (MV-Edm) derivative of measles virus results in lysis of cancer cells and has been tested in clinical trials for numerous tumor types including mesothelioma. Many factors play a role in MV-Edm tumor cell selectivity and cytopathic activity while also sparing non-cancerous cells. The MV-Edm receptor CD46 (cluster of differentiation 46) was demonstrated to be significantly higher in mesothelioma cells than in control cells. In contrast, mesothelioma cells are not reliant upon the alternative MV-Edm receptor nectin-4 for entry. MV-Edm treatment of mesothelioma reduced cell viability and also invoked apoptotic cell death. Forced expression of eIF4E or translation stimulation following IGF-I (insulin-like growth factor 1) exposure strengthened the potency of measles virus oncolytic activity. It was also shown that repression of cap-dependent translation by treatment with agents [4EASO, 4EGI-1] that suppress host cell translation or by forcing cells to produce an activated repressor protein diminishes the strength of oncolytic viral efficacy.

Microenvironment-dependent phenotypic changes in a SCID mouse model for malignant mesothelioma

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Eva eDarai-Ramqvist

2013-08-01

Full Text Available Background and Aims: Malignant mesothelioma is an aggressive, therapy-resistant tumor. Mesothelioma cells may assume an epithelioid or a sarcomatoid phenotype, and presence of sarcomatoid cells predicts poor prognosis. In this study, we investigated differentiation of mesothelioma cells in a xenograft model, where mesothelioma cells of both phenotypes were induced to form tumors in SCID mice. Methods: Xenografts were established and thoroughly characterized using a comprehensive immunohistochemical panel, array comparative genomic hybridization of chromosome 3, fluorescent in situ hybridization and electron microscopy.Results: Epithelioid and sarcomatoid cells gave rise to xenografts of similar epithelioid morphology. While sarcomatoid-derived xenografts had higher growth rates, the morphology and expression of differentiation-related markers was similar between xenografts derived from both phenotypes. Array comparative genomic hybridization showed a convergent genotype for both xenografts, resembling the original aggressive sarcomatoid cell sub-line.Conclusions: Human mesothelioma xenografts from sarcomatoid and epithelioid phenotypes converged to a similar differentiation state, and genetic analyses suggested that clonal selection in the mouse microenvironment was a major contributing factor. This thoroughly characterized animal model can be used for further studies of molecular events underlying tumor cell differentiation.

CT diagnosis and pathological basis of localized malignant peritoneal mesothelioma

International Nuclear Information System (INIS)

Zheng Xiangwu; Wu Enfu; Yin Weiwei; Zhou Weizhong; Zhu Qijian; Zheng Xiaofeng

2001-01-01

Objective: To study the value of CT diagnosis in localized malignant peritoneal mesothelioma. Methods: CT features of 4 cases with localized malignant peritoneal mesothelioma and the pathological basis were analyzed. Results: All 4 cases showed a large localized mass with an average size of 13 cm. 3 of 4 cases were cystic-solid predominantly multi-cystic; another case was solid accompanied by necrosis. Contrast CT demonstrated marked enhancement in the solid portion of tumor in all 4 cases, the highest CT density was 106 HU(average 76 HU). There was no distant metastasis and ascites. Conclusion: Multi-cysts, remarkable enhancement of the solid area and no distant metastasis may be the main characteristic CT features of localized malignant peritoneal mesothelioma

Comparative study of mesothelioma and asbestosis using computed tomography and conventional chest radiography

International Nuclear Information System (INIS)

Rabinowitz, T.G.; Efremidis, S.C.; Cohen, B.; Dan, S.; Efremidis, A.; Chahinian, A.P.; Teirstein, A.S.

1982-01-01

A comparative study using computed tomography and conventional posteroanterior radiography was performed on 27 patients with mesothelioma and 13 patients with advanced asbestosis. The major pathologic features of both asbestosis and mesothelioma were well demonstrated by both modalities; computed tomography demonstrated the findings more frequently and in greater detail. No distinguishing features could be established based on configuration and size of the lesion. Many pleural plaques associated with advanced asbestosis were large and irregular and resembled those associated with mesothelioma. However, nodular involvement of the pleural fissures, pleural effusion, and ipsilateral volume loss with a fixed mediastinum were features predominating in mesothelioma. Growth determination of the plaques associated with asbestosis may be of minimal value since such plaques also undergo growth due to active inflammatory changes

Capacity of tumor necrosis factor to augment lymphocyte-mediated tumor cell lysis of malignant mesothelioma

International Nuclear Information System (INIS)

Bowman, R.V.; Manning, L.S.; Davis, M.R.; Robinson, B.W.

1991-01-01

Recombinant human tumor necrosis factor (rHuTNF) was evaluated both for direct anti-tumor action against human malignant mesothelioma and for its capacity to augment the generation and lytic phases of lymphocyte-mediated cytotoxicity against this tumor. rHuTNF was directly toxic by MTT assay to one of two mesothelioma cell lines evaluated, but had no effect on susceptibility to subsequent lymphocyte-mediated lysis of either line. TNF alone was incapable of generating anti-mesothelioma lymphokine-activated killer cell (LAK) activity. Furthermore, it did not augment the degree or LAK activity produced by submaximal interleukin-2 (IL-2) concentrations nor did it augment lysis of mesothelioma cells by natural killer (NK) or LAK effector cells during the 4-hr 51chromium release cytolytic reaction. The studies also suggest that mesothelioma targets are less responsive to TNF plus submaximal IL-2 concentrations than the standard LAK sensitive target Daudi, raising the possibility that intermediate LAK sensitive tumors such as mesothelioma may require separate and specific evaluation in immunomodulation studies. This in vitro study indicates that use of low-dose rHuTNF and IL-2 is unlikely to be an effective substitute for high-dose IL-2 in generation and maintenance of LAK activity in adoptive immunotherapy for mesothelioma

A Single-Institution Experience in Percutaneous Image-Guided Biopsy of Malignant Pleural Mesothelioma

International Nuclear Information System (INIS)

Welch, B. T.; Eiken, P. W.; Atwell, T. D.; Peikert, T.; Yi, E. S.; Nichols, F.; Schmit, G. D.

2017-01-01

PurposeMesothelioma has been considered a difficult pathologic diagnosis to achieve via image-guided core needle biopsy. The purpose of this study was to assess the diagnostic sensitivity of percutaneous image-guided biopsy for diagnosis of pleural mesothelioma.Materials and MethodsRetrospective review was performed to identify patients with a confirmed diagnosis of pleural mesothelioma and who underwent image-guided needle biopsy between January 1, 2002, and January 1, 2016. Thirty-two patients with pleural mesothelioma were identified and included for analysis in 33 image-guided biopsy procedures. Patient, procedural, and pathologic characteristics were recorded. Complications were characterized via standardized nomenclature [Common Terminology for Clinically Adverse Events (CTCAE)].ResultsPercutaneous image-guided biopsy was associated with an overall sensitivity of 81%. No CTCAE clinically significant complications were observed. No image-guided procedures were complicated by pneumothorax or necessitated chest tube placement. No patients had tumor seeding of the biopsy tract.ConclusionPercutaneous image-guided biopsy can achieve high sensitivity for pathologic diagnosis of pleural mesothelioma with a low procedural complication rate, potentially obviating need for surgical biopsy.

A Single-Institution Experience in Percutaneous Image-Guided Biopsy of Malignant Pleural Mesothelioma

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Welch, B. T., E-mail: Welch.brian@mayo.edu; Eiken, P. W.; Atwell, T. D. [Mayo Clinic, Department of Radiology (United States); Peikert, T. [Mayo Clinic, Department of Pulmonary and Critical Care Medicine (United States); Yi, E. S. [Mayo Clinic, Department of Pathology (United States); Nichols, F. [Mayo Clinic, Department of Thoracic Surgery (United States); Schmit, G. D. [Mayo Clinic, Department of Radiology (United States)

2017-06-15

PurposeMesothelioma has been considered a difficult pathologic diagnosis to achieve via image-guided core needle biopsy. The purpose of this study was to assess the diagnostic sensitivity of percutaneous image-guided biopsy for diagnosis of pleural mesothelioma.Materials and MethodsRetrospective review was performed to identify patients with a confirmed diagnosis of pleural mesothelioma and who underwent image-guided needle biopsy between January 1, 2002, and January 1, 2016. Thirty-two patients with pleural mesothelioma were identified and included for analysis in 33 image-guided biopsy procedures. Patient, procedural, and pathologic characteristics were recorded. Complications were characterized via standardized nomenclature [Common Terminology for Clinically Adverse Events (CTCAE)].ResultsPercutaneous image-guided biopsy was associated with an overall sensitivity of 81%. No CTCAE clinically significant complications were observed. No image-guided procedures were complicated by pneumothorax or necessitated chest tube placement. No patients had tumor seeding of the biopsy tract.ConclusionPercutaneous image-guided biopsy can achieve high sensitivity for pathologic diagnosis of pleural mesothelioma with a low procedural complication rate, potentially obviating need for surgical biopsy.

Pleural Mesothelioma Surveillance: Validity of Cases from a Tumour Registry

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France Labrèche

2012-01-01

Full Text Available BACKGROUND: Pleural mesothelioma is a rare tumour associated with exposure to asbestos fibres. Fewer than than one-quarter of cases registered in the Quebec Tumour Registry (QTR have been compensated as work-related. While establishing a surveillance system, this led to questioning as to whether there has been over-registration of cases that are not authentic pleural mesotheliomas in the QTR.

Expression profile and function of Wnt signaling mechanisms in malignant mesothelioma cells

International Nuclear Information System (INIS)

Fox, Simon A.; Richards, Alex K.; Kusumah, Ivonne; Perumal, Vanathi; Bolitho, Erin M.; Mutsaers, Steven E.; Dharmarajan, Arun M.

2013-01-01

Highlights: •Expression profile of Wnt pathway related genes in mesothelioma cells. •Differential expression of key Wnt pathway molecules and regulators. •Wnt3a stimulated mesothelioma growth whereas sFRP4 was inhibitory. •Targeting β-Catenin can sensitise mesothelioma cells to cytotoxic drugs. -- Abstract: Malignant mesothelioma (MM) is an uncommon and particularly aggressive cancer associated with asbestos exposure, which currently presents an intractable clinical challenge. Wnt signaling has been reported to play a role in the neoplastic properties of mesothelioma cells but has not been investigated in detail in this cancer. We surveyed expression of Wnts, their receptors, and other key molecules in this pathway in well established in vitro mesothelioma models in comparison with primary mesothelial cultures. We also tested the biological response of MM cell lines to exogenous Wnt and secreted regulators, as well as targeting β-catenin. We detected frequent expression of Wnt3 and Wnt5a, as well as Fzd 2, 4 and 6. The mRNA of Wnt4, Fzd3, sFRP4, APC and axin2 were downregulated in MM relative to mesothelial cells while LEF1 was overexpressed in MM. Functionally, we observed that Wnt3a stimulated MM proliferation while sFRP4 was inhibitory. Furthermore, directly targeting β-catenin expression could sensitise MM cells to cytotoxic drugs. These results provide evidence for altered expression of a number of Wnt/Fzd signaling molecules in MM. Modulation of Wnt signaling in MM may prove a means of targeting proliferation and drug resistance in this cancer

Expression profile and function of Wnt signaling mechanisms in malignant mesothelioma cells

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Fox, Simon A., E-mail: s.fox@curtin.edu.au [Molecular Pharmacology Laboratory, School of Pharmacy, Curtin Health Innovation Research Institute, Curtin University, Bentley, WA (Australia); Richards, Alex K.; Kusumah, Ivonne; Perumal, Vanathi [Molecular Pharmacology Laboratory, School of Pharmacy, Curtin Health Innovation Research Institute, Curtin University, Bentley, WA (Australia); Bolitho, Erin M. [Western Australian Institute for Medical Research, The University of Western Australia Centre for Medical Research, Perth, WA (Australia); Mutsaers, Steven E. [Lung Institute of Western Australia, Centre for Asthma Allergy and Respiratory Research, University of Western Australia, Nedlands (Australia); Centre for Cell Therapy and Regenerative Medicine, School of Medicine and Pharmacology, University of Western Australia and Western Australian Institute for Medical Research, Nedlands (Australia); Dharmarajan, Arun M. [School of Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University, Bentley, WA (Australia)

2013-10-11

Highlights: •Expression profile of Wnt pathway related genes in mesothelioma cells. •Differential expression of key Wnt pathway molecules and regulators. •Wnt3a stimulated mesothelioma growth whereas sFRP4 was inhibitory. •Targeting β-Catenin can sensitise mesothelioma cells to cytotoxic drugs. -- Abstract: Malignant mesothelioma (MM) is an uncommon and particularly aggressive cancer associated with asbestos exposure, which currently presents an intractable clinical challenge. Wnt signaling has been reported to play a role in the neoplastic properties of mesothelioma cells but has not been investigated in detail in this cancer. We surveyed expression of Wnts, their receptors, and other key molecules in this pathway in well established in vitro mesothelioma models in comparison with primary mesothelial cultures. We also tested the biological response of MM cell lines to exogenous Wnt and secreted regulators, as well as targeting β-catenin. We detected frequent expression of Wnt3 and Wnt5a, as well as Fzd 2, 4 and 6. The mRNA of Wnt4, Fzd3, sFRP4, APC and axin2 were downregulated in MM relative to mesothelial cells while LEF1 was overexpressed in MM. Functionally, we observed that Wnt3a stimulated MM proliferation while sFRP4 was inhibitory. Furthermore, directly targeting β-catenin expression could sensitise MM cells to cytotoxic drugs. These results provide evidence for altered expression of a number of Wnt/Fzd signaling molecules in MM. Modulation of Wnt signaling in MM may prove a means of targeting proliferation and drug resistance in this cancer.

Pleural mesothelioma: management updates and nursing initiatives to improve patient care

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Lehto RH

2014-05-01

Full Text Available Rebecca H LehtoCollege of Nursing, Michigan State University, East Lansing, MI, USAAbstract: Malignant pleural mesothelioma is a relatively rare but aggressive malignancy that is primarily associated with occupational asbestos exposure. While treatment options for mesothelioma have expanded, the disease carries a poor prognosis, with a median of 8 months to 1 year of survival postdiagnosis. This article synthesizes current disease-management practices, including the diagnostic workup, treatment modalities, emerging therapies, and symptom management, and identifies comprehensive nursing strategies that result in the best care based on updated evidence. Multidisciplinary coordination, palliative care initiation, survivorship, and end-of-life care are discussed. Findings may be applied in clinical environments as a resource to help nurses better understand treatment options and care for patients facing malignant pleural mesothelioma. Recommendations for future research are made to move nursing science forward and to improve patient well-being and health-related quality-of-life outcomes for patients and their family members.Keywords: pleural mesothelioma, cancer, symptom management, evidence-based care

Well differentiated papillary mesothelioma of abdomen- a rare case with diagnostic dilemma.

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Saha, Aniruddha; Mandal, Palash Kumar; Manna, Anupam; Khan, Kalyan; Pal, Subrata

2018-01-01

Well-differentiated papillary mesothelioma is a rare tumor occurring predominantly in the peritoneum of young women, a few with history of asbestos exposure. A 28-year-old woman presented with ascites and pain abdomen. Ultrasonography and computed tomography scan of the abdomen revealed a mass in the retroperitoneum measuring 15 cm × 12 cm. Histopathological examination along with immunohistochemistry (IHC) confirmed it to be a papillary mesothelioma in the peritoneum. It is difficult to differentiate from more common malignant mesothelioma and papillary adenocarcinoma, which also have poorer prognosis. The difficulty can be resolved by clinico-radiological correlation along with histopathological examination and IHC.

Role of CT in management of mesothelioma

International Nuclear Information System (INIS)

Godwin, J.D.; Rusch, V.W.; Shuman, W.P.

1987-01-01

The authors examined the accuracy of CT in determining the extent of disease and its role in the follow-up of patients with malignant pleural mesothelioma. Twenty patients underwent complex CT-anatomic correlation. CT was unable to demonstrate small tumor implants in the chest wall (four cases), upper abdomen (two cases), or contralateral hemidiaphragm (one case). Occasionally there was difficulty distinguishing tumor invasion of soft tissues from simple contiguity, benign from malignant nodes, and recurrent tumor from surgical changes. In six of eight treated patients, CT demonstrated recurrence -8 months before signs or symptoms appeared. Despite its limitations, CT is essential in the initial evaluation and follow-up of patients with mesothelioma

Biological Complexities in Radiation Carcinogenesis and Cancer Radiotherapy: Impact of New Biological Paradigms

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Hossein Mozdarani

2012-01-01

Full Text Available Although radiation carcinogenesis has been shown both experimentally and epidemiologically, the use of ionizing radiation is also one of the major modalities in cancer treatment. Various known cellular and molecular events are involved in carcinogenesis. Apart from the known phenomena, there could be implications for carcinogenesis and cancer prevention due to other biological processes such as the bystander effect, the abscopal effect, intrinsic radiosensitivity and radioadaptation. Bystander effects have consequences for mutation initiated cancer paradigms of radiation carcinogenesis, which provide the mechanistic justification for low-dose risk estimates. The abscopal effect is potentially important for tumor control and is mediated through cytokines and/or the immune system (mainly cell-mediated immunity. It results from loss of growth and stimulatory and/or immunosuppressive factors from the tumor. Intrinsic radiosensitivity is a feature of some cancer prone chromosomal breakage syndromes such as ataxia telangectiasia. Radiosensitivity is manifested as higher chromosomal aberrations and DNA repair impairment is now known as a good biomarker for breast cancer screening and prediction of prognosis. However, it is not yet known whether this effect is good or bad for those receiving radiation or radiomimetic agents for treatment. Radiation hormesis is another major concern for carcinogenesis. This process which protects cells from higher doses of radiation or radio mimic chemicals, may lead to the escape of cells from mitotic death or apoptosis and put cells with a lower amount of damage into the process of cancer induction. Therefore, any of these biological phenomena could have impact on another process giving rise to genome instability of cells which are not in the field of radiation but still receiving a lower amount of radiation. For prevention of radiation induced carcinogenesis or risk assessment as well as for successful radiation

Carcinogenesis

International Nuclear Information System (INIS)

Anon.

1976-01-01

Progress is reported on studies at the molecular, biochemical, and immunological level of carcinogenesis induced in mice by viruses, radiation, or environmental chemicals alone or in combinations. Emphasis was placed on the identification and assessments of cocarcinogens and studies on their mechanisms of action. Data are included on mechanisms of carcinogenesis in the liver, thyroid, Harderian glands, skin, and lungs. The effects of the food additive butylated hydroxytoluene (BHT), phenobarbitol, DDT, uv irradiation, the herbicide 3-amino-1,2,4-triazole(AT), the pituitary hormone prolactin, topically applied 8-methoxypsoralen (8-MOP), and benzo(a) pyrene(BaP) on tumor induction or enhancement were studied

Radiofrequency Ablation Effectively Treated Focal Recurrence of Mesothelioma.

Science.gov (United States)

Nakamura, Akifumi; Takuwa, Teruhisa; Hashimoto, Masaki; Kondo, Nobuyuki; Takaki, Haruyuki; Fujiwara, Masayuki; Yamakado, Koichiro; Hasegawa, Seiki

2018-02-01

A 55-year-old man with malignant pleural mesothelioma underwent multimodality treatment comprising induction chemotherapy followed by extrapleural pneumonectomy and radiation therapy. After 2.5 years, focal recurrence occurred, with computed tomography revealing a tumor in the left cardiophrenic angle. Surgery was considered a problem for the patient because of the previous extrapleural pneumonectomy and difficult tumor location. Radiofrequency ablation was thus performed; the course was uneventful, and there was no recurrence. Radiofrequency ablation should be considered an option to treat recurrence of malignant pleural mesothelioma. Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Malignant pleural mesothelioma: a phase II trial with docetaxel.

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Vorobiof, D A; Rapoport, B L; Chasen, M R; Abratt, R P; Cronje, N; Fourie, L; McMichael, G; Hacking, D

2002-03-01

Current cytotoxic therapy has been of limited benefit to patients with malignant pleural mesothelioma. Single agent chemotherapy has been extensively evaluated in small series of phase II clinical trials, with disappointing responses. Docetaxel, an effective taxane in the treatment of advanced breast cancer and non-small-cell lung cancer, was administered intravenously at a dose of 100 mg/m2 every 3 weeks to 30 chemotherapy naive patients with malignant pleural mesothelioma in a prospective multi-institutional phase II clinical trial. An objective response rate (partial responses) of 10% was documented. Additionally, 21% of the patients had minor responses (intention-to-treat analysis). Three patients died within 2 weeks post-first cycle of therapy, although only one patient's death was directly attributed to the investigational drug, whilst in the majority of the patients, manageable and treatable toxicities were encountered. In this phase II clinical trial, docetaxel proved to be mildly effective in the treatment of patients with malignant pleural mesothelioma.

Caffeine markedly sensitizes human mesothelioma cell lines to pemetrexed

Science.gov (United States)

Min, Sang Hee; Goldman, I. David; Zhao, Rongbao

2013-01-01

Pemetrexed is a new generation antifolate approved for the treatment of mesothelioma and non-small cell lung cancer. Caffeine is known to augment radiation or chemotherapeutic drug-induced cell killing. The current study addresses the impact of caffeine on the activity of pemetrexed in mesothelioma cell lines. Caffeine enhanced pemetrexed activity in all four mesothelioma cell lines tested (H2052, H2373, H28 and MSTO-211H). Caffeine sensitized H2052 cells in a dose- and schedule-dependent manner, and was associated with a markedly decreased clonogenic survival. Caffeine sensitization occurred only in cells subjected to pulse, but not continuous, exposure to pemetrexed. Similar pemetrexed sensitization was also observed with the clinically better tolerated caffeine analog, theobromine. Pemetrexed sensitization by caffeine was associated with an increase in pemetrexed-induced phosphorylation of ataxia-telangiectasia-mutated (ATM) and Chk1. These data indicate that caffeine and its analog, theobromine, may be a useful approach to enhance pemetrexed-based chemotherapy. PMID:17594092

CT diagnosis and differential diagnosis of malignant pleural mesothelioma

International Nuclear Information System (INIS)

Xiong Juxin; Yang Zenian; Luo Zhongyao

2008-01-01

Objective: To study the CT features of malignant pleural mesothelioma and improve diagnostic accuracy. Methods: The CT findings of 14 patients with malignant pleural mesothelioma proven by surgery or histopathology were analyzed retrospectively. CT plain scan was performed in all cases, 9 cases received both CT plain scan and contrast CT scan. Results: All the cases demonstrated various pleural thickening including diffuse pleural thickening (n=10). Among all the cases, there were nodular pleural thickening (n=4), lumpy pleural thickening (n=7), ring-like pleural thickening (n=3). Pleural thickness which was more than 1.0 cm was found in 12 cases. Pleural effusion (n=10), mediastinum immobilization (n=10) and thoracic cavity stricture in the trouble side (n=10) were also revealed. Conclusion: Obvious characteristics in cases with malignant pleural mesothelioma was showed in CT examination, which plays an important role in the diagnosis and differential diagnosis of this disease. (authors)

Porcelain Factory Worker With Asbestos-related Mesothelioma

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Meng-Ting Tsou

2009-10-01

Full Text Available Malignant mesothelioma is a rare tumor among the general population, but for people exposed to asbestos, the lifetime risk is high. A 58-year old man presented with suffering from chest pain, upper back pain, shortness of breath, and coughing that had continued for several months. A chest X-ray revealed right-side pleural effusion; however, pleural biopsy from drainage treatment confirmed a diagnosis of malignant mesothelioma. According to his occupational and environmental history, the patient had worked continuously in a porcelain factory for 30 years. The specific characteristics of his work, making asbestos wallboards and gaskets, entailed working in high-temperature conditions with a high fine-particle content in the atmosphere. The high working temperature caused asbestos debris and dust to fall down regularly from the wallboards, however, it was not until recently that the patient had started to wear personal protection. Asbestos is a significant source of hazardous exposure in old buildings, and this case serves as a reminder of the importance of asbestos-related exposure history, which facilitated the correct diagnosis of pulmonary malignant mesothelioma. Asbestos-containing materials that are now banned or regulated are still present in older buildings and remain an exposure hazard; they continue to be a serious health concern in many countries.

Variations in mesothelioma mortality rates among migrants to Australia and Australian-born.

Science.gov (United States)

Si, Si; Peters, Susan; Reid, Alison

2018-07-01

Australia's use and consumption of asbestos occurred at the same time as its immigration boom. Our objective was to investigate mesothelioma death rates among migrants and Australian-born between 1981 and 2012. Australian national mesothelioma deaths from 1981 to 2002 and 2006 to 2012 together with national censuses from 1981 to 2011 were extracted and combined. Directly standardised rates and negative binomial regression were applied examining differences in mesothelioma death rates with regard to country of birth. Migrants from the UK and Ireland, Italy and Germany had significantly higher mesothelioma death rates than Australian-born; lower rates were observed among migrants from other countries. Our findings suggest there may have been differences in occupational health and safety between foreign and Australian-born. Because of changes in the demographics of migrants to Australia since the 1970s and changes in occupational circumstances over time, further comparisons of occupational-related health outcomes between foreign and Australian-born could identify potential occupational inequalities that may still exist today.

Mesothelioma of tunica vaginalis of "uncertain malignant potential" - an evolving concept: case report and review of the literature

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Yilmaz Asli

2011-08-01

Full Text Available Abstract Mesothelioma of tunica vaginalis is a rare neoplasm, typically demonstrating frankly malignant morphology and aggressive behavior. Rare cases of well-differentiated papillary mesotheliomas have also been reported, which, in contrast, demonstrate indolent behavior. There are, however, cases which do not fit into the well-differentiated or diffuse malignant mesothelioma categories and can be considered mesothelioma of tunica vaginalis of "uncertain malignant potential", which is an emerging diagnostic category. A 57-year-old man presented with a neoplasm in a hydrocele sac. The neoplasm was non-invasive, but showed focal complex and solid growth and it was difficult to categorize either as well-differentiated papillary mesotheliomas or malignant mesothelioma. After the initial limited resection, the patient underwent radical orchiectomy with hemiscrotectomy and is alive and without disease progression after 6 years. Documentation of these rare tumors will allow their distinction from true malignant mesotheliomas and will facilitate the development of specific treatment recommendations.

Benign cystic mesothelioma of the appendix presenting in a woman: a case report

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Beddy David

2010-12-01

Full Text Available Abstract Introduction Benign cystic mesothelioma or peritoneal inclusion cysts are rare benign abdominal tumors usually occurring in females of reproductive age. These cysts present as abdominopelvic pain or masses but are often found on imaging or incidentally at surgery. They are commonly associated with pelvic inflammatory disease, endometriosis, or ovarian cysts. We report what is, to the best of our knowledge, the first case of a benign cystic mesothelioma complicating a presentation of acute appendicitis. Case Presentation A 19-year-old Irish Caucasian woman presented with abdominal pain. Imaging suggested appendicitis with abscess formation. She was treated with antibiotics and scheduled for interval appendicectomy. At laparoscopy, an unusual cystic mass was found arising from the appendix. Histology revealed benign cystic mesothelioma. Conclusion We report what is, to the best of our knowledge, the first case of a benign cystic mesothelioma arising from the appendix and complicating a presentation of acute appendicitis. This is a benign pathology, but recurrences are not uncommon. Benign cystic mesothelioma should be included in the differential when investigating pelvic masses or abscesses associated with either appendicitis or pelvic inflammatory disease in women.

Benign cystic mesothelioma of the appendix presenting in a woman: a case report

LENUS (Irish Health Repository)

O' Connor, Donal B

2010-12-03

Abstract Introduction Benign cystic mesothelioma or peritoneal inclusion cysts are rare benign abdominal tumors usually occurring in females of reproductive age. These cysts present as abdominopelvic pain or masses but are often found on imaging or incidentally at surgery. They are commonly associated with pelvic inflammatory disease, endometriosis, or ovarian cysts. We report what is, to the best of our knowledge, the first case of a benign cystic mesothelioma complicating a presentation of acute appendicitis. Case Presentation A 19-year-old Irish Caucasian woman presented with abdominal pain. Imaging suggested appendicitis with abscess formation. She was treated with antibiotics and scheduled for interval appendicectomy. At laparoscopy, an unusual cystic mass was found arising from the appendix. Histology revealed benign cystic mesothelioma. Conclusion We report what is, to the best of our knowledge, the first case of a benign cystic mesothelioma arising from the appendix and complicating a presentation of acute appendicitis. This is a benign pathology, but recurrences are not uncommon. Benign cystic mesothelioma should be included in the differential when investigating pelvic masses or abscesses associated with either appendicitis or pelvic inflammatory disease in women.

Primary malignant mesothelioma of the pericardium : a case report

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Park, Hee Hong; Choi, Young Hi; Kim, Tae Hoon; Lee, Yeon Hee; Kim, Young Kwon; Han, Dong Sun; Cho, Jeong Hee; Yu, Pil Mun [Dankook Univ. College of Medicine, Chonan (Korea, Republic of)

1996-09-01

Primary malignant mesothelioma of the pericardium is a very rare and highly lethal neoplasm. Diagnosis is a difficult problem and most of the cases reported in the literature were diagnosed at postmortem. We report a case of primary malignant mesothelioma of the pericardium in a 22 year-old man. CT and MR imaging both showed diffuse irregular pericardial thickening, soft tissue density with cystic lesion, nodular bulging into the myocardium, permeative growth of the tumor, and encasement of the hear and two great vessels.

[Prevalence of pleural malignant mesothelioma in Poland in 1980-1993].

Science.gov (United States)

Szeszenia-Dabrowska, N; Szymczak, W; Wilczyńska, U

1996-01-01

Malignant pleural mesothelioma is subject of special interest for environmental epidemiologists due to its proven cause-effect relationship with the exposure to asbestos dust, particularly crocidolite. The paper discusses the prevalence trends and geographical distribution of pleural mesothelioma in Poland based on the death rate analysis. In 1993 the crude death rate for that neoplasm was found to be 4.48 per 1 million for men and 3.14 per 1 million for women. While interpreting the numerical data, such aspects were considered as the problems with histopathological diagnosis of pleural mesothelioma; the long latency period of 30-40 years; and consequently, the possibility that for the male population the results may have been affected by other causes of death owing to its relatively short average lifespan. The volume and types of asbestos used in Poland were also taken into account.

Malignant peritoneal mesothelioma associated with deep vein thrombosis following radiotherapy for seminoma of the testis

International Nuclear Information System (INIS)

Sato, Fuminori; Yamazaki, Hajime; Ataka, Ken; Mashima, Ichiro; Suzuki, Kenta; Takahashi, Toru; Umezu, Hajime; Gejyo, Fumitake

2000-01-01

A 52-year-old man developed malignant peritoneal mesothelioma 17 years after radiotherapy for seminoma of the testis. Although asbestos exposure is considered to be the major risk factor for the development of malignant mesothelioma, prior therapeutic radiation has also been postulated as a causative factor. The unexplained appearance of ascites or pleural effusion within a previously irradiated area should be considered suggestive of malignant mesothelioma in any long-term survivor of cancer. In addition, the patient suffered a deep vein thrombosis four years before the diagnosis of mesothelioma. Deep vein thrombosis is a common complication of malignant disease, and is often the first clue to occult malignancy. (author)

Malignant peritoneal mesothelioma associated with deep vein thrombosis following radiotherapy for seminoma of the testis

Energy Technology Data Exchange (ETDEWEB)

Sato, Fuminori; Yamazaki, Hajime; Ataka, Ken; Mashima, Ichiro; Suzuki, Kenta; Takahashi, Toru; Umezu, Hajime; Gejyo, Fumitake [Niigata Univ. (Japan). School of Medicine

2000-11-01

A 52-year-old man developed malignant peritoneal mesothelioma 17 years after radiotherapy for seminoma of the testis. Although asbestos exposure is considered to be the major risk factor for the development of malignant mesothelioma, prior therapeutic radiation has also been postulated as a causative factor. The unexplained appearance of ascites or pleural effusion within a previously irradiated area should be considered suggestive of malignant mesothelioma in any long-term survivor of cancer. In addition, the patient suffered a deep vein thrombosis four years before the diagnosis of mesothelioma. Deep vein thrombosis is a common complication of malignant disease, and is often the first clue to occult malignancy. (author)

Incidental finding of multiple well-differentiated papillary mesotheliomas in peritoneum

DEFF Research Database (Denmark)

Jakobsen, Mark; Engvad, Birte; Jensen, Thor

2016-01-01

We present a case of multiple well-differentiated papillary mesotheliomas (WDPM) in the peritoneum found incidentally in a 63-year-old man with urothelial carcinoma of the bladder. When multiple tumors are seen, malignant mesothelioma should be excluded by histopathological examination as this ma...... with a good prognosis. Great care is needed when diagnosing mesothelial proliferations, given the crucial nature of a benign vs malignant diagnosis. No standardized treatment has yet been established....

Papillary mesothelioma of the albuginea testis

NARCIS (Netherlands)

Tjandra, B. S.; Daemen, M. J.; Weil, E. H.

1994-01-01

An eleven-year-old boy is presented with symptom of a torsion of the testis. Scrotal exploration revealed a papillary mesothelioma of the tunica albuginea which is extremely rare in childhood. We report 1 case and review the literature

Pleural mesothelioma in differential diagnostics of a tubercular exudative pleuritis

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O.M. Raznatovskaya

2017-02-01

Full Text Available Background. Difficulties of differential diagnostics of exudative pleuritis due to pleura mesothelioma and such one of tubercular etiology can take a long time that is the reason of delayed well-timed and correct treatment order. Etiological diagnostics of exudative pleuritis has to be based on an integrated approach taking into account the data of clinical inspection of a patient, a laboratory research of pleural exudate, radial, instrumental, pathomorphological and surgical methods. The aim of our study is to establish the features of diagnosis of exudative pleuritis due to pleura mesothelioma by determining of informativeness and value of applied diagnostic methods for further use for differential diagnostics with exudative pleuritis of tubercular etiology on the cases of own clinical observations. Materials and methods. Four clinical cases of diagnostics of pleura mesothelioma in the patients with exudative pleuritis at Municipal Institution “Zaporizhzhia Regional Antituberculous Clinical Dispensary” were analyzed. Results. Four cases of pleura mesothelioma were diagnosed at Municipal Institution “Zaporizhzhia Regional Antituberculous Clinical Dispensary” within differential diagnostics of exudative pleuritis of obscure origin. In all cases the following similar features of pleura mesothelioma were observed: patients were male; patients complained about dyspnoea at exercise stress, thorax pain (on the side of mesothelioma localization, general weakness, periodic cough; the patients denied tuberculosis contact; the general blood test revealed only lymphopenia against the background of the accelerated ESR; micobacteria of tuberculosis were not revealed at all; steady accumulation of an exudate, despite its systematic evacuation; cytologic research of pleural liquid was characterized by a moderate turbidity, serous (serous and hemorrhagic character, with the specific weight of 1015–1016, rising of protein to 33–66 g/l, positive

Mesothelioma Cells Escape Heat Stress by Upregulating Hsp40/Hsp70 Expression via Mitogen-Activated Protein Kinases

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Michael Roth

2009-01-01

Full Text Available Therapy with hyperthermal chemotherapy in pleural diffuse malignant mesothelioma had limited benefits for patients. Here we investigated the effect of heat stress on heat shock proteins (HSP, which rescue tumour cells from apoptosis. In human mesothelioma and mesothelial cells heat stress (39–42°C induced the phosphorylation of two mitogen activated kinases (MAPK Erk1/2 and p38, and increased Hsp40, and Hsp70 expression. Mesothelioma cells expressed more Hsp40 and were less sensitive to heat stress compared to mesothelial cells. Inhibition of Erk1/2 MAPK by PD98059 or by Erk1 siRNA down-regulated heat stress-induced Hsp40 and Hsp70 expression and reduced mesothelioma cell survival. Inhibition of p38MAPK by SB203580 or siRNA reduced Hsp40, but not Hsp70, expression and also increased mesothelioma cell death. Thus hyperthermia combined with suppression of p38 MAPK or Hsp40 may represent a novel approach to improve mesothelioma therapy.

Induction of human breast cell carcinogenesis by triclocarban and intervention by curcumin

Energy Technology Data Exchange (ETDEWEB)

Sood, Shilpa; Choudhary, Shambhunath; Wang, Hwa-Chain Robert, E-mail: hcrwang@utk.edu

2013-09-06

Highlights: •Triclocarban exposure induces breast epithelial cell carcinogenesis. •Triclocarban induces the Erk–Nox pathway, ROS elevation, and DNA damage. •Physiological doses of triclocarban induce cellular carcinogenesis. •Non-cytotoxic curcumin blocks triclocarban-induced carcinogenesis and pathways. -- Abstract: More than 85% of breast cancers are sporadic and attributable to long-term exposure to environmental carcinogens and co-carcinogens. To identify co-carcinogens with abilities to induce cellular pre-malignancy, we studied the activity of triclocarban (TCC), an antimicrobial agent commonly used in household and personal care products. Here, we demonstrated, for the first time, that chronic exposure to TCC at physiologically-achievable nanomolar concentrations resulted in progressive carcinogenesis of human breast cells from non-cancerous to pre-malignant. Pre-malignant carcinogenesis was measured by increasingly-acquired cancer-associated properties of reduced dependence on growth factors, anchorage-independent growth and increased cell proliferation, without acquisition of cellular tumorigenicity. Long-term TCC exposure also induced constitutive activation of the Erk–Nox pathway and increases of reactive oxygen species (ROS) in cells. A single TCC exposure induced transient induction of the Erk–Nox pathway, ROS elevation, increased cell proliferation, and DNA damage in not only non-cancerous breast cells but also breast cancer cells. Using these constitutively- and transiently-induced changes as endpoints, we revealed that non-cytotoxic curcumin was effective in intervention of TCC-induced cellular pre-malignancy. Our results lead us to suggest that the co-carcinogenic potential of TCC should be seriously considered in epidemiological studies to reveal the significance of TCC in the development of sporadic breast cancer. Using TCC-induced transient and constitutive endpoints as targets will likely help identify non-cytotoxic preventive

Occupational asbestos exposure: how to deal with suspected mesothelioma cases--the Dutch approach

NARCIS (Netherlands)

Baas, P.; van 't Hullenaar, N.; Wagenaar, J.; Kaajan, J. P. G.; Koolen, M.; Schrijver, M.; Schlösser, N.; Burgers, J. A.

2006-01-01

Patients with asbestos-related diseases, such as malignant mesothelioma (MM), are not uniformly treated in Europe when they apply for compensation. In The Netherlands, the Institute of Asbestos Victims (IAV) acts on behalf of patients with a malignant mesothelioma. In the majority of cases, the

[Mesothelioma in construction workers: risk estimate, lung content of asbestos fibres, claims for compensation for occupational disease in the Veneto Region mesothelioma register].

Science.gov (United States)

Merler, E; Bressan, Vittoria; Somigliana, Anna

2009-01-01

Work in the construction industry is causing the highest number of mesotheliomas among the residents of the Veneto Region (north-east Italy, 4,5 million inhabitants). To sum up the results on occurrence, asbestos exposure, lung fibre content analyses, and compensation for occupational disease. Case identification and asbestos exposure classification: active search of mesotheliomas that were diagnosed via histological or cytological examinations occurring between 1987 and 2006; a probability of asbestos exposure was attributed to each case, following interviews with the subjects or their relatives and collection of data on the jobs held over their lifetime. Risk estimate among construction workers: the ratio between cases and person-years, the latter derived from the number of construction workers reported by censuses. Lung content of asbestos fibres: examination of lung specimens by Scanning Electron Microscope to determine number and type of fibres. Claims for compensation and compensation awarded: data obtained from the National Institute for Insurance against Occupational Diseases available for the period 1999-2006. of 952 mesothelioma cases classified as due to asbestos exposure, 251 were assigned to work in the construction industry (21 of which due to domestic of environmental exposures), which gives a rate of 4.1 (95% CI 3.6-4.8) x 10(5) x year among construction workers. The asbestos fibre content detected in the lungs of 11 construction workers showed a mean of 1.7 x 10(6) fibres/g dry tissue (range 350,000-3 million) for fibres > 1 micro, almost exclusively due to amphibole fibres. 62% of the claims for compensation were granted but the percentage fell to less than 40% when claims were submitted by a relative, after the death of the subject. The prevalence of mesothelioma occurring among construction workers is high and is associated with asbestos exposure; the risk is underestimated by the subjects and their relatives. All mesotheliomas occurring among

Radiation therapy of peritoneal mesothelioma

International Nuclear Information System (INIS)

Lederman, G.; Recht, A.

1986-01-01

The role of radiation therapy in the treatment of peritoneal mesotheliomas remains ill-defined despite its association with the few long-term survivals reported for this disease. The rationale for local therapy is clear as the disease most often is confined to the peritoneal cavity at the time of initial diagnosis and remains there for much of the subsequent course. Effective local treatment of this intra-abdominal disease would likely improve survival. The absence of randomized studies has made analysis of the various treatments of the disease and the few reported success difficult. Nonetheless, scrutiny of the available data may offer insights and guide future clinical trials, as well as the clinician responsible for the treatment of current patients with peritoneal mesothelioma. The radiotherapeutic approach to oncology stresses anatomic considerations in an attempt to understand the patterns of spread of the primary tumor. The observed location and bulk of disease by clinical examination, radiologic study, surgical exploration, and autopsy suggest mechanisms of metastases (direct extension, lymphatic or hematogenous). This dictates the administration of radiation that best achieves a successful outcome

Mesothelioma associated with the shipbuilding industry in coastal Virginia.

Science.gov (United States)

Tagnon, I; Blot, W J; Stroube, R B; Day, N E; Morris, L E; Peace, B B; Fraumeni, J F

1980-11-01

A case-control study was undertaken to clarify reasons for a four-fold increased incidence of mesothelioma discovered among white males in coastal Tidewater, Va., from 1972 to 1978. Sixty-one cases were identified. Interviews with next of kin revealed that the excess was linked to employment in area shipyards. Three-fourths of the cases had been employed in the shipbuilding industry, nearly all beginning employment prior to 1950. Most were career employees, but an increased risk was also found among those who worked only temporarily, mainly during World War II, and were reportedly exposed to asbestos. More of the cases than controls were pipecoverers or pipefitters, but cases were reported to work in a variety of shipyard trades. Few of the mesothelioma cases were heavy smokers, a trend that may be related in part to the competing risks for fatal diseases caused by the interactions of smoking and asbestos exposure. Information obtained by interview for five of the six white females diagnosed with mesothelioma revealed that the husband of four had been employed in the shipbuilding industry.

Pleural mesothelioma and lung cancer risks in relation to occupational history and asbestos lung burden

Science.gov (United States)

Gilham, Clare; Rake, Christine; Burdett, Garry; Nicholson, Andrew G; Davison, Leslie; Franchini, Angelo; Carpenter, James; Hodgson, John; Darnton, Andrew; Peto, Julian

2016-01-01

Background We have conducted a population-based study of pleural mesothelioma patients with occupational histories and measured asbestos lung burdens in occupationally exposed workers and in the general population. The relationship between lung burden and risk, particularly at environmental exposure levels, will enable future mesothelioma rates in people born after 1965 who never installed asbestos to be predicted from their asbestos lung burdens. Methods Following personal interview asbestos fibres longer than 5 µm were counted by transmission electron microscopy in lung samples obtained from 133 patients with mesothelioma and 262 patients with lung cancer. ORs for mesothelioma were converted to lifetime risks. Results Lifetime mesothelioma risk is approximately 0.02% per 1000 amphibole fibres per gram of dry lung tissue over a more than 100-fold range, from 1 to 4 in the most heavily exposed building workers to less than 1 in 500 in most of the population. The asbestos fibres counted were amosite (75%), crocidolite (18%), other amphiboles (5%) and chrysotile (2%). Conclusions The approximate linearity of the dose–response together with lung burden measurements in younger people will provide reasonably reliable predictions of future mesothelioma rates in those born since 1965 whose risks cannot yet be seen in national rates. Burdens in those born more recently will indicate the continuing occupational and environmental hazards under current asbestos control regulations. Our results confirm the major contribution of amosite to UK mesothelioma incidence and the substantial contribution of non-occupational exposure, particularly in women. PMID:26715106

Pelvic and lumbar metastasis detected by bone scintigraphy in malignant pleural mesothelioma

International Nuclear Information System (INIS)

Ruiz Hernandez, G.; Castillo Pallares, F.J.; Llorens Banon, L.; Romero de Avila y Avalos, C.; Garcia Garc'ia, T.; Azagra Ros, P.; Maruenda Paulino, J.I.; Ferrer Albiach, C.

1999-01-01

A case of a 43-year-old man suffering from pleural mesothelioma with distant bone metastasis is reported. The results of bone scintigraphy and NMR findings allowed the diagnosis. The current case describes a hematogenous metastasis to the pelvis and vertebral column from a malignant pleural mesothelioma that was detected initally by bone scintigraphy. (orig.) [de

Protumorigenic role of HAPLN1 and its IgV domain in malignant pleural mesothelioma.

Science.gov (United States)

Ivanova, Alla V; Goparaju, Chandra M V; Ivanov, Sergey V; Nonaka, Daisuke; Cruz, Christina; Beck, Amanda; Lonardo, Fulvio; Wali, Anil; Pass, Harvey I

2009-04-15

Tumor extracellular matrix (ECM) plays a crucial role in cancer progression mediating and transforming host-tumor interactions. Targeting the ECM is becoming an increasingly promising therapeutic approach in cancer treatment. We find that one of the ECM proteins, HAPLN1, is overexpressed in the majority of mesotheliomas. This study was designed to characterize the protumorigenic role of HAPLN1 in mesothelioma. Overexpression of HAPLN1 was assessed and validated on a large set of normal/mesothelioma specimens on the RNA and protein levels. We also analyzed DNA copy number alterations in the HAPLN1 genomic locus using the array-based comparative genomic hybridization representational oligonucleotide microarray analysis tool. Tumorigenic activities of the HAPLN1 domains were evaluated in vitro on mesothelioma cells transfected with HAPLN1-expressing constructs. We found that HAPLN1 is 23-fold overexpressed in stage I mesothelioma and confirmed it for 76% samples (n = 53) on RNA and 97% (n = 40) on protein levels. The majority of lung cancers showed no differential expression of HAPLN1. Analysis of DNA copy number alterations identified recurrent gain in the 5q14.3 HAPLN1 locus in approximately 27% of tumors. Noteworthy, high expression of HAPLN1 negatively correlated with time to progression (P = 0.05, log-rank test) and overall survival (P = 0.006). Proliferation, motility, invasion, and soft-agar colony formation assays on mesothelioma cells overexpressing full-length HAPLN1 or its functional domains strongly supported the protumorigenic role of HAPLN1 and its SP-IgV domain. Overexpression of HAPLN1 and its SP-IgV domain increases tumorigenic properties of mesothelioma. Thus, targeting the SP-IgV domain may be one of the therapeutic approaches in cancer treatment.

Malignant mesothelioma: biology, diagnosis and therapeutic approaches

Czech Academy of Sciences Publication Activity Database

Tomasetti, M.; Amati, M.; Santarelli, L.; Alleva, R.; Neužil, Jiří

2009-01-01

Roč. 2, č. 2 (2009), s. 190-206 ISSN 1874-4672 Institutional research plan: CEZ:AV0Z50520514 Keywords : malignant mesothelioma * biology * diagnosis and therapeutic approaches Subject RIV: EB - Genetics ; Molecular Biology

Mesothelioma: Identification of the Key Molecular Events Triggered by BAP1

Science.gov (United States)

2016-04-01

germline BAP1 heterozygous mice is associated with deregulated inflammatory response and increased risk of mesothelioma. Oncogene. 2015 Jun 29. (Epub...Tommaso Campanella Cancer Center. 2015, September. Catanzaro, Italy. 5. 7th International Symposium DAMPS and HMGB. 2015, September. Bonn, Germany . 6...with deregulated inflammatory response and increased risk of mesothelioma A Napolitano1,2, L Pellegrini1, A Dey3, D Larson1, M Tanji1, EG Flores1, B

Malignant pleural mesothelioma: an update on biomarkers and treatment.

Science.gov (United States)

Ray, Mandira; Kindler, Hedy Lee

2009-09-01

Although the insulating properties of asbestos have been known for millennia, the link between asbestos exposure and mesothelioma was not recognized until 1960, when it was first described in South African asbestos miners. The incidence of mesothelioma parallels asbestos usage with a latency of 20 to 40+ years; thus, patient numbers are declining in the United States but rising in the developing world. Radiation, genetics, and possibly simian virus 40 are less common causes. Diagnosis can be challenging, since the results of pleural fluid cytology testing are often negative despite repeated sampling. No staging system adequately predicts prognosis in the unresected patient. Newly described biomarkers, including soluble mesothelin-related peptide, megakaryocyte potentiation factor, and osteopontin, may predict which asbestos-exposed individuals will develop mesothelioma, and may prove useful in assessing response to treatment. Since surgery cannot eradicate all residual microscopic disease, a multimodality approach is encouraged. Metaanalysis suggests that pleurectomy/decortication may achieve outcomes similar to those of extrapleural penumonectomy. The standard first-line chemotherapy for unresectable disease is pemetrexed plus cisplatin. This combination improves response, survival, time to progression, pulmonary function, and disease-related symptoms. Carboplatin is often substituted, with similar results. Other active agents include raltitrexed, gemcitabine, and vinorelbine. Novel agents in clinical trials include inhibitors of the epidermal growth factor receptor, vascular endothelial growth factor, mesothelin, and histone deacetylases. Although disappointing results of early trials did not confirm promising preclinical data, recent studies have suggested that some novel agents may be effective. As we learn more about mesothelioma biology, molecularly targeted agents may become treatment options.

Zebularine exerts its antiproliferative activity through S phase delay and cell death in human malignant mesothelioma cells.

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Takemura, Yukitoshi; Satoh, Motohiko; Hatanaka, Kenichi; Kubota, Shunichiro

2018-04-24

Malignant mesothelioma is an asbestos-related aggressive tumor and current therapy remains ineffective. Zebularine as a DNA methyltransferase (DNMT) inhibitor has an anti-tumor effect in several human cancer cells. The aim of the present study was to investigate whether zebularine could induce antiproliferative effect in human malignant mesothelioma cells. Zebularine induced cell growth inhibition in a dose-dependent manner. In addition, zebularine dose-dependently decreased expression of DNMT1 in all malignant mesothelioma cells tested. Cell cycle analysis indicated that zebularine induced S phase delay. Zebularine also induced cell death in malignant mesothelioma cells. In contrast, zebularine did not induce cell growth inhibition and cell death in human normal fibroblast cells. These results suggest that zebularine has a potential for the treatment of malignant mesothelioma by inhibiting cell growth and inducing cell death.

Review of pemetrexed in combination with cisplatin for the treatment of malignant pleural mesothelioma

Directory of Open Access Journals (Sweden)

Ranjit K Goudar

2008-03-01

Full Text Available Ranjit K GoudarDepartment of Medicine, Division of Hematology, Medical Oncology and Cellular Therapy, Duke University Medical Center, Durham, NC, USAAbstract: Malignant pleural mesothelioma is a resistant form of lung cancer, and its incidence continues to rise in Europe and Australia. Until recently, chemotherapy had not been shown to be effective in the treatment of this slowly progressive disease. In 2004, the combination of pemetrexed and cisplatin was shown to induce high response rates in MPM. This article reviews the published literature describing the development and testing of this therapeutic combination in mesothelioma, and examines in detail the key phase III clinical trial that led to the approval of pemetrexed by the US FDA. Ongoing research will further define the role of pemetrexed plus cisplatin in the treatment of MPM.Keywords: malignant pleural mesothelioma, mesothelioma, pemetrexed, cisplatin

[Malignant pleural mesothelioma].

Science.gov (United States)

Sritharan, Sajitha Sophia; Frandsen, Jens Lundby; Omland, Øyvind; Bruun, Jens Meldgaard

2018-04-09

Malignant pleural mesothelioma (MPM) is a rare cancer with a poor prognosis. The disease is of importance, since the incidence in Denmark is increasing despite cessation of the use of asbestos in the 1980s. MPM has a long latency period, and the first symptom is often dyspnoea, typically caused by pleural effusion. The diagnosis is a challenge, because cytology often is non-conclusive, and thoracoscopy is needed to obtain biopsies for immunohistochemistry. The occupational history is important, since the patients are entitled to compensation. The treatment is often limited to palliation.

Re-challenge with pemetrexed in advanced mesothelioma: a multi-institutional experience

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Bearz Alessandra

2012-09-01

Full Text Available Abstract Background Although first-line therapy for patients affected by advanced mesothelioma is well established, there is a lack of data regarding the impact of second-line treatment. Methods We retrospectively collected data of patients affected by advanced mesothelioma, already treated with first-line therapy based on pemetrexed and platin, with a response (partial response or stable disease lasting at least 6 months, and re-treated with a pemetrexed-based therapy at progression. The primary objective was to describe time to progression and overall survival after re-treatment. Results Overall across several Italian oncological Institutions we found 30 patients affected by advanced mesothelioma, in progression after a 6-month lasting clinical benefit following a first-line treatment with cisplatin and pemetrexed, and re-challenged with a pemetrexed-based therapy. In these patients we found a disease control rate of 66%, with reduction of pain in 43% of patients. Overall time to progression and survival were promising for a second-line setting of patients with advanced mesothelioma, being 5.1 and 13.6 months, respectively. Conclusions In our opinion, when a patient has a long-lasting benefit from previous treatment with pemetrexed combined with a platin compound, the same treatment should be offered at progression.

Pharmacological targeting of p53 through RITA is an effective antitumoral strategy for malignant pleural mesothelioma.

Science.gov (United States)

Di Marzo, Domenico; Forte, Iris Maria; Indovina, Paola; Di Gennaro, Elena; Rizzo, Valeria; Giorgi, Francesca; Mattioli, Eliseo; Iannuzzi, Carmelina Antonella; Budillon, Alfredo; Giordano, Antonio; Pentimalli, Francesca

2014-01-01

Malignant mesothelioma, a very aggressive tumor associated to asbestos exposure, is expected to increase in incidence, and unfortunately, no curative modality exists. Reactivation of p53 is a new attractive antitumoral strategy. p53 is rarely mutated in mesothelioma, but it is inactivated in most tumors by the lack of p14(ARF). Here, we evaluated the feasibility of this approach in pleural mesothelioma by testing RITA and nutlin-3, two molecules able to restore p53 function through a different mechanism, on a panel of mesothelioma cell lines representing the epithelioid (NCI-H28, NCI-H2452, IST-MES 2), biphasic (MSTO-211H), and sarcomatoid (NCI-H2052) histotypes compared with the normal mesothelial HMC-hTERT. RITA triggered robust caspase-dependent apoptosis specifically in epithelioid and biphasic mesothelioma cell lines, both through wild-type and mutant p53, concomitant to p21 downregulation. Conversely, nutlin-3 induced a p21-dependent growth arrest, rather than apoptosis, and was slightly toxic on HMC-hTERT.   Interestingly, we identified a previously undetected point mutation of p53 (p.Arg249Ser) in IST-MES 2, and showed that RITA is also able to reactivate this p53 mutant protein and its apoptotic function. RITA reduced tumor growth in a MSTO-211H-derived xenograft model of mesothelioma and synergized with cisplatin, which is the mainstay of treatment for this tumor. Our data indicate that reactivation of p53 and concomitant p21 downregulation effectively induce cell death in mesothelioma, a tumor characterized by a high intrinsic resistance to apoptosis. Altogether, our findings provide the preclinical framework supporting the use of p53-reactivating agents alone, or in combination regimens, to improve the outcome of patients with mesothelioma.

Pleural malignant mesothelioma causing cord infiltration through the nerve root. Case report.

Science.gov (United States)

Okura, Hidehiro; Suga, Yasuo; Akiyama, Osamu; Kudo, Kentaro; Tsutsumi, Satoshi; Abe, Yusuke; Yasumoto, Yukimasa; Ito, Masanori; Izumi, Hiroshi; Shiomi, Kazu

2009-04-01

A 61-year-old man presented with a rare pleural malignant mesothelioma of the spine manifesting as progressive weakness of the bilateral lower extremities, numbness in the body and both legs, and dysfunction of the bladder and bowel. He had previous occupational exposure to asbestos while working at a car repair shop and had undergone right panpleuropneumonectomy under a diagnosis of sarcomatous type mesothelioma in the right pleural space. Magnetic resonance imaging of the spine with gadolinium showed an enhanced intramedullary tumor at the T4 level. Operative findings disclosed the clouded and swollen right posterior nerve root, and the pial surface was covered by clouded arachnoid-like membrane. The removed part of the T4 posterior nerve root and intramedullary tumor revealed malignant mesothelioma with invasion spreading along the posterior nerve root. He died of respiratory failure 3 months after the diagnosis. This case shows that spinal metastasis must be considered if a patient with pleural malignant mesothelioma shows neurological worsening and neuroimaging shows an abnormal lesion in the thoracic spinal cord. However, the patient's neurological condition is very difficult to improve in the presence of spinal cord infiltration.

Proteome screening of pleural effusions identifies galectin 1 as a diagnostic biomarker and highlights several prognostic biomarkers for malignant mesothelioma.

Science.gov (United States)

Mundt, Filip; Johansson, Henrik J; Forshed, Jenny; Arslan, Sertaç; Metintas, Muzaffer; Dobra, Katalin; Lehtiö, Janne; Hjerpe, Anders

2014-03-01

Malignant mesothelioma is an aggressive asbestos-induced cancer, and affected patients have a median survival of approximately one year after diagnosis. It is often difficult to reach a conclusive diagnosis, and ancillary measurements of soluble biomarkers could increase diagnostic accuracy. Unfortunately, few soluble mesothelioma biomarkers are suitable for clinical application. Here we screened the effusion proteomes of mesothelioma and lung adenocarcinoma patients to identify novel soluble mesothelioma biomarkers. We performed quantitative mass-spectrometry-based proteomics using isobaric tags for quantification and used narrow-range immobilized pH gradient/high-resolution isoelectric focusing (pH 4-4.25) prior to analysis by means of nano liquid chromatography coupled to MS/MS. More than 1,300 proteins were identified in pleural effusions from patients with malignant mesothelioma (n = 6), lung adenocarcinoma (n = 6), or benign mesotheliosis (n = 7). Data are available via ProteomeXchange with identifier PXD000531. The identified proteins included a set of known mesothelioma markers and proteins that regulate hallmarks of cancer such as invasion, angiogenesis, and immune evasion, plus several new candidate proteins. Seven candidates (aldo-keto reductase 1B10, apolipoprotein C-I, galectin 1, myosin-VIIb, superoxide dismutase 2, tenascin C, and thrombospondin 1) were validated by enzyme-linked immunosorbent assays in a larger group of patients with mesothelioma (n = 37) or metastatic carcinomas (n = 25) and in effusions from patients with benign, reactive conditions (n = 16). Galectin 1 was identified as overexpressed in effusions from lung adenocarcinoma relative to mesothelioma and was validated as an excellent predictor for metastatic carcinomas against malignant mesothelioma. Galectin 1, aldo-keto reductase 1B10, and apolipoprotein C-I were all identified as potential prognostic biomarkers for malignant mesothelioma. This analysis of the effusion proteome

Occupation and mesothelioma in Sweden: updated incidence in men and women in the 27 years after the asbestos ban

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Nils Plato

2016-09-01

Full Text Available OBJECTIVES We updated the Swedish component of the Nordic Occupational Cancer (NOCCA Study through 2009 in order to investigate the incidence of mesothelioma of the peritoneum and pleura in both genders, and explored occupational exposures that may be associated with mesothelioma. METHODS The Swedish component of the NOCCA Study includes 6.78 million individuals. Data from this cohort were linked to the population-based Swedish Cancer Registry and Swedish Total Population Registry for three periods between 1961 and 2009, and then further linked to the Swedish NOCCA job-exposure matrix, which includes 25 carcinogenic substances and the corresponding exposure levels for 280 occupations. Multivariate analysis was used to calculate standardized incidence ratios (SIRs for mesothelioma of the peritoneum and pleura by gender, occupational category, carcinogenic substance, and for multiple occupational exposures simultaneously. RESULTS A total of 3,716 incident mesotheliomas were recorded (21.1% in women. We found a significantly increased risk of mesothelioma in 24 occupations, as well as clear differences between the genders. Among men, increased risks of mesothelioma of the pleura were observed in male-dominated occupations, with the greatest elevation of risk among plumbers (SIR, 4.99; 95% confidence interval, 4.20 to 5.90. Among women, increased risks were observed in sewing workers, canning workers, packers, cleaners, and postal workers. In multivariate analysis controlling for multiple occupational exposures, significant associations were only observed between asbestos exposure and mesothelioma. CONCLUSIONS Asbestos exposure was associated with mesothelioma incidence in our study. The asbestos ban of 1982 has yet to show any clear effect on the occurrence of mesothelioma in this cohort. Among women, the occupations of canning workers and cleaners showed increased risks of mesothelioma of the pleura without evidence of asbestos exposure.

Epidemiology and quantitation of environmental risk in humans from radiation and other agents

International Nuclear Information System (INIS)

Castellani, Amleto

1985-01-01

The identification and quantitation of environmental risk in humans is one of the main problems to be solved in order to improve the protection of individuals and of human populations against physical and chemical pollutants. Epidemiology plays a central role in the evaluation of health risk directly in human populations. In this volume are collected 33 lectures presented at the AS! course on ''Epidemiology and quantitation of environmental risk in humans from radiation and other agents: potential and limitations'', sponsored by NATO and Italian Association of Radiobiology and organized by ENEA. The course has been devoted to a number of aspects of environmental risk analysis and evaluation based on epidemiological investigation. Basic epidemiological concepts and methods have been reviewed. Fundamentals of dosimetry and microdosimetry were presented in relation to the contribution of epidemiology in defining the dose effect relationships for radiation carcinogenesis and its relation with age, sex and ethnicity. The mechanisms of carcinogenesis as a multi-stage process were illustrated. One of the main topics was 'cancer epidemiology' and its correlation with: - occupational and non-occupational exposure to radiation - diagnostic and therapeutic irradiation - cancer proneness - hereditary and familiar diseases - abnormal response to carcinogens - environmental pollution in air and water - exposure to radon in mines and in building material - atomic bomb explosion - chemotherapy - dioxin and related compounds

Paraneoplastic Encephalitis Associated with Anti-Ma2 Antibodies and Mesothelioma-Like Poorly Differentiated Lung Cancer

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Can Ebru Bekircan

2009-06-01

Full Text Available We report a case of paraneoplastic encephalitis associated with anti-Ma2 antibodies. Medical history and thorax computed tomog- raphy findings suggested malignant mesothelioma. Pleural biopsy results were compatible with high-grade neoplastic infiltration. Alt- hough the biopsy could not differentiate the type of neoplasm, mesothelioma was considered a strong possibility in this poorly dif- ferentiated lung carcinoma. To the best of our knowledge this is the first case report of paraneoplastic encephalitis associated with anti-Ma2 antibodies and mesothelioma

In Vivo Imaging of Human Malignant Mesothelioma Grown Orthotopically in the Peritoneal Cavity of Nude Mice

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Mingqian Feng, Jingli Zhang, Miriam Anver, Raffit Hassan, Mitchell Ho

2011-01-01

Full Text Available Malignant mesothelioma (MM causes significant morbidity and mortality in patients. With increasing efforts devoted to developing therapeutics targeting mesothelioma, a xenograft mouse model with in vivo tumor imaging is especially desired for evaluating anti-tumor therapies. In the present study, we fluorescently labeled the NCI-H226 human mesothelioma cell line by a lentiviral vector harboring a luciferase-GFP (Luc/GFP fusion gene driven by the RNA polymerase II promoter. After single-cell cloning by flow cytometry, a clone (named LMB-H226-GL that stably expresses high levels of Luc/GFP was obtained. The in vivo tumorigenicity of Luc/GFP-labeled LMB-H226-GL was determined by using intraperitoneal injections of the cells in nude mice. LMB-H226-GL was found to be able to consistently form solid tumors in the peritoneum of mice. Tumor growth and aggressive progression could be quantitated via in vivo bioluminescence imaging. The model exhibited the pathological hallmarks consistent with the clinical progression of MM in terms of tumor growth and spread inside the peritoneal cavity. To evaluate the in vivo efficacy of drugs targeting mesothelioma, we treated mice with SS1P, a recombinant immunotoxin currently evaluated in Phase II clinical trials for treatment of mesothelioma. All the tumor-bearing mice had a significant response to SS1P treatment. Our results showed that this is a well-suited model for mesothelioma, and may be useful for evaluating other novel agents for mesothelioma treatment in vivo.

[Primary Malignant Pericardial Mesothelioma;Report of a Case].

Science.gov (United States)

Ichikawa, Seiji; Murakami, Fumihiko; Ogiwara, Hiroaki

2018-02-01

A 69-year-old male was referred to our hospital after being diagnosed as having pericarditis with pericardial effusion. The symptoms of tamponade disappeared after the effusion was drained;although the cause of pericarditis remained unidentified. About 4 months later, the tamponade symptoms recurred due to the thickened nodular pericardium. Partial pericardiectomy was performed, however the patient died on the 52nd day after surgery. Immunohistological examination with calretinin led to the diagnosis of primary malignant pericardial mesothelioma, which was an extremely rare pathology. Because the hyaluronic acid content of the effusion has been reported as a diagnostic aid for malignant mesothelioma, routine examination of the hyaluronic acid content for pericarditis with pericardial effusion may be necessary for early diagnosis and to improve prognosis.

Mesothelioma and other lung disease in taconite miners; the uncertain role of non-asbestiform EMP.

Science.gov (United States)

Mandel, Jeffrey H; Odo, Nnaemeka U

2018-04-10

The purpose of this paper was to assess the role of non-asbestiform amphibole EMPs in the etiology of mesotheliomas and other lung disease in taconite (iron ore) miners. Increased mesothelioma rates have been described in Minnesota taconite workers since the late 1990s. Currently, over 100 cases have been reported by the Minnesota Department of Health within the complete cohort of miners in Minnesota. Geologic sampling has indicated that only the eastern part of the iron range contains non-asbestiform amphibole elongate mineral particles (EMPs), in close proximity to the ore. This type of EMP has been less studied and also exists in talc and gold mining. A series of investigations into the state's taconite industry have been recently completed. Results from a cohort mortality study indicated an SMR of 2.77 (95% CI = 1.87-3.96) for mesothelioma. In a case-control study, the odds ratio for mesothelioma for high vs. low EMP exposure was 2.25 (5% CI = 1.13-4.5) but EMPs in this study were counted by phase contrast microscopy. Odds ratios were not elevated in mines located in the eastern part of the Mesabi iron range. The overall findings suggest that mesothelioma in taconite miners is related to EMP exposure. Because of the way EMPs were counted, results from these studies cannot allow a firm conclusion about the association between EMP exposure and the reported excess mesothelioma. Copyright © 2018 Elsevier Inc. All rights reserved.

Radiation carcinogenesis

International Nuclear Information System (INIS)

Adams, G.E.

1987-01-01

In this contribution about carcinogenesis induced by ionizing radiation some radiation dose-response relationships are discussed. Curves are shown of the relation between cell survival and resp. low and high LET radiation. The difference between both curves can be ascribed to endogenous repair mechanisms in the cell. The relation between single-gen mutation frequency and the surviving fractions of irradiated cells indicates that these repairing mechanisms are not error free. Some examples of reverse dose-response relationships are presented in which decreasing values of dose-rate (LET) correspond with increasing radiation induced cell transformation. Finally some molecular aspects of radiation carcinogenesis are discussed. (H.W.). 22 refs.; 4 figs

Treatment of malignant pleural mesothelioma with carboplatin, liposomized doxorubicin, and gemcitabine: a phase II study

DEFF Research Database (Denmark)

Hillerdal, G.; Sundstrom, S.; Riska, H.

2008-01-01

BACKGROUND: Malignant pleural mesothelioma has a poor prognosis and there is limited effect of treatment. The Nordic Mesothelioma groups decided in the year 2000 to investigate a combination of liposomized doxorubicin, carboplatin, and gemcitabine for this disease in a phase II study. METHODS: From...... January 2001, to December 2003, 173 evaluable patients with biopsy-verified malignant mesothelioma were included. Two patients were lost to follow-up, but all the others were followed for at least 4 years or until death. RESULTS: Toxicity was fairly low. There were 56 responses (32.4%), of which 2 were...

Recent progress in nickel carcinogenesis. [Cornybacterium; E. coli; S. typhimurium; B. subtillis

Energy Technology Data Exchange (ETDEWEB)

Sunderman, F.W. Jr.

1984-01-01

Research on nickel carcinogenesis from 1979 to 1983 is reviewed. Epidemiological studies have strengthened the evidence that workers in nickel refineries have increased risks of lung and sinonasal cancers, but have not substantiated increased risks of respiratory cancers in other nickel-exposed workers. Carcinogenesis bioassays have demonstrated carcinogenicity of certain nickel sulfide, hydroxide, selenide, arsenide, antimonide, and telluride compounds following parenteral administration to rodents. Positive bacterial mutagenesis tests have been obtained with Ni(II) in Cornybacterium, but not in E. coli, S. typhimurium, or B. subtilis. Transformation assays of several soluble and crystalline Ni compounds have been positive in Syrian hamster embryo cells. Ni(II) binds to DNA, RNA, and nucleoproteins, and becomes localized in nucleoli. Genotoxic effects of Ni include: (a) chromosomal aberrations, including sister-chromatid exchanges, (b) DNA strandbreaks and DNA-protein cross-links, (c) inhibition of DNA and RNA synthesis, (d) infidelity of DNA transcription, and (e) mutations at the HGPRTase locus in Chinese hamster cells and the TK locus in mouse lymphoma cells. These findings are consistent with somatic mutation as the mechanism for initiation of nickel carcinogenesis. Ni compounds cause reversible transition of double-stranded poly(dG-dC) DNA from the right-handed B-helix to the left-handed Z-helix, suggesting a mechanism whereby nickel might modulate oncogene expression. 99 references, 6 tables.

Newly established ELISA for N-ERC/mesothelin improves diagnostic accuracy in patients with suspected pleural mesothelioma.

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Sato, Tadashi; Suzuki, Yohei; Mori, Takanori; Maeda, Masahiro; Abe, Masaaki; Hino, Okio; Takahashi, Kazuhisa

2014-10-01

Pleural mesothelioma is an aggressive tumor, commonly caused by exposure to asbestos. The prognosis of mesothelioma remains disappointing despite multimodal treatment. We reported previously that N-ERC/mesothelin could be a useful biomarker for the early diagnosis of pleural mesothelioma and developed an enzyme-linked immunosorbent assay (ELISA) system for its detection. However, the reproducibility of our previous 7-16 ELISA system has been revealed to be unsatisfactory. To measure N-ERC/mesothelin more precisely, we developed a new 7-20 ELISA system. The subjects of this study were patients who were referred to our department with suspected pleural mesothelioma. The current study demonstrated that the newly established 7-20 ELISA system improved the sensitivity and specificity for diagnosing pleural mesothelioma compared with the previous system. Moreover, the 7-20 ELISA system showed better reproducibility and displayed the tendency of both higher sensitivity and higher specificity in plasma than in serum. Particularly for the epithelioid type, the area under the curve (AUC) and the diagnostic accuracy of N-ERC/mesothelin were excellent; the AUC was 0.91, the sensitivity was 0.95, and the specificity was 0.76 in plasma. In conclusion, assessment of N-ERC/mesothelin with our newly established 7-20 ELISA system is clinically useful for the precise diagnosis of pleural mesothelioma. © 2014 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Inhibition of autophagy initiation potentiates chemosensitivity in mesothelioma.

Science.gov (United States)

Follo, Carlo; Cheng, Yao; Richards, William G; Bueno, Raphael; Broaddus, Virginia Courtney

2018-03-01

The benefits of inhibiting autophagy in cancer are still controversial, with differences in outcome based on the type of tumor, the context and the particular stage of inhibition. Here, we investigated the impact of inhibiting autophagy at different stages on chemosensitivity using 3-dimensional (3D) models of mesothelioma, including ex vivo human tumor fragment spheroids. As shown by LC3B accumulation, we successfully inhibited autophagy using either an early stage ULK1/2 inhibitor (MRT 68921) or a late stage inhibitor (hydroxychloroquine). We found that inhibition of autophagy at the early stage, but not at late stage, potentiated chemosensitivity. This effect was seen only in those spheroids with high autophagy and active initiation at steady state. Inhibition of autophagy alone, at either early or late stage, did not cause cell death, showing that the inhibitors were non-toxic and that mesothelioma did not depend on autophagy at baseline, at least over 24 h. Using ATG13 puncta analysis, we found that autophagy initiation identified tumors that are more chemosensitive at baseline and after autophagy inhibition. Our results highlight a potential role of autophagy initiation in supporting mesothelioma cells during chemotherapy. Our work also highlights the importance of testing the inhibition of different stages in order to uncover the role of autophagy and the potential of its modulation in the treatment of cancer. © 2017 Wiley Periodicals, Inc.

Late cutaneous metastases to the face from malignant pleural mesothelioma: A case report and review of the literature

Directory of Open Access Journals (Sweden)

Lawrence Julia

2009-11-01

Full Text Available Abstract Background Malignant Mesothelioma is a rare primary neoplasm affecting the serosal membranes. During its relative short course, this malignant neoplasm can give local and, rarely, distant haematogenous metastases in different organs. The reported metastatic sites include liver, lung, heart, brain, thyroid, adrenals, kidneys, pancreas, bone, soft tissue, skin and lymph nodes. Case Presentation We report a sixty one year-old man with a history of malignant pleural epithelioid mesothelioma treated with six cycles of Pemetrexed and Carboplatin completed 03/11/04 followed by radiotherapy to the drain site 250 Kv/TD20Gy/5F completed 13/12/2004. Then he developed multiple facial skin lesions 4 years later. These lesions were proved to be metastatic malignant sarcomatoid mesothelioma. Conclusion Mesothelioma metastases should be suspected in any known Mesothelioma patient with newly developed skin lesion.

MESOTHELIOMA PRESENTING WITH PNEUMOTHORAX AND INTERLOBAR TUMOR

NARCIS (Netherlands)

MANNES, GPM; GOUW, ASH; BERENDSEN, HH; VERHOEFF, AJ; POSTMUS, PE

A patient presented with a pneumothorax, a parahilar mass and a pleural effusion on the left side. Histology proved that this was caused by a malignant mesothelioma, epithelial type. The pneumothorax persisted, even after chest drainage and pleurodesis with talc powder and tetracycline.

Antibiotic suppression of intestinal microbiota reduces heme-induced lipoperoxidation associated with colon carcinogenesis in rats.

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Martin, O C B; Lin, C; Naud, N; Tache, S; Raymond-Letron, I; Corpet, D E; Pierre, F H

2015-01-01

Epidemiological studies show that heme iron from red meat is associated with increased colorectal cancer risk. In carcinogen-induced-rats, a heme iron-rich diet increases the number of precancerous lesions and raises associated fecal biomarkers. Heme-induced lipoperoxidation measured by fecal thiobarbituric acid reagents (TBARs) could explain the promotion of colon carcinogenesis by heme. Using a factorial design we studied if microbiota could be involved in heme-induced carcinogenesis, by modulating peroxidation. Rats treated or not with an antibiotic cocktail were given a control or a hemoglobin-diet. Fecal bacteria were counted on agar and TBARs concentration assayed in fecal water. The suppression of microbiota by antibiotics was associated with a reduction of crypt height and proliferation and with a cecum enlargement, which are characteristics of germ-free rats. Rats given hemoglobin diets had increased fecal TBARs, which were suppressed by the antibiotic treatment. A duplicate experiment in rats given dietary hemin yielded similar results. These data show that the intestinal microbiota is involved in enhancement of lipoperoxidation by heme iron. We thus suggest that microbiota could play a role in the heme-induced promotion of colorectal carcinogenesis.

PERICARDIAL MESOTHELIOMA WITH THROMBOVASCULAR COMPLICATIONS (CASE FROM PRACTICE

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N. Yu. Karpova

2017-01-01

Full Text Available Primary mesothelioma of the pericardium is a rare heart tumor with a difficult diagnosis, revealed in vivo in less than a quarter of cases. The disease occurs at any age, more common in men and variably exhibits a broad spectrum of non-specific symptoms of congestive heart failure, constrictive pericarditis, pericardial effusion or cardiac tamponade. Patients are usually observed with peripheral edema, ascites, dyspnea, cough, chest pain and atrial fibrillation. Such symptoms, in the absence of cancer alertness, are erroneously attributed by doctors to more common cardiovascular diseases. As a result, primary mesothelioma is detected in 75-90% of cases only at necropsy. The article describes a case of detection at autopsy of primary pericardial mesothelioma sarcomatous type with invasion into the myocardium in a patient of 74 years old. The patient also suffered from concomitant coronary artery disease with a long history of chronic heart failure and recurrent pulmonary embolism, associated with deep vein thrombosis at the final stage of the disease. An objective study revealed signs of chronic heart failure. The laboratory data included mild iron deficiency anemia, insignificant leukocytosis and leukocyturia, as well as signs of moderate chronic kidney disease. Instrumental results corresponded to long-term course of hypertension, signs of congestive heart failure in the presence of atrial fibrillation, atherosclerosis of lower limbs arteries in patient with abdominal obesity. Thus, there were no clinical signs of pericardial damage in a standard examination of the patient. The article describes the complexity of the disease diagnosis, variable clinical picture, as well as the diagnostic value of various instrumental methods from the perspective of evidence-based medicine. It is noted that clinical alertness is still the most important factor in the lifetime diagnosis of pericardial mesothelioma. Disease should be considered in patients with

Mechanisms of radiation carcinogenesis

International Nuclear Information System (INIS)

Bekkum, D.W. van

1975-01-01

This speculative review on radiation carcinogenesis deals mainly with its immunological aspects. It need not be emphasized that the role of immunology in carcinogenesis is not yet well understood. Immunological aspects of radiation carcinogenesis comprise a large number of different parameters on the part of the host as well as on the part of the tumor itself. Only two aspects, both related to radiation, will be discussed here. One is the way in which the carcinogenic exposure to ionizing radiation may affect the immune reactivity of the irradiated organism, thereby perhaps changing its responses against the malignant cells. The second aspect is the immunological properties of cells transformed by ionizing irradiation, which may provide the targets for a host-anti-tumor reaction

Mesothelioma: treatment and survival of a patient population and review of the literature.

Science.gov (United States)

Stathopoulos, John; Antoniou, Dimosthenis; Stathopoulos, George P; Rigatos, Sotiris K; Dimitroulis, John; Koutandos, John; Michalopoulou, Pinelopi; Athanasiades, Athanasios; Veslemes, Marinos

2005-01-01

Our purpose was to evaluate the survival of patients with pleural and intraperitoneal malignant mesothelioma and, particularly, to estimate the efficacy of chemotherapy as well as radiotherapy and surgery. A review of the literature with respect to these parameters is included. Thirty-five patients with malignant mesothelioma (28 with pleural and 7 with intraperitoneal) were enrolled. Twenty-eight patients underwent chemotherapy, 7/35 radiation and 9/35 surgery (2 with pleural and 7 with abdominal disease). Combination chemotherapy included cisplatin-gemcitabine, cisplatin (or carboplatin) with premetrexed and doxorubicin-cyclophosphamide. In 2/28 patients with pleural mesothelioma the tumor was excised and in 7 with intraperitoneal disease, surgical therapy was palliative and there was survival prolongation. Radiotherapy was only palliative. Chemotherapy produced a very low response: 2/28 (7.14%) patients achieved a partial response. The median survival was 17 months, 4-year survival, 24.4% and 5-year survival, 12.12%. No serious toxicity was observed. Malignant mesothelioma of the pleura and intraperitoneum is a slow-growing disease which is indicated by the long survival, despite the failure of chemotherapy, radiation therapy and surgery.

Mesothelioma Treatment: Recovery, Side Effects, What to Expect

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... Recognition Societies Percentage Donations Other Giving/Fundraising Opportunities Bitcoin Donation Form The Meso Foundation saves lives by ... Recognition Societies Percentage Donations Other Giving/Fundraising Opportunities Bitcoin Donation Form © 2017 Mesothelioma Applied Research Foundation, Inc. ...

International Activities in Radiation-Induced Carcinogenesis. Survey Paper

Energy Technology Data Exchange (ETDEWEB)

Komarov, E. [World Health Organization, Geneva (Switzerland)

1969-11-15

During the past 10 years special attention has been paid to the problem of late effects of radiation and in particular to radiation-induced carcinogenesis and leukaemogenesis. In the UNSCEAR report of 1958-1962 this.problem was mentioned as being of considerable importance from the point of view of estimation of risk to the population from environmental radiation. In 1964 a special report was prepared by UNSCEAR on radiation- induced carcinogenesis. In the ICRP publication No. 8, a chapter dealing with assessment of somatic risks discussed the problem of leukaemia and other neoplasms and particularly stressed the problem of thyroid carcinoma-and bone sarcoma. WHO panels of experts discussed the problem in 1960-1966 and made some recommendations for international activity in this field. In spite of the amount of scientific attention that has been given in recent years to experimental radiobiology in animals and lower forms, it has become abundantly clear that information directly applicable to humans is woefully inadequate and that there is a desperate need for carefully collected data from man on which to base public health planning and day to day work in radiation protection. This has long been recognized in the technical program of WHO in the emphasis given to the practical importance of epidemiology in human radiobiology and the degree to which it depends upon international collaboration.

Chemical Profiling of Primary Mesothelioma Cultures Defines Subtypes with Different Expression Profiles and Clinical Responses.

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Schunselaar, Laurel M; Quispel-Janssen, Josine M M F; Kim, Yongsoo; Alifrangis, Constantine; Zwart, Wilbert; Baas, Paul; Neefjes, Jacques

2018-04-01

Purpose: Finding new treatment options for patients with malignant pleural mesothelioma is challenging due to the rarity and heterogeneity of this cancer type. The absence of druggable targets further complicates the development of new therapies. Current treatment options are therefore limited, and prognosis remains poor. Experimental Design: We performed drug screening on primary mesothelioma cultures to guide treatment decisions of corresponding patients that were progressive after first- or second-line treatment. Results: We observed a high concordance between in vitro results and clinical outcomes. We defined three subgroups responding differently to the anticancer drugs tested. In addition, gene expression profiling yielded distinct signatures that segregated the differently responding subgroups. These genes signatures involved various pathways, most prominently the fibroblast growth factor pathway. Conclusions: Our primary mesothelioma culture system has proved to be suitable to test novel drugs. Chemical profiling of primary mesothelioma cultures allows personalizing treatment for a group of patients with a rare tumor type where clinical trials are notoriously difficult. This personalized treatment strategy is expected to improve the poor prospects of patients with mesothelioma. Clin Cancer Res; 24(7); 1761-70. ©2017 AACR See related commentary by John and Chia, p. 1513 . ©2017 American Association for Cancer Research.

A population-based case-control study of mesothelioma deaths among U.S. railroad workers.

Science.gov (United States)

Schenker, M B; Garshick, E; Muñoz, A; Woskie, S R; Speizer, F E

1986-09-01

We have completed a case-control analysis of mesothelioma deaths among current and retired U.S. railroad employees. Cause-specific death certificates were obtained for 87% of 15,059 deaths reported by the railroad retirement board, and 20 mesotheliomas were identified according to death certificate diagnosis. A 10:1 matched analysis with railroad workers dying of nonmalignant, nonaccidental causes yielded a very strong association with prior railroad work in jobs with potential asbestos exposure (odds ratio = 7.2, 95% lower confidence limit = 3.3). Consideration of railroad occupations with regular asbestos exposures (e.g., skilled trades, steam locomotive repair) yielded an odds ratio of 21.4 (95% lower confidence limit = 8.7), but the occupations with potential intermittent exposure (e.g., engineers, firemen, carmen) yielded a nonsignificant odds ratio of 2.3 (95% lower confidence limit = 0.5). Applying mesothelioma mortality rates from this study to the population of U.S. railroad workers at risk yields an estimate of 416 cases of mesothelioma occurring among U.S. railroad workers between 1981 and 2000.

(Radiation carcinogenesis in the whole body system)

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Fry, R.J.M.

1990-12-14

The objectives of the trip were: to take part in and to give the summary of a Symposium on Radiation Carcinogenesis at Tokyo, and to give a talk at the National Institute of Radiological Sciences at Chiba. The breadth of the aspects considered at the conference was about as broad as is possible, from effects at the molecular level to human epidemiology, from the effects of tritium to cancer induction by heavy ions. The events induced by cancer that lead to cancer and the events that are secondary are beginning to come into better focus but much is still not known. Interest in suppressor genes is increasing rapidly in the studies of human tumors and many would predict that the three or four suppressor genes associated with cancer are only the first sighting of a much larger number.

Role of bacteria in oral carcinogenesis

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R Rajeev

2012-01-01

Full Text Available Oral cancer is the most common cancer diagnosed in Indian men and is the leading cause of cancer deaths. It is considered as a multistep and multifactorial disease. Besides accumulation of genetic mutations, numerous other carcinogens are involved. In this category, viral and chemical carcinogens are well studied and documented. However, in the oral cavity, the role of microbiota in carcinogenesis is not known. Microbial populations on mouth mucosa differ between healthy and malignant sites, and certain oral bacterial species have been linked with malignancies, but the evidence is still weak in this respect. Nevertheless, oral microorganisms inevitably up-regulate cytokines and other inflammatory mediators that affect the complex metabolic pathways, and may thus be involved in carcinogenesis. Poor oral health associates statistically with prevalence of many types of cancer such as pancreatic and gastrointestinal cancer. This review presents possible carcinogenesis pathway involved in bacterial carcinogenesis, commonly implicated bacteria in oral carcinogenesis, and their role in cancer therapeutics as well.

Peritoneal mesothelioma in a woman who has survived for seven years: a case report

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Pourgholami Mohammad H

2011-01-01

Full Text Available Abstract Introduction Malignant peritoneal mesothelioma is a rare cancer with poor patient survival. Female gender has been identified as a positive prognostic factor. Recently, it has been suggested that the expression of estrogen receptor β in malignant mesothelioma leads to tumor suppression and a better prognosis. Case presentation We report the case of a 48-year-old Caucasian woman who is alive and disease-free seven years after the initial diagnosis and treatment of malignant peritoneal mesothelioma. Conclusion This patient's long survival may be attributable to a combination of factors, including minimal disease, complete cytoreductive surgery and hyperthermic intraperitoneal chemotherapy plus the estrogen receptor β positivity of the tumor.

Mesothelioma With a Large Prevascular Lymph Node: N1 Involvement or Something Different?

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Berzenji, Lawek; Van Schil, Paul E; Snoeckx, Annemie; Hertoghs, Marjan; Carp, Laurens

2018-05-01

A 64-year-old man presented with a large amount of right-sided pleural fluid on imaging, together with calcified pleural plaques and an enlarged nodular structure in the prevascular mediastinum, presumably an enlarged lymph node. Pleural biopsies were obtained during video-assisted thoracoscopic surgery to exclude malignancy. Histopathology showed an epithelial malignant pleural mesothelioma. Induction chemotherapy with cisplatin and pemetrexed was administered followed by an extended pleurectomy and decortication with systematic nodal dissection. Histopathology confirmed the diagnosis of a ypT3N0M0 (stage IB) mesothelioma, and an unexpected thymoma type B2 (stage II) was discovered in the prevascular nodule. Simultaneous occurrence of a mesothelioma and thymoma is extremely rare. Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

The next mesothelioma wave: mortality trends and forecast to 2030 in Brazil.

Science.gov (United States)

Algranti, Eduardo; Saito, Cézar Akiyoshi; Carneiro, Ana Paula Scalia; Moreira, Bruno; Mendonça, Elizabete Medina Coeli; Bussacos, Marco Antonio

2015-10-01

There are limited data on mesothelioma mortality in industrializing countries, where, at present, most of the asbestos consumption occurs. To analyze temporal trends and to calculate mortality rates from mesothelioma and cancer of the pleura in Brazil from 2000 to 2012 and to estimate future mortality rates. We retrieved records of deaths from mesothelioma (ICD-10C45) and cancer of the pleura (ICD-10C38.4) from 2000 to 2012 in adults aged 30 years and over. Crude and age-standardized mortality rates (ASMR) were calculated. Rate ratios of mean crude mortality for selected municipalities were compared to the Brazilian rate. A regression was carried out of the annual number of deaths against asbestos consumption using a Generalized Additive Model (GAM). The best model was chosen to estimate the future burden and peak period of deaths. There were 929C45 and 1379 C38.4 deaths. The ratio of men to women for C45 was 1.4. A positive trend in C45 numbers was observed in Brazil (p=0.0012), particularly in São Paulo (p=0.0004) where ASMRs presented an increasing linear trend (p=0.0344). Selected municipalities harboring asbestos manipulation presented 3.7-11 fold rate ratios of C45 compared to Brazil. GAM presented best fits for latencies of 34 years or more. It is estimated that the peak incidence of C45 mortality will occur between 2021 and 2026. The observed ASMRs and the gender ratio close to 1 suggest underreporting. Even so, deaths are increasing and mesothelioma clusters were identified. Compared to industrialized countries Brazil displays a 15-20 year lag in estimated peak mesothelioma mortality which is consistent with the lag of asbestos peak consumption in the country. Copyright © 2015 Elsevier Ltd. All rights reserved.

Overexpression of activin-A and -B in malignant mesothelioma – Attenuated Smad3 signaling responses and ERK activation promote cell migration and invasive growth

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Tamminen, Jenni A.; Yin, Miao [Research Programs Unit, Translational Cancer Biology, University of Helsinki (Finland); Transplantation Laboratory, Haartman Institute, University of Helsinki (Finland); Rönty, Mikko [Helsinki University Central Hospital Laboratory, Helsinki (Finland); Department of Pathology, University of Helsinki (Finland); Sutinen, Eva [Helsinki University Central Hospital Laboratory, Helsinki (Finland); Department of Medicine, Division of Pulmonary Medicine, University of Helsinki (Finland); Pasternack, Arja; Ritvos, Olli [Helsinki University Central Hospital Laboratory, Helsinki (Finland); Department of Bacteriology and Immunology, University of Helsinki (Finland); Myllärniemi, Marjukka [Transplantation Laboratory, Haartman Institute, University of Helsinki (Finland); Helsinki University Central Hospital Laboratory, Helsinki (Finland); Department of Medicine, Division of Pulmonary Medicine, University of Helsinki (Finland); Koli, Katri, E-mail: katri.koli@helsinki.fi [Research Programs Unit, Translational Cancer Biology, University of Helsinki (Finland); Transplantation Laboratory, Haartman Institute, University of Helsinki (Finland)

2015-03-01

Activin-A and activin-B, members of the TGF-β superfamily, are regulators of reproductive functions, inflammation and wound healing. These dimeric molecules regulate various cellular activities such as proliferation, migration and suvival. Malignant mesothelioma is an asbestos exposure related tumor affecting mainly pleura and it usually has a dismal prognosis. Here, we demonstrate that both activin-A and -B are abundantly expressed in mesothelioma tumor tissue as well as in cultured primary and established mesothelioma cells. Migratory and invasive mesothelioma cells were also found to have attenuated activation of the Smad2/3 pathway in response to activins. Migration and invasive growth of the cells in three-dimentional matrix was prevented by inhibition of activin activity using a soluble activin receptor 2B (sActR2B-Fc). This was associated with decreased ERK activity. Furthermore, migration and invasive growth was significantly inhibited by blocking ERK phosphorylation. Mesothelioma tumors are locally invasive and our results clearly suggest that acivins have a tumor-promoting function in mesothelioma through increasing expression and switching from canonical Smad3 pathway to non-canonical ERK pathway signaling. Blocking activin activity offers a new therapeutic approach for inhibition of mesothelioma invasive growth. - Highlights: • Activin-A and activin-B are highly expressed in mesothelioma. • Mesothelioma cell migration and invasive growth can be blocked with sActR2B. • Activin induced Smad3 activity is attenuated in invasive mesothelioma cells. • Activins induce ERK activity in mesothelioma cells.

Zoledronic acid produces combinatory anti-tumor effects with cisplatin on mesothelioma by increasing p53 expression levels.

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Shinya Okamoto

Full Text Available We examined anti-tumor effects of zoledronic acid (ZOL, one of the bisphosphonates agents clinically used for preventing loss of bone mass, on human mesothelioma cells bearing the wild-type p53 gene. ZOL-treated cells showed activation of caspase-3/7, -8 and -9, and increased sub-G1 phase fractions. A combinatory use of ZOL and cisplatin (CDDP, one of the first-line anti-cancer agents for mesothelioma, synergistically or additively produced the cytotoxicity on mesothelioma cells. Moreover, the combination achieved greater anti-tumor effects on mesothelioma developed in the pleural cavity than administration of either ZOL or CDDP alone. ZOL-treated cells as well as CDDP-treated cells induced p53 phosphorylation at Ser 15, a marker of p53 activation, and up-regulated p53 protein expression levels. Down-regulation of p53 levels with siRNA however did not influence the ZOL-mediated cytotoxicity but negated the combinatory effects by ZOL and CDDP. In addition, ZOL treatments augmented cytotoxicity of adenoviruses expressing the p53 gene on mesothelioma. These data demonstrated that ZOL-mediated augmentation of p53, which was not linked with ZOL-induced cytotoxicity, played a role in the combinatory effects with a p53 up-regulating agent, and suggests a possible clinical use of ZOL to mesothelioma with anti-cancer agents.

Mesothelioma as a rapidly developing Giant Abdominal Cyst

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Vyas Dinesh

2012-12-01

Full Text Available Abstract The benign cystic mesothelioma of the peritoneum is a rare lesion and is known for local recurrence. This is first case report of a rapidly developing massive abdominal tumor with histological finding of benign cystic mesothelioma (BCM. We describe a BCM arising in the retroperitoneal tis[sue on the right side, lifting ascending colon and cecum to the left side of abdomen. Patient was an active 58-year-old man who noticed a rapid abdominal swelling within a two month time period with a weight gain of 40 pounds. Patient had no risk factors including occupational (asbestos, cadmium, family history, social (alcohol, smoking or history of trauma. We will discuss the clinical, radiologic, intra-operative, immunohistochemical, pathologic findings, and imaging six months after surgery. Patient has no recurrence and no weight gain on follow up visits and imaging.

A case of mesothelioma in a Holstein cow

International Nuclear Information System (INIS)

Francoz, D.

2004-01-01

A seven-year old Holstein cow was referred to the Saint Hyacinth (Quebec) veterinary school for anorexia, progressive weight loss, rapid decline in milk production and abdominal pain. Due to the presence of abdominal and thoracic fluid, abdominal pain and tachycardia with jugular pulse, initially a possible diagnosis was traumatic reticuloperitonitis and pericarditis, but excluded after radiography and ultrasonography. On exploratory laparotomy, numerous 1 to 50 mm diameter nodules were seen on the peritoneum and throughout the abdominal serosa. The animal was euthanased due to the presence of generalised tumour. On histopathology, a mesothelioma was diagnosed. Mesothelioma is rarely diagnosed in cattle. However, it is impossible to know whether this is due to its rarity or to the fact that it may be easily mistaken for other diseases and its histological diagnosis is currently difficult [it

Use of F-18 fluoro deoxyglucose (FDG) positron emission tomography (PET) in the assessment of malignant mesothelioma

International Nuclear Information System (INIS)

Brown, F.M.M.; Pathmaraj, K.; Berlangieri, S.U.; Knight, S.; Clarke, C.P.; Scott, A.M.

2002-01-01

Full text: Australia has the highest mesothelioma incidence rate in the world and the incidence of Mesothelioma is increasing. Therapy for Mesothelioma involves surgery (including phototherapy), radiotherapy and chemotherapy. Computed tomography (CT) is frequently used to stage the extent of Mesothelioma. This study aimed to evaluate the utility of FDG PET in staging Mesothelioma and monitoring response to therapy. Nineteen F-18 FDG PET was performed at the A and RMC Centre for PET in 14 patients (13M: 1F, age range 39-77 years, mean age 58 years) with biopsy proven malignant pleural Mesothelioma. Patients were referred for staging (5 patients) or evaluation of patients post surgery or phototherapy (9 patients). 3 patients had more than 1 PET scan. FDG scans were reviewed with full access to the CT report. Standardised Uptake Values (SUV) were performed in all scans in regions of maximal FDG uptake corresponding to CT abnormality. Normal lung SUVs were also calculated. Follow-up was possible in all patients to the time of death or December 2001 (Follow-up 4 - 45 months, mean 16 months; 3 patients still alive). All FDG PET scans were positive for FDG-avid pleural tissue. No surgery was deferred due to FDG PET findings. In 3 patients mediastinal nodes were identified pre-surgery. Post surgical therapy assessment by FDG PET (9 patients) guided therapy by confirming disease progression or further characterising post-operative changes when CT findings were uncertain. FDG PET was able to more accurately distinguish between collapse/consolidation and recurrent disease than CT scan. Almost all post-surgical scans were performed in patients who received phototherapy. Different Mesothelioma histological subtypes could not be differentiated by SUV criteria. False positive FDG PET studies were seen in 3 patients, all of whom had post-surgical empyemas. In conclusion, FDG PET has a potential role in the management of malignant mesothelioma patients, particularly in the post

Local Acetaldehyde—An Essential Role in Alcohol-Related Upper Gastrointestinal Tract Carcinogenesis

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Mikko T. Nieminen

2018-01-01

Full Text Available The resident microbiome plays a key role in exposure of the upper gastrointestinal (GI tract mucosa to acetaldehyde (ACH, a carcinogenic metabolite of ethanol. Poor oral health is a significant risk factor for oral and esophageal carcinogenesis and is characterized by a dysbiotic microbiome. Dysbiosis leads to increased growth of opportunistic pathogens (such as Candida yeasts and may cause an up to 100% increase in the local ACH production, which is further modified by organ-specific expression and gene polymorphisms of ethanol-metabolizing and ACH-metabolizing enzymes. A point mutation in the aldehyde dehydrogenase 2 gene has randomized millions of alcohol consumers to markedly increased local ACH exposure via saliva and gastric juice, which is associated with a manifold risk for upper GI tract cancers. This human cancer model proves conclusively the causal relationship between ACH and upper GI tract carcinogenesis and provides novel possibilities for the quantitative assessment of ACH carcinogenicity in the human oropharynx. ACH formed from ethanol present in “non-alcoholic” beverages, fermented food, or added during food preparation forms a significant epidemiologic bias in cancer epidemiology. The same also concerns “free” ACH present in mutagenic concentrations in multiple beverages and foodstuffs. Local exposure to ACH is cumulative and can be reduced markedly both at the population and individual level. At best, a person would never consume tobacco, alcohol, or both. However, even smoking cessation and moderation of alcohol consumption are associated with a marked decrease in local ACH exposure and cancer risk, especially among established risk groups.

Prognostic significance of DNA aneuploidy in diffuse malignant mesothelioma

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Isobe, Hiroshi; Sridhar, K.S.; Doria, R. [Univ. of Miami School of Medicine, FL (United States)] [and others

1995-01-01

DNA ploidy of pepsin digested preparations of 48 paraffin-embedded specimens from 19 patients with histologically confirmed malignant mesothelioma was determined by laser flow cytometry. Eight of the 19 tumors (42%) were diploid and 11 (58%) were aneuploid. Of the aneuploid tumors, only one showed multiploidy. The median survival time of the patients with diploid tumors was 19, 16, and 14 months from the onset of symptoms, diagnosis, and treatment, respectively. The median survival in patients with aneuploid tumors was 8, 7, and 7 months from the onset of first symptoms, diagnosis, and treatment. Thus, patients with diploid tumors lived longer than patients with aneuploid tumors. These results suggest that DNA ploidy analysis may be of prognostic value in malignant mesothelioma. 31 refs., 2 figs., 3 tabs.

Report of National Cancer Institute symposium: comparison of mechanisms of carcinogenesis by radiation and chemical agents. I. Common molecular mechanisms

International Nuclear Information System (INIS)

Borg, D.C.

1984-01-01

Some aspects of molecular mechanisms common to radiation and chemical carcinogenesis are discussed, particularly the DNA damage done by these agents. Emphasis is placed on epidemiological considerations and on dose-response models used in risk assessment to extrapolate from experimental data obtained at high doses to the effects from long-term, low-level exposures. 3 references, 6 figures

Report of National Cancer Institute symposium: comparison of mechanisms of carcinogenesis by radiation and chemical agents. I. Common molecular mechanisms

Energy Technology Data Exchange (ETDEWEB)

Borg, D.C.

1984-01-01

Some aspects of molecular mechanisms common to radiation and chemical carcinogenesis are discussed, particularly the DNA damage done by these agents. Emphasis is placed on epidemiological considerations and on dose-response models used in risk assessment to extrapolate from experimental data obtained at high doses to the effects from long-term, low-level exposures. 3 references, 6 figures. (ACR)

A 26-Year-Old Male with Mesothelioma Due to Asbestos Exposure

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P. Zarogoulidis

2011-01-01

Full Text Available Mesothelioma is a malignancy with poor prognosis, with an average 5-year survival rate being less than 9%. This type of cancer is almost exclusively caused by exposure to asbestos. A long exposure can cause mesothelioma and so can short ones, as each exposure is cumulative. We report a case of a 26-year-old male who was exposed to asbestos during his primary school years from the age of 6 to 12. Although the tumor mainly affects older men who in their youth were occupationally exposed to asbestos, malignant mesothelioma can also occur in young adults. A medical history was carefully taken and asbestos exposure was immediately mentioned by the patient. We conducted biopsy on the right supraclavicular lymph node. The patient was not a candidate for surgery, and chemotherapy treatment was initiated. While patient's chemotherapy is still ongoing, no other similar cases of students or teachers have been traced up to date from his school. The school building was demolished in January 2009.

Epigenetic mechanism of radiation carcinogenesis

International Nuclear Information System (INIS)

Niwa, Ohtsura

1995-01-01

Carcinogenic action of radiations has long been thought to be due to its mutagenic activity. Since DNA damage is induced and distributes in a stochastic fashion, radiation induction of cancers was also assumed to follow a stochastic kinetics. However, recent progress in radiation research has revealed that some features of radiation carcinogenesis are not explainable by the simple action of radiation as a DNA damaging and mutagenic agent. Firstly, frequencies of radiation-induced transformation in vitro and radiation-induced mammary cancers in rats are too high to be accounted for by the frequency of radiation-induced mutation. Secondly, trans-generation carcinogenesis among F1 mice born to irradiated parents occurs also much more frequently than to be predicted by the frequency of radiation induced germline mutation. Thirdly, multistage carcinogenesis theory predicts that carcinogens give hits to the target cells so as to shorten the latency of cancers. However, latencies of radiation induced solid cancers among atomic bomb survivors are similar to those of the control population. Fourthly, although radiation elevates the frequency of cancers, the induced cancers seem to share the same spectrum of cancer types as in the unirradiated control populations. This suggests that radiation induces cancer by enhancement of the spontaneous carcinogenesis process. These data suggest that the first step of radiation carcinogenesis may not be the direct induction of mutation. Radiation may induce genetic instability which increases the spontaneous mutation rate in the cells to produce carcinogenic mutations. Growth stimulatory effect of radiation may also contribute to the process. Thus, epigenetic, but not genetic effect of radiation might better contribute in the process of carcinogenesis. (author)

Dysphagia as an unusual complication of pleural mesothelioma

International Nuclear Information System (INIS)

Khan, S.; But, N.; Bajwa, F.

2008-01-01

Dysphagia is an unusual presentation of pleural mesothelioma and carries a grim prognosis. A case of an elderly patient is presented herein, in whom the diagnosis was confirmed histologically, and the patient was still surviving 6 months after palliation. (author)

Imaging in pleural mesothelioma: a review of the 11th International Conference of the International Mesothelioma Interest Group.

Science.gov (United States)

Armato, Samuel G; Labby, Zacariah E; Coolen, Johan; Klabatsa, Astero; Feigen, Malcolm; Persigehl, Thorsten; Gill, Ritu R

2013-11-01

Imaging of malignant pleural mesothelioma (MPM) is essential to the diagnosis, assessment, and monitoring of this disease. The complex morphology and growth pattern of MPM, however, create unique challenges for image acquisition and interpretation. These challenges have captured the attention of investigators around the world, some of whom presented their work at the 2012 International Conference of the International Mesothelioma Interest Group (iMig 2012) in Boston, Massachusetts, USA, September 2012. The measurement of tumor thickness on computed tomography (CT) scans is the current standard of care in the assessment of MPM tumor response to therapy; in this context, variability among observers in the measurement task and in the tumor response classification categories derived from such measurements was reported. Alternate CT-based tumor response criteria, specifically direct measurement of tumor volume change and change in lung volume as a surrogate for tumor response, were presented. Dynamic contrast-enhanced CT has a role in other settings, but investigation into its potential use for imaging mesothelioma tumor perfusion only recently has been initiated. Magnetic resonance imaging (MRI) and positron-emission tomography (PET) are important imaging modalities in MPM and complement the information provided by CT. The pointillism sign in diffusion-weighted MRI was reported as a potential parameter for the classification of pleural lesions as benign or malignant, and PET parameters that measure tumor activity and functional tumor volume were presented as indicators of patient prognosis. Also reported was the use of PET/CT in the management of patients who undergo high-dose radiation therapy. Imaging for MPM impacts everything from initial patient diagnosis to the outcomes of clinical trials; iMig 2012 captured this broad range of imaging applications as investigators exploit technology and implement multidisciplinary approaches toward the benefit of MPM patients

ERC/mesothelin as a marker for chemotherapeutic response in patients with mesothelioma.

Science.gov (United States)

Tajima, Ken; Hirama, Michihiro; Shiomi, Kazu; Ishiwata, Toshiji; Yoshioka, Masataka; Iwase, Akihiko; Iwakami, Shinichiro; Yamazaki, Mariko; Toba, Michie; Tobino, Kazunori; Sugano, Koji; Ichikawa, Masako; Hagiwara, Yoshiaki; Takahashi, Kazuhisa; Hino, Okio

2008-01-01

It has been recently reported that soluble mesothelin-related protein (SMRP), serum mesothelin, and osteopontin (OPN) are considered as relevant biomarkers for the diagnosis of mesothelioma. The aim of this study was to investigate whether serum N-ERC/mesothelin, an NH3-terminal fragment of mesothelin, and plasma OPN reflect chemotherapeutic effect in patients with mesothelioma. Serum N-ERC/mesothelin and plasma osteopontin were determined with a sandwich enzyme-linked immunosorbent assay (ELISA) system. The average N-ERC ratio, determined by dividing the N-ERC levels following chemotherapy by those prior to chemotherapy, in the partial response (PR) group was significantly lower than that of the stable disease (SD)/progressive disease (PD) group. In contrast, the average OPN ratio, determined by dividing the OPN levels following chemotherapy by those prior to chemotherapy, in the PR group was not statistically different from that of the SD/PD group. N-ERC/mesothelin is considered as relevant in monitoring chemotherapeutic response in patients with mesothelioma.

Evaluation of the efficacy of the guideline on reading CT images of malignant pleural mesothelioma with reference CT films for improving the proficiency of radiologists

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Zhou, Huashi, E-mail: zhouhua@u-fukui.ac.jp [Department of Environmental Health, School of Medicine University of Fukui, 23-3 Shimoaitsuki, Matsuoka, Eihezi-cho, Fukui Prefecture, 910-1193 (Japan); Tamura, Taro, E-mail: tarou@u-fukui.ac.jp [Department of Environmental Health, School of Medicine University of Fukui, 23-3 Shimoaitsuki, Matsuoka, Eihezi-cho, Fukui Prefecture, 910-1193 (Japan); Kusaka, Yukinori, E-mail: kusakayk@gmail.com [Department of Environmental Health, School of Medicine University of Fukui, 23-3 Shimoaitsuki, Matsuoka, Eihezi-cho, Fukui Prefecture, 910-1193 (Japan); Suganuma, Narufumi, E-mail: nsuganuma@kochi-u.ac.jp [Department of Environmental Medicine, Kochi University School of Medicine (Japan); Subhannachart, Ponglada, E-mail: pongladas@gmail.com [Central Chest Disease Institute of Thailand, 39 Moo 9, Tiwanon Road, Muang Nonthaburi, 11000 (Thailand); Vijitsanguan, Chomphunut, E-mail: Chompoo_vj@yahoo.com [Central Chest Disease Institute of Thailand, 39 Moo 9, Tiwanon Road, Muang Nonthaburi, 11000 (Thailand); Noisiri, Weeraya, E-mail: weeraya_tat@yahoo.com [Central Chest Disease Institute of Thailand, 39 Moo 9, Tiwanon Road, Muang Nonthaburi, 11000 (Thailand); Hering, Kurt G., E-mail: k.g.hering@t-online.de [Department of Diagnostic Radiology, Radiooncology and Nuclear Medicine, Radiological Clinic, Miner' s Hospital, Radiologische Klinik, Lansppaschaftskranhaus Dortmund, Wieckesweg 27, 44309, Dortmund (Germany); Akira, Masanori, E-mail: akira@kch.hosp.go.jp [Department of Radiology, National Hospital Organization Kinki-Chuo Chest Medical Center, 1180 Nagasone-cho, Kita-ku, Sakai, Osaka, 591-8555 (Japan); Itoh, Harumi, E-mail: hitoh@fmsrsa.fukui-med.ac.jp [Department of Environmental Health, School of Medicine University of Fukui, 23-3 Shimoaitsuki, Matsuoka, Eihezi-cho, Fukui Prefecture, 910-1193 (Japan); Department of Radiology, School of Medicine, University of Fukui, 23-3 Shimoaitsuki Matsuoka, Eiheizi-cho, Fukui Prefecture, 910-1193 (Japan); and others

2013-01-15

Purpose: To assess the efficacy of the developed guideline on reading CT images of malignant pleural mesothelioma for improving radiologists’ reading proficiency. Materials and Methods: Three radiologists independently read the CT films of 22 cases including definite mesothelioma and non-mesothelioma cases at two times before and after studying the malignant pleural mesothelioma CT Guideline. The sensitivity and specificity for mesothelioma were calculated and compared between the 1st and 2nd trials. The kappa statistics was examined for agreement with experts for mesothelioma probability and for mesothelioma features recorded by three radiologists. Results: After studying the mesothelioma CT Guideline, the sensitivity for mesothelioma shown by the three radiologists at the 2nd trial was 100%, 100% and 80%, which were higher than 80%, 85% and 60% at the 1st trial, respectively. The average kappa for agreement between radiologists and experts on dichotomized mesothelioma probability were 0.69 (good) at the 2nd trial vs. 0.38 (fair) at the 1st trial. The average kappa for the agreement with experts for each of 7 features by three radiologists were 0.52–0.80 at the 2nd trial, which were significantly higher than 0.34–0.58 at the 1st trial (Wilcoxon Signed Rank Test: P < 0.01), and as to five features “unilateral pleural effusion”, “nodular pleural thickening”, “tumoral encasement of lung”, “mediastinal pleural thickening”, and “diminished lung”, they achieved good agreement with average kappa of 0.61–0.80. Conclusion: The developed mesothelioma CT Guideline was suggested to have substantial effect in improving the radiologists’ proficiency for reading CT images of mesothelioma, and may contribute to accurate diagnosis of mesothelioma.

Evaluation of the efficacy of the guideline on reading CT images of malignant pleural mesothelioma with reference CT films for improving the proficiency of radiologists

International Nuclear Information System (INIS)

Zhou, Huashi; Tamura, Taro; Kusaka, Yukinori; Suganuma, Narufumi; Subhannachart, Ponglada; Vijitsanguan, Chomphunut; Noisiri, Weeraya; Hering, Kurt G.; Akira, Masanori; Itoh, Harumi

2013-01-01

Purpose: To assess the efficacy of the developed guideline on reading CT images of malignant pleural mesothelioma for improving radiologists’ reading proficiency. Materials and Methods: Three radiologists independently read the CT films of 22 cases including definite mesothelioma and non-mesothelioma cases at two times before and after studying the malignant pleural mesothelioma CT Guideline. The sensitivity and specificity for mesothelioma were calculated and compared between the 1st and 2nd trials. The kappa statistics was examined for agreement with experts for mesothelioma probability and for mesothelioma features recorded by three radiologists. Results: After studying the mesothelioma CT Guideline, the sensitivity for mesothelioma shown by the three radiologists at the 2nd trial was 100%, 100% and 80%, which were higher than 80%, 85% and 60% at the 1st trial, respectively. The average kappa for agreement between radiologists and experts on dichotomized mesothelioma probability were 0.69 (good) at the 2nd trial vs. 0.38 (fair) at the 1st trial. The average kappa for the agreement with experts for each of 7 features by three radiologists were 0.52–0.80 at the 2nd trial, which were significantly higher than 0.34–0.58 at the 1st trial (Wilcoxon Signed Rank Test: P < 0.01), and as to five features “unilateral pleural effusion”, “nodular pleural thickening”, “tumoral encasement of lung”, “mediastinal pleural thickening”, and “diminished lung”, they achieved good agreement with average kappa of 0.61–0.80. Conclusion: The developed mesothelioma CT Guideline was suggested to have substantial effect in improving the radiologists’ proficiency for reading CT images of mesothelioma, and may contribute to accurate diagnosis of mesothelioma

Experimental radiation carcinogenesis is studies at NIRS

International Nuclear Information System (INIS)

Sado, Toshihiko

1992-01-01

Experimental radiation carcinogenesis studies conducted during the past decade at NIRS are briefly reviewed. They include the following: 1) Age dependency of susceptibility to radiation carcinogenesis. 2) Radiation-induced myeloid leukemia. 3) Mechanism of fractionated X-irradiation (FX) induced thymic lymphomas. 4) Significance of radiation-induced immunosuppression in radiation carcinogenesis in vivo. 5) Other ongoing studies. (author)

Benign multicystic mesothelioma: a case report of three sisters

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Thomas Rutherford

2009-12-01

Full Text Available Benign multicystic mesothelioma (BMCM is a rare tumor of the abdomen-peritoneum of unknown etiology. This benign tumor was initially described by Plaut in 1928 when he observed loose cysts in the pelvis during a surgery for a uterine leiomyoma.2 The mesothelial origin was later confirmed by electron micro-scopy by Mennemeyer and Smith in 1979.3 To date, there are approximately 140 cases of BMCM reported in the literature.4 This disease primarily occurs in pre-menopausal women and is associated with a history of pelvic inflammatory disease, prior abdominal surgery, and endometriosis.4,5 The pathogenesis of this disease remains controversial, with possible etiologies including a neoplastic versus a reactive process.5 In the literature, a few case reports discuss a possible genetic or familial association with BMCM.6 Specifically, one report describes a man with familial Mediterranean fever who developed BMCM. Although familial Mediter-ranean fever is associated with malignant mesothelioma, he had only BMCM, and did not suffer from malignant mesothelioma.6 A genetic evaluation and chromosomal analysis were not able to identify a specific genetic cause of the family’s pattern of disease. This case report describes two female siblings diagnosed with BMCM. In addition, a third sister also had findings consistent with BMCM, however, the discrete histological diagnosis was never confirmed.

Targeting eukaryotic translation in mesothelioma cells with an eIF4E-specific antisense oligonucleotide.

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Blake A Jacobson

Full Text Available BACKGROUND: Aberrant cap-dependent translation is implicated in tumorigenesis in multiple tumor types including mesothelioma. In this study, disabling the eIF4F complex by targeting eIF4E with eIF4E-specific antisense oligonucleotide (4EASO is assessed as a therapy for mesothelioma. METHODS: Mesothelioma cells were transfected with 4EASO, designed to target eIF4E mRNA, or mismatch-ASO control. Cell survival was measured in mesothelioma treated with 4EASO alone or combined with either gemcitabine or pemetrexed. Levels of eIF4E, ODC, Bcl-2 and β-actin were assessed following treatment. Binding to a synthetic cap-analogue was used to study the strength of eIF4F complex activation following treatment. RESULTS: eIF4E level and the formation of eIF4F cap-complex decreased in response to 4EASO, but not mismatch control ASO, resulting in cleavage of PARP indicating apoptosis. 4EASO treatment resulted in dose dependent decrease in eIF4E levels, which corresponded to cytotoxicity of mesothelioma cells. 4EASO resulted in decreased levels of eIF4E in non-malignant LP9 cells, but this did not correspond to increased cytotoxicity. Proteins thought to be regulated by cap-dependent translation, Bcl-2 and ODC, were decreased upon treatment with 4EASO. Combination therapy of 4EASO with pemetrexed or gemcitabine further reduced cell number. CONCLUSION: 4EASO is a novel drug that causes apoptosis and selectively reduces eIF4E levels, eIF4F complex formation, and proliferation of mesothelioma cells. eIF4E knockdown results in decreased expression of anti-apoptotic and pro-growth proteins and enhances chemosensitivity.

EGFR-dependent signalling reduced and p38 dependent apoptosis required by Gallic acid in Malignant Mesothelioma cells.

Science.gov (United States)

Demiroglu-Zergeroglu, Asuman; Candemir, Gulsife; Turhanlar, Ebru; Sagir, Fatma; Ayvali, Nurettin

2016-12-01

The unrestrained EGFR signalling contributes to malignant phenotype in a number of cancers including Malignant Mesotheliomas. Present study was designed to evaluate EGFR-dependent anti-proliferative and apoptotic effects of Gallic acid in transformed Mesothelial (MeT-5A) and Malignant Mesothelioma (SPC212) cells. Gallic acid reduced the viability of Malignant Mesothelioma cells in a concentration and time-dependent manner. However, viability of mesothelial cells reduced only at high concentration and longer time periods. Gallic acid restrained the activation of EGFR, ERK1/2 and AKT proteins and down regulated expression of Cyclin D and Bcl-2 genes, but upregulated the expression of p21 gene in EGF-induced SPC212 cells. GA-induced transitory G1 arrest and triggered mitochondrial and death receptor mediated apoptosis, which requires p38MAPK activation. The data provided here indicate that GA is able to inhibit EGFR dependent proliferation and survival signals and induces p38 pathway dependent apoptosis in Malignant Mesothelioma cells. On the basis of these experimental findings it is worthwhile to investigate further the biological activity of Gallic acid on other Mesothelioma cell lines harbouring aberrant EGFR signals. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Oesphageal Stenting for palliation of malignant mesothelioma

Directory of Open Access Journals (Sweden)

Rahamim Joseph

2008-01-01

Full Text Available Abstract Dyspahgia in patients with malignant mesothelioma is usually due to direct infiltration of the eosophagus by the tumour. It can be distressing for the patient and challenging for the physician to treat. We describe three cases in which this condition has been successfully palliated with self expanding esophageal stents.

INTRAOPERATIVE PHOTODYNAMIC THERAPY FOR PERITONEAL MESOTHELIOMA

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A. D. Kaprin

2017-01-01

Full Text Available Abstract Results of application of a new technology of intraoperative photodynamic therapy (IOFDT in patients with peritoneal mesothelioma developed at P. Herzen Moscow Oncology Research Institute are presented. The study included 8 patients. 3 patients underwent surgery in various amount: 1 – limited peritonectomy in the volume of tumor foci resection and resection of a large omentum, 1 – limited peritonectomy in the volume of tumor foci resection and atypical resection of the right lobe of the liver, 1 – only resection of the large omentum due to the fact that the tumor was located only in a large omentum and no signs of lesions of the parietal peritoneum was revealed by intraoperative revision. Surgical intervention in these patients was concluded by IOPDT. The remaining 5 patients underwent only IOPDT. After the treatment, two patients underwent additional courses of laparoscopic IOPDT. Of the 8 patients enrolled in the study, 4 died from the underlying disease, 1 from cardiovascular disease with recurrence of the disease, 1 from cardiovascular disease without signs of recurrence, 2 were monitored for 6 months and 146 months (12 years. Thus, in the group of patients with peritoneal mesothelioma, the maximum observation period was 146.44 months, the median survival was 48.4 months, the total specific 1-year survival was 85.7±13.2%, the three-year survival was 68.5±18.6%, the 5-year survival was 45.7 ± 22.4 %. The average life expectancy after treatment of patients with repeated courses of laparoscopic IOPDT was 87 months, without repeated courses – 35.8 months. Thus, life expectancy was higher in patients with repeated courses of laparoscopic IOPDT. Small sample size caused to the rarity of this pathology does not allow for statistically significant conclusions. However, the results of the study indicate the prospects of multi-course intraoperative photodynamic therapy in patients with peritoneal mesothelioma.

Malignant Mesothelioma Presenting as a Giant Chest, Abdominal and Pelvic Wall Mass

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Shao, Zhi Hong; Gao, Xiao Long; Yi, Xiang Hua; Wang, Pei Jun [Tongji Hospital of Tongji University, Shanghai (China)

2011-11-15

Malignant mesothelioma (MM) is a relatively rare carcinoma of the mesothelial cells, and it is usually located in the pleural or peritoneal cavity. Here we report on a unique case of MM that developed in the chest, abdominal and pelvic walls in a 77-year-old female patient. CT and MRI revealed mesothelioma that manifested as a giant mass in the right flank and bilateral pelvic walls. The diagnosis was confirmed by the pathology and immunohistochemistry. Though rare, accurate investigation of the radiological features of a body wall MM may help make an exact diagnosis.

Malignant Mesothelioma Presenting as a Giant Chest, Abdominal and Pelvic Wall Mass

International Nuclear Information System (INIS)

Shao, Zhi Hong; Gao, Xiao Long; Yi, Xiang Hua; Wang, Pei Jun

2011-01-01

Malignant mesothelioma (MM) is a relatively rare carcinoma of the mesothelial cells, and it is usually located in the pleural or peritoneal cavity. Here we report on a unique case of MM that developed in the chest, abdominal and pelvic walls in a 77-year-old female patient. CT and MRI revealed mesothelioma that manifested as a giant mass in the right flank and bilateral pelvic walls. The diagnosis was confirmed by the pathology and immunohistochemistry. Though rare, accurate investigation of the radiological features of a body wall MM may help make an exact diagnosis.

Benign multicystic peritoneal mesothelioma mimicking recurrence of an ovarian borderline tumor: a case report

Directory of Open Access Journals (Sweden)

Takemoto Shuji

2012-05-01

Full Text Available Abstract Introduction Benign multicystic peritoneal mesothelioma is an extremely rare tumor that occurs mainly in women in their reproductive age. Its preoperative diagnosis and adequate treatment are quite difficult to attain. Case presentation Our patient was a 23-year-old Japanese woman who had a history of right oophorectomy and left ovarian cystectomy for an ovarian tumor at 20 years of age. The left ovarian tumor had been diagnosed on histology as a mucinous borderline tumor. Two years and nine months after the initial operation, multiple cysts were found in our patient. A laparotomy was performed and her uterus, left ovary, omentum and pelvic lymph nodes were removed due to suspicion of recurrence of the borderline tumor. A histological examination, however, revealed that the cysts were not a recurrence of the borderline tumor but rather benign multicystic peritoneal mesothelioma. There were no residual lesions and our patient was followed up with ultrasonography. She remains free from recurrence nine months after treatment. Conclusion We report a case of benign multicystic peritoneal mesothelioma mimicking recurrence of an ovarian borderline tumor. Benign multicystic peritoneal mesothelioma should be suspected when a multicystic lesion is present in the pelvis as in the case presented here, especially in patients with previous abdominal surgery.

Coalescent pleural malignant mesothelioma and adenocarcinoma of the lung, involving only minor asbestos exposure.

Science.gov (United States)

Tsuzuki, Toyonori; Ninomiya, Hironori; Natori, Yuji; Ishikawa, Yuichi

2008-07-01

Coexistence of pulmonary adenocarcinoma and pleural malignant mesothelioma is extremely rare, although both are asbestos-related. Herein is presented a rare case of coalescent lung tumor made up of a malignant mesothelioma and a pulmonary adenocarcinoma in a 62-year-old Japanese man, a high-school teacher with only minor asbestos exposure. Preoperative diagnosis of adenocarcinoma was made on transbronchial biopsy. At surgery, multiple small white nodules were observed on the parietal pleural surface, opposite to the lung tumor. They were confirmed to be malignant mesothelioma on histopathology of paraffin section. The pulmonary tumor mass itself consisted of two distinct portions. The major part contained papillary proliferation of hobnail and columnar cells. Peripherally, neoplastic cells grew in a lepidic fashion and micropapillary growth was also detected. The other component featured tubular structures. The former was positive for adenocarcinoma markers such as CEA, Ber-EP4, PE-10, thyroid transcription factor-1 and Napsin A, and negative for mesothelial markers including calretinin, D2-40, WT-1 and HBME, while the latter was the opposite, resulting in a diagnosis of coalescing malignant mesothelioma and adenocarcinoma. The panel of antibodies used for immunohistochemistry was useful to distinguish the two different components in the one tumor.

Toxicology and Epidemiology: Improving the Science with a Framework for Combining Toxicological and Epidemiological Evidence to Establish Causal Inference

Science.gov (United States)

Adami, Hans-Olov; Berry, Sir Colin L.; Breckenridge, Charles B.; Smith, Lewis L.; Swenberg, James A.; Trichopoulos, Dimitrios; Weiss, Noel S.; Pastoor, Timothy P.

2011-01-01

Historically, toxicology has played a significant role in verifying conclusions drawn on the basis of epidemiological findings. Agents that were suggested to have a role in human diseases have been tested in animals to firmly establish a causative link. Bacterial pathogens are perhaps the oldest examples, and tobacco smoke and lung cancer and asbestos and mesothelioma provide two more recent examples. With the advent of toxicity testing guidelines and protocols, toxicology took on a role that was intended to anticipate or predict potential adverse effects in humans, and epidemiology, in many cases, served a role in verifying or negating these toxicological predictions. The coupled role of epidemiology and toxicology in discerning human health effects by environmental agents is obvious, but there is currently no systematic and transparent way to bring the data and analysis of the two disciplines together in a way that provides a unified view on an adverse causal relationship between an agent and a disease. In working to advance the interaction between the fields of toxicology and epidemiology, we propose here a five-step “Epid-Tox” process that would focus on: (1) collection of all relevant studies, (2) assessment of their quality, (3) evaluation of the weight of evidence, (4) assignment of a scalable conclusion, and (5) placement on a causal relationship grid. The causal relationship grid provides a clear view of how epidemiological and toxicological data intersect, permits straightforward conclusions with regard to a causal relationship between agent and effect, and can show how additional data can influence conclusions of causality. PMID:21561883

Well-differentiated papillary mesothelioma of tunica vaginalis testis of unknown malignant potential: Sonographic appearance.

Science.gov (United States)

Ko, K W S; Tse, K S; Shek, K W; Hau, M N; Ting, S H

2017-10-09

Paratesticular mesothelioma is a rare differential diagnosis in the presence of scrotal hydrocele. A 17-year-old boy presented with a 3-year history of progressive hydrocele. Sonography revealed a large left paratesticular mass within the hydrocele. Serum tumor markers were negative. Left hydrocelectomy was performed and pathological analysis of the epididymal mass revealed a well-differentiated papillary mesothelioma. We discuss the sonographic and pathological findings of this rare neoplasm. © 2017 Wiley Periodicals, Inc.

Heterogeneity of exposure and attribution of mesothelioma: Trends and strategies in two American counties

International Nuclear Information System (INIS)

Case, B W; Abraham, J L

2009-01-01

As mesothelioma risk has begun to decline in the United States, two trends are gaining relative importance. 'Legacy' exposures causing this disease are most important in locales having past asbestos industry, shipyards, and/or local distribution of asbestos amphibole-containing material as a result. 'Future' exposures are of particular concern in relation to so-called 'naturally occurring asbestos' (NOA) areas which include unequivocally asbestiform amphibole. In this paper, Jefferson Parish, Louisiana is used as an example of the first trend, and El Dorado County, California as an example of the second. Available tumor registry, epidemiology, historical and mineralogical data, and lung-retained fibre content are used as indicators of disease and exposure. Jefferson Parish, LA was chosen as the prototype of 'legacy' exposures on the basis of historical evidence of asbestos plants with known mesotheliomas in the workforce, known shipyards in the same area, EPA records of distribution of crocidolite-containing scrap to and remediation of over 1400 properties, NIOSH published data on mesothelioma by county, and exposure data including lung-retained fibre analyses in victims, where available. El Dorado, CA was chosen as the prototype of NOA amphibole exposures on the basis of tumor registry data, activity-based EPA sampling data in one area, and lung-retained fibre analyses in area pets, and future risk assessment based on tremolite-specific modelling in Libby, Montana and elsewhere. As expected, the legacy exposure area was high in mesothelioma incidence and mortality. Lung-retained fibre content confirms crocidolite exposures in exposed plant-workers and those exposed to crocidolite-containing scrap, and amosite in shipyard workers. In contrast, to date, cancer registry data in the NOA-amphibole ('future') county does not show a clear increase in incidence or mortality, but grouped county data from the area show a shift in higher incidence rates to the NOA areas and

Heterogeneity of exposure and attribution of mesothelioma: Trends and strategies in two American counties

Science.gov (United States)

Case, B. W.; Abraham, J. L.

2009-02-01

As mesothelioma risk has begun to decline in the United States, two trends are gaining relative importance. "Legacy" exposures causing this disease are most important in locales having past asbestos industry, shipyards, and/or local distribution of asbestos amphibole-containing material as a result. "Future" exposures are of particular concern in relation to so-called "naturally occurring asbestos" (NOA) areas which include unequivocally asbestiform amphibole. In this paper, Jefferson Parish, Louisiana is used as an example of the first trend, and El Dorado County, California as an example of the second. Available tumor registry, epidemiology, historical and mineralogical data, and lung-retained fibre content are used as indicators of disease and exposure. Jefferson Parish, LA was chosen as the prototype of "legacy" exposures on the basis of historical evidence of asbestos plants with known mesotheliomas in the workforce, known shipyards in the same area, EPA records of distribution of crocidolite-containing scrap to and remediation of over 1400 properties, NIOSH published data on mesothelioma by county, and exposure data including lung-retained fibre analyses in victims, where available. El Dorado, CA was chosen as the prototype of NOA amphibole exposures on the basis of tumor registry data, activity-based EPA sampling data in one area, and lung-retained fibre analyses in area pets, and future risk assessment based on tremolite-specific modelling in Libby, Montana and elsewhere. As expected, the legacy exposure area was high in mesothelioma incidence and mortality. Lung-retained fibre content confirms crocidolite exposures in exposed plant-workers and those exposed to crocidolite-containing scrap, and amosite in shipyard workers. In contrast, to date, cancer registry data in the NOA-amphibole ("future") county does not show a clear increase in incidence or mortality, but grouped county data from the area show a shift in higher incidence rates to the NOA areas and

Heterogeneity of exposure and attribution of mesothelioma: Trends and strategies in two American counties

Energy Technology Data Exchange (ETDEWEB)

Case, B W [Department of Pathology and School of Environment, McGill University, Montreal, Quebec (Canada); Abraham, J L, E-mail: bruce.case@mcgill.c [Department of Pathology, SUNY Upstate Medical University, Syracuse, NY 13210 (United States)

2009-02-01

As mesothelioma risk has begun to decline in the United States, two trends are gaining relative importance. 'Legacy' exposures causing this disease are most important in locales having past asbestos industry, shipyards, and/or local distribution of asbestos amphibole-containing material as a result. 'Future' exposures are of particular concern in relation to so-called 'naturally occurring asbestos' (NOA) areas which include unequivocally asbestiform amphibole. In this paper, Jefferson Parish, Louisiana is used as an example of the first trend, and El Dorado County, California as an example of the second. Available tumor registry, epidemiology, historical and mineralogical data, and lung-retained fibre content are used as indicators of disease and exposure. Jefferson Parish, LA was chosen as the prototype of 'legacy' exposures on the basis of historical evidence of asbestos plants with known mesotheliomas in the workforce, known shipyards in the same area, EPA records of distribution of crocidolite-containing scrap to and remediation of over 1400 properties, NIOSH published data on mesothelioma by county, and exposure data including lung-retained fibre analyses in victims, where available. El Dorado, CA was chosen as the prototype of NOA amphibole exposures on the basis of tumor registry data, activity-based EPA sampling data in one area, and lung-retained fibre analyses in area pets, and future risk assessment based on tremolite-specific modelling in Libby, Montana and elsewhere. As expected, the legacy exposure area was high in mesothelioma incidence and mortality. Lung-retained fibre content confirms crocidolite exposures in exposed plant-workers and those exposed to crocidolite-containing scrap, and amosite in shipyard workers. In contrast, to date, cancer registry data in the NOA-amphibole ('future') county does not show a clear increase in incidence or mortality, but grouped county data from the area show a

Metachronous Uterine Endometrioid Adenocarcinoma and Peritoneal Mesothelioma in Lynch Syndrome: A Case Report.

Science.gov (United States)

Lu, Yuxin; Milchgrub, Sara; Khatri, Gaurav; Gopal, Purva

2017-05-01

Lynch syndrome is a hereditary disease with germline mutation in a DNA mismatch repair gene, most often presenting with colorectal and/or endometrial carcinomas; however, the spectrum of Lynch syndrome-associated tumors is expanding. In this article, we report a case of a primary peritoneal epithelioid mesothelioma that developed in a Lynch syndrome patient 10 months after diagnosis of uterine endometrioid adenocarcinoma. To our knowledge, this is the first reported case of a Lynch syndrome patient with metachronous uterine endometrioid adenocarcinoma and primary peritoneal mesothelioma.

Loss of BAP1 expression is very rare in peritoneal and gynecologic serous adenocarcinomas and can be useful in the differential diagnosis with abdominal mesothelioma.

Science.gov (United States)

Andrici, Juliana; Jung, Jason; Sheen, Amy; D'Urso, Lisa; Sioson, Loretta; Pickett, Justine; Parkhill, Thomas R; Verdonk, Brandon; Wardell, Kathryn L; Singh, Arjun; Clarkson, Adele; Watson, Nicole; Toon, Christopher W; Gill, Anthony J

2016-05-01

Gynecologic and primary peritoneal serous carcinoma may be difficult to distinguish from abdominal mesotheliomas clinically, morphologically, and immunohistochemically. BAP1 double-hit inactivation and subsequent loss of protein expression have been reported in more than half of all abdominal mesotheliomas. We therefore sought to investigate the expression of BAP1 in serous carcinoma and explore its potential utility as a marker in the differential diagnosis with mesothelioma. We searched the computerized database of the Department of Anatomical Pathology, Royal North Shore Hospital, Australia, for all cases of gynecologic and peritoneal serous carcinomas and mesotheliomas diagnosed between 1998 and 2014. Immunohistochemistry for BAP1 was then performed on tissue microarray sections. Cases with completely absent nuclear staining in the presence of a positive internal control in nonneoplastic cells were considered negative. If staining was equivocal (eg, absent nuclear staining but no internal control), staining was repeated on whole sections. Loss of BAP1 expression was found in only 1 of 395 (0.3%) serous carcinomas but in 6 of 9 (67%) abdominal mesotheliomas (P < .001) and 131 of 277 (47%) thoracic mesotheliomas (P < .001). We conclude that BAP1 loss occurs extremely infrequently in gynecologic and peritoneal serous adenocarcinomas, whereas it is very common in mesotheliomas including abdominal mesothelioma. Therefore, although positive staining for BAP1 cannot be used to exclude a diagnosis of mesothelioma, loss of BAP1 expression can be used to very strongly support a pathological diagnosis of abdominal mesothelioma over serous carcinoma. Copyright © 2015 Elsevier Inc. All rights reserved.

Pelvic and lumbar metastasis detected by bone scintigraphy in malignant pleural mesothelioma

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Ruiz Hernandez, G.; Castillo Pallares, F.J.; Llorens Banon, L.; Romero de Avila y Avalos, C. [Hospital Clinic Universitari de Valencia (Spain). Servei de Medicina Nuclear; Garcia Garc`ia, T.; Azagra Ros, P. [Hospital Clinic Universitari de Valencia (Spain). Servei d`Oncologia; Maruenda Paulino, J.I. [Hospital Clinic Universitari de Valencia (Spain). Servei Traumatologia; Ferrer Albiach, C. [Hospital Clinic Universitari de Valencia (Spain). Servei Radioterapia

1999-05-01

A case of a 43-year-old man suffering from pleural mesothelioma with distant bone metastasis is reported. The results of bone scintigraphy and NMR findings allowed the diagnosis. The current case describes a hematogenous metastasis to the pelvis and vertebral column from a malignant pleural mesothelioma that was detected initally by bone scintigraphy. (orig.) [Deutsch] Fallbericht ueber einen 43jaehrigen Mann mit Pleural-Mesotheliom und Knochenmetastasen. Die Diagnose wurde durch Knochenszintigraphie und NMR gestellt. Der vorliegende Fall beschreibt die haematogene Metastasierung ins Becken und in die Wirbelsaeule, ausgehend von einem malignen Pleural-Mesotheliom, das urspruenglich durch Knochenszintigraphie diagnostiziert wurde. (orig.)

Malignant mesothelioma in situ.

Science.gov (United States)

Churg, Andrew; Hwang, Harry; Tan, Larry; Qing, Gefei; Taher, Altaf; Tong, Amy; Bilawich, Ana M; Dacic, Sanja

2018-05-01

The existence of malignant mesothelioma in situ (MIS) is often postulated, but there are no accepted morphological criteria for making such a diagnosis. Here we report two cases that appear to be true MIS on the basis of in-situ genomic analysis. In one case the patient had repeated unexplained pleural unilateral effusions. Two thoracoscopies 9 months apart revealed only visually normal pleura. Biopsies from both thoracoscopies showed only a single layer of mildly reactive mesothelial cells. However, these cells had lost BRCA1-associated protein 1 (BAP1) and showed loss of cyclin-dependent kinase inhibitor 2 (CDKN2A) (p16) by fluorescence in-situ hybridisation (FISH). NF2 was not deleted by FISH but 28% of the mesothelial cells showed hyperploidy. Six months after the second biopsy the patient has persisting effusions but no evidence of pleural malignancy on imaging. The second patient presented with ascites and minimal omental thickening on imaging, but no visual evidence of tumour at laparoscopy. Omental biopsy showed a single layer of minimally atypical mesothelial cells with rare tiny foci of superficial invasion of fat. BAP1 immunostain showed loss of nuclear BAP1 in all the surface mesothelial cells and the invasive cells. There was CDKN2A deletion, but no deletion of NF2 by FISH. These cases show that morphologically bland single-layered surface mesothelial proliferations with molecular alterations seen previously only in invasive malignant mesotheliomas exist, and presumably represent malignant MIS. More cases are need to understand the frequency of such changes and the time-course over which invasive tumour develops. © 2018 John Wiley & Sons Ltd.

Malignant Pleural Mesothelioma Prognostic Marker: A Review of ...

African Journals Online (AJOL)

This article is a review of a series of three studies that proved the involvement of osteopontin as a prognostic marker in malignant pleural mesothelioma (MPM) cancers. The approach used involved synthesizing and analysing the three articles. The first proves the utilization of osteopontin and mesothelin for diagnostic and ...

Autocrine CSF-1R signaling drives mesothelioma chemoresistance via AKT activation

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Cioce, M; Canino, C; Goparaju, C; Yang, H; Carbone, M; Pass, H I

2014-01-01

Clinical management of malignant pleural mesothelioma (MPM) is very challenging because of the uncommon resistance of this tumor to chemotherapy. We report here increased expression of macrophage colony-stimulating-factor-1-receptor (M-CSF/CSF-1R) mRNA in mesothelioma versus normal tissue specimens and demonstrate that CSF-1R expression identifies chemoresistant cells of mesothelial nature in both primary cultures and mesothelioma cell lines. By using RNAi or ligand trapping, we demonstrate that the chemoresistance properties of those cells depend on autocrine CSF-1R signaling. At the single-cell level, the isolated CSF-1Rpos cells exhibit a complex repertoire of pluripotency, epithelial–mesenchymal transition and detoxifying factors, which define a clonogenic, chemoresistant, precursor-like cell sub-population. The simple activation of CSF-1R in untransformed mesothelial cells is sufficient to confer clonogenicity and resistance to pemetrexed, hallmarks of mesothelioma. In addition, this induced a gene expression profile highly mimicking that observed in the MPM cells endogenously expressing the receptor and the ligands, suggesting that CSF-1R expression is mainly responsible for the phenotype of the identified cell sub-populations. The survival of CSF1Rpos cells requires active AKT (v-akt murine thymoma viral oncogene homolog 1) signaling, which contributed to increased levels of nuclear, transcriptionally competent β-catenin. Inhibition of AKT reduced the transcriptional activity of β-catenin-dependent reporters and sensitized the cells to senescence-induced clonogenic death after pemetrexed treatment. This work expands what is known on the non-macrophage functions of CSF-1R and its role in solid tumors, and suggests that CSF-1R signaling may have a critical pathogenic role in a prototypical, inflammation-related cancer such as MPM and therefore may represent a promising target for therapeutic intervention. PMID:24722292

[Benign multicystic peritoneal mesothelioma (BMPM) - a surprising differential diagnosis in case of an expected intraabdominal abscess formation].

Science.gov (United States)

Lipp, Michael Josef; Jusufi, Maximilian Stanley; Backer, Christoph; Feyerabend, Bernd; Weilert, Hauke; Oldhafer, Karl Jürgen

2017-03-01

The benign multicystic peritoneal mesothelioma is a rare disease. Most frequently, young women in reproductive age are affected by this disease. Nevertheless, there are known cases of multicystic peritoneal mesothelioma in male patients. The pathogenesis remains uncertain. Whereas asbestos fibers can cause the development of malignant mesothelioma, the exposure to asbestos particles cannot induce this type of mesothelioma. An inflammatory genesis is discussed as well as the idea of a neoplastic development. Since a high rate of recurrence after surgery is observed, an aggressive surgical treatment is recommended. The complete resection of affected tissue is recently considered to be the therapy of choice. The combination of complete surgical tumor reduction with an intraperitoneal hyperthermic chemotherapy (HIPEC) seems to be promising. Although malignant transformation is detected very rarely a close follow up in centers with high surgical and oncological expertise is recommended. © Georg Thieme Verlag KG Stuttgart · New York.

Multicystic mesothelioma--a rare case of ascites: case report.

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Manuc, M; Lamatic, C; Pop, C; Dobrea, C; Becheanu, G; Grasu, M; Iosif, D; Diculescu, M

2007-01-01

We present the case of a 37-year-old male, admitted to our clinic with abdominal tenderness, right supraclavicular tumour, and ascites. The presence of ascites was incidentally reported 6 years before, but no other evaluation was done at that moment or during this period. Abdominal ultrasound and CT scan revealed moderate ascites, perivascular adenopathies, and multiple abdominal cystic lesions, while thoracic CT scan revealed the same lesions in mediastinum. Laboratory data were within normal limits, including the tumoral markers, and the tests for hydatid cysts. A biopsy from the right supraclavicular nodule was performed, and based on usual and immunohistochemical stains (calretinin, mesotheline, CK 5/6, CK 7, CK18 diffusely positive in mesothelial cells, and CEA -M, bcl-2 and vimentin negative), suggested the diagnosis of mesothelioma. Based on these results, the diagnosis of "multicystic mesothelioma" was made. The patient was referred for surgery.

Pleural mesothelioma: Case-report of uncommon occupational asbestos exposure in a small furniture industry.

Science.gov (United States)

Oddone, Enrico; Imbriani, Marcello

2016-01-01

The relationship between asbestos exposure and malignant mesothelioma is no longer disputed, although it is not always easy to trace past occupational exposure. This report describes a case of uncommon asbestos exposure of a small furniture industry worker, who subsequently died of pleural malignant mesothelioma, to stress the crucial importance of a full reconstruction of the occupational history, both for legal and compensation purposes. Sarcomatoid pleural mesothelioma was diagnosed in a 70-year-old man, who was previously employed as a carpenter in a small furniture industry. He worked for about 6 years in the small factory, was exposed to asbestos during the assembly of the furniture inspired by classical architecture, in which asbestos cement tubes were used to reproduce classical columns. During this production process no specific work safety measures were applied, nor masks or local aspirators. No extra-professional exposure to asbestos was identified. This mesothelioma case was investigated by the Public Prosecutor's assignment that commissioned expert evidence on the legal accountability for the disease. Despite its uncommon expositive circumstance, the length of latency (about 30 years), the duration of exposure, the clinical and histochemical features are all consistent with literature evidence, accounting for the occupational origin of this malignancy. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

Mesothelioma in Two Nondomestic Felids: North American Cougar (Felis concolor and Cheetah (Acinonyx jubatus

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Amanda Whiton

2013-01-01

Full Text Available A 15-year-old male North American cougar (Felis concolor presented with a 2-day history of anorexia, restlessness, and dyspnea. White blood cell count ( cells/μL and absolute segmented neutrophil count ( cells/μL were increased, and BUN (143 mg/dL, creatinine (6.3 mg/dL, and phosphorus (8.5 mg/dL concentrations indicated chronic renal disease. Thoracic radiographs showed severe pleural and pericardial effusion. During attempts to remove the fluid, cardiac tamponade developed and the cat died. At necropsy, nodular masses decorated the pericardium at the level of the base of the heart. The final microscopic diagnosis was mesothelioma of the pericardium, tunica adventitia of the main pulmonary artery, left auricle epicardium, and left ventricular epicardium. A 15-year-old female cheetah (Acinonyx jubatus was evaluated for acute respiratory distress. The white blood cell count ( cells/μL and absolute segmented neutrophil count ( cells/μL were increased. Radiographically pleural effusion and a cranial thoracic mass were seen. The cheetah was euthanized, and a gross diagnosis of disseminated pleural mesothelioma with thoracic effusion was made. Histologically, pleural mesothelioma was confirmed with local invasion of the lung and pulmonary arterial emboli and infarction. In both cases, a diagnosis of mesothelioma was made based on cellular morphology, microscopic architecture, and neoplastic cell coexpression of cytokeratin and vimentin.

Evaluation of pleural disease using MR and CT: With special reference to malignant pleural mesothelioma

International Nuclear Information System (INIS)

Knuuttila, A.; Kivisaari, L.; Kivisaari, A.; Palomaeki, M.; Tervahartiala, P.; Mattson, K.

2001-01-01

Purpose: To evaluate MR imaging and CT in differentiating malignant pleural mesothelioma from other malignancies or benign pleural disease. Material and Methods: Thirty-four patients (18 pleural mesothelioma, 9 other malignancies, 7 benign pleural diseases) were examined using enhanced CT and MR. Two radiologists reviewed the CT and two others the MR images. Comparisons were made between the diagnostic groups and the imaging methods. Results: The abnormalities commonly found in malignant disease, but significantly less frequently in benign pleural disease, were focal thickening and enhancement of inter lobar fissures. In mesothelioma, enhancement of inter lobar fissures, tumour invasion of the diaphragm, mediastinal soft tissue or chest wall, were significantly more often observed than in other malignancies and MR was the most sensitive method. In other malignancies, invasion of bony structures was a more common finding and was also better shown by MR. The contrast-enhanced T1 fat-suppressed (CET1fs) sequence detected these features better than other MR sequences. Conclusion: MR, especially the CET1fs sequence in three planes, gave more information than enhanced CT. Focal thickening and enhancement of inter lobar fissures were early abnormalities indicating malignant pleural disease. MR could be clinically useful for differentiating mesothelioma from other pleural diseases

Evaluation of pleural disease using MR and CT: With special reference to malignant pleural mesothelioma

Energy Technology Data Exchange (ETDEWEB)

Knuuttila, A. [Helsinki Univ. Central Hospital (Finland). Dept. of Medicine; Kivisaari, L.; Kivisaari, A.; Palomaeki, M.; Tervahartiala, P. [Helsinki Univ. Central Hospital (Finland). Dept. of Radiology; Mattson, K. [Helsinki Univ. Central Hospital (Finland). Dept. of Medicine

2001-09-01

Purpose: To evaluate MR imaging and CT in differentiating malignant pleural mesothelioma from other malignancies or benign pleural disease. Material and Methods: Thirty-four patients (18 pleural mesothelioma, 9 other malignancies, 7 benign pleural diseases) were examined using enhanced CT and MR. Two radiologists reviewed the CT and two others the MR images. Comparisons were made between the diagnostic groups and the imaging methods. Results: The abnormalities commonly found in malignant disease, but significantly less frequently in benign pleural disease, were focal thickening and enhancement of inter lobar fissures. In mesothelioma, enhancement of inter lobar fissures, tumour invasion of the diaphragm, mediastinal soft tissue or chest wall, were significantly more often observed than in other malignancies and MR was the most sensitive method. In other malignancies, invasion of bony structures was a more common finding and was also better shown by MR. The contrast-enhanced T1 fat-suppressed (CET1fs) sequence detected these features better than other MR sequences. Conclusion: MR, especially the CET1fs sequence in three planes, gave more information than enhanced CT. Focal thickening and enhancement of inter lobar fissures were early abnormalities indicating malignant pleural disease. MR could be clinically useful for differentiating mesothelioma from other pleural diseases.

OccIDEAS: An Innovative Tool to Assess Past Asbestos Exposure in the Australian Mesothelioma Registry

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Ewan MacFarlane

2012-03-01

Full Text Available Malignant mesothelioma is an uncommon but rapidly fatal disease for which the principal aetiological agent is exposure to asbestos. Mesothelioma is of particular significance in Australia where asbestos use was very widespread from the 1950s until the 1980s. Exposure to asbestos includes occupational exposure associated with working with asbestos or in workplaces where asbestos is used and also ‘take-home’ exposure of family members of asbestos exposed workers. Asbestos exposure may also be nonoccupational, occurring as a consequence of using asbestos products in non-occupational contexts and passive exposure is also possible, such as exposure to asbestos products in the built environment or proximity to an environmental source of exposure, for example an asbestos production plant. The extremely long latency period for this disease makes exposure assessment problematic in the context of a mesothelioma registry. OccIDEAS, a recently developed online tool for retrospective exposure assessment, has been adapted for use in the Australian Mesothelioma Registry (AMR to enable systematic retrospective exposure assessment of consenting cases. Twelve occupational questionnaire modules and one non-occupational module have been developed for the AMR, which form the basis of structured interviews using OccIDEAS, which also stores collected data and provides a framework for generating metrics of exposure.

Characterisation of mesothelioma-initiating cells and their susceptibility to anti-cancer agents.

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Elham Alizadeh Pasdar

Full Text Available Malignant mesothelioma (MM is an aggressive type of tumour causing high mortality. One reason for this paradigm may be the existence of a subpopulation of tumour-initiating cells (TICs that endow MM with drug resistance and recurrence. The objective of this study was to identify and characterise a TIC subpopulation in MM cells, using spheroid cultures, mesospheres, as a model of MM TICs. Mesospheres, typified by the stemness markers CD24, ABCG2 and OCT4, initiated tumours in immunodeficient mice more efficiently than adherent cells. CD24 knock-down cells lost the sphere-forming capacity and featured lower tumorigenicity. Upon serial transplantation, mesospheres were gradually more efficiently tumrigenic with increased level of stem cell markers. We also show that mesospheres feature mitochondrial and metabolic properties similar to those of normal and cancer stem cells. Finally, we show that mesothelioma-initiating cells are highly susceptible to mitochondrially targeted vitamin E succinate. This study documents that mesospheres can be used as a plausible model of mesothelioma-initiating cells and that they can be utilised in the search for efficient agents against MM.

Predictors of trimodality therapy and trends in therapy for malignant pleural mesothelioma.

Science.gov (United States)

Nelson, David B; Rice, David C; Niu, Jiangong; Atay, Scott M; Vaporciyan, Ara A; Antonoff, Mara B; Hofstetter, Wayne L; Walsh, Garrett L; Swisher, Stephen G; Roth, Jack A; Tsao, Anne S; Gomez, Daniel R; Giordano, Sharon H; Mehran, Reza J; Sepesi, Boris

2018-05-01

Malignant pleural mesothelioma is an aggressive and rare malignancy that frequently recurs despite aggressive therapy. We evaluated the frequency of treatment with surgery, radiation or chemotherapy, changes in therapy and survival over time and factors associated with the receipt of trimodality therapy. The National Cancer Database (NCDB) was used to query patients with histologically proven malignant pleural mesothelioma (2004-14). Treatment over time was evaluated using the Armitage trend test. Factors associated with the receipt of trimodality therapy were analysed using logistic regression. Among 20 561 patients, only 4028 (20%) underwent cancer-directed surgery; 533 (2.6%) of whom received trimodality therapy. From 2004 to 2014, the use of surgery with chemotherapy increased 87% (P 26 miles for treatment were more likely to undergo trimodality therapy. Additional factors associated with the receipt of trimodality therapy include age less than 70, Charlson comorbidity score of 0 and presence of private insurance. Many malignant pleural mesothelioma patients are not treated with trimodality therapy, with significant variation in treatment patterns. Referrals to high-volume and specialized centres may help offer more therapeutic options and trial or registry enrolment.

Role of fibulin-3 in the diagnosis of malignant mesothelioma

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Mohammed A. Agha

2014-01-01

Conclusions: Fibulin-3 in the serum and pleural fluid is a good biomarker in the diagnosis of MPM and in differentiation between MPM from malignant pleural metastasis other than mesothelioma and also from benign pleural effusions.

Double contrast barium enema combined with non-invasive imaging in peritoneal mesothelioma

International Nuclear Information System (INIS)

Cozzi, G.; Bellomi, M.; Frigerio, L.F.; Ostinelli, C.; Marchiano, A.; Petrillo, R.; Severini, A.; Milan Univ.

1989-01-01

Mesotheliomas are rare tumors arising from serosal linings of the major serous cavities. Five patients with peritoneal mesothelioma underwent a double contrast barium enema (DCBE) and ultrasonography (US) (2 patients), computed tomography (CT) (3 patients) and/or magnetic resonance imaging (MRI) (3 patients). The diagnosis was confirmed at laparotomy. The radiologic pattern at DCBE is unspecific and consists of compression and dislocation of bowel loops by extrinsic masses. Mesenteric retraction and segmental stenosis may be present. In one patient DCBE was normal. US, CT and MRI findings are also unspecific but when combined with information obtained from DCBE the site and abdominal extension of the disease are well defined. (orig.)

Asbestos exposure and mesothelioma in South Africa | Rees | South ...

African Journals Online (AJOL)

Objectives. To describe the exposure experiences of South African mesothelioma cases, with emphasis on the contribution made to the caseload by different fibre types, the proportion of subjects with no recall of asbestos exposure and only environmental contact, and the importance of putative causes other than asbestos.

Mesothelioma among employees with likely contact with in-place asbestos-containing building materials.

Science.gov (United States)

Anderson, H A; Hanrahan, L P; Schirmer, J; Higgins, D; Sarow, P

1991-12-31

The occurrence of mesothelioma is a sentinel event in occupational and environmental disease. A mesothelioma surveillance system was established utilizing existing computerized Wisconsin vital statistics data maintained since 1959 and a Cancer Reporting System (CRS) established in 1978. Review of the death certificate listing of usual occupation and industry from 487 mesothelioma deaths in Wisconsin from 1959 to 1989 led to the investigation of 41 persons with likely exposure to inplace asbestos-containing building materials (ACBM): 12 school teachers, 10 school maintenance employees, 7 public building maintenance workers, 5 private building maintenance workers, and 7 commercial and factory workers performing maintenance activities. For 10 (34%) of the 29 maintenance workers the only source of asbestos exposure identified was their maintenance work. For five (17%) histories indicated some prior employment in occupations and industries with probable asbestos exposures. Opportunities for indirect occupational exposure were identified for ten who had been employed in the residential construction industry. One maintenance worker was exposed to asbestos in the household and another had neighborhood exposure. For 9 (75%) of the school teachers, the only identifiable potential source of asbestos exposure was derived from in-place ACBM in schools. One teacher had spent a season in the merchant marine aboard an iron ore-hauling ship and 2 had worked in the residential construction industry. Two of the teachers were sisters, and in two instances, two teachers had taught in the same school facility. We conclude that individuals occupationally exposed to in-place ACBM are at risk for the subsequent development of mesothelioma.

Gallium-67 scanning in patients with malignant pleural mesothelioma

International Nuclear Information System (INIS)

Nakano, Takashi; Maeda, Juichiro; Iwahashi, Noriaki; Tamura, Shinsuke; Hada, Toshikazu; Higashino, Kazuya

1990-01-01

The findings of gallium-67 scans in eleven patients with malignant pleural mesothelioma were reviewed and compared to those of chest CT findings. All patients had an abnormal thoracic Ga-67 accumulation. Six out of 11 showed a diffuse accumulation over the entire involved hemithorax and a localized uptake was shown in 5. A marked diffuse thickening of pleura in the absence of adequate gallium accumulation was observed in one patient. Two out of 11 had a reduction of gallium uptake after having combination chemotherapy. These results suggest that a diffusely increased uptake over the entire involved hemithorax is the most characteristic finding of Ga-67 scan in malignant pleural mesothelioma, and that Ga-67 scans may be helpful as a valuable indicator of the proper therapy. However, the superiority of Ga-67 scan to thoracic CT as a means of determining the extent of disease process could not be verified. (author)

Use of imaging in the management of malignant pleural mesothelioma

Energy Technology Data Exchange (ETDEWEB)

Benamore, R.E. [Department of Radiology, University Hospitals of Leicester, Leicester (United Kingdom); O' Doherty, M.J. [Clinical PET Centre, Guy' s and St Thomas' Hospital, London (United Kingdom); Entwisle, J.J. [Department of Radiology, University Hospitals of Leicester, Leicester (United Kingdom)]. E-mail: james.entwisle@uhl-tr.nhs.uk

2005-12-15

Malignant pleural mesothelioma (MPM) is an increasingly prevalent tumour. The death rate associated with MPM is predicted to peak in the next 10 years, although radiologists and clinicians will be encountering cases for the next few decades. Contrast-enhanced CT is an established technique for evaluating suspected malignant pleural disease, but MPM can be reliably diagnosed only by histological sampling. However, even with adequate sampling and the use of immunocytochemistry, histological diagnosis is known to be difficult; definitive diagnosis may involve a combination of clinical presentation, radiological and histological appearances. Percutaneous biopsy is a promising technique for sampling the pleura. In view of its pattern of growth, MPM is a challenging disease to image by any method, and it behaves quite differently from lung cancer. This review aims to highlight the practical aspects of assessing malignant pleural mesothelioma.

Mutagenesis and carcinogenesis resulting from environment pollution

International Nuclear Information System (INIS)

Dimitrov, B.

2001-01-01

The paper reviews different ways of environmental contamination with natural and artificial harmful substances (chemical and radioactive) and their role in the processes of mutagenesis and carcinogenesis. The recent studies of the mechanism of mutagenesis and carcinogenesis due to environmental pollution are discussed

Vorinostat eliminates multicellular resistance of mesothelioma 3D spheroids via restoration of Noxa expression.

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Dario Barbone

Full Text Available When grown in 3D cultures as spheroids, mesothelioma cells acquire a multicellular resistance to apoptosis that resembles that of solid tumors. We have previously found that resistance to the proteasome inhibitor bortezomib in 3D can be explained by a lack of upregulation of Noxa, the pro-apoptotic BH3 sensitizer that acts via displacement of the Bak/Bax-activator BH3-only protein, Bim. We hypothesized that the histone deacetylase inhibitor vorinostat might reverse this block to Noxa upregulation in 3D. Indeed, we found that vorinostat effectively restored upregulation of Noxa protein and message and abolished multicellular resistance to bortezomib in the 3D spheroids. The ability of vorinostat to reverse resistance was ablated by knockdown of Noxa or Bim, confirming the essential role of the Noxa/Bim axis in the response to vorinostat. Addition of vorinostat similarly increased the apoptotic response to bortezomib in another 3D model, the tumor fragment spheroid, which is grown from human mesothelioma ex vivo. In addition to its benefit when used with bortezomib, vorinostat also enhanced the response to cisplatin plus pemetrexed, as shown in both 3D models. Our results using clinically relevant 3D models show that the manipulation of the core apoptotic repertoire may improve the chemosensitivity of mesothelioma. Whereas neither vorinostat nor bortezomib alone has been clinically effective in mesothelioma, vorinostat may undermine chemoresistance to bortezomib and to other therapies thereby providing a rationale for combinatorial strategies.

Vorinostat Eliminates Multicellular Resistance of Mesothelioma 3D Spheroids via Restoration of Noxa Expression

Science.gov (United States)

Barbone, Dario; Cheung, Priscilla; Battula, Sailaja; Busacca, Sara; Gray, Steven G.; Longley, Daniel B.; Bueno, Raphael; Sugarbaker, David J.; Fennell, Dean A.; Broaddus, V. Courtney

2012-01-01

When grown in 3D cultures as spheroids, mesothelioma cells acquire a multicellular resistance to apoptosis that resembles that of solid tumors. We have previously found that resistance to the proteasome inhibitor bortezomib in 3D can be explained by a lack of upregulation of Noxa, the pro-apoptotic BH3 sensitizer that acts via displacement of the Bak/Bax-activator BH3-only protein, Bim. We hypothesized that the histone deacetylase inhibitor vorinostat might reverse this block to Noxa upregulation in 3D. Indeed, we found that vorinostat effectively restored upregulation of Noxa protein and message and abolished multicellular resistance to bortezomib in the 3D spheroids. The ability of vorinostat to reverse resistance was ablated by knockdown of Noxa or Bim, confirming the essential role of the Noxa/Bim axis in the response to vorinostat. Addition of vorinostat similarly increased the apoptotic response to bortezomib in another 3D model, the tumor fragment spheroid, which is grown from human mesothelioma ex vivo. In addition to its benefit when used with bortezomib, vorinostat also enhanced the response to cisplatin plus pemetrexed, as shown in both 3D models. Our results using clinically relevant 3D models show that the manipulation of the core apoptotic repertoire may improve the chemosensitivity of mesothelioma. Whereas neither vorinostat nor bortezomib alone has been clinically effective in mesothelioma, vorinostat may undermine chemoresistance to bortezomib and to other therapies thereby providing a rationale for combinatorial strategies. PMID:23300762

Environment and breast cancer - the role of xenooestrogens in breast cancer carcinogenesis

International Nuclear Information System (INIS)

Plesnicar, A.; Kralj, B.; Druzina, B.; Kovac, V.

2002-01-01

Background. The survival rate of breast cancer patients has not changed much in the last few decades in developed countries. In order to improve the efficacy of breast cancer prevention and treatment, the role of xenooestrogens in the mechanisms of its development has been evaluated. These industrial chemicals bear little structural resemblance to each other and bind to the oestrogen receptors of exposed cells and/or trigger oestrogenic responses in laboratory test systems. Exposure to xenooestrogens has been regarded as a risk factor for carcinogenesis and a preventable cause of breast carcinoma. Several epidemiological and experimental studies in in vivo and in in vitro conditions of the influence of xenooestrogens on the occurrence of breast cancer have been conducted in the last decades and have shown ambiguous results. Conclusions. No increase in breast carcinoma incidence could be found in women who were exposed to relatively high concentrations of xenooestrogens for extended periods and small quantities of these compounds that are present in the environment probably cannot act as etiological agents for the occurrence of this disease. A multi step approach is suggested regarding the sequence of studies and measures that should be taken to further assess the importance of xenooestrogens on breast cancer carcinogenesis. (author)

Effect of complex polyphenols on colon carcinogenesis.

Science.gov (United States)

Caderni, G; Remy, S; Cheynier, V; Morozzi, G; Dolara, P

1999-06-01

Complex polyphenols and tannins from wine (WCPT) are being considered increasingly as potential cancer chemopreventive agents, since epidemiological studies suggest that populations consuming a high amount of polyphenols in the diet may have a lower incidence of some types of cancer. We studied the effect of WCPT on a series of parameters related to colon carcinogenesis in rats. WCPT were administered to F344 rats at a dose of 14 or 57 mg/kg/d, mixed with the diet. The higher dose is about ten times the exposure to polyphenols of a moderate drinker of red wine. In rats treated with WCPT, we measured fecal bile acids and long chain fatty acids, colon mucosa cell proliferation, apoptosis and, after administration of colon carcinogens, the number and size of aberrant crypt foci (ACF) and nuclear aberrations. Colon mucosa proliferation was not varied by chronic administration (90 d) of WCPT (14 or 57 mg/kg/d). The highest dose of WCPT decreased the number of cells in the colon crypts, but did not increase apoptosis. WCPT (57 mg/kg) administered before or after the administration of azoxymethane (AOM) did not vary the number or multiplicity of ACF in the colon. The number of nuclear aberrations (NA) in colon mucosa was studied after administration of 1,2-dimethylhydrazine (DMH) and 2-amino-3-methylimidazo (4,5-f)quinoline (IQ), colon-specific carcinogens which require metabolic activation. The effect of DMH and IQ was not varied by pre-feeding WCPT (57 mg/kg) for 10 d. Similarly, the levels of total, secondary bile acids and long chain fatty acids did not varied significantly in animals fed WCPT for 90 d. WCPT administration does not influence parameters related to colon carcinogenesis in the rat.

A biomarker profile for predicting efficacy of cisplatin-vinorelbine therapy in malignant pleural mesothelioma

DEFF Research Database (Denmark)

Zimling, Zarah Glad; Sørensen, Jens Benn; Gerds, Thomas Alexander

2012-01-01

Malignant pleural mesothelioma (MPM) has a dismal prognosis. Treatment results may be improved by biomarker-directed therapy. We investigated the baseline expression and impact on outcome of predictive biomarkers ERCC1, BRCA1, and class III β-tubulin in a cohort of MPM patients treated with cispl......Malignant pleural mesothelioma (MPM) has a dismal prognosis. Treatment results may be improved by biomarker-directed therapy. We investigated the baseline expression and impact on outcome of predictive biomarkers ERCC1, BRCA1, and class III β-tubulin in a cohort of MPM patients treated...

Epidemiological studies on radiation carcinogenesis in human populations following acute exposure: nuclear explosions and medical radiation

International Nuclear Information System (INIS)

Fabrikant, J.I.

1981-01-01

The present review provides an understanding of our current knowledge of the carcinogenic effect of low-dose radiation in man, and surveys the epidemiological studies of human populations exposed to nuclear explosions and medical radiation. Discussion centers on the contributions of quantitative epidemiology to present knowledge, the reliability of the dose-incidence data, and those relevant epidemiological studies that provide the most useful information for risk estimation of cancer induction in man. Reference is made to dose-incidence relationships from laboratory animal experiments where they may obtain, for problems and difficulties in extrapolation from data obtained at high doses to low doses, and from animal data to the human situation. The paper describes the methods of application of such epidemiological data for estimation of excess risk of radiation-induced cancer in exposed human populations and discusses the strengths and limitations of epidemiology in guiding radiation protection philosophy and public health policy

Oleuropein-Enriched Olive Leaf Extract Affects Calcium Dynamics and Impairs Viability of Malignant Mesothelioma Cells

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Carla Marchetti

2015-01-01

Full Text Available Malignant mesothelioma is a poor prognosis cancer in urgent need of alternative therapies. Oleuropein, the major phenolic of olive tree (Olea europaea L., is believed to have therapeutic potentials for various diseases, including tumors. We obtained an oleuropein-enriched fraction, consisting of 60% w/w oleuropein, from olive leaves, and assessed its effects on intracellular Ca2+ and cell viability in mesothelioma cells. Effects of the oleuropein-enriched fraction on Ca2+ dynamics and cell viability were studied in the REN mesothelioma cell line, using fura-2 microspectrofluorimetry and MTT assay, respectively. Fura-2-loaded cells, transiently exposed to the oleuropein-enriched fraction, showed dose-dependent transient elevations of cytosolic Ca2+ concentration (Ca2+i. Application of standard oleuropein and hydroxytyrosol, and of the inhibitor of low-voltage T-type Ca2+ channels NNC-55-0396, suggested that the effect is mainly due to oleuropein acting through its hydroxytyrosol moiety on T-type Ca2+ channels. The oleuropein-enriched fraction and standard oleuropein displayed a significant antiproliferative effect, as measured on REN cells by MTT cell viability assay, with IC50 of 22 μg/mL oleuropein. Data suggest that our oleuropein-enriched fraction from olive leaf extract could have pharmacological application in malignant mesothelioma anticancer therapy, possibly by targeting T-type Ca2+ channels and thereby dysregulating intracellular Ca2+ dynamics.

The psychological distress and care needs of mesothelioma patients and asbestos-exposed subjects: A systematic review of published studies.

Science.gov (United States)

Bonafede, Michela; Ghelli, Monica; Corfiati, Marisa; Rosa, Valentina; Guglielmucci, Fanny; Granieri, Antonella; Branchi, Claudia; Iavicoli, Sergio; Marinaccio, Alessandro

2018-05-01

The purpose of this study is to present the results of a systematic review of published research that focuses on psychological aspects of malignant mesothelioma patients and asbestos-exposed people. Our research includes primary studies published between 1980 and 2016, using information from the Cochrane Library, the Psychology Behavioral Sciences Collection, PsychINFO, PubMed, PubGet, PubPsych, and Scopus, in compliance with PRISMA guidelines. We identified 12 papers that investigated the psychological distress and care needs of mesothelioma patients, and nine papers for asbestos-exposed subjects. This paper highlights the paucity of studies on the psychological distress and care needs of mesothelioma patients and asbestos-exposed subjects. It confirms that malignant mesothelioma is associated with the physical, emotional, and social functioning of patients, while also suggesting that the risk of developing asbestos-related diseases among asbestos-exposed subjects is associated with high levels of psychological distress, despair, and mental health difficulties. © 2018 Wiley Periodicals, Inc.

Diode-Pumped Laser for Lung-Sparing Surgical Treatment of Malignant Pleural Mesothelioma.

Science.gov (United States)

Bölükbas, Servet; Biancosino, Christian; Redwan, Bassam; Eberlein, Michael

2017-06-01

Surgical resection represents one of the essential cornerstones in multimodal treatment of malignant pleural mesothelioma. In cases of tumor infiltration of the lung, lung-scarifying procedures such as lobectomies or pneumonectomies might be necessary to achieve macroscopic complete resection. However, this increases the morbidity of the patients because it leads to possible delay of the planned chemotherapy or radiotherapy. Innovative surgical techniques are therefore required to enable salvage of the lung parenchyma and optimization of surgical treatment. Here we report our first experience with a diode-pumped neodymium-doped yttrium aluminium garnet laser for parenchyma-sparing lung resection during surgery for malignant pleural mesothelioma. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Malignant Mesothelioma Versus Metastatic Carcinoma of the Pleura: A CT Challenge

International Nuclear Information System (INIS)

Bakhshayesh Karam, Mehrdad; Karimi, Shirin; Mosadegh, Leila; Chaibakhsh, Samira

2016-01-01

Malignant pleural mesothelioma (MPM) is a rare malignant neoplasm of the pleura that typically affects individuals occupationally exposed to asbestos through a variety of industries. MPM presents with several CT features similar to more common pleural diseases such as metastatic pleural malignancy. The aim of this study is to differentiate malignant pleural mesothelioma from metastatic carcinoma of the pleura by pathological and radiological assessment in order to investigate accuracy of CT scan in this regard and to compare CT features of these two malignancies. Chest CT scans of 55 pleural malignancy patients including MPM and metastatic pleural malignancy were evaluated in this retrospective study. The pathologist made the definite diagnosis based on immunohistochemistry. A chest radiologist unaware of the pathology diagnosis observed all CT scans. Several parameters including pleural thickening, pleural effusion, thickening of inter lobar fissure, contralateral extension, contraction of involved hemithorax, parenchymal involvement (infiltration, nodules, fibrosis), pleural mediastinal involvement, lymphadenopathy, extrapleural invasion (hepatic, chest wall, diaphragm, intraperitoneal), and pericardial involvement were checked. Data analysis was carried out using SPSS version 16, and the ability of CT scan to differentiate malignant pleural mesothelioma and metastatic pleural diseases was investigated. Totally 29 males and 26 females were assessed in this study. Based on pathology, 17 MPM and 38 metastatic pleural malignancies were diagnosed. According to CT study, about 82% of the patients with MPM and about 79% of the patients with metastatic pleural diseases were correctly diagnosed by a radiologist. The most common findings suggestive of MPM were pleural thickening (88.2%), loculated effusion (58.8%), and thickening of the interlobar fissure (47.1%). Whereas free pleural effusion (71.7%), parenchymal infiltration (65.8%) and pleural thickening (63.2%) were

In vitro studies of human lung carcinogenesis.

Science.gov (United States)

Harris, C C; Lechner, J F; Yoakum, G H; Amstad, P; Korba, B E; Gabrielson, E; Grafstrom, R; Shamsuddin, A; Trump, B F

1985-01-01

Advances in the methodology to culture normal human lung cells have provided opportunities to investigate fundamental problems in biomedical research, including the mechanism(s) of carcinogenesis. Using the strategy schematically shown in Figure 1, we have initiated studies of the effects of carcinogens on the normal progenitor cells of the human cancers caused by these carcinogens. Extended lifespans and aneuploidy were found after exposure of mesothelial cells to asbestos and bronchial epithelial cells to nickel sulfate. These abnormal cells may be considered to be preneoplastic and at an intermediate position in the multistage process of carcinogenesis. Human bronchial epithelial cells can also be employed to investigate the role of specific oncogenes in carcinogenesis and tumor progression. Using the protoplast fusion method for high frequency gene transfection, vHa-ras oncogene initiates a cascade of events in the normal human bronchial cells leading to their apparent immortality, aneuploidy, and tumorigenicity in athymic nude mice. These results suggest that oncogenes may play an important role in human carcinogenesis.

Initiator of carcinogenesis selectively and stably inhibits stem cell differentiation: a concept that initiation of carcinogenesis involves multiple phases

International Nuclear Information System (INIS)

Scott, R.E.; Maercklein, P.B.

1985-01-01

A concept of carcinogenesis was recently devised in our laboratory that suggests the development of defects in the control of cell differentiation is associated with an early phase of carcinogenesis. To test this proposal directly, the effects of an initiator of carcinogenesis (i.e., UV irradiation) on proadipocyte stem cell differentiation and proliferation was assayed. In this regard, 3T3 T proadipocytes represent a nontransformed mesenchymal stem cell line that possesses the ability to regulate its differentiation at a distinct state in the G 1 phase of the cell cycle as well as the ability to regulate its proliferation at two additional G 1 states. The results establish that a slow dosage of 254 nm UV irradiation selectivity and stably inhibits the differentiation of a high percentage of proadipocyte stem cells without significantly altering their ability to regulate cellular proliferation in growth factor-deficient or nutrient-deficient culture conditions. Differentiation-defect proadipocyte stem cells are demonstrated not to be completely transformed but to show an increased spontaneous transformation rate, as evidenced by the formation of type III foci in high density cell cultures. These data support the role of defects in the control of differentiation in the inhibition of carcinogenesis. These observations support a concept that the initiation of carcinogenesis involves multiple phases

Consensus Report of the 2015 Weinman International Conference on Mesothelioma

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On November 9 and 10, 2015, the International Conference on Mesothelioma in Populations Exposed to Naturally Occurring Asbestiform Fibers was held at the University of Hawaii Cancer Center in Honolulu, Hawaii. The meeting was cosponsored by the International Association for the S...

Sphingosine kinase 1 is required for mesothelioma cell proliferation: role of histone acetylation.

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Satish Kalari

Full Text Available Malignant pleural mesothelioma (MPM is a devastating disease with an overall poor prognosis. Despite the recent advances in targeted molecular therapies, there is a clear and urgent need for the identification of novel mesothelioma targets for the development of highly efficacious therapeutics.In this study, we report that the expression of Sphingosine Kinase 1 (SphK1 protein was preferentially elevated in MPM tumor tissues (49 epithelioid and 13 sarcomatoid compared to normal tissue (n = 13. In addition, we also observed significantly elevated levels of SphK1 and SphK2 mRNA and SphK1 protein expression in MPM cell lines such as H2691, H513 and H2461 compared to the non-malignant mesothelial Met5 cells. The underlying mechanism appears to be mediated by SphK1 induced upregulation of select gene transcription programs such as that of CBP/p300 and PCAF, two histone acetyl transferases (HAT, and the down regulation of cell cycle dependent kinase inhibitor genes such as p27Kip1 and p21Cip1. In addition, using immunoprecipitates of anti-acetylated histone antibody from SphK inhibitor, SphK-I2 treated Met5A and H2691 cell lysates, we also showed activation of other cell proliferation related genes, such as Top2A (DNA replication, AKB (chromosome remodeling and mitotic spindle formation, and suppression of p21 CIP1 and p27KIP1. The CDK2, HAT1 and MYST2 were, however, unaffected in the above study. Using SphK inhibitor and specific siRNA targeting either SphK1 or SphK2, we also unequivocally established that SphK1, but not SphK2, promotes H2691 mesothelioma cell proliferation. Using a multi-walled carbon nanotubes induced peritoneal mesothelioma mouse model, we showed that the SphK1-/- null mice exhibited significantly less inflammation and granulamatous nodules compared to their wild type counterparts.The lipid kinase SphK1 plays a positive and essential role in the growth and development of malignant mesothelioma and is therefore a likely

Targeting mesothelin receptors with drug-loaded bacterial nanocells suppresses human mesothelioma tumour growth in mouse xenograft models.

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Mohamed A Alfaleh

Full Text Available Human malignant mesothelioma is a chemoresistant tumour that develops from mesothelial cells, commonly associated with asbestos exposure. Malignant mesothelioma incidence rates in European countries are still rising and Australia has one of the highest burdens of malignant mesothelioma on a population basis in the world. Therapy using systemic delivery of free cytotoxic agents is associated with many undesirable side effects due to non-selectivity, and is thus dose-limited which limits its therapeutic potential. Therefore, increasing the selectivity of anti-cancer agents has the potential to dramatically enhance drug efficacy and reduce toxicity. EnGeneIC Dream Vectors (EDV are antibody-targeted nanocells which can be loaded with cytotoxic drugs and delivered to specific cancer cells via bispecific antibodies (BsAbs which target the EDV and a cancer cell-specific receptor, simultaneously. BsAbs were designed to target doxorubicin-loaded EDVs to cancer cells via cell surface mesothelin (MSLN. Flow cytometry was used to investigate cell binding and induction of apoptosis, and confocal microscopy to visualize internalization. Mouse xenograft models were used to assess anti-tumour effects in vivo, followed by immunohistochemistry for ex vivo evaluation of proliferation and necrosis. BsAb-targeted, doxorubicin-loaded EDVs were able to bind to and internalize within mesothelioma cells in vitro via MSLN receptors and induce apoptosis. In mice xenografts, the BsAb-targeted, doxorubicin-loaded EDVs suppressed the tumour growth and also decreased cell proliferation. Thus, the use of MSLN-specific antibodies to deliver encapsulated doxorubicin can provide a novel and alternative modality for treatment of mesothelioma.

Desmoplastic malignant mesothelioma of the pericardium: Description of a case and review of the literature

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Antonello Nicolini

2011-01-01

Full Text Available Desmoplastic mesothelioma (DMM is a rare and highly lethal subtype of diffuse malignant mesothelioma and is often difficult to distinguish from reactive pleural fibrosis. The term "desmoplastic" refers to the growth of fibrous or connective tissue. We report the clinical, radiological, and pathological features of a primary DMM of the pericardium and a short review of the literature. A 72-year-old man was admitted presenting shortness of breath, cough, and asthenia. Computed tomography scan showed thickenings and effusions both in the pleura and in the pericardium. Histopathological diagnosis was performed by surgical pericardial biopsy and confirmed by autopsy. The patient had a history of asbestos exposure. Primary mesothelioma of the pericardium is a rare tumor occurring in the fourth to seventh decades with nonspecific symptoms and a rapid clinical course. The diagnosis is difficult and often needing a surgical pericardial biopsy. The prognosis is poor although newer antiblastic drugs seem to prolong survival times.

Malignant Pleural Mesothelioma with Marked Lymphatic Involvement: A Report of Two Autopsy Cases

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Reiko Ideguchi

2017-01-01

Full Text Available We herein report two cases of malignant pleural mesothelioma with marked lymphangiosis. The patients included a 68-year-old man and a 67-year-old man who both had a history of exposure to asbestos. Computed tomography (CT on admission showed pleural effusion with pleural thickening. In both cases, a histopathological examination of the pleura confirmed the diagnosis of epithelioid malignant mesothelioma. They received chemotherapy, but the treatment was only palliative. The chest CT assessments during admission revealed marked pleural effusion and mediastinal lymphadenopathy. CT also showed a consolidative mass with bronchovascular bundle and septal thickening in the lungs suggesting pulmonary parenchymal involvement and the lymphangitic spread of the tumor. These CT findings mimicked lung cancer with pleuritis and lymphangitic carcinomatosis. Autopsy was performed in both cases. Macroscopically, the tumor cells infiltrated the lung with the marked lymphatic spread of the tumor. Microscopy also revealed that the tumor had invaded the pulmonary parenchyma with the marked lymphatic spread of the tumor. Although this growth pattern is unusual, malignant pleural mesothelioma should be considered as the differential diagnosis, especially in patients with pleural lesions.

Carcinogenesis induced by low-dose radiation

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Piotrowski Igor

2017-11-01

Full Text Available Although the effects of high dose radiation on human cells and tissues are relatively well defined, there is no consensus regarding the effects of low and very low radiation doses on the organism. Ionizing radiation has been shown to induce gene mutations and chromosome aberrations which are known to be involved in the process of carcinogenesis. The induction of secondary cancers is a challenging long-term side effect in oncologic patients treated with radiation. Medical sources of radiation like intensity modulated radiotherapy used in cancer treatment and computed tomography used in diagnostics, deliver very low doses of radiation to large volumes of healthy tissue, which might contribute to increased cancer rates in long surviving patients and in the general population. Research shows that because of the phenomena characteristic for low dose radiation the risk of cancer induction from exposure of healthy tissues to low dose radiation can be greater than the risk calculated from linear no-threshold model. Epidemiological data collected from radiation workers and atomic bomb survivors confirms that exposure to low dose radiation can contribute to increased cancer risk and also that the risk might correlate with the age at exposure.

Pleomorphic Malignant Mesothelioma in a Broiler Breeder Infected with Avian Leucosis Virus Subgroup J.

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Murakami, T; Sassa, Y

2018-04-01

Avian leucosis virus (ALV) is an oncogenic retrovirus that induces tumours including lymphoid leucosis and myeloid leucosis. Pleomorphic malignant mesothelioma and myelocytoma, which were thought to be induced by ALV subgroup J (ALV-J) infection, were identified in a 432-day-old broiler breeder. The bird showed no clinical signs; however, at necropsy examination there were multiple nodules in the alimentary tract. Microscopical analysis showed that these consisted of pleomorphic cells and myelocyte-like cells. Immunohistochemistry revealed that the pleomorphic cells were atypical and expressed cytokeratin, vimentin, c-kit, calretinin and ALV. The myelocyte-like cells were also positive for ALV. Retroviral type C particles were observed by electron microscopy. ALV-E and ALV-J nucleotide sequences were detected in DNA extracted from formalin-fixed and paraffin wax-embedded small intestinal tissue. Based on these results, the tumours were diagnosed as pleomorphic malignant mesothelioma and myelocytoma and were thought to have been induced by ALV-J infection. This is the first report of malignant mesothelioma associated with naturally acquired ALV-J infection. Copyright © 2018 Elsevier Ltd. All rights reserved.

Mutiple simultaneous event model for radiation carcinogenesis

International Nuclear Information System (INIS)

Baum, J.W.

1979-01-01

Theoretical Radiobiology and Risk Estimates includes reports on: Multiple Simultaneous Event Model for Radiation Carcinogenesis; Cancer Risk Estimates and Neutron RBE Based on Human Exposures; A Rationale for Nonlinear Dose Response Functions of Power Greater or Less Than One; and Rationale for One Double Event in Model for Radiation Carcinogenesis

Understanding Carcinogenesis for Fighting Oral Cancer

OpenAIRE

Tanaka, Takuji; Ishigamori, Rikako

2011-01-01

Oral cancer is one of the major global threats to public health. Oral cancer development is a tobacco-related multistep and multifocal process involving field cancerization and carcinogenesis. The rationale for molecular-targeted prevention of oral cancer is promising. Biomarkers of genomic instability, including aneuploidy and allelic imbalance, are able to measure the cancer risk of oral premalignancies. Understanding of the biology of oral carcinogenesis will give us important advances for...

Caelyx (TM) in malignant mesothelioma : A phase II EORTC study

NARCIS (Netherlands)

Baas, P; van Meerbeeck, J; Groen, H; Schouwink, H; Burgers, S; Daamen, S; Giaccone, G

Background: The use of doxorubicin has shown some activity in malignant mesothelioma but prolonged administration is hampered by cardiotoxicity. Caelyx(TM), a new liposomal and pegylated form of doxorubicin has shown a better pharmacokinetic and toxic profile then doxorubicin. In a phase II study,

Radiation-induced mammary carcinogenesis in rodent models. What's different from chemical carcinogenesis?

International Nuclear Information System (INIS)

Imaoka, Tatsuhiko; Nishimura, Mayumi; Iizuka, Daisuke; Daino, Kazuhiro; Takabatake, Takashi; Okamoto, Mieko; Kakinuma, Shizuko; Shimada, Yoshiya

2009-01-01

Ionizing radiation is one of a few well-characterized etiologic factors of human breast cancer. Laboratory rodents serve as useful experimental models for investigating dose responses and mechanisms of cancer development. Using these models, a lot of information has been accumulated about mammary gland cancer, which can be induced by both chemical carcinogens and radiation. In this review, we first list some experimental rodent models of breast cancer induction. We then focus on several topics that are important in understanding the mechanisms and risk modification of breast cancer development, and compare radiation and chemical carcinogenesis models. We will focus on the pathology and natural history of cancer development in these models, genetic changes observed in induced cancers, indirect effects of carcinogens, and finally risk modification by reproductive factors and age at exposure to the carcinogens. In addition, we summarize the knowledge available on mammary stem/progenitor cells as a potential target of carcinogens. Comparison of chemical and radiation carcinogenesis models on these topics indicates certain similarities, but it also indicates clear differences in several important aspects, such as genetic alterations of induced cancers and modification of susceptibility by age and reproductive factors. Identification of the target cell type and relevant translational research for human risk management may be among the important issues that are addressed by radiation carcinogenesis models. (author)

Primary pericardial mesothelioma: a case report

Energy Technology Data Exchange (ETDEWEB)

Kobayashi, Yuko; Murakami, Ryusuke; Ogura, Junko; Yamamoto, Kanae; Ichikawa, Taro [Dept. of Radiology, Tama-Nagayama Hospital, Tokyo (Japan); Nagasawa, Kouichi [Dept. of Internal Medicine, Tama-Nagayama Hospital, Tokyo (Japan); Hosone, Masaru [Dept. of Pathology, Tama-Nagayama Hospital, Tokyo (Japan); Kumazaki, Tatsuo [Dept. of Radiology, Nippon Medical School, Tokyo (Japan)

2001-11-01

The imaging features of primary pericardial mesothelioma have rarely been described. Herein we present a case report of its diagnostic-pathologic features. Chest computed tomography (CT) revealed an irregularly enhanced mass occupying the entire pericardial space and surrounding the superior vena cava. At autopsy, the tumor was found to fill the pericardial space completely, and to extend to the superior vena cava through the superior pericardial sinus. The CT features of the tumor were correlated well with those revealed at autopsy, and provided satisfactory information regarding the presence and the extension of the tumor. (orig.)

Mesothelioma in Qingdao, PRC (2000 - 2007)

Science.gov (United States)

Frank, Arthur L.; Zengchang, Pang; Huaqiang, Zhang; Yun, Zhang

2009-02-01

The city of Qingdao, PRC has been the site of two asbestos product facilities that operated for almost fifty years, as well as a shipyard. Because of a new computerized data collection system for death certificates, almost all 48,000 yearly deaths from a population base of 7.5 million are now recorded with cause of death and "usual occupation". All mesothelioma deaths from 2000 through 2007 are reviewed and the unusual finding is that of a predominance of cases in females. The issues of competing causes of death and potential underreporting are discussed.

The economic burden of lung cancer and mesothelioma due to occupational and para-occupational asbestos exposure.

Science.gov (United States)

Tompa, Emile; Kalcevich, Christina; McLeod, Chris; Lebeau, Martin; Song, Chaojie; McLeod, Kim; Kim, Joanne; Demers, Paul A

2017-11-01

To estimate the economic burden of lung cancer and mesothelioma due to occupational and para-occupational asbestos exposure in Canada. We estimate the lifetime cost of newly diagnosed lung cancer and mesothelioma cases associated with occupational and para-occupational asbestos exposure for calendar year 2011 based on the societal perspective. The key cost components considered are healthcare costs, productivity and output costs, and quality of life costs. There were 427 cases of newly diagnosed mesothelioma cases and 1904 lung cancer cases attributable to asbestos exposure in 2011 for a total of 2331 cases. Our estimate of the economic burden is $C831 million in direct and indirect costs for newly identified cases of mesothelioma and lung cancer and $C1.5 billion in quality of life costs based on a value of $C100 000 per quality-adjusted life year. This amounts to $C356 429 and $C652 369 per case, respectively. The economic burden of lung cancer and mesothelioma associated with occupational and para-occupational asbestos exposure is substantial. The estimate identified is for 2331 newly diagnosed, occupational and para-occupational exposure cases in 2011, so it is only a portion of the burden of existing cases in that year. Our findings provide important information for policy decision makers for priority setting, in particular the merits of banning the mining of asbestos and use of products containing asbestos in countries where they are still allowed and also the merits of asbestos removal in older buildings with asbestos insulation. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Primary pleural angiosarcoma as a mimicker of mesothelioma: a case report **VS**

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Kao Yu-Chien

2011-12-01

Full Text Available Abstract Primary pleural angiosarcoma is a rare and clinically aggressive tumor. Patients usually present with chest pain, dyspnea, hemoptysis and/or cough. Radiologic studies reveal diffuse pleural thickening and pleural effusion with or without mass lesion. The clinical and radiological features both resemble those of mesothelioma, and its definite diagnosis requires careful histologic examination. However, frequent epithelioid feature and immunoreactivity to cytokeratin in primary pleural angiosarcoma further complicate the pathologic diagnosis. The use of proper immunohistochemical stains is often needed to support endothelial differentiation in the tumor cells and to exclude metastatic carcinoma and mesothelioma. We report the case of a 49-year-old male patient with primary pleural angiosarcoma, who presented with initial hemothorax, followed by a rapid progress to an inoperable status.

Molecular analysis of the effects of Piroxicam and Cisplatin on mesothelioma cells growth and viability

Science.gov (United States)

Verdina, Alessandra; Cardillo, Irene; Nebbioso, Angela; Galati, Rossella; Menegozzo, Simona; Altucci, Lucia; Sacchi, Ada; Baldi, Alfonso

2008-01-01

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been proposed for prevention and treatment of a variety of human cancers. Piroxicam, in particular, has been recently shown to exert significant anti-tumoral activity in combination with cisplatin (CDDP) on mesothelioma cells. However, the mechanisms through which NSAIDs regulate the cell cycle as well as the signal pathways involved in the growth inhibition, remain unclear. In the present study, using two mesothelioma cell lines, MSTO-211H and NCI-H2452, we have investigated the influence of piroxicam alone and in association with CDDP on proliferation, cell cycle regulation and apoptosis. In both cell lines a significant effect on cell growth inhibition, respect to the control, was observed with all the drugs tested. Moreover, treatment with piroxicam or CDDP alone altered the cell cycle phase distribution as well as the expression of some cell cycle regulatory proteins in both cell lines. These effects were increased, even if in a not completely overlapping manner, after treatment with the association of piroxicam and CDDP. In particular, the two drugs in NCI cell line had a synergistic effect on apoptosis, probably through activation of caspase 8 and caspase 9, while the most evident targets among the cell cycle regulators were cyclin D1 and p21waf1. These results suggest that the association of piroxicam and CDDP specifically triggers cell cycle regulation and apoptosis in different mesothelioma cell lines and may hold promise in the treatment of mesothelioma. PMID:18498639

Pleural Intensity-Modulated Radiotherapy for Malignant Pleural Mesothelioma

International Nuclear Information System (INIS)

Rosenzweig, Kenneth E.; Zauderer, Marjorie G.; Laser, Benjamin; Krug, Lee M.; Yorke, Ellen; Sima, Camelia S.; Rimner, Andreas; Flores, Raja; Rusch, Valerie

2012-01-01

Purpose: In patients with malignant pleural mesothelioma who are unable to undergo pneumonectomy, it is difficult to deliver tumoricidal radiation doses to the pleura without significant toxicity. We have implemented a technique of using intensity-modulated radiotherapy (IMRT) to treat these patients, and we report the feasibility and toxicity of this approach. Methods and Materials: Between 2005 and 2010, 36 patients with malignant pleural mesothelioma and two intact lungs (i.e., no previous pneumonectomy) were treated with pleural IMRT to the hemithorax (median dose, 46.8 Gy; range, 41.4–50.4) at Memorial Sloan-Kettering Cancer Center. Results: Of the 36 patients, 56% had right-sided tumors. The histologic type was epithelial in 78%, sarcomatoid in 6%, and mixed in 17%, and 6% had Stage I, 28% had Stage II, 33% had Stage III, and 33% had Stage IV. Thirty-two patients (89%) received induction chemotherapy (mostly cisplatin and pemetrexed); 56% underwent pleurectomy/decortication before IMRT and 44% did not undergo resection. Of the 36 patients evaluable for acute toxicity, 7 (20%) had Grade 3 or worse pneumonitis (including 1 death) and 2 had Grade 3 fatigue. In 30 patients assessable for late toxicity, 5 had continuing Grade 3 pneumonitis. For patients treated with surgery, the 1- and 2-year survival rate was 75% and 53%, and the median survival was 26 months. For patients who did not undergo surgical resection, the 1- and 2-year survival rate was 69% and 28%, and the median survival was 17 months. Conclusions: Treating the intact lung with pleural IMRT in patients with malignant pleural mesothelioma is a safe and feasible treatment option with an acceptable rate of pneumonitis. Additionally, the survival rates were encouraging in our retrospective series, particularly for the patients who underwent pleurectomy/decortication. We have initiated a Phase II trial of induction chemotherapy with pemetrexed and cisplatin with or without pleurectomy

Pleural Intensity-Modulated Radiotherapy for Malignant Pleural Mesothelioma

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Rosenzweig, Kenneth E., E-mail: ken.rosenzweig@mountsinai.org [Department of Radiation Oncology, Mount Sinai Medical Center, New York, NY (United States); Zauderer, Marjorie G. [Department of Medicine, Thoracic Oncology Service, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Laser, Benjamin [Department of Radiation Oncology, Henry Ford Hospital, Detroit, MI (United States); Krug, Lee M. [Department of Medicine, Thoracic Oncology Service, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Yorke, Ellen [Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Sima, Camelia S. [Department of Epidemiology/Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Rimner, Andreas [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Flores, Raja [Department of Surgery, Mount Sinai Medical Center, New York, NY (United States); Rusch, Valerie [Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY (United States)

2012-07-15

Purpose: In patients with malignant pleural mesothelioma who are unable to undergo pneumonectomy, it is difficult to deliver tumoricidal radiation doses to the pleura without significant toxicity. We have implemented a technique of using intensity-modulated radiotherapy (IMRT) to treat these patients, and we report the feasibility and toxicity of this approach. Methods and Materials: Between 2005 and 2010, 36 patients with malignant pleural mesothelioma and two intact lungs (i.e., no previous pneumonectomy) were treated with pleural IMRT to the hemithorax (median dose, 46.8 Gy; range, 41.4-50.4) at Memorial Sloan-Kettering Cancer Center. Results: Of the 36 patients, 56% had right-sided tumors. The histologic type was epithelial in 78%, sarcomatoid in 6%, and mixed in 17%, and 6% had Stage I, 28% had Stage II, 33% had Stage III, and 33% had Stage IV. Thirty-two patients (89%) received induction chemotherapy (mostly cisplatin and pemetrexed); 56% underwent pleurectomy/decortication before IMRT and 44% did not undergo resection. Of the 36 patients evaluable for acute toxicity, 7 (20%) had Grade 3 or worse pneumonitis (including 1 death) and 2 had Grade 3 fatigue. In 30 patients assessable for late toxicity, 5 had continuing Grade 3 pneumonitis. For patients treated with surgery, the 1- and 2-year survival rate was 75% and 53%, and the median survival was 26 months. For patients who did not undergo surgical resection, the 1- and 2-year survival rate was 69% and 28%, and the median survival was 17 months. Conclusions: Treating the intact lung with pleural IMRT in patients with malignant pleural mesothelioma is a safe and feasible treatment option with an acceptable rate of pneumonitis. Additionally, the survival rates were encouraging in our retrospective series, particularly for the patients who underwent pleurectomy/decortication. We have initiated a Phase II trial of induction chemotherapy with pemetrexed and cisplatin with or without pleurectomy

Mesothelioma and thymic tumors: Treatment challenges in (outside) a network setting.

Science.gov (United States)

Imbimbo, Martina; Maury, Jean-Michel; Garassino, Marina; Girard, Nicolas

2018-02-02

The management of patients with mesothelioma and thymic malignancy requires continuous multidisciplinary expertise at any step of the disease. A dramatic improvement in our knowledge has occurred in the last few years, through the development of databases, translational research programs, and clinical trials. Access to innovative strategies represents a major challenge, as there is a lack of funding for clinical research in rare cancers and their rarity precludes the design of robust clinical trials that could lead to specific approval of drugs. In this context, patient-centered initiatives, such as the establishment of dedicated networks, are warranted. International societies, such as IMIG (International Mesothelioma Interest Group) and ITMIG (International Thymic Malignancy Interest Group) provide infrastructure for global collaboration, and there are many advantages to having strong regional groups working on the same issues. There may be regional differences in risk factors, susceptibility, management and outcomes. The ability to address questions both regionally as well as globally is ideal to develop a full understanding of mesothelioma and thymic malignancies. In Europe, through the integration of national networks with EURACAN, the collaboration with academic societies and international groups, the development of networks in thoracic oncology provides multiplex integration of clinical care and research, ultimately ensuring equal access to high quality care to all patients, with the opportunity of conducting high level clinical and translational research projects. Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

Glycosaminoglycan, computed tomography and gallium-67 scanning in malignant pleural mesothelioma

International Nuclear Information System (INIS)

Nakano, Takashi; Fujii, Junji; Yamakawa, Kiyohiro; Tamura, Shinsuke; Amuro, Yoshiki; Nabeshima, Kenji; Hada, Toshikazu; Higashino, Kazuya; Horai, Takeshi.

1985-01-01

Malignant pleural mesothelioma is an unusual disease, often difficult to diagnose. This paper describes the results of quantitative studies on glycosaminoglycan (GAG) in tumor tissues and the findings of chest computed tomography (CT) and gallium-67 scanning in 5 malignant pleural mesotheliomas. The total amount of GAG in tumor tissue was 2.3 to 17.0 times as high as that in adenocarcinoma of the lung. The amount of hyaluronic acid was 3.5 to 170 times higher than that in adenocarcinoma. Also, the amount of chondroitin sulfate increased 2.6 to 10.0 times, but there were no changes in dermatan sulfate and heparan sulfate contents in this neoplasm when compared with adenocarcinoma. The present study suggests that a marked increase of the total amount of GAG and elevation of either hyaluronic acid and chondroitin sulfate content or both is a characteristic abnormality in this neoplasm. In most cases, CT scan of the chest showed pleural effusion, irregular pleural tumorous thickening surrounding the whole lung surface and extension into the fissure. In 3 cases, tumorous lesions extending into the chest wall at the site of pleural biopsy could be visualized on CT. In the terminal stage, the thoracic cavity was occupied by tumor tissues. Gallium-67 scanning showed a diffusely increased radionuclide accumulation over the involved hemithorax with or without particular intensity in the periphery. Conversely, identification of these characteristic findings of CT and gallium-67 scanning indicates the possibility of malignant pleural mesothelioma. (author)

[Archives of "comprehensive approach on asbestos-related diseases" supported by the "special coordination funds for promoting science and technology (H18-1-3-3-1)"-- overview of group research project, care and specimen registration, cellular characteristics of mesothelioma and immunological effects of asbestos].

Science.gov (United States)

Otsuki, Takemi; Nakano, Takashi; Hasegawa, Seiki; Okada, Morihito; Tsujimura, Tohru; Sekido, Yoshitaka; Toyokuni, Shinya; Nishimoto, Hiroshi; Fukuoka, Kazuya; Tanaka, Fumihiro; Kumagai, Naoko; Maeda, Megumi; Nishimura, Yasumitsu

2011-05-01

The research project entitled "Comprehensive approach on asbestos-related diseases" supported by the "Special Coordination Funds for Promoting Science and Technology (H18-1-3-3-1)" began in 2006 and was completed at the end of the Japanese fiscal year of 2010. This project included four parts; (1) malignant mesothelioma (MM) cases and specimen registration, (2) development of procedures for the early diagnosis of MM, (3) commencement of clinical investigations including multimodal approaches, and (4) basic research comprising three components; (i) cellular and molecular characterization of mesothelioma cells, (ii) immunological effects of asbestos, and (iii) elucidation of asbestos-induced carcinogenesis using animal models. In this special issue of the Japanese Journal of Hygiene, we briefly introduce the achievements of our project. The second and third parts and the third component of the fourth part are described in other manuscripts written by Professors Fukuoka, Hasegawa, and Toyokuni. In this manuscript, we introduce a brief summary of the first part "MM cases and specimen registration", the first component of the fourth part "Cellular and molecular characterization of mesothelioma cells" and the second component of the fourth part "Immunological effects of asbestos". In addition, a previous special issue presented by the Study Group of Fibrous and Particulate Substances (SGFPS) (chaired by Professor Otsuki, Kawasaki Medical School, Japan) for the Japanese Society of Hygiene and published in Environmental Health and Preventive Medicine Volume 13, 2008, included reviews of the aforementioned first component of the fourth part of the project. Taken together, our project led medical investigations regarding asbestos and MM progress and contributed towards the care and examination of patients with asbestos-related diseases during these five years. Further investigations are required to facilitate the development of preventive measures and the cure of asbestos

Review on clinical trials of targeted treatments in malignant mesothelioma

DEFF Research Database (Denmark)

Jakobsen, Jan Nyrop; Sørensen, Jens Benn

2011-01-01

Malignant mesothelioma (MM) is an aggressive tumor of the serosal surfaces with a poor prognosis. Advances in the understanding of tumor biology have led to the development of several targeted treatments, which have been evaluated in clinical trials. This article is a comprehensive review of all...

Recovering missing mesothelioma deaths in death certificates using hospital records.

Science.gov (United States)

Santana, Vilma S; Algranti, Eduardo; Campos, Felipe; Cavalcante, Franciana; Salvi, Leonardo; Santos, Simone A; Inamine, Rosemeire N; Souza, William; Consonni, Dario

2018-04-02

In Brazil, underreporting of mesothelioma and cancer of the pleura (MCP) is suspected to be high. Records from death certificates (SIM) and hospital registers (SIH-SUS) can be combined to recover missing data but only anonymous databases are available. This study shows how common data can be used for linkage and as an assessment of accuracy. Mesothelioma (all sites, ICD-10 codes C45.0-C45.9) and cancer of the pleura (C38.4) were retrieved from both information systems and combined using a linkage algorithm. Accuracy was examined with non-anonymous databases, limited to the state of São Paulo. We found 775 cases in death certificates and 283 in hospital registers. The linkage matched 57 cases, all accurately paired. Three cases, 0.4% in SIM and 1.3% in SIH-SUS, could not be matched because of data inconsistencies. A computer linkage can recover MCP cases from hospital records not found in death certificates in Brazil. © 2018 Wiley Periodicals, Inc.

Malignant Mesothelioma of Spermatic Cord in an Elderly Man With a History of Asbestos Exposure.

Science.gov (United States)

D'Antonio, Antonio; Mastella, Federica; Colucci, Angelo; Silvestre, Gianmarco

2016-01-01

We report a case of malignant mesothelioma of the spermatic cord in 80-year-old man presented with retained testis, hydrocele, and right inguinal mass. The patient had a long history of asbestos exposure as a railway worker. The patient was submitted to inguinal radical orchiectomy. One year after surgery, the patient is alive without signs of disease. Malignant mesothelioma of spermatic cord is a very rare disease, but this diagnosis should be suspected in patient with a history of asbestos exposure. Copyright © 2015 Elsevier Inc. All rights reserved.

Retroperitoneal extension via the retrocrural space of malignant thymoma and malignant pleural mesothelioma. Retrospective evaluation by CT

Energy Technology Data Exchange (ETDEWEB)

Ohkawara, Kiyoshi; Furuse, Makoto; Mizutani, Yoshihide; Ohsawa, Tadashi; Fujii, Takeshi [Jichi Medical School, Minamikawachi, Tochigi (Japan)

1995-01-01

We reviewed CT findings of 31 patients with malignant thymoma and one patient with malignant pleural mesothelioma in our institution. Transdiaphragmatic extension into the retroperitoneum via the retrocrural space was observed in 10% of malignant thymomas. In the same way, this spread from chest to abdomen was demonstrated in the case of malignant pleural mesothelioma. CT is especially useful in assessing extent of these tumors and determining the optimal treatment plan. (author).

Retroperitoneal extension via the retrocrural space of malignant thymoma and malignant pleural mesothelioma. Retrospective evaluation by CT

International Nuclear Information System (INIS)

Ohkawara, Kiyoshi; Furuse, Makoto; Mizutani, Yoshihide; Ohsawa, Tadashi; Fujii, Takeshi

1995-01-01

We reviewed CT findings of 31 patients with malignant thymoma and one patient with malignant pleural mesothelioma in our institution. Transdiaphragmatic extension into the retroperitoneum via the retrocrural space was observed in 10% of malignant thymomas. In the same way, this spread from chest to abdomen was demonstrated in the case of malignant pleural mesothelioma. CT is especially useful in assessing extent of these tumors and determining the optimal treatment plan. (author)

BTS guideline for the investigation and management of malignant pleural mesothelioma.

Science.gov (United States)

Woolhouse, Ian; Bishop, Lesley; Darlison, Liz; de Fonseka, Duneesha; Edey, Anthony; Edwards, John; Faivre-Finn, Corinne; Fennell, Dean A; Holmes, Steve; Kerr, Keith M; Nakas, Apostolos; Peel, Tim; Rahman, Najib M; Slade, Mark; Steele, Jeremy; Tsim, Selina; Maskell, Nick A

2018-01-01

The full guideline for the investigation and management of malignant pleural mesothelioma is published in Thorax . The following is a summary of the recommendations and good practice points. The sections referred to in the summary refer to the full guideline.

Experimental results using 3-bromopyruvate in mesothelioma: in vitro and in vivo studies.

Science.gov (United States)

Icard, Philippe; Philippe, Icard; Zhang, Xiao-Dong; Xiao-Dong, Zhang; Lemoisson, Edwige; Edwige, Lemoisson; Louis, Marie-Hélène; Marie-Hélène, Louis; Allouche, Stéphane; Stéphane, Allouche; Lincet, Hubert; Hubert, Lincet; Poulain, Laurent; Laurent, Poulain

2012-02-01

Over many years we have taken advantage of the special metabolism of cancer cells involving an increased consumption of glucose associated with lactic acid production even in the presence of oxygen, a phenomenon referred to as the "Warburg effect", to counteract cancer cell growth. We have tested 3-bromopyruvate (3-BrPA), an inhibitor of pyruvate-associated reactions. Firstly, we tested this agent, in vitro, in two mesothelioma cell lines. Cellular response would appear to depend on the mode of administration (immediately or 24 h after seeding). Depending on the line, 3-BrPA induced a cytostatic or cytotoxic effect. This effect was accompanied by cell death induction even in cells highly refractory to cisplatin. Mitochondrial apoptotic death appeared to involve both lines; however, a different death pathway such as necrosis cannot be excluded. Interestingly, 3-BrPA leads to a diminution of the expression of the anti-apotptoic protein Mcl-1. We then tested 3-BrPA in vivo. Survival of nude mice bearing human mesothelioma was significantly prolonged (p < 0.0001). Toxicity and clinical studies should be performed to test 3- BrPA as local therapy for patients suffering from pleural or peritoneal mesothelioma. Association with cisplatin should be particularly considered.

Initiation-promotion skin carcinogenesis and immunological competence.

Science.gov (United States)

Curtis, G L; Stenbäck, F; Ryan, W L

1975-10-01

The immune competence of mice during initiation-promotion skin carcinogenesis was determined by skin allograft rejection and lymphocyte mitogenesis. The carcinogen 7, 12-dimethylbenzanthracene inhibited the cellular immune competence of mice while lymphocytes from croton oil treated mice had enhanced PWM response. Chlorphenesin, a stimulator of cellular immunity, was found to inhibit tumorigenesis in initiation-promotion skin carcinogenesis when injected during promotion.

Mechanisms of caffeine-induced inhibition of UVB carcinogenesis

Directory of Open Access Journals (Sweden)

Allan H Conney

2013-06-01

Full Text Available Sunlight-induced nonmelanoma skin cancer is the most prevalent cancer in the United States with more than 2 million cases per year. Several studies have shown an inhibitory effect of caffeine administration on UVB-induced skin cancer in mice, and these studies are paralleled by epidemiology studies that indicate an inhibitory effect of coffee drinking on nonmelanoma skin cancer in humans. Strikingly, decaffeinated coffee consumption had no such inhibitory effect.Mechanism studies indicate that caffeine has a sunscreen effect that inhibits UVB-induced formation of thymine dimers and sunburn lesions in the epidermis of mice. In addition, caffeine administration has a biological effect that enhances UVB-induced apoptosis thereby enhancing the elimination of damaged precancerous cells, and caffeine administration also enhances apoptosis in tumors. Caffeine administration enhances UVB-induced apoptosis by p53-dependent and p53-independent mechanisms. Exploration of the p53-independent effect indicated that caffeine administration enhanced UVB-induced apoptosis by inhibiting the UVB-induced increase in ATR-mediated formation of phospho-Chk1 (Ser345 and abolishing the UVB-induced decrease in cyclin B1 which resulted in caffeine-induced premature and lethal mitosis in mouse skin. In studies with cultured primary human keratinocytes, inhibition of ATR with siRNA against ATR inhibited Chk1 phosphorylation and enhanced UVB-induced apoptosis. Transgenic mice with decreased epidermal ATR function that were irradiated chronically with UVB had 69% fewer tumors at the end of the study compared with irradiated littermate controls with normal ATR function. These results, which indicate that genetic inhibition of ATR (like pharmacologic inhibition of ATR via caffeine inhibits UVB-induced carcinogenesis and supports the concept that ATR-mediated phosphorylation of Chk1 is an important target for caffeine’s inhibitory effect on UVB-induced carcinogenesis.

Isolated thoracic perfusion with chemofiltration for progressive malignant pleural mesothelioma

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Aigner KR

2017-06-01

Full Text Available Karl Reinhard Aigner, Emir Selak, Sabine Gailhofer Department of Surgical Oncology, Medias Klinikum, Burghausen, Germany Introduction: Therapy of malignant pleural mesothelioma and especially the adequate role of surgery in this context remain the subject of controversial discussions. Radical surgery in particular, which is associated with substantial morbidity, failed to translate into a definite survival advantage. We report on interim results of an ongoing Phase II study of regional chemotherapy in terms of isolated thoracic perfusion with chemofiltration (ITP-F.Patients and methods: Twenty-eight patients (25 male, 3 female, mean age 63.4 years with advanced pleural mesothelioma were included in this study. Isolation of the chest was achieved by insertion of a venous and arterial stop-flow balloon catheter via a femoral access. The aorta and inferior vena cava were blocked at the level of the diaphragm and the upper arms were blocked by pneumatic cuffs. Chemotherapy, consisting of 60 mg/m² cisplatin and 15 mg/m² mitoxantrone, was administered directly into the aorta. The isolated circuit was maintained for 15 minutes followed by ~45 minutes of chemofiltration with a hemoprocessor until 5 L of filtrate were reached. The endpoints of the study were overall survival and quality of life (QoL.Results: Out of 28 patients enrolled in the study, 5 had prior surgeries, 10 patients had systemic chemotherapy, and 5 patients additional irradiation. In all patients in restaging, clinical progress was noted. In all, 162 cycles were administered. Due to chemofiltration, toxicity was within tolerable limits, revealing World Health Organization grade I leucopenia and thrombocytopenia in 9 patients and mucositis grade I in 6 patients. The major surgical complication was inguinal lymphatic fistula in 40% of the cases. Gastrointestinal toxicity and/or neurotoxicity were never observed. One-year survival was 49%, 2-year and 3-year survival was 31%, and 5

Meat processing and colon carcinogenesis: cooked, nitrite-treated, and oxidized high-heme cured meat promotes mucin-depleted foci in rats

OpenAIRE

Santarelli, Raphaëlle L; Vendeuvre, Jean-Luc; Naud, Nathalie; Taché, Sylviane; Guéraud, Françoise; Viau, Michelle; Genot, Claude; Corpet, Denis E; Pierre, Fabrice H F

2010-01-01

International audience; Processed meat intake is associated with colorectal cancer risk, but no experimental study supports the epidemiologic evidence. To study the effect of meat processing on carcinogenesis promotion, we first did a 14-day study with 16 models of cured meat. Studied factors, in a 2 x 2 x 2 x 2 design, were muscle color (a proxy for heme level), processing temperature, added nitrite, and packaging. Fischer 344 rats were fed these 16 diets, and we evaluated fecal and urinary ...

Pulmonary asbestos body counts and electron probe analysis of asbestos body cores in patients with mesothelioma: a study of 25 cases

International Nuclear Information System (INIS)

Roggli, V.L.; McGavran, M.H.; Subach, J.; Sybers, H.D.; Greenberg, S.D.

1982-01-01

Malignant mesotheliomas of the pleura and peritoneum are well-recognized risks of asbestos exposure. We determined the asbestos body content of the lungs from 24 cases of malignant mesothelioma (19 pleural, five peritoneal) and compared such to the content of lungs from 50 consecutive adult autopsies and four cases of overt asbestosis using a Clorox-digestion concentration technique. The cores of 90 asbestos bodies were examined by energy dispersive x-ray analysis and compared with similar data from 120 standard asbestos fibers and 20 fiberglass fibers. The malignant mesothelioma patients had asbestos body counts intermediate between those of the general population and those of patients with asbestosis, although some of the mesothelioma cases overlapped with the general population. These latter cases often lacked an identifiable occupational exposure to asbestos. EDXA studies demonstrated an amphibole core in 88 of the 90 asbestos bodies (amosite or crocidolite in 80 of 88, anthophyllite or tremolite in eight of 88), and chrysotile in two instances

Tranexamic acid treatment of hemothorax in two patients with malignant mesothelioma

NARCIS (Netherlands)

de Boer, W. A.; Koolen, M. G.; Roos, C. M.; ten Cate, J. W.

1991-01-01

Patients with malignant mesothelioma may present with hemothorax. We used a combination of oral and intrapleural tranexamic acid to treat two patients with this severe complication. Initiation of treatment with this potent anti-fibrinolytic drug resulted in rapid reduction of bleeding and of

Update of predictions of mortality from pleural mesothelioma in the Netherlands

NARCIS (Netherlands)

O. Segura; A. Burdorf (Alex); C.W.N. Looman (Caspar)

2003-01-01

textabstractAIMS: To predict the expected number of pleural mesothelioma deaths in the Netherlands from 2000 to 2028 and to study the effect of main uncertainties in the modelling technique. METHODS: Through an age-period-cohort modelling technique, age specific mortality rates

Pulmonary toxicity following IMRT after extrapleural pneumonectomy for malignant pleural mesothelioma

DEFF Research Database (Denmark)

Kristensen, C.A.; Nottrup, T.J.; Berthelsen, A.K.

2009-01-01

BACKGROUND AND PURPOSE: The combination of chemotherapy, surgery, and radiotherapy has improved the prognosis for patients with malignant pleural mesothelioma (MPM). Intensity-modulated radiotherapy (IMRT) has allowed for an increase in dose to the pleural cavity and a reduction in radiation doses...

Polyneuropathy in a patient with malignant pleural mesothelioma: a paraneoplastic syndrome

DEFF Research Database (Denmark)

Bech, C.; Sørensen, Jens Benn

2008-01-01

Paraneoplastic syndromes have only been reported in malignant pleural mesothelioma (MPM) in a few cases. In this case, we describe a 57-year-old man with MPM who developed sensory-motor polyneuropathy 18 days after diagnosis. Thorough endocrinological, neurological, and paraclinical examinations...

Aberrant Pax-8 expression in well-differentiated papillary mesothelioma and malignant mesothelioma of the peritoneum: a clinicopathologic study.

Science.gov (United States)

Xing, Deyin; Banet, Natalie; Sharma, Rajni; Vang, Russell; Ronnett, Brigitte M; Illei, Peter B

2018-02-01

Serous ovarian neoplasms can overlap morphologically with peritoneal mesothelial proliferations, including well-differentiated papillary mesothelioma (WDPM) and malignant epithelioid mesothelioma (MM). Accurate histologic classification of these neoplasms is important for clinical management. The Pax-8 protein is commonly used for differentiating peritoneal MM from serous carcinoma, but the diagnostic value of Pax-8 for distinguishing WDPM from borderline or low-grade serous tumors is unknown. We used immunohistochemistry staining to assess Pax-8 expression in 33 WDPMs, 34 peritoneal MMs, 48 pleural MMs, 11 adenomatoid tumors, 5 peritoneal inclusion cysts, and 51 benign/reactive mesothelium specimens. Staining was noted in 20 WDPMs (61%), with 17 showing strong and diffuse nuclear staining and 3 patchy/focal staining. Calretinin was expressed in 33 cases (100%), whereas focal BerEP4 staining was noted in 2 of 29 cases (7%). In contrast, 4 peritoneal MM (12%) were Pax-8 positive (3 diffuse and 1 focal staining). All adenomatoid tumors and peritoneal inclusion cysts were negative for Pax-8. Of the 48 pleural MM cases, 2 (4%) showed focal weak to moderate nuclear labeling for Pax-8, and 2 cases (4%) of reactive mesothelium demonstrated focal and scattered Pax-8 staining. Pax-8 appears to be a useful marker for distinguishing MM from gynecologic malignancies but is not reliable for distinguishing WDPM from borderline or low-grade gynecologic lesions. Copyright © 2017 Elsevier Inc. All rights reserved.

Diarachidonoylphosphoethanolamine induces apoptosis of malignant pleural mesothelioma cells through a Trx/ASK1/p38 MAPK pathway

OpenAIRE

Ayako Tsuchiya; Yoshiko Kaku; Takashi Nakano; Tomoyuki Nishizaki

2015-01-01

1,2-Diarachidonoyl-sn-glycero-3-phosphoethanolamine (DAPE) induces both necrosis/necroptosis and apoptosis of NCI-H28 malignant pleural mesothelioma (MPM) cells. The present study was conducted to understand the mechanism for DAPE-induced apoptosis of NCI-H28 cells. DAPE induced caspase-independent apoptosis of NCI-H28 malignant pleural mesothelioma (MPM) cells, and the effect of DAPE was prevented by antioxidants or an inhibitor of NADPH oxidase (NOX). DAPE generated reactive oxygen species ...

Mesothelioma in Qingdao, PRC (2000 - 2007)

Energy Technology Data Exchange (ETDEWEB)

Frank, Arthur L [Drexel University School of Public Health, Philadelphia, PA 19102 (United States); Pang Zengchang; Zhang Yun [Qingdao Center for Disease Control and Prevention, Qingdao (China); Zhang Huaqiang, E-mail: alf13@drexel.ed [Qingdao Institute of Women' s and Children' s Health Care, Qingdao (China)

2009-02-01

The city of Qingdao, PRC has been the site of two asbestos product facilities that operated for almost fifty years, as well as a shipyard. Because of a new computerized data collection system for death certificates, almost all 48,000 yearly deaths from a population base of 7.5 million are now recorded with cause of death and {sup u}sual occupation{sup .} All mesothelioma deaths from 2000 through 2007 are reviewed and the unusual finding is that of a predominance of cases in females. The issues of competing causes of death and potential underreporting are discussed.

Malignant Peritoneal Mesothelioma Mimicking Ischemic Colitis

Directory of Open Access Journals (Sweden)

Yuusuke Mitsuka

2010-07-01

Full Text Available The prognosis of malignant peritoneal mesothelioma is extremely poor with a mean survival time of 12 months. The initial symptoms are poor and atypical. Because of its rare entity and little knowledge of its treatments, there are few reports of long-term survival. We encountered a very unique case with strong impression on radiological findings of malignant peritoneal methothelioma. We had misdiagnosed it because of the findings and because the time course was similar to that of ischemic colitis. The radiological findings on CT and enema disappeared within one week after antibiotic therapy.

Integration of a radiation biomarker into modeling of thyroid carcinogenesis and post-Chernobyl risk assessment.

Science.gov (United States)

Kaiser, Jan Christian; Meckbach, Reinhard; Eidemüller, Markus; Selmansberger, Martin; Unger, Kristian; Shpak, Viktor; Blettner, Maria; Zitzelsberger, Horst; Jacob, Peter

2016-12-01

Strong evidence for the statistical association between radiation exposure and disease has been produced for thyroid cancer by epidemiological studies after the Chernobyl accident. However, limitations of the epidemiological approach in order to explore health risks especially at low doses of radiation appear obvious. Statistical fluctuations due to small case numbers dominate the uncertainty of risk estimates. Molecular radiation markers have been searched extensively to separate radiation-induced cancer cases from sporadic cases. The overexpression of the CLIP2 gene is the most promising of these markers. It was found in the majority of papillary thyroid cancers (PTCs) from young patients included in the Chernobyl tissue bank. Motivated by the CLIP2 findings we propose a mechanistic model which describes PTC development as a sequence of rate-limiting events in two distinct paths of CLIP2-associated and multistage carcinogenesis. It integrates molecular measurements of the dichotomous CLIP2 marker from 141 patients into the epidemiological risk analysis for about 13 000 subjects from the Ukrainian-American cohort which were exposed below age 19 years and were put under enhanced medical surveillance since 1998. For the first time, a radiation risk has been estimated solely from marker measurements. Cross checking with epidemiological estimates and model validation suggests that CLIP2 is a marker of high precision. CLIP2 leaves an imprint in the epidemiological incidence data which is typical for a driver gene. With the mechanistic model, we explore the impact of radiation on the molecular landscape of PTC. The model constitutes a unique interface between molecular biology and radiation epidemiology. © The Author 2016. Published by Oxford University Press.

Analysis of current trends in United States mesothelioma incidence; Analyse des tendances actuelles de l'incidence du mesotheliome aux Etats-Unis

Energy Technology Data Exchange (ETDEWEB)

Price, B.

1998-03-01

The objectives of this study are to analyze the mesotheliomas incidence in the United States and to estimate the risk of mesothelioma on the whole life by generation, as also the annual number of cases expected for the next seventy years. (N.C.)

Novel computer-aided diagnosis of mesothelioma using nuclear structure of mesothelial cells in effusion cytology specimens

Science.gov (United States)

Tosun, Akif Burak; Yergiyev, Oleksandr; Kolouri, Soheil; Silverman, Jan F.; Rohde, Gustavo K.

2014-03-01

diagnostic standard is a pleural biopsy with subsequent histologic examination of the tissue demonstrating invasion by the tumor. The diagnostic tissue is obtained through thoracoscopy or open thoracotomy, both being highly invasive procedures. Thoracocenthesis, or removal of effusion fluid from the pleural space, is a far less invasive procedure that can provide material for cytological examination. However, it is insufficient to definitively confirm or exclude the diagnosis of malignant mesothelioma, since tissue invasion cannot be determined. In this study, we present a computerized method to detect and classify malignant mesothelioma based on the nuclear chromatin distribution from digital images of mesothelial cells in effusion cytology specimens. Our method aims at determining whether a set of nuclei belonging to a patient, obtained from effusion fluid images using image segmentation, is benign or malignant, and has a potential to eliminate the need for tissue biopsy. This method is performed by quantifying chromatin morphology of cells using the optimal transportation (Kantorovich-Wasserstein) metric in combination with the modified Fisher discriminant analysis, a k-nearest neighborhood classification, and a simple voting strategy. Our results show that we can classify the data of 10 different human cases with 100% accuracy after blind cross validation. We conclude that nuclear structure alone contains enough information to classify the malignant mesothelioma. We also conclude that the distribution of chromatin seems to be a discriminating feature between nuclei of benign and malignant mesothelioma cells.

A molecular targeting against nuclear factor-κB, as a chemotherapeutic approach for human malignant mesothelioma

International Nuclear Information System (INIS)

Nishikawa, Sho; Tanaka, Akane; Matsuda, Akira; Oida, Kumiko; Jang, Hyosun; Jung, Kyungsook; Amagai, Yosuke; Ahn, Ginae; Okamoto, Noriko; Ishizaka, Saori; Matsuda, Hiroshi

2014-01-01

Chronic inflammation due to the absorption of asbestos is an important cause of mesothelioma. Although the increased prevalence of mesothelioma is a serious problem, the development of effective chemotherapeutic agents remains incomplete. As the nuclear factor-κB (NF-κB) pathway contributes to malignant transformation of various types of cells, we explored NF-κB activity in three different pathological types of malignant mesothelioma cells, and evaluated the therapeutic potential of a recently reported NF-κB inhibitor, IMD-0354. NF-κB was constantly activated in MSTO-211H, NCI-H28, and NCI-H2052 cells, and the proliferation of these cell lines was inhibited by IMD-0354. D-type cyclins were effectively suppressed in mixed tissue type MSTO-211H, leading to cell cycle arrest at sub G 1 /G 1 phase. IMD-0354 reduced cyclin D3 in both epithelial tissue type NCI-H28 and sarcomatoid tissue type NCI-H2052. In a sphere formation assay, IMD-0354 effectively decreased the number and diameter of MSTO-211H spheres. Preincubation of MSTO-211H cells with IMD-0354 delayed tumor formation in transplanted immunodeficient mice. Furthermore, administration of IMD-0354 markedly rescued the survival rate of mice that received intrathoracic injections of MSTO-211H cells. These results indicate that a targeted drug against NF-κB might have therapeutic efficacy in the treatment of human malignant mesothelioma

The development and deployment of Common Data Elements for tissue banks for translational research in cancer – An emerging standard based approach for the Mesothelioma Virtual Tissue Bank

Directory of Open Access Journals (Sweden)

Farhat Ghada

2008-04-01

Full Text Available Abstract Background Recent advances in genomics, proteomics, and the increasing demands for biomarker validation studies have catalyzed changes in the landscape of cancer research, fueling the development of tissue banks for translational research. A result of this transformation is the need for sufficient quantities of clinically annotated and well-characterized biospecimens to support the growing needs of the cancer research community. Clinical annotation allows samples to be better matched to the research question at hand and ensures that experimental results are better understood and can be verified. To facilitate and standardize such annotation in bio-repositories, we have combined three accepted and complementary sets of data standards: the College of American Pathologists (CAP Cancer Checklists, the protocols recommended by the Association of Directors of Anatomic and Surgical Pathology (ADASP for pathology data, and the North American Association of Central Cancer Registry (NAACCR elements for epidemiology, therapy and follow-up data. Combining these approaches creates a set of International Standards Organization (ISO – compliant Common Data Elements (CDEs for the mesothelioma tissue banking initiative supported by the National Institute for Occupational Safety and Health (NIOSH of the Center for Disease Control and Prevention (CDC. Methods The purpose of the project is to develop a core set of data elements for annotating mesothelioma specimens, following standards established by the CAP checklist, ADASP cancer protocols, and the NAACCR elements. We have associated these elements with modeling architecture to enhance both syntactic and semantic interoperability. The system has a Java-based multi-tiered architecture based on Unified Modeling Language (UML. Results Common Data Elements were developed using controlled vocabulary, ontology and semantic modeling methodology. The CDEs for each case are of different types: demographic

[Malignant mesothelioma in Emilia-Romagna: incidence and asbestos exposure].

Science.gov (United States)

Mangone, Lucia; Romanelli, Antonio; Campari, Cinzia; Candela, Silvia

2002-01-01

This paper describes the activity, the sources of informations, methods and results of the "Emilia-Romagna Mesothelioma Registry" (ReM). The Registry started in 1996 and collects all cases of Malignant Mesothelioma (MM) occurring in Emilia-Romagna. 323 new cases (225 males and 98 females) have been detected during the period 1996-2001. Most cases (n = 286) concerned pleura. Other observed localizations were: peritoneum (n = 30), tunica vaginalis testis (n = 4) and pericardium (n = 3). Most of the cases were reported by the Institutes of Pathology and Occupational Health and by the Safety Services (respectively the 62% and the 18%). 87% of all the cases were histologically, 8% TC, 4% radiologically and only 1% clinically confirmed. The regional incidence rate (for 10(5) person-years, age standardized on the 1991 Italian population), has been estimated to be 1.98 in males and 0.88 in females. The highest rates were registered in Piacenza and Reggio Emilia province among men and Reggio Emilia and Ravenna province among women. 72% of cases have been classified as exposed to asbestos (64% occupationally and 8% as domestic/environmentally exposed).

The Intersection of HPV Epidemiology, Genomics and Mechanistic Studies of HPV-Mediated Carcinogenesis.

Science.gov (United States)

Mirabello, Lisa; Clarke, Megan A; Nelson, Chase W; Dean, Michael; Wentzensen, Nicolas; Yeager, Meredith; Cullen, Michael; Boland, Joseph F; Schiffman, Mark; Burk, Robert D

2018-02-13

Of the ~60 human papillomavirus (HPV) genotypes that infect the cervicovaginal epithelium, only 12-13 "high-risk" types are well-established as causing cervical cancer, with HPV16 accounting for over half of all cases worldwide. While HPV16 is the most important carcinogenic type, variants of HPV16 can differ in their carcinogenicity by 10-fold or more in epidemiologic studies. Strong genotype-phenotype associations embedded in the small 8-kb HPV16 genome motivate molecular studies to understand the underlying molecular mechanisms. Understanding the mechanisms of HPV genomic findings is complicated by the linkage of HPV genome variants. A panel of experts in various disciplines gathered on 21 November 2016 to discuss the interdisciplinary science of HPV oncogenesis. Here, we summarize the discussion of the complexity of the viral-host interaction and highlight important next steps for selected applied basic laboratory studies guided by epidemiological genomic findings.

A randomised controlled trial of intervention site radiotherapy in malignant pleural mesothelioma

International Nuclear Information System (INIS)

O'Rourke, Noelle; Garcia, Jose Curto; Paul, Jim; Lawless, Claire; McMenemin, Rhona; Hill, Jennifer

2007-01-01

Background and purpose: To assess the effectiveness of radiotherapy in preventing tumour seeding after chest drain or pleural biopsy in patients with malignant mesothelioma and to determine, if tract metastases appear, whether they are tender or troublesome to patients. Patients and methods: Patients with a histological diagnosis of pleural mesothelioma and an invasive procedure within the preceding 21 days were stratified by age, performance status and treatment centre. Randomisation was performed between immediate drain site radiotherapy 21 Gy in three fractions (XRT arm) or best supportive care (BSC) with follow-up to 12 months. Patients were asked to complete questionnaires on treatment toxicity and on symptoms from any tract metastases detected. Results: Sixty-one patients were recruited from two centres between 1998 and 2004; 56 men, 5 women, median age 70. 31 were allocated to drain site radiotherapy. Seven patients developed tract metastases associated with the drain site (four XRT arm, three BSC) and four developed metastases associated with subsequent procedures at other sites (three XRT, one BSC). Two patients each developed two tract metastases. Of the 12 metastases, nine overlay the previous drain site but three were adjacent to the site. No statistically significant difference was found in the risk of tract metastasis associated with the drain site between the arms (p = 0.748). Conclusions: Prophylactic drain site radiotherapy in malignant pleural mesothelioma does not reduce the incidence of tumour seeding by the margin indicated by previous studies

Tumor exosomes induce tunneling nanotubes in lipid raft-enriched regions of human mesothelioma cells

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Thayanithy, Venugopal [Department of Medicine, Division of Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, MN 55455 (United States); Babatunde, Victor [Moore Laboratory, Department of Cell Biology, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, NY 10021 (United States); Dickson, Elizabeth L. [Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of Minnesota, Minneapolis, MN 55455 (United States); Wong, Phillip [Department of Medicine, Division of Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, MN 55455 (United States); Oh, Sanghoon; Ke, Xu; Barlas, Afsar; Fujisawa, Sho; Romin, Yevgeniy [Molecular Cytology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021 (United States); Moreira, André L. [Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021 (United States); Downey, Robert J. [Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10021 (United States); Steer, Clifford J. [Departments of Medicine and Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, MN 55455 (United States); Subramanian, Subbaya [Department of Surgery, University of Minnesota, Minneapolis, MN 55455 (United States); Manova-Todorova, Katia [Molecular Cytology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021 (United States); Moore, Malcolm A.S. [Moore Laboratory, Department of Cell Biology, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, NY 10021 (United States); Lou, Emil, E-mail: emil-lou@umn.edu [Department of Medicine, Division of Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, MN 55455 (United States)

2014-04-15

Tunneling nanotubes (TnTs) are long, non-adherent, actin-based cellular extensions that act as conduits for transport of cellular cargo between connected cells. The mechanisms of nanotube formation and the effects of the tumor microenvironment and cellular signals on TnT formation are unknown. In the present study, we explored exosomes as potential mediators of TnT formation in mesothelioma and the potential relationship of lipid rafts to TnT formation. Mesothelioma cells co-cultured with exogenous mesothelioma-derived exosomes formed more TnTs than cells cultured without exosomes within 24–48 h; and this effect was most prominent in media conditions (low-serum, hyperglycemic medium) that support TnT formation (1.3–1.9-fold difference). Fluorescence and electron microscopy confirmed the purity of isolated exosomes and revealed that they localized predominantly at the base of and within TnTs, in addition to the extracellular environment. Time-lapse microscopic imaging demonstrated uptake of tumor exosomes by TnTs, which facilitated intercellular transfer of these exosomes between connected cells. Mesothelioma cells connected via TnTs were also significantly enriched for lipid rafts at nearly a 2-fold higher number compared with cells not connected by TnTs. Our findings provide supportive evidence of exosomes as potential chemotactic stimuli for TnT formation, and also lipid raft formation as a potential biomarker for TnT-forming cells. - Highlights: • Exosomes derived from malignant cells can stimulate an increased rate in the formation of tunneling nanotubes. • Tunneling nanotubes can serve as conduits for intercellular transfer of these exosomes. • Most notably, exosomes derived from benign mesothelial cells had no effect on nanotube formation. • Cells forming nanotubes were enriched in lipid rafts at a greater number compared with cells not forming nanotubes. • Our findings suggest causal and potentially synergistic association of exosomes and

Tumor exosomes induce tunneling nanotubes in lipid raft-enriched regions of human mesothelioma cells

International Nuclear Information System (INIS)

Thayanithy, Venugopal; Babatunde, Victor; Dickson, Elizabeth L.; Wong, Phillip; Oh, Sanghoon; Ke, Xu; Barlas, Afsar; Fujisawa, Sho; Romin, Yevgeniy; Moreira, André L.; Downey, Robert J.; Steer, Clifford J.; Subramanian, Subbaya; Manova-Todorova, Katia; Moore, Malcolm A.S.; Lou, Emil

2014-01-01

Tunneling nanotubes (TnTs) are long, non-adherent, actin-based cellular extensions that act as conduits for transport of cellular cargo between connected cells. The mechanisms of nanotube formation and the effects of the tumor microenvironment and cellular signals on TnT formation are unknown. In the present study, we explored exosomes as potential mediators of TnT formation in mesothelioma and the potential relationship of lipid rafts to TnT formation. Mesothelioma cells co-cultured with exogenous mesothelioma-derived exosomes formed more TnTs than cells cultured without exosomes within 24–48 h; and this effect was most prominent in media conditions (low-serum, hyperglycemic medium) that support TnT formation (1.3–1.9-fold difference). Fluorescence and electron microscopy confirmed the purity of isolated exosomes and revealed that they localized predominantly at the base of and within TnTs, in addition to the extracellular environment. Time-lapse microscopic imaging demonstrated uptake of tumor exosomes by TnTs, which facilitated intercellular transfer of these exosomes between connected cells. Mesothelioma cells connected via TnTs were also significantly enriched for lipid rafts at nearly a 2-fold higher number compared with cells not connected by TnTs. Our findings provide supportive evidence of exosomes as potential chemotactic stimuli for TnT formation, and also lipid raft formation as a potential biomarker for TnT-forming cells. - Highlights: • Exosomes derived from malignant cells can stimulate an increased rate in the formation of tunneling nanotubes. • Tunneling nanotubes can serve as conduits for intercellular transfer of these exosomes. • Most notably, exosomes derived from benign mesothelial cells had no effect on nanotube formation. • Cells forming nanotubes were enriched in lipid rafts at a greater number compared with cells not forming nanotubes. • Our findings suggest causal and potentially synergistic association of exosomes and

Carcinogenicity of multi-walled carbon nanotubes: challenging issue on hazard assessment.

Science.gov (United States)

Fukushima, Shoji; Kasai, Tatsuya; Umeda, Yumi; Ohnishi, Makoto; Sasaki, Toshiaki; Matsumoto, Michiharu

2018-01-25

This report reviews the carcinogenicity of multi-walled carbon nanotubes (MWCNTs) in experimental animals, concentrating on MWNT-7, a straight fibrous MWCNT. MWCNTs were administered to mice and rats by intraperitoneal injection, intrascrotal injection, subcutaneous injection, intratracheal instillation and inhalation. Intraperitoneal injection of MWNT-7 induced peritoneal mesothelioma in mice and rats. Intrascrotal injection induced peritoneal mesothelioma in rats. Intratracheal instillation of MWCNT-N (another straight fibrous MWCNT) induced both lung carcinoma and pleural mesothelioma in rats. In the whole body inhalation studies, in mice MWNT-7 promoted methylcholanthrene-initiated lung carcinogenesis. In rats, inhalation of MWNT-7 induced lung carcinoma and lung burdens of MWNT-7 increased with increasing concentration of airborne MWNT-7 and increasing duration of exposure. Straight, fibrous MWCNTs exerted carcinogenicity in experimental animals. Phagocytosis of MWCNT fibers by macrophages was very likely to be a principle factor in MWCNT lung carcinogenesis. Using no-observed-adverse-effect level-based approach, we calculated that the occupational exposure limit (OEL) of MWNT-7 for cancer protection is 0.15 μg/m 3 for a human worker. Further studies on the effects of the shape and size of MWCNT fibers and mode of action on the carcinogenicity are required.

CREST biorepository for translational studies on malignant mesothelioma, lung cancer and other respiratory tract diseases: Informatics infrastructure and standardized annotation.

Science.gov (United States)

Ugolini, Donatella; Neri, Monica; Bennati, Luca; Canessa, Pier Aldo; Casanova, Georgia; Lando, Cecilia; Leoncini, Giacomo; Marroni, Paola; Parodi, Barbara; Simonassi, Claudio; Bonassi, Stefano

2012-03-01

Advances in molecular epidemiology and translational research have led to the need for biospecimen collection. The Cancer of the Respiratory Tract (CREST) biorepository is concerned with pleural malignant mesothelioma (MM) and lung cancer (LC). The biorepository staff has collected demographic and epidemiological data directly from consenting subjects using a structured questionnaire, in agreement with The Public Population Project in Genomics (P(3)G). Clinical and follow-up data were collected. Sample data were also recorded. The architecture is based on a database designed with Microsoft Access. Data standardization was carried out to conform with established conventions or procedures. As from January 31, 2011, the overall number of recruited subjects was 1,857 (454 LC, 245 MM, 130 other cancers and 1,028 controls). Due to its infrastructure, CREST was able to join international projects, sharing samples and/or data with other research groups in the field. The data management system allows CREST to be involved, through a minimum data set, in the national project for the construction of the Italian network of Oncologic BioBanks (RIBBO), and in the infrastructure of a pan-European biobank network (BBMRI). The CREST biorepository is a valuable tool for translational studies on respiratory tract diseases, because of its simple and efficient infrastructure.

Unusual presentation of a late-onset recurrence of malignant peritoneal mesothelioma

NARCIS (Netherlands)

Wijnberge, Marije; Daniels, Lidewine; Cliteur, Vincent; Winkelhagen, Jasper

2017-01-01

A man aged 79 years with a history of malignant peritoneal mesothelioma presented 8 years after primary presentation with a suspected right-sided painful inguinal hernia and hydrocele, both present for 5 months. During surgery, however, the inguinal swelling appeared to be a tumour. Laboratory

The incidence of mesothelioma has not decreased for the last twenty ...

African Journals Online (AJOL)

Background: Malignant pleural Mesothelioma (MPM) is a very rarely encountered tumor in the normal population. Objectives: To investigate the variations in incidence of MPM in Southeast region of Turkey. Methods: We retrospectively investigated the data of 161 MPM patients who were diagnosed from January 2000 to ...

Emerging role of bacteria in oral carcinogenesis: a review with special reference to perio-pathogenic bacteria.

Science.gov (United States)

Perera, Manosha; Al-Hebshi, Nezar Noor; Speicher, David J; Perera, Irosha; Johnson, Newell W

2016-01-01

Oral cancer, primarily oral squamous cell carcinoma (OSCC), continues to be a major global health problem with high incidence and low survival rates. While the major risk factors for this malignancy, mostly lifestyle related, have been identified, around 15% of oral cancer cases remain unexplained. In light of evidence implicating bacteria in the aetiology of some cancer types, several epidemiological studies have been conducted in the last decade, employing methodologies ranging from traditional culture techniques to 16S rRNA metagenomics, to assess the possible role of bacteria in OSCC. While these studies have demonstrated differences in microbial composition between cancerous and healthy tissues, they have failed to agree on specific bacteria or patterns of oral microbial dysbiosis to implicate in OSCC. On the contrary, some oral taxa, particularly Porphyromonas gingivalis and Fusobacterium nucleatum, show strong oral carcinogenic potential in vitro and in animal studies. Bacteria are thought to contribute to oral carcinogenesis via inhibition of apoptosis, activation of cell proliferation, promotion of cellular invasion, induction of chronic inflammation, and production of carcinogens. This narrative review provides a critical analysis of and an update on the association between bacteria and oral carcinogenesis and the possible mechanisms underlying it.

Microcystic variant malignant mesothelioma presenting as a localized paraspinal mass

Directory of Open Access Journals (Sweden)

Hyang Mi Ko

2014-01-01

Full Text Available A 58-year-old man presented with productive cough and fever. Computed tomography (CT scan of the chest showed an upper right paraspinal mass. CT-guided fine-needle aspiration biopsy showed lobules of vacuolated cells against a background of myxoid material. The cells demonstrated moderate to severe nuclear atypia and occasional mitoses. Immunohistochemistry revealed tumor cells to be immunoreactive for calretinin, WT-1, D2-40, cytokeratin (CK 7, AE1/AE3, high molecular weight keratin, vimentin and epithelial membrane antigen, and negative for thyroid transcription factor-1, Ber-EP4, carcinoembryonic antigen, S100 protein, CK20, and CDX2. The combined morphologic and immunohistochemical findings confirmed the diagnosis of microcystic variant of localized malignant mesothelioma. The subsequent lung resection showed a pleural-based mass in the right upper lobe and confirmed the diagnosis. Awareness of the existence of unusual morphologic variants and localized forms of mesothelioma are necessary to avoid misdiagnosis of fine needle biopsy samples. Recognition of characteristic cytomorphologic features along with optimal use of panel of immunohistochemistry studies is crucial for making a specific diagnosis.

Radiation carcinogenesis in scid mice

Energy Technology Data Exchange (ETDEWEB)

Ishii, Hiroko; Nishimura, Mayumi; Kobayashi, Shigeru; Tsuji, Hideo; Shimada, Yoshiya; Ogiu, Toshiaki [National Inst. of Radiological Sciences, Chiba (Japan); Suzuki, Fumio; Sado, Toshihiko

1999-06-01

Scid mice which have the defect of DNA-dependent protein kinase catalitic subunit, exhibit the limited activities of repair from DNA double strand breaks, and are sensitive to ionizing radiation. In order to study the relationship between repair capacity for DNA double strand breaks and carcinogenesis, the effects of ionizing radiation were studied using scid homozygotes (scid/scid), scid heterozygotes (scid/+) and CB-17 (+/+) mice. Both the Scid bone marrow cells and fibroblast cell lines from Scid embryos were highly sensitivity to acute effects of ionizing radiation. Carcinogenesis experiments showed the high incidence of thymic lymphomas (80 to 90%) in 1 to 3 Gy {sup 137}Cs-{gamma}-ray-irradiated Scid mice. (author)

Diet, lifestyle, and molecular alterations that drive colorectal carcinogenesis

NARCIS (Netherlands)

Diergaarde, B.

2004-01-01

Environmental factors have been repeatedly implicated in the etiology of colorectal cancer, and much is known about the molecular events involved in colorectal carcinogenesis. The relationships between environmental risk factors and the molecular alterations that drive colorectal carcinogenesis are

The Intersection of HPV Epidemiology, Genomics and Mechanistic Studies of HPV-Mediated Carcinogenesis

Directory of Open Access Journals (Sweden)

Lisa Mirabello

2018-02-01

Full Text Available Of the ~60 human papillomavirus (HPV genotypes that infect the cervicovaginal epithelium, only 12–13 “high-risk” types are well-established as causing cervical cancer, with HPV16 accounting for over half of all cases worldwide. While HPV16 is the most important carcinogenic type, variants of HPV16 can differ in their carcinogenicity by 10-fold or more in epidemiologic studies. Strong genotype-phenotype associations embedded in the small 8-kb HPV16 genome motivate molecular studies to understand the underlying molecular mechanisms. Understanding the mechanisms of HPV genomic findings is complicated by the linkage of HPV genome variants. A panel of experts in various disciplines gathered on 21 November 2016 to discuss the interdisciplinary science of HPV oncogenesis. Here, we summarize the discussion of the complexity of the viral–host interaction and highlight important next steps for selected applied basic laboratory studies guided by epidemiological genomic findings.

Specific expression of human intelectin-1 in malignant pleural mesothelioma and gastrointestinal goblet cells.

Directory of Open Access Journals (Sweden)

Kota Washimi

Full Text Available Malignant pleural mesothelioma (MPM is a fatal tumor. It is often hard to discriminate MPM from metastatic tumors of other types because currently, there are no reliable immunopathological markers for MPM. MPM is differentially diagnosed by some immunohistochemical tests on pathology specimens. In the present study, we investigated the expression of intelectin-1, a new mesothelioma marker, in normal tissues in the whole body and in many cancers, including MPM, by immunohistochemical analysis. We found that in normal tissues, human intelectin-1 was mainly secreted from gastrointestinal goblet cells along with mucus into the intestinal lumen, and it was also expressed, to a lesser extent, in mesothelial cells and urinary epithelial cells. Eighty-eight percent of epithelioid-type MPMs expressed intelectin-1, whereas sarcomatoid-type MPMs, biphasic MPMs, and poorly differentiated MPMs were rarely positive for intelectin-1. Intelectin-1 was not expressed in other cancers, except in mucus-producing adenocarcinoma. These results suggest that intelectin-1 is a better marker for epithelioid-type MPM than other mesothelioma markers because of its specificity and the simplicity of pathological assessment. Pleural intelectin-1 could be a useful diagnostic marker for MPM with applications in histopathological identification of MPM.

[Relationship between asbestos exposure and malignant pleural mesothelioma: occurrence near the old Japanese naval shipyard].

Science.gov (United States)

Kishimoto, T

1994-12-01

Kure City, Hiroshima Prefecture, was the site of a Japanese naval shipyard before World War II, and commercial ships were built there after the War. Large amounts of asbestos were used in this area primarily for shipbuilding, from before the war to around 1975. Probably due to exposure to asbestos, the incidence of malignant pleural mesothelioma is high in this city. Of the 31 patients with this disease, 27 were men. Patients over 60 years of age constituted a high percentage of the total and 28 had a history of asbestos exposure: 12 in the Japanese naval shipyard and 12 in the commercial shipyards. The average period of asbestos exposure for these 28 patients was 20 years. Malignant pleural mesothelioma developed more than 40 years after the first exposure to asbestos. Many asbestos particles and fibers were detected in the lungs and tumors of these patients. Most of the asbestos fibers detected were crocidolites or amosites. Considering that the amount of asbestos used in Japanese has been higher than in any other country, the incidence of malignant pleural mesothelioma may be expected to increase in this country. Countermeasures are now advisable.

Epithelioid malignant mesothelioma of tunica vaginalis with deciduoid features: An unusual malignancy clinically masquerading an inguinal hernia

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Sharique Ahmed

2012-01-01

Full Text Available Paratesticular/scrotal and inguinal canal mass lesions in elderly patients may pose a diagnostic challenge to both the surgeon as well as the pathologist. In most cases, these represent hernial sacs with their contents, and true neoplasms like lipomas, rhabdomyosarcomas, and fibrous pseudotumors are infrequent. Malignant mesotheliomas arising from the tunica layers are rare cause of inguinal and paratesticular tumors. Herein, we report a case of an elderly patient who presented with an inguinal hernia which pathologically had features of deciduoid malignant mesothelioma.

Exposure to asbestos in patients with malignant mesothelioma in Iran

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Gholamreza Pouryaghoub

2014-05-01

Conclusion: The results of our study specified the jobs with high risks of exposure to asbestos and approved the relationship between the exposure to asbestos and the inci-dence of mesothelioma in Iran, according to researches in other countries. So the con-sumption of asbestos in Iran, like 20 other countries in the world is necessary to be banned.

International Analysis of Age-Specific Mortality Rates From Mesothelioma on the Basis of the International Classification of Diseases, 10th Revision

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Paolo Boffetta

2017-08-01

Full Text Available Past analyses of mortality data from mesothelioma relied on unspecific codes, such as pleural neoplasms. We calculated temporal trends in age-specific mortality rates in Canada, the United States, Japan, France, Germany, Italy, the Netherlands, Poland, the United Kingdom, and Australia on the basis of the 10th version of the International Classification of Diseases, which includes a specific code for mesothelioma. Older age groups showed an increase (in the United States, a weaker decrease during the study period, whereas in young age groups, there was a decrease (in Poland, a weaker increase, starting, however, from low rates. Results were consistent between men and women and between pleural and peritoneal mesothelioma, although a smaller number of events in women and for peritoneal mesothelioma resulted in less precise results. The results show the heterogeneous effect of the reduction of asbestos exposure on different age groups; decreasing mortality in young people reflects reduced exposure opportunity, and increasing mortality in the elderly shows the long-term effect of early exposures.

Mesothelioma and anti-Ma paraneoplastic syndrome; heterogeneity in immunogenic tumours increases.

Science.gov (United States)

Archer, Hilary Anne; Panopoulou, Aikaterini; Bhatt, Nidhi; Edey, Anthony James; Giffin, Nicola Jane

2014-02-01

We present a patient with opsoclonus and diffuse cerebellar signs who had an anti-Ma2 antibody-associated paraneoplastic syndrome secondary to a sarcomatoid mesothelioma. This case highlights the importance of early tumour detection, instigation of therapeutic measures, and the heterogeneity of underlying malignancies in neurological paraneoplastic syndromes.

Open access phone triage for veterans with suspected malignant pleural mesothelioma.

Science.gov (United States)

Siegert, Charles Jeff; Fisichella, Piero Marco; Moseley, Jennifer M; Shoni, Melina; Lebenthal, Abraham

2017-01-01

Phone triaging patients with suspected malignant pleural mesothelioma (MPM) within the Veterans Healthcare Administration (VHA) system offers a model for rapid, expert guided evaluation for patients with rare and treatable diseases within a national integrated healthcare system. To assess feasibility of national open access telephone triage using evidence-based treatment recommendations for patients with MPM, measure timelines of the triage and referral process and record the impact on "intent to treat" for patients using our service. A retrospective study. The main outcome measures were: (1) ability to perform long distance phone triage, (2) to assess the speed of access to a mesothelioma surgical specialist for patients throughout the entire VHA, and (3) to determine if access to a specialist would alter the plan of care. Sixty veterans were screened by our phone triage program, 38 traveled an average of 997 miles to VA Boston Healthcare system. On average, 14 d elapsed from initial phone contact until the patient was physically evaluated in our general thoracic clinic in Boston. The treatment plan was altered for 71% of patients evaluated at VA Boston Healthcare system based on 2012 International Mesothelioma Interest Group guidelines. Our initial experience demonstrates that in-network centralized care for Veterans with MPM is feasible within the VHA. National open access phone triage improves access to expert surgical advice and can be delivered in a timely manner for Veterans using our service. Guideline-based treatment recommendations ("intent to treat") changed the therapeutic course for the majority of patients who used our service. Copyright © 2016 Elsevier Inc. All rights reserved.

Pathology analysis for mesothelioma study in the United Kingdom: Current practice and historical development.

Science.gov (United States)

Case, B W

2016-01-01

Following up on the largest case-control study of malignant mesothelioma yet performed, investigators at the London School of Hygiene and Tropical Medicine assessed 1732 male and 670 female cases as of May 2013. Epidemiological findings of a subset of these were published previously, excluding patients who died or who refused to be interviewed. Pathology reports were collected for subjects, including those both eligible and ineligible for epidemiology study based on vital status. The current investigation examined 860 cases having pathology reports available. Sixty-one cases were diagnosed using cytology only, often with equivocal diagnoses, while 799 reported at least a biopsy of the tumor. Of these, 748 had pathology sufficiently detailed for evaluation. These reports were examined for basis of diagnosis, differences between study cases and ineligible cases, pathology characteristics, and immunohistochemical and other tests used. The most prominent subtype was epithelioid (64% of study cases but only 49% of ineligible cases). Biphasic subtype was present in 10% of study cases and 16% of those ineligible. Sarcomatoid subtype was present in 7% of study cases and 19% of ineligible cases, most of whom died. Twelve percent of study cases displayed no specified subtype, versus 7% of ineligible cases. Of recorded immunohistochemical stains specific for mesothelial cell origin, calretinin (95%) and CK 5/6 or CK5 alone (84%) were by far the most common. Calretinin and CK 5/6 or CK 5 alone were also most sensitive and positive in 92% of cases presenting with surgical pathology report. Ninety percent of cases had at least one immunohistochemical marker for possible lung carcinoma applied, with BER-Ep4 and TTF-1 the most frequent at 68% and CEA at 58%. TTF-1 and CEA were positive in 1% or less of cases. Patterns of use and positive and negative results for each of these as well as other immunohistochemical stains are presented and discussed, along with a brief historical

Malignant paratesticular mesothelioma

Directory of Open Access Journals (Sweden)

Leonardo Gomes da Fonseca

2014-03-01

Full Text Available Mesothelioma of the tunica vaginalis testis (MTVT is a rare tumor that usually affects patients after the sixth decade of life. Exposure to asbestos is a known risk factor. Enlargement of the scrotal volume is the most common initial clinical manifestation, and about 15% of cases present metastasis at diagnosis. The treatment relies on surgical resection while the role of adjuvant chemotherapy and radiotherapy remains unclear. The prognosis for patients is generally poor, with a lethal outcome in 30% over a 24-month period. The authors report a case of a 62-year-old patient with the diagnosis of MTVT without a history of asbestos exposure. After surgical treatment, metastatic disease ensued. Chemotherapy was initiated, but could not be continued due to marked and fast clinical deterioration. The authors call attention to the difficulty of early diagnosis of MTVT due to a nonspecific clinical picture, the lack of action by the patient when the scrotal enlargement was first noticed, and the lack of tumor markers. Delayed diagnosis is definitely related to unfavorable prognosis.

A phase II study of gemcitabine in patients with malignant pleural mesothelioma

NARCIS (Netherlands)

van Meerbeeck, JP; Bass, P; Debruyne, C; Groen, HJ; Manegold, C; Ardizzoni, A; Gridelli, C; van Marck, EA; Lentz, M; Giaccone, G

1999-01-01

BACKGROUND, Gemcitabine has shown activity in patients with less chemosensitive solid tumors. Phase II screening of novel drugs is an accepted method with which to investigate new therapies in malignant mesothelioma. The European Organization for Research and Treatment of Cancer-Lung Cancer

Diagnostic importance of US and TC in peritoneal mesothelioma. A case report

Energy Technology Data Exchange (ETDEWEB)

Bighi, S; Lupi, L; Limone, G L

1986-01-01

Peritoneal mesothelioma is a highly malignant neoplasm rarely occuring; its incidence is in US less than 1 case per million per year. A case is here described and the importance of US and CT in obtaining a correct diagnosis is stressed out.

Mushroom Ganoderma lucidum Prevents Colitis-Associated Carcinogenesis in Mice

Science.gov (United States)

Sliva, Daniel; Loganathan, Jagadish; Jiang, Jiahua; Jedinak, Andrej; Lamb, John G.; Terry, Colin; Baldridge, Lee Ann; Adamec, Jiri; Sandusky, George E.; Dudhgaonkar, Shailesh

2012-01-01

Background Epidemiological studies suggest that mushroom intake is inversely correlated with gastric, gastrointestinal and breast cancers. We have recently demonstrated anticancer and anti-inflammatory activity of triterpene extract isolated from mushroom Ganoderma lucidum (GLT). The aim of the present study was to evaluate whether GLT prevents colitis-associated carcinogenesis in mice. Methods/Principal Findings Colon carcinogenesis was induced by the food-borne carcinogen (2-Amino-1-methyl-6-phenylimidazol[4,5-b]pyridine [PhIP]) and inflammation (dextran sodium sulfate [DSS]) in mice. Mice were treated with 0, 100, 300 and 500 mg GLT/kg of body weight 3 times per week for 4 months. Cell proliferation, expression of cyclin D1 and COX-2 and macrophage infiltration was assessed by immunohistochemistry. The effect of GLT on XRE/AhR, PXR and rPXR was evaluated by the reporter gene assays. Expression of metabolizing enzymes CYP1A2, CYP3A1 and CYP3A4 in colon tissue was determined by immunohistochemistry. GLT treatment significantly suppressed focal hyperplasia, aberrant crypt foci (ACF) formation and tumor formation in mice exposed to PhIP/DSS. The anti-proliferative effects of GLT were further confirmed by the decreased staining with Ki-67 in colon tissues. PhIP/DSS-induced colon inflammation was demonstrated by the significant shortening of the large intestine and macrophage infiltrations, whereas GLT treatment prevented the shortening of colon lengths, and reduced infiltration of macrophages in colon tissue. GLT treatment also significantly down-regulated PhIP/DSS-dependent expression of cyclin D1, COX-2, CYP1A2 and CYP3A4 in colon tissue. Conclusions Our data suggest that GLT could be considered as an alternative dietary approach for the prevention of colitis-associated cancer. PMID:23118901

18F-Fluorodeoxyglucose PET/CT and dynamic contrast-enhanced MRI as imaging biomarkers in malignant pleural mesothelioma

OpenAIRE

Hall, D. O.; Hooper, C. E.; Searle, J.; Darby, M.; White, P.; Harvey, J. E.; Braybrooke, J. P.; Maskell, N. A.; Masani, V.; Lyburn, I. D.

2018-01-01

Purpose\\ud \\ud The purpose of this study was to compare the use of fluorine-18-fluorodeoxyglucose (18F-FDG) PET with computed tomography (CT) and dynamic contrast-enhanced (DCE) MRI to predict prognosis and monitor treatment in malignant pleural mesothelioma.\\ud \\ud Patients and methods\\ud \\ud 18F-FDG PET/CT and DCE-MRI studies carried out as part of the South West Area Mesothelioma Pemetrexed trial were used. 18F-FDG PET/CT and DCE-MRI studies were carried out before treatment, and after two...

Multicystic mesothelioma of the peritoneum : a case report

Energy Technology Data Exchange (ETDEWEB)

Lee, Chang Dae; Park, Jeong Hee; Chun, Hye Jeong; Lim, Jong Nam; Seong, Mu Kyung; Yun, Sang Ae [Konkuk univ. College of Medicine, Seoul (Korea, Republic of)

1996-04-01

We report a case of multicystic mesothelioma in the visceral peritoneum anterior of the ascending colon. A 39-year-old female patient visited hospital with a palpable tender mass in the right flank. An ultrasonogram showed multiple cystic mass lesions in the right flank and CT scan showed a multicystic rative mass with enhancing wall and septum in front of the ascending colon. The patient underwent explolaparotomy and the mass, which in pathology turned out to be a benign multicystic masothelioma, was removed.

What is the role of a specialist regional mesothelioma multidisciplinary team meeting? A service evaluation of one tertiary referral centre in the UK.

Science.gov (United States)

Bibby, Anna C; Williams, Katie; Smith, Sarah; Bhatt, Nidhi; Maskell, Nick A

2016-09-08

Multidisciplinary team meetings are standard care for cancer in the UK and Europe. Professional bodies recommend that mesothelioma cases should be discussed at specialist multidisciplinary team meetings. However, no evidence exists exploring the role of the specialist mesothelioma multidisciplinary team meeting. To evaluate the clinical activity of 1 specialist mesothelioma multidisciplinary team meeting and to determine how often a definitive diagnosis was made, whether the core requirements of the meeting were met and whether there was any associated benefit or detriment. A service evaluation using routinely collected data from 1 specialist mesothelioma multidisciplinary team meeting in a tertiary referral hospital in the South-West of England. All cases discussed between 1/1/2014 and 31/12/2015. The primary outcome measure was whether a definitive diagnosis was made. Secondary outcomes included whether treatment advice was offered, information on clinical trials provided or further investigations suggested. Additional benefits of the multidisciplinary team meeting and time taken from referral to outcome were also collected. A definitive diagnosis was reached in 171 of 210 cases discussed (81%). Mesothelioma was diagnosed in 153/210 (73%). Treatment advice was provided for 127 of 171 diagnostic cases (74%) and further investigations suggested for all 35 non-diagnostic cases. 86/210 cases (41%) were invited to participate in a trial, of whom 43/86 (50%) subsequently enrolled. Additional benefits included the avoidance of postmortem examination if the coroner was satisfied with the multidisciplinary team decision. The overall process from referral to outcome dispatch was specialist mesothelioma multidisciplinary team meeting was effective at making diagnoses and providing recommendations for further investigations or treatment. The core requirements of a specialist mesothelioma multidisciplinary team meeting were met. The process was timely, with most outcomes

Cisplatin and vinorelbine first-line chemotherapy in non-resectable malignant pleural mesothelioma

DEFF Research Database (Denmark)

Frank, H.; Palshof, T.; Sørensen, Jens Benn

2008-01-01

The aim was to evaluate the activity of cisplatin and vinorelbine in previously untreated, inoperable patients having histologically verified malignant pleural mesothelioma (MPM), normal organ function, and performance status 0-2. Treatment was vinorelbine 25 mg m(-2) i.v. weekly and cisplatin 100...

Ultraviolet radiation-induced carcinogenesis: mechanisms and experimental models

International Nuclear Information System (INIS)

Ramasamy, Karthikeyan; Shanmugam, Mohana; Balupillai, Agilan; Govindhasamy, Kanimozhi; Gunaseelan, Srithar; Muthusamy, Ganesan; Robert, Beualah Mary; Nagarajan, Rajendra Prasad

2017-01-01

Ultraviolet radiation (UVR) is a very prominent environmental toxic agent. UVR has been implicated in the initiation and progression of photocarcinogenesis. UVR exposure elicits numerous cellular and molecular events which include the generation of inflammatory mediators, DNA damage, epigenetic modifications, and oxidative damages mediated activation of signaling pathways. UVR-initiated signal transduction pathways are believed to be responsible for tumor promotion effects. UVR-induced carcinogenic mechanism has been well studied using various animal and cellular models. Human skin-derived dermal fibroblasts, epidermal keratinocytes, and melanocytes served as excellent cellular model systems for the understanding of UVR-mediated carcinogenic events. Apart from this, scientists developed reconstituted three-dimensional normal human skin equivalent models for the study of UVR signaling pathways. Moreover, hairless mice such as SKH-1, devoid of Hr gene, served as a valuable model for experimental carcinogenesis. Scientists have also used transgenic mice and dorsal portion shaved Swiss albino mice for UVR carcinogenesis studies. In this review, we have discussed the current progress in the study on ultraviolet B (UVB)-mediated carcinogenesis and outlined appropriate experimental models for both ultraviolet A- and UVB-mediated carcinogenesis. (author)

Autologous Dendritic Cells Pulsed with Allogeneic Tumor Cell Lysate in Mesothelioma: From Mouse to Human.

Science.gov (United States)

Aerts, Joachim G J V; de Goeje, Pauline L; Cornelissen, Robin; Kaijen-Lambers, Margaretha E H; Bezemer, Koen; van der Leest, Cor H; Mahaweni, Niken M; Kunert, André; Eskens, Ferry A L M; Waasdorp, Cynthia; Braakman, Eric; van der Holt, Bronno; Vulto, Arnold G; Hendriks, Rudi W; Hegmans, Joost P J J; Hoogsteden, Henk C

2018-02-15

Purpose: Mesothelioma has been regarded as a nonimmunogenic tumor, which is also shown by the low response rates to treatments targeting the PD-1/PD-L1 axis. Previously, we demonstrated that autologous tumor lysate-pulsed dendritic cell (DC) immunotherapy increased T-cell response toward malignant mesothelioma. However, the use of autologous tumor material hampers implementation in large clinical trials, which might be overcome by using allogeneic tumor cell lines as tumor antigen source. The purpose of this study was to investigate whether allogeneic lysate-pulsed DC immunotherapy is effective in mice and safe in humans. Experimental Design: First, in two murine mesothelioma models, mice were treated with autologous DCs pulsed with either autologous or allogeneic tumor lysate or injected with PBS (negative control). Survival and tumor-directed T-cell responses of these mice were monitored. Results were taken forward in a first-in-human clinical trial, in which 9 patients were treated with 10, 25, or 50 million DCs per vaccination. DC vaccination consisted of autologous monocyte-derived DCs pulsed with tumor lysate from five mesothelioma cell lines. Results: In mice, allogeneic lysate-pulsed DC immunotherapy induced tumor-specific T cells and led to an increased survival, to a similar extent as DC immunotherapy with autologous tumor lysate. In the first-in-human clinical trial, no dose-limiting toxicities were established and radiographic responses were observed. Median PFS was 8.8 months [95% confidence interval (CI), 4.1-20.3] and median OS not reached (median follow-up = 22.8 months). Conclusions: DC immunotherapy with allogeneic tumor lysate is effective in mice and safe and feasible in humans. Clin Cancer Res; 24(4); 766-76. ©2017 AACR . ©2017 American Association for Cancer Research.

Heterogeneity in Immune Cell Content in Malignant Pleural Mesothelioma.

Science.gov (United States)

Minnema-Luiting, Jorien; Vroman, Heleen; Aerts, Joachim; Cornelissen, Robin

2018-03-30

Malignant pleural mesothelioma (MPM) is a highly aggressive cancer with limited therapy options and dismal prognosis. In recent years, the role of immune cells within the tumor microenvironment (TME) has become a major area of interest. In this review, we discuss the current knowledge of heterogeneity in immune cell content and checkpoint expression in MPM in relation to prognosis and prediction of treatment efficacy. Generally, immune-suppressive cells such as M2 macrophages, myeloid-derived suppressor cells and regulatory T cells are present within the TME, with extensive heterogeneity in cell numbers. Infiltration of effector cells such as cytotoxic T cells, natural killer cells and T helper cells is commonly found, also with substantial patient to patient heterogeneity. PD-L1 expression also varied greatly (16-65%). The infiltration of immune cells in tumor and associated stroma holds key prognostic and predictive implications. As such, there is a strong rationale for thoroughly mapping the TME to better target therapy in mesothelioma. Researchers should be aware of the extensive possibilities that exist for a tumor to evade the cytotoxic killing from the immune system. Therefore, no "one size fits all" treatment is likely to be found and focus should lie on the heterogeneity of the tumors and TME.

Cystic mesothelioma of the peritoneum.

Science.gov (United States)

Datta, R V; Paty, P B

1997-10-01

A 48-year-old man presented with a 3-month history of weight loss and progressive right lower quadrant abdominal pain. His medical history was notable for appendectomy at age 17. Ultrasonography and computed tomography of the abdomen revealed a 12 cm multicystic mass in the right paracolic space. At laparotomy a large serous cyst was found arising from the lateral wall of the cecum, and four additional small cysts were found on the small bowel mesentery, greater omentum, liver capsule, and right hemi-diaphragm. Complete removal of the tumor was accomplished by right colectomy with extraperitoneal dissection of the large cyst and simple excision of the four smaller cysts. Final pathology with immunohistochemical staining confirmed cystic mesothelioma of the peritoneum. In this report we discuss the diagnostic workup and treatment of this rare disease.

High RRM1 Expression Is Associated with Adverse Outcome in Patients with Cisplatin/Vinorelbine-treated Malignant Pleural Mesothelioma

DEFF Research Database (Denmark)

Zimling, Zarah Glad; Santoni-Rugiu, Eric; Bech, Cecilia

2015-01-01

BACKGROUND/AIM: A possible predictive impact of ribonucleotide-reductase subunit-1 (RRM1) on vinorelbine efficacy in non-small cell lung cancer (NSCLC) has been previously reported. The present study aimed to further explore this finding in malignant pleural mesothelioma (MPM). MATERIALS AND METH......BACKGROUND/AIM: A possible predictive impact of ribonucleotide-reductase subunit-1 (RRM1) on vinorelbine efficacy in non-small cell lung cancer (NSCLC) has been previously reported. The present study aimed to further explore this finding in malignant pleural mesothelioma (MPM). MATERIALS...

Benign Cystic Mesothelioma Misdiagnosed as Peritoneal Carcinomatosis

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Hyun Deok Shin

2016-04-01

Full Text Available Benign cystic mesothelioma (BCM is a rare benign disease that forms multicystic masses in the abdomen, pelvis, and retroperitoneum. It occurs predominantly in young to middle-aged women. The majority of cases were associated with a history of abdominal or pelvic operation, a history of endometriosis, and pelvic inflammatory disease. We present a unique case of BCM which is different to the previous cases. The patient was a 52-year-old man showing features of peritoneal carcinomatosis accompanied by ascites on abdominal computed tomography scans. We herein report a case of BCM misdiagnosed with peritoneal carcinomatosis.

Genetic alterations during radiation-induced carcinogenesis

International Nuclear Information System (INIS)

Kodama, Seiji

1995-01-01

This paper reviews radiation-induced genetic alterations and its carcinogenesis, focusing on the previous in vitro assay outcome. A colony formation assay using Syrian hamster fetal cells and focus formation assay using mouse C3H10T1/2 cells are currently available to find malignant transformation of cells. Such in vitro assays has proposed the hypothesis that radiation-induced carcinogenesis arises from at least two-stage processes; i.e., that an early step induced by irradiation plays an important role in promoting the potential to cause the subsequent mutation. A type of genetic instability induced by radiation results in a persistently elevated frequency of spontaneous mutations, so-called the phenomenon of delayed reproductive death. One possible mechanism by which genetic instability arises has been shown to be due to the development of abnormality in the gene group involved in the maintenance mechanism of genome stability. Another possibility has also been shown to stem from the loss of telomere (the extremities of a chromosome). The importance of search for radiation-induced genetic instability is emphasized in view of the elucidation of carcinogenesis. (N.K.)

Analysis about X-ray and CT images of pleural mesothelioma case of death. Examination about 2003 mesothelioma case of death 878 examples

International Nuclear Information System (INIS)

Kato, Katsuya; Kanazawa, Susumu; Kishimoto, Takumi; Genba, Kenichi; Aoe, Keisuke; Takeshima, Yukio; Inai, Kouki

2008-01-01

We investigated a clinical record and images for 212 examples in 878 examples diagnosed as mesothelioma in the death votes of 2003. CT images demonstrated pleural plaque to be obtained 42.0%, but in chest X-ray films only 9.8% demonstrated pleural plaque. For examination of CT findings of 117 examples, cases to present extensive irregular findings of pleura were 81.2%. Cases we made the ''no irregularity'' and ''slightness irregularity'' were 18.8%. (author)

Colorectal Carcinogenesis: Role of Oxidative Stress and Antioxidants.

Science.gov (United States)

Carini, Francesco; Mazzola, Margherita; Rappa, Francesca; Jurjus, Abdo; Geagea, Alice Gerges; Al Kattar, Sahar; Bou-Assi, Tarek; Jurjus, Rosalyn; Damiani, Provvidenza; Leone, Angelo; Tomasello, Giovanni

2017-09-01

One of the contributory causes of colon cancer is the negative effect of reactive oxygen species on DNA repair mechanisms. Currently, there is a growing support for the concept that oxidative stress may be an important etiological factor for carcinogenesis. The purpose of this review is to elucidate the role of oxidative stress in promoting colorectal carcinogenesis and to highlight the potential protective role of antioxidants. Several studies have documented the importance of antioxidants in countering oxidative stress and preventing colorectal carcinogenesis. However, there are conflicting data in the literature concerning its proper use in humans, since these studies did not yield definitive results and were performed mostly in vitro on cell populations, or in vivo in experimental animal models. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

The diagnostic value of immunohistochemically detected methylthioadenosine phosphorylase deficiency in malignant pleural mesotheliomas

DEFF Research Database (Denmark)

Zimling, Zarah Glad; Jørgensen, Anne; Santoni-Rugiu, Eric

2012-01-01

  Malignant pleural mesothelioma (MPM) often causes diagnostic difficulties for pathologists. We assessed whether loss of methylthioadenosine phosphorylase (MTAP), a key enzyme in the intracellular recycling of adenosine triphosphate (ATP) often deleted in MPM, could be detected with immunohistoc...

Identification of cancer stem cell markers in human malignant mesothelioma cells

Energy Technology Data Exchange (ETDEWEB)

Ghani, Farhana Ishrat; Yamazaki, Hiroto; Iwata, Satoshi; Okamoto, Toshihiro [Division of Clinical Immunology, Institute of Medical Science, University of Tokyo, Tokyo (Japan); Aoe, Keisuke; Okabe, Kazunori; Mimura, Yusuke [Departments of Medical Oncology, Yamaguchi-Ube Medical Center, Yamaguchi (Japan); Fujimoto, Nobukazu; Kishimoto, Takumi [Department of Respiratory Medicine, Okayama Rosai Hospital, Okayama (Japan); Yamada, Taketo [Department of Pathology, Keio University School of Medicine, Tokyo (Japan); Xu, C. Wilson [Drug Development Program, Nevada Cancer Institute, Las Vegas, NV (United States); Morimoto, Chikao, E-mail: morimoto@ims.u-tokyo.ac.jp [Division of Clinical Immunology, Institute of Medical Science, University of Tokyo, Tokyo (Japan); Drug Development Program, Nevada Cancer Institute, Las Vegas, NV (United States)

2011-01-14

Research highlights: {yields} We performed serial transplantation of surgical samples and established new cell lines of malignant mesothelioma. {yields} SP cell and expressions of CD9/CD24/CD26 were often observed in mesothelioma cell lines. {yields} SP and CD24{sup +} cells proliferated by asymmetric cell division-like manner. CD9{sup +} and CD24{sup +} cells have higher potential to generate spheroid colony. {yields} The marker-positive cells have clear tendency to generate larger tumors in mice. -- Abstract: Malignant mesothelioma (MM) is an aggressive and therapy-resistant neoplasm arising from the pleural mesothelial cells and usually associated with long-term asbestos exposure. Recent studies suggest that tumors contain cancer stem cells (CSCs) and their stem cell characteristics are thought to confer therapy-resistance. However, whether MM cell has any stem cell characteristics is not known. To understand the molecular basis of MM, we first performed serial transplantation of surgical samples into NOD/SCID mice and established new cell lines. Next, we performed marker analysis of the MM cell lines and found that many of them contain SP cells and expressed several putative CSC markers such as CD9, CD24, and CD26. Interestingly, expression of CD26 closely correlated with that of CD24 in some cases. Sorting and culture assay revealed that SP and CD24{sup +} cells proliferated by asymmetric cell division-like manner. In addition, CD9{sup +} and CD24{sup +} cells have higher potential to generate spheroid colony than negative cells in the stem cell medium. Moreover, these marker-positive cells have clear tendency to generate larger tumors in mouse transplantation assay. Taken together, our data suggest that SP, CD9, CD24, and CD26 are CSC markers of MM and could be used as novel therapeutic targets.

Measurement of mesothelioma on thoracic CT scans: A comparison of manual and computer-assisted techniques

International Nuclear Information System (INIS)

Armato, Samuel G. III; Oxnard, Geoffrey R.; MacMahon, Heber; Vogelzang, Nicholas J.; Kindler, Hedy L.; Kocherginsky, Masha; Starkey, Adam

2004-01-01

Our purpose in this study was to evaluate the variability of manual mesothelioma tumor thickness measurements in computed tomography (CT) scans and to assess the relative performance of six computerized measurement algorithms. The CT scans of 22 patients with malignant pleural mesothelioma were collected. In each scan, an initial observer identified up to three sites in each of three CT sections at which tumor thickness measurements were to be made. At each site, five observers manually measured tumor thickness through a computer interface. Three observers repeated these measurements during three separate sessions. Inter- and intra-observer variability in the manual measurement of tumor thickness was assessed. Six automated measurement algorithms were developed based on the geometric relationship between a specified measurement site and the automatically extracted lung regions. Computer-generated measurements were compared with manual measurements. The tumor thickness measurements of different observers were highly correlated (r≥0.99); however, the 95% limits of agreement for relative inter-observer difference spanned a range of 30%. Tumor thickness measurements generated by the computer algorithms also correlated highly with the average of observer measurements (r≥0.93). We have developed computerized techniques for the measurement of mesothelioma tumor thickness in CT scans. These techniques achieved varying levels of agreement with measurements made by human observers

Present status of theories and data analyses of mathematical models for carcinogenesis

International Nuclear Information System (INIS)

Kai, Michiaki; Kawaguchi, Isao

2007-01-01

Reviewed are the basic mathematical models (hazard functions), present trend of the model studies and that for radiation carcinogenesis. Hazard functions of carcinogenesis are described for multi-stage model and 2-event model related with cell dynamics. At present, the age distribution of cancer mortality is analyzed, relationship between mutation and carcinogenesis is discussed, and models for colorectal carcinogenesis are presented. As for radiation carcinogenesis, models of Armitage-Doll and of generalized MVK (Moolgavkar, Venson, Knudson, 1971-1990) by 2-stage clonal expansion have been applied to analysis of carcinogenesis in A-bomb survivors, workers in uranium mine (Rn exposure) and smoking doctors in UK and other cases, of which characteristics are discussed. In analyses of A-bomb survivors, models above are applied to solid tumors and leukemia to see the effect, if any, of stage, age of exposure, time progression etc. In miners and smokers, stages of the initiation, promotion and progression in carcinogenesis are discussed on the analyses. Others contain the analyses of workers in Canadian atomic power plant, and of patients who underwent the radiation therapy. Model analysis can help to understand the carcinogenic process in a quantitative aspect rather than to describe the process. (R.T.)

MRI, CT, and sonography in the preoperative evaluation of primary tumor extension in malignant pleural mesothelioma

International Nuclear Information System (INIS)

Layer, G.; Steudel, A.; Schild, H.H.; Schmitteckert, H.; Tuengerthal, S.; Schirren, J.; Kaick, G. van

1999-01-01

Purpose: Evaluation of the diagnostic value of the imaging modalities computed tomography (CT), magnetic resonance imaging (MRI), and thoracic sonography in the preoperative staging of malignant pleural mesothelioma. Results: The accuracy rates for CT were 85%, 98%, 83%, 73%, 71%, and 83%. MRI had an accuracy of 71%, 92%, 71%, 83%, 71%, and 96%, the thoracic ultrasound examinations of 76%, 63%, 51%, 60%, 71% and 89%. Conclusions: According to these results CT remains the method of choice in the preoperative assessment of T-stage of malignant pleural mesothelioma. MRI is of nearly the same value, but is not a must. Sonography may be supplementary method for operation planning. (orig./AJ) [de

Comparison of conventional and novel PET tracers for imaging mesothelioma in nude mice with subcutaneous and intrapleural xenografts

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Tsuji, Atsushi B.; Sogawa, Chizuru; Sugyo, Aya [Diagnostic Imaging Group, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555 (Japan); Sudo, Hitomi [Diagnostic Imaging Group, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555 (Japan); Department of Pathology and Oncology, Juntendo University School of Medicine, Tokyo, 113-8421 (Japan); Toyohara, Jun [Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, 206-8670 (Japan); Koizumi, Mitsuru [Diagnostic Imaging Group, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555 (Japan); Abe, Masaaki; Hino, Okio [Department of Pathology and Oncology, Juntendo University School of Medicine, Tokyo, 113-8421 (Japan); Harada, Yoshi-nobu; Furukawa, Takako [Diagnostic Imaging Group, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555 (Japan); Suzuki, Kazutoshi [Molecular Probe Group, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555 (Japan); Saga, Tsuneo [Diagnostic Imaging Group, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555 (Japan)], E-mail: saga@nirs.go.jp

2009-05-15

Introduction: Malignant mesothelioma is a highly aggressive tumor originating in the pleura, peritoneum and pericardium, and the prognosis of patients undergoing current treatment remains poor. To develop new therapies, it is important to have a noninvasive imaging system for evaluating the efficacy of such prospective treatments. We have established clinically relevant mouse models and evaluated conventional and novel positron emission tomography (PET) tracers. Methods: Epithelioid and sarcomatoid mesothelioma cells were inoculated subcutaneously and intrapleurally into nude mice. Biodistribution and PET imaging studies were conducted by injecting [{sup 18}F]fluoro-2-deoxy-D-glucose (FDG), 3'-[{sup 18}F]fluoro-3'-doxythymidine (FLT) or 4'-methyl-[{sup 11}C]thiothymidine (S-dThd) into the mouse models. In vitro cellular uptake of [{sup 14}C]FDG and [{sup 3}H]FLT and thymidine kinase 1 (TK{sub 1}) activity in both cell lines were measured. Expression of glucose transporter 1 (GLUT-1) and Ki-67 in xenografted tumors was evaluated by immunohistochemical staining. Results: In epithelioid mesothelioma models, biodistribution experiments showed that tumor uptake of [{sup 11}C]S-dThd was significantly higher than that of [{sup 18}F]FDG. On the other hand, in sarcomatoid models, [{sup 18}F]FDG showed significantly higher accumulation than the other two tracers. These differential uptakes of the three tracers were confirmed by PET imaging. The cellular uptake of [{sup 14}C]FDG and [{sup 3}H]FLT and TK{sub 1} activity in sarcomatoid cells were higher than those of epithelioid cells. GLUT-1 protein was strongly expressed in sarcomatoid but not in epithelioid tumor. We observed a high percentage of Ki-67-positive cells in both epithelioid and sarcomatoid tumors. Conclusions: We established nude mouse models of epithelioid and sarcomatoid subtypes of mesothelioma. PET tracers applicable for the evaluation of epithelioid and sarcomatoid mesothelioma would vary

Secretion of intelectin-1 from malignant pleural mesothelioma into pleural effusion.

Science.gov (United States)

Tsuji, S; Tsuura, Y; Morohoshi, T; Shinohara, T; Oshita, F; Yamada, K; Kameda, Y; Ohtsu, T; Nakamura, Y; Miyagi, Y

2010-08-10

Malignant pleural mesothelioma (MPM) is a rare but fatal tumour. Although most MPM patients show pleural effusion at even the early stage, it is hard to diagnose as MPM at the early stage because a sensitive and reliable diagnostic marker for MPM has not been found in plasma or pleural effusion. In this study, we investigated whether intelectin-1 was specifically contained in MPM cells and the pleural effusion of MPM patient by immunohistochemistry, western blotting, and enzyme-linked immunosorbent assay. Malignant pleural mesothelioma cell lines, but not lung adenocarcinoma cell lines, secreted intelectin-1. In immunohistochemistry, epithelioid-type MPMs, but neither pleura-invading lung adenocarcinomas nor reactive mesothelial cells near the lung adenocarcinomas, were stained with anti-intelectin antibodies. Pleural effusion of MPM patients contained a higher concentration of intelectin-1 than that of lung cancer patients. These results suggest that detection of intelectin-1 may be useful for a differential diagnosis of epithelioid-type MPM in immunohistochemistry and that a high concentration of intelectin-1 in pleural effusion can be used as a new marker for clinical diagnosis of MPM.

Effect of Dendrobium officinale Extraction on Gastric Carcinogenesis in Rats

Directory of Open Access Journals (Sweden)

Yi Zhao

2016-01-01

Full Text Available Dendrobium officinale (Tie Pi Shi Hu in Chinese has been widely used to treat different diseases in China. Anticancer effect is one of the important effects of Dendrobium officinale. However, the molecular mechanism of its anticancer effect remains unclear. In the present study, gastric carcinogenesis in rats was used to evaluate the effect of Dendrobium officinale on cancer, and its pharmacological mechanism was explored. Dendrobium officinale extracts (4.8 and 2.4 g/kg were orally administered to the rats of the gastric carcinogenesis model. Compared with the cancer model group, the high dose of Dendrobium officinale extracts significantly inhibited the rate of carcinogenesis. Further analysis revealed that Dendrobium officinale extracts could regulate the DNA damage, oxidative stress, and cytokines related with carcinogenesis and induce cell apoptosis in order to prevent gastric cancer.

The use of biologically based cancer risk models in radiation epidemiology

International Nuclear Information System (INIS)

Krewski, D.; Zielinski, J.M.; Hazelton, W.D.; Garner, M.J.; Moolgavkar, S.H.

2003-01-01

Biologically based risk projection models for radiation carcinogenesis seek to describe the fundamental biological processes involved in neoplastic transformation of somatic cells into malignant cancer cells. A validated biologically based model, whose parameters have a direct biological interpretation, can also be used to extrapolate cancer risks to different exposure conditions with some confidence. In this article, biologically based models for radiation carcinogenesis, including the two-stage clonal expansion (TSCE) model and its extensions, are reviewed. The biological and mathematical bases for such models are described, and the implications of key model parameters for cancer risk assessment examined. Specific applications of versions of the TSCE model to important epidemiologic datasets are discussed, including the Colorado uranium miners' cohort; a cohort of Chinese tin miners; the lifespan cohort of atomic bomb survivors in Hiroshima and Nagasaki; and a cohort of over 200,000 workers included in the National Dose Registry (NDR) of Canada. (author)

Oral Carcinogenesis and Oral Cancer Chemoprevention: A Review

OpenAIRE

Tanaka, Takuji; Tanaka, Mayu; Tanaka, Takahiro

2011-01-01

Oral cancer is one of the major global threats to public health. The development of oral cancer is a tobacco-related multistep and multifocal process involving field cancerization and carcinogenesis. The rationale for molecular-targeted prevention of oral cancer is promising. Biomarkers of genomic instability, including aneuploidy and allelic imbalance, are possible to measure the cancer risk of oral premalignancies. Understanding of the biology of oral carcinogenesis will yield important adv...

A review of the toxicology and epidemiology of wollastonite.

Science.gov (United States)

Maxim, L Daniel; McConnell, E E

2005-08-01

Wollastonite is a naturally occurring calcium silicate (CaSiO(3)) that is produced in both powder and fibrous forms. It is a valuable industrial mineral used in plastics, ceramics, metallurgical applications, paint, and friction products. For some applications wollastonite serves as an asbestos replacement. To varying degrees, wollastonite grades contain respirable particles/fibers, some of which have lengths and diameters that might be biologically active if deposited and retained in the lung. In this review we provide background information on wollastonite properties, markets, production and use, regulatory classification, and occupational exposure limits. We also summarize the available studies on the toxicology and epidemiology of wollastonite. We conclude that there is inadequate evidence for the carcinogenicity of wollastonite in animals and, based on strong evidence that wollastonite is not biopersistent, believe that a well-designed animal inhalation bioassay would have a negative result. The epidemiological evidence for wollastonite is limited, but does not suggest that workers are at significant risk of an increased incidence of pulmonary fibrosis, lung cancer, or mesothelioma. Morbidity studies have demonstrated a nonspecific increase in bronchitis and reduced lung function. It is prudent, however, to continue product stewardship efforts by wollastonite producers to control workplace exposures and to monitor scientific developments.

Clinical evaluation of circulating miR-548a-3p and -20a expression in malignant pleural mesothelioma patients.

Science.gov (United States)

Matboli, Marwa; Shafei, Ayman E; Azazy, Ahmed Em; Reda, Maged; El-Khazragy, Nashwa; Nagy, Ahmed Aly; Ali, Mahmoud A; Sobhi, Mohamed; Abdel-Rahman, Omar

2018-02-01

miRNAs may act as promising diagnostic and prognostic biomarkers of mesothelioma. This study integrates serum  miR-548a-3p and miR-20a expression based on in silico data analysis followed by clinical validation in malignant mesothelioma patients (malignant pleural mesothelioma [MPM]). Serum miR-548a-3p and  miR-20a level was assessed in the serum of patients with MPM, chronic asbestos exposure and healthy volunteers by quantitative real-time PCR. The expression of serum miR-548a-3p and  miR-20a was positive in 91.6 and 96.7% MPM patients, respectively. Both miRNAs were able to segregate between cases and controls. The sensitivity of the combined chosen serum miRNAs reached 100% in the diagnosis of MPM. The current work revealed that sera miR-548a-3p and miR-20a may serve as promising novel diagnostic tools for MPM.

Thalidomide versus active supportive care for maintenance in patients with malignant mesothelioma after first-line chemotherapy (NVALT 5): an open-label, multicentre, randomised phase 3 study

NARCIS (Netherlands)

Buikhuisen, Wieneke A.; Burgers, Jacobus A.; Vincent, Andrew D.; Korse, Catharina M.; van Klaveren, Rob J.; Schramel, Franz M. N. H.; Pavlakis, Nick; Nowak, Anna K.; Custers, Frank L. J.; Schouwink, J. Hugo; Gans, Steven J. M.; Groen, Harry J. M.; Strankinga, Wim F. M.; Baas, Paul

2013-01-01

Standard chemotherapy does not lead to long-term survival in patients with malignant pleural mesothelioma. Malignant pleural mesothelioma is strongly dependent on vasculature with high vessel counts and high concentrations of serum vascular growth factors. Thalidomide has shown antiangiogenic

Treatment of Malignant Pleural Mesothelioma: American Society of Clinical Oncology Clinical Practice Guideline.

Science.gov (United States)

Kindler, Hedy L; Ismaila, Nofisat; Armato, Samuel G; Bueno, Raphael; Hesdorffer, Mary; Jahan, Thierry; Jones, Clyde Michael; Miettinen, Markku; Pass, Harvey; Rimner, Andreas; Rusch, Valerie; Sterman, Daniel; Thomas, Anish; Hassan, Raffit

2018-05-01

Purpose To provide evidence-based recommendations to practicing physicians and others on the management of malignant pleural mesothelioma. Methods ASCO convened an Expert Panel of medical oncology, thoracic surgery, radiation oncology, pulmonary, pathology, imaging, and advocacy experts to conduct a literature search, which included systematic reviews, meta-analyses, randomized controlled trials, and prospective and retrospective comparative observational studies published from 1990 through 2017. Outcomes of interest included survival, disease-free or recurrence-free survival, and quality of life. Expert Panel members used available evidence and informal consensus to develop evidence-based guideline recommendations. Results The literature search identified 222 relevant studies to inform the evidence base for this guideline. Recommendations Evidence-based recommendations were developed for diagnosis, staging, chemotherapy, surgical cytoreduction, radiation therapy, and multimodality therapy in patients with malignant pleural mesothelioma. Additional information is available at www.asco.org/thoracic-cancer-guidelines and www.asco.org/guidelineswiki .

Air pollution and genomic instability: The role of particulate matter in lung carcinogenesis

International Nuclear Information System (INIS)

Santibáñez-Andrade, Miguel; Quezada-Maldonado, Ericka Marel; Osornio-Vargas, Álvaro; Sánchez-Pérez, Yesennia; García-Cuellar, Claudia M.

2017-01-01

In this review, we summarize and discuss the evidence regarding the interaction between air pollution, especially particulate matter (PM), and genomic instability. PM has been widely studied in the context of several diseases, and its role in lung carcinogenesis gained relevance due to an increase in cancer cases for which smoking does not seem to represent the main risk factor. According to epidemiological and toxicological evidence, PM acts as a carcinogenic factor in humans, inducing high rates of genomic alterations. Here, we discuss not only how PM is capable of inducing genomic instability during the carcinogenic process but also how our genetic background influences the response to the sources of damage. - Highlights: • Air pollution represents a worldwide problem with impact on human health. • Particulate matter (PM) has a recognized carcinogenic potential in humans. • Lung cancer susceptibility depends on gene-environment interactions. • Epidemiological and experimental evidence links PM exposure to genomic instability. • PM and genomic instability are co-dependent factors during cancer continuum. - We summarize the association between particulate matter (a component of air pollution) and genomic instability as well as discuss how new strategies to study the impact of air pollution on genomic instability and lung-cancer development could improve our understanding of the lung-cancer genome.

Pleural localized malignant mesothelioma mimicking a benign solitary fibrous tumor of the pleura on chest computed tomography: A case report

Energy Technology Data Exchange (ETDEWEB)

Park, Hwi Ryong; Chong, Se Min; Kim, Mi Kyung [Dept. of Radiology, (Korea, Republic of)

2017-06-15

Pleural malignant mesotheliomas arise from mesothelial cells in the pleura. They are characterized as diffuse or localized malignant mesotheliomas (LMM). Diffuse malignant mesotheliomas spread diffusely along pleural surfaces, while LMM are well-circumscribed nodular lesions with no gross or microscopic diffuse pleural spreading. Therefore, LMM can be radiologically confused with solitary fibrous tumors of the pleura (SFTP), which commonly presents as a solitary, well-demarcated peripheral mass abutting the pleural surface upon the completion of a computed tomography (CT). Therefore, this study reports on a 63-year-old female patient with a pathologically-proven LMM of the pleura, mimicking a benign SFTP upon having a chest CT. Although LMM is extremely rare, FDG PET/CT should be recommended for adequate tumor management in order to avoid misdiagnosing the tumor as a benign SFTP when an interfissural or pleural-based mass is seen on the chest CT.

Pleural localized malignant mesothelioma mimicking a benign solitary fibrous tumor of the pleura on chest computed tomography: A case report

International Nuclear Information System (INIS)

Park, Hwi Ryong; Chong, Se Min; Kim, Mi Kyung

2017-01-01

Pleural malignant mesotheliomas arise from mesothelial cells in the pleura. They are characterized as diffuse or localized malignant mesotheliomas (LMM). Diffuse malignant mesotheliomas spread diffusely along pleural surfaces, while LMM are well-circumscribed nodular lesions with no gross or microscopic diffuse pleural spreading. Therefore, LMM can be radiologically confused with solitary fibrous tumors of the pleura (SFTP), which commonly presents as a solitary, well-demarcated peripheral mass abutting the pleural surface upon the completion of a computed tomography (CT). Therefore, this study reports on a 63-year-old female patient with a pathologically-proven LMM of the pleura, mimicking a benign SFTP upon having a chest CT. Although LMM is extremely rare, FDG PET/CT should be recommended for adequate tumor management in order to avoid misdiagnosing the tumor as a benign SFTP when an interfissural or pleural-based mass is seen on the chest CT

[Value of immunocytochemistry in differential diagnosis of gastric adenocarcinoma, reactive mesothelial cells and malignant epithelial mesothelioma in metastatic effusion fluid].

Science.gov (United States)

Lyu, M; Cha, N; Zou, Y F; Leng, J H; Xu, L; Sun, Y; Hao, Y Y

2018-03-08

Objective: To investigate the diagnostic value of some antibodies in peritoneal fluid of patients with gastric cancer and malignant epithelioid mesothelioma in serous effusion. Methods: One hundred and eighty-two cases of serous effusion were collected at Jilin Cancer Hospital, from July 2012 to July 2016. The expression of GLUT1, CDX2, Villin, calretinin and WT1 was evaluated using SP immunocytochemical technique in peritoneal fluid samples collected from 98 patients with gastric cancer and 74 patients with reactive mesothelial cells. The expression of GLUT1, calretinin and WT1 was also evaluated in serous effusion from 10 patients with mesothelioma. Results: The sensitivity of GLUT1, CDX2 and Villin in adenocarcinoma cells was 91.8%(90/98), 68.4% (67/98) and 88.8%(87/98), respectively. The specificity was 95.9% (71/74), 100.0%(74/74) and 100.0% (74/74), respectively. The sensitivity of calretinin and WT1 for reactive mesothelium was 93.2% (69/74) and 79.7% (59/74), respectively. The specificity was 96.9% (95/98) and 100.0% (98/98), respectively. The sensitivity of GLUT1, calretinin and WT1 for mesothelioma was 9/10, 9/10 and 7/10. The reactivity of GLUT1, CDX2, Villin, calretinin and WT1 showed a significant difference ( P <0.01) between adenocarcinoma cells and reactive mesothelium. The reactivity of GLUT1 showed a significant difference ( P <0.01) between mesothelioma and reactive mesothelium. Conclusions: The optimal combination is a panel of GLUT1, CDX2, Villin, calretinin and WT1 for differential diagnosis between adenocarcinoma cells and reactive mesothelium in peritoneal fluid of patients with gastric cancer. Whereas GLUT1, calretinin and WT1 is the best for differential diagnosis between reactive mesothelium and mesothelioma in serous effusions.

Carcinogenesis. Genetics and circumstances

International Nuclear Information System (INIS)

Hino, Okio

2005-01-01

Described are the author's study and aspect concerning carcinogenesis and radiation carcinogenesis, where he thinks cancer is not automatic, has a process and takes time. For radiation carcinogenic studies, he has used a model of the rat with genetically determined kidney cancer which is highly radiosensitive. That is, mutation by the so-called 2nd-hit of the causal gene (tumor suppressing gene Tsc2) is studied in the animal where the 1st-hit has been done by retrotransposon insertion, with and without exposure to radiations (X-ray, heavy particle beam and cosmic ray) for elucidating the mutation spectrum of the causal gene, the carcinogenic target, for the ultimate aim to prevent human cancer. He discusses the drama-type molecular mechanisms leading to cancer, gene abnormality and disease crisis, discontinuity in continuity in cancer formation, and importance of the timely diagnosis and appropriate therapy, and concludes the present age is becoming such one as that the nature of cancer even if genetic can be controlled by circumstances like timely and appropriate intervention. (S.I.)

The development and characterization of a human mesothelioma in vitro 3D model to investigate immunotoxin therapy.

Directory of Open Access Journals (Sweden)

Xinran Xiang

2011-01-01

Full Text Available Tumor microenvironments present significant barriers to penetration by antibodies and immunoconjugates. Tumor microenvironments, however, are difficult to study in vitro. Cells cultured as monolayers exhibit less resistance to therapy than those grown in vivo and an alternative research model more representative of the in vivo tumor is more desirable. SS1P is an immunotoxin composed of the Fv portion of a mesothelin-specific antibody fused to a bacterial toxin that is presently undergoing clinical trials in mesothelioma.Here, we examined how the tumor microenvironment affects the penetration and killing activity of SS1P in a new three-dimensional (3D spheroid model cultured in vitro using the human mesothelioma cell line (NCI-H226 and two primary cell lines isolated from the ascites of malignant mesothelioma patients. Mesothelioma cells grown as monolayers or as spheroids expressed comparable levels of mesothelin; however, spheroids were at least 100 times less affected by SS1P. To understand this disparity in cytotoxicity, we made fluorescence-labeled SS1P molecules and used confocal microscopy to examine the time course of SS1P penetration within spheroids. The penetration was limited after 4 hours. Interestingly, we found a significant increase in the number of tight junctions in the core area of spheroids by electron microscopy. Expression of E-Cadherin, a protein involved in the assembly and sealing of tight junctions and highly expressed in malignant mesothelioma, was found significantly increased in spheroids as compared to monolayers. Moreover, we found that siRNA silencing and antibody inhibition targeting E-Cadherin could enhance SS1P immunotoxin therapy in vitro.This work is one of the first to investigate immunotoxins in 3D tumor spheroids in vitro. This initial description of an in vitro tumor model may offer a simple and more representative model of in vivo tumors and will allow for further investigations of the microenvironmental

Malignant pleural mesothelioma in a child

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Jed Brendan Scharf

2015-10-01

Full Text Available Malignant pleural mesothelioma (MPM is an aggressive malignancy that occurs extremely rarely in the pediatric population. It carries a dismal prognosis. Adult studies are often used to guide therapy in the pediatric population, as a limited number of case reports form the body of pediatric literature. Herein, we document the course and treatment of an 8-year old male diagnosed with MPM. The diagnosis came after he presented to his family physician with dyspnea and was found to have a large right-sided chest mass on subsequent imaging. Through an initial right pneumonectomy and subsequent chest wall excision, followed by chemotherapy with Pemetrexed and Cisplatin he remains virtually disease free today, almost 2 years following surgery.

Pegylated liposomal doxorubicin in malignant pleural mesothelioma: a possible guardian for long-term survival

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Zarogoulidis P

2012-09-01

Full Text Available Paul Zarogoulidis,1,2 Maria Mavroudi,1 Konstantinos Porpodis,1 Kalliopi Domvri,1 Antonios Sakkas,3 Nikolaos Machairiotis,1 Aikaterini Stylianaki,1 Anastasios Tsiotsios,1 Nikolaos Courcoutsakis,4 Konstantinos Zarogoulidis11Pulmonary Department-Oncology Unit, “G Papanikolaou” General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece; 2Pulmonary Department-Interventional Unit, Ruhrland Klinik, University of Essen, Essen, Germany; 3Department of Pathology, “G Papanikolaou” General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece; 4Department of Radiology, University General Hospital of Alexandroupolis, Democritus University of Thrace, Alexandroupolis, GreeceAbstract: Malignant pleural mesothelioma is a rare and aggressive malignancy of the pleura correlated with exposure to asbestos, with a medium survival of 11–12 months after diagnosis. A case of a 67-year-old male who had previously worked in the asbestos industry and is a current smoker is reported. The computed tomography evaluation revealed a right pleural mass with pleural thickening, and the pleural biopsy confirmed a diagnosis of malignant pleural mesothelioma. He was treated with chemotherapy consisting of etoposide, paclitaxel, and pegylated liposomal doxorubicin hydrochloride. After completion of chemotherapy, radiologic evaluation confirmed a reduction of pleural thickening and improvement in his symptoms. A complete presentation of each drug formulation and characteristics are also included in this paper. The patient’s follow-up is continuing, and computed tomography reveals stable disease 9 years after initial examination.Keywords: mesothelioma, asbestos, pegylated liposomal doxorubicin

A Fantastic Epidemiology Journey: from China to Africa and back

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Dr. Ann Hsing is a professor of medicine at Stanford University and a co-leader of the Population Sciences Program at Stanford Cancer Institute. She is also a professor in the Department of Health Research and Policy (epidemiology, by courtesy) and a faculty fellow for the Center for Innovation in Global Health. In addition, she chairs the Pacific Rim Alliance for Population Health at Stanford’s Center for Population Health Sciences. Prior to joining Stanford School of Medicine, Dr. Hsing served four years as Chief Scientific Officer at the Cancer Prevention Institute of California and 22 years as an intramural scientist (tenured senior investigator) at the Division of Cancer Epidemiology and Genetics, National Cancer Institute. Dr. Hsing received her PhD in epidemiology from the Johns Hopkins University and is widely recognized as a leading expert in the epidemiology of prostate and hepatobiliary cancer, as well as hormonal carcinogenesis and molecular epidemiology. She has authored more than 280 peer-reviewed articles and mentored over 60 pre- and post-doctoral fellows and junior scholars. At Stanford, she leads the Liver Cancer Working Group and the LDCT Screening Group, and serves as the principal investigator (PI) for wellness cohort studies in China, Taiwan, and Singapore as well as liver cancer studies in the Bay area, Taiwan, Mongolia, and Africa.

Experimental, statistical, and biological models of radon carcinogenesis

International Nuclear Information System (INIS)

Cross, F.T.

1991-09-01

Risk models developed for underground miners have not been consistently validated in studies of populations exposed to indoor radon. Imprecision in risk estimates results principally from differences between exposures in mines as compared to domestic environments and from uncertainties about the interaction between cigarette-smoking and exposure to radon decay products. Uncertainties in extrapolating miner data to domestic exposures can be reduced by means of a broad-based health effects research program that addresses the interrelated issues of exposure, respiratory tract dose, carcinogenesis (molecular/cellular and animal studies, plus developing biological and statistical models), and the relationship of radon to smoking and other copollutant exposures. This article reviews experimental animal data on radon carcinogenesis observed primarily in rats at Pacific Northwest Laboratory. Recent experimental and mechanistic carcinogenesis models of exposures to radon, uranium ore dust, and cigarette smoke are presented with statistical analyses of animal data. 20 refs., 1 fig

The role of CT in the differential diagnosis of malignant pleural mesothelioma and diffuse metastatic pleural involvement

International Nuclear Information System (INIS)

Kirova, G.; Beeva, M.; Sergieva, S.; Tsenkov, Kh.; Tsonev, P.

1997-01-01

The purpose of the study was to establish the presence of similarities and differences in the CT finding of patients presenting histologically proved diffuse pleural metastases and malignant pleural mesothelioma. Twenty-six patients with diffuse metastatic involvement of the pleura divided in two groups according to histological diagnosis, made on basis of findings at examination of the specimens obtained by pneumonectomy and pleural biopsy, are subjected to retrospective investigation. Group one is of ten patients with malignant pleural mesothelioma, and group two - sixteen patients presenting diffuse metastatic changes in the pleural membranes. All scanograms are separately evaluated in terms of state of the pulmonary parenchyma and that of of the pleurae, chest wall and mediastinum. As shown by the summed up data, the CT image of the pleura in malignant pleural mesothelioma and diffuse metastatic pleural disease lacks clearcut distinction, and its roentgenological characterization does not warrant a specific morphological diagnosis. There is difference in the degree of manifestation of so-called additional signs such as enlarged hilum and mediastinal lymph nodes, metastatic lesions to the pulmonary parenchyma and destruction of adjacent bone structures

Development of positron emission tomography imaging by 64Cu-labeled Fab for detecting ERC/mesothelin in a mesothelioma mouse model.

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Yoshida, Chisato; Sogawa, Chizuru; Tsuji, Atsushi B; Sudo, Hitomi; Sugyo, Aya; Uehara, Tomoya; Hino, Okio; Yoshii, Yukie; Fujibayashi, Yasuhisa; Fukumura, Toshimitsu; Koizumi, Mitsuru; Arano, Yasushi; Saga, Tsuneo

2010-05-01

Malignant mesothelioma is a highly aggressive form of cancer. Curative surgery is the only effective therapy for mesothelioma, and therefore early diagnosis is important. However, early diagnosis is difficult using current diagnostic imaging techniques, and a new imaging method for early diagnosis is urgently required. We evaluated the affinity of radiolabeled monoclonal antibodies to the C-terminal fragment of ERC/mesothelin for this purpose. In-labeled or I-labeled IgG against C-terminal fragment of ERC and its Fab fragment were evaluated in vitro by cell binding, competitive inhibition, and cellular internalization assays, and in vivo by biodistribution in mice bearing ERC-expressing tumors. Next, the Fab fragment was labeled with the positron emitter Cu and evaluated by positron emission tomography (PET). Radiolabeled IgG and Fab showed specific binding to ERC-expressing mesothelioma cells with high affinity. Both radiolabeled IgG and Fab internalized into cells after binding to ERC on the cell surface. In-labeled IgG accumulated in ERC-expressing tumors and resulted in a moderate tumor-to-blood ratio at 4 days after injection. Furthermore, PET using Cu-labeled Fab visualized the tumor at 6 h after injection. Cu-labeled Fab can be useful for ERC-specific PET imaging, and can thus facilitate improved diagnosis of patients with early-stage mesothelioma.

Detection, modeling and matching of pleural thickenings from CT data towards an early diagnosis of malignant pleural mesothelioma

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Chaisaowong, Kraisorn; Kraus, Thomas

2014-03-01

Pleural thickenings can be caused by asbestos exposure and may evolve into malignant pleural mesothelioma. While an early diagnosis plays the key role to an early treatment, and therefore helping to reduce morbidity, the growth rate of a pleural thickening can be in turn essential evidence to an early diagnosis of the pleural mesothelioma. The detection of pleural thickenings is today done by a visual inspection of CT data, which is time-consuming and underlies the physician's subjective judgment. Computer-assisted diagnosis systems to automatically assess pleural mesothelioma have been reported worldwide. But in this paper, an image analysis pipeline to automatically detect pleural thickenings and measure their volume is described. We first delineate automatically the pleural contour in the CT images. An adaptive surface-base smoothing technique is then applied to the pleural contours to identify all potential thickenings. A following tissue-specific topology-oriented detection based on a probabilistic Hounsfield Unit model of pleural plaques specify then the genuine pleural thickenings among them. The assessment of the detected pleural thickenings is based on the volumetry of the 3D model, created by mesh construction algorithm followed by Laplace-Beltrami eigenfunction expansion surface smoothing technique. Finally, the spatiotemporal matching of pleural thickenings from consecutive CT data is carried out based on the semi-automatic lung registration towards the assessment of its growth rate. With these methods, a new computer-assisted diagnosis system is presented in order to assure a precise and reproducible assessment of pleural thickenings towards the diagnosis of the pleural mesothelioma in its early stage.

Characterisation of Mesothelioma-Initiating Cells and Their Susceptibility to Anti-Cancer Agents

Czech Academy of Sciences Publication Activity Database

Pasdar, E.A.; Smits, M.; Stapelberg, M.; Bajziková, Martina; Stantic, M.; Goodwin, J.; Yan, B.; Štursa, J.; Kovářová, Jaromíra; Sachaphibulkij, K.; Bezawork-Geleta, A.; Sobol, Margaryta; Philimonenko, Anatoly; Tomasetti, M.; Zobalová, Renata; Hozák, Pavel; Dong, L.F.; Neužil, Jiří

2015-01-01

Roč. 10, č. 5 (2015), e0119549 E-ISSN 1932-6203 R&D Projects: GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:86652036 ; RVO:68378050 Keywords : MALIGNANT PLEURAL MESOTHELIOMA * EMBRYONIC STEM-CELLS * ALPHA-TOCOPHERYL SUCCINATE Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.057, year: 2015

Hyaluronan and N-ERC/mesothelin as key biomarkers in a specific two-step model to predict pleural malignant mesothelioma.

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Mundt, Filip; Nilsonne, Gustav; Arslan, Sertaç; Csürös, Karola; Hillerdal, Gunnar; Yildirim, Huseyin; Metintas, Muzaffer; Dobra, Katalin; Hjerpe, Anders

2013-01-01

Diagnosis of malignant mesothelioma is challenging. The first available diagnostic material is often an effusion and biochemical analysis of soluble markers may provide additional diagnostic information. This study aimed to establish a predictive model using biomarkers from pleural effusions, to allow early and accurate diagnosis. Effusions were collected prospectively from 190 consecutive patients at a regional referral centre. Hyaluronan, N-ERC/mesothelin, C-ERC/mesothelin, osteopontin, syndecan-1, syndecan-2, and thioredoxin were measured using ELISA and HPLC. A predictive model was generated and validated using a second prospective set of 375 effusions collected consecutively at a different referral centre. Biochemical markers significantly associated with mesothelioma were hyaluronan (odds ratio, 95% CI: 8.82, 4.82-20.39), N-ERC/mesothelin (4.81, 3.19-7.93), CERC/mesothelin (3.58, 2.43-5.59) and syndecan-1 (1.34, 1.03-1.77). A two-step model using hyaluronan and N-ERC/mesothelin, and combining a threshold decision rule with logistic regression, yielded good discrimination with an area under the ROC curve of 0.99 (95% CI: 0.97-1.00) in the model generation dataset and 0.83 (0.74-0.91) in the validation dataset, respectively. A two-step model using hyaluronan and N-ERC/mesothelin predicts mesothelioma with high specificity. This method can be performed on the first available effusion and could be a useful adjunct to the morphological diagnosis of mesothelioma.

Hyaluronan and N-ERC/mesothelin as key biomarkers in a specific two-step model to predict pleural malignant mesothelioma.

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Filip Mundt

Full Text Available PURPOSE: Diagnosis of malignant mesothelioma is challenging. The first available diagnostic material is often an effusion and biochemical analysis of soluble markers may provide additional diagnostic information. This study aimed to establish a predictive model using biomarkers from pleural effusions, to allow early and accurate diagnosis. PATIENTS AND METHODS: Effusions were collected prospectively from 190 consecutive patients at a regional referral centre. Hyaluronan, N-ERC/mesothelin, C-ERC/mesothelin, osteopontin, syndecan-1, syndecan-2, and thioredoxin were measured using ELISA and HPLC. A predictive model was generated and validated using a second prospective set of 375 effusions collected consecutively at a different referral centre. RESULTS: Biochemical markers significantly associated with mesothelioma were hyaluronan (odds ratio, 95% CI: 8.82, 4.82-20.39, N-ERC/mesothelin (4.81, 3.19-7.93, CERC/mesothelin (3.58, 2.43-5.59 and syndecan-1 (1.34, 1.03-1.77. A two-step model using hyaluronan and N-ERC/mesothelin, and combining a threshold decision rule with logistic regression, yielded good discrimination with an area under the ROC curve of 0.99 (95% CI: 0.97-1.00 in the model generation dataset and 0.83 (0.74-0.91 in the validation dataset, respectively. CONCLUSIONS: A two-step model using hyaluronan and N-ERC/mesothelin predicts mesothelioma with high specificity. This method can be performed on the first available effusion and could be a useful adjunct to the morphological diagnosis of mesothelioma.

A challenge to mutation theory of radiation carcinogenesis

International Nuclear Information System (INIS)

Watanabe, Masami

2006-01-01

This paper presents an objection against the commonly accepted mutation theory in radiation carcinogenesis. First, author's studies of X-ray irradiated syrian hamster embryo (SHE) cells on malignant morphological changes and mutational change of HGPRT gene showed that the changing patterns were quite different, and as well, other studies in mice gave the essentially similar results. Thus radiation-induced carcinogenesis in cells does not simply occur by an accumulation of radiation-induced mutation. Second, as cultured cells usually used for oncogenesis studies already have the infinitively proliferative ability, the author used the primary cell culture obtained from the rodent embryo. Even those cells became immortal to be cancerous after repeated culture passage with the higher frequency of 10 3 -10 4 relative to somatic cell mutation. Cells thus seem to be easily changeable to cancerous ones. Bystander effect can cause transformation in non-irradiated cells and genetic instability by radiation can form the potentially unstable chromatin region, which induces telomere instability. The author has found that, while short-lived radicals yielded by X-ray irradiation attack DNA to induce cell death and chromosome aberration, long-lived radicals in biomolecules do not, but can cause mutation and carcinogenesis, which are reduced by vitamine C supplementation. The author concludes that the primary target in the radiation carcinogenesis in cells and even in the whole individuals is conceivably protein and not DNA. (T.I.)

Epidemiological studies on the effects of low-level ionizing radiation on cancer risk

International Nuclear Information System (INIS)

Akiba, Suminori

2010-01-01

The health effects of low-level ionizing radiation are yet unclear. As pointed out by Upton in his review (Upton, 1989), low-level ionizing radiation seems to have different biological effects from what high-level radiation has. If so, the hazard identification of ionizing radiation should he conducted separately for low- and high-level ionizing radiation; the hazard identification of low-level radiation is yet to be completed. What makes hazard identification of ionizing radiation difficult, particularly in the case of carcinogenic effect, is the difficulty in distinguishing radiation-induced cancer from other cancers with respect to clinicopathological features and molecular biological characteristics. Actually, it is suspected that radiation-induced carcinogenesis involves mechanisms not specific for radiation, such as oxidative stress. Excess risk per dose in medium-high dose ranges can be extrapolated to a low-dose range if dose-response can be described by the linear-non-threshold model. The cancer risk data of atomic-bomb survivors describes leukemia risk with a linear-quadratic (LQ) model and solid-cancer risk with linear non-threshold (LNT) model. The LQ model for leukemia and the LNT model for solid cancer correspond to the two-hit model and the one-hit model, respectively. Although the one-hit model is an unlikely dose-response for carcinogenesis, there is no convincing epidemiological evidence supporting the LQ model or non-threshold model for solid cancer. It should be pointed out, however, even if the true dose response is non-linear various noises involved in epidemiological data may mask the truth. In this paper, the potential contribution of epidemiological studies on nuclear workers and residents in high background radiation areas will be discussed. (author)

Pleural malignant mesothelioma and non occupational exposure to asbestos in Casale Monferrato, Italy; Mesotheliome pleural malin et exposition environnementale l'amiante a Casale Monferrato, Italy

Energy Technology Data Exchange (ETDEWEB)

Magnani, C.; Terracini, B.; Ivaldi, C.; Botta, M.; Mancini, A.; Andrion, A.

1998-03-01

The objective is to study the possibility of the risk of a pleural malignant mesothelioma associated to an environmental exposure to asbestos coming from industry, by estimating the incidence of mesotheliomas in a population without professional exposure but living near a asbestos-cement factory.

New Perspectives on Diagnosis and Therapy of Malignant Pleural Mesothelioma

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Marika Rossini

2018-04-01

Full Text Available Malignant pleural mesothelioma (MPM is a rare, but severe form of cancer, with an incidence that varies significantly within and among different countries around the world. It develops in about one to two persons per million of the general population, leading to thousands of deaths every year worldwide. To date, the MPM is mostly associated with occupational asbestos exposure. Asbestos represents the predominant etiological factor, with approximately 70% of cases of MPM with well-documented occupational exposure to asbestos, with the exposure time, on average greater than 40 years. Environmental exposure to asbestos is increasingly becoming recognized as a cause of mesothelioma, together with gene mutations. The possible roles of other cofactors, such as viral infection and radiation exposure, are still debated. MPM is a fatal tumor. This cancer arises during its early phase without clinical signs. Consequently, its diagnosis occurs at advanced stages. Standard clinical therapeutic approaches include surgery, chemo- and radiotherapies. Preclinical and clinical researches are making great strides in the field of this deadly disease, identifying new biomarkers and innovative therapeutic approaches. Among the newly identified markers and potential therapeutic targets, circulating microRNAs and the Notch pathway represent promising avenues that could result in the early detection of the tumor and novel therapeutic approaches.

New Perspectives on Diagnosis and Therapy of Malignant Pleural Mesothelioma.

Science.gov (United States)

Rossini, Marika; Rizzo, Paola; Bononi, Ilaria; Clementz, Anthony; Ferrari, Roberto; Martini, Fernanda; Tognon, Mauro G

2018-01-01

Malignant pleural mesothelioma (MPM) is a rare, but severe form of cancer, with an incidence that varies significantly within and among different countries around the world. It develops in about one to two persons per million of the general population, leading to thousands of deaths every year worldwide. To date, the MPM is mostly associated with occupational asbestos exposure. Asbestos represents the predominant etiological factor, with approximately 70% of cases of MPM with well-documented occupational exposure to asbestos, with the exposure time, on average greater than 40 years. Environmental exposure to asbestos is increasingly becoming recognized as a cause of mesothelioma, together with gene mutations. The possible roles of other cofactors, such as viral infection and radiation exposure, are still debated. MPM is a fatal tumor. This cancer arises during its early phase without clinical signs. Consequently, its diagnosis occurs at advanced stages. Standard clinical therapeutic approaches include surgery, chemo- and radiotherapies. Preclinical and clinical researches are making great strides in the field of this deadly disease, identifying new biomarkers and innovative therapeutic approaches. Among the newly identified markers and potential therapeutic targets, circulating microRNAs and the Notch pathway represent promising avenues that could result in the early detection of the tumor and novel therapeutic approaches.

New Perspectives on Diagnosis and Therapy of Malignant Pleural Mesothelioma

Science.gov (United States)

Rossini, Marika; Rizzo, Paola; Bononi, Ilaria; Clementz, Anthony; Ferrari, Roberto; Martini, Fernanda; Tognon, Mauro G.

2018-01-01

Malignant pleural mesothelioma (MPM) is a rare, but severe form of cancer, with an incidence that varies significantly within and among different countries around the world. It develops in about one to two persons per million of the general population, leading to thousands of deaths every year worldwide. To date, the MPM is mostly associated with occupational asbestos exposure. Asbestos represents the predominant etiological factor, with approximately 70% of cases of MPM with well-documented occupational exposure to asbestos, with the exposure time, on average greater than 40 years. Environmental exposure to asbestos is increasingly becoming recognized as a cause of mesothelioma, together with gene mutations. The possible roles of other cofactors, such as viral infection and radiation exposure, are still debated. MPM is a fatal tumor. This cancer arises during its early phase without clinical signs. Consequently, its diagnosis occurs at advanced stages. Standard clinical therapeutic approaches include surgery, chemo- and radiotherapies. Preclinical and clinical researches are making great strides in the field of this deadly disease, identifying new biomarkers and innovative therapeutic approaches. Among the newly identified markers and potential therapeutic targets, circulating microRNAs and the Notch pathway represent promising avenues that could result in the early detection of the tumor and novel therapeutic approaches. PMID:29666782

Video-assisted thoracoscopic PlasmaJet ablation for malignant pleural mesothelioma.

Science.gov (United States)

Perikleous, Periklis; Asadi, Nizar; Anikin, Vladimir

2018-01-01

The role of surgery in malignant pleural mesothelioma (MPM) remains debatable; nonetheless the relative advantages of different surgical approaches are frequently reassessed and reconsidered. While extensive operations and longer recovery periods can be justified for a group of carefully selected patients, many will present at an advanced stage of their disease or with associated co-morbidities which will exclude them from selection criteria for radical treatment. For these patients, minimally invasive video-assisted procedures may be considered, for purposes of cytoreduction and/or symptomatic relief. Even though there is currently not enough clinical evidence to suggest an improvement in overall survival with limited debulking procedures, it has been suggested that they can improve quality of life over drainage and pleurodesis alone. We consider video-assisted PlasmaJet ablation to potentially have a role in mesothelioma surgery, as it may be used for effective cytoreduction while minimising the risk for complications often associated with extensive pleurectomy procedures, and we report on the use of the PlasmaJet Surgical System in our centre for surgical management of a patient with MPM. After demonstrating safety and absence of major adverse events with this approach, we feel justified in offering the procedure to more of our patients as we aim to collect additional data.

Epidemiological studies of groups with occupational exposure to radiation

International Nuclear Information System (INIS)

Davies, J.M.

1985-01-01

The exposure of man to radiation and the resulting risk of carcinogenesis continues to be of concern to the public. In this context, there is often a tendency to carry out epidemiological studies concerning the induction of cancer in radiation workers and members of the public which are not supported by a statistically valid data base or whose results are misinterpreted or misused. To assist national authorities in evaluating radiological risks, the Nuclear Energy Agency has sponsored a critical review of the methodologies for, and the limitations of, these epidemiological studies, and of the precautions to be adopted in interpreting their results. Prepared by a consultant, Dr. Joan M. Davies, the review focuses on the problems encountered when carrying out epidemiological studies on groups of workers occupationally exposed to radiations, and using their results for radiological protection purposes. It is published under the responsibility of the Secretary General of the OECD, and does not necessarily reflect the views of Member Governments. The primary objective is to provide background material to be used by national authorities that have responsibilities in the field of radiological protection as well as by other persons interested in this subject

Nuclear grade and necrosis predict prognosis in malignant epithelioid pleural mesothelioma: a multi-institutional study.

Science.gov (United States)

Rosen, Lauren E; Karrison, Theodore; Ananthanarayanan, Vijayalakshmi; Gallan, Alexander J; Adusumilli, Prasad S; Alchami, Fouad S; Attanoos, Richard; Brcic, Luka; Butnor, Kelly J; Galateau-Sallé, Françoise; Hiroshima, Kenzo; Kadota, Kyuichi; Klampatsa, Astero; Stang, Nolween Le; Lindenmann, Joerg; Litzky, Leslie A; Marchevsky, Alberto; Medeiros, Filomena; Montero, M Angeles; Moore, David A; Nabeshima, Kazuki; Pavlisko, Elizabeth N; Roggli, Victor L; Sauter, Jennifer L; Sharma, Anupama; Sheaff, Michael; Travis, William D; Vigneswaran, Wickii T; Vrugt, Bart; Walts, Ann E; Tjota, Melissa Y; Krausz, Thomas; Husain, Aliya N

2018-04-01

A recently described nuclear grading system predicted survival in patients with epithelioid malignant pleural mesothelioma. The current study was undertaken to validate the grading system and to identify additional prognostic factors. We analyzed cases of epithelioid malignant pleural mesothelioma from 17 institutions across the globe from 1998 to 2014. Nuclear grade was computed combining nuclear atypia and mitotic count into a grade of I-III using the published system. Nuclear grade was assessed by one pathologist for three institutions, the remaining were scored independently. The presence or absence of necrosis and predominant growth pattern were also evaluated. Two additional scoring systems were evaluated, one combining nuclear grade and necrosis and the other mitotic count and necrosis. Median overall survival was the primary endpoint. A total of 776 cases were identified including 301 (39%) nuclear grade I tumors, 354 (45%) grade II tumors and 121 (16%) grade III tumors. The overall survival was 16 months, and correlated independently with age (P=0.006), sex (0.015), necrosis (0.030), mitotic count (0.001), nuclear atypia (0.009), nuclear grade (<0.0001), and mitosis and necrosis score (<0.0001). The addition of necrosis to nuclear grade further stratified overall survival, allowing classification of epithelioid malignant pleural mesothelioma into four distinct prognostic groups: nuclear grade I tumors without necrosis (29 months), nuclear grade I tumors with necrosis and grade II tumors without necrosis (16 months), nuclear grade II tumors with necrosis (10 months) and nuclear grade III tumors (8 months). The mitosis-necrosis score stratified patients by survival, but not as well as the combination of necrosis and nuclear grade. This study confirms that nuclear grade predicts survival in epithelioid malignant pleural mesothelioma, identifies necrosis as factor that further stratifies overall survival, and validates the grading system across multiple

Alpha-tocopheryl succinate inhibits malignant mesothelioma by disrupting the fibroblast growth factor autocrine loop

Czech Academy of Sciences Publication Activity Database

Stapelberg, M.; Gellert, N.; Swettenham, E.; Tomasetti, M.; Witting, P. K.; Procopio, A.; Neužil, Jiří

2005-01-01

Roč. 280, č. 27 (2005), s. 25369-25376 ISSN 0021-9258 Institutional research plan: CEZ:AV0Z50520514 Keywords : alpha-tocopheryl succinate * malignant mesothelioma * fibroblast growth factor Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.854, year: 2005

Clinical significance of circulating miR-126 quantification in malignant mesothelioma patients

Czech Academy of Sciences Publication Activity Database

Tomasetti, M.; Staffolani, S.; Nocchi, L.; Neužil, Jiří; Strafella, E.; Manzella, N.; Mariotti, L.; Bracci, M.; Matteo, V.A.; Amati, M.; Santarelli, L.

2012-01-01

Roč. 45, 7-8 (2012), s. 575-581 ISSN 0009-9120 R&D Projects: GA ČR(CZ) GA204/08/0811 Institutional research plan: CEZ:AV0Z50520701 Keywords : Circulating miRNA markers * relative qRT-PCR * pleural mesothelioma Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.450, year: 2012

Drug repurposing in malignant pleural mesothelioma: a breath of fresh air?

Science.gov (United States)

Boyer, Arnaud; Pasquier, Eddy; Tomasini, Pascale; Ciccolini, Joseph; Greillier, Laurent; Andre, Nicolas; Barlesi, Fabrice; Mascaux, Celine

2018-03-31

Drug repurposing is the use of known drugs for new indications. Malignant pleural mesothelioma (MPM) is a rare cancer with a poor prognosis. So far, few treatments have been approved in this disease. However, its incidence is expected to increase significantly, particularly in developing countries. Consequently, drug repurposing appears as an attractive strategy for drug development in MPM, since the known pharmacology and safety profile based on previous approvals of repurposed drugs allows for faster time-to-market for patients and lower treatment cost. This is critical in low- and middle-income countries where access to expensive drugs is limited. This review assesses the published preclinical and clinical data about drug repurposing in MPM.In this review, we identified 11 therapeutic classes that could be repositioned in mesothelioma. Most of these treatments have been evaluated in vitro , half have been evaluated in vivo in animal models of MPM and only three ( i.e. valproate, thalidomide and zoledronic acid) have been investigated in clinical trials, with limited benefits so far. Efforts could be coordinated to pursue further investigations and test promising drugs identified in preclinical experiments in appropriately designed clinical trials. Copyright ©ERS 2018.

Induction chemotherapy vs post-operative adjuvant therapy for malignant pleural mesothelioma.

Science.gov (United States)

Marulli, Giuseppe; Faccioli, Eleonora; Bellini, Alice; Mammana, Marco; Rea, Federico

2017-08-01

Malignant pleural mesothelioma (MPM) is an aggressive neoplasia. Multidisciplinary treatments, including the association of induction and/or adjuvant therapeutic regimens with surgery, have been reported to give encouraging results. Current therapeutic options are not well standardized yet, especially regarding the best association between surgery and medical treatments. The present review aims to assess safety, efficacy and outcomes of different therapies for MPM. Areas covered: This article focuses on the multimodality treatment of mesothelioma. A systematic review was performed by using electronic databases to identify studies that considered induction and adjuvant approaches in MPM therapy in a multidisciplinary setting, including surgery. Endpoints included overall survival, disease free survival, disease recurrence, and complications. Expert commentary: This systematic review offers a comprehensive view of current multidisciplinary therapeutic strategies for MPM, suggesting that multimodality therapy offers acceptable outcomes with better results reported for trimodality approaches. Individualization of care for each patient is fundamental in choosing the most appropriate treatment. The growing complexity of treatment protocols mandates that MPM patients be referred to specialized Centers, in which every component of the interdisciplinary team can provide the necessary expertise and quality of care.

Personalized Chemosensitivity Assays for Mesothelioma: Are They Worth the Effort?

Science.gov (United States)

John, Thomas; Chia, Puey Ling

2018-04-01

Cell lines formed from an individual's tumor can be used to predict response to specific therapies and determine genomic predictors. For mesothelioma, where chemotherapy remains the backbone of current therapeutic paradigms, such assays could be used to treat patients with the most effective agents specific to their "chemical profile." Clin Cancer Res; 24(7); 1513-5. ©2018 AACR See related article by Schunselaar et al., p. 1761 . ©2018 American Association for Cancer Research.

First reported finding of a malignant pleural mesothelioma in a patient post liver transplant

LENUS (Irish Health Repository)

Gleeson, J

2016-03-01

The case history of a liver transplant recipient is presented, who presented with acute dyspnoea after an innocuous fall. His early management was complicated and he was eventually diagnosed with malignant mesothelioma. This is the first such case report in the literature.

Radiation carcinogenesis: radioprotectors and photosensitizers

International Nuclear Information System (INIS)

Fry, R.J.M.

1982-01-01

This paper outlines 1) some of the salient features of radiation carcinogenesis that are pertinent to the questions of how the carcinogenic effects might be influenced, 2) the effects of radioprotectors on ionizing radiation-induced cancer, and 3) the effect of photosensitizers on UVR-induced skin cancer

Radiation carcinogenesis: radioprotectors and photosensitizers

Energy Technology Data Exchange (ETDEWEB)

Fry, R.J.M.

1982-01-01

This paper outlines 1) some of the salient features of radiation carcinogenesis that are pertinent to the questions of how the carcinogenic effects might be influenced, 2) the effects of radioprotectors on ionizing radiation-induced cancer, and 3) the effect of photosensitizers on UVR-induced skin cancer.

Epidemiology of brain tumors in childhood--a review

International Nuclear Information System (INIS)

Baldwin, Rachel Tobias; Preston-Martin, Susan

2004-01-01

Malignant brain tumors are the leading cause of cancer death among children and the second most common type of pediatric cancer. Despite several decades of epidemiologic investigation, the etiology of childhood brain tumors (CBT) is still largely unknown. A few genetic syndromes and ionizing radiation are established risk factors. Many environmental exposures and infectious agents have been suspected of playing a role in the development of CBT. This review, based on a search of the medical literature through August 2003, summarizes the epidemiologic evidence to date. The types of exposures discussed include ionizing radiation, N-nitroso compounds (NOC), pesticides, tobacco smoke, electromagnetic frequencies (EMF), infectious agents, medications, and parental occupational exposures. We have chosen to focus on perinatal exposures and review some of the recent evidence indicating that such exposures may play a significant role in the causation of CBT. The scientific community is rapidly learning more about the molecular mechanisms by which carcinogenesis occurs and how the brain develops. We believe that advances in genetic and molecular biologic technology, including improved histologic subtyping of tumors, will be of huge importance in the future of epidemiologic research and will lead to a more comprehensive understanding of CBT etiology. We discuss some of the early findings using these technologies

Carcinogenesis of the Oral Cavity: Environmental Causes and Potential Prevention by Black Raspberry.

Science.gov (United States)

El-Bayoumy, Karam; Chen, Kun-Ming; Zhang, Shang-Min; Sun, Yuan-Wan; Amin, Shantu; Stoner, Gary; Guttenplan, Joseph B

2017-01-17

Worldwide, cancers of the oral cavity and pharynx comprise the sixth most common malignancies. Histologically, more than 90% of oral cancers are squamous cell carcinoma (SCC). Epidemiologic data strongly support the role of exogenous factors such as tobacco, alcohol, and human papilloma virus infection as major causative agents. Avoidance of risk factors has only been partially successful, and survival rates have not improved despite advances in therapeutic approaches. Therefore, new or improved approaches to prevention and/or early detection are critical. Better understanding of the mechanisms of oral carcinogenesis can assist in the development of novel biomarkers for early detection and strategies for disease prevention. Toward this goal, several animal models for carcinogenesis in the oral cavity have been developed. Among these are xenograft, and transgenic animal models, and others employing the synthetic carcinogens such as 7,12-dimethylbenz[a]anthracene in hamster cheek pouch and 4-nitroquinoline-N-oxide in rats and mice. Additional animal models employing environmental carcinogens such as benzo[a]pyrene and N'-nitrosonornicotine have been reported. Each model has certain advantages and disadvantages. Models that (1) utilize environmental carcinogens, (2) reflect tumor heterogeneity, and (3) accurately represent the cellular and molecular changes involved in the initiation and progression of oral cancer in humans could provide a realistic platform. To achieve this goal, we introduced a novel nonsurgical mouse model to study oral carcinogenesis induced by dibenzo[a,l]pyrene (DB[a,l]P), an environmental pollutant and tobacco smoke constituent, and its diol epoxide metabolite (±)-anti-11,12-dihydroxy-13,14-epoxy-11,12,13,14-tetrahydrodibenzo[a,l]pyrene [(±)-anti-DB[a,l]PDE]. On the basis of a detailed comparison of oral cancer induced by DB[a,l]P with that induced by the other above-mentioned oral carcinogens with respect to dose, duration, species and

Cadmium carcinogenesis

International Nuclear Information System (INIS)

Waalkes, Michael P.

2003-01-01

Cadmium is a heavy metal of considerable environmental and occupational concern. Cadmium compounds are classified as human carcinogens by several regulatory agencies. The most convincing data that cadmium is carcinogenic in humans comes from studies indicating occupational cadmium exposure is associated with lung cancer. Cadmium exposure has also been linked to human prostate and renal cancer, although this linkage is weaker than for lung cancer. Other target sites of cadmium carcinogenesis in humans, such as liver, pancreas and stomach, are considered equivocal. In animals, cadmium effectively induces cancers at multiple sites and by various routes. Cadmium inhalation in rats induces pulmonary adenocarcinomas, in accord with its role in human lung cancer. Cadmium can induce tumors and/or preneoplastic lesions within the rat prostate after ingestion or injection. At relatively high doses, cadmium induces benign testicular tumors in rats, but these appear to be due to early toxic lesions and loss of testicular function, rather than from a specific carcinogenic effect of cadmium. Like many other metals, cadmium salts will induce mesenchymal tumors at the site of subcutaneous (s.c.) or intramuscular (i.m.) injections, but the human relevance of these is dubious. Other targets of cadmium in rodents include the liver, adrenal, pancreas, pituitary, and hematopoietic system. With the exception of testicular tumors in rodents, the mechanisms of cadmium carcinogenesis are poorly defined. Cadmium can cause any number of molecular lesions that would be relevant to oncogenesis in various cellular model systems. Most studies indicate cadmium is poorly mutagenic and probably acts through indirect or epigenetic mechanisms, potentially including aberrant activation of oncogenes and suppression of apoptosis

Cadmium carcinogenesis

Energy Technology Data Exchange (ETDEWEB)

Waalkes, Michael P

2003-12-10

Cadmium is a heavy metal of considerable environmental and occupational concern. Cadmium compounds are classified as human carcinogens by several regulatory agencies. The most convincing data that cadmium is carcinogenic in humans comes from studies indicating occupational cadmium exposure is associated with lung cancer. Cadmium exposure has also been linked to human prostate and renal cancer, although this linkage is weaker than for lung cancer. Other target sites of cadmium carcinogenesis in humans, such as liver, pancreas and stomach, are considered equivocal. In animals, cadmium effectively induces cancers at multiple sites and by various routes. Cadmium inhalation in rats induces pulmonary adenocarcinomas, in accord with its role in human lung cancer. Cadmium can induce tumors and/or preneoplastic lesions within the rat prostate after ingestion or injection. At relatively high doses, cadmium induces benign testicular tumors in rats, but these appear to be due to early toxic lesions and loss of testicular function, rather than from a specific carcinogenic effect of cadmium. Like many other metals, cadmium salts will induce mesenchymal tumors at the site of subcutaneous (s.c.) or intramuscular (i.m.) injections, but the human relevance of these is dubious. Other targets of cadmium in rodents include the liver, adrenal, pancreas, pituitary, and hematopoietic system. With the exception of testicular tumors in rodents, the mechanisms of cadmium carcinogenesis are poorly defined. Cadmium can cause any number of molecular lesions that would be relevant to oncogenesis in various cellular model systems. Most studies indicate cadmium is poorly mutagenic and probably acts through indirect or epigenetic mechanisms, potentially including aberrant activation of oncogenes and suppression of apoptosis.

Asbestos fibres in indoor and outdoor air and the epidemiology of asbestos-related diseases in Quebec : summary and recommendation of the reports

Energy Technology Data Exchange (ETDEWEB)

DeGuire, L.; Lajoie, P.; Lemieux, C.; Poulin, M.

2004-07-01

An asbestos advisory committee was created in 1997 by Quebec's Ministry of Health to address concerns regarding exposure to asbestos fibres. Two sub-committees were subsequently formed. One sub-committee evaluated the pertinence and feasibility of assessing exposure in the general population, particularly in public buildings such as schools, while the other reviewed epidemiological studies in Quebec on mesothelioma, pulmonary cancers and asbestosis. Each sub-committee produced a report. This document summarizes the two reports and outlines the current scientific knowledge on the effects of asbestos on human health. The preventive programs and subsequent evaluations undertaken in Quebec with respect to sprayed asbestos in schools was described along with studies of asbestos exposure among workers in the mining sector. A study was also conducted within the asbestos processing industry to identify how many workers exceeded standard exposure limits. The standard time-weighted average exposure value currently in force in Quebec is 1 fibre per ml for chrysotile and 0.2 fibres per ml for amosite and crocidolite. A recommendation was made to revise this standard. In terms of outdoor air, the concentrations measured in recent years in mining towns have been generally very low. Along with asbestos-asphalt, asbestos waste taken to landfill sites may represent a significant source of exposure. A screening for asbestosis in the building and public works sector has shown that 1,500 workers (insulators, plumber-pipe fitters, elevator mechanics, fire protection mechanics and boiler-makers) experienced significant exposure to high concentrations of asbestos fibres in the ambient air. The 3 main health effects of asbestos exposure include mesothelioma of the pleura and peritoneum, pulmonary cancer and asbestosis. Each of these diseases appears after a latency period of 20 to 40 years, depending on the pathology. Epidemiological studies show a statistically significant increase

Disseminated Pleural Siliconoma Mimicking Malignant Pleural Mesothelioma.

Science.gov (United States)

Tanaka, Toshiki; Tao, Hiroyuki; Hayashi, Tatsuro; Yoshiyama, Koichi; Furukawa, Masashi; Yoshida, Kumiko; Okabe, Kazunori

2015-12-01

A 48-year-old woman with a 3-month history of back pain was admitted for further examination of multiple left pleural nodules. She had undergone bilateral breast augmentation with silicone implants 10 years previously. Nine years after the operation, both ruptured implants were removed, and autologous fat was injected. Computed tomography revealed multiple pleural nodules suggestive of malignant pleural mesothelioma. Thoracoscopic exploration revealed multiple pleural nodules with massive pleural adhesions. The nodules were filled with viscous liquid and were histologically determined to be siliconomas. Disseminated pleural siliconoma should be recognized as a late adverse event of silicone breast implantation. Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

MicroRNA-31 Regulates Chemosensitivity in Malignant Pleural Mesothelioma

Directory of Open Access Journals (Sweden)

Hannah L. Moody

2017-09-01

Full Text Available Malignant pleural mesothelioma (MPM is associated with an extremely poor prognosis, and most patients initially are or rapidly become unresponsive to platinum-based chemotherapy. MicroRNA-31 (miR-31 is encoded on a genomic fragile site, 9p21.3, which is reportedly lost in many MPM tumors. Based on previous findings in a variety of other cancers, we hypothesized that miR-31 alters chemosensitivity and that miR-31 reconstitution may influence sensitivity to chemotherapeutics in MPM. Reintroduction of miR-31 into miR-31 null NCI-H2452 cells significantly enhanced clonogenic resistance to cisplatin and carboplatin. Although miR-31 re-expression increased chemoresistance, paradoxically, a higher relative intracellular accumulation of platinum was detected. This was coupled to a significantly decreased intranuclear concentration of platinum. Linked with a downregulation of OCT1, a bipotential transcriptional regulator with multiple miR-31 target binding sites, we subsequently identified an indirect miR-31-mediated upregulation of ABCB9, a transporter associated with drug accumulation in lysosomes, and increased uptake of platinum to lysosomes. However, when overexpressed directly, ABCB9 promoted cellular chemosensitivity, suggesting that miR-31 promotes chemoresistance largely via an ABCB9-independent mechanism. Overall, our data suggest that miR-31 loss from MPM tumors promotes chemosensitivity and may be prognostically beneficial in the context of therapeutic sensitivity. Keywords: malignant pleural mesothelioma, microRNA-31, chemoresistance, cisplatin, ABCB9

Different imaging methods in the assessment of radiation-induced lung injury following hemithorax irradiation for pleural mesothelioma

International Nuclear Information System (INIS)

Maasilta, P.; Kivisaari, L.; Mattson, K.

1990-01-01

The authors have characterized the radiation-induced lung-injury on serial chest X-rays, CTs and ultralow field MRs and evaluated the clinical value and cost/benefit ratio of the different imaging methods in 30 patients receiving high-dose hemithorax irradiation for pleural mesothelioma. Lung injury was severe in all patients, but non-specific and essentially as described in text-books. CT provided no clinically relevant, cost effective diagnostic advantage over conventional X-rays in the detection of early or late radiation-induced lung injury, but it was necessary for the evaluation of the disease status of the mesothelioma. The possible advantage of MR over CT could not be evaluated and needs further studies. Optimal time-points for imaging CTs or MRs to detect early radiation-induced lung injury following high dose hemithorax irradiation were during the latter part of the treatment or very shortly after the end of the irradiation. Late injury or irreversible fibrosis develop rapidly after 6 months and was clearly documented by chest X-rays. The authors recommend serial chest X-rays at 1-2, 6 and 12 months following radiotherapy as a cost-effective method for the detection of radiation-induced lung injury with additional CTs to document the stage of mesothelioma, when needed. (author). 31 refs.; 4 figs

Chemotherapy induced pathologic complete response in malignant pleural mesothelioma: a review and case report

DEFF Research Database (Denmark)

Bech, Cecilia; Sørensen, Jens Benn

2010-01-01

Malignant pleural mesothelioma is a rare aggressive disease with a poor prognosis and usually modest responses to chemotherapy. Complete responses (CRs) to chemotherapy are rare. Evaluation is usually based on radiology, and CR is therefore clinical CR (cCR) and whether this indicates absence...

Comfrey (Symphytum officinale. L. and Experimental Hepatic Carcinogenesis: A Short-Term Carcinogenesis Model Study

Directory of Open Access Journals (Sweden)

Maria Fernanda Pereira Lavieri Gomes

2010-01-01

Full Text Available Comfrey or Symphytum officinale (L. (Boraginaceae is a very popular plant used for therapeutic purposes. Since the 1980s, its effects have been studied in long-term carcinogenesis studies, in which Comfrey extract is administered at high doses during several months and the neoplastic hepatic lesions are evaluated. However, the literature on this topic is very poor considering the studies performed under short-term carcinogenesis protocols, such as the ‘resistant hepatocyte model’ (RHM. In these studies, it is possible to observe easily the phenomena related to the early phases of tumor development, since pre-neoplastic lesions (PNLs rise in about 1–2 months of chemical induction. Herein, the effects of chronic oral treatment of rats with 10% Comfrey ethanolic extract were evaluated in a RHM. Wistar rats were sequentially treated with N-nitrosodiethylamine (ip and 2-acetilaminofluorene (po, and submitted to hepatectomy to induce carcinogenesis promotion. Macroscopic/microscopic quantitative analysis of PNL was performed. Non-parametric statistical tests (Mann–Whitney and χ2 were used, and the level of significance was set at P ≤ 0.05. Comfrey treatment reduced the number of pre-neoplastic macroscopic lesions up to 1 mm (P ≤ 0.05, the percentage of oval cells (P = 0.0001 and mitotic figures (P = 0.007, as well as the number of Proliferating Cell Nuclear Antigen (PCNA positive cells (P = 0.0001 and acidophilic pre-neoplastic nodules (P = 0.05. On the other hand, the percentage of cells presenting megalocytosis (P = 0.0001 and vacuolar degeneration (P = 0.0001 was increased. Scores of fibrosis, glycogen stores and the number of nucleolus organizing regions were not altered. The study indicated that oral treatment of rats with 10% Comfrey alcoholic extract reduced cell proliferation in this model.

Comfrey (Symphytum Officinale. l.) and Experimental Hepatic Carcinogenesis: A Short-term Carcinogenesis Model Study.

Science.gov (United States)

Gomes, Maria Fernanda Pereira Lavieri; de Oliveira Massoco, Cristina; Xavier, José Guilherme; Bonamin, Leoni Villano

2010-06-01

Comfrey or Symphytum officinale (L.) (Boraginaceae) is a very popular plant used for therapeutic purposes. Since the 1980s, its effects have been studied in long-term carcinogenesis studies, in which Comfrey extract is administered at high doses during several months and the neoplastic hepatic lesions are evaluated. However, the literature on this topic is very poor considering the studies performed under short-term carcinogenesis protocols, such as the 'resistant hepatocyte model' (RHM). In these studies, it is possible to observe easily the phenomena related to the early phases of tumor development, since pre-neoplastic lesions (PNLs) rise in about 1-2 months of chemical induction. Herein, the effects of chronic oral treatment of rats with 10% Comfrey ethanolic extract were evaluated in a RHM. Wistar rats were sequentially treated with N-nitrosodiethylamine (ip) and 2-acetilaminofluorene (po), and submitted to hepatectomy to induce carcinogenesis promotion. Macroscopic/microscopic quantitative analysis of PNL was performed. Non-parametric statistical tests (Mann-Whitney and χ(2)) were used, and the level of significance was set at P ≤ 0.05. Comfrey treatment reduced the number of pre-neoplastic macroscopic lesions up to 1 mm (P ≤ 0.05), the percentage of oval cells (P = 0.0001) and mitotic figures (P = 0.007), as well as the number of Proliferating Cell Nuclear Antigen (PCNA) positive cells (P = 0.0001) and acidophilic pre-neoplastic nodules (P = 0.05). On the other hand, the percentage of cells presenting megalocytosis (P = 0.0001) and vacuolar degeneration (P = 0.0001) was increased. Scores of fibrosis, glycogen stores and the number of nucleolus organizing regions were not altered. The study indicated that oral treatment of rats with 10% Comfrey alcoholic extract reduced cell proliferation in this model.

Methodology for lognormal modelling of malignant pleural mesothelioma survival time distributions: a study of 5580 case histories from Europe and USA

Energy Technology Data Exchange (ETDEWEB)

Mould, Richard F [41 Ewhurst Avenue, South Croydon, Surrey CR2 0DH (United Kingdom); Lahanas, Michael [Klinikum Offenbach, Strahlenklinik, 66 Starkenburgring, 63069 Offenbach am Main (Germany); Asselain, Bernard [Institut Curie, Biostatistiques, 26 rue d' Ulm, 75231 Paris Cedex 05 (France); Brewster, David [Director, Scottish Cancer Registry, Information Services (NHS National Services Scotland) Area 155, Gyle Square, 1 South Gyle Crescent, Edinburgh EH12 9EB (United Kingdom); Burgers, Sjaak A [Department of Thoracic Oncology, Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX Amsterdam, The (Netherlands); Damhuis, Ronald A M [Rotterdam Cancer Registry, Rochussenstraat 125, PO Box 289, 3000 AG Rotterdam, The (Netherlands); Rycke, Yann De [Institut Curie, Biostatistiques, 26 rue d' Ulm, 75231 Paris Cedex 05 (France); Gennaro, Valerio [Liguria Mesothelioma Cancer Registry, Etiology and Epidemiology Department, National Cancer Research Institute, Pad. Maragliano, Largo R Benzi, 10-16132 Genoa (Italy); Szeszenia-Dabrowska, Neonila [Department of Occupational and Environmental Epidemiology, National Institute of Occupational Medicine, PO Box 199, Swietej Teresy od Dzieciatka Jezus 8, 91-348 Lodz (Poland)

2004-09-07

A truncated left-censored and right-censored lognormal model has been validated for representing pleural mesothelioma survival times in the range 5-200 weeks for data subsets grouped by age for males, 40-49, 50-59, 60-69, 70-79 and 80+ years and for all ages combined for females. The cases available for study were from Europe and USA and totalled 5580. This is larger than any other pleural mesothelioma cohort accrued for study. The methodology describes the computation of reference baseline probabilities, 5-200 weeks, which can be used in clinical trials to assess results of future promising treatment methods. This study is an extension of previous lognormal modelling by Mould et al (2002 Phys. Med. Biol. 47 3893-924) to predict long-term cancer survival from short-term data where the proportion cured is denoted by C and the uncured proportion, which can be represented by a lognormal, by (1 - C). Pleural mesothelioma is a special case when C = 0.

Methodology for lognormal modelling of malignant pleural mesothelioma survival time distributions: a study of 5580 case histories from Europe and USA

International Nuclear Information System (INIS)

Mould, Richard F; Lahanas, Michael; Asselain, Bernard; Brewster, David; Burgers, Sjaak A; Damhuis, Ronald A M; Rycke, Yann De; Gennaro, Valerio; Szeszenia-Dabrowska, Neonila

2004-01-01

A truncated left-censored and right-censored lognormal model has been validated for representing pleural mesothelioma survival times in the range 5-200 weeks for data subsets grouped by age for males, 40-49, 50-59, 60-69, 70-79 and 80+ years and for all ages combined for females. The cases available for study were from Europe and USA and totalled 5580. This is larger than any other pleural mesothelioma cohort accrued for study. The methodology describes the computation of reference baseline probabilities, 5-200 weeks, which can be used in clinical trials to assess results of future promising treatment methods. This study is an extension of previous lognormal modelling by Mould et al (2002 Phys. Med. Biol. 47 3893-924) to predict long-term cancer survival from short-term data where the proportion cured is denoted by C and the uncured proportion, which can be represented by a lognormal, by (1 - C). Pleural mesothelioma is a special case when C = 0

Novel genes and pathways modulated by syndecan-1: implications for the proliferation and cell-cycle regulation of malignant mesothelioma cells.

Directory of Open Access Journals (Sweden)

Tünde Szatmári

Full Text Available Malignant pleural mesothelioma is a highly malignant tumor, originating from mesothelial cells of the serous cavities. In mesothelioma the expression of syndecan-1 correlates to epithelioid morphology and inhibition of growth and migration. Our previous data suggest a complex role of syndecan-1 in mesothelioma cell proliferation although the exact underlying molecular mechanisms are not completely elucidated. The aim of this study is therefore to disclose critical genes and pathways affected by syndecan-1 in mesothelioma; in order to better understand its importance for tumor cell growth and proliferation. We modulated the expression of syndecan-1 in a human mesothelioma cell line via both overexpression and silencing, and followed the transcriptomic responses with microarray analysis. To project the transcriptome analysis on the full-dimensional picture of cellular regulation, we applied pathway analysis using Ingenuity Pathway Analysis (IPA and a novel method of network enrichment analysis (NEA which elucidated signaling relations between differentially expressed genes and pathways acting via various molecular mechanisms. Syndecan-1 overexpression had profound effects on genes involved in regulation of cell growth, cell cycle progression, adhesion, migration and extracellular matrix organization. In particular, expression of several growth factors, interleukins, and enzymes of importance for heparan sulfate sulfation pattern, extracellular matrix proteins and proteoglycans were significantly altered. Syndecan-1 silencing had less powerful effect on the transcriptome compared to overexpression, which can be explained by the already low initial syndecan-1 level of these cells. Nevertheless, 14 genes showed response to both up- and downregulation of syndecan-1. The "cytokine - cytokine-receptor interaction", the TGF-β, EGF, VEGF and ERK/MAPK pathways were enriched in both experimental settings. Most strikingly, nearly all analyzed pathways

Preclinical Cancer Chemoprevention Studies Using Animal Model of Inflammation-Associated Colorectal Carcinogenesis

Energy Technology Data Exchange (ETDEWEB)

Tanaka, Takuji [Cytopatholgy Division, Tohkai Cytopathology Institute, Cancer Research and Prevention (TCI-CaRP), 5-1-2 Minami-uzura, Gifu 500-8285 (Japan); Department of Tumor Pathology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194 (Japan)

2012-07-16

Inflammation is involved in all stages of carcinogenesis. Inflammatory bowel disease, such as ulcerative colitis and Crohn’s disease is a longstanding inflammatory disease of intestine with increased risk for colorectal cancer (CRC). Several molecular events involved in chronic inflammatory process are reported to contribute to multi-step carcinogenesis of CRC in the inflamed colon. They include over-production of free radicals, reactive oxygen and nitrogen species, up-regulation of inflammatory enzymes in arachidonic acid biosynthesis pathway, up-regulation of certain cytokines, and intestinal immune system dysfunction. In this article, firstly I briefly introduce our experimental animal models where colorectal neoplasms rapidly develop in the inflamed colorectum. Secondary, data on preclinical cancer chemoprevention studies of inflammation-associated colon carcinogenesis by morin, bezafibrate, and valproic acid, using this novel inflammation-related colorectal carcinogenesis model is described.

Lymphotoxin prevention of diethylnitrosamine carcinogenesis in vivo

International Nuclear Information System (INIS)

Ransom, J.H.; Evans, C.H.; DiPaolo, J.A.

1982-01-01

Development of intervention measures to control cancer would be facilitated by being able to monitor in vivo carcinogenesis by in vitro quantitation of early indices of neoplastic transformation to assess the in vivo effectiveness of preventive-therapeutic measures. Pregnant Syrian golden hamsters were used in an in vivo-in vitro transplacental model of carcinogenesis to determine the extent that in vivo administration of immunologic hormone preparations along with chemical carcinogen would prevent morphologic transformation assessed in vitro. Pregnant hamsters at 10-11 days of gestation were given injections ip of 3 mg diethylnitrosamine (DENA)/100 g body weight and were killed 2 days later when fetal cells were seeded for colony formation. The frequency of morphologically transformed colonies was assessed after 7 days of growth. Cloning efficiency and mean transformation frequency after DENA exposure were 3.6% and 1 X 10(-4) per cell seeded, respectively. The ip injection of an immunologic hormone preparation reduced the transformation frequency by 46%. The hormone preparation, containing 10,000 U of lymphotoxin but no detectable interferon, was the ultrafiltered lymphokines (greater than 10,000 mol wt) from phytohemagglutinin-stimulated hamster peritoneal leukocytes. The effect of lymphotoxin on cocarcinogenic exposure of fetal cells to DENA in vivo followed by X-irradiation in vitro was also determined. Cells exposed to 250 rad in vitro had a cloning efficiency of 0.5% and a transformation frequency of 0.4 X 10(-4) per cell seeded. After DENA injection and X-irradiation, the transformation frequency increased to 1 X 10(-4) and was inhibited 64% by lymphotoxin in vivo. Thus immunologic hormones (e.g., lymphotoxin) can prevent carcinogenesis in vivo. Furthermore, in vitro quantitation of transformation is a rapid means for evaluating therapeutic and autochthonous effector mechanisms for their ability to prevent or otherwise modulate carcinogenesis in vivo

Mesothelioma of the testis and nephrotic syndrome: a case report

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Bacchetta Justine

2009-06-01

Full Text Available Abstract Introduction Paraneoplastic glomerulopathies are rare manifestations of neoplastic disease to be distinguished from iatrogenic renal damage. Solid tumors are preferentially associated with membranous nephropathy, whereas Hodgkin's lymphomas are associated with minimal change disease. Case presentation We report a 63-year-old Caucasian male diagnosed with a mesothelioma of the tunica vaginalis testis who, secondary to this, also presented with a nephrotic syndrome due to minimal change disease. In the present case, the paraneoplastic etiology of the nephrotic syndrome can be discussed on four unusual elements: minimal change lesions were found; the glomerulopathy was very sensitive to corticosteroids; the nephrotic syndrome occurred 11 months after the diagnosis of the primary malignancy, but concomitantly with the recurrence; and the nephrotic syndrome did not decrease with tumor control and did not recur when the mesothelioma escaped treatment. No other etiologies could nevertheless explain this phenomenon. Conclusion Paraneoplastic nephrotic syndrome is often associated with membranous nephropathy in patients with solid tumors, especially in patients with lung and gastrointestinal tract neoplasia. The management of these patients is associated with a symptomatic treatment such as sodium and water restriction, diuretics and ACE inhibitors and a prophylaxis of specific complications of nephrotic syndrome including thromboembolism, infections and lipid abnormalities. Treatment of neoplasia must be undertaken rapidly, treatments must be regularly analyzed and drugs binding to albumin may be used with precaution.

Chapter 8. Tea and Cancer Prevention: Epidemiological Studies

Science.gov (United States)

Yuan, Jian-Min; Sun, Canlan; Butler, Lesley M.

2011-01-01

Experimental studies have consistently shown the inhibitory activities of tea extracts on tumorigenesis in multiple model systems. Epidemiologic studies, however, have produced inconclusive results in humans. A comprehensive review was conducted to assess the current knowledge on tea consumption and risk of cancers in humans. In general, consumption of black tea was not associated with lower risk of cancer. High intake of green tea was consistently associated with reduced risk of upper gastrointestinal tract cancers after sufficient control for confounders. Limited data support a protective effect of green tea on lung and hepatocellular carcinogenesis. Although observational studies do not support a beneficial role of tea intake on prostate cancer risk, phase II clinical trials have demonstrated an inhibitory effect of green tea extract against the progression of prostate pre-malignant lesions. Green tea may exert beneficial effects against mammary carcinogenesis in premenopausal women and recurrence of breast cancer. There is no sufficient evidence that supports a protective role of tea intake on the development of cancers of the colorectum, pancreas, urinary tract, glioma, lymphoma, and leukemia. Future prospective observational studies with biomarkers of exposure and phase III clinical trials are required to provide definitive evidence for the hypothesized beneficial effect of tea consumption on cancer formation in humans. PMID:21419224

Adjuvant radiotherapy after extrapleural pneumonectomy for mesothelioma. Prospective analysis of a multi-institutional series

International Nuclear Information System (INIS)

Tonoli, Sandro; Vitali, Paola; Scotti, Vieri; Bertoni, Filippo; Spiazzi, Luigi; Ghedi, Barbara; Buonamici, Fabrizio Banci; Marrazzo, Livia; Guidi, Gabriele; Meattini, Icro; Bastiani, Paolo; Amichetti, Maurizio; Schwarz, Marco; Magrini, Stefano Maria

2011-01-01

Background and purpose: To evaluate survival, locoregional control and toxicity in a series of 56 mesothelioma patients treated from May 2005 to May 2010 with post-operative radiotherapy after extrapleural pneumonectomy (EPP) in three Italian Institutions (Brescia, Florence, and Modena). Material and methods: Fifty-six patients treated with adjuvant radiotherapy (RT) after EPP were analyzed. Four patients were treated with 3DCRT, 50 with IMRT and two with helical tomotherapy. Forty-five to 50 Gy in 25 fractions were given to the affected hemithorax and to ipsilateral mediastinum, with a simultaneous integrated boost to the sites of microscopically involved margins up to 60 Gy in 20/56 cases. Results: Three year locoregional control (LRC), distant metastasis free (DMF), disease free (DF), disease specific (DSS) and overall survival (OS) rates are 90%, 66%, 57%, 62%, and 60%, respectively. Conclusion: Postoperative RT with modern techniques is an effective method to obtain excellent local control and cure rates in mesothelioma patients submitted to EPP.

Radiation carcinogenesis, laboratory studies

International Nuclear Information System (INIS)

Shellabarger, C.J.

1974-01-01

Laboratory studies on radioinduced carcinogenesis are reviewed. Some topics discussed are: radioinduced neoplasia in relation to life shortening; dose-response relationships; induction of skin tumors in rats by alpha particles and electrons; effects of hormones on tumor response; effects of low LET radiations delivered at low dose-rates; effects of fractionated neutron radiation; interaction of RBE and dose rate effects; and estimates of risks for humans from animal data. (U.S.)

Detection and cultivation of circulating tumor cells in malignant pleural mesothelioma.

Science.gov (United States)

Bobek, Vladimir; Kacprzak, Grzegorz; Rzechonek, Adam; Kolostova, Katarina

2014-05-01

Malignant pleural mesothelioma (MPM) is an aggressive disease with very poor prognosis which tends to affect older patients. Progress in the management of this group of patients has been limited by the rarity of the disease and hence, difficulty in conducting randomized trials. The vast majority of cancer deaths occur due to metastasis of the primary tumor to distant sites via circulating tumor cells (CTCs) in the circulation. CTCs are extremely rare and limits in technology used to capture these cells hamper our complete understanding over the metastatic process. In the present study we present a new method for detection and cultivation of CTCs isolated from peripheral blood of MPM patients. Patients with diagnosed MPM were enrolled into this study. A size-based separation method for viable CTC enrichment from unclothed peripheral blood has been introduced; MetaCell. The size-based enrichment process was based on filtration of peripheral blood (PB) through porous polycarbonate membrane. The separated CTCs are cultured on the membrane in vitro under standard cancer cell culture conditions and observed by an inverted microscope. The reported methodology allows for quick and easy enrichment of CTCs and their cultivation. The cultivated cells can be used for next specification of gene expression and histological/biological specificity of concrete mesothelioma.

A seven-year disease-free survivor of malignant pleural mesothelioma treated with hyperthermia and chemotherapy: a case report

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Okonogi Noriyuki

2012-12-01

Full Text Available Abstract Introduction Malignant pleural mesothelioma was once a rare finding but its incidence is increasing worldwide, most likely because of widespread exposure to asbestos. Although complete surgical resection is considered the only curative treatment, the results of surgery have shown a median survival time of only one year. In inoperable cases, chemotherapy, radiotherapy, and a combination of both have been considered as palliative therapy. Therefore, outcomes for inoperable cases have been poor. Here, we report the case of a long-term survivor treated with hyperthermia and chemotherapy. Case presentation A 61-year-old Japanese man with a performance status of 1 due to chest pain was referred to our hospital. He had a history of asbestos exposure for approximately five years. A computed tomography scan showed diffuse extensive right pleural thickening with small nodular lesions, and video-assisted thoracoscopy revealed tumor invasion of the ipsilateral chest wall muscles. The histopathologic findings were consistent with a diagnosis of malignant pleural mesothelioma (sarcomatoid type. The tumor was diagnosed as being stage cT3N0M0. Our patient refused any invasive therapies including surgery and radiotherapy, and was therefore treated with hyperthermia and systemic chemotherapy with agents such as cisplatin and irinotecan. He underwent three hyperthermia sessions and a single course of chemotherapy without any severe complications. One month after treatment, a follow-up computed tomography scan showed no definitive abnormality in the thoracic space. Our patient has subsequently survived without any evident disease for more than seven years. Conclusions The combination of hyperthermia and chemotherapy may be a novel and safe therapeutic option for malignant pleural mesothelioma, and can be considered for patients ineligible for radical treatment. Further clinical studies of the combination of hyperthermia and chemotherapy are needed to

Malignant pleural mesothelioma with heterologous osteoblastic differentiation: case report of the characteristic CT and bone scan findings

International Nuclear Information System (INIS)

Cho, Young Jun; Kim, Joung Sook; Kim, Ji Young; Choi, Soo Jeon; Choi, Sang Bong

2008-01-01

Malignant pleural mesothelioma is an uncommon neoplasm which is accompanied extremely rarely by osteoblastic heterologous elements. The CT manifestations of this tumor have been reported in several references. And, to our knowledge, only one case report provides a description of the bone scan findings. Here, we report the case of a rapidly progressing malignant pleural mesothelioma with heterologous osteoblastic elements. A CT scan reveals diffuse irregular pleural thickening and very coarse nodular calcifications along the right pleura and major fissure. A bone scan revealed an area of extensive increased radioactivity consistent with the pleural calcifications on the CT scan in the right hemithorax. A follow-up CT scan performed 40 days later suggests the presence of rapidly progressing nodular coarse calcifications

Malignant pleural mesothelioma with heterologous osteoblastic differentiation: case report of the characteristic CT and bone scan findings

Energy Technology Data Exchange (ETDEWEB)

Cho, Young Jun; Kim, Joung Sook; Kim, Ji Young; Choi, Soo Jeon; Choi, Sang Bong [Sanggye Paik Hospital, Inje University College of Medicine, Seoul (Korea, Republic of)

2008-06-15

Malignant pleural mesothelioma is an uncommon neoplasm which is accompanied extremely rarely by osteoblastic heterologous elements. The CT manifestations of this tumor have been reported in several references. And, to our knowledge, only one case report provides a description of the bone scan findings. Here, we report the case of a rapidly progressing malignant pleural mesothelioma with heterologous osteoblastic elements. A CT scan reveals diffuse irregular pleural thickening and very coarse nodular calcifications along the right pleura and major fissure. A bone scan revealed an area of extensive increased radioactivity consistent with the pleural calcifications on the CT scan in the right hemithorax. A follow-up CT scan performed 40 days later suggests the presence of rapidly progressing nodular coarse calcifications.

Breast cancer as heterogeneous disease: contributing factors and carcinogenesis mechanisms.

Science.gov (United States)

Kravchenko, Julia; Akushevich, Igor; Seewaldt, Victoria L; Abernethy, Amy P; Lyerly, H Kim

2011-07-01

The observed bimodal patterns of breast cancer incidence in the U.S. suggested that breast cancer may be viewed as more than one biological entity. We studied the factors potentially contributing to this phenomenon, specifically focusing on how disease heterogeneity could be linked to breast carcinogenesis mechanisms. Using empirical analyses and population-based biologically motivated modeling, age-specific patterns of incidence of ductal and lobular breast carcinomas from the SEER registry (1990-2003) were analyzed for heterogeneity and characteristics of carcinogenesis, stratified by race, stage, grade, and estrogen (ER)/progesterone (PR) receptor status. The heterogeneity of breast carcinoma age patterns decreased after stratification by grade, especially for grade I and III tumors. Stratification by ER/PR status further reduced the heterogeneity, especially for ER(+)/PR(-) and ER(-)/(-) tumors; however, the residual heterogeneity was still observed. The number of rate-limiting events of carcinogenesis and the latency of ductal and lobular carcinomas differed, decreasing from grade I to III, with poorly differentiated tumors associated with the least number of carcinogenesis stages and the shortest latency. Tumor grades play important role in bimodal incidence of breast carcinoma and have distinct mechanisms of carcinogenesis. Race and cancer subtype could play modifying role. ER/PR status contributes to the observed heterogeneity, but is subdominant to tumor grade. Further studies on sources of "remaining" heterogeneity of population with breast cancer (such as genetic/epigenetic characteristics) are necessary. The results of this study could suggest stratification rather than unification of breast cancer prevention strategies, risk assessment, and treatment.

Safety of natural radiation exposure. A meta-analysis of epidemiological studies on natural radiation

International Nuclear Information System (INIS)

Osaki, S.

2000-01-01

People have been exposed every time and everywhere to natural radiation and ''intuitively'' know the safety of this radiation exposure. On the other hand the theory of no threshold value on radiological carcinogenesis is known widely, and many people feel danger with even a smallest dose of radiation exposure. The safety of natural radiation exposure can be used for the risk communication with the public. For this communication, the safety of natural radiation exposure should be proved ''scientifically''. Safety is often discussed scientifically as the risks of the mortality from many practices, and the absolute risks of safe practices on the public are 1E-5 to 1E-6. The risks based on the difference of natural radiation exposure on carcinogenesis have been analyzed by epidemiological studies. Much of the epidemiological studies have been focused on the relationship between radiation doses and cancer mortalities, and their results have been described as relative risks or correlation factors. In respect to the safety, however, absolute risks are necessary for the discussion. Cancer mortalities depend not only on radiation exposure, but also on ethnic groups, sexes, ages, social classes, foods, smoking, environmental chemicals, medical radiation, etc. In order to control these confounding factors, the data are collected from restricted groups or/and localities, but any these ecological studies can not perfectly compensate the confounding factors. So positive or negative values of relative risks or the meaningful correlation factors can not be confirmed that their values are derived originally from the difference of their exposure doses. The absolute risks on these epidemiological studies are also affected by many factors containing radiation exposure. The absolute risk or the upper value of the confidence limit obtained from the epidemiological study which is well regulated confounding factors is possible to be a maximum risk on the difference of the exposure doses

Epidemiologic studies on possible health effects of intake of pyrolyzates of foods, with reference to mortality among Japanese Seventh-Day Adventists.

OpenAIRE

Kuratsune, M; Ikeda, M; Hayashi, T

1986-01-01

To elucidate the effect of intake of mutagenic and/or carcinogenic pyrolysis products of proteins and amino acids on carcinogenesis in man, we have undertaken two epidemiologic cohort studies: one concerning the possible association of broiled fish consumption with cancer and the other concerning the cancer mortality among Japanese Seventh-Day Adventists. The main findings of these studies are described.

Epidemiologic studies on possible health effects of intake of pyrolyzates of foods, with reference to mortality among Japanese Seventh-Day Adventists.

Science.gov (United States)

Kuratsune, M; Ikeda, M; Hayashi, T

1986-08-01

To elucidate the effect of intake of mutagenic and/or carcinogenic pyrolysis products of proteins and amino acids on carcinogenesis in man, we have undertaken two epidemiologic cohort studies: one concerning the possible association of broiled fish consumption with cancer and the other concerning the cancer mortality among Japanese Seventh-Day Adventists. The main findings of these studies are described.

Biomarkers in molecular epidemiology study of oral squamous cell carcinoma in the era of precision medicine

Directory of Open Access Journals (Sweden)

Qing-Hao Zhu

2017-01-01

Full Text Available Oral cancer, which occurs in the mouth, lips, and tongue, is a multifactorial disease whose etiology involves environment, genetic, and epigenetic factors. Tobacco use and alcohol consumption are regarded as the primary risk factors for oral squamous cell carcinoma (OSCC, and betel use, other chemicals, radiation, environmental, and genetics are reported as relevant risk factors for oral carcinogenesis. The human papillomavirus infection is an independent risk factor. Traditional epidemiology studies have revealed that environmental carcinogens are risk factors for OSCC. Molecular epidemiology studies have revealed that the susceptibility to OSCC is influenced by both environmental and genetic risk factors. However, the details and mechanisms of risk factors involved in OSCC are unclear. Advanced methods and techniques used in human genome studies provide great opportunities for researchers to explore and identify (a the details of such risk factors and (b genetic susceptibility involved in OSCC. Human genome epidemiology is a new branch of epidemiology, which leads the epidemiology study from the molecular epidemiology era into the era of genome-wide association study. In the era of precision medicine, molecular epidemiology studies should focus on biomarkers for cancer genomics and their potential utility in clinical practice. Here, we briefly reviewed several molecular epidemiology studies of OSCC, focusing on biomarkers as valuable utility in risk assessment, clinical screening, diagnosis, and prognosis prediction of OSCC in the era of precision medicine.

Radiogenic cell transformation and carcinogenesis

Science.gov (United States)

Yang, T. C.; Georgy, K. A.; Mei, M.; Durante, M.; Craise, L. M.

1995-01-01

Radiation carcinogenesis is one of the major biological effects considered important in the risk assessment for space travel. Various biological model systems, including both cultured cells and animals, have been found useful for studying the carcinogenic effects of space radiations, which consist of energetic electrons, protons and heavy ions. The development of techniques for studying neoplastic cell transformation in culture has made it possible to examine the cellular and molecular mechanisms of radiation carcinogenesis. Cultured cell systems are thus complementary to animal models. Many investigators have determined the oncogenic effects of ionizing and nonionizing radiation in cultured mammalian cells. One of the cell systems used most often for radiation transformation studies is mouse embryonic cells (C3H10T1/2), which are easy to culture and give good quantitative dose-response curves. Relative biological effectiveness (RBE) for heavy ions with various energies and linear energy transfer (LET) have been obtained with this cell system. Similar RBE and LET relationship was observed by investigators for other cell systems. In addition to RBE measurements, fundamental questions on repair of sub- and potential oncogenic lesions, direct and indirect effect, primary target and lesion, the importance of cell-cell interaction and the role of oncogenes and tumor suppressor genes in radiogenic carcinogenesis have been studied, and interesting results have been found. Recently several human epithelial cell systems have been developed, and ionizing radiation have been shown to transform these cells. Oncogenic transformation of these cells, however, requires a long expression time and/or multiple radiation exposures. Limited experimental data indicate high-LET heavy ions can be more effective than low-LET radiation in inducing cell transformation. Cytogenetic and molecular analyses can be performed with cloned transformants to provide insights into basic genetic

Ga-67 tumor scan in malignant diffuse mesothelioma. Comparison with CT and pathological findings

International Nuclear Information System (INIS)

Yoshida, Shoji; Fukumoto, Mitsutaka; Motohara, Tomofumi; Oobayashi, Kayoko; Takada, Yoshiki; Tsubota, Noriaki; Sashikata, Terumasa

1999-01-01

Malignant diffuse mesothelioma is characterized by more difficult diagnosis and worse prognosis than other pleural tumors. In the Department of Thoracic Surgery, Hyogo Medical Center for Adults, 11 patients underwent panpleuropneumonectomy for this disease between January, 1988 and March, 1993. In 7 of these cases, Ga-67 scans were obtained before the operation. To clarify the factors affecting Ga-67 uptake in the pleural tumor, we compared Ga-67 uptake on the involved side of the thorax with CT and the pathological findings of the tumor. Regarding the use of Ga-67 scan imaging for the diagnosis of this disease, a number of related findings must be considered, such as an encircled wide Ga-67 uptake in the thickened pleural involvement and a diffuse slight Ga-67 uptake on the affected side with very slight involvement of the pleura. When the involved pleural thickness was over 6 mm, a definite correlation was found between the degree of Ga-67 uptake and the macroscopic thickness of mesothelioma in resected specimens. Thickness of the pleura on CT images demonstrates the real tumor thickness in the case of thickened involvement but in the case of thin involvement the real thickness of active mesothelioma could not be identified. No definite correlation was found between the degree of Ga-67 uptake and the histological type, or among microscopic findings, such as the extent of tumor parenchyma, interstitial volume and tumor vascularity. Our results suggest that the Ga-67 scan is very useful for revealing the extent of pleural involvement, especially when this involvement is more than 6 mm thick. (author)

Ga-67 tumor scan in malignant diffuse mesothelioma. Comparison with CT and pathological findings

Energy Technology Data Exchange (ETDEWEB)

Yoshida, Shoji; Fukumoto, Mitsutaka [Kochi Medical School, Nankoku (Japan); Motohara, Tomofumi; Oobayashi, Kayoko; Takada, Yoshiki; Tsubota, Noriaki; Sashikata, Terumasa

1999-02-01

Malignant diffuse mesothelioma is characterized by more difficult diagnosis and worse prognosis than other pleural tumors. In the Department of Thoracic Surgery, Hyogo Medical Center for Adults, 11 patients underwent panpleuropneumonectomy for this disease between January, 1988 and March, 1993. In 7 of these cases, Ga-67 scans were obtained before the operation. To clarify the factors affecting Ga-67 uptake in the pleural tumor, we compared Ga-67 uptake on the involved side of the thorax with CT and the pathological findings of the tumor. Regarding the use of Ga-67 scan imaging for the diagnosis of this disease, a number of related findings must be considered, such as an encircled wide Ga-67 uptake in the thickened pleural involvement and a diffuse slight Ga-67 uptake on the affected side with very slight involvement of the pleura. When the involved pleural thickness was over 6 mm, a definite correlation was found between the degree of Ga-67 uptake and the macroscopic thickness of mesothelioma in resected specimens. Thickness of the pleura on CT images demonstrates the real tumor thickness in the case of thickened involvement but in the case of thin involvement the real thickness of active mesothelioma could not be identified. No definite correlation was found between the degree of Ga-67 uptake and the histological type, or among microscopic findings, such as the extent of tumor parenchyma, interstitial volume and tumor vascularity. Our results suggest that the Ga-67 scan is very useful for revealing the extent of pleural involvement, especially when this involvement is more than 6 mm thick. (author)

Impact of renal failure on the tumor markers of mesothelioma, N-ERC/mesothelin and osteopontin.

Science.gov (United States)

Shiomi, Kazu; Shiomi, Satoko; Ishinaga, Yuji; Sakuraba, Motoki; Hagiwara, Yoshiaki; Miyashita, Kazuya; Maeda, Masahiro; Suzuki, Kenji; Takahashi, Kazuhisa; Hino, Okio

2011-04-01

Knowledge of the characteristics and effective use of tumour markers for mesothelioma is essential for early-stage diagnosis of mesothelioma. We examined whether renal dysfunction influences blood concentrations of promising new tumour markers, N-ERC/mesothelin (N-ERC) and osteopontin (OPN), to an important degree. Levels of serum N-ERC and plasma OPN in 32 patients with chronic renal dysfunction, 22 of whom were on hemodialysis (CKD group), and 102 healthy volunteers were measured. Serum concentrations of N-ERC and plasma concentrations of OPN in the CKD group were significantly higher than those in volunteers, regardless of diabetes status and age. Blood concentrations of these markers increased as renal function decreased. N-ERC and OPN concentrations are significantly influenced by renal function. Therefore, the extent of renal failure must be considered when inferring the existence of tumours and chemotherapeutic response from the values of these markers in routine practice.

Liver Development, Regeneration, and Carcinogenesis

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Janet W. C. Kung

2010-01-01

Full Text Available The identification of putative liver stem cells has brought closer the previously separate fields of liver development, regeneration, and carcinogenesis. Significant overlaps in the regulation of these processes are now being described. For example, studies in embryonic liver development have already provided the basis for directed differentiation of human embryonic stem cells and induced pluripotent stem cells into hepatocyte-like cells. As a result, the understanding of the cell biology of proliferation and differentiation in the liver has been improved. This knowledge can be used to improve the function of hepatocyte-like cells for drug testing, bioartificial livers, and transplantation. In parallel, the mechanisms regulating cancer cell biology are now clearer, providing fertile soil for novel therapeutic approaches. Recognition of the relationships between development, regeneration, and carcinogenesis, and the increasing evidence for the role of stem cells in all of these areas, has sparked fresh enthusiasm in understanding the underlying molecular mechanisms and has led to new targeted therapies for liver cirrhosis and primary liver cancers.

Hyaluronic acid enhances cell migration and invasion via the YAP1/TAZ-RHAMM axis in malignant pleural mesothelioma.

Science.gov (United States)

Shigeeda, Wataru; Shibazaki, Masahiko; Yasuhira, Shinji; Masuda, Tomoyuki; Tanita, Tatsuo; Kaneko, Yuka; Sato, Tatsuhiro; Sekido, Yoshitaka; Maesawa, Chihaya

2017-11-07

Most malignant mesotheliomas (MPMs) frequently show activated forms of Yes-associated protein 1 (YAP1) and transcriptional co-activator with PDZ-binding motif (TAZ), which transcriptionally regulates the receptor for hyaluronic acid-mediated motility (RHAMM). As RHAMM is involved in cell migration and invasion in various tumors, we speculated that hyaluronic acid (HA) in pleural fluid might affect the progression of mesothelioma by stimulating cell migration and invasion through RHAMM. The level of RHAMM expression was decreased by YAP1/TAZ knockdown, and conversely increased by forced expression of the active form of YAP1, suggesting that RHAMM was regulated by YAP1/TAZ in MPM cells. Cell migration and invasion were also decreased by YAP1/TAZ or RHAMM knockdown. Notably, HA treatment increased cell motility and invasion, and this was abolished by RHAMM knockdown, suggesting that HA may augment local progression of MPM cells via RHAMM. Furthermore, treatment with fluvastatin, which regulates RHAMM transcription by modulating YAP1/TAZ activity, decreased the motility and invasion of MPM cells. Collectively, these data suggest that HA is an "unfavorable" factor because it promotes malignancy in mesothelioma and that the YAP1/TAZ-RHAMM axis may have potential value as a therapeutic target for inhibition of disease progression in MPM.

Epidemiology, biology and therapy of Merkel cell carcinoma: conclusions from the EU project IMMOMEC

DEFF Research Database (Denmark)

Becker, Juergen C.; Stang, Andreas; zur Hausen, Axel

2018-01-01

Merkel cell carcinoma (MCC) is a highly aggressive, often lethal neuroendocrine cancer. Its carcinogenesis may be either caused by the clonal integration of the Merkel cell polyomavirus into the host genome or by UV-induced mutations. Notably, virally-encoded oncoproteins and UV-induced mutations...... knowledge on epidemiology, biology and therapy of MCC as conclusion of the project 'Immune Modulating strategies for treatment of Merkel Cell Carcinoma', which was funded over a 5-year period by the European Commission to investigate innovative immunotherapies for MCC....

Nanoparticle tumor localization, disruption of autophagosomal trafficking, and prolonged drug delivery improve survival in peritoneal mesothelioma.

Science.gov (United States)

Liu, Rong; Colby, Aaron H; Gilmore, Denis; Schulz, Morgan; Zeng, Jialiu; Padera, Robert F; Shirihai, Orian; Grinstaff, Mark W; Colson, Yolonda L

2016-09-01

The treatment outcomes for malignant peritoneal mesothelioma are poor and associated with high co-morbidities due to suboptimal drug delivery. Thus, there is an unmet need for new approaches that concentrate drug at the tumor for a prolonged period of time yielding enhanced antitumor efficacy and improved metrics of treatment success. A paclitaxel-loaded pH-responsive expansile nanoparticle (PTX-eNP) system is described that addresses two unique challenges to improve the outcomes for peritoneal mesothelioma. First, following intraperitoneal administration, eNPs rapidly and specifically localize to tumors. The rate of eNP uptake by tumors is an order of magnitude faster than the rate of uptake in non-malignant cells; and, subsequent accumulation in autophagosomes and disruption of autophagosomal trafficking leads to prolonged intracellular retention of eNPs. The net effect of these combined mechanisms manifests as rapid localization to intraperitoneal tumors within 4 h of injection and persistent intratumoral retention for >14 days. Second, the high tumor-specificity of PTX-eNPs leads to delivery of greater than 100 times higher concentrations of drug in tumors compared to PTX alone and this is maintained for at least seven days following administration. As a result, overall survival of animals with established mesothelioma more than doubled when animals were treated with multiple doses of PTX-eNPs compared to equivalent dosing with PTX or non-responsive PTX-loaded nanoparticles. Copyright © 2016 Elsevier Ltd. All rights reserved.

Introduction to Genetic Mechanisms of Carcinogenesis

International Nuclear Information System (INIS)

Yang, W.K.

1983-01-01

Recent technical advances in nucleic acid research and molecular biology have made it possible to explore the complicated genetic systems of eukaryotic cells. One of the fields showing rapid progress concerns genes and gene regulatory functions related to neoplastic processes. Thus, the 35th Annual Conference of the Biology Division of Oak Ridge National Laboratory, held at Gatlinburg, April 12-15, 1982, was organized with the intention to bring together investigators working on seemingly diverse fields of cancer research to discuss and exchange their views on the genetic mechanisms of carcinogenesis. The meeting was attended by workers from chemical, physical as well as biological carcinogenesis fields, by classical geneticists as well as by molecular biologists, and by researchers interested in experimental as well as in human cancers. Included in this volume are papers by the invited speakers of the symposium as well as by those presenting poster papers at the meeting

Epidemiological studies of general population groups exposed to low-level radiation

International Nuclear Information System (INIS)

Davies, J.M.; Inskip, H.

1986-01-01

The exposure of man to radiation and the resulting risk of carcinogenesis continue to be of concern to the public. In this context, there is often a tendency to carry out epidemiological studies concerning the induction of cancer in radiation workers and members of the public which are not supported by a statistically valid data base or whose result are misinterpreted or misused. To assist national authorities in evaluating radiological risks, the Nuclear Energy Agency has sponsored a critical review of the methodologies for, and the limitations of, these epidemiological studies, and of the precautions to be adopted in interpreting their results. Prepared by two consultants, Dr. Joan M. Davies and Dr. Hazel Inskip, the review focuses on the problems encountered when carrying out epidemiological studies on groups of the general population exposed to radiation, and using their results for radiological protection purposes. The primary objective is to provide background material for national authorities who have responsibilities in the field of radiological protection, as well as to other persons interested in this subject. It is published under the responsibility of the Secretary General of the OECD, and does not necessarily reflect the views of Member Governments

Meat processing and colon carcinogenesis: cooked, nitrite-treated, and oxidized high-heme cured meat promotes mucin-depleted foci in rats.

Science.gov (United States)

Santarelli, Raphaëlle L; Vendeuvre, Jean-Luc; Naud, Nathalie; Taché, Sylviane; Guéraud, Françoise; Viau, Michelle; Genot, Claude; Corpet, Denis E; Pierre, Fabrice H F

2010-07-01

Processed meat intake is associated with colorectal cancer risk, but no experimental study supports the epidemiologic evidence. To study the effect of meat processing on carcinogenesis promotion, we first did a 14-day study with 16 models of cured meat. Studied factors, in a 2 x 2 x 2 x 2 design, were muscle color (a proxy for heme level), processing temperature, added nitrite, and packaging. Fischer 344 rats were fed these 16 diets, and we evaluated fecal and urinary fat oxidation and cytotoxicity, three biomarkers of heme-induced carcinogenesis promotion. A principal component analysis allowed for selection of four cured meats for inclusion into a promotion study. These selected diets were given for 100 days to rats pretreated with 1,2-dimethylhydrazine. Colons were scored for preneoplastic lesions: aberrant crypt foci (ACF) and mucin-depleted foci (MDF). Cured meat diets significantly increased the number of ACF/colon compared with a no-meat control diet (P = 0.002). Only the cooked nitrite-treated and oxidized high-heme meat significantly increased the fecal level of apparent total N-nitroso compounds (ATNC) and the number of MDF per colon compared with the no-meat control diet (P nitrite-treated and oxidized cured meat specifically increased the MDF number compared with similar nonnitrite-treated meat (P = 0.03) and with similar nonoxidized meat (P = 0.004). Thus, a model cured meat, similar to ham stored aerobically, increased the number of preneoplastic lesions, which suggests colon carcinogenesis promotion. Nitrite treatment and oxidation increased this promoting effect, which was linked with increased fecal ATNC level. This study could lead to process modifications to make nonpromoting processed meat. 2010 AACR.

[Causation in the court: the complex case of malignant mesothelioma].

Science.gov (United States)

Lageard, Giovanni

2011-01-01

The aim of this paper is to carry out an analysis of the legal evolution in Italy of the assessment of causation i.e. cause and effect, in oncological diseases, a question taken into consideration by the High Court almost exclusively with reference to pleural mesothelioma. The most debated question when defining the causal association between asbestos exposure and mesothelioma is the possible role that any multiple potentially causative exposures could assume in the induction and development of the disease, and in particular the role of any asbestos exposure over the successive employment periods. Indeed, this is a subject on which, to date, no agreement has yet been reached in scientific doctrine: these divergences bear important practical significance from a legal point of view, since sustaining one thesis or another may constitute determining factors when ascertaining responsibility for individuals who, in the past, had decisional statuses in the workplace. Jurisprudence in the High Court took on an oscillating position on this question as from the early 2000s, which was divided into those who sustained the thesis of the relevance of any asbestos exposure over the successive employment periods and those who were of a different opinion, i.e. only the first exposure period has relevant causative effect. The point under discussion concerns, in particular, the adequacy of a probabilistic law only governing such a question. An important turning point was made in the year 2010 when two sentences were announced in the High Court, reiterating, in strict compliance with the principles affirmed by the United Sections in 2002, that a judge cannot, and must not, be satisfied with a general causation, but must rather reach a judgment on the basis of an individual causation. In particular, not only did the second of these two sentences recognise the multifactorial nature of mesothelioma, something which had almost always been denied in jurisprudence in the past, but it also

Pericardial Mesothelioma in a Yellow-naped Amazon Parrot (Amazona auropalliata).

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McCleery, Brynn; Jones, Michael P; Manasse, Jorden; Johns, Sara; Gompf, Rebecca E; Newman, Shelley

2015-03-01

A 37-year-old female yellow-naped Amazon parrot (Amazona auropalliata) was presented with a history of lethargy, inappetence, and decreased vocalizations. On examination, the coelom was moderately distended and palpated fluctuant, and the heart was muffled on auscultation. Coelomic ultrasound, coelomocentesis, and radiographs were performed and revealed an enlarged cardiac silhouette and marked coelomic effusion. Pericardial effusion was confirmed by echocardiography. A well-circumscribed, hyperechoic soft tissue density was observed at the level of the right atrium on initial echocardiography; however, a cardiac mass was not identified by computed tomography scan or repeat echocardiograms. Ultrasound-guided pericardiocentesis was performed under anesthesia, and cytology results were consistent with hemorrhage; no neoplastic cells were identified. A repeat echocardiogram 4 days after pericardiocentesis revealed recurrence of the pericardial effusion. Due to the grave prognosis, the owners declined endoscopic pericardiectomy, and the patient died the following day. On postmortem examination, the pericardial surface of the heart was covered in a white to yellow, multinodular mass layer. Histologic analysis revealed a multinodular mass extending from the atria, running along the epicardium distally, and often extending into the myocardium. Neoplastic cells present in the heart mass and pericardium did not stain with a Churukian-Schenk stain, and thyroglobulin immunohistochemistry was negative. Cytokeratin and vimentin stains showed positive expression in the neoplastic cells within the mass. These results are consistent with a diagnosis of mesothelioma. This is the first report of mesothelioma in a psittacine bird.

Malignant pleural mesothelioma in bakers and pastry cooks.

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Ascoli, V; Calisti, R; Carnovale-Scalzo, C; Nardi, F

2001-10-01

The occurrence of malignant pleural mesothelioma (MPM) among bakers and pastry cooks has never been documented. We detected eight cases of MPM in bakers, pastry cooks, and biscuit cooks engaged in making, baking/cooking, and selling pastry/bread in two hospital-based series (Rome and Orbassano/Turin, Italy; period 1990-1997; 222 cases). Field-investigations revealed asbestos-containing material (ACM) in ovens for baking bread, that were manufactured prior to the 1980s. It is suggested that there is a possible new association of the risk of having worked as a baker or pastry cook and MPM. Presumptive source of exposure to asbestos was the use of asbestos-insulated ovens. Copyright 2001 Wiley-Liss, Inc.

Tissue misrepair hypothesis for radiation carcinogenesis

International Nuclear Information System (INIS)

Kondo, Sohei

1991-01-01

Dose-response curves for chronic leukemia in A-bomb survivors and liver tumors in patients given Thorotrast (colloidal thorium dioxide) show large threshold effects. The existence of these threshold effects can be explained by the following hypothesis. A high dose of radiation causes a persistent wound in a cellrenewable tissue. Disorder of the injured cell society partly frees the component cells from territorial restraints on their proliferation, enabling them to continue development of their cellular functions toward advanced autonomy. This progression might be achieved by continued epigenetic and genetic changes as a result of occasional errors in the otherwise concerted healing action of various endogeneous factors recruited for tissue repair. Carcinogenesis is not simply a single-cell problem but a cell-society problem. Therefore, it is not warranted to estimate risk at low doses by linear extrapolation from cancer data at high doses without knowledge of the mechanism of radiation carcinogenesis. (author) 57 refs

Malignant mesothelioma effusions are infiltrated by CD3+ T cells highly expressing PD-L1 and the PD-L1+ tumor cells within these effusions are susceptible to ADCC by the anti-PD-L1 antibody avelumab

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Khanna, Swati; Thomas, Anish; Abate-Daga, Daniel; Zhang, Jingli; Morrow, Betsy; Steinberg, Seth M.; Orlandi, Augusto; Ferroni, Patrizia; Schlom, Jeffrey; Guadagni, Fiorella; Hassan, Raffit

2016-01-01

INTRODUCTION The functional aspects of programmed death 1 (PD-1) and PD ligand 1 (PD-L1) immune checkpoints in malignant mesothelioma have not been studied. METHODS Tumor samples from 65 patients with mesothelioma were evaluated for PD-L1 expression by immunohistochemistry and its prognostic significance. Malignant effusions from patients with pleural and peritoneal mesothelioma were evaluated for PD-1+ and PD-L1+ infiltrating lymphocytes and their role in inducing tumor cell PD-L1 expression. Antibody dependent cellular cytotoxicity (ADCC) of avelumab, a fully humanized IgG1 anti PD-L1 antibody towards primary mesothelioma cell lines was evaluated in presence of autologous and allogeneic NK cells. RESULTS Of 65 pleural and peritoneal mesothelioma tumors examined, 41 (63%) were PD-L1 positive, which was associated with slightly inferior overall survival compared to patients with PD-L1 negative tumors (median 23.0 vs. 33.3 months; p=0.35). The frequency of PD-L1 expression was similar in pleural and peritoneal mesothelioma patients with 62% and 64% of samples positive, respectively. Of nine mesothelioma effusion samples evaluated, the fraction of cells expressing PD-L1 ranged from 12 to 83%. Of 7 patients with paired malignant effusion and peripheral blood mononuclear cells (PBMC) samples, PD-L1 expression was significantly higher on CD3+ T cells present in malignant effusions as compared with PBMC (p=0.016). In addition, CD14+PD-1+ cells were elevated in malignant effusions compared with PBMC (p=0.031). The lymphocytes present in malignant effusions recognized autologous tumor cells and induced IFN-γ-mediated PD-L1 expression on the tumor cell surface. Of the three primary mesothelioma cell lines tested, two were susceptible to avelumab mediated ADCC in presence of autologous NK cells. CONCLUSION The majority of pleural as well as peritoneal mesothelioma express PD-L1. Malignant effusions in this disease are characterized by presence of tumor cells and CD3+ T

Differential protective effects of red wine polyphenol extracts (RWEs) on colon carcinogenesis.

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Mazué, Frédéric; Delmas, Dominique; Murillo, Genoveva; Saleiro, Diana; Limagne, Emeric; Latruffe, Norbert

2014-04-01

Various epidemiological studies have shown that a regular and moderate consumption of red wine is correlated with a decreased relative risk of developing coronary heart disease and cancer. These health benefits are commonly attributed to high contents of polyphenols, particularly resveratrol, representing important sources of antioxidants. However, resveratrol does not seem to be the only bioactive compound present in the wine which contains numerous other polyphenols. The present study investigates the efficiency of red wine extracts (RWEs), containing different polyphenols, on colon cancer cell proliferation in vitro and on colonic aberrant crypt foci (ACF) in vivo. Proliferation, cell cycle analysis and incidence of ACF were monitored to examine the effects of RWEs. RWEs derived from a long vinification process exhibit superior anti-proliferative activity in colon cancer cells and prevent the appearance of ACF in mice. Interestingly, quercetin and resveratrol, representing two major bio-active polyphenols, exhibit synergistic anti-proliferative effects. These data suggest that the efficacy of RWEs on colon carcinogenesis may depend on the polyphenolic content, synergistic interaction of bio-active polyphenols and modulation of cellular uptake of polyphenols.

The relevance of cell transformation to carcinogenesis in vivo

International Nuclear Information System (INIS)

Little, J.B.

1989-01-01

Despite the caveats concerning rodent as opposed to human cell transformation systems, the author concludes there are several areas in which cell transformation studies with rodent cells have shown clear relevance to carcinogenesis in vivo, especially studies of carcinogenic effects of high LET radiation, particularly dependence on dose rate. In vitro studies firmly established the generality of promotion by phorbol esters tumour promotors. Initial studies on suppression of transformation, notably by protease inhibitors, has led to the confirmation of this phenomenon in in vivo carcinogenesis; development of inhibitor preparations from natural sources suitable for long-term supplementation in human diet, is under investigation. The potential importance of these modifiers is further emphasized by mechanistic studies suggesting that radiation may initiate a large fraction of exposed cell population, and expression of transformation may be controlled to a large extent by environmental conditions including the presence of promoting or suppressing agents. Finally, cell transformation systems offer the opportunity for mechanistic studies of the initial stages of carcinogenesis. Provocative results have arisen in several areas consistent with findings in experimental animals. (author)

Experimental gastric carcinogenesis in Cebus apella nonhuman primates.

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Joana de Fátima Ferreira Borges da Costa

Full Text Available The evolution of gastric carcinogenesis remains largely unknown. We established two gastric carcinogenesis models in New-World nonhuman primates. In the first model, ACP03 gastric cancer cell line was inoculated in 18 animals. In the second model, we treated 6 animals with N-methyl-nitrosourea (MNU. Animals with gastric cancer were also treated with Canova immunomodulator. Clinical, hematologic, and biochemical, including C-reactive protein, folic acid, and homocysteine, analyses were performed in this study. MYC expression and copy number was also evaluated. We observed that all animals inoculated with ACP03 developed gastric cancer on the 9(th day though on the 14(th day presented total tumor remission. In the second model, all animals developed pre-neoplastic lesions and five died of drug intoxication before the development of cancer. The last surviving MNU-treated animal developed intestinal-type gastric adenocarcinoma observed by endoscopy on the 940(th day. The level of C-reactive protein level and homocysteine concentration increased while the level of folic acid decreased with the presence of tumors in ACP03-inoculated animals and MNU treatment. ACP03 inoculation also led to anemia and leukocytosis. The hematologic and biochemical results corroborate those observed in patients with gastric cancer, supporting that our in vivo models are potentially useful to study this neoplasia. In cell line inoculated animals, we detected MYC immunoreactivity, mRNA overexpression, and amplification, as previously observed in vitro. In MNU-treated animals, mRNA expression and MYC copy number increased during the sequential steps of intestinal-type gastric carcinogenesis and immunoreactivity was only observed in intestinal metaplasia and gastric cancer. Thus, MYC deregulation supports the gastric carcinogenesis process. Canova immunomodulator restored several hematologic measurements and therefore, can be applied during/after chemotherapy to increase the

Restricted Field IMRT Dramatically Enhances IMRT Planning for Mesothelioma

International Nuclear Information System (INIS)

Allen, Aaron M.; Schofield, Deborah; Hacker, Fred; Court, Laurence E.; Czerminska, Maria M.S.

2007-01-01

Purpose: To improve the target coverage and normal tissue sparing of intensity-modulated radiotherapy (IMRT) for mesothelioma after extrapleural pneumonectomy. Methods and Materials: Thirteen plans from patients previously treated with IMRT for mesothelioma were replanned using a restricted field technique. This technique was novel in two ways. It limited the entrance beams to 200 o around the target and three to four beams per case had their field apertures restricted down to the level of the heart or liver to further limit the contralateral lung dose. New constraints were added that included a mean lung dose of <9.5 Gy and volume receiving ≥5 Gy of <55%. Results: In all cases, the planning target volume coverage was excellent, with an average of 97% coverage of the planning target volume by the target dose. No change was seen in the target coverage with the new technique. The heart, kidneys, and esophagus were all kept under tolerance in all cases. The average mean lung dose, volume receiving ≥20 Gy, and volume receiving ≥5 Gy with the new technique was 6.6 Gy, 3.0%, and 50.8%, respectively, compared with 13.8 Gy, 15%, and 90% with the previous technique (p < 0.0001 for all three comparisons). The maximal value for any case in the cohort was 8.0 Gy, 7.3%, and 57.5% for the mean lung dose, volume receiving ≥20 Gy, and volume receiving ≥5 Gy, respectively. Conclusion: Restricted field IMRT provides an improved method to deliver IMRT to a complex target after extrapleural pneumonectomy. An upcoming Phase I trial will provide validation of these results

Mesothelioma mortality surveillance and asbestos exposure tracking in Italy

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Lucia Fazzo

2012-01-01

Full Text Available INTRODUCTION: Spatial distribution of mortality from pleural mesothelioma (which in the ICD-10 Revision has a specific code: C45.0 in Italy for the period 2003-2009 is described. Previous mortality studies at national level employed the topographic code "Malignant neoplasms of pleura", because of unavailability of a specific code in ICD-9 Revision for pleural mesothelioma. METHODS: Standardized mortality ratios were computed for all municipalities, using each regional population as reference; for municipalities in Regions with rate higher than the national rate, the latter has been used as reference. SMRs were computed specifically also for each Italian Polluted Sites "of national concern for environmental remediation" (IPS with asbestos exposure sources, composed by one or more municipalities, using regional rate as reference. Spatial Scan Statistics procedure, using SatScan software, was applied in cluster analysis: the country was divided into geographic macro-areas and the relative risks (RR express the ratio of risk within the cluster to the risk of the macro-area outside the cluster. Clusters with p-value < 0.10 were selected. RESULTS: The national standardized annual mortality rate was 1.7 cases per 100 000. Several areas with evident burden of asbestos-related disease were detected. Significant clusters were found in correspondence to asbestos-cement industries (e.g. Casale Monferrato, women: RR = 28.7, shipyards (e.g. Trieste, men: RR = 4.8, petrochemical industries (e.g. Priolo, men: RR = 6.9 and a stone quarry contaminated by fluoro-edenite fibres (Biancavilla, women: RR = 25.9. Some of the increased clusters correspond to IPS. CONCLUSIONS: The results may contribute to detect asbestos exposure and to set priorites for environmental remediation.

Mesothelioma incidence in the neighbourhood of an asbestos-cement plant located in a national priority contaminated site

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Lucia Fazzo

2014-12-01

Full Text Available BACKGROUND: An epidemic of asbestos-related disease is ongoing in most industrialized countries, mainly attributable to past occupational exposure but partly due to environmental exposure. In this perspective, the incidence of pleural mesothelioma close to a former asbestos-cement plant in a national contaminated site was estimated. METHODS: The census-tracts interested by atmospheric dispersion of facilities in the contaminated site were identified. Two subareas with different estimated environmental asbestos impact were distinguished. An ecological study at micro-geographic level was performed. The standardized incidence ratios (SIR for study area and the two subareas, in comparison with region and municipality were computed. The standardized incidence rate ratio (IRR between the two subareas was computed. RESULTS: Mesothelioma incidence in the study area was increased: 46 cases were observed with respect to 22.23 expected (SIR: 2.02. The increase was confirmed in analysis considering only the subjects without an occupationally exposure to asbestos: 19 cases among men (SIR = 2.48; 95% CI: 1.49-3.88; 11 case among women (SIR = 1.34; 95% CI: 0.67-2.40. The IRR between the two subareas is less than one in overall population considering all age-classes and of 3 fold (IRR = 3.14, 95% CI: 0.65-9.17 in the age-classes below 55 years. CONCLUSIONS: The findings indicate an increased incidence of pleural mesothelioma in the neighbourhood of asbestos-cement plant, and a possible etiological contribution of asbestos environmental exposure in detected risks.

A Biphasic Pleural Tumor with Features of an Epithelioid and Small Cell Mesothelioma: Morphologic and Molecular Findings

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Sarah Hackman

2016-01-01

Full Text Available Malignant mesotheliomas are generally classified into epithelioid, sarcomatoid, desmoplastic, and biphasic types with rare reports of a small cell form. These small cell variants display some morphologic overlap with desmoplastic small round cell tumors (DSRCTs which generally occur within the abdominal cavity of young males and are defined by a characteristic t(11;22(p13;q12 translocation. However, there are rare reports of DSRCTs lacking this translocation. We present a 78-year-old man with a pleura-based biphasic neoplasm with features of both epithelioid mesothelioma and a small cell blastema-like neoplasm. The epithelioid portion showed IHC reactivity for pan cytokeratin, CK5/6, D2-40, and calretinin and the small cell portion marked with CD99, pan cytokeratin, WT1, FLI1, S100, CD200, MyoD1, and CD15. Fluorescence in situ hybridization testing for the t(11;22(p13;q12 translocation disclosed loss of the EWSR1 gene in 94% of tumor cell nuclei, but there was no evidence of the classic translocation. Array based-comparative genomic hybridization (a-CGH confirmed the tumor had numerous chromosome copy number losses, including 11p15.5-p11.12 and 22q12.1-q13.33, with loss of the EWSR1 and WT1 gene regions. Herein, we report novel complex CGH findings in a biphasic tumor and review the molecular genetic alterations in both mesothelioma and DSRCTs.

Malignant Mesothelioma Effusions Are Infiltrated by CD3+ T Cells Highly Expressing PD-L1 and the PD-L1+ Tumor Cells within These Effusions Are Susceptible to ADCC by the Anti-PD-L1 Antibody Avelumab.

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Khanna, Swati; Thomas, Anish; Abate-Daga, Daniel; Zhang, Jingli; Morrow, Betsy; Steinberg, Seth M; Orlandi, Augusto; Ferroni, Patrizia; Schlom, Jeffrey; Guadagni, Fiorella; Hassan, Raffit

2016-11-01

The functional aspects of programmed death 1 (PD-1) and PD ligand 1 (PD-L1) immune checkpoints in malignant mesothelioma have not been studied. Tumor samples from 65 patients with mesothelioma were evaluated for PD-L1 expression by immunohistochemistry, and its prognostic significance was examined. Malignant effusions from patients with pleural and peritoneal mesothelioma were evaluated for PD-1-positive and PD-L1-positive infiltrating lymphocytes and their role in inducing PD-L1 expression in tumor cells. Antibody-dependent cellular cytotoxicity (ADCC) of avelumab, a fully humanized immunoglobulin G1 anti PD-L1 antibody against primary mesothelioma cell lines, was evaluated in presence of autologous and allogeneic natural killer cells. Of 65 pleural and peritoneal mesothelioma tumors examined, 41 (63%) were PD-L1-positive, which was associated with slightly inferior overall survival compared to patients with PD-L1-negative tumors (median 23.0 versus 33.3 months, p = 0.35). The frequency of PD-L1 expression was similar in patients with pleural and peritoneal mesothelioma, with 62% and 64% of samples testing positive, respectively. In nine mesothelioma effusion samples evaluated, the fraction of cells expressing PD-L1 ranged from 12% to 83%. In seven patients with paired malignant effusion and peripheral blood mononuclear cell (PBMC) samples, PD-L1 expression was significantly higher on CD3-positive T cells present in malignant effusions as compared with PBMCs (p = 0.016). In addition, the numbers of CD14-positive PD-1-positive cells were increased in malignant effusions compared with PBMCs (p = 0.031). The lymphocytes present in malignant effusions recognized autologous tumor cells and induced interferon-γ-mediated PD-L1 expression on the tumor cell surface. Of the three primary mesothelioma cell lines tested, two were susceptible to avelumab-mediated ADCC in the presence of autologous natural killer cells. Most pleural as well as peritoneal mesotheliomas

Combined circulating epigenetic markers to improve mesothelin performance in the diagnosis of malignant mesothelioma

Czech Academy of Sciences Publication Activity Database

Santarelli, L.; Staffolani, S.; Strafella, E.; Nocchi, L.; Manzella, N.; Grossi, P.; Bracci, M.; Pignotti, E.; Alleva, R.; Borghi, B.; Pompili, C.; Sabbatini, A.; Rubini, C.; Zuccatosta, L.; Bichisecchi, E.; Valentino, M.; Horwood, K.; Comar, M.; Bovenzi, M.; Dong, L. F.; Neužil, Jiří; Amati, M.; Tomasetti, M.

2015-01-01

Roč. 90, č. 3 (2015), s. 457-464 ISSN 0169-5002 R&D Projects: GA ČR(CZ) GAP301/10/1937; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:86652036 Keywords : Mesothelioma * Lung cancer * Mesothelin * BREAST-CANCER METASTASIS Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.767, year: 2015

Advances in diagnosis and treatment of malignant pleural mesothelioma

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Giorgio Vittorio Scagliotti

2011-12-01

Full Text Available Malignant pleural mesothelioma (MPM is an aggressive but relatively rare malignancy with median survival ranging from 8 to 14 months depending on stage and presentation of disease. New diagnostic procedures are urgently needed, selecting patients in earlier stages to evaluate therapeutic approaches which combine chemotherapy, surgery and radiotherapy. Combination chemotherapy represents the only resource available for advanced disease.The combination of cisplatin and pemetrexed is the treatment of choice. This review summarizes the latest developments in diagnostic techniques and the available therapeutic options for the management of MPM. Particular attention is given to the molecular basis of biologically targeted therapies to be used in the future.

The role of TGFBI in mesothelioma and breast cancer: association with tumor suppression

International Nuclear Information System (INIS)

Li, Bingyan; Wen, Gengyun; Zhao, Yongliang; Tong, Jian; Hei, Tom K

2012-01-01

Transforming growth factor β induced (TGFBI) product, an extracellular matrix (ECM) protein, has been implicated as a putative tumor suppressor in recent studies. Our previous findings revealed that expression of TGFBI gene is down-regulated in a variety of cancer cell lines and clinical tissue samples. In this study, ectopic expression of TGFBI was used to ascertain its role as a tumor suppressor and to determine the underlying mechanism of mesothelioma and breast cancer. Cells were stably transfected with pRc/CMV2-TGFBI and pRc/CMV2-empty vector with Lipofectamine Plus. Ectopic expression of TGFBI was quantified by using quantitative PCR and Western-blotting. Characterization of cell viability was assessed using growth curve, clonogenic survival and soft agar growth. The potential of tumor formation was evaluated by an in vivo mouse model. Cell cycle was analyzed via flow cytometry. Expressions of p21, p53, p16 and p14 were examined using Western-blotting. Senescent cells were sorted by using a Senescence β-Galactosidase Staining Kit. Telomerase activity was measured using quantitative telomerase detection kit. In this study, an ectopic expression of TGFBI in two types of cancer cell lines, a mesothelioma cell line NCI-H28 and a breast cancer cell line MDA-MB-231 was found to have reduced the cellular growth, plating efficiency, and anchorage-independent growth. The tumorigenicity of these cancer cell lines as determined by subcutaneous inoculation in nude mice was similarly suppressed by TGFBI expression. Likewise, TGFBI expression reduced the proportion of S-phase while increased the proportion of G1 phase in these cells. The redistribution of cell cycle phase after re-expression of TGFBI was correspondent with transiently elevated expression of p21 and p53. The activities of senescence-associated β-galactosidase and telomerase were enhanced in TGFBI-transfected cells. Collectively, these results imply that TGFBI plays a suppressive role in the development

Apoptosis by [Pt(O,O'-acac)(γ-acac)(DMS)] requires PKC-δ mediated p53 activation in malignant pleural mesothelioma.

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Muscella, Antonella; Vetrugno, Carla; Cossa, Luca Giulio; Antonaci, Giovanna; Barca, Amilcare; De Pascali, Sandra Angelica; Fanizzi, Francesco Paolo; Marsigliante, Santo

2017-01-01

Mesothelioma cancer cells have epithelioid or sarcomatoid morphology. The worst prognosis is associated with sarcomatoid phenotype and resistance to therapy is affected by cells heterogeneity. We recently showed that in ZL55 mesothelioma cell line of epithelioid origin [Pt(O,O'-acac)(γ-acac)(DMS)] (Ptac2S) has an antiproliferative effect in vitro and in vivo. Aim of this work was to extend the study on the effects of Ptac2S on ZL34 cell line, representative of sarcomatoid mesothelioma. ZL34 cells were used to assay the antitumor activity of Ptac2S in a mouse xenograft model in vivo. Then, both ZL34 and ZL55 cells were used in order to assess the involvement of p53 protein in (a) the processes underlying the sensitivity to chemotherapy and (b) the activation of various transduction proteins involved in apoptosis/survival processes. Ptac2S increases ZL34 cell death in vivo compared with cisplatin and, in vitro, Ptac2S was more efficacious than cisplatin in inducing apoptosis. In Ptac2S-treated ZL34 and ZL55 cells, p53 regulated gene products of apoptotic BAX and anti-apoptotic Bcl-2 proteins via transcriptional activation. Ptac2S activated PKC-δ and PKC-ε; their inhibition by PKC-siRNA decreased the apoptotic death of cells. PKC-δ was responsible for JNK1/2 activation that has a role in p53 activation. In addition, PKC-ε activation provoked phosphorylation of p38MAPK, concurring to apoptosis. In ZL34 cells, Ptac2S also activated PKC-α thus provoking ERK1/2 activation; inhibition of PKC-α, or ERK1/2, increased Ptac2S cytotoxicity. Results confirm that Ptac2S is a promising therapeutic agent for malignant mesothelioma, giving a substantial starting point for its further validation.

The Association Between the FTO rs9939609 Variant and Malignant Pleural Mesothelioma Risk: A Case-Control Study.

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Khella, Mina S; Salem, Ahmed M; Abdel-Rahman, Omar; Saad, Amr S

2018-02-01

Despite the established link between malignant pleural mesothelioma (MPM) and asbestos exposure, genetic risk factors may play a key role in MPM pathogenesis. The rs9939609 polymorphism in the FTO gene has recently been implicated as a risk factor for some types of cancer, such as breast, pancreatic, and prostate cancers. FTO variation is associated with altered adipocytokine expression and oxidative stress inflammation, which may influence asbestos mediated-carcinogenesis. This is the first study to investigate a possible association between this polymorphism and MPM risk. FTO rs9939609 (T >A) genotypes were screened using a TaqMan ® Genotyping Assay in a total of 235 Egyptian subjects (86 MPM patients versus 149 controls). The chi-square test and logistic regression were used to evaluate the association between the candidate variant and MPM risk using a case-control design. In the additive genetic model, the AT and AA genotypes were associated with a 2.48-fold (95% confidence intervals [CI] = 1.04-5.92, p = 0.04) and a 3.46-fold (95% CI = 0.99-12.01, p = 0.051) increase in the odds of developing MPM, respectively, when compared to the TT genotype after adjustment for body mass index, age, and gender. Additionally, in the dominant genetic model AT/AA genotypes were associated with a 2.63-fold increase in the odds of developing MPM (95% CI = 1.13-6.12, p = 0.025). The present study shows for the first time that rs9939609 polymorphism in the FTO gene may be a genetic risk factor for MPM. This study highlights the association of this genetic polymorphism with cancer susceptibility, and therefore, it should be investigated in various other populations, in relation to different types of cancer, and with larger sample sizes.

Association of MiR-126 with Soluble Mesothelin-Related Peptides, a Marker for Malignant Mesothelioma

Czech Academy of Sciences Publication Activity Database

Santarelli, L.; Strafella, E.; Staffolani, S.; Amati, M.; Emanuelli, M.; Sartini, D.; Pozzi, V.; Carbonari, D.; Bracci, M.; Pignotti, E.; Mazzanti, P.; Sabbatini, A.; Ranaldi, R.; Gasparini, S.; Neužil, Jiří; Tomasetti, M.

2011-01-01

Roč. 6, č. 4 (2011), e18232 E-ISSN 1932-6203 R&D Projects: GA ČR(CZ) GA204/08/0811 Institutional research plan: CEZ:AV0Z50520701 Keywords : Malignant pleural mesothelioma * microRNAs * soluble mesothelin-related peptides Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.092, year: 2011

Three-dimensional evaluation of chemotherapy response in malignant pleural mesothelioma

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Ak, Guntulu [Department of Chest Disease, Eskisehir Osmangazi University, Medical Faculty, Eskisehir (Turkey)], E-mail: guntuluak@yahoo.com; Metintas, Muzaffer [Department of Chest Disease, Eskisehir Osmangazi University, Medical Faculty, Eskisehir (Turkey); Metintas, Selma [Department of Public Health, Eskisehir Osmangazi University, Medical Faculty, Eskisehir (Turkey); Yildirim, Huseyin [Department of Chest Disease, Eskisehir Osmangazi University, Medical Faculty, Eskisehir (Turkey); Ozkan, Ragip [Department of Radiology, Eskisehir Osmangazi University, Medical Faculty, Eskisehir (Turkey); Ozden, Hilmi [Department of Anatomy, Eskisehir Osmangazi University, Medical Faculty, Eskisehir (Turkey)

2010-04-15

Objectives: Measurement of tumor response to chemotherapy in malignant pleural mesothelioma (MPM) is problematic because of non-spherical tumor growth patterns and difficulty in choosing target lesion. In this study, we aimed to determine the effectiveness of tumor volume measurement for evaluating chemotherapy response. Methods: Fifty-seven MPM patients were included. Chemotherapy responses were evaluated by computed tomography (CT) using volumetric method, World Health Organization (WHO), and modified Response Evaluation Criteria in Solid Tumor (RECIST). The tumor volume was measured using the Cavalieri principle of stereological approaches. Results: According to the volumetric method, median survival was 10.0 months for progressive disease (PD), 14.0 months for stable disease (SD) and 16.0 months for objective response (OR). According to the WHO method, median survival was 11.3, 14.0, and 13.0 months, respectively. For modified RECIST, median survival was 10.0, 14.0, and 14.0 months, respectively. The correspondence between the WHO and modified RECIST methods was substantial (K = 0.66), as was that between the volumetric and WHO methods (K = 0.64); however the correspondence between the volumetric and modified RECIST methods was only moderate (K = 0.52). Conclusions: The most suitable chemotherapy response measurement technique is the volumetric method because of non-spherical tumor growth patterns in MPM. However, larger studies should be performed to better establish the suitability of this method. We recommend our method for determining the chemotherapy response in mesothelioma cases. However, modified RECIST criteria can also be applied due to favourable prediction of survival, ease of application, and moderate correspondence with the volumetric method.

Towards a systemic paradigm in carcinogenesis: linking epigenetics and genetics.

Science.gov (United States)

Burgio, Ernesto; Migliore, Lucia

2015-04-01

For at least 30 years cancer has been defined as a genetic disease and explained by the so-called somatic mutation theory (SMT), which has dominated the carcinogenesis field. Criticism of the SMT has recently greatly increased, although still not enough to force all SMT supporters to recognize its limits. Various researchers point out that cancer appears to be a complex process concerning a whole tissue; and that genomic mutations, although variably deleterious and unpredictably important in determining the establishment of the neoplastic phenotype, are not the primary origin for a malignant neoplasia. We attempt to describe the inadequacies of the SMT and demonstrate that epigenetics is a more logical cause of carcinogenesis. Many previous models of carcinogenesis fall into two classes: (i) in which some biological changes inside cells alone lead to malignancy; and (ii) requiring changes in stroma/extracellular matrix. We try to make clear that in the (ii) model genomic instability is induced by persistent signals coming from the microenvironment, provoking epigenetic and genetic modifications in tissue stem cells that can lead to cancer. In this perspective, stochastic mutations of DNA are a critical by-product rather then the primary cause of cancer. Indirect support for such model of carcinogenesis comes from the in vitro and vivo experiments showing apparent 'reversion' of cancer phenotypes obtained via physiological factors of cellular differentiation (cytokines and other signaling molecules) or drugs, even if the key mutations are not 'reversed'.

Mesothelioma incidence and community asbestos exposure; Incidence du mesotheliome et exposition environnementale a l'amiante

Energy Technology Data Exchange (ETDEWEB)

Berry, M.

1998-03-01

The objective of this study is to examine the importance of environmental exposure, non professional, to asbestos in the supervening of mesothelioma among the inhabitants of Manville( Somerset county, New Jersey, United States) where is the most important factory making products with asbestos of the North America. (N.C.)

Genes Associated With Prognosis After Surgery For Malignant Pleural Mesothelioma Promote Tumor Cell Survival In Vitro

International Nuclear Information System (INIS)

Gordon, Gavin J; Bueno, Raphael; Sugarbaker, David J

2011-01-01

Mesothelioma is an aggressive neoplasm with few effective treatments, one being cytoreductive surgery. We previously described a test, based on differential expression levels of four genes, to predict clinical outcome in prospectively consented mesothelioma patients after surgery. In this study, we determined whether any of these four genes could be linked to a cancer relevant phenotype. We conducted a high-throughput RNA inhibition screen to knockdown gene expression levels of the four genes comprising the test (ARHGDIA, COBLL1, PKM2, TM4SF1) in both a human lung-derived normal and a tumor cell line using three different small inhibitory RNA molecules per gene. Successful knockdown was confirmed using quantitative RT-PCR. Detection of statistically significant changes in apoptosis and mitosis was performed using immunological assays and quantified using video-assisted microscopy at a single time-point. Changes in nuclear shape, size, and numbers were used to provide additional support of initial findings. Each experiment was conducted in triplicate. Specificity was assured by requiring that at least 2 different siRNAs produced the observed change in each cell line/time-point/gene/assay combination. Knockdown of ARHGDIA, COBLL1, and TM4SF1 resulted in 2- to 4-fold increased levels of apoptosis in normal cells (ARHGDIA only) and tumor cells (all three genes). No statistically significant changes were observed in apoptosis after knockdown of PKM2 or for mitosis after knockdown of any gene. We provide evidence that ARHGDIA, COBLL1, and TM4SF1 are negative regulators of apoptosis in cultured tumor cells. These genes, and their related intracellular signaling pathways, may represent potential therapeutic targets in mesothelioma

Molecular mechanisms in radiation carcinogenesis: introduction

International Nuclear Information System (INIS)

Setlow, R.B.

1975-01-01

Molecular studies of radiation carcinogenesis are discussed in relation to theories for extrapolating from cellular and animal models to man. Skin cancer is emphasized because of sunlight-induced photochemical damage to DNA. It is emphasized that cellular and animal models are needed as well as molecular theories for quantitative evaluation of hazardous environmental agents. (U.S.)

Low ERCC1 expression in malignant pleural mesotheliomas treated with cisplatin and vinorelbine predicts prolonged progression-free survival

DEFF Research Database (Denmark)

Zimling, Zarah Glad; Sørensen, Jens Benn; Gerds, Thomas Alexander

2012-01-01

The relationship between excision repair cross-complementation group 1 (ERCC1) expression and outcome, in patients with malignant pleural mesothelioma (MPM), treated with cisplatin/vinorelbine combination-therapy, was retrospectively evaluated in a patient population from a previously published...

18F-Fluorodeoxyglucose PET/CT and dynamic contrast-enhanced MRI as imaging biomarkers in malignant pleural mesothelioma.

Science.gov (United States)

Hall, David O; Hooper, Clare E; Searle, Julie; Darby, Michael; White, Paul; Harvey, John E; Braybrooke, Jeremy P; Maskell, Nick A; Masani, Vidan; Lyburn, Iain D

2018-02-01

The purpose of this study was to compare the use of fluorine-18-fluorodeoxyglucose (F-FDG) PET with computed tomography (CT) and dynamic contrast-enhanced (DCE) MRI to predict prognosis and monitor treatment in malignant pleural mesothelioma. F-FDG PET/CT and DCE-MRI studies carried out as part of the South West Area Mesothelioma Pemetrexed trial were used. F-FDG PET/CT and DCE-MRI studies were carried out before treatment, and after two cycles of chemotherapy, on patients treated with pemetrexed and cisplatin. A total of 73 patients were recruited, of whom 65 had PET/CT and DCE-MRI scans. Baseline measurements from F-FDG PET/CT (maximum standardized uptake value, metabolic tumour volume and total lesion glycolysis) and DCE-MRI (integrated area under the first 90s of the curve and washout slope) were compared with overall survival (OS) using Kaplan-Meier and Cox regression analyses, and changes in imaging measurements were compared with disease progression. PET/CT and DCE-MRI measurements were not correlated with each other. Maximum standardized uptake value, metabolic tumour volume and total lesion glycolysis were significantly related to OS with Cox regression analysis and Kaplan-Meir analysis, and DCE-MRI washout curve shape was significantly related to OS. DCE-MRI curve shape can be combined with F-FDG PET/CT to give additional prognostic information. Changes in measurements were not related to progression-free survival. F-FDG PET/CT and DCE-MRI give prognostic information in malignant pleural mesothelioma. Neither PET/CT nor DCE-MRI is useful for monitoring disease progression.

Putative cancer stem cells may be the key target to inhibit cancer cell repopulation between the intervals of chemoradiation in murine mesothelioma.

Science.gov (United States)

Wu, Licun; Blum, Walter; Zhu, Chang-Qi; Yun, Zhihong; Pecze, Laszlo; Kohno, Mikihiro; Chan, Mei-Lin; Zhao, Yidan; Felley-Bosco, Emanuela; Schwaller, Beat; de Perrot, Marc

2018-04-27

Cancer cell repopulation during chemotherapy or radiotherapy is a major factor limiting the efficacy of treatment. Cancer stem cells (CSC) may play critical roles during this process. We aim to demonstrate the role of mesothelioma stem cells (MSC) in treatment failure and eventually to design specific target therapies against MSC to improve the efficacy of treatment in malignant mesothelioma. Murine mesothelioma AB12 and RN5 cells were used to compare tumorigenicity in mice. The expression of CSC-associated genes was evaluated by quantitative real-time PCR in both cell lines treated with chemo-radiation. Stemness properties of MSC-enriched RN5-EOS-Puro2 cells were characterized with flow cytometry and immunostaining. A MSC-specific gene profile was screened by microarray assay and confirmed thereafter. Gene Ontology analysis of the selected genes was performed by GOMiner. Tumor growth delay of murine mesothelioma AB12 cells was achieved after each cycle of cisplatin treatment, however, tumors grew back rapidly due to cancer cell repopulation between courses of chemotherapy. Strikingly, a 10-times lower number of irradiated cells in both cell lines led to a similar tumor incidence and growth rate as with untreated cells. The expression of CSC-associated genes such as CD24, CD133, CD90 and uPAR was dramatically up-regulated, while others did not change significantly after chemoradiation. Highly enriched MSC after selection with puromycin displayed an increasing GFP-positive population and showed typical properties of stemness. Comparatively, the proportion of MSC significantly increased after RN5-EOS parental cells were treated with either chemotherapy, γ-ray radiation, or a combination of the two, while MSC showed more resistance to the above treatments. A group of identified genes are most likely MSC-specific, and major pathways related to regulation of cell growth or apoptosis are involved. Upregulation of the gene transcripts Tnfsf18, Serpinb9b, Ly6a

Radiation carcinogenesis. Comprehensive final report, 16 May 1979-31 December 1980

International Nuclear Information System (INIS)

Warren, S.; Brown, C.E.; Gates, O.

1981-03-01

This abstract covers three main areas of investigation: mesothelioma induction by asbestos, radiation tumorigenesis and transplantable tumors. Canadian and Rhodesian asbestos fibers have been administered under anesthesia to rats by intratracheal, intrapleural and intraperitoneal injection. Additional groups were given 3-methylcholanthrene or x-radiation along with asbestos. A large series of mice also treated as above have displayed mesotheliomas. In addition, glass fiber injections and feeding of asbestos were done and have produced negative results to date. The carcinogenic effect of whole-body radiation on hemi-irradiated parabiont partners exposed to a single 1000 R dose of x-ray was evidenced by a significant increase in the incidence of malignant tumors in only six tissues: skin, supporting soft tissue, kidney, bone, pancreatic islets and ovary. In the male adrenal medulla and in the female breast genetic and parabiotic hormonal factors were judged to exert a significant effect. The occurrence of incisional (anastomotic) sarcomas in significant numbers in hemi-irradiated and parabiont control pairs suggests the operation of mechanical factors complicating the healing process, only slightly enhanced by radiation. One of the very valuable but unanticipated developments of the rat radiation program was the isolation of two transplantable endocrine tumors with strong hormonal potentials: an insulinoma of the pancreas and a pheochromocytoma of the adrenal medulla

Glyco-Immune Diagnostic Signatures and Therapeutic Targets of Mesothelioma

Science.gov (United States)

2014-07-01

malignant pleural mesothelioma. Expert Rev Anticancer Ther Feb;8(2):293-303, 2008. Korchagina, E.Y., Pochechueva, T.V., Obukhova, P.S., Formanovsky...over tract  3. Stomach membrane highly porforated +  liquid  release upon pressure 4. Meso contained within perionteum  5. Ascitic Fluid: 17mLs 6. GI...Used to be in cage  788 170.4 1. Horizontal incision to show natural colors of control  animal organs and natural  pleural  cavity architecture  X X 47

Prevention of mammary carcinogenesis by short-term estrogen and progestin treatments

International Nuclear Information System (INIS)

Rajkumar, Lakshmanaswamy; Guzman, Raphael C; Yang, Jason; Thordarson, Gudmundur; Talamantes, Frank; Nandi, Satyabrata

2004-01-01

Women who have undergone a full-term pregnancy before the age of 20 have one-half the risk of developing breast cancer compared with women who have never gone through a full-term pregnancy. This protective effect is observed universally among women of all ethnic groups. Parity in rats and mice also protects them against chemically induced mammary carcinogenesis. Seven-week-old virgin Lewis rats were given N-methyl-N-nitrosourea. Two weeks later the rats were treated with natural or synthetic estrogens and progestins for 7–21 days by subcutaneous implantation of silastic capsules. In our current experiment, we demonstrate that short-term sustained exposure to natural or synthetic estrogens along with progestins is effective in preventing mammary carcinogenesis in rats. Treatment with 30 mg estriol plus 30 mg progesterone for 3 weeks significantly reduced the incidence of mammary cancer. Short-term exposure to ethynyl estradiol plus megesterol acetate or norethindrone was effective in decreasing the incidence of mammary cancers. Tamoxifen plus progesterone treatment for 3 weeks was able to confer only a transient protection from mammary carcinogenesis, while 2-methoxy estradiol plus progesterone was effective in conferring protection against mammary cancers. The data obtained in the present study demonstrate that, in nulliparous rats, long-term protection against mammary carcinogenesis can be achieved by short-term treatments with natural or synthetic estrogen and progesterone combinations

Inflammatory and redox reactions in colorectal carcinogenesis.

Science.gov (United States)

Guina, Tina; Biasi, Fiorella; Calfapietra, Simone; Nano, Mario; Poli, Giuseppe

2015-03-01

It has been established that there is a relationship between chronic inflammation and cancer development. The constant colonic inflammation typical of inflammatory bowel diseases is now considered a risk factor for colorectal carcinoma (CRC) development. The inflammatory network of signaling molecules is also required during the late phases of carcinogenesis, to enable cancer cells to survive and to metastasize. Oxidative reactions are an integral part of the inflammatory response, and are generally associated with CRC development. However, when the malignant phenotype is acquired, increased oxidative status induces antioxidant defenses in cancer cells, favoring their aggressiveness. This contradictory behavior of cancer cells toward redox status is of great significance for potential anticancer therapies. This paper summarizes the essential background information relating to the molecules involved in regulating oxidative stress and inflammation during carcinogenesis. Understanding more of their function in CRC stages might provide the foundation for future developments in CRC treatment. © 2015 New York Academy of Sciences.

SU-F-207-06: CT-Based Assessment of Tumor Volume in Malignant Pleural Mesothelioma

International Nuclear Information System (INIS)

Qayyum, F; Armato, S; Straus, C; Husain, A; Vigneswaran, W; Kindler, H

2015-01-01

Purpose: To determine the potential utility of computed tomography (CT) scans in the assessment of physical tumor bulk in malignant pleural mesothelioma patients. Methods: Twenty-eight patients with malignant pleural mesothelioma were used for this study. A CT scan was acquired for each patient prior to surgical resection of the tumor (median time between scan and surgery: 27 days). After surgery, the ex-vivo tumor volume was measured by a pathologist using a water displacement method. Separately, a radiologist identified and outlined the tumor boundary on each CT section that demonstrated tumor. These outlines then were analyzed to determine the total volume of disease present, the number of sections with outlines, and the mean volume of disease per outlined section. Subsets of the initial patient cohort were defined based on these parameters, i.e. cases with at least 30 sections of disease with a mean disease volume of at least 3mL per section. For each subset, the R- squared correlation between CT-based tumor volume and physical ex-vivo tumor volume was calculated. Results: The full cohort of 28 patients yielded a modest correlation between CT-based tumor volume and the ex-vivo tumor volume with an R-squared value of 0.66. In general, as the mean tumor volume per section increased, the correlation of CT-based volume with the physical tumor volume improved substantially. For example, when cases with at least 40 CT sections presenting a mean of at least 2mL of disease per section were evaluated (n=20) the R-squared correlation increased to 0.79. Conclusion: While image-based volumetry for mesothelioma may not generally capture physical tumor volume as accurately as one might expect, there exists a set of conditions in which CT-based volume is highly correlated with the physical tumor volume. SGA receives royalties and licensing fees through the University of Chicago for computer-aided diagnosis technology

SU-F-207-06: CT-Based Assessment of Tumor Volume in Malignant Pleural Mesothelioma

Energy Technology Data Exchange (ETDEWEB)

Qayyum, F; Armato, S; Straus, C; Husain, A; Vigneswaran, W; Kindler, H [The University of Chicago, Chicago, IL (United States)

2015-06-15

Purpose: To determine the potential utility of computed tomography (CT) scans in the assessment of physical tumor bulk in malignant pleural mesothelioma patients. Methods: Twenty-eight patients with malignant pleural mesothelioma were used for this study. A CT scan was acquired for each patient prior to surgical resection of the tumor (median time between scan and surgery: 27 days). After surgery, the ex-vivo tumor volume was measured by a pathologist using a water displacement method. Separately, a radiologist identified and outlined the tumor boundary on each CT section that demonstrated tumor. These outlines then were analyzed to determine the total volume of disease present, the number of sections with outlines, and the mean volume of disease per outlined section. Subsets of the initial patient cohort were defined based on these parameters, i.e. cases with at least 30 sections of disease with a mean disease volume of at least 3mL per section. For each subset, the R- squared correlation between CT-based tumor volume and physical ex-vivo tumor volume was calculated. Results: The full cohort of 28 patients yielded a modest correlation between CT-based tumor volume and the ex-vivo tumor volume with an R-squared value of 0.66. In general, as the mean tumor volume per section increased, the correlation of CT-based volume with the physical tumor volume improved substantially. For example, when cases with at least 40 CT sections presenting a mean of at least 2mL of disease per section were evaluated (n=20) the R-squared correlation increased to 0.79. Conclusion: While image-based volumetry for mesothelioma may not generally capture physical tumor volume as accurately as one might expect, there exists a set of conditions in which CT-based volume is highly correlated with the physical tumor volume. SGA receives royalties and licensing fees through the University of Chicago for computer-aided diagnosis technology.

Interaction Between Dietary Factors and Inflammation in Prostate Carcinogenesis

National Research Council Canada - National Science Library

De Marzo, Angelo M

2007-01-01

We are investigating whether inflammation can enhance prostate carcinogenesis in a rat model of dietary charred meat carcinogen induced cancers, and, whether antioxidant and other chemopreventative...

Interactions between Dietary Factors and Inflammation in Prostate Carcinogenesis

National Research Council Canada - National Science Library

DeMarzo, Angelo M

2006-01-01

We are investigating whether inflammation can enhance prostate carcinogenesis in a rat model of dietary charred meat carcinogen induced cancers, and, whether antioxidant and other chemopreventative...

A central role for heme iron in colon carcinogenesis associated with red meat intake.

Science.gov (United States)

Bastide, Nadia M; Chenni, Fatima; Audebert, Marc; Santarelli, Raphaelle L; Taché, Sylviane; Naud, Nathalie; Baradat, Maryse; Jouanin, Isabelle; Surya, Reggie; Hobbs, Ditte A; Kuhnle, Gunter G; Raymond-Letron, Isabelle; Gueraud, Françoise; Corpet, Denis E; Pierre, Fabrice H F

2015-03-01

Epidemiology shows that red and processed meat intake is associated with an increased risk of colorectal cancer. Heme iron, heterocyclic amines, and endogenous N-nitroso compounds (NOC) are proposed to explain this effect, but their relative contribution is unknown. Our study aimed at determining, at nutritional doses, which is the main factor involved and proposing a mechanism of cancer promotion by red meat. The relative part of heme iron (1% in diet), heterocyclic amines (PhIP + MeIQx, 50 + 25 μg/kg in diet), and NOC (induced by NaNO₂+ NaNO₂; 0.17 + 0.23 g/L of drinking water) was determined by a factorial design and preneoplastic endpoints in chemically induced rats and validated on tumors in Min mice. The molecular mechanisms (genotoxicity, cytotoxicity) were analyzed in vitro in normal and Apc-deficient cell lines and confirmed on colon mucosa. Heme iron increased the number of preneoplastic lesions, but dietary heterocyclic amines and NOC had no effect on carcinogenesis in rats. Dietary hemoglobin increased tumor load in Min mice (control diet: 67 ± 39 mm²; 2.5% hemoglobin diet: 114 ± 47 mm², P = 0.004). In vitro, fecal water from rats given hemoglobin was rich in aldehydes and was cytotoxic to normal cells, but not to premalignant cells. The aldehydes 4-hydroxynonenal and 4-hydroxyhexenal were more toxic to normal versus mutated cells and were only genotoxic to normal cells. Genotoxicity was also observed in colon mucosa of mice given hemoglobin. These results highlight the role of heme iron in the promotion of colon cancer by red meat and suggest that heme iron could initiate carcinogenesis through lipid peroxidation. . ©2015 American Association for Cancer Research.