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Sample records for mesothelioma epidemiology carcinogenesis

  1. Mesotheliomas in Lebanon: Witnessing a Change in Epidemiology.

    Science.gov (United States)

    Kattan, Joseph; Eid, Roland; Kourie, Hampig Raphael; Farhat, Fadi; Ghosn, Marwan; Ghorra, Claude; Tomb, Roland

    2016-01-01

    Mesotheliomas are relatively rare tumors in Lebanon. The only previous study goes back to 14 years ago, when we published epidemiological characteristics of mesotheliomas in Lebanon, showing that the pleural location accounted for the vast majority of cases, with clear evidence of asbestos exposure from the Eternit factory of Chekka region. The objective of this current study was to estimate the incidence of mesothelioma in the past decade and to identify its epidemiological, clinical and therapeutic characteristics, making comparisons with our first study published in 2001. Between 2002 and 2014, patients diagnosed with malignant mesothelioma at Hotel-Dieu de France University Hospital were investigated. Epidemiological data focusing on asbestos exposure history were collected from medical records and interviews with the families. A total of 26 patients were diagnosed with mesothelioma, 21 of which were successfully investigated. The mean age of these 21 patients is 62.5 (19-82). Only 3 (14.29%) are women. 18 (85.71%) were smokers. Among the 21 available mesotheliomas, 15 (71.4%) are pleural, while 5 (23.8%) are peritoneal and 1 (4.8%) pericardial. Only 60% of patients with pleural mesothelioma and 50% of those with an obvious exposure to asbestos lived and/or worked in Chekka region. The mean time of asbestos exposure in patients with mesothelioma is 24.5 (1-50) years and the mean latency is 37.4 (4-61) years. Of the 21 patients, 10 (47.6%) underwent surgery during their treatment, 16 (76.2%) received chemotherapy and 3 (14.3%) received best supportive care. Compared to the previous study (1991-2000), substantial changes in the epidemiology of mesothelioma in Lebanon were observed, such as an increase in peritoneal localizations and a lower correlation with Chekka region asbestos contamination.

  2. 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

  3. Radiation carcinogenesis: Epidemiology and biological significance

    International Nuclear Information System (INIS)

    Boice, J.D.; Fraumeni, J.F.

    1984-01-01

    Epidemiologic studies of populations exposed to radiation have led to the identification of a preventable cause of cancer, but in the long run perhaps the most important contribution of radiation studies will be to provide insights into the basic processes of human carcinogenesis. In this volume, key investigators of major epidemiologic projects summarize their observations to date, including information to help assess the effects of low-level exposures. Experimentalists and theorists emphasize the relevance of laboratory and epidemiologic data in elucidating carcinogenic risks and mechanisms in man. This volume was prepared with several objectives in mind: (a) organize and synthesize knowledge on radiation carcinogenesis through epidemiologic and experimental approaches; (b) illustrate and explore ways of utilizing this information to gain insights into the fundamental mechanisms of cancer development; (c) stimulate the formation of hypotheses suited to experimental or epidemiologic testing, theoretical modeling, and multidisciplinary approaches; and (d) identify recent advances that clarify dose-response relationships and the influence of low-dose exposures, provide leads to carcinogenic mechanisms and host-environmental interactions, and suggest strategies for future research and preventive action

  4. Mesothelioma

    Science.gov (United States)

    ... stomach, heart, and other organs is called mesothelium. Mesothelioma is a tumor of that tissue. It usually ... be benign (not cancer) or malignant (cancer.) Malignant mesothelioma is a rare but serious type of cancer. ...

  5. Epidemiology of malignant peritoneal mesothelioma: A population-based study.

    Science.gov (United States)

    Salo, Silja A S; Ilonen, Ilkka; Laaksonen, Sanna; Myllärniemi, Marjukka; Salo, Jarmo A; Rantanen, Tuomo

    2017-12-01

    Malignant peritoneal mesothelioma (MPeM) is a rare cancer of the mesothelial cells in the peritoneum with poor prognosis. Earlier reports from other countries indicate an incidence of 0.2-3 new cases per million per year. No previous studies have examined the national epidemiology of MPeM in Nordic countries. This study aimed to clarify the epidemiology of MPeM in Finland over a 12-year period. The data consisted of cancer notifications, laboratory notifications, and death certificate information in the Finnish Cancer Registry (FCR) and Statistics Finland (SF) of all MPeM patients from 2000 to 2012 in Finland. We also collected data on occupational disease compensations from the Workers' Compensation Center (WCC) of Finland. Any missing information was collected from the respective patient's file of every patient obtained from health institutions that had treated the patients. Between January 1, 2000 and December 31, 2012, 90 new MPeM cases (56 males, 34 females) occurred in Finland. Median annual incidence was four new cases, which corresponded to 0.74 new cases per million per year. MPeM was deemed an occupational disease in 21 patients (23.3%). 71 patients (78.9%) of whom had a known cause of death, with a median survival of 4 months. The number of deaths linked to other disease than mesothelioma was 28/74 (37.8%). Our study indicates that MPeM in Finland is rare and fatal, which is in accordance with previous reports from other countries. MPeM is also a fatal disease, since most of the patients died due to MPeM. Copyright © 2017. Published by Elsevier Ltd.

  6. Cosmetic talc as a risk factor for pleural mesothelioma: a weight of evidence evaluation of the epidemiology.

    Science.gov (United States)

    Finley, Brent L; Benson, Stacey M; Marsh, Gary M

    2017-03-01

    Due to some historical (and inaccurate) reports that asbestos might be present in some cosmetic talc products, questions are occasionally raised regarding the potential pleural mesothelioma risks associated with cosmetic talc products. Our objective was to determine the incidence of pleural mesothelioma of individuals exposed to cosmetic talc. We conducted a systematic review of the epidemiological literature for cosmetic talc miners and millers and found three occupational cohort studies that evaluated pleural mesothelioma incidence in workers in Italy, Norway, France, and Austria. We conducted a second literature review to evaluate the incidence and mortality of pleural mesothelioma among patients who received talc pleurodesis treatments before 1965 and found retrospective clinical studies including over 300 patients with follow-up ranging from 14 to 40 years. There were no mesotheliomas reported in any of the cosmetic talc miner and miller cohorts. A pooled analysis of data from the cohort mortality studies indicated that four mesothelioma deaths would have been expected from the 90,022 person-years of observation, and this was associated with 84% and 67% statistical power to observe a 3-fold or 2.5-fold increase in pleural mesothelioma mortality, respectively. None of the patients who received talc pleurodesis treatments developed mesothelioma. We conclude that there is no epidemiological evidence to support the hypothesis that exposure to cosmetic talc is associated with the development of pleural mesothelioma.

  7. The epidemiology of malignant mesothelioma in women: gender differences and modalities of asbestos exposure.

    Science.gov (United States)

    Marinaccio, Alessandro; Corfiati, Marisa; Binazzi, Alessandra; Di Marzio, Davide; Scarselli, Alberto; Ferrante, Pierpaolo; Bonafede, Michela; Verardo, Marina; Mirabelli, Dario; Gennaro, Valerio; Mensi, Carolina; Schallemberg, Gert; Mazzoleni, Guido; Merler, Enzo; Girardi, Paolo; Negro, Corrado; D'Agostin, Flavia; Romanelli, Antonio; Chellini, Elisabetta; Silvestri, Stefano; Pascucci, Cristiana; Calisti, Roberto; Stracci, Fabrizio; Romeo, Elisa; Ascoli, Valeria; Trafficante, Luana; Carrozza, Francesco; Angelillo, Italo Francesco; Cavone, Domenica; Cauzillo, Gabriella; Tallarigo, Federico; Tumino, Rosario; Melis, Massimo; Iavicoli, Sergio

    2018-04-01

    The epidemiology of gender differences for mesothelioma incidence has been rarely discussed in national case lists. In Italy an epidemiological surveillance system (ReNaM) is working by the means of a national register. Incident malignant mesothelioma (MM) cases in the period 1993 to 2012 were retrieved from ReNaM. Gender ratio by age class, period of diagnosis, diagnostic certainty, morphology and modalities of asbestos exposure has been analysed using exact tests for proportion. Economic activity sectors, jobs and territorial distribution of mesothelioma cases in women have been described and discussed. To perform international comparative analyses, the gender ratio of mesothelioma deaths was calculated by country from the WHO database and the correlation with the mortality rates estimated. In the period of study a case list of 21 463 MMs has been registered and the modalities of asbestos exposure have been investigated for 16 458 (76.7%) of them. The gender ratio (F/M) was 0.38 and 0.70 (0.14 and 0.30 for occupationally exposed subjects only) for pleural and peritoneal cases respectively. Occupational exposures for female MM cases occurred in the chemical and plastic industry, and mainly in the non-asbestos textile sector. Gender ratio proved to be inversely correlated with mortality rate among countries. The consistent proportion of mesothelioma cases in women in Italy is mainly due to the relevant role of non-occupational asbestos exposures and the historical presence of the female workforce in several industrial settings. Enhancing the awareness of mesothelioma aetiology in women could support the effectiveness of welfare system and prevention policies. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  8. Epidemiology of malignant mesothelioma in Italy: surveillance systems, territorial clusters and occupations involved.

    Science.gov (United States)

    Marinaccio, Alessandro; Binazzi, Alessandra; Bonafede, Michela; Di Marzio, Davide; Scarselli, Alberto

    2018-01-01

    As a legacy of the large asbestos consumption until the definitive ban in 1992, Italy is currently suffering a severe epidemic of asbestos related diseases. The aim of this paper is to describe the surveillance system for mesothelioma incidence and to provide evidences regarding the occurrence of the disease in Italy and the circumstances of asbestos exposure. Italian National Register of Malignant Mesotheliomas (ReNaM) is a permanent surveillance system of mesothelioma incidence, with Regional Operating Centres (CORs) active in each Italian region, identifying incident malignant mesothelioma (MM) cases from health care structures. Occupational history, lifestyle habits and residential history are obtained using a standardised questionnaire, administered by a trained interviewer, to the subject or to the next of kin. Descriptive epidemiological figures, occupations involved in exposures and territorial maps of MM cases have been produced. At December 2016, ReNaM has collected 27,356 MM cases for the incidence period between 1993 and 2015. The modalities of exposure to asbestos have been investigated for 21,387 (78%) and an occupational exposure has been defined for around 70% of interviewed cases (14,818). Non-occupational exposure is still relevant with 4.9% and 4.4% of cases for which respectively a familial exposure (due to the cohabitation with an occupational exposed subject) and an environmental exposure (due to the residence near a contaminated site) has been detected. The epidemiological surveillance of MM incident cases, by the means of a national register for estimating the occurrence of the disease and identifying the circumstances of asbestos exposure, is a relevant tool for preventing asbestos exposure, for supporting the effectiveness of insurance system and for estimating reliable epidemiological figures.

  9. HGF/Met Signaling Is a Key Player in Malignant Mesothelioma Carcinogenesis

    Directory of Open Access Journals (Sweden)

    Giovanni Gaudino

    2014-11-01

    Full Text Available Malignant mesothelioma (MM is a highly aggressive cancer related to asbestos or erionite exposure and resistant to current therapies. Hepatocyte Growth Factor (HGF and its tyrosine kinase receptor Met regulate cell growth, survival, motility/migration, and invasion. HGF and Met are expressed in MM cells, suggesting that the HGF/Met signaling plays a role in development and progression of this tumor, by autocrine and/or paracrine mechanisms. Upregulation and ligand-independent activation of Met, which is under suppressive control of miR-34 family members, correlate with enhanced invasion, migration and metastatic potential in several cancers, including MM. Moreover, Simian Virus 40 (SV40 Tag expression also induces a HGF autocrine circuit in an Rb-dependent manner in human mesothelial cells (HM and possibly other cell types, enhancing cell adhesion, invasion and angiogenesis. The resulting activation of Met causes HM transformation and cell cycle progression, and contributes to virus particle assembling and infection of adjacent cells. The constitutive activation of Met, frequently occurring in MM, has been successfully targeted in preclinical models of MM. In conclusion, Met expression, activation state, subcellular localization and also HGF co-receptors expression, such as CD44, have clinical relevance for novel targeted therapies in a cancer for which no effective treatment is currently available.

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

    International Nuclear Information System (INIS)

    Fabrikant, J.I.

    1981-05-01

    The current knowledge of the carcinogenic effect of radiation in man is considered. The discussion is restricted to dose-incidence data in humans, particularly to certain of those epidemiological studies of human populations that are used most frequently for risk estimation for low-dose radiation carcinogenesis in man. Emphasis is placed solely on those surveys concerned with nuclear explosions and medical exposures

  11. National Trends in the Epidemiology of Malignant Pleural Mesothelioma: A National Cancer Data Base Study.

    Science.gov (United States)

    Saddoughi, Sahar A; Abdelsattar, Zaid M; Blackmon, Shanda H

    2018-02-01

    Malignant pleural mesothelioma (MPM) remains an aggressive malignancy that is difficult to cure. However, the treatment paradigm of MPM has evolved, and the national practice patterns are unknown. This study examined the national trends in the epidemiology, national treatment patterns, and survival of patients with this disease. We identified all patients (n = 19,134) with MPM from the National Cancer Data Base from 2004 to 2013. We analyzed patient, tumor characteristics, and treatment patterns using descriptive statistics and used Kaplan-Meier and Cox proportional hazards models to estimate survival stratified by the type of therapy administered. Four histologic subtypes were represented in the National Cancer Data Base, these included sarcomatoid (n = 2,355 [12.3%]), epithelioid (n = 6,858 [35.8%]), biphasic (n = 13,617 [11%]), and not otherwise specified (n = 8,560 [44.7%]). Across all subtypes, the prevalence of mesothelioma was highest among white men. Sarcomatoid had the worst survival (adjusted hazard ratio, 2.2; p Data Base. Although survival remains poor, multimodality therapy with surgical resection is associated with the best survival for MPM. Further research is needed to improve survival and overall patient outcomes. Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  12. Carcinogenesis

    International Nuclear Information System (INIS)

    Fry, R.J.M.

    1975-01-01

    The long-term aims are concerned with various aspects of the natural history and biology of cancer, the mechanism of induction and of the advancement of time of appearance of tumors, the development of systems suitable for the assay of oncogenesis and cocarcinogenesis, and the elucidation of some of the factors important to the problem of extrapolation of estimates of risk made in experimental systems to the estimate of risk in man. It is necessary to have a number of test systems in order to study the various factors related to cocarcinogenesis; some of these are clearly tissue specific. The liver tumor system is clearly useful for certain compounds, and the liver is an excellent tissue for the study of the mechanisms of cocarcinogenesis. This year we report on the relatively rapid induction of what appears histologically to be carcinoma of the thyroid by aminotriazole. In a collaborative study with the Neutron and Gamma-Ray Toxicity Group, we have established a new example of synergism in carcinogenesis, namely between radiation and pituitary hormone(s) in the production of Harderian gland tumors. Not only does a synergistic effect on incidence occur, but also on the degree of malignancy of the tumor induced. We thus have three different model systems for the study of various aspects of cocarcinogenesis: various chemicals, including nononcogenic polycyclic hydrocarbons, in liver tumorigenesis; ionizing radiation and aminotriazole in thyroid tumorigenesis; and in conjunction with the JANUS Program, the interaction of radiation and hormones in the production of Harderian gland, mammary gland, and other tumors

  13. Mesothelioma incidence surveillance systems and claims for workers’ compensation. Epidemiological evidence and prospects for an integrated framework

    Science.gov (United States)

    2012-01-01

    Background Malignant mesothelioma is an aggressive and lethal tumour strongly associated with exposure to asbestos (mainly occupational). In Italy a large proportion of workers are protected from occupational diseases by public insurance and an epidemiological surveillance system for incident mesothelioma cases. Methods We set up an individual linkage between the Italian national mesothelioma register (ReNaM) and the Italian workers’ compensation authority (INAIL) archives. Logistic regression models were used to identify and test explanatory variables. Results We extracted 3270 mesothelioma cases with occupational origins from the ReNaM, matching them with 1625 subjects in INAIL (49.7%); 91.2% (1,482) of the claims received compensation. The risk of not seeking compensation is significantly higher for women and the elderly. Claims have increased significantly in recent years and there is a clear geographical gradient (northern and more developed regions having higher claims rates). The highest rates of compensation claims were after work known to involve asbestos. Conclusions Our data illustrate the importance of documentation and dissemination of all asbestos exposure modalities. Strategies focused on structural and systematic interaction between epidemiological surveillance and insurance systems are needed. PMID:22545679

  14. Mesothelioma incidence surveillance systems and claims for workers’ compensation. Epidemiological evidence and prospects for an integrated framework

    Directory of Open Access Journals (Sweden)

    Marinaccio Alessandro

    2012-07-01

    Full Text Available Abstract Background Malignant mesothelioma is an aggressive and lethal tumour strongly associated with exposure to asbestos (mainly occupational. In Italy a large proportion of workers are protected from occupational diseases by public insurance and an epidemiological surveillance system for incident mesothelioma cases. Methods We set up an individual linkage between the Italian national mesothelioma register (ReNaM and the Italian workers’ compensation authority (INAIL archives. Logistic regression models were used to identify and test explanatory variables. Results We extracted 3270 mesothelioma cases with occupational origins from the ReNaM, matching them with 1625 subjects in INAIL (49.7%; 91.2% (1,482 of the claims received compensation. The risk of not seeking compensation is significantly higher for women and the elderly. Claims have increased significantly in recent years and there is a clear geographical gradient (northern and more developed regions having higher claims rates. The highest rates of compensation claims were after work known to involve asbestos. Conclusions Our data illustrate the importance of documentation and dissemination of all asbestos exposure modalities. Strategies focused on structural and systematic interaction between epidemiological surveillance and insurance systems are needed.

  15. Mesothelioma from asbestos exposures: Epidemiologic patterns and impact in the United States.

    Science.gov (United States)

    Lemen, Richard A

    2016-01-01

    Mesothelioma, a rare tumor, is highly correlated with asbestos exposure. Mesothelioma, similar to all asbestos-related diseases, is dose/intensity dependent to some degree, and studies showed the risk of mesothelioma rises with cumulative exposures. Multiple processes occur in an individual before mesothelioma occurs. The impact of mesothelioma in the United States has been continuous over the last half century, claiming between 2,000 and 3,000 lives each year. Mesothelioma is a preventable tumor that is more frequently reported as associated with asbestos exposure among men than women. However, the rate of asbestos-associated mesothelioma is on the rise among women due to better investigation into their histories of asbestos exposure. It is of interest that investigators detected asbestos-associated cases of mesothelioma in women from nonoccupational sources-that is, bystander, incidental, or take-home exposures. It is postulated that asbestos-associated mesotheliomas, in both men and women, are likely underreported. However, with the implementation of the most recent ICD-10 coding system, the correlation of mesothelioma with asbestos exposure is expected to rise to approximately 80% in the United States. This study examined the demographic and etiological nature of asbestos-related mesothelioma.

  16. Environmental risk of mesothelioma in the United States: An emerging concern-epidemiological issues.

    Science.gov (United States)

    Baumann, Francine; Carbone, Michele

    2016-01-01

    Despite predictions of decline in mesothelioma following the ban of asbestos in most industrial countries, the incidence is still increasing globally, particularly in women. Because occupational exposure to asbestos is the main cause of mesothelioma, it occurs four- to eightfold more frequently in men than women, at a median age of 74 years. When mesothelioma is due to an environmental exposure, the M:F sex ratio is 1:1 and the median age at diagnosis is ~60 years. Studying environmental risk of mesothelioma is challenging because of the long latency period and small numbers, and because this type of exposure is involuntary and unknown. Individual-based methods cannot be used, and new approaches need to be found. To better understand the most recent trends of mesothelioma in the United States, all mesothelioma deaths reported to the Centers for Disease Control and Prevention (CDC) during 1999-2010 were analyzed. Among all mesothelioma deaths in the United States, the 1920s birth cohort significantly predominated, and the proportion of younger cohorts constantly decreased with time, suggesting a decline in occupational exposure in these cohorts. The M:F mesothelioma sex ratio fell with time, suggesting an increased proportion of environmental cases. Environmental exposures occur in specific geographic areas. At the large scale of a state, mesotheliomas related to environmental exposure are diluted among occupational cases. The spatial analysis at a smaller scale, such as county, enables detection of areas with higher proportions of female and young mesothelioma cases, thus indicating possible environmental exposure, where geological and environmental investigations need to be carried out.

  17. [Update on epidemiology, pathophysiology, diagnosis and treatment of malignant pleural mesothelioma].

    Science.gov (United States)

    Gopar-Nieto, Rodrigo; Cabello-López, Alejandro; Juárez-Pérez, Cuauhtémoc Arturo; Haro-García, Luis Cuauhtémoc; Jiménez-Ramírez, Carmina; Aguilar-Madrid, Guadalupe

    2016-01-01

    Malignant pleural mesothelioma is an occupational tumor caused by asbestos exposure. In Mexico, as asbestos usage is not prohibited, an increase in the number of cases is expected. Asbestos exposure is ubiquitous due to the great amount of products in which it is present. Its carcinogenicity is caused as the inhaled asbestos fibers cannot be eliminated by macrophages and, thus, they travel to the pleura through lymphatic pathways, producing a persistent inflammatory response. Diagnosis approach includes occupational history, along with clinical signs and symptoms, and paraclinical studies, such as pleural fluid cytology, chest x-rays, computed tomography, magnetic resonance imaging, and biopsy with immunohistochemistry. The main differential diagnosis is lung adenocarcinoma. Regarding the treatment of this tumor, it mainly comprises palliative care, even though chemotherapy, radiotherapy, and, in selected cases, surgical treatments have been used. There is an urgent need for general physicians and specialists to identify asbestos exposure, in order to make a timely diagnosis. Research is necessary to develop screening and prompt diagnostic tools, along with an epidemiological surveillance program for the workers and the general population exposed to asbestos.

  18. Biologically-based mechanistic models of radiation-related carcinogenesis applied to epidemiological data.

    Science.gov (United States)

    Rühm, Werner; Eidemüller, Markus; Kaiser, Jan Christian

    2017-10-01

    Biologically-based mechanistic models that are used in combining current understanding of human carcinogenesis with epidemiological studies were reviewed. Assessment was made of how well they fit the data, whether they account for non-linear radiobiological low-dose effects, and whether they suggest any implications for the dose response at low doses and dose rates. However, the present paper does not make an attempt to provide a complete review of the existing literature on biologically-based models and their application to epidemiological data. In most studies the two-stage clonal expansion (TSCE) model of carcinogenesis was used. The model provided robust estimates of identifiable parameters and radiation risk. While relatively simple, it is flexible, so that more stages can easily be added, and tests made of various types of radiation action. In general, the model performed similarly or better than descriptive excess absolute and excess relative risk models, in terms of quality of fit and number of parameters. Only very rarely the shape of dose-response predicted by the models was investigated. For some tumors, when more detailed biological information was known, additional pathways were included in the model. The future development of these models will benefit from growing knowledge on carcinogenesis processes, and in particular from use of biobank tissue samples and advances in omics technologies. Their use appears a promising approach to investigate the radiation risk at low doses and low dose rates. However, the uncertainties involved are still considerable, and the models provide only a simplified description of the underlying complexity of carcinogenesis. Current assumptions in radiation protection including the linear-non-threshold (LNT) model are not in contradiction to what is presently known on the process of cancer development.

  19. Peritoneal mesothelioma

    International Nuclear Information System (INIS)

    Raptopoulos, V.

    1985-01-01

    The definitive diagnosis of peritoneal mesothelioma and its differentiation from metastatic peritoneal carcinomatosis may be difficult because of the clinical, macroscopic, and microscopic variability of the tumor. To this purpose, a combination of criteria, including the clinical picture, the gross pathologic findings, the exclusion of other primary neoplasms, and the microscopic findings, must be taken into consideration. Conventionally, these criteria may be established only after surgical exploration and extensive sampling. Experience with patients with peritoneal mesothelioma and metastatic peritoneal carcinomatosis, as well as a review of the recent imaging literature, shows excellent correlation between computed tomography or ultrasound and the operative or autopsy findings. These imaging modalities showed soft-tissue masses or nodules; thickened omentum (omental cake), peritoneum, mesentery, and bowel wall; pleural plaques; and usually disproportionally small, if any, ascites. The latter two observations may be useful in differentiating mesothelioma from carcinomatosis macroscopically. Furthermore, fine-needle aspiration biopsy, after performing wide sampling of the tumors in different locations under ultrasonic or computed tomographic guidance, produced diagnostic cytologic specimens. Thus, the need for exploratory surgery may be alleviated, and the diagnosis of peritoneal mesothelioma may be made prospectively and relatively noninvasively with the use of computed tomography or ultrasound and fine-needle aspiration biopsy. Since epidemiologic studies predict increasing incidence of this neoplasm, especially among asbestos workers, it is suggested that these techniques be seriously considered as screening methods for high-risk populations.67 references

  20. 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

  1. 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.

  2. Malignant mesothelioma

    OpenAIRE

    Parker Robert J; Moore Alastair J; Wiggins John

    2008-01-01

    Abstract Malignant mesothelioma is a fatal asbestos-associated malignancy originating from the lining cells (mesothelium) of the pleural and peritoneal cavities, as well as the pericardium and the tunica vaginalis. The exact prevalence is unknown but it is estimated that mesotheliomas represent less than 1% of all cancers. Its incidence is increasing, with an expected peak in the next 10–20 years. Pleural malignant mesothelioma is the most common form of mesothelioma. Typical presenting featu...

  3. Investigational Approaches for Mesothelioma

    International Nuclear Information System (INIS)

    Surmont, Veerle F.; Thiel, Eric R. E. van; Vermaelen, Karim; Meerbeeck, Jan P. van

    2011-01-01

    Malignant pleural mesothelioma (MPM) is a rare, aggressive tumor with a poor prognosis. In view of the poor survival benefit from first-line chemotherapy and the lack of subsequent effective treatment options, there is a strong need for the development of more effective treatment approaches for patients with MPM. This review will provide a comprehensive state of the art of new investigational approaches for mesothelioma. In an introductory section, the etiology, epidemiology, natural history, and standard of care treatment for MPM will be discussed. This review provide an update of the major clinical trials that impact mesothelioma treatment, discuss the impact of novel therapeutics, and provide perspective on where the clinical research in mesothelioma is moving. The evidence was collected by a systematic analysis of the literature (2000–2011) using the databases Medline (National Library of Medicine, USA), Embase (Elsevier, Netherlands), Cochrane Library (Great Britain), National Guideline Clearinghouse (USA), HTA Database (International Network of Agencies for Health Technology Assessment – INAHTA), NIH database (USA), International Pleural Mesothelioma Program – WHOLIS (WHO Database), with the following keywords and filters: mesothelioma, guidelines, treatment, surgery, chemotherapy, radiotherapy, review, investigational, drugs. Currently different targeted therapies and biologicals are under investigation for MPM. It is important that the molecular biologic research should first focus on mesothelioma-specific pathways and biomarkers in order to have more effective treatment options for this disease. The use of array technology will be certainly an implicit gain in the identification of new potential prognostic or biomarkers or important pathways in the MPM pathogenesis. Probably a central mesothelioma virtual tissue bank may contribute to the ultimate goal to identify druggable targets and to develop personalized treatment for the MPM patients.

  4. Investigational approaches for mesothelioma

    Directory of Open Access Journals (Sweden)

    Veerle F Surmont

    2011-08-01

    Full Text Available MPM is a rare, aggressive tumour with a poor prognosis. In view of the poor survival benefit from first-line chemotherapy and the lack of subsequent effective treatment options, there is a strong need for the development of more effective treatment approaches for patients with MPM. This review will provide a comprehensive state of the art of new investigational approaches for mesothelioma. In an introductory section, the aetiology, epidemiology, natural history and standard of care treatment for MPM will be discussed. This review provide an update of the major clinical trials that impact mesothelioma treatment, discuss the impact of novel therapeutics and provide perspective on where the clinical research in mesothelioma is moving.The evidence was collected by a systematic analysis of the literature (2000–2011 using the databases Medline (National Library of Medicine, USA, Embase (Elsevier, Netherlands, Cochrane Library (Great Britain, National Guideline Clearinghouse (USA, HTA Database (International Network of Agencies for Health Technology Assessment – INAHTA, NIH database (USA, International Pleural Mesothelioma Program – WHOLIS (WHO Database , with the following keywords and filters: mesothelioma, guidelines, treatment, surgery, chemotherapy, radiotherapy, review, investigational, drugsCurrently different targeted therapies and biologicals are under investigation for MPM. It is important that the molecular biologic research should first focus on mesothelioma-specific pathways and biomarkers in order to have more effective treatment options for this disease. The use of array technology will be certainly an implicit gain in the identification of new potential prognostic or biomarkers or important pathways in the MPM pathogenesis. Probably a central mesothelioma virtual tissue bank may contribute to the ultimate goal to identify druggable targets and to develop personalized treatment for the MPM patients.

  5. Malignant mesothelioma

    Directory of Open Access Journals (Sweden)

    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.

  6. III Italian Consensus Conference on Malignant Mesothelioma of the Pleura. Epidemiology, Public Health and Occupational Medicine related issues.

    Science.gov (United States)

    Magnani, C; Bianchi, C; Chellini, E; Consonni, D; Fubini, B; Gennaro, V; Marinaccio, A; Menegozzo, M; Mirabelli, D; Merler, E; Merletti, F; Musti, M; Oddone, E; Romanelli, A; Terracini, B; Zona, A; Zocchetti, C; Alessi, M; Baldassarre, A; Dianzani, I; Maule, M; Mensi, C; Silvestri, S

    2015-09-09

    The III Italian Consensus Conference on Pleural Mesothelioma (MM) convened on January 29th 2015. This report presents the conclusions of the 'Epidemiology, Public Health and Occupational Medicine' section. MM incidence in 2011 in Italy was 3.64 per 100,000 person/years in men and 1.32 in women. Incidence trends are starting to level off. Ten percent of cases are due to non-occupational exposure. Incidence among women is very high in Italy, because of both non-occupational and occupational exposure. The removal of asbestos in place is proceeding slowly, with remaining exposure. Recent literature confirms the causal role of chrysotile. Fibrous fluoro-edenite was classified as carcinogenic by IARC (Group 1) on the basis of MM data. A specific type (MWCNT-7) of Carbon Nanotubes was classified 2B. For pleural MM, after about 45 years since first exposure, the incidence trend slowed down; with more studies needed. Cumulative exposure is a proxy of the relevant exposure, but does not allow to distinguish if duration or intensity may possibly play a prominent role, neither to evaluate the temporal sequence of exposures. Studies showed that duration and intensity are independent determinants of MM. Blood related MM are less than 2.5%. The role of BAP1 germline mutations is limited to the BAP1 cancer syndrome, but negligible for sporadic cases. Correct MM diagnosis is baseline; guidelines agree on the importance of the tumor gross appearance and of the hematoxylin-eosin-based histology. Immunohistochemical markers contribute to diagnostic confirmation: the selection depends on morphology, location, and differential diagnosis. The WG suggested that 1) General Cancer Registries and ReNaM Regional Operational Centres (COR) interact and systematically compare MM cases; 2) ReNaM should report results presenting the diagnostic certainty codes and the diagnostic basis, separately; 3) General Cancer Registries and COR should interact with pathologists to assure the up

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

    Energy Technology Data Exchange (ETDEWEB)

    Fabrikant, J.I.

    1982-08-01

    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.

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

    International Nuclear Information System (INIS)

    Fabrikant, J.I.

    1982-08-01

    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

  9. 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

  10. Peritoneal Mesothelioma

    Science.gov (United States)

    ... 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. ...

  11. Peritoneal mesothelioma

    International Nuclear Information System (INIS)

    Ros, P.R.; Yuschok, T.J.; Buck, J.L.; Shekitka, K.M.; Kaude, J.V.; Armed Forces Inst. of Pathology, Washington, DC

    1991-01-01

    Previous imaging reports of peritoneal mesothelioma have described a variety of radiologic appearances, but have not included its pathologic classification. We retrospectively reviewed 10 cases of peritoneal mesothelioma representing the following histologic categories: 7 epithelial, 2 sarcomatoid, and one biphasic. By imaging, epithelial mesotheliomas demonstrated diffuse thickening of the peritoneum and mesentery and/or multiple small nodules. The sarcomatoid-type appeared as a mass and the biphasic-type had radiologic and gross pathologic features of both sarcomatoid and epithelial types. We conclude that peritoneal mesothelioma presents with a wide spectrum of radiographic appearances and should therefore be included in the differential diagnoses of diffuse as well as localized peritoneal processes. (orig.)

  12. 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.

  13. Mesothelioma Applied Research Foundation

    Science.gov (United States)

    Mesothelioma Foundation Experts Can Answer Your Questions! The Mesothelioma Applied Research Foundation's team of experts is available ... up for our e-newsletter . Our Impact Against Mesothelioma 9.8 Million in research funded 600 People ...

  14. Chemical carcinogenesis

    Directory of Open Access Journals (Sweden)

    Paula A. Oliveira

    2007-12-01

    Full Text Available The use of chemical compounds benefits society in a number of ways. Pesticides, for instance, enable foodstuffs to be produced in sufficient quantities to satisfy the needs of millions of people, a condition that has led to an increase in levels of life expectancy. Yet, at times, these benefits are offset by certain disadvantages, notably the toxic side effects of the chemical compounds used. Exposure to these compounds can have varying effects, ranging from instant death to a gradual process of chemical carcinogenesis. There are three stages involved in chemical carcinogenesis. These are defined as initiation, promotion and progression. Each of these stages is characterised by morphological and biochemical modifications and result from genetic and/or epigenetic alterations. These genetic modifications include: mutations in genes that control cell proliferation, cell death and DNA repair - i.e. mutations in proto-oncogenes and tumour suppressing genes. The epigenetic factors, also considered as being non-genetic in character, can also contribute to carcinogenesis via epigenetic mechanisms which silence gene expression. The control of responses to carcinogenesis through the application of several chemical, biochemical and biological techniques facilitates the identification of those basic mechanisms involved in neoplasic development. Experimental assays with laboratory animals, epidemiological studies and quick tests enable the identification of carcinogenic compounds, the dissection of many aspects of carcinogenesis, and the establishment of effective strategies to prevent the cancer which results from exposure to chemicals.A sociedade obtém numerosos benefícios da utilização de compostos químicos. A aplicação dos pesticidas, por exemplo, permitiu obter alimento em quantidade suficiente para satisfazer as necessidades alimentares de milhões de pessoas, condição relacionada com o aumento da esperança de vida. Os benefícios estão, por

  15. Advances in diffuse malignant peritoneal mesothelioma

    Directory of Open Access Journals (Sweden)

    Tristan D. Yan

    2011-12-01

    Full Text Available Malignant mesothelioma is a highly aggressive neoplasm. The incidence of malignant mesothelioma is increasing worldwide. Diffuse malignant peritoneal mesothelioma (DMPM represents one-fourth of all mesotheliomas. Association of asbestos exposure with DMPM has been observed, especially in males. A great majority of patients present with abdominal pain and distension, caused by accumulation of tumors and ascitic fluid. In the past, DMPM was considered a pre-terminal condition; therefore attracted little attention. Patients invariably died from their disease within a year. Recently, several prospective trials have demonstrated median survival of 40 to 90 months and 5-year survival of 30% to 60% after the combined treatment using cytoreductive surgery and perioperative intraperitoneal chemotherapy. This improvement in survival has prompted new searches into the medical science related to DMPM, a disease previously ignored as uninteresting. This review article focuses on the key advances in the epidemiology, diagnosis, staging, treatments and prognosis of DMPM that have occurred in the past decade.

  16. Advances in treatment of mesothelioma.

    Science.gov (United States)

    Maggioni, C; Barletta, G; Rijavec, E; Biello, F; Gualco, E; Grossi, F

    2016-06-01

    Malignant pleural mesothelioma (MPM) is an uncommon, aggressive cancer, derived from pleural mesothelial cells, that has a close relationship to asbestos exposure. To date, MPM prognosis is poor and very few treatment options are available for both localized and advanced MPM. The standard of care is still chemotherapy with platinum derivates and antifolate agents. In the last few years, several new agents have been studied on the basis of mesothelioma carcinogenesis and invasiveness mechanisms; however, the recent results are poor and few drugs have been tested in phase III trials because of toxicity or because they did not improve patient outcomes. The aim of this review is to focus on the current available treatment for MPM through the analysis of the results comes from the phase III trials and to discuss the future perspectives in the pathogenesis, diagnosis and treatment. Many compounds are currently under investigation in different subsets of patients. Interesting data have come from preliminary studies on immunotherapy, but randomized studies are needed to confirm the preliminary positive results of this new strategy. A better comprehension of MPM pathogenesis should be obtained to improve and develop new diagnostic tools and target therapies.

  17. Recent advances in metal carcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Sunderman, F.W. Jr.

    Recent advances in metal carcinogenesis are comprehensively reviewed, including (a) epidemiological and clinical aspects, (b) carcinogenesis bioassays, (c) bacterial mutagenesis, (d) mammalian cell mutagenesis, (e) chromosomal damage, (f) mammalian cell transformation, (g) microsomal metabolism, (h) DNA strandbreaks and crosslinks, (i) DNA polymerase infidelity, (j) RNA strand initiation, and (k) helical transition of B-DNA to Z-DNA. Based upon these observations, several hypotheses are proposed for the molecular pathogenesis of carcinogenesis by metal compounds. These hypotheses are amenable to experimental test by existing techniques of molecular biology.

  18. The Cappadocia mesothelioma epidemic: its influence in Turkey and abroad.

    Science.gov (United States)

    Emri, Salih A

    2017-06-01

    The epidemic of mesothelioma in Cappadocia, Turkey, is unprecedented in medical history. In three Cappadocian villages, Karain, Tuzkoy and "old" Sarihidir, about 50% of all deaths (including neonatal deaths and traffic fatalities) have been caused by mesothelioma. No other epidemic in medical history has caused such a high incidence of death. This is even more unusual when considering that (I) epidemics are caused by infectious agents, not cancer, and (II) mesothelioma is a rare cancer. World-wide mesothelioma incidence varies between 1/10 6 in areas with no asbestos industry to about 10-30/10 6 in areas with asbestos industry. This article reviews how the mesothelioma epidemic was discovered in Cappadocia by Dr. Baris (my mentor), how we initially linked the epidemic to erionite exposure, and later (with Dr. Carbone) to the interaction between genetic predisposition and environmental exposure. Our team's work had an important positive impact on the lives of those living in Cappadocia and also in many genetically predisposed families living around the world. I will discuss how the work that started in three remote Cappadocian villages led to the award of a NCI P01 grant to support our studies. Our studies proved that genetics modulates mineral fiber carcinogenesis and led to the discovery that carriers of germline BAP1 mutations have a very high risk of developing mesothelioma and other malignancies. A new, very active field of research developed following our discoveries to elucidate the mechanism by which BAP1 modulates mineral fiber carcinogenesis as well as to identify additional genes that when mutated increase the risk of mesothelioma and other environmentally related cancers. I am the only surviving member of this research team who saw all the phases of this research and I believe it is important to provide an accurate report, which hopefully will inspire others.

  19. Induction Therapy for Mesothelioma.

    Science.gov (United States)

    Opitz, Isabelle; Weder, Walter

    2015-01-01

    One particular approach of multimodality treatment for mesothelioma is induction therapy followed by surgery. Among its several advantages, the most important is downstaging of the tumor into a resectable stage, although morbidity and mortality might be increased. In this article we review the principles and outcome of different modalities for induction treatment of mesothelioma. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. 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

  1. 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

  2. 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.)

  3. Statistical modeling and extrapolation of carcinogenesis data

    International Nuclear Information System (INIS)

    Krewski, D.; Murdoch, D.; Dewanji, A.

    1986-01-01

    Mathematical models of carcinogenesis are reviewed, including pharmacokinetic models for metabolic activation of carcinogenic substances. Maximum likelihood procedures for fitting these models to epidemiological data are discussed, including situations where the time to tumor occurrence is unobservable. The plausibility of different possible shapes of the dose response curve at low doses is examined, and a robust method for linear extrapolation to low doses is proposed and applied to epidemiological data on radiation carcinogenesis

  4. Malignant pleural mesothelioma: an update on investigation, diagnosis and treatment.

    Science.gov (United States)

    Bibby, Anna C; Tsim, Selina; Kanellakis, Nikolaos; Ball, Hannah; Talbot, Denis C; Blyth, Kevin G; Maskell, Nick A; Psallidas, Ioannis

    2016-12-01

    Malignant pleural mesothelioma is an aggressive malignancy of the pleural surface, predominantly caused by prior asbestos exposure. There is a global epidemic of malignant pleural mesothelioma underway, and incidence rates are predicted to peak in the next few years.This article summarises the epidemiology and pathogenesis of malignant pleural mesothelioma, before describing some key factors in the patient experience and outlining common symptoms. Diagnostic approaches are reviewed, including imaging techniques and the role of various biomarkers. Treatment options are summarised, including the importance of palliative care and methods of controlling pleural effusions. The evidence for chemotherapy, radiotherapy and surgery is reviewed, both in the palliative setting and in the context of trimodality treatment. An algorithm for managing malignant pleural effusion in malignant pleural mesothelioma patients is presented. Finally new treatment developments and novel therapeutic approaches are summarised. Copyright ©ERS 2016.

  5. Mesothelioma - benign-fibrous

    Science.gov (United States)

    ... the cancerous type of this disease, called malignant mesothelioma , which is caused by exposure to asbestos. SFT is not caused by asbestos exposure. Treatment Treatment is usually to remove the tumor. Outlook ( ...

  6. Drugs Approved for Malignant Mesothelioma

    Science.gov (United States)

    ... about Your Treatment Research Drugs Approved for Malignant Mesothelioma This page lists cancer drugs approved by the ... are not listed here. Drugs Approved for Malignant Mesothelioma Alimta (Pemetrexed Disodium) Pemetrexed Disodium Drug Combinations Used ...

  7. 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)

  8. Mesothelioma Treatment: Recovery, Side Effects, What to Expect

    Science.gov (United States)

    ... Treatment > Mesothelioma Treatment > Mesothelioma Treatment Recovery Side Effects Mesothelioma Treatment and Recovery Scenarios: e-News Signup Click ... questions. (877) END-MESO (877) 363-6376 Testimonials Mesothelioma Treatment: Recovery, Side Effects, What to Expect Mesothelioma ...

  9. 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

  10. Mesothelioma in Mongolia: case report.

    Science.gov (United States)

    Damiran, Naransukh; Davaajav, Khishigtogtokh; Erdenebayar, Erdenechimeg; Gomboloi, Burmaa; Frank, Arthur L

    2015-01-01

    More than 80% of cases of mesothelioma worldwide have a history of asbestos exposure. In Mongolia, workers in coal burning thermal power plants (TPP) have widely utilized asbestos as an insulation material. We describe the case of a 47-year-old woman diagnosed with a malignant pleural mesothelioma. She worked in a TPP in Ulaanbaatar, Mongolia for 28 years. A computer tomography (CT) scan showed a circumferential ring around her left lung, and tissues' samples had a biphasic variant of mesothelioma with epithelioid and sarcomatoid components. This is the first reported case of mesothelioma in Mongolia. We expect additional cases of mesothelioma, as well as other asbestos related diseases, will be identified in the future. In order to properly track asbestos related diseases in the country, we recommend the creation of an asbestos related disease registry.

  11. 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)

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  13. Mesothelioma in Australia: a review.

    Science.gov (United States)

    Musk, Arthur Bill W; de Klerk, Nicholas; Brims, Fraser J

    2017-11-20

    The incidence of malignant mesothelioma in Australia is among the highest in the world as a result of widespread use of asbestos by industry and in construction throughout the 20th century. The risk of developing malignant mesothelioma after asbestos exposure is dose-related; a transient, low dose exposure confers a correspondingly very low risk of disease. Malignant mesothelioma is a heterogeneous disease, partly explaining the limited role of biomarkers in screening and diagnosis. The prognosis remains poor, and early advice on medico-legal compensation and a collaborative team approach to managing malignant mesothelioma are both essential. Chemotherapy can have a modest treatment effect in some people. New therapies, such as immunotherapy, do not yet have a defined role in the treatment of malignant mesothelioma. As treatment options for malignant mesothelioma are limited and no cure is available, there is no established role for early detection or screening of at risk populations. A multidisciplinary approach to caring for patients with malignant mesothelioma and their carers is vital.

  14. [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.

  15. Malignant Mesothelioma: Facts, Myths and Hypotheses

    Science.gov (United States)

    Carbone, Michele; Ly, Bevan H.; Dodson, Ronald F.; Pagano, Ian; Morris, Paul T.; Dogan, Umran A.; Gazdar, Adi F.; Pass, Harvey I.; Yang, Haining

    2011-01-01

    Malignant mesothelioma (MM) is a neoplasm arising from mesothelial cells lining the pleural, peritoneal, and pericardial cavities. Over 20 million people in the US are at risk of developing MM due to asbestos exposure. MM mortality rates are estimated to increase by 5-10% per year in most industrialized countries until about 2020. The incidence of MM in men has continued to rise during the past 50 years, while the incidence in women appears largely unchanged. It is estimated that about 50-80% of pleural MM in men and 20-30% in women developed in individuals whose history indicates asbestos exposure(s) above that expected from most background settings. While rare for women, about 30% of peritoneal mesothelioma in men has been associated with exposure to asbestos. Erionite is a potent carcinogenic mineral fiber capable of causing both pleural and peritoneal MM. Since erionite is considerably less widespread than asbestos, the number of MM cases associated with erionite exposure is smaller. Asbestos induces DNA alterations mostly by inducing mesothelial cells and reactive macrophages to secrete mutagenic oxygen and nitrogen species. In addition, asbestos carcinogenesis is linked to the chronic inflammatory process caused by the deposition of a sufficient number of asbestos fibers and the consequent release of pro-inflammatory molecules, especially HMGB-1, the master switch that starts the inflammatory process, and TNF-alpha by macrophages and mesothelial cells. Genetic predisposition, radiation exposure and viral infection are co-factors that can alone or together with asbestos and erionite cause MM. PMID:21412769

  16. Optimization Aspects of Carcinogenesis

    OpenAIRE

    Brutovsky, B.; Horvath, D.

    2009-01-01

    Any process in which competing solutions replicate with errors and numbers of their copies depend on their respective fitnesses is the evolutionary optimization process. As during carcinogenesis mutated genomes replicate according to their respective qualities, carcinogenesis obviously qualifies as the evolutionary optimization process and conforms to common mathematical basis. The optimization view accents statistical nature of carcinogenesis proposing that during it the crucial role is actu...

  17. 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

  18. 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

  19. [National epidemiological surveillance systems of mesothelioma cases].

    Science.gov (United States)

    Ferrante, Pierpaolo; Binazzi, Alessandra; Branchi, Claudia; Marinaccio, Alessandro

    2016-01-01

    INTRODUZIONE: sebbene la relazione causale tra esposizione ad amianto e malattie neoplastiche sia ben nota, in molti Paesi il consumo del materiale è ancora rilevante e crescente. A causa della lunga latenza, nei Paesi dove è stato bandito (come in Italia) è oggi in corso un'epidemia di malattie correlate ad amianto. OBIETTIVI: descrivere i sistemi di sorveglianza dei mesoteliomi attivi nel mondo mediante un'analisi comparativa. è stata condotta una revisione bibliografica della letteratura disponibile sui sistemi di sorveglianza epidemiologica dei mesoteliomi attivi nel mondo, comparando metodi e risultati disponibili. RISULTATI: sistemi di ricerca dei casi incidenti e di analisi anamnestica dei soggetti ammalati sono attivi solo in Italia, Francia e Corea del Sud. I Paesi presso i quali sono attivi sistemi di rilevazione e controllo dei casi incidenti di mesotelioma sono quelli in cui vige il bando dell'amianto e che hanno sperimentato consumi rilevanti in passato. Non sono stati istituiti sistemi epidemiologici di sorveglianza in molti Paesi dove il consumo di amianto è ancora importante (inclusi Russia, Cina, India e Brasile). CONCLUSIONI: si conferma l'importanza dei sistemi di sorveglianza epidemiologica dei mesoteliomi per la sanità pubblica, il sostegno alle politiche di welfare e la prevenzione dei rischi. Lo sviluppo di progetti per tendere a una maggiore uniformità nei metodi di ricerca dei casi, di classificazione delle diagnosi e dell'esposizione e nelle tecniche di analisi dei dati potrebbe consentire una maggiore fruibilità dei dati aggregati. La disponibilità di dati internazionali confrontabili può essere di stimolo all'adozione di provvedimenti di bando internazionale.

  20. 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.

  1. Malignant peritoneal mesothelioma and Crohn disease.

    Science.gov (United States)

    Butnor, Kelly J; Pavlisko, Elizabeth N; Sporn, Thomas A; Roggli, Victor L

    2017-03-01

    Mesothelial reaction simulating peritoneal diffuse malignant mesothelioma (MM) has been reported in the setting of Crohn ileitis. To our knowledge, peritoneal MM arising in patients with inflammatory bowel disease (IBD) has not been reported. The purpose of this study is to report the clinicopathological characteristics of patients with peritoneal MM and IBD. A database of approximately 3800 MM was reviewed for cases of MM in patients with IBD. Three patients (0.08%) with peritoneal MM and Crohn disease (CD) were identified, including two women and one man ranging in age from 56 to 65 years. All had a long-standing history of diarrhoea and an established diagnosis of CD of 3 years or greater duration. Two had epithelial MM and one had biphasic MM. Only one had documented asbestos exposure. Peritoneal MM occurs rarely in patients with IBD, but interestingly, has only been observed in the setting of CD and not in patients with ulcerative colitis. Chronic inflammation has been associated with the development of MM in rare instances and these three cases suggest that CD with transmural inflammation may also be a precursor. The precise role of CD-related transmural inflammation in the carcinogenesis of peritoneal MM remains to be determined. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

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

    Science.gov (United States)

    Amin, Waqas; Parwani, Anil V; Schmandt, Linda; Mohanty, Sambit K; Farhat, Ghada; Pople, Andrew K; Winters, Sharon B; Whelan, Nancy B; Schneider, Althea M; Milnes, John T; Valdivieso, Federico A; Feldman, Michael; Pass, Harvey I; Dhir, Rajiv; Melamed, Jonathan; Becich, Michael J

    2008-08-13

    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. 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. 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. 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 research. Furthermore, it protects patient privacy by disclosing only

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

    Directory of Open Access Journals (Sweden)

    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

  4. 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.)

  5. Malignant mesothelioma: ultrastructural distinction from adenocarcinoma.

    Science.gov (United States)

    Warhol, M J; Hickey, W F; Corson, J M

    1982-06-01

    Mesotheliomas and metastatic adenocarcinomas involving the pleura are frequently difficult to distinguish by light-microscopic and histochemical methods. In a double-blind study, we have compared ultrastructural features of 10 mesotheliomas of epithelial type and 10 adenocarcinomas from the lung, breast, and upper GI tract, i.e., sites known to give rise to metastases which mimic mesothelioma. Mesotheliomas were observed to have a significantly greater microvillus length/diameter ratio (LDR) than adenocarcinomas (p less than 0.01) and more abundant intermediate filaments (p less than 0.001). Mesotheliomas had more complex microvilli than adenocarcinomas, whereas adenocarcinomas had rootlets (2/10 cases) and lamellar inclusion bodies (2/10 cases), both of which were absent in the mesotheliomas. This study provides quantitative and qualitative ultrastructural features of potential utility in the differential diagnosis of pleural mesotheliomas and adenocarcinomas.

  6. Malignant pleural mesothelioma: history, controversy and future of a manmade epidemic

    Directory of Open Access Journals (Sweden)

    Oluf Dimitri Røe

    2015-03-01

    Full Text Available Asbestos is the term for a family of naturally occurring minerals that have been used on a small scale since ancient times. Industrialisation demanded increased mining and refining in the 20th century, and in 1960, Wagner, Sleggs and Marchand from South Africa linked asbestos to mesothelioma, paving the way to the current knowledge of the aetiology, epidemiology and biology of malignant pleural mesothelioma. Pleural mesothelioma is one of the most lethal cancers, with increasing incidence worldwide. This review will give some snapshots of the history of pleural mesothelioma discovery, and the body of epidemiological and biological research, including some of the controversies and unresolved questions. Translational research is currently unravelling novel circulating biomarkers for earlier diagnosis and novel treatment targets. Current breakthrough discoveries of clinically promising noninvasive biomarkers, such as the 13-protein signature, microRNAs and the BAP1 mesothelioma/cancer syndrome, are highlighted. The asbestos history is a lesson to not be repeated, but here we also review recent in vivo and in vitro studies showing that manmade carbon nanofibres could pose a similar danger to human health. This should be taken seriously by regulatory bodies to ensure thorough testing of novel materials before release in the society.

  7. Malignant mesothelioma following radiation therapy.

    Science.gov (United States)

    Hofmann, J; Mintzer, D; Warhol, M J

    1994-10-01

    Studies of the growing population of long-term survivors of cancer have led to increased recognition of the neoplastic complications of therapy. The causes of secondary malignancies are probably multifactorial, but radiation therapy and chemotherapy have certainly been implicated in the development of posttherapy neoplasia. A case of pleural mesothelioma after successful radiation therapy for Hodgkin's disease is described with a review of radiation-associated mesotheliomas reported in the literature. In Hodgkin's disease, patients may receive radiation, chemotherapy, or combined treatment; the most common secondary malignancy is acute nonlymphocytic leukemia while sarcomas are the second most common solid tumors. Although mesothelioma is an uncommon sarcoma, its occurrence has been documented numerous times after exposure to diagnostic or therapeutic radiation.

  8. 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

  9. 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.

  10. Establishment of a novel specific ELISA system for rat N- and C-ERC/mesothelin. Rat ERC/mesothelin in the body fluids of mice bearing mesothelioma.

    Science.gov (United States)

    Hagiwara, Yoshiaki; Hamada, Yukiko; Kuwahara, Maki; Maeda, Masahiro; Segawa, Tatsuya; Ishikawa, Kiyoshi; Hino, Okio

    2008-04-01

    Mesothelioma is a type of malignant tumor that most commonly arises from the pleural or peritoneal membrane and is usually associated with previous exposure to asbestos. In humans, ERC/mesothelin is expressed on the normal mesothelium and in some cancers such as mesothelioma or ovarian carcinoma. Recently, several enzyme-linked immunosorbent assay (ELISA) systems for ERC/mesothelin have been developed, the reported usefulness of which has been assessed and demonstrated as a diagnostic tool. However, the basic roles or physiological functions of, and relationship between, ERC/mesothelin and asbestos exposure-mediated carcinogenesis remain to be resolved. In order to elucidate the precise mechanism, animal models of mesothelioma are desperately needed. In this study, we consider the development of a novel specific ELISA system for not only rat N-ERC/mesothelin but also C-ERC/mesothelin, and the first data on the presence of rat ERC/mesothelin in the body fluids of rat malignant mesothelioma-bearing nude mice. The transplanted mice have revealed the higher concentrations of rat N-ERC/mesothelin in the blood and ascites than C-ERC/mesothelin. We hope these novel ELISA systems are useful in the rat model system to clarify the mechanism of asbestos-induced carcinogenesis and to develop new effective drugs for mesothelioma.

  11. Immunotherapy advances for mesothelioma treatment.

    Science.gov (United States)

    Bakker, Emyr; Guazzelli, Alice; Ashtiani, Firozeh; Demonacos, Constantinos; Krstic-Demonacos, Marija; Mutti, Luciano

    2017-09-01

    Mesothelioma is a rare type of cancer that is strongly tied to asbestos exposure. Despite application of different modalities such as chemotherapy, radiotherapy and surgery, patient prognosis remains very poor and therapies are ineffective. Much research currently focuses on the application of novel approaches such as immunotherapy towards this disease. Areas covered: The types, stages and aetiology of mesothelioma are detailed, followed by a discussion of the current treatment options such as radiotherapy, surgery, and chemotherapy. A description of innate and adaptive immunity and the principles and justification of immunotherapy is also included. Clinical trials for different immunotherapeutic modalities are described, and lastly the article closes with an expert commentary and five-year view, the former of which is summarised below. Expert commentary: Current efforts for novel mesothelioma therapies have been limited by attempting to apply treatments from other cancers, an approach which is not based on a solid understanding of mesothelioma biology. In our view, the influence of the hostile, hypoxic microenvironment and the gene expression and metabolic changes that resultantly occur should be characterised to improve therapies. Lastly, clinical trials should focus on overall survival rather than surrogate endpoints to avoid bias and inaccurate reflections of treatment effects.

  12. 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)

  13. [Mesothelioma--asbestos in Lebanon: a problem to be considered].

    Science.gov (United States)

    Kattan, J; Faraj, H; Ghosn, M; Chahine, G; Assaf, E; Abadjian, G; Khoury, F

    2001-01-01

    To estimate the incidence of pleural mesothelioma and its relationship with the occupational and environmental exposure to asbestos in Chekka region. Between 1991 and 2000, 22 cases of malignant mesothelioma were diagnosed at Hôtel-Dieu de France Hospital. Eighteen cases were epidemiologically investigated. Fifteen among these 18 patients (83%) had a positive exposure history: exposure was occupational in 11 cases and environmental in 4 cases. The tumor was attributable to Eternit Company in 12 cases among the exposed 15 (80%). These 12 cases were secondary to occupational exposures in 8 and to environmental exposure in 4 cases. Mean latency period between exposition and diagnosis was 29 years. Fifteen patients died from the progression of their disease after a median survival of 8 months. The relationship between pleural mesothelioma and Eternit Company with the related occupational and environmental risk in Chekka region is obvious. The assessment of the incidence needs a national cancer registry. Despite the protective measures taken by the government since 1996, an increase in the incidence is suspected in the coming ten years because of the long latency period of the disease.

  14. Optimization aspects of carcinogenesis.

    Science.gov (United States)

    Brutovsky, B; Horvath, D

    2010-05-01

    Any process in which competing solutions replicate with errors and numbers of their copies depend on their respective fitnesses is the evolutionary optimization process. As during carcinogenesis mutated genomes replicate according to their respective qualities, carcinogenesis obviously qualifies as the evolutionary optimization process and conforms to common mathematical basis. The optimization view accents statistical nature of carcinogenesis proposing that during it the crucial role is actually played by the allocation of trials. Optimal allocation of trials requires reliable schemas' fitnesses estimations which necessitate appropriate, fitness landscape dependent, statistics of population. In the spirit of the applied conceptual framework, features which are known to decrease efficiency of any evolutionary optimization procedure (or inhibit it completely) are anticipated as "therapies" and reviewed. Strict adherence to the evolutionary optimization framework leads us to some counterintuitive implications which are, however, in agreement with recent experimental findings, such as sometimes observed more aggressive and malignant growth of therapy surviving cancer cells.

  15. 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

  16. 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).

  17. 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)

  18. Changing Pattern in Malignant Mesothelioma Survival

    Directory of Open Access Journals (Sweden)

    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.

  19. Experimental radiation carcinogenesis

    International Nuclear Information System (INIS)

    Walburg, H.E. Jr.

    1974-01-01

    Literature on radioinduced carcinogenesis in experimental animals is reviewed with emphasis on the basic principles which could lead to a better predictability of radiation effects in man. It was concluded that the animal systems studied thus far are quantitatively inadequate for determining radiation risk estimates in man. (350 references.) (U.S.)

  20. Malignant mesothelioma not related to asbestos exposure: Analytical scanning electron microscopic analysis of 83 cases and comparison with 442 asbestos-related cases.

    Science.gov (United States)

    Kraynie, Alyssa; de Ridder, Gustaaf G; Sporn, Thomas A; Pavlisko, Elizabeth N; Roggli, Victor L

    2016-01-01

    Epidemiological studies indicate that 80-90% of mesotheliomas are asbestos related. This suggests that 10-20% are not. Lung fiber burden analysis provides objective information about past exposures to asbestos. We have performed lung fiber burden analysis on a large cohort of mesothelioma cases and compared the findings with a reference population. Herein we report our findings along with demographic and exposure data.

  1. Radiosensitivity of mesothelioma cell lines

    International Nuclear Information System (INIS)

    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.)

  2. 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,

  3. 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

  4. 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,

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

    Data.gov (United States)

    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...

  6. Carcinogenesis of cutaneous malignancies.

    Science.gov (United States)

    Buzzell, R A

    1996-03-01

    Over the past several years significant progress has been made in identifying the cellular and biochemical mechanisms underlying carcinogenesis. This review summarizes recent advances that have helped clarify the process of malignant transformation in cutaneous tumors. Ultraviolet radiation-induced mutations in the p53 tumor suppressor gene and human papilloma virus inhibition of the p53 and retinoblastoma tumor suppressor gene products appear to play significant roles in the development of many cutaneous squamous cell carcinomas. Studies of patients with the nevoid basal cell carcinoma syndrome suggest the existence of an additional regulatory gene that may be involved in the development of basal cell carcinomas. Carcinogenesis is multistep process involving genetic and epigenetic alterations to specific proto-oncogene and tumor suppressor gene products that progressively release the cell from normal controlled growth and replication.

  7. 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.)

  8. 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.

  9. Germline mutations in DNA repair genes predispose asbestos-exposed patients to malignant pleural mesothelioma.

    Science.gov (United States)

    Betti, Marta; Casalone, Elisabetta; Ferrante, Daniela; Aspesi, Anna; Morleo, Giulia; Biasi, Alessandra; Sculco, Marika; Mancuso, Giuseppe; Guarrera, Simonetta; Righi, Luisella; Grosso, Federica; Libener, Roberta; Pavesi, Mansueto; Mariani, Narciso; Casadio, Caterina; Boldorini, Renzo; Mirabelli, Dario; Pasini, Barbara; Magnani, Corrado; Matullo, Giuseppe; Dianzani, Irma

    2017-10-01

    Malignant pleural mesothelioma (MPM) is a rare, aggressive cancer caused by asbestos exposure. An inherited predisposition has been suggested to explain multiple cases in the same family and the observation that not all individuals highly exposed to asbestos develop the tumor. Germline mutations in BAP1 are responsible for a rare cancer predisposition syndrome that includes predisposition to mesothelioma. We hypothesized that other genes involved in hereditary cancer syndromes could be responsible for the inherited mesothelioma predisposition. We investigated the prevalence of germline variants in 94 cancer-predisposing genes in 93 MPM patients with a quantified asbestos exposure. Ten pathogenic truncating variants (PTVs) were identified in PALB2, BRCA1, FANCI, ATM, SLX4, BRCA2, FANCC, FANCF, PMS1 and XPC. All these genes are involved in DNA repair pathways, mostly in homologous recombination repair. Patients carrying PTVs represented 9.7% of the panel and showed lower asbestos exposure than did all the other patients (p = 0.0015). This suggests that they did not efficiently repair the DNA damage induced by asbestos and leading to carcinogenesis. This study shows that germline variants in several genes may increase MPM susceptibility in the presence of asbestos exposure and may be important for specific treatment. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  10. 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.

  11. Radiosensitivity of mesothelioma cell lines

    Energy Technology Data Exchange (ETDEWEB)

    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.).

  12. 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)

  13. Duodenal Metastasis of Malignant Pleural Mesothelioma

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  15. 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.)

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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.)

  1. Cell proliferation in carcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Cohen, S.M.; Ellwein, L.B. (Univ. of Nebraska Medical Center, Omaha (USA))

    1990-08-31

    Chemicals that induce cancer at high doses in animal bioassays often fail to fit the traditional characterization of genotoxins. Many of these nongenotoxic compounds (such as sodium saccharin) have in common the property that they increase cell proliferation in the target organ. A biologically based, computerized description of carcinogenesis was used to show that the increase in cell proliferation can account for the carcinogenicity of nongenotoxic compounds. The carcinogenic dose-response relationship for genotoxic chemicals (such as 2-acetylaminofluorene) was also due in part to increased cell proliferation. Mechanistic information is required for determination of the existence of a threshold for the proliferative (and carcinogenic) response of nongenotoxic chemicals and the estimation of risk for human exposure.

  2. 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.)

  3. 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

  4. 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.)

  5. Malignant mesothelioma: development to therapy.

    Science.gov (United States)

    Thompson, Joyce K; Westbom, Catherine M; Shukla, Arti

    2014-01-01

    Malignant mesothelioma (MM) is an aggressive cancer of the mesothelium caused by asbestos. Asbestos use has been reduced but not completely stopped. In addition, natural or man-made disasters will continue to dislodge asbestos from old buildings into the atmosphere and as long as respirable asbestos is available, MM will continue to be a threat. Due to the long latency period of MM development, it would still take decades to eradicate this disease if asbestos was completely removed from our lives today. Therefore, there is a need for researchers and clinicians to work together to understand this deadly disease and find a solution for early diagnosis and treatment. This article focuses on developmental mechanisms as well as current therapies available for MM. © 2013 Wiley Periodicals, Inc.

  6. Glyco-Immune Diagnostic Signatures and Therapeutic Targets of Mesothelioma

    Science.gov (United States)

    2013-07-01

    experiments using rat model of human Mesothelioma should also provide leads into the immuno-preventive and immuno- therapeutic approaches to treatments ...experiments involving injection of rat Mesothelioma cells and treatments of the resulting tumors. These experiments will begin as soon as we have...Targets of Mesothelioma PRINCIPAL INVESTIGATOR: Harvey Pass, M.D. CONTRACTING ORGANIZATION: New York University School of Medicine

  7. 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.

  8. Mesothelioma incidence and asbestos exposure in Italian national priority contaminated sites.

    Science.gov (United States)

    Binazzi, Alessandra; Marinaccio, Alessandro; Corfiati, Marisa; Bruno, Caterina; Fazzo, Lucia; Pasetto, Roberto; Pirastu, Roberta; Biggeri, Annibale; Catelan, Dolores; Comba, Pietro; Zona, Amerigo

    2017-11-01

    Objectives This study aimed to (i) describe mesothelioma incidence in the Italian national priority contaminated sites (NPCS) on the basis of data available from the Italian National Mesothelioma Registry (ReNaM) and (ii) profile NPCS using Bayesian rank analysis. Methods Incident cases of mesothelioma and standardized incidence ratios (SIR) were estimated for both genders in each of the 39 selected NPCS in the period 2000-2011. Age-standardized rates of Italian geographical macro areas were used to estimate expected cases. Rankings of areas were produced by a hierarchical Bayesian model. Asbestos exposure modalities were discussed for each site. Results In the study period, 2683 incident cases of mesothelioma (1998 men, 685 women) were recorded. An excess of mesothelioma incidence was confirmed in sites with a known past history of direct use of asbestos (among men) such as Balangero (SIR 197.1, 95% CI 82.0-473.6), Casale Monferrato (SIR 910.7, 95% CI 816.5-1012.8), and Broni (SIR 1288.5, 95% CI 981.9-1691.0), in sites with shipyards and harbors (eg, Trieste, La Spezia, Venice, and Leghorn), and in settings without documented direct use of asbestos. The analysis ranked the sites of Broni and Casale Monferrato (both genders) and Biancavilla (only for women) the highest. Conclusions The present study confirms that asbestos pollution is a risk for people living in polluted areas, due to not only occupational exposure in industrial settings with direct use of asbestos but also the presence of asbestos in the environment. Epidemiological surveillance of asbestos-related diseases is a fundamental tool for monitoring the health profile in NPCS.

  9. Ras pathway activation in malignant mesothelioma.

    Science.gov (United States)

    Patel, Manish R; Jacobson, Blake A; De, Arpita; Frizelle, Sandra P; Janne, Pasi; Thumma, Saritha C; Whitson, Brian A; Farassati, Faris; Kratzke, Robert A

    2007-09-01

    Mutations in Ras family genes are rare in malignant mesothelioma. The role of activation of the Ras signaling pathway in the pathogenesis of mesothelioma is not clear. We studied the activation status of the Ras pathway and the status of other Ras-associated kinases in a panel of human mesothelioma cell lines. In addition, we tested the effect of inhibition of several kinase pathways on mesothelioma cell proliferation. The potential role of kinase signaling on the regulation of cap-dependent translation was also studied. In general, Ras-guanosine triphosphate (GTP) was higher in mesothelioma cell lines when compared with a nontransformed mesothelial cell line (LP9). Furthermore, known Ras effectors such as extracellular-regulated kinase 1/2, p38 mitogen-activated protein kinase, and c-Jun N-terminal kinase were found to be active in most of the mesothelioma cell lines tested. Exposure to specific inhibitors of extracellular-regulated kinase 1/2 (U0126) and c-Jun N-terminal kinase (SP600125) significantly decreased the proliferation of H2596 and H2373 cells compared with mock-treated cells. SP600125-mediated c-Jun N-terminal kinase inhibition, but not extracellular-regulated kinase 1/2 inhibition, resulted in a decrease in phosphorylation of 4E-BP1, consequently decreasing cap-dependent activation. These experiments provide a rationale for targeting Ras and associated signaling pathways in mesothelioma and also suggest cap-dependent translation as one mechanism by which Ras induces proliferation in this disease.

  10. Tsc1-Tp53 loss induces mesothelioma in mice, and evidence for this mechanism in human mesothelioma

    Science.gov (United States)

    Guo, Yanan; Chirieac, Lucian R.; Bueno, Raphael; Pass, Harvey; Wu, Wenhao; Malinowska, Izabela A.; Kwiatkowski, David J.

    2014-01-01

    Mesothelioma is diagnosed in approximately 2,500 patients in the United States every year, most often arising in the pleural space, but also occurring as primary peritoneal mesothelioma. The vast majority of patients with mesothelioma die from their disease within 3 years. We developed a new mouse model of mesothelioma by bladder or intra-peritoneal injection of adenovirus Cre into mice with conditional alleles of each of Tp53 and Tsc1. Such mice began to develop malignant ascites about 6 months after injection, which was due to peritoneal mesothelioma, based on tumor morphology and immunohistochemical staining. Mesothelioma cell lines were established which showed loss of both Tsc1 and Tp53, with mTORC1 activation. Treatment of mice with malignant ascites due to mesothelioma with rapamycin led to a marked reduction in ascites, extended survival, and a 95–99% reduction in mesothelioma tumor volume, in comparison to vehicle-treated mice. To see if TSC1/TSC2 loss was a common genetic event in human mesothelioma, we examined 9 human mesothelioma cell lines, and found that 4 of 9 showed persistent activation of mTORC1 though none had loss of TSC1 or TSC2. A tissue microarray analysis of 198 human mesothelioma specimens showed that 33% of cases had reduced TSC2 expression and 60% showed activation of mTOR, indicating that mTOR activation is common in human mesothelioma and suggesting that it is a potential therapeutic target. PMID:23851502

  11. Secondary Malignant Peritoneal Mesothelioma of the Greater Omentum after Therapy for Primary Pleural Mesothelioma

    Directory of Open Access Journals (Sweden)

    Andreas Gutzeit

    2013-04-01

    Full Text Available Mesothelioma is the most common malignant primary tumor of the pleura and usually associated with inhalation of asbestos fibers. In contrast, peritoneal mesothelioma is a rare entity whose pathomechanism is not yet fully understood. The coexistence of pleural mesothelioma with secondary involvement of the abdominal cavity has not been addressed in the literature. In this case report, we describe secondary malignant mesothelioma of the greater omentum. A 69-year-old man with histologically proven pleural mesothelioma on the right side and no past medical history of asbestos exposure received palliative treatment consisting of a talc pleurodesis. After a 6-month interval of stable disease, a local progressive tumor of the right pleura was seen on a CT scan. Eleven months later, during follow-up, the patient presented at our emergency department with a sudden onset of diffuse abdominal pain. Abdominal ultrasound revealed a mass within the greater omentum and the coexistence of free fluid. Subsequent abdominal CT scans demonstrated tumor infiltration from the right pleura by a transdiaphragmatic route into the abdomen, where diffuse infiltration of the greater omentum was observed. Aspiration of the ascites and the biopsy of the greater omentum confirmed the diagnosis of secondary malignant mesothelioma of the peritoneum. In conclusion, we present the extremely rare diagnosis of secondary malignant mesothelioma of the abdomen, which arose as a result of local progression from the right pleura into the abdomen.

  12. Gene amplification in carcinogenesis

    Directory of Open Access Journals (Sweden)

    Lucimari Bizari

    2006-01-01

    Full Text Available Gene amplification increases the number of genes in a genome and can give rise to karyotype abnormalities called double minutes (DM and homogeneously staining regions (HSR, both of which have been widely observed in human tumors but are also known to play a major role during embryonic development due to the fact that they are responsible for the programmed increase of gene expression. The etiology of gene amplification during carcinogenesis is not yet completely understood but can be considered a result of genetic instability. Gene amplification leads to an increase in protein expression and provides a selective advantage during cell growth. Oncogenes such as CCND1, c-MET, c-MYC, ERBB2, EGFR and MDM2 are amplified in human tumors and can be associated with increased expression of their respective proteins or not. In general, gene amplification is associated with more aggressive tumors, metastases, resistance to chemotherapy and a decrease in the period during which the patient stays free of the disease. This review discusses the major role of gene amplification in the progression of carcinomas, formation of genetic markers and as possible therapeutic targets for the development of drugs for the treatment of some types of tumors.

  13. contribution to carcinogenesis

    Directory of Open Access Journals (Sweden)

    Aneta Białkowska

    2014-01-01

    Full Text Available The centrosomes are subcellular organelles composed of two centrioles surrounded by a pericentriolar material. In animal cells they are responsible for the organization of the interphase microtubule cytoskeleton including microtubule nucleation and elongation, their attachment and release. The centrosomes are also involved in the construction of the mitotic spindle and chromosome segregation. More than a century ago it was suggested that these structures might be involved in human diseases, including cancer. Cancer cells show a high frequency of centrosome aberrations, especially amplification. Centrosome defects may increase the incidence of multipolar mitoses that lead to chromosomal segregation abnormalities and aneuploidy, which is the predominant type of genomic instability found in human solid tumors. The number of these organelles in cells is strictly controlled and is dependent on the proper process of centrosome duplication. Multiple genes that are frequently found mutated in cancers encode proteins which participate in the regulation of centrosome duplication and the numeral integrity of centrosomes. In recent years there has been growing interest in the potential participation of centrosomes in the process of carcinogenesis, especially because centrosome abnormalities are observed in premalignant stages of cancer development. The common presence of abnormal centrosomes in cancer cells and the role these organelles play in the cells suggest that the factors controlling the number of centrosomes may be potential targets for cancer therapy.

  14. Novel induction therapies for pleural mesothelioma.

    Science.gov (United States)

    Donahoe, Laura; Cho, John; de Perrot, Marc

    2014-01-01

    Malignant mesothelioma is becoming increasingly common, and rates of diagnosis are expected to continue to increase in the coming years because of the extensive use of asbestos in industrialized countries and the long time interval between exposure and onset of disease. Although much research has been done on the optimal treatment for this disease, the overall prognosis remains grim. The main components of therapy are surgery, chemotherapy, and radiation therapy, but there is controversy in the literature about the optimal inclusion and sequencing of these treatments, as each has unique risk profiles. We have developed a new Surgery for Mesothelioma After Radiation Therapy protocol consisting of induction-accelerated hemithoracic radiation followed by extrapleural pneumonectomy. The rationale behind this protocol is to maximize both the tumoricidal and immunogenic potential of the radiotherapy while minimizing the radiation toxicity to the ipsilateral lung. Our initial trial demonstrated the feasibility of this approach and has shown encouraging results in patients with epithelial histology. In this article, we reviewed the current literature on induction chemotherapy for mesothelioma as well as described the Surgery for Mesothelioma After Radiation Therapy protocol and upcoming studies of novel induction therapies for mesothelioma. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Transgenerational teratogenesis and carcinogenesis by radiation

    International Nuclear Information System (INIS)

    Nomura, Taisei

    2000-01-01

    This paper thoroughly reviews studies on transgenerational teratogenesis and carcinogenesis induced by radiation and summarizes currently available data from animal studies. The discussions focus on the incidence of tumors, malformations, and mutations in the offspring after parental exposure to radiation, as well as estimated relative risks of congenital malformations and stillbirths in the offspring after parental X-ray exposure. The data suggest that different types of tumors are induced in offspring, because of strain differences in the experimental animals. The results of epidemiological studies in human populations, such as the children of atomic bomb survivors, conflict with the findings in animal studies. The author points to the following reasons for the differences between the results in animals and humans: differences in radiation doses, timing of exposure, and genetic predisposition, etc. While pointing out issues that need to be investigated further, the author indicates that clear strain differences exist in types of tumors induced and in tumor incidences in the offspring of animals that were irradiated before the offspring were conceived, and that genetic predisposition is therefore important in transgenerational carcinogenesis. (K.H.)

  16. Transgenerational teratogenesis and carcinogenesis by radiation

    Energy Technology Data Exchange (ETDEWEB)

    Nomura, Taisei [Osaka Univ., Suita (Japan). Graduate School of Medicine

    2000-07-01

    This paper thoroughly reviews studies on transgenerational teratogenesis and carcinogenesis induced by radiation and summarizes currently available data from animal studies. The discussions focus on the incidence of tumors, malformations, and mutations in the offspring after parental exposure to radiation, as well as estimated relative risks of congenital malformations and stillbirths in the offspring after parental X-ray exposure. The data suggest that different types of tumors are induced in offspring, because of strain differences in the experimental animals. The results of epidemiological studies in human populations, such as the children of atomic bomb survivors, conflict with the findings in animal studies. The author points to the following reasons for the differences between the results in animals and humans: differences in radiation doses, timing of exposure, and genetic predisposition, etc. While pointing out issues that need to be investigated further, the author indicates that clear strain differences exist in types of tumors induced and in tumor incidences in the offspring of animals that were irradiated before the offspring were conceived, and that genetic predisposition is therefore important in transgenerational carcinogenesis. (K.H.)

  17. Mesothelioma

    Science.gov (United States)

    ... Diagnosis & treatment Doctors & departments Care at Mayo Clinic Advertisement Mayo Clinic does not endorse companies or products. ... a Job Site Map About This Site Twitter Facebook Google YouTube Pinterest Mayo Clinic is a not- ...

  18. Mesothelioma

    Science.gov (United States)

    ... fibers at work. Workers who may encounter asbestos fibers include: Miners Factory workers Insulation manufacturers Ship builders Construction workers Auto mechanics Ask your employer whether you ...

  19. Mesothelioma

    Science.gov (United States)

    ... include: Miners Factory workers Insulation manufacturers Ship builders Construction workers Auto mechanics Ask your employer whether you ... testis: Diagnostic studies and differential diagnosis. Archives of Pathology & Laboratory Medicine. 2012;136:113. Mirarabshahii P, et ...

  20. (Radiation carcinogenesis in the whole body system)

    Energy Technology Data Exchange (ETDEWEB)

    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.

  1. 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

  2. Benign multicystic peritoneal mesothelioma: a case report

    Directory of Open Access Journals (Sweden)

    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.

  3. 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.

  4. 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

  5. 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.

  6. 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

  7. 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

  8. [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.

  9. Modeling Multiple Causes of Carcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Jones, T D

    1999-01-24

    An array of epidemiological results and databases on test animal indicate that risk of cancer and atherosclerosis can be up- or down-regulated by diet through a range of 200%. Other factors contribute incrementally and include the natural terrestrial environment and various human activities that jointly produce complex exposures to endotoxin-producing microorganisms, ionizing radiations, and chemicals. Ordinary personal habits and simple physical irritants have been demonstrated to affect the immune response and risk of disease. There tends to be poor statistical correlation of long-term risk with single agent exposures incurred throughout working careers. However, Agency recommendations for control of hazardous exposures to humans has been substance-specific instead of contextually realistic even though there is consistent evidence for common mechanisms of toxicological and carcinogenic action. That behavior seems to be best explained by molecular stresses from cellular oxygen metabolism and phagocytosis of antigenic invasion as well as breakdown of normal metabolic compounds associated with homeostatic- and injury-related renewal of cells. There is continually mounting evidence that marrow stroma, comprised largely of monocyte-macrophages and fibroblasts, is important to phagocytic and cytokinetic response, but the complex action of the immune process is difficult to infer from first-principle logic or biomarkers of toxic injury. The many diverse database studies all seem to implicate two important processes, i.e., the univalent reduction of molecular oxygen and breakdown of aginuine, an amino acid, by hydrolysis or digestion of protein which is attendant to normal antigen-antibody action. This behavior indicates that protection guidelines and risk coefficients should be context dependent to include reference considerations of the composite action of parameters that mediate oxygen metabolism. A logic of this type permits the realistic common-scale modeling of

  10. Malignant Mesothelioma after Household Exposure to Asbestos

    Directory of Open Access Journals (Sweden)

    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.

  11. 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

  12. Quantitative structure - mesothelioma potency model ...

    Science.gov (United States)

    Cancer potencies of mineral and synthetic elongated particle (EP) mixtures, including asbestos fibers, are influenced by changes in fiber dose composition, bioavailability, and biodurability in combination with relevant cytotoxic dose-response relationships. A unique and comprehensive rat intra-pleural (IP) dose characterization data set with a wide variety of EP size, shape, crystallographic, chemical, and bio-durability properties facilitated extensive statistical analyses of 50 rat IP exposure test results for evaluation of alternative dose pleural mesothelioma response models. Utilizing logistic regression, maximum likelihood evaluations of thousands of alternative dose metrics based on hundreds of individual EP dimensional variations within each test sample, four major findings emerged: (1) data for simulations of short-term EP dose changes in vivo (mild acid leaching) provide superior predictions of tumor incidence compared to non-acid leached data; (2) sum of the EP surface areas (ÓSA) from these mildly acid-leached samples provides the optimum holistic dose response model; (3) progressive removal of dose associated with very short and/or thin EPs significantly degrades resultant ÓEP or ÓSA dose-based predictive model fits, as judged by Akaike’s Information Criterion (AIC); and (4) alternative, biologically plausible model adjustments provide evidence for reduced potency of EPs with length/width (aspect) ratios 80 µm. Regar

  13. Germline BAP1 mutations predispose to malignant mesothelioma

    Science.gov (United States)

    Testa, Joseph R.; Cheung, Mitchell; Pei, Jianming; Below, Jennifer E.; Tan, Yinfei; Sementino, Eleonora; Cox, Nancy J.; Dogan, A. Umran; Pass, Harvey I.; Trusa, Sandra; Hesdorffer, Mary; Nasu, Masaki; Powers, Amy; Rivera, Zeyana; Comertpay, Sabahattin; Tanji, Mika; Gaudino, Giovanni; Yang, Haining; Carbone, Michele

    2011-01-01

    Because only a small fraction of asbestos-exposed individuals develop malignant mesothelioma1, and because mesothelioma clustering is observed in some families1, we searched for genetic predisposing factors. We discovered germline mutations in BAP1 (BRCA1-associated protein 1) in two families with a high incidence of mesothelioma. Somatic alterations affecting BAP1 were observed in familial mesotheliomas, indicating biallelic inactivation. Besides mesothelioma, some BAP1 mutation carriers developed uveal melanoma. Germline BAP1 mutations were also found in two of 26 sporadic mesotheliomas: both patients with mutant BAP1 were previously diagnosed with uveal melanoma. Truncating mutations and aberrant BAP1 expression were common in sporadic mesotheliomas without germline mutations. These results reveal a BAP1-related cancer syndrome characterized by mesothelioma and uveal melanoma. We hypothesize that other cancers may also be involved, and that mesothelioma predominates upon asbestos exposure. These findings will help identify individuals at high risk of mesothelioma who could be targeted for early intervention. PMID:21874000

  14. 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)

  15. Checkpoint Blockade in Lung Cancer and Mesothelioma.

    Science.gov (United States)

    Lievense, Lysanne A; Sterman, Daniel H; Cornelissen, Robin; Aerts, Joachim G

    2017-08-01

    In the last decade, immunotherapy has emerged as a new treatment modality in cancer. The most success has been achieved with the class of checkpoint inhibitors (CPIs), antibodies that unleash the antitumor immune response. After the success in melanoma, numerous clinical trials are being conducted investigating CPIs in lung cancer and mesothelioma. The programmed death protein (PD) 1-PD ligand 1/2 pathway and cytotoxic T lymphocyte-associated protein 4 are currently the most studied immunotherapeutic targets in these malignancies. In non-small cell lung cancer, anti-PD-1 antibodies have become part of the approved treatment arsenal. In small cell lung cancer and mesothelioma, the efficacy of checkpoint inhibition has not yet been proven. In this Concise Clinical Review, an overview of the landmark clinical trials investigating checkpoint blockade in lung cancer and mesothelioma is provided. Because response rates are around 20% in the majority of clinical trials, there is much room for improvement. Predictive biomarkers are therefore essential to fully develop the potential of CPIs. To increase efficacy, multiple clinical trials investigating the combination of cytotoxic T lymphocyte-associated protein 4 inhibitors and PD-1/PD ligand 1 blockade in lung cancer and mesothelioma are being conducted. Given the potential benefit of immunotherapy, implementation of current and new knowledge in trial designs and interpretation of results is essential for moving forward.

  16. Reproducibility for histologic parameters in peritoneal mesothelioma.

    Science.gov (United States)

    Hartman, Douglas J; Borczuk, Alain; Dacic, Sanja; Krasinskas, Alyssa

    2017-09-01

    Histologic subtype is recognized as a prognostic factor in malignant pleural mesothelioma. Specifically, epithelial morphology is associated with a better prognosis than other subtypes, and the same association is observed in peritoneal malignant mesothelioma. Recently, prognostic differences based on morphologic subtypes of epithelial peritoneal malignant mesothelioma were reported. Herein, we report the interobserver variability across four pathologists at three institutions. The authors independently reviewed 67 cases of malignant peritoneal epithelioid mesotheliomas and subclassified them according to their epithelial subtype: papillary, tubulopapillary, trabecular, micropapillary, solid and/or pleomorphic. The cases were also evaluated by each author for several other histopathologic parameters including depth of invasion, nuclear grade, lymphocytic host response, mitotic count/index, presence of lymphovascular invasion, and stromal desmoplasia. The interobserver agreement for histopathologic parameters was highest for mitotic rate (κ=0.36) and primary epithelial subtype (κ=0.32). The interobserver variability for solid subtype pattern was moderate (κ=0.49). We found that the interobserver variability for most histopathologic parameters is poor. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. 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.

  18. 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.

  19. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  1. 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 findings are based on small numbers of patients, they need to be confirmed. We examined mesothelioma risk in 2567 5-year survivors of Hodgkin lymphoma. The risk was almost 30-fold increased in Hodgkin lymphoma patients treated with irradiation compared with the general population. Although histology...... and survival of the mesothelioma cases were comparable with cases from the general population, asbestos exposure and the proportion of males were lower than expected. The evidence for radiotherapy as cause for mesothelioma independent of exposure to asbestos is expanding, and the diagnosis of mesothelioma...

  2. 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)

  3. 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

  4. 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.

  5. Role of the Inflammasome in Asbestos-Induced Mesothelioma Formation

    Science.gov (United States)

    2012-10-01

    CRI as a potential target for the prevention or treatment of MM. 15. SUBJECT TERMS inflammasome, mesothelioma , asbestos, inflammation 16. SECURITY...AD ________________ Award Number: W81XWH-10-1-0462 TITLE: Role of the Inflammasome in Asbestos-Induced Mesothelioma Formation PRINCIPAL INVESTIGATOR...TITLE AND SUBTITLE Role of the Inflammasome in Asbestos-Induced Mesothelioma 5a. CONTRACT NUMBER Formation 5b. GRANT NUMBER W81XWH-10-1-0462

  6. CD30 is a potential therapeutic target in malignant mesothelioma

    Science.gov (United States)

    Dabir, Snehal; Kresak, Adam; Yang, Michael; Fu, Pingfu; Wildey, Gary; Dowlati, Afshin

    2015-01-01

    CD30 is a cytokine receptor belonging to the tumor necrosis factor superfamily (TNFRSF8) that acts as a regulator of apoptosis. The presence of CD30 antigen is important in the diagnosis of Hodgkin’s disease and anaplastic large cell lymphoma. There have been sporadic reports of CD30 expression in non-lymphoid tumors, including malignant mesothelioma. Given the remarkable success of brentuximab vedotin, an antibody-drug conjugate directed against CD30 antigen, in lymphoid malignancies, we undertook a study to examine the incidence of CD30 in mesothelioma and to investigate the ability to target CD30 antigen in mesothelioma. Mesothelioma tumor specimens (N = 83) were examined for CD30 expression by immunohistochemistry. Positive CD30 expression was noted in 13 mesothelioma specimens, primarily those of epithelial histology. There was no significant correlation of CD30 positivity with either tumor grade, stage or survival. Examination of four mesothelioma cell lines (H28, H2052, H2452, and 211H) for CD30 expression by both FACS analysis and confocal microscopy showed that CD30 antigen localized to the cell membrane. Brentuximab vedotin treatment of cultured mesothelioma cells produced a dose-dependent decrease in cell growth and viability at clinically relevant concentrations. Our studies validate the presence of CD30 antigen in a subgroup of epithelial-type mesothelioma tumors and indicate that selected mesothelioma patients may derive benefit from brentuximab vedotin treatment. PMID:25589494

  7. Plastics and carcinogenesis: The example of vinyl chloride

    Directory of Open Access Journals (Sweden)

    Paul Wesley Brandt-Rauf

    2012-01-01

    Full Text Available The manufacture, use and disposal of various plastics can pose numerous health risks, including the risk of cancer. A model example of carcinogenic risk from plastics is provided by polyvinyl chloride, since it is composed of the known human carcinogen vinyl chloride (VC. In recent years, much has been learned about the molecular biological pathways of VC carcinogenesis. This has led to molecular epidemiologic studies of VC carcinogenesis in exposed human populations which have identified useful biomarkers of exposure, effect and susceptibility for VC. These studies have in turn provided the basis for new molecular approaches for the prevention and treatment of VC cancers. This model could have much wider applicability for many other carcinogenic exposures and many other human cancers.

  8. Life Expectancy in Pleural and Peritoneal Mesothelioma

    Directory of Open Access Journals (Sweden)

    Robert Shavelle

    2017-01-01

    Full Text Available Background. Mesothelioma is a rare cancer with a historically dire prognosis. We sought to calculate life expectancies for patients with pleural or peritoneal mesothelioma, both at time of diagnosis and several years later, and to examine whether survival has improved in recent years. Methods. Data on 10,258 pleural and 1,229 peritoneal patients from the SEER US national cancer database, 1973–2011, were analyzed using the Cox proportional hazards regression model. Results. The major factors related to survival were age, sex, stage, grade, histology, and treatment. Survival improved only modestly over the study period: 0.5% per year for pleural and 2% for peritoneal. Conclusions. Life expectancies were markedly reduced from normal, even amongst 5-year survivors with the most favorable characteristics and treatment options.

  9. 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

  10. Carcinogenesis mechanisms of Fusobacterium nucleatum.

    Science.gov (United States)

    Gholizadeh, Pourya; Eslami, Hosein; Kafil, Hossein Samadi

    2017-05-01

    Transformed cells of cancers may be related to stromal cells, immune cells, and some bacteria such as Fusobacterium nucleatum. This review aimed to evaluate carcinogenesis mechanisms of Fusobacterium spp. in the oral cavity, pancreatic and colorectal cancers. These cancers are the three of the ten most prevalence cancer in the worldwide. Recent findings demonstrated that F. nucleatum could be considered as the risk factor for these cancers. The most important carcinogenesis mechanisms of F. nucleatum are chronic infection, interaction of cell surface molecules of these bacteria with immune system and stromal cells, immune evasion and immune suppression. However, there are some uncertainty carcinogenesis mechanisms about these bacteria, but this review evaluates almost all the known mechanisms. Well-characterized virulence factors of F. nucleatum such as FadA, Fap2, LPS and cell wall extracts may act as effector molecules in the shift of normal epithelial cells to tumor cells. These molecules may provide new targets, drugs, and strategies for therapeutic intervention. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  11. Simian virus 40 and malignant mesothelioma (Review).

    Science.gov (United States)

    Cerrano, Paolo Giuseppe; Jasani, Bharat; Filiberti, Rosangela; Neri, Monica; Merlo, Franco; De Flora, Silvio; Mutti, Luciano; Puntoni, Riccardo

    2003-01-01

    Simian virus 40 (SV40) was recognized as a contaminant of early poliovirus vaccines that were provided to millions of individuals in Europe and in the USA between 1955 and 1963. SV40, a DNA virus of the family of papovaviridae, was proven to be oncogenic in rodents and able to transform human and animal cells in vitro. In 1993 SV40 was accidentally discovered to produce mesotheliomas in hamsters when it was injected in visceral cavities. Afterwards, SV40 DNA sequences were detected with significative frequency in human pleural mesotheliomas by using polymerase chain reaction (PCR) and then SV40 DNA oncogenicity was associated with its large T antigen (Tag). This finding was confirmed by many laboratories, while a few research groups failed to replicate these data and argued that the SV40 DNA detection might be a PCR contamination artefact. In this review the dispute is examined in the light of recent experiments performed to identify molecular and cellular aspects of carcinogenicity and/or co-carcinogenicity of SV40 in human mesothelioma.

  12. Diagnosis and treatment of malignant pleural mesothelioma.

    Science.gov (United States)

    Rodríguez Panadero, Francisco

    2015-04-01

    There are three major challenges in the diagnosis of malignant pleural mesothelioma: mesothelioma must be distinguished from benign mesothelial hyperplasia; malignant mesothelioma (and its subtypes) must be distinguished from metastatic carcinoma; and invasion of structures adjacent to the pleura must be demonstrated. The basis for clarifying the first two aspects is determination of a panel of monoclonal antibodies with appropriate immunohistochemical evaluation performed by highly qualified experts. Clarification of the third aspect requires sufficiently abundant, deep biopsy material, for which thoracoscopy is the technique of choice. Video-assisted needle biopsy with real-time imaging can be of great assistance when there is diffuse nodal thickening and scant or absent effusion. Given the difficulties of reaching an early diagnosis, cure is not generally achieved with radical surgery (pleuropneumonectomy), so liberation of the tumor mass with pleurectomy/decortication combined with chemo- or radiation therapy (multimodal treatment) has been gaining followers in recent years. In cases in which surgery is not feasible, chemotherapy (a combination of pemetrexed and platinum-derived compounds, in most cases) with pleurodesis or a tunneled pleural drainage catheter, if control of pleural effusion is required, can be considered. Radiation therapy is reserved for treatment of pain associated with infiltration of the chest wall or any other neighboring structure. In any case, comprehensive support treatment for pain control in specialist units is essential: this acquires particular significance in this type of malignancy. Copyright © 2014 SEPAR. Published by Elsevier Espana. All rights reserved.

  13. Imaging of mesothelioma of tunica vaginalis testis

    Energy Technology Data Exchange (ETDEWEB)

    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.)

  14. 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

  15. 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)

  16. 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,

  17. New roads open up for implementing immunotherapy in mesothelioma

    NARCIS (Netherlands)

    R. Cornelissen (Robin); M.E. Heuvers (Marlies); A.W.P.M. Maat (Alex); R.W. Hendriks (Rudi); H.C. Hoogsteden (Henk); J.G.J.V. Aerts (Joachim); J.P.J.J. Hegmans (Joost)

    2012-01-01

    textabstractTreatment options for malignant mesothelioma are limited, and the results with conventional therapies have been rather disappointing to this date. Chemotherapy is the only evidence-based treatment for mesothelioma patients in good clinical condition, with an increase in median survival

  18. Malignant pleural mesothelioma: incidence, etiology, diagnosis, treatment, and occupational health.

    Science.gov (United States)

    Neumann, Volker; Löseke, Stefan; Nowak, Dennis; Herth, Felix J F; Tannapfel, Andrea

    2013-05-01

    The incidence of malignant mesothelioma in Germany is about 20 cases per million persons per year. Its association with asbestos exposure, usually occupational, has been unequivocally demonstrated. Even though the industrial use of asbestos was forbidden many years ago, new cases of mesothelioma continue to appear because of the long latency of the disease (median, 50 years). Its diagnosis and treatment still present a major challenge for ambulatory and in-hospital care and will do so for years to come. This article is based on a selective review of the literature, along with data from the German Mesothelioma Register. 1397 people died of mesothelioma in Germany in 2010. A plateau in the incidence of the disease is predicted between 2015 and 2030. Most mesotheliomas arise from the pleura. The histological subtype and the Karnofsky score are the main prognostic factors. Only limited data are now available to guide treatment with a combination of the available methods (chemotherapy, surgery, radiotherapy). The prognosis is still poor, with a median survival time of only 12 months. Symptom control and the preservation of the patient's quality of life are the main aspects of care for patients with mesothelioma. The incidence of mesothelioma is not expected to drop in the next few years. The available treatments are chemotherapy, surgery, and radiotherapy. Specialized treatment centers now increasingly provide multimodal therapy for treatment of mesothelioma.

  19. 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

  20. 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

  1. Benign Multicystic Mesothelioma in the Left Round Ligament: Case Report

    Energy Technology Data Exchange (ETDEWEB)

    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.

  2. 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

  3. Deferasirox induces mesenchymal-epithelial transition in crocidolite-induced mesothelial carcinogenesis in rats.

    Science.gov (United States)

    Nagai, Hirotaka; Okazaki, Yasumasa; Chew, Shan Hwu; Misawa, Nobuaki; Yasui, Hiroyuki; Toyokuni, Shinya

    2013-11-01

    Asbestos was used worldwide in huge quantities in the past century. However, because of the unexpected carcinogenicity to mesothelial cells with an extremely long incubation period, many countries face this long-lasting social problem. Mesothelioma is often diagnosed in an advanced stage, for which no effective therapeutic protocols are yet established. We previously reported on the basis of animal experiments that the major pathology in asbestos-induced mesothelial carcinogenesis is local iron overload. Here, we undertook to find an effective strategy to prevent, delay, or lower the malignant potential of mesothelioma during asbestos-induced carcinogenesis. We used intraperitoneal injections of crocidolite to rats. We carried out a 16-week study to seek the maximal-tolerated intervention for iron reduction via oral deferasirox administration or intensive phlebotomy. Splenic iron deposition was significantly decreased with either method, and we found that Perls' iron staining in spleen is a good indicator for iron reduction. We injected a total of 10 mg crocidolite at the age of six weeks, and the preventive measures were via repeated oral administration of 25 to 50 mg/kg/d deferasirox or weekly to bimonthly phlebotomy of 4 to 10 mL/kg/d. The animals were observed until 110 weeks. Deferasirox administration significantly increased the fraction of less malignant epithelioid subtype. Although we found a slightly prolonged survival in deferasirox-treated female rats, larger sample size and refinement of the current protocol are necessary to deduce the cancer-preventive effects of deferasirox. Still, our results suggest deferasirox serves as a potential preventive strategy in people already exposed to asbestos via iron reduction. ©2013 AACR.

  4. Exocrine pancreatic carcinogenesis and autotaxin expression.

    Directory of Open Access Journals (Sweden)

    Sandeep Kadekar

    Full Text Available Exocrine pancreatic cancer is an aggressive disease with an exceptionally high mortality rate. Genetic analysis suggests a causative role for environmental factors, but consistent epidemiological support is scarce and no biomarkers for monitoring the effects of chemical pancreatic carcinogens are available. With the objective to identify common traits for chemicals inducing pancreatic tumors we studied the National Toxicology Program (NTP bioassay database. We found that male rats were affected more often than female rats and identified eight chemicals that induced exocrine pancreatic tumors in males only. For a hypothesis generating process we used a text mining tool to analyse published literature for suggested mode of actions (MOA. The resulting MOA analysis suggested inflammatory responses as common feature. In cell studies we found that all the chemicals increased protein levels of the inflammatory protein autotaxin (ATX in Panc-1, MIA PaCa-2 or Capan-2 cells. Induction of MMP-9 and increased invasive migration were also frequent effects, consistent with ATX activation. Testosterone has previously been implicated in pancreatic carcinogenesis and we found that it increased ATX levels. Our data show that ATX is a target for chemicals inducing pancreatic tumors in rats. Several lines of evidence implicate ATX and its product lysophosphatidic acid in human pancreatic cancer. Mechanisms of action may include stimulated invasive growth and metastasis. ATX may interact with hormones or onco- or suppressor-genes often deregulated in exocrine pancreatic cancer. Our data suggest that ATX is a target for chemicals promoting pancreatic tumor development.

  5. Carcinogenesis induced by low-dose radiation

    Directory of Open Access Journals (Sweden)

    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.

  6. Diffuse malignant epithelioid mesothelioma in a background of benign multicystic peritoneal mesothelioma: a case report and review of the literature.

    Science.gov (United States)

    Mino, Jeffrey S; Monteiro, Rosebel; Pigalarga, Rodolfo; Varghese, Sumi; Guisto, Laura; Rezac, Craig

    2014-02-05

    Peritoneal mesotheliomas are unusual entities with diverse origins and outcomes. Both benign and malignant variants exist. Benign multicystic peritoneal mesotheliomas (BMPMs), also known as multiple or multilocular peritoneal inclusion cysts, are extremely rare tumours arising from the peritoneal mesothelium covering the abdominal serous cavity. Even though these entities are considered benign tumours, BMPMs tend to recur after surgical resection, and in two cases have been reported to undergo malignant transformation. In contrast, diffuse malignant peritoneal mesotheliomas, while also quite rare, are the second most common form of malignant mesothelioma after the pleural variety with extremely high mortality and poor response to many treatments to date. We present a rare case of diffuse malignant peritoneal mesothelioma within a large component of a BMPM in a young man admitted to our service.

  7. Frequency of Surgery in Black Patients with Malignant Pleural Mesothelioma

    Directory of Open Access Journals (Sweden)

    Emanuela Taioli

    2015-01-01

    Full Text Available Introduction. Malignant Pleural Mesothelioma (MPM is a rare disease, even less frequently described in minority patients. We used a large population-based dataset to study the role of race in MPM presentation, treatment, and survival. Methods. All cases of pathologically proven MPM were identified in the Surveillance, Epidemiology, and End Results (SEER database. Age, sex, diagnosis year, stage, cancer-directed surgery, radiation, and vital status were analyzed according to self-reported race (black or white. Results. There were 13,046 white and 688 black MPM patients (incidence: 1.1 per 100,000 whites; 0.5 per 100,000 blacks; age-adjusted, p=0.01. Black patients were more likely to be female, younger, and with advanced stage and less likely to undergo cancer-directed surgery than whites, after adjustment by stage. On multivariable analysis, younger age and having surgery were associated with longer survival for both cohorts; female gender (HR 0.82 (0.77–0.88 and early stage at diagnosis (HR 0.83 (0.76–0.90 were predictive of longer survival in white, but not in black, patients. Conclusions. Surgery was associated with improved survival for both black and white MPM patients. However, black patients were less likely to undergo cancer-directed surgery. Increased surgical intervention in MPM black patients with early stage disease may improve their survival.

  8. Carcinogenesis

    International Nuclear Information System (INIS)

    Reilly, C.A. Jr.

    1979-01-01

    This section contains summaries of research in the following areas: use of liver for mechanistic studies of multistage hepatocarcinogenesis and for screening of environmental contaminants for tumor initiating and promoting activity; molecular properties of rat liver ornithine aminotransferase; regulation of gene expression in rat liver; methods of tumor detection; mechanisms of radiation and viral oncogenesis; biphenyl metabolism by rat liver microsomes; and studies on aryl hydrocarbon hydroxylase activity

  9. Carcinogenesis

    International Nuclear Information System (INIS)

    Buess, E.M.; Cerny, E.A.; Chan, E.W.

    1977-01-01

    The first section deals with the assessment of carcinogens and cocarcinogens and the underlying mechanisms of their actions. The second concerns cancer induction by bone-seeking radionuclides and seeks to provide a firm foundation for estimating cancer risks to human populations in the event of accidental incorporation of radionuclides. The third is aimed at defining the role of oncornavirus activation in tumor induction by radiation and other environmental pollutants. The other two sections describe the new studies, one dealing with the development of an in vitro cell system (murine teratocarcinoma cells) to screen chemicals rapidly for carcinogenic and mutagenic capacity, and the other investigating the potential use of plasma isozymes as indicators of mutagenesis in mammals. Accomplishments and projections for each of these studies follow

  10. 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.

  11. 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)

  12. 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.

  13. Liver Development, Regeneration, and Carcinogenesis

    Directory of Open Access Journals (Sweden)

    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.

  14. INTRAOPERATIVE PHOTODYNAMIC THERAPY FOR PERITONEAL MESOTHELIOMA

    Directory of Open Access Journals (Sweden)

    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.

  15. Benign Cystic Mesothelioma Misdiagnosed as Peritoneal Carcinomatosis

    Directory of Open Access Journals (Sweden)

    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.

  16. DNA repair systems in malignant mesothelioma.

    Science.gov (United States)

    Toumpanakis, Dimitrios; Theocharis, Stamatios E

    2011-12-22

    Malignant mesothelioma (MM) is an aggressive tumor of serosal surfaces with increasing incidence and poor prognosis. Asbestos exposure is the main cause of MM and asbestos-induced DNA damage is critical for MM pathogenesis. The present review summarizes the implications of DNA repair systems in MM development, focusing on gene expression alterations and single nucleotide polymorphisms of genes encoding for DNA repair enzymes. The involvement of DNA repair systems in MM improves understanding of MM pathogenesis and provides novel therapeutical targets. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  17. 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.)

  18. 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.

  19. 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.

  20. 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.

  1. Novel insights into mesothelioma biology and implications for therapy.

    Science.gov (United States)

    Yap, Timothy A; Aerts, Joachim G; Popat, Sanjay; Fennell, Dean A

    2017-07-25

    Malignant mesothelioma is a universally lethal cancer that is increasing in incidence worldwide. There is a dearth of effective therapies, with only one treatment (pemetrexed and cisplatin combination chemotherapy) approved in the past 13 years. However, the past 5 years have witnessed an exponential growth in our understanding of mesothelioma pathobiology, which is set to revolutionize therapeutic strategies. From a genomic standpoint, mesothelioma is characterized by a preponderance of tumour suppressor alterations, for which novel therapies are currently in development. Other promising antitumour agents include inhibitors against angiogenesis, mesothelin and immune checkpoints, which are at various phases of clinical trial testing.

  2. 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.

  3. Malignant pleural mesothelioma in a 13-year-old girl

    Energy Technology Data Exchange (ETDEWEB)

    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.)

  4. 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.)

  5. 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.

  6. Mesothelioma in a wine cellar man: detailed description of working procedures and past asbestos exposure estimation.

    Science.gov (United States)

    Nemo, Alessandro; Silvestri, Stefano

    2014-11-01

    A pleural mesothelioma arose in an employee of a wine farm whose work history shows an unusual occupational exposure to asbestos. The information, gathered directly from the case and from a work colleague, clarifies some aspects of the use of asbestos in the process of winemaking which has not been previously reported in such details. The man had worked as a winemaker from 1960 to 1988 in a farm, which in those years produced around 2500 hectoliters of wine per year, mostly white. The wine was filtered to remove impurities; the filter was created by dispersing in the wine asbestos fibers followed by diatomite while the wine was circulating several times and clogging a prefilter made of a dense stainless steel net. Chrysotile asbestos was the sole asbestos mineralogical variety used in these filters and exposure could occur during the phase of mixing dry fibers in the wine and during the filter replacement. A daily and annual time weighted average level of exposure and cumulative dose have been estimated in the absence of airborne asbestos fiber monitoring performed in that workplace. Since 1993, the Italian National Mesothelioma Register, an epidemiological surveillance system, has recorded eight cases with at least one work period spent as winemaker. Four of them never used asbestos filters and presented exposures during other work periods, the other four used asbestos filters but had also other exposures in other industrial divisions. For the information hitherto available, this is the first mesothelioma case with exclusive exposure in the job of winemaking. © The Author 2014. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.

  7. Synergistic effect of gefitinib and rofecoxib in mesothelioma cells

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    Sacchi Ada

    2010-02-01

    Full Text Available Abstract Background Malignant mesothelioma (MM is an aggressive tumor that is resistant to conventional modes of treatment with chemotherapy, surgery or radiation. Research into the molecular pathways involved in the development of MM should yield information that will guide therapeutic decisions. Epidermal growth factor receptor (EGFR and cyclooxygenase-2 (COX-2 are involved in the carcinogenesis of MM. Combination of COX-2 and EGFR inhibitors, therefore, could be an effective strategy for reducing cell growth in those lines expressing the two molecular markers. Results In order to verify the effect of COX-2 and EGFR inhibitors, five MM cell lines NCI-2452, MPP89, Ist-Mes-1, Ist-Mes-2 and MSTO-211 were characterized for COX-2 and EGFR and then treated with respective inhibitors (rofecoxib and gefitinib alone and in combination. Only MPP89, Ist-Mes-1 and Ist-Mes-2 were sensitive to rofecoxib and showed growth-inhibition upon gefitinib treatment. The combination of two drugs demonstrated synergistic effects on cell killing only in Ist-Mes-2, the cell line that was more sensitive to gefitinib and rofecoxib alone. Down-regulation of COX-2, EGFR, p-EGFR and up-regulation of p21 and p27 were found in Ist-Mes-2, after treatment with single agents and in combination. In contrast, association of two drugs resulted in antagonistic effect in Ist-Mes-1 and MPP89. In these cell lines after rofecoxib exposition, only an evident reduction of p-AKT was observed. No change in p-AKT in Ist-Mes-1 and MPP89 was observed after treatment with gefitinib alone and in combination with rofecoxib. Conclusions Gefitinib and rofecoxib exert cell type-specific effects that vary between different MM cells. Total EGFR expression and downstream signalling does not correlate with gefitinib sensitivity. These data suggest that the effect of gefitinib can be potentiated by rofecoxib in MM cell lines where AKT is not activated.

  8. [Health expenditures for cases of pleural mesothelioma].

    Science.gov (United States)

    Zocchetti, C

    2015-09-09

    Through the study of 65 cases of probable pleural mesothelioma currently under discussion in 4 criminal trials in the Lombardy Region, who died between 2002 and 2015, this study aimed to provide economical information regarding the health expenditures sustained by the Regional Health Service (RHS) for providing hospitalization, outpatient services and drugs to such patients. Health information regarding the services provided for the cases under study were electronically retrieved from the RHS information system. For each pleural mesothelioma case the costs (on average) were about 67,000 euros, 37,000 of which were spent after the date of diagnosis. Drugs formed the largest part of health expenditure (about 37,000 euros per person). Per capita expenditures showed a peak near (before and after) the date of diagnosis, rising when approaching the date of death and with increasing age of the patient, and did not vary with survival time. This information, reported for the first time in detail in this paper, will be useful for out-of-court agreements and for setting up reimbursement schemes, and describe per capita expenditures which are higher than estimations proposed in recent criminal trials in Italy and to those reported in the international literature.

  9. New therapeutic strategies for malignant pleural mesothelioma.

    Science.gov (United States)

    Bonelli, Mara A; Fumarola, Claudia; La Monica, Silvia; Alfieri, Roberta

    2017-01-01

    Malignant pleural mesothelioma (MPM) is a rare and aggressive malignant disease affecting the mesothelium, commonly associated to asbestos exposure. Therapeutic actions are limited due to the late stage at which most patients are diagnosed and the intrinsic chemo-resistance of the tumor. The recommended systemic therapy for MPM is cisplatin/pemetrexed regimen with a mean overall survival of about 12months and a median progression free survival of less than 6months. Considering that the incidence of this tumor is expected to increase in the next decade and that its prognosis is poor, novel therapeutic approaches are urgently needed. For some tumors, such as lung cancer and breast cancer, druggable oncogenic alterations have been identified and targeted therapy is an important option for these patients. For MPM, clinical guidelines do not recommend biological targeted therapy, mainly because of poor target definition or inappropriate trial design. Further studies are required for a full comprehension of the molecular pathogenesis of MPM and for the development of new target agents. This review updates pre-clinical and clinical data on the efficacy of targeted therapy and immune checkpoint inhibition in the treatment of mesothelioma. Finally, future perspectives in this deadly disease are also discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Advances in the management of peritoneal mesothelioma

    Science.gov (United States)

    Raza, Ali; Huang, Wei-Ching; Takabe, Kazuaki

    2014-01-01

    Malignant peritoneal mesothelioma (PM) is an infrequent disease which has historically been associated with a poor prognosis. Given its long latency period and non-specific symptomatology, a diagnosis of PM can be suggested by occupational exposure history, but ultimately relies heavily on imaging and diagnostic biopsy. Early treatment options including palliative operative debulking, intraperitoneal chemotherapy, and systemic chemotherapy have marginally improved the natural course of the disease with median survival being approximately one year. The advent of cytoreduction (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has dramatically improved survival outcomes with wide median survival estimates between 2.5 to 9 years; these studies however remain largely heterogeneous, with differing study populations, tumor biology, and specific treatment regimens. More recent investigations have explored extent of cytoreduction, repeated operative intervention, and choice of chemotherapy but have been unable to offer definitive conclusions. CRS and HIPEC remain morbid procedures with complication rates ranging between 30% to 46% in larger series. Accordingly, an increasing interest in identifying molecular targets and developing targeted therapies is emerging. Among such novel targets is sphingosine kinase 1 (SphK1) which regulates the production of sphingosine-1-phosphate, a biologically active lipid implicated in various cancers including malignant mesothelioma. The known action of specific SphK inhibitors may warrant further exploration in peritoneal disease. PMID:25206274

  11. Recurrent chromosome 6 abnormalities in malignant mesothelioma.

    Science.gov (United States)

    Ribotta, M; Roseo, F; Salvio, M; Castagneto, B; Carbone, M; Procopio, A; Giordano, A; Mutti, L

    1998-04-01

    The long latency period between asbestos exposure and the onset of malignant mesothelioma (MM) suggests that a multistep tumorigenesis process occurs whilst the capability of asbestos fibres to interfere directly with chromosomes focuses on the critical role of the chromosomal abnormalities in this neoplasm. The aim of our study was to identify any recurrent chromosomal changes in ten primary MM cell cultures derived from pleural effusions of patients with MM from the same geographic area and environmental and/or occupational exposure to asbestos fibers. Cytogenetic analysis was performed in accordance with International System for Human Cytogenetic Nomenclature. Our results confirmed a great number of cytogenetic abnormalities in MM cells. Recurrent loss of the long arms of chromosome 6 (6q-) was the most frequent abnormality detected (four epithelial and two mixed subtypes) while, on the whole, abnormalities of chromosome 6 were found in nine out of ten cases whereas chromosome 6 was normal only in the case with fibromatous subtype. Monosomy 13 and 17 was found in five cases, monosomy 14 in four cases and 22 in three cases. Since deletion of 6q- was detected even in relatively undisturbed karyotype, we hypothesize a multistep carcinogenic process in which deletion of 6q- is an early event in the development and progression of malignant mesothelioma.

  12. Biological aspects of radiation carcinogenesis

    International Nuclear Information System (INIS)

    Upton, A.C.

    1984-01-01

    Ionizing radiation has been observed to increase the incidence of virtually every type of neoplasm, and carcinogenic effects have been noted in all species investigated. Susceptibility varies markedly, however, with species, strain, organ, cell type, sex, age at irradiation, physiological condition, exposure to other physical or chemical agents, and additional variables. Because of the multicausal, multistage nature of the cancer process, and the diversity of mechanisms through which carcinogenesis may be influenced by irradiation, the variety of observed dose-incidence relationships is not unexpected. The data are consistent with the concept that cancer arises from a single transformed cell, through a stepwise succession of undefined changes, and that the process of transformation may be initiated by radiation-induced damage to the DNA of the affected cell. There is also evidence that intercellular interactions may play an important role in the evolution of the neoplastic process, the nature and radiobiology of which remain to be determined

  13. Genetic factors for breast carcinogenesis

    Directory of Open Access Journals (Sweden)

    Pedro Enrique Miguel-Soca

    2016-12-01

    Full Text Available Breast cancer is a multifactorial genenetic disease in which oncogenes derived from normal cellular genes intervene, which constitute positive signals of cellular proliferation and tumour suppressor genes and represent negative signals of cells multiplication and differentiation. Although these alterations which affect germinal cells produce inherited cancers, in most of the cases somatic cell genes are affected. To the susceptibility of cancer due to genes as BRCA1 and BCRA2, the effect of factors associated to environment, life style and toxic habits are added, these determine a complex interrelation genes-environment which imply an activation of oncogenes and inactivation of tumour suppressors. The objective of this review in to offer an updated view about the main genes implied in breast carcinogenesis. The topic is controversial y currently deeply investigated.

  14. Environmental carcinogenesis and genetic variability

    International Nuclear Information System (INIS)

    Knudsen, A.G. Jr

    1977-01-01

    It was found that carcinogenesis in man may involve the interaction of genetic and environmental forces, and that mutation, whether germinal or somatic, seems to be involved in the origin of many, perhaps all cancers. The cancers of man may be visualized as occurring in four groups of individuals according to whether (1) neither genetic nor environmental factors are dominant, i.e. 'background' or 'spontaneous' cancer, (2) heredity alone is dominant, (3) environment alone is important, or (4) both are operating (Knudsen, 1977). The last two groups together are widely thought to contribute 70-80% of cancer cases in the United States; the relative contribution of each group is a major question to be answered

  15. Time factors in radiation carcinogenesis

    International Nuclear Information System (INIS)

    Sasaki, Shunsaku

    1995-01-01

    Results of experiments using B6C3F 1 female mice were made subject of analysis on the time factors in radiation carcinogenesis. In the experiment for examination of influence of age at irradiation on the lifetime risk and on distribution of ages at death, mice were irradiated at day 12, 14 or 17 of the prenatal period, or day 0, 7, 35, 105, 240 or 365 of the postnatal period with doses ranging from 0.48 to 5.7 Gy gamma-rays from 137 Cs. In the experiment to examine the reduction factor for carcinogenic effect by multiple fractionation of gamma-rays dose 1.9 or 3.8 Gy was divided into 10 fractions, which were delivered once a week during period from 5 to 15 weeks of age. All mice were allowed to live out their life spans under a specific pathogen free condition. The cumulative relative risk for mortality from all causes except lymphoma and leukemia was shown to decrease with age when mice were irradiated at the fetal, neonatal, suckling, adolescent or young adult period, whereas, the decrease in the cumulative relative risk was very little when gamma-rays were given at the intermediate adult period. The lifetime risk for the increase in mortality and for the induction of solid tumors was highest in mice irradiated during neonatal, suckling or adolescent period. Age-dependence of susceptibility to radiation carcinogenesis was different for each type of neoplasm. However, the most susceptible period for induction of each type of neoplasm concentrated in the age from neonatal to adolescent period. Radiation-induced late effects were apparently reduced by multiple fractionation of radiation dose, but the reduction factor for the increase in the long-term mortality did not exceed 2.0. (author)

  16. Benign Multicystic Peritoneal Mesothelioma: A Rare Tumour of the Abdomen

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    Soundappan Somasundaram

    2015-01-01

    Full Text Available Benign multicystic peritoneal mesothelioma: a rare tumor of the abdomen, is a diagnostic dilemma. This report emphasizes the importance of diagnostic laparoscopy in the diagnosis of the tumour.

  17. Pleural malignant mesothelioma in dental laboratory technicians: A case series.

    Science.gov (United States)

    Mensi, Carolina; Ciullo, Francesco; Barbieri, Gino Pietro; Riboldi, Luciano; Somigliana, Anna; Rasperini, Giulio; Pesatori, Angela Cecilia; Consonni, Dario

    2017-05-01

    Asbestos was used in dentistry as a binder in periodontal dressings and as lining material for casting rings and crucible. However, until now, only one case of malignant mesothelioma with occupational exposure to asbestos in dental practice has been reported. We present 4 pleural mesotheliomas out of 5344 cases identified in Lombardy, Italy, in 2000-2014. Three men had been working as dental laboratory technicians, with asbestos exposure for 10, 34, and 4 years, and one woman had been helping her husband for 30 years in manufacturing dental prostheses. The men described the use of asbestos as a lining material for casting rings, while the woman was not able to confirm this use. We confirm the association of malignant mesothelioma with dental technician work. Dental technicians suffering from mesothelioma should be questioned about past occupational asbestos exposure. © 2017 Wiley Periodicals, Inc.

  18. Malignant pleural mesothelioma: an update on diagnosis and treatment options.

    Science.gov (United States)

    Kondola, Sanjana; Manners, David; Nowak, Anna K

    2016-06-01

    Malignant pleural mesothelioma (MPM) represents a significant diagnostic and therapeutic challenge and is almost always a fatal disease. Imaging abnormalities are common, but have a limited role in distinguishing mesothelioma from metastatic pleural disease. Similarly, minimally invasive biomarkers have shown promise but also have limitations in the diagnosis of mesothelioma. In experienced centers, cytology and immunohistochemistry are now sufficient to diagnose the epithelioid subtype of mesothelioma, which can reduce the need for more invasive diagnostic investigations. Prognosis of MPM is modestly impacted by oncological treatments. Chemotherapy with cisplatin and pemetrexed is considered the standard of care, though the addition of bevacizumab to the platinum doublet may be the new standard of care. New targeted therapies have demonstrated some promise and are being addressed in clinical trials. This review focuses on the current data on the diagnostic and therapeutic issues of MPM. © The Author(s), 2016.

  19. Malignant peritoneal mesothelioma. Is there a new treatment?

    Directory of Open Access Journals (Sweden)

    David J. Kerr

    2009-12-01

    Full Text Available The authors report a novel, alternative approach to treat malignant peritoneal mesothelioma (MPeM targeting, vascular endothelial growth factor (VEGF using anti-VEGF (bevacizumab chemotherapy combination.

  20. Malignant Mesothelioma of the Tunica Vaginalis (Case Report

    Directory of Open Access Journals (Sweden)

    MR Haji Esmaeili

    2009-07-01

    Full Text Available Malignant mesothelioma of the tunica vaginalis constitutes a very rare but often fatal malignancy of the male genitalia. This diagnosis should be suspected in patients exposed to asbestos and those presenting with clinical symptoms of either hydrocele or inguinal hernia. We report here a case of malignant mesothelioma of the tunica vaginalis. A 69-year-old man with a left hydrocele and inguinal mass was referred for left inguinal orchidectomy and hernioraphy. Histologic examination showed a malignant mesothelioma. Malignant mesothelioma of the tunica vaginalis testis is a very rare occupational neoplasm with highly aggressive biological behaviour. Treatment is difficult, and widespread local invasion and/or metastatic disease at presentation are associated with a poor prognosis.

  1. 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.

  2. 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)

  3. 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.

  4. Malignant Mesothelioma Mimicking Invasive Mammary Carcinoma in a Male Breast

    Directory of Open Access Journals (Sweden)

    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.

  5. MesobanK UK: an international mesothelioma bioresource

    OpenAIRE

    Rintoul, Robert C; Rassl, Doris M; Gittins, Jacki; Marciniak, Stefan J

    2015-01-01

    Malignant pleural mesothelioma causes the greatest societal burden of all the asbestos related diseases. Progress in better understanding tumour biology will be facilitated by the availability of quality-assured annotated tissue. MesobanK has been created to establish a bioresource of pleural mesothelioma tissue linked to detailed anonymised clinical data. When complete, the bioresource will comprise a 750 patient tissue microarray and prospectively collected tissue, blood and pleural fluid f...

  6. A catalogue of treatment and technologies for malignant pleural mesothelioma.

    Science.gov (United States)

    Schunselaar, Laurel M; Quispel-Janssen, Josine M M F; Neefjes, Jacques J C; Baas, Paul

    2016-01-01

    Malignant pleural mesothelioma is an aggressive fatal malignancy with a prognosis that has not significantly improved in the last decades. This review summarizes the current state of treatment and the various attempts that are made to improve overall survival for patients with malignant pleural mesothelioma. It also discusses technologies and protocols to test new and hopefully more effective compounds in a more individualized manner. These developments are expected to improve the prognosis for this group of patients.

  7. 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.

  8. Localized fibrous mesothelioma of the liver: a case report

    Energy Technology Data Exchange (ETDEWEB)

    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.

  9. Relative risk of mesothelioma among railroad machinists exposed to chrysotile.

    Science.gov (United States)

    Mancuso, T F

    1988-01-01

    This study challenges the assertion of low relative risk of chrysotile in the causation of mesothelioma. Data are provided on the time period use of various types of asbestos in the United States and in insulation materials. The focus of the study is on mesothelioma among railroad machinists employed in the steam locomotive era who were exposed to chrysotile. Within a cohort of machinists alive January 1, 1945, a sub-cohort method was applied to all successive machinists hired in each of the respective years (1920-1929) followed through 1986. The total cohort was 181 and the number of deaths 156, with 14 mesotheliomas identified among 41 cancer deaths. The findings demonstrated an extremely high relative risk for machinists exposed to chrysotile for the induction of mesothelioma in the individual year of hire cohorts. A similar observation was noted for other crafts hired in the same time period. One mesothelioma occurred for every 13 machinists hired in the succeeding years (1920-1929) and constituted 34% of all cancer deaths. It is concluded that chrysotile is far more hazardous in the induction of mesotheliomas and that the asbestos cancer risk in the steam locomotive eras was much higher than had been previously estimated.

  10. [Clinical Pathological Diagnosis, and Treatment for Pleural Mesothelioma].

    Science.gov (United States)

    Kishimoto, Takumi; Fujimoto, Nobukazu; Nishi, Hideyuki

    2016-05-01

    For the differential diagnosis between fibrous pleuritis and other malignancies such as lung cancer, multiple immunostaining is essential to diagnose pleural mesothelioma. For cytological diagnosis of pleural effusions, differentiation between mesothelioma cells and reactive mesothelial cells is very difficult. Therefore, histological diagnoses of tumor tissues obtained via biopsy are essential. To diagnose epthelioid mesothelioma, more than 2 positive and negative markers must be consistent with those known for mesothelioma. To diagnose sarcomatoid mesothelioma, keratin is usually positive, differentiating the diagnosis from that for real sarcoma. For surgical treatment for pleural mesothelioma, extrapleural pneumonectomy (EPP) and pleurectomy/decortication (P/D) are usually performed. The proportion of P/D increases because of the low death rates with surgery and similar survivals. However, a trimodal approach, such as EPP with chemotherapy and radiotherapy, is best for longer survival and expected to be curative. For chemotherapy, only cisplatin (CDDP) combined with pemetrexed (PEM) is effective, and no other agents have been identified for this disease. Nowadays, clinical immunotherapy trials start with phase II study.

  11. Primary Pericardial Mesothelioma: Report of a Patient and Literature Review

    Directory of Open Access Journals (Sweden)

    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.

  12. Lipoblastic differentiation in a primary localized fibrous mesothelioma of the peritoneum.

    Science.gov (United States)

    Donna, A; Betta, P G; Ribotta, M

    1996-12-01

    Lipoblastic differentiation in fibrous mesotheliomas is an extremely rare occurrence. We present the histological and immunohistochemical features of a case of localized peritoneal mesothelioma with lipoblastic differentiation in an 80-year old man and discuss the differential diagnosis with liposarcoma.

  13. Diffuse malignant epithelioid mesothelioma in a background of benign multicystic peritoneal mesothelioma: a case report and review of the literature

    OpenAIRE

    Mino, Jeffrey S; Monteiro, Rosebel; Pigalarga, Rodolfo; Varghese, Sumi; Guisto, Laura; Rezac, Craig

    2014-01-01

    Peritoneal mesotheliomas are unusual entities with diverse origins and outcomes. Both benign and malignant variants exist. Benign multicystic peritoneal mesotheliomas (BMPMs), also known as multiple or multilocular peritoneal inclusion cysts, are extremely rare tumours arising from the peritoneal mesothelium covering the abdominal serous cavity. Even though these entities are considered benign tumours, BMPMs tend to recur after surgical resection, and in two cases have been reported to underg...

  14. Imaging in Pleural Mesothelioma: A Review of the 13th International Conference of the International Mesothelioma Interest Group

    Science.gov (United States)

    Armato, Samuel G.; Blyth, Kevin G.; Keating, Jane J.; Katz, Sharyn; Tsim, Selina; Coolen, Johan; Gudmundsson, Eyjolfur; Opitz, Isabelle; Nowak, Anna K.

    2016-01-01

    Imaging plays an important role in the detection, diagnosis, staging, response assessment, and surveillance of malignant pleural mesothelioma. The etiology, biology, and growth pattern of mesothelioma present unique challenges for each modality used to capture various aspects of this disease. Clinical implementation of imaging techniques and information derived from images continue to evolve based on active research in this field worldwide. This paper summarizes the imaging-based research presented orally at the 2016 International Conference of the International Mesothelioma Interest Group (iMig) in Birmingham, United Kingdom, held May 1–4, 2016. Presented topics included intraoperative near-infrared imaging of mesothelioma to aid the assessment of resection completeness, an evaluation of tumor enhancement improvement with increased time delay between contrast injection and image acquisition in standard clinical magnetic resonance imaging (MRI) scans, the potential of early contrast enhancement analysis to provide MRI with a role in mesothelioma detection, the differentiation of short- and long-term survivors based on MRI tumor volume and histogram analysis, the response-assessment potential of hemodynamic parameters derived from dynamic contrast-enhanced computed tomography (DCE-CT) scans, the correlation of CT-based tumor volume with the post-surgical tumor specimen weight, and consideration of the need to update the mesothelioma tumor response assessment paradigm. PMID:27794408

  15. Cynara scolymus affects malignant pleural mesothelioma by promoting apoptosis and restraining invasion

    OpenAIRE

    Pulito, Claudio; Mori, Federica; Sacconi, Andrea; Casadei, Luca; Ferraiuolo, Maria; Valerio, Maria Cristina; Santoro, Raffaela; Goeman, Frauke; Maidecchi, Anna; Mattoli, Luisa; Manetti, Cesare; Di Agostino, Silvia; Muti, Paola; Blandino, Giovanni; Strano, Sabrina

    2015-01-01

    Malignant pleural mesothelioma is a poorly treated neoplasia arising from the pleural mesothelial lining. Here we document that the leaf extract of Cynara scolymus exerts broad antitumoral effects both in vitro and in vivo on mesothelioma cell lines. We found that Cynara scolymus treatment affects strongly cell growth, migration and tumor engraftment of mesothelioma cell lines. Strikingly, dietary feeding with Cynara scolymus leaf extract reduces the growth of mesothelioma xenografted tumors ...

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

    Directory of Open Access Journals (Sweden)

    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.

  17. Malignant pleural mesothelioma in a child

    Directory of Open Access Journals (Sweden)

    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.

  18. Comprehensive immunoproteogenomic analyses of malignant pleural mesothelioma.

    Science.gov (United States)

    Lee, Hyun-Sung; Jang, Hee-Jin; Choi, Jong Min; Zhang, Jun; de Rosen, Veronica Lenge; Wheeler, Thomas M; Lee, Ju-Seog; Tu, Thuydung; Jindra, Peter T; Kerman, Ronald H; Jung, Sung Yun; Kheradmand, Farrah; Sugarbaker, David J; Burt, Bryan M

    2018-04-05

    We generated a comprehensive atlas of the immunologic cellular networks within human malignant pleural mesothelioma (MPM) using mass cytometry. Data-driven analyses of these high-resolution single-cell data identified 2 distinct immunologic subtypes of MPM with vastly different cellular composition, activation states, and immunologic function; mass spectrometry demonstrated differential abundance of MHC-I and -II neopeptides directly identified between these subtypes. The clinical relevance of this immunologic subtyping was investigated with a discriminatory molecular signature derived through comparison of the proteomes and transcriptomes of these 2 immunologic MPM subtypes. This molecular signature, representative of a favorable intratumoral cell network, was independently associated with improved survival in MPM and predicted response to immune checkpoint inhibitors in patients with MPM and melanoma. These data additionally suggest a potentially novel mechanism of response to checkpoint blockade: requirement for high measured abundance of neopeptides in the presence of high expression of MHC proteins specific for these neopeptides.

  19. Malignant mesothelioma and asbestos-related lung cancer: diagnosis, prognosis and burden

    NARCIS (Netherlands)

    van der Bij, S.

    2012-01-01

    The negative health-related consequences of the use of asbestos have become very clear and widely recognized. This thesis focused on the most frequent asbestos induced cancers: mesothelioma and lung cancer. Mesothelioma A confirmed diagnosis of malignant mesothelioma is important to ensure proper

  20. 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)

  1. 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

  2. Recent progress in nickel carcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Sunderman, F.W. Jr.

    1984-01-01

    Positive bacterial mutagenesis tests have been obtained with Ni(II) in Corynybacterium, 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 crosslinks, (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, 4 tables.

  3. Digestive forms of Chagas disease and carcinogenesis: a study of association

    OpenAIRE

    Gullo, Caio Eduardo; Estofolete, Cássia Fernanda; Gil, Cristiane Damas; Christiano, Adriana Borgonovi; Netinho, João Gomes

    2012-01-01

    The authors analyze the relation between gastrointestinal carcinogenesis and Chagas disease, based on detailed review of the literature. To this end, epidemiological, experimental and human material pathology description studies have been selected. The article discusses the possibility of protection being afforded by not fully known morphokinetic cellular, immune and neuroendocrine factors that would be secondary to plexus degeneration. Also aspects related to the parasite-host interaction fr...

  4. Malignant Mesothelioma Mortality - United States, 1999-2015.

    Science.gov (United States)

    Mazurek, Jacek M; Syamlal, Girija; Wood, John M; Hendricks, Scott A; Weston, Ainsley

    2017-03-03

    Malignant mesothelioma is a neoplasm associated with occupational and environmental inhalation exposure to asbestos* fibers and other elongate mineral particles (EMPs) (1-3). Patients have a median survival of approximately 1 year from the time of diagnosis (1). The latency period from first causative exposure to malignant mesothelioma development typically ranges from 20 to 40 years but can be as long as 71 years (2,3). Hazardous occupational exposures to asbestos fibers and other EMPs have occurred in a variety of industrial operations, including mining and milling, manufacturing, shipbuilding and repair, and construction (3). Current exposures to commercial asbestos in the United States occur predominantly during maintenance operations and remediation of older buildings containing asbestos (3,4). To update information on malignant mesothelioma mortality (5), CDC analyzed annual multiple cause-of-death records † for 1999-2015, the most recent years for which complete data are available. During 1999-2015, a total of 45,221 deaths with malignant mesothelioma mentioned on the death certificate as the underlying or contributing cause of death were reported in the United States, increasing from 2,479 deaths in 1999 to 2,597 in 2015 (in the same time period the age-adjusted death rates § decreased from 13.96 per million in 1999 to 10.93 in 2015). Malignant mesothelioma deaths increased for persons aged ≥85 years, both sexes, persons of white, black, and Asian or Pacific Islander race, and all ethnic groups. Despite regulatory actions and the decline in use of asbestos the annual number of malignant mesothelioma deaths remains substantial. The continuing occurrence of malignant mesothelioma deaths underscores the need for maintaining measures to prevent exposure to asbestos fibers and other causative EMPs and for ongoing surveillance to monitor temporal trends.

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

    Science.gov (United States)

    Zhou, Huashi; Tamura, Taro; Kusaka, Yukinori; Suganuma, Narufumi; Subhannachart, Ponglada; Vijitsanguan, Chomphunut; Noisiri, Weeraya; Hering, Kurt G; Akira, Masanori; Itoh, Harumi; Arakawa, Hiroaki; Ishikawa, Yuichi; Kumagai, Shinji; Kurumatani, Norio

    2012-12-01

    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. 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. 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. 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. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  6. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  8. 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

  9. Reactive oxygen species a double-edged sword for mesothelioma

    Science.gov (United States)

    Catalani, Simona; Galati, Rossella

    2015-01-01

    It is well known that oxidative stress can lead to chronic inflammation which, in turn, could mediate most chronic diseases including cancer. Oxidants have been implicated in the activity of crocidolite and amosite, the most powerful types of asbestos associated to the occurrence of mesothelioma. Currently rates of mesothelioma are rising and estimates indicate that the incidence of mesothelioma will peak within the next 10–15 years in the western world, while in Japan the peak is predicted not to occur until 40 years from now. Although the use of asbestos has been banned in many countries around the world, production of and the potentially hazardous exposure to asbestos is still present with locally high incidences of mesothelioma. Today a new man-made material, carbon nanotubes, has arisen as a concern; carbon nanotubes may display ‘asbestos-like’ pathogenicity with mesothelioma induction potential. Carbon nanotubes resulted in the greatest reactive oxygen species generation. How oxidative stress activates inflammatory pathways leading to the transformation of a normal cell to a tumor cell, to tumor cell survival, proliferation, invasion, angiogenesis, chemoresistance, and radioresistance, is the aim of this review. PMID:26078352

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

    Directory of Open Access Journals (Sweden)

    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

  11. Cul4A overexpression associated with Gli1 expression in malignant pleural mesothelioma

    Science.gov (United States)

    Yang, Yi-Lin; Ni, Jian; Hsu, Ping-Chih; Mao, Jian-Hua; Hsieh, David; Xu, Angela; Chan, Geraldine; Au, Alfred; Xu, Zhidong; Jablons, David M; You, Liang

    2015-01-01

    Malignant pleural mesothelioma (mesothelioma) is a highly aggressive cancer without an effective treatment. Cul4A, a scaffold protein that recruits substrates for degradation, is amplified in several human cancers, including mesothelioma. We have recently shown that Cul4A plays an oncogenic role in vitro and in a mouse model. In this study, we analysed clinical mesothelioma tumours and found moderate to strong expression of Cul4A in 70.9% (51/72) of these tumours, as shown by immunohistochemistry. In 72.2% mesothelioma tumours with increased Cul4A copy number identified by fluorescence in situ hybridization analysis, Cul4A protein expression was moderate to strong. Similarly, Cul4A was overexpressed and Cul4A copy number was increased in human mesothelioma cell lines. Because Gli1 is highly expressed in human mesothelioma cells, we compared Cul4A and Gli1 expression in mesothelioma tumours and found their expression associated (P mesothelioma cell lines, inhibiting Cul4A by siRNA decreased Gli1 expression, suggesting that Gli1 expression is, at least in part, regulated by Cul4A in mesothelioma cells. Our results suggest a linkage between Cul4A and Gli1 expression in human mesothelioma. PMID:26218750

  12. VEGF targeting in mesotheliomas using an interleukin-6 signal inhibitor based on adenovirus gene delivery.

    Science.gov (United States)

    Adachi, Yasuo; Yoshio-Hoshino, Naoko; Aoki, Chieko; Nishimoto, Norihiro

    2010-06-01

    Malignant mesotheliomas reportedly secrete interleukin-6 (IL-6) which augments production of vascular endothelial growth factor (VEGF) from mesothelioma cells. We previously reported the development of a new receptor inhibitor of IL-6 (NRI) by genetically engineering tocilizumab, a humanized anti-IL-6 receptor monoclonal antibody. Since NRI is encoded on a single gene, it is easily applicable to a gene delivery system using virus vehicles. In this study, we report VEGF targeting through NRI expression based on adenovirus-mediated gene delivery in mesothelioma cells. We constructed an NRI expression vector in the context of a tropism-modified adenovirus vector that had enhanced infectivity in mesothelioma cells. This virus effectively induced NRI secretion from mesothelioma cells. This virus infection also reduced the VEGF production in mesothelioma cells. These results indicate that NRI shows potential as an agent in the treatment of mesotheliomas.

  13. Radical multimodality therapy for malignant pleural mesothelioma.

    Science.gov (United States)

    Abdel-Rahman, Omar; Elsayed, Zeinab; Mohamed, Hadeer; Eltobgy, Mostafa

    2018-01-08

    Malignant pleural mesothelioma is an almost always fatal tumour, for which palliative platinum-based chemotherapy is currently the standard treatment. Multimodal therapeutic strategies incorporating surgery, radiation therapy or photodynamic therapy and chemotherapy have been recommended for selected patients but there is no consensus about their effectiveness. To assess the benefits and harms of radical multimodal treatment options (including radical surgery ± radical radiotherapy ± photodynamic therapy ± systemic therapy) compared to each other or to palliative treatments, for people with malignant pleural mesothelioma. We reviewed data from the Cochrane Lung Cancer group's Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and Embase. We also checked reference lists of primary original studies, review articles and relevant conference proceedings manually for further related articles up to 21 March 2017. We included parallel-group randomised controlled trials of multimodal therapy for people with malignant pleural mesothelioma (stages I, II or III) that measured at least one of the following endpoints: overall survival, health-related health-related quality of life, adverse events or progression-free survival. We considered studies regardless of language or publication status. Two review authors independently extracted relevant information on participant characteristics, interventions, study outcomes, and data on the outcomes for this review, as well as information on the design and methodology of the studies. Two review authors assessed the risk of bias in the included trials using pre-defined 'Risk of bias' domains. We assessed the methodological quality using GRADE. We conducted this review in accordance with the published Cochrane protocol. Two randomised clinical trials with 104 participants fulfilled our inclusion criteria. Both trials were at high risk of bias (for outcomes other than overall survival), and we rated

  14. 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

  15. Role of bacteria in oral carcinogenesis

    Directory of Open Access Journals (Sweden)

    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.

  16. Oral cyclophosphamide and etoposide in treatment of malignant pleural mesothelioma.

    Science.gov (United States)

    Gunduz, Seyda; Mutlu, Hasan; Goksu, Sema Sezgin; Arslan, Deniz; Tatli, Ali Murat; Uysal, Mukremin; Coskun, Hasan Senol; Bozcuk, Hakan; Ozdogan, Mustafa; Savas, Burhan

    2014-01-01

    Malignant mesothelioma (MM) is almost always fatal and few treatment options are available. The aim of this study was to evaluate the efficacy of oral cyclophosphamide and etoposide for patients who underwent standard treatment for advanced MM. This study included 22 malignant pleural mesothelioma patients who were treated with oral cyclophosphamide and etoposide (EE). The average follow-up period of the patients was 39.1 months. Under the treatment of oral EE, median progression- free survival was 7.7 months [95%CI HR (4.3-11.1)] and median overall survival was 28.1 months [95%CI HR (5.8-50.3)]. The treatment response rates were as follows: 4 patients (27.3%) had a partial response (PR), 12 (54.5%) had stable disease (SD), and progressive disease (PD) was observed in 6 (35.9%). Oral EE can be administered effectively to patients with inoperable malignant mesothelioma who had previously received standard treatments.

  17. MR imaging features of peritoneal adenomatoid mesothelioma: a case report

    Energy Technology Data Exchange (ETDEWEB)

    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)

  18. 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)

  19. 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)

  20. 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

  1. Multimodal treatment for resectable epithelial type malignant pleural mesothelioma

    Directory of Open Access Journals (Sweden)

    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.

  2. Bacterionomics and vironomics in carcinogenesis

    Directory of Open Access Journals (Sweden)

    Pratiwi Sudarmono

    2017-02-01

    Full Text Available Virus and bacteria are microbes which are very common cause human infection. Most of the bacterial infection can be eradicated by antibiotics and infection symptoms disappear. But for virus infection, once infected, the virus will persistently stay in the host, even undergo not only a lytic cycle but also integrated into host genome. Nowadays, at least 6 virus type are consistently related to human cancer, such as EBV,HPV,HTLV,HBV,HCV,HKSV, and the new one Merkel Virus (MCV. Although not every infected people will get cancer, but around 20% of the whole cancer in human are caused by viral oncogene. Class one oncogenic bacterial is Helicobacter pylori. Infection with this bacteria can cause persistent gastro duodenal inflammation which cause some alteration in gastric cell growth into transformation. Expression of Cag gene and Vac gene and some expression of OMP protein usually link to gastric cancer. Molecular mechanisms of carcinogenesis for every virus which cause infection  is a very complex , which include several processes caused by cell transformation. Besides, other host and environmental factors are also play a significant role in cancer development. Some scientist put a Hallmark analysis as a model to quickly summarize what pathobiology process will happen and what gene or protein caused the process. The Hallmark analysis comprise of several process which may happen simultaneously because some of the Hallmark is caused by the same protein. The Hallmark consists of various virus strategies in oncogenesis such as promoting angiogenesis, avoiding immune destruction, genome instability and mutation, deregulating cellular energetic, resisting cell death, sustaining proliferative signaling, evading growth suppressors, enabling cellular immortality, promoting inflammation and activation metastasis. For example, infection by HPV, will cause low grade dysplasia which can continue to invasive cervical cancer. After host cell transformation, in

  3. Malignant pleural mesothelioma: Computed tomography and correlation with histology

    International Nuclear Information System (INIS)

    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

  4. Malignant pleural mesothelioma: Computed tomography and correlation with histology

    Energy Technology Data Exchange (ETDEWEB)

    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

  5. A worrying increase in the incidence of mesothelioma in Israel.

    Science.gov (United States)

    Ariad, S; Barchana, M; Yukelson, A; Geffen, D B

    2000-11-01

    Exposure to asbestos is the main established cause of mesothelioma; the incidence of this tumor is thus often interpreted as an index of past exposure. Asbestos has been widely used in Israel in industry and building, exposing certain population groups to the risk of developing mesothelioma. To analyze the incidence of mesothelioma in Israel during the years 1960-96, and to project its trend for the following years. We conducted a population-based study of the incidence of mesothelioma reported to the Israel Cancer Registry during 1960-96. Time trends were analyzed from data on the annual import of asbestos to Israel, which may indicate the magnitude of past exposure. Based on these findings, trends in the incidence of mesothelioma in Israel were projected for the subsequent years. A total of 327 cases of mesothelioma were reported to the Israel Cancer Registry during the study period. The incidence in Jews was higher than in Arabs (age-standardized incidence rate 2.64 vs. 1.35 per million/year, respectively). Among the Jewish population, Israeli-born males and males born in Europe and America showed the highest incidence (ASR 4.23 and 4.15 per million/year, respectively). Israeli-born males were 20 years younger than Jewish males born elsewhere. The incidence was twice as high among males than females and increased sevenfold from its nadir (1.17 per million/year) in 1978-80 to its peak (8.5 per million/year) in 1993-96. During a similar period the incidence among females increased from 0.33 to 2.56 per million/year. The incidence in both sexes does not appear to level off. The large wave of immigration from the former Soviet Union that began in 1989 only partly accounts for the increased incidence in 1993-96. The time trend in the incidence of mesothelioma in both sexes parallels the use of asbestos in Israel, which peaked in the years 1976-78. The incidence of mesothelioma in Israel has increased sharply in recent years, unrelated to a wave of immigration from

  6. Primary malignant mesothelioma of the pericardium : a case report

    Energy Technology Data Exchange (ETDEWEB)

    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.

  7. 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.

  8. [Benign multicystic peritoneal mesothelioma in a patient with Crohn disease].

    Science.gov (United States)

    Fluxá, Daniela; Kronberg, Udo; Lubascher, Jaime; O'Brien, Andrés; Las Heras, Facundo; Ibáñez, Patricio; Quera, Rodrigo

    2016-12-01

    Benign multicystic peritoneal mesothelioma is an uncommon lesion arising from the peritoneal mesothelium. It is asymptomatic or presents with unspecific symptoms. Imaging techniques may reveal it, however the final diagnosis can only be made by histopathology. Surgery is the only effective treatment considering its high recurrence rate. We report a 19 years old male with Crohn’s disease. Due to persistent abdominal pain, an abdominal magnetic resonance imaging was performed, showing a complex cystic mass in the lower abdomen. The patient underwent surgery and the lesion was completely resected. The pathological study reported a benign multicystic peritoneal mesothelioma.

  9. Tremelimumab for the treatment of malignant mesothelioma.

    Science.gov (United States)

    Guazzelli, Alice; Hussain, Michelle; Krstic-Demonacos, Marija; Mutti, Luciano

    2015-01-01

    Tremelimumab demonstrated therapeutic activity in different malignancies, including malignant pleural mesothelioma (MPM); however, continued research could improve the therapeutic index of this agent. This review describes tremelimumab's clinical efficacy, administration and safety in patients affected with MPM and reports the state of the art clinical trials of tremelimumab. A literature search using the PubMed database was conducted using the search terms tremelimumab, MPM, current therapy, immune checkpoint blockage and cytotoxic T lymphocyte-associated antigen-4. Data was also obtained from meeting abstracts and clinical trial registries. The use of immunotherapy has been extended from melanoma to thoracic malignancies or lung cancer and MPM. The first clinical trials for MPM with drugs modulating immune checkpoints have been tested or are currently being tested with the first results now under critical consideration. Among these drugs, tremelimumab has been attracting attention as a potential new treatment for MPM. Nevertheless, even though clinical efficacy has been preliminarily demonstrated, the cost/benefit ratio of this drug for this neoplasm is yet to be ascertained.

  10. Survey and biological insights of pemetrexed-related therapeutic improvement in mesothelioma: The Nancy Centre of Biological Resources' Mesothelioma Cohort.

    Science.gov (United States)

    Vlastos, Fotis; Hillas, Georgios; Vidal, Philippe; Lacomme, Stéphanie; Galateau-Sallé, Françoise; Vollmer, Ekkehard; Guzman-Costabel, Josune; Vignaud, Jean Michel; Martinet, Nadine

    2009-10-01

    We report a survey of mesothelioma survival rates with insights into the survival benefit because of pemetrexed. We also studied a potential link between specific single nucleotide polymorphisms of transcobalamin II (TCII) gene and susceptibility to both asbestos and pemetrexed. Clinical and occupational data from 287 consecutive mesothelioma patients were collected from the north-east region of France (1989-2007). Blood or paired tumoral and normal samples were collected from the last 210 French patients to study the TCII single nucleotide polymorphisms at the codon 259 (quantitative polymerase chain reaction). Results were compared with those obtained from a group of 263 French control healthy subjects and to a group of 91 German mesothelioma patients. Patients' characteristics and genotypes results were statistically analyzed for significant correlations. The mean overall patient's survival was 18.19 +/- 21.07 months. Pemetrexed increased the patients' survival by 50% (21.81 versus 16.99 months). The TCII allele Proline (Pro) was overrepresented into the mesothelioma cohort when compared with the controls (35 versus 19.77%). This also concerned German patients. The alleles Pro and Proline Arginine (ProArg) were more frequent among patients exposed to asbestos (p = 0.005, p < 0.001, respectively). The allele ProArg was associated with the longest survival while under pemetrexed (p = 0.007). No difference was found in the genotypes of patients untreated with pemetrexed. Pemetrexed treatment is related to a survival increase in mesothelioma patients. The allele Pro seems overrepresented in mesothelioma patients. Those having the allele ProArg present a better outcome under pemetrexed.

  11. 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

  12. 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%.

  13. 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.

  14. Experimental radiation carcinogenesis: what have we learned

    International Nuclear Information System (INIS)

    Fry, R.J.M.

    1980-01-01

    The author reviews the need for animal experiments in development of a biological model for radioinduced carcinogenesis. He concludes they are vital for: (1) study of mechanisms; (2) establishment of generalizations; (3) elucidation of dose-response and time-dose relationships; and (4) determination of dose-distributions and their results, particularly for radionuclides

  15. 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.)

  16. Radiation carcinogenesis and related radiobiology. Special listing

    International Nuclear Information System (INIS)

    1980-01-01

    The special listing of Current Cancer Research Projects is a publication of the International Cancer Research Data Bank (ICRDB) Program of the National Cancer Institute. Each Listing contains descriptions of ongoing projects in one selected cancer research area. The research areas include: Human cancer and exposure to radiation; Experimental radiation carcinogenesis and radiation biology

  17. 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...... clinical trials evaluating the effect of targeted treatments in MM....

  18. Legal claims for malignant mesothelioma: dealing with all cases

    NARCIS (Netherlands)

    van der Bij, Sjoukje; Baas, Paul; van de Vijver, Marc J.; de Mol, Bas A. J. M.; Burgers, Jacobus A.

    2013-01-01

    Apart of medical reasons, a definitive diagnosis of malignant mesothelioma may be required as a basis for a claim of financial compensation although a pathological source of conclusive evidence is missing. Clinical assessment of all available data is then the only option to come to a final

  19. A Potential Therapeutic Strategy for Malignant Mesothelioma with Gene Medicine

    Science.gov (United States)

    Tada, Yuji; Shimada, Hideaki; Hiroshima, Kenzo; Tagawa, Masatoshi

    2013-01-01

    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. PMID:23484132

  20. 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...

  1. 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.

  2. 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 ...

  3. Consensus Report of the 2015 Weinman International Conference on Mesothelioma

    Science.gov (United States)

    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...

  4. 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,

  5. 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

  6. Oral mucosal carcinogenesis in SENCAR mice.

    Science.gov (United States)

    Kim, Tae-Won; Chen, Qianming; Shen, Xiaodong; Regezi, Joseph A; Ramos, Daniel M; Tanaka, Hironori; Jordan, Richard C K; Kramer, Randall H

    2002-01-01

    Animal models of oral carcinogenesis have been developed but most use the hamster buccal pouch or rat oral mucosa. With completion of human and murine genome sequencing, the development of a mouse model of oral carcinogenesis may prove useful for future genomic studies of oral carcinogenesis. To achieve this objective, 30 SENCAR mice were initiated by brush application of palatal, buccal and tongue mucosa with 200 nmol 7,12-dimethylbenz[a]anthracene (DMBA) using 3 treatment regimens, and promoted by brush application with 5 nmol 12-O-tetradecanoylphorbol-13-acetate (TPA) for a total of 28 weeks. Alternatively, 5 mice were treated with 0.5% 4-nitroquinoline-1-oxide (4NQO) alone by brush application for 28 weeks. There were another 6 control mice treated with vehicle alone. The tumor samples were analyzed for the presence of H-ras codon 61 gene mutations using a mutant-allele-specific amplification-polymerase chain reaction (MASA-PCR) technique. The results showed that among the group of 24 mice initiated with DMBA for 2 or 6 weeks, a range of papilliferous lesions were seen on the buccal mucosa comprising papillomas, papillomas with dysplasia and 7 squamous cell carcinomas (SCC). In those 6 mice initiated with 1 week of DMBA, only papillomas developed. In the 5 mice treated with 4NQO, one developed papillomas with dysplasia and two had SCCs in the tongue mucosa but not the buccal mucosa. Both carcinogens induced codon 61 mutation of the H-ras gene at a high frequency. The results indicated that DMBA/TPA and 4NQO in SENCAR mice reliably produced preneoplastic and malignant oral cavity lesions, which resemble the multistages for human oral carcinogenesis, and targeted to site-specific zones of the oral mucosa, namely the buccal mucosa and tongue, respectively. These results show that SENCAR mice can be used as a unique model of oral carcinogenesis with the potential for detailed molecular studies of neoplastic progression to SCC.

  7. Malignant Mesothelioma: Clinical, Pathological and Radiological Findings

    Directory of Open Access Journals (Sweden)

    Yeşim Yıldırım

    2012-01-01

    Full Text Available Aim: Malignant pleural mesothelioma is a tumor of locally invasive character and of fatal course, frequently arising following asbest exposure. In the present study we attempted to retrospectively evaluate the clinical, pathological, and radiological findings of 27 cases diagnosed with MPM. Material and Method: 27 cases diagnosed with MPM in our medical facility have been included into the study, 14 females, and 13 males. Of the cases, 4 have been diagnosed based on transthoracic pleural biopsy, and 23 %u2013 using surgical methods (VYTC, thoracotomy. Result: Radiological evaluation revealed pleural thickening in 23 (85.2%, pleural effusion in 20 (74.1%, volume loss in 15 (55.6%, pleural nodulation in 14 (51.9%, mediastinal shift in 4 (14.8%, pneumothorax in 1 (3.7%, and hydropneumothorax in 1 (3.7% of the cases, respectively. Histopathological examination failed to reveal any typing in 17 (63% of the cases. On the other hand, 5 (18.5% of the remainder cases were of the epitheloid type, 4 (14.8% were of the sarcomatoid type, and 1 (3.7% was of the biphasic MPM type. Mean survival rate of the 3 (11.1% Stage I cases was 1449 days, of the 6 (22.2% Stage II cases was 480 days, of the 18 (66.7% Stage III cases was 214 days. We had no Stage IV cases at the time of diagnosis. A statistically significant difference has been established between the Stage and the mean survival rate of the cases. Discussion: In diagnosing MPM, proper histopathological exam followed by proper radiological staging should be carried out. A multimodality approach comprises the present MPM treatment, but total cure cannot be provided.

  8. Mushroom Ganoderma lucidum prevents colitis-associated carcinogenesis in mice.

    Directory of Open Access Journals (Sweden)

    Daniel Sliva

    Full Text Available 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.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.Our data suggest that GLT could be considered as an alternative dietary approach for the prevention of colitis-associated cancer.

  9. 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.

  10. 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

  11. Cervical carcinogenesis: the role of co-factors and generation of reactive oxygen species

    Directory of Open Access Journals (Sweden)

    Giuliano Anna

    2003-01-01

    Full Text Available Several HPV co-factors have been proposed, some more or less consistently associated with cervical dysplasia and cancer risk. More research, using prospective cohort designs, is needed to further describe where in carcinogenesis these factors are working and to assess the biological mechanism of these factors. In addition, further research is needed to define the role of various hormonal contraceptive formulations in promoting cervical carcinogenesis. While many interesting scientific questions remain to be answered, results from the numerous epidemiological studies conducted to date indicate that cervical dysplasia and cancer may be reduced if the oxidant antioxidant ratio is shifted to more of and antioxidant profile. In addition to cervical cancer screening, a reduction in cervical cancer incidence may be accomplished by reducing tobacco use, increasing nutritional status, and utilizing barrier contraception to prevent infection with other sexually acquired infections.

  12. 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

  13. 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

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

    Science.gov (United States)

    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.

  15. Estimated future incidence of malignant mesothelioma in South Korea: Projection from 2014 to 2033.

    Science.gov (United States)

    Kwak, Kyeong Min; Paek, Domyung; Hwang, Seung-Sik; Ju, Young-Su

    2017-01-01

    Malignant mesothelioma is a malignant tumor on the pleura or the peritoneum caused mostly by asbestos. Although asbestos is not currently used in South Korea, the incidence of mesothelioma is increasing due to its long latent period. This study predicted the incidence of malignant mesothelioma in South Korea over the next 20 years using an age-period-cohort (APC) model. Data regarding mesothelioma incidence from 1994-2013 were acquired from the Korea Central Cancer Registry (KCCR). Demographic data, including prospective resident data, were acquired from the Korean Statistical Information Service (KOSIS) for 1994-2033. An APC model with Møller's power-link function was utilized to predict the incidence of mesothelioma. It was predicted that 2,380 and 1,199 new cases of mesothelioma in men and women, respectively, would occur over the next 20 years. For both sexes, the mesothelioma incidence rate was predicted to be greater in 2029-2033 compared to that in 2009-2013 (men, 0.282 vs 0.563; women, 0.155 vs 0.217). For men, the age-standardized incidence rate was predicted to be slightly greater in 2029-2033 relative to the rate in 2009-2013 (0.228 vs 0.235), while the age-standardized incidence rate in women decreased within the same timeframe (0.113 vs 0.109). The changes in mesothelioma incidence were mostly caused by changes in the population structure due to aging and not by changes in the mesothelioma risk ratio. The results of this study project a continuous increase in mesothelioma incidence in South Korea over the next 20 years. Although the projected increase in mesothelioma incidence was not related to an increase in the mesothelioma risk ratio, continuous preventive efforts are necessary to reduce the exposure to asbestos and prevent the trend from worsening.

  16. The Fate of Intrapleurally Injected Bone Marrow-Derived Stem Cells in Mice with Pleural Mesothelioma

    Science.gov (United States)

    2012-12-01

    11-1-0574 TITLE: The Fate of Intrapleurally Injected Bone Marrow-Derived Stem Cells in Mice with Pleural Mesothelioma PRINCIPAL...Mice with Pleural Mesothelioma 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-11-1-0574 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Jonathan M...stem cells (BMSCs) as potential therapeutics against malignant mesothelioma (MM). Our over-arching goal was to determine whether fluorescently

  17. The role of 18F-FDG-PET/ceCT in peritoneal mesothelioma.

    Science.gov (United States)

    Dubreuil, Julien; Giammarile, Francesco; Rousset, Pascal; Rubello, Domenico; Bakrin, Naoual; Passot, Guillaume; Isaac, Sylvie; Glehen, Olivier; Skanjeti, Andrea

    2017-04-01

    The aim of this study was to assess glucose metabolism of multicystic peritoneal mesothelioma and epithelioid peritoneal mesothelioma by fluorine-18 fluorodeoxyglucose (F-FDG)-PET/contrast-enhanced computed tomography (ceCT) and to assess its prognostic impact. Twenty-three (14 women) patients, without previous treatment, underwent F-FDG-PET/ceCT before peritoneal mesothelioma cytoreductive surgery and intraperitoneal chemotherapy. F-FDG-PET/ceCT was interpreted prospectively as positive or negative. Maximum standardized uptake value (SUVmax) of each lesion was measured retrospectively on the basis of postsurgery data. At laparotomy, disease extension was estimated with the Peritoneal Cancer Index. The median follow-up was 27 months (95% confidence interval: 12.9-37.8); progression-free survival (PFS) was recorded. Nine patients were affected by multicystic and 14 were affected by epithelioid peritoneal mesothelioma. PET showed mild focal uptake in one case of multicystic peritoneal mesothelioma, whereas in eight patients, no abnormal uptake was observed. PET was positive in 12/14 patients with epithelioid peritoneal mesothelioma. Sensitivity, specificity and accuracy were respectively 86, 89 and 87%; the qualitative assessment was statistically different (P=0.0020, χ). Multicystic peritoneal mesothelioma histology was significantly associated with lower SUVmaxlesion (P=0.0061), SUVmaxlesion/liver (P=0.0025), Peritoneal Cancer Index, younger age, and it was observed only in women.Recurrence was observed on nine patients affected by epithelioid peritoneal mesothelioma, whereas no recurrences were observed among multicystic peritoneal mesothelioma patients. SUVmaxlesion (P=0.0278) and age (P=0.0241) were significantly associated with PFS in patients with epithelioid peritoneal mesothelioma. F-FDG-PET/ceCT showed significant differences between multicystic and epithelioid peritoneal mesothelioma, whereas SUVmaxlesion was associated with PFS in the latter. Although

  18. Diagnostic Ultrasound of Diffuse-Nodu lar Pleural Mesotheliomas — Echosemiotics, Growth Characteristics, and Scanning Techniques

    OpenAIRE

    D.V. Safonov; А.А. Sozinova

    2014-01-01

    The aim of the investigation was the optimization of chest ultrasound technique in the diagnosis of diffuse-nodular pleural mesotheliomas, development and systematization of their ultrasound semiotics. Materials and Methods. We studied the ultrasonic picture of 32 mesotheliomas (31 malignant), among them 30 — diffuse-nodular, 2 — focal. Results. There were developed the assessment criteria of diffuse-nodular mesothelioma echosemiotics: significant (over 15 mm) diffuse thickening of co...

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

    Directory of Open Access Journals (Sweden)

    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.

  20. Extracellular signal regulated kinase 5 and inflammasome in progression of mesothelioma

    Science.gov (United States)

    Thompson, Joyce K.; Shukla, Anurag; Leggett, Alan L.; Munson, Phillip B.; Miller, Jill M.; MacPherson, Maximilian B.; Beuschel, Stacie L.; Pass, Harvey I.; Shukla, Arti

    2018-01-01

    Malignant mesothelioma is an aggressive cancer in desperate need of treatment. We have previously shown that extracellular signaling regulated kinase 5 (ERK5) plays an important role in mesothelioma pathogenesis using ERK5 silenced human mesothelioma cells exhibiting significantly reduced tumor growth in immunocompromised mice. Here, we used a specific ERK 5 inhibitor, XMD8-92 in various in vitro and in vivo models to demonstrate that inhibition of ERK5 can slow down mesothelioma tumorigenesis. First, we show a dose dependent toxicity of XMD8-92 to 2 human mesothelioma cell lines growing as a monolayer. We also demonstrate the inhibition of ERK5 phosphorylation in various human mesothelioma cell lines by XMD8-92. We further confirmed the toxicity of XMD8-92 towards mesothelioma cell lines grown as spheroids in a 3-D model as well as in intraperitoneal (immune-competent) and intrapleural (immune-deficient) mouse models with and without chemotherapeutic drugs. To ascertain the mechanism, we explored the role of the nod-like receptor family member containing a pyrin domain 3 (NLRP3) inflammasome in the process. We found XMD8-92 attenuated naïve and chemotherapeutic-induced inflammasome priming and activation in mesothelioma cells. It can thus be concluded that ERK5 inhibition attenuates mesothelioma tumor growth and this phenomenon in part is regulated by the inflammasome. PMID:29416614

  1. 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)

  2. 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)

  3. Preclinical studies identify novel targeted pharmacological strategies for treatment of human malignant pleural mesothelioma

    Science.gov (United States)

    Favoni, Roberto E; Daga, Antonio; Malatesta, Paolo; Florio, Tullio

    2012-01-01

    The incidence of human malignant pleural mesothelioma (hMPM) is still increasing worldwide. hMPM prognosis is poor even if the median survival time has been slightly improved after the introduction of the up-to-date chemotherapy. Nevertheless, large phase II/III trials support the combination of platinum derivatives and pemetrexed or raltitrexed, as preferred first-line schedule. Better understanding of the molecular machinery of hMPM will lead to the design and synthesis of novel compounds targeted against pathways identified as crucial for hMPM cell proliferation and spreading. Among them, several receptors tyrosine kinase show altered activity in subsets of hMPM. This observation suggests that these kinases might represent novel therapeutic targets in this chemotherapy-resistant disease. Over these foundations, several promising studies are ongoing at preclinical level and novel molecules are currently under evaluation as well. Yet, established tumour cell lines, used for decades to investigate the efficacy of anticancer agents, although still the main source of drug efficacy studies, after long-term cultures tend to biologically diverge from the original tumour, limiting the predictive potential of in vivo efficacy. Cancer stem cells (CSCs), a subpopulation of malignant cells capable of self-renewal and multilineage differentiation, are believed to play an essential role in cancer initiation, growth, metastasization and relapse, being responsible of chemo- and radiotherapy refractoriness. According to the current carcinogenesis theory, CSCs represent the tumour-initiating cell (TIC) fraction, the only clonogenic subpopulation able to originate a tumour mass. Consequently, the recently described isolation of TICs from hMPM, the proposed main pharmacological target for novel antitumoural drugs, may contribute to better dissect the biology and multidrug resistance pathways controlling hMPM growth. PMID:22289125

  4. 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

  5. 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

  6. 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

  7. Somatic Host Cell Alterations in HPV Carcinogenesis

    OpenAIRE

    Tamara R. Litwin; Megan A. Clarke; Michael Dean; Nicolas Wentzensen

    2017-01-01

    High-risk human papilloma virus (HPV) infections cause cancers in different organ sites, most commonly cervical and head and neck cancers. While carcinogenesis is initiated by two viral oncoproteins, E6 and E7, increasing evidence shows the importance of specific somatic events in host cells for malignant transformation. HPV-driven cancers share characteristic somatic changes, including apolipoprotein B mRNA editing catalytic polypeptide-like (APOBEC)-driven mutations and genomic instability ...

  8. Radiation carcinogenesis and related radiobiology. Special listing

    International Nuclear Information System (INIS)

    1978-01-01

    This Special Listing of Current Cancer Research Projects is a service of the International Cancer Research Data Bank (ICRDB) program of the National Cancer Institute. Each listing contains descriptions of ongoing projects in one selected cancer research area. The descriptions are provided by cancer scientists in about 50 different countries. Research areas covered in this listing are: Human cancer and exposure to radiation; experimental radiation carcinogenesis and radiation biology

  9. Inhibition of carcinogenesis by retinoids. [Review

    Energy Technology Data Exchange (ETDEWEB)

    Nettesheim, P.

    1979-01-01

    Progress made in recent years in the search for retinoids with anticarcinogenic activity is reviewed. There are many studies to be found in the literature which show no substantial effect of retinoids on carcinogenesis or tumor growth. Some of these negative findings may be related to the carcinogen dose used, the type of retinoid used, the dose, dose schedule or mode of administration of the retinoid. Others may indicate that the particular type of tumor or tumor system is, indeed, refractory to retinoids in general or to those retinoids that were tested. A great gap still exists in our knowledge concerning the pharmake-kinetics of most retinoids their availability to various normal and cancerous tissues, and the role and existence of transport and binding proteins. There are studies which indicate that under certain conditions, particularly conditions of topical application, some retinoids may even enhance carcinogenesis. It seems, however, indisputable by now that some retinoids are effective inhibitors of carcinogenesis in some organ systems and can even inhibit the growth of some established tumors. While the mechanisms of these inhibitory effects are presently not understood, it does seem clear that they are not mediated via the cytotoxic mechanisms typical of chemotherapeutic agents. The hope that retinoids might become an effective tool to halt the progression of some neoplastic diseases, seems to be justified.

  10. 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.)

  11. Oxidative stress in prostate hypertrophy and carcinogenesis

    Directory of Open Access Journals (Sweden)

    Waldemar M. Przybyszewski

    2009-07-01

    Full Text Available Aging, significant impairment of the oxidation/reduction balance, infection, and inflammation are recognized risk factors of benign hyperplasia and prostate cancer. Chronic symptomatic and asymptomatic prostate inflammatory processes generate significantly elevated levels of reactive oxygen and nitrogen species, and halogenated compounds. Prostate cancer patients showed significantly higher lipid peroxidation and lower antioxidant levels in peripheral blood than healthy controls, whereas patients with prostate hyperplasia did not show such symptoms. Oxidative/nitrosative/halogenative stress causes DNA modifications leading to genome instability that may initiate carcinogenesis; however, it was shown that oxidative damage alone is not sufficient to initiate this process. Peroxidation products induced by reactive oxygen and nitrogen species seem to take part in epigenetic mechanisms regulating genome activity. One of the most common changes occurring in more than 90�0of all analyzed prostate cancers is the silencing of GSTP1 gene activity. The gene encodes glutathione transferase, an enzyme participating in detoxification processes. Prostate hyperplasia is often accompanied by chronic inflammation and such a relationship was not observed in prostate cancer. The participation of infection and inflammation in the development of hyperplasia is unquestionable and these factors probably also take part in initiating the early stages of prostate carcinogenesis. Thus it seems that therapeutic strategies that prevent genome oxidative damage in situations involving oxidative/nitrosative/halogenative stress, i.e. use of antioxidants, plant steroids, antibiotics, and non-steroidal anti-inflammatory drugs, could help prevent carcinogenesis.

  12. Profesi Epidemiologi

    Directory of Open Access Journals (Sweden)

    Buchari Lapau

    2011-01-01

    Full Text Available Makalah ini pertama kali menjelaskan perlu adanya profesi kesehatan masyarakat dalam rangka pembangunan kesehatan. Lalu dijelaskan apa profesi itu dan standar keberadaan profesi, atas dasar mana dapat ditetapkan bahwa pelayanan epidemiologi merupakan salah satu profesi. Dalam rangka pembinaan profesi kesehatan masyarakat, IAKMI dan APTKMI telah membentuk Majelis Kolegium Kesehatan Masyarakat Indonesia (MKKMI yang terdiri atas 8 kolegium antara lain Kolegium Epidemiologi, yang telah menyusun Standar Profesi Epidemiologi yang terdiri atas beberapa standar. Masing-masing standar dijelaskan mulai dari kurikulum, standar pelayanan epidmiologi, profil epidemiolog kesehatan, peran epidemiolog kesehatan, fungsi epidemiolog kesehatan, standar kompetensi epidemiologi, dan standar pendidikan profesi epidemiologi.

  13. 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

  14. 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.

  15. [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.

  16. Prognostic significance of DNA aneuploidy in diffuse malignant mesothelioma

    Energy Technology Data Exchange (ETDEWEB)

    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.

  17. Pleural mesothelioma in differential diagnostics of a tubercular exudative pleuritis

    Directory of Open Access Journals (Sweden)

    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

  18. 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)

  19. Exosomes in Development and Therapy of Malignant Mesothelioma

    Science.gov (United States)

    2015-09-01

    sapiens GN=PTGFRN PE=1 SV=2 FPRP_HUMAN Isoform 3 of Immunoglobulin superfamily member 8 OS=Homo sapiens GN=IGSF8 sp|Q969P0-3|IGSF8_HUMAN (+1) 40S...observed that the protein profile of exosomes changes drastically when grown under stressed conditions (0.5% FBS) compared to normal conditions (10...causing mesothelioma. Second, exosomes released from stressed cancer cells have a more distinct proteomic signature than unstressed cancer cells

  20. Glyco-Immune Diagnostic Signatures and Therapeutic Targets of Mesothelioma

    Science.gov (United States)

    2015-09-01

    glycogenes ” responsible for presentation of glyco-conjugates on surfaces of mesothelioma cells and in circulation will allow (a) identification of...were found disease- free at the end- point necropsy. Among the 25 animals that developed Blinded Assignment AE or MPM 0 20 40 60 80 100 0 20 40 60 80...necropsies out of 32 animals injected with silica, 31 animals were found disease- free and one animal was found to have developed a sarcoma tumor. All

  1. Peritoneal malignant mesothelioma in a patient with recurrent peritonitis

    International Nuclear Information System (INIS)

    Riddell, R.H.; Goodman, M.J.; Moossa, A.R.

    1981-01-01

    A patient is presented who developed a peritoneal malignant mesothelioma in association with severe persistent and recurrent diverticulitis. The case is unusual in that a spectrum of mesothelial proliferation was documented beginning initially as benign foci of mesothelial proliferation and passing through a stage of atypical proliferation before terminating as a malignant process. The possible role of the diverticular disease in the pathogenesis of the tumor is discussed

  2. Peritoneal malignant mesothelioma in a patient with recurrent peritonitis

    Energy Technology Data Exchange (ETDEWEB)

    Riddell, R.H.; Goodman, M.J.; Moossa, A.R.

    1981-07-01

    A patient is presented who developed a peritoneal malignant mesothelioma in association with severe persistent and recurrent diverticulitis. The case is unusual in that a spectrum of mesothelial proliferation was documented beginning initially as benign foci of mesothelial proliferation and passing through a stage of atypical proliferation before terminating as a malignant process. The possible role of the diverticular disease in the pathogenesis of the tumor is discussed.

  3. Second line therapy in malignant pleural mesothelioma: A systematic review.

    Science.gov (United States)

    Buikhuisen, Wieneke A; Hiddinga, Birgitta I; Baas, Paul; van Meerbeeck, Jan P

    2015-09-01

    After the implementation of standard first line chemotherapy with platinum and antifolates in pleural mesothelioma, patients are confronted with a need for second line treatment at relapse or progression. We conducted a systematic review of the literature for the activity, effectiveness and toxicity of second line treatment. The results are presented according to the class of drugs: chemotherapy and targeted or biological agent. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  4. Pericardial mesothelioma in a Bengal tiger (Panthera tigris).

    Science.gov (United States)

    Wiedner, Ellen B; Isaza, Ramiro; Lindsay, William A; Case, Allison L; Decker, Joshua; Roberts, John

    2008-03-01

    A 17-year-old Bengal tiger (Panthera tigris) presented with dyspnea and tachypnea. Radiographs revealed severe pleural and pericardial effusion, but no obvious mass. During attempts to remove the fluid under anesthesia, the cat developed cardiac tamponade and died. At necropsy, a nodular mass was found at the heart base and was identified as a pericardial mesothelioma. This is the first report of this tumor in any large cat.

  5. 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.

  6. 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

  7. 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.

  8. 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.

  9. 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.

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

    Science.gov (United States)

    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.

  11. 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

  12. Porcelain Factory Worker With Asbestos-related Mesothelioma

    Directory of Open Access Journals (Sweden)

    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.

  13. Benign multicystic mesothelioma: a case report of three sisters

    Directory of Open Access Journals (Sweden)

    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.

  14. Primary malignant pericardial sarcomatoid mesothelioma: An autopsy report.

    Science.gov (United States)

    Muta, Hiroko; Sugita, Yasuo; Ohshima, Koichi; Otsubo, Hitoshi

    2017-06-01

    Primary malignant pericardial sarcomatoid mesothelioma (PMPSM) is an extremely rare tumor with poor prognosis. We present an autopsy case in an 80-year-old man admitted for heart failure after one month of treatment at an outpatient clinic. He died three months after symptom onset. A complete autopsy revealed localization of the tumor to the pericardium without other lesions. Histologically, mainly spindle-shaped atypical cells with hyperchromatic nuclei and nucleoli were observed. Immunohistochemical markers for mesothelioma were positive for calretinin, cytokeratin AE1/AE3, and cytokeratin CAM5.2. Thus, we diagnosed primary sarcomatoid malignant mesothelioma of the pericardium. To our knowledge, only four PMPSM cases have been reported in the English literature in the past 30 years. Although PMPSM is rare, clinicians and pathologists should recognize it as a possible diagnosis of pericardial tumors. It is necessary to accumulate clinical and pathological diagnostic findings to establish early detection methods for this extremely rare disease. © 2017 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.

  15. Surgery as part of radical treatment for malignant pleural mesothelioma.

    Science.gov (United States)

    Waller, David A; Tenconi, Sara

    2017-07-01

    To review the latest developments in surgery for malignant pleural mesothelioma both in patient selection, surgical technique, and strategy. The International Association for the Study of Lung Cancer mesothelioma staging project has produced data to inform the 8th tumour node metastasis revision. The difficulty in clinical N staging and clinical T staging are highlighted and the importance of tumour volume is recognized. New imaging techniques can be utilized to assess tumour volume. The transition from extrapleural pneumonectomy to lung-sparing pleurectomy/decortication has extended the role of cancer-directed surgery into a more elderly population. More aggressive multimodality regimes, including induction radiotherapy are available to a selected population and adjuvant radiotherapy and chemotherapy are feasible in the elderly majority. Additional chemotherapy should not be delayed in those with poorer prognosis node positive, nonepithelioid disease. Radical surgery for malignant pleural mesothelioma can achieve significant survival when targeted in those with the best prognosis by careful staging. It can be made more accessible by lung preservation without compromising outcome. It should be part of multimodality therapy.

  16. Targeting immune checkpoints: New opportunity for mesothelioma treatment?

    Science.gov (United States)

    Marcq, Elly; Pauwels, Patrick; van Meerbeeck, Jan P; Smits, Evelien L J

    2015-12-01

    Malignant pleural mesothelioma is an aggressive cancer linked to asbestos exposure in most patients. Due to the long latency between exposure and presentation, incidence is expected to further increase in the next decade, despite the ban on asbestos import which occurred at the end of last century in industrialized countries. Platinum-based palliative chemotherapy is the only treatment with proven benefit on outcome, resulting in selected patients in a median overall survival of about 1 year. Therefore, there is room for therapeutic improvement using a new strategy to prolong survival. Dealing with cancer cell induced immunosuppression is a promising approach. Reactivating immune responses that are silenced by immune checkpoints recently gained a lot of interest. Checkpoint blockade has already shown promising preclinical and clinical results in several cancer types and is currently also being investigated in mesothelioma. Here, we discuss the expression patterns and mechanisms of action of CTLA-4 and PD-1 as the two most studied and of TIM-3 and LAG-3 as two interesting upcoming immune checkpoints. Furthermore, we review the clinical results of molecules blocking these immune checkpoints and point out their future opportunities with a special focus on mesothelioma. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. 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.

  18. Asbestos exposure and differences in occurrence of peritoneal mesothelioma between men and women across countries

    NARCIS (Netherlands)

    A. Burdorf (Alex); B. Järvholm; S. Siesling (Sabine)

    2007-01-01

    textabstractObjective: In several countries the incidence of peritoneal mesotheliomas among women closely mirrors the pattern among men. The aim was to investigate the role of asbestos exposure in the aetiology of peritoneal mesotheliomas in women and men. Methods: All cases of peritoneal

  19. 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

  20. An ultrastructural comparison of mesotheliomas and adenocarcinomas of the ovary and endometrium.

    Science.gov (United States)

    Warhol, M J; Hunter, N J; Corson, J M

    1982-01-01

    The ultrastructural features of 16 malignant mesotheliomas were compared qualitatively and quantitatively with nine ovarian adenocarcinomas and 11 endometrial adenocarcinomas. The mesotheliomas could be distinguished ultrastructurally by their significantly greater content of tonofilaments (p less than 0.001) and their lack of structures found in both ovarian and endometrial adenocarcinomas, specifically abundant mucin, numerous cilia, and dense core granules of the neurosecretory type.

  1. Targeting Immune Suppression to Refine Dendritic Cell-based Immunotherapy in Mesothelioma

    NARCIS (Netherlands)

    J.D. Veltman (Joris)

    2010-01-01

    textabstractMalignant mesothelioma (MM) is a highly aggressive neoplasm caused by neoplastic transformation of mesothelial cells that line the body’s serous cavities and the internal organs. In the majority of patients mesothelioma is localized within the pleural cavity. At this moment, no curative

  2. 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

  3. 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

  4. 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

  5. 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

  6. Latest developments in our understanding of the pathogenesis of mesothelioma and the design of targeted therapies.

    Science.gov (United States)

    Bononi, Angela; Napolitano, Andrea; Pass, Harvey I; Yang, Haining; Carbone, Michele

    2015-10-01

    Malignant mesothelioma is an aggressive cancer whose pathogenesis is causally linked to occupational exposure to asbestos. Familial clusters of mesotheliomas have been observed in settings of genetic predisposition. Mesothelioma incidence is anticipated to increase worldwide in the next two decades. Novel treatments are needed, as current treatment modalities may improve the quality of life, but have shown modest effects in improving overall survival. Increasing knowledge on the molecular characteristics of mesothelioma has led to the development of novel potential therapeutic strategies, including: molecular targeted approaches, that is the inhibition of vascular endothelial growth factor with bevacizumab; immunotherapy with chimeric monoclonal antibody, immunotoxin, antibody drug conjugate, vaccine and viruses; inhibition of asbestos-induced inflammation, that is aspirin inhibition of HMGB1 activity may decrease or delay mesothelioma onset and/or growth. We elaborate on the rationale behind new therapeutic strategies, and summarize available preclinical and clinical results, as well as efforts still ongoing.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  8. 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).

  9. The Role of the Stroma in Carcinogenesis

    Directory of Open Access Journals (Sweden)

    Nurija Bilalović

    2006-02-01

    Full Text Available This systematic review considers the most recent attitudes and news regarding the influence of the stroma on tumor initiation and progression. It is now widely accepted that tumor stroma plays an active role in carcinogenesis. Many different signaling molecules, ligands and signaling pathways recently have been discovered. This review considers the complexity of interactions between malignant cells and its stroma (cross-talk. The recent advances and better understanding of the tumor-stroma interactions will have important impact on the new and combined therapeutic approaches and modalities.

  10. Mechanisms of carcinogenesis prevention by flavonoids

    Directory of Open Access Journals (Sweden)

    G. A. Belitsky

    2014-01-01

    Full Text Available The mechanisms of anticancerogenic effects of flavanoids and isocyanates from the plants widely consumed in the midland belt of Russia were reviewed. Data of studies both in vitro and in vivo were analyzed. Special attention was paid to inhibition of targets responsible for carcinogen metabolic activation, carcinogenesis promotion and tumor progression as well as neoangiogenesis. Besides that the antioxidant properties of flavonoids and their effects on cell cycle regulation, apoptosis initiation and cell mobility were considered.

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

    International Nuclear Information System (INIS)

    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

  12. Asbestos textile production linked to malignant peritoneal and pleural mesothelioma in women: Analysis of 28 cases in Southeast China.

    Science.gov (United States)

    Gao, Zhibin; Hiroshima, Kenzo; Wu, Xiaodong; Zhang, Jixian; Shao, Dichu; Shao, Huajiang; Yang, Hanqing; Yusa, Toshikazu; Kiyokawa, Takako; Kobayashi, Makio; Shinohara, Yasushi; Røe, Oluf D; Zhang, Xing; Morinaga, Kenji

    2015-10-01

    Chrysotile had been used in asbestos textile workshops in Southeast China but a clear relation to mesothelioma is lacking. All patients diagnosed with mesothelioma from 2003 to 2010 at Yuyao People's Hospital were re-evaluated by multiple expert pathologists with immunohistochemistry and asbestos exposure data were collected. Of 43 patients with a mesothelioma diagnosis, 19 peritoneal and nine pleural cases were finally diagnosed as mesothelioma. All were females, and the mean age of the patients with peritoneal or pleural mesothelioma was 52.4 and 58.2 years, respectively. All these cases had a history of domestic or occupational exposure to chrysotile. Two-thirds of the patients were from two adjoining towns with multiple small asbestos textile workshops. Contamination of tremolite was estimated to be less than 0.3%. This is a report of mesothelioma in women exposed to chrysotile asbestos at home and at work, with an over-representation of peritoneal mesothelioma. © 2015 Wiley Periodicals, Inc.

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

    Directory of Open Access Journals (Sweden)

    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.

  14. Curcumin: the spicy modulator of breast carcinogenesis.

    Science.gov (United States)

    Banik, Urmila; Parasuraman, Subramani; Adhikary, Arun Kumar; Othman, Nor Hayati

    2017-07-19

    Worldwide breast cancer is the most common cancer in women. For many years clinicians and the researchers are examining and exploring various therapeutic modalities for breast cancer. Yet the disease has remained unconquered and the quest for cure is still going on. Present-day strategy of breast cancer therapy and prevention is either combination of a number of drugs or a drug that modulates multiple targets. In this regard natural products are now becoming significant options. Curcumin exemplifies a promising natural anticancer agent for this purpose. This review primarily underscores the modulatory effect of curcumin on the cancer hallmarks. The focus is its anticancer effect in the complex pathways of breast carcinogenesis. Curcumin modulates breast carcinogenesis through its effect on cell cycle and proliferation, apoptosis, senescence, cancer spread and angiogenesis. Largely the NFkB, PI3K/Akt/mTOR, MAPK and JAK/STAT are the key signaling pathways involved. The review also highlights the curcumin mediated modulation of tumor microenvironment, cancer immunity, breast cancer stem cells and cancer related miRNAs. Using curcumin as a therapeutic and preventive agent in breast cancer is perplexed by its diverse biological activity, much of which remains inexplicable. The information reviewed here should point toward potential scope of future curcumin research in breast cancer.

  15. Oncogenomic disruptions in arsenic-induced carcinogenesis.

    Science.gov (United States)

    Sage, Adam P; Minatel, Brenda C; Ng, Kevin W; Stewart, Greg L; Dummer, Trevor J B; Lam, Wan L; Martinez, Victor D

    2017-04-11

    Chronic exposure to arsenic affects more than 200 million people worldwide, and has been associated with many adverse health effects, including cancer in several organs. There is accumulating evidence that arsenic biotransformation, a step in the elimination of arsenic from the human body, can induce changes at a genetic and epigenetic level, leading to carcinogenesis. At the genetic level, arsenic interferes with key cellular processes such as DNA damage-repair and chromosomal structure, leading to genomic instability. At the epigenetic level, arsenic places a high demand on the cellular methyl pool, leading to global hypomethylation and hypermethylation of specific gene promoters. These arsenic-associated DNA alterations result in the deregulation of both oncogenic and tumour-suppressive genes. Furthermore, recent reports have implicated aberrant expression of non-coding RNAs and the consequential disruption of signaling pathways in the context of arsenic-induced carcinogenesis. This article provides an overview of the oncogenomic anomalies associated with arsenic exposure and conveys the importance of non-coding RNAs in the arsenic-induced carcinogenic process.

  16. Modifying factors in urinary bladder carcinogenesis

    Science.gov (United States)

    Ito, Nobuyuki; Fukushima, Shoji; Shirai, Tomoyuki; Nakanishi, Keisuke; Hasegawa, Ryohei; Imaida, Katsumi

    1983-01-01

    N-Butyl-N-(4-hydroxybutyl)nitrosamine (BBN) is a potent carcinogen in the urinary bladder of animals. The BBN model of bladder cancer is an excellent model of human urinary bladder cancer and has already led to a greater knowledge of its pathogenesis. In our studies, histogenesis and morphological characteristics of BBN urinary bladder cancer were analyzed in different animal species such as rats, mice, hamsters and guinea pigs and also in different rat strains. Papillary or nodular hyperplasia (PN hyperplasia) is found to be a preneoplastic lesion of the rat urinary bladder. Therefore, the promoting and inhibitory effects of various chemicals in two-stage urinary bladder carcinogenesis were judged by measuring PN hyperplasia in rats. Dose-dependent and organ-specific effects of the urinary bladder promoter, saccharin, in the induction of PN hyperplasia were shown in rats after initiation by BBN. The promoting effect of saccharin was seen more clearly in the urinary bladder of rats after potent initiation. A strain difference in susceptibility of the urinary bladder to the promoter was also shown. These results suggest that the above various factors may also have modifying activities on urinary bladder carcinogenesis in man. PMID:6832095

  17. Vitamin D3Produced by Skin Exposure to UVR Inhibits Murine Basal Cell Carcinoma Carcinogenesis.

    Science.gov (United States)

    Makarova, Anastasia; Wang, Grace; Dolorito, John A; Kc, Subheksha; Libove, Eileen; Epstein, Ervin H

    2017-12-01

    The effect of UVR on human basal cell carcinoma (BCC) epidemiology is complex-the incidence rises until approximately 30,000 hours of lifetime sunlight exposure and then plateaus. We hypothesize that UVR has opposing effects on BCC carcinogenesis-stimulatory via mutagenesis and inhibitory via production of hedgehog-inhibiting vitamin D 3 (D 3 ). We find that UVR exposure of ionizing radiation-treated Ptch1 +/- mice accelerates BCC carcinogenesis in male mice, in which UVR does not produce D 3 . By contrast, in female mice, in which UVR does produce D 3 , UVR fails to accelerate BCC carcinogenesis, thus mirroring the plateauing in humans. However, if D 3 production is attenuated in female mice by deletion of keratinocyte lathosterol 5-desaturase, then UVR accelerates ionizing radiation-induced BCC carcinogenesis. Congruently, chronic topical application of D 3 inhibits ionizing radiation-induced BCC tumorigenesis. These findings confirm that UVR-induced production of D 3 in keratinocytes significantly restrains murine BCC tumorigenesis and demonstrate the counterintuitive conclusion that UVR has anti-BCC carcinogenic effects that can explain, at least in part, the complex relationship between exposure to UVR and BCC incidence. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  18. 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

  19. Diagnostic utility of BAP1 and EZH2 expression in malignant mesothelioma.

    Science.gov (United States)

    Shinozaki-Ushiku, Aya; Ushiku, Tetsuo; Morita, Shigeki; Anraku, Masaki; Nakajima, Jun; Fukayama, Masashi

    2017-04-01

    Malignant mesothelioma is a highly aggressive cancer that is usually diagnosed at advanced stages; thus, highly sensitive and specific markers are necessary for its early definitive diagnosis. The aim of this study was to evaluate the diagnostic utility and prognostic significance of BAP1 and EZH2 in malignant mesothelioma. The expression of BAP1 and EZH2 was investigated by immunohistochemistry in 32 malignant mesotheliomas and 44 benign mesothelial proliferative lesions, including well-differentiated papillary mesothelioma (n = 4), mesothelial inclusion cyst (n = 22), and reactive mesothelial hyperplasia (n = 18). BAP1 loss and high EZH2 expression were observed in 17 (53%) and 22 (66%) malignant mesothelioma cases, respectively, whereas none of the benign lesions showed BAP1 loss or high EZH2 expression. The combination of BAP1 loss and high EZH2 expression as markers to differentiate epithelioid/biphasic malignant mesothelioma from benign mesothelial lesions was highly sensitive (90%) and specific (100%). There were no statistically significant associations between parameters such as age and sex of patients, tumour location, asbestos exposure, treatment, histology, and BAP1 or EZH2 expression. Survival analysis revealed that BAP1 loss, but not high EZH2 expression, was associated with a better prognosis. BAP1 loss and high EZH2 expression were highly specific to malignant mesothelioma in differentiating it from benign mesothelial proliferations, and the combination of these two markers improved the diagnostic accuracy. © 2016 John Wiley & Sons Ltd.

  20. 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

  1. 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.

  2. Isolated thoracic perfusion with chemofiltration for progressive malignant pleural mesothelioma

    Directory of Open Access Journals (Sweden)

    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

  3. 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.

  4. Advances in diagnosis and treatment of malignant pleural mesothelioma

    Directory of Open Access Journals (Sweden)

    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.

  5. MECHANISM OF CARCINOGENESIS OF THE POLYCYCLIC AROMATICHYDROCARBONS

    Energy Technology Data Exchange (ETDEWEB)

    Cavalieri, E.; Calvin, M.

    1970-08-01

    The carcinogenic activity of the benzo[a]pyrene 1, the 7,12-dimethylbenz[a]anthracene 2 and the 3-methylcholanthrene 3 is suggested to be determine by the electrophilic attack of the active oxygen, induced by the hydroxylating enzyme systems, on the most reactive substituting carbon atom(s). The cationic intermediate(s) with the charge mainly localized on a complementary, interrelated position(s) of the hydroxyl substituted position(s) reacts further with the cellular nucleophiles. The electrophilic nature of the ultimate chemical carcinogens constitutes the common distinctive feature that correlates their different structures and allows us to understand their carcinogenicity. The formation of a covalent bond with the nucleophiles of the biological macromolecules, nucleic acids and proteins, appears to be the essential requirement in the primary process of carcinogenesis.

  6. Angiogenesis, Thrombospondin-1 and Cervical Carcinogenesis

    Directory of Open Access Journals (Sweden)

    Ming-Ping Wu

    2005-06-01

    Full Text Available Angiogenesis, the growth of new vessels from existing vasculature, plays an essential role in tumor development. The process involves interaction among cancer cells, endothelial cells, and components of the extracellular matrix, and is regulated by the balance of angiogenesis activators and angiogenesis inhibitors. This review profiles some fundamental concepts of angiogenesis, the importance of angiogenesis in cervical neoplasm, and the role of thrombospondin-1 as an angiogenesis inhibitor in cervical carcinogenesis. The usefulness and limitations of microvessel density in evaluation of angiogenic status are also discussed. Recent research and evolving concepts have led to a paradigm shift in anticancer therapy, from conventional cancer-centered chemotherapy to angiogenic or “metronomic” chemotherapy and/or combined angiogenesis inhibitors. The epigenetic strategy, which views the tumor system as a whole, transcends the cancer gene-centered approach.

  7. Parasite Infection, Carcinogenesis and Human Malignancy

    Directory of Open Access Journals (Sweden)

    Hoang van Tong

    2017-02-01

    Full Text Available Cancer may be induced by many environmental and physiological conditions. Infections with viruses, bacteria and parasites have been recognized for years to be associated with human carcinogenicity. Here we review current concepts of carcinogenicity and its associations with parasitic infections. The helminth diseases schistosomiasis, opisthorchiasis, and clonorchiasis are highly carcinogenic while the protozoan Trypanosoma cruzi, the causing agent of Chagas disease, has a dual role in the development of cancer, including both carcinogenic and anticancer properties. Although malaria per se does not appear to be causative in carcinogenesis, it is strongly associated with the occurrence of endemic Burkitt lymphoma in areas holoendemic for malaria. The initiation of Plasmodium falciparum related endemic Burkitt lymphoma requires additional transforming events induced by the Epstein-Barr virus. Observations suggest that Strongyloides stercoralis may be a relevant co-factor in HTLV-1-related T cell lymphomas. This review provides an overview of the mechanisms of parasitic infection-induced carcinogenicity.

  8. Fibulin-3 as a Blood and Effusion Biomarker for Pleural Mesothelioma

    Science.gov (United States)

    Pass, Harvey I.; Levin, Stephen M.; Harbut, Michael R.; Melamed, Jonathan; Chiriboga, Luis; Donington, Jessica; Huflejt, Margaret; Carbone, Michele; Chia, David; Goodglick, Lee; Goodman, Gary E.; Thornquist, Mark D.; Liu, Geoffrey; de Perrot, Marc; Tsao, Ming-Sound; Goparaju, Chandra

    2012-01-01

    BACKGROUND New biomarkers are needed to detect pleural mesothelioma at an earlier stage and to individualize treatment strategies. We investigated whether fibulin-3 in plasma and pleural effusions could meet sensitivity and specificity criteria for a robust biomarker. METHODS We measured fibulin-3 levels in plasma (from 92 patients with mesothelioma, 136 asbestos-exposed persons without cancer, 93 patients with effusions not due to mesothelioma, and 43 healthy controls), effusions (from 74 patients with mesothelioma, 39 with benign effusions, and 54 with malignant effusions not due to mesothelioma), or both. A blinded validation was subsequently performed. Tumor tissue was examined for fibulin-3 by immunohistochemical analysis, and levels of fibulin-3 in plasma and effusions were measured with an enzyme-linked immunosorbent assay. RESULTS Plasma fibulin-3 levels did not vary according to age, sex, duration of asbestos exposure, or degree of radiographic changes and were significantly higher in patients with pleural mesothelioma (105±7 ng per milliliter in the Detroit cohort and 113±8 ng per milliliter in the New York cohort) than in asbestos-exposed persons without mesothelioma (14±1 ng per milliliter and 24±1 ng per milliliter, respectively; Pmesothelioma (694±37 ng per milliliter in the Detroit cohort and 636±92 ng per milliliter in the New York cohort) than in patients with effusions not due to mesothelioma (212±25 and 151±23 ng per milliliter, respectively; Pmesothelioma, the receiver-operating-characteristic curve for plasma fibulin-3 levels had a sensitivity of 96.7% and a specificity of 95.5% at a cutoff value of 52.8 ng of fibulin-3 per milliliter. In a comparison of patients with early-stage mesothelioma with asbestos-exposed persons, the sensitivity was 100% and the specificity was 94.1% at a cutoff value of 46.0 ng of fibulin-3 per milliliter. Blinded validation revealed an area under the curve of 0.87 for plasma specimens from 96 asbestos

  9. Malignant mesothelioma of the tunica vaginalis: a rare case report and description of multimodal treatment.

    Science.gov (United States)

    Andresen, Eric D; Henning, Grant; Uhlman, Matthew A; Gupta, Amit

    2016-12-01

    Malignant mesothelioma is an uncommon neoplasm that develops from serous surfaces, and rarely from the tunica vaginalis. Although atypical in any location, paratesticular presentation is exceedingly infrequent as only 0.3% to 1.4% of mesothelioma cases arise from the tunica vaginalis. Fewer than 300 cases have been reported with very few descriptions of long term follow up and multimodal therapy. Here we describe a patient with 2 years of follow up for metastatic mesothelioma treated with orchiectomy, chemotherapy and robot-assisted laparoscopic retroperitoneal lymph node dissection.

  10. Malignant Mesothelioma of the Tunica Vaginalis: Presenting with Intermittent Scrotal Pain and Hydrocele

    Directory of Open Access Journals (Sweden)

    Tarık Esen

    2012-01-01

    Full Text Available Paratesticular mesotheliomas are very rare tumors. In this paper, we present the management of a 38-year-old male patient with paratesticular malignant mesothelioma who was initially misdiagnosed and treated as recurrent epididymitis. After the final pathology report defining paratesticular mesothelioma during scrotal exploration, he underwent radical orchiectomy and hemiscrotal excision as a complementary, secondary procedure. His metastatic workup did not show any dissemination. Therefore, he did not receive any adjuvant treatment and remained disease-free for more than 2 years.

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

    Science.gov (United States)

    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.

  12. 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 may...... have a similar focal appearance to WDPM. True stromal invasion is by far the most reliable criterion of mesothelial malignancy. In doubtful cases, a conservative diagnostic approach has been recommended. Compared to malignant mesotheliomas, WDPMs are rare and have a relatively indolent clinical course...

  13. 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...

  14. 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.

  15. Methoxyamine, Cisplatin, and Pemetrexed Disodium in Treating Patients With Advanced Solid Tumors or Mesothelioma That Cannot Be Removed by Surgery or Mesothelioma That Is Refractory to Pemetrexed Disodium and Cisplatin or Carboplatin

    Science.gov (United States)

    2018-04-16

    Advanced Malignant Solid Neoplasm; Advanced Peritoneal Malignant Mesothelioma; Advanced Pleural Malignant Mesothelioma; Recurrent Peritoneal Malignant Mesothelioma; Recurrent Pleural Malignant Mesothelioma; Stage III Non-Small Cell Lung Cancer AJCC v7; Stage III Ovarian Cancer AJCC v6 and v7; Stage III Pleural Malignant Mesothelioma AJCC v7; Stage IIIA Non-Small Cell Lung Cancer AJCC v7; Stage IIIA Ovarian Cancer AJCC v6 and v7; Stage IIIB Non-Small Cell Lung Cancer AJCC v7; Stage IIIB Ovarian Cancer AJCC v6 and v7; Stage IIIC Ovarian Cancer AJCC v6 and v7; Stage IV Non-Small Cell Lung Cancer AJCC v7; Stage IV Ovarian Cancer AJCC v6 and v7; Stage IV Pleural Malignant Mesothelioma AJCC v7; Thymoma; Unresectable Solid Neoplasm

  16. [Asbestos exposure assessment in the first case of intrasplenic mesothelioma].

    Science.gov (United States)

    Miscetti, Giorgio; Bodo, Patrizia; Lumare, A; Abbritti, E P; Garofani, Patrizia; Burani, V

    2016-01-20

    In 2013 the International Journal of Surgical Pathology published a case report of intrasplenic malignant mesothelioma (MM) in a 48-year-old man: it was the first report in literature describing a case of primitive intra-splenic MM, described without  a history of asbestos exposure. To verify the possible past exposure to asbestos, ignored by the patient himself, by studying in depth his environmental and occupational history. Information about the occupational and non-occupational history of the subject was collected by Experts of the Operational Unit of Occupational Health and Safety Control (UOC PSAL) of the Local Health Unit Umbria 1 - Perugia, using the Italian National Mesothelioma Register (ReNaM) questionnaire and guide lines; an inspection was  carried out at the past canning industry where the patient worked in the period 1982-1990 and material was taken to be analysed by MOCF and SEM. Samples showed the presence of asbestos  fibres belonging to the amphibole class (amosite and crocidolite) and to the serpentine class (chrysotile). The survey described the past occupational exposure to asbestos in a canning industry, where  the subject worked in the period 1982-1990,  unknown to the patient himself. The authors strongly confirm the  usefulness of standardized methods, such as the ReNaM Questionnaire, and the importance of technical expertise of the investigator to find and analyse the suspect materials and to demonstrate  possible past occupational exposure to asbestos.

  17. [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).

  18. Mesothelioma of the testis and nephrotic syndrome: a case report

    Directory of Open Access Journals (Sweden)

    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.

  19. Malignant mesothelioma due to asbestos exposure in dental tape.

    Science.gov (United States)

    Markowitz, Steven B; Moline, Jacqueline M

    2017-05-01

    Although most cases of malignant mesothelioma of the pleura are caused by one or more readily recognized sources of exposure to asbestos, cases of the disease with more occult exposure occur, especially since asbestos has been used in over 3,000 products. Dental lining tape contained asbestos from the 1930s until at least the 1970s and was used in the lost wax method of casting crowns, bridges, and other metal dental prosthetic devices. We report six cases of pathology-verified malignant mesothelioma, mostly among dentists, following exposure to airborne dust from asbestos dental tape, which resulted in asbestos tort litigation. According to evidence available at present, chrysotile asbestos was the type of asbestos used in dental tape in the past in the United States, and the described cases followed relatively brief and intermittent exposure to this type of asbestos. These cases underscore the need for comprehensive exposure histories to determine exposure scenarios. Am. J. Ind. Med. 60:437-442, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  20. Microcystic variant malignant mesothelioma presenting as a localized paraspinal mass

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    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.

  1. 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.

  2. 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.

  3. 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.

  4. Oxidative status and acute phase reactants in patients with environmental asbestos exposure and mesothelioma.

    Science.gov (United States)

    Sezgi, Cengizhan; Taylan, Mahsuk; Sen, Hadice Selimoglu; Evliyaoğlu, Osman; Kaya, Halide; Abakay, Ozlem; Abakay, Abdurrahman; Tanrıkulu, Abdullah Cetin; Senyiğit, Abdurrahman

    2014-01-01

    The aim of this study was to investigate inflammatory indicators and oxidative status in patients with asbestos exposure with and without mesothelioma and to compare results with data from healthy subjects. Eighty people with exposure to environmental asbestos and without any disease, 46 mesothelioma patients, and a control group of 50 people without exposure to environmental asbestos were enrolled in this prospective study. Serum total oxidant level (TOL), total antioxidant capacity (TAC), and oxidative stress index (OSI), CRP, transferrin, ceruloplasmin, α-1 antitrypsin, ferritin, and copper levels were measured. Mesothelioma group exhibited higher TOL, OSI, α1-antitrypsin, ferritin and copper levels as compared to the other groups (P acute phase reactants and oxidative stress markers (TOL and OSI) in the mesothelioma group can be used as predictive markers for the development of asbestos-related malignancy.

  5. The distinction of mesothelioma from adenocarcinoma in malignant effusions by electron microscopy.

    Science.gov (United States)

    Kobzik, L; Antman, K H; Warhol, M J

    1985-01-01

    To determine the usefulness of the electron microscopic (EM) differential diagnosis between malignant mesothelioma and metastatic adenocarcinoma in cytologic specimens of serous fluids, we undertook a prospective study of 17 pleural and peritoneal effusions from 14 patients. In the nine effusions identified as malignant by routine cytologic examination, EM correctly diagnosed three mesotheliomas and six adenocarcinomas. EM resolved the differential diagnosis of mesothelioma versus adenocarcinoma in three cases in which routine cytologic examination could not. As with tissue specimens, EM cannot be used to diagnose the malignancy of cytologic specimens; it can, however, reliably identify the origin of cells diagnosed as malignant by routine cytologic examination. We conclude that, when EM is used to evaluate cytologically malignant effusions, it can accurately distinguish mesothelioma from adenocarcinoma. This technique will be diagnostically useful in selected cases and may be helpful in avoiding more invasive procedures as well as delays in diagnosis and therapy.

  6. 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

  7. 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.

  8. 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

  9. 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.

  10. 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)

  11. 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.

  12. [Intrascrotal malignant mesothelioma diagnosed after surgery for hydrocele testis: a case report].

    Science.gov (United States)

    Kato, Ryuichi; Matsuda, Yohei; Maehana, Takeshi; Miyao, Noriomi; Konishi, Yasuhiro; Kon, Shin-Ichiro

    2012-01-01

    We report here a case of intrascrotal malignant mesothelioma, arising from the tunica vaginalis, which was diagnosed after surgery for hydrocele testis. A 52-year-old man underwent left hydrocelectomy for hydrocele testis. After pathological diagnosis as malignant mesothelioma from the specimen of tunica vaginalis, left radical orchiectomy was performed. The patient had no exposure to asbestos and there has been no evidence of recurrence.

  13. Mesothelioma: Identification of the Key Molecular Events Triggered by BAP1

    Science.gov (United States)

    2016-04-01

    Recent insights emerging from malignant mesothelioma genome sequencing. J Thorac Oncol. 2015 Mar ;10(3):409-11. PMID: 25695218 5. Yang H, Pelegrini L...mesothelioma genome sequencing. J Thorac Oncol. 2015 Mar ;10(3):409-11. PMID: 25695218 37. Yang H, Pelegrini L, Napolitano A, Giorgi C, Jube S, Preti A...Sandro Jube Vishal Singh Negi 2) Research assistant fellow training: Agata Szymiczek Dusty Behner Elia Bruno Ronghui Xu Shuangjing Li Sylvia

  14. Mesothelioma Tumor Cells Modulate Dendritic Cell Lipid Content, Phenotype and Function

    Science.gov (United States)

    Gardner, Joanne K.; Mamotte, Cyril D. S.; Patel, Priya; Yeoh, Teong Ling; Jackaman, Connie; Nelson, Delia J.

    2015-01-01

    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. PMID:25886502

  15. 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.

  16. 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......  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...

  17. 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.

  18. 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

  19. Histopathologic features predict survival in diffuse pleural malignant mesothelioma on pleural biopsies.

    Science.gov (United States)

    Habougit, Cyril; Trombert-Paviot, Béatrice; Karpathiou, Georgia; Casteillo, François; Bayle-Bleuez, Sophie; Fournel, Pierre; Vergnon, Jean-Michel; Tiffet, Olivier; Péoc'h, Michel; Forest, Fabien

    2017-06-01

    Malignant pleural mesothelioma is a rare tumor with a poor prognosis. The only universally recognized pathological prognostic factor is histopathological subtype with a shorter survival in non-epithelioid subtypes. Recently, a grading of epithelioid mesothelioma on surgical resection has been proposed. The aim of our work is to assess the prognostic role of several histopathological factors on a retrospective cohort of 116 patients diagnosed as a pleural mesothelioma for more than 95% of patients on pleural biopsy. Our work shows that mitotic count mesothelioma. The presence of atypical mitoses was found to be related to a worse median survival in non-epithelioid mesothelioma. Mitotic count, necrosis, nuclear atypia, and nucleoli size are not associated with overall survival in non-epithelioid mesothelioma. Our work highlights that histopathological prognostic factors can be assessed on pleural biopsies and can predict reliably median overall survival. This is of interest in order to define subgroups of patients who could benefit of different therapies and select patients who could benefit of surgical excision.

  20. Personalized oncogenomics: clinical experience with malignant peritoneal mesothelioma using whole genome sequencing.

    Directory of Open Access Journals (Sweden)

    Brandon S Sheffield

    Full Text Available Peritoneal mesothelioma is a rare and sometimes lethal malignancy that presents a clinical challenge for both diagnosis and management. Recent studies have led to a better understanding of the molecular biology of peritoneal mesothelioma. Translation of the emerging data into better treatments and outcome is needed. From two patients with peritoneal mesothelioma, we derived whole genome sequences, RNA expression profiles, and targeted deep sequencing data. Molecular data were made available for translation into a clinical treatment plan. Treatment responses and outcomes were later examined in the context of molecular findings. Molecular studies presented here provide the first reported whole genome sequences of peritoneal mesothelioma. Mutations in known mesothelioma-related genes NF2, CDKN2A, LATS2, amongst others, were identified. Activation of MET-related signaling pathways was demonstrated in both cases. A hypermutated phenotype was observed in one case (434 vs. 18 single nucleotide variants and was associated with a favourable outcome despite sarcomatoid histology and multifocal disease. This study represents the first report of whole genome analyses of peritoneal mesothelioma, a key step in the understanding and treatment of this disease.

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

    Science.gov (United States)

    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.

  2. 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.

  3. Genetically Modified T Cells in Treating Patients With Stage III-IV Non-small Cell Lung Cancer or Mesothelioma

    Science.gov (United States)

    2018-01-12

    Advanced Pleural Malignant Mesothelioma; HLA-A*0201 Positive Cells Present; Recurrent Non-Small Cell Lung Carcinoma; Recurrent Pleural Malignant Mesothelioma; Stage III Non-Small Cell Lung Cancer AJCC v7; Stage III Pleural Malignant Mesothelioma AJCC v7; Stage IIIA Non-Small Cell Lung Cancer AJCC v7; Stage IIIB Non-Small Cell Lung Cancer AJCC v7; Stage IV Non-Small Cell Lung Cancer AJCC v7; Stage IV Pleural Malignant Mesothelioma AJCC v7; WT1 Positive

  4. 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.

  5. 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.

  6. The Association Between the FTO rs9939609 Variant and Malignant Pleural Mesothelioma Risk: A Case-Control Study.

    Science.gov (United States)

    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.

  7. Inflammation, oxidative DNA damage, and carcinogenesis

    International Nuclear Information System (INIS)

    Lewis, J.G.; Adams, D.O.

    1987-01-01

    Inflammation has long been associated with carcinogenesis, especially in the promotion phase. The mechanism of action of the potent inflammatory agent and skin promoter 12-tetradecanoyl phorbol-13-acetate (TPA) is unknown. It is though that TPA selectively enhances the growth of initiated cells, and during this process, initiated cells progress to the preneoplastic state and eventually to the malignant phenotype. The authors and others have proposed that TPA may work, in part, by inciting inflammation and stimulating inflammatory cells to release powerful oxidants which then induce DNA damage in epidermal cells. Macrophages cocultured with target cells and TPA induce oxidized thymine bases in the target cells. This process is inhibited by both catalase and inhibitors of lipoxygenases, suggesting the involvement of both H 2 O 2 and oxidized lipid products. In vivo studies demonstrated that SENCAR mice, which are sensitive to promotion by TPA, have a more intense inflammatory reaction in skin that C57LB/6 mice, which are resistant to promotion by TPA. In addition, macrophages from SENCAR mice release more H 2 O 2 and metabolites of AA, and induce more oxidative DNA damage in cocultured cells than macrophages from C57LB/6 mice. These data support the hypothesis that inflammation and the release of genotoxic oxidants may be one mechanism whereby initiated cells receive further genetic insults. They also further complicate risk assessment by suggesting that some environmental agents may work indirectly by subverting host systems to induce damage rather than maintaining homeostasis

  8. Somatic Host Cell Alterations in HPV Carcinogenesis.

    Science.gov (United States)

    Litwin, Tamara R; Clarke, Megan A; Dean, Michael; Wentzensen, Nicolas

    2017-08-03

    High-risk human papilloma virus (HPV) infections cause cancers in different organ sites, most commonly cervical and head and neck cancers. While carcinogenesis is initiated by two viral oncoproteins, E6 and E7, increasing evidence shows the importance of specific somatic events in host cells for malignant transformation. HPV-driven cancers share characteristic somatic changes, including apolipoprotein B mRNA editing catalytic polypeptide-like (APOBEC)-driven mutations and genomic instability leading to copy number variations and large chromosomal rearrangements. HPV-associated cancers have recurrent somatic mutations in phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha ( PIK3CA ) and phosphatase and tensin homolog ( PTEN ), human leukocyte antigen A and B ( HLA-A and HLA-B ) -A/B , and the transforming growth factor beta (TGFβ) pathway, and rarely have mutations in the tumor protein p53 ( TP53 ) and RB transcriptional corepressor 1 ( RB1 ) tumor suppressor genes. There are some variations by tumor site, such as NOTCH1 mutations which are primarily found in head and neck cancers. Understanding the somatic events following HPV infection and persistence can aid the development of early detection biomarkers, particularly when mutations in precancers are characterized. Somatic mutations may also influence prognosis and treatment decisions.

  9. Somatic Host Cell Alterations in HPV Carcinogenesis

    Directory of Open Access Journals (Sweden)

    Tamara R. Litwin

    2017-08-01

    Full Text Available High-risk human papilloma virus (HPV infections cause cancers in different organ sites, most commonly cervical and head and neck cancers. While carcinogenesis is initiated by two viral oncoproteins, E6 and E7, increasing evidence shows the importance of specific somatic events in host cells for malignant transformation. HPV-driven cancers share characteristic somatic changes, including apolipoprotein B mRNA editing catalytic polypeptide-like (APOBEC-driven mutations and genomic instability leading to copy number variations and large chromosomal rearrangements. HPV-associated cancers have recurrent somatic mutations in phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA and phosphatase and tensin homolog (PTEN, human leukocyte antigen A and B (HLA-A and HLA-B-A/B, and the transforming growth factor beta (TGFβ pathway, and rarely have mutations in the tumor protein p53 (TP53 and RB transcriptional corepressor 1 (RB1 tumor suppressor genes. There are some variations by tumor site, such as NOTCH1 mutations which are primarily found in head and neck cancers. Understanding the somatic events following HPV infection and persistence can aid the development of early detection biomarkers, particularly when mutations in precancers are characterized. Somatic mutations may also influence prognosis and treatment decisions.

  10. Hypoxia and Angiogenesis in Endometrioid Endometrial Carcinogenesis

    Directory of Open Access Journals (Sweden)

    Nicole Horrée

    2007-01-01

    Full Text Available Background: Hypoxia-inducible factor 1α (HIF-1α plays an essential role in the adaptive response of cells to hypoxia, triggering biologic events associated with aggressive tumor behavior. Methods: Expression of HIF-1α and proteins in the HIF-1α pathway (Glut-1, CAIX, VEGF in paraffin-embedded specimens of normal (n = 17, premalignant (n = 17 and endometrioid endometrial carcinoma (n = 39 was explored by immunohistochemistry, in relation to microvessel density (MVD. Results: HIF-1α overexpression was absent in inactive endometrium but present in hyperplasia (61% and carcinoma (87%, with increasing expression in a perinecrotic fashion pointing to underlying hypoxia. No membranous expression of Glut-1 and CAIX was noticed in inactive endometrium, in contrast with expression in hyperplasia (Glut-1 0%, CAIX 61%, only focal and diffuse and carcinoma (Glut-1 94.6%, CAIX 92%, both mostly perinecrotically. Diffuse HIF-1α was accompanied by activation of downstream targets. VEGF was significantly higher expressed in hyperplasias and carcinomas compared to inactive endometrium. MVD was higher in hyperplasias and carcinomas than in normal endometrium (p < 0.001. Conclusion: HIF-1α and its downstream genes are increasingly expressed from normal through premalignant to endometrioid adenocarcinoma of the endometrium, paralleled by activation of its downstream genes and increased angiogenesis. This underlines the potential importance of hypoxia and its key regulator HIF-1α in endometrial carcinogenesis.

  11. Multistage chemical carcinogenesis in mouse skin

    Energy Technology Data Exchange (ETDEWEB)

    Slaga, T.J.; Fischer, S.M.; Weeks, C.E.; Klein-Szanto, A.J.P.

    1979-01-01

    Skin tumors in mice can be induced by the sequential application of a subthreshold dose of a carcinogen (initiation phase) followed by repetitive treatment with a noncarcinogenic tumor promoter. The initiation phase requires only a single application of either a direct acting carcinogen or a procarcinogen which has to be metabolized before being active and is essentially an irreversible step which probably involves a somatic cell mutation. There is a good correlation between the skin tumor initiating activites of several polycyclic aromatic hydrocarbons (PAH) and their ability to bind covalently to epidermal DNA. Laboratory results suggest that bay region diol-epoxides are the ultimate carcinogenic form of PAH carcinogens. Potent inhibitors and stimulators of PAH tumor initiation appear to affect the level of the PAH diol-epoxide reacting with specific DNA bases. Reecent data suggests that the tumor promotion stage involves at least three important steps: (1) the induction of embryonic looking cells (dark cells) in adult epidermis; (2) an increased production of epidermal prostaglandins and polyamines; (3) sustained proliferation of dark cells. Retinoic acid specifically inhibits step two whereas the anti-inflammatory steriod fluocinolone acetonide is a potent inhibitor of steps one and three. The mechanism and the importance of a specific sequence for each step in chemical carcinogenesis in mouse skin are detailed.

  12. Experimental carcinogenesis induced by incorporated plutonium

    Energy Technology Data Exchange (ETDEWEB)

    Oghiso, Yoichi [National Inst. of Radiological Sciences, Chiba (Japan)

    1999-06-01

    The carcinogenic effects of an alpha-emitter, {sup 239}Pu, were investigated by animal experiments as focused on both pulmonary tumors after inhalation exposures to insoluble oxide aerosols and tumor spectra induced by injection of soluble citrate. The life-span study using Wistar strain rats exposed to Pu dioxide aerosols has shown differential dose-related responses of malignancies and histopathological phenotypes of lung tumors, suggesting a threshold dose around 1.0 Gy of the lung dose. As abnormality of tumor-related genes could be supposed for the background of pulmonary carcinogenesis, the mutations of p53 tumor suppressor gene were examined by PCR-SSCP analysis using DNA fragments extracted from lung tumors. While mutations were detected in 23 cases (about 28%) among 82 lung tumors, their relations to either malignancies, histological phenotypes, dose, or oncogenesis are not yet to be elucidated. The life-span study using C3H strain mice injected with Pu citrate has shown contrast dose responses between osteosarcomas and lymphoid tumors around 10 Gy of the skeletal dose, and further indicated specific tumor spectra differed from low LET radiation exposures as shown by much more frequency of B cell type leukemic lymphomas and none of myeloid leukemias. (author)

  13. Loss of HLTF function promotes intestinal carcinogenesis

    Directory of Open Access Journals (Sweden)

    Sandhu Sumit

    2012-03-01

    Full Text Available Abstract Background HLTF (Helicase-like Transcription Factor is a DNA helicase protein homologous to the SWI/SNF family involved in the maintenance of genomic stability and the regulation of gene expression. HLTF has also been found to be frequently inactivated by promoter hypermethylation in human colon cancers. Whether this epigenetic event is required for intestinal carcinogenesis is unknown. Results To address the role of loss of HLTF function in the development of intestinal cancer, we generated Hltf deficient mice. These mutant mice showed normal development, and did not develop intestinal tumors, indicating that loss of Hltf function by itself is insufficient to induce the formation of intestinal cancer. On the Apcmin/+ mutant background, Hltf- deficiency was found to significantly increase the formation of intestinal adenocarcinoma and colon cancers. Cytogenetic analysis of colon tumor cells from Hltf -/-/Apcmin/+ mice revealed a high incidence of gross chromosomal instabilities, including Robertsonian fusions, chromosomal fragments and aneuploidy. None of these genetic alterations were observed in the colon tumor cells derived from Apcmin/+ mice. Increased tumor growth and genomic instability was also demonstrated in HCT116 human colon cancer cells in which HLTF expression was significantly decreased. Conclusion Taken together, our results demonstrate that loss of HLTF function promotes the malignant transformation of intestinal or colonic adenomas to carcinomas by inducing genomic instability. Our findings highly suggest that epigenetic inactivation of HLTF, as found in most human colon cancers, could play an important role in the progression of colon tumors to malignant cancer.

  14. Pulmonary carcinogenesis from plutonium-containing particles

    International Nuclear Information System (INIS)

    Thomas, R.G.; Smith, D.M.; Anderson, E.C.

    1980-01-01

    Induction of lung tumors by various types of radiation is of paramount concern to the nuclear industry. The data presented were obtained by exposing the pulmonary system of Syrian hamsters to particles of zirconium oxide containing various amounts of either plutonium-238 or -239 as the alpha radiation source. These particles were injected intravenously and lodged permanently in the capillary bed of the lung. When less than 20% of the lung tissue was irradiated, simulating the ''hot particle'' mode, tumors were not evident with lung burdens up to 500 nCi plutonium. More diffuse irradiation significantly increased the tumor incidence, with lung burdens of 50 to 150 nCi. When plutonium-laden microspheres were administered intratracheally, tumor production was considerably increased and the addition of 3 mg of iron oxide intratracheally further increased the incidence. Using the zirconium oxide matrix for the carrier of plutonium in aerosol particles produced tumor incidences of up to 50% in Syrian hamsters exposed by inhalation. Initial pulmonary (alveolar) burdens reached 100 nCi of plutonium. Similar inhalation studies using plutonium dioxide alone (no matrix) failed to produce any increase in lung tumorigenesis. The results are discussed in terms of possible mechanisms necessary for lung carcinogenesis. (H.K.)

  15. [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

  16. 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

  17. Pleural Intensity-Modulated Radiotherapy for Malignant Pleural Mesothelioma

    Energy Technology Data Exchange (ETDEWEB)

    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

  18. 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)

  19. Multipoint targeting of the PI3K/mTOR pathway in mesothelioma

    Science.gov (United States)

    Zhou, S; Liu, L; Li, H; Eilers, G; Kuang, Y; Shi, S; Yan, Z; Li, X; Corson, J M; Meng, F; Zhou, H; Sheng, Q; Fletcher, J A; Ou, W-B

    2014-01-01

    Background: Mesothelioma is a notoriously chemotherapy-resistant neoplasm, as is evident in the dismal overall survival for patients with those of asbestos-associated disease. We previously demonstrated co-activation of multiple receptor tyrosine kinases (RTKs), including epidermal growth factor receptor (EGFR), MET, and AXL in mesothelioma cell lines, suggesting that these kinases could serve as novel therapeutic targets. Although clinical trials have not shown activity for EGFR inhibitors in mesothelioma, concurrent inhibition of various activated RTKs has pro-apoptotic and anti-proliferative effects in mesothelioma cell lines. Thus, we hypothesised that a coordinated network of multi-RTK activation contributes to mesothelioma tumorigenesis. Methods: Activation of PI3K/AKT/mTOR, Raf/MAPK, and co-activation of RTKs were evaluated in mesotheliomas. Effects of RTK and downstream inhibitors/shRNAs were assessed by measuring mesothelioma cell viability/growth, apoptosis, activation of signalling intermediates, expression of cell-cycle checkpoints, and cell-cycle alterations. Results: We demonstrate activation of the PI3K/AKT/p70S6K and RAF/MEK/MAPK pathways in mesothelioma, but not in non-neoplastic mesothelial cells. The AKT activation, but not MAPK activation, was dependent on coordinated activation of RTKs EGFR, MET, and AXL. In addition, PI3K/AKT/mTOR pathway inhibition recapitulated the anti-proliferative effects of concurrent inhibition of EGFR, MET, and AXL. Dual targeting of PI3K/mTOR by BEZ235 or a combination of RAD001 and AKT knockdown had a greater effect on mesothelioma proliferation and viability than inhibition of individual activated RTKs or downstream signalling intermediates. Inhibition of PI3K/AKT was also associated with MDM2-p53 cell-cycle regulation. Conclusions: These findings show that PI3K/AKT/mTOR is a crucial survival pathway downstream of multiple activated RTKs in mesothelioma, underscoring that PI3K/mTOR is a compelling target for

  20. [Malignant pleural mesothelioma in housewives in the province of Catania].

    Science.gov (United States)

    Proietti, Lidia; Migliore, Marcello; Polosa, Riccardo; Comba, Pietro; Circo, Cristina; Di Maria, Giuseppe U

    2004-01-01

    Our study reports pleural malignant mesothelioma (PMM) in seven female patients. All patients were resident in Catania area (Sicily), the median age was 69.2 years and ranged from 59 to 81 years. They were housewife. Their anamnesis was negative for both direct and indirect previous exposure to asbestos; the partners of all patients were also not exposed to asbestos. The exposure to X-rays was also excluded for these patients. Different pathogenetic mechanisms for the appearance of PMM in these patients can be hypothesized, for example, SV40 infection and genetic susceptibility; a minimal domestic exposure to asbestos can be not excluded. Therefore, further studies in a more large number of subjects are necessary to determine whether one or all of these hypothetic pathogenetic mechanisms are more significant for the develop of PMM.

  1. Malignant pleural mesothelioma in bakers and pastry cooks.

    Science.gov (United States)

    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.

  2. Tumorigenic properties of alternative osteopontin isoforms in mesothelioma

    Energy Technology Data Exchange (ETDEWEB)

    Ivanov, Sergey V., E-mail: Sergey.Ivanov@med.nyu.edu [Thoracic Surgery Laboratory, Cardiothoracic Surgery Department, NYU Langone Medical Center, 462 First Ave., Bellevue Hospital, Room 15N20, NY 10016 (United States); Ivanova, Alla V.; Goparaju, Chandra M.V.; Chen, Yuanbin; Beck, Amanda; Pass, Harvey I. [Thoracic Surgery Laboratory, Cardiothoracic Surgery Department, NYU Langone Medical Center, 462 First Ave., Bellevue Hospital, Room 15N20, NY 10016 (United States)

    2009-05-08

    Osteopontin (SPP1) is an inflammatory cytokine that we previously characterized as a diagnostic marker in patients with asbestos-induced malignant mesothelioma (MM). While SPP1 shows both pro- and anti-tumorigenic biological effects, little is known about the molecular basis of these activities. In this study, we demonstrate that while healthy pleura possesses all three differentially spliced SPP1 isoforms (A-C), in clinical MM specimens isoform A is markedly up-regulated and predominant. To provide a clue to possible functions of the SPP1 isoforms we next performed their functional evaluation via transient expression in MM cell lines. As a result, we report that isoforms A-C demonstrate different activities in cell proliferation, wound closure, and invasion assays. These findings suggest different functions for SPP1 isoforms and underline pro-tumorigenic properties of isoforms A and B.

  3. Improving Outcome in Malignant Pleural Mesothelioma (MPM) Using Pulsed-Protracted External Beam Radiation (PERT) and Intrapleural Delivery of Stem Cells

    Science.gov (United States)

    2014-09-01

    Malignant Pleural Mesothelioma (MPM) survival remains poor despite multidisciplinary treatment involving aggressive surgery, chemotherapy and... Mesothelioma (MPM) survival remains poor despite multidisciplinary treatment involving aggressive surgery, chemotherapy and adjuvant radiotherapy (RT... Mesothelioma (MPM) Using Pulsed-Protracted External Beam Radiation (PERT) and Intrapleural Delivery of

  4. 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.

    Science.gov (United States)

    Zhou, Huashi; Tamura, Taro; Kusaka, Yukinori; Suganuma, Narufumi; Subhannachart, Ponglada; Vijitsanguan, Chomphunut; Noisiri, Weeraya; Hering, Kurt G; Akira, Masanori; Itoh, Harumi; Arakawa, Hiroaki; Ishikawa, Yuichi; Kumagai, Shinji; Kurumatani, Norio

    2013-01-01

    To assess the efficacy of the developed guideline on reading CT images of malignant pleural mesothelioma for improving radiologists' reading proficiency. 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. 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: Preading CT images of mesothelioma, and may contribute to accurate diagnosis of mesothelioma. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  5. The potential role of infectious agents and pelvic inflammatory disease in ovarian carcinogenesis

    DEFF Research Database (Denmark)

    Ingerslev, Kasper; Hogdall, Estrid; Schnack, Tine Henrichsen

    2017-01-01

    BACKGROUND: The etiological cause of ovarian cancer is poorly understood. It has been theorized that bacterial or viral infection as well as pelvic inflammatory disease could play a role in ovarian carcinogenesis. AIM: To review the literature on studies examining the association between ovarian...... cancer and bacterial or viral infection or pelvic inflammatory disease. METHODS: Database search through MEDLINE, applying the medical subject headings: "Ovarian neoplasms", AND "Chlamydia infections", "Neisseria gonorrhoeae", "Mycoplasma genitalium", "Papillomaviridae", or "pelvic inflammatory disease...... than in studies from Western countries. Cytomegalovirus was the only other virus to be detected and was found in 50% of cases in a case-control study. The association between ovarian cancer and pelvic inflammatory disease was examined in seven epidemiological studies, two of which, reported...

  6. Pleural mesothelioma in New Caledonia: associations with environmental risk factors.

    Science.gov (United States)

    Baumann, Francine; Maurizot, Pierre; Mangeas, Morgan; Ambrosi, Jean-Paul; Douwes, Jeroen; Robineau, Bernard

    2011-05-01

    High incidences of malignant mesothelioma (MM) have been observed in New Caledonia. Previous work has shown an association between MM and soil containing serpentinite. We studied the spatial and temporal variation of MM and its association with environmental factors. We investigated the 109 MM cases recorded in the Cancer Registry of New Caledonia between 1984 and 2008 and performed spatial, temporal, and space-time cluster analyses. We conducted an ecological analysis involving 100 tribes over a large area including those with the highest incidence rates. Associations with environmental factors were assessed using logistic and Poisson regression analyses. The highest incidence was observed in the Houaïlou area with a world age-standardized rate of 128.7 per 100,000 person-years [95% confidence interval (CI), 70.41-137.84]. A significant spatial cluster grouped 18 tribes (31 observed cases vs. 8 expected cases; p = 0.001), but no significant temporal clusters were identified. The ecological analyses identified serpentinite on roads as the greatest environmental risk factor (odds ratio = 495.0; 95% CI, 46.2-4679.7; multivariate incidence rate ratio = 13.0; 95% CI, 10.2-16.6). The risk increased with serpentinite surface, proximity to serpentinite quarries and distance to the peridotite massif. The association with serpentines was stronger than with amphiboles. Living on a slope and close to dense vegetation appeared protective. The use of whitewash, previously suggested to be a risk factor, was not associated with MM incidence. Presence of serpentinite on roads is a major environmental risk factor for mesothelioma in New Caledonia.

  7. 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

  8. Mesothelioma mortality surveillance and asbestos exposure tracking in Italy

    Directory of Open Access Journals (Sweden)

    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.

  9. Forensic Epidemiology in Italy: principles and practice.

    Science.gov (United States)

    Chiesa, Valentina; Odone, Anna; Signorelli, Carlo

    2017-10-23

    Forensic epidemiology (FE) implies the use of epidemiological data in the processes and the involvement of epidemiologists in judicial proceedings. FE is essential for the assessment of causal association between the exposure to specific agents and the occurrence of diseases. In this paper we describe FE principles and applications in the Italian context as in recent years FE emerged increasingly as well as the need of experienced and trained epidemiological experts able to navigate legal proceedings. In the literature, the principles of FE have been widely described by different authors, among them: Kennet Rothman who introduced the definition of cause, Sir Austin Bradford Hill who proposed an analytic framework to assess the causal association, and recently by Sana Loue who described the actual legislation and application of FE in the United States. Despite the legislation varies among different countries epidemiological methods and theories represent the foundation for the application of FE we illustrate in this paper. The association between environmental pollution and disease, mobile phones and cancer, vaccines and autism, asbestos and pleural mesothelioma are all situations that underscore the need for FE investigations in criminal acts. Causal association is a complex process: in real life only in limited cases causal associations are assessed by gathering robust scientific evidence, while cases with doubts and situations where different approaches to questions may lead to discordant arguments to questions may lead to discordant arguments are more frequent. Therefore, during the assessment of causation in civil and criminal matters the choice the epidemiological expert - with his knowledge and expertise - and the evidence from well-designed studies are crucial to fill the gaps between clinical and epidemiological data and the low.

  10. Implications of tyrosine phosphoproteomics in cervical carcinogenesis

    Directory of Open Access Journals (Sweden)

    DeFord James

    2008-01-01

    Full Text Available Abstract Background Worldwide cervical cancer remains a leading cause of mortality from gynecologic malignancies. The link between cervical cancer and persistent infection with HPV has been established. At a molecular level little is known about the transition from the precancerous state to invasive cancer. To elucidate this process, cervical biopsies from human specimens were obtained from precancerous state to stage III disease. Methods Cervical biopsies were obtained from patients with a diagnosis of cervical cancer undergoing definitive surgery or staging operation. Biopsies were obtained from patients with precancerous lesions at the time of their excisional procedure. Control samples were obtained from patients undergoing hysterectomy for benign conditions such as fibroids. Samples were subjected to proteomic profiling using two dimensional gel electrophoresis with subsequent trypsin digestion followed by MALDI-TOF protein identification. Candidate proteins were then further studied using western blotting, immunoprecipitation and immunohistochemistry. Results Annexin A1 and DNA-PKcs were found to be differentially expressed. Phosphorylated annexin A1 was up regulated in diseased states in comparison to control and its level was strongly detected in the serum of cervical cancer patients compared to controls. DNA-PKcs was noted to be hyperphosphorylated and fragmented in cancer when compared to controls. By immunohistochemistry annexin A1 was noted in the vascular environment in cancer and certain precancerous samples. Conclusion This study suggests a probable role for protein tyrosine phosphorylation in cervical carcinogenesis. Annexin A1 and DNA-PK cs may have synergistic effects with HPV infection. Precancerous lesions that may progress to cervical cancer may be differentiated from lesions that will not base on similar immunohistochemical profile to invasive squamous cell carcinoma.

  11. Mustard gas exposure and carcinogenesis of lung.

    Science.gov (United States)

    Hosseini-khalili, Alireza; Haines, David D; Modirian, Ehsan; Soroush, Mohammadreza; Khateri, Shahriar; Joshi, Rashmi; Zendehdel, Kazem; Ghanei, Mostafa; Giardina, Charles

    2009-08-01

    Sulfur mustard (SM), also known as mustard gas, is an alkylating compound used as a chemical weapon in World War I and by Iraqi forces against Iranians and indigenous Iraqi Kurds during the Iran-Iraq War of the 1980s. Although SM is a proven carcinogen there are conflicting views regarding the carcinogenicity of a single exposure. The present study characterizes lung cancers formed in mustard gas victims from the Iran-Iraq War. Demographic information and tumor specimens were collected from 20 Iranian male lung cancer patients with single high-dose SM exposures during the Iran-Iraq War. Formalin-fixed, paraffin-embedded lung cancers were analyzed by immunohistochemistry for p53 protein. In addition, DNA was extracted from the tissues, PCR amplified and sequenced to identify mutations in the p53 and KRAS genes associated with SM exposure. A relatively early age of lung cancer onset (ranging from 28 to 73 with a mean of 48) in mustard gas victims, particularly those in the non-smoking population (mean age of 40.7), may be an indication of a unique etiology for these cancers. Seven of the 20 patients developed lung cancer before the age of 40. Five of 16 cancers from which DNA sequence data was obtainable provided information on eight p53 mutations (within exons 5-8). These mutations were predominately G to A transitions; a mutation consistent with the DNA lesion caused by SM. Two of the lung cancers had multiple p53 point mutations, similar to results obtained from factory workers chronically exposed to mustard agent. No mutations were detected in the KRAS gene. The distinguishing characteristics of lung carcinogenesis in these mustard gas victims suggest that a single exposure may increase the risk of lung cancer development in some individuals.

  12. Epidemiology of Lung Cancer

    Science.gov (United States)

    Brock, Malcolm V.; Ford, Jean G.; Samet, Jonathan M.; Spivack, Simon D.

    2013-01-01

    Background: Ever since a lung cancer epidemic emerged in the mid-1900s, the epidemiology of lung cancer has been intensively investigated to characterize its causes and patterns of occurrence. This report summarizes the key findings of this research. Methods: A detailed literature search provided the basis for a narrative review, identifying and summarizing key reports on population patterns and factors that affect lung cancer risk. Results: Established environmental risk factors for lung cancer include smoking cigarettes and other tobacco products and exposure to secondhand tobacco smoke, occupational lung carcinogens, radiation, and indoor and outdoor air pollution. Cigarette smoking is the predominant cause of lung cancer and the leading worldwide cause of cancer death. Smoking prevalence in developing nations has increased, starting new lung cancer epidemics in these nations. A positive family history and acquired lung disease are examples of host factors that are clinically useful risk indicators. Risk prediction models based on lung cancer risk factors have been developed, but further refinement is needed to provide clinically useful risk stratification. Promising biomarkers of lung cancer risk and early detection have been identified, but none are ready for broad clinical application. Conclusions: Almost all lung cancer deaths are caused by cigarette smoking, underscoring the need for ongoing efforts at tobacco control throughout the world. Further research is needed into the reasons underlying lung cancer disparities, the causes of lung cancer in never smokers, the potential role of HIV in lung carcinogenesis, and the development of biomarkers. PMID:23649439

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

    Directory of Open Access Journals (Sweden)

    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.

  14. 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

  15. Estimation of the global burden of mesothelioma deaths from incomplete national mortality data.

    Science.gov (United States)

    Odgerel, Chimed-Ochir; Takahashi, Ken; Sorahan, Tom; Driscoll, Tim; Fitzmaurice, Christina; Yoko-O, Makoto; Sawanyawisuth, Kittisak; Furuya, Sugio; Tanaka, Fumihiro; Horie, Seichi; Zandwijk, Nico van; Takala, Jukka

    2017-12-01

    Mesothelioma is increasingly recognised as a global health issue and the assessment of its global burden is warranted. To descriptively analyse national mortality data and to use reported and estimated data to calculate the global burden of mesothelioma deaths. For the study period of 1994 to 2014, we grouped 230 countries into 59 countries with quality mesothelioma mortality data suitable to be used for reference rates, 45 countries with poor quality data and 126 countries with no data, based on the availability of data in the WHO Mortality Database. To estimate global deaths, we extrapolated the gender-specific and age-specific mortality rates of the countries with quality data to all other countries. The global numbers and rates of mesothelioma deaths have increased over time. The 59 countries with quality data recorded 15 011 mesothelioma deaths per year over the 3 most recent years with available data (equivalent to 9.9 deaths per million per year). From these reference data, we extrapolated the global mesothelioma deaths to be 38 400 per year, based on extrapolations for asbestos use. Although the validity of our extrapolation method depends on the adequate identification of quality mesothelioma data and appropriate adjustment for other variables, our estimates can be updated, refined and verified because they are based on commonly accessible data and are derived using a straightforward algorithm. Our estimates are within the range of previously reported values but higher than the most recently reported values. © 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.

  16. Pleural mesothelioma in household members of asbestos-exposed workers in Friuli Venezia Giulia, Italy.

    Science.gov (United States)

    D' Agostin, Flavia; de Michieli, Paola; Negro, Corrado

    2017-05-08

    Malignant mesothelioma is closely associated to asbestos exposure. One such exposure may occur through contact with occupationally exposed household members and their belongings. This study examines the features of pleural mesothelioma attributable only to asbestos brought home by another family member. The data sources were 1063 mesothelioma cases diagnosed between 1995 and 2014, from the Friuli Venezia Giulia Mesothelioma Register. In all cases the diagnosis of mesothelioma was based on the pathology report. Exposure information and demographic data were acquired by an occupational medical standardized questionnaire/interview. Household-exposure mesothelioma cases included 33 women and 2 men. Relationships were: wives (N = 22), daughters (N = 9), sons (N = 2), and mothers (N = 2). Asbestos exposure in the workers predominantly occurred in shipyards. Out of the 35 pleural cases, 19 were epithelial, 9 biphasic, 3 sarcomatoid, and 4 not specified. The mean age at diagnosis was 77 years old. The mean latency was 59 years, with wives having a significant shorter latency than offspring. Latency was not significantly related to morphology and asbestosis. The overall mean survival was 16 months (median 11 months) but treatment was beneficial (mean 16 months vs. 7 months). Biphasic/sarcomatoid histology and presence of asbestosis were associated with a decreased survival, although not with statistical significance. Our data confirms that household exposure increases the risk for pleural mesothelioma amongst women with no history of occupational asbestos exposure. This is an ongoing problem in many countries, as well as in Italy, where the evaluation of a framework for the compensation of these cases is under debate. Int J Occup Med Environ Health 2017;30(3):419-431.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  19. A feasibility study evaluating Surgery for Mesothelioma After Radiation Therapy: the "SMART" approach for resectable malignant pleural mesothelioma.

    Science.gov (United States)

    Cho, B C John; Feld, Ron; Leighl, Natasha; Opitz, Isabelle; Anraku, Masaki; Tsao, Ming-Sound; Hwang, David M; Hope, Andrew; de Perrot, Marc

    2014-03-01

    We developed an innovative approach for malignant pleural mesothelioma (MPM) with a short accelerated course of high-dose hemithoracic intensity-modulated radiation therapy (IMRT) followed by extrapleural pneumonectomy (EPP). This phase I/II study assessed the feasibility of Surgery for Mesothelioma After Radiation Therapy (SMART). All resectable clinical T1-3N0M0 histologically proven, previously untreated MPMs were eligible. Patients received 25 Gy in five daily fractions during 1 week to the entire ipsilateral hemithorax with concomitant 5 Gy boost to areas at risk followed by EPP within 1 week of completing neoadjuvant IMRT. Adjuvant chemotherapy was offered to ypN2 patients on final pathologic findings. The primary end point was treatment-related mortality and secondary end points were overall survival, disease-free survival, treatment-related morbidity, and patterns of failure. Targeted accrual of 25 patients was completed between November 2008 and October 2012. All patients completed SMART. IMRT was well tolerated with no grade 3+ toxicities. EPP was performed 6 ± 2 days after completing IMRT without any perioperative mortality. Thirteen patients developed grade 3+ surgical complications. One patient (4%) died from treatment-related toxicity (empyema) during follow-up. All but one patient had stage III or IV disease on final pathologic findings. Five of 13 ypN2 patients received adjuvant chemotherapy. After a median follow-up of 23 months (range, 6-51), the cumulative 3-year survival reached 84% in epithelial subtypes compared with 13% in biphasic subtypes (p = 0.0002). SMART is feasible in resectable MPM patients. This innovative protocol presents encouraging results and supports future studies looking at long-term outcome in patients with epithelial subtypes.

  20. A second case of pericardial mesothelioma mimicking systemic lupus erythematosus in the literature in over 30 years: a case report.

    Science.gov (United States)

    Mensi, Carolina; Romano, Alessandro; Berti, Alvise; Dore, Roberto; Riboldi, Luciano

    2017-03-29

    Mesothelioma is a rare neoplasm which commonly develops in the pleura of people exposed to asbestos. Pericardial mesothelioma accounts for only 0.7 % of all malignant mesotheliomas and it usually presents with pericardial effusion, mimicking serositis. To date, there are approximately 200 cases of pericardial mesothelioma described in the medical literature, and little knowledge exists about the systemic manifestations of this pathology. The first and only described case of pericardial mesothelioma with autoimmune features dates back to 1984 and, in our case report, we describe the second. We report a case of a 45-year-old white woman whose pericardial mesothelioma was initially misdiagnosed as pericardial involvement of an autoimmune disease (systemic lupus erythematosus). After several relapses of pericardial effusion, a computed tomography scan and a biopsy with histological analysis were performed revealing neoplastic growth. We describe a rare case of pericardial mesothelioma in a patient with a clinical presentation compatible with lupus serositis. Clinicians should consider malignant mesothelioma in the differential diagnosis of pericardial effusion, especially when it is recurrent and not clearly explained by other causes. Cytological samples should always be obtained and, if imaging tools are suggestive for solid processes, histological confirmation is mandatory.

  1. 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

  2. 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.

    Science.gov (United States)

    Mohanty, Sambit K; Mistry, Amita T; Amin, Waqas; Parwani, Anil V; Pople, Andrew K; Schmandt, Linda; Winters, Sharon B; Milliken, Erin; Kim, Paula; Whelan, Nancy B; Farhat, Ghada; Melamed, Jonathan; Taioli, Emanuela; Dhir, Rajiv; Pass, Harvey I; Becich, Michael J

    2008-04-08

    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). 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). Common Data Elements were developed using controlled vocabulary, ontology and semantic modeling methodology. The CDEs for each case are of different types: demographic, epidemiologic data, clinical history, pathology data

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

    Science.gov (United States)

    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.

  4. Oxidative Status and Acute Phase Reactants in Patients with Environmental Asbestos Exposure and Mesothelioma

    Directory of Open Access Journals (Sweden)

    Cengizhan Sezgi

    2014-01-01

    Full Text Available Background and Objectives. The aim of this study was to investigate inflammatory indicators and oxidative status in patients with asbestos exposure with and without mesothelioma and to compare results with data from healthy subjects. Methods. Eighty people with exposure to environmental asbestos and without any disease, 46 mesothelioma patients, and a control group of 50 people without exposure to environmental asbestos were enrolled in this prospective study. Serum total oxidant level (TOL, total antioxidant capacity (TAC, and oxidative stress index (OSI, CRP, transferrin, ceruloplasmin, α-1 antitrypsin, ferritin, and copper levels were measured. Results. Mesothelioma group exhibited higher TOL, OSI, α1-antitrypsin, ferritin and copper levels as compared to the other groups (P<0.001, P=0.007, P<0.0001, P<0.001, and P<0.001, resp.. Transferrin was lower in the mesothelioma group than in the other two groups (P<0.001. The asbestos group had higher TOL, TAC, α1-antitrypsin, and transferrin levels (P<0.001, P<0.001, P<0.001, and P<0.001, resp., as well as lower OSI and ferritin levels as compared to the control group (P<0.001 and P<0.001. Conclusions. We believe that elevated acute phase reactants and oxidative stress markers (TOL and OSI in the mesothelioma group can be used as predictive markers for the development of asbestos-related malignancy.

  5. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  7. 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.

  8. Small-molecule inhibition of oncogenic eukaryotic protein translation in mesothelioma cells.

    Science.gov (United States)

    Chen, Esther Z; Jacobson, Blake A; Patel, Manish R; Okon, Aniekan M; Li, Shui; Xiong, Kerry; Vaidya, Abhishek J; Bitterman, Peter B; Wagner, Carston R; Kratzke, Robert A

    2014-08-01

    Deranged cap-mediated translation is implicated in the genesis, maintenance and progression of many human cancers including mesothelioma. In this study, disrupting the eIF4F complex by antagonizing the eIF4E-mRNA-cap interaction is assessed as a therapy for mesothelioma. Mesothelioma cells were treated with 4Ei-1, a membrane permeable prodrug that when converted to the active drug, 7-benzyl guanosine monophosphate (7Bn-GMP) displaces capped mRNAs from the eIF4F complex. Colony formation was measured in mesothelioma treated with 4Ei-1 alone or combined with pemetrexed. Proliferation was examined in cells treated with 4Ei-1. Binding to a synthetic cap-analogue was used to study the strength of eIF4F complex activation in lysates exposed to 4Ei-1. 4Ei-1 treatment resulted in a dose dependent decrease in colony formation and cell viability. Combination therapy of 4Ei-1 with pemetrexed further reduced colony number. Formation of eIF4F cap-complex decreased in response to 4Ei-1 exposure. 4Ei-1 is a novel prodrug that reduces proliferation, represses colony formation, diminishes association of eIF4F with the mRNA cap, and sensitizes mesothelioma cells to pemetrexed.

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

    Science.gov (United States)

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

    2017-06-01

    Mesothelioma 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. Retrospective 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)]. Percutaneous 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. Percutaneous 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    Science.gov (United States)

    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.

  12. The prognostic significance of BAP1, NF2, and CDKN2A in malignant peritoneal mesothelioma.

    Science.gov (United States)

    Singhi, Aatur D; Krasinskas, Alyssa M; Choudry, Haroon A; Bartlett, David L; Pingpank, James F; Zeh, Herbert J; Luvison, Alyssa; Fuhrer, Kimberly; Bahary, Nathan; Seethala, Raja R; Dacic, Sanja

    2016-01-01

    Cytoreductive surgery and hyperthermic intraperitoneal chemoperfusion for patients with malignant peritoneal mesothelioma has resulted in improved disease control and increased survival. Despite these results, there are significant perioperative risks associated with this aggressive procedure that necessitate consideration of prognostic markers during patient selection. The molecular pathogenesis of peritoneal mesothelioma remains relatively unknown, but extrapolation of findings from their pleural counterpart would suggest frequent alterations in CDKN2A, NF2, and BAP1. Homozygous deletions in CDKN2A portend a worse overall survival in peritoneal mesothelioma. However, the prevalence and prognostic significance of NF2 and BAP1 abnormalities has not been studied. Dual-color fluorescence in situ hybridization using CDKN2A and NF2 locus-specific probes and BAP1 immunohistochemistry identified homozygous CDKN2A deletions (n=25, 29%), hemizygous NF2 loss (n=30, 35%), and/or loss of BAP1 protein expression (n=49, 57%) in 68 of 86 (79%) peritoneal mesotheliomas. Homozygous CDKN2A deletions or hemizygous NF2 loss correlated with shorter progression-free survival (Pguide future treatment decisions for patients with peritoneal mesothelioma.

  13. 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.

  14. 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

  15. Experimental, statistical and biological models of radon carcinogenesis

    International Nuclear Information System (INIS)

    Cross, F.T.

    1992-01-01

    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 with 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 programme 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 co-pollutant 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. (author)

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

    Directory of Open Access Journals (Sweden)

    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.

  17. Risk, assessment and multiple stages in radiation carcinogenesis

    International Nuclear Information System (INIS)

    Burns, F.J.; Sawey, M.J.; Hosselet, S.; Garte, S.J.

    1989-01-01

    The authors discuss the multistage theory of carcinogenesis in terms of time-response and dose-response function, considering various workers' studies using irradiated rat skin. The authors' own results of experiments conducted to determine if two or more individual radiation doses add together to produce carcinogenic effects are presented (no such effect was observed due to skin cell repair), together with their data comparing the induction and repair kinetics of DNA breaks with carcinogenesis in the rat skin, which indicated that single strand breaks are not the initial lesion in the dual action theory. (UK)

  18. An ultrastructural comparison of mesotheliomas with adenocarcinomas of the lung and breast.

    Science.gov (United States)

    Warhol, M J; Corson, J M

    1985-01-01

    The ultrastructural features of 15 mesotheliomas were compared with those of equal numbers of adenocarcinomas of the lung and of the breast in a double-blind study. Combined quantitative and qualitative features were evaluated to provide criteria for distinguishing among these three tumors, which may present as either primary or metastatic pleural tumors. mesotheliomas could be distinguished from adenocarcinomas of the lung by length of microvilli (mean ratios of length to diameter [LDR], 15.7 and 8.7, respectively; P less than 0.01) and content of tonofilaments. Length of microvilli was also useful in distinguishing mesotheliomas from breast adenocarcinomas (mean LDR, 15.7 and 6.9, respectively; P less than 0.001). Adenocarcinomas of the lung could be distinguished from adenocarcinomas of the breast by tonofilament content and the presence of intracytoplasmic lumina. Combined quantitative and qualitative criteria are essential for maximal ultrastructural discrimination among these tumors.

  19. Soluble Mesothelin-Related Peptides Levels in Patients with Malignant Mesothelioma

    Directory of Open Access Journals (Sweden)

    Alenka Franko

    2012-01-01

    Full Text Available Soluble mesothelin-related peptides (SMRP are a potential tumor marker for malignant mesothelioma. The aim of this study was to determine the differences in SMRP levels in patients with malignant mesothelioma before treatment and in various responses to treatment and to investigate whether SMRP level could be useful in evaluating tumor response to treatment. The study included patients with malignant mesothelioma treated at the Institute of Oncology Ljubljana between March 2007 and December 2009. Blood samples were collected before treatment and/or in various responses to treatment. SMRP levels were determined using ELISA assay based upon a combination of two monoclonal antibodies. Mann-Whitney test was used to determine the differences in SMRP levels in various responses to treatment.

  20. Radio-immunotherapy and chemo-immunotherapy as a novel treatment paradigm in malignant pleural mesothelioma

    Science.gov (United States)

    Wu, Licun

    2017-01-01

    Malignant pleural mesothelioma (MPM) is an aggressive neoplasm with poor outcome. Novel radical radiation techniques using intensity modulated radiation therapy (IMRT) have become an important component of therapy in mesothelioma. Immunotherapy also provides new therapeutic options. However, how best to integrate immunotherapy with standard therapy such as radiation, chemotherapy and surgery remains unknown. A change of paradigm from adjuvant normofractionation to induction accelerated hypofractionated hemithoracic radiation could provide a platform to combine immunotherapy due to the potential benefit of short course high dose radiation on the immune system. Immunotherapy can also be combined with chemotherapy. Although chemotherapy is generally considered immunosuppressive, some chemotherapeutic agents do induce cell death that can be immunogenic and stimulate a specific immune response against the tumor. Immunotherapy could also be used in between cycles of chemotherapy to limit tumor cell repopulation and optimize the results of both treatments. The integration of immunotherapy into a multimodality approach is opening new avenue of treatment for mesothelioma. PMID:28713677

  1. 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...... complete; the median time to progression was 8.6 months, and the median overall survival was 13 months. Some patients had their responses 4 to 6 months after last treatment. For 116 patients with epitheloid subtype, median survival was 17 months. A subgroup of these patients with good performance status...

  2. Malignant mesothelioma of tunica vaginalis: an extremely rare case presenting without risk factors

    Science.gov (United States)

    Akin, Yigit; Bassorgun, Ibrahim; Basara, Isil; Yucel, Selcuk

    2015-01-01

    Testicular tumours have many different manifestations, including hydrocele formation. Herein, we present an extremely rare case of testicular mesothelioma presenting with left hydrocele, but without risk factors. Left radical inguinal orchidectomy was performed, and pathological examination revealed a malignant mesothelioma of the tunica vaginalis of the testis. No infiltration of the spermatic cord was evident, and upon advanced radiological evaluation, no sign of metastasis was detected. Follow-up was still ongoing in our urology outpatient clinic at the time of this report. Although hydrocele is a simple and common condition that is easy to diagnose, a detailed investigation should be performed. Thus, when encountering a patient with hydrocele, the clinician should evaluate the possibility of the presence of an underlying testicular/paratesticular tumour, including a rare one such as mesothelioma of the tunica vaginalis. PMID:25820862

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  6. 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

  7. 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.)

  8. Primary diffuse malignant peritoneal mesothelioma in a striped skunk (Mephitis mephitis).

    Science.gov (United States)

    Kim, Su-Min; Oh, Yeonsu; Oh, Suk-Hun; Han, Jeong-Hee

    2016-03-01

    A 10-year-old female striped skunk (Mephitis mephitis) was admitted with severe abdominal distension and lethargy. Cytological examination of the peritoneal fluid revealed activated mesothelial cells. At necropsy, numerous growing together, projecting, 2 to 20 mm in diameter tawny to white masses were scattered throughout the peritoneum including the mesentery, omentum and intestinal serosa. Microscopically, the tumor was composed of prominent papillo-tubular structures, and immunohistochemically, the spindle to polygonal-shaped tumor cells with nuclear polymorphism were strongly reactive for calretinin. Based on those diagnostic features, the neoplasia was diagnosed as malignant mesothelioma. This is the first case report of mesothelioma in the skunk.

  9. 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

  10. Nintedanib Plus Pemetrexed/Cisplatin in Patients With Malignant Pleural Mesothelioma

    DEFF Research Database (Denmark)

    Grosso, Federica; Steele, Nicola; Novello, Silvia

    2017-01-01

    Purpose LUME-Meso is a phase II/III randomized, double-blind trial designed to assess efficacy and safety of nintedanib plus chemotherapy as first-line treatment of malignant pleural mesothelioma (MPM). Phase II results are reported here. Patients and Methods Chemotherapy-naïve patients with unre......Purpose LUME-Meso is a phase II/III randomized, double-blind trial designed to assess efficacy and safety of nintedanib plus chemotherapy as first-line treatment of malignant pleural mesothelioma (MPM). Phase II results are reported here. Patients and Methods Chemotherapy-naïve patients...

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

    Energy Technology Data Exchange (ETDEWEB)

    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.)

  12. 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...

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  14. 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.

  15. Gynaekologisk epidemiologi

    DEFF Research Database (Denmark)

    Lidegaard, Øjvind

    2006-01-01

    Epidemiological research has good possibilities in Denmark due to the fact that all people have a personal PIN code and due to our many National health registers. In gynaecology the National Register of Patients, the Birth Registry, IVF-registry, Cancer Registry and latest the National Prescription...... Database offer unique possibilities of linking exposure data with many clinical outcomes. Danish epidemiology has contributed with morbidity analyses on children concieved by in vitro fertilisation, pharmacoepidemiological studies on short and long term effects of oral contraceptives and hormone therapy...

  16. Gynaekologisk epidemiologi

    DEFF Research Database (Denmark)

    Lidegaard, Øjvind

    2006-01-01

    Database offer unique possibilities of linking exposure data with many clinical outcomes. Danish epidemiology has contributed with morbidity analyses on children concieved by in vitro fertilisation, pharmacoepidemiological studies on short and long term effects of oral contraceptives and hormone therapy......Epidemiological research has good possibilities in Denmark due to the fact that all people have a personal PIN code and due to our many National health registers. In gynaecology the National Register of Patients, the Birth Registry, IVF-registry, Cancer Registry and latest the National Prescription...

  17. Prognostic Factors in Patients with Malignant Pleural Mesothelioma

    Directory of Open Access Journals (Sweden)

    Vyacheslav P. Kurchin

    2015-03-01

    Full Text Available The aim of the present study was to examine the factors of prognosis in patients with malignant pleural mesothelioma (MPM after combined and multimodality treatment, including the prognostic significance of preoperative intrapleural perfusion hyperthermo-chemotherapy (IPHC. Material and Methods: The study included 20 patients (11 men and 9 women aged from 30 to 70 years (mean age 51.9±8.5 years who underwent surgical treatment for MPM. The diagnosis of MPM was verified by immunohistochemical data. The patients were divided into two groups. Group 1 included 9 patients who underwent combined treatment that included the extrapleural pneumonectomy (EPP and 4 courses of adjuvant chemotherapy. Group 2 included 11 patients who received multimodality treatment (IPHC, EPP, and 4 courses of adjuvant chemotherapy. All patients were followed prospectively at three-monthly intervals for the first year and six-monthly thereafter until the last time of contact or death. Statistical analysis was performed by using Kaplan-Meier method and the log-rank test. Cox-regression model was used for multivariate analysis. Results: Patient’s age over 60 years and the sarcomatoid type of the tumor can be regarded as prognostic factors for poor survival in patients with MPM who underwent EPP. Application of IPHC as a part of a multimodality treatment enhances the survivability of MPM patients.

  18. Deterioration in lung function following hemithorax irradiation for pleural mesothelioma

    International Nuclear Information System (INIS)

    Maasilta, P.

    1991-01-01

    Thirty-four patients receiving high-dose hemithorax irradiation as part of the treatment for pleural mesothelioma were studied with regard to changes in lung function following irradiation, and these changes were correlated with the radiologically-assessed lung injury. The latter was scored from 0 to 500 and found to be severe by 6 months (mean score 360), very severe by 9 months (mean score 430), and nearly total by 12 months (mean score 480) after treatment. Forced vital capacity and diffusing capacity both showed a significant decline at 1.5-2 months following the end of radiotherapy and thereafter up to the end of the 1 year follow-up period. Neither of these variables could be correlated consistently with the radiologically-assessed changes. Hypoxemia and pathological physiological shunting increased transiently 1-2 months after irradiation in 2 of the 6 patients monitored. The observed radiologically-assessed final effects of high-dose hemithorax irradiation are compatible with a total loss of lung function on the irradiated side. Before this form of treatment is used, lung function should be evaluated as for pneumonectomy

  19. Multicellular contractility contributes to the emergence of mesothelioma nodules

    Science.gov (United States)

    Czirok, Andras

    Malignant pleural mesothelioma (MPM) nodules arise from the mesothelial lining of the pleural cavity by a poorly understood mechanism. We demonstrate that macroscopic multicellular aggregates, reminiscent of the MPM nodules found in patients, develop when MPM cell lines are cultured at high cell densities for several weeks. Surprisingly, the nodule-like aggregates do not arise by excessive local cell proliferation, but by myosin II-driven cell contractility. Contractile nodules contain prominent actin cables that can span several cells. Several features of the in vitro MPM nodule development can be explained by a computational model that assumes uniform and steady intercellular contractile forces within a monolayer of cells, and a mechanical load-dependent lifetime of cell-cell contacts. The model behaves as a self-tensioned Maxwell fluid and exhibits an instability that leads to pattern formation. Altogether, our findings suggest that inhibition of the actomyosin system may provide a hitherto not utilized therapeutic approach to affect MPM growth. NIH R01-GM102801.

  20. Fast neutron radiotherapy in the treatment of malignant pleural mesothelioma.

    Science.gov (United States)

    Patel, Shilpen A; Kusano, Aaron S; Truong, Anh; Stelzer, Keith J; Laramore, George E

    2015-02-01

    Malignant pleural mesothelioma (MPM) is a fatal disease lacking standardized treatment. We describe the use of fast neutron radiation therapy in MPM patients referred to the Department of Radiation Oncology at the University of Washington Medical Center. Retrospective chart review of MPM patients receiving neutron radiotherapy treatment from 1980 to 2012. A total of 30 MPM patients received fast neutron radiotherapy as part of their treatment regimen. Median age at diagnosis was 59.6 years (range, 46.6 to 72.3 y). Eighteen patients received fast neutron radiotherapy as a component of trimodality treatment. Median overall survival was 20.3 months (range, 5.5 to 73.3 mo) with 1 patient censored at 34.8 months and all other patients with confirmed dates of death. One patient receiving radiotherapy alone as a palliative measure died during radiation treatment. One patient was unable to tolerate radiotherapy and stopped before completing prescribed treatment. On univariate analysis, Brigham Stage at presentation was a significant predictor of survival (Ptreatment compared to those who did not. Fast neutron radiotherapy may be utilized in the management of MPM patients. However, treatment with fast neutron radiotherapy did not significantly improvement outcome, even when used in a trimodality regimen.

  1. Current Issues in Malignant Pleural Mesothelioma Evaluation and Management

    Science.gov (United States)

    Ai, Jing

    2014-01-01

    Malignant pleural mesothelioma (MPM) is an uncommon disease most often associated with occupational asbestos exposure and is steadily increasing in worldwide incidence. Patients typically present at an older age, with advanced clinical stage and other medical comorbidities, making management quite challenging. Despite great efforts, the prognosis of MPM remains poor, especially at progression after initial treatment. Macroscopic complete resection of MPM can be achieved through extrapleural pneumonectomy (EPP) or extended (ie, radical) pleurectomy (e-P/D) in selected patients and can result in prolonged survival when incorporated into a multimodality approach. Given the morbidity associated with surgical resection of MPM, optimizing identification of appropriate patients is essential. Unfortunately, most patients are not candidates for EPP or e-P/D due to advanced stage, age, and/or medical comorbidity. Pemetrexed and platinum combination chemotherapy has become the cornerstone of therapy for patients with unresectable disease because the combination is associated with improved survival and quality of life in treated patients. However, MPM eventually becomes resistant to initial therapy, and benefit to further lines of therapy has not been substantiated in randomized clinical trials. Translational research has provided exciting insights into tumorigenesis, biomarkers, and immune response in MPM, leading to the development of multiple novel therapeutic agents that are currently in clinical trials. These advances hold the promise of a new era in the treatment of MPM and suggest that this disease will not be left behind in the war on cancer. PMID:25061089

  2. Updates in the diagnosis and treatment of malignant pleural mesothelioma.

    Science.gov (United States)

    Katzman, Daniel; Sterman, Daniel H

    2018-03-16

    This review article describes current diagnostic and treatment modalities for malignant pleural mesothelioma (MPM). Few randomized trials in MPM have demonstrated improved survival with current therapies. A randomized trial of first-line chemotherapy with and without bevacizumab in unresectable MPM is the only randomized trial of a new treatment regimen to demonstrate a survival benefit since cisplatin with pemetrexed became the standard of care for unresectable MPM in 2003. Unfortunately, in unresectable MPM, first-line chemotherapy alone or in combination with bevacizumab has demonstrated only limited improvements in overall survival. Recently, in nonrandomized observational studies, multimodality treatments with chemotherapy, surgery, radiation, and novel therapies have been associated with prolonged survival in select patients. Currently, there are no FDA approved second-line therapies, and clinical trial enrollment is recommended for second-line treatment. MPM remains difficult to treat and has an overall poor prognosis despite current multimodality treatment. Thoracoscopy with multiple pleural biopsies can provide adequate tissue specimens for diagnostic testing to distinguish histologic MPM subtypes and perform molecular profiling, which influence prognosis and treatment options. In early clinical trials, immunotherapies and therapies directed against cancer-associated antigens and oncogenic alterations are emerging as promising future treatments.

  3. PET-guided dose escalation tomotherapy in malignant pleural mesothelioma

    Energy Technology Data Exchange (ETDEWEB)

    Fodor, Andrei; Dell' Oca, Italo; Pasetti, Marcella; Di Muzio, Nadia Gisella [San Raffaele Scientific Institute, Milan (Italy). Dept. of Radiotherapy; Fiorino, Claudio; Broggi, Sara; Cattaneo, Giovanni Mauro; Calandrino, Riccardo [San Raffaele Scientific Institute, Milan (Italy). Medical Physics; Gianolli, Luigi [San Raffaele Scientific Institute, Milan (Italy). Dept. of Nuclear Medicine

    2011-11-15

    To test the feasibility of salvage radiotherapy using PET-guided helical tomotherapy in patients with progressive malignant pleural mesothelioma (MPM). A group of 12 consecutive MPM patients was treated with 56 Gy/25 fractions to the planning target volume (PTV); FDG-PET/CT simulation was always performed to include all positive lymph nodes and MPM infiltrations. Subsequently, a second group of 12 consecutive patients was treated with the same dose to the whole pleura adding a simultaneous integrated boost of 62.5 Gy to the FDG-PET/CT positive areas (BTV). Good dosimetric results were obtained in both groups. No grade 3 (RTOG/EORTC) acute or late toxicities were reported in the first group, while 3 cases of grade 3 late pneumonitis were registered in the second group: the duration of symptoms was 2-10 weeks. Median overall survival was 8 months (1.2-50.5 months) and 20 months (4.3-33.8 months) from the beginning of radiotherapy, for groups I and II, respectively (p = 0.19). A significant impact on local relapse from radiotherapy was seen (median time to local relapse: 8 vs 17 months; 1-year local relapse-free rate: 16% vs 81%, p = 0.003). The results of this pilot study support the planning of a phase III study of combined sequential chemoradiotherapy with dose escalation to BTV in patients not able to undergo resection. (orig.)

  4. Malignant pleural mesothelioma risk among nuclear workers: a review

    Energy Technology Data Exchange (ETDEWEB)

    Metz-Flamant, C; Guseva Canu, I; Laurier, D, E-mail: camille.metz@irsn.fr [Laboratory of Epidemiology, Institute of Radiological Protection and Nuclear Safety (IRSN), Fontenay-aux-Roses (France)

    2011-03-01

    Exposure to ionising radiation has been suggested as a causal risk factor for malignant pleural mesothelioma (MPM). Studies of patients treated by radiotherapy for primary cancers have suggested that radiation contributes to the development of secondary MPM. Here we examined the risk to nuclear workers of MPM related to exposure to low doses of occupational radiation at low dose rates. All results concerning MPM risk in published studies of nuclear workers were examined for their association with radiation exposure and potential confounders. We found 19 relevant studies. Elevated risks of pleural cancer were reported in most (15/17) of these studies. Eight reported risks higher for radiation monitored workers than for other workers. However, of 12 studies that looked at associations with ionising radiation, only one reported a significant dose-risk association. Asbestos was an important confounder in most studies. We conclude that studies of nuclear workers have not detected an association between ionising radiation exposure and MPM. Further investigations should improve the consideration of asbestos exposure at the same time as they address the risk of MPM related to occupational exposure of nuclear workers to low doses of ionising radiation at low dose rates. (review)

  5. Carcinogenesis related to intense pulsed light and UV exposure

    DEFF Research Database (Denmark)

    Hedelund, L; Lerche, C; Wulf, H C

    2006-01-01

    This study examines whether intense pulsed light (IPL) treatment has a carcinogenic potential itself or may influence ultraviolet (UV)-induced carcinogenesis. Secondly, it evaluates whether UV exposure may influence IPL-induced side effects. Hairless, lightly pigmented mice (n=144) received three...

  6. Chronology of p53 protein accumulation in gastric carcinogenesis

    NARCIS (Netherlands)

    Craanen, M. E.; Blok, P.; Dekker, W.; Offerhaus, G. J.; Tytgat, G. N.

    1995-01-01

    p53 Protein accumulation in early gastric carcinoma was studied in relation to the histological type (Lauren classification) and the type of growth pattern, including the chronology of p53 protein accumulation during carcinogenesis. Forty five, paraffin embedded gastrectomy specimens from early

  7. Lack of cyclin D1 overexpression in gastric carcinogenesis

    NARCIS (Netherlands)

    Blok, P.; Craanen, M. E.; van Diest, P. J.; Dekker, W.; Tytgat, G. N.

    2000-01-01

    Cyclin D1 overexpression was examined in early gastric carcinomas and precursor lesions with the following aims; (1) to assess the chronology of cyclin D1 overexpression in various stages of gastric carcinogenesis, (2) to correlate cyclin D1 overexpression with the Lauren type, the grade of

  8. Hypoxia and cell cycle deregulation in endometrial carcinogenesis

    NARCIS (Netherlands)

    Horrée, N.

    2007-01-01

    Because uterine endometrial carcinoma is the most common malignancy of the female genital tract and 1 of every 5 patients dies of this disease, understanding the mechanisms of carcinogenesis and progression of endometrial carcinoma is important. In general, this thesis can be summarized as a study

  9. 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.

  10. Epidemiological causality.

    Science.gov (United States)

    Morabia, Alfredo

    2005-01-01

    Epidemiological methods, which combine population thinking and group comparisons, can primarily identify causes of disease in populations. There is therefore a tension between our intuitive notion of a cause, which we want to be deterministic and invariant at the individual level, and the epidemiological notion of causes, which are invariant only at the population level. Epidemiologists have given heretofore a pragmatic solution to this tension. Causal inference in epidemiology consists in checking the logical coherence of a causality statement and determining whether what has been found grossly contradicts what we think we already know: how strong is the association? Is there a dose-response relationship? Does the cause precede the effect? Is the effect biologically plausible? Etc. This approach to causal inference can be traced back to the English philosophers David Hume and John Stuart Mill. On the other hand, the mode of establishing causality, devised by Jakob Henle and Robert Koch, which has been fruitful in bacteriology, requires that in every instance the effect invariably follows the cause (e.g., inoculation of Koch bacillus and tuberculosis). This is incompatible with epidemiological causality which has to deal with probabilistic effects (e.g., smoking and lung cancer), and is therefore invariant only for the population.

  11. 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.

  12. 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.

  13. 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

  14. 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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  15. Analysis of Gene Expression in 3D Spheroids Highlights a Survival Role for ASS1 in Mesothelioma

    Science.gov (United States)

    Barbone, Dario; Van Dam, Loes; Follo, Carlo; Jithesh, Puthen V.; Zhang, Shu-Dong; Richards, William G.; Bueno, Raphael; Fennell, Dean A.; Broaddus, V. Courtney

    2016-01-01

    To investigate the underlying causes of chemoresistance in malignant pleural mesothelioma, we have studied mesothelioma cell lines as 3D spheroids, which acquire increased chemoresistance compared to 2D monolayers. We asked whether the gene expression of 3D spheroids would reveal mechanisms of resistance. To address this, we measured gene expression of three mesothelioma cell lines, M28, REN and VAMT, grown as 2D monolayers and 3D spheroids. A total of 209 genes were differentially expressed in common by the three cell lines in 3D (138 upregulated and 71 downregulated), although a clear resistance pathway was not apparent. We then compared the list of 3D genes with two publicly available datasets of gene expression of 56 pleural mesotheliomas compared to normal tissues. Interestingly, only three genes were increased in both 3D spheroids and human tumors: argininosuccinate synthase 1 (ASS1), annexin A4 (ANXA4) and major vault protein (MVP); of these, ASS1 was the only consistently upregulated of the three genes by qRT-PCR. To measure ASS1 protein expression, we stained 2 sets of tissue microarrays (TMA): one with 88 pleural mesothelioma samples and the other with additional 88 pleural mesotheliomas paired with matched normal tissues. Of the 176 tumors represented on the two TMAs, ASS1 was expressed in 87 (50%; staining greater than 1 up to 3+). For the paired samples, ASS1 expression in mesothelioma was significantly greater than in the normal tissues. Reduction of ASS1 expression by siRNA significantly sensitized mesothelioma spheroids to the pro-apoptotic effects of bortezomib and of cisplatin plus pemetrexed. Although mesothelioma is considered by many to be an ASS1-deficient tumor, our results show that ASS1 is elevated at the mRNA and protein levels in mesothelioma 3D spheroids and in human pleural mesotheliomas. We also have uncovered a survival role for ASS1, which may be amenable to targeting to undermine mesothelioma multicellular resistance. PMID:26982031

  16. 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.

  17. 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

  18. 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.

  19. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  1. 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.

  2. The ultrastructural localization of keratin proteins and carcinoembryonic antigen in malignant mesotheliomas.

    Science.gov (United States)

    Warhol, M J

    1984-09-01

    The immunoultrastructural localization of keratin proteins and carcinoembryonic antigen (CEA) in mesothelioma cells was accomplished with a low-temperature embedding colloidal gold technique. The keratin antiserum labeled only intermediate filaments. These filaments surrounded the cytoplasmic organelles and were inserted into desmosomes. The CEA antiserum labeled cytoplasmic vesicles and droplets. No definite labeling of microvilli was observed.

  3. 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

  4. 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

  5. Incidental fallopian tube mesothelioma diagnosed at time of elective bilateral salpingectomy for sterilisation: A case report

    OpenAIRE

    Phillips-Yelland, J.; Payton, D.; Land, R.; Kaur, A.

    2017-01-01

    Highlights ? Incidental finding of a fallopian tube lesion at the time of bilateral salpingectomy ? Histopathological appearance not consistent with mucinous or serous carcinoma, appearance of mesothelioma ? Very rare known primary neoplasm of tubal mesothelium, favours an indolent course ? Recommendation for prophylactic hysterectomy and bilateral oophorectomy ? If nil further spread, generally nil further treatment is required

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

    Directory of Open Access Journals (Sweden)

    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.

  7. Promising investigational drug candidates in phase I and phase II clinical trials for mesothelioma.

    Science.gov (United States)

    Guazzelli, Alice; Bakker, Emyr; Tian, Kun; Demonacos, Constantinos; Krstic-Demonacos, Marija; Mutti, Luciano

    2017-08-01

    Malignant mesothelioma is a rare and lethal malignancy primarily affecting the pleura and peritoneum. Mesothelioma incidence is expected to increase worldwide and current treatments remain ineffective, leading to poor prognosis. Within this article potential targets to improve the quality of life of the patients and assessment of further avenues for research are discussed. Areas covered: This review highlights emerging therapies currently under investigation for malignant mesothelioma with a specific focus on phase I and phase II clinical trials. Three main areas are discussed: immunotherapy (immune checkpoint blockade and cancer vaccines, among others), multitargeted therapy (such as targeting pro-angiogenic genes) and gene therapy (such as suicide gene therapy). For each, clinical trials are described to detail the current or past investigations at phase I and II. Expert opinion: The approach of applying existing treatments from other cancers does not show significant benefit, with the most promising outcome being an increase in survival of 2.7 months following combination of chemotherapy with bevacizumab. It is our opinion that the hypoxic microenvironment, the role of the stroma, and the metabolic status of mesothelioma should all be assessed and characterised to aid in the development of new treatments to improve patient outcomes.

  8. A Case Report of Primary Pericardial Malignant Mesothelioma Treated with Pemetrexed and Cisplatin.

    Science.gov (United States)

    Kim, Jung Sun; Lim, Sang Yup; Hwang, Jinwook; Kang, Eun Joo; Choi, Yoon Ji

    2017-11-01

    Primary pericardial malignant mesothelioma (PPM) is a very rare malignancy, with an incidence of less than 0.002% and represents less than 5% of all mesotheliomas. The cause of pericardial mesothelioma is uncertain that differ from pleural mesothelioma which is associated with asbestos exposure. This malignancy is terribly aggressive and has very poor prognosis with less than six months of overall survival. We present a case of a 71-year-old woman who was diagnosed with cardiac tamponade caused by PPM and received chemotherapy with pemetrexed and cisplatin for six months. During two years she was alive without disease progression. To better understand the clinical, pathologic features and treatment outcome of this entity, we reviewed 23 cases described in the English literature from 2009, together with our case, provided a total of 24 cases. Based on this review, we suggest that PPM must be considered in patients who have unexplained massive pericardial effusion and recommend chemotherapy with pemetrexed and cisplatin for the better outcome of PPM. © 2017 The Korean Academy of Medical Sciences.

  9. Comparative Elongated Mineral Particle Toxicology & Erionite’s Apparent  High Potency for Inducing Mesothelioma

    Science.gov (United States)

    Recent NHEERL research under EPA's Libby Action Plan has determined that elongated particle relative potency for rat pleural mesothelioma is best predicted on the basis of total external surface area (TSA) of slightly acid leached test samples which simulate particle bio-durabili...

  10. Paclitaxel for malignant pleural mesothelioma : A phase II study of the EORTC Lung Cancer Cooperative Group

    NARCIS (Netherlands)

    vanMeerbeeck, J; Debruyne, C; vanZandwijk, N; Postmus, PE; Pennucci, MC; vanBreukelen, F; Galdermans, D; Groen, H; Pinson, P; vanGlabbeke, M; vanMarck, E; Giaccone, G

    The EORTC Lung Cancer Cooperative Group undertook a phase II study of paclitaxel in 25 chemotherapy-naive patients with malignant pleural mesothelioma. Paclitaxel was given intravenously at a dose of 200 mg m(-2), as a 3 h infusion every 3 weeks, after standard premedication with corticosteroids and

  11. 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

  12. Etoposide in malignant pleural mesothelioma : Two phase II trials of the EORTC Lung Cancer Cooperative Group

    NARCIS (Netherlands)

    Sahmoud, T; Postmus, PE; van Pottelsberghe, C; Mattson, K; Tammilehto, L; Splinter, TAW; Planting, AST; Sutedja, T; van Pawel, J; van Zandwijk, N; Baas, P; Roozendaal, KJ; Schrijver, M; Kirkpatrick, A; Van Glabbeke, M; Ardizzoni, A; Giaccone, G

    1997-01-01

    Intravenous and oral etoposide (VP 16-213) were tested in two sequential phase II trials in chemotherapy-naive patients with malignant pleural mesothelioma. In the first trial, etoposide was given intravenously (i.v.) at a dose of 150 mg/m(2) on days 1, 3 and 5 every 3 weeks. The second trial

  13. The value of pemetrexed for the treatment of malignant pleural mesothelioma: a comprehensive review.

    NARCIS (Netherlands)

    Boons, C.C.L.M.; Tulder, M.W. van; Burgers, J.A.; Beckeringh, J.J.; Wagner, C.; Hugtenburg, J.G.

    2013-01-01

    This review aims to provide insight into treatment of malignant pleural mesothelioma (MPM) considering effects on survival, quality of life (QoL) and costs, in order to determine the value of pemetrexed in MPM treatment. Cisplatin in combination with pemetrexed or raltitrexed increased survival in

  14. 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.

  15. Asbestos in commercial cosmetic talcum powder as a cause of mesothelioma in women

    Science.gov (United States)

    Gordon, Ronald E; Fitzgerald, Sean; Millette, James

    2014-01-01

    Background: Cosmetic talcum powder products have been used for decades. The inhalation of talc may cause lung fibrosis in the form of granulomatose nodules called talcosis. Exposure to talc has also been suggested as a causative factor in the development of ovarian carcinomas, gynecological tumors, and mesothelioma. Purpose: To investigate one historic brand of cosmetic talcum powder associated with mesothelioma in women. Methods: Transmission electron microscope (TEM) formvar-coated grids were prepared with concentrations of one brand of talcum powder directly, on filters, from air collections on filters in glovebox and simulated bathroom exposures and human fiber burden analyses. The grids were analyzed on an analytic TEM using energy-dispersive spectrometer (EDS) and selected-area electron diffraction (SAED) to determine asbestos fiber number and type. Results: This brand of talcum powder contained asbestos and the application of talcum powder released inhalable asbestos fibers. Lung and lymph node tissues removed at autopsy revealed pleural mesothelioma. Digestions of the tissues were found to contain anthophyllite and tremolite asbestos. Discussion: Through many applications of this particular brand of talcum powder, the deceased inhaled asbestos fibers, which then accumulated in her lungs and likely caused or contributed to her mesothelioma as well as other women with the same scenario. PMID:25185462

  16. Risk factors for malignant mesothelioma in people with no known exposure to asbestos

    NARCIS (Netherlands)

    Musk, Bill; Gordon, Len; Alfonso, Helman; Reid, Alison; Olsen, Nola; Mina, Robin; Franklin, Peter; Peters, Susan|info:eu-repo/dai/nl/304822930; Brims, Fraser; Hui, Jennie; de Klerk, Nicholas

    2017-01-01

    OBJECTIVES: Malignant mesothelioma (MM) is a rare and generally fatal cancer, usually caused by asbestos, although about 5-10% of cases report no asbestos exposure. This study aimed to identify sources whereby people in Western Australia (WA) may be unknowingly exposed to asbestos or to other

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

    Directory of Open Access Journals (Sweden)

    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.

  18. 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

  19. 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

  20. Leser–Trélat syndrome in malignant mesothelioma and pulmonary adenocarcinoma

    DEFF Research Database (Denmark)

    Jepsen, Rikke Karlin; Skov, Anne Guldhammer; Skov, Birgit Guldhammer

    2014-01-01

    . The pathogenesis is unclear but might be explained by circulating tumor-associated growth factors. We present two thoracic malignancies associated with LT: adenocarcinoma of the lung (ACL) and pleural malignant mesothelioma (MM). Both malignant tumors expressed high levels of epidermal growth factor receptors...