Cause Of Mesothelioma Research Articles

Asbestos-Related lung Cancer: An underappreciated oncological issue

Asbestos, a group of class I (WHO) carcinogenic fibers, is the main cause of mesothelioma. Asbestos inhalation also increases the risk to develop other solid tumours with lung cancer as the most prominent example [91]. The incidence of asbestos-related lung cancer (ARLC) is estimated to be to six times larger than the mesothelioma incidence thereby becoming an important health issue [86]. Although the pivotal role of asbestos in inducing lung cancer is well established, the precise causal relationships between exposures to asbestos, tobacco smoke, radon and ‘particulate’ (PM2.5) air pollution remain obscure and new knowledge is needed to establish appropriate preventive measures and to tailor existing screening practices[22,61,65]. We hypothesize that a part of the increasing numbers of lung cancer diagnoses in never-smokers can be explained by (historic and current) exposures to asbestos as well as combinations of different forms of air pollution (PM2.5, asbestos and silica).

Mental health and wellbeing in mesothelioma: A qualitative study exploring what helps the wellbeing of those living with this illness and their informal carers

PurposeMesothelioma is an incurable, asbestos related cancer with a poor prognosis. Little is known about how patients and carers living with the condition manage their mental health and wellbeing needs. This paper reports findings on interventions being used by patients and informal carers living with mesothelioma and those which they find most helpful. MethodsIn-depth interviews with patients (n = 10) and (informal) carers (n = 11) living with mesothelioma in the UK. We analysed our data inductively using a reflexive thematic analysis approach. ResultsParticipants described the importance of both smaller and larger actions and strategies which helped with their mental health. This included spending more time with family and friends and going on holidays. Professionals who participants said supported their mental health journey included not only specialist nurses and mental health professionals but also legal and Asbestos Support Group professionals. The latter demonstrates the unique needs and support required for this population. Exposure to asbestos as the cause of mesothelioma, has led to a social justice aspect of the experience of living with this cancer. Participants reported the importance of collective action to their mental health and wellbeing. The data indicate that patients and carers may have distinct mental health and wellbeing requirements and need to manage these in different ways at different times. ConclusionsFindings have implications for nurses and other key professionals working in healthcare, community and legal settings supporting this client group, and for those living with mesothelioma who want to understand ways to enhance their own wellbeing.

A Critique of Helsinki Criteria for Using Lung Fiber Levels to Determine Causation in Mesothelioma Cases.

Asbestos is a known human carcinogen and the chief known cause of mesothelioma. In 1997, a group of experts developed the Helsinki Criteria, which established criteria for attribution of mesothelioma to asbestos. The criteria include two methods for causation attribution: 1) a history of significant occupational, domestic, or environmental exposure and/or 2) pathologic evidence of exposure to asbestos. In 2014, the Helsinki Criteria were updated, and these attribution criteria were not changed. However, since the Helsinki Criteria were first released in 1997, some pathologists, cell biologists, and others have claimed that a history of exposure cannot establish causation unless the lung asbestos fiber burden exceeds “the background range for the laboratory in question to attribute mesothelioma cases to exposure to asbestos.” This practice ignores the impact on fiber burden of clearance/translocation over time, which in part is why the Helsinki Criteria concluded that a history of exposure to asbestos was independently sufficient to attribute causation to asbestos.After reviewing the Helsinki Criteria, we conclude that their methodology is fatally flawed because a quantitative assessment of a background lung tissue fiber level cannot be established. The flaws of the Helsinki Criteria are both technical and substantive. The 1995 paper that served as the scientific basis for establishing background levels used inconsistent methods to determine exposures in controls and cases. In addition, historic controls cannot be used to establish background fiber levels for current cases because ambient exposures to asbestos have decreased over time and control cases pre-date current cases by decades. The use of scanning electron microscope (SEM) compounded the non-compatibility problem; the applied SEM cannot distinguish talc from anthophyllite because it cannot perform selected area electron diffraction, which is a crucial identifier in ATEM for distinguishing the difference between serpentine asbestos, amphibole asbestos, and talc.

Mesothelioma in immigrants from Turkey: Genes have a minor role

ObjectiveTo examine the incidence and epidemiology of malignant mesothelioma in immigrants from Karain where there is an extraordinarily high incidence of mesothelioma, Cappadocia, Turkey, to Stockholm, Sweden, and their children over 20 years of age born in Stockholm, i.e. two genetically similar populations with and without erionite exposure. MethodsThis survey was conducted as a retrospective cohort study. Standardized average annual mesothelioma incidence rates (AAMIRs) and mesothelioma standardized incidence ratio (mSIR) were calculated. Cox regression analysis was used to determine the importance of different factors related to mesothelioma risk. ResultsThe cohort consisted of 337 people, 203 of whom were born and/or lived in Karain before immigrating to Sweden (erionite-exposed), and 134 who were born in Stockholm (erionite-unexposed). There were 69 deaths, 42 (61%) due to mesothelioma, and two patients with the disease who were still alive. Of these 44 patients, 22 were men. All mesothelioma patients were in the erionite-exposed group. In the age group 30–49 years, mesothelioma developed in 11 of 38 (29%) with erionite exposure, while there were no cases among 86 persons in the non-exposed group. For men, the AAMIR was 253.9 per 100,000 persons in the whole cohort, and for women, it was 350.9. The mSIR was 71.9 for men and 393.1 for women. Exposure to erionite exceeding 20 years and age over 40 years were associated with increased mesothelioma risk. ConclusionExposure to erionite is the leading cause of mesothelioma in Karain villagers, and genetic factors are probably of minor importance.

A quantitative weight of evidence assessment of Hill's guidelines for causal inference for cosmetic talc as a cause of mesothelioma

Cosmetic talc has been suggested to cause mesothelioma. To assess a potential causal relationship between cosmetic talc and mesothelioma, a quantitative weight of evidence analysis was performed in accordance with Hill's nine original guidelines for causal inference using a published empirical model to weight each respective guideline. Various epidemiological, toxicological, and exposure studies related to cosmetic talc and risk of mesothelioma were included in an evaluation of each of Hill's guidelines. Probabilities that the guidelines were true were assigned based on expert judgment. We applied a sensitivity analysis to evaluate the variability of our probability estimates. The overall probability of causality for cosmetic talc and mesothelioma was approximately 1.29% (range: 0.73%–3.96%). This low probability of causality supports the conclusion that cosmetic talc is not related to the development of mesothelioma.

Malignant mesothelioma following repeated exposures to cosmetic talc: A case series of 75 patients.

BackgroundAsbestos is the primary known cause of malignant mesothelioma. Some cosmetic talc products have been shown to contain asbestos. Recently, repeated exposures to cosmetic talc have been implicated as a cause of mesothelioma.MethodsSeventy‐five individuals (64 females; 11 males) with malignant mesothelioma, whose only known exposure to asbestos was repeated exposures to cosmetic talcum powders, were reviewed in medical‐legal consultation. Out of the 75 cases, 11 were examined for asbestiform fibers.ResultsAll subjects had pathologically confirmed malignant mesothelioma. The mean age at diagnosis was 61 ± 17 years. The mean latency from exposure to diagnosis was 50 ± 13 years. The mean exposure duration was 33 ± 16 years. Four mesotheliomas (5%) occurred in individuals working as barbers/cosmetologists, or in a family member who swept the barber shop. Twelve (16%) occurred in individuals less than 45 years old (10 females; 2 males). Forty‐eight mesotheliomas were pleural (40 females; 8 males), 23 were peritoneal (21 females; 2 males). Two presented with concomitant pleural and peritoneal disease. There was one pericardial, and one testicular mesothelioma. The majority (51) were of the epithelioid histological subtype, followed by 13 biphasic, 8 sarcomatoid, 2 lymphohistiocytoid, and 1 poorly differentiated. Of the 11 individuals whose nontumorous tissues were analyzed for the presence of asbestiform fibers, all showed the presence of anthophyllite and/or tremolite asbestos.ConclusionsMesotheliomas can develop following exposures to cosmetic talcum powders. These appear to be attributable to the presence of anthophyllite and tremolite contaminants in cosmetic talcum powder.

SV40 and human mesothelioma.

Simian virus 40 (SV40) is a DNA tumor virus capable of infecting and transforming human mesothelial (HM) cells in vitro. Hamsters injected intracardially to expose most tissue types to SV40 preferentially develop mesotheliomas. In humans, asbestos is the main cause of mesothelioma, and asbestos and SV40 are co-carcinogens in transforming HM cells in tissue culture and in causing mesothelioma in hamsters. Laser microdissection experiments conducted in the laboratory of Adi Gazdar demonstrated that SV40 was present specifically in the malignant mesothelioma cells and not in nearby stromal cells. Further experiments demonstrated that SV40 remains episomal in HM cells and astrocytes because of the production of a long antisense RNA that represses viral capsid protein production. Thus, the potent SV40 oncoprotein, T-antigen (Tag), is expressed, but because the capsid proteins are not produced, the cells are not lysed and, instead, become transformed. Together this evidence suggests that SV40 may contribute to the development of mesotheliomas in humans. However, epidemiological evidence to support this hypothesis is lacking. This chapter also summarizes the introduction of SV40, a monkey virus, into the human population as an unrecognized contaminant of early poliovaccines. In addition to mesotheliomas, SV40 now is linked with brain cancers, osteosarcomas, and lymphomas in humans. Explanations are provided for the apparent geographic variations in SV40 prevalence and for controversies about the role of SV40 in human cancer.

Population‐based cohort study on health effects of asbestos exposure in Japan

Occupational asbestos exposure occurs in many workplaces and is a well‐known cause of mesothelioma and lung cancer. However, the association between nonoccupational asbestos exposure and those diseases is not clearly described. The aim of this study was to investigate cause‐specific mortality among the residents of Amagasaki, a city in Japan with many asbestos factories, and evaluate the potential excess mortality due to established and suspected asbestos‐related diseases. The study population consisted of 143 929 residents in Amagasaki City before 1975 until 2002, aged 40 years or older on January 1, 2002. Follow‐up was carried out from 2002 to 2015. Standardized mortality ratio (SMR) with its 95% confidence interval (CI) was calculated by sex, using the mortality rate of the Japanese population as reference. A total of 38 546 deaths (including 303 from mesothelioma and 2683 from lung cancer) were observed. The SMRs in the long‐term residents’ cohort were as follows: death due to all causes, 1.12 (95% CI, 1.10‐1.13) in men and 1.07 (95% CI, 1.06‐1.09) in women; lung cancer, 1.28 (95% CI, 1.23‐1.34) in men and 1.23 (95% CI, 1.14‐1.32) in women; and mesothelioma, 6.75 (95% CI, 5.83‐7.78) in men and 14.99 (95% CI, 12.34‐18.06) in women. These SMRs were significantly higher than expected. The increased SMR of mesothelioma suggests the impact of occupational asbestos exposure among men and nonoccupational asbestos exposure among women in the long‐term residents’ cohort. In addition, the high level of excess mortality from mesothelioma has persisted, despite the mixture of crocidolite and chrysotile no longer being used for three or four decades.

New Perspectives on Diagnosis and Therapy of Malignant Pleural Mesothelioma

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.

Malignant Mesothelioma and Its Non-Asbestos Causes.

- Although many mesotheliomas are related to asbestos exposure, not all are, and there is increasing information on other causes of mesothelioma. - To provide a review of non-asbestos causes for malignant mesothelioma. - Review of relevant published literature via PubMed and other search engines. - Currently, most pleural mesotheliomas (70% to 90%) in men in Europe and North America are attributable to asbestos exposure; for peritoneal mesothelioma the proportion is lower. In North America few mesotheliomas in women at any site are attributable to asbestos exposure, but in Europe the proportion is higher and varies considerably by locale. In certain geographic locations other types of mineral fibers (erionite, fluoro-edenite, and probably balangeroite) can induce mesothelioma. Therapeutic radiation for other malignancies is a well-established cause of mesothelioma, with relative risks as high as 30. Carbon nanotubes can also induce mesotheliomas in animals but there are no human epidemiologic data that shed light on this issue. Chronic pleural inflammation may be a cause of mesothelioma but the data are scanty. Although SV40 can induce mesotheliomas in animals, in humans the epidemiologic data are against a causative role. A small number of mesotheliomas (probably in the order of 1%) are caused by germline mutations/deletions of BRCA1-associated protein-1 ( BAP1) in kindreds that also develop a variety of other cancers. All of these alternative etiologies account for a small proportion of tumors, and most mesotheliomas not clearly attributable to asbestos exposure are spontaneous (idiopathic).

Causal understandings: Controversy, social context, and mesothelioma research

Asbestos-related diseases are often considered a ‘thing of the past’ in the global North. Yet, asbestos products remain widely used in the global South, especially in low cost housing. Like many occupational diseases, the history of asbestos is fraught with scientific controversy. The role of the asbestos industry in fostering uncertainty has been investigated for decades. But, less is known about the ways in which publicly-funded, not industry-funded, science has produced ignorance about the health consequences of exposure. To explore the contribution of publicly-funded science to the construction of ignorance, we examine the continuities and discontinuities among three hypotheses of mesothelioma causality: the amphibole hypothesis, the SV40 hypothesis, and the genetic hypothesis. Placing our analysis of scientific controversy in the context of asbestos mining in South Africa, we summarize the key features of the long-standing amphibole hypothesis, track in detail the emergence of SV40 as a causal agent, and outline the ongoing debate over genes as causes of mesothelioma. Regardless of the source of funding, we argue that by operating within conceptually closed biomedical frameworks, each hypothesis generated scientific controversy that made the political, social, and economic context of asbestos mining, milling, and manufacture in South Africa and other regions of the global South invisible, thereby limiting causal understanding.

Modulation of reactive oxygen species via ERK and STAT3 dependent signalling are involved in the response of mesothelioma cells to exemestane.

Pleural mesothelioma is a deadly form of cancer. The prognosis is extremely poor due to the limited treatment modalities. Uptake of asbestos fibres, the leading cause of mesothelioma, lead to the accumulation of reactive-oxygen-species (ROS). Interestingly, increasing ROS production by using ROS-generating drugs may offer a strategy to selectively trigger cell death. Exemestane, an aromatase inhibitor, has previously shown anti-tumor properties in mesothelioma preclinical models suggesting a role of G protein-coupled receptor 30 (GPR30) in the drug response. As exemestane, in addition to blocking estrogen biosynthesis, generates ROS that are able to arrest the growth of breast cancer, we explored the role of ROS, antioxidant defense system, and ROS-induced signalling pathways in mesothelioma cells during exemestane response. Here we report that exemestane treatment reduced cell proliferation with an increase in ROS production and reduction of cyclic adenosine monophosphate (cAMP) levels in MSTO-H211, Ist-Mes1, Ist-Mes2 and MPP89 exemestane-sensitive mesothelioma cell lines, but not in NCI-H2452 exemestane-insensitive mesothelioma cells. Exemestane induced a significant antioxidant response in NCI-H2452 cells, as highlighted by an increase in γ-glutamylcysteine levels, catalase (Cat), superoxide-dismutase and (SOD) and glutathione-peroxidase (GSH-Px) activity and nuclear factor E2-related factor 2 (Nrf2) activation, responsible for drug insensitivity. Conversely, exemestane elevated ROS levels along with increased ERK phosphorylation and a reduction of p-STA3 in exemestane-sensitive mesothelioma cells. ROS generation was the crucial event of exemestane action because ROS inhibitor N-acetyl-L-cysteine (NAC) abrogated p-ERK and p-STAT3 modulation and cellular death. Exemestane also modulates ERK and STAT3 signalling via GPR30. Results indicate an essential role of ROS in the antiproliferative action of exemestane in mesothelioma cells. It is likely that the additional oxidative insults induced by exemestane results in the lethal effects of mesothelioma cells by increasing ROS production. As such, manipulating ROS levels with exemestane seems to be a feasible strategy to selectively kill mesothelioma cells with less toxicity to normal cells by regulating ERK and STAT3 activity.

Current Treatment of Malignant Mesothelioma

Malignant mesothelioma is a cancer of the mesothelium. Although mesothelioma is a rare malignancy, it has a poor prognosis. The incidence rate of malignant mesothelioma has been rising since the mid twentieth century century. Asbestos is the most common cause of mesothelioma. Chemotherapy combined with radiation therapy is currently the best choice of treatment and monoclonal antibody therapy is a new treatment option for the future. In the present study, we thoroughly reviewed the pathogenesis, clinical features, laboratory diagnosis, modalities of treatment, and clinical outcomes of this condition.

Peritoneal Mesothelioma: A Rare Cause of Abdominal Ascites

Mesothelioma is a fatal malignancy typically located in the pleura of men in their 50's, many years after asbestos exposure. Peritoneal mesothelioma is rare and may be difficult to diagnose by cytologic analysis of ascetic fluid as it is often negative or inconclusive. Patients commonly present with nonspecific symptoms, however, the Gastroenterologist may be called to consider this in the work-up of ascites. A 23 year old female presented with increased abdominal girth, weight gain, and abdominal cramping. Pelvic ultrasound revealed moderate to large amount of simple-appearing nonspecific free fluid in the cul-de-sac and bilateral adnexal regions. Various examinations over the next few months revealed increased free fluid progressing to perihepatic ascites. Transvaginal paracentesis was performed with fluid sent for cytology revealing reactive mesothelial cells. The patient underwent exploratory laparoscopy and ascites analysis showed low serum ascites albumin gradient (SAAG) with high total protein. During the laparoscopy, several nodules attached to the peritoneum in the upper abdomen were biopsied. Histologic and immunohistochemical analysis of the biopsies demonstrated malignant mesothelioma, epithelioid type. The patient was subsequently referred to a tertiary cancer center for treatment with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.Figure 1Figure 2Figure 3This is a case of peritoneal mesothelioma, a rare fatal tumor, presenting with malignancy-related ascites in a young woman. Occupational and environmental exposure to asbestos remains the leading cause of mesothelioma with exposure preceding diagnosis by 15-60 years. 85% of cases of mesothelioma occur in men in their mid-50's who have identifiable asbestos exposure. This patient presents a rare case: a young female with peritoneal mesothelioma with no identifiable asbestos exposure. There are only 200-400 cases of peritoneal mesothelioma diagnosed in the United States each year which account for 10-15% of cases of mesothelioma overall. Symptoms are often non-specific and routine laboratory tests are not helpful in making this diagnosis. Although cytology of ascites fluid is usually helpful with peritoneal carcinomatosis, it is often inconclusive in instances of peritoneal mesothelioma, as demonstrated in this patient. Review of the literature indicates that this diagnosis was expected to peak in 2015 making increased awareness of this disease and its diagnostic challenges vital.

Fluoro-edenite induced disease in the Sicilian site of Biancavilla (Italy).

Objectives Fluoro-edenite, a fibrous amphibole present in the soil and building materials of Biancavilla, (Sicily), was allocated in 2014 by the International Agency for Research on Cancer to the Group 1 as cause of mesothelioma. The aim of our research is to monitor the occurrence of mesothelioma and to evaluate data on non-malignant respiratory diseases among Biancavilla residents to better target prevention action. Methods Mesothelioma mortality and pleural cancer hospitalization (2006-2012) as well as incidence data (1998-2003) were analyzed. Standardized Mortality Ratio (SMR), Standardized Hospitalization Ratio (SHR), Standardized Incidence Ratio (SIR) were estimated with respect to regional rates. A descriptive research of the hospitalized pneumoconiosis cases in Biancavilla residents was undertaken (2006-2013). Results A statistically significant death excess from Pleural Mesothelioma (SMR 632) was observed; very high figures and 0.5 sex ratio (M/W) were shown in the younger age groups. Pleural cancer hospitalization showed significant excesses (SHR 399) in particular among younger persons. Mesothelioma incidence was increased in men (SIR 346) and in women (SIR 1221) with a sex ratio equal to one. Twenty-eight cases of pneumoconiosis (18 men and 10 women) were found. Conclusions The study confirms the role of exposure to fluoro-edenite fibres as source of mesothelioma, and the observed sex ratio, regarding mortality, hospitalization and incidence, corroborates the role of an environmental exposure. The higher excesses of death, hospitalizations, and incidence among young subjects suggest early exposure, in teenage/childhood years. The occurrence of unexpected hospitalization for pneumoconiosis in Biancavilla underlines the importance of further investigation on non malignant respiratory diseas

Environmental risk of mesothelioma in the United States: An emerging concern—epidemiological issues

ABSTRACTDespite 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.

An asbestos-exposed family with multiple cases of pleural malignant mesothelioma without inheritance of a predisposing BAP1 mutation

We report a family with domestic exposure to asbestos and diagnosis of multiple cancers, including eight pleural malignant mesotheliomas and several other lung or pleural tumors. DNA sequence analysis revealed no evidence for an inherited mutation of BAP1. Sequence analysis of other potentially relevant genes, including TP53, CDKN2A, and BARD1, also revealed no mutation. DNA microarray analysis of tissue from two mesotheliomas revealed multiple genomic imbalances, including consistent losses of overlapping segments in 2q, 6q, 9p, 14q, 15q, and 22q, but no losses of chromosome 3 harboring the BAP1 locus. However, the results of immunohistochemical analysis demonstrated loss of nuclear BAP1 staining in three of six mesotheliomas tested, suggesting that somatic alterations of BAP1 occurred in a subset of tumors from this family. Since mesothelioma could be confirmed in only a single generation, domestic exposure to asbestos may be the predominant cause of mesothelioma in this family. Given the existence of unspecified malignant pleural tumors and lung cancers in a prior generation, we discuss the possibility that some other tumor susceptibility or modifier gene(s) may contribute to the high incidence of mesothelioma in this family. Because the incidence of mesothelioma in this family is higher than that expected even in workers heavily exposed to asbestos, we conclude that both asbestos exposure and genetic factors have played a role in the high rate of mesothelioma and potentially other pleural or lung cancers seen in this family.

RE: Gordon R, Fitzgerald S, and Millette J. Asbestos in commercial cosmetic talcum powder as a cause of mesothelioma in women. Int J Occup Environ Health. 2014;20(4):318-332.

Dear Editor:Thank you for the opportunity to reply to the letter you received from by Dr. Lee and Mr. Van Orden.1 It is clear that Dr. Lee and Mr. Van Orden have no idea of what constitutes a true ...

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

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. To investigate one historic brand of cosmetic talcum powder associated with mesothelioma in women. 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. 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. 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.

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

Chronic inflammation due to the absorption of asbestos is an important cause of mesothelioma. Although the increased prevalence of mesothelioma is a serious problem, the development of effective chemotherapeutic agents remains incomplete. As the nuclear factor-κB (NF-κB) pathway contributes to malignant transformation of various types of cells, we explored NF-κB activity in three different pathological types of malignant mesothelioma cells, and evaluated the therapeutic potential of a recently reported NF-κB inhibitor, IMD-0354. NF-κB was constantly activated in MSTO-211H, NCI-H28, and NCI-H2052 cells, and the proliferation of these cell lines was inhibited by IMD-0354. D-type cyclins were effectively suppressed in mixed tissue type MSTO-211H, leading to cell cycle arrest at sub G1/G1 phase. IMD-0354 reduced cyclin D3 in both epithelial tissue type NCI-H28 and sarcomatoid tissue type NCI-H2052. In a sphere formation assay, IMD-0354 effectively decreased the number and diameter of MSTO-211H spheres. Preincubation of MSTO-211H cells with IMD-0354 delayed tumor formation in transplanted immunodeficient mice. Furthermore, administration of IMD-0354 markedly rescued the survival rate of mice that received intrathoracic injections of MSTO-211H cells. These results indicate that a targeted drug against NF-κB might have therapeutic efficacy in the treatment of human malignant mesothelioma.