Quoted from http://clincancerres.aacrjournals.org/content/18/3/598.abstract?maxtoshow=&HITS=10&hits=7&RESULTFORMAT=&andorexacttitleabs=and&fulltext=mesothelioma&andorexactfulltext=and&searchid=1&usestrictdates=yes&resourcetype=HWCIT&ct

Molecular Pathways: Targeting Mechanisms of Asbestos and Erionite Carcinogenesis in Mesothelioma

1. Michele Carbone1,2 and
2. Haining Yang1,2

+ Author Affiliations

1. Authors’ Affiliations:1University of Hawaii Cancer Center and 2Department of Pathology, John A. Burns School of Medicine, University of Hawaii, Honolulu, Hawaii

1. Corresponding Author:
   Haining Yang, 651 Ilalo Street, BSB Rm. 231, Honolulu, HI 96813. Phone: 808-440-4588; Fax: 808-587-0790; E-mail: hyang@cc.hawaii.edu

Abstract

Malignant mesothelioma is an aggressive malignancy related to asbestos and erionite exposure. AP-1 transcriptional activity and the NF-?B signaling pathway have been linked to mesothelial cell transformation and tumor progression. HGF and c-Met are highly expressed in mesotheliomas. Phosphoinositide 3-kinase, AKT, and the downstream mTOR are involved in cell growth and survival, and they are often found to be activated in mesothelioma. p16INK4a and p14ARF are frequently inactivated in human mesothelioma, and ?50% of mesotheliomas contain the NF2 mutation. Molecular therapies aimed at interfering with these pathways have not improved the dismal prognosis of mesothelioma, except possibly for a small subset of patients who benefit from certain therapies. Recent studies have shown the importance of asbestos-induced inflammation in the initiation and growth of mesothelioma, and HMGB1 and Nalp3 inflammasome have been identified as key initiators of this process. Asbestos induces cell necrosis, causing the release of HMGB1, which in turn may activate Nalp3 inflammasome, a process that is enhanced by asbestos-induced production of reactive oxygen species. HMGB1 and Nalp3 induce proinflammatory responses and lead to interleukin-1? and TNF-? secretion and NF-?B activity, thereby promoting cell survival and tumor growth. Novel strategies that interfere with asbestos- and erionite-mediated inflammation might prevent or delay the onset of mesothelioma in high-risk cohorts, including genetically predisposed individuals, and/or inhibit tumor growth. The very recent discovery that germline BAP1 mutations cause a new cancer syndrome characterized by mesothelioma, uveal melanoma, and melanocytic tumors provides researchers with a novel target for prevention and early detection. Clin Cancer Res; 18(3); 598–604. ©2011 AACR.

• Received September 15, 2011.
• Revision received October 18, 2011.
• Accepted October 20, 2011.

• ©2011 American Association for Cancer Research.

Quoted from http://ar.iiarjournals.org/content/32/2/609.abstract?maxtoshow=&HITS=10&hits=2&RESULTFORMAT=&andorexacttitle=or&andorexacttitleabs=and&fulltext=asbestos&andorexactfulltext=and&searchid=1&usestrictdates=yes&resourcetype=HWCIT&ct

A Retrospective Study of Chemotherapy with and without Pemetrexed in Malignant Pleural Mesothelioma

Abstract

Background: The current standard first-line chemotherapy for malignant pleural mesothelioma (MPM) is pemetrexed and cisplatin. However, other regimens, with or without a platinum agent, are reported to be effective in the treatment of MPM.

Patients and Methods: Patients who were diagnosed with MPM and treated with chemotherapy between January 1999 and June 2010 at the Osaka Prefectural Medical Center for Respiratory and Allergic Diseases were studied, and the outcomes of these patients were retrospectively analyzed in relation to therapy.

Results: In total, 48 patients with MPM (42 men and 6 women) treated with chemotherapy were included in the current analysis. The median survival time (MST) and one-year survival rate in the pemetrexed-containing group were 541 days and 63.2%, respectively. The MST and one-year survival rate in the non-pemetrexed group were 516 days and 66.7%, respectively. Overall survival did not differ significantly with respect to the pemetrexed-containing regimen.

Conclusion: The superiority of pemetrexed-containing regimens is equivocal. Non-pemetrexed-containing regimens may be potent alternatives.

Quoted from http://www.ajronline.org/content/198/2/359.abstract

Epithelial Malignant Pleural Mesothelioma After Extrapleural Pneumonectomy: Stratification of Survival With CT-Derived Tumor Volume

Abstract

 

OBJECTIVE. The purpose of this study was to assess the usefulness of CT-derived tumor volume, with control for other prognostic factors, for stratifying survival after surgery-based multimodality treatment of a large cohort of patients with epithelial malignant pleural mesothelioma.

MATERIALS AND METHODS. We retrospectively reviewed 338 patients with mesothelioma who underwent extrapleural pneumonectomy between 2001 and 2007. The study cohort comprised 88 patients with epithelial subtype tumors, DICOM-format CT scans, and data regarding neoadjuvant and adjuvant therapy. Tumor volume was calculated, and Kaplan-Meier survival and Cox regression analyses were performed to compare the estimated survival functions of patient subgroups based on volume and other covariates related to outcome (sex, age, preoperative platelet count, hemoglobin concentration, WBC count, clinical and pathologic TNM category, and administration of neoadjuvant and adjuvant therapy). A multivariate regression model was derived on the basis of the most significant univariate predictors.

RESULTS. The median estimated tumor volume was 319 cm3 (range, 4–3256 cm3). In univariate analysis, tumor volume, hemoglobin concentration, platelet count, pathologic TNM category, and administration of adjuvant chemotherapy or radiation therapy met the criteria for inclusion in the reverse stepwise regression analysis. In the final model, tumor volume, hemoglobin concentration, and administration of adjuvant chemotherapy or radiotherapy were identified as independently associated with overall survival.

CONCLUSION. With control of prognostic covariates, CT-derived tumor volume can be used to stratify survival of patients with epithelial mesothelioma after extrapleural pneumonectomy and should be included in prognostic evaluation of patients for whom resection is being considered.

Quoted from http://www.heraldsun.com.au/news/breaking-news/asbestos-victims-get-cash-boost/story-e6frf7kf-1226243527082

Asbestos victims get cash boost

• From: AAP
• January 13, 2012 1:22PM

A MULTI-million dollar injection of funding for asbestos victims will make New South Wales a world leader in the treatment of mesothelioma, a cancer specialist says.

The NSW Government today announced the Asbestos Diseases Research Institute would receive $3.5 million to improve outcomes for people with asbestos-related cancer and their families.

The money comes from the State Government’s translational cancer research program, which will also award $3.47 million to researchers working on the diagnosis and treatment of blood cancers.

Chief Cancer Officer and CEO of the Cancer Institute of NSW Professor David Currow says the translational cancer grants will benefit cancer patients across the state.

Australia had the world’s highest incidence of malignant mesothelioma, a fatal cancer caused by asbestos, Professor Currow said in a statement today.

[Article continues at original source]

Quoted from http://www.jnccn.org/content/10/1/26.extract

Malignant Pleural Mesothelioma

NOTE:  Since this article has no abstract, we have provided an extract of the first 250 words of the full text.

Overview

Mesothelioma is a rare cancer that is estimated to occur in approximately 2500 people in the United States every year.1,2 These NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) focus on malignant pleural mesothelioma (MPM), which is the most common type; mesothelioma can also occur in other sites (e.g., peritoneum, pericardium, tunica vaginalis testis). The disease is difficult to treat.

NCCN Clinical Practice Guidelines in Oncology for Malignant Pleural Mesothelioma

NCCN Categories of Evidence and Consensus

Category 1: Based upon high-level evidence, there is uniform NCCN consensus that the intervention is appropriate.

Category 2A: Based upon lower-level evidence, there is uniform NCCN consensus that the intervention is appropriate.

Category 2B: Based upon lower-level evidence, there is NCCN consensus that the intervention is appropriate.

Category 3: Based upon any level of evidence, there is major NCCN disagreement that the intervention is appropriate.

All recommendations are category 2A unless otherwise noted.

Clinical trials: NCCN believes that the best management for any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged. median overall survival is only approximately 1 year. MPM occurs mainly in older men (median age, 72 years) who have been exposed to asbestos, although it occurs decades after exposure (20-40 years later).3,4

The incidence of MPM is leveling off in the United States, because asbestos use has decreased since the 1970s; however, the United States still has more cases than anywhere else in the world.5,6 Although asbestos is no longer mined in the United States, it is still imported.6 The incidence of MPM is increasing in other countries, such as Russia, Western Europe, China, and India.1,5,7-11 Mortality rates from MPM are highest in the United Kingdom, Netherlands, and Australia, and are increasing in several other countries, such as Japan, Argentina, and Brazil.7

[Full Text of this Article]

Quoted from http://erj.ersjournals.com/content/early/2011/12/16/09031936.00040911.abstract

A breath test for malignant mesothelioma using an electronic nose

Abstract

Malignant mesothelioma (MM) is a rare tumour usually caused by asbestos exposure. MM is difficult to diagnose in its early stages and is invariably fatal. Earlier detection of MM could potentially improve survival. Exhaled breath sampling of volatile organic compounds (VOCs) using a carbon polymer array (CPA) electronic nose recognises specific breath profiles characteristic of different diseases. VOC breath profiling can distinguish between patients with lung cancer and controls, but there is only one prior report in MM, and the potential confounding effect of other asbestos-related diseases was not highlighted.

A CPA electronic nose will distinguish patients with MM from those with benign asbestos-related diseases (ARDs) and normal subjects with high sensitivity and specificity.

Eighty patients (MM n=20, ARDs n=18, controls n=42) participated in a cross-sectional, case control study. Breath samples were analysed using the Cyranose 320, using canonical discriminant analysis and principal component reduction. Repeatability was assessed by evaluating the samples in duplicate.

20 MM, 18 ARDs and 42 control subjects could be distinguished by their breath profiles. 10 MM subjects created the training set. Smellprints from 10 new MM patients were distinguished from control subjects with an accuracy of 95%. Patients with MM, ARDs and control subjects were correctly identified in 88% of cases.

Exhaled breath VOC profiling can accurately distinguish between patients with MM, ARDs and healthy controls. The CPA eNOSE is a novel method for distinguishing patients with MM. This could eventually translate into a screening tool for high risk populations.

Quoted from http://erj.ersjournals.com/content/early/2011/12/01/09031936.00153611.abstract?maxtoshow=&HITS=10&hits=5&RESULTFORMAT=&andorexacttitleabs=and&fulltext=mesothelioma&andorexactfulltext=and&searchid=1&usestrictdates=yes&resourcetype=HWCIT&ct

Population-based survival for malignant mesothelioma after introduction of novel chemotherapy

Abstract

Malignant mesothelioma is known for its dismal prognosis and poor response to conventional treatment. Chemotherapy with cisplatin-antifolate combinations recently showed promising response rates and prolonged survival in randomised trials.

To assess the impact of this development on clinical practice and survival at a population-based level, treatment patterns and survival trends were studied for patients diagnosed with mesothelioma in the period 1995–2006. 4731 records were retrieved from the Netherlands Cancer Registry and chemotherapy use and median survival were analysed.

For the periods 1995–1998 to 2005–2006, chemotherapy use increased from 8% to 36%. Median survival increased over time from 7.1 months to 9.2 months. For pleural mesothelioma, multivariable analysis demonstrated that survival was poorer for elderly patients and sarcomatoid tumours. The prognostic impact of chemotherapy increased with time. Median survival for chemotherapy treated patients improved from 10.1 months (1995–1998) to 13.1 months (2005–2006). For peritoneal mesothelioma, median survival was poor (3.9 months) but better for females and younger patients.

This study demonstrates that chemotherapy use increased at a national level and coincided with an improvement in survival. The novel chemotherapy regimen appears to be more effective but, due to the observational nature of this study, alternative explanations cannot be excluded.

Quoted from http://erj.ersjournals.com/content/38/6/1420.abstract

Predicting survival in malignant mesothelioma

Abstract

Malignant mesothelioma (MM) of the pleura or peritoneum is a universally fatal disease attracting an increasing range of medical interventions and escalating healthcare costs.

Changes in survival and the factors affecting survival of all patients ever diagnosed with MM in Western Australia over the past five decades and confirmed by the Western Australian Mesothelioma Registry to December 2005 were examined. Sex, age, date and method of diagnosis, site of disease and histological type were recorded. Date of onset of symptoms and performance status were obtained from clinical notes for a sample of cases. Cox regression was used to examine the association of the clinical variables and the 10-yr periods of disease onset with survival after diagnosis.

Survival was inversely related to age, being worse for males (hazard ratio (HR) 1.4, 95% CI 1.2–1.6), and those with peritoneal mesothelioma (HR 1.4, 95% CI 1.1–1.7). Patients with sarcomatoid histology had worse prognosis than patients with epithelioid and biphasic histological subtypes. Survival improved after the 1970s and has made incremental improvements since then. Median (interquartile range) survival by decade, from 1960 until 2005, was 64 (0–198), 177 (48–350), 221 (97–504), 238 (108–502) and 301 (134–611) days; ?4 weeks of this apparent improvement can be attributed to earlier diagnosis.

With increasing resources and treatment costs for MM over the past 40 yrs, there have been modest improvements in survival but no complete remissions.

Quoted from http://erj.ersjournals.com/content/early/2011/11/09/09031936.00005111.abstract

 

Temporal patterns of occupational asbestos exposure and risk of pleural mesothelioma

 

Abstract

 

Asbestos is the primary cause of pleural mesothelioma (PM). The objective of this study was to elucidate the importance of different temporal patterns of occupational asbestos exposure on the risk of PM, using case-control data in males.

Cases were selected from a French case-control study conducted in 1987–1993 and the French National Mesothelioma Surveillance Program in 1998–2006. Population controls were frequency matched to cases by year of birth. Occupational asbestos exposure was evaluated with a job-exposure matrix. The dose-response relationships were estimated using restricted cubic spline functions in logistic regression models.

A total of 2,466 ever asbestos exposed males (1,041 cases and 1,425 controls) were used. After adjustment for intensity and total duration of occupational asbestos exposure, the risk of PM was lower for subjects first exposed after the age of 20 years and continued to increase until 30 years after cessation of exposure. The effect of total duration of exposure decreased when age at first exposure and time since last exposure increased.

These results based on a large population-based case-control study underline the need to take into account the temporal pattern of exposure on risk assessment.

 [Link to original item]