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Kao S.C.-H.,Asbestos Diseases Research Institute | Kao S.C.-H.,Concord Repatriation General Hospital | Kao S.C.-H.,University of Sydney | Armstrong N.,Garvan Institute of Medical Research | And 10 more authors.
Cancer | Year: 2012

BACKGROUND: Malignant mesothelioma (MM) is an aggressive cancer of serosal membranes, mostly pleura. It is related to asbestos exposure and its incidence in most industrialized countries is projected to remain stable or to increase until 2020. Prognosis remains poor. Clinical prognostic scoring systems lack precision. No prognostic tissue markers are available. Aquaporin 1 (AQP1) is a cell membrane channel involved in water transport, cell motility, and proliferation. A blocker and an agonist are available. METHODS: Two independent cohorts of MM were studied. Cohort 1 consisted of 80 consecutive patients who underwent radical surgery (extrapleural pneumonectomy [EPP]). Cohort 2 included 56 conservatively managed patients from another institution. Clinical information was obtained from files. Diagnoses were histologically verified. Immunohistochemical labeling for AQP1 was performed on tumor tissue and the percentage of positive cells was scored. RESULTS: We demonstrated expression of AQP1 in normal and neoplastic mesothelium at the apical aspect of the cell, in keeping with a role in water transport. For both cohorts, expression of AQP1 by ≥50% of tumor cells was associated with significantly enhanced survival (9.4 months vs 30.4 months in EPP patients and 5 months vs 15 months in conservatively treated patients). This was independent of established prognostic factors, including histologic subtype, pathologic stage, sex, and age at time of diagnosis. CONCLUSION: Expression of AQP1 correlated significantly with prognosis in MM, irrespective of treatment or established prognostic factors. Immunohistochemical labeling for AQP1 should be included in the routine histopathologic workup. An agonist or blocker may become useful for treatment. © 2011 American Cancer Society.


Bernardo B.C.,Baker IDI Heart and Diabetes Institute | Ooi J.Y.Y.,Baker IDI Heart and Diabetes Institute | Lin R.C.Y.,Asbestos Diseases Research Institute | Lin R.C.Y.,University of New South Wales | And 2 more authors.
Future Medicinal Chemistry | Year: 2015

miRNAs are small non-coding RNAs (ncRNAs), which regulate gene expression. Here, the authors describe the contribution of miRNAs to cardiac biology and disease. They discuss various strategies for manipulating miRNA activity including antisense oligonucleotides (antimiRs, blockmiRs), mimics, miRNA sponges, Tough Decoys and miRNA mowers. They review developments in chemistries (e.g., locked nucleic acid) and modifications (sugar, 'ZEN', peptide nucleic acids) and miRNA delivery tools (viral vectors, liposomes, nanoparticles, pHLIP). They summarize potential miRNA therapeutic targets for heart disease based on preclinical studies. Finally, the authors review current progress of miRNA therapeutics in clinical development for HCV and cancer, and discuss challenges that will need to be overcome for similar therapies to enter the clinic for patients with cardiac disease. © 2015 Future Science Ltd.


Kao S.C.H.,Sydney Cancer Center | Kao S.C.H.,Asbestos Diseases Research Institute | Pavlakis N.,Royal North Shore Hospital | Harvie R.,Royal North Shore Hospital | And 5 more authors.
Clinical Cancer Research | Year: 2010

Purpose: Asbestos-induced chronic inflammation is implicated in the pathogenesis of malignant mesothelioma (MM). We have investigated blood neutrophil-to-lymphocyte ratio (NLR), an index of systemic inflammation, as a prognostic factor in MM patients. Experimental Design: Patients with MM who had systemic therapy at participating institutes were studied. Potential prognostic factors such as age, gender, performance status, histologic subtype, and baseline laboratory parameters, including NLR, were analyzed. Overall survival from commencement of therapy was determined by the Kaplan-Meier method. Multivariate analyses using Cox Regression model were performed with significant factors (P ≤ 0.05) to determine their independent effect. Results: A total of 173 MM patients undergoing systemic therapy including 119 patients receiving firstline therapy and 54 patients receiving second- or third-line therapy were included in this retrospective evaluation. Forty-two percent of patients had an elevated NLR at baseline. The following variables were predictive of survival: female gender (P = 0.044), epithelioid histologic subtype (P < 0.001), baseline white blood cell count less than 8.3 × 109/L (P = 0.008), baseline platelet count 400 × 109/L or less (P = 0.05), and NLR of 5 or less (P < 0.001). After multivariate analysis, histologic epithelioid subtype [hazard ratio (HR) = 2.0; 95% confidence interval (CI) = 1.3-2.9; P = 0.001], and NLR less than 5 (HR = 2.7; 95% CI = 1.8-3.9; P < 0.001) remained independent predictors. The 1-year survival rate was 60% versus 26%, whereas the 2-year survival rate was 34% versus 10% for NLR less than 5 and 5 or greater, respectively. In the separate analyses of chemotherapy-naive and previously treated patient groups, NLR was an independent predictor of survival in both groups. Conclusion: Our results indicate that NLR is an independent predictor of survival for patients with MM undergoing systemic therapy. ©2010 AACR.


Linton A.,Asbestos Diseases Research Institute | Linton A.,Concord Repatriation General Hospital | Linton A.,University of Sydney | Vardy J.,Concord Repatriation General Hospital | And 5 more authors.
Critical Reviews in Oncology/Hematology | Year: 2012

The relationship between asbestos exposure and malignant mesothelioma (MM) has been well established. Despite bans on asbestos use in an increasing number of nations, the prolonged latency from exposure to diagnosis, and the ongoing presence and use of these dangerous fibres, have led to the increasing prevalence of this deadly disease worldwide. Whilst occupational contact has been implicated in the bulk of diagnosed cases over the past 50 years, a significant proportion of disease has been linked to para-occupational, domestic and environmental exposure. In this review, we will provide an update on the impact of historical and ongoing asbestos contact in both occupational and non-occupational settings. Furthermore, we will address the unresolved controversies surrounding the use of chrysotile asbestos, the effect of gender and genetics on development of this disease, childhood mesothelioma and co-aetiological factors including SV40 exposure. © 2012 Elsevier Ireland Ltd.


Patent
Asbestos Diseases Research Institute | Date: 2013-03-13

The invention relates to microRNA mimics, corresponding to the miR-15/107 family, and to methodology for using microRNA mimics to treat malignant pleural mesothelioma (MPM) by restoring regulation of the expression of target genes of the miR-15/107 family in MPM tumor cells.


Patent
Asbestos Diseases Research Institute | Date: 2015-04-10

The invention relates to microRNA mimics, corresponding to the miR-15/107 family, and to methodology for using microRNA mimics to treat malignant pleural mesothelioma (MPM) by restoring regulation of the expression of target genes of the miR-15/107 family in MPM tumor cells.


PubMed | University of Zürich, University of New South Wales, University of Sydney and Asbestos Diseases Research Institute
Type: | Journal: Genomics data | Year: 2016

Malignant pleural mesothelioma (MPM) is a tumor originating in the mesothelium, the membrane lining the thoracic cavities, and is induced by exposure to asbestos. Australia suffers one of the worlds highest rates of MPM and the incidence is yet to peak. The prognosis for patients with MPM is poor and median survival following diagnosis is 4-18months. Currently, no or few effective therapies exist for MPM. Trials of targeted agents such as antiangiogenic agents (VEGF, EGFR) or ribonuclease inhibitors (ranpirnase) largely failed to show efficacy in MPM Tsao et al. (2009) [1]. A recent study, however, showed that cisplatin/pemetrexed+bevacizumab (a recombinant humanized monoclonal antibody that inhibit VEGF) treatment has a survival benefit of 2.7months Zalcman et al. (2016) [2]. It remains to be seen if this targeted therapy will be accepted as a new standard for MPM. Thus the unmet needs of MPM patients remain very pronounced and almost every patient will be confronted with drug resistance and recurrence of disease. We have identified unique gene signatures associated with prolonged survival in mesothelioma patients undergoing radical surgery (EPP, extrapleural pneumonectomy), as well as patients who underwent palliative surgery (pleurectomy/decortication). In addition to data published in Molecular Oncology, 2015;9:715-26 (GSE59180) Kirschner et al. (2015) , we describe here additional data using a system-based approach that support our previous observations. This data provides a resource to further explore microRNA dynamics in MPM.


PubMed | Asbestos Diseases Research Institute, Hungarian Academy of Sciences, Semmelweis University, University of Zürich and 5 more.
Type: | Journal: European journal of cancer (Oxford, England : 1990) | Year: 2016

The deregulation of activin expression is often observed in various malignancies. Previous studies indicate that activin A plays a protumourigenic role in malignant pleural mesothelioma (MPM). The aim of the study was to evaluate circulating activin A level as a biomarker in MPM.Plasma samples were collected from 129 MPM patients in four institutions at the time of diagnosis or before surgical resection. Samples from 45 healthy individuals and from 16 patients with non-malignant pleural diseases served as controls. Circulating activin A was measured by enzyme-linked immunosorbent assay and correlated to clinicopathological variables.Plasma activin A level was significantly elevated in MPM patients (86283pg/ml) when compared to healthy controls (39121pg/ml; P<0.0001). Patients with pleuritis or fibrosis only showed a modest increase (versus controls; 62595pg/ml; P=0.0067). Sarcomatoid (n=10, 1629202pg/ml, P=0.0019) and biphasic (n=23, 1164233pg/ml, P=0.0188) morphology were associated with high activin A levels when compared to epithelioid histology (n=94, 71275pg/ml). The tumour volume showed a positive correlation with increased circulating activin A levels. MPM patients with below median activin A levels had a significantly longer overall survival when compared to those with high activin A levels (median survival 735 versus 365d, P<0.0001). Importantly, circulating activin A levels were exclusively prognostic in epithelioid MPM.Our findings suggest that the measurement of circulating activin A may support the histological classification of MPM and at the same time help to identify epithelioid MPM patients with poor prognosis.


PubMed | Asbestos Diseases Research Institute and Public Health Observatory
Type: | Journal: Respirology (Carlton, Vic.) | Year: 2017

Whilst the impact of clinicopathological factors on the prognosis of malignant pleural mesothelioma (MPM) is well understood, socioeconomic and geographic factors have received less attention. We analysed the relationship between geographic and socioeconomic factors upon survival and treatment provision in a large series of patients with MPM.We assessed MPM patients awarded compensation between 2002 and 2009 with additional MPM incidence data from the New South Wales (NSW) Cancer Registry. The impact of geographic remoteness, distance from oncological multidisciplinary team (MDT) and Index of Relative Socioeconomic Advantage and Disadvantage (IRSAD) upon survival, clinical features and treatment received was analysed.We identified 910 patients (67% residing in major cities; 92% <50km from MDT). Median overall survival was 10.0months. On multivariate analysis, age >70 (hazard ratio (HR)=1.39), male gender (HR=1.36), non-epithelioid histological subtype (HR=2.18) and IRSAD status by decreasing quintile (HR=1.06) were independent prognostic factors. There was no significant advantage for patients residing in major cities (10.6months vs 8.8months; P=0.162) or within 50km of MDT (10.3months vs 7.8months; P=0.539). Patients geographic location and distance to MDT did not impact chemotherapy, adjuvant radiotherapy or extrapleural pneumonectomy provision. Socioeconomically disadvantaged patients were significantly less likely to receive chemotherapy (37.4% vs 54.8%; P=0.001).This study provides evidence for differences in the treatment and survival according to socioeconomic status for compensated MPM patients in NSW. Further research is warranted to seek additional explanations for the differences noted by comparing the treatments and outcomes of compensated and non-compensated MPM patients in NSW.


News Article | November 16, 2016
Site: www.nanotech-now.com

Abstract: The search for a cure for mesothelioma is in no way limited to the shores of the United States. The toxic impact of asbestos is felt internationally, with the highest incidence of malignant mesothelioma per capita being found in Australia, where over 700 new cases are diagnosed each year. According to the country’s Asbestos Diseases Research Institute (ADRI) more than 10,000 Australians have died of mesothelioma since the early 1980s and the organization expects another 25,000 to be lost over the next forty years. But ADRI researchers have teamed up with a New Zealand-born associate professor at the University of Sydney Medical School, Dr. Glen Reid, along with a Sydney-based biotech company called EnGelIC to research the way that the disease responds to chemotherapeutic drugs and find a better solution. What they’ve come up with is a “futuristic new drug delivery system that relies on nanotechnology and guiding antibodies” The bottom line – they’ve found that it works. According to Dr. Reid, the group has been treating mesothelioma tumors with antibody-guided minicells containing micro RNAs that work like a Trojan Horse. “We have found an amazing inhibition of tumor growth. The results were far in excess of what we have seen with other experimental therapies in this model, and we are very excited about it.” He goes on to explain, “A nano cell is a delivery vehicle. You can package basically anything in there that you like, so a chemotherapy drug, or in our case a mini-gene – and then it’s injected into the body.” The group is still in the midst of its research, but its excitement is based in large part on the results they have seen in a single patient, 51-year old Bradley Selmon, who was diagnosed with mesothelioma in 2013. After failing to respond to chemotherapy, he elected to join Dr. Reid’s clinical trial and in a two-month period his tumor has been virtually eliminated. He is one of only ten patients in the phase one trial and is the only one to respond so well, so the researchers are working to remind people that it is important to remain measured in their enthusiasm and response. Still, according to Selmon’s oncologist, Dr. Steven Kao of the Chris O’Brien Lifehouse cancer center in Sydney, the treatment “has the potential for a paradigm shift in the management of other treatment resistant tumors.” About Mesothelioma.net Author: Terri Oppenheimer Terri Oppenheimer is an independent writer, editor and proofreader. She graduated from the College of William and Mary with a degree in English. Her dreams of a writing career were diverted by a need to pay her bills. She spent a few years providing copy for a major retailer, then landed a lucrative career in advertising sales. With college bills for all three of her kids paid, she left corporate America for a return to her original goal of writing. She specializes in providing content for websites and finds tremendous enjoyment in the things she learns while doing her research. Her specific areas of interest include health and fitness, medical research, and the law. For more information, please click If you have a comment, please us. Issuers of news releases, not 7th Wave, Inc. or Nanotechnology Now, are solely responsible for the accuracy of the content.

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