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Mesothelioma: HELP
Articles by Catherine M. Westbom
Based on 5 articles published since 2008
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Between 2008 and 2019, Catherine Westbom wrote the following 5 articles about Mesothelioma.
 
+ Citations + Abstracts
1 Article Inflammasome Modulation by Chemotherapeutics in Malignant Mesothelioma. 2015

Westbom, Catherine / Thompson, Joyce K / Leggett, Alan / MacPherson, Maximilian / Beuschel, Stacie / Pass, Harvey / Vacek, Pamela / Shukla, Arti. ·Department of Pathology and Laboratory Medicine, University of Vermont College of Medicine, Burlington, VT, United States of America. · Department of Cardiothoracic Surgery, New York University School of Medicine, New York, New York, United States of America. · Department of Medical Biostatistics, University of Vermont College of Medicine, Burlington, VT, United States of America. ·PLoS One · Pubmed #26689911.

ABSTRACT: Malignant mesothelioma (MM) is a fatal disease in dire need of therapy. The role of inflammasomes in cancer is not very well studied, however, literature supports both pro-and anti-tumorigenic effects of inflammasomes on cancer depending upon the type of cancer. Asbestos is a causative agent for MM and we have shown before that it causes inflammasome priming and activation in mesothelial cells. MM tumor cells/tissues showed decreased levels of inflammasome components like NLRP3 and caspase-1 as compared to human mesothelial cells or normal tissue counterpart of tumor. Based on our preliminary findings we hypothesized that treatment of MMs with chemotherapeutic drugs may elevate the levels of NLRP3 and caspase-1 resulting in increased cell death by pyroptosis while increasing the levels of IL-1β and other pro-inflammatory molecules. Therefore, a combined strategy of chemotherapeutic drug and IL-1R antagonist may play a beneficial role in MM therapy. To test our hypothesis we used two human MM tumor cell lines (Hmeso, H2373) and two chemotherapeutic drugs (doxorubicin, cisplatin). Through a series of experiments we showed that both chemotherapeutic drugs caused increases in NLRP3 levels, caspase-1 activation, pyroptosis and pro-inflammatory molecules released from MM cells. In vivo studies using SCID mice and Hmeso cells showed that tumors were smaller in combined treatment group of cisplatin and IL-1R antagonist (Anakinra) as compared to cisplatin alone or untreated control groups. Taken together our study suggests that chemotherapeutic drugs in combination with IL-1R antagonist may have a beneficial role in MM treatment.

2 Article CREB-induced inflammation is important for malignant mesothelioma growth. 2014

Westbom, Catherine M / Shukla, Anurag / MacPherson, Maximilian B / Yasewicz, Elizabeth C / Miller, Jill M / Beuschel, Stacie L / Steele, Chad / Pass, Harvey I / Vacek, Pamela M / Shukla, Arti. ·Department of Pathology, College of Medicine, University of Vermont, Burlington, Vermont. · Department of Medicine, University of Alabama at Birmingham School of Medicine, Birmingham, Alabama. · Langone Medical Center, NYU School of Medicine, New York, New York. · Department of Medical Biostatistics, College of Medicine, University of Vermont, Burlington, Vermont. · Department of Pathology, College of Medicine, University of Vermont, Burlington, Vermont. Electronic address: arti.shukla@uvm.edu. ·Am J Pathol · Pubmed #25111229.

ABSTRACT: Malignant mesothelioma (MM) is an aggressive tumor with no treatment regimen. Previously we have demonstrated that cyclic AMP response element binding protein (CREB) is constitutively activated in MM tumor cells and tissues and plays an important role in MM pathogenesis. To understand the role of CREB in MM tumor growth, we generated CREB-inhibited MM cell lines and performed in vitro and in vivo experiments. In vitro experiments demonstrated that CREB inhibition results in significant attenuation of proliferation and drug resistance of MM cells. CREB-silenced MM cells were then injected into severe combined immunodeficiency mice, and tumor growth in s.c. and i.p. models of MM was followed. We observed significant inhibition in MM tumor growth in both s.c. and i.p. models and the presence of a chemotherapeutic drug, doxorubicin, further inhibited MM tumor growth in the i.p. model. Peritoneal lavage fluids from CREB-inhibited tumor-bearing mice showed a significantly reduced total cell number, differential cell counts, and pro-inflammatory cytokines and chemokines (IL-6, IL-8, regulated on activation normal T cell expressed and secreted, monocyte chemotactic protein-1, and vascular endothelial growth factor). In vitro studies showed that asbestos-induced inflammasome/inflammation activation in mesothelial cells was CREB dependent, further supporting the role of CREB in inflammation-induced MM pathogenesis. In conclusion, our data demonstrate the involvement of CREB in the regulation of MM pathogenesis by regulation of inflammation.

3 Article Curcumin: a double hit on malignant mesothelioma. 2014

Miller, Jill M / Thompson, Joyce K / MacPherson, Maximilian B / Beuschel, Stacie L / Westbom, Catherine M / Sayan, Mutlay / Shukla, Arti. ·Department of Pathology, University of Vermont College of Medicine, 89 Beaumont Avenue, HSRF 216, Burlington, VT 05405-0068. arti.shukla@uvm.edu. ·Cancer Prev Res (Phila) · Pubmed #24431405.

ABSTRACT: Inflammation is a key mediator in the development of malignant mesothelioma, which has a dismal prognosis and poor therapeutic strategies. Curcumin, a naturally occurring polyphenol in turmeric, has been shown to possess anticarcinogenic properties through its anti-inflammatory effects. Inflammasomes, a component of inflammation, control the activation of caspase-1 leading to pyroptosis and processing of proinflammatory cytokines, interleukin (IL)-1β and IL-18. In the present study, we investigate the role of curcumin in pyroptotic cell death of malignant mesothelioma cells. Using in vitro models with mouse and human malignant mesothelioma cells, curcumin is shown to induce pyroptosis through activation of caspase-1 and increased release of high-mobility group box 1 (HMGB1) without processing of IL-1β and IL-18. Absence of IL-1β processing in response to curcumin-mediated caspase-1 activation is attributed to blockade of pro-IL-1β priming through inhibition of the NF-κB pathway. Furthermore, curcumin's cytotoxicity in malignant mesothelioma cells is demonstrated to be dependent on pyroptosis as inhibition of caspase-1 resulted in protection against curcumin-induced cell death. We also demonstrate that curcumin-mediated caspase-1 activation is oxidant dependent by using N-acetyl-L-cysteine (NAC) to inhibit pyroptosis. PCR array analysis using the human inflammasome template revealed that curcumin significantly downregulated levels of inflammasome-related gene expression involved in inflammation, e.g., NF-κB, toll-like receptors (TLR), and IL-1β. Our data indicate that curcumin has a double effect on malignant mesothelioma cells through induction of pyroptosis while subsequently protecting against inflammation.

4 Article Malignant mesothelioma: development to therapy. 2014

Thompson, Joyce K / Westbom, Catherine M / Shukla, Arti. ·Pathology Department, University of Vermont, College of Medicine, Burlington, Vermont. ·J Cell Biochem · Pubmed #23959774.

ABSTRACT: 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.

5 Article Asbestos and erionite prime and activate the NLRP3 inflammasome that stimulates autocrine cytokine release in human mesothelial cells. 2013

Hillegass, Jedd M / Miller, Jill M / MacPherson, Maximilian B / Westbom, Catherine M / Sayan, Mutlay / Thompson, Joyce K / Macura, Sherrill L / Perkins, Timothy N / Beuschel, Stacie L / Alexeeva, Vlada / Pass, Harvey I / Steele, Chad / Mossman, Brooke T / Shukla, Arti. ·Department of Pathology, University of Vermont College of Medicine, Burlington, VT, USA. ·Part Fibre Toxicol · Pubmed #23937860.

ABSTRACT: BACKGROUND: Pleural fibrosis and malignant mesotheliomas (MM) occur after exposures to pathogenic fibers, yet the mechanisms initiating these diseases are unclear. RESULTS: We document priming and activation of the NLRP3 inflammasome in human mesothelial cells by asbestos and erionite that is causally related to release of IL-1β, IL-6, IL-8, and Vascular Endothelial Growth Factor (VEGF). Transcription and release of these proteins are inhibited in vitro using Anakinra, an IL-1 receptor antagonist that reduces these cytokines in a human peritoneal MM mouse xenograft model. CONCLUSIONS: These novel data show that asbestos-induced priming and activation of the NLRP3 inflammasome triggers an autocrine feedback loop modulated via the IL-1 receptor in mesothelial cell type targeted in pleural infection, fibrosis, and carcinogenesis.