scholarly journals P2.06-19 Targeting Polyamines as Potential Adjuvant Therapy in Malignant Pleural Mesothelioma Xenograft Models

2018 ◽  
Vol 13 (10) ◽  
pp. S749-S750
Author(s):  
S.K. Lam ◽  
S. Yan ◽  
S. Xu ◽  
J.C. Ho
Keyword(s):  
Adjuvant Therapy ◽  
Malignant Pleural Mesothelioma ◽  
Pleural Mesothelioma ◽  
Xenograft Models

Therapeutic targeting of polyamines in malignant pleural mesothelioma xenograft models.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20060-e20060
Author(s):  
James C. M. Ho ◽  
Sheng Yan ◽  
Sze Kwan Lam
Keyword(s):  
Adjuvant Therapy ◽  
Tumor Growth ◽  
Malignant Pleural Mesothelioma ◽  
Nude Mice ◽  
Pleural Mesothelioma ◽  
Term Survival ◽  
Early Stage Disease ◽  
Therapeutic Setting ◽  
Metastatic Setting ◽  
Humane Endpoint

e20060 Background: Although the use of asbestos has been restricted, the incidence of malignant pleural mesothelioma (MPM) is still rising. The US FDA approved a combination of pemetrexed with cisplatin for treatment of unresectable MPM. And development of novel adjuvant therapeutic options for resected early-stage disease is also urgently needed. From our preliminary data, ornithine decarboxylase (ODC) is highly expressed in MPM xenografts and clinical tumor samples. Upregulation of ODC increases polyamines production and enhances tumor growth. a-difluoromethylornithine (DFMO) is a specific ODC inhibitor. This study aims to disclose the adjuvant (minimal residual disease setting) and therapeutic (metastatic setting) effects of DFMO in MPM xenografts. Methods: In adjuvant therapy setting, nude mice were fed with DFMO in drinking water 7 days before subcutaneous inoculation of 200,000 tumor cells. In therapeutic setting, 107 corresponding cells were injected subcutaneously into nude mice which were randomized for treatment after established tumor growth. Mice with tumor size > 600mm3 were considered reaching humane endpoint. Spermidine levels, protein expression, cytokines concentration, and apoptosis were investigated by Dot plot, Western blot, ELISA, and TUNEL assay respectively. Results: In adjuvant therapy setting, DFMO suppressed tumor growth and increased median survival in both 211H and H226 xenografts. In H226 xenografts, 43% of treated mice have not yet reached humane endpoint, mimicking long-term survival. Upon DFMO treatment, decrease in spermidine level, increase in nitrotyrosine content, and activation of apoptosis were observed in both xenografts. In addition, increase in nitrosocysteine level, intratumoral IL-6, keratinocyte chemoattractant and TNFα, DNA lesions and inhibition of Akt/mTOR pathway were induced by DFMO in H226 xenografts, which may explain higher potency of DFMO in these xenografts. In therapeutic setting, DFMO also suppressed tumor growth in both xenografts with similar mechanisms. Conclusions: DFMO may have a potential role as adjuvant therapy in MPM especially epithelioid mesothelioma.

Targeting polyamine as a novel therapy in xenograft models of malignant pleural mesothelioma

Lung Cancer ◽  
2020 ◽  
Vol 148 ◽  
pp. 138-148
Author(s):  
Sze-Kwan Lam ◽  
Sheng Yan ◽  
Shi Xu ◽  
James Chung-Man Ho
Keyword(s):  
Malignant Pleural Mesothelioma ◽  
Pleural Mesothelioma ◽  
Novel Therapy ◽  
Xenograft Models

O-202 Adjuvant therapy, stage and tumor histology impact prognosis after resection of malignant pleural mesothelioma

Lung Cancer ◽  
2003 ◽  
Vol 41 ◽  
pp. S59-S60 ◽  
Author(s):  
Valerie W. Rusch ◽  
Ennapadam Venkatraman ◽  
Kenneth E. Rosenzweig ◽  
Lee M. Krug
Keyword(s):  
Adjuvant Therapy ◽  
Malignant Pleural Mesothelioma ◽  
Pleural Mesothelioma ◽  
Tumor Histology

Induction chemotherapy vs post-operative adjuvant therapy for malignant pleural mesothelioma

2017 ◽  
Vol 11 (8) ◽  
pp. 649-660 ◽  
Author(s):  
Giuseppe Marulli ◽  
Eleonora Faccioli ◽  
Alice Bellini ◽  
Marco Mammana ◽  
Federico Rea
Keyword(s):  
Adjuvant Therapy ◽  
Induction Chemotherapy ◽  
Malignant Pleural Mesothelioma ◽  
Pleural Mesothelioma
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