Cancer

Modulation of u-PA, MMPs and their inhibitors by a novel nutrient mixture in human lung cancer and mesothelioma cell lines

M.Waheed Roomi, Tatiana Kalinovsky, Aleksandra Niedzwiecki* and Matthias Rath
Dr Rath Research Institute, Santa Clara, CA
International Journal of Oncology 2013, DOI: 10.3892/ijo.2013.1880

Abstract
Lung cancer, the most prevalent cancer worldwide, and malignant mesothelioma are highly aggressive tumors that are characterized by high levels of matrix metalloproteinase (MMP)-2 and -9 secretion. Proteases play a key role in tumor cell invasion and metastasis by digesting the basement membrane and ECM components. Strong clinical and experimental evidence demonstrates association of elevated levels of u-PA and MMPs with cancer progression, metastasis and shortened patient survival. MMP activities are regulated by specific tissue inhibitors of metalloproteinases (TIMPS).

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Modulation of MMP-2 and MMP-9 by cytokines, mitogens and inhibitors in lung cancer and malignant mesothelioma cell lines

M.W. Roomi, J.C. Monterrey, T. Kalinovsky, A. Niedzwiecki and M. Rath
Oncology Reports 2009; 22(6):1283-1291

Abstract:
Matrix metalloproteinases (MMPs) secreted by lung cancer (LC) and malignant mesothelioma (MM), especially MMP-2 and MMP-9, play crucial roles in tumor invasion and metastasis. We examined the effect of cytokines, mitogens, and inhibitors on MMP-2 and MMP-9 expression in LC and MM cell lines. Human LC (A-549) and MM (MSTO-211H) cell lines were cultured in appropriate media.

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Chemopreventive effect of a novel nutrient mixture on lung tumorigenesis induced by urethane in male A/J mice

M.W. Roomi, N.W. Roomi, T. Kalinovsky, M. Rath and A. Niedzwiecki

Tumori 2009; 95(4): 508-513

Abstract:
Lung cancer, a leading cause of cancer death, is associated with exposure to inhalation carcinogens, most commonly those found in tobacco smoke. We investigated the in vivo effect of dietary supplementation with a nutrient mixture containing lysine, proline, ascorbic acid and green tea extract (NM) on the development of urethane-induced lung tumors in male A/J mice.

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Inhibition of Malignant Mesothelioma Cell Matrix Metalloproteinase Production and Invasion by a Novel Nutrient mixture

M.W. Roomi, V. Ivanonv, T. Kalinovsky, A. Niedzwiecki, M. Rath
Experimental Lung Research 2006, 32(3&4): 69-79

Introduction:
Malignant mesothelioma (MM), an asbestos-associated cancer with no known cure, is a highly aggressive tumor causing profound morbidity and nearly universal mortality. Extracellular matrix (ECM) matrix metalloproteinases (MMPs) produced by tumor and stromal cells play a key role in tumor invasion and metastasis. Prevention of ECM degradation by MMP inhibition has been shown to be a promising therapeutic approach to inhibition of cancer development. A nutrient mixture (NM) containing lysine, proline, ascorbic acid and green tea extract, has shown significant anticancer activity against a number of cancer cell lines.

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In Vivo and In Vitro Anti-tumor Effect of a Unique Nutrient Mixture on Lung Cancer Cell Line A-549

M.W. Roomi, V. Ivanov, T. Kalinovsky, A. Niedzwiecki, M. Rath
Experimental Lung Research 2006, 32(9):441-453

Introduction:
The high incidence of lung cancer and ineffective toxic action of current mono and doublet chemotherapy approaches result in poor patient survival. Enzymes called matrix metalloproteinases (MMPs), which degrade the extracellular matrix are implicated in neoplastic invasion and metastasis. A nutrient mixture (NM) containing lysine, proline, arginine, ascorbic acid, and green tea extract has shown significant antitumor effects, including inhibition of MMPs and invasion. Based on this, we investigated the effect of NM on human lung carcinoma cell A-549 cells in vitro and in vivo.

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