Modulation of u-PA, MMPs and their inhibitors by a novel nutrient mixture in adult human sarcoma cell lines

M.Waheed Roomi, Tatiana Kalinovsky, Aleksandra Niedzwiecki* and Matthias Rath
Dr. Rath Research Institute, Santa Clara, CA
International Journal of Oncology 2013; 43: 39-49

Abstract: 
Adult sarcomas are highly aggressive tumors that are characterized by high levels of matrix metalloproteinase (MMP)-2 and -9 secretions that degrade the ECM and basement membrane, allowing cancer cells to spread to distal organs. 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 u-PA, MMPs and their inhibitors by a novel nutrient mixture in pediatric human sarcoma cell lines

M.Waheed Roomi, Tatiana Kalinovsky, Aleksandra Niedzwiecki* and Matthias Rath
Dr. Rath Research Institute, Santa Clara, CA
International Journal of Oncology 2013; 43: 1027-1035

Abstract:
Pediatric sarcomas are highly aggressive tumors that are characterized by high levels of matrix metalloproteinase (MMP)-2 and -9 secretions that degrade the ECM and basement membrane, allowing cancer cells to spread to distal organs. 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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In vitro modulation of MMP-2 and MMP-9 in adult human sarcoma cell lines by cytokines, inducers, and inhibitors

M.W. Roomi, T. Kalinovsky, J. Monterrey, M. Rath, A. Niedzwiecki
Dr. Rath Research Institute, 1260 Memorex Drive, Santa Clara, CA 95050
International Journal of Oncology 2013, DOI: 10.3892/ijo.2013.2113

Abstract
The highly aggressive adult sarcomas are characterized by high levels of matrix metalloproteinase (MMP)-2 and -9, which play crucial roles in tumor invasion and metastasis by degradation of the extracellular membrane leading to cancer cell spread to distal organs. We examined the effect of cytokines, mitogens, inducers and inhibitors on MMP-2 and MMP-9 secretion in chondrosarcoma (SW-1353), fibrosarcoma (HT-1080), liposarcoma (SW-872) and synovial sarcoma (SW-982) cell lines.

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In vitro anticarcinogenic effect of a nutrient mixture on human rhabdomyosarcoma cells

M.W. Roomi, V. Ivanov, T. Kalinovsky, A. Niedzwiecki, M. Rath
Gene Therapy and Molecular Biology 2007, 11: 133-142

Abstract:
Rhabdomyosarcoma, the most common pediatric soft tissue sarcoma of mesenchymal origin, has metastasized in ~25% of all patients at time of diagnosis. Though current treatment strategies have achieved some success, they are associated with severe adverse effects. We investigated the effect of a nutrient mixture (NM), which has shown antitumor effects on various cancer cell lines, on rhabdomyosarcoma cell growth, apoptosis, MMP secretion, and invasion. Human rhabdomyosarcoma cells, grown in DME, were treated at near confluence with NM at 0, 10, 50, 100, 500 and 1000 μg/ml in triplicate at each dose.

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Inhibition of Cell Invasion and MMP Production by a Nutrient Mixture in Malignant Liposarcoma Cell Line SW-872

M.W. Room, V. Ivanov, T. Kalinovsky, A. Niedzwiecki, M. Rath
Medical Oncology 2007, 24: 394-401

Abstract:
Liposarcoma, a malignancy of fat cells, is the most common soft tissue sarcoma. Though rare, poorly differentiated liposarcomas commonly metastasize to lungs and liver, leading to poor prognosis. Prevention of Extracellular matrix (ECM) degradation by inhibition of matrix metalloproteinases (MMPs) activity has been shown to be a promising therapeutic approach to inhibition of cancer progression. 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. We investigated the effect of NM on liposarcoma cell line SW-872 proliferation (MTT assay), MMP secretion (gelatinase zymography), invasion through Matrigel, and apoptosis and morphology (live green caspase kit and H&E).

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