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Cellular Medicine in Cancer

Cellular Medicine provides a new perspective in the developmental steps of cancer and its metastasis and new safe, effective therapeutic options.

Choices and Outcomes in Cancer Treatment:
For decades, standard treatment for cancer has consisted of surgery, radiation and chemotherapy. Radiation and chemotherapy, the most frequently used therapies, not only are ineffective in providing a cure, but also indiscriminately attack all cells – healthy and cancerous, causing cellular damage and destruction of the body’s connective tissue, the defense against cancer metastasis. Both radiation and chemotherapy trigger the development of new cancers and damage the immune system and body organs. In addition, these interventions activate enzymes that facilitate the release of cancer cells from a localized area to spread to other organs.

At Matthias Rath Research, we have achieved a breakthrough in cancer research by defining the cellular mechanisms involved in cancer proliferation and metastasis and developed a natural means of controlling these mechanisms. Efficient control of the spread of a disease by collagen-dissolving enzyme blocks has been successful with several diseases. This is especially important in diseases for which orthodox medicine has no preventive or healing therapies yet. A combination of natural nutrients formulated to support the body in curbing metastasis and reversing tumor growth, has been shown to be effective against a variety of human cancer cell lines, without adverse effects on normal cells. Please select a title below to read the respective research study.

How Cancer Spreads (Metastasis):
All forms of cancer spread with the help of a collagen dissolving mechanism. To reproduce and spread to other parts in the body, cancer cells degrade the extracellular matrix (ECM) by secreting various matrix metalloproteinases (MMPs), which have been correlated with the aggressiveness of tumor growth. With the help of these collagen-dissolving enzymes, cancer cells can bull doze their way though the extracellular matrix (ECM) and capsule enclosing the tumor and through an adjacent blood vessel wall, to be carried to other sites where the cancer cells can invade other organs, as shown below.

 

Cancer Metastasis – Normal cells become cancerous cells, which secrete matrix metalloproteinases (MMPS). MMPs destroy the extracellular matrix (ECM), enabling cancer cells to escape and spread to distal organs through the bloodstream.

Click image to enlarge

     
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Bladder Cancer
Antitumor Effect of Ascorbic Acid, Lysine, Proline, Arginine, and Green Tea Extract on Bladder Cancer Cell Line T-24
M.W. Roomi, V. Ivanonv, T. Kalinovsky, A. Niedzwiecki, M. Rath
Published in: International Journal of Urology 2006; 13: 413-417.
 
  Our results suggest that NM is an excellent candidate for therapeutic use in the treatment of bladder cancer, by inhibiting critical steps in cancer development and spread, such as MMP secretion and invasion.
Antitumor Effect of Nutrient Synergy on Human Bladder Cancer Cell Lines T-24 (2004)
M.W. Roomi, V. Ivanov, A. Niedzwiecki, M. Rath
Matthias Rath Research., Cancer Research Division, Santa Clara,CA 95050

Presented at: Mayo Clinic Conference on Dietary Factors and Cancer Prevention, Rochester, MN, September 23-25, 2004.
Published in: Dietary Factors and Cancer Prevention: Current Premises and Future Promises, Abstract #25, pg 51.
  Bladder cancer, a cancer that develops mainly in older adults, is the fourth most frequently diagnosed cancer in men. Once the cells have metastasized, prognosis is poor. We investigated the antitumor effect of a unique nutrient formulation containing lysine, proline, arginine, ascorbic acid, and epigallocatechin gallate on human bladder cancer cells T-24 in cell culture, by measuring critical parameters in cancer development and spread, such as MMP expression and cancer cell invasive potential. Our results showed significant inhibition of invasion and of MMP-2 and –9 expression, which suggest that this nutrient combination is potentially an excellent candidate for prevention and treatment of bladder cancer.
Bone Cancer
Effect of Ascorbic Acid, Lysine, Proline and Green Tea Extract on Human Osteosarcoma Cell Line MNNG-HOS Xenografts in Nude Mice
M.W. Roomi, V. Ivanonv, T. Kalinovsky, A. Niedzwiecki, M. Rath
Published in: Medical Oncology, vol.23, no.3, 411-417, 2006.
In Vitro and In Vivo Antitumor Effect of a Nutrient Mixture Containing Ascorbic Acid, Lysine, Proline, and Green Tea Extract on Human Synovial Sarcoma Cancer Cells
M.W. Roomi, V. Ivanonv, T. Kalinovsky, A. Niedzwiecki, M. Rath
Published in: JANA, vol.9, no.2, 30-34, 2006.
Anti-Angiogenic Effect of Nutrient Synergy on Human Synovial Sarcoma Cell Line SW 982
M.W. Roomi, V. Ivanov, A. Niedzwiecki, M. Rath
Matthias Rath Research., Cancer Research Division, Santa Clara, CA 95050
Presented at: International Research Conference on Food, Nutrition and Cancer in Washington DC, July 15-16, 2004.
Published in: Conference proceedings, Abstract #29, pg 31.
  Standard treatment of synovial sarcoma, a soft tissue with a high (50%) metastatic rate has met with poor results. In this study, we investigated the inhibitory effect of a unique nutrient mixture (NS) containing lysine, proline, arginine, ascorbic acid, and epigallocatechin gallate on metastatic potential of human synovial sarcoma cells SW 982, by measuring MMP expression and Matrigel invasion in cell culture. We found NS to inhibit the expression of both MMP-2 and -9 in a dose-dependent fashion with virtual total inhibition of MMP-2 at 500 µg/ml and MMP-9 at 50 µg/ml concentration of NS. The invasion of human synovial sarcoma cells through Matrigel was significantly reduced at 500 µg/ml (79%) and totally inhibited at 1000 µg/ml concentration of the synergistically acting nutrient mixture (p<0.0001). These results are important as they demonstrate that NS is an excellent candidate for treatment of synovial sarcoma by inhibiting critical steps in metastasis.
Breast Cancer
Inhibition of N-Methyl-N-Nitrosourea-Induced Mammary Tumors by Nutrient Synergy – A Novel Anti-Cancer Agent (2004)
M.W. Roomi, N. W. Roomi, V. Ivanov, A. Niedzwiecki, M. Rath
Presented at: 95th Annual Meeting of American Association for Cancer Research
Orlando, FL, March 27-31, 2004

  Incidence and mortality from breast cancer in women, the third most prevalent cancer worldwide, is steadily increasing, especially in developed societies. This study examined the synergistic effect of a specific formulation of nutrients containing lysine, proline, ascorbic acid and green tea extract on the growth of mammary tumors induced in 50-day-old female Sprague-Dawley rats by the carcinogen N-methyl-N-nitrosourea (MNU). Nutrient Synergy significantly inhibited the incidence, as well as the growth, of MNU-induced mammary tumors, indicating that it has strong potential as a useful therapeutic regimen for inhibiting breast cancer development.
A Specific Combination of Ascorbic Acid, Lysine, Proline and Epigallocatechin Gallate Inhibits Proliferation and Extracellular Matrix Invasion of Various Human Cancer Cell Lines (2003)
S.P. Netke, M.W. Roomi, N.W. Roomi, V. Ivanov, A. Niedzwiecki, M. Rath
Published in: Research Communications in Pharmacology and Toxicology: Emerging Drugs, 2:37-5, 2003.
  This study demonstrated significant anti-proliferative and anti-metastatic effects in vitro against some human cancer cell lines (breast, colon, and melanoma) using a specific combination of ascorbic acid, proline, and lysine. The addition of epigallocatechin gallate (EGCG) to the nutrient mixture enhanced the inhibitory effect on both cellular proliferation and invasion. These results are significant in showing the great potential of the control of cancer growth and metastasis using a safe nutrient approach.
Inhibition of Tumor Growth of Human Breast, Prostate, Colon, and Melanoma Cancer Xenografts by Nutrient Synergy in Nude Mice (2003)
M.W. Roomi, N.W. Roomi, V. Ivanov, S.P. Netke, A. Niedzwiecki, M. Rath
Presented at: American Society for Cell Biology Meeting, San Francisco, CA, Dec 2003
Published in: Conference proceedings
  This study demonstrated the synergistic anticancer effects of lysine, proline, arginine, ascorbic acid and EGCG (from green tea extract) on human breast, colon, prostate, melanoma, fibrosarcoma, and synovial sarcoma cancer cell growth in nude mice without any adverse effects. Nude mice are used since they are athymic, and thus are unable to mount most types of immune responses, including the ability to kill malignant cells by a cell-mediated immune response. The results of this study imply that Nutrient Synergy has great potential as a safe and effective therapeutic regimen for cancer treatment.
Nutrient Synergy Counteracts Carcinogenic Activity of Estrogen in Cultured Human Cancer Cells (2003)
V. Ivanov, M.W. Roomi, A. Niedzwiecki, M. Rath
Presented at: American College of Nutrition
Nashville, Tennessee, October 9-12, 2003

  Recent clinical studies have shown that hormone replacement therapy (HRT) in menopausal women increases the risk of tumor development in estrogen-sensitive tissues. In this study, estradiol stimulated breast cancer (MCF-7) cell growth, MMP expression, matrix invasion, and VEGF secretion (measure of angiogenesis) were observed in culture. These pro-carcinogenic effects of estradiol were significantly inhibited by Nutrient Synergy, suggesting this is an excellent candidate for preventative and therapeutic use in the treatment of estrogen-related breast cancer.
Anti-Tumorigenic Activity of Nutrient Synergy in Human Breast Cancer Lines MDA-MB-231 and MCF-7 (2003)
M.W. Roomi, V. Ivanov, A. Niedzwiecki, M. Rath
Presented at: The 8th Annual Multidisciplinary Symposium on Breast Disease
Amelia Island, FL, February 13-16, 2003
  Breast cancer, worldwide the most prevalent cancer and the second leading cause of cancer deaths in women today (after lung cancer), metastasizes by the enzymatic destruction of surrounding connective tissue to metastasize. This study demonstrated that the nutrient mixture of lysine, proline, ascorbic acid and epigallocatechin gallate exerted potent synergistic anti-metastatic effect on human breast MDA-MB-231 cancer cells by inhibiting MMP expression and Matrigel invasion. These results suggest that this nutrient formulation is a valuable and promising candidate for treating estrogen- insensitive breast cancer.
Nutrient Synergy – A Specific Formulation of Nutrients Containing Lysine, Proline, Ascorbic Acid, and Epigallocatechin Gallate Inhibits Matrix Metalloproteinases Activity and Invasion Potential of Human Cancer Cell Lines (2002)
M.W. Roomi, S.P. Netke, V. Ivanov, A. Niedzwiecki, M. Rath
Presented at: European Organization for Research and Treatment of Cancer (EORTC), AACR and NCI Symposium on Molecular Targets and Cancer Therapeutics
Frankfurt, Germany, Nov. 19-22, 2002

  These results demonstrated that the synergistic effect of ascorbic acid, lysine, proline, and epigallocatechin gallate significantly inhibited the metastasis potential of human melanoma, breast and liver cancer cells by inhibiting the expression of MMPs and Matrigel invasion, suggesting this non-toxic agent as a promising candidate for the treatment of human cancers.
Inhibitory Effects of Ascorbic Acid, Proline, and Lysine Supplementation on Matrigel Invasion by Human Breast Cancer Cells MDA-MB-231 (2002)
S.P. Netke, V. Ivanov, M.W. Roomi, A. Niedzwiecki, M. Rath
Presented at: 19th Annual Miami Breast Cancer Conference
Miami Beach, Florida, February 27 – March 3, 2002
  The results from this study demonstrated that while an individual nutrient, such as ascorbic acid, can inhibit the invasion of cancer cells through Matrigel (a model for extracellular matrix), the synergistic effect of a combination of ascorbic acid, lysine, and proline significantly enhances the inhibition of invasion. This implies that this nutrient mixture is a promising candidate for therapeutic use in the treatment of breast cancer cells, by blocking metastasis.
Cervical Cancer
Suppression of Human Cervical Cancer Cell Lines Hela and DoTc2 4510 MMP Expression and Matrigel Invasion by a mixture of lysine, proline, ascorbic acid, and green tea extract
M.W. Roomi, V. Ivanonv, T. Kalinovsky, A. Niedzwiecki, M. Rath
Published in: Int J Gynecol Cancer 2006, 16, 1241-1247.
  Our results suggest that the mixture of lysine, proline, arginine, ascorbic acid, and green tea extract has potential in the treatment of cervical cancer, by inhibiting critical steps in cancer development and spread.
Suppression of MMP Expression and Invasion of Human Cervical Cancer Cell lines Hela and DoTc2 4510 by Nutrients
M.W. Roomi, V. Ivanov, A. Niedzwiecki, M. Rath
Presented at: 44th Annual Meeting of the Society of Toxicology, New Orleans, March 6-10, 2005.
Published in: Proceedings of the 44th Annual Meeting of the Society of Toxicology, Abstract #1494
  Cervical cancer is the seventh most common cancer worldwide and the second most common cancer in women. Untreated dysplasia and carcinoma in situ leads to 30% to 40% invasion within ten years. We studied the synergistic effect of a unique nutrient formulation containing lysine, proline, arginine, ascorbic acid, and epigallocatechin gallate on metastatic parameters on human cervical cancer cells such as effect on MMP-2 and –9 expression and cancer cell invasive potential. Our results demonstrated complete inhibition of Hela MMP-2 expression at 1000 µg/ml and MMP-9 at 500 µg/ml, and of Matrigel invasion at 500 µg/ml. NM demonstrated complete inhibition of cervical DoTc2 4510 cell expression of MMP-9 at 500 µg/ml and of invasion at 1000 µg/ml. These findings are significant as they suggest that the nutrient mixture would be an effective and safe therapeutic regimen for treatment of cervical cancer.
Colon Cancer
A Specific Combination of Ascorbic Acid, Lysine, Proline and Epigallocatechin Gallate Inhibits Proliferation and Extracellular Matrix Invasion of Various Human Cancer Cell Lines (2003)
S.P. Netke, M.W. Roomi, N.W. Roomi, V. Ivanov, A. Niedzwiecki, M. Rath
Published in: Research Communications in Pharmacology and Toxicology: Emerging Drugs, 2:37-5, 2003.
  This study demonstrated significant anti-proliferative and anti-metastatic effects in vitro against some human cancer cell lines (breast, colon, and melanoma) using a specific combination of ascorbic acid, proline, and lysine. The addition of epigallocatechin gallate (EGCG) to the nutrient mixture enhanced the inhibitory effect on both cellular proliferation and invasion. These results are significant in showing the great potential of the control of cancer growth and metastasis using a safe nutrient approach.
Inhibition of Tumor Growth of Human Breast, Prostate, Colon and Melanoma Cancer Xenografts by Nutrient Synergy in Nude Mice (2003)
M.W. Roomi, N.W. Roomi, V. Ivanov, S.P. Netke, A. Niedzwiecki, M. Rath
Presented at: 43rd Annual Meeting of the American Society for Cell Biology
San Francisco, CA, December 13-17, 2003

  This study demonstrated the synergistic anticancer effects of lysine, proline, arginine, ascorbic acid and EGCG (from green tea extract) on human breast, colon, prostate, melanoma, fibrosarcoma, and synovial sarcoma cancer cell growth in nude mice without any adverse effects. Nude mice are used since they are athymic, and thus are unable to mount most types of immune responses, including the ability to kill malignant cells by a cell-mediated immune response. The results of this study imply that Nutrient Synergy has great potential as a safe and effective therapeutic regimen for cancer treatment.
Anti-Metastatic Activity of Nutrient Synergy on Human Colon Cancer Cell Line HCT 116 (2003)
M.W. Roomi, N.W. Roomi, V. Ivanov, S.P. Netke, A. Niedzwiecki, M. Rath
Presented at: International Research Conference on Food, Nutrition and Cancer
Washington D.C., July 17-18, 2003

  Colon cancer, the second leading cause of cancer death in the United States, results in 55,000 deaths per year, mainly secondary to metastasis. In this study, NS was found to significantly inhibit the metastatic parameters of MMP-9 expression and Matrigel invasion without alteration in cell morphology. These results suggest that Nutrient Synergy not only has great anti-metastatic potential as a therapeutic agent for colon cancer, but also is safe to use.
Metastatic and Cytotoxic Effects of Ascorbigen and Iso-Ascorbigen in Human Cancer Cells (2002)
M.W. Roomi, A. Bogale, S.P. Netke, V. Ivanov, A. Niedzwiecki, M. Rath
Presented at: American College of Nutrition, 43rd Annual Meeting
San Antonio, Texas, Oct. 3-6, 2002

  Diets high in cruciferous vegetables, such as cabbage, have been associated with prevention of certain types of cancers. In this study, ascorbigen, a major indole-containing compound in cabbage, was found to be toxic to human melanoma, liver, and colon cancer cell lines. In addition, it was found to inhibit cellular MMP expression, a measure of metastatic potential.
Fibrosarcoma
In Vivo and In Vitro Antitumor Effect of Ascorbic Acid, Lysine, Proline, Arginine, and Green Tea Extract on Human Fibrosarcoma Cells HT-1080 - NEW -
M.W. Roomi, V. Ivanov, T. Kalinovsky, A. Niedzwiecki, M. Rath
Published in: Medical Oncology – 2006; 23(1),105-112
  These results offer promise in the therapeutic use of the nutrient mixture of lysine, proline, arginine, ascorbic acid, and green tea extract tested in the treatment of fibrosarcoma.
Inhibitory Effect of Nutrient Synergy, A Specific Formulation of Nutrients Containing Lysine, Proline, Ascorbic Acid, and Epigallocatechin Gallate, on Matrix Metalloproteinase Activity and Invasion of Human Fibrosarcoma HT-1080 Cells
M.W. Roomi, V. Ivanov, S.P. Netke, A. Niedzwiecki, M. Rath
Presented at: FASEB (Federation of American Societies for Experimental Biology) Conference
San Diego, CA, April 11-15, 2003
  To reproduce and spread to other parts in the body, cancer cells degrade the extracellular matrix (ECM) by secreting various matrix metalloproteinases (MMPs), which have been correlated with the aggressiveness of tumor growth. In this study, Nutrient Synergy, a specific mixture of nutrients, including lysine, proline, ascorbic acid, and epigallocatechin gallate, significantly inhibited the expression of both MMP-2 and MMP-9, and the invasion of human fibrosarcoma HT-1080 cells through Matrigel in a dose dependent fashion, without toxic effect to cells. These results suggest that Nutrient Synergy has great potential as a natural, non-toxic therapeutic regimen based on its anti-metastatic activity.
Cancer - General
Inhibition of Human Neuroblastoma Cell Line SK-N-MC In Vivo and In Vitro By a Novel Nutrient Mixture
- NEW -
M.W.Roomi, V. Ivanov, A. Niedzwiecki, M. Rath
Presented at: 21st Annual Meeting of the ISBTC, October 26-29, 2006, Los Angeles, CA
Published in: Proceedings of the 21st Annual Meeting of the ISBTC, abstract #116
  This study shows that specific nutrients combined in a synergy have a potential to curb neuroblastoma tumor growth in vivo by about 30%. In addition, by inhibiting secretion of MMPs, the enzymes essential for degradation of collagen and connective tissue surrounding all cancer cells, they can curb cancer spread in the body. Prevention of ECM degradation by inhibition of MMP activity has been shown to be a promising therapeutic target in cancer. Our unique nutrient mixture (NM) containing lysine, proline, ascorbic acid and green tea extract inhibited the secretion of both MMP-2 and MMP-9 with their total blockage at NM concentration of 100 mg/ml. These results are significant as they demonstrate therapeutic potential in treatment of neuroblastoma by safe and effective micronutrient synergy.
Antineoplastic Effect of Nutrient Mixture on Human Burkitt’s Lymphoma Raji Cells
- NEW -
M.W. Roomi, N.W. Roomi, V. Ivanov, A. Niedzwiecki and M. Rath
Dr. Rath Research Institute, Oncology Division, Santa Clara, CA 95050
Presented at: 97th Annual Meeting of the AACR, Washington D.C., April 1-5, 2006
Published in: Proceedings of the 97th Annual Meeting of the AACR, Abstract #1915
  Chemotherapy, the current treatment for Burkitt’s lymphoma (BL) is toxic and has limited success in AIDS-related forms. We investigated the antineoplastic effect of a nutrient mixture (NM) on BL in vitro. NM significantly inhibited BL cellular proliferation, MMP-9 secretion, and invasion through Matrigel, with total block of invasion at 100 ?g/ml NM. These results are significant as they indicated NM has strong potential in treatment of BL.
A Nutrient Mixture Consisting of Lysine, Proline, Ascorbic Acid and Green Tea Extract Inhibit Lung Metastasis by B16FO Melanoma Cells in Mice
- NEW -
M.W. Roomi, N.W. Roomi, V. Ivanov, A. Niedzwiecki, M. Rath
Dr. Rath Research Institute, Oncology Division, Santa Clara, CA 95050
Presented at: 97th Annual Meeting of the AACR, Washington DC, April 1-5, 2006
Published in: Proceedings of the 97th Annual Meeting of the AACR, Abstract #1903
  Tumor metastasis is a major reason for treatment failure in cancer patients. Metastatic malignant melanoma is an extremely aggressive cancer with no current viable therapy. The primary objective of our study was to investigate whether a unique non-toxic nutrient mixture (NM) that has shown potent anti-tumor effects in a number of cancer cell lines, could inhibit experimentally induced lung metastasis of melanoma cells in C57BL/6 mice. Intravenous injection of melanoma cells into C57BL/6 mice has been shown to result in pulmonary metastasis, providing an excellent model to assess test agents on metastasis. This study demonstrated the effectiveness of NM in halting metastasis of B16FO cells in mice, especially when delivered by iv or ip. Furthermore, pre-incubation of tumor cells with NM for 18 hrs prior to injection into the mice completely prevented the development of lung tumors in these mice. These results are significant since they clearly demonstrate the anti-metastatic potential of NM, a non-toxic nutrient mixture.
Antileukemic Effect of a Novel Nutrient Mixture on Human JURKAT T Cells
- NEW -
M.W. Roomi, V. Ivanov, A. Niedzwiecki, M. Rath
Dr. Rath Research Institute, 1260 Memorex Drive, Santa Clara, CA 95050
Presented at: FASEB, San Francisco, CA, April 1-5, 2006
Published in: The FASEB Journal, Abstract #107
  Cellular production of matrix metalloproteinases contributes to tumor progression, invasion and metastasis. We investigated whether cellular invasion and production of MMPs by a leukemia cell line, Jurkat T, can be affected by a unique nutrient mixture (NM) consisting primarily of lysine, proline, ascorbic acid and green tea extract. We have demonstrated previously (Harakeh et al. 2006) that this nutrient mixture was effective in inducing apoptosis in this and other leukemia cell lines. In addition, it has been shown to exhibit anti-tumor activity both in vitro and in vivo against a number of cancer cell lines. NM exhibited antiproliferative effect on human acute Jurkat T cells at 500?g/ml, and dose-dependent inhibition of MMP-9 secretion and Matrigel invasion, with total blockage of MMP-9 secretion at 500 ?g/ml NM and of invasion at 1000 ?g/ml NM. These results are significant as they confirm previous data and indicate that NM is potentially a promising therapeutic agent for acute leukemia.
Antiangiogenic Effects of a Nutrient Mixture on Human Umbilical Vein Endothelial Cells - NEW -
M.W. Roomi, N. Roomi, V. Ivanov, T. Kalinovsky, A. Niedzwiecki, M. Rath
Published in: Oncology Reports – Dec;14(6):1399-404.
 

These results with our earlier findings suggest that NM is a relatively non-toxic formulation with anti-angiogenic effects, such as inhibiting vascular tube formation and endothelial cell invasion and migration.

Inhibitory Effect Of A Mixture Containing Ascorbic Acid, Lysine, Proline, And Green Tea Extract On Critical Parameters In Angiogenesis - NEW -
M.W. Roomi, N. Roomi, V. Ivanov, T. Kalinovsky, A. Niedzwiecki, M. Rath
Published in: Oncology Reports 2005, 14(4), 807-815
  These results with our earlier findings suggest that NM is a relatively non-toxic formulation that inhibits growth, invasion, metastasis, and angiogenesis of tumor cells.
Inhibitory Effect Of A Novel Mixture Containing Ascorbic Acid, Lysine, Proline And Green Tea Extract On Critical Parameters In Cancer Progression - NEW -
M.W. Roomi, V. Ivanov, T. Kalinovsky, A. Niedzwiecki, M. Rath
Dr. Rath Research Institute, 1260 Memorex Drive, Santa Clara, CA 95050
Presented at: 10th World Congress on Advances in Oncology and 8th International Symposium on Molecular Medicine, Crete, Greece, October 13-15, 2005.
Published in: International Journal of Molecular Medicine, abstract #121, page S10.
  Degradation of extracellular matrix (ECM) is a hallmark of tumor invasion, metastasis and angiogenesis. Based on a multitargeted approach to cancer by using natural substances to control ECM stability and enhancing its strength we developed a novel formulation (NM) of lysine, proline, ascorbic acid and green tea extract that has shown significant anti-cancer activity against a number of cancer cell lines. Using various in vitro and in vivo experimental models, we found that NM significantly inhibited angiogenesis and metastasis of various cancer cell lines. These results suggest that the nutrient mixture (NM) has strong therapeutic potential treating various cancers by blocking angiogenesis and tumor invasion and metastasis.

Studies On The Bioenhancing Effects Of Red Onions And Other Nutrients On The Absorption Of Epigallocatechin Gallate From Green Tea Extract In Human Volunteers
- NEW -
Anup Kale1, Sonia Gawande1, Swati Kotwal1, Shrirang Netke2, Waheed Roomi2, Vadim Ivanov2, Aleksandra Niedzwiecki2 and Matthias Rath2
1 Post Graduate Department of Biochemistry, University of Nagpur, Nagpur, M.S. 440033, India
2 Dr Matthias Rath Institute of Cellular Research,1260 Memorex Drive, Santa Clara, CA 95050, US
Presented at: 2nd International Conference on Tumor Progression & Therapeutic Resistance, Boston, September 18-20, 2005
Published in: 2nd International Conference on Tumor Progression & Therapeutic Resistance Proceedings, page 89.

  Consumption of high amounts of tea has been associated with lower incidence of stomach cancer. Furthermore, In vitro and in vivo studies have demonstrated the anti-cancer activity of green tea, black tea and their active constituents. However, plasma levels of EGCG after human consumption of green tea products indicate poor absorption of EGCG. We sought to determine if EGCG absorption could be enhanced with red onion (quercetin) supplementation. The results demonstrated that increasing the amount of quercetin given along with EGCG could increase absorption of EGCG from the intestine. Thus, the anticancer activity of the nutrient mixture (EF) can be enhanced with quercetin intake by increasing plasma levels of EGCG.
A Novel Approach to Inhibition of Cancer Development by Nutrient Supplement
M.W. Roomi, V. Ivanov, A. Niedzwiecki, M. Rath
Oral Presentation at: American Chemical Society National Meeting, San Diego, CA, March 13-17, 2005
Published in: Book of Abstracts, 229th ACS National Meeting, Abstract #86
  Cancer, one of the most dreaded diseases, is the second leading cause of death in the United States. The standard treatment protocols of chemotherapy and radiation are toxic to normal cells and potentially enhance metastasis. In contrast, the nutrient mixture of ascorbic acid, lysine, proline and green tea extract addresses different aspects of cancer development:
• Inhibits tumor growth/ proliferation
• Impairs invasion
• Inhibits metastasis
• Inhibits angiogenesis
Head and Neck

Marked inhibition of tumor growth, MMP secretion and invasion by a nutrient mixture on head and neck squamous carcinoma cell line FaDu: in vitro and in vivo studies
- NEW -
M.W.Roomi, V. Ivanov, A. Niedzwiecki, M. Rath
Dr. Rath Research Institute, Oncology, 1260 Memorex Drive, Santa Clara, CA 95050

Presented at: 18th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics, November 7-10, 2006, Prague, Czechoslovakia.
Published in: The European Journal of Cancer 2006, vol 4(12), abstract #520.

  Head and neck squamous cell carcinomas (HNSCC), the sixth most common malignancies in the United States, are known for their aggressive growth and propensity to invade and metastasize. We investigated the effect of a novel nutrient mixture (NM) containing ascorbic acid, lysine, proline, and green tea extract, shown to have potent antitumor effects on many cancer cell lines, on the growth of human HNSCC xenografts in athymic nude mice, as well as investigating this cell line in vitro, evaluating viability, MMP secretion, invasion and morphology. NM inhibited the growth of tumors by 50% and exhibited dose-response toxicity to cells in vitro, with 50% toxicity at 1000 µg/ml. In addition, NM inhibited the invasive parameters of MMP secretion and Matrigel invasion by cells in a dose-dependent manner with total block of MMPs at 1000 µg/ml and invasion at 500 µg/ml. These results are significant as they suggest that NM, a relatively safe therapeutic agent, has great potential in treatment of HNSCC in suppressing tumor growth and metastasis.
Kidney
Anticancer Effect of Lysine, Proline, Arginine, Ascorbic Acid and Green Tea Extract on Human Renal Adenocarcinoma Line 786-0 - NEW -
M.W. Roomi, V. Ivanov, T. Kalinovsky, A. Niedzwiecki and M. Rath
Published in: Oncology Reports 2006; 16(5):943-7.
  Our results support a potential role for the nutrient mixture tested in the treatment of renal cell carcinoma, by inhibition of MMP-2 and MMP-9 secretion and invasion.
Modulation of Human Renal Cel Carcinoma 786-0 MMP-2 and MMP-9 Activity by Inhibitors and Inducers in Vitro - NEW -
M.W. Roomi, N. Roomi, V. Ivanov,T. Kalinovsky, A. Niedzwiecki, M. Rath
Published in: Medical Oncology 2006; 23(2):245-250.
  In conclusion, this study has shown that exposure of the highly metastatic renal cell carcinoma cell line 786-0 to different growth factors increases secretion of MMP-9 but not MMP-2; MMP-2 and-9 activity was decreased by exposure to inhibitors. Further studies are in progress to confirm the role of MMP-9 on Matrigel invasion using PMA, cytokines and LPS.
Anticancer Effect of Lysine, Proline, Arginine, Ascorbic Acid and Green Tea Extract on Human Renal Adenocarcinoma Line 786-0 (2004)
M.W. Roomi, V. Ivanov, A. Niedzwiecki, M. Rath
Presented at: Third International Kidney Cancer Symposium, Chicago, Illinois, November 12-14 2004.
Published in: The Third International Kidney Cancer Symposium proceedings, Abstract #39, pg 39.
  Renal adenocarcinoma, the 17th most frequent cancer worldwide, is associated with good prognosis if treated when still localized to the kidney; however, once metastasized, prognosis is poor. We investigated the effect of a unique nutrient formulation (NM) of lysine, proline, arginine, ascorbic acid, and epigallocatechin gallate on its effect in vitro on modulation of metastatic parameters in human renal adenocarcinoma cell line 786-0. NM significantly inhibited MMP expression and Matrigel invasion in a dose-dependent fashion, with total inhibition of MMP-2 at 500 µg/ml, MMP-9 at 100 µg/ml and invasion at 1000 µg/ml. These results indicate NM has great potential in therapeutic use for treatment of renal carcinoma.
In vitro Expression of MMP-2 and MMP-9 by Human Renal Cell Carcinoma with Modulation by Phorbol Ester, TNF-alpha, Il-1 beta and Lipopolysaccharides (2004)
M.W. Roomi, V. Ivanov, A. Niedzwiecki, M. Rath
Presented at: Third International Kidney Cancer Conference, Chicago, Illinois, November 12-14, 2004.
Published in: Third International Kidney Cancer Symposium proceedings, Abstract #40, pg 40.
  Renal cell carcinoma invasion is associated with its ability to degrade the extracellular matrix by local production of gelatinase enzymes (MMP-2 and MMP-9). Although many studies on renal carcinoma have demonstrated the importance of MMPs, very little information is currently known regarding the effect of inhibitors and inducers of MMPs. We studied the effect of inducers (PMA, TNF-alpha, IL-1 beta, and LPS) and inhibitors (EGCG, doxycycline, actinomycin D, cyclohexamide, retinoic acid, dexamethasone and H-7) on RCC 786-0 MMP expression. Our results indicate that MMP-2 expression was not influenced by inducers such as PMA, cytokines (IL-1b, TNFa), and LPS; the induction of MMP-9 was associated with the specific inducer used: highest with PMA, intermediate with cytokines, and none with LPS. The inhibitors tested affected both MMP-2 and MMP-9 expression. Further studies are in progress to confirm the role of MMP-9 on Matrigel invasion using PMA, cytokines and LPS.
Leukemia

Apoptosis Induction by Nutrient Synergy in HTLV-1 Positive and Negative Malignant T-Cells
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S. Harakeh, M. Diab-Assaf, A. Niedzwiecki, J. Khalife, K. Abu-El-Ardat, M. Rath
Published in: Leukemia Research 30, (2006) 869-881.

  The effects of a novel nutrient formulation Nutrient Synergy (NS) were evaluated on proliferation and induction of apoptosis using non-cytotoxic concentrations against HTLV-1 positive (HuT-102 & C91-PL) and negative (CEM & Jurkat) cells. NS showed anti-proliferative effect as determined by MTT assay and TGF mRNA protein expression using RT-PCR. NS resulted in the down-regulation of TGF-alpha and an up-regulation in TGF-beta2. NS caused a significant increase in apoptotic cells in the preG(1) phase. These results were confirmed using Cell Death ELISA and Annexin V-FITC. Induction of apoptosis was caused by an up-regulation of p53, p21 and Bax protein levels and a down-regulation of Bcl-2alpha protein expression level.

Anticancer Activity of a Nutrient Mixture in Malignant Leukemia Cell Line P-388 in vitro #96
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M.W. Roomi, V. Ivanov, A. Niedzwiecki and M. Rath
Matthias Rath Research Institute, Cancer Division, Santa Clara, CA 95050
Presented at: International Society for Biological Therapy of Cancer, Nov 10-13 2005, Alexandria, VA
Published in: International Society for Biological Therapy of Cancer Proceedings, Abstract #96

  Leukemia, a disorder of bone marrow characterized by unrestrained white blood cell proliferation, results in formation of metastatic colonies and penetration through matrix barriers and blood vessel walls. Degradation and invasion through matrix barriers and vessel walls is mediated by secretion of MMPs. A nutrient mixture (NM) containing lysine, proline, ascorbic acid and green tea extract exhibited significant inhibition of Matrigel invasion (with total block at 1000 µg/ml) and significant antiproliferative effect at 500 µg/ml (70%) and 1000 µg/ml (90%). These results are important as they indicate NM is a promising therapeutic agent for leukemia.
A Novel Nutrient Mixture As An Antileukemic Agent With Matrix Metalloproteinase And Invasion Inhibitory Activities - NEW -
M.W. Roomi, V. Ivanov, A. Niedzwiecki, M. Rath
Dr. Rath Research Institute, 1260 Memorex Drive, Santa Clara, CA 95050
Presented at: 2nd International Tumor Metabolism Summit, Genova, Italy, October 7-8, 2005
Published in: 2nd International Tumor Metabolism Summit Proceedings
  Acute myeloid leukemia (AML), the most common leukemia in adults, is characterized by uncontrolled proliferation of myeloid blasts or lymphoid cell lines. Although chemotherapy and supportive management have resulted in high remission rates, fewer than 50% of young patients and 10%-15% of patients over 60 years are cured of their disease. We found that the nutrient mixture (NM) of ascorbic acid, lysine, proline, and green tea extract demonstrated a potent synergistic anticancer effect by inhibiting human promyelocytic leukemia cell HL-60 proliferation, MMP activity, and invasion through Matrigel in vitro. Our results are significant as they indicate that this nutrient mixture is a promising non-toxic therapeutic agent for acute myeloid leukemia.
Anti-Proliferative Effects of Antioxidants Using HTLV-1 Positive and Negative Malignant T-cells
Harakeh SM, Diab-Assaf M, Niedzwiecki A, Khalife J, Abu-El-Ardat K, Roomi MW, Rath M. American University of Beirut, Beirut, Lebanon
Dr. Rath Research Institute, Santa Clara, CA

Presented at: 104th General Meeting of the American Society for Microbiology
New Orleans, Louisiana, May 23-27, 2004

Published in: American Society for Microbiology Final Program, p. 143, Abstract #T-021.
  Adult T-cell leukemia (ATL) is an aggressive malignancy caused by HTLV-1, for which currently there is no proven therapy. Nutrients, such as ascorbic acid, lysine, and EGCG used individually and in combination with other nutrients (e.g., proline and N-Acetyl-L-Cysteine), were effective in inhibiting the growth of virus-infected and virus-negative leukemia cell types. These nutrients were used in concentrations that did not affect the viability of normal cells, but were effective in killing leukemia cells. Our study results confirm our previous findings that a specific combination of nutrients can be a powerful tool in suppressing cancer cell growth and viability, including blood cancers such as ATL.
Liposarcoma
Inhibition Of Cell Invasion And Mmp Production By A Nutrient Mixture In Malignant Liposarcoma Cell Line Sw-872 - NEW -
M.W. Roomi, V. Ivanov, A. Niedzwiecki, M. Rath
Dr. Rath Research Institute, 1260 Memorex Drive, Santa Clara, CA 95050
Presented at: International Research Conference on Food, Nutrition, and Cancer, Washington, DC, July 14-15, 2005
Published in: Poster Abstract Book, Abstract # 36
  Liposarcoma, a fat cell malignancy, commonly metastasizes (usually to lungs and liver). Overall 5-year survival rate of patients with deep high-grade liposarcoma is less than 50%. Extracellular matrix (ECM) matrix metalloproteinases (MMPs) produced by tumor and stromal cells play a key role in tumor invasion and metastasis. The nutrient mixture (NM) of lysine, proline, ascorbic acid and green tea extract significantly inhibited liposarcoma cell growth, MMP expression and invasion - important parameters for cancer prevention. These results are significant as they indicate that the nutrient mixture has therapeutic potential as a non-toxic treatment strategy for liposarcoma.
Liver Cancer
Nutrient Synergy – A Specific Formulation of Nutrients Containing Lysine, Proline, Ascorbic Acid, and Epigallocatechin Gallate Inhibits Matrix Metalloproteinases Activity and Invasion Potential of Human Cancer Cell Lines (2002)
M.W. Roomi, S.P. Netke, V. Ivanov, A. Niedzwiecki, M. Rath
Presented at: European Organization for Research and Treatment of Cancer (EORTC), AACR and NCI Symposium on Molecular Targets and Cancer Therapeutics
Frankfurt, Germany, Nov. 19-22, 2002

  These results demonstrated that the synergistic effect of ascorbic acid, lysine, proline, and epigallocatechin gallate significantly inhibited metastasis potential of human melanoma, breast and liver cancer cells by inhibiting the expression of MMPs and Matrigel invasion, suggesting this non-toxic agent as a promising candidate for the treatment of human cancers.
Metastatic and Cytotoxic Effects of Ascorbigen and Iso-Ascorbigen in Human Cancer Cells (2002)
M.W. Roomi, A. Bogale, S.P. Netke, V. Ivanov, A. Niedzwiecki, M. Rath
Presented at: American College of Nutrition, 43rd Annual Meeting
San Antonio, Texas, Oct. 3-6, 2002

  Diets high in cruciferous vegetables, such as cabbage, have been associated with prevention of certain types of cancers. In this study, ascorbigen, a major indole-containing compound in cabbage, was found to be toxic to human melanoma, liver, and colon cancer cell lines. In addition, it was found to inhibit cellular MMP expression, a measure of metastatic potential.
Cytotoxic Effect of Lipophilic Substitution at 2-, 6-, and 2,6-Positions in Ascorbic Acid and Expression of Matrix Metalloproteinases in Hep G2 Cells, Melanoma Cells, and Normal Human Dermal Fibroblast (2001)
M.W. Roomi, S.P. Netke, V. Ivanov, A. Niedzwiecki, M. Rath
Presented at: American College of Nutrition, 42nd Annual Meeting
Orlando, Florida, Oct. 3-7, 2001

  Ascorbic acid and its derivatives have been shown to be cytotoxic and inhibit the growth of a number of malignant and non-malignant cell lines in culture and in animal models. In this study, ascorbic acid, which is water-soluble, was not toxic to the melanoma and liver cancer lines tested; however, the lipophilic (lipid soluble) derivatives studied were found to be markedly toxic to these cell lines. This implies that these lipid-soluble derivatives, which can cross cell membranes and the blood brain barrier, have therapeutic potential in the treatment of cancer.
Lung

Inhibition of Pulmonary Metatasis of Melanoma B16FO Cells in C57BL/6 Mice by a Nutrient Mixture Consisting of Ascorbic Acid, Lysine, Proline, Arginine, and Green Tea Extract
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M.W. Roomi, N. Roomi, V. Ivanov, T. Kalinovsky, A. Niedzwiecki, M. Rath
Published in: Experimental Lung Research, 2006 Nov-Dec; 32(10):517-530.

  The results of this study show that this nutrient mixture administered in a diet was effective in a significant inhibition of metastasis of B16FO melanoma cells to the lungs. By exposure to higher concentrations of NM, such as obtained through iv or ip delivery, an enhanced inhibitory effect was obtained (up to 86%). It is important to note that the exposure of tumor cells to NM before their injection to the mice completely prevented development of lung tumors (100% inhibition of metastasis).
In Vivo and In Vitro Anti-tumor Effect of a Unique Nutrient Mixture