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Scientific Presentations in Cancer

Antineoplastic Activity of a Novel Nutrient Mixture on Malignant Retinoblastoma Cell Line Y79
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M. Waheed Roomi, Vadim Ivanov, Aleksandra Niedzwiecki, Matthias Rath.
Dr Rath Research Institute, Santa Clara, California, USA
Presented at: International Congress of Toxicology, Montreal, Canada, July 15-19, 2007
Published in: International Congress of Toxicology, Carcinogenesis, July 2007, Abstract #PW2.042,page 84

  Currently there is no effective treatment for retinoblastoma (Rb), a malignant tumor of the retina which affects children under the age of six. Rb metastasizes to extraocular organs including bone, lung and brain. We investigated the in vitro antineoplastic activity of a non-toxic nutrient mixture (NM) consisting of lysine, proline, ascorbic acid and green tea extract that has shown anticancer activity against a number of cancer cell lines on human malignant retinoblastoma cell line Y79. Rb cells exhibited 25% toxicity to 10-100 µg/ml NM and profound toxicity at 500 and 1000 µg/ml NM. Zymography demonstrated production of only MMP-2. NM at 10-100 µg/ml had no effect on MMP-2, but completely blocked it at 500 µg/ml. PMA treatment did not induce MMP-9. Interestingly, Rb cells were not invasive through Matrigel. These results are significant as they suggest NM may have therapeutic potential in the treatment of retinoblastoma.

Pattern of MMP-2 and MMP-9 Secretion in Human Cancer Cell Lines
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M.W. Roomi, J. Monterrey, V. Ivanov, A. Niedzwiecki and M. Rath
Dr. Rath Research Institute, Oncology Division, 1260 Memorex Drive, Santa Clara, CA
Presented at: 98th Annual Meeting of the AACR, Los Angeles, CA, April 14-18, 2007
Published in: Proceedings of the 98th Annual Meeting of the AACR, Abstract #559, p 114

  Matrix metalloproteinases (MMPs), a class of zinc dependent neutral proteinases encoded by a multigene family, have been implicated in cancer. MMP-2 and MMP-9 secretion is elevated in several types of human cancers and their elevated expression has been associated with poor prognosis. Expression of MMPs is highly regulated by cytokines and signal transduction pathways, including those activated by PMA. In this study, we examined the effect of PMA on MMP-2 and MMP-9 secretion in several human cancer cell lines. Based on the MMP-2 and MMP-9 secretion with and without PMA treatment, the various human cancer cell lines fell into three groups: 1) Those secreting only MMP-2 and not stimulated by PMA; 2) Those secreting MMP-9 only, which was either stimulated further by PMA or unaffected by PMA, and 3) Those secreting both MMP-2 and MMP-9, with PMA stimulation of only MMP-9. The finding that irrespective of MMP-2 secretion, only MMP-9 levels are increased, suggest that this enzyme might play a more vital role in invasion and metastasis and may be a valuable indicator of the prognosis of the pathological conditions.

Inhibition of 7,12-Dimethylbenzanthracene-Induced Skin Tumor by a Nutrient Mixture
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M.W. Roomi, N.W. Roomi, V. Ivanov, A. Niedzwiecki and M. Rath
Dr. Rath Research Institute, Oncology Division, 1260 Memorex Drive, Santa Clara, CA
Presented at: Annual Meeting of the AACR, Los Angeles, CA, April 14-18, 2007
Published in: Proceedings of the 98th Annual Meeting of the AACR, Abstract #2634, p 231

  The annual incidence of skin cancer, the most common of all human cancers, is increasing each year. Nearly half of Americans who live to the age of 65 will develop skin cancer. We examined the effect of a unique nutrient mixture (NM) that contains lysine, proline, ascorbic acid and green tea extract on the development of skin cancer induced by topical application of 7,12-dimethylbezanthracene (DMBA) in female SENCAR mice. Groups of mice were treated with NM by diet and or topically or with saline. NM significantly inhibited DMBA-induced skin tumors. Topical NM treatment prior to DMBA application was the most effective treatment (reducing the incidence of skin tumors by 86%), followed by 2-week pretreatment with a diet enriched with NM (69% reduction in tumors) and treatment with dietary NM during the study (59% reduction in tumors). These results are significant as they indicate that NM has strong potential as a therapeutic regimen for prevention and treatment of skin cancer.

A Novel Nutrient Mixture Inhibits Cell Proliferation, MMP Secretion and Invasion in HepG2 Hepatoma Cell Line
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M.W. Roomi, V. Ivanov, A. Niedzwiecki, M. Rath
Dr. Rath Research Institute, 1260 Memorex Drive, Santa Clara, CA 95050
Presented at: 46th Annual Meeting of the Society of Toxicology; Charlotte, NC; March 25-29, 2007
Published in: The Toxicologists (suppl Toxicological Sciences), Abstract #610, pg 126, 2007

  To provide a better understanding of the preventive effect of NM (a unique nutrient mixture containing lysine, proline, ascorbic acid and green tea extract) on liver cancer, we examined NM on HepG2 cell proliferation, MMP secretion, invasion, morphology, and apoptosis. NM showed dose-dependent inhibition of MMP-2, with virtual total inhibition at 500 µg/ml and dose-dependent inhibition of Matrigel invasion and migration of human hepatocellular carcinoma HepG2 with 97% inhibition at 500 µg/ml and total blockage at 1000 µg/ml. HepG2 cells showed no morphological changes below 500 µg/ml and obvious apoptosis at higher concentrations. Moderate apoptosis was observed at 100 µg/ml NM and profound at 500 and 1000 µg/ml NM. These results are significant since they suggest NM has therapeutic potential in liver cancer by inducing apoptosis and inhibiting invasive parameters.

A Novel Nutrient Mixture Induces Apoptosis in Human Prostate Cancer Cell Line Du-145
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M.W. Roomi, N.W. Roomi, V. Ivanov, A. Niedzwiecki and M. Rath
Dr. Rath Research Institute, 1260 Memorex Drive, Santa Clara, CA 95050
Presented at: GTCbio Apoptosis in Drug Discovery; San Diego, CA; March 22-23, 2007
Published in: Proccedings of the GTCbio Conference on Apoptosis in Drug Discovery

  A novel antineoplastic agent, a nutrient mixture (NM) containing lysine, proline, ascorbic acid and green tea extract demonstrates a broad spectrum of antitumor activity against a number of human cancer cell lines. We investigated whether the cytotoxic effect of NM on DU145 was consistent with its apoptotic effect on these cells. DU-145 cells treated with NM at 500 and 1000 µg/ml demonstrated profound toxicity and obvious apoptotic cells morphologically. Using caspases kit, slight apoptosis was observed at 100 µg, moderate at 500 and significant at 1000 µg/ml concentrations. The results are significant as they suggest NM as a therapeutic agent for prostate cancer, the major cancer affecting males and second most deadly cancer in the United States.

Apoptosis of Human Cervical and Ovarian Cancer Cell Lines Induced by a Novel Nutrient Mixture
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M.W. Roomi, N.W. Roomi, V. Ivanov, A. Niedzwiecki and M. Rath
Dr. Rath Research Institute, 1260 Memorex Drive, Santa Clara, CA 95050
Presented at: GTCbio Apoptosis in Drug Discovery; San Diego, CA; March 22-23, 2007
Published in: Proceedings of the GTCbio Conference on Apoptosis in Drug Discovery

  A unique antitumor agent, a nutrient mixture (NM) containing lysine, proline, ascorbic acid and green tea extract has demonstrated anticarcinogenic activity against a number of human cancer cell lines, including ovarian and cervical cancer. We investigated whether the antitumor effect of NM on cervical and ovarian cancer cell lines was due to apoptosis. NM was toxic to cervical (Hela) cells but did not affect ovarian cancer (SK-OV-3) cells. However, morphology and caspase apoptosis assays indicated that NM induced apoptosis in both cells lines – moderate at 100 µg/ml and profound at 1000 µg/ml. These results are significant as they suggest that NM has therapeutic potential in treatment of ovarian and cervical cancer.

Suppression of Growth In Vivo and In Vitro of Murine B16FO Melanoma Cells by a Novel Nutrient Mixture
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M.W. Roomi, V. Ivanov, A. Niedzwiecki and M. Rath
Presented at: 46th
Annual Meeting of The American Society for Cell Biology, San Diego December
9-13, 2006
Published in: 46th Annual Meeting of The American Society for Cell Biology, San Diego, December 9-13, 2006 Proceedings, Abstract # 1280.

  Melanoma is a very serious and highly metastatic form of skin cancer, which causes the most skin cancer-related deaths. In its advanced stages melanoma is resistant to existing therapies. We investigated the effect of a unique nutrient mixture (NM) containing lysine, proline, ascorbic acid and green tea extract on murine B16FO melanoma cells in vitro and also in vivo by injecting these melanoma cells under the skin of nude mice. After 4 weeks of supplementation with NM growth of melanoma tumors in mice was inhibited by 50%. Melanoma cells exposed to 500 and 1000 mg/ml NM concentration in vitro, exhibited 50% toxicity over the control. At these concentrations a moderate and extensive apoptosis (natural cell death) was observed respectively. These results are significant as they suggest NM as a therapeutic agent for melanoma.

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
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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.

Inhibition of Human Neuroblastoma Cell Line SK-N-MC In Vivo and In Vitro By a Novel Nutrient Mixture
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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.

In Vitro Inhibition of MMPS, Invasion and Growth of Human Fanca and Fancc Lymphoblasts by a Unique Nutrient Mixture
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M.W.Roomi, V. Ivanov, A. Niedzwiecki, M. Rath
Dr. Rath Research Institute, Oncology, 1260 Memorex Drive, Santa Clara, CA 95050
Presented at: 18th Annual Fanconi Anemia Research Fund Scientific Symposium, October 19-22, 2006, Bethesda, Maryland
Published in: 18th Annual Fanconi Anemia Research Fund Scientific Symposium proceedings, pg 64

  Fanconi anemia (FA) is a rare genetic disorder with high propensity to development of cancer. Biological agents that prevent extracellular matrix degradation by MMPs have been shown to be promising therapeutic approaches to cancer A micronutrient mixture (NM) containing ascorbic acid, lysine, proline and green tea extract has shown significant anticancer activity against a number of cancer cell lines. We investigated the effect of NM on human FANCA and FANCC lymphoblasts for viability, MMP secretion and invasion. NM inhibited MMP secretion and Matrigel invasion in FANCA, and invasion and proliferation in FANCC lymphoblasts, suggesting NM has a potential therapeutic use in the treatment strategy in FA neoplasia.

Inhibition of Hemangioendothelioma In Vivo and Invasion and Growth In Vitro by a Unique Nutrient Mixture
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M.W. Roomi, V. Ivanov, A. Niedzwiecki and M. Rath
Dr. Rath Research Institute, Oncology Division, Santa Clara, CA 95050
Presented at: 47th Annual Meeting of the American College of Nutrition, October 5-8, 2006, Reno, NV
Published in: Journal of the American College of Nutrition vol 25(5), October 2006, abstract #23

  Current treatment for infantile hemangioendothelioma includes toxic agents such as systemic corticosteroids, vincristine, and interferon-alpha. We investigated the effect of a unique non-toxic micronutrient mixture (NM) containing lysine, proline, ascorbic acid and green tea extract, which has shown significant anti-angiogenic and anti-tumor effect against a number of cancer cell lines, on nude mice injected subcutaneously with EOMA cells. In addition, we tested NM in vitro on EOMA cells evaluating its effect on cell proliferation, invasion, and cell morphology. NM inhibited the growth of tumors by 50% and exhibited dose response toxicity and inhibition of EOMA Matrigel invasion. EOMA cell morphology was not affected even at highest concentration tested. These results are significant as they indicate NM is a potential non-toxic alternative agent for treatment of infantile hemangioendothelioma.

Inhibitory Effect of a Novel Nutrient Mixture on MMP Secretion and Invasion on Human Thyroid Cancer Cell Line SW 579: In Vitro Study
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: AICR International Research Conference on Food, Nutrition and Cancer, July 13-14, 2006, Washington DC
Published in: AICR International Research Conference on Food, Nutrition and Cancer Poster Abstract Book, Abstract #42

  Mortality from thyroid cancer, the most common type of endocrine malignancy, results mainly from the tumor invading local tissues and metastasizing to vital organs such as the liver, lung, and brain. Metastasis depends upon degradation of the ECM and is mediated by MMPs. A novel nutrient mixture (NM) containing ascorbic acid, lysine, proline and green tea extract has exhibited MMP inhibition and significant anticancer activity against a number of cancer cell lines. Our in vitro study on the effect of NM on thyroid cancer cells SW 579 demonstrated inhibition of invasive parameters such as MMP secretion and Matrigel invasion, without toxicity to cells, indicating NM has therapeutic potential in treatment of thyroid cancer.

A Nutrient Mixture Consisting of Lysine, Proline, Ascorbic Acid and Green Tea Extract Inhibit Lung Metastasis by B16FO Melanoma Cells in Mice
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

A Nutrient Mixture Consisting of Lysine, Proline, Ascorbic Acid and Green Tea Extract Inhibit Lung Metastasis by B16FO Melanoma Cells in Mice
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
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.

Inhibition of MMP Activity and Cell Invasion by a Novel Nutrient Mixture on Glioma Cell Line A-172: in vitro Study
M.W. Roomi, V. Ivanov, A. Niedzwiecki and M. Rath
Dr. Rath Research Institute, Oncology Division, 1260 Memorex Drive, Santa Clara, CA 95050
Presented at: 45th Annual Meeting of The American Society for Cell Biology, San Francisco, December 10-14, 2005
Published in: 45th Annual Meeting of The American Society for Cell Biology, San Francisco, December 10-14, 2005 Proceedings, Abstract #L461

  Five-year survival rates for brain tumors are among the lowest of all cancers (pancreatic and lung being the shortest). The median survival of patients with malignant glioma is 14-36 weeks, depending upon treatment regimens, mainly due to invasion into the surrounding brain. A unique non-toxic nutrient mixture (NM) consisting of lysine, proline, ascorbic acid and green tea extract, shown to exhibit anti-tumor effects in a number of cancer cell lines both in vitro and in vivo, significantly inhibited glioma cell MMP secretion and invasion in vitro, suggesting NM as a potentially effective treatment strategy to block cell invasion of gliomas.

in vivo and in vitro Antitumor Effect of Ascrobic Acid, Lysine, Proline, and Green Tea Extract on Human Melanoma a2058 Cells
M.W. Roomi, V. Ivanov, A. Niedzwiecki, M. Rath
Dr. Rath Research Institute, Cancer Division, Santa Clara, CA 95050, USA

Presented at: AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics: Discovery, Biology, and Clinical Applications, November 14-18, 2005
Published in:
Program and Proceedings of AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics: Discovery, Biology, and Clinical Applications, Abstract #B133

  Due to metastasis, melanoma causes the most skin cancer-related deaths. MMPs, VEGF, ki 67 (proliferative protein), and constituents of ECM play critical roles in neoplastic invasion and metastasis. We found that nutrient supplemented (NM 0.5%) nude mice with melanoma xenografts developed significantly smaller tumors than did the control group of nude mice accompanied by reduced tumor tissue MMP-9 and VEGF levels and reduced mitotic index. These findings were supported by in vitro studies on melanoma A2058 cells that demonstrated NM inhibition of MMP-9 and MMP-2 secretion and dose-dependent inhibition in Matrigel invasion by these cells. Morphology was not affected even at the highest concentration of NM. These results are important as they indicate tumor growth and metastatic parameters are reduced with use of the non-toxic nutrient mixture, offering a potentially safe and effective therapeutic agent in treatment of melanoma.

Anti-Cancer Activity of a Nutrient Mixture in Malignant Leukemia Cell Line P-388 In Vitro
M.W. Roomi, V. Ivanov, A. Niedzwiecki, M. Rath
Dr. 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 _g/ml) and significant antiproliferative effect at 500 _g/ml (70%) and 1000 _g/ml (90%). These results are important as they indicate NM is a promising therapeutic agent for leukemia.

Regulation of MMP-2 and MMP-9 Expression in Childhood Osteosarcoma by Inducers and Inhibitors #95
M.W. Roomi, V. Ivanov, A. Niedzwiecki, M. Rath
Dr. Rath Research Institute, Cancer Division, Santa Clara, CA 95050, USA
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 #95

  Osteosarcoma, the most frequent malignant bone tumor of childhood, is highly invasive, leading to pulmonary metastases and eventual death, despite conventional chemotherapy and surgical treatments. Degradation of the extracellular matrix, which leads to invasion and metastasis occurs secondary to secretion of matrix metalloproteinases (MMPs), in particular MMP-2 and MMP-9. In this study the inducers and inhibitors of MMP-2 and –9 by osteosarcoma U-20S cells were studied in vitro. MMP-2 secretion by osteosarcoma cell line U-2OS was not influenced by PMA, cytokines and LPS. However, the induction of MMP-9 was associated with the inducer used, strongest with PMA, followed by cytokines, and least with LPS. MMP-2 and MMP-9 were down regulated with inhibitors. These results are important since they indicate that inhibitors such as EGCG, doxycycline and others have a significant inhibitory effect on osteosarcoma MMP-2 and MMP-9 secretion in vitro, and thus have potential in treatment of osteosarcoma.

Inhibitory Effect of a Novel Mixture Containing Ascorbic Acid, Lysine, Proline and Green Tea Extract on Critical Parameters in Cancer Progression
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.

  egradation 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.

A Novel Nutrient Mixture as an Antileukemic Agent with Matrix Metalloproteinase and Invasion Inhibitory Activities
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.

Down Regulation of Matrix Metalloproteinases and Inhibition of Cell Invasion by a Novel Nutrient Mixture in Human FA Fibroblast Cell Lines: in vitro Study
M.Waheed. Roomi, Vadim. Ivanov, Aleksandra. Niedzwiecki and Matthias Rath
Matthias Rath Research Institute, Cancer Division, Santa Clara, CA

Presented at: 17th Annual Fanconi Anemia Scientific Symposium, Geneva, Switzerland, September 29-October 2, 2005
Published in: 17th Annual Fanconi Anemia Scientific Symposium Proceedings, Poster #110

  Fanconi anemia (FA is characterized by a high probability of developing malignancies at an early age. Extracellular matrix (ECM) matrix metalloproteinases (MMPs) produced by tumor and stromal cells, in particular MMP-2 and MMP-9, play a key role in tumor invasion and metastasis. Our in vitro studies demonstrated that the nutrient mixture (NM) of ascorbic acid, lysine, proline, and green tea extract inhibited FA cell MMP expression and invasion - important parameters for cancer prevention. These results are significant as they indicate that the nutrient mixture has strong potential as a non-toxic treatment strategy in FA neoplasia.

Novel Anticarcinogenic Effect of a Nutrient Mixture: Inhibition of MMPs, Invasion and Growth of Human Rhabdomyosarcoma in vitro
Roomi MW, Ivanov V, Niedzwiecki A and Rath M
Matthias Rath Research Institute, Cancer Division, Santa Clara, CA 95050

Presented at: 46th Annual Meeting of the American College of Nutrition, Charleston, South Carolina, Sept 22-25, 2005
Published in: Journal of the American College of Nutrition, vol 24(5), Oct 2005, abstract #75

  Rhabdomyosarcoma is the most common soft tissue sarcoma of mesenchymal origin in infants and children. We investigated the effect of a nutrient mixture (NM) of lysine, proline, ascorbic acid and green tea extract, shown previously to have potent antitumor effects on various cancer cell lines, on MMP expression, invasion and growth of pediatric rhabdomyosarcoma. Matrix metalloproteinases (MMPs) play a crucial role in tumor cell invasion, metastasis and angiogenesis, due to their ability to digest ECM and basement membrane. NM inhibited MMP-2 and MMP-9 secretion in a dose-dependent fashion, with virtual total inhibition at 500 ?g/ml NM and blocked Matrigel invasion at 10, 50, 100 and 500 ?g/ml by 70%, 80%, 90% and 100% respectively. H&E staining did not indicate any change even at the highest concentration. Our results are significant as they indicate that the relatively non-toxic NM has strong potential in rhabdomyosarcoma treatment.

Studies on the Bioenhancing Effects of Red Onions and Other Nutrients on the Absorption of Epigallocatechin Gallate from Green Tea Extract in Human Volunteers
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.

Inhibition of Malignant Mesothelioma Cell Matrix Metalloproteinase Production and Invasion by a Novel Nutrient Supplement
M.W. Roomi, V. Ivanov, A. Niedzwiecki and M.Rath
Matthias Rath Research Institute, Cancer Division, Santa Clara, CA

Presented at: Directions and Needs in Asbestos Research, University of Montana, July 28-29, 2005
Published in: Conference proceedings

  Malignant mesothelioma (MM) is an asbestos-associated cancer with no known cure. It 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. The nutrient mixture (NS) of ascorbic acid, lysine, proline, arginine and green tea extract significantly inhibited MM cell MMP expression and invasion- both important parameters for cancer prevention, suggesting this nutrient mixture has strong therapeutic potential for treatment of malignant mesothelioma.

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

Anti-Angiogenic Activity of a Novel Nutrient Mixture of Lysine, Proline, Ascorbic Acid and Green Tea Extract.
M.W. Roomi, N.W. Roomi, V. Ivanov, A. Niedzwiecki and M. Rath
Matthias Rath Research, Cancer Division, 1260 Memorex Drive, Santa Clara, CA 95050
Presented at: 1st International Symposium on Cancer Metastasis and Lymphovascular System, San Francisco, CA, April 28-30, 2005

Published in: 1st International Symposium on Cancer Metastasis and Lymphovascular System: Basis for Rational Therapy, Abstract #18

  Endothelial cell proliferation, migration and subsequent invasion of the underlying stoma is critical to angiogenesis. We studied the effects of a nutrient mixture (NM) of lysine, proline, arginine, ascorbic acid, and green tea extract on angiogenic parameters of human umbilical endothelial cells (HUVECs). NM showed dose-dependent inhibition of MMP-2, Matrigel invasion, cell migration, and vascular tube with complete blockage of all parameters at 500 µg/ml. NM did not significantly decrease cell proliferation or morphology. The results are important as they indicate that NM is an effective anti-angiogenic agent with no apparent cell toxicity.

Anti-Angiogenic and Antimetastatic Activities of a Novel Nutrient Formulation of Lysine, Proline, Ascorbic Acid, and Green Tea Extract
M.W. Roomi, V. Ivanov, A. Niedzwiecki and M. Rath
Matthias Rath Research, Cancer Research Division,
1260 Memorex Drive, Santa Clara, CA 95050
Presented at: 96th Annual Meeting of the AACR, Anaheim, CA, April 16-20, 2005.
Published in: Proceedings of the 96th Annual Meeting of the AACR, Abstract #2991.

  Angiogenesis, a process of abnormal new blood vessel development from pre-existing capillaries, is a main prerequisite for tumor growth. It is a complex multi-step process that plays an important role in tumor growth, invasion and metastasis. We designed a novel formulation (NM) of ascorbic acid, lysine, proline and green tea extract that has shown significant anti-cancer activity against a number of cancer cell lines. The aim of the present study was to determine whether NM exhibits anti-angiogenic and antimetastatic effects using in vitro and in vivo experimental models. Since angiogenesis depends on the interaction between tumor cells and endothelial cells, we sought to determine the effect of NM on both cell types.

Chemoprevention with Chlorophyllin by Inhibiting MMP Expression and Invasiveness: In Vitro Studies
M.W. Roomi, V. Ivanov, A. Niedzwiecki, M. Rath
Presented at: XXV International Congress of Physiological Sciences, March 31-April 5, 2005, San Diego
Published in: The FASEB Journal, Abstracts, Abstract #860.11

  Fibrosarcoma is an aggressive and highly metastatic cancer with poor prognosis associated with both the aggressive metastatic spread characteristic of this cancer and the lack of efficacy in current treatment modalities to prevent, counteract or slow tumor progression. Chlorophyllin (CHL), a water-soluble derivative of chlorophyll, used as a food colorant and over-the counter medicine, exhibited potent antimetastatic activity on human fibrosarcoma HT180cells in vitro; it inhibited Matrigel invasion and MMP expression - both important parameters for cancer prevention.

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

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 #149

  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.

Suppression of Human Rheumatoid Synovial Fibroblast MMP-2 Expression and Marix Invasion by Nutrient Synergy
M.W. Roomi, V. Ivanov, A. Niedzwiecki and M. Rath
Matthias Rath Research, Cancer Research Division,
Santa Clara, CA 95050
Presented at: 9th World Congress of the Osteoarthritis Research Society International, Chicago, Illinois, December 2-5, 2004.
Published in: Osteoarthritis and Cartilage, Abstract #193.

  In patients with rheumatoid arthritis and other inflammatory diseases, MMPs are expressed in synovial membranes and have been implicated in synovial tissue invasion into adjacent cartilage and bone. Standard anti- arthritic drugs, used for prolonged periods, have been associated with serious side effects. We studied the in vitro effect of a mixture of nutrients containing ascorbic acid, lysine, arginine and epigallocatechin gallate on human synovial fibroblast growth, MMP expression, and invasive potential. Our results demonstrated complete inhibition of MMP-2 expression and invasive potential of synovial fibroblasts at 500 _g/ml, suggesting this nutrient mixture has excellent potential as a safe anti-inflammatory agent.

Nutrient Synergy - an Important Inhibitor of MMP-2 Expression and Invasion by Human Ovarian Cancer Cell Line SK-OV-3
M.W. Roomi, V. Ivanov, A. Niedzwiecki and M. Rath
Matthias Rath Research., Cancer Research Division,
Santa Clara, CA 95050
Presented at: International Society for Biological Therapy of Cancer, San Francisco, November 4-7, 2004.
Published in: Journal of Immunotherapy (Official journal of International Society for Biological Therapy of Cancer) volume 27, number 6, page S8, November/December 2004.

  Due to high metastasis rates, ovarian cancer is the deadliest of the gynecologic cancers and the fifth leading cause of cancer death among U.S. women. We studied the synergistic effect of a unique nutrient formulation containing lysine, proline, arginine, ascorbic acid, and epigallocatechin gallate on metastatic parameters on human ovarian cancer cells SK-OV-3, such as effect on MMP-2 and –9 expression and cancer cell invasive potential. Our results demonstrated complete inhibition of MMP-2 expression at 50 mg/ml and of Matrigel invasion at 1000 mg/ml. These findings are significant as they suggest that nutrient synergy would be an effective and safe therapeutic regimen for treatment of ovarian cancer.

Naturally Produced Extracellular Matrix Inhibits Growth Rate and Invasiveness of Human Osteosarcoma Cancer Cells
V. Ivanov, V. Ivanova, M.W. Roomi, A. Niedzwiecki and M. Rath
Matthias Rath BV, Santa Clara, CA 95050
Presented at: American College of Nutrition Symposium on Advances on Clinical Nutrition, Long Beach, CA, September 30-October 3, 2004
Published in: ACN Symposium on Advances on Clincal Nutrition Proceedings, Abstract #49,
pg 465

  Enhanced supplementation with certain naturally occurring nutrients and vitamins has been associated with a reduction in occurrence and progression of human cancer. The exact mechanisms of this action are still under investigation. Extracellular matrix (ECM) plays a key role in the development of cancer. Therefore, we studied whether nutrients could exert anti-cancer effects through alteration of ECM biological properties. The results demonstrated that the ECM produced by normal fibroblasts treated with a mixture of ascorbic acid, lysine, proline, arginine, cysteine, and green tea polyphenols significantly reduced the growth rate and invasive activity of osteosarcoma cells in contrast to the non-supplemented control. We conclude that anti-cancer effects of nutrients involve beneficial changes in ECM biological properties.

Nutrition Synergy Inhibits MMP Expression and Invasion Potential of Human Lung Carcinoma Cell Line A-549
M.W. Roomi,V. Ivanov, A. Niedzwiecki and M. Rath
Matthias Rath Research, Cancer Division, Santa Clara, CA 95050
Presented at: American College of Nutrition Symposium on Advances on Clinical Nutrition, Long Beach, CA, September 30-October 3, 2004
Published in: ACN Symposium on Advances in Clinical Nutrition Program, Abstract #50, pg 465.

  Lung cancer, the most common form of cancer diagnosed in the United States, has one of the lowest survival rates of any cancer due to a high metastatic rate and poor results with standard treatment regimens. There is compelling evidence that invasion and metastasis depend on degradation of the extracellular matrix (ECM), particularly by MMP –2 and –9 expression. In this study of the effect of a unique combination of lysine, proline, arginine, ascorbic acid, and epigallocatechin gallate on human lung cancer cell A-549 MMP expression and matrix invasion in vitro, we found complete inhibition of MMP-2 and –9 expression and Matrigel invasion at 500 _g/ml NM. These results suggest that the nutrient combination tested has great potential as a safe but effective therapeutic regimen for this highly aggressive cancer.

Antitumor Effect of Nutrient Synergy on Human Bladder Cancer Cell Lines T-24
M.W. Roomi, V. Ivanov, A. Niedzwiecki and M. Rath
A. Niedzwiecki
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.

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.

Anti-Angiogenic Effect of Nutrient Synergy on Human Synovial Sarcoma Cell Line SW 982 (2004)
Roomi MW, Ivanov V, Niedzwiecki A, Rath M.
Presented at: International Research Conference on Food, Nutrition and Cancer in Washington DC, July 15-16, 2004.
Published in: Conference Proceedings, pg. 31, Abstract #29.

  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.
Anti-Proliferative Effects of Antioxidants Using HTLV-1 Positive and Negative Malignant T-Cells (2004)
Harakeh SM, Diab-Assaf M, Niedzwiecki A, Khalife J, Abu-El-Ardat K, Roomi MW, Rath M. American University of Beirut, Beirut, Lebanon.
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.
Inhibition of N-Methyl-N-Nitrosourea-Induced Mammary Tumors by Nutrient Synergy – A Novel Anti-Cancer Agent (2004)
Roomi MW, Roomi NW, Ivanov V, Niedzwiecki A, Rath M.
Presented at: 95th Annual Meeting of American Association for Cancer Research, Orlando, FL, March 27-31, 2004.
Published in: 95th Annual Meeting of American Association for Cancer Research Proceedings, 45:881, March 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.
Inhibition of Tumor Growth of Human Breast, Prostate, Colon and Melanoma Cancer Xenografts by Nutrient Synergy in Nude Mice (2003)
Roomi MW, Roomi NW, Ivanov V, Netke SP, Niedzwiecki A, Rath M.
Presented at: 43rd Annual Meeting of the American Society for Cell Biology
Published in: The American Society for Cell Biology 43rd Annual Meeting Abstract, p. 921, Abstract #B132, December 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-Tumor Effect of Nutrient Synergy: A Novel MMP Inhibitor in Pancreatic Cancer Cell Line MIA PaCa-2 (2003)
Roomi MW, Ivanov V, Niedzwiecki A, Rath M.
Presented at: AACR-NCI-EORTC International Conference on Molecular Targets and Cancer, Boston, November 17-21, 2003.
Published in: Program Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer, p. 165, Abstract #B196.
  Cancer of the pancreas is a highly lethal disease with the poorest likelihood of survival among all major malignancies; metastasis is associated with more than 80% of the cases. This study demonstrated significant inhibition of the metastatic parameters of MMP expression, invasion, and angiogenesis, suggesting NS is an excellent candidate for therapeutic use in the treatment of pancreatic cancer.
Nutrient Synergy Counteracts Carcinogenic Activity of Estrogen in Cultured Human Cancer Cells (2003)
Ivanov V, Roomi MW, Niedzwiecki A, Rath M.
Presented at: American College of Nutrition, Nashville, Tennessee, October 9-12, 2003.
Published in: Journal of the American College of Nutrition, 22 (5):466, Abstract #44.
  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.
Serum Markers of the Liver, Heart, and Kidney and Lipid Profile and Histopathology in ODS Rats Treated With Nutrient Synergy (2003)
Roomi MW, Ivanov V, Netke SP, Niedzwiecki A, Rath M.
Presented at: American College of Nutrition, Nashville, Tennessee, October 9-12, 2003.
Published in: Journal of the American College of Nutrition, 22 (5):477, Abstract #86.
  These results demonstrate that Nutrient Synergy has neither adverse effects on vital organs nor on the associated serum enzymes, and i