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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.
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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. |
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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 |
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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.
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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. |
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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.
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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. |
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| Bone
Cancer |
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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.
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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.
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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.
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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. |
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| Breast
Cancer |
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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
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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. |
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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.
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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. |
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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
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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. |
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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
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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. |
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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 |
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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. |
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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
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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. |
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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 |
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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. |
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| Cervical
Cancer |
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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. |
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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.
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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 |
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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.
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| Colon
Cancer |
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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.
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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. |
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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
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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. |
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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
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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. |
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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
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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. |
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| Fibrosarcoma |
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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 |
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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. |
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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 |
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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. |
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| Cancer
- General |
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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 |
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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. |
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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 |
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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. |
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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 |
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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. |
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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 |
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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. |
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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. |
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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. |
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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 |
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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. |
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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. |
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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. |
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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. |
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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. |
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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
- NEW -
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
- NEW -
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
- NEW -
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
on Lung Cancer Cell Line A-549- NEW -
M.Waheed Roomi, Vadim Ivanov, Tatiana
Kalinovsky, Aleksandra Niedzwiecki, and Matthias Rath
Published in: Experimental Lung Research, 2006, 32:1-13. |
|
|
| |
Suppression of lung tumor growth in nude mice and inhibition of MMP secretion and Matrigel
invasion suggest NM as a potential non-toxic therapeutic agent for lung cancer. |
|
|
Inhibition
of Malignant Mesothelioma Cell Matrix Metalloproteinase Production
and Invasion by a Novel Nutrient mixture-
NEW -
M.W. Roomi,
V. Ivanonv, T. Kalinovsky, A. Niedzwiecki, M. Rath
Published in: Experimental Lung Research,
32:69-79, 2006. |
|
|
| |
In
conclusion, NM significantly inhibited MM cell MMP secretion
and invasion- both important parameters for cancer prevention,
suggesting NM as an effective treatment strategy for MM. |
|
|
Inhibition
Of Malignant Mesothelioma Cell Matrix Metalloproteinase Production
And Invasion By A Novel Nutrient Supplement -
NEW -
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. |
|
|
Nutrition
Synergy Inhibits MMP Expression and Invasion Potential of
Human Lung Carcinoma Cell Line A-549 (2004)
M.W.
Roomi, V. Ivanov, A. Niedzwiecki, 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 µg/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. |
|
| Melanoma |
|
Suppression
of Growth In Vivo and In Vitro of Murine B16FO Melanoma Cells
by a Novel Nutrient Mixture
- NEW -
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 # 1280.32. |
|
|
| |
Taken
together these results suggest that NM has many attractive
features as a new anti-tumor agent. |
|
|
In Vitro and In Vivo Antitumor Effect
of Ascorbic Acid, Lysine, Proline, And Green Tea Extract
On Human Melanoma Cell Line A2058
- NEW -
M.W. Roomi, N. Roomi, V. Ivanov, T.
Kalinovsky, A. Niedzwiecki, M. Rath
Published in: In Vivo
– 2006;20(1):25-32. |
|
|
| |
The
results of this study demonstrated that the nutrient mixture
tested significantly suppressed tumor growth of melanoma cancer
A2058 in male athymic nude mice and significantly inhibited
MMP secretion, and invasion of melanoma cells in vitro, offering
promise for therapeutic use in the treatment of melanoma. |
|
|
in
vivo and in vitro Antitumor Effect of Ascrobic
Acid, Lysine, Proline, and Green Tea Extract on Human Melanoma
a2058 Cells - NEW -
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. |
|
|
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. |
|
|
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. |
|
| Methodology |
| |
A
Novel In Vitro Bioassay for Screening Matrix Metalloproteinase
Activity in Human Cancer Cell Lines (2003)
M.W.
Room, V. Ivanov, S.P. Netke, A. Niedzwiecki, M. Rath
Presented at: 94th Annual Meeting of AACR
(American Association for Cancer Research)
Washington DC, July 11-14, 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. There is compelling
evidence to suggest that MMP-2 and MMP-9 play important roles
in tumor invasion and metastasis. This study demonstrated
that the technique of co-culture assay offers a superior screening
system for potential cancer drugs or agents that have either
enhancing or inhibitory effects on MMPs. |
|
| Osteosarcoma |
|
Naturally
Produced Extracellular Matrix Inhibits Growth Rate and Invasiveness
of Human Osteosarcoma Cancer Cells (2004)
V.
Ivanov, S. Ivanova, M.W. Roomi, A. Niedzwiecki, 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 Clinical 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. |
|
| Ovarian
Cancer |
|
Inhibition of Matrix Metalloprotenase-2 Secretion and Invasion by Human Ovarian Cancer Line SK-OV-3
with Lysine, Proline, Arginine, Ascorbic Acid and Green Tea Extract
M.W. Roomi, V. Ivanov, T. Kalinovsky, A. Niedzwiecki and M. Rath
Published in: Journal of Obstetrics and Gynecology -
2006; 32(2):148-154. |
|
|
| |
The combination of lysine,
proline, arginine, ascorbic acid, and green tea extract tested inhibited critical
steps in cancer development and spread, such as MMP secretion and invasion, indicating
its potential as a treatment modality against ovarian cancer. |
|
|
Nutrient
Synergy - an Important Inhibitor of MMP-2 Expression and Invasion
by Human Ovarian Cancer Cell Line SK-OV-3 (2004)
M.W.
Roomi, V. Ivanov, A. Niedzwiecki, 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.
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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 µg/ml and of Matrigel
invasion at 1000 µg/ml. These findings are significant
as they suggest that nutrient synergy would be an effective
and safe therapeutic regimen for treatment of ovarian cancer. |
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| Pancreatic
Cancer |
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Anti-Tumor
Effect of Nutrient Synergy: A Novel MMP Inhibitor in Pancreatic
Cancer Cell Line MIA PaCa-2 (2003)
M.W.
Roomi, V. Ivanov V, Niedzwiecki, M. Rath
Presented at: AACR-NCI-EORTC International
Conference on Molecular Targets and Cancer
Boston, MA, November 17-21, 2003
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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. |
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| Pediatric
Cancers |
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In Vitro Inhibition of MMPs, Invasion and Growth of Human FANCA and FANCC
Lymphoblasts by a Unique Nutrient Mixture
- 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 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. |
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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. |
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Regulation
of MMP-2 and MMP-9 Expression in Childhood Osteosarcoma by
Inducers and Inhibitors #95
- NEW -
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 |
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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. |
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Inhibition
of MMP Activity and Cell Invasion by a Novel Nutrient Mixture
on Glioma Cell Line A-172: in vitro Study
- NEW -
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 |
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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. |
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Novel
Anticarcinogenic Effect Of A Nutrient Mixture: Inhibition
Of Mmps, Invasion And Growth Of Human Rhabdomyosarcoma In
Vitro - NEW -
M.W.
Roomi, V. Ivanov, A. Niedzwiecki, M. Rath
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
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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. |
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Down
Regulation Of Matrix Metalloproteinases And Inhibition Of
Cell Invasion By A Novel Nutrient Mixture In Human Fa Fibroblast
Cell Lines: In Vitro Study
- NEW -
M.W. Roomi, V. Ivanov,
A. Niedzwiecki, M. 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
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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. |
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| Prostate
Cancer |
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Inhibition
of Tumor Growth of Human Breast, Prostate, Colon and Melanoma
Cancer Xenografts by Nutrient Synergy in Nude Mice
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 |
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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. |
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| Thyroid
Cancer |
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Inhibitory
Effect of a Novel Nutrient Mixture on MMP Secretion and Invasion
on Human Thyroid Cancer Cell Line SW 579: In Vitro
Study
- NEW -
M.W. Roomi, N.W. Roomi, V. Ivanov, A.
Niedzwiecki, M. Rath
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
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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. |
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