Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Reexamination Certificate
2000-06-05
2002-08-27
Goldberg, Jerome D. (Department: 1614)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
C514S460000
Reexamination Certificate
active
06441029
ABSTRACT:
STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT
Not applicable.
BACKGROUND
Sundry mevalonate-derived constituents (isoprenoids) of fruits, vegetables and cereal grains suppress chemically-initiated carcinogenesis. This action has been attributed to the isoprenoid-mediated induction of detoxifying activities and to the antioxidant activity of some isoprenoids. Neither action explains the potent impact isoprenoids have on the promotion/progression stage of chemically-initiated carcinogenesis and on the growth of chemically established and implanted tumors (reviewed by Elson, 1995; Elson and Yu, 1994). Isoprenoids differ substantially in the impact they have on tumor growth. Isoprenoids suppress, via post-transcriptional actions (Correll, et al., 1994; Parker, et al., 1993; D. M. Peffley and A. K. Gayen, personal communication), 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity, the activity deemed to be rate-limiting for the synthesis of cholesterol. The statins are competitive inhibitors of HMG-CoA reductase. Correlations between the late stage tumor-suppressive potency of diverse isoprenoids and their impact on HMG-CoA reductase activity approach unity. The reductase activity of tumors differs from that of liver in being resistant to sterol feedback regulation. The tumor activity however retains high sensitivity to post-transcriptional regulation as triggered by diverse isoprenoids. As a consequence of the isoprenoid-mediated suppression of HMG-CoA reductase activity the pools of mevalonate pathway intermediates become limiting for the post-translational processing of growth-associated proteins (reviewed by Elson, 1995; Elson and Yu, 1994).
One recent review presented a list of structurally diverse isoprenoids with varying capacity to suppress mevalonate synthesis (Elson, 1995).
SUMMARY OF THE INVENTION
In one embodiment, the present invention is a method for inhibiting tumor cell growth. The method comprises treating the cell with a combination of at least two products of the mevalonate pathway selected from the group consisting of statins, ionones and tocotrienols.
In one preferred embodiment, the ionone is selected from the group consisting of &bgr;-ionone; 6-10-dimethyl-undec-3,5-ene-2,9-dione; 6,10-dimethyl-9,10-epoxy-undec-3,5-ene-2-one; 9,10-diacetoxy-6,10-dimethyl-undec-3,5-ene-2-one; 6,10-dimethyl-9,10-diol-undec-3,5-ene-2-one and &agr;-ionone. Preferred tocotrienols include d-&ggr;-tocotrienol, 2-desmethyltocotrienol, d-&dgr;-tocotrienol and d-tocotrienol. Preferred statins include lovastatin, pravastatin, simvastatin and fluvastatin.
In another form, the present invention is a pharmaceutical composition for treating or preventing tumors comprising effective amounts of at least two agents selected from the group consisting of tocotrienols, statins and ionones.
It is an object of the present invention to prevent or reduce tumor growth and metastasis.
It is another object of the present invention to increase the duration of survival of a tumor patient following detection of tumor.
It is another object of the present invention to prevent tumor formation.
Other objects, advantages and features of the present invention will become apparent to one of skill in the art after review of the specification, claims and drawings.
REFERENCES:
patent: 4789554 (1988-12-01), Scavone et al.
patent: RE33885 (1992-04-01), Mattson
patent: 5157132 (1992-10-01), Tan et al.
patent: 5190618 (1993-03-01), Top et al.
patent: 5204373 (1993-04-01), Pearce et al.
patent: 5217992 (1993-06-01), Wright et al.
patent: RE34617 (1994-05-01), Jandacek et al.
patent: 5376361 (1994-12-01), Perricone
patent: 5391765 (1995-02-01), Pearce et al.
patent: 5393776 (1995-02-01), Pearce
patent: 5411969 (1995-05-01), Pearce et al.
patent: 5475029 (1995-12-01), Bradfute et al.
patent: 5500154 (1996-03-01), Bacon et al.
patent: 5554647 (1996-09-01), Perricone
patent: 5574063 (1996-11-01), Perricone
patent: 5591772 (1997-01-01), Lane et al.
patent: 5605930 (1997-02-01), Samid
patent: 0 382 075 (1990-02-01), None
patent: WO 93/16690 (1993-09-01), None
patent: WO 93/20183 (1993-10-01), None
patent: WO 93/23034 (1993-11-01), None
Carroll et al., Nutr., Lipids, Health, Dis., (1995), 117-21 Abstract Only.*
Larsson, Glycobiology (1993), 3(5), 475-9 Abstract Only.*
S.A. Broitman, et al., “Effect of monoterpenes and mevinolin on murine colon tumor CT-26 in vitro and its hepatic ‘metastases’ in vivo,” Dietary Phytochemicals in Cancer Prevention and Treatment, American Institute for Cancer Research, Plenum Press, New, York pp 111-13 (1996).
K.K. Carroll, et al., “In vitro inhibition of proliferation of MDA-MB-45 human breast cancer cells by combinations of tocotrienols and flavonoids,” FASEB J. 9:A868, 1995 (Abstract).
G.L. Case, et al., “Induction of geranyl pyrophosphate pyrophosphatase activity by cholesterol-suppressive isoprenoids,” Lipids 30(4):357-359, 1995.
C.E. Elson, “Cholesterol-suppressive and anticarcinogenic actions of anutrient, isoprenoid-derived constituents of food,” J. Opt. Nut. 1:16-20, 1992.
C.E. Elson, “The impact of palm oil on experimental carcinogenesis,” In Vitamin E in Health and Disease, ed. L. Packer and J. Fuchs, Marcel Dekker, Inc., New York, pp. 533-545, 1993.
C.E. Elson, “Dietary fat and cancer: Anamolous responses to dietary palm oil,” Perspectives, A Quarterly Report on New Developments in Fats and Oils Nutrition & Health, pp. 1-4, 1993.
C.E. Elson and S.G. Yu, “Coupling the cholesterol- and tumor-suppressive actions of palm oil to the impact of its minor constituents on mevalonate synthesis,” Perspectives, A Periodic Report on New Developments in Fats and Oils Nutrition & Health, p. 1, 1994.
C.E. Elson, Dietary fat and cardiovascular disease: Periodic report on new developments in fats and oils nutrition & health, p. 1, 1994.
C.E. Elson and S.G. Yu, “The chemoprevention of cancer by mevalonate-derived constituents of fruits and vegetables,” Am. Ins. Nutr. pp. 607-614, 1994.
C.E. Elson, “Suppression of mevalonate pathway activities by dietary isoprenoids: Protective roles in cancer and cardiovascular disease,” Am. Ins. Nutr. pp. 1666S-1672S, 1995.
C.E. Elson, et al., “The cholesterol- and tumor-suppressive actions of palm oil isoprenoids,” Nutrition, Lipids, Health and Disease, Ong, A.S.H., et al., AOCS Press, Champaign, IL, pp. 109-116, 1995.
C.E. Elson, “Dietary fat and cardiovascular disease: Anomalous responses to palm oil,” Malaysian Oil Sci. & Tech. 4:18-22, 1995.
C.E. Elson and A.A. Qureshi, “Coupling the cholesterol- and tumor-suppressive actions of palm oil to the impact of its minor constituents of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity,” Prostagland. Leukot. Essen. Fat. Acids 52:205-208, 1995.
C.E. Elson, “Novel lipids and cancer: Isoprenoids and other phytochemicals,” Dietary Fats, Lipids, Hormones, and Tumorigenesis; Heber and Kritchevsky, Plenum Press, New York, pp. 71-86, 1996.
C.E. Elson, et al., “Functional consequences fo the modulation of 3-hydroxy-3-methylglutaryl coenzyme A(1) reductase by isoprenoids,” Mar. 28-Apr. 1, 1998 (AACR Abstract).
S.H. Goh, et al., “Inhibition of tumour promotion by various palm-oil tocotrienols,” Int. J. Cancer 57:529-531, 1994.
M.N. Gould, et al., “A comparison of tocopherol and tocotrienol of the chemoprevention of chemically induced rat mammary tumors,” Am. J. Nutr. 53:1068S-1070S, 1991.
N. Guthrie, et al., “Inhibition of proliferation of MDA-MB-435 human breast cancer cells by individual tocotrienols from palm oil,” AACR Proc. 35:629, 1994 (Abstract).
N. Guthrie, et al., “In vitro inhibition of proliferation fo receptor-positive MCF-7 human breast cancer cells by palm oil tocotrienols,” FASEB J. 9:A988, 1995 (Abstract).
N. Guthrie, et al., “Effect of palm oil tocotrienols on the proliferation of ras-transformed NIH-3T3 cells an on farnesyl: and geranylgeranyl:protein transferase activity,” FASEB J. 10:A559, 1996 (Abstract).
N. Guthrie, et al., “Combined effects of palm oil tocotrienols, flavonoids and tamoxifen on the proliferation of estrogen receptor-positive MCF-7 human breast cancer c
Goldberg Jerome D.
Quarles & Brady LLP
Wisconsin Alumni Research Foundation
LandOfFree
Method of suppressing tumor growth with combinations of... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Method of suppressing tumor growth with combinations of..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Method of suppressing tumor growth with combinations of... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2931656