Research
Summary
Recent
Publications
Contact Information
Lab Members
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RESEARCH
SUMMARY
The scope of Strang’s clinical research program extends from preclinical studies to clinical trials, focusing on chemopreventive agents and mechanisms that inhibit neoplasia; results identify the effects of novel chemopreventive agents and gene-nutrient interactions that occur in tumor inhibition. Findings in some preclinical studies are advanced to clinical trials thus extending the observations to human populations. We have developed a wide variety of new experimental models to aid these objectives. Current preclinical studies have focused on the effects of various chemopreventive regimens for colon, breast and prostate gland. In recent preclinical studies mutations in Apc and mismatch repair genes induced intestinal tumors in mice, and increasing dietary calcium and vitamin D decreased these tumors. Modifying rodent diets to mimic human Western diets also induced precancerous lesions in rodent breast tissue, and caused adenomas and carcinoma to develop in intestine.
Current clinical protocols are analyzing the effects of nutrients on differential gene expression in colonic cells under controlled dietary conditions, and include modulation of gene expression by calcium, vitamin D and folic acid. A further protocol is analyzing estrogen effect on vitamin D receptor expression in colonic cells, and possible interrelationships of estrogen and vitamin D in inhibiting tumors in the colon. In a recent clinical study, increasing dietary calcium by ingesting calcium-enriched foods normalized the growth and maturation of human colonic epithelial cells, extending previous observations on dietary calcium’s efficacy as a putative chemopreventive agent in the colon. A recent clinical study also indicated that estrogen increased the activity of vitamin D in colonic cells, identifying an interrelationship between the mechanism of action of vitamin D and estrogen both of which have antitumor effects in the colon. Other agents are also under study in preclinical as well as clinical protocols.
SELECTED
RECENT PUBLICATIONS
Yang G, Scherer SJ, Shell SS, Yang K, Kim M, Lipkin M, Kucherlapati R, Kolodner RD, Edelmann W. Dominant effects of an Msh6 missense mutation on DNA repair and cancer susceptibility. Cancer Cell 2004; 6: 139-150.
Lamprecht SA, Lipkin M. Chemoprevention of colon cancer by calcium, vitamin D, and folate: molecular mechanisms. Nature Reviews Cancer 2003; 3: 601-614.
Holt, P.R., Arber, N., Halmos, B., Forde, K., Kissileff, H., McGlynn, KA., Moss, SF., Fan, K., Yang, K., Kurihara, N., Lipkin, M. Colonic Epithelial Cell Proliferation Decreases with Increasing Levels of Serum 25-Hydroxy Vitamin D. Cancer Epidemiology Biomarkers Prevention 2002; 11: 113-119.
Lin DP, Wang Y, Scherer SJ, Clark AB, Yang K, Avdievich E, Jin B, Werling U, Parris T, Kurihara N, Umar A, Kucherlapati R, Lipkin M, Kunkel TA, Edelmann W. An Msh2 point mutation uncouples DNA mismatch repair and apoptosis. Cancer Research 2004; 64: 517-522.
Lipkin,
M. Early Development of Cancer Chemopreventive Clinical Trials:
Studies of Dietary Calcium as a Chemopreventive Agent for Human
Subjects. European Journal of Cancer Prevention 2002; 11:S1-S7
Velcich, A., Yang, WC., Heyer, J., Fragale, A., Nicholas, C., Viani,
S., Kucherlapati, R., Lipkin, M., Yang, K., Augenlicht, L. Colorectal
Cancer In Mice Genetically Deficient in the Mucin Muc2. Science
2002; 295: 1726-
Lamprecht, S.A., Lipkin, M. Cellular Mechanisms of Calcium and Vitamin
D in the Inhibition of Colorectal Carcinogenesis. Annals of New
York, Academy of Sciences 2001; 952: 73-85
Tangpricha, V., Flanagan, J.N., Whitlatch, L.W., Tseng, C.C., Chen,
T.C., Holt, P.R., Lipkin, M., Holick, M.F. 25-hydroxyvitamin D-1a-hydroxylase
in normal and malignant colon tissue. The Lancet 2001; 357: 1673-1674.
Holt, P.R., Arber, N., Halmos, B., Forde, K., Kissileff, H., McGlynn,
KA., Moss, SF., Fan, K., Yang, K., Kurihara, N., Lipkin, M. Colonic
Epithelial Cell Proliferation Decreases with Increasing Levels of
Serum 25-Hydroxy Vitamin D. Cancer Epidemiology Biomarkers Prevention
2002; 11: 113-119.
Newmark, HL., Yang, K., Lipkin, M., Kopelovich, L., Liu, Y., Fan,
K., Shinozaki, H. A Western-style diet induces benign and malignant
neoplasms in the colon of normal C57Bl/6 mice. Carcinogenesis 2001;
11: 1871-1875.
Edelmann, W., Umar, A., Yang, K., Heyer, J., Kucherlapati, M., Lia,
M., Kneitz, B., Avdievich, E., Fan, K., Wong, E., Crouse, G., Kunkel,
T., Lipkin, M., Kolodner, R.D., Kucherlapati, R. The DNA Mismatch
Repair Genes Msh3 and Msh6 Cooperate in Intestinal Tumor Suppression.
Cancer Research 2000; 60: 803-807.
CONTACT
INFORMATION
Martin
Lipkin, MD
Strang
Cancer Research Laboratory
The Rockefeller University
1230 York Avenue
New York, NY 10021
Telephone:
212-734-0567 ext.208
Fax: 212-570-6995
e-mail: lipkin@rockvax.rockefeller.edu
LINKS
New
York Presbyterian Hospital
Weill Medical College of Cornell
University
The Rockefeller University
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