Minnie Malik
USUHS, Obstetrics and Gynecology, Faculty Member
Curcumin has antioxidative, anti-inflammatory, and chemopreventive activities. To determine whether aging affects the inhibition of colon carcinogenesis by curcumin, young (6 wk), mature (12 mo), and old (22 mo) F344 male rats were fed... more
Curcumin has antioxidative, anti-inflammatory, and chemopreventive activities. To determine whether aging affects the inhibition of colon carcinogenesis by curcumin, young (6 wk), mature (12 mo), and old (22 mo) F344 male rats were fed either AIN-93 containing 0.6% curcumin or AIN-93 control diet. Aberrant crypt foci (ACF) were induced with two weekly s.c. injections of azoxymethane. After an additional 3 mo on the diets, the number, multiplicity, and distribution of ACF were evaluated. Addition of curcumin to the diet reduced the number of ACF by 49% in young rats and by 55% in old rats (P < 0.05). However, interestingly, no reduction of ACF was found in mature rats fed curcumin. Inhibition of large ACF was also affected by age, with the greatest reduction of large ACF occurring in old rats. However, animal age did not significantly alter the effect of dietary curcumin on reduction of cyclooxygenase-2 mRNA expression in the liver or reduction of serum total cholesterol levels. These results indicate that age may play a significant role in the efficacy of chemoprevention of colon cancer by curcumin.
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Soy isoflavones are popular supplements among middle-aged and older women based on their potential protection against cancer and their use as alternative hormone replacement therapy. The purpose of this study was to investigate the... more
Soy isoflavones are popular supplements among middle-aged and older women based on their potential protection against cancer and their use as alternative hormone replacement therapy. The purpose of this study was to investigate the effects of dietary soy isoflavones on early stage colon cancer in various ages of female rats. Young (1month), mature (11month) and old (22month) female Fisher 344 rats were fed either the control diet or a diet containing 0.4% soy isoflavone isolate for 1week, injected once with 20mg/kg azoxymethane (AOM) and maintained on the diets for another 15weeks. The concentration of isoflavones in the diet was 2g/kgdiet, composed of 1.2g/kg genistin, 0.7g/kg daidzin and 0.1g/kg other isoflavones including glycitin, acetylgenistin, acetyldaidzin, genistein, daidzein, and glycitein. There was no difference over all ages in the development of preneoplastic colonic aberrant crypt foci between rats fed the soy compared to the control diet, indicating that the soy diet did not provide protection against early stage colonic carcinogenesis. On the contrary, several adverse effects of soy supplementation in female AOM-treated rats were observed. Soy-supplemented rats had greater weight loss and a slower recovery of body weight following the AOM injection compared to rats fed the control diet and these changes increased with age. Five of the 21 rats fed the soy supplement died before the end of the experiment while all animals on the control diet survived to term. The density of normal crypts lining the colonic mucosa was reduced in rats fed the soy compared to control diet, indicating gastrointestinal damage. Uterine weights, serum estradiol and serum isoflavone levels were increased in mature and old female rats fed the soy-supplemented diets compared to age-matched controls, suggesting an increasing estrogenic response with age to isoflavone supplementation. These adverse effects of soy isoflavones in aged female animals need further examination because women, and particularly older women, are the prime target population for consumption of soy supplements.
Research Interests: Endocrinology, Aging, Biology, Internal Medicine, Female, and 15 moreAnimals, Dietary Supplements, Colon cancer, Body Weight, Food Sciences, Genistein, Colon, Estradiol, Hormone Replacement Therapy, Daidzein, Adverse effect, isoflavones, aberrant crypt foci, Estrogen Receptor beta, and Colonic Neoplasms
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Research Interests: Molecular Biology, Biology, Membrane Proteins, Capillary electrophoresis, Medicine, and 15 moreHumans, Automation, Organization Development, Chemoprevention, Agarose Gel Electrophoresis, Public health systems and services research, Isoenzymes, Cost Benefit Analysis, Multiplex, Gene expression profiling, Ethidium bromide, reverse transcriptase polymerase chain reaction, Colonic Neoplasms, multiplex polymerase chain reaction, and Cyclooxygenase
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Uterine leiomyomata are the most common benign tumors of the gynecologic tract impacting up to 80% of women by 50 years of age. It is well established that these tumors are the leading cause for hysterectomy with an estimated total... more
Uterine leiomyomata are the most common benign tumors of the gynecologic tract impacting up to 80% of women by 50 years of age. It is well established that these tumors are the leading cause for hysterectomy with an estimated total financial burden greater than $30 billion per year in the United States. However, for the woman who desires future fertility or is a poor surgical candidate, definitive management with hysterectomy is not an optimal management plan. Typical gynecologic symptoms of leiomyoma include infertility, abnormal uterine bleeding (AUB)/heavy menstrual bleeding (HMB) and/or intermenstrual bleeding (IMB) with resulting iron-deficiency anemia, pelvic pressure and pain, urinary incontinence, and dysmenorrhea. The morbidity caused by these tumors is directly attributable to increases in tumor burden. Interestingly, leiomyoma cells within a tumor do not rapidly proliferate, but rather the increase in tumor size is secondary to production of an excessive, stable, and aber...
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Uterine leiomyomata (fibroids) are prevalent, sex hormone-dependent tumors with an altered response to mechanical stress. Ulipristal acetate, a selective progesterone receptor modulator (SPRM), significantly reduces fibroid size in... more
Uterine leiomyomata (fibroids) are prevalent, sex hormone-dependent tumors with an altered response to mechanical stress. Ulipristal acetate, a selective progesterone receptor modulator (SPRM), significantly reduces fibroid size in patients. However, progesterone receptor signaling in fibroids and its relationship to mechanical signaling is incompletely understood. Our prior studies revealed that A-kinase Anchoring Protein 13 (AKAP13) was overexpressed in fibroids and contributed to altered mechanotransduction in fibroids. Since AKAP13 augmented nuclear receptor signaling in other tissues, we sought to determine whether AKAP13 might influence progesterone receptor signaling in fibroids. Fibroid samples from patients treated with ulipristal acetate or placebo were examined for AKAP13 expression by immunohistochemistry. In immortalized uterine fibroid cell lines and COS-7 cells, we observed that AKAP13 increased ligand-dependent progesterone receptor (PR) activation of luciferase repo...