The nutritional herb inhibits the growth in a model for the Luminal A molecular subtype of breast cancer.

The Luminal A subtype of breast cancer expresses the estrogen receptor (ER)-α and progesterone receptor (PR), but not the human epidermal growth factor receptor (HER)-2 oncogene. This subtype of breast cancer responds to endocrine therapy involving the use of selective estrogen receptor modulators and/or inhibitors of estrogen biosynthesis. However, these therapeutic agents are frequently associated with long-term systemic toxicity and acquired tumor resistance, emphasizing the need to identify non-toxic alternative treatments for chemo-endocrine therapy responsive breast cancer.

Evaluation of 3,3'-diindolylmethane with gardasil quadrivalent HPV vaccine in K14-HPV16-transgenic mice cervical histology.

Background: The effects of 3,3'-diindolylmethane (DIM) together with the Gardasil vaccine on cervical histology were evaluated using the K14-HPV16-transgenic mouse model. The possibility that DIM could enhance the efficacy of this preventive vaccine in this model was explored.

Materials And Methods: Transgenic mice were given 1000 mg/kg of DIM in the diet for 28 weeks.

Polychlorinated biphenyl exposure, diabetes and endogenous hormones: a cross-sectional study in men previously employed at a capacitor manufacturing plant.

Background: Studies have shown associations of diabetes and endogenous hormones with exposure to a wide variety of organochlorines. We have previously reported positive associations of polychlorinated biphenyls (PCBs) and inverse associations of selected steroid hormones with diabetes in postmenopausal women previously employed in a capacitor manufacturing plant.

Methods: This paper examines associations of PCBs with diabetes and endogenous hormones in 63 men previously employed at the same plant who in 1996 underwent surveys of their exposure and medical history and collection of bloods and urine for measurements of PCBs, lipids, liver function, hematologic markers and endogenous hormones.

3,3'-Diindolylmethane increases serum interferon-γ levels in the K14-HPV16 transgenic mouse model for cervical cancer.

Unlabelled: While cervical cancer incidence and mortality rates have declined in the United States, this cancer represents a worldwide threat. Human papilloma viral infection causes cervical neoplasia (CIN). 3,3'-Diindolylmethane (DIM) prevents or inhibits the progression from cervical dysplasia to cancer.

Adipocyte-derived factor as a modulator of oxidative estrogen metabolism: implications for obesity and estrogen-dependent breast cancer.

The role of body fat as a risk factor for breast cancer has been well established. A decrease in the urinary 2/16α-hydroxyestrone ratio has also been shown to be a risk marker for breast cancer. These two observations are connected by the fact that obese women have decreased levels of 2-hydroxyestrone.

Results from a dose-response study using 3,3'-diindolylmethane in the K14-HPV16 transgenic mouse model: cervical histology.

The human papilloma virus is the major cause of cervical cancer. Viral infection initiates cervical intraepithelial neoplasia, which progresses through several stages to cervical cancer. The objective of this study is to identify the minimum effective dose of diindolylmethane that prevents the progression from cervical dysplasia to carcinoma in situ.

3,3'-diindolylmethane modulates estrogen metabolism in patients with thyroid proliferative disease: a pilot study.

Background: The incidence of thyroid cancer is four to five times higher in women than in men, suggesting a role for estrogen (E₂) in the pathogenesis of thyroid proliferative disease (TPD) that comprises cancer and goiter. The objective of this study was to investigate the antiestrogenic activity of 3,3'-diindolylmethane (DIM), a bioactive compound derived from cruciferous vegetables, in patients with TPD.

Methods: In this limited phase I clinical trial study, patients found to have TPD were administered 300 mg of DIM per day for 14 days.

Effects of a breast-health herbal formula supplement on estrogen metabolism in pre- and post-menopausal women not taking hormonal contraceptives or supplements: a randomized controlled trial.

Introduction: Both indole-3-carbinol and dietary lignans have beneficial effects on estrogen metabolism and breast cancer risk. There is no published literature on the effects of a combination product. This study was designed to investigate the impact of a combination product on estrogen metabolism.

Diindolylmethane inhibits cervical dysplasia, alters estrogen metabolism, and enhances immune response in the K14-HPV16 transgenic mouse model.

This study was designed to establish whether 3,3'-diindolylmethane (DIM) can inhibit cervical lesions, alter estrogen metabolism in favor of C-2 hydroxylation, and enhance immune function in the K14-HPV16 transgenic mouse model. Mice were bred, genotyped, implanted with E(2) pellets (0.25 mg/90-day release) under anesthesia, and divided into groups.

Lycium barbarum inhibits growth of estrogen receptor positive human breast cancer cells by favorably altering estradiol metabolism.

Selective estrogen receptor modulators represent accepted therapy for estrogen receptor positive (ER+) breast cancer, exhibit adverse side effects, and reduce patient compliance. The use of phytoestrogen containing herbal medicines is limited because of efficacy and safety concerns. The ER+ MCF-7 model examined growth inhibitory effects of the medicinal herb Lycium barbarum (LB) and identified mechanistic leads for its efficacy.

Dietary seaweed modifies estrogen and phytoestrogen metabolism in healthy postmenopausal women.

Seaweed and soy foods are consumed daily in Japan, where breast cancer rates for postmenopausal women are significantly lower than in the West. Likely mechanisms include differences in diet, especially soy consumption, and estrogen metabolism. Fifteen healthy postmenopausal women participated in this double-blind trial of seaweed supplementation with soy challenge.

Estrogen hydroxylation--the good and the bad.

Although estradiol itself is primarily responsible for female development, the metabolites are responsible for many of the other positive and negative properties of estrogens. Phase I metabolism of estradiol is exclusively oxidative unlike the other steroid hormones and involves a series of hydroxylations. The specific hydroxylations can be induced or suppressed by endogenous or exogenous compounds that influence the cytochrome enzymes that act on specific sites on the molecule.

Omega oxidation of 3-hydroxy fatty acids by the human CYP4F gene subfamily enzyme CYP4F11.

Long-chain 3-hydroxydicarboxylic acids (3-OHDCAs) are thought to arise via beta-oxidation of the corresponding dicarboxylic acids (DCAs), although long-chain DCAs are neither readily transported into nor beta-oxidized in mitochondria. We thus examined whether omega-hydroxylation of 3-hydroxy fatty acids (3-OHFAs), formed via incomplete mitochondrial oxidation, is a more likely pathway for 3-OHDCA production. NADPH-fortified human liver microsomes converted 3-hydroxystearate and 3-hydroxypalmitate to their omega-hydroxylated metabolites, 3,18-dihydroxystearate and 3,16-dihydroxypalmitate, respectively, as identified by GC-MS.

Variants in estrogen metabolism and biosynthesis genes and urinary estrogen metabolites in women with a family history of breast cancer.

We examined associations between polymorphisms in genes related to estrogen metabolism (CYP1B1 codon 432G --> C rs#1056836, CYP1B1 codon 453A --> G rs#1800440, COMT codon 158G --> A rs#4680) and biosynthesis (CYP17 T --> C promoter rs#743572, CYP19 exon 4 TTTA repeat) and urinary estrogen metabolites (2-hydroxyestrogens (2-OHE), 16alpha-hydroxyestrone (16alpha-OHE1), and their ratio) in a pilot study of 64 pre- and post-menopausal women with a family history of breast cancer. Women were participants in the Metropolitan New York Registry of Breast Cancer Families, one of six international sites of the National Cancer Institute's Breast Cancer Family Registry. We used linear regression to examine the effects of genetic variants on log-transformed urinary estrogen metabolites.

A hormonal association between estrogen metabolism and proliferative thyroid disease.

Objective: To illustrate a relationship between proliferative thyroid disease and estrogen metabolism through the analysis of urinary estrogen metabolites.

Study Design And Setting: Case-control study of 49 subjects with proliferative thyroid disorders and matching them to 49 controls. Urinary estrogen metabolite ratios were obtained, measuring 2-hydroxyestrone, an anti-proliferative metabolite, to 16alpha-hydroxyestrone, a proliferative metabolite.

Estrogen metabolism and breast cancer.

Background: Specific pathways involved in estrogen metabolism may play a role in the etiology of breast cancer. We used data from a large population-based case-control study to assess the association of the urinary estrogen metabolites 2-hydroxyestrone (2-OHE1), 16alpha-hydroxyestrone (16-OHE1), and their ratio (2/16) with both invasive and in situ breast cancer.

Methods: Study participants from the Long Island Breast Cancer Study Project provided a spot urine specimen and completed a comprehensive interviewer-administered questionnaire.

Urinary estrogen metabolites, prostate specific antigen, and body mass index among African-American men in South Carolina.

Introduction: Estrogen metabolites have been linked to risk of breast cancer, and we were interested in whether they are associated with prostate specific antigen (PSA) and other factors associated with prostate cancer. African-American (AA) men in South Carolina have among the highest prostate cancer rates in the world, and thus provide an ideal population in which to investigate this hypothesis.

Methods: We recruited AA men attending prostate cancer screenings in and around Columbia, South Carolina.

A common CYP1B1 polymorphism is associated with 2-OHE1/16-OHE1 urinary estrone ratio.

Cytochrome P450 (CYP) is a multigene family of enzymes involved in important life functions; some of these genes are inducible and are implicated in the oxidative metabolic activation and detoxification of many endogenous and exogenous compounds. CYP1B1 codes for an enzyme that catalyses the production of a 2- and 4-hydroxyl group in estrone and estradiol, while CYP1A1 catalyzes the 2-hydroxylation of estradiol in endometrium. The two genes were evaluated in a cohort of 150 subjects: African-American women had significantly lower 2-hydroxyl estrone/16-hydroxyl estrone (2-OHE1/16-OHE1) urinary metabolite ratios than Caucasian women (2.

Comparison of plasma and urinary levels of 2-hydroxyestrogen and 16 alpha-hydroxyestrogen metabolites.

A modified ELISA assay for measurement of the two estrogen metabolites 2-hydroxyestrone (2OHE1) and 16alpha-hydroxyestrone (16alphaOHE1) in plasma and serum has been developed. Previously, these have only been measured in urine. It is not known how well the measurements of these metabolites in urine and plasma are correlated.

Urinary estrogen metabolites and their ratio among Asian American women.

Controversy persists regarding the role of a low ratio of 2-hydroxyestone (2-OHE(1))/16alpha-hydroxyestrone (16alpha-OHE(1)) as a potential estrogen metabolism marker of increased risk for breast cancer. Most of the evidence has been provided by case-control studies, where tumor effects on hormone metabolism are not known. Studies in populations at various risk of breast cancer are not consistent, with some suggesting that levels of the ratio may be altered by changes in diet and exercise.

Steroids as procarcinogenic agents.

Although hormones produced in the body are normally considered to be beneficial in such matters as life, male and female development, fertility, and blood pressure regulation, these same compounds can act in some circumstances as carcinogens or carcinogen facilitators, In some such cases increased amounts of the hormone or changes in the formation of its metabolites might be responsible. In other cases the timing of hormone release plays a critical role. In some cases the hormone acts independently, while in others two or more compounds act in concert to promote cancer.

Diet and breast cancer.

The preponderance of evidence suggests a role for fat and alcohol as risk factors for breast cancer. The role of milk is more controversial with some studies suggesting that milk is a risk factor and others that consumption of milk is protective against breast cancer. No other major nutrient appears to play a significant role in increasing breast cancer risk.

Effect of soy protein on endogenous hormones in postmenopausal women.

Background: The long-term clinical effects of soy protein containing various concentrations of isoflavones on endogenous hormones are unknown.

Objective: We examined the effects of ingestion of soy protein containing various concentrations of isoflavones on hormone values in postmenopausal women.

Design: Seventy-three hypercholesterolemic, free-living, postmenopausal women participated in a 6-mo double-blind trial in which 40 g protein as part of a National Cholesterol Education Program Step I diet was provided as casein from nonfat dry milk (control), isolated soy protein (ISP) containing 56 mg isoflavones (ISP56), or ISP containing 90 mg isoflavones (ISP90).