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2024 AUG 10 (NewsRx) -- By a News Reporter-Staff News Editor at Obesity, Fitness & Wellness Week -- A new study on genitourinary tract agents is now available. According to [...]

2022 OCT 22 (NewsRx) -- By a News Reporter-Staff News Editor at Obesity, Fitness & Wellness Week -- Investigators publish new report on antidiuretic hormones. According to news reporting out [...]

2022 JUL 2 (NewsRx) -- By a News Reporter-Staff News Editor at Obesity, Fitness & Wellness Week -- Investigators discuss new findings in Proteins - Steroid Receptors. According to news [...]

Background Contralateral second primary breast cancers occur in 4% of female breast cancer survivors. Little is known about differences in risk for second primary breast cancers related to the estrogen and progesterone receptor (hormone receptor [HR]) status of the first tumor. Methods We calculated standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) for contralateral primary breast cancers among 4927 women diagnosed with a first breast cancer between January 1, 1992, and December 31, 2004, using the National Cancer Institute's Surveillance, Epidemiology, and End Results database. Results For women whose first breast tumors were HR positive, risk of contralateral primary breast cancer was elevated, compared with the general population, adjusted for age, race, and calendar year (SIR = 2.22, 95% CI = 2.15 to 2.29, absolute risk [AR] = 13 cases per 10000 person-years [PY]), and was not related to the HR status of the second tumor. For women whose first breast tumors were HR negative, the risk of a contralateral primary tumor was statistically significantly higher than that for women whose first tumors were HR positive (SIR = 3.57, 95% CI = 3.38 to 3.78, AR = 18 per 10000 PY), and it was associated with a much greater likelihood of an HR-negative second tumor (SIR for HR-positive second tumors = 1.94, 95% CI = 1.77 to 2.13, AR = 20 per 10000 PY; SIR for HR-negative second tumors = 9.81, 95% CI = 9.00 to 10.7, AR = 24 per 10000 PY). Women who were initially diagnosed with HR-negative tumors when younger than 30 years had greatly elevated risk of HR-negative contralateral tumors, compared with the general population (SIR = 169, 95% CI = 106 to 256, AR = 77 per 10000 PY). Incidence rates for any contralateral primary cancer following an HR-negative or HR-positive tumor were higher in non-Hispanic blacks, Hispanics, and Asians or Pacific Islanders than in non-Hispanic whites. Conclusions Risk for contralateral second primary breast cancers varies substantially by HR status of the first tumor, age, and race and/or ethnicity. Women with HR-negative first tumors have nearly a 10-fold elevated risk of developing HR-negative second tumors, compared with the general population. These findings warrant intensive surveillance for second breast cancers in women with HR-negative tumors.

Background: Calcium may potentially influence the risk of breast cancer because of its role in regulating cell proliferation, differentiation, and apoptosis. However, prospective studies of calcium intake in relation to breast cancer incidence are sparse. Objective: The objective of this study was to prospectively examine and show the association, if any, of dietary calcium intake with risk of breast cancer by estrogen receptor (ER) and progesterone receptor (PR) status of the tumor. Design: The Swedish Mammography Cohort is a population-based prospective cohort of 61,433 women who were cancer-free at enrollment in 1987-1990. Dietary calcium intake was assessed with a food-frequency questionnaire at baseline and again in 1997. Cox proportional hazards models were used to estimate rate ratios (RRs) and 95% CIs, adjusted for breast cancer risk factors. Results: During an average of 17.4 y of follow-up, 2952 incident cases of invasive breast cancer were ascertained. Dietary calcium intake was not associated with risk of overall breast cancer; the multivariate RR for the highest compared with the lowest quintile of calcium intake was 0.97 (95% CI: 0.87, 1.09; P for trend: 0.49). There was a statistically significant inverse trend for ER-negative/ PR-negative (ER-/PR-) breast cancer (P for trend: 0.02); the multivariate RR for the comparison of extreme quintiles of calcium intake was 0.66 (95% CI: 0.44, 0.99). Calcium intake was not associated with ER-positive/PR-positive (ER+/PR+) or ER+/PR-tumors. Conclusions: Our findings do not support an association between dietary calcium intake and overall breast cancer risk. The inverse relation between calcium intake and ER-/PR- breast cancer requires confirmation in other studies.

Background: Several studies have reported that carriers of the 103I allele of the melanocortin-4 receptor (MC4R) gene had lower body weight than did persons with the wild-type genotype. A recent study found an association of the MC4R 103I variant with carbohydrate intake, which may mediate some of the association of this variant with leanness. Objective: The purpose of the study was to investigate the association between the MC4R V 103I polymorphism and the dietary intake of persons with severe obesity, which was derived by using the Willett food-frequency questionnaire. Design: The MC4R V 103I polymorphism was genotyped in a group of 1029 severely obese white subjects with an average body mass index (BMI; in kg/[m.sup.2]) of 46.0 (range: 33-92). Results: Carriers of the 1031 allele had significantly higher daily energy (364- kcal/d or 19%; P = 0.03) and carbohydrate (57 g/d or 27%; P = 0.01) intakes than did noncarriers, but there was no relation with BMI. No notable association of this polymorphism with lipid and glucose variables of the metabolic syndrome was observed. Conclusions: The higher dietary intake of carbohydrates in severely obese persons with the MC4R 103I variant is in line with previous findings. It may indicate a differential effect on body size measures in extremely obese subjects as compared with the general population. Am J Clin Nutr 2008;88:797-800.

cAMP is required for normal glucose-induced insulin release by pancreatic Β-cells. In a previous study, we showed that cAMP production in Β-cells depends on the expression of receptors for glucagon, [...]

Background: The oxidative metabolism of estrogens in humans is mediated primarily by cytochrome P450, many isoenzymes of which are inducible by dietary and pharmacologic agents. One major pathway, 2-hydroxylation, is induced by dietary indole-3-carbinol (I3C), which is present in cruciferous vegetables (e.g., cabbage and broccoli). Purpose: Because the pool of available estrogen substrates for all pathways is limited, we hypothesized that increased 2-hydroxylation of estrogens would lead to decreased activity in competing metabolic pathways. Methods: Urine samples were collected from subjects before and after oral ingestion of I3C (6-7 mg/kg per day). In the first study, seven men received I3C for 1 week; in the second study, 10 women received I3C for 2 months. A profile of 13 estrogens was measured in each sample by gas chromatography-mass spectrometry. Results: In both men and women, I3C significantly increased the urinary excretion of C-2 estrogens. The urinary concentrations of nearly all other estrogen metabolites, including levels of estradiol, estrone, estriol, and 16 [Alpha]-hydroxyestrone, were lower after I3C treatment. Conclusions: These findings support the hypothesis that I3C-induced estrogen 2-hydroxylation results in decreased concentrations of several metabolites known to activate the estrogen receptor. This effect may lower estrogenic stimulation in women. implications: I3C may have chemopreventive activity against breast cancer in humans, although the long-term effects of higher catechol estrogen levels in women require further investigation. [J Natl Cancer Inst 1997;89:718-23]

The breast cancer drug tamoxifen may increase the growth of uterine polyps or cancer through an action similar to estrogen. Researchers analyzed the uterine linings of 19 postmenopausal breast cancer patients who had been treated with tamoxifen. Tamoxifen treatment was associated with an increase in progesterone receptors and a decrease in estrogen receptors in the uterine lining. Fewer estrogen receptors were found in tamoxifen-treated uterine polyps. A reduction of estrogen receptors may lead to increased estrogenic activity and an increased risk of uterine cancer. Higher doses and duration of tamoxifen increase uterine cancer risk.

Background. Gonadotropin-releasing hormone (Gn-RH) analogs have been used in the therapy of the endocrine-dependent cancers. The authors attempted to determine the frequency with which Gn-RH receptor (Gn-RHR) is present in gynecological cancers. Methods. Experiments were performed on gynecologic tumors that had been surgically removed and their cloned cell lines. Gn-RHR was characterized by [sup.3.H]Gn-RH binding to plasma membrane preparations. Gn-RHR messenger ribonucleic acid was determined by reverse transcription-polymerase chain reaction using oligonucleotide primers synthesized according to the published human Gn-RHR sequence. Results. High affinity binding sites with nanomolar range of Kd and Gn-RHR mRNA were detected in a high proportion (over 90 %) of the specimens from endometrium (6 of 6) and endometrial carcinomas (16 of 17), myometrium (6 of 6) and myomas (4 of 5), epithelial carcinoma (21 of 23), and stromal tumors (3 of 3) of the ovary. There was no substantial Gn-RHR in cervical carcinomas or germ cell-derived tumors of the ovary. Cloned cell lines gave identical results to those obtained in their respective mother tumors. Conclusions. We detected Gn-RHR in a wide range of the carcinomas and tissues originating from the endometrium and ovary, but not in the uterine cervix or germ cell-derived tumors. The expression of Gn-RH receptor raises the possibility that Gn-RH may play a direct regulatory role in the growth of these carcinomas, and provides a possible point of attack for therapeutic approaches using Gn-RH analogs in these malignancies. Cancer 1994;74:2555-61.

Background. Endometrial carcinoma is the most common female pelvic genital malignancy. Many studies suggest that approximately 75% of all endometrial cancers are clinical Stage I. More than 50% of cancer deaths are in patients with clinical Stage I disease. As a result, prognostic factors have been evaluated in an attempt to identify those patients with presumed early stage disease who will be at high risk for recurrence. Recently, hormone receptor status (estrogen [ER], progesterone [PR] in endometrial cancer has been suggested to be a prognostic factor. Methods. Two hundred seventeen patients with Stage I and II endometrial cancers were evaluated for cytoplasmic steroid-receptor status. These results were compared with other prognostic factors in both univariant and multivariant analysis. Results. When ER and PR and combined ER/PR status were analyzed separately, patients with receptor-positive lesions had significantly better disease-free survival than those with receptor-negative lesions. The receptor status was also a significant independent prognostic factor when evaluated by stepwise proportional hazards regression analysis. Conclusions. Hormone receptor status in endometrial cancer appears to be an important prognostic factor. Cancer 1993; 71:1467-70.

Gastrin is a hormone that influences cells of the gastrointestinal system. In addition to its normal function, gastrin may also help to stimulate the growth of malignant cells. In one study, more than half the specimens of colorectal cancer tested were found to have high-affinity receptors for gastrin on their cell surfaces. Only 33 percent had no gastrin receptors at all. This raises the possibility that antagonists of the gastrin receptors might be used to slow the growth of cancers. A preliminary study to evaluate the feasibility of this approach was conducted using laboratory cultures of colorectal cancer cells. An experimental antagonist of the gastrin receptor, known only as L-365,260, was added to growing specimens of two different human colorectal cancer cell cultures. The growth of one cell line was inhibited by 44 percent, while the growth of the other was inhibited by 64 percent. A related series of experiments utilized nude mice. These laboratory mice have a seriously impaired cellular immune system, and therefore cannot destroy experimentally injected cancer cells as easily as normal mice. The experimenters injected the mice with cells from a rat pancreatic cancer that was known to have gastrin receptors. The administration of G17, a form of gastrin, hastened the growth of the cancers in these animals. However, if L-365,260 was given to the mice, the G17 no longer stimulated the progression of the cancer. Since many human cancers of the gastrointestinal tract have gastrin receptors, the authors hope that gastrin receptor antagonists may find application in the treatment of these cancers. (Consumer Summary produced by Reliance Medical Information, Inc.)

Hormonal therapy is effective in only one third of breast cancer patients. Research has demonstrated that the response to hormonal therapy is largely determined by the presence of hormone receptors on the breast cancer cells. In tumor tissue that lacks both estrogen and progesterone receptors, the response rate is about 10 percent. For tumors that are estrogen receptor-positive, but lack the progesterone receptor, the response rate is about 30 percent. When both estrogen and progesterone receptors are present, the response rate jumps to 80 percent. There are too few patients with cells positive for only the progesterone receptor to draw any conclusions about such cells. It is clear, however, that the progesterone receptor is an important determinant of response to hormonal treatment. Varying hypotheses have been put forward to explain the variations of receptor expression and the variations of response to antiestrogen treatment. However, it has been observed clinically that if a patient with estrogen receptor-positive cells relapses after treatment, the cells still express estrogen receptor. The authors suggest that this supports the notion that the original tumor cells lack both receptors, but in the course of tumor growth some cells differentiate to express the estrogen receptor first, and then both progesterone and estrogen receptors. To examine this idea, researchers attempted to correlate the proliferative capacity of breast cancer cells with the expression of hormone receptors. It was found that the cell populations that expressed neither receptor incorporated more radioactive thymidine, indicating a higher rate of DNA synthesis. Cells that possessed the progesterone receptor had a thymidine labelling index of 0.21, while the cells that lacked the progesterone receptor had a thymidine labelling index over four times greater, at 0.94. The indices of cells with and without the estrogen receptor were intermediate at 0.53 and 0.74, respectively. These results indicate that the expression of progesterone receptors is associated with a reduction in DNA synthesis and therefore a reduction in proliferation. The results also suggest that the population of cells expressing the estrogen receptor is different from, but overlaps with, the population of cells expressing the progesterone receptor. (Consumer Summary produced by Reliance Medical Information, Inc.)

Leptin, a pleiotropic cytokine, regulates various metabolic and endocrine responses, has emerged as an important regulator of inflammation. Also, hyperleptinemia has been reported as a component of metabolic syndrome. Periodontitis [...]

Since researchers first identified the presence or absence of hormone receptors on breast cancer cells, large numbers of observations have been made concerning the prognostic value of these hormone receptors. A trend has been noted in which more advanced cancers are more likely to be negative for estrogen and progesterone receptors. This has caused some conjecture that virtually all breast cancers are positive for these receptors at the time of the cancer's inception. To provide more information on this question, an investigation was performed on 557 biopsy and surgical breast cancer specimens, including 52 biopsies of nonpalpable cancers (which are detected by mammography an estimated three years sooner than they would otherwise be found). If the prevailing notion is correct, then the nonpalpable cancers should have a higher proportion of cells positive for the hormone receptors. These nonpalpable cancers represent the earliest stage of human breast cancer that can be studied. As predicted, these early cancers were more likely to be positive for the receptors than the later stages; 84 percent were positive for the estrogen receptor and 79 for the progesterone receptor. This is in contrast to 65 and 63 percent positive estrogen and progesterone receptor status, respectively, by the time the cancers became palpable. The trend toward high receptor positivity with decreasing tumor stage is true for both premenopausal and postmenopausal women. The evidence supports the notion that all breast cancers may begin life positive for both the estrogen and progesterone receptors. The authors point out that by the time a nonpalpable tumor becomes large enough to be detectable over half its life is complete. At a size of about 5 millimeters, the discernable size on mammography, the cancer has already undergone about 22 cell doublings. Without exception, 14 more doublings would be lethal. (Consumer Summary produced by Reliance Medical Information, Inc.)