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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Estrogen receptor (ER) and progesterone receptor (PgR) levels were determined in patients with a ductal infiltrating breast carcinoma. In premenopausal patients, the distribution of the PgR was higher than that of the ER. With increasing age of the patients, the concentration of the ER increased, whereas the PgR values showed an inverse relationship. According to the menstrual status, ER and PgR values were found to be higher in postmenopausal patients than in premenopausal ones. In relation to body fat distribution, in premenopausal patients the ER or PgR values were not found to be statistically significantly different (data no shown). In postmenopausal patients, the concentration of ER was diminished by 20% in patients with obesity of the upper body segment and by 40% in patients with obesity of the lower body segment as compared with the ER values of nonobese patients. While the PgR values diminished by 20% in patients with obesity of the lower body segment, in relation to PgR values of patients with obesity of the upper body segment, we found no statistically significant differences when compared with the PgR values of nonobese patients. With regard to the body mass index, this has remained constant in both types of body fat distribution. When body mass index values were compared with serum ER and PgR levels, no statistically significant differences were found.
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PMID:Hormone-related factors associated with hormone receptor levels in breast cancer. 1172 42

In 1994, Zhang et al. of Rockefeller University in New York reported the first successful complementary DNA (cDNA) cloning of leptin by the positional cloning method. Leptin was identified as the gene of ob/ob mouse in genetic obesity syndromes. It has very strong food intake control, and body weight and energy expenditure. The name "leptin" derived from the Greek word leptos, meaning "thin." We hereby review major advances leading to our current finding of leptin, leptin receptor and its structure, the outline of homozygote, and also influence of leptin in the pituitary. (The structure of leptin) The mouse obese gene has been localized to chromosome 6. With human leptin gene on chromosome 7q31.3, its DNA has more than 15000 base pairs and consists of three exons and two introns. For bioactivation of leptin the importance of disulfide-binding site is suggested. Human leptin which replaced the 128-th arginine with glutamine has the function of an aldosteron antagonist, which is reported to have the function of athrocytosis inhibition. The resemblance of leptin precursor of human, mouse and rat is very high, i.e., mouse and rat homology is 96% and mouse and human homology is 83%. (The structure of leptin receptor) The mutant gene, which is the cause of obesity, was shown on map on diabetic mouse (db/db) chromosome 4, and it was proven to be the same as the leptin receptor gene cloned by Tartaglia et all. Further studies have found the Zucker fatty rat (fa/fa) to be incorporated into a linkage map of rat chromosome 5, whose region of rat is the equivalent to the region of conserved synteny of the db/db mouse gene. The leptin receptor is glycoprotein consisting of a single transmembrane-spanning component. The primary structure of leptin receptor belongs to the cytokine-class1 family, the single membrane-spanning receptor, and is highly related to the gp130 signal-transducing component of the interleukin-6 (IL-6) receptor, the granulocyte colony-stimulating factor (G-CSF) receptor, and the leukemia inhibitory factor (LIF) receptor. The leptin receptor is known to have at least six existing isoforms (Ob-Ra, b, c, d, e, f) from the difference in splicing. (Homozygote Mutation of Leptin and Leptin Receptor :Hormone Secretion Disorders) The point mutation of ob/ob mouse and the splicing mutation of db/db mouse show remarkable obesity and hyperphagia. These obesity models show a reproduction disorder with both the male and the female, and they develop with homozygote. The cause is thought to be the gonadotropin secretory abnormality in pituitary. Three family lines report the cases of this deficiency, and it is considered that the secretory abnormality in pituitary develops into hypogonadotropic. These patients show low value in plasma FSHbeta (follicle stimulating hormone-beta and LHbeta (luteinizing hormone-beta which are produced from pituitary, and the plasma GnRH (gonadotropin releasing hormone) level is also low. Furthermore, the leptin receptor deficient family line was reported in 1998, in which case only the homozygote developed. The plasma leptin concentration of normal human is about 8.0 ng/ml, and this case with leptin receptor deficiency has high value of 500-700 ng/ml, which is the equivalent to the db/db mouse. (Role of Leptin in Hypothalamus-Pituitary-Periphery Function) The role of leptin which regulates pituitary hormones suggests the promotion the GHRH (growth hormone releasing hormone) secretion in hypothalamus-pituitary axis, with the possibility of the rise in secretion of GH (growth hormone) in pituitary, i.e. effects of icv (intracerebroventricular) infusion of leptin has spontaneously stimulated GHRH, which promotes GH secretion in the normal rats. On the other hand, topical treatment of GH3 (derived from a rat pituitary GH-secreting cell line) with leptin directly inhibits cell proliferation. The obesity model animals (ob/ob, db/db, fa/fa) have equally plump body compared to the normal models, which shows signs of sufficient growth. (Localization and Functional Relevance of Leptin and Leptin Receptor in Rodents Pituitary) Aside from being the food intake inhibitor and the energy control factor, leptin takes part in controlling the pituitary hormones. Promoting the secretion of GH, PRL (prolactin), TSHbeta (thyroid stimulating hormone-beta, FSHbeta/LHbeta, and inhibiting the secretion of ACTH (adrenocorticotropic hormone) are the major changes of pituitary hormones which are brought on by leptin. The expressive localization is specific, and immunohistochemistry (IHC) method recognized leptin in granular state in FSHbeta, LHbeta and TSHbeta positive cells. In our biochemical examination, the bulk of the expression of leptin is recognized in fraction of the secretory granule. In particular, FSHbeta cells had the highest percentage rate of colocalized leptin in rat pituitary. On the other hand, leptin receptor has been reported to be found only in normal rat pituitary, human pituitary adenoma, and respective cell lines in pituitaries by the RT-PCR method until now, but we disclosed for the first time the localization of leptin receptor on the plasma membrane of GH-secreting cells with the IHC method that has not been cleared so far. These findings show that leptin and leptin receptor have been expressed in different cells, and that the rat pituitary glands entertain paracrine mechanism between leptin (FSHbeta/LHbeta cells) and leptin receptor (GH cells). The function of paracrine in this pituitary suggests a new point of view in hypothalamus-pituitary axis, and it shall be concerned with many aspects such as hormone secretions and proliferation/inhibition. (Human Pituitary Adenoma) Preliminary report of leptin and leptin-receptor relationship with pituitary adenoma that has secretion abnormality has been filed, and its manifestation is being observed by the RT-PCR. Leptin and leptin receptor are expressed in most adenoma, and it is thought to function by autocrine and paracrine pathway in the adenomas. Leptin has been located in ACTH-secreting adenoma most frequently, especially in ACTH carcinoma. The leptin receptor is detected in all adenomas with high percentage rate, with both long and short forms, and then many cases of nonfunctioning pituitary adenomas, compared with other adenomas, have been reported to be positive with both long and short forms of leptin receptor as detected by RT-PCR. The HP75 cell line is derived from the nonfunctioning pituitary adenoma, which produces FSHbeta and LHbeta. The expression of leptin receptor in nonfunctioning pituitary adenoma, and the suppression of HP75 multiplication may lead to the possible hypothesis of leptin becoming one factor for the treatment of pituitary adenoma, especially in gonadotropin adenomas.
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PMID:Leptin and the pituitary. 1182 4

Gastro-oesophageal reflux disease (GERD) is common in obese patients. Apart from the physical discomfort and the economic burden, GERD may increase morbidity and mortality through its association with oesophageal carcinoma. The pathophysiology of GERD differs between obese and lean subjects. First, obese subjects are more sensitive to the presence of acid in the oesophagus. Second, hiatal hernia, capable of promoting GERD by several mechanisms, is more prevalent among the obese. Third, obese subjects have increased intra-abdominal pressure that displaces the lower oesophageal sphincter and increases the gastro-oesophageal gradient. Finally, vagal abnormalities associated with obesity may cause a higher output of bile and pancreatic enzymes, which makes the refluxate more toxic to the oesophageal mucosa. The altered body composition associated with obesity affects the pharmacokinetics of drugs. There are no data regarding the efficacy of any of the drugs used for GERD treatment. The dosages of cimetidine and ranitidine should be calculated according to the patient's ideal body weight, not their actual weight. Of the operative procedures used for weight loss, Roux-en-Y gastric bypass was found to be most effective for GERD, while gastric banding was associated with a high prevalence of reflux. This review outlines the pathophysiology and the treatment of GERD in obesity with emphasis on the therapeutic considerations in this population of patients.
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PMID:Gastro-oesophageal reflux disease in obesity: pathophysiological and therapeutic considerations. 1211 61

There have been many new published articles on the association between oral contraception (OC) and carcinogenic effects. Risk of benign breast cancer seems to be about 3/1000 in women under OC treatment. According to a study by the Royal College of General Practitioners this decrease is in proportion to the dose of progesterone used. Incidence of malignant breast cancer in OC users varies greatly; it is about 13/100,000 in Japan and 71.4/100,000 in the U.S.: the influence of the environment seems to be as responsible for side effects as genetic and obstetrical factors. Risk of malignant endometrial cancer is increased by age over 40, obesity, and nulliparity. However, since 1975, there has been an increase in the reported incidence of endometrial adenocarcinoma in young women. There is only 1 published study which shows that OC may decrease endometrial effects in OC users. Cervical pathology in OC users includes endocervical polypus, which are asymptomatic, and dysplasia and carcinoma, which are both related to age at 1st sexual encounter and to the number of sexual partners. The incidence of hepatic carcinoma in relation to OC is only 1/50,000. Risk of thromboembolism and hypertension are increased by age over 35, obesity, smoking, and family or antecedent history of cardiovascular problems.
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PMID:[Risks and follow-up of women taking combination oral contraceptives]. 1227 53

The pathogenesis of breast cancer is Extensive tests isolate 3 distinct factors: genetic, hormonal and viral. Thus, the risk factor is increased 2-3 times by hereditary predisposition whereas (bilateral) ovariectomy, blocking production of ovarian hormones, reduces the risk by 10 times. Childbirth reduces the risk in reverse proportion to its frequency; however, less protection is afforded if not accompanied by lactation. Nulliparity was recognized as a risk factor in 1926, but recent studies have proven less conclusive. Also included as risk factors are the intake of fatty nutrients and obesity. Further indications include older age at 1st pregnancy, menstrual disorders, and a prolonged reproductive life as a result of precocious menarche and/or delayed menopause. The longer menopause is delayed, the greater the premenopausal period characterized by hyperestrinization, anovulation, and a modest production of progesterone. Metabolism of estrogens oriented towards more active metabolites compounds the risk factors. It has been impossible to verify an etiologic connection between estrogenic preparations administered during post-menopause and breast cancer. Oral contraceptives, in general, do not seem to pose any risk. A connection between prolactin and cancer has been demonstrated in rodents, but not in humans. Antiprolactin pharmaceuticals are capable of inducing regression of neoplasia, indicating a plausible, however unproven, active role of prolactin. Progesterone acting as an antiestrogen reduces the levels of cytoplasmic receptors, thus probably acting protectively. Basically, two approaches are possible for endocrine treatment of metastasized breast carcinoma: ablative surgery based on hormone deprivation (ovariectomy, suprarenalectomy, hypophysectomy) or additive therapy based on hormonal interference (estrogens, androgens, progestins, antiestrogens).
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PMID:[Hormonodependence and hormonosensibility of the gynecological neoplasias. III. The breast carcinoma]. 1228 88

The question is whether the administration of estrogenic substances to the human female causes cancer of the endometrium. Current data seems to indicate that in predisposed individuals the unopposed action of estrogenic substances for a considerable period of time will result in endometrial adenomatous hyperplasia, carcinoma in situ (atypical adenomatous hyperplasia), and eventually carcinoma. The relationship of estrogenic substances to the development of endometrial hyperplasia of all degrees is clear, but the relationship of these substances to invasive endometrial cancer is blurred by assumptions based on individual case reports, retrospective reasoning, and uncontrolled experimentation. 4 published reports reviewed here have compared the use of exogenous estrogen by patients with endometrial cancer to that by controls. These studies have not been comprehensive and they raise more questions than they answer. If a physician chooses to use estrogen for the treatment of symptoms or signs of estrogen insufficiency, the selection of patients is crucial. Obesity, hypertension, diabetes, and infertility associated with oligo-ovulation are predisposing factors in the development of endometrial cancer, and patients with these conditions should have endometrial biopsy or uterine aspiration before the institution of therapy. There are 2 therapeutic regimens which can be used to prevent or even reverse the endometrial hyperplasia that may otherwise result from excessive and continuous estrogen administration.
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PMID:Estrogen controversy updated. 1233 9

The arachidonate cascade includes the cyclooxygenase (COX) pathway to form prostanoids and the lipoxygenase (LOX) pathway to generate several oxygenated fatty acids, collectively called eicosanoids. Eicosanoids are suggested to play a dual role in regulating cell survival and apoptosis in various types of cells through an unknown mechanism. We found apoptosis in cultured Madin-Darby canine kidney (MDCK) cells treated with 12-O-tetradecanoylphorbol beta-acetate (TPA), a potent tumor promoter, and nordihydroguaiaretic acid (NDGA), a LOX inhibitor. The effect of TPA was synergistically stimulated along with NDGA. Aspirin, a COX inhibitor, was not effective. The target of NDGA might be different from the mechanism involving a LOX activity in some kinds of carcinoma cells because the increased expression of 12-LOX was not detected in MDCK cells treated with TPA. Caspase and poly(ADP-ribose) metabolites were found to be involved in the signal transduction pathway of the TPA- and NDGA-induced apoptosis in MDCK cells. Alternatively, hydrogen peroxide-induced apoptosis was not affected by NDGA. Thus, the TPA-induced response involved the mechanism independent of the oxidative stress. Obesity is a risk factor for severe diseases including noninsulin-dependent diabetes and atherosclerosis characterized by the changes of cell properties of adipocytes. We found that conjugated linolenic acid from bitter gourd was able to induce apoptosis in mouse preadipogenic 3T3-L1 cells. The findings provide the potential use of conjugated fatty acids to regulate obesity.
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PMID:Regulation of apoptosis through arachidonate cascade in mammalian cells. 1239 27

Adenocarcinoma of the esophagus and the gastroesophageal junction is the twentieth most common malignancy in the United States. In developed countries, the incidence of esophageal adenocarcinoma is increasing 5% to 10% per year. Despite the use of endoscopy for earlier detection, mortality from esophageal adenocarcinoma has not declined. Using an evidence-based approach, we review screening methods for esophageal adenocarcinoma, including the use of a symptom questionnaire, identification of patients with a family history of Barrett's esophagus, peroral or transnasal endoscopy, barium swallow, fecal occult blood testing, and brush and balloon cytology. Screening has not been shown to reduce rate of progression of Barrett's esophagus to esophageal cancer. Many treatment options for dysplastic Barrett's esophagus or early carcinoma appear effective, but long-term follow-up data are not available. There is currently insufficient evidence supporting population-based screening for Barrett's esophagus. Several risk factors, including severe reflux symptoms, male sex, and obesity, may identify patients with gastroesophageal reflux disease who are at the greatest risk of the development of cancer.
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PMID:Screening for esophageal adenocarcinoma: an evidence-based approach. 1242

The share of seroso-papillary endometrial carcinoma (SPEC) for the past 4 years has been 6.4%--101 out of 1,567 endometrial cancers. There has been lower incidence of obesity, diabetes mellitus and infertility in cases of SPEC than endometrioid carcinoma (EEC)--18.8 and 53.7; 12.9 and 23.3; 8.8 and 20.6%, respectively, (p < 0.05). Only 60.4% of SPEC patients had locally-advanced tumors (stage I--35.6; stage II--24.8%) while tumor dissemination was reported in 39.6% (stage III--27.7 and stage IV--11.9%). Among EEC patients, locally-advanced tumors were detected in 89.6% (stage I--62.9 and stage II--26.7%) and disseminated tumor incidence was 3 times lower than in SPEC--10.4% (stage III--8.1 and stage IV--2.3%). Deep invasion into the stroma (more than 10 mm) was registered in 27.7% (SPEC) while in EEC--6.0% (p(0.05). Lymphogenous metastasis was much more common in SPEC (13.9%) as compared with less than 4.1% in EEC patients. There was no correlation between its presence and depth of invasion in the myometrium (p(0.05). High incidence of association of metastasis and superficial or deep invasion was reported for SPEC. This tumor should be classified as pathogenetic variant II of clinico-morphological changes.
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PMID:[Serous-papillary endometrial carcinoma (clinico-morphological features)]. 1253 Feb 63

The purpose of our study was to determine if specific host factors, such as age at diagnosis, obesity, and hormone status, influence the prognosis of canine mammary gland carcinomas and to confirm if previously reported risk factors (ie, histologic subtype, tumor size, and World Health Organization [WHO] stage) were important in a large series of affected dogs. Ninety-nine female dogs with mammary gland carcinomas, no previous therapy, an excisional biopsy, and known cause of death were studied. No significant association with survival was noted for age at diagnosis (chronologic or physiologic), obesity, or hormone status (ie, spayed versus intact, regardless of time of being spayed). Of the tumor factors analyzed, the histologic subtype anaplastic carcinoma (P = .02), WHO stage I (P = .01), evidence of metastasis at the time of diagnosis (P = .004), and tumor size of 3 cm or smaller (P = .005) all significantly influenced survival. Dogs that were classified as having tumor-related mortality had a shorter postoperative survival compared to dogs that died of other causes (14 months versus 23 months; P = .03). In conclusion, histologic subtype, WHO stage, and tumor size remain important prognostic factors in canine mammary gland tumors. Further study of other prognostic factors is needed to determine which tumors are adequately addressed with local therapy only and which dogs may require adjuvant treatment with chemotherapy.
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PMID:Influence of host factors on survival in dogs with malignant mammary gland tumors. 1256 34


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