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https://www.readbyqxmd.com/read/27859423/from-obesity-to-cancer-a-review-on-proposed-mechanisms
#1
REVIEW
Zoya Tahergorabi, Majid Khazaei, Mitra Moodi, Elham Chamani
Nowadays, obesity is considered as a serious and growing global health problem. It is documented that the overweight and obesity are major risk factors for a series of noncommunicable diseases, and in recent years, the obesity-cancer link has received much attention. Numerous epidemiological studies have shown that obesity is associated with increased risk of several cancer types, including colon, breast, endometrium, liver, kidney, esophagus, gastric, pancreatic, gallbladder, and leukemia, and can also lead to poorer treatment...
November 9, 2016: Cell Biochemistry and Function
https://www.readbyqxmd.com/read/27845161/downregulation-of-autophagy-gene-expression-in-endometria-from-women-with-polycystic-ovary-syndrome
#2
Mirjana Sumarac-Dumanovic, Milica Apostolovic, Kristina Janjetovic, Danka Jeremic, Dusan Popadic, Aleksandar Ljubic, Jelena Micic, Jelena Dukanac-Stamenkovic, Aleksandra Tubic, Darko Stevanovic, Dragan Micic, Vladimir Trajkovic
Autophagy, a process of controlled cellular self-digestion, could be involved in cyclic remodeling of the human endometrium. We investigated endometrial mRNA expression of 23 autophagy-related (ATG) genes and transcription factors in healthy controls (n = 12) and anovulatory polycystic ovary syndrome (PCOS) patients (n = 24), as well as in their subgroup (n = 12) before and after metformin treatment. The mRNA levels of transcription factor forkhead box protein O1 (FOXO1) and several molecules involved in autophagosome formation (ATG13, RB1-inducible coiled-coil 1), autophagosome nucleation (ATG14, beclin 1, SH3-domain GRB2-like endophilin B1), autophagosome elongation (ATG3, ATG5, γ-aminobutyric acid receptor-associated protein - GABARAP), and delivery of ubiquitinated proteins to autophagosomes (sequestosome 1), were significantly reduced in anovulatory PCOS compared to healthy endometrium...
November 11, 2016: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/27745917/prospective-evaluation-of-the-molecular-effects-of-metformin-on-the-endometrium-in-women-with-newly-diagnosed-endometrial-cancer-a-window-of-opportunity-study
#3
Pamela T Soliman, Qian Zhang, Russell R Broaddus, Shannon N Westin, David Iglesias, Mark F Munsell, Rosemarie Schmandt, Melinda Yates, Lois Ramondetta, Karen H Lu
OBJECTIVE: Metformin reduces cancer incidence and improves overall survival in diabetic patients. In preclinical studies, metformin decreases endometrial cancer (EC) cell growth by activation of AMPK/mTOR inhibition. We sought to determine the effects of metformin on serum/tumor biomarkers in women with EC. METHODS: In this prospective trial, newly diagnosed EC patients underwent pre-treatment blood draw/endometrial biopsy, were administered oral metformin 850mg daily for ≥7days, and underwent post-treatment blood draw/definitive surgery...
December 2016: Gynecologic Oncology
https://www.readbyqxmd.com/read/27636742/metformin-inhibits-estrogen-dependent-endometrial-cancer-cell-growth-by-activating-the-ampk-foxo1-signal-pathway
#4
Jingfang Zou, Liangli Hong, Chaohuan Luo, Zhi Li, Yuzhang Zhu, Tianliang Huang, Yongneng Zhang, Huier Yuan, Yaqiu Hu, Tengfei Wen, Wanling Zhuang, Bozhi Cai, Xin Zhang, Jiexiong Huang, Jidong Cheng
Metformin is an oral biguanide commonly used for the treating type II diabetes and has recently been demonstrated to possess anti-proliferative properties that can be exploited for the prevention and treatment of a variety of cancers. The mechanisms underlying this effect have not been fully elucidated. Our study demonstrated a marked loss of AMP-activated protein kinase (AMPK) phosphorylation and nuclear FOXO1 protein in estrogen-dependent endometrial cancer (EC) tumors compared to normal control endometrium...
September 16, 2016: Cancer Science
https://www.readbyqxmd.com/read/27569685/proinflammatory-environment-and-role-of-tnf-%C3%AE-in-endometrial-function-of-obese-women-having-polycystic-ovarian-syndrome-pcos
#5
L Oróstica, I Astorga, F Plaza-Parrochia, C Vera, V García, R Carvajal, F Gabler, C Romero, M Vega
BACKGROUND/OBJECTIVES: A high percentage of women having PCOS exhibit hyperinsulinemia and obesity. Transforming necrosis factor-alpha (TNF-α) is an adipokine that increases in obesity and negatively affects insulin action in several tissues, including the endometrium. In fact, it has been reported that insulin signaling is altered in the endometrium of PCOS women, affecting its reproductive function. The aim of this study was to determine the pro-inflammatory environment and TNF-α signaling in endometrium from obese women with PCOS, and also to evaluate the effect of TNF-α on endometrial cell energy homeostasis...
August 29, 2016: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/27515096/decreased-expression-of-nr4a-nuclear-receptors-in-adenomyosis-impairs-endometrial-decidualization
#6
Yue Jiang, Ruiwei Jiang, Xi Cheng, Qun Zhang, Yali Hu, Hui Zhang, Yun Cao, Mei Zhang, Junxia Wang, Lijun Ding, Zhenyu Diao, Haixiang Sun, Guijun Yan
STUDY QUESTION: How do NR4A receptors drive decidualization of human endometrial stromal cells (hESCs)? SUMMARY ANSWER: NR4A receptors modulate endometrial decidualization by transcriptional activation of FOXO1A, and in adenomyosis patients, the reduced expression of NR4A receptors in the eutopic endometrium may represent a novel mechanism to explain impaired decidualization and subfertility. WHAT IS KNOWN ALREADY: A close relationship between impaired decidualization and subfertility has been established...
September 2016: Molecular Human Reproduction
https://www.readbyqxmd.com/read/27512005/effect-of-adiponectin-on-the-steroidogenic-acute-regulatory-protein-p450-side-chain-cleavage-enzyme-and-3%C3%AE-hydroxysteroid-dehydrogenase-gene-expression-progesterone-and-androstenedione-production-by-the-porcine-uterus-during-early-pregnancy
#7
N Smolinska, K Dobrzyn, M Kiezun, K Szeszko, A Maleszka, T Kaminski
Adiponectin and its receptors are expressed in the human and porcine uterus and this endocrine system has important role in the regulation of reproductive processes. The expression of steroidogenic acute regulatory protein (StAR) and 3β-hydroxysteroid dehydrogenase (HSD3B1) were observed in the human and porcine uterus during the oestrous cycle and pregnancy. The de novo synthesis of steroids in the uterus might be a crucial factor for effective implantation and maintenance of pregnancy. We hypothesized that adiponectin modulates the expression of key enzymes in the synthesis of the steroids: StAR, P450 side chain cleavage enzyme (CYP11A1) and HSD3B1, as well as progesterone (P4) and androstenedione (A4) secretion by the porcine uterus...
June 2016: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/27484063/perifollicular-blood-flow-and-its-relationship-with-endometrial-vascularity-follicular-fluid-eg-vegf-igf-1-and-inhibin-a-levels-and-ivf-outcomes
#8
Fisun Vural, Birol Vural, Emek Doğer, Yiğit Çakıroğlu, Mustafa Çekmen
PURPOSE: The aim of this study is to investigate the association of perifollicular blood flow (PFBF) with follicular fluid EG-VEGF, inhibin-a, and insulin-like growth factor-1 (IGF-1) concentrations, endometrial vascularity, and IVF outcomes. METHODS: Forty women with tubal factor infertility were included in a prospective cohort study. Each woman underwent IVF/ICSI procedure. Individual follicles of ≥16 mm (n = 156) were evaluated by power Doppler analysis and categorized as well-vascularized follicles (WVFs) or poorly vascularized follicles (PVFs)...
October 2016: Journal of Assisted Reproduction and Genetics
https://www.readbyqxmd.com/read/27325575/gestation-related-gene-expression-and-protein-localization-in-endometrial-tissue-of-suffolk-and-cheviot-ewes-at-gestation-day-19-after-transfer-of-suffolk-or-cheviot-embryos
#9
M Sequeira, S J Pain, V de Brun, A Meikle, P R Kenyon, H T Blair
The objective of this study was to investigate the gene expression of progesterone and estrogen receptor α (PR, ERα), insulin-like growth factor (IGF) 1, IGF-2, their receptor (IGFR1), IGF-binding proteins (BP) 1 to 6, insulin receptor, adiponectin receptors (AdipoR1/2), cyclooxygenase 2 (PTGS2), mucin 1 and to localize PR, ERα, IGF-1, IGFR1, PTGS2, and proliferating cellular nuclear antigen (PCNA) in the endometrium of pregnant (Day 19) Suffolk and Cheviot ewes carrying Suffolk and Cheviot embryos transferred within and reciprocally between breeds...
October 1, 2016: Theriogenology
https://www.readbyqxmd.com/read/27313119/overexpression-of-il-18-in-the-proliferative-phase-endometrium-of-patients-with-polycystic-ovary-syndrome
#10
Xiaoyu Long, Rong Li, Yan Yang, Jie Qiao
Women with polycystic ovary syndrome (PCOS) exhibit low implantation rate and high abortion rate. To explore the effect of low-grade chronic inflammation on endometrium of women with PCOS, we investigated the expression of interleukin 18 (IL-18) in the endometrium of 23 women with PCOS and 20 healthy women. Endometrial tissue samples were obtained during hysteroscopic surgery. We found that IL-18 was significantly increased in the endometrium of women with PCOS compared with normal groups. In overweight women, IL-18 was obviously overexpressed in the PCOS group compared to the healthy group...
June 16, 2016: Reproductive Sciences
https://www.readbyqxmd.com/read/27156350/polycystic-ovary-syndrome-endometrial-markers
#11
Terhi T Piltonen
Women with polycystic ovarian syndrome (PCOS) present with several endometrial abnormalities possibly explaining some of the adverse endometrium-related outcomes in these women. PCOS and an increased miscarriage rate have been suggested to coincide, but the results are conflicting. Recent studies have also shown increased risks of pregnancy-induced hypertension, preeclampsia, and premature delivery that may be related to altered decidualization/placentation in affected women. In the long run, PCOS per se is associated with the occurrence of endometrial cancer (EC), with obesity aggravating the risk...
April 1, 2016: Best Practice & Research. Clinical Obstetrics & Gynaecology
https://www.readbyqxmd.com/read/27125830/insulin-igf-and-sex-hormone-axes-in-human-endometrium-and-associations-with-endometrial-cancer-risk-factors
#12
Melissa A Merritt, Howard D Strickler, Mark H Einstein, Hannah P Yang, Mark E Sherman, Nicolas Wentzensen, Jurriaan Brouwer-Visser, Maria Jose Cossio, Kathleen D Whitney, Herbert Yu, Marc J Gunter, Gloria S Huang
PURPOSE: Experimental and observational data link insulin, insulin-like growth factor (IGF), and estrogens to endometrial tumorigenesis. However, there are limited data regarding insulin/IGF and sex hormone axes protein and gene expression in normal endometrial tissues, and very few studies have examined the impact of endometrial cancer risk factors on endometrial tissue biology. METHODS: We evaluated endometrial tissues from 77 premenopausal and 30 postmenopausal women who underwent hysterectomy for benign indications and had provided epidemiological data...
June 2016: Cancer Causes & Control: CCC
https://www.readbyqxmd.com/read/27088794/differential-expression-of-ir-a-ir-b-and-igf-1r-in-endometrial-physiology-and-distinct-signature-in-adenocarcinoma
#13
Clare A Flannery, Farrah L Saleh, Gina H Choe, Daryl J Selen, Pinar H Kodaman, Harvey J Kliman, Teresa L Wood, Hugh S Taylor
CONTEXT: Type 2 diabetes and obesity are risk factors for endometrial hyperplasia and cancer, suggesting that hyperinsulinemia contributes to pathogenesis. Insulin action through insulin receptor (IR) splice variants IR-A and IR-B regulates cellular mitogenesis and metabolism, respectively. OBJECTIVE: We hypothesized that IR-A and IR-B are differentially regulated in normal endometrium, according to mitogenic and metabolic requirements through the menstrual cycle, as well as in endometrial hyperplasia and cancer...
July 2016: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/26974839/glucose-availability-and-amp-activated-protein-kinase-link-energy-metabolism-and-innate-immunity-in-the-bovine-endometrium
#14
Matthew L Turner, James G Cronin, Pablo G Noleto, I Martin Sheldon
Defences against the bacteria that usually infect the endometrium of postpartum cattle are impaired when there is metabolic energy stress, leading to endometritis and infertility. The endometrial response to bacteria depends on innate immunity, with recognition of pathogen-associated molecular patterns stimulating inflammation, characterised by secretion of interleukin (IL)-1β, IL-6 and IL-8. How metabolic stress impacts tissue responses to pathogens is unclear, but integration of energy metabolism and innate immunity means that stressing one system might affect the other...
2016: PloS One
https://www.readbyqxmd.com/read/26841672/-the-characteristics-of-systemic-and-local-immune-reactions-under-habitual-non-carrying-of-pregnancy
#15
S Yu Yuriev, I S Popova, L R Mustafina, I A Zakonova, A E Sazonov, A B Poletaev
The study was carried out to evaluate clinical informativeness ofstudies of immunological parameters of structural and functional elements of endometrium in complex with profile of embritropic autoimmune antibodies under non-carrying of pregnancy The sampling consisted of 19 women of reproductive age with episodes of non-carrying in first semester. They were examined for inherited thrombophilia and profiles of immune reactivity of natural regulatory auto-antibodies (ELI-P-Complex). The biopsy material of endometrium was subjected to histological and immune histochemical (CD16, CD56, CD68, CB138, estrogen and progesterone receptors) analyses...
October 2015: Klinicheskaia Laboratornaia Diagnostika
https://www.readbyqxmd.com/read/26802879/up-regulation-of-genes-involved-in-the-insulin-signalling-pathway-igf1-pten-and-igfbp1-in-the-endometrium-may-link-polycystic-ovarian-syndrome-and-endometrial-cancer
#16
Mohamad Nasir Shafiee, Claire Seedhouse, Nigel Mongan, Caroline Chapman, Suha Deen, Jafaru Abu, William Atiomo
BACKGROUND: Endometrial cancer (EC) is the most common gynaecological cancer amongst women in the UK. Although previous studies have found that women with polycystic ovary syndrome (PCOS) have at least a three-fold increase in endometrial cancer (EC) risk compared to women without PCOS, the precise molecular mechanisms which link between PCOS and EC remain unclear. It has been suggested that insulin resistance may contribute to the increased risk of EC in PCOS. The specific expression of genes related to the insulin-signalling pathway including the IGF system in the endometrium of women with PCOS has however never been measured and compared to that in women with EC without PCOS and control women without EC or PCOS...
March 15, 2016: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/26744532/infiltrating-macrophages-induce-er%C3%AE-expression-through-an-il17a-mediated-epigenetic-mechanism-to-sensitize-endometrial-cancer-cells-to-estrogen
#17
Chengcheng Ning, Bingying Xie, Lin Zhang, Chunsheng Li, Weiwei Shan, Bingyi Yang, Xuezhen Luo, Chao Gu, Qizhi He, Hongyan Jin, Xiaojun Chen, Zhenbo Zhang, Youji Feng
Persistent unopposed estrogen stimulation is a central oncogenic mechanism driving the formation of type I endometrial cancer. Recent epidemiologic and clinical studies of endometrial cancer have also revealed a role for insulin resistance, clinically manifested by chronic inflammation. However, the role of inflammation in estrogen-driven endometrial cancer is not well characterized. In this study, we investigated the association between infiltrating macrophages and estrogen sensitivity in endometrial cancer...
March 15, 2016: Cancer Research
https://www.readbyqxmd.com/read/26604029/triclosan-and-bisphenol-a-affect-decidualization-of-human-endometrial-stromal-cells
#18
Maurizio Forte, Luigi Mita, Luigi Cobellis, Verdiana Merafina, Raffaella Specchio, Sergio Rossi, Damiano Gustavo Mita, Lavinia Mosca, Maria Antonietta Castaldi, Maria De Falco, Vincenza Laforgia, Stefania Crispi
In recent years, impaired fertility and endometrium related diseases are increased. Many evidences suggest that environmental pollution might be considered a risk factor for endometrial physiopathology. Among environmental pollutants, endocrine disrupting chemicals (EDCs) act on endocrine system, causing hormonal imbalance which, in turn, leads to female and male reproductive dysfunctions. In this work, we studied the effects of triclosan (TCL) and bisphenol A (BPA), two widespread EDCs, on human endometrial stromal cells (ESCs), derived from endometrial biopsies from woman not affected by endometriosis...
February 15, 2016: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/26578736/phase-ii-study-of-medroxyprogesterone-acetate-plus-metformin-as-a-fertility-sparing-treatment-for-atypical-endometrial-hyperplasia-and-endometrial-cancer
#19
A Mitsuhashi, Y Sato, T Kiyokawa, M Koshizaka, H Hanaoka, M Shozu
BACKGROUND: Metformin, widely used in the treatment of type 2 diabetes mellitus, reduces the risk of cancer and relapse after treatment. Fertility-sparing treatment for endometrial cancer (EC) with progestin is associated with a high chance of disease regression, and the high relapse rate continues to be a problem. We assessed the efficacy of metformin in preventing recurrence after medroxyprogesterone acetate (MPA) as fertility-sparing treatment for atypical endometrial hyperplasia (AEH) and EC...
February 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/26548420/protective-effects-of-bazedoxifene-paired-with-conjugated-estrogens-on-pancreatic-%C3%AE-cell-dysfunction
#20
Jun Ho Kim, Jin Hyup Lee, Young Jun Kim
Bazedoxifene (BZA) is a novel selective estrogen receptor modulator that exhibits estrogen agonist activity in the bone but estrogen antagonist activity in the breast and uterus. We recently demonstrated that BZA mimics estrogenic actions in reversing metabolic abnormalities while protecting the endometrium from estrogen stimulation in ovariectomized (OVX) mice. However, it is unknown whether BZA, alone or paired with estrogens, can protect pancreatic β-cell function or survival. Thus, the aim of this study was to evaluate the preventive effects of estrogens [17β-estradiol or conjugated estrogens (CE)], BZA and their combinations against β-cell failure...
November 6, 2015: Biological & Pharmaceutical Bulletin
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