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https://www.readbyqxmd.com/read/28428557/the-prognostic-significance-of-cdc6-and-cdt1-in-breast-cancer
#1
Ravikiran Mahadevappa, Henrique Neves, Shun Ming Yuen, Yuchen Bai, Cian M McCrudden, Hiu Fung Yuen, Qing Wen, Shu Dong Zhang, Hang Fai Kwok
DNA replication is a critical step in cell proliferation. Overexpression of MCM2-7 genes correlated with poor prognosis in breast cancer patients. However, the roles of Cdc6 and Cdt1, which work with MCMs to regulate DNA replication, in breast cancers are largely unknown. In the present study, we have shown that the expression levels of Cdc6 and Cdt1 were both significantly correlated with an increasing number of MCM2-7 genes overexpression. Both Cdc6 and Cdt1, when expressed in a high level, alone or in combination, were significantly associated with poorer survival in the breast cancer patient cohort (n = 1441)...
April 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28424084/durable-complete-remission-with-aromatase-inhibitor-therapy-in-a-patient-with-metastatic-uterine-carcinosarcoma-with-poor-performance-status-and-coagulation-disorders-a-case-report
#2
P Martin-Romano, M Jurado, M A Idoate, L Arbea, J L Hernandez-Lizoain, D Cano, J A Paramo, S Martin-Algarra
BACKGROUND: Chemotherapy is considered the most appropriate treatment for metastatic uterine sarcoma, despite its limited efficacy. No other treatment has been conclusively proved to be a real alternative, but some reports suggest that anti-hormonal therapy could be active in a small subset of patients. We report the case of a patient with metastatic uterine carcinosarcoma with positive hormonal receptors and a complete pathological response. CASE PRESENTATION: A 54-year-old white woman presented to our emergency room with hypovolemic shock and serious vaginal bleeding...
April 19, 2017: Journal of Medical Case Reports
https://www.readbyqxmd.com/read/28423275/single-or-multiple-access-channels-to-the-cyp450s-active-site-an-answer-from-free-energy-simulations-of-the-human-aromatase-enzyme
#3
Alessandra Magistrato, Jacopo Sgrignani, Rolf Krause, Andrea Cavalli
Cytochromes P450 (CYP450), in particular CYP19A1 and CYP17A1, are key clinical targets of breast and prostate anticancer therapies, critical players in drug metabolism and their overexpression in tumours is associated with drug resistance. In these enzymes ligands (substrates, drugs) metabolism occurs in deeply buried active sites accessible only via several gruelling channels, whose exact biological role remains unclear. Gaining direct insights on the mechanism by which ligands travel in and out, is becoming increasingly important given that channels are involved in the modulation of binding/dissociation kinetics and the specificity of ligands toward a CYP450...
April 19, 2017: Journal of Physical Chemistry Letters
https://www.readbyqxmd.com/read/28398491/pregnancy-and-neonatal-outcomes-following-letrozole-use-in-frozen-thawed-single-embryo-transfer-cycles
#4
T Tatsumi, S C Jwa, A Kuwahara, M Irahara, T Kubota, H Saito
STUDY QUESTION: Are pregnancy and neonatal outcomes following letrozole use comparable with natural and HRT cycles in patients undergoing single frozen-thawed embryo transfer (FET)? SUMMARY ANSWER: Letrozole use was significantly associated with higher rates of clinical pregnancy, clinical pregnancy with fetal heart beat and live birth, and with a lower rate of miscarriage, compared with natural and HRT cycles. WHAT IS KNOWN ALREADY: Letrozole is the most commonly used aromatase inhibitor for mild ovarian stimulation in ART...
April 7, 2017: Human Reproduction
https://www.readbyqxmd.com/read/28380313/cholesterol-cholesterol-lowering-medication-use-and-breast-cancer-outcome-in-the-big-1-98-study
#5
Signe Borgquist, Anita Giobbie-Hurder, Thomas P Ahern, Judy E Garber, Marco Colleoni, István Láng, Marc Debled, Bent Ejlertsen, Roger von Moos, Ian Smith, Alan S Coates, Aron Goldhirsch, Manuela Rabaglio, Karen N Price, Richard D Gelber, Meredith M Regan, Beat Thürlimann
Purpose Cholesterol-lowering medication (CLM) has been reported to have a role in preventing breast cancer recurrence. CLM may attenuate signaling through the estrogen receptor by reducing levels of the estrogenic cholesterol metabolite 27-hydroxycholesterol. The impact of endocrine treatment on cholesterol levels and hypercholesterolemia per se may counteract the intended effect of aromatase inhibitors. Patients and Methods The Breast International Group (BIG) conducted a randomized, phase III, double-blind trial, BIG 1-98, which enrolled 8,010 postmenopausal women with early-stage, hormone receptor-positive invasive breast cancer from 1998 to 2003...
April 10, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28369967/a-simulation-study-to-compare-the-treatment-effect-of-tamoxifen-by-cyp2d6-genotypes-and-third-generation-aromatase-inhibitors
#6
Gwan Cheol Park, Jin-A Jung, Kyun-Seop Bae, Hyeong-Seok Lim
Some prospective, randomized clinical trials, including ATAC and BIG 1-98, demonstrated superior treatment effect of third-generation aromatase inhibitors (AIs) versus tamoxifen in postoperative therapy for patients with breast cancer. In retrospective genotyping analyses of the 2 studies using tumor samples, no difference in the treatment effect of tamoxifen was observed by CYP2D6 genotypes. However, those analyses did not consider loss of heterozygosity that could have occurred when genotyping using tumor tissue...
April 3, 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28364779/the-effects-of-nobiletin-hesperetin-and-letrozole-in-a-combination-on-the-activity-and-expression-of-aromatase-in-breast-cancer-cells
#7
S T Rahideh, M Keramatipour, M Nourbakhsh, F Koohdani, M Hoseini, F Shidfar
Nobiletin (NOB) and hesperetin (HES) are the citrus polymethoxyflavone and flavonone. Aromatase or cytochrome P450 (CYP19) enzyme is a key enzyme in estrogen biosynthesis. The objective of this study was to investigate the combinational effects of HES, NOB and letrozole (LET) as aromatase inhibitors on the activity and expression of aromatase in MCF-7 cells. In this study, aromatase enzyme activity based on the conversion of androgen substrate testosterone to 17β-Estradiol was determined. Estradiol concentrations were measured using an electrochemiluminescence immunoassay...
February 28, 2017: Cellular and Molecular Biology
https://www.readbyqxmd.com/read/28353144/comparing-the-administration-of-letrozole-and-megestrol-acetate-in-the-treatment-of-women-with-simple-endometrial-hyperplasia-without-atypia-a-randomized-clinical-trial
#8
Sanam Moradan, Niaz Nikkhah, Majid Mirmohammadkhanai
INTRODUCTION: The present study was conducted as a pilot to compare the therapeutic effects and the potential side effects of oral Megestrol acetate and Letrozole in the treatment of simple hyperplasia in perimenopausal women. METHODS: The participants of this randomized clinical trial consisted of two groups of 25 women aged 44-50 presenting with abnormal uterine bleeding diagnosed with simple endometrial hyperplasia without cytologic atypia confirmed by transvaginal ultrasonography and biopsy...
March 28, 2017: Advances in Therapy
https://www.readbyqxmd.com/read/28351480/melasma-treatment-a-novel-approach-using-a-topical-agent-that-contains-an-anti-estrogen-and-a-vascular-endothelial-growth-factor-inhibitor
#9
Philip R Cohen
Melasma is an acquired disorder of pigmentation that presents with asymptomatic symmetric darkening of the face. The pathogenesis of this condition is multifactorial and influenced by several factors including female sex hormones, genetic predisposition and ultraviolet light exposure. The management of melasma is usually directed at more than one of the causative etiologic factors and often incorporates a combination of topical agents, with or without the addition of physical modalities. Estrogen and angiogenesis are significant factors in the etiology of melasma...
April 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/28346074/germline-genetic-predictors-of-aromatase-inhibitor-concentrations-estrogen-suppression-and-drug-efficacy-and-toxicity-in-breast-cancer-patients
#10
Daniel L Hertz, N Lynn Henry, James M Rae
The third-generation aromatase inhibitors (AIs), anastrozole, letrozole and exemestane, are highly effective for the treatment of estrogen receptor-positive breast cancer in postmenopausal women. AIs inhibit the aromatase (CYP19A1)-mediated production of estrogens. Most patients taking AIs achieve undetectable blood estrogen concentrations resulting in drug efficacy with tolerable side effects. However, some patients have suboptimal outcomes, which may be due, in part, to inherited germline genetic variants...
March 27, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28345445/the-role-of-patient-financial-assistance-programs-in-reducing-costs-for-cancer-patients
#11
Leah L Zullig, Steven Wolf, Lisa Vlastelica, Veena Shankaran, S Yousuf Zafar
BACKGROUND: Limited transparency exists regarding eligibility and benefits for patient financial assistance programs (PAPs). OBJECTIVE: To describe oral anticancer medication costs, insurance coverage, and the degree of financial assistance provided by PAPs. METHODS: This was a retrospective study of prescription anticancer medication costs and PAP coverage. The study used data from an academic cancer center's specialty pharmacy. Medication, cost, and coverage data were collected from the specialty pharmacy database for prescriptions filled from January 2013 to November 2015...
April 2017: Journal of Managed Care & Specialty Pharmacy
https://www.readbyqxmd.com/read/28344042/exercise-differentially-affects-metabolic-functions-and-white-adipose-tissue-in-female-letrozole-and-dihydrotestosterone-induced-mouse-models-of-polycystic-ovary-syndrome
#12
Rodrigo R Marcondes, Manuel Maliqueo, Romina Fornes, Anna Benrick, Min Hu, Niklas Ivarsson, Mattias Carlström, Samuel W Cushman, Karin G Stenkula, Gustavo A R Maciel, Elisabet Stener-Victorin
Here we hypothesized that exercise in dihydrotestosterone (DHT) or letrozole (LET)-induced polycystic ovary syndrome mouse models improves impaired insulin and glucose metabolism, adipose tissue morphology, and expression of genes related to adipogenesis, lipid metabolism, Notch pathway and browning in inguinal and mesenteric fat. DHT-exposed mice had increased body weight, increased number of large mesenteric adipocytes. LET-exposed mice displayed increased body weight and fat mass, decreased insulin sensitivity, increased frequency of small adipocytes and increased expression of genes related to lipolysis in mesenteric fat...
March 24, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28333356/the-safety-and-efficacy-of-controlled-ovarian-hyperstimulation-for-fertility-preservation-in-women-with-early-breast-cancer-a-systematic-review
#13
Rachael J Rodgers, Geoffrey D Reid, Juliette Koch, Rebecca Deans, William L Ledger, Michael Friedlander, Robert B Gilchrist, Kirsty A Walters, Jason A Abbott
STUDY QUESTION: Can controlled ovarian hyperstimulation (COH) for fertility preservation be effectively conducted in women with breast cancer without worsening their prognosis? SUMMARY ANSWER: COH with co-administration of letrozole suppresses oestradiol levels without significantly impacting oocyte yield or decreasing disease-free survival rates. WHAT IS KNOWN ALREADY: Oestradiol has the capacity to stimulate the proliferation of breast cancer cells...
May 1, 2017: Human Reproduction
https://www.readbyqxmd.com/read/28333207/endometrial-thickness-in-women-undergoing-iui-with-ovarian-stimulation-how-thick-is-too-thin-a-systematic-review-and-meta-analysis
#14
N S Weiss, M N van Vliet, J Limpens, P G A Hompes, C B Lambalk, M H Mochtar, F van der Veen, B W J Mol, M van Wely
STUDY QUESTION: Is pre-ovulatory endometrial thickness (EMT) in women with unexplained subfertility undergoing IUI with ovarian stimulation (OS) associated with pregnancy chances? SUMMARY ANSWER: We found no evidence for an association between EMT and pregnancy chances. WHAT IS KNOWN ALREADY: It has been suggested that OS with clomiphene citrate (CC) results in a lower EMT than with gonadotrophins or aromatase inhibitors, but the clinical consequences in terms of pregnancy are unclear...
May 1, 2017: Human Reproduction
https://www.readbyqxmd.com/read/28325261/cdk4-6-inhibitors-in-her2-positive-breast-cancer
#15
REVIEW
Silvia Paola Corona, Andrea Ravelli, Daniele Cretella, Maria Rosa Cappelletti, Laura Zanotti, Martina Dester, Angela Gobbi, Pier Giorgio Petronini, Daniele Generali
Notwithstanding the continuous progress made in cancer treatment in the last 20 years, and the availability of new targeted therapies, metastatic Breast Cancer (BC) is still incurable. Targeting the cell cycle machinery has emerged as an attractive strategy to tackle cancer progression, showing very promising results in the preclinical and clinical settings. The first selective inhibitors of CDK4/6 received breakthrough status and FDA approval in combination with letrozole (February 2015) and fulvestrant (February 2016) as first-line therapy in ER-positive advanced and metastatic BC...
April 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28324026/gonadotropin-inhibitory-hormone-the-piscine-ortholog-of-lpxrfa-participates-in-17%C3%AE-estradiol-feedback-in-female-goldfish-reproduction
#16
Xin Qi, Wenyi Zhou, Qingqing Wang, Liang Guo, Danqi Lu, Haoran Lin
Gonadotropin-inhibitory hormone (GnIH) plays a critical role in regulating gonadotropin-releasing hormone, gonadotropin hormone, and steroidogenesis in teleosts. In the present study, we sought to determine whether 17β-estradiol (E2) acts directly on GnIH neurons to regulate reproduction in goldfish, a seasonal breeder, and we investigated the role of estrogen receptors (ERs) in mediating this process. We found that GnIH neurons coexpress three types of ERs. Ovariectomy and letrozole implantation into female goldfish at the vitellogenic stage elicited a substantial decrease in the expression of GnIH messenger RNA (mRNA), and E2 supplementation abolished this effect...
April 1, 2017: Endocrinology
https://www.readbyqxmd.com/read/28287854/polypharmacy-and-adherence-to-adjuvant-endocrine-therapy-for-breast-cancer
#17
Gregory S Calip, Shan Xing, Da-Hae Jun, Wan-Ju Lee, Kent F Hoskins, Naomi Y Ko
PURPOSE: Many patients with breast cancer are treated for other conditions and experience polypharmacy with multiple concurrent medications. Our aim was to evaluate polypharmacy in relation to adherence to adjuvant endocrine therapy (AET) in breast cancer. METHODS: We conducted a retrospective cohort study of women with incident, invasive breast cancer initiating AET (tamoxifen, letrozole, anastrozole, exemestane) between 2009 and 2013 in the Truven Health MarketScan Database...
March 13, 2017: Journal of Oncology Practice
https://www.readbyqxmd.com/read/28285614/effectiveness-of-co-treatment-with-traditional-chinese-medicine-and-letrozole-for-polycystic-ovary-syndrome-a-meta-analysis
#18
Qian-Wen Ma, Yong Tan
BACKGROUND: Polycystic ovary syndrome (PCOS) is an endocrine disease that affects gynecological health. Treatment of PCOS remains a big challenge for clinicians. OBJECTIVE: This meta-analysis was developed to compare the efficacy of co-treatment with traditional Chinese medicine (TCM) and letrozole against letrozole monotherapy in the treatment of PCOS. SEARCH STRATEGY: Randomized controlled trials (RCTs) were electronically retrieved from PubMed, Cochrane Library, China Biomedical Literature Database, China National Knowledge Infrastructure and Wanfang Data; related papers that were not available electronically were manually checked...
March 2017: Journal of Integrative Medicine
https://www.readbyqxmd.com/read/28283467/responsiveness-of-brca1-and-trp53-deficiency-induced-mammary-preneoplasia-to-selective-estrogen-modulators-versus-an-aromatase-inhibitor-in-mus-musculus
#19
Sahar J Alothman, Weisheng Wang, David S Goerlitz, Md Islam, Xiaogang Zhong, Archana Kishore, Redha I Azhar, Bhaskar V Kallakury, Priscilla A Furth
An intervention study initiated at age 4 months compared the impact of tamoxifen (25 mg), raloxifene (22.5 mg), and letrozole (2.5 mg) administered by 60-day release subcutaneous pellet on mammary preneoplasia prevalence at age 6 months in conditional genetically engineered mouse models with different Breast cancer 1 (Brca1) gene dosages targeted to mammary epithelial cells and germline Tumor protein P53 (Trp53) haploinsufficiency (10-16/cohort). The proportion of unexposed control mice demonstrating mammary preneoplasia at age 6 months was highest in Brca1(fl11/fl11/Cre/p53-/+) (54%) mice followed by Brca1(WT/fl11/Cre/p53-/+) mice (30%)...
April 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/28280800/clomiphene-citrate-versus-letrozole-with-gonadotropins-in-intrauterine-insemination-cycles-a-randomized-trial
#20
Leila Pourali, Sedigheh Ayati, Shirin Tavakolizadeh, Hourieh Soleimani, Fatemeh Teimouri Sani
BACKGROUND: Clomiphene citrate is one of the effective drugs for infertility treatment due to oligo-ovulation or anovulation. Intrauterine insemination (IUI) is one of more adherent methods for treatment of infertile cases which is followed by controlled ovarian hyperstimulation (COH). OBJECTIVE: the aim of this study was to evaluate Clomiphene citrate versus letrozole with gonadotropins in IUI cycles. MATERIALS AND METHODS: In this prospective randomized trial, 180 infertile women who were referred to Milad Hospital were selected...
January 2017: International Journal of Reproductive Biomedicine (Yazd, Iran)
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