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https://www.readbyqxmd.com/read/28109841/disruption-of-aromatase-homeostasis-as-the-cause-of-a-multiplicity-of-ailments-a-comprehensive-review
#1
REVIEW
Seema Patel
Human health is beset with a legion of ailments, which is exacerbated by the lifestyle errors. Out of the numerous enzymes in human body, aromatase, a cytochromes P450 enzyme is particularly very critical. Occurring at the crossroads of multiple signalling pathways, its homeostasis is vital. Unfortunately, medications, hormone therapy, chemical additives in food, and endocrine-disrupting personal care products are oscillating the aromatase concentration beyond the permissible level. As this enzyme converts androgens (C19) into estrogens (C18), its agitation has different outcomes in different genders and age groups...
January 18, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28108667/effects-on-circulating-steroid-hormones-and-gene-expression-along-the-hypothalamus-pituitary-gonadal-axis-in-adult-japanese-quail-exposed-to-17%C3%AE-trenbolone-across-multiple-generations
#2
Natalie K Karouna-Renier, Yu Chen, Paula F P Henry, Catherine M Maddox, Daniel T Sprague
We investigated the effects of the androgenic growth promoter 17ß-trenbolone (17βTB) on adult Japanese quail (Coturnix japonica) exposed across three generations. The F0 generation was exposed after sexual maturity to 0, 1, 5, 10, 20, and 40 ppm through feed. The F1 generation was exposed in ovo by maternal transfer and through feed at the same doses as their parents. The F2 generation was exposed in ovo only. Levels of plasma sex steroids, gonadal Cytochrome P450 aromatase (CYP19A1) mRNA and select brain neuroendocrine peptide mRNAs were measured...
January 20, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28107821/effects-of-a-single-20%C3%A2-mg-dose-of-letrozole-on-ovarian-function-post-dominant-follicle-selection-an-exploratory-randomized-controlled-trial
#3
H C M Allaway, D R Chizen, G P Adams, R A Pierson
BACKGROUND: Our objective was to explore the impact of a single dose of an aromatase inhibitor (letrozole) administered at defined times of the follicular phase or immediately after ovulation on dominant follicle development, luteogenesis and new follicle wave emergence. METHODS: A prospective pilot study using a randomized complete block, controlled, open label design was conducted at an academic clinical research center. Forty-five healthy, female volunteers (25...
January 21, 2017: Journal of Ovarian Research
https://www.readbyqxmd.com/read/28107349/using-breast-cancer-risk-associated-polymorphisms-to-identify-women-for-breast-cancer-chemoprevention
#4
Elad Ziv, Jeffrey A Tice, Brian Sprague, Celine M Vachon, Steven R Cummings, Karla Kerlikowske
BACKGROUND: Breast cancer can be prevented with selective estrogen receptor modifiers (SERMs) and aromatase inhibitors (AIs). The US Preventive Services Task Force recommends that women with a 5-year breast cancer risk ≥3% consider chemoprevention for breast cancer. More than 70 single nucleotide polymorphisms (SNPs) have been associated with breast cancer. We sought to determine how to best integrate risk information from SNPs with other risk factors to risk stratify women for chemoprevention...
2017: PloS One
https://www.readbyqxmd.com/read/28106545/the-alterations-of-serum-fgf-21-levels-metabolic-and-body-composition-in-early-breast-cancer-patients-receiving-adjuvant-endocrine-therapy
#5
Murat Akyol, Ahmet Alacacioglu, Leyla Demir, Yuksel Kucukzeybek, Yasar Yildiz, Zehra Gumus, Mete Kara, Tarik Salman, Umut Varol, Halil Taskaynatan, Utku Oflazoglu, Vedat Bayoglu, Mustafa Oktay Tarhan
BACKGROUND: In early breast cancer patients, the effects of hormonal therapy (tamoxifen and aromatase inhibitors) on plasma fibroblast growth factor 21 (FGF-21), lipid levels and body composition have not yet been investigated. Therefore, we aimed to analyze the relationship between FGF-21 and body composition as well as the effects of tamoxifen and aromatase inhibitors on plasma lipid levels, FGF-21, and body composition. METHODS: A total of 72 patients were treated with either tamoxifen or aromatase inhibitors due to their menopausal status after adjuvant radiotherapy...
January 13, 2017: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/28104509/morphometric-vertebral-fractures-in-breast-cancer-patients-treated-with-adjuvant-aromatase-inhibitor-therapy-a-cross-sectional-study
#6
Rebecca Pedersini, Sara Monteverdi, Gherardo Mazziotti, Vito Amoroso, Elisa Roca, Filippo Maffezzoni, Lucia Vassalli, Filippo Rodella, Anna Maria Formenti, Stefano Frara, Roberto Maroldi, Alfredo Berruti, Edda Simoncini, Andrea Giustina
BACKGROUND: The impact of long-term adjuvant therapy with aromatase inhibitors (AIs) on vertebral fracture (VF) risk is still unclear. OBJECTIVE: In this cross-sectional study, we explored the prevalence and determinants of VFs in breast cancer (BC) patients before and during AI therapy. Each woman underwent a dual-energy X-ray absorptiometry (DXA) to evaluate bone mineral density (BMD) and identify VFs by a quantitative morphometric approach. Blood samples were collected to measure serum hormone and calcium levels...
January 16, 2017: Bone
https://www.readbyqxmd.com/read/28104404/dibutyl-phthalate-impairs-steroidogenesis-and-a-subset-of-lh-dependent-genes-in-cultured-human-mural-granulosa-cell-in-vitro
#7
Michal Adir, Catherine M H Combelles, Abdallah Mansur, Libby Ophir, Ariel Hourvitz, Raoul Orvieto, Jehoshua Dor, Ronit Machtinger
Exposure to di-butyl phthalate (DBP) exerts negative effects on female fertility in animal models, but human studies remain limited. Here, the effects of DBP exposure on mural granulosa cell function were investigated in primary cultures from women undergoing in vitro fertilization. Cultured cells treated with various doses of DBP (0, 0.01μg/mL, 0.1μg/mL, 1μg/mL, 10μg/mL, or 100μg/mL) for 48h were assessed using enzyme-linked immunosorbent assay and qRT-PCR. Treatment with 100μg/mL DBP resulted in significantly lower 17β-estradiol and progesterone production (p<0...
January 16, 2017: Reproductive Toxicology
https://www.readbyqxmd.com/read/28101033/maximizing-the-benefit-cost-ratio-of-anthracyclines-in-metastatic-breast-cancer-case-report-of-a-patient-with-a-complete-response-to-high-dose-doxorubicin
#8
Kevin Shee, Alan T Kono, Susan P D'Anna, Mark A Seltzer, Xiaoying Lu, Todd W Miller, Mary D Chamberlin
Despite the clinical efficacy of anthracycline agents such as doxorubicin, dose-limiting cardiac toxicities significantly limit their long-term use. Here, we present the case of a 33-year-old female patient with extensive metastatic ER+/PR+/HER2- mucinous adenocarcinoma of the breast, who was started on doxorubicin/cyclophosphamide therapy after progressing on paclitaxel and ovarian suppressor goserelin with aromatase inhibitor exemestane. The patient was comanaged by cardiology, who carefully monitored measures of cardiac function, including EKGs, serial echocardiograms, and profiling of lipids, troponin, and pro-BNP every 2 months...
September 2016: Case Reports in Oncology
https://www.readbyqxmd.com/read/28100869/gonadotoropin-actions-on-spermatogenesis-and-hormonal-therapies-for-spermatogenic-disorders-review
#9
Koji Shiraishi, Hideyasu Matsuyama
Microdissection testicular sperm extraction and intracytoplasmic sperm injection have made it possible for men with non-obstructive azoospermia (NOA) to conceive a child. A majority of men cannot produce sperm because spermatogenesis per se is believed to be "irreversibly" disturbed. For these men, it and has been thought that any hormonal therapy will be ineffective. Further understandings of endocrinological regulation of spermatogenesis are needed and LH or FSH receptor knock out (KO) mice have revealed the roles of gonadotropin separately...
January 19, 2017: Endocrine Journal
https://www.readbyqxmd.com/read/28093793/the-sex-dependent-effects-of-letrozole-on-anxiety-in-middle-aged-rats
#10
Veronika Borbélyová, Emese Domonkos, Melinda Csongová, Mária Kačmárová, Daniela Ostatníková, Peter Celec, Július Hodosy
Aromatase catalyzes the conversion of testosterone to estradiol and is involved in physiological effects of sex hormones on brain functions. Animal experiments have shown that the aromatase inhibitor, letrozole, can induce anxiety in young ovariectomized females that are used as a model of aging. Whether or not these effects would be similar in intact middle-aged animals is unknown. The aim of our study was to analyze the effects of letrozole on anxiety in middle-aged rats of both sexes. Fifteen months old male and female rats were treated daily with either letrozole or vehicle for 2 weeks...
January 16, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28078217/testosterone-replacement-in-the-infertile-man
#11
REVIEW
Ahmad Majzoub, Edmund Sabanegh
Hypogonadism is a common clinical condition affecting men of different age groups. In addition to its sexual consequences, it has several implications posing significant concerns for a man's health and well-being. Recent advances in testosterone (T) supplementation have facilitated hypogonadism treatment. Despite that, patients complaining of infertility or seeking conception are still hindered by the unfavorable effects supplemental T has on testicular function. Consequently, alternative approaches that can stimulate endogenous T production are favored...
December 2016: Translational Andrology and Urology
https://www.readbyqxmd.com/read/28077765/acute-embryonic-anoxia-exposure-favours-the-development-of-a-dominant-and-aggressive-phenotype-in-adult-zebrafish
#12
Catherine M Ivy, Cayleih E Robertson, Nicholas J Bernier
Eutrophication and climate change are increasing the incidence of severe hypoxia in fish nursery habitats, yet the programming effects of hypoxia on stress responsiveness in later life are poorly understood. In this study, to investigate whether early hypoxia alters the developmental trajectory of the stress response, zebrafish embryos were exposed to 4 h of anoxia at 36 h post-fertilization and reared to adults when the responses to secondary stressors were assessed. While embryonic anoxia did not affect basal cortisol levels or the cortisol response to hypoxia in later life, it had a marked effect on the responses to a social stressor...
January 11, 2017: Proceedings. Biological Sciences
https://www.readbyqxmd.com/read/28076829/comparing-the-effect-of-aromatase-inhibitor-letrozole-cabergoline-dostinex-and-letrozole-alone-on-uterine-myoma-regression-a-randomized-clinical-trial
#13
M Sayyah-Melli, M Mobasseri, P M Gharabaghi, E Ouladsahebmadarek, V Rahmani
OBJECTIVE: To evaluate the effect of letrozole in combination with cabergoline and letrozole alone on regression of symptomatic uterine myomas in women of reproductive age. DESIGN: Randomized controlled clinical trial. SETTING: University hospital. PATIENTS: Ninety-one women of reproductive age were enrolled in the study and 88 women were eligible. Eight participants were excluded from the study. INTERVENTIONS: Eighty women of reproductive age with symptomatic myomas >4cm were evaluated in two groups...
December 23, 2016: European Journal of Obstetrics, Gynecology, and Reproductive Biology
https://www.readbyqxmd.com/read/28068170/factors-associated-with-early-discontinuation-of-study-treatment-in-the-mammary-prevention-3-breast-cancer-chemoprevention-trial
#14
Olivia Meggetto, Elizabeth Maunsell, Rowan Chlebowski, Paul Goss, Dongsheng Tu, Harriet Richardson
Purpose Aromatase inhibitors are established breast cancer chemoprevention interventions. However, nonadherence remains a significant challenge. We investigated the association between worsening menopause-specific quality of life, baseline participant characteristics, and early treatment discontinuation within the Mammary Prevention.3 (MAP.3) breast cancer prevention trial. Methods In the MAP.3 randomized, placebo-controlled trial evaluating exemestane, participants completed the Menopause-Specific Quality of Life Questionnaire (MENQOL) at entry and at 6 months...
January 9, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28065637/the-steroid-metabolite-16-%C3%AE-oh-androstenedione-generated-by-cyp21a2-serves-as-a-substrate-for-cyp19a1
#15
J Neunzig, M Milhim, L Schiffer, Y Khatri, J Zapp, A Sánchez-Guijo, M F Hartmann, S A Wudy, R Bernhardt
The 21-hydroxylase (CYP21A2) is a steroidogenic enzyme crucial for the synthesis of mineralo- and glucocorticoids. It is described to convert progesterone as well as 17-OH-progesterone, through a hydroxylation at position C21, into 11-deoxycorticosterone (DOC) and 11-deoxycortisol (RSS), respectively. In this study we unraveled CYP21A2 to have a broader steroid substrate spectrum than assumed. Utilizing a reconstituted in vitro system, consisting of purified human CYP21A2 and human cytochrome P450 reductase (CPR) we demonstrated that CYP21A2 is capable to metabolize DOC, RSS, androstenedione (A4) and testosterone (T)...
January 5, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28060751/the-small-heat-shock-protein-b8-hspb8-modulates-proliferation-and-migration-of-breast-cancer-cells
#16
Margherita Piccolella, Valeria Crippa, Riccardo Cristofani, Paola Rusmini, Mariarita Galbiati, Maria Elena Cicardi, Marco Meroni, Nicola Ferri, Federica F Morelli, Serena Carra, Elio Messi, Angelo Poletti
Breast cancer (BC) is one of the major causes of cancer death in women and is closely related to hormonal dysregulation. Estrogen receptor (ER)-positive BCs are generally treated with anti hormone therapy using antiestrogens or aromatase inhibitors. However, BC cells may become resistant to endocrine therapy, a process facilitated by autophagy, which may either promote or suppress tumor expansion. The autophagy facilitator HSPB8 has been found overexpressed in some BC. Here we found that HSPB8 is highly expressed and differentially modulated by natural or synthetic selective ER modulators (SERMs), in the triple-positive hormone-sensitive BC (MCF-7) cells, but not in triple-negative MDA-MB-231 BC cells...
January 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28059043/natural-products-as-anticancerous-therapeutic-molecules-with-special-reference-to-enzymatic-targets-topoisomerase-cox-lox-and-aromatase
#17
Swati Singh, Manika Awasthi, Veda P Pandey, Upendra Dwivedi
Cancer, characterized by uncontrolled growth and proliferation of cells, is affecting millions of people every year and estimated as the second leading cause of death. Its successful treatment yet remains a challenge due to the lack of selectivity, toxicity and the development of multi-drug resistant cells to the currently available drugs. Plant derived natural products hold great promise for discovery and development of new pharmaceuticals against cancer as evident by the fact that out of 121 drugs prescribed for cancer treatment till date, 90 are derived from plant sources...
January 5, 2017: Current Protein & Peptide Science
https://www.readbyqxmd.com/read/28058096/breast-ductal-carcinoma-in-situ-a-literature-review-of-adjuvant-hormonal-therapy
#18
REVIEW
Stephen Kinsey-Trotman, Zumin Shi, Beverley Fosh
This review paper analyzed publications of adjuvant tamoxifen and aromatase inhibitor use following surgery for breast ductal carcinoma in situ (DCIS). Key endpoint analyses were risk of invasive and noninvasive malignancies and new contralateral breast cancers. Metaanalysis of three studies showed a relative risk of 0.69 (95% confidence interval, 0.60-0.79, P<0.05) for breast malignancies with tamoxifen treatment in a mixed radiotherapy treatment/naïve cohort. Subgroup analysis of DCIS populations in multiple studies showed a trend to benefit with aromatase inhibitor treatment...
October 10, 2016: Oncology Reviews
https://www.readbyqxmd.com/read/28057567/prenatal-administration-of-letrozole-reduces-sdn-and-scn-volume-and-cell-number-independent-of-partner-preference-in-the-male-rat
#19
Sandra Olvera-Hernández, Miguel Tapia-Rodríguez, Dick F Swaab, Alonso Fernández-Guasti
During development, the exposure to testosterone, and its conversion to estradiol by an enzyme complex termed aromatase, appears to be essential in adult male rats for the expression of typical male sexual behavior and female-sex preference. Some hypothalamic areas are the supposed neural bases of sexual preference/orientation; for example, male-oriented rams have a reduced volume of the sexually dimorphic nucleus (oSDN), while in homosexual men this nucleus does not differ from that of heterosexual men. In contrast, homosexual men showed a larger number of vasopressinergic cells in the suprachiasmatic nucleus (SCN)...
January 3, 2017: Physiology & Behavior
https://www.readbyqxmd.com/read/28057171/predicting-high-impact-pharmacological-targets-by-integrating-transcriptome-and-text-mining-features
#20
Anatoly Mayburd, Ancha Baranova
PURPOSE: Novel, "outside of the box" approaches are needed for evaluating candidate molecules, especially in oncology. Throughout the years of 2000-2010, the efficiency of drug development fell to barely acceptable levels, and in the second decade of this century, levels have improved only marginally. This dismal condition continues despite unprecedented progress in the development of a variety of high-throughput tools, computational methods, aggregated databases, drug repurposing programs and innovative chemistries...
October 2016: Journal of Pharmacy & Pharmaceutical Sciences: a Publication of the Canadian Society for Pharmaceutical Sciences
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