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https://www.readbyqxmd.com/read/29642911/gnrh-dysregulation-in-polycystic-ovarian-syndrome-pcos-is-a-manifestation-of-an-altered-neurotransmitter-profile
#1
Nirja Chaudhari, Mitali Dawalbhakta, Laxmipriya Nampoothiri
BACKGROUND: GnRH is the master molecule of reproduction that is influenced by several intrinsic and extrinsic factors such as neurotransmitters and neuropeptides. Any alteration in these regulatory loops may result in reproductive-endocrine dysfunction such as the polycystic ovarian syndrome (PCOS). Although low dopaminergic tone has been associated with PCOS, the role of neurotransmitters in PCOS remains unknown. The present study was therefore aimed at understanding the status of GnRH regulatory neurotransmitters to decipher the neuroendocrine pathology in PCOS...
April 11, 2018: Reproductive Biology and Endocrinology: RB&E
https://www.readbyqxmd.com/read/29626484/neuroestradiol-in-regulation-of-gnrh-release
#2
REVIEW
Ei Terasawa
The concept that the positive feedback effect of ovarian estradiol (E2 ) results in GnRH and gonadotropin surges is a well-established principle. However, a series of studies investigating the rapid action of E2 in female rhesus monkeys has led to a new concept that neuroestradiol, synthesized and released in the hypothalamus, also contributes to regulation of the preovulatory GnRH surge. This unexpected finding started from our surprising observation that E2 induces rapid stimulatory action in GnRH neurons in vitro...
April 4, 2018: Hormones and Behavior
https://www.readbyqxmd.com/read/29623577/use-of-dual-mtor-inhibitor-mln0128-against-everolimus-resistant-breast-cancer
#3
Karineh Petrossian, Duc Nguyen, Chiao Lo, Noriko Kanaya, George Somlo, Yvonne Xiaoyong Cui, Chiun-Sheng Huang, Shiuan Chen
PURPOSE: HR+/HER2- aromatase inhibitor-resistant metastatic breast cancer can be treated with everolimus and a second AI until the cancer recurs. Targeting these everolimus-resistant patients with the latest standard of care, CDK4/6 inhibitors, has not been clearly addressed. Understanding the signaling transduction pathways, which everolimus resistance activates, will elucidate the mechanisms and offer treatment strategies of everolimus resistance. METHODS: To mimic the clinical setting, letrozole-resistant cells were used to generate an everolimus-resistant model (RAD-R)...
April 5, 2018: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/29615083/therapeutic-potentials-of-quercetin-in-management-of-polycystic-ovarian-syndrome-using-letrozole-induced-rat-model-a-histological-and-a-biochemical-study
#4
Sarwat Jahan, Abira Abid, Sidra Khalid, Tayyaba Afsar, Qurat-Ul-Ain, Ghazala Shaheen, Ali Almajwal, Suhail Razak
BACKGROUND: PCOS is a leading endocrinopathy of young women instigating androgens elevation, insulin resistance, obesity, cardiometabolic and menstrual complications. The study investigated the effects of quercetin in a letrozole induced rat model of polycystic ovarian syndrome, which displayed both clinical and metabolic features as in PCOS women. METHODS: Female Sprague Dawley (SD) rats were divided into four groups; control group received aqueous solution of carboxymethyl (CMC 0...
April 3, 2018: Journal of Ovarian Research
https://www.readbyqxmd.com/read/29609880/progression-free-survival-with-first-line-endocrine-based-therapies-among-postmenopausal-women-with-hr-her2-metastatic-breast-cancer-a-network-meta-analysis
#5
REVIEW
Rajeev Ayyagari, Derek Tang, Oscar Patterson-Lomba, Zhou Zhou, Jipan Xie, David Chandiwana, Anand A Dalal, Polly Ann Niravath
PURPOSE: The comparative efficacy of endocrine-based therapies (ETs) for hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer (mBC) is not well characterized. This network meta-analysis (NMA) synthesized available evidence on progression-free survival (PFS) with first-line ETs for postmenopausal HR+/HER2- mBC. METHODS: A systematic literature review identified randomized controlled trials of first-line ETs...
March 30, 2018: Clinical Therapeutics
https://www.readbyqxmd.com/read/29588307/comprehensive-genomic-profiling-aids-in-treatment-of-a-metastatic-endometrial-cancer
#6
Jatinder Dhami, Kim M Hirshfield, Shridar Ganesan, Mira Hellmann, Veronica Rojas, Judith K Amorosa, Gregory M Riedlinger, Hua Zhong, Siraj M Ali, Dean Pavlick, Julia A Elvin, Lorna Rodriguez-Rodriguez
PURPOSE: FGFR-TACC fusions, including FGFR3-TACC3, have been identified as potential oncogenic drivers and actionable alterations in a number of different cancer types. The clinical relevance of FGFR3-TACC3 fusions in endometrial cancer has not yet been described. METHODS: Formalin-fixed, paraffin-embedded metastatic endometrial carcinoma from the spleen and peritoneum were sent for comprehensive genomic profiling (CGP) using the FoundationOne platform as part of a prospective tumor genomic profiling protocol...
March 27, 2018: Cold Spring Harbor Molecular Case Studies
https://www.readbyqxmd.com/read/29581135/er-breast-cancers-resistant-to-prolonged-neoadjuvant-letrozole-exhibit-an-e2f4-transcriptional-program-sensitive-to-cdk4-6-inhibitors
#7
Angel Guerrero-Zotano, Thomas Stricker, Luigi Formisano, Katherine E Hutchinson, Daniel G Stover, Kyung-Min Lee, Luis J Schwarz, Jennifer M Giltnane, Monica V Estrada, Valerie M Jansen, Alberto Servetto, Joaquín Gavilá, José Alejandro Pérez-Fidalgo, Ana Lluch, Antonio Llombart-Cussac, Mohamed Amine Bayar, Stefan Michiels, Fabrice Andre, Monica Arnedos, Vicente Guillem, Amparo Ruiz-Simon, Carlos L Arteaga
PURPOSE: This study aimed to identify biomarkers of resistance to endocrine therapy in ER+ breast cancers (BC) treated with prolonged neoadjuvant letrozole. Experimental Design: We performed targeted DNA and RNA-sequencing in 68 ER+ BC from patients treated with preoperative letrozole (median 7 months). Results:Twenty-four tumors (35%) exhibited a PEPI score ≥4 and/or recurred after a median of 58 months and were considered endocrine resistant. Integration of the 47 most upregulated genes (log FC>1, FDR<0...
March 26, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29576606/gastric-metastasis-as-the-first-presentation-one-year-before-diagnosis-of-primary-breast-cancer
#8
Joohyun Woo, Joo-Ho Lee, Kyoung Eun Lee, Sun Hee Sung, Woosung Lim
BACKGROUND Metastasis to the stomach can be found as the first presentation of breast cancer, although it is very rare. The authors report an unusual case of metastasis to the stomach as the first presentation of breast cancer, which had a good prognosis. CASE REPORT A 51-year-old female underwent radical subtotal gastrectomy and chemotherapy because of gastric cancer with distant metastasis. At the time of diagnosis of gastric cancer, she had a negative result from routine mammography. One year later, a newly detected lesion on routine mammography was confirmed as breast cancer...
March 26, 2018: American Journal of Case Reports
https://www.readbyqxmd.com/read/29566104/everolimus-plus-endocrine-therapy-for-postmenopausal-women-with-estrogen-receptor-positive-human-epidermal-growth-factor-receptor-2-negative-advanced-breast-cancer-a-clinical-trial
#9
Melanie Royce, Thomas Bachelot, Cristian Villanueva, Mustafa Özgüroglu, Sergio J Azevedo, Felipe Melo Cruz, Marc Debled, Roberto Hegg, Tatsuya Toyama, Carla Falkson, Joon Jeong, Vichien Srimuninnimit, William J Gradishar, Christina Arce, Antonia Ridolfi, Chinjune Lin, Fatima Cardoso
Importance: Cotargeting the mammalian target of rapamycin pathway and estrogen receptor may prevent or delay endocrine resistance in patients receiving first-line treatment for advanced breast cancer. Objective: To investigate the combination of everolimus plus endocrine therapy in first-line and second-line treatment settings for postmenopausal women with estrogen receptor-positive, human epidermal growth receptor 2-negative advanced breast cancer. Design, Setting, and Participants: In the multicenter, open-label, single-arm, phase 2 BOLERO-4 (Breast Cancer Trials of Oral Everolimus) clinical trial, 245 patients were screened for eligibility; 202 were enrolled between March 7, 2013, and December 17, 2014...
March 22, 2018: JAMA Oncology
https://www.readbyqxmd.com/read/29564925/luteal-phase-ovarian-stimulation-increases-the-number-of-mature-oocytes-in-older-women-with-severe-diminished-ovarian-reserve
#10
Justin Rashtian, John Zhang
In older women with severe diminished ovarian response (DOR), in vitro fertilization (IVF) treatment is much less successful due to the low number of mature oocytes collected. The objective of this study was to assess whether follicular-phase stimulation (FPS) and luteal-phase stimulation (LPS) in the same menstrual cycle (double ovarian stimulation) in older women with severe DOR will produce a higher number of oocytes compared to FPS alone. Women with DOR (n = 69; mean age = 42.4) who underwent double ovarian stimulation for IVF were included...
March 22, 2018: Systems Biology in Reproductive Medicine
https://www.readbyqxmd.com/read/29564315/the-serum-estradiol-oocyte-ratio-in-patients-with-breast-cancer-undergoing-ovarian-stimulation-with-letrozole-and-gonadotropins
#11
Yoo Jin Shim, Aeran Seol, Dayong Lee, Seul Ki Kim, Jung Ryeol Lee, Byung Chul Jee, Chang Suk Suh, Seok Hyun Kim
Objective: To investigate the patterns of estradiol-oocyte ratio (EOR) and estradiol-mature oocyte ratio (EMOR) in patients with breast cancer undergoing controlled ovarian stimulation (COS) using letrozole and gonadotropins for fertility preservation. Methods: This retrospective study included 32 breast cancer patients underwent COS for fertility preservation and no patients had previously undergone gonadotoxic treatments. Basal characteristics and in vitro fertilization (IVF) outcomes were compared according to the age of women (age <35 vs...
March 2018: Obstetrics & Gynecology Science
https://www.readbyqxmd.com/read/29561210/preparation-and-characterization-of-letrozole-loaded-poly-d-l-lactide-nanoparticles-for-drug-delivery-in-breast-cancer-therapy
#12
Bayan Alemrayat, Abdelbary Elhissi, Husam M Younes
Letrozole (LTZ), an aromatase inhibitor used for the treatment of hormonally-positive breast cancer in postmenopausal women, has poor water solubility, rapid metabolism, and a range of side effects. In this study, polymer-based nanoparticles (NPs) incorporating the drug have been designed and characterized, aimed to control the release, potentially maximize the therapeutic efficiency, and minimize the side effects of the drug. LTZ was incorporated into poly(d,l-lactide) (PDLLA) NPs by employing the emulsion-solvent evaporation technique using a range of drug concentrations...
April 5, 2018: Pharmaceutical Development and Technology
https://www.readbyqxmd.com/read/29560610/investigating-the-effect-of-testosterone-by-itself-and-in-combination-with-letrozole-on-1-25-dihydroxy-vitamin-d-and-fgf23-in-male-rats
#13
F Saki, S R Kasaee, F Sadeghian, F Koohpeyma, G H R Omrani
BACKGROUND: Testosterone deficiency might be associated with vitamin D levels in hypogonadal men, but it is not clear whether testosterone can affect vitamin D and fibroblast growth factor-23 (FGF23), either directly or indirectly via aromatization to estradiol. We aimed to investigate the role of testosterone on vitamin D metabolism and serum FGF23 in male rats. METHODS: A total of 48 male rats were divided into 4 equal groups: sham; O, orchiectomy; O + T, orchiectomized rats treated with testosterone; and O + T + L, orchiectomized rats treated with combination of testosterone and letrozole...
March 20, 2018: Journal of Endocrinological Investigation
https://www.readbyqxmd.com/read/29536789/in-case-of-anastrozole-related-hallucinations-can-switching-to-letrozole-be-a-treatment-option-a-case-report-and-literature-review
#14
Yakup Bozkaya, Gökmen Umut Erdem, Nebi Serkan Demirci
Arthralgia, myalgia, paresthesia, reduced bone mineral density, vasomotor side effects including hot flashes and night sweats, genitourinary symptoms including decreased libido, vaginal dryness and dyspareunia are common side effects of aromatase inhibitors. Unlike the common side effects, the information on neurological side effects like hallucination of aromatase inhibitor was limited in literature cases. Herein, we reported a case of hallucination related to anastrozole in a patient with metastatic breast cancer...
January 1, 2018: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/29523051/verapamil-as-a-culprit-of-palbociclib-toxicity
#15
Jasmine L Gowarty, Jon D Herrington
A promising drug, palbociclib, received accelerated approval as a first line treatment when used with the aromatase inhibitor, letrozole, for postmenopausal women with hormone receptor positive advanced or metastatic breast cancer. We report a case of a patient who presented with febrile neutropenia, grade 3 stomatitis with lip swelling, periorbital edema, and transaminitis while on palbociclib and verapamil. Labs normalized upon discontinuation of verapamil and our patient was able to continue treatment with palbociclib and letrozole...
January 1, 2018: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/29522952/azoles-additively-inhibit-cytochrome-p450-1-erod-and-19-aromatase-in-rainbow-trout-oncorhynchus-mykiss
#16
Kristina Beijer, Maria Jönsson, Siraz Shaik, Daphné Behrens, Björn Brunström, Ingvar Brandt
Antifungal azoles are widely used in medicine, agriculture, and material protection and several antifungal azoles have been found in environmental samples. Although these compounds were designed to inhibit fungal enzymes such as lanosterol-14-demethylase (cytochrome P450 (CYP) 51), it is well established that the inhibitory actions of azoles are not specific for fungal CYP isozymes. We refined a gill filament assay to determine the inhibition of CYP1, measured as reduced 7-ethoxyresorufin-O-deethylase (EROD) activity, in rainbow trout (Oncorhynchus mykiss) gill tissue ex vivo...
February 21, 2018: Aquatic Toxicology
https://www.readbyqxmd.com/read/29521126/lapatinib-nano-delivery-systems-a-promising-future-for-breast-cancer-treatment
#17
Gunjan Vasant Bonde, Sarita Kumari Yadav, Sheetal Chauhan, Pooja Mittal, Gufran Ajmal, Sathish Thokala, Brahmeshwar Mishra
Breast cancer stands the second prominent cause of death among women. For its efficient treatment, Lapatinib (LAPA) was developed as a selective tyrosine kinase inhibitor of receptors, overexpressed by breast cancer cells. Various explored delivery strategies for LAPA indicated its controlled release with enhanced aqueous solubility, improved bioavailability, decreased plasma protein binding, reduced dose and toxicity to the other organs with maximized clinical efficacy, compared to its marketed tablet formulation...
March 14, 2018: Expert Opinion on Drug Delivery
https://www.readbyqxmd.com/read/29510649/the-effects-of-letrozole-and-clomiphene-citrate-on-ligands-expression-of-wnt3-wnt7a-and-wnt8b-in-proliferative-endometrium-of-women-with-polycystic-ovarian-syndrome
#18
Shayesteh Mehdinejadiani, Fardin Amidi, Mehdi Mehdizadeh, Mahmood Barati, Leili Safdarian, Reza Aflatoonian, Ashraf Alyasin, Marzieh Aghahosseini, Azar Pazhohan, Parisa Hayat, Farzaneh Mohammadzadeh Kazorgah, Aligholi Sobhani
Polycystic ovarian syndrome (PCOS) is a common endocrinologic disorder in women of reproductive age characterized by polycystic ovaries, oligo/anovulation, and hyperandrogenism. Not only anovulation but also endometrial dysfunction can reduce fertility in PCOS patients. Wnt pathway is responsible for endometrial proliferation which be strongly regulated by estradiol. To determine the effects of clomiphene citrate (CC) and letrozole, we measured the expression of some main ligands of Wnt/β-catenin signaling including Wnt7a, Wnt3, and Wnt8b in the endometrial samples taken from PCOS women on day 12 of the menses who received 100 mg CC or 5 mg letrozole as well as from women without treatment...
March 6, 2018: Gynecological Endocrinology
https://www.readbyqxmd.com/read/29507656/estrogen-receptor-alpha-drives-mtorc1-inhibitor-induced-feedback-activation-of-pi3k-akt-in-er-breast-cancer
#19
Wei Yang, Gary N Schwartz, Jonathan D Marotti, Vivian Chen, Nicole A Traphagen, Jiang Gui, Todd W Miller
The mTORC1 inhibitor RAD001 (everolimus) is approved for treatment of recurrent/metastatic estrogen receptor (ER)-positive breast cancer in combination with the aromatase inhibitor (AI) exemestane. The benefits of A) continued anti-estrogen therapy for anti-estrogen-resistant disease in the context of mTORC1 inhibition, and B) adjuvant everolimus in combination with anti-estrogen therapy for early-stage disease are being tested clinically, but molecular rationale remains unclear. We hypothesized that mTORC1 inhibition activates the IGF-1R/InsR/IRS-1/2 axis in an ER-dependent manner to drive PI3K/AKT and promote cancer cell survival, implicating ER in survival signaling induced by mTORC1 inhibition...
February 6, 2018: Oncotarget
https://www.readbyqxmd.com/read/29505837/expression-profiles-of-mrna-and-long-noncoding-rna-in-the-ovaries-of-letrozole-induced-polycystic-ovary-syndrome-rat-model-through-deep-sequencing
#20
Lu-Lu Fu, Ying Xu, Dan-Dan Li, Xiao-Wei Dai, Xin Xu, Jing-Shun Zhang, Hao Ming, Xue-Ying Zhang, Guo-Qing Zhang, Ya-Lan Ma, Lian-Wen Zheng
Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in reproductive-aged women. However, the exact pathophysiology of PCOS remains largely unclear. We performed deep sequencing to investigate the mRNA and long noncoding RNA (lncRNA) expression profiles in the ovarian tissues of letrozole-induced PCOS rat model and control rats. A total of 2147 mRNAs and 158 lncRNAs were differentially expressed between the PCOS models and control. Gene ontology analysis indicated that differentially expressed mRNAs were associated with biological adhesion, reproduction, and metabolic process...
March 2, 2018: Gene
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