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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
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
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
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 9, 2018: Expert Opinion on Drug Delivery
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
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
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
Yukiko Hara, Kenichi Sakurai, Keita Adachi, Asako Fujiwara, Yoko Ono, Eiko Waga, Tomohiro Hirano, Katsuhisa Enomoto
We report a case of primary advanced breast cancer that was locally controlled by treatment with bevacizumab. A 69-yearold woman presented at our hospital complaining of left breast hemorrhage. Her left breast had a large mass with an ulcer, and there was bleeding. Breast ultrasonography showed a large tumor that involved the whole left breast, and some swollen axillary lymph nodes. Breast MRI showed a mass of 77mm and skin invasion around the medial area of the left breast. Histopathological examination indicated invasive ductal carcinoma, ER(+), PgR(+), HER2(-), Ki-67 20%...
February 2018: Gan to Kagaku Ryoho. Cancer & Chemotherapy
Sabino De Placido, Ciro Gallo, Michelino De Laurentiis, Giancarlo Bisagni, Grazia Arpino, Maria Giuseppa Sarobba, Ferdinando Riccardi, Antonio Russo, Lucia Del Mastro, Alessio Aligi Cogoni, Francesco Cognetti, Stefania Gori, Jennifer Foglietta, Antonio Frassoldati, Domenico Amoroso, Lucio Laudadio, Luca Moscetti, Filippo Montemurro, Claudio Verusio, Antonio Bernardo, Vito Lorusso, Adriano Gravina, Gabriella Moretti, Rossella Lauria, Antonella Lai, Carmen Mocerino, Sergio Rizzo, Francesco Nuzzo, Paolo Carlini, Francesco Perrone
BACKGROUND: Uncertainty exists about the optimal schedule of adjuvant treatment of breast cancer with aromatase inhibitors and, to our knowledge, no trial has directly compared the three aromatase inhibitors anastrozole, exemestane, and letrozole. We investigated the schedule and type of aromatase inhibitors to be used as adjuvant treatment for hormone receptor-positive early breast cancer. METHODS: FATA-GIM3 is a multicentre, open-label, randomised, phase 3 trial of six different treatments in postmenopausal women with hormone receptor-positive early breast cancer...
February 23, 2018: Lancet Oncology
Xuan Wang, Min Jin, Qingqing Ye, Meng Wang, Yan Hu, Yonghua Yang, Jiyuan Yang, Jun Cai
RATIONALE: Advanced breast cancer frequently metastasizes to the lungs, liver, and bones. Metastatic involvement of the duodenal bulb is extremely rare and difficult to detect by endoscopy. PATIENT CONCERNS: A 51-year-old menopausal woman presented with abdominal fullness and obstructive symptoms, and was diagnosed with adenocarcinoma in the duodenal bulb. The patient had undergone modified radical mastectomy of the left breast for infiltrating ductal carcinoma (IDC) 8 years previously...
January 2018: Medicine (Baltimore)
Genevieve E Ryan, Shaddy Malik, Pamela L Mellon
Polycystic ovary syndrome (PCOS), the most common endocrinopathy in women of reproductive age, is characterized by hyperandrogenism, anovulation, and polycystic ovaries. Although its etiology is unknown, excess androgens are thought to be a critical factor driving the pathology of PCOS. We previously demonstrated that continuous exposure to the aromatase inhibitor letrozole (LET) in mice produces many hallmarks of PCOS, including elevated testosterone (T) and luteinizing hormone, anovulation, and obesity. In the current study, we sought to determine whether androgen receptor (AR) actions are responsible for any of the phenotypes observed in LET mice...
April 1, 2018: Endocrinology
Allan Ramos-Esquivel, Hellen Hernández-Steller, Marie-France Savard, Denis Ulises Landaverde
BACKGROUND: To compare the efficacy and toxicity of the combination of cyclin-dependent kinase 4/6 (CDK 4/6) inhibitors and nonsteroidal aromatase inhibitors (AI) versus AI alone as first-line therapy for patients with advanced hormone receptor-positive breast cancer. MATERIALS AND METHODS: Phase III randomized clinical trials (RCT) were identified after a systematic review of electronic databases. A random-effect model was used to determine the pooled hazard ratio (HR) for progression-free survival (PFS) using the inverse-variance method...
February 22, 2018: Breast Cancer: the Journal of the Japanese Breast Cancer Society
Alon Eliakim
The Pediatric Exercise Science "Year That Was" section aims to highlight the most important (to the author's opinion) manuscripts that were published in 2017 in the field of endocrinology and pediatric exercise science. This year's selection includes studies showing that 1) in pubertal swimmers, there is a decrease in insulin-like growth factor-1 (IGF-I) and IGF-binding protein-3 (IGFBP-3) during intense training (a catabolic-type hormonal response) with an anabolic "rebound" characterized by a significant increase of these growth factors during training tapering down...
February 22, 2018: Pediatric Exercise Science
Jikai Zhao, Chen Bian, Mengying Liu, Yangang Zhao, Tao Sun, Fangzhou Xing, Jiqiang Zhang
Hippocampal synaptic plasticity is the basis of spatial memory and cognition and is strongly regulated by both testicular androgens (testosterone, T) and hippocampal estrogens (17β-estradiol, E2) converted from T by aromatase, which is inhibited by letrozole (LET), but the contribution of each pathway to spatial memory and the associated mechanisms are unclear. In this study, we first used orchiectomy (ORX) and LET injection to investigate the effects of T and hippocampal E2 on spatial memory and hippocampal synaptic plasticity...
February 13, 2018: Journal of Steroid Biochemistry and Molecular Biology
Ugne Sabale, Mattias Ekman, Daniel Thunström, Claire Telford, Christopher Livings
OBJECTIVES: In Sweden, breast cancer (BC) represents 30% of newly diagnosed cancers and is the most common cancer in women. For hormone-dependent BC, endocrine therapies varying in efficacy and price are available. The aim of this study is to assess the cost effectiveness of fulvestrant 500 mg as a second-line hormonal therapy for postmenopausal women with estrogen receptor-positive metastatic or locally advanced BC versus letrozole, anastrozole, and exemestane in Sweden. METHODS: A three-state (pre-progression, post-progression, and death) partitioned-survival model was used to estimate progression-free (PFS) and overall survival (OS) by extrapolating trial results beyond the trial period to capture costs and benefits over a lifetime perspective...
December 2017: PharmacoEconomics Open
Anand Shah, Erik Bloomquist, Shenghui Tang, Wentao Fu, Youwei Bi, Qi Liu, Jingyu Yu, Ping Zhao, Todd R Palmby, Kirsten B Goldberg, C J George Chang, Paresma Patel, Elleni Alebachew, Amy Tilley, William F Pierce, Amna Ibrahim, Gideon M Blumenthal, Rajeshwari Sridhara, Julia A Beaver, Richard Pazdur
On March 13, 2017, the U.S. Food and Drug Administration approved ribociclib (KISQALI, Novartis Pharmaceuticals Corp.), a cyclin-dependent kinase 4/6 inhibitor, in combination with an aromatase inhibitor as initial endocrine-based therapy for the treatment of postmenopausal women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer. The approval was based on a randomized, double-blind, placebo-controlled, international clinical trial (MONALEESA-2)...
February 7, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Wolfgang Janni, Emilio Alba, Thomas Bachelot, Sami Diab, Miguel Gil-Gil, Thaddeus J Beck, Larisa Ryvo, Rafael Lopez, Michaela Tsai, Francisco J Esteva, Pilar Zamora Auñón, Zdenek Kral, Patrick Ward, Paul Richards, Timothy J Pluard, Santosh Sutradhar, Michelle Miller, Mario Campone
PURPOSE: The phase 3 MONALEESA-2 study demonstrated that addition of ribociclib (RIB) to letrozole (LET) significantly improved progression-free survival (PFS) in patients (pts) with hormone receptor-positive (HR+), HER2-negative (HER2-) advanced breast cancer (ABC). Here, we evaluated duration of response (DoR), tumor shrinkage, PFS by treatment-free interval (TFI), and health-related quality of life (HRQoL). METHODS: Postmenopausal women (N = 668) with HR+ , HER2- ABC and no prior systemic therapy for ABC were randomized to RIB (600 mg/day; 3 weeks on/1 week off) plus LET (2...
February 5, 2018: Breast Cancer Research and Treatment
Takashi Katsumori, Hisami Ohshima, Hiromitsu Hamaguchi, Shinichi Yamamoto, Yukika Tsukamoto, Tomohiro Iwanaga, Susumu Ohkawara
A 50s-year-old woman underwent left partial mastectomy with axillary lymphadenectomy for breast cancer. Histological examination indicated invasive ductal carcinoma, pT1c, pN0, Stage I , ly(+), ER(+), PgR(+). She received adjuvant therapy with tamoxifen and 50 Gy of irradiation to the residual breast. Four years after mastectomy, she was found to have left Rotter lymph node metastasis; then, anastrozole was administered instead of tamoxifen. Nine months later, she was found to have liver metastasis. Immunohistostaining revealed that the breast cancer was HER2-positive; she received AC followed by paclitaxel(PTX)with trastuzumab(T), and achieved complete response(CR)...
November 2017: Gan to Kagaku Ryoho. Cancer & Chemotherapy
Shifu Hu, Qiong Yu, Yingying Wang, Mei Wang, Wei Xia, Changhong Zhu
PURPOSE: Polycystic ovary syndrome (PCOS) is a common endocrine disturbance affecting women in the reproductive age group. The present study aimed to compare the effects of letrozole (LE) and clomiphene citrate (CC) for ovulation induction in women with PCOS. METHODS: The PUBMED, Web of Science, and EMBASE databases were screened systematically for randomized controlled trials (RCTs) published from database inception to July 2017. RESULTS: Eleven RCTs involving 2255 patients were included, and data were independently extracted and analyzed using 95% risk ratios (RRs) and confidence intervals (CIs) based on a random- or fixed-effect model (as appropriate)...
February 1, 2018: Archives of Gynecology and Obstetrics
Nigel P Murray
The presence of micrometastatic disease will ultimately determine the breast cancer-specific mortality of patients treated according to current guidelines. Minimal residual disease (i.e., occult tumor, not detected by conventional tests) may exist in two forms: a dormant form of only micrometastasis and a more aggressive "awakened" form where CTCs (circulating tumor cells) are actively disseminating. The hypothesis is that patients with CTCs have a more advanced or aggressive disease (that the cancer has "awoken" and there is active dissemination), whereas those patients with only micrometastasis have "dormant" disease and, although at risk of future relapse, may not do so for many years...
July 27, 2017: Curēus
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