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ovarian growth factors

I Nakachi, B A Helfrich, M A Spillman, E A Mickler, C J Olson, J L Rice, C D Coldren, L E Heasley, M W Geraci, R S Stearman
Src kinase is recognized as a key target for molecular cancer therapy. However, methods to efficiently select patients responsive to Src inhibitors are lacking. We explored the sensitivity of ovarian cancer cell lines to the Src kinase inhibitor saracatinib to identify predictive markers of drug sensitivity using gene microarrays. Pituitary tumor transforming gene 1 (PTTG1) was selected as a potential biomarker as mRNA levels were correlated with saracatinib resistance, as well as higher PTTG1 protein expression...
October 20, 2016: Clinical and Translational Science
Li Bo, Huchuan Cui, Zhengxian Fang, Tao Qun, Caoyun Xia
Resistance to taxol represents a major obstacle for long-term remission in ovarian cancer. Transforming Growth Factor-β-Activated Kinase 1 (TAK1) is a critical component in immune response pathway. However, the role of TAK1 in the development of chemoresistance in ovarian cancer remains unknown. Here, we showed that in vitro, taxol-resistant cells expressed higher TAK1, and the ratio of p-TAK1/TAK1 positively associated with taxol resistance in ovarian cancer cells. Inactivation of TAK1 by inhibitor 5Z-7-oxozeaenol or gene knockdown sensitized taxol cytotoxicity in vitro, promoting cell apoptosis and mitosis arrest...
October 17, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Yoon Kim, Amin Tamadon, Seung-Yup Ku
In vitro culture of ovarian follicles is a promising bioengineering technique for preserving fecundity in reproductive age female by providing fertilizable oocytes. Successful clinical application should be preceded by developing the protocols that can efficiently overcome follicular cell apoptosis since the apoptosis is a critical phenomenon in in vivo folliculogenesis and in in vitro follicular maturation. Numerous pro-survival and anti-apoptotic molecules including follicular developmental regulators have been reported to be involved in the intra-ovarian apoptosis...
October 20, 2016: Tissue Engineering. Part B, Reviews
Funda Akpinar, Berna Dilbaz, Derya A Cırık, Saynur Yilmaz, Sadiman Kiykac, Ertugrul Karahanoglu, Leyla Mollamahmutoglu
To investigate factors associated with the response to ovarian stimulation in patients with polycystic ovary syndrome. Methods: The records of patients with polycystic ovary syndrome and infertility who underwent ovulation induction with clomiphene citrate were reviwed between January 2011 and December 2014 in Etlik Zübeyde Hanim Women's Health Training and Research Hospital Ankara, Turkey. The anthropometric and endocrine factors of patients who were resistant to treatment at a dose of 150 mg/day (n=84) were compared with those who responded with growth of at least one graaffian follicle at a dose of 50 mg/day (n=342)...
November 2016: Saudi Medical Journal
Lola Corzo, Susana Rodríguez, Ramón Alejo, Lucía Fernández-Novoa, Gjumrakch Aliev, Ramón Cacabelos
Menopause is a natural event in women´s lives leading to the cessation of menstruation and the reproductive function due to loss of the ovarian follicular function. Menopause-derived estrogen deprivation and related endocrine factors are linked to some symptoms of middle-aged women, such as hot flashes, aches, joint pain, stiffness, depressed mood, bone degeneration, nutritional dysfunction, or difficulty to maintain body mass. Clinical approaches to these problems often involve hormone replacement therapy (HRT) and other modalities of therapeutic intervention...
October 14, 2016: Current Drug Metabolism
Alexander Reinthaller
Angiogenesis plays a pivotal role in normal ovarian physiology as well as in the formation and progression of ovarian cancer. Several well-designed phase II and III trials studied the efficacy of antiangiogenic agents in advanced ovarian cancer. The results of these trials demonstrated significantly prolonged progression-free survival when antiangiogenic agents were used as a maintenance therapy. To date, no effect on overall survival could be ascertained. The most widely studied antiangiogenic agent, bevacizumab - a monoclonal humanized antibody against vascular endothelial growth factor - was effective in all phases of the disease (first-line therapy, platinum-sensitive and platinum-resistant recurrence)...
2016: Memo
Magdalena Pertynska-Marczewska, Evanthia Diamanti-Kandarakis
OBJECTIVE: The hypothalamic gonadotropin-releasing hormone pulse generator, the pituitary gonadotropes, the ovaries, and the uterus play a crucial role in female fertility. A decline in reproductive performance represents a complex interplay of actions at all levels of the hypothalamic-pituitary-ovarian axis. Recently, in the field of female reproductive aging attention is drawn to the carbonyl stress theory. Advanced glycation end products (AGEs) contribute directly to protein damage, induce a chain of oxidative stress (OS) reactions, and increase inflammatory reactions...
October 3, 2016: Menopause: the Journal of the North American Menopause Society
Radoslava Vlčková, Drahomíra Sopková, Zuzana Andrejčáková, Igor Valocký, Attila Kádasi, Abdel Halim Harrath, Vladimír Petrilla, Alexander V Sirotkin
Yucca (Yucca schidigera) is a popular medicinal plant due to its many positive effects on animal and human physiology, including their reproductive systems. To examine the effect of supplemental yucca feeding on sheep reproduction, including ovarian functions and their hormonal regulators, ewes were fed (or not fed, control) yucca powder (1.5 g/head/day, 30 days). Macromorphometric indexes of the oviduct, ovary, and ovarian folliculogenesis were measured. Reproductive hormone levels in the blood were measured using a radioimmunoassay...
September 21, 2016: Theriogenology
H L M Tucker, K L Beaudry, C L M Parsons, S E Ellis, R M Akers
Prepubertal mammary development involves elongation and branching of ducts and stromal tissue remodeling. This process is closely linked with ovarian and pituitary hormones, growth factors, and local regulators. Accumulating evidence suggests that the myoepithelial cells also play a role in ductal development in addition to their well-recognized importance in the milk ejection reflex. Following reports that myoepithelial cells changed in correspondence with decreased mammary growth after ovariectomy of prepubertal heifers, we evaluated myoepithelial cells in mammary tissue collected from prepubertal heifers treated with the antiestrogen tamoxifen...
October 13, 2016: Journal of Dairy Science
Soha R Abd El Hadi, Deena S Lasheen, Mahmoud A Hassan, Khaled A M Abouzid
Dual inhibition of the epidermal growth factor receptor (EGFR) and the human epidermal growth factor receptor 2 (HER-2) is an attractive cancer therapeutic approach. In this study, new series of 4-anilinothieno[2,3-d]pyrimidines were designed, synthesized, and tested as dual EGFR/HER-2 kinase inhibitors. Five compounds (8a, 8b, 8e-g) demonstrated low to submicromolar inhibition of both kinases with IC50 values of 1.2, 0.6, 0.3, 0.2, 0.4 μM and 8.2, 3.4, 1.3, 0.5, 2.7 μM for the EGFR and HER-2, respectively...
October 13, 2016: Archiv der Pharmazie
Emiliano Calvo, Jean-Charles Soria, Wen Wee Ma, Tao Wang, Rastilav Bahleda, Anthony Tolcher, Diana Gernhardt, Joseph O'Connell, Robert Millham, Nagdeep Giri, Michael J Wick, Alex A Adjei, Manuel Hidalgo
PURPOSE: This phase I, open-label, single-arm trial assessed the safety and tolerability of dacomitinib-figitumumab combination therapy in patients with advanced solid tumors. EXPERIMENTAL DESIGN: A standard 3+3 dose escalation/de-escalation design was utilized. Starting doses were figitumumab 20 mg/kg administered intravenously once every 3 weeks (q3w) and dacomitinib 30 mg administered orally once daily. We also performed an independent study of the combination in patient-derived xenograft (avatar mouse) models of adenoid cystic carcinoma (ACC)...
October 12, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
J Cadenas, J Leiva-Revilla, L A Vieira, L B Apolloni, F L N Aguiar, B G Alves, C H Lobo, A P R Rodrigues, G A Apgar, J Smitz, J R Figueiredo, C Maside
The aim of the present study was to evaluate the effect of growth hormone (GH) and vascular endothelial growth factor (VEGF) added alone, sequentially or in combination, in the presence of insulin at physiological concentration (10 ng/mL) on the IVC of two different follicular categories: preantral (experiment 1; Exp.1) and early antral (experiment 2; Exp.2). Isolated follicles were individually cultured for 24 (Exp.1) and 18 days (Exp.2) in the following treatments: αMEM(+) (Control), or Control medium supplemented with 50 ng/mL GH (GH), 100 ng/mL VEGF (VEGF), the combination of both (GH + VEGF), GH during the first 12 days and VEGF from Day 12 until the end of the culture (GH/VEGF) and vice versa (VEGF/GH)...
September 13, 2016: Theriogenology
Hilal S Khalil, Simon P Langdon, Alexey Goltsov, Tero Soininen, David J Harrison, James Bown, Yusuf Y Deeni
Nuclear erythroid related factor-2 (NRF2) is known to promote cancer therapeutic detoxification and crosstalk with growth promoting pathways. HER2 receptor tyrosine kinase is frequently overexpressed in cancers leading to uncontrolled receptor activation and signaling. A combination of HER2 targeting monoclonal antibodies shows greater anticancer efficacy than the single targeting antibodies, however, its mechanism of action is largely unclear. Here we report novel actions of anti-HER2 drugs, Trastuzumab and Pertuzumab, involving NRF2...
October 4, 2016: Oncotarget
Min Zhao, Zhiying Su, Shiyang Zhang, Liangjin Zhuang, Yudi Xie, Xiaodong Li
Ovarian cancer (OC) is one of the most common gynecological malignancies. MicroRNAs (miRs) play a crucial role in the development and progression of OC, but the underlying mechanism remains largely unclear. Our study investigated the regulatory role of miR-148a in OC cell proliferation and invasion. We found that miR-148a was significantly downregulated in OC tissues compared to their matched adjacent nontumor tissues. In addition, its expression was also reduced in OC cell lines (SKOV3, ES-2, OVCAR, and A2780) compared to normal ovarian epithelial cells...
2016: Oncology Research
Somayeh Tavana, Mahnaz Azarnia, Mojtaba Rezazadeh Valojerdi, Abdolhossein Shahverdi
One of the problems encountered during ovarian transplantation is that the number of primordial follicles in the grafts is considerably reduced 2 d after transplantation due to post-transplantation ischemia. This study investigates if the use of hyaluronic acid-based hydrogel (HABH) with and without vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) could prevent or minimize ischemia-induced follicle loss during ovarian autotransplantation and thereby restore ovarian tissue function in the rat model...
October 6, 2016: Biomedical Materials
Jane Antony, Tuan Zea Tan, Zoe Kelly, Jeffrey Low, Mahesh Choolani, Chiara Recchi, Hani Gabra, Jean Paul Thiery, Ruby Yun-Ju Huang
Ovarian cancer is a complex disease with heterogeneity among the gene expression molecular subtypes (GEMS) between patients. Patients with tumors of a mesenchymal ("Mes") subtype have a poorer prognosis than patients with tumors of an epithelial ("Epi") subtype. We evaluated GEMS of ovarian cancer patients for molecular signaling profiles and assessed how the differences in these profiles could be leveraged to improve patient clinical outcome. Kinome enrichment analysis identified AXL as a particularly abundant kinase in Mes-subtype tumor tissue and cell lines...
October 4, 2016: Science Signaling
Ayako Aihara, Natsuki Abe, Koichiro Saruhashi, Tatsuro Kanaki, Taito Nishino
Anticancer drug discovery efforts have employed two-dimensional (2D)-cell-based assay models, which fail to forecast in vivo efficacy and result in a lower success rate of clinical approval. Recent three-dimensional (3D) cell culture models are expected to bridge the gap between 2D and in vivo models. However, 3D cell culture methods that are available for practical anticancer drug screening have not yet been fully attained. In this study, we screened several polymers for their ability to suspend cells or cell spheroids homogeneously in a liquid medium without changing the viscosity behavior, and identified gellan gum (FP001), as the most potent polymer...
October 3, 2016: Cancer Science
Fernanda Silva, Ana Félix, Jacinta Serpa
Epithelial ovarian cancer is the most lethal gynecologic malignancy, despite advances in treatment. The most common histological type, high-grade ovarian serous carcinoma (OSC) is usually diagnosed at an advanced stage, and although these types of tumors frequently respond to surgery and platinum-based chemotherapy, they usually recur. Ovarian clear cell carcinoma (OCCC) is an unusual histological type, which is known to be intrinsically chemoresistant and is associated with poor prognosis in advanced stages...
October 2016: Oncology Letters
Lovisa Göstring, Sture Lindegren, Lars Gedda
The geldanamycin derivative 17-allylamino-17-demethoxygeldanamycin (17-AAG) is known to induce internalisation and degradation of the otherwise internalisation-resistant human epidermal growth factor receptor 2 (HER2) receptor. In the present study, 17-AAG was used to increase internalisation of the HER2-specific Affibody molecule ABY-025. The cellular redistribution of halogen-labelled (211)At-ABY-025 and radiometal-labelled (111)In-ABY-025 following treatment with 17-AAG was studied. 17-AAG treatment of SKOV-3 human ovarian carcinoma and SKBR-3 human breast carcinoma cells to some extent shifted the localisation of (111)In-ABY-025 from the cell surface to intracellular compartments in the two cell lines...
October 2016: Oncology Letters
Sayantan Jana, Kasturi Chatterjee, Amlan K Ray, Pramathes DasMahapatra, Snehasikta Swarnakar
Endometriosis is characterized by the ectopic development of the endometrium which relies on angiogenesis. Although studies have identified the involvement of different matrix metalloproteinases (MMPs) in endometriosis, no study has yet investigated the role of MMP-2 in endometriosis-associated angiogenesis. The present study aims to understand the regulation of MMP-2 activity in endothelial cells and on angiogenesis during progression of ovarian endometriosis. Histological and biochemical data showed increased expressions of vascular endothelial growth factor (VEGF), VEGF receptor-2, cycloxygenase (COX)-2, von Willebrand factor along with angiogenesis during endometriosis progression...
2016: PloS One
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