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https://www.readbyqxmd.com/read/28429794/bone-in-culture-array-as-a-platform-to-model-early-stage-bone-metastases-and-discover-anti-metastasis-therapies
#1
Hai Wang, Lin Tian, Amit Goldstein, Jun Liu, Hin-Ching Lo, Kuanwei Sheng, Thomas Welte, Stephen T C Wong, Zbigniew Gugala, Fabio Stossi, Chenghang Zong, Zonghai Li, Michael A Mancini, Xiang H-F Zhang
The majority of breast cancer models for drug discovery are based on orthotopic or subcutaneous tumours. Therapeutic responses of metastases, especially microscopic metastases, are likely to differ from these tumours due to distinct cancer-microenvironment crosstalk in distant organs. Here, to recapitulate such differences, we established an ex vivo bone metastasis model, termed bone-in-culture array or BICA, by fragmenting mouse bones preloaded with breast cancer cells via intra-iliac artery injection. Cancer cells in BICA maintain features of in vivo bone micrometastases regarding the microenvironmental niche, gene expression profile, metastatic growth kinetics and therapeutic responses...
April 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28428684/innate-immunity-of-adipose-tissue-in-rodent-models-of-local-and-systemic-staphylococcus-aureus-infection
#2
Andreas Schmid, Thomas Karrasch, Miriam Thomalla, Jutta Schlegel, Bernd Salzberger, Andreas Schäffler, Frank Hanses
Background. The role of adipose tissue in systemic inflammation during bacterial infection is unclear. Effects of Staphylococcus aureus infection on adipocytes in rodent models of experimental endocarditis and peritonitis, the impact of S. aureus infection on gene expression in epididymal and subcutaneous adipose tissue, and effects of S. aureus infection on the toll-like receptor-2- (TLR2-) cathelicidin pathway in vivo and in vitro were investigated. Material and methods. The rat model of catheter-induced S...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28421996/obesity-does-not-diminish-the-efficacy-of-il-6-signalling-blockade-in-mice-with-collagen-induced-arthritis
#3
Miho Suzuki, Keisuke Tanaka, Hiroto Yoshida, Kenji Yogo, Yoshihiro Matsumoto
OBJECTIVES: Obese rheumatoid arthritis patients often have higher disease activity and a poorer response to treatment than do non-obese patients. The present study aims to clarify the influence of obesity on the action of IL-6 and to evaluate the efficacy of IL-6 signalling blockade in arthritis with obesity. METHODS: Mice were fed a high-fat diet for 5 weeks, and the influence of this diet on macrophages and type II collagen-induced arthritis was investigated. RESULTS: The mice fed the high-fat diet showed greater expression of macrophage marker F4/80, not only in subcutaneous fat but also in knee synovium and the calcaneal region, than did the mice fed a normal diet...
April 18, 2017: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/28420820/high-insulin-impaired-ovarian-function-in-early-pregnant-mice-and-the-role-of-autophagy-in-this-process
#4
Yan Su, Juan Wu, Junlin He, Xueqing Liu, Xuemei Chen, Yubin Ding, Chen Zhang, Wenqi Chen, Yingxiong Wang, Rufei Gao
Metabolic disorders, such as PCOS (polycystic ovarian syndrome) and T2DM (type 2 diabetes mellitus), are associated with menstrual dysfunction, anovulation, infertility, and early pregnancy loss. Ovarian dysfunction is not only related to low pregnancy rates but also to the increased risk of miscarriage. Women with PCOS or T2DM, characterized by hyperinsulinemia, commonly experience ovarian dysfunction. In this study, we first explored whether high insulin levels directly affected ovarian functioning during embryo implantation...
April 18, 2017: Endocrine Journal
https://www.readbyqxmd.com/read/28420089/suppression-of-ghs-r-in-agrp-neurons-mitigates-diet-induced-obesity-by-activating-thermogenesis
#5
Chia-Shan Wu, Odelia Y N Bongmba, Jing Yue, Jong Han Lee, Ligen Lin, Kenji Saito, Geetali Pradhan, De-Pei Li, Hui-Lin Pan, Allison Xu, Shaodong Guo, Yong Xu, Yuxiang Sun
Ghrelin, an orexigenic hormone released primarily from the gut, signals the hypothalamus to stimulate growth hormone release, enhance appetite and promote weight gain. The ghrelin receptor, aka Growth Hormone Secretagogue Receptor (GHS-R), is highly expressed in the brain, with highest expression in Agouti-Related Peptide (AgRP) neurons of the hypothalamus. We recently reported that neuron-specific deletion of GHS-R completely prevents diet-induced obesity (DIO) in mice by activating non-shivering thermogenesis...
April 14, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28413791/safety-and-tolerability-of-peg-grafeel-%C3%A2-a-pegfilgrastim-for-the-prophylactic-treatment-of-chemotherapy-induced-neutropenia-and-febrile-neutropenia-a-prospective-observational-postmarketing-surveillance-study-in-india
#6
Vineet Talwar, Sharanabasappa S Nirni, Krishna Mohan Mallavarapu, Anupama Ramkumar, Nitu Sinha
BACKGROUND: A granulocyte colony-stimulating factor, pegfilgrastim, is efficacious though expensive for prophylactic treatment of chemotherapy-induced neutropenia and febrile neutropenia. Biologics available and accessible today, having acceptable safety-efficacy profiles, require postapproval studies for better understanding of such drugs in clinical settings. AIM: This postmarketing surveillance study evaluated the safety of prophylactic Peg-grafeel(™) (pegfilgrastim) in cancer patients with chemotherapy-induced neutropenia...
January 2017: South Asian Journal of Cancer
https://www.readbyqxmd.com/read/28411231/angiotensin-1-7-attenuates-angiotensin-ii-induced-cardiac-hypertrophy-via-a-sirt3-dependent-mechanism
#7
Lirong Guo, Ankang Yin, Qi Zhang, Tiecheng Zhong, Stephen T O'Rourke, Chengwen Sun
The objectives of the current study were to investigate the effect of Ang-(1-7) on the development of cardiac hypertrophy, and to identify the intracellular mechanism underlying this action of Ang-(1-7). Blood pressure and heart rate were recorded using radiotelemetry before and after chronic subcutaneous infusion of control (PBS), Ang II, Ang-(1-7), or Ang II+Ang-(1-7) for 4 weeks in normotensive rats. Chronic administration of Ang-(1-7) did not affect either basal blood pressure or the Ang II-induced elevation in blood pressure...
April 14, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28410190/dietary-oleuropein-inhibits-tumor-angiogenesis-and-lymphangiogenesis-in-the-b16f10-melanoma-allograft-model-a-mechanism-for-the-suppression-of-high-fat-diet-induced-solid-tumor-growth-and-lymph-node-metastasis
#8
Hyerim Song, Do Young Lim, Jae In Jung, Han Jin Cho, So Young Park, Gyoo Taik Kwon, Young-Hee Kang, Ki Won Lee, Myung-Sook Choi, Jung Han Yoon Park
Previously, we reported that high-fat-diet (HFD)-induced obesity stimulates melanoma progression in the B16F10 allograft model. In this study, we examined whether oleuropein (OL), the most abundant phenolic compound in olives, inhibits HFD-induced melanoma progression. Four-week-old male C57BL/6N mice were fed a HFD-diet with or without OL. After 16 weeks of feeding, B16F10-luc cells were subcutaneously injected and the primary tumor was resected 3 weeks later. OL suppressed HFD-induced solid tumor growth. In the tumor tissues, OL reduced HFD-induced expression of angiogenesis (CD31, VE-cadherin, VEGF-A, and VEGFR2), lymphangiogenesis (LYVE-1, VEGF-C, VEGF-D, and VEGFR3), and hypoxia (HIF-1α and GLUT-1) markers as well as HFD-induced increases in lipid vacuoles and M2 macrophages (MΦs)...
March 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28408435/neurturin-and-a-glp-1-analogue-act-synergistically-to-alleviate-diabetes-in-zucker-diabetic-fatty-rats
#9
James L Trevaskis, Chester Bittencourt Sacramento, Hani Jouihan, Safina Ali, John Le Lay, Stephanie Oldham, Nicholas Bhagroo, Brandon B Boland, Jennifer Cann, Yuan Chang, Terrence O'Day, Victor Howard, Christina Reers, Maria Sorhede Winzell, David M Smith, Michael Feigh, Pernille Barkholt, Kay Schreiter, Matthias Austen, Uwe Andag, Simon Thompson, Lutz Jermutus, Matthew P Coghlan, Joseph Grimsby, Cord Dohrmann, Christopher J Rhodes, Cristina M Rondinone, Arun Sharma
Neurturin (NRTN), a member of the glial-derived neurotrophic factor (GDNF) family, was identified from an embryonic chicken pancreatic cDNA library in a screen for secreted factors. Here, we assessed the potential antidiabetic activities of NRTN relative to liraglutide, a GLP-1 receptor agonist, in Zucker diabetic fatty (ZDF) rats. Subcutaneous administration of NRTN to 8-week-old male ZDF rats prevented the development of hyperglycemia and improved metabolic parameters similar to liraglutide. NRTN treatment increased pancreatic insulin content and β-cell mass, and prevented deterioration of islet organization...
April 13, 2017: Diabetes
https://www.readbyqxmd.com/read/28407783/exosomal-transfer-of-tumor-associated-macrophage-derived-mir-21-confers-cisplatin-resistance-in-gastric-cancer-cells
#10
Peiming Zheng, Lei Chen, Xiangliang Yuan, Qin Luo, Yi Liu, Guohua Xie, Yanhui Ma, Lisong Shen
BACKGROUND: Cisplatin-based chemotherapy is frequently used to treat advanced gastric cancer (GC). However, the resistance often occurs with the mechanisms being not well understood. Recently, emerging evidence indicates that tumor-associated macrophages (TAMs) play an important role in chemoresistance of cancer. As the important mediators in intercellular communications, exosomes secreted by host cells mediate the exchange of genetic materials and proteins to be involved in tumor aggressiveness...
April 13, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28404966/a-novel-bispecific-c-met-pd-1-antibody-with-therapeutic-potential-in-solid-cancer
#11
Zu-Jun Sun, Yi Wu, Wei-Hua Hou, Yu-Xiong Wang, Qing-Yun Yuan, Hui-Jie Wang, Min Yu
The bispecific antibody is a novel antibody, which can target two different antigens and mediate specific killing effects by selectively redirecting effector cells to the target cells. Here, we designed and synthesized a bispecific antibody (BsAb) that can bind cellular-mesenchymal to epithelial transition factor (c-MET, overexpressed in several human solid tumor), and programmed death-1 (PD-1, involved in cancer cell immune evasion) with high affinity and specificity. We found that BsAb can induce the degradation of c-MET protein in cancer cells, including MKN45, a gastric cancer cell line, and A549, a lung cancer cell line...
March 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28400502/cholinergic-agonists-reduce-blood-pressure-in-a-mouse-model-of-systemic-lupus-erythematosus
#12
Amber S Fairley, Keisa W Mathis
Increased inflammation arising from an abnormal immune response can damage healthy tissue and lead to disease progression. An important example of this is the accumulation of inflammatory mediators in the kidney, which can subsequently lead to hypertension and renal injury. The origin of this inflammation may involve neuro-immune interactions. For example, the novel vagus nerve-to-spleen mechanism known as the "cholinergic anti-inflammatory pathway" controls inflammation upon stimulation. However, if this pathway is dysfunctional, inflammation becomes less regulated and chronic inflammatory diseases such as hypertension may develop...
April 2017: Physiological Reports
https://www.readbyqxmd.com/read/28397162/sustained-placental-growth-factor-2-treatment-does-not-aggravate-advanced-atherosclerosis-in-ischemic-cardiomyopathy
#13
Ming Wu, Peter Pokreisz, Melissa Swinnen, Ellen Caluwe, Hilde Gillijns, Nina Vanden Driessche, Andrea Casazza, Erik Verbeken, Desire Collen, Stefan Janssens
Angiogenic growth factor therapy for ischemic cardiovascular disease carries a risk of stimulating atherosclerotic plaque growth. We evaluated risk benefit ratio of sustained administration of recombinant human placental growth factor (rhPlGF)-2 in mice with advanced atherosclerosis and chronic ischemic cardiomyopathy. We maintained apolipoprotein E-deficient mice on a high cholesterol diet and induced myocardial infarction by transient ligation at 4 weeks. At 8 weeks, we assessed left ventricular (LV) function and randomized mice to receive rhPlGF-2 or vehicle (VEH) subcutaneously for 28 days...
April 10, 2017: Journal of Cardiovascular Translational Research
https://www.readbyqxmd.com/read/28396979/nanoparticulate-tetrac-inhibits-growth-and-vascularity-of-glioblastoma-xenografts
#14
Thangirala Sudha, Dhruba J Bharali, Stewart Sell, Noureldien H E Darwish, Paul J Davis, Shaker A Mousa
Thyroid hormone as L-thyroxine (T4) stimulates proliferation of glioma cells in vitro and medical induction of hypothyroidism slows clinical growth of glioblastoma multiforme (GBM). The proliferative action of T4 on glioma cells is initiated nongenomically at a cell surface receptor for thyroid hormone on the extracellular domain of integrin αvβ3. Tetraiodothyroacetic acid (tetrac) is a thyroid hormone derivative that blocks T4 action at αvβ3 and has anticancer and anti-angiogenic activity. Tetrac has been covalently bonded via a linker to a nanoparticle (Nanotetrac, Nano-diamino-tetrac, NDAT) that increases the potency of tetrac and broadens the anticancer properties of the drug...
April 10, 2017: Hormones & Cancer
https://www.readbyqxmd.com/read/28392382/angiogenenic-effects-of-bplec-a-c-type-lectin-isolated-from-bothrops-pauloensis-snake-venom
#15
Letícia Eulalio Castanheira, Daiana Silva Lopes, Sarah Natalie Cirilo Gimenes, Simone Ramos Deconte, Bruno Antônio Ferreira, Patricia Terra Alves, Luiz Ricardo Goulart Filho, Tatiana Carla Tomiosso, Renata Santos Rodrigues, Kelly Aparecida Geraldo Yoneyama, Fernanda de Assis Araújo, Veridiana de Melo Rodrigues
The present work reports the effects of a C-type lectin (BpLec) isolated from Bothrops pauloensis snake venom upon in vitro and in vivo angiogenesis models. Initially, we noted that BpLec was not cytotoxic to endothelial cells (tEnd) in doses up to 40μg/mL, but lower doses (2.5μg/mL, 5μg/mL, 10μg/mL and 20μg/mL) reduced tEnd cells adhesion to some extracellular matrix proteins and inhibited the in vitro vessel formation in Matrigel assay stimulated by bFGF. β-galactosides (d-lactose, N-acetyl-d-galactosamine and d-galactose) at 400mM reversed the effect of BpLec on tEnd cells adhesion, whereas d-galactose (400mM) partially reversed BpLec property of inhibiting vessel formation by tEnd cells in Matrigel...
April 6, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28388910/effect-of-teriparatide-rh-pth-1-34-versus-bisphosphonate-on-the-healing-of-osteoporotic-vertebral-compression-fracture-a-retrospective-comparative-study
#16
Akira Iwata, Masahiro Kanayama, Fumihiro Oha, Tomoyuki Hashimoto, Norimasa Iwasaki
BACKGROUND: Teriparatide (recombinant human parathyroid hormone 1-34) is increasingly used for the treatment of severe osteoporosis because it stimulates bone formation and may potentially enhance fracture healing. The objective of this study was to investigate the effects of teriparatide versus a bisphosphonate on radiographic outcomes in the treatment of osteoporotic vertebral compression fractures (OVCF). METHODS: A total of 98 patients undergoing non-operative treatment for recent single-level OVCF were reviewed retrospectively...
April 7, 2017: BMC Musculoskeletal Disorders
https://www.readbyqxmd.com/read/28381248/reproductive-hormonal-variations-and-adenohypophyseal-lesions-in-pre-pubertal-buffalo-heifers-inoculated-with-pasteurella-multocida-type-b-2-and-its-immunogens
#17
Faez Firdaus Abdullah Jesse, Hayder Hamzah Ibrahim, Yusuf Abba, Eric Lim Teik Chung, Ali Dhiaa Marza, Mazlina Mazlan, Mohd Zamri-Saad, Abdul Rahman Omar, Md Zuki Abu Bakar Zakaria, Abdul Aziz Saharee, Abd Wahid Haron, Mohd Azmi Mohd Lila
BACKGROUND: Hemorrhagic septicemia is a fatal disease of cattle and buffaloes caused by P. multocida. Although the pathogenesis of the bacteria has been well established in literature, there is a paucity of information on the possible role of the bacteria and its immunogens; lipopolysaccharide (LPS) and outer membrane proteins (OMPs) on the reproductive capacity of buffalo heifers. METHODS: In this study, twenty one healthy prepubertal female buffaloes aged 8 months were divided into seven groups of 3 buffaloes each (G1-G7)...
April 5, 2017: BMC Veterinary Research
https://www.readbyqxmd.com/read/28376567/hypoxia-inducible-factor-1-alpha-potentiates-jagged-1-mediated-angiogenesis-by-mesenchymal-stem-cell-derived-exosomes
#18
Hernán Gonzalez-King, Nahuel A García, Imelda Ontoria-Oviedo, María Ciria, José Anastasio Montero, Pilar Sepúlveda
Insufficient vessel growth associated with ischemia remains an unresolved issue in vascular medicine. Mesenchymal stem cells (MSCs) have been shown to promote angiogenesis via a mechanism that is potentiated by hypoxia. Overexpression of hypoxia inducible factor (HIF)-1α in MSCs improves their therapeutic potential by inducing angiogenesis in transplanted tissues. Here we studied the contribution of exosomes released by HIF-1α-overexpressing donor MSCs (HIF-MSC) to angiogenesis by endothelial cells. Exosome secretion was enhanced in HIF-MSC...
April 4, 2017: Stem Cells
https://www.readbyqxmd.com/read/28371625/injectable-and-inherently-vascularizing-semi-interpenetrating-polymer-network-for-delivering-cells-to-the-subcutaneous-space
#19
Redouan Mahou, David K Y Zhang, Alexander E Vlahos, Michael V Sefton
Injectable hydrogels are suitable for local cell delivery to the subcutaneous space, but the lack of vasculature remains a limiting factor. Previously we demonstrated that biomaterials containing methacrylic acid promoted vascularization. Here we report the preparation of a semi-interpenetrating polymer network (SIPN), and its evaluation as an injectable carrier to deliver cells and generate blood vessels in a subcutaneous implantation site. The SIPN was prepared by reacting a blend of vinyl sulfone-terminated polyethylene glycol (PEG-VS) and sodium polymethacrylate (PMAA-Na) with dithiothreitol...
March 24, 2017: Biomaterials
https://www.readbyqxmd.com/read/28367305/changes-of-the-uterine-tissue-in-rats-with-polycystic-ovary-syndrome-induced-by-estradiol-valerate
#20
Ghadire Mirabolghasemi, Zahra Kamyab
BACKGROUND: Polycystic ovary syndrome (PCOS) is one of the most common hormonal disorders that can lead to irregular menstrual cycles and hyperandrogenism. Reduced levels of progesterone and increased estrogen in these women can perpetually stimulate the endometrial tissue of the uterus. In this study, we assess the effect of PCOS induction by estradiol valerate (EV) in a rat model. MATERIALS AND METHODS: In this experimental study, adult female Wistar rats that weighed approximately 200 g were divided into control, sham, and experimental groups (n=6 per group)...
April 2017: International Journal of Fertility & Sterility
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