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https://www.readbyqxmd.com/read/29346400/the-mechanisms-how-heparin-affects-the-tumor-cell-induced-vegf-and-chemokine-release-from-platelets-to-attenuate-the-early-metastatic-niche-formation
#1
Jan Moritz Ponert, Svenja Schwarz, Reza Haschemi, Jens Müller, Bernd Pötzsch, Gerd Bendas, Martin Schlesinger
Metastasis is responsible for the majority of cancer associated fatalities. Tumor cells leaving the primary tumor and entering the blood flow immediately interact with platelets. Activated platelets contribute in different ways to cancer cell survival and proliferation, e.g. in formation of the early metastatic niche by release of different growth factors and chemokines. Here we show that a direct interaction between platelets and MV3 melanoma or MCF7 breast cancer cells induces platelet activation and a VEGF release in citrated plasma that cannot be further elevated by the coagulation cascade and generated thrombin...
2018: PloS One
https://www.readbyqxmd.com/read/29346344/development-of-immune-and-microbial-environments-is-independently-regulated-in-the-mammary-gland
#2
K Niimi, K Usami, Y Fujita, M Abe, M Furukawa, Y Suyama, Y Sakai, M Kamioka, N Shibata, E J Park, S Sato, H Kiyono, H Yoneyama, H Kitazawa, K Watanabe, T Nochi, H Aso
Breastfeeding is important for mammals, providing immunological and microbiological advantages to neonates, together with the nutritional supply from the mother. However, the mechanisms of this functional diversity in the mammary gland remain poorly characterized. Here, we show that, similar to the gastrointestinal tract, the mammary gland develops immune and microbial environments consisting of immunoglobulin A (IgA) and the microflora, respectively, both of which are important for protecting neonates and the mother from infectious diseases...
December 20, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/29345636/promoting-the-accumulation-of-tumor-specific-t-cells-in-tumor-tissues-by-dendritic-cell-vaccines-and-chemokine-modulating-agents
#3
Nataša Obermajer, Julie Urban, Eva Wieckowski, Ravikumar Muthuswamy, Roshni Ravindranathan, David L Bartlett, Pawel Kalinski
This protocol describes how to induce large numbers of tumor-specific cytotoxic T cells (CTLs) in the spleens and lymph nodes of mice receiving dendritic cell (DC) vaccines and how to modulate tumor microenvironments (TMEs) to ensure effective homing of the vaccination-induced CTLs to tumor tissues. We also describe how to evaluate the numbers of tumor-specific CTLs within tumors. The protocol contains detailed information describing how to generate a specialized DC vaccine with augmented ability to induce tumor-specific CTLs...
February 2018: Nature Protocols
https://www.readbyqxmd.com/read/29345350/activation-of-the-sympathetic-nervous-system-modulates-neutrophil-function
#4
Alyce J Nicholls, Shu Wen Wen, Pam Hall, Michael J Hickey, Connie H Y Wong
Emerging evidence has revealed that noradrenaline (NA), the main neurotransmitter of the sympathetic nervous system (SNS), regulates a variety of immune functions via binding to adrenergic receptors present on immune cells. In this study, we examined the role of NA in the regulation of neutrophil functions. Neutrophils were isolated from the bone marrow of naïve mice and treated with NA at various concentrations to assess the effect on various neutrophil functions. Additionally, we performed cremaster intravital microscopy to examine neutrophil-endothelial cell interactions following NA superfusion in vivo...
December 21, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29345324/autocrine-signals-increase-ovine-mesenchymal-stem-cells-migration-through-aquaporin-1-and-cxcr4-overexpression
#5
Alessandra Pelagalli, Anna Nardelli, Enrico Lucarelli, Antonella Zannetti, Arturo Brunetti
Sheep is a relevant large animal model that is frequently used to test innovative tissue engineering (TE) approaches especially for bone reconstruction. Mesenchymal stem cells (MSCs) are used in TE applications because they represent key component of adult tissue repair. Importantly, MSCs from different species show similar characteristics, which facilitated their application in translational studies using animal models. Nowadays, many researches are focusing on the use of ovine mesenchymal stem cells (oMSCs) in orthopedic preclinical settings for regenerative medicine purposes...
January 18, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29345065/fingolimod-targets-cerebral-endothelial-activation-to-block-leukocyte-recruitment-in-the-central-nervous-system
#6
Yawei Zhao, Dongyan Shi, Kelei Cao, Fengjiao Wu, Xingxing Zhu, Shuang Wen, Qiang You, Keqi Zhang, Lixin Liu, Hong Zhou
Fingolimod (FTY720), an immunomodulator, is approved as an oral treatment for patients with relapsing forms of multiple sclerosis. Its effects are largely attributed to its mechanism of selectively retaining lymphocytes in the lymph nodes to reduce autoreactive T-cell recruitment in the CNS. In this study, we investigated the therapeutic effect of FTY720 on an animal model of CNS inflammation induced by intracerebral ventricle LPS injection. We found that FTY720 treatment significantly prevented LPS-induced neutrophil recruitment in the CNS by inhibiting leukocyte recruitment in cerebral microvessels...
January 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29345045/the-in-vitro-release-of-cytokines-and-growth-factors-from-fibrin-membranes-produced-through-horizontal-centrifugation
#7
E S Lourenço, C F A B Mourão, P E C Leite, J M Granjeiro, M D Calasans-Maia, G G Alves
Platelet-rich fibrin (PRF) membranes are biomaterials widely used for therapeutic purposes, and canonically produced through the processing of peripheral blood with fixed-angle rotor centrifuges. In this work, we evaluate the in vitro stability and release of cytokines and growth factors when these biomaterials are produced with a horizontal swing-out clinical centrifuge. Membranes produced from the blood of 14 donors were morphologically evaluated by scanning electron microscopy and fluorescence microscopy, and their stability was assessed by photographic recording after incubation in culture medium for up to 28 days...
January 18, 2018: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/29344240/cxcl5-as-an-autocrine-or-paracrine-cytokine-is-associated-with-proliferation-and-migration-of-hepatoblastoma-hepg2-cells
#8
Yang Yang, Jie Hou, Mingliang Shao, Wei Zhang, Yaling Qi, Shengnan E, Shuqiu Wang, Hongyu Sui, Dexin Meng, Baixin Wang, Mingfu Wang, Yang Han, Yu Cao, Xiaoqing Huang, Yue Li, Pengxia Zhang, Weiqun Wang
C-X-C motif chemokine ligand 5 (CXCL5) is a CXC-type chemokine that is a crucial inflammatory mediator and a powerful attractant for granulocytic immune cells. Increasing evidence has indicated that CXCL5 is involved in the tumorigenesis of various malignancies. The present investigation demonstrated that CXCL5 was expressed in both hepatoblastoma HepG2 cells and liver stellate LX-2 cells, and CXCL5's receptor C-X-C chemokine receptor type 2 (CXCR2) was expressed in HepG2 cells by reverse transcription-polymerase chain reaction (RT-PCR), western blotting and ELISA assays...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29344142/isolation-and-identification-of-tumor-initiating-cell-properties-in-human-gallbladder-cancer-cell-lines-using-the-marker-cluster-of-differentiation-133
#9
Jiwei Yu, Zhaohui Tang, Wei Gong, Mingdi Zhang, Zhiwei Quan
The present study aimed to isolate and identify the properties of the cluster of differentiation (CD)133+ subset in human gallbladder cancer cells. The CD133+ and CD133- subpopulations of the GBC-SD cell line were separated using immunomagnetic separation, and the biological features of the two subpopulations were analyzed in vitro and in vivo. In particular, the present study aimed to determine whether the two subpopulations were resistant to anti-tumor reagents and to identify the underlying molecular mechanisms involved...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29343654/intestinal-epithelial-cell-specific-deletion-of-%C3%AE-mannosidase-ii-ameliorates-experimental-colitis
#10
Koichiro Suzuki, Takahiro Yamada, Keiko Yamazaki, Masato Hirota, Narumi Ishihara, Mizuki Sakamoto, Daisuke Takahashi, Hideki Iijima, Koji Hase
Inflammatory bowel disease (IBD) is a refractory disease of the gastrointestinal tract that is believed to develop in genetically susceptible individuals. Glycosylation, a type of post-translational modification, is involved in the development of a wide range of diseases, including IBD, by modulating the function of various glycoproteins. To identify novel genes contributing to the development of IBD, we analyzed single nucleotide polymorphisms (SNPs) of glycosylation-related genes in IBD patients and identified MAN2A1, encoding alpha-mannosidase II (α-MII), as a candidate gene...
January 18, 2018: Cell Structure and Function
https://www.readbyqxmd.com/read/29343553/molecular-mechanisms-of-biased-and-probe-dependent-signaling-at-cxcr3-induced-by-negative-allosteric-modulators
#11
Regine Brox, Lampros Milanos, Noureldin Saleh, Paul Baumeister, Armin Buschauer, Dagmar Hofmann, Markus R Heinrich, Timothy Clark, Nuska Tschammer
Our recent explorations of allosteric modulators (AMs) with improved properties resulted in the identification of two biased negative AMs, N-1-{[3-(4-Ethoxyphenyl)-4-oxo-3,4-dihydropyrido[2,3-d]pyrimi-din2yl]ethyl}-4-(4-fluorobutoxy)-N-[(1-methylpiperidin-4-yl)me-thyl}]butanamide (BD103) and {5-[(N-{1-[3-(4-ethoxyphenyl)-4-oxo-3,4-dihydropyrido[2,3-d]pyrimidin-2-yl]ethyl-2-[4-fluoro-3-(trifluoromethyl)phenyl]acetamido)methyl]-2-fluorophenyl}boronic acid (BD064), that exhibited probe-dependent inhibition of the chemokine receptor CXCR3 signaling...
January 17, 2018: Molecular Pharmacology
https://www.readbyqxmd.com/read/29342870/biomarkers-of-progression-after-hiv-acute-early-infection-nothing-compares-to-cd4%C3%A2-%C2%BA-t-cell-count
#12
Gabriela Turk, Yanina Ghiglione, Macarena Hormanstorfer, Natalia Laufer, Romina Coloccini, Jimena Salido, César Trifone, María Julia Ruiz, Juliana Falivene, María Pía Holgado, María Paula Caruso, María Inés Figueroa, Horacio Salomón, Luis D Giavedoni, María de Los Ángeles Pando, María Magdalena Gherardi, Roberto Daniel Rabinovich, Pedro A Pury, Omar Sued
Progression of HIV infection is variable among individuals, and definition disease progression biomarkers is still needed. Here, we aimed to categorize the predictive potential of several variables using feature selection methods and decision trees. A total of seventy-five treatment-naïve subjects were enrolled during acute/early HIV infection. CD4⁺ T-cell counts (CD4TC) and viral load (VL) levels were determined at enrollment and for one year. Immune activation, HIV-specific immune response, Human Leukocyte Antigen (HLA) and C-C chemokine receptor type 5 (CCR5) genotypes, and plasma levels of 39 cytokines were determined...
January 13, 2018: Viruses
https://www.readbyqxmd.com/read/29342173/hormone-induced-differential-transcriptome-analysis-of-sertoli-cells-during-postnatal-maturation-of-rat-testes
#13
Mukesh Gautam, Indrashis Bhattacharya, Umesh Rai, Subeer S Majumdar
Sertoli cells (Sc) are unique somatic cells of testis that are the target of both FSH and testosterone (T) and regulate spermatogenesis. Although Sc of neonatal rat testes are exposed to high levels of FSH and T, robust differentiation of spermatogonial cells becomes conspicuous only after 11-days of postnatal age. We have demonstrated earlier that a developmental switch in terms of hormonal responsiveness occurs in rat Sc at around 12 days of postnatal age during the rapid transition of spermatogonia A to B...
2018: PloS One
https://www.readbyqxmd.com/read/29341885/deletion-of-the-duffy-antigen-receptor-for-chemokines-darc-promotes-insulin-resistance-and-adipose-tissue-inflammation-during-high-fat-feeding
#14
Tyler W Benson, Daniel S Weintraub, Matthew Crowe, Nicole K H Yiew, Orishebawo Popoola, Ajay Pillai, Joel Joseph, Krystal Archer, Charlotte Greenway, Tapan K Chatterjee, James Mintz, David W Stepp, Brian K Stansfield, Weiqin Chen, Julia Brittain, Vladimir Y Bogdanov, Yan Gao, James G Wilson, Yaoliang Tang, Ha Won Kim, Neal L Weintraub
OBJECTIVE: Inflammation in adipose tissues in obesity promotes insulin resistance and metabolic disease. The Duffy antigen receptor for chemokines (DARC) is a promiscuous non-signaling receptor expressed on erythrocytes and other cell types that modulates tissue inflammation by binding chemokines such as monocyte chemoattractant protein-1 (MCP-1) and by acting as a chemokine reservoir. DARC allelic variants are common in humans, but the role of DARC in modulating obesity-related metabolic disease is unknown...
January 13, 2018: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/29341428/epigenetic-silencing-of-tap1-in-aldefluor-breast-cancer-stem-cells-contributes-to-their-enhanced-immune-evasion
#15
Mohammad Sultan, Dejan Vidovic, Arianne S Paine, Thomas T Huynh, Krysta M Coyle, Margaret L Thomas, Brianne M Cruickshank, Cheryl A Dean, Derek R Clements, Youra Kim, Kristin Lee, Shashi A Gujar, Ian C Weaver, Paola Marcato
Avoiding detection and destruction by immune cells is key for tumor initiation and progression. The important role of cancer stem cells (CSC) in tumor initiation has been well established, yet their ability to evade immune detection and targeting is only partly understood. To investigate the ability of breast CSCs to evade immune detection we identified a highly tumorigenic population in a spontaneous murine mammary tumor based on increased aldehyde dehydrogenase (ALDH) activity. We performed tumor growth studies in immunocompetent and immunocompromised mice...
January 17, 2018: Stem Cells
https://www.readbyqxmd.com/read/29341316/deferoxamine-promotes-mesenchymal-stem-cell-homing-in-noise-induced-injured-cochlea-through-pi3k-akt-pathway
#16
A A Peyvandi, H-A Abbaszadeh, N Ahmady Roozbahany, A Pourbakht, S Khoshsirat, H Haddadzade Niri, H Peyvandi, S Niknazar
OBJECTIVE: Over 5% of the world's population suffers from disabling hearing loss. Stem cell homing in target tissue is an important aspect of cell-based therapy, which its augmentation increases cell therapy efficiency. Deferoxamine (DFO) can induce the Akt activation, and phosphorylation status of AKT (p-AKT) upregulates CXC chemokine receptor-4 (CXCR4) expression. We examined whether DFO can enhance mesenchymal stem cells (MSCs) homing in noise-induced damaged cochlea by PI3K/AKT dependent mechanism...
January 17, 2018: Cell Proliferation
https://www.readbyqxmd.com/read/29340070/a-novel-orally-available-syk-src-jak2-inhibitor-sklb-850-showed-potent-anti-tumor-activities-in-b-cell-lymphoma-bcl-models
#17
Nannan Zhang, Guo Zhang, Ning Liu, Wanting Lin, Sen Ji, Mingwu Zheng, Kai Chen, Xiao Liang, Guobo Li, Yu Ma, Jun Zhu, Ting Niu, Lin-Li Li, Jiong Li, Yu-Quan Wei, Sheng-Yong Yang
B cell lymphoma (BCL) is the most frequently diagnosed type of non-Hodgkin lymphoma (NHL), and accounts for about 4% of all cancers in the USA. Kinases spleen tyrosine kinase (Syk), Src, and Janus kinase 2 (JAK2) have been thought as potential targets for the treatment of BCL. We have recently developed a multikinase inhibitor, SKLB-850, which potently inhibits Syk, Src, and JAK2. The aim of this study is to investigate the anti-BCL activities and mechanisms of action of SKLB-850 both in vitro and in vivo. Our results showed that SKLB-850 significantly inhibited BCL cell proliferation, and induced apoptosis of BCL cells...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29339716/to-explore-the-mechanism-of-the-grm4-gene-in-osteosarcoma-by-rna-sequencing-and-bioinformatics-approach
#18
Yunguo Pang, Jinmin Zhao, Mitra Fowdur, Yun Liu, Hao Wu, Maolin He
BACKGROUND Glutamate metabotropic receptor 4 (GRM4) has been correlated with the pathogenesis of osteosarcoma. The objective of this study was to explore the underlying molecular mechanism of GRM4 in osteosarcoma. MATERIAL AND METHODS The expression levels of GRM4 in four human osteosarcoma cell lines and hFOB1.19 cells were examined by real-time quantitative PCR (RT-qPCR). The U2OS cells of the highest GRM4 expression were transfected with lentivirus-mediated small interfering RNA (siRNA). The differentially expressed genes (DEGs) after GRM4 gene silencing were screened through RNA sequencing, and analyzed by bioinformatics...
January 17, 2018: Medical Science Monitor Basic Research
https://www.readbyqxmd.com/read/29339520/targeted-knockout-of-a-chemokine-like-gene-increases-anxiety-and-fear-responses
#19
Jung-Hwa Choi, Yun-Mi Jeong, Sujin Kim, Boyoung Lee, Krishan Ariyasiri, Hyun-Taek Kim, Seung-Hyun Jung, Kyu-Seok Hwang, Tae-Ik Choi, Chul O Park, Won-Ki Huh, Matthias Carl, Jill A Rosenfeld, Salmo Raskin, Alan Ma, Jozef Gecz, Hyung-Goo Kim, Jin-Soo Kim, Ho-Chul Shin, Doo-Sang Park, Robert Gerlai, Bradley B Jamieson, Joon S Kim, Karl J Iremonger, Sang H Lee, Hee-Sup Shin, Cheol-Hee Kim
Emotional responses, such as fear and anxiety, are fundamentally important behavioral phenomena with strong fitness components in most animal species. Anxiety-related disorders continue to represent a major unmet medical need in our society, mostly because we still do not fully understand the mechanisms of these diseases. Animal models may speed up discovery of these mechanisms. The zebrafish is a highly promising model organism in this field. Here, we report the identification of a chemokine-like gene family, samdori (sam), and present functional characterization of one of its members, sam2 We show exclusive mRNA expression of sam2 in the CNS, predominantly in the dorsal habenula, telencephalon, and hypothalamus...
January 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29339479/hif-signaling-in-osteoblast-lineage-cells-promotes-systemic-breast-cancer-growth-and-metastasis-in-mice
#20
Claire-Sophie Devignes, Yetki Aslan, Audrey Brenot, Audrey Devillers, Koen Schepers, Stéphanie Fabre, Jonathan Chou, Amy-Jo Casbon, Zena Werb, Sylvain Provot
Bone metastasis involves dynamic interplay between tumor cells and the local stromal environment. In bones, local hypoxia and activation of the hypoxia-inducible factor (HIF)-1α in osteoblasts are essential to maintain skeletal homeostasis. However, the role of osteoblast-specific HIF signaling in cancer metastasis is unknown. Here, we show that osteoprogenitor cells (OPCs) are located in hypoxic niches in the bone marrow and that activation of HIF signaling in these cells increases bone mass and favors breast cancer metastasis to bone locally...
January 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
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