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https://www.readbyqxmd.com/read/28817816/exosomes-derived-from-human-bone-marrow-mesenchymal-stem-cells-promote-tumor-growth-through-hedgehog-signaling-pathway
#1
Jin Qi, Yali Zhou, Zuoyi Jiao, Xu Wang, Yang Zhao, Yangbin Li, Huijuan Chen, Luxi Yang, Hongwen Zhu, Yumin Li
BACKGROUND/AIMS: Mesenchymal stem/stromal cells (MSCs) are known to home to sites of tumor microenvironments where they participate in the formation of the tumor microenvironment and to interplay with tumor cells. However, the potential functional effects of MSCs on tumor cell growth are controversial. Here, we, from the view of bone marrow MSC-derived exosomes, study the molecular mechanism of MSCs on the growth of human osteosarcoma and human gastric cancer cells. METHODS: MSCs derived from human bone marrow (hBMSCs) were isolated and cultured in complete DMEM/F12 supplemented with 10% exosome-depleted fetal bovine serum and 1% penicillin-streptomycin, cell culture supernatants containing exosomes were harvested and exosome purification was performed by ultracentrifugation...
August 16, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28817117/increased-tumor-infiltrating-cd45ra-ccr7-regulatory-t-cell-subset-with-immunosuppressive-properties-foster-gastric-cancer-progress
#2
Fang-Yuan Mao, Hui Kong, Yong-Liang Zhao, Liu-Sheng Peng, Weisan Chen, Jin-Yu Zhang, Ping Cheng, Ting-Ting Wang, Yi-Pin Lv, Yong-Sheng Teng, Xiao-Long Fu, Yu-Gang Liu, Xiao-Long Wu, Chuan-Jie Hao, Nan You, Ping Luo, Pei-Wu Yu, Quan-Ming Zou, Gang Guo, Yuan Zhuang
Regulatory T cells (Tregs) are major components of tumor-infiltrating immune cells with potent immunosuppressive properties in gastric cancer (GC) microenvironment. However, different subsets of the Tregs and their relevance to GC are unknown. Here, we found that patients with GC showed a significantly higher Tregs infiltration in tumors, and CD45RA(-)CCR7(-) Treg subset constituted most tumor-infiltrating Tregs. Tumor-infiltrating CD45RA(-)CCR7(-) Treg subset with an effector/memory phenotype accumulated in tumors and expressed low level of HLA-DR...
August 17, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28816713/radiation-therapy-to-the-primary-in-metastatic-prostate-cancer-palliation-only-or-altering-tumor-biology
#3
Pierre Blanchard, Alberto Bossi, Karim Fizazi
PURPOSE OF REVIEW: Despite improvement in systemic treatment, the prognosis of men with de novo metastatic prostate cancer remains poor. Treating the local disease may not only reduce the occurrence of local urologic symptoms, but also slow the metastatic process, either by reducing the seeding from the primary tumor or by altering the microenvironment and thus minimizing the formation of new metastatic sites. RECENT FINDINGS: Retrospective and population-based studies have suggested that the addition of local treatment to systemic therapy may improve survival in this patient group...
August 14, 2017: Current Opinion in Urology
https://www.readbyqxmd.com/read/28816624/comparison-of-two-rabbit-models-with-deficiency-of-corneal-epithelium-and-limbal-stem-cells-established-by-different-methods
#4
Hening Zhang, Shaochun Lin, Min Zhang, Qijiong Li, Weihua Li, Wencong Wang, Minglei Zhao, Yaojue Xie, Zhiquan Li, Mian Huang, Zhichong Wang, Xiulan Zhang, Bing Huang
Limbal stem cell defect model is an important animal model that provides a basis for the study of ocular surface diseases. The rabbit cornea is of moderate size and is widely used in such studies as an experimental animal model. At present, the main modeling methods are alkali burns, and corneal limbus girdling and corneal epithelium doctoring. Each method has its own characteristics. In this study, we observed rabbit models with severe ocular surface defect established by the two methods and changes after amniotic membrane transplantation...
August 14, 2017: Tissue Engineering. Part C, Methods
https://www.readbyqxmd.com/read/28816413/porcine-spermatogonial-stem-cells-self-renew-effectively-in-a-three-dimensional-culture-microenvironment
#5
Ji Eun Park, Min Hee Park, Min Seong Kim, Yeo Reum Park, Jung Im Yun, Hee Tae Cheong, Minseok Kim, Jung Hoon Choi, Eunsong Lee, Seung Tae Lee
Generally, self-renewal of spermatogonial stem cells (SSCs) is maintained in vivo in a three-dimensional (3D) microenvironment consisting of the seminiferous tubule basement membrane, indicating the importance of the 3D microenvironment for in vitro culture of SSCs. Here, we report a 3D culture microenvironment that effectively maintains porcine SSC self-renewal during culture. Porcine SSCs were cultured in an agarose-based 3D hydrogel and in 2D culture plates either with or without feeder cells. Subsequently, the effects of 3D culture on the maintenance of undifferentiated SSCs were identified by analyzing cell colony formation and morphology, AP activity, and transcriptional and translational regulation of self-renewal-related genes and the effects on proliferation by analyzing cell viability and single cell-derived colony number...
August 17, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28816238/acute-myeloid-leukemia-transforms-the-bone-marrow-niche-into-a-leukemia-permissive-microenvironment-through-exosome-secretion
#6
B Kumar, M Garcia, L Weng, X Jung, J L Murakami, X Hu, T McDonald, A Lin, A R Kumar, D L DiGiusto, A S Stein, V A Pullarkat, S K Hui, N Carlesso, Y-H Kuo, R Bhatia, G Marcucci, C-C Chen
Little is known about how leukemia cells alter the bone marrow (BM) niche to facilitate their own growth and evade chemotherapy. Here, we provide evidence that acute myeloid leukemia (AML) blasts remodel the BM niche into a leukemia-growth-permissive and normal-hematopoiesis-suppressive microenvironment through exosome secretion. Either engrafted AML cells or AML-derived exosomes increased mesenchymal stromal progenitors and blocked osteolineage development and bone formation in vivo. Pre-conditioning with AML-derived exosomes 'primed' the animals for accelerated AML growth...
August 17, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28816141/combined-radiation-therapy-and-immune-checkpoint-blockade-therapy-for-breast-cancer
#7
REVIEW
Zishuo I Hu, Alice Y Ho, Heather L McArthur
PURPOSE: Treatment with checkpoint inhibitors has shown durable responses in a number of solid tumors, including melanoma, lung, and renal cell carcinoma. However, most breast cancers are resistant to monotherapy with checkpoint inhibitors. Radiation therapy (RT) has been shown to have a number of immunostimulatory effects, including priming the immune system, recruiting immune cells to the tumor environment, and altering the immunosuppressive effects of the tumor microenvironment. RT therefore represents a promising adjuvant therapy to checkpoint blockade in breast cancer...
September 1, 2017: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/28816053/in-vitro-exposure-systems-and-dosimetry-assessment-tools-for-inhaled-tobacco-products-workshop-proceedings-conclusions-and-paths-forward-for-in-vitro-model-use
#8
Holger Behrsing, Erin Hill, Hans Raabe, Raymond Tice, Suzanne Fitzpatrick, Robert Devlin, Kent Pinkerton, Günter Oberdörster, Chris Wright, Roman Wieczorek, Michaela Aufderheide, Sandro Steiner, Tobias Krebs, Bahman Asgharian, Richard Corley, Michael Oldham, Jason Adamson, Xiang Li, Irfan Rahman, Sonia Grego, Pei-Hsuan Chu, Shaun McCullough, Rodger Curren
In 2009, the passing of the Family Smoking Prevention and Tobacco Control Act facilitated the establishment of the FDA Center for Tobacco Products (CTP), and gave it regulatory authority over the marketing, manufacture and distribution of tobacco products, including those termed 'modified risk'. On 4-6 April 2016, the Institute for In Vitro Sciences, Inc. (IIVS) convened a workshop conference entitled, In Vitro Exposure Systems and Dosimetry Assessment Tools for Inhaled Tobacco Products, to bring together stakeholders representing regulatory agencies, academia and industry to address the research priorities articulated by the FDA CTP...
July 2017: Alternatives to Laboratory Animals: ATLA
https://www.readbyqxmd.com/read/28815755/large-scale-synthesis-of-freestanding-layer-structured-pbi2-and-mapbi3-nanosheets-for-high-performance-photodetection
#9
Changyong Lan, Ruoting Dong, Ziyao Zhou, Lei Shu, Dapan Li, SenPo Yip, Johnny C Ho
Recently, due to the possibility of thinning down to the atomic thickness to achieve exotic properties, layered materials have attracted extensive research attention. In particular, PbI2 , a kind of layered material, and its perovskite derivatives, CH3 NH3 PbI3 (i.e., MAPbI3 ), have demonstrated impressive photoresponsivities for efficient photodetection. Herein, the synthesis of large-scale, high-density, and freestanding PbI2 nanosheets is demonstrated by manipulating the microenvironment during physical vapor deposition...
August 17, 2017: Advanced Materials
https://www.readbyqxmd.com/read/28815730/loss-of-bmi-1-dampens-migration-and-emt-of-colorectal-cancer-in-inflammatory-microenvironment-through-tlr4-md-2-myd88-mediated-nf-%C3%AE%C2%BAb-signaling
#10
Kai Ye, Qi-Wei Chen, Ya-Feng Sun, Jian-An Lin, Jian-Hua Xu
Increasing evidence from various clinical and experimental studies has demonstrated that the inflammatory microenvironment created by immune cells facilitates tumor migration. Epithelial-mesenchymal transition (EMT) is involved in the progression of cancer invasion and metastasis in an inflammatory microenvironment. B-lymphoma Moloney murine leukemia virus insertion region 1 (BMI-1) acts as an oncogene in various tumors. Ectopic expression of Bmi-1 have an effect on EMT and invasiveness. The purpose of this study was to investigate the efficacy of BMI-1 on inflammation-induced tumor migration and EMT and the underlying mechanism...
August 16, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28815527/discovery-and-roles-of-er-endolysosomal-contact-sites-in-disease
#11
William Mike Henne
Inter-organelle membrane contact sites (MCSs) serve as unique microenvironments for the sensing and exchange of cellular metabolites and lipids. Though poorly defined, ER-endolysosomal contact sites are quickly becoming recognized as centers for inter-organelle lipid exchange and metabolic decision-making. Here, we review the discovery and current state of knowledge of ER-endolysosomal MCSs with particular focus on the molecular players that establish and/or utilize these contact sites in metabolism. We also discuss associations of ER-endolysosomal MCS-associated proteins in human disease, as well as the therapeutic promise these contact sites hold in modulating cellular physiology...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28815347/the-tumor-stromal-ratio-as-a-strong-prognosticator-for-advanced-gastric-cancer-patients-proposal-of-a-new-tsnm-staging-system
#12
Chunwei Peng, Jiuyang Liu, Guifang Yang, Yan Li
BACKGROUND: Insufficient attention is paid to the underlying tumor microenvironment (TME) evolution, that resulting in tumor heterogeneity and driving differences in cancer aggressiveness and treatment outcomes. The morphological evaluation of the proportion of the stroma at the most invasive part of primary tumor (tumor-stromal ratio, TSR) in cancer is gaining momentum as evidence strengthens for the clinical relevance. METHODS: Tissue samples from the most invasive part of the primary gastric cancer (GC) of 494 patients were analyzed for their TSR, and a new TSNM (tumor-stromal node metastasis) staging system based on patho-biological behaviors was established and assessed...
August 16, 2017: Journal of Gastroenterology
https://www.readbyqxmd.com/read/28815045/tumor-derived-exosomes-induce-cd8-t-cell-suppressors
#13
Brian T Maybruck, Lukas W Pfannenstiel, Marcela Diaz-Montero, Brian R Gastman
BACKGROUND: The suppressive nature of immune cells in the tumor microenvironment plays a major role in regulating anti-tumor immune responses. Our previous work demonstrated that a soluble factor from tumor cells is able to induce a suppressor phenotype (SP) in human CD8(+) T cells typified by loss of CD27/CD28 expression and acquisition of a potent suppressor function. The present study hypothesized that the soluble mechanism that is inducing the SP in CD8(+) T cells are tumor-derived exosomes (TDEs)...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28815044/agonist-anti-gitr-antibody-significantly-enhances-the-therapeutic-efficacy-of-listeria-monocytogenes-based-immunotherapy
#14
Rajeev Shrimali, Shamim Ahmad, Zuzana Berrong, Grigori Okoev, Adelaida Matevosyan, Ghazaleh Shoja E Razavi, Robert Petit, Seema Gupta, Mikayel Mkrtichyan, Samir N Khleif
BACKGROUND: We previously demonstrated that in addition to generating an antigen-specific immune response, Listeria monocytogenes (Lm)-based immunotherapy significantly reduces the ratio of regulatory T cells (Tregs)/CD4(+) and myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment. Since Lm-based immunotherapy is able to inhibit the immune suppressive environment, we hypothesized that combining this treatment with agonist antibody to a co-stimulatory receptor that would further boost the effector arm of immunity will result in significant improvement of anti-tumor efficacy of treatment...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28815043/the-mek-inhibitor-selumetinib-complements-ctla-4-blockade-by-reprogramming-the-tumor-immune-microenvironment
#15
Edmund Poon, Stefanie Mullins, Amanda Watkins, Geoffrey S Williams, Jens-Oliver Koopmann, Gianfranco Di Genova, Marie Cumberbatch, Margaret Veldman-Jones, Shaun E Grosskurth, Vasu Sah, Alwin Schuller, Corrine Reimer, Simon J Dovedi, Paul D Smith, Ross Stewart, Robert W Wilkinson
BACKGROUND: T-cell checkpoint blockade and MEK inhibitor combinations are under clinical investigation. Despite progress elucidating the immuno-modulatory effects of MEK inhibitors as standalone therapies, the impact of MEK inhibition on the activity of T-cell checkpoint inhibitors remains incompletely understood. Here we sought to characterize the combined effects of MEK inhibition and anti-CTLA-4 mAb (anti-CTLA-4) therapy, examining effects on both T-cells and tumor microenvironment (TME)...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28815003/glioblastoma-stem-like-cells-secrete-the-pro-angiogenic-vegf-a-factor-in-extracellular-vesicles
#16
Lucas Treps, Raul Perret, Sébastien Edmond, Damien Ricard, Julie Gavard
Glioblastoma multiforme (GBM) are mortifying brain tumours that contain a subpopulation of tumour cells with stem-like properties, termed glioblastoma stem-like cells (GSCs). GSCs largely contribute to tumour initiation, propagation and resistance to current anti-cancer therapies. GSCs are situated in perivascular niches, closely associated with brain microvascular endothelial cells, thereby involved in bidirectional molecular and cellular interactions. Moreover, extracellular vesicles are suspected to carry essential information that can adapt the microenvironment to the tumour's needs, including tumour-induced angiogenesis...
2017: Journal of Extracellular Vesicles
https://www.readbyqxmd.com/read/28814649/wnt-ligand-presentation-and-reception-from-the-stem-cell-niche-to-tissue-engineering
#17
REVIEW
Kate M Mills, James L A Szczerkowski, Shukry J Habib
Stem cells reside in niches where spatially restricted signals maintain a delicate balance between stem cell self-renewal and differentiation. Wnt family proteins are particularly suited for this role as they are modified by lipids, which constrain and spatially regulate their signalling range. In recent years, Wnt/β-catenin signalling has been shown to be essential for the self-renewal of a variety of mammalian stem cells. In this review, we discuss Wnt-responsive stem cells in their niche, and mechanisms by which Wnt ligands are presented to responsive cells...
August 2017: Open Biology
https://www.readbyqxmd.com/read/28813700/regenerative-medicine-approaches-for-age-related-muscle-loss-and-sarcopenia-a-mini-review
#18
Juan Diego Naranjo, Jenna L Dziki, Stephen F Badylak
Sarcopenia is a complex and multifactorial disease that includes a decrease in the number, structure and physiology of muscle fibers, and age-related muscle mass loss, and is associated with loss of strength, increased frailty, and increased risk for fractures and falls. Treatment options are suboptimal and consist of exercise and nutrition as the cornerstone of therapy. Current treatment principles involve identification and modification of risk factors to prevent the disease, but these efforts are of limited value to the elderly individuals currently affected by sarcopenia...
August 17, 2017: Gerontology
https://www.readbyqxmd.com/read/28813661/tissue-resident-macrophages-in-pancreatic-ductal-adenocarcinoma-originate-from-embryonic-hematopoiesis-and-promote-tumor-progression
#19
Yu Zhu, John M Herndon, Dorothy K Sojka, Ki-Wook Kim, Brett L Knolhoff, Chong Zuo, Darren R Cullinan, Jingqin Luo, Audrey R Bearden, Kory J Lavine, Wayne M Yokoyama, William G Hawkins, Ryan C Fields, Gwendalyn J Randolph, David G DeNardo
Tumor-associated macrophages (TAMs) are essential components of the cancer microenvironment and play critical roles in the regulation of tumor progression. Optimal therapeutic intervention requires in-depth understanding of the sources that sustain macrophages in malignant tissues. In this study, we investigated the ontogeny of TAMs in murine pancreatic ductal adenocarcinoma (PDAC) models. We identified both inflammatory monocytes and tissue-resident macrophages as sources of TAMs. Unexpectedly, significant portions of pancreas-resident macrophages originated from embryonic development and expanded through in situ proliferation during tumor progression...
August 15, 2017: Immunity
https://www.readbyqxmd.com/read/28813180/inflammatory-signaling-cascades-and-autophagy-in-cancer
#20
Teresa Monkkonen, Jayanta Debnath
Tumor-associated inflammation is predictive of poor prognosis and drives a variety of tumorigenic phenotypes, including tumor proliferation and survival, angiogenesis, invasiveness, and metastasis. Here, we review mammalian data addressing the interaction of macroautophagy/autophagy with key signaling cascades associated with tumor inflammation. Although our understanding of this area remains incomplete, certain inflammatory pathways have emerged as important mediators of the crosstalk between autophagy and inflammation in tumors...
August 16, 2017: Autophagy
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