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https://www.readbyqxmd.com/read/28440285/ionizing-radiation-abrogates-the-pro-tumorigenic-capacity-of-cancer-associated-fibroblasts-co-implanted-in-xenografts
#1
Maria Tunset Grinde, Jørg Vik, Ketil André Camilio, Inigo Martinez-Zubiaurre, Turid Hellevik
Cancer-associated fibroblasts (CAFs) are abundantly present in solid tumors and affect tumorigenesis and therapeutic responses. In the context of clinical radiotherapy, the impact of irradiated CAFs to treatment outcomes is largely unexplored. Aiming at improving radiotherapy efficacy, we have here explored the effect of radiation on the inherent pro-tumorigenic capacity of CAFs in animals. Ionizing radiation was delivered to cultured CAFs as single-high or fractionated doses. Tumor development was compared in mice receiving A549 lung tumor cells admixed with irradiated or control CAFs...
April 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28439989/using-size-controlled-multicellular-spheroids-of-murine-adenocarcinoma-cells-to-efficiently-establish-pulmonary-tumors-in-mice
#2
Tomoko Nishikawa, Yutaro Tanaka, Makiya Nishikawa, Kosuke Kusamori, Narumi Mizuno, Yuya Mizukami, Yuka Ogino, Kazunori Shimizu, Satoshi Konishi, Yuki Takahashi, Yoshinobu Takakura
Previous studies demonstrated that multicellular spheroids developed using polydimethylsiloxane-based microwells exhibited superior functions, such as insulin secretion from pancreatic cells, over suspended cells. To successfully apply these spheroids, the effect of spheroid size on cellular functions must be determined. In this study, using murine adenocarcinoma colon26 cells, we examined whether such spheroids were useful for developing tumor-bearing animal models, which requires the efficient and stable engraftment of cancer cells at implanted sites and/or metastatic sites...
April 25, 2017: Biotechnology Journal
https://www.readbyqxmd.com/read/28439910/abo-incompatibility-in-mismatched-unrelated-donor-allogeneic-hematopoietic-cell-transplantation-for-acute-myeloid-leukemia-a-report-from-the-acute-leukemia-working-party-of-the-ebmt
#3
Jonathan Canaani, Bipin N Savani, Myriam Labopin, Mauricette Michallet, Charles Craddock, Gerard Socié, Lisa Volin, Johan A Maertens, Charles Crawley, Didier Blaise, Per T Ljungman, Jan Cornelissen, Nigel Russell, Frédéric Baron, Norbert Gorin, Jordi Esteve, Fabio Ciceri, Christoph Schmid, Sebastian Giebel, Mohamad Mohty, Arnon Nagler
ABO incompatibility is commonly observed in stem cell transplantation and its impact in this setting has been extensively investigated. HLA-mismatched unrelated donors (MMURD) are often used as an alternative stem cell source but are associated with increased transplant related complications. Whether ABO incompatibility affects outcome in MMURD transplantation for acute myeloid leukemia (AML) patients is unknown. We evaluated 1013 AML patients who underwent MMURD transplantation between 2005 and 2014. Engraftment rates were comparable between ABO matched and mismatched patients, as were relapse incidence [34%; 95% confidence interval (CI), 28-39; for ABO matched vs...
April 25, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28439700/filgrastim-alone-versus-pegylated-filgrastim-alone-for-autologous-peripheral-blood-stem-cells-mobilization-in-newly-diagnosed-multiple-myeloma-patients
#4
Barbara Skopec, Matevz Skerget, Darja Zontar, Vesna Zadnik, Samo Zver
BACKGROUND: Autologous hematopoietic stem cell transplantation (aHSCT) is the recommended standard upfront treatment for transplant eligible myeloma patients. Considering possible complications related to chemotherapy-cytokine mobilization, cytokine-alone mobilization is often used. We compared mobilization with filgrastim alone to pegfilgrastim alone in newly diagnosed myeloma patients after induction treatment with bortezomib and dexamethasone. The comparison was made between peripheral blood stem cell (PBSC) yields, number of apheresis, hematopoietic stem cell subsets, and time to neutrophil and platelet engraftment after aHSCT...
April 24, 2017: Wiener Klinische Wochenschrift
https://www.readbyqxmd.com/read/28439674/adipose-derived-stem-cell-asc-enriched-fat-grafting-experiments-using-white-rabbits-and-an-automated-cell-processing-apparatus
#5
Natsuko Kakudo, Naoki Morimoto, Takeshi Ogawa, Masakatsu Hihara, Fangyuan Lai, Kenji Kusumoto
The grafting of fat mixed with adipose-derived stem cells (ASCs) is being increasingly applied to compensate for the disadvantages of previous fat grafting methods. Devices that automatically isolate fat stem cells also have recently been developed. ASCs were isolated from the inguinal region of White rabbits using Icellator(®), and the number of cells and their viability were measured. The cell count per fat graft (mL) was adjusted to the following concentrations and subcutaneously transplanted into the back: Control group, Fat + PBS; Fat + ASCs (×0...
April 24, 2017: Medical Molecular Morphology
https://www.readbyqxmd.com/read/28438506/diacylglycerol-kinase-%C3%AE-limits-cytokine-dependent-expansion-of-cd8-t-cells-with-broad-antitumor-capacity
#6
Elena Andrada, Rosa Liébana, Isabel Merida
Interleukin-2 and -15 drive expansion/differentiation of cytotoxic CD8(+) T cells that eliminate targets via antigen-independent killing. This property is clinically relevant for the improvement of T cell-based antitumor therapies. Diacylglycerol kinase α and ζ (DGKα/ζ) metabolize the diacylglycerol generated following antigen recognition by T lymphocytes. Enhanced expression of these two lipid kinases in tumor-infiltrating CD8(+) T cells promotes a hyporesponsive state that contributes to tumor immune escape...
April 14, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28436946/essential-role-for-bim-in-mediating-the-apoptotic-and-antitumor-activities-of-immunotoxins
#7
A Antignani, D Segal, N Simon, R J Kreitman, D Huang, D J FitzGerald
Protein synthesis is crucial for regulating cell homeostasis and, when unrestricted, it can lead to tumorigenesis. Immunotoxins derived from Pseudomonas exotoxin are antibody-toxin fusion proteins that inhibit protein synthesis of mammalian cells via ADP-ribosylation of the eukaryotic elongation factor-2. Here we investigate the role of the Bcl-2 family proteins in the response of cancer cells to immunotoxin challenge. Besides the well-known reduction of the prosurvival Bcl-2 family member, Mcl-1, following inhibition of protein synthesis, we show for the first time that immunotoxins also reduce the levels of selected proapoptotic BH-3-only proteins...
April 24, 2017: Oncogene
https://www.readbyqxmd.com/read/28436117/early-introduction-of-oral-paricalcitol-in-renal-transplant-recipients-an-open-label-randomized-study
#8
Hege Kampen Pihlstrøm, Franscesca Gatti, Clara Hammarström, Ivar Anders Eide, Monika Kasprzycka, Junbai Wang, Guttorm Haraldsen, My Hanna Sofia Svensson, Karsten Midtvedt, Geir Mjøen, Dag Olav Dahle, Anders Hartmann, Hallvard Holdaas
In stable renal transplant recipients with hyperparathyroidism, previous studies have indicated that vitamin D agonist treatment might have anti-proteinuric effects. Animal studies indicate possible anti-fibrotic and anti-inflammatory effects. Early introduction of paricalcitol in de-novo renal transplant recipients might reduce proteinuria and prevent progressive allograft fibrosis. We performed a single-centre, prospective, randomized, open-label trial investigating effects of paricalcitol 2μg/day added to standard care...
April 24, 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/28433514/cox-2-inhibition-potentiates-mouse-bone-marrow-stem-cell-engraftment-and-differentiation-mediated-wound-repair
#9
Ramasatyaveni Geesala, Neha R Dhoke, Amitava Das
BACKGROUND: Engraftment of transplanted stem cells is often limited by cytokine and noncytokine proinflammatory mediators at the injury site. We examined the role of Cyclooxygenase-2 (Cox-2)-induced cytokine-mediated inflammation on engraftment of transplanted bone marrow stem cells (BMSCs) at the wound site. METHODS: BMSCs isolated from male C57/BL6J mice were transplanted onto excisional splinting wounds in syngenic females in presence or absence of celecoxib, Cox-2 specific inhibitor (50 mg/kg, body weight [b wt]), to evaluate engraftment and wound closure...
April 19, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28432872/human-effector-memory-t-helper-cells-engage-with-mouse-macrophages-and-cause-graft-versus-host-like-pathology-in-skin-of-humanized-mice-used-in-a-nonclinical-immunization-study
#10
Bala S Sundarasetty, Valery Volk, Sebastian J Theobald, Susanne Rittinghausen, Dirk Schaudien, Vanessa Neuhaus, Constanca Figueiredo, Andreas Schneider, Laura Gerasch, Adele Mucci, Thomas Moritz, Constantin von Kaisenberg, Loukia M Spineli, Katherina Sewald, Armin Braun, Henning Weigt, Arnold Ganser, Renata Stripecke
Humanized mice engrafted with human hematopoietic stem cells and developing functional human T-cell adaptive responses are in critical demand to test human-specific therapeutics. We previously showed that humanized mice immunized with long-lived induced-dendritic cells loaded with the pp65 viral antigen (iDCpp65) exhibited a faster development and maturation of T cells. Herein, we evaluated these effects in a long-term (36 weeks) nonclinical model using two stem cell donors to assess efficacy and safety. Relative to baseline, iDCpp65 immunization boosted the output of effector memory CD4(+) T cells in peripheral blood and lymph nodes...
April 19, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28432130/do-the-microbiota-influence-vaccines-and-protective-immunity-to-pathogens-engaging-our-endogenous-adjuvants
#11
Nicholas Collins, Yasmine Belkaid
The reliance of the immune system on constitutive microbial stimulation support the idea that both responsiveness to vaccines and vaccine design need to be considered in the context of host-microbiota interactions. Manipulation of microbe function or composition via diet alteration or microbiota engraftment may soon become a viable approach to control immunity and, as such, vaccine responses. Learning from our endogenous original adjuvants could be critical in overcoming the enormous hurdle of vaccine design against the numerous pathogens that cause chronic infection...
April 21, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28431402/micrometastasis-of-endometriosis-to-distant-organs-in-a-murine-model
#12
Elham N Samani, Ramanaiah Mamillapalli, Fei Li, Levent Mutlu, Demetra Hufnagel, Graciela Krikun, Hugh S Taylor
Endometriosis is an inflammatory gynecological disorder among reproductive-aged women caused by the engraftment and proliferation of endometrial cells outside the uterus, most commonly in the pelvis. It is thought that the disease arises primarily from retrograde menstruation where cells from the endometrium travel through the fallopian tubes to the peritoneal cavity. However, migration of endometriosis-derived cells to distant organs outside of the peritoneal cavity have not been explored. In the present study, we developed and validated a mouse model of disseminated endometriosis using syngeneic DsRed endometrial tissue introduced into the peritoneum of immunocompetent mice...
April 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28428537/human-cytomegalovirus-induces-cellular-and-humoral-virus-specific-immune-responses-in-humanized-blt-mice
#13
Lindsey B Crawford, Rebecca Tempel, Daniel N Streblow, Craig Kreklywich, Patricia Smith, Louis J Picker, Jay A Nelson, Patrizia Caposio
The strict species specificity of Human Cytomegalovirus (HCMV) has impeded our understanding of antiviral adaptive immune responses in the context of a human immune system. We have previously shown that HCMV infection of human hematopoietic progenitor cells engrafted in immune deficient mice (huNSG) results in viral latency that can be reactivated following G-CSF treatment. In this study, we characterized the functional human adaptive immune responses in HCMV latently-infected huBLT (humanized Bone marrow-Liver-Thymus) mice...
April 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28423196/melatonin-enhances-neural-stem-cell-differentiation-and-engraftment-by-increasing-mitochondrial-function
#14
Miguel Mendivil-Perez, Viviana Soto-Mercado, Ana Guerra-Librero, Beatriz I Fernandez-Gil, Javier Florido, Ying-Qiang Shen, Miguel A Tejada, Vivian Capilla-Gonzalez, Iryna Rusanova, José M Garcia-Verdugo, Darío Acuña-Castroviejo, Luis Carlos López, Carlos Velez-Pardo, Marlene Jimenez-Del-Rio, José M Ferrer, Germaine Escames
Neural stem cells (NSCs) are regarded as a promising therapeutic approach to protecting and restoring damaged neurons in neurodegenerative diseases (NDs) such as Parkinson's disease and Alzheimer's disease (PD and AD, respectively). However, new research suggests that NSC differentiation is required to make this strategy effective. Several studies have demonstrated that melatonin increases mature neuronal markers, which reflects NSC differentiation into neurons. Nevertheless, the possible involvement of mitochondria in the effects of melatonin during NSC differentiation has not yet been fully established...
April 19, 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/28420436/autophagy-mediates-the-beneficial-effect-of-hypoxic-preconditioning-on-bone-marrow-mesenchymal-stem-cells-for-the-therapy-of-myocardial-infarction
#15
Zheng Zhang, Chao Yang, Mingzhi Shen, Ming Yang, Zhitao Jin, Liping Ding, Wei Jiang, Junke Yang, Haixu Chen, Feng Cao, Taohong Hu
BACKGROUND: Stem cell therapy has emerged as a promising therapeutic strategy for myocardial infarction (MI). However, the poor viability of transplanted stem cells hampers their therapeutic efficacy. Hypoxic preconditioning (HPC) can effectively promote the survival of stem cells. The aim of this study was to investigate whether HPC improved the functional survival of bone marrow mesenchymal stem cells (BM-MSCs) and increased their cardiac protective effect. METHODS: BM-MSCs, isolated from Tg(Fluc-egfp) mice which constitutively express both firefly luciferase (Fluc) and enhanced green fluorescent protein (eGFP), were preconditioned with HPC (1% O2) for 12 h, 24 h, 36 h, and 48 h, respectively, followed by 24 h of hypoxia and serum deprivation (H/SD) injury...
April 18, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28420418/adult-muscle-derived-stem-cells-engraft-and-differentiate-into-insulin-expressing-cells-in-pancreatic-islets-of-diabetic-mice
#16
Violeta Mitutsova, Wendy Wai Yeng Yeo, Romain Davaze, Celine Franckhauser, El-Habib Hani, Syahril Abdullah, Patrice Mollard, Marie Schaeffer, Anne Fernandez, Ned J C Lamb
BACKGROUND: Pancreatic beta cells are unique effectors in the control of glucose homeostasis and their deficiency results in impaired insulin production leading to severe diabetic diseases. Here, we investigated the potential of a population of nonadherent muscle-derived stem cells (MDSC) from adult mouse muscle to differentiate in vitro into beta cells when transplanted as undifferentiated stem cells in vivo to compensate for beta-cell deficiency. RESULTS: In vitro, cultured MDSC spontaneously differentiated into insulin-expressing islet-like cell clusters as revealed using MDSC from transgenic mice expressing GFP or mCherry under the control of an insulin promoter...
April 18, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28415816/targeting-the-pim-protein-kinases-for-the-treatment-of-a-t-cell-acute-lymphoblastic-leukemia-subset
#17
Sathish K R Padi, Libia A Luevano, Ningfei An, Ritu Pandey, Neha Singh, Jin H Song, Jon C Aster, Xue-Zhong Yu, Shikhar Mehrotra, Andrew S Kraft
New approaches are needed for the treatment of patients with T-cell acute lymphoblastic leukemia (T-ALL) who fail to achieve remission with chemotherapy. Analysis of the effects of pan-PIM protein kinase inhibitors on human T-ALL cell lines demonstrated that the sensitive cell lines expressed higher PIM1 protein kinase levels, whereas T-ALL cell lines with NOTCH mutations tended to have lower levels of PIM1 kinase and were insensitive to these inhibitors. NOTCH-mutant cells selected for resistance to gamma secretase inhibitors developed elevated PIM1 kinase levels and increased sensitivity to PIM inhibitors...
March 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28412561/metastatic-human-breast-cancer-to-the-spine-produces-mechanical-hyperalgesia-and-gait-deficits-in-rodents
#18
Rachel Sarabia-Estrada, Alejandro Ruiz-Valls, Hugo Guerrero-Cazares, Ana M Ampuero, Ismael Jimenez-Estrada, Samantha De Silva, Lydia J Bernhardt, C Rory Goodwin, A Karim Ahmed, Yuxin Li, Neil A Phillips, Ziya L Gokaslan, Alfredo Quiñones-Hinojosa, Daniel M Sciubba
BACKGROUND CONTEXT: Metastases to the spine are a common source of severe pain in cancer patients. The secondary effects of spinal metastases include pain, bone fractures, hypercalcemia, and neurological deficits. As the disease progresses, pain severity can increase until it becomes refractory to medical treatments and leads to a decreased quality of life for patients. A key obstacle in the study of pain-induced spinal cancer is the lack of reliable and reproducible spine cancer animal models...
April 13, 2017: Spine Journal: Official Journal of the North American Spine Society
https://www.readbyqxmd.com/read/28410215/cardiac-glycosides-suppress-the-maintenance-of-stemness-and-malignancy-via-inhibiting-hif-1%C3%AE-in-human-glioma-stem-cells
#19
Dae-Hee Lee, Sang Cheul Oh, Amber J Giles, Jinkyu Jung, Mark R Gilbert, Deric M Park
Tissue hypoxia contributes to solid tumor pathogenesis by activating a series of adaptive programs. We previously showed that hypoxia promotes the preferential expansion and maintenance of CD133 positive human glioma stem cells (GSC) in a hypoxia inducible factor 1 alpha (HIF-1α)-dependent mechanism. Here, we examined the activity of digitoxin (DT), a cardiac glycoside and a putative inhibitor of HIF-1α, on human GSC in vitro and in vivo. During hypoxic conditions (1% O2), we observed the effect of DT on the intracellular level of HIF-1α and the extracellular level of vascular endothelial growth factor (VEGF) in human GSC...
March 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28408761/endothelial-and-astrocytic-support-by-human-bone-marrow-stem-cell-grafts-into-symptomatic-als-mice-towards-blood-spinal-cord-barrier-repair
#20
Svitlana Garbuzova-Davis, Crupa Kurien, Avery Thomson, Dimitri Falco, Sohaib Ahmad, Joseph Staffetti, George Steiner, Sophia Abraham, Greeshma James, Ajay Mahendrasah, Paul R Sanberg, Cesario V Borlongan
Vascular pathology, including blood-CNS barrier (B-CNS-B) damage via endothelial cell (EC) degeneration, is a recently recognized hallmark of Amyotrophic Lateral Sclerosis (ALS) pathogenesis. B-CNS-B repair may be a new therapeutic approach for ALS. This study aimed to determine effects of transplanted unmodified human bone marrow CD34+ (hBM34+) cells into symptomatic G93A mice towards blood-spinal cord barrier (BSCB) repair. Thirteen weeks old G93A mice intravenously received one of three different doses of hBM34+ cells...
April 13, 2017: Scientific Reports
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