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https://www.readbyqxmd.com/read/29336105/senescence-chips-for-ultrahigh-throughput-isolation-and-removal-of-senescent-cells
#1
Yuchao Chen, Pan Mao, Antoine M Snijders, Daojing Wang
Cellular senescence plays an important role in organismal aging and age-related diseases. However, it is challenging to isolate low numbers of senescent cells from small volumes of biofluids for downstream analysis. Furthermore, there is no technology that could selectively remove senescent cells in a high-throughput manner. In this work, we developed a novel microfluidic chip platform, termed senescence chip, for ultrahigh-throughput isolation and removal of senescent cells. The core component of our senescence chip is a slanted and tunable 3D micropillar array with a variety of shutters in the vertical direction for rapid cell sieving, taking advantage of the characteristic cell size increase during cellular senescence...
January 16, 2018: Aging Cell
https://www.readbyqxmd.com/read/29330393/haploidentical-bone-marrow-transplantation-with-post-transplant-cyclophosphamide-for-patients-with-x-linked-adrenoleukodystrophy-a-suitable-choice-in-an-urgent-situation
#2
Juliana Folloni Fernandes, Carmem Bonfim, Fábio Rodrigues Kerbauy, Morgani Rodrigues, Iracema Esteves, Nathalia Halley Silva, Alessandra Prandini Azambuja, Luiz Fernando Mantovani, José Mauro Kutner, Gisele Loth, Cilmara Cristina Kuwahara, Clarissa Bueno, Andrea Tiemi Kondo, Andreza Alice Feitosa Ribeiro, Fernando Kok, Nelson Hamerschlak
Allogeneic hematopoietic stem cell transplantation (HSCT) is the only treatment that enhances survival and stabilizes neurologic symptoms in X-linked adrenoleukodystrophy (X-ALD) with cerebral involvement, a severe demyelinating disease of childhood. Patients with X-ALD who lack a well-matched HLA donor need a rapid alternative. Haploidentical HSCT using post transplant cyclophosphamide (PT/Cy) has been performed in patients with malignant and nonmalignant diseases showing similar outcomes compared to other alternative sources...
January 12, 2018: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/29330392/haploidentical-hematopoietic-sct-using-helical-tomotherapy-for-total-body-irradiation-and-targeted-dose-boost-in-patients-with-high-risk-refractory-acute-lymphoblastic-leukemia
#3
Zujun Jiang, Junsong Jia, Chunyan Yue, Yan Pang, Zenghui Liu, Ling Ouyang, Hongbo Li, Jinjian Zhang, Ting Wen, Jing Li, Zhiqiang Li, Yan Wang, Yang Xiao, Haowen Xiao
A novel conditioning regimen using helical tomotherapy (HT) was developed to deliver 10 Gy for total body irradiation (TBI) and simultaneously augment dose to 12 Gy for targeted dose boost to total marrow, central nervous system leukemia, and extramedullary disease sites in patients with high-risk or relapsed/refractory acute lymphoblastic leukemia (ALL) receiving haploidentical allogeneic hematopoietic stem cell transplantation (allo-HSCT). Fourteen patients were included, eight of these patients were in first complete remission (CR1), one was in CR2, one had a partial response and four patients had refractory disease at transplantation...
January 12, 2018: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/29285056/effects-of-yak-activated-protein-on-hematopoiesis-and-related-cytokines-in-radiation-induced-injury-in-mice
#4
Yabin Duan, Xingchen Yao, Junbo Zhu, Yongping Li, Juanling Zhang, Xuejiao Zhou, Yijie Qiao, Meng Yang, Xiangyang Li
The aim of the present study was to investigate the protective effects of yak-activated protein on hematopoiesis and cytokine function in radiation-induced injury in mice. A total of 180 Kunming mice were randomly divided into three groups (A, B and C). Of these, 60 were randomly divided into a normal control group, a radiation model group, a positive control group and 3 yak-activated protein groups (high, medium and low dose groups; 10, 5 and 2.5 mg/kg, respectively). The other 120 mice were used for the subsequent experiments on days 7 and 14 following radiation...
December 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29251550/mri-study-on-the-changes-of-bone-marrow-microvascular-permeability-and-fat-content-after-total-body-x-ray-irradiation
#5
Kejun Wang, Yunfei Zha, Hao Lei, Xiao Xu
In this study, we investigated microvascular perfusion status, changes to fat content and fatty acid composition in the bone marrow of rat femurs after total-body irradiation by quantitative permeability parameters of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and ex vivo high-resolution magic angle spinning (HRMAS) 1H nuclear magnetic resonance spectroscopy (NMRS). Thirty-six Sprague-Dawley rats were randomly assigned to either an irradiated or nonirradiated control group. Permeability imaging using DCE-MRI and HRMAS 1H NMRS was performed before irradiation, as well as at days 4 and 7 postirradiation...
December 18, 2017: Radiation Research
https://www.readbyqxmd.com/read/29242852/prospective-study-of-nonmyeloablative-hla-mismatched-unrelated-bmt-with-high-dose-posttransplantation-cyclophosphamide
#6
Yvette L Kasamon, Richard F Ambinder, Ephraim J Fuchs, Marianna Zahurak, Gary L Rosner, Javier Bolaños-Meade, Mark J Levis, Douglas E Gladstone, Carol Ann Huff, Lode J Swinnen, William H Matsui, Ivan Borrello, Robert A Brodsky, Richard J Jones, Leo Luznik
Allogeneic blood or marrow transplantation (BMT) candidates may lack HLA-matched, related haploidentical, and unrelated umbilical cord options. Barriers to partially HLA-mismatched, unrelated donor (mMUD) BMT include excess graft-versus-host disease (GVHD), graft failure, and death. We prospectively studied nonmyeloablative (NMA) mMUD BMT with high-dose posttransplantation cyclophosphamide (PTCy) for patients with hematologic malignancies. Three transplants were performed with busulfan/fludarabine conditioning, with subsequent change to fludarabine/Cy/total body irradiation (flu/Cy/TBI)...
2017: Blood Advances
https://www.readbyqxmd.com/read/29225252/reactivation-of-hemophagocytic-lymphohistiocytosis-triggered-by-antithymocyte-globulin
#7
Kensuke Matsuda, Kazuhiro Toyama, Takashi Toya, Masako Ikemura, Fumihiko Nakamura, Mineo Kurokawa
A 16-year-old boy with Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (HLH) underwent allogeneic hematopoietic stem cell transplantation after conditioning with fludarabine, melphalan, total body irradiation, and rabbit antithymocyte globulin (ATG). A severe, persistent infusion reaction occurred after the initial administration of ATG. Investigations showed a rapid increase in the levels of liver enzymes and ferritin, and the reactivation of HLH was confirmed by marked hemophagocytosis in the bone marrow...
December 8, 2017: Internal Medicine
https://www.readbyqxmd.com/read/29220591/cholinergic-and-cytoprotective-signaling-cascades-mediate-the-mitigative-effect-of-erythropoietin-on-acute-radiation-syndrome
#8
Shereen Mohamed Galal, Mohamed Khairy Abdel-Rafei, Hesham Hasan
The present investigation aimed to evaluate the radiomitigative efficacy of the recombinant human erythropoietin (rhEPO) against acute radiation syndrome (ARS) in a rat model. Rats were irradiated with a single sublethal dose of γ- radiation (7 Gy; total body irradiation; TBI) at the 1st day of experimental course, then received EPO (5000 IU/kg; i.p) 24 hrs post irradiation, rats were observed for 30 days of survival analysis. Administration of EPO improved 30 days survival, alleviated TBI- induced myelosuppression and pancytopenia, by augmenting lymphocytes and WBCs in the peripheral blood of rats, while bone marrow (BM) and spleen cellularity were restored...
December 8, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/29197676/intravenous-busulfan-compared-to-total-body-irradiation-pre-transplant-conditioning-for-adults-with-acute-lymphoblastic-leukemia
#9
Partow Kebriaei, Claudio Anasetti, Mei-Jie Zhang, Hai-Lin Wang, Ibrahim Aldoss, Marcos de Lima, H Jean Khoury, Brenda M Sandmaier, Mary M Horowitz, Andrew Artz, Nelli Bejanyan, Stefan Ciurea, Hillard M Lazarus, Robert Peter Gale, Mark Litzow, Christopher Bredeson, Matthew D Seftel, Michael A Pulsipher, Jaap-Jan Boelens, Joseph Alvarnas, Richard Champlin, Stephen Forman, Vinod Pullarkat, Daniel Weisdorf, David I Marks
Total body irradiation (TBI) has been included in standard conditioning for acute lymphoblastic leukemia (ALL) before hematopoietic cell transplantation (HCT). Non-TBI regimens have incorporated busulfan (BU) to decrease toxicity. This retrospective study analyzed TBI and BU on outcomes of ALL patients aged 18-60 years, in first or second complete remission (CR), undergoing HLA-compatible sibling, related or unrelated donor HCT, reported to the Center for International Blood and Marrow Transplant Research from 2005 to 2014...
November 29, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29181845/interventions-for-preventing-oral-mucositis-in-patients-with-cancer-receiving-treatment-cytokines-and-growth-factors
#10
REVIEW
Philip Riley, Anne-Marie Glenny, Helen V Worthington, Anne Littlewood, Luisa M Fernandez Mauleffinch, Jan E Clarkson, Martin G McCabe
BACKGROUND: Oral mucositis is a side effect of chemotherapy, head and neck radiotherapy, and targeted therapy, affecting over 75% of high-risk patients. Ulceration can lead to severe pain and difficulty with eating and drinking, which may necessitate opioid analgesics, hospitalisation and supplemental nutrition. These complications may disrupt cancer therapy, which may reduce survival. There is also a risk of death from sepsis if pathogens enter the ulcers of immunocompromised patients...
November 28, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/29141658/thioredoxin-mitigates-radiation-induced-hematopoietic-stem-cell-injury-in-mice
#11
Pasupathi Sundaramoorthy, Qinhong Wang, Zhihong Zheng, Yiqun Jiao, Benny J Chen, Phuong L Doan, Nelson J Chao, Yubin Kang
BACKGROUND: Radiation exposure poses a significant threat to public health. Hematopoietic injury is one of the major manifestations of acute radiation sickness. Protection and/or mitigation of hematopoietic stem cells (HSCs) from radiation injury is an important goal in the development of medical countermeasure agents (MCM). We recently identified thioredoxin (TXN) as a novel molecule that has marked protective and proliferative effects on HSCs. In the current study, we investigated the effectiveness of TXN in rescuing mice from a lethal dose of total body radiation (TBI) and in enhancing hematopoietic reconstitution following a lethal dose of irradiation...
November 15, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29140165/improved-total-body-irradiation-survival-by-delivery-of-two-radiation-mitigators-that-target-distinct-cell-death-pathways
#12
Justin Steinman, Michael Epperly, Wen Hou, John Willis, Hong Wang, Renee Fisher, Bing Liu, Ivet Bahar, Travis McCaw, Valerian Kagan, Hulya Bayir, Jian Yu, Peter Wipf, Song Li, M Saiful Huq, Joel S Greenberger
The acute lethality of total-body irradiation (TBI) involves damage to multiple organs, including bone marrow and intestine. Ionizing radiation mitigators that are effective when delivered 24 h or later after TBI include the anti-apoptotic drug, JP4-039 and the anti-necroptotic drug, necrostatin-1. In contrast to effective delivery of JP4-039 at 24 h after TBI, necrostatin-1 is most effective when delivery is delayed until 48 h, a time that correlates with the elevation of necroptosis-inducing inflammatory cytokines and necroptosis-induced serine phosphorylation of receptor-interacting serine/threonine-protein kinase-3 (RIP3) in tissues...
November 15, 2017: Radiation Research
https://www.readbyqxmd.com/read/29100905/post-transplant-cyclophosphamide-ptcy-as-sole-gvhd-prophylaxis-is-feasible-in-patients-undergoing-peripheral-blood-stem-cell-transplantation-for-severe-aplastic-anaemia-using-matched-sibling-donors
#13
Biju George, Nisham Pn, Anup J Devasia, Uday Kulkarni, Anu Korula, Kavitha M Lakshmi, Aby Abraham, Alok Srivastava, Vikram Mathews
High-dose cyclophosphamide (PTCY) following allogeneic hematopoietic cell transplantation (HSCT) has been shown to be effective in preventing graft-versus-host disease (GVHD) following HLA-matched bone marrow transplantation. We performed a phase II study of PTCY given at 50 mg/kg IV on days 3 and 4 as sole GVHD prophylaxis following HSCT for severe aplastic anemia (SAA) receiving G-CSF-mobilized peripheral blood stem cell (PBSC) grafts from HLA-matched related donors following conditioning with fludarabine, cyclophosphamide and single dose Total Body Irradiation (TBI)...
October 31, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29097738/pharmacologically-induced-reversible-hypometabolic-state-mitigates-radiation-induced-lethality-in-mice
#14
Subhajit Ghosh, Namita Indracanti, Jayadev Joshi, Jharna Ray, Prem Kumar Indraganti
Therapeutic hypothermia has proven benefits in critical care of a number of diseased states, where inflammation and oxidative stress are the key players. Here, we report that adenosine monophosphate (AMP) triggered hypometabolic state (HMS), 1-3 hours after lethal total body irradiation (TBI) for a duration of 6 hours, rescue mice from radiation-induced lethality and this effect is mediated by the persistent hypothermia. Studies with caffeine and (6)N-cyclohexyladenosine, a non-selective antagonist and a selective agonist of adenosine A1 receptor (A1AR) respectively, indicated the involvement of adenosine receptor (AR) signaling...
November 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29065747/a-phase-1-trial-of-autologous-stem-cell-transplantation-conditioned-with-melphalan-200%C3%A2-mg-m-2-and-total-marrow-irradiation-tmi-in-patients-with-relapsed-refractory-multiple-myeloma
#15
Pritesh Patel, Annie L Oh, Matthew Koshy, Karen Sweiss, Santosh L Saraf, John G Quigley, Irum Khan, Nadim Mahmud, Eileen Hacker, Howard Ozer, David J Peace, Ralph R Weichselbaum, Bulent Aydogan, Damiano Rondelli
In this phase 1 study, we tested increasing doses of total marrow irradiation (TMI) in addition to standard intravenous melphalan at 200 mg/m(2) (Mel200) in the conditioning regimen prior to autologous stem cell transplant (ASCT) for multiple myeloma (NCT02043847). Twelve patients aged 18-75 with relapsed myeloma were enrolled in the study and received Mel200 and TMI 3 Gy (n = 3), 6 Gy (n = 3), or 9 Gy (n = 6) prior to transplant. There were no grade 4 extra-hematologic toxicities and a maximum tolerated dose was not reached...
October 25, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29035281/young-endothelial-cells-revive-aging-blood
#16
Vivian Y Chang, Christina M Termini, John P Chute
The hematopoietic system declines with age, resulting in decreased hematopoietic stem cell (HSC) self-renewal capacity, myeloid skewing, and immune cell depletion. Aging of the hematopoietic system is associated with an increased incidence of myeloid malignancies and a decline in adaptive immunity. Therefore, strategies to rejuvenate the hematopoietic system have important clinical implications. In this issue of the JCI, Poulos and colleagues demonstrate that infusions of bone marrow (BM) endothelial cells (ECs) from young mice promoted HSC self-renewal and restored immune cell content in aged mice...
November 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29032268/total-marrow-lymphoid-irradiation-fludarabine-melphalan-conditioning-for-allogeneic-hematopoietic-cell-transplantation
#17
Lindsay G Jensen, Tracey Stiller, Jeffrey Y C Wong, Joycelynne Palmer, Anthony Stein, Joseph Rosenthal
Reduced-intensity conditioning (RIC) regimens for hematopoietic stem cell transplantation (HCT) can reduce morbidity and mortality, but patients with advanced disease may require alternative approaches. In an initial report of RIC with fludarabine (FLU) and melphalan (MEL) with total marrow lymphoid irradiation (TMLI) in HCT for advanced hematologic malignancies in 33 patients, we found that the addition of TMLI to RIC was feasible and safe. Here we report long-term outcomes for these patients. This prospective study included 61 patients treated with TMLI to a dose of 12 Gy (1...
October 12, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29024236/mesenchymal-stromal-cell-derived-extracellular-vesicles-provide-long-term-survival-after-total-body-irradiation-without-additional-hematopoietic-stem-cell-support
#18
Jill-Sandra Schoefinius, Bärbel Brunswig-Spickenheier, Thomas Speiseder, Sabrina Krebs, Ursula Just, Claudia Lange
The therapeutic effect of mesenchymal stromal cells (MSC) in tissue regeneration is based mainly on the secretion of bioactive molecules. Here, we report that the radioprotective effect of mouse bone marrow derived mesenchymal stromal cells (mMSC) can be attributed to extracellular vesicles (EV) released from mMSC. The transplantation of mMSC-derived EV into lethally irradiated mice resulted in long-term survival but no improvement in short-term reconstitution of the recipients. Importantly, the radiation rescue was efficient without additional hematopoietic support...
October 11, 2017: Stem Cells
https://www.readbyqxmd.com/read/28994728/dose-and-ion-dependent-effects-in-the-oxidative-stress-response-to-space-like-radiation-exposure-in-the-skeletal-system
#19
Joshua S Alwood, Luan H Tran, Ann-Sofie Schreurs, Yasaman Shirazi-Fard, Akhilesh Kumar, Diane Hilton, Candice G T Tahimic, Ruth K Globus
Space radiation may pose a risk to skeletal health during subsequent aging. Irradiation acutely stimulates bone remodeling in mice, although the long-term influence of space radiation on bone-forming potential (osteoblastogenesis) and possible adaptive mechanisms are not well understood. We hypothesized that ionizing radiation impairs osteoblastogenesis in an ion-type specific manner, with low doses capable of modulating expression of redox-related genes. 16-weeks old, male, C57BL6/J mice were exposed to low linear-energy-transfer (LET) protons (150 MeV/n) or high-LET (56)Fe ions (600 MeV/n) using either low (5 or 10 cGy) or high (50 or 200 cGy) doses at NASA's Space Radiation Lab...
October 10, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28993772/rescuing-self-transient-isolation-and-autologous-transplantation-of-bone-marrow-mitigates-radiation-induced-hematopoietic-syndrome-and-mortality-in-mice
#20
Subhajit Ghosh, Namita Indracanti, Jayadev Joshi, Prem Kumar Indraganti
The inflamed bone marrow niche shortly after total body irradiation (TBI) is known to contribute to loss of hematopoietic stem cells in terms of their number and function. In this study, autologous bone marrow transfer (AL-BMT) was evaluated as a strategy for mitigating hematopoietic form of the acute radiation syndrome by timing the collection phase (2 h after irradiation) and reinfusion (24 h after irradiation) using mice as a model system. Collection of bone marrow (BM) cells (0.5 × 10(6) total marrow cells) 2 h after lethal TBI rescued different subclasses of hematopoietic stem and progenitor cells (HSPCs) from the detrimental inflammatory and damaging milieu in vivo...
2017: Frontiers in Immunology
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