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total marrow irradiation

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https://www.readbyqxmd.com/read/29141658/thioredoxin-mitigates-radiation-induced-hematopoietic-stem-cell-injury-in-mice
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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...
October 16, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29032268/total-marrow-lymphoid-irradiation-fludarabine-melphalan-conditioning-for-allogeneic-hematopoietic-cell-transplantation
#7
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
#8
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
#9
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
#10
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
https://www.readbyqxmd.com/read/28985133/organ-doses-associated-with-partial-body-irradiation-with-2-5-bone-marrow-sparing-of-the-non-human-primate-a-retrospective-study
#11
C Prado, T J MacVittie, A W Bennett, A Kazi, A M Farese, K Prado
A partial-body irradiation model with approximately 2.5% bone marrow sparing (PBI/BM2.5) was established to determine the radiation dose-response relationships for the prolonged and delayed multi-organ effects of acute radiation exposure. Historically, doses reported to the entire body were assumed to be equal to the prescribed dose at some defined calculation point, and the dose-response relationship for multi-organ injury has been defined relative to the prescribed dose being delivered at this point, e.g...
October 6, 2017: Radiation Research
https://www.readbyqxmd.com/read/28981105/calcium-calmodulin-dependent-kinase-kinase-2-regulates-hematopoietic-stem-and-progenitor-cell-regeneration
#12
Luigi Racioppi, William Lento, Wei Huang, Stephanie Arvai, Phuong L Doan, Jeffrey R Harris, Fernando Marcon, Helder I Nakaya, Yaping Liu, Nelson Chao
Hematopoietic stem and progenitor cells (HSPCs) are predominantly quiescent in adults, but proliferate in response to bone marrow (BM) injury. Here, we show that deletion of Ca(2+)/calmodulin (CaM)-dependent protein kinase kinase 2 (CaMKK2) promotes HSPC regeneration and hematopoietic recovery following radiation injury. Using Camkk2-enhanced green fluorescent protein (EGFP) reporter mice, we found that Camkk2 expression is developmentally regulated in HSPC. Deletion of Camkk2 in HSPC results in a significant downregulation of genes affiliated with the quiescent signature...
October 5, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28954235/low-dose-irradiation-promotes-persistent-oxidative-stress-and-decreases-self-renewal-in-hematopoietic-stem-cells
#13
Sarah Rodrigues-Moreira, Stéphanie G Moreno, Giulia Ghinatti, Daniel Lewandowski, Françoise Hoffschir, Federica Ferri, Anne-Sophie Gallouet, Denise Gay, Hozumi Motohashi, Masayuki Yamamoto, Michael C Joiner, Nathalie Gault, Paul-Henri Romeo
Despite numerous observations linking protracted exposure to low-dose (LD) radiation and leukemia occurrence, the effects of LD irradiation on hematopoietic stem cells (HSCs) remain poorly documented. Here, we show that adult HSCs are hypersensitive to LD irradiation. This hyper-radiosensitivity is dependent on an immediate increase in the levels of reactive oxygen species (ROS) that also promotes autophagy and activation of the Keap1/Nrf2 antioxidant pathway. Nrf2 activation initially protects HSCs from the detrimental effects of ROS, but protection is transient, and increased ROS levels return, promoting a long-term decrease in HSC self-renewal...
September 26, 2017: Cell Reports
https://www.readbyqxmd.com/read/28948859/whole-body-distribution-of-leukemia-and-functional-total-marrow-irradiation-based-on-flt-pet-and-dual-energy-ct
#14
Taiki Magome, Jerry Froelich, Shernan G Holtan, Yutaka Takahashi, Michael R Verneris, Keenan Brown, Kathryn Dusenbery, Jeffrey Wong, Susanta K Hui
This report describes a multimodal whole-body 3'-deoxy-3'[(18)F]-fluorothymidine positron emission tomography (FLT-PET) and dual-energy computed tomography (DECT) method to identify leukemia distribution within the bone marrow environment (BME) and to develop disease- and/or BME-specific radiation strategies. A control participant and a newly diagnosed patient with acute myeloid leukemia prior to induction chemotherapy were scanned with FLT-PET and DECT. The red marrow (RM) and yellow marrow (YM) of the BME were segmented from DECT using a basis material decomposition method...
January 2017: Molecular Imaging
https://www.readbyqxmd.com/read/28945662/incidence-and-outcome-of-pericardial-effusion-in-pediatric-patients-after-hematopoietic-stem-cell-transplant-a-single-institution-experience
#15
Melissa Diamond, Catalina Ruiz-Mesa, Fernando F Corrales-Medina, Leonardo J Tamariz, Edward Ziga, Sethuraman Swaminathan
BACKGROUND: Pericardial effusion (PE) is a known complication after hematopoietic stem cell transplant (HSCT). Limited data is currently available regarding the incidence and outcomes of PE in pediatric HSCT. METHODS: We conducted a retrospective study on a cohort of patients who underwent HSCT between 2004 and 2015. Risk factors associated with development of PE were evaluated. RESULTS: In 111 HSCT, stem cell source was bone marrow in 37 (33...
September 22, 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/28931604/sublethal-total-body-irradiation-causes-long-term-deficits-in-thymus-function-by-reducing-lymphoid-progenitors
#16
Shiyun Xiao, Ivo D Shterev, Wen Zhang, Lauren Young, Jae-Hung Shieh, Malcolm Moore, Marcel van den Brink, Gregory D Sempowski, Nancy R Manley
Total body irradiation (TBI) damages hematopoietic cells in the bone marrow and thymus; however, the long-term effects of irradiation with aging remain unclear. In this study, we found that the impact of radiation on thymopoiesis in mice varied by sex and dose but, overall, thymopoiesis remained suppressed for ≥12 mo after a single exposure. Male and female mice showed a long-term dose-dependent reduction in thymic cKit(+) lymphoid progenitors that was maintained throughout life. Damage to hematopoietic stem cells (HSCs) in the bone marrow was dose dependent, with as little as 0...
October 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28922655/zymosan-a-protects-the-hematopoietic-system-from-radiation-induced-damage-by-targeting-tlr2-signaling-pathway
#17
Jicong Du, Ying Cheng, Suhe Dong, Pei Zhang, Jiaming Guo, Jiaqi Han, Fu Gao, Hainan Zhao, Ding Sun, Jianguo Cui, Jianming Cai, Cong Liu
BACKGROUND/AIMS: The hematopoietic system is vulnerable to ionizing radiation and is often severely damaged by radiation. Molecules affecting radioresistance include Toll-like receptor 2. We investigated whether Zymosan-A, a novel TLR2 agonist, can protect the hematopoietic system from radiation-induced damage after total body irradiation. METHODS: Mice were exposed to total body radiation after treatment with Zymosan-A or normal saline, and their survival was recorded...
2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28865761/predicting-severe-hematologic-toxicity-from-extended-field-chemoradiation-of-para-aortic-nodal-metastases-from-cervical-cancer
#18
Kevin Yan, Ezequiel Ramirez, Xian-Jin Xie, Xuejun Gu, Yin Xi, Kevin Albuquerque
PURPOSE: The purpose of this study was to determine factors predictive for severe hematologic toxicity (HT) in cervical cancer patients with para-aortic lymph node metastasis treated with concurrent cisplatin chemoradiation to an extended field (EFCRT). METHODS AND MATERIALS: Thirty-eight patients with cervical cancer and para-aortic lymph node metastasis who underwent EFCRT were analyzed. Active bone marrow was defined as the region within irradiated total bone marrow (BMTOT) with a standard uptake value on (18)F-fluorodeoxyglucose positron emission tomography/computed tomography greater than the mean standard uptake value for BMTOT...
July 8, 2017: Practical Radiation Oncology
https://www.readbyqxmd.com/read/28807769/reduced-intensity-haploidentical-bone-marrow-transplantation-with-post-transplant-cyclophosphamide-for-solid-tumors-in-pediatric-and-young-adult-patients
#19
Nicolas J Llosa, Kenneth R Cooke, Allen Chen, Christopher Gamper, Orly Klein, Elias Zambidis, Brandon Luber, Gary Rosner, Nicholas Siegel, Mary Jo Holuba, Nancy Robey, Masanori Hayashi, Richard J Jones, Ephraim Fuchs, Matthias Holdhoff, David M Loeb, Heather J Symons
High-risk, recurrent, or refractory solid tumors in pediatric, adolescent, and young adult (AYA) patients have an extremely poor prognosis despite current intensive treatment regimens. We piloted an allogeneic bone marrow transplant platform using reduced-intensity conditioning (RIC) and partially HLA-mismatched (haploidentical) related donors for this population of pediatric and AYA solid tumor patients. Sixteen patients received fludarabine, cyclophosphamide, melphalan, and low-dose total body irradiation RIC haploidentical BMT (haploBMT) followed by post-transplantation cyclophosphamide (PTCy), mycophenolate mofetil, and sirolimus...
August 12, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28782442/whole-body-proton-irradiation-causes-acute-damage-to-bone-marrow-hematopoietic-progenitor-and-stem-cells-in-mice
#20
Jianhui Chang, Yingying Wang, Rupak Pathak, Vijayalakshmi Sridharan, Tamako Jones, Xiao Wen Mao, Gregory Nelson, Marjan Boerma, Martin Hauer-Jensen, Daohong Zhou, Lijian Shao
PURPOSE: Exposure to proton irradiation during missions in deep space can lead to bone marrow injury. The acute effects of proton irradiation on hematopoietic stem and progenitor cells remain undefined and thus were investigated. MATERIALS AND METHODS: We exposed male C57BL/6 mice to 0.5 and 1.0 Gy proton total body irradiation (proton-TBI, 150 MeV) and examined changes in peripheral blood cells and bone marrow (BM) progenitors and LSK cells 2 weeks after exposure...
August 7, 2017: International Journal of Radiation Biology
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