p53-Based Strategy for Protection of Bone Marrow From Y-90 Ibritumomab Tiuxetan

Su, Hang; Ganapathy, Suthakar; Li, Xiaolei; Yuan, Zhi-Min; Ha, Chul S.

doi:10.1016/J.IJROBP.2015.04.003

Title: p53-Based Strategy for Protection of Bone Marrow From Y-90 Ibritumomab Tiuxetan

Full Record
Other Related Research

Abstract

Purpose: The main drawbacks of radioimmunotherapy have been severe hematological toxicity and potential development of myelodysplastic syndrome and secondary leukemia. Activation of p53 follows a major pathway by which normal tissues respond to DNA-damaging agents, such as chemotherapy and radiation therapy, that result in injuries and pathological consequences. This pathway is separate from the tumor suppressor pathway of p53. We have previously reported that use of low-dose arsenic (LDA) temporarily and reversibly suppresses p53 activation, thereby ameliorating normal tissue toxicity from exposure to 5-fluorouracil and X rays. We have also demonstrated that LDA-mediated protection requires functional p53 and thus is selective to normal tissues, as essentially every cancer cell has dysfunctional p53. Here we tested the protective efficacy of LDA for bone marrow tissue against radioimmunotherapy through animal experiments. Methods and Materials: Mice were subjected to LDA pretreatment for 3 days, followed by treatment with Y-90 ibritumomab tiuxetan. Both dose course (10, 25, 50, 100, and 200 μCi) and time course (6, 24, and 72 hours and 1 and 2 weeks) experiments were performed. The response of bone marrow cells to LDA was determined by examining the expression of NFκB, Glut1, and Glut3. Staining with hematoxylin and eosin, γ-H2AX, and terminal deoxynucleotidyl transferase dUTPmore »« less

Authors:

Su, Hang ^[1]; Ganapathy, Suthakar ^[2]; Li, Xiaolei ^[1]; Yuan, Zhi-Min ^[2]; Ha, Chul S. ^[1]

Department of Radiation Oncology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas (United States)
Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, Massachusetts (United States)

Publication Date:: Sat Aug 01 00:00:00 EDT 2015

OSTI Identifier:: 22462409

Resource Type:: Journal Article

Journal Name:: International Journal of Radiation Oncology, Biology and Physics

Additional Journal Information:: Journal Volume: 92; Journal Issue: 5; Other Information: Copyright (c) 2015 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0360-3016

Country of Publication:: United States

Language:: English

Subject:: 62 RADIOLOGY AND NUCLEAR MEDICINE; ARSENIC; BONE MARROW; BONE MARROW CELLS; CHEMOTHERAPY; DNA; DNA DAMAGES; EOSIN; HEMATOXYLIN; HUMAN POPULATIONS; LABELLING; LEUKEMIA; LYMPHOMAS; MICE; MORPHOLOGY; RADIATION DOSES; RADIOIMMUNOTHERAPY; TOXICITY; URACILS; YTTRIUM 90

Citation Formats


                    Su, Hang, Ganapathy, Suthakar, Li, Xiaolei, Yuan, Zhi-Min, and Ha, Chul S. p53-Based Strategy for Protection of Bone Marrow From Y-90 Ibritumomab Tiuxetan.  United States: N. p., 2015. 
        Web.  doi:10.1016/J.IJROBP.2015.04.003.

Copy to clipboard


                    Su, Hang, Ganapathy, Suthakar, Li, Xiaolei, Yuan, Zhi-Min, & Ha, Chul S. p53-Based Strategy for Protection of Bone Marrow From Y-90 Ibritumomab Tiuxetan.  United States.  https://doi.org/10.1016/J.IJROBP.2015.04.003

Copy to clipboard


                    Su, Hang, Ganapathy, Suthakar, Li, Xiaolei, Yuan, Zhi-Min, and Ha, Chul S. 2015.  
        "p53-Based Strategy for Protection of Bone Marrow From Y-90 Ibritumomab Tiuxetan".  United States.  https://doi.org/10.1016/J.IJROBP.2015.04.003.

Copy to clipboard


                    
@article{osti_22462409,

  title        = {p53-Based Strategy for Protection of Bone Marrow From Y-90 Ibritumomab Tiuxetan},

  author       = {Su, Hang and Ganapathy, Suthakar and Li, Xiaolei and Yuan, Zhi-Min and Ha, Chul S.},

  abstractNote = {Purpose: The main drawbacks of radioimmunotherapy have been severe hematological toxicity and potential development of myelodysplastic syndrome and secondary leukemia. Activation of p53 follows a major pathway by which normal tissues respond to DNA-damaging agents, such as chemotherapy and radiation therapy, that result in injuries and pathological consequences. This pathway is separate from the tumor suppressor pathway of p53. We have previously reported that use of low-dose arsenic (LDA) temporarily and reversibly suppresses p53 activation, thereby ameliorating normal tissue toxicity from exposure to 5-fluorouracil and X rays. We have also demonstrated that LDA-mediated protection requires functional p53 and thus is selective to normal tissues, as essentially every cancer cell has dysfunctional p53. Here we tested the protective efficacy of LDA for bone marrow tissue against radioimmunotherapy through animal experiments. Methods and Materials: Mice were subjected to LDA pretreatment for 3 days, followed by treatment with Y-90 ibritumomab tiuxetan. Both dose course (10, 25, 50, 100, and 200 μCi) and time course (6, 24, and 72 hours and 1 and 2 weeks) experiments were performed. The response of bone marrow cells to LDA was determined by examining the expression of NFκB, Glut1, and Glut3. Staining with hematoxylin and eosin, γ-H2AX, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) was used to examine morphology, DNA damage response, and apoptotic cell populations. Results: Elevated levels of NFκB, Glut1, and Glut3 were observed in bone marrow cells after LDA treatment. Bone marrow damage levels induced by Y-90 ibritumomab tiuxetan were greatly reduced by LDA pretreatment. Consistent with this observation, significantly less DNA damage and fewer apoptotic cells were accumulated after Y-90 ibritumomab tiuxetan treatment in LDA-pretreated mice. Furthermore, in the mouse xenograft model implanted with human Karpas-422 lymphoma cells, LDA pretreatment did not have any detectable effect on either tumor growth or Y-90 ibritumomab tiuxetan (200 μCi)-induced tumor suppression. Conclusions: LDA pretreatment protected bone marrow without compromising tumor control caused by Y-90 ibritumomab tiuxetan.},

  doi          = {10.1016/J.IJROBP.2015.04.003},

  url          = {https://www.osti.gov/biblio/22462409},
  journal      = {International Journal of Radiation Oncology, Biology and Physics},

  issn         = {0360-3016},

  number       = 5,

  volume       = 92,

  place        = {United States},

  year         = {Sat Aug 01 00:00:00 EDT 2015},

  month        = {Sat Aug 01 00:00:00 EDT 2015}

}

Copy to clipboard

Journal Article:

https://doi.org/10.1016/J.IJROBP.2015.04.003

Other availability

Find in Google Scholar

Search WorldCat to find libraries that may hold this journal

Save / Share:

Export Metadata

Save to My Library

Similar records in OSTI.GOV collections:

MIRD Dose Estimate Report No. 20: Radiation Absorbed-Dose Estimates for 111In- and 90Y-Ibritumomab Tiuxetan

Journal Article Fisher, Darrell; Shen, Sui; Meredith, Ruby - Journal of Nuclear Medicine, 50(4):644-652

Absorbed dose calculations provide a scientific basis for evaluating the biological effects associated with administered radiopharmaceuticals. In cancer therapy, radiation dosimetry also supports treatment planning, dose-response analyses, predictions of therapy effectiveness, and completeness of patient medical records. In this study, we evaluated the organ radiation absorbed doses resulting from intravenously administered 111In- and 90Y-Ibritumomab Tiuxetan (Zevalin). Methods: Ten patients (six male, four female) with non-Hodgkin’s lymphoma, cared for at three different medical centers, were administered tracer 111In-Ibritumomab Tiuxetan and were assessed using planar scintillation camera imaging at five time points, blood clearance measurements, and CT-organ volumetrics, to determine patient-specific organmore »« less
https://doi.org/10.2967/jnumed.108.057331
Logistics of therapy with the ibritumomab tiuxetan regimen

Journal Article Meredith, Ruby - International Journal of Radiation Oncology, Biology and Physics

Radioimmunotherapy is an important new modality for treating patients with B-cell non-Hodgkin's lymphoma (NHL). Clinical trials have shown the safety and efficacy of agents that deliver radiation directly to malignant cells by attaching the {sup 131}I or {sup 9}Y radionuclide to monoclonal antibodies against CD20. In clinical trials, {sup 9}Y ibritumomab tiuxetan has produced rates of response as high as 83% in patients with relapsed or refractory CD20+ NHL. The ibritumomab tiuxetan regimen is conveniently given in an outpatient setting over the course of 7-9 days. This article describes the logistics for initiating treatment, coordinating a multidisciplinary team, identifying eligiblemore »« less
https://doi.org/10.1016/j.ijrobp.2006.06.009
External Beam Radiotherapy Followed by {sup 90}Y Ibritumomab Tiuxetan in Relapsed or Refractory Bulky Follicular Lymphoma

Journal Article Burdick, Michael; Neumann, Donald; Pohlman, Brad; ... - International Journal of Radiation Oncology, Biology and Physics

Purpose: We combined external beam radiotherapy (EBRT) with yttrium-90 ibritumomab tiuxetan ({sup 90}Y-IT) in an attempt to improve therapeutic response in patients with relapsed or refractory bulky follicular lymphoma (RRBFL). Methods and Materials: Between February 2006 and September 2007, 11 patients with RRBFL were treated with EBRT followed by {sup 90}Y-IT. Bulky disease (BD) was defined as >5 cm. EBRT was delivered to BD as 2,400 cGy in eight fractions using computed tomography (CT)-based planning. BD was contoured as the gross tumor volume. A planning margin of 1 to 2 cm was added depending on anatomical location. After recovery ofmore »« less
https://doi.org/10.1016/j.ijrobp.2009.12.030
Phorate-induced oxidative stress, DNA damage and transcriptional activation of p53 and caspase genes in male Wistar rats

Journal Article Saquib, Quaiser; Attia, Sabry; Siddiqui, Maqsood; ... - Toxicology and Applied Pharmacology

Male Wistar rats exposed to a systemic organophosphorus insecticide, phorate [O,O-diethyl S-[(ethylthio) methyl] phosphorothioate] at varying oral doses of 0.046, 0.092 or 0.184 mg phorate/kg bw for 14 days, exhibited substantial oxidative stress, cellular DNA damage and activation of apoptosis-related p53, caspase 3 and 9 genes. The histopathological changes including the pyknotic nuclei, inflammatory leukocyte infiltrations, renal necrosis, and cardiac myofiber degeneration were observed in the liver, kidney and heart tissues. Biochemical analysis of catalase and glutathione revealed significantly lesser activities of antioxidative enzymes and lipid peroxidation in tissues of phorate exposed rats. Furthermore, generation of intracellular reactive oxygen speciesmore »« less
https://doi.org/10.1016/J.TAAP.2011.12.006
Gamma camera scans and pretreatment tumor volumes as predictors of response and progression after Y-90 anti-CD20 radioimmunotherapy

Journal Article Gokhale, Abhay; Mayadev, Jyoti; Pohlman, Brad; ... - International Journal of Radiation Oncology, Biology and Physics

Purpose: To evaluate two potential approaches to predicting site-specific patterns of recurrence after yttrium-90 ibritumomab tiuxetan radioimmunotherapy (RIT) for CD20+ B-cell Non-Hodgkin's lymphoma. These predictive methods may be useful in evaluating the utility of local intensification of individual nodal or extranodal sites using external beam radiotherapy. Methods and Materials: Records and images were evaluated for 20 patients previously treated with yttrium-90 ibritumomab RIT. Intensity of isotope uptake on the pretreatment two-dimensional antibody scans and maximal extent of tumor deposits found on computed tomography images of each anatomic site were correlated with response and subsequent patterns of recurrence or progression. Results:more »« less
https://doi.org/10.1016/j.ijrobp.2005.01.017

Similar Records