scholarly journals Protective effect of hydrogen gas inhalation on radiation-induced bone marrow damage in cancer patients: a retrospective observational study

2020 ◽  
Author(s):  
Shin-ichi Hirano ◽  
Yukimasa Aoki ◽  
Ryosuke Kurokawa ◽  
Xiao-Kang Li ◽  
Naotsugu Ichimaru ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Observational Study ◽  
Cancer Patients ◽  
Blood Cells ◽  
Inhalation Therapy ◽  
Control Group ◽  
Gas Treatment ◽  
Bone Marrow Damage ◽  
Radiation Induced ◽  
Gas Inhalation

Abstract Background: Although intensity-modulated radiation therapy (IMRT) has been developed as an alternative to conventional radiotherapy, but reducing bone marrow damage is limited in the patients with multiple tumor lesions and large irradiation volume. Thus, novel technology is needed to mitigate further IMRT-induced bone marrow damage. Molecular hydrogen (H2) was recently reported as a preventive and therapeutic antioxidant that selectively scavenges hydroxyl radical (·OH) and peroxynitrite (ONOO-). This observational study aims to examine whether H2 gas treatment improves IMRT-induced bone marrow damage in cancer patients. Methods: The patients with end stage of cancer were received IMRT once per day for 1 to 4 weeks except Saturday and Sunday. After each course of IMRT, the patients of control group (n = 7) were housed in health care chamber (HCC, mild hyperbaric oxygen chamber) for 30 minutes, and the patients of H2 group (n = 16) were also housed in HCC and received 5% H2 gas for 30 minutes once per day. Radiation-induced bone marrow damage was evaluated by hematological examination of peripheral blood obtained before and after IMRT, and the data was expressed the ratio of after treatment to before treatment.Results: The total number of radiation courses and total exposure doses of radiation were similar between the control and H2 groups. IMRT with HCC therapy significantly reduced white blood cells (WBC) and platelets (PLT), but not red blood cells (RBC), hemoglobin (HGB) and hematocrit (HT). In contrast, H2 gas treatment significantly alleviates reducing effects of WBC and PLT (p=0.0011 and p=0.0275, respectively). Bone marrow damage index calculated by total exposure dose and WBC ratio also demonstrated the radioprotective effects of H2 gas (p=0.0231). Tumor responses to IMRT were similar between the two groups, and 4 of 7 (57%) patients in the control group and 7 of 16 (44%) patients in the H2 group achieved a complete response (CR) or partial response (PR). In addition, 3 of 16 (19%) patients in the H2 group achieved stable disease (SD).Conclusion: The results obtained demonstrated that H2 gas inhalation therapy alleviated IMRT-induced bone marrow damage without compromising the anti-tumor effects of IMRT. The present study suggests that this novel approach of H2 gas inhalation therapy may be applicable to IMRT-induced bone marrow damage in cancer patients.

Hydrogen Gas Inhalation Alleviates Radiation-Induced Bone Marrow Damage in Cancer Patients

2019 ◽  
Author(s):  
Shin-ichi Hirano ◽  
Yukimasa Aoki ◽  
Ryosuke Kurokawa ◽  
Xiao-Kang Li ◽  
Naotsugu Ichimaru ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cancer Patients ◽  
Hydrogen Gas ◽  
Bone Marrow Damage ◽  
Radiation Induced ◽  
Gas Inhalation ◽  
Hydrogen Gas Inhalation

scholarly journals COMP-Ang1, Angiopoietin-1 Variant Protects Radiation-Induced Bone Marrow Damage in C57BL/6 Mice

2008 ◽  
Vol 49 (3) ◽  
pp. 313-320 ◽  
Author(s):  
Hae June LEE ◽  
Sang Woo BAE ◽  
Gou Young KOH ◽  
Yun Sil LEE
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Damage ◽  
Radiation Induced ◽  
Angiopoietin 1

scholarly journals Pharmacokinetic and Maximum Tolerated Dose Study of Micafungin in Combination with Fluconazole versus Fluconazole Alone for Prophylaxis of Fungal Infections in Adult Patients Undergoing a Bone Marrow or Peripheral Stem Cell Transplant

2005 ◽  
Vol 49 (4) ◽  
pp. 1331-1336 ◽  
Author(s):  
J. Hiemenz ◽  
P. Cagnoni ◽  
D. Simpson ◽  
S. Devine ◽  
N. Chao ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Cancer Patients ◽  
Fungal Infections ◽  
High Risk Patient ◽  
Maximum Tolerated Dose ◽  
Saline Control ◽  
Control Group ◽  
Cell Transplant ◽  
Dose Escalation Study

ABSTRACT In this dose escalation study, 74 adult cancer patients undergoing bone marrow or peripheral blood stem cell transplantation received fluconazole (400 mg/day) and either normal saline (control) (12 subjects) or micafungin (12.5 to 200 mg/day) (62 subjects) for up to 4 weeks. The maximum tolerated dose (MTD) of micafungin was not reached, based on the development of Southwest Oncology Group criteria for grade 3 toxicity; drug-related toxicities were rare. Commonly occurring adverse events considered related to micafungin were headache (6.8%), arthralgia (6.8%), hypophosphatemia (4.1%), insomnia (4.1%), maculopapular rash (4.1%), and rash (4.1%). Pharmacokinetic profiles for micafungin on days 1 and 7 were similar. The mean half-life was approximately 13 h, with little variance after repeated or increasing doses. Mean maximum concentrations of the drug in serum and areas under the concentration-time curve from 0 to 24 h were approximately proportional to dose. There was no clinical or kinetic evidence of interaction between micafungin and fluconazole. Five of 12 patients (42%) in the control group and 14 of 62 (23%) in the micafungin-plus-fluconazole groups had a suspected fungal infection during treatment which resulted in empirical treatment with amphotericin B. The combination of micafungin and fluconazole was found to be safe in this high-risk patient population. The MTD of micafungin was not reached even at doses up to 200 mg/day for 4 weeks. The pharmacokinetic profile of micafungin in adult cancer patients with blood or marrow transplants is consistent with the profile in healthy volunteers, and the area under the curve is proportional to dose.

Parvovirus B19 and Aplastic Anemia: Case Control Study: Preliminary Report from the ITESM Hematology Study Group.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3765-3765
Author(s):  
Jose R. Borbolla Escoboza ◽  
Marcos E. Garza-Madrid ◽  
Luis Villela ◽  
Manuel A. Lopez-Hernandez ◽  
Jorge Vela-Ojeda
Keyword(s):  
Bone Marrow ◽  
Aplastic Anemia ◽  
Peripheral Blood ◽  
Blood Cells ◽  
Parvovirus B19 ◽  
Bone Marrow Failure ◽  
Control Group ◽  
Number Of Patients ◽  
Two Samples ◽  
Sense Primer

Abstract Aplastic anemia (AA) is a classic bone marrow failure syndrome simply defined as peripheral blood pancytopenia and a hypocelular bone marrow, yet the diagnosis must be made by excluding other causes of bone marrow failure. The incidence rate of AA reported by the International Aplastic Anemia and Agranulocytosis Study (IAAAS) in the 1980s was 2 cases per 1 million people. This disease is known to be caused by exposure to radiation, chemotherapy and some viral agents, yet most of the cases are idiopathic. Epstein Barr virus and non-A, non-B or non-C Hepatitis virus have classically been related to the development of some AA cases. Recently there have been some reports of AA following Parvovirus B19 (PvB19) infection. This virus, the only parvoviridae virus capable of infecting humans, attacks erythrocyte precursors attaching to the P antigen in their surface and requiring Beta1 integrin for viral entry. Although PvB19 seems to infect only erytroid precursors, it is widely recognized that the infection with this virus can cause not only anemia, but neutropenia and thrombocytopenia as well, producing aplastic crisis of varying intensity. A correlation has recently been found between PvB19 DNA in peripheral blood and AA in children. We pretend to corroborate this observation and include adult patients in order to improve our understanding of the relationship between PvB19 and AA. So far we have taken peripheral blood samples from 9 AA patients and 9 controls paired by age, sex and community; we plan to include 100 AA patients and their controls from several hospitals around Mexico. DNA was extracted using the PUREGENE DNA extraction kit (Gentra, Minneapolis MN). Nested PCR was performed using the sense primer (P1) 5-AATACACTGTGGTTTTATGGGCCG-3, antisense (P2) 5-CCATTGCTGGTTATAACCACAGGT-3 for the first round and the sense primer (P3) 5-AATGAAAACTTTCCATTTAATGATGTAG-3 and antisense primer (P4) 5-CTAAAATGGCTTTTGCAGCTTCTAC-3for the second round. A DNA sample from a patient with active infectious mononucleosis with positive IgG and IgM against PvB19 in serum was used as positive control. Two samples from the AA group (22%) and 1 from the control group (11%) have turned positive for PvB19 DNA. The reported incidence for the presence of this virusDNA in the peripheral blood of the population is 3%. We expect that, as the number of patients grows, the percentage of positive samples in the control group will decrease, while the percentage of positive samples in the AA group will rise or be sustained. Our partial results point towards a possible relationship between AA and the presence of PvB19 DNA in the peripheral blood cells. It is possible that this virus is one of many factors capable of precipitating the development of AA by limiting the bone marrows capacity to produce blood cells. We are in the process of gathering more samples to prove if a relationship really exists and, if so, future studies will likely shed light upon the mechanism by which PvB19 contributes to the development of AA and other marrow failure syndromes.

Thrombopoietin-Mimetic Romiplostim Confers the Complete Survival Rate to Mice Exposed to Lethal Ionizing Radiation

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2390-2390 ◽  
Author(s):  
Masaru Yamaguchi ◽  
Tokuhisa Hirouchi ◽  
Mitsuru Chiba ◽  
Satoru Monzen ◽  
Hironori Yoshino ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Blood Cells ◽  
Bone Marrow Cells ◽  
Hematopoietic Progenitor Cells ◽  
Peripheral Blood Cells ◽  
Blood Cell Count ◽  
Hematopoietic Progenitor ◽  
Γ Irradiation ◽  
Radiation Induced ◽  
Marrow Cells

Abstract Radiation-related casualties following exposure to a lethal dose of ionizing radiation show severe acute radiation syndromes (ARS) involving bone marrow death and gastrointestinal death. ARS cause decreases in red blood cell count, white blood cell count, platelet count and gastrointestinal dysfunction, finally leading to death caused by systemic bleeding. Therefore, reconstitution and restoration of hematopoiesis is a top priority. Although bone marrow transplantation (BMT) is also available for recovery from radiation-induced bone marrow damage, BMT for victims in radiation accidents has many limitations, including histocompatibility, age constraints, HLA type and the fact that immunosuppression would be required to reduce the risk of graft versus host rejection. In contrast, pharmacological approaches can accommodate a large number of victims with few limitations. Our previous study showed that the combined administration of erythropoietin, granulocytecolony stimulating factor and nandrolone decanoate after lethal ionizing irradiation resulted in the survival of approximately 50% of irradiated mice at day 30. When a c-Mpl agonist (Romiplostim: RP) was added to this protocol, 100% survival was obtained. Finally, we found that RP play a key role in the survival of irradiated mice. In the present study, we examined the effects of RP alone on mice exposed to lethal radiation. RP was administered at a dosage of 50 μg/kg of body weight/day to 8-weekold female C57BL/6JJcl mice for 1, 3, or 5 days immediately following exposure to a lethal 7 Gy dose of 137Cs γ-rays. The condition of each animal was analyzed via morphological evaluations of the small intestine and various parameters such as the numbers of peripheral blood cells, bone marrow cells, and hematopoietic progenitor cells along with cell surface antigen expression. By day 30, all untreated irradiated control mice died, whereas RP administration for 3 or 5 consecutive days after irradiation led to a 100% survival rate among the irradiated mice. At this time, the numbers of peripheral blood cells, bone marrow cells and hematopoietic progenitor cells were not significantly different between RP-untreated non-irradiated and RP-treated irradiated mice. In addition, the expression of macrophages, granulocytes and erythroid progenitors-related cell surface antigens on the bone marrow cells was significantly recovered in RP-treated irradiated mice compared to RP-untreated irradiated mice until day 20 after γ-irradiation. And, to estimate the effects of RP on gastrointestinal tissues in each individual, morphological evaluation H&E stain of the small intestine was performed until day 20 after γ-irradiation. As a result, RP promoted the recovery of gastrointestinal tissues damages in RP-treated irradiated mice compared to RP-untreated irradiated mice. Regarding cell death, radiation-induced gamma-H2AX expression in the nuclear of bone marrow cell was significantly decreased in RP-treated irradiated mice compared to RP-untreated irradiated mice immediately and after a period of 24 hours following a lethal 7 Gy dose of X-irradiation, indicating that the rate of apoptotic bone marrow cells was significantly decreased by RP-treatment. Meanwhile, 53BP1, which is well known as non-homologous end joining (NHEJ) factor, was significantly increased, showing that RP promoted NHEJ DNA repair in bone marrow cells treated with RP. These results demonstrate that c-Mpl agonist RP promotes the recovery of serious damages caused by lethal irradiation to the hematopoietic and gastrointestinal systems, and RP might be a useful radiomitigator in the case of ARS. Disclosures No relevant conflicts of interest to declare.

Plasma Flt-3 ligand concentration correlated with radiation-induced bone marrow damage during local fractionated radiotherapy

2003 ◽  
Vol 57 (2) ◽  
pp. 508-515 ◽  
Author(s):  
Aymeri Huchet ◽  
Yazid Belkacémi ◽  
Johanna Frick ◽  
Marie Prat ◽  
Ioanna Muresan-Kloos ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Ligand Concentration ◽  
Fractionated Radiotherapy ◽  
Bone Marrow Damage ◽  
Radiation Induced

scholarly journals Recombinant glycosylated human interleukin-6 accelerates peripheral blood platelet count recovery in radiation-induced bone marrow depression in baboons

Blood ◽  
1992 ◽  
Vol 80 (3) ◽  
pp. 688-695 ◽  
Author(s):  
F Herodin ◽  
JC Mestries ◽  
D Janodet ◽  
S Martin ◽  
J Mathieu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Platelet Count ◽  
Interleukin 6 ◽  
Neutron Radiation ◽  
The Body ◽  
Radiation Absorption ◽  
Control Group ◽  
Platelet Recovery ◽  
Adequate Model ◽  
Radiation Induced

Abstract This report was aimed at confirming the potential clinical use for a genetically engineered glycosylated human interleukin-6 (rhIL-6) in hematopoiesis. Its tolerance and efficacy were assessed on hematopoietic restoration after neutron radiation-induced bone marrow injury on baboons, which represent an adequate model of parallelism for studying hematology in the human. The particular neutron radiation absorption pattern in the body allows the preservation of underexposed bone marrow areas that mimics an autotransplantation-like situation. An initial dose finding study (1 microgram up to 20 micrograms/kg/d for 8 consecutive days) in normal baboons established a dose-dependent response regarding the peripheral platelet count (range of increase, 1.5- to 4-fold). A significant elevation in white blood cell (WBC) count, as well as a substantial reversible normochromic normocytic anemia, were observed for the highest doses only (10 and 20 micrograms/kg/d). All rhIL-6 administered doses were clinically well tolerated. In myelosuppressed baboons, a selected dose of 10 micrograms/kg/d of rhIL-6 for 13 consecutive days significantly lessened the degree of induced thrombocytopenia as compared with the control group (P = .01) and shortened the time to occurrence of the nadir, showing that the onset of recovery occurs much earlier, ie, an average of 5 days (P = .003), in the treated group. Moreover, this accelerated platelet recovery is evidenced by an 8-day shorter mean time back to baseline values (P = .03) in the rhIL-6--treated animals. At this dose no effect was observed on the WBC recovery pattern. Importantly rhIL-6 did not accentuate the radiation-induced anemia and was clinically well tolerated. All tested monkeys recovered from their induced pancytopenia and no animal loss was recorded. IL-6, tumor necrosis factor, and IL-1 blood measurements are reported. In conclusion, rhIL-6 is a potent thrombopoietic factor for the treatment of induced thrombocytopenia in nonhuman primates at a clinically well- tolerated dose.

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