The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform

Daohong Zhou - One of the best experts on this subject based on the ideXlab platform.

  • ionizing radiation induces hematopoietic stem cell senescence and long term Bone Marrow Suppression in a p16ink4a arf independent manner
    Blood, 2011
    Co-Authors: Lijian Shao, Yong Wang, Wei Feng, Norman E Sharpless, Daohong Zhou
    Abstract:

    Abstract 1345 Many patients receiving chemotherapy and/or ionizing radiation (IR) develop residual (or long-term) Bone Marrow (BM) injury that can not only limit the success of cancer treatment but also adversely affect their quality of life. Although residual BM injury has been largely attributed to the induction of hematopoietic stem cell (HSC) senescence, neither the molecular mechanisms by which chemotherapy and/or IR induce HSC senescence have been clearly defined, nor has an effective treatment been developed to ameliorate the injury. The Ink4a-Arf locus encodes two important tumor suppressors, p16Ink4a (p16) and Arf. Both of them have been implicated in mediating the induction of cellular senscence in a variety of cells including HSCs. Therefore, we examined the role of p16 and/or Arf in IR-induced HSC senescence and long-term BM Suppression using a total body irradiation (TBI) mouse model. The results from our studies show that exposure of wild-type (WT) mice to a sublethal dose (6 Gy) of TBI induces HSC senescence and long-term BM Suppression. The induction of HSC senescence is not associated with a reduction in telemore length in HSCs and their progeny, but is associated with significant increases in the production of reactive oxygen species (ROS), the expression of p16 and Arf mRNA, and the activity of senescence-associated β-galacotosidase (SA-β-gal) in HSCs. However, genetical deletion of Ink4a and/or Arf has no effect on TBI-induced HSC senescence, as HSCs from the Ink4a and/or Arf knockout mice after exposure to TBI exhibit similar changes as those seen in the cells from irradiated WT mice in comparison with the cells from un-irradiated mice with correspondent genotypes. In addition, TBI-induced long-term BM Suppression is also not attenuated by the deletion of the Ink4a and/or Arf genes. These findings suggest that IR induces HSC senescence and long-term BM Suppression in a p16Ink4a/Arf-independent manner. Disclosures: No relevant conflicts of interest to declare.

  • mitigation of ionizing radiation induced Bone Marrow Suppression by p38 inhibition and g csf administration
    Journal of Radiation Research, 2011
    Co-Authors: Yueying Wang, Heng Zhang, Jianhui Chang, Zhibin Zhai, Junling Zhang, Yong Wang, Daohong Zhou, Aimin Meng
    Abstract:

    p38 mitogen-activated protein kinases (p38) has been shown to be activated in hematopoietic stem and progenitors cells after exposure to ionizing radiation (IR) and its activation has been implicated in Bone Marrow (BM) Suppression under various pathological conditions. Therefore, in the present study we investigated whether inhibition of p38 activity alone with SB203580 (SB, a specific p38 inhibitor) or in combination with granulocyte colony-stimulating factor (G-CSF) can mitigate total body irradiation (TBI)-induced BM damage and lethality. Our results showed that p38 inhibition with SB had no significant effect on the 30-day survival rates of the mice exposed to 7.2 Gy TBI when it was used alone but increased the survival of the mice when it was combined with G-CSF. This combined effect may be attributable to a better preservation or stimulation of hematopoietic stem and progenitor cells, because BM cells from SB and G-CSF-treated mice produced more colony forming units-granulocyte-macrophage (CFU-GM) and 4-week cobblestone area forming cells (CAFCs) than the cells from either SB or G-CSF-treated mice after TBI in a colony forming cell assay and a CAFC assay, respectively. These findings suggest that the combined therapy with SB and G-GSF is more effective in mitigating TBI-induced acute BM injury than either agent alone.

  • mn iii meso tetrakis n ethylpyridinium 2 yl porphyrin mitigates total body irradiation induced long term Bone Marrow Suppression
    Free Radical Biology and Medicine, 2011
    Co-Authors: Yong Wang, Daohong Zhou, Aimin Meng, Senthil K Pazhanisamy, Lijian Shao, Ines Batinichaberle
    Abstract:

    Abstract Our recent studies showed that total body irradiation (TBI) induces long-term Bone Marrow (BM) Suppression in part by induction of hematopoietic stem cell (HSC) senescence through reactive oxygen species (ROS). In this study, we examined if Mn(III) meso -tetrakis-( N -ethylpyridinium-2-yl) porphyrin (MnTE), a superoxide dismutase mimetic and potent antioxidant, can mitigate TBI-induced long-term BM injury in a mouse model. Our results showed that post-TBI treatment with MnTE significantly inhibited the increases in ROS production and DNA damage in HSCs and the reduction in HSC frequency and clonogenic function induced by TBI. In fact, the clonogenic function of HSCs from irradiated mice after MnTE treatment was comparable to that of HSCs from normal controls on a per-HSC basis, suggesting that MnTE treatment inhibited the induction of HSC senescence by TBI. This suggestion is supported by the finding that MnTE treatment also reduced the expression of p16 Ink4a (p16) mRNA in HSCs induced by TBI and improved the long-term and multilineage engraftment of irradiated HSCs after transplantation. Therefore, the results from this study demonstrate that MnTE has the potential to be used as a therapeutic agent to mitigate TBI-induced long-term BM Suppression by inhibiting ionizing radiation-induced HSC senescence through the ROS–p16 pathway.

Kristin A. Bradley - One of the best experts on this subject based on the ideXlab platform.

  • Bone Marrow Suppression as a complication of total skin helical tomotherapy in the treatment of mycosis fungoides
    Radiation Oncology, 2018
    Co-Authors: Eric M. Schaff, Stephen A. Rosenberg, Stephanie J. Olson, Steven P. Howard, Kristin A. Bradley
    Abstract:

    Total skin electron beam therapy (TSEBT) is an effective treatment in mycosis fungoides. Total skin helical tomotherapy (TSHT) may be an alternative to TSEBT and may offer several dosimetric and treatment advantages. There are currently very few published treatment results using TSHT in place of TSEBT for treatment of mycosis fungoides. Two patients with mycosis fungoides were treated at our institution using TSHT. The first patient was a 69-year-old Caucasian female with stage IVA2 (T2 N3 M0 B2) disease who was treated to a dose of 12 Gy in 8 fractions, with a Bone Marrow mean dose of 1.66 Gy and V10 = 0.41%. Two weeks after ending treatment the patient developed myeloSuppression including grade 4 thrombocytopenia and required blood and platelet transfusions. The second patient was a 29-year-old Caucasian female with stage I (T2 N0 M0 B0) disease. This patient previously had been treated for mycosis fungoides using helical tomotherapy (HT) at a dose of 20 Gy to a localized region and experienced mild thrombocytopenia at that time. The patient then underwent retreatment 17 months later with TSHT to a dose of 12 Gy in 6 fractions with a mean Bone Marrow dose of 2.3 Gy and V10 = 4.28%. This patient once again experienced myeloSuppression that included grade 4 thrombocytopenia. She also required blood and platelet transfusions. Both patients treated with TSHT experienced severe Bone Marrow Suppression including grade 4 thrombocytopenia. This was more severe than expected considering the relatively low overall prescription dose and despite a planning constraint placed on the Bone Marrow of a mean dose of < 2 Gy. These outcomes suggest that patients treated using TSHT should be closely monitored for myeloSuppression and caution used even when treating to a dose of 12 Gy.

  • Bone Marrow Suppression as a complication of total skin helical tomotherapy in the treatment of mycosis fungoides
    BMC, 2018
    Co-Authors: Eric M. Schaff, Stephen A. Rosenberg, Stephanie J. Olson, Steven P. Howard, Kristin A. Bradley
    Abstract:

    Abstract Background Total skin electron beam therapy (TSEBT) is an effective treatment in mycosis fungoides. Total skin helical tomotherapy (TSHT) may be an alternative to TSEBT and may offer several dosimetric and treatment advantages. There are currently very few published treatment results using TSHT in place of TSEBT for treatment of mycosis fungoides. Case presentation Two patients with mycosis fungoides were treated at our institution using TSHT. The first patient was a 69-year-old Caucasian female with stage IVA2 (T2 N3 M0 B2) disease who was treated to a dose of 12 Gy in 8 fractions, with a Bone Marrow mean dose of 1.66 Gy and V10 = 0.41%. Two weeks after ending treatment the patient developed myeloSuppression including grade 4 thrombocytopenia and required blood and platelet transfusions. The second patient was a 29-year-old Caucasian female with stage I (T2 N0 M0 B0) disease. This patient previously had been treated for mycosis fungoides using helical tomotherapy (HT) at a dose of 20 Gy to a localized region and experienced mild thrombocytopenia at that time. The patient then underwent retreatment 17 months later with TSHT to a dose of 12 Gy in 6 fractions with a mean Bone Marrow dose of 2.3 Gy and V10 = 4.28%. This patient once again experienced myeloSuppression that included grade 4 thrombocytopenia. She also required blood and platelet transfusions. Conclusions Both patients treated with TSHT experienced severe Bone Marrow Suppression including grade 4 thrombocytopenia. This was more severe than expected considering the relatively low overall prescription dose and despite a planning constraint placed on the Bone Marrow of a mean dose of

Toshikazu Yoshikawa - One of the best experts on this subject based on the ideXlab platform.

  • protective effect of the japanese traditional medicine juzentaihoto on myeloSuppression induced by the anticancer drug ts 1 and identification of a potential biomarker of this effect
    BMC Complementary and Alternative Medicine, 2012
    Co-Authors: Kazuo Ogawa, Tatsushi Omatsu, Chinami Matsumoto, Naoko Tsuchiya, Masahiro Yamamoto, Yuji Naito, Toshikazu Yoshikawa
    Abstract:

    TS-1 is an oral anticancer drug containing a 5-fluorouracil derivative (Tegafur) that is widely used in Japan for the treatment of cancer, especially gastrointestinal tumors. Frequently, however, TS-1 therapy has to be discontinued because of leukopenia. If it were possible to predict the development of Bone Marrow Suppression before the white blood cell (WBC) count had actually decreased, treatment could be improved by strict dosage control and/or the prophylactic administration of hematopoietic drugs. Juzentaihoto (JTT), a traditional Japanese medicine (Kampo), has been reported to activate hematopoiesis and reduce the side effects associated with chemotherapy and radiotherapy. Here, we 1) evaluate the efficacy of JTT in alleviating myeloSuppression induced by TS-1 therapy in mice, and 2) explore biomarkers that reflect both induction by TS-1 and alleviation by JTT of Bone Marrow Suppression using a proteomics approach. Ten mg/kg of TS-1 was administered to Balb/c mice with or without 1 g/kg of oral JTT for 3, 5 and 7 days. WBC count and ratio of CD34+ Bone Marrow cells (BMCs) were estimated by flow cytometry. Plasma samples were analyzed using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI TOF-MS). A biomarker candidate from SELDI profiling was identified using a combination of cation exchange spin column purification, SDS-PAGE, enzymatic digestion and LC-MS/MS. After administration of TS-1, a significant decrease in WBC count and CD34+ BMC ratio were observed at days 5 and 3, respectively. JTT treatment improved WBC count on day 7 and CD34+ BMC ratio on days 5 and 7. SELDI analysis highlighted three protein peaks that had increased on day 3 after treatment with TS-1 but remained unchanged in mice co-treated with JTT. One of the three peaks, m/z 4223.1, was further investigated and identified as a specific C-terminal fragment of albumin. This study indicates that Bone Marrow Suppression by treatment with TS-1 in mice might be improved by coadministration of JTT. A C-terminal fragment of albumin was identified as a candidate biomarker for predicting TS-1-induced myeloSuppression. However, the sensitivity and specificity of the biomarker candidate must be validated in future clinical studies.

Dania Hirsch - One of the best experts on this subject based on the ideXlab platform.

Keiichi Nakagawa - One of the best experts on this subject based on the ideXlab platform.

  • helical skin radiation therapy including total skin radiation therapy using tomotherapy for primary cutaneous lymphoma with Bone Marrow Suppression as a related adverse event
    Practical radiation oncology, 2021
    Co-Authors: Mayuka Kitaguchi, Hideomi Yamashita, Ryosuke Takenaka, Kae Okuma, Kanabu Nawa, Keiichi Nakagawa
    Abstract:

    Abstract Purpose Total skin electron beam therapy (TSEBT) is useful for primary cutaneous lymphoma. However, helical skin radiation therapy (HSRT) using tomotherapy may avoid the complexity and uncertainty of TSEBT. Methods and Materials All patients with primary cutaneous lymphoma who underwent HSRT at our hospital between June 2015 and July 2019 were investigated, including 7 patients registered in a clinical trial approved by an institutional review board (ID UMIN000022142). HSRT was performed in 3 partitioned skin areas: head and neck, trunk and arms, and legs. Results A total of 24 patients with 53 skin areas (including 8 patients with 24 skin areas who had undergone sequential total skin irradiation), with a median follow-up time of 13 months (range, 2-50), were investigated. Twenty patients (83.3%) had mycosis fungoides (MF). For 41 of 53 (77.4%) cases, a dose of 20 Gy in 10 fractions was used. The overall response rate in the treated fields of each HSRT in patients with MF was 100%, including 38 (80.9%) complete response, 4 (8.5%) good partial response, and 5 (10.6%) partial response. Eight patients with MF who underwent sequential total skin irradiation showed a 100% complete response. For patients with MF, the median survival time after a first round of HSRT was 22 months (95% confidence interval [CI], 13.6-30.4 months), the median response duration of each HSRT was 5 months (95% CI, 3.67-6.32 months), and the median time to in-field reirradiation for each HSRT was 15 months (95% CI, 9.76-20.24 months). Bone Marrow Suppression (grade ≥3) often occurred (94.1%) with HSRT on trunk and arm skin. An early patient died of HSRT-caused grade 5 leukopenia. Conclusions HSRT targeting trunk and arm skin induced severe Bone Marrow Suppression that led to a temporary palliative effect. TSEBT should still be considered standard treatment for primary cutaneous lymphoma covering the total body surface area.