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Qiang Huang - One of the best experts on this subject based on the ideXlab platform.

  • experimental study on hyperbaric oxygen combined with Nimustine in targeting human glioma stem cells model
    Chin J Naut Med & Hyperbar Med, 2017
    Co-Authors: Yanping Xue, Bing Liu, Honghua Cai, Yujing Sheng, Yanming Chen, Cungang Dai, Qiang Huang
    Abstract:

    Objective To explore therapeutic effects of hyperbaric oxygen(HBO) combined with Nimustine(ACNU)on human glioma stem cells model, and analyze the related mechanism involved. Methods Balb/c nude mice were inoculated subcutaneously with human glioma stem cell line SU3, then were divided randomly into 4 groups, i. e., the ACNU group, the HBO group, the ACNU+ HBO group and the blank control group. The body weight and tumor volume of the tumor-bearing mice were measured regularly during the experiment. Unisense microelectrode was applied to detect oxygen level in tumor-bearing mice after HBO treatment. Upon completion of treatment, the tumor-bearing mice were sacrificed and tumors were weighed. Histomorphological analyses of the transplanted tumors were also performed to analyze hypoxia, necrosis and expression levels of angiogenic related factors. Results Following HBO therapy, the oxygen level in the tumor tissue of the tumor-bearing mice was significantly increased(P<0.01), and necrotic hemorrhage experienced a sharp decrease, when compared with the control group. The tumor weight of the ACNU+ HBO group was the lowest(1.43±0.38)g, and statistical differences could be seen, when compared with those of the other 3 groups(P<0.05). Tumor inhibition rates of the ACNU+ HBO group, the ACNU group and the HBO group were respectively 76.29%, 43.79% and 31.51%. The expression levels of TNF-α, HIF-1α, NF-κB and VEGF and the density of inflammatory cell infiltration were negatively correlated with tumor inhibition rate. Conclusions HBO therapy could alter the hypoxic microenvironment in which tumor stem cells survive, and could also inhibit tumor cell proliferation and tumor-related inflammatory cell infiltration triggered by glioma stem cells to a certain extent. Besides, combined HBO therapy could improve the curative effect of ACNU, and reverse the hypoxia micro-environment of tumor stem cell niche via negative regulation on the expressions of NF-κB, HIF-1α, TNF-α and VEGF. Key words: Glioma stem cells; Hyperbaric oxygen; Nimustine; Immune inflammatory reaction; Mice

  • hyperbaric oxygen therapy sensitizes Nimustine treatment for glioma in mice
    Cancer Medicine, 2016
    Co-Authors: Bing Liu, Chungang Dai, Tao Xie, Jun Dong, Qing Lan, Qiang Huang
    Abstract:

    Nimustine (ACNU) has antitumor activities in patients with malignant glioma. Hyperbaric oxygen (HBO) may enhance the efficacy of certain therapies that are hampered by the hypoxic microenvironment. We examined the combined effects of ACNU and HBO in a GFP transgenic nude mice bearing human glioma model. Mice inoculated with human glioma cells SU3 were randomly divided into the four groups: (A) the control group, (B) the HBOT (HBO therapy) group, (C) the ACNU group, and (D) the HBOT+ACNU group. Tumor size was measured at the indicated time intervals with a caliper; mice were sacrificed 28 days after treatment, and immunohistochemistry staining and western blot analysis were carried out. By the end of the trial, the tumor weights of groups A, B, C, and D were (P < 0.05), 6.03 ± 1.47, 4.13 ± 1.82 (P < 0.05), 2.39 ± 0.25 (P < 0.05), and 1.43 ± 0.38 (P < 0.01), respectively. The expressions of TNF-α, MMP9, HIF-α, VEGF, NF-κB, and IL-1β were associated with the infiltration of inflammatory cells and the inhibition rate of tumor cells. Hyperbaric oxygen therapy (HBOT) could inhibit glioma cell proliferation and inflammatory cell infiltration, and exert a sensitizing effect on ACNU therapy partially through enhancing oxygen pressure (PO2) in tumor tissues and lower expression levels of HIF-1α, TNF-α, IL-1β, VEGF, MMP9, and NF-κB.

  • Hyperbaric oxygen therapy sensitizes Nimustine treatment for glioma in mice.
    Cancer medicine, 2016
    Co-Authors: Bing Liu, Chungang Dai, Tao Xie, Jun Dong, Qing Lan, Qiang Huang
    Abstract:

    Nimustine (ACNU) has antitumor activities in patients with malignant glioma. Hyperbaric oxygen (HBO) may enhance the efficacy of certain therapies that are hampered by the hypoxic microenvironment. We examined the combined effects of ACNU and HBO in a GFP transgenic nude mice bearing human glioma model. Mice inoculated with human glioma cells SU3 were randomly divided into the four groups: (A) the control group, (B) the HBOT (HBO therapy) group, (C) the ACNU group, and (D) the HBOT+ACNU group. Tumor size was measured at the indicated time intervals with a caliper; mice were sacrificed 28 days after treatment, and immunohistochemistry staining and western blot analysis were carried out. By the end of the trial, the tumor weights of groups A, B, C, and D were (P 

M. R. Rajeswari - One of the best experts on this subject based on the ideXlab platform.

  • A Structural Insight into Major Groove Directed Binding of Nitrosourea Derivative Nimustine with DNA: A Spectroscopic Study
    2016
    Co-Authors: Shweta Agarwal, Deepak Kuma Jangi, Ranjana Mehrotra, Neelam Lohani, M. R. Rajeswari
    Abstract:

    Nitrosourea therapeutics occupies a definite place in cancer therapy but its exact mechanism of action has yet to be established. Nimustine, a chloroethyl nitrosourea derivative, is used to treat various types of malignancy including gliomas. The present work focuses on the understanding of Nimustine interaction with DNA to delineate its mechanism at molecular level. Attenuated total reflection-Fourier transform infrared (ATR-FTIR) has been used to determine the binding sites of Nimustine on DNA. Circular dichroism (CD) spectroscopy has been used to confirm conformational variations in DNA molecule upon Nimustine-DNA interaction. Thermodynamic parameters of Nimustine-DNA reaction have been calculated by isothermal titration calorimetry. Results of the present study demonstrate that Nimustine is not a simple alkylating agent rather it causes major grove-directed-alkylation. Spectroscopic data suggest binding of Nimustine with nitrogenous bases guanine (C6 =O6) and thymine (C4 =O4) in DNA major groove. CD spectra of Nimustine-DNA complexes point toward the perturbation of native B-conformation of DNA and its partial transition into C-form. Thermodynamically, Nimustine-DNA interaction is an entropy driven endothermic reaction, which suggests hydrophobic interaction of Nimustine in DNA-major groove pocket. Spectral results suggest base binding and local conformational changes in DNA upon Nimustine interaction. Investigation of drug-DNA interaction is an essential part of rational drug designing that also provides information about the drug’s action at molecular level. Results, demonstrated here, may contribute in the development of new nitrosoure

  • A structural insight into major groove directed binding of nitrosourea derivative Nimustine with DNA: a spectroscopic study.
    PLoS ONE, 2014
    Co-Authors: Shweta Agarwal, Ranjana Mehrotra, Neelam Lohani, Deepak Kumar Jangir, M. R. Rajeswari
    Abstract:

    Nitrosourea therapeutics occupies a definite place in cancer therapy but its exact mechanism of action has yet to be established. Nimustine, a chloroethyl nitrosourea derivative, is used to treat various types of malignancy including gliomas. The present work focuses on the understanding of Nimustine interaction with DNA to delineate its mechanism at molecular level. Attenuated total reflection-Fourier transform infrared (ATR-FTIR) has been used to determine the binding sites of Nimustine on DNA. Circular dichroism (CD) spectroscopy has been used to confirm conformational variations in DNA molecule upon Nimustine-DNA interaction. Thermodynamic parameters of Nimustine-DNA reaction have been calculated by isothermal titration calorimetry. Results of the present study demonstrate that Nimustine is not a simple alkylating agent rather it causes major grove-directed-alkylation. Spectroscopic data suggest binding of Nimustine with nitrogenous bases guanine (C6 = O6) and thymine (C4 = O4) in DNA major groove. CD spectra of Nimustine-DNA complexes point toward the perturbation of native B-conformation of DNA and its partial transition into C-form. Thermodynamically, Nimustine-DNA interaction is an entropy driven endothermic reaction, which suggests hydrophobic interaction of Nimustine in DNA-major groove pocket. Spectral results suggest base binding and local conformational changes in DNA upon Nimustine interaction. Investigation of drug-DNA interaction is an essential part of rational drug designing that also provides information about the drug's action at molecular level. Results, demonstrated here, may contribute in the development of new nitrosourea therapeutics with better efficacy and fewer side effects. Times Cited: 4 (fro

  • Percentage effect of Nimustine on DNA major groove.
    2014
    Co-Authors: Shweta Agarwal, Deepak Kuma Jangi, Ranjana Mehrotra, Neelam Lohani, M. R. Rajeswari
    Abstract:

    Percentage effect of Nimustine on DNA nitrogenous base guanine (G- C6 = O6) 1715 cm cm−1 and thymine (T- C4 = O4) 1657 cm cm−1) and other bases of DNA adenine (A) and cytosine (C) was observed as a function of Nimustine concentration.

  • FTIR spectra of free DNA and Nimustine-DNA complexes.
    2014
    Co-Authors: Shweta Agarwal, Ranjana Mehrotra, Neelam Lohani, Deepak Kumar Jangir, M. R. Rajeswari
    Abstract:

    FTIR spectra of free calf thymus DNA and its complexes with nitrosourea derivative Nimustine at different molar ratios were collected in the region of 1800 cm−1 to 700 cm cm−1.

  • Chemical structure of Nimustine.
    2014
    Co-Authors: Shweta Agarwal, Ranjana Mehrotra, Neelam Lohani, Deepak Kumar Jangir, M. R. Rajeswari
    Abstract:

    Chemical structure of Nimustine.

Teiji Tominaga - One of the best experts on this subject based on the ideXlab platform.

  • DDEL-08. CONVECTION-ENHANCED DELIVERY OF Nimustine HYDROCHLORIDE (ACNU) AGAINST PEDIATRIC DIFFUSE INTRINSIC PONTINE GLIOMAS
    Neuro-Oncology, 2020
    Co-Authors: Ryuta Saito, Masayuki Kanamori, Teiji Tominaga
    Abstract:

    Abstract Diffuse intrinsic pontine gliomas (DIPGs) are amongst the most challenging tumors to treat. Surgery is not an option, the effects of radiation therapy are temporary, and no chemotherapeutic agent has demonstrated significant efficacy. Intracerebral infusion technique of convection-enhanced delivery (CED) for patients with brain tumors could offer a novel approach for effective chemotherapy. We have been working to develop an effective chemotherapy using Nimustine hydrochloride (ACNU) with this drug delivery method. After several studies targeting supratentorial recurrent malignant gliomas and recurrent gliomas affecting brainstem, we conducted phase 1 study to evaluate the safety of combination of convection-enhanced delivery of Nimustine hydrochloride and systemic temozolomide against recurrent gliomas affecting brainstem. In this study, we demonstrated the safety and feasibility of CED of ACNU as well as real time monitoring of drug distribution by mixing ACNU with contrast agent; Gd-DOTA. We also defined the maximum tolerable concentration in this study and proceeded to phase 2 trial against recurrent gliomas affecting brain stem. However, these trials revealed the difficulty of treating pediatric DIPG at the time of recurrence. Therefore, we decided to treat pediatric DIPG cases at their initial diagnosis in the subsequent study. Aiming at obtaining Shonin approval both for intraparenchymal infusion catheter and drug to infuse into brain parenchyma, we are now conducting Phase II physician-led trial against initially diagnosed pediatric DIPG cases.

  • Safety and feasibility of convection-enhanced delivery of Nimustine hydrochloride co-infused with free gadolinium for real-time monitoring in the primate brain.
    Neurological research, 2012
    Co-Authors: Shin-ichiro Sugiyama, Ryuta Saito, Yukihiko Sonoda, Toshihiro Kumabe, Mika Watanabe, Taigen Nakamura, Yoji Yamashita, Michiko Yokosawa, Teiji Tominaga
    Abstract:

    AbstractObjectives: Convection-enhanced delivery (CED) has been developed as an effective drug-delivery strategy for brain tumors. Ideally, direct visualization of the tissue distribution of drugs infused by CED would assure successful delivery of therapeutic agents to the brain tumor while minimizing exposure of the normal brain tissue. We previously showed the anti-tumor efficacy of Nimustine hydrochloride (ACNU) delivered via CED against a rodent intracranial xenografted tumor model. Here, we developed a method to monitor the drug distribution using a non-human primate brain.Methods: CED of a mixture of ACNU with gadodiamide was performed using three non-human primates under real-time magnetic resonance imaging monitoring. Animals were clinically observed for any toxicity after infusion. Two months later, their brains were subjected to histological examination for the evaluation of local toxicity. Another one animal was euthanized immediately after CED of a mixture of ACNU, gadodiamide, and Evans blue ...

  • Local convection-enhanced delivery of chemotherapeutic agent transiently opens blood–brain barrier and improves efficacy of systemic chemotherapy in intracranial xenograft tumor model
    Cancer letters, 2011
    Co-Authors: Taigen Nakamura, Ryuta Saito, Yukihiko Sonoda, Toshihiro Kumabe, Shin-ichiro Sugiyama, Teiji Tominaga
    Abstract:

    Recently, local chemotherapy proved its efficacy against malignant gliomas. Under the hypothesis that local delivery of chemotherapeutic agents into the brain parenchyma induce opening of the blood–brain barrier (BBB), we evaluated the opening of BBB after convection-enhanced delivery of Nimustine hydrochloride into the brain parenchyma. Local convection-enhanced delivery of Nimustine hydrochloride transiently opened the BBB from about 7–12 days after delivery in normal rodent brain. Systemic chemotherapy during this period of BBB disruption had synergistic effects resulting in prolonged survival of tumor-bearing rats. The present strategy may provide a new approach for glioma chemotherapy.

  • regression of recurrent glioblastoma infiltrating the brainstem after convection enhanced delivery of Nimustine hydrochloride case report
    Journal of Neurosurgery, 2011
    Co-Authors: Ryuta Saito, Yukihiko Sonoda, Toshihiro Kumabe, Ken-ichi Nagamatsu, Mika Watanabe, Teiji Tominaga
    Abstract:

    This 13-year-old boy with a history of cranial irradiation for the CNS recurrence of acute lymphocytic leukemia developed a glioblastoma in the right cerebellum. Resection and chemo- and radiotherapy induced remission of the disease. However, recurrence was noted in the brainstem region 8 months later. Because no effective treatment was available for this recurrent lesion, the authors decided to use convection-enhanced delivery (CED) to infuse Nimustine hydrochloride. On stereotactic insertion of the infusion cannula into the brainstem lesion, CED of Nimustine hydrochloride was performed with real-time MR imaging to monitor the co-infused chelated gadolinium. The patient's preinfusion symptom of diplopia disappeared after treatment. Follow-up MR imaging revealed the response of the tumor. The authors report on a case of recurrent glioblastoma infiltrating the brainstem that regressed after CED of Nimustine hydrochloride.

  • Regression of recurrent glioblastoma infiltrating the brainstem after convection-enhanced delivery of Nimustine hydrochloride
    Journal of neurosurgery. Pediatrics, 2011
    Co-Authors: Ryuta Saito, Yukihiko Sonoda, Toshihiro Kumabe, Ken-ichi Nagamatsu, Mika Watanabe, Teiji Tominaga
    Abstract:

    This 13-year-old boy with a history of cranial irradiation for the CNS recurrence of acute lymphocytic leukemia developed a glioblastoma in the right cerebellum. Resection and chemo- and radiotherapy induced remission of the disease. However, recurrence was noted in the brainstem region 8 months later. Because no effective treatment was available for this recurrent lesion, the authors decided to use convection-enhanced delivery (CED) to infuse Nimustine hydrochloride. On stereotactic insertion of the infusion cannula into the brainstem lesion, CED of Nimustine hydrochloride was performed with real-time MR imaging to monitor the co-infused chelated gadolinium. The patient's preinfusion symptom of diplopia disappeared after treatment. Follow-up MR imaging revealed the response of the tumor. The authors report on a case of recurrent glioblastoma infiltrating the brainstem that regressed after CED of Nimustine hydrochloride.

Shweta Agarwal - One of the best experts on this subject based on the ideXlab platform.

  • Investigation of Anti-Cancer Drug Nimustine Interaction with Calf Thymus DNA
    MAPAN, 2016
    Co-Authors: Deepti Chadha, Shweta Agarwal, Ranjana Mehrotra
    Abstract:

    Nimustine, a chloroethyl nitrosourea derivative (CENU), is an antineoplastic agent, which is used for the treatment of various types of cancer. The present study focuses on the prediction and investigation of binding properties of Nimustine with DNA using molecular modeling and UV–Visible spectroscopic technique. The docking study show that Nimustine plausibly binds within the major groove of DNA. Further analysis of docking suggests direct interaction of Nimustine with the moieties of heterocyclic nitrogenous bases of DNA. The free binding energy value of the best Nimustine-DNA docked conformer is predicted as −4.31 kcal/mol using docking results.The molecular modeling study also reveals that the interaction between Nimustine and DNA is majorly governed by van der Waals forces, hydrogen bonding and hydrophobic interactions, whereas the contribution of electrostatic forces stands negligible. Further, UV–Visible spectra of free calf thymus DNA and its complexes with varying concentration of Nimustine indicate the binding constant ( K _ a ) value as 3.27 × 10^3 M^−1, which suggests moderate interaction of Nimustine with DNA. The spectroscopic results are further used to calculate the binding free energy of the complex using the relation Δ G = − RT ln ( K _ a ). This accounts for a value of −4.79 kcal/mol. It corroborates well with the docking outcomes. The results of present study may help in designing and synthesis of new chloroethyl nitrosourea derivatives with improved efficacy and specificity for the target molecules.

  • Investigation of Anti-Cancer Drug Nimustine Interaction with Calf Thymus DNA
    MAPAN, 2016
    Co-Authors: Deepti Chadha, Shweta Agarwal, Ranjana Mehrotra
    Abstract:

    Nimustine, a chloroethyl nitrosourea derivative (CENU), is an antineoplastic agent, which is used for the treatment of various types of cancer. The present study focuses on the prediction and investigation of binding properties of Nimustine with DNA using molecular modeling and UV–Visible spectroscopic technique. The docking study show that Nimustine plausibly binds within the major groove of DNA. Further analysis of docking suggests direct interaction of Nimustine with the moieties of heterocyclic nitrogenous bases of DNA. The free binding energy value of the best Nimustine-DNA docked conformer is predicted as −4.31 kcal/mol using docking results.The molecular modeling study also reveals that the interaction between Nimustine and DNA is majorly governed by van der Waals forces, hydrogen bonding and hydrophobic interactions, whereas the contribution of electrostatic forces stands negligible. Further, UV–Visible spectra of free calf thymus DNA and its complexes with varying concentration of Nimustine indicate the binding constant ( K _ a ) value as 3.27 × 10^3 M^−1, which suggests moderate interaction of Nimustine with DNA. The spectroscopic results are further used to calculate the binding free energy of the complex using the relation Δ G = − RT ln ( K _ a ). This accounts for a value of −4.79 kcal/mol. It corroborates well with the docking outcomes. The results of present study may help in designing and synthesis of new chloroethyl nitrosourea derivatives with improved efficacy and specificity for the target molecules.

  • A Structural Insight into Major Groove Directed Binding of Nitrosourea Derivative Nimustine with DNA: A Spectroscopic Study
    2016
    Co-Authors: Shweta Agarwal, Deepak Kuma Jangi, Ranjana Mehrotra, Neelam Lohani, M. R. Rajeswari
    Abstract:

    Nitrosourea therapeutics occupies a definite place in cancer therapy but its exact mechanism of action has yet to be established. Nimustine, a chloroethyl nitrosourea derivative, is used to treat various types of malignancy including gliomas. The present work focuses on the understanding of Nimustine interaction with DNA to delineate its mechanism at molecular level. Attenuated total reflection-Fourier transform infrared (ATR-FTIR) has been used to determine the binding sites of Nimustine on DNA. Circular dichroism (CD) spectroscopy has been used to confirm conformational variations in DNA molecule upon Nimustine-DNA interaction. Thermodynamic parameters of Nimustine-DNA reaction have been calculated by isothermal titration calorimetry. Results of the present study demonstrate that Nimustine is not a simple alkylating agent rather it causes major grove-directed-alkylation. Spectroscopic data suggest binding of Nimustine with nitrogenous bases guanine (C6 =O6) and thymine (C4 =O4) in DNA major groove. CD spectra of Nimustine-DNA complexes point toward the perturbation of native B-conformation of DNA and its partial transition into C-form. Thermodynamically, Nimustine-DNA interaction is an entropy driven endothermic reaction, which suggests hydrophobic interaction of Nimustine in DNA-major groove pocket. Spectral results suggest base binding and local conformational changes in DNA upon Nimustine interaction. Investigation of drug-DNA interaction is an essential part of rational drug designing that also provides information about the drug’s action at molecular level. Results, demonstrated here, may contribute in the development of new nitrosoure

  • A structural insight into major groove directed binding of nitrosourea derivative Nimustine with DNA: a spectroscopic study.
    PLoS ONE, 2014
    Co-Authors: Shweta Agarwal, Ranjana Mehrotra, Neelam Lohani, Deepak Kumar Jangir, M. R. Rajeswari
    Abstract:

    Nitrosourea therapeutics occupies a definite place in cancer therapy but its exact mechanism of action has yet to be established. Nimustine, a chloroethyl nitrosourea derivative, is used to treat various types of malignancy including gliomas. The present work focuses on the understanding of Nimustine interaction with DNA to delineate its mechanism at molecular level. Attenuated total reflection-Fourier transform infrared (ATR-FTIR) has been used to determine the binding sites of Nimustine on DNA. Circular dichroism (CD) spectroscopy has been used to confirm conformational variations in DNA molecule upon Nimustine-DNA interaction. Thermodynamic parameters of Nimustine-DNA reaction have been calculated by isothermal titration calorimetry. Results of the present study demonstrate that Nimustine is not a simple alkylating agent rather it causes major grove-directed-alkylation. Spectroscopic data suggest binding of Nimustine with nitrogenous bases guanine (C6 = O6) and thymine (C4 = O4) in DNA major groove. CD spectra of Nimustine-DNA complexes point toward the perturbation of native B-conformation of DNA and its partial transition into C-form. Thermodynamically, Nimustine-DNA interaction is an entropy driven endothermic reaction, which suggests hydrophobic interaction of Nimustine in DNA-major groove pocket. Spectral results suggest base binding and local conformational changes in DNA upon Nimustine interaction. Investigation of drug-DNA interaction is an essential part of rational drug designing that also provides information about the drug's action at molecular level. Results, demonstrated here, may contribute in the development of new nitrosourea therapeutics with better efficacy and fewer side effects. Times Cited: 4 (fro

  • Percentage effect of Nimustine on DNA major groove.
    2014
    Co-Authors: Shweta Agarwal, Deepak Kuma Jangi, Ranjana Mehrotra, Neelam Lohani, M. R. Rajeswari
    Abstract:

    Percentage effect of Nimustine on DNA nitrogenous base guanine (G- C6 = O6) 1715 cm cm−1 and thymine (T- C4 = O4) 1657 cm cm−1) and other bases of DNA adenine (A) and cytosine (C) was observed as a function of Nimustine concentration.

Bing Liu - One of the best experts on this subject based on the ideXlab platform.

  • experimental study on hyperbaric oxygen combined with Nimustine in targeting human glioma stem cells model
    Chin J Naut Med & Hyperbar Med, 2017
    Co-Authors: Yanping Xue, Bing Liu, Honghua Cai, Yujing Sheng, Yanming Chen, Cungang Dai, Qiang Huang
    Abstract:

    Objective To explore therapeutic effects of hyperbaric oxygen(HBO) combined with Nimustine(ACNU)on human glioma stem cells model, and analyze the related mechanism involved. Methods Balb/c nude mice were inoculated subcutaneously with human glioma stem cell line SU3, then were divided randomly into 4 groups, i. e., the ACNU group, the HBO group, the ACNU+ HBO group and the blank control group. The body weight and tumor volume of the tumor-bearing mice were measured regularly during the experiment. Unisense microelectrode was applied to detect oxygen level in tumor-bearing mice after HBO treatment. Upon completion of treatment, the tumor-bearing mice were sacrificed and tumors were weighed. Histomorphological analyses of the transplanted tumors were also performed to analyze hypoxia, necrosis and expression levels of angiogenic related factors. Results Following HBO therapy, the oxygen level in the tumor tissue of the tumor-bearing mice was significantly increased(P<0.01), and necrotic hemorrhage experienced a sharp decrease, when compared with the control group. The tumor weight of the ACNU+ HBO group was the lowest(1.43±0.38)g, and statistical differences could be seen, when compared with those of the other 3 groups(P<0.05). Tumor inhibition rates of the ACNU+ HBO group, the ACNU group and the HBO group were respectively 76.29%, 43.79% and 31.51%. The expression levels of TNF-α, HIF-1α, NF-κB and VEGF and the density of inflammatory cell infiltration were negatively correlated with tumor inhibition rate. Conclusions HBO therapy could alter the hypoxic microenvironment in which tumor stem cells survive, and could also inhibit tumor cell proliferation and tumor-related inflammatory cell infiltration triggered by glioma stem cells to a certain extent. Besides, combined HBO therapy could improve the curative effect of ACNU, and reverse the hypoxia micro-environment of tumor stem cell niche via negative regulation on the expressions of NF-κB, HIF-1α, TNF-α and VEGF. Key words: Glioma stem cells; Hyperbaric oxygen; Nimustine; Immune inflammatory reaction; Mice

  • Experimental study on hyperbaric oxygen combined with Nimustine in targeting human glioma stem cells model
    2017
    Co-Authors: Xue Yanping, Bing Liu, Honghua Cai, Yujing Sheng, Yanming Chen, Cungang Dai, Lu Zhaohui, Huang Qiang
    Abstract:

    Objective To explore therapeutic effects of hyperbaric oxygen(HBO) combined with Nimustine(ACNU)on human glioma stem cells model, and analyze the related mechanism involved. Methods Balb/c nude mice were inoculated subcutaneously with human glioma stem cell line SU3, then were divided randomly into 4 groups, i. e., the ACNU group, the HBO group, the ACNU+ HBO group and the blank control group. The body weight and tumor volume of the tumor-bearing mice were measured regularly during the experiment. Unisense microelectrode was applied to detect oxygen level in tumor-bearing mice after HBO treatment. Upon completion of treatment, the tumor-bearing mice were sacrificed and tumors were weighed. Histomorphological analyses of the transplanted tumors were also performed to analyze hypoxia, necrosis and expression levels of angiogenic related factors. Results Following HBO therapy, the oxygen level in the tumor tissue of the tumor-bearing mice was significantly increased(P

  • hyperbaric oxygen therapy sensitizes Nimustine treatment for glioma in mice
    Cancer Medicine, 2016
    Co-Authors: Bing Liu, Chungang Dai, Tao Xie, Jun Dong, Qing Lan, Qiang Huang
    Abstract:

    Nimustine (ACNU) has antitumor activities in patients with malignant glioma. Hyperbaric oxygen (HBO) may enhance the efficacy of certain therapies that are hampered by the hypoxic microenvironment. We examined the combined effects of ACNU and HBO in a GFP transgenic nude mice bearing human glioma model. Mice inoculated with human glioma cells SU3 were randomly divided into the four groups: (A) the control group, (B) the HBOT (HBO therapy) group, (C) the ACNU group, and (D) the HBOT+ACNU group. Tumor size was measured at the indicated time intervals with a caliper; mice were sacrificed 28 days after treatment, and immunohistochemistry staining and western blot analysis were carried out. By the end of the trial, the tumor weights of groups A, B, C, and D were (P < 0.05), 6.03 ± 1.47, 4.13 ± 1.82 (P < 0.05), 2.39 ± 0.25 (P < 0.05), and 1.43 ± 0.38 (P < 0.01), respectively. The expressions of TNF-α, MMP9, HIF-α, VEGF, NF-κB, and IL-1β were associated with the infiltration of inflammatory cells and the inhibition rate of tumor cells. Hyperbaric oxygen therapy (HBOT) could inhibit glioma cell proliferation and inflammatory cell infiltration, and exert a sensitizing effect on ACNU therapy partially through enhancing oxygen pressure (PO2) in tumor tissues and lower expression levels of HIF-1α, TNF-α, IL-1β, VEGF, MMP9, and NF-κB.

  • Hyperbaric oxygen therapy sensitizes Nimustine treatment for glioma in mice.
    Cancer medicine, 2016
    Co-Authors: Bing Liu, Chungang Dai, Tao Xie, Jun Dong, Qing Lan, Qiang Huang
    Abstract:

    Nimustine (ACNU) has antitumor activities in patients with malignant glioma. Hyperbaric oxygen (HBO) may enhance the efficacy of certain therapies that are hampered by the hypoxic microenvironment. We examined the combined effects of ACNU and HBO in a GFP transgenic nude mice bearing human glioma model. Mice inoculated with human glioma cells SU3 were randomly divided into the four groups: (A) the control group, (B) the HBOT (HBO therapy) group, (C) the ACNU group, and (D) the HBOT+ACNU group. Tumor size was measured at the indicated time intervals with a caliper; mice were sacrificed 28 days after treatment, and immunohistochemistry staining and western blot analysis were carried out. By the end of the trial, the tumor weights of groups A, B, C, and D were (P