Optimization and Limitation of Calcium Ionophore to Generate DCs from Acute Myeloid Leukemic Cells

Thanh-Nhan Nguyen Pham,최보화,강현규,진춘시,Nguyen Hoang Tuyet Minh,김상기,남종희,양덕환,김여경,김형준,정익주,이제중 대한암학회 2007 Cancer Research and Treatment Vol.39 No.4

Purpose: Calcium ionophore (CI) is used to generate dendritic cells (DCs) from progenitor cells, monocytes, or leukemic cells. The aim of this study was to determine the optimal dose of CI and the appropriate length of cell culture required for acute myeloid leukemia (AML) cells and to evaluate the limitations associated with CI.Materials and Methods: To generate leukemic DCs, leukemic cells (4×106 cells) from six AML patients were cultured with various concentrations of CI and/or IL-4 for 1, 2 or 3 days.Results: Potent leukemic DCs were successfully generated from all AML patients, with an average number of 1.2×106 cells produced in the presence of CI (270 ng/ml) for 2 days. Several surface molecules were clearly upregulated in AML cells supplemented with CI and IL-4, but not CD11c. Leukemic DCs cultured with CI had a higher allogeneic T cell stimulatory capacity than untreated AML cells, but the addition of IL-4 did not augment the MLR activity of these cells. AML cells cultured with CI in the presence or absence of IL-4 showed increased levels of apoptosis in comparison to primary cultures of AML cells.Conclusion:Although CI appears to be advantageous in terms of time and cost effectiveness, the results of the present study suggest that the marked induction of apoptosis by CI limits its application to the generation of DCs from AML cells. (Cancer Res Treat. 2007;39:175-180) Purpose: Calcium ionophore (CI) is used to generate dendritic cells (DCs) from progenitor cells, monocytes, or leukemic cells. The aim of this study was to determine the optimal dose of CI and the appropriate length of cell culture required for acute myeloid leukemia (AML) cells and to evaluate the limitations associated with CI.Materials and Methods: To generate leukemic DCs, leukemic cells (4×106 cells) from six AML patients were cultured with various concentrations of CI and/or IL-4 for 1, 2 or 3 days. Results: Potent leukemic DCs were successfully generated from all AML patients, with an average number of 1.2×106 cells produced in the presence of CI (270 ng/ml) for 2 days. Several surface molecules were clearly upregulated in AML cells supplemented with CI and IL-4, but not CD11c. Leukemic DCs cultured with CI had a higher allogeneic T cell stimulatory capacity than untreated AML cells, but the addition of IL-4 did not augment the MLR activity of these cells. AML cells cultured with CI in the presence or absence of IL-4 showed increased levels of apoptosis in comparison to primary cultures of AML cells.Conclusion:Although CI appears to be advantageous in terms of time and cost effectiveness, the results of the present study suggest that the marked induction of apoptosis by CI limits its application to the generation of DCs from AML cells. (Cancer Res Treat. 2007;39:175-180)

Lenalidomide Synergistically Enhances the Effect of Dendritic Cell Vaccination in a Model of Murine Multiple Myeloma

Nguyen-Pham, Thanh-Nhan,Jung, Sung-Hoon,Vo, Manh-Cuong,Thanh-Tran, Huong-Thi,Lee, Youn-Kyung,Lee, Hyun-Ju,Choi, Nu-Ri,Hoang, My-Dung,Kim, Hyeoung-Joon,Lee, Je-Jung Lippincott-Raven 2015 Journal of immunotherapy Vol.38 No.8

We investigated the efficacy of lenalidomide (LEN) in combination with dendritic cell (DC) vaccination in the MOPC-315 murine myeloma model. After tumor growth, LEN was injected intraperitoneally for 4 consecutive days in combination with DC vaccination. The combination of LEN and vaccination efficiently inhibited tumor growth compared with the single agents alone. A cytotoxic assay revealed that the anticancer effects of DC vaccination plus LEN involved not only generation of antigen-specific cytotoxic T lymphocytes but also NK cells. Vaccinated mice had reduced numbers of suppressor cells, including both myeloid-derived suppressor cells and regulatory T cells, in the spleen. The proportions of CD4 and CD8 T cells increased in the spleen, and a Th1 cytokine (interferon-&ggr;) rather than a Th2 cytokine (interleukin-10) was synthesized in response to tumor antigens. LEN enhanced the innate immune response by modulating NK cell numbers and function. In addition, LEN reduced the production levels of angiogenesis-inducing factors in tumor-bearing mice. Together, these results suggest that a combination of LEN and DC vaccination may synergistically enhance anticancer immunity in the murine myeloma model, by inhibiting immunosuppressor cells and stimulating effector cells, as well as effectively polarizing the Th1/Th2 balance in favor of a Th1-specific immune response.

Type I and II interferons enhance dendritic cell maturation and migration capacity by regulating CD38 and CD74 that have synergistic effects with TLR agonists

Nguyen-Pham, Thanh-Nhan,Lim, Mi-Seon,Nguyen, Truc Anh Thi,Lee, Youn-Kyung,Jin, Chun-Ji,Lee, Hyun Ju,Hong, Cheol Yi,Ahn, Jae-Sook,Yang, Deok-Hwan,Kim, Yeo-Kyeoung,Chung, Ik-Joo,Park, Byoung Chul,Kim, H Springer Science and Business Media LLC 2011 CELLULAR AND MOLECULAR IMMUNOLOGY Vol.8 No.4

Cellular immunotherapy using dendritic cells against multiple myeloma

Nguyen-Pham, Thanh-Nhan,Lee, Youn-Kyung,Lee, Hyun-Ju,Kim, Mi-Hyun,Yang, Deok-Hwan,Kim, Hyeoung-Joon,Lee, Je-Jung Korean Society of Hematology; Korean Society of Bl 2012 Blood Research Vol.47 No.1

<P>Cellular therapy with dendritic cells (DCs) is emerging as a useful immunotherapeutic tool to treat multiple myeloma (MM). DC-based idiotype vaccination was recently suggested to induce idiotype-specific immune responses in MM patients. However, the clinical results so far have been largely disappointing, and the clinical effectiveness of such vaccinations in MM still needs to be demonstrated. DC-based therapies against MM may need to be boosted with other sources of tumor-associated antigens, and potent DCs should be recruited to increase the effectiveness of treatment. DCs with both high migratory capacity and high cytokine production are very important for effective DC-based cancer vaccination in order to induce high numbers of Th1-type CD4<SUP>+</SUP> T cells and CD8<SUP>+</SUP> cytotoxic T lymphocytes. The tumor microenvironment is also important in the regulation of tumor cell growth, proliferation, and the development of therapeutic resistance after treatment. In this review, we discuss how the efficacy of DC vaccination in MM can be improved. In addition, novel treatment strategies that target not only myeloma cells but also the tumor microenvironment are urgently needed to improve treatment outcomes.</P>

Enhancement of antitumor effect using dendritic cells activated with natural killer cells in the presence of Toll-like receptor agonist

Pham, Thanh Nhan Nguyen,Hong, Cheol-Yi,Min, Jung-Joon,Rhee, Joon-Haeng,Nguyen, Truc-Anh Thi,Park, Byoung-Chul,Yang, Deok-Hwan,Park, Young-Kyu,Kim, Hyeong-Rok,Chung, Ik-Joo,Kim, Hyeoung-Joon,Lee, Je-Ju Korean Society for Biochemistry and Molecular Bion 2010 Experimental and molecular medicine Vol.42 No.6

Dendritic cells (DCs) play a role in natural killer (NK) cell activation, while NK cells are also able to activate and mature DCs. Toll-like receptors (TLRs) on the surface of DCs and NK cells induce the maturation and activation of these cells when engaged with their cognate ligand. We investigated to generate potent DCs by maturation with NK cells in the presence of TLR agonist in vitro and tested the efficacy of these DC vaccinations in mouse colon cancer model. The optimal ratios of DCs versus NK cells were 1:1 to 1:2. Immature DCs were mature with NK cells in the presence of lipopolysaccharide, which is TLR4 agonist, and further addition of IL-2 induced phenotypically and functionally mature bone marrow-derived DCs. These potent DCs exhibited not only high expression of several costimulatory molecules and high production of IL-12p40 and IL-12p70, but also high allogeneic T cells stimulatory capacity, and the induction of the high activities to generate tumor-specific CTLs. Consistently, vaccination with these DCs efficiently inhibited CT-26 tumor growth in mouse colon cancer model when compared to other vaccination strategies. Interestingly, combination therapy of these DC-based vaccines and with low-dose cyclophosphamide showed dramatic inhibition effects of tumor growth. These results suggest that the DCs maturated with NK cells in the presence of TLR agonist are potent inducer of antitumor immune responses in mouse model and may provide a new source of DC-based vaccines for the development of immunotherapy against colon cancer.

Cellular immunotherapy using dendritic cells against multiple myeloma

Thanh Nhan Nguyen Pham,Youn-Kyung Lee,이현주,Mi-Hyun Kim,양덕환,김형준,이제중 대한혈액학회 2012 Blood Research Vol.47 No.1

Cellular therapy with dendritic cells (DCs) is emerging as a useful immunotherapeutic tool to treat multiple myeloma (MM). DC-based idiotype vaccination was recently suggested to induce idiotype-specific immune responses in MM patients. However, the clinical results so far have been largely disappointing, and the clinical effectiveness of such vaccinations in MM still needs to be demonstrated. DC-based therapies against MM may need to be boosted with other sources of tumor-associated antigens, and potent DCs should be recruited to increase the effectiveness of treatment. DCs with both high migratory capacity and high cytokine production are very important for effective DC-based cancer vaccination in order to induce high numbers of Th1-type CD4+ T cells and CD8+ cytotoxic T lymphocytes. The tumor microenvironment is also important in the regulation of tumor cell growth, proliferation, and the development of therapeutic resistance after treatment. In this review, we discuss how the efficacy of DC vaccination in MM can be improved. In addition, novel treatment strategies that target not only myeloma cells but also the tumor microenvironment are urgently needed to improve treatment outcomes.

Enhancement of antitumor effect using dendritic cells activated with natural killer cells in the presence of Toll-like receptor agonist

Thanh Nhan Nguyen Pham,Cheol Yi Hong,민정준,이준행,Truc-Anh Thi Nguyen,박병철,양덕환,박영규,김형록,정익주,김형준,이제중 생화학분자생물학회 2010 Experimental and molecular medicine Vol.42 No.6

Dendritic cells (DCs) play a role in natural killer (NK) cell activation, while NK cells are also able to activate and mature DCs. Toll-like receptors (TLRs) on the surface of DCs and NK cells induce the maturation and activation of these cells when engaged with their cognate ligand. We investigated to generate potent DCs by maturation with NK cells in the presence of TLR agonist in vitro and tested the efficacy of these DC vaccinations in mouse colon cancer model. The optimal ratios of DCs versus NK cells were 1:1 to 1:2. Immature DCs were mature with NK cells in the presence of lipopolysaccharide,which is TLR4 agonist, and further addition of IL-2 induced phenotypically and functionally mature bone marrow-derived DCs. These potent DCs exhibited not only high expression of several costimulatory molecules and high production of IL-12p40and IL-12p70, but also high allogeneic T cells stimulatory capacity, and the induction of the high activities to generate tumor-specific CTLs. Consistently, vaccination with these DCs efficiently inhibited CT-26 tumor growth in mouse colon cancer model when compared to other vaccination strategies. Interestingly, combination therapy of these DC-based vaccines and with low-dose cyclophosphamide showed dramatic inhibition effects of tumor growth. These results suggest that the DCs maturated with NK cells in the presence of TLR agonist are potent inducer of antitumor immune responses in mouse model and may provide a new source of DC-based vaccines for the development of immunotherapy against colon cancer.

Some Results of Recent Investigation and Application of Rubber Blends in Vietnam

Bui Chuong,Nguyen Thanh Liem,Dang Viet Hung,Nguyen Huy Tung,Nguyen Pham Duy Linh,Nguyen Thanh Nhan,Pham Ngoc Linh,Le Anh Kien,Chu Chien Huu 한국고분자학회 2021 한국고분자학회 학술대회 연구논문 초록집 Vol.46 No.1

We have investigated the change of tensile strength (TS) of Natural rubber/chloroprene rubber (NR/CR) blends during combination ageing, including heating and dynamic mechanical loading. Using model of statistical experiment, we built the equation describing the dependence of TS on four factors: temperature T, number of cyclic loadings N, contents of NR (C_NR) and chloroprene (CCR). This equation allows predict the TS change of NR/CR blends after combination ageing with accepted inaccuracy – less than 10%. We also investigated the effect of nanofillers, such as nanoclay, SiO2, Fe₃O4, on adhesion of some rubber blends to polyester and steel cords. It was found, in the case of EPDM/CIIR rubber blends, both nanoclay and SiO2 have no effect on adhesion to steel cords, while nano SiO2 may enhance adhesion to polyester cords. On other side, Fe₃O4 may remarkably enhance adhesion of NR/CR blends to steel. Mentioned results are successfully applied in some practical rubber products working under fatigue conditions, such as rubber/steel antivibration pad for locomotive, heat resistant conveyor, water dam, underwater lift bag.

physical properties of La0.67Ca0.33Mn0.9TM0.1O3 [TM = Fe, Co, Ni] and their spin dynamics in the paramagnetic regime studied by EPR

Pham Hong Quang,유성초,Do Hong Minh,Huynh Thanh Nhan,Nguyen Huy Sinh 한국물리학회 2004 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.45 No.3

Substitution of Mn by Fe, Co, and Ni ions suppresses double exchange (DE), leading to a reduction in ferromagnetic interaction, or equivalently to lower values of Curie temperature, TC. The intensity of the electron paramagnetic resonance (EPR) line decreases exponentially with temperature, and the temperature dependence of EPR linewidth undergoes a minimum near TC. The activation energy values, Ea, derived from the temperature dependence of EPR line intensity, are equal to 0.074 eV, 0.093 eV and 0.086 eV for TM = Fe, Co, and Ni, respectively. In the case of cobalt substitution, an anomaly in the thermal evolution of the EPR linewidth has been observed. We attribute the cause of this anomaly to a Jahn-Teller transition or an electronic phase separation.

A Numerical Calculation of the Nuclear Spin-Parity and Magnetic Moment Based on the Single-Particle Shell Model

Nguyen Ngoc Duy,Latsamy Xayavong,Nguyen Kim Uyen,Vinh Nguyen Thanh Pham,Tran Viet Nhan Hao 한국물리학회 2019 새물리 Vol.69 No.10

Nuclear physics is an obligatory subject for the general physics program of undergraduates in most of the natural science universities worldwide. In nuclear physics, the shell model is one of the most important models, and is well used to determine the spin-parity and the magnetic moment of a nucleus. Over ten years of teaching general physics, we have realize that most undergraduate students find calculating these parameters by using this shell model to be difficult due to the classification of the subshells and the intrinsic spin of nucleons. With the hope to help these students, in the present study, we introduce a graphical-user-interface (GUI) program to execute our selfdeveloped Shell Model Calculator (SMC) code written in the Visual Basic 6.0 (VB6) programming language. Our SMC validation results for the quantum quantities in a series of nuclei Z = 1 - 20 were compared with experimental data and found to be in good agreement. In general, we successfully developed an SMC program that can be used for teaching, learning, and researching nuclear physics in universities.