• Archives of Pharmacal Research
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• v.29 no.10
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• pp.866-873
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• 2006

When patients with cancers are treated with chemotherapeutic agents a long time, some of the cancer cells develop the multidrug resistance (MDR) phenotype. MDR cancer cells are characterized by the overexpression of multidrug resistance1 (MDR1) gene which encodes P-glycoprotein (Pgp), a surface protein of tumor cells that functions to produce an excessive efflux and thereby an insufficient intracellular concentration of chemotherapeutic agents. A variety of studies have sought potent MDR modulators to decrease MDR1 gene expression in cancer cells. Our previous study has shown that curcumin exhibits characteristics of a MDR modulator in KB-V1 multidrug-resistant cells. The aim of this study was to further investigate the effect of curcumin on MDR1 gene expression in patient leukemic cells. The leukemic cells were collected from 78 childhood leukemia patients admitted at Maharaj Nakorn Chiang Mai Hospital, Chiang Mai, Thailand, in the period from July 2003 to February 2005. There were 61 cases of acute lymphoblastic leukemia (ALL), 14 cases of acute myeloblastic leukemia (AML), and 3 cases of chronic myelocytic leukemia (CML). There were 47 males and 31 females ranging from 1 to 15 years old. Bone marrows were collected. The leukemic cells were separated and cultured in the presence or absence of $10{\mu}M$ curcumin for 48 hours. MDR1 mRNA levels were determined by RT-PCR. It was found that curcumin reduced MDR1 gene expression in the cells from 33 patients (42%). Curcumin affected the MDR1 gene expression in 5 of 11 relapsed cases (45%), 10 of 26 cases of drug maintenance (38%), 7 of 18 cases of completed treatment (39%), and 11 of 23 cases of new patients (48%). The expression levels of MDR1 gene in leukemic patient cells as compared to that of KB-V1 cells were classified as low level (1-20%) in 5 of 20 cases (25%), medium level (21-60%) in 14 of 32 cases (44%), and high level (61-100%) in 14 of 20 cases (70%). In summary, curcumin decreased MDR1 mRNA level in patient leukemic cells, especially in high level of MDR1 gene groups. Thus, curcumin treatment may provide a lead for clinical treatment of leukemia patients in the future.

• The Journal of the Korean bone and joint tumor society
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• v.11 no.1
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• pp.54-61
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• 2005

Purpose: The granulocytic sarcoma which developed in leukemic patients are quite rare and it will have bad prognosis, but it's tumor pathogenesis and also their treatment are not yet established. Through this study we have tried to know their clinical course, prognosis and their end result of recent treatment. Material and Methods: Total 20 patients of granulocytic sarcoma which were developed in total 2,197 leukemic patients from April, 1998 to September, 2004 were treated at the leukemic center and the orthopaedic department of St. Mary's hospital, Catholic University of Korea, and followed them for 1~78 months(average 18 months). Results: Total 20 cases of granulocytic sarcoma was found in 14 cases of total 1,331 acute myelocytic leukemic patients(AML), 4 cases of total 744 of chronic myelocytic leukemic patients(CML), and only one case in total 122 of acute biphenotype of leukemia. And so their occurrence rate in leukmic patients are actually 0.91%, total 20 cases of granulocytic sarcoma in total 2,197 leukemic patients at same period. Their ages are average 28.3 years(4~52 years), and male are predominant(13 cases) than female(7 cases). Single involvement was found in 11 cases but multiple lesions are in 9 cases, and spine, brain, extremities, chest, and pelvic bone are involved in frequency. The granulocytic sarcoma was developed in various stages of the leukemia, ie, 8 cases in complete remission of leukemia, and 12 cases in the treatment process of AML. The pathohistologic evaluation of granulocytic sarcoma was done in 6 cases which was developed in their extremities, and confirmed numerous immature myeloblasts and lymphocytes mixed. The treatment of these granulocytic sarcoma was mainly limited for the treatment of leukemia by Glivac and massive steroid therapy(19cases) and also combined with the bone marrow transplantation(13 cases), but radiation therapy with average 3,500 rads in 15 cases out of total 20 sarcomas was also done, and followed them for average 17.5 months after development of granulocytic sarcomas. Finally their prognosis was so bad that 12 patients(60%) out of total 20 granulocytic sarcoma were dead in 6.5 months after sarcoma developed and we found the granulocytic sarcoma was more fatal if they are developed during the process of CML(mortality: 100%(4/4cases). Conclusion: The prognosis of granulocytic sarcomas in leukemic patients are quite fatal, and much more studies for their pathogenesis and ways of treatment should be performed continuously.

• Journal of Microbiology and Biotechnology
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• v.13 no.4
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• pp.607-612
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• 2003

To elucidate the action mechanism of MCS-C2, a novel analogue of toyocamycin and sangivamycin, its effect on the expression of cell cycle-related proteins in the human myelocytic leukemia cell line HL-60 was examined using Western blotting and a flow cytometric analysis. MCS-C2, a selective inhibitor of cyclin-dependent kinases, was found to inhibit cell growth in a time- and dose-dependent manner, and inhibits cell cycle progression by inducing the arrest at G1 and G2/M phases, in HL-60 cells. The flow cytometric analysis revealed an appreciable arrest of cells in the G2/M phase of the cell cycle after treatment with MCS-C2. The HL-60 cell population increased gradually from 13% at 0 h, to 28% at 12 h in the G2/M phase, after exposure to $2{\;}\mu\textrm{M}$ MCS-C2. Furthermore, Western blot analysis demonstrated that MCS-C2 induced the cell cycle arrest at G1 phase through the inhibition of pRb phosphorylation. Hypophosphorylated pRb accumulated after treatment with $5{\;}\mu\textrm{M}$ MCS-C2 for 12 h, whereas, the level of hyperphosphorylated pRb was reduced. Thus, treatment of the cell with MCS-C2 suppressed the hyperphosphorylated form of pRb with a commensurate increase in the hypophosphorylated form.

• Journal of Physiology & Pathology in Korean Medicine
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• v.16 no.3
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• pp.514-520
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• 2002

Paljinhangahm-dan is an Oriental herbal formulation for its ability to modulate cancer cell growth and survival. This research was performed to study the anti-cancer effects of Paljinhangahm-dan water extract(PHWE) in human pro myelocytic leukemia(HL-60) cells. After HL-60 cells were routinely cultured, tetrazolium-based colorimetric(MTT) assay was performed for cytotoxicity test. To explore the mechanism of cytotoxicity. I used several measures of apoptosis to determine whether this processes was involved in PHWE-induced cell death in HL-60 cells. In addition, the experiment was practised 1 H-NMR spectroscopy to examine molecular structure of PHWE. This study suggested that PHWE control cancer cell growth through of apoptosis with less cytotoxicity in normal cells.

• Journal of Microbiology and Biotechnology
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• v.19 no.2
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• pp.155-160
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• 2009

Mast cells and basophils perform important functions as pivotal effector cells in IgE-mediated allergic reactions. KU812F cells, a human basophilic cell line isolated originally from chronic myelocytic leukemia, express a high affinity receptor of IgE, $Fc{\varepsilon}RI$. Kaempferol was extracted and isolated from a methanolic extract of flavonoid-rich Nelumbo nucifera stamens. In the present study, the inhibitory effects of kaempferol on $Fc{\varepsilon}RI$ expression in human basophilic KU812F cells was examined. Flow cytometric analysis revealed that $Fc{\varepsilon}RI$ expression on the cell surface was suppressed in a concentration-dependent manner when the cells were cultured with kaempferol. Moreover, RT-PCR analysis showed that the mRNA levels for $Fc{\varepsilon}RI$ ${\alpha}-\;and\;{\gamma}$-chains were reduced as the result of kaempferol treatment in a concentration-dependent manner. Kaempferol showed its suppressive effects on intracellular $Ca^{2+}$ concentration and histamine release from anti-$Fc{\varepsilon}RI$ ${\alpha}$-chain antibody-stimulated cells in a concentration-dependent manner. These observations indicate that kaempferol may exert antiallergic effect via down regulation of $Fc{\varepsilon}RI$ expression and degranulation.

• Journal of the korean academy of Pediatric Dentistry
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• v.32 no.2
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• pp.251-255
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• 2005

Radiotherapy for head and neck tumors is a viable treatment modality. However, a wide range of potentially debilitating dental complications may be accompanied by this treatment. We report two cases of developmental disturbance of permanent tooth germs after radiotherapy. The one was that of a seven-year-old girl, who had congenitally missing teeth, and microdontia of permanent tooth germs. she had received radiotherapy for acute myelocytic leukemia at the age of 19 months. The other was that of a nine-year-old boy, in which congenitally missing teeth, microdontia, root hypoplasia, and enamel hypoplasia of permanent teeth were observed. He had undergone a course of radiotherapy for bilateral retinoblastoma at the age of 13 months.

• Applied Chemistry for Engineering
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• v.26 no.1
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• pp.111-115
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• 2015

Two new analogs of bestatin were prepared from $\small{D}$-leucine and $\small{D}$-valine in a stereoselective and efficient way. An aminopeptidase inhibitor bestatin shows significant biological effects on immunomodulation and is marketed for the treatment of acute myelocytic leukemia. The key intermediates, trans-oxazolidine methyl esters 2a and 2b, were obtained with more than 20 to 1 stereoselectivity in a one-pot procedure by the three cascade reactions between N-hydroxymethyl protected ${\alpha}$-amino aldehydes (4a and 4b) and phenylsulfonylnitromethane ($PhSO_2CH_2NO_2$) and the following in-situ ozonolysis. Basic hydrolysis of 2a and 2b, and then the peptide coupling with $\small{L}$-Leu-OMe produced the protected derivatives of two new bestatin analogs, 3a and 3b, respectively. The new isobutyl and isopropyl analogs of bestatin (1a and 1b) were produced in overall 51% and 38% yields, respectively, with high stereoselectivity from the corresponding protected ${\alpha}$-amino aldehydes 4 in a six-step process.

• Biomedical Science Letters
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• v.18 no.2
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• pp.131-138
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• 2012

Autologous peripheral blood stem cell transplantation (PBSCT) has been used as a major treatment strategy for hematological malignancies. The number of CD34 positive cells in the harvested product is a very important factor for achieving successful transplantation. We studied the factors that can predict the number of CD34 positive cells in the harvested product of acute myelocytic leukemia (AML), multiple myeloma (MM) and Non-Hodgkin's lymphoma (NHL) patients after mobilizing them with chemotherapy plus G-CSF. A total of 73 patients (AML 19 patients, MM 28 patients, NHL 26 patients) with hematological malignancies had been mobilized with chemotherapy and granulocyte colony-stimulating growth factor from April, 2000 to February, 2012. Group's characteristics, checkup opinion of pre-peripheral blood on the day of harvest & outcome of PBSC were analyzed and evaluated using SPSS statistics program after grouping patients as below; group 1: CD34 cell counts < $2{\times}10^6/kg$ (n=16); group 2: $2{\times}10^6/kg{\leq}CD34$ cell counts < $6{\times}10^6/kg$ (n=32); group 3: CD34 cell counts ${\geq}6{\times}10^6/kg$ (n=25). We analyzed the clinical characteristics, the peripheral blood (PB) parameters and the number of CD34 positive cells in the PB and their correlation with the yield of CD34 positive cells collected from the mobilized patients. The total number of leukapheresis sessions was 263 (mean: 3.55 session per patient), and the mean number of harvested CD34 positive cells per patient was $7.37{\times}10^6/kg$. The number of CD34 positive cells in product was significantly correlated with the number of platelet and CD34 positive cells in peripheral blood (P<0.05). The number of PB CD34 positive cells was the best significant factor for the quantity of harvested CD34 positive cells on the linear regression analysis (P<0.05). Many factors could influence the mobilization of peripheral blood stem cells. Platelet count and PB CD34 positive cells count were the two variables which remained to be significant in multivariate analysis. Therefore, the number of platelet and CD34 positive cells in peripheral blood on the day of harvest can be used as an accurate predictor for successful peripheral blood stem cell collection.

• Asian Oncology Nursing
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• v.8 no.1
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• pp.1-7
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• 2008

Purpose: Peripheral blood stem cell transplantation (PBSCT) has been widely used. The optimal time for collection is a critical factor to obtain proper counts of CD34 cell by peripheral blood stem cell collection (PBSC). The purpose of this study was to identify the factors influencing peripheral blood stem cell collection in order to figure out the more effective timing for PBSC. Method: The subjects of this study were 189 patients undergoing 3 leukapheresis from January 28, 2005 to December 31,2006. Group's characteristics, checkup opinion of pre-peripheral blood on the day of harvest & outcome of PBSC were analyzed and evaluated using SAS statistics program after grouping patients as below; group 1-CD34 cell counts $<2{\times}10^6/kg$ (n=97); group $2-2{\times}10^6/kg$ ${\leq}CD34$ cell counts $<4{\times}10^6/kg$ (n=26); group 3-CD34 cell counts ${\geq}4{\times}10^6/kg$ (n=63). Results: Based on outcome of peripheral blood stem cell according to diagnosis, acute myelocytic leukemia (AML) was 65.5% at Group 1, Lymphoma was 21.7% at Group 2 and multiple myeloma (MM) was 70.8% at Group 3. There were significant differences in CD34 cell counts according to diagnosis (p=0.00004). Type of cytokine mobilization according to diagnosis, Lenograsim was using 62.5% of MM & 38.2% of AML and filgrastim is using 22.0% of AML only. Circular peripheral blood CD34 cell counts prior to harvest was $258.1/{\mu}L$ at Group 3 which was much higher comparing to Group 1 ($10.5/{\mu}L$) and Group 2 ($39.9/{\mu}L$) (p<0.001). TNC counts of collected peripheral blood stem cell was $15.36{\times}10^6/kg$ at Group 3 and it's much higher than Group 2 ($13.16{\times}10^6/kg$) and Group 1 ($12.36{\times}10^6/kg$) (p=0.083). There was no significant difference in MNC counts inbetween 3 groups. Conclusions: Circular peripheral blood CD34+ cell counts prior to harvest was much higher at Group 3 than Group 1 and Group 2. Therefore, the number of CD34+ cells on the day of harvest can be used as an accurate predictor for peripheral blood stem cell.