• Title/Summary/Keyword: leukemia cell

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Time - and Concentration - Dependent Effects of Resveratrol on miR 15a and miR16-1 Expression and Apoptosis in the CCRF-CEM Acute Lymphoblastic Leukemia Cell Line

  • Azimi, Ako;Hagh, Majid Farshdousti;Talebi, Mehdi;Yousefi, Bahman;feizi, Abbas Ali Hossein pour;Baradaran, Behzad;Movassaghpour, Ali Akbar;Shamsasenjan, Karim;Khanzedeh, Taghi;Ghaderi, Abdol Hasan;Heydarabad, Milad Zadi
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.15
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    • pp.6463-6468
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    • 2015
  • Background: Chemotherapy is one of the common approaches in treatment of cancers, especially leukemia. However, drug resistance phenomena reduce the likelihood of treatment success. Resveratrol is a herbal compound which through complicated processes makes some selected cells sensitive to treatment and induction of apoptosis. In the present study, the effects of resveratrol on the expression of miR 15a and miR16-1 and apoptosis in the CCRF-CEM cell line were investigated. Materials and Methods: The CCRF-CEM cell line was cultured under standard conditions and changes in miR 15a and miR 16-1 expression were analyzed by real time-PCR technique, with attention to reveratrol dose and time dependence. Also, apoptosis is evaluated by flow cytometry using annexin V and PI. Results: CCRF-CEM cells underwent dose-dependent apoptotic cell death in response to resveratrol. MiR 15a and miR 16-1 expression was up-regulated after 24 and 48 hours resveratrol treatment (p<0.05). Conclusions: The results of our study indicate that resveratrol induces apoptosis in a time and dose-dependent manner in CCRF-CEM cells. Also, increased expression level of miR 16-1 and miR 15a by means of resveratrol in CCRF-CEM cells might have a role in apoptosis induction and predisposition. According to our results resveratrol can be regarded as a dietary supplement to improve efficacy of anti-leukemia therapies.

Activity of the Extracts from Polyporus umbellatus as a Apoptosis Inducer (저령의 암세포증식 억제효능)

  • 신유진;김봉선;서용준;조덕제;최원일;이용규
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.33 no.6
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    • pp.1074-1077
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    • 2004
  • The effect of gradient eluted fractions from Et$_2$O extracts of Polyporus umbellatus screlotium was investigated on the viability of leukemia cell lines, K-562, L-1210, HL-60 and U-937 cells. Among those fractions, fraction 2 showed mild cytotoxic effect on L-1210 and HL-60 cells. Fraction 3 showed cytotoxic effect on 4 cell lines, and cytotoxic effect was the most potent on L-1210. The hallmark of apoptosis, DNA fragmentation, also appeared by fraction 3 on L-1210 after 48 hr treatment. Furthermore, this fraction was shown to be able to induce cell death on L-1210 cells by the inhibition of DNA synthesis in [$^3$H]thymidine incorporation test. From these results, P. umbellatus involves a potent chemical component that inhibits the viability of leukemia cell lines, L-1210. Further studies about the components of fraction 3 to function as a apoptosis inducer are necessary.

Clinical outcomes of hematopoietic stem cell transplantation from HLA-matched parental donor in childhood acute leukemia (소아 급성 백혈병 환자에서 주조직적합항원 일치 부모자식간 조혈모세포 이식 후 임상경과)

  • Cha, Eun Young;Lee, Moon Hee;Lee, Jae Wook;Kwon, Young Joo;Lee, Dae Hyoung;Park, Young-Shil;Chung, Nak Gyun;Jeong, Dae Chul;Cho, Bin;Kim, Hack Ki
    • Clinical and Experimental Pediatrics
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    • v.51 no.1
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    • pp.67-72
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    • 2008
  • Purpose : In this study, we retrospectively analyzed the clinical outcomes of patients who underwent allogeneic hematopoietic stem cell transplantation (HSCT) grafted from HLA-matched parents. Methods : Seven children with acute leukemia (4 acute lymphoblastic leukemia, 3 acute myeloid leukemia) in first complete remission received allogeneic HSCT from their respective parents at the St. Marys Hospital between April, 1999 and October, 2005. The median age of patients at transplantation was 5 years (range, 1-11 years; 2 male, 5 female) and the median age of donors was 35 years (range, 30-41 years; 5 male, 2 female). We investigated the clinical outcomes such as engraftment, acute and chronic graft-versus-host disease (GVHD), transplant-related morbidity and mortality, relapse and survival. Results : Median time from transplantation to last follow-up was 69.5 months (range, 18.8-96.5 months). All patients were successfully engrafted, with a median time of 11 days (range, 10-16 days) and 26 days (range, 13-39 days) for neutrophil and platelet recovery, respectively. Grade II acute GVHD occurred in 3, and grade III acute GVHD in 1 of 7 recipients. Extensive chronic GVHD developed in 2, and limited chronic GVHD in 1 of 7 recipients. Death from transplant-related complications occurred in 1, and relapse occurred in 1 of 7 recipients. Estimated 5-year overall survival was $83{\pm}15%$. Conclusion : The clinical outcomes of recipients who underwent HSCT from HLA-matched parents were comparable to those of patients who received HSCT grafted from HLA-matched sibling donors in childhood leukemia. HLA typing of parents, as well as siblings will increase the likelihood of finding an HLA-matched family donor for patients who need HSCT.

Surface Marker Analysis in Acute Leukemias (백혈병의 면역학적 표지자검사의 결과분석)

  • Moon, Jin-Young;Lee, Chae-Hoon;Kim, Kyung-Dong;Kim, Chung-Sook
    • Journal of Yeungnam Medical Science
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    • v.14 no.2
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    • pp.359-369
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    • 1997
  • We studied the expression of the cell surface antigen associated with myeloid and lymphoid leukemias on bone marrow or peripheral blood blast cells from 153 leukemic patients including 61 cases of acute myelogenous leukemias(AML), 46 of acute lymphocytic leukemias(ALL) and 12 of acute leukemias. They were analyzed by direct or indirect immunofluorescence method for reactivity with the monoclonal antibodies to B cells(CD10, CD19, SmIg), T cells(CD2, CD5, CD7, CD3, CD4, CD8), myeloid antigen(CD13, CD14, CD33, CD61) and a nonspecific antigen, HLA-DR. Lymphoid associated markers detected on AML is CD7 32.8%, CD10 14.8%, CD5 13.1%, CD2 6.6% and CD19 1.6%. TdT was positive in 4.9% of AMLs. Hybrid leukemias were 8 cases out 61 AML cases and were mainly composed of monocytic lineage, M4 and M5a. Myeloid markers detected in ALL were CD13 2.2% and CD33 2.2%. In this study, immunologically classified ALLs were composed of 65.2% of CALLA (+) B precursor type, 10.9% of CALLA (-) B precursor pattern, 8.7% of T cell type, 2.2% of B cell type, 4.5% of mixed lymphoid lineage(B&T), 2.2% of undifferentiated leukemia, and 6.5% of hybrid leukemia. Twelve cases of acute leukemias ware finally diagnosed to be 5 cases of hybrid leukemia, 3 cases of B lineage, 3 case of T lineage and 1 case of mixed lymphoid(B&T) leukemia. In summary, we think the best method for typing acute leukemias is by using a combination of FAB classification and immunophenotying.

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Esculetin Induces Apoptosis through Caspase-3 Activation in Human Leukemia U937 Cells (Esculetin의 caspase-3 활성을 통한 U937 인체 혈구암세포의 세포사멸 유도)

  • Park, Cheol;Hyun, Sook-Kyung;Shin, Woo-Jin;Chung, Kyung-Tae;Choi, Byung-Tae;Kwon, Hyun-Ju;Hwang, Hye-Jin;Kim, Byung-Woo;Park, Dong-Il;Lee, Won-Ho;Choi, Yung-Hyun
    • Journal of Life Science
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    • v.19 no.2
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    • pp.249-255
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    • 2009
  • Esculetin, a coumarin compound, has been known to inhibit proliferation and induce apoptosis in several types of human cancer cells. However, the molecular mechanisms involved in esculetin-induced apoptosis are still uncharacterized in human leukemia cells. In this study, we have investigated whether esculetin exerts anti-proliferative and apoptotic effects on human leukemia U937 cells. It was found that esculetin could inhibit cell viability in a time-dependent manner, which was associated with the induction of apoptotic cell death such as increased populations of apoptotic- sub G1 phase. Apoptosis of U937 cells by esculetin was associated with an inhibition of Bcl-2/Bax binding activity, formation of tBid, down-regulation of X-linked inhibitor of apoptotic protein (XIAP) expression, and up-regulation of death receptor 4 (DR4) and FasL expression. Esculetin treatment also induced the degradation of ${\beta}$-catenin and DNA fragmentation factor 45/inhibitor of caspase-activated DNase (DFF45/ICAD). Furthermore, a caspase-3 specific inhibitor, z-DEVD-fmk, significantly inhibited sub-G1 phase DNA content, morphological changes and degradation of ${\beta}$-catenin and DEE45/ICAD. These results indicated that a key regulator in esculetin-induced apoptosis was caspase-3 in human leukemia U937 cells.

Hematological Change of Korean Native Goats Experimentally Infected with Bovine Leukemia Virus (Bovine Leukemia Virus에 실험감염된 한국재래산양의 혈액상의 변동)

  • 이필돈;김종호;전무형
    • Korean Journal of Veterinary Service
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    • v.18 no.1
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    • pp.1-21
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    • 1995
  • To elucidate pathogenesis of bovine leukemia virus(BLV) in Korean native goats, the goats experimentally infected with BLV were studied especially for the aspects of infectivity and hematological changes. The experimental goats were examined for 27 months by agar-gel immunodiffusion(AGID) test and syncytium formation assay. During this period, changes of total leucocyte, absolute Iymphocyte and atypical Iymphocyte were examined, and the distribution of surface immunoglobulin ( sIg ) -bearing cells and rosette forming cell (RFC) in the peripheral Iymphocyte were also investigated. By indirect immunofluorescence (IFA) and complement dependent antibody cytotoxicity (CDAC) assay using monoclonal antibody(Mab) against bovine leukosis tumor-associated anti-gen(BL-TAA), changes of BL-TAA positive Iymphocyte in peripheral blood were measured. The results obtained through the experiment were summarized as follows. 1. Antibody titers were measured by AGID using gP51 and P24 antigens. The animals were serologically converted at 2 months post-inoculation(pi) in gP51 antigen, whereas sero-converted at 4 months pi in P24 antigen. In comparison with antibody titers for gP51, P24 antigen showed lower titers throughout the trial period. 2. The peripheral lymphocytes from all of the infected goats, as co-cultivated with F8l cells manifested syncytial formation at 4 months pi. 3. On counting total leucocyte, Iymphocyte and atypical Iymphocyte, two out of four infected goats showed normal distribution, while No 2 of the remaining two revealed temporal and No 3, Persistant increasing number of the cells. 4. The optimal condition of rosette formation of the peripheral Iymphocyte of normal Korean native goats was shown in the sheep erythrocyte treated with 0.1M AET for 30 nun at $37^{\circ}C$. When the Iymphocytes were treated in nylon wool column, the number of sIg-bear-ing cell were increased in the nylon wool adherent cells, but RFC was increased in the non-adherent cells. Of the infected goats, No 2 and No 3 showed significantly increasing number of sIg-bearing cells at 18 months pi. 5. The Iymphocytes of No 2 and No 3 goats reacted positively in IFA using Mab against BL-TAA at 12 months pi and 18 months pi, respectively. In CDAC test, all of four infected goats revealed positive reaction at 24 months pi. The higher positive rates were observed in No 2 and No 3 as compared with the remainders.

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Cytotoxic Effects on Human Cancer Cells and Apoptosis of a Sesquiterpene Lactone from Saussure lappa

  • Jin, Mirim;Ryu, Jae-Ha;Ryu, Shi-Yong;Chung, Kyu-Sun
    • Biomolecules & Therapeutics
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    • v.8 no.1
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    • pp.22-26
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    • 2000
  • In order to study the cytotoxic properties of sesquitepenes, dehydrocostus lactone (DL) and costunolide from Saussurea lappa, cytotoxicity was measured by SRB method using various human cancer cell lines. Dehydrocostus lactone(DL) and costunolide exhibited significant cytotoxicity against A-549, SK-OV-3, SK-MEL-2, XF-498 and HCT 15 cells. The U937 human leukemia cells treated with DL showed several apoptotic evidences like chromosome condensation and formation of apoptotic bodies. From the results of FACS analysis, early apoptosis was observed by phosphatidylserine externalization detected by annexin V-FITC. Furethermore, these studies determined hypodiploid contents and effects on the cell phase distribution of DL-treated U937 cells. After exposure of U937 cells to $30\mu\textrm{M}$ DL effectively led to G2/M modified cell cycle distribution within 24hr. These observations suggest that DL can be used efficiently for the cancer treatment.

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Growth Inhibition of Red Ginseng Extracts Against Human Tumor Cell Line by Clonogenic Assay (Clonogenic assay을 이용한 홍삼추출물의 인체종양세포에 대한 증식억제효과)

  • Kim, Chang-Han;Lee, Gyeong-Ho;Byeon, Eun-Gyeong
    • Journal of Ginseng Research
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    • v.22 no.3
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    • pp.188-192
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    • 1998
  • We established the model of clonogenic assay with human tumor cell line such as Calu-3 (lung carcinoma), HEC- lB (endometrial adenocarcinoma) , HEp-2 (larnyx carcinoma), Hs-5787 (breast carcinoma), K-562 (chronic myelogenous leukemia), SF-188 (brain carcinoma), SNU-1 (stomach carcinoma) and WiDr (colon carcinoma) . We investigated growth inhibition of solvent (EtOH, MeOH) and water (100$^{\circ}C$, 121$^{\circ}C$) extracts from Korean red ginseng by clonogenic assay. The results of clonogenic assay showed that EtOH extract had growth inhibition against Calu-3, SF-188 and SNU-1, MeOH extract had growth inhibition against Calu-3, Hs-5787, K-562, and WiDr, but water extract at 100$^{\circ}C$ and water extract at 121$^{\circ}C$ had not growth inhibition against used cell lines.

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Comparison of the Antihistaminic Activity Between Cetirizine Enantiomers

  • Park-Choo, Hae-Young;Choi, Sun-Ok;Lee, Seok-Ho
    • Biomolecules & Therapeutics
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    • v.9 no.4
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    • pp.282-284
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    • 2001
  • The antiallergic drug, cetirizine, inhibits the histamine release from a rat basophilic leukemia (RBL-2H3) cell line, which is frequently used as a mast cell model. By investigating inhibitory activities of (+)- and (-)-cetirizine in RBL-2H3 cells on the histamine release, we aimed to evaluate the effect of their structual characteristics on the antihistamine activity. The study on RBL-2H3 cell has clearly demonstrated that the (-)-cetirizine is significantly more potent than the (+)- or the racemic cetirizine, although there was no difference in pharmacokinetics between (+)- and (-)-cetirizine in rats.

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Specific Cell-Signal Targets for Cancer Chemotherapy

  • Aszalos, Adorjan
    • Archives of Pharmacal Research
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    • v.25 no.1
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    • pp.1-10
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    • 2002
  • Attempts to develop drugs, specific for cancer cells, are dealt here according to the intended cell-target. While many target specific drugs were developed, they reach only moderate successes in clinics for reasons, such as, delivery problem, lack of in vivo efficacy or toxicity. However, recent efforts focusing on the diversity of tyrosine kinases, participating in cell-signal transduction, brought fruit. The first such drug, Givec, approved by the USFDA recently, is used in clinics with great success to threat CML. The drug inhibits tyrosin kinase of bcr-abl, c-abl and v-abl. Work is progressing on other tyrosin kinase inhibitors and on other type of specific cancer cell signal protein inhibitors. These efforts are hoped to yield better cures for cancer in the near future.