• Journal of Yeungnam Medical Science
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• 제32권2호
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• pp.98-101
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• 2015

Bronchiolitis obliterans (BO), which is associated with graft-versus-host disease after allogenic hematopoietic stem cell transplantation, is a major obstacle to survival after bone marrow transplantation due to its gradual progress, eventually leading to respiratory failure. Pumpless extracorporeal interventional lung assist (iLA) is effective in treatment of reversible hypercapnic respiratory failure. In this paper, we present a 23-year-old female patient who underwent allogeneic peripheral blood stem cell transplantation (PBSCT) for acute lymphocytic leukemia. After 6 months, she complained of shortness of breath and was diagnosed with BO. Five months later, she developed an upper respiratory tract infection that worsened her BO and caused life-threatening hypercapnia. Since mechanical ventilation failed to eliminate $CO_2$ effectively, iLA was applied as rescue therapy. Her hypercapnia and respiratory acidosis showed significant improvement within a few hours, and she was successfully weaned off iLA after 12 days. This is the first case report of iLA application for temporarily aggravated hypercapnia of PBSCT-associated BO followed by successful weaning. This rescue therapy should be considered in ventilator-refractory reversible hypercapnia in BO patients.

• Asian Pacific Journal of Cancer Prevention
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• 제16권8호
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• pp.3509-3515
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• 2015

Background: Diallyl disulfide (DADS) may exert potent anticancer action both in vitro and in vivo. Although its effects on cancer are significant, the underlying mechanisms remain unknown. In this study, we sought to elucidate possible links between DADS and pyruvate kinase (PKM2). Materials and Methods: $KG1{\alpha}$, a leukemia cell line highly expressing PKM2 was used with a cell counting kit (CCK)-8 and flow cytometry (FCM) to investigate the effects of DADS. Relationships between PKM2 and DADS associated with phosphorylation of EGFR, ERK1/2 and MEK, were assessed by western blot analysis. Results: In $KG1{\alpha}$ cells highly expressing PKM2, we found that DADS could affect proliferation, apoptosis and EGFR/ERK/PKM2 signaling pathways, abrogating EGF-induced nuclear accumulation of PKM2. Conclusions: These results suggested that DADS suppressed the proliferation of $KG1{\alpha}$ cells, providing evidence that its proapoptotic effects are mediated through the inhibition of EGFR/ERK/PKM2 signaling pathways.

• 동의생리병리학회지
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• 제16권3호
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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.

• Preventive Nutrition and Food Science
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• 제8권2호
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• pp.113-118
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• 2003

We recently extracted lignans such as matairesinol and 2-hydroxyarctigenin from safflower seeds and found that they exhibit a potent cytotoxic effect on human promyleocytic leukemia HL-60 cells. In this study, we investigated whether mechanisms of the matairesinol-induced cell death are associated with the programmed cell death, apoptosis. Matairesinol dose-dependently reduced viability of HL-60 cells with an IC/sun 50/ value of 60 $\mu$M. Staining of cells with Hoechst 33342 revealed distinct morphological features of apoptosis, such as the nuclei broken into chromatin containing fragments of various sizes in the cells exposed to 100 $\mu$M matairesinol for 24 hr. Agarose gel electrophoresis of DNA from the cells treated with matairesinol showed internucleosomal DNA degradation into oligonucleosomal sizes. DNA ladder like patterns were easily detected after treatment with matairesinol concentrations ranging from 10 to 100 $\mu$M after 24 hr. In cells treated with 100 $\mu$M matairesinol for differing time periods, the DNA ladder was detectable from 6 hr onward. A time course histogram of the DNA content analyzed by flow cytometry revealed a rapid increase in subdiploid cells and a concomitant decrease in diploid cells exposed to 100 $\mu$M matairesinol. These results indicate that matairesinol-induced HL-60 cell death was due to the DNA damage and apoptosis.

• 동의생리병리학회지
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• 제21권4호
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• pp.940-945
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• 2007

We have examined the induction of HL-60 cell differentiation by treatment of 2-chloromethyl-1-dihydroxyphosphinyl pyrrolidine(2C-1DPP), which is derivative of piperidine and pyrrolidine by ${\alpha}-phosphoramidoakylation$ reaction. It was observed that HL-60 cell proliferation was dose- and time-dependently inhibited by treatment with 2C-1DPP. 2C-1DPP treatment caused a significant change in NBT reduction and enhanced ATRA-induced NBT reduction. Treatment of 2C-1DPP to HL-60 cells increased only CD11b expression in the cells, and also increased markedly G0/G1 stage arrest of HL-60 cells. These results can suggest that 2C-1DPP induced the differentiation of HL-60 cells to granulocytes lineage and enhanced ATRA-induced differentiation. Moreover, DNA expression levels of p27 were up-regulated during 2C-1DPP-dependent HL-60 cell differentiation. Our results suggest that 2C-1DPP have potential as a therapeutic agent in human leukemia.

• Asian Pacific Journal of Cancer Prevention
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• 제15권12호
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• pp.4773-4780
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• 2014

Background: To investigate the effects of small interference RNA (siRNA) targeting BCR/ABL mRNA on proliferation and apoptosis in the K562 human chronic myeloid leukemia (CML) cell line and to provide a theoretical rationale and experimental evidence for its potential clinical application for anti-CML treatment. Materials and Methods: The gene sequence for BCR/ABL mRNA was found from the GeneBank. The target gene site on the BCR/ABL mRNA were selected according to Max-Planck-Institute (MPI) and rational siRNA design rules, the secondary structure of the candidate targeted mRNA was predicted, the relevant thermodynamic parameters were analyzed, and the targeted gene sequences were compared with BLAST to eliminate any sequences with significant homology. Inhibition of proliferation was evaluated by MTT assay and colony-formation inhibiting test. Apoptosis was determined by flow cytometry (FCM) and the morphology of apoptotic cells was identified by Giemsa-Wright staining. Western blotting was used to analyze the expression of BCR/ABL fusion protein in K562 cells after siRNA treatment. Results: The mRNA local secondary structure calculated by RNA structure software, and the optimal design of specific siRNA were contributed by bioinformatics rules. Five sequences of BCR/ABL siRNAs were designed and synthesized in vitro. Three sequences, siRNA1384, siRNA1276 and siRNA1786, which showed the most effective inhibition of K562 cell growth, were identified among the five candidate siRNAs, with a cell proliferative inhibitory rate nearly 50% after exposure to 12.5nmol/L~50nmol/L siRNA1384 for 24,48 and 72 hours. The 50% inhibitory concentrations ($IC_{50}$) of siRNA1384, siRNA1276 and siRNA1786 for 24hours were 46.6 nmol/L, 59.3 nmol/L and 62.6 nmol/L, respectively, and 65.668 nmol/L, 76.6 nmol/L, 74.4 nmol/L for 72 hours. The colony-formation inhibiting test also indicated that, compared with control, cell growth of siRNA treated group was inhibited. FCM results showed that the rate of cell apoptosis increased 24 hours after transfecting siRNA. The results of annexinV/PI staining indicated that the rate of apoptosis imcreased (1.53%, 15.3%, 64.5%, 57.5% and 21.5%) following treamtne with siRNAs (siRNA34, siRNA372, siRNA1384, siRNA1276 and siRNA1786). Morphological analysis showed td typical morphologic changes of apoptosis such as shrunken, fragmentation nucleus as well as "apoptotic bodies" after K562 cell exposure to siRNA. Western blot analysis showed that BCR/ABL protein was reduced sharply after a single dose of 50nmol/L siRNA transfection. Conclusions: Proliferation of K562 cells was remarkbly inhibited by siRNAs (siRNA1384, siRNA1276 and siRNA1786) in a concentration-dependent manner in vitro, with effective induction of apoptosis at a concentration of 50 nmol/L. One anti-leukemia mechanism in K562 cells appeared that BCR/ABL targeted protein was highly down-regulated. The siRNAs (siRNA1384, siRNA1276 and siRNA1786) may prove valuable in the treatment of CML.

• Clinical and Experimental Reproductive Medicine
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• 제28권1호
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• pp.41-46
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• 2001

Objective: To determine the effects of leukemia inhibitory factor (LIF) on embryonal development in in vitro culture. Methods: This is designed in vitro model using eggs from mouse. The eggs from mouse were assigned 29 for control group, 53 for 20 ng/ml of LIF, 88 for 40 ng/ml of LIF, 68 for 80 ng/ml of LIF respectively for in vitro fertilization. And 26 fertilized eggs at 2 cell stage from mouse also were assigned. The mouse embryos of all groups were cultured in medium supplemented with LIF in different concentrations, whereas the eggs in control group was cultured in medium without supplement of LIF. Results: At 72 hours culture of eggs from in vitro fertilization, there was a slight increas in rate of embryonal development to morula in both LIF-20 and LIF-40 as results of 64.15% and 75% respectively, while 42.65% in inferior rate of LIF-80, compare with 51.72% in control group. But the difference between these each groups were not significant in statistically ($p{\le}0.05$). And after 96 hours culture of eggs, the rates blastocyst formation was significantly higher in both LIF-20 and LIF-40 as 56.6% and 63.63% than those in control and LIF-80 as 44.83% and 35.29% respectively. On culturing eggs from in vivo fertilization, the rates of blastocyst formation was significantly not only higher as 85% and 81.81% respectively in medium supplemented with LIF-40 and LIF-80 than 42.3% in LIF-20 but also embryonal cell viability were remakedly improved at 96 hours after culture. Conclusion: The LIF in low dose is embryotrophic, but LIF in high dose is embryotoxic on eggs from in vitro fertilization. Whereas on culturing eggs from in vivo fertilization, LIF is more beneficial with dose dependent in high concentration.

• 한국식품저장유통학회지
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• 제12권1호
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• pp.80-85
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• 2005

일상생활에서 식용 또는 약용으로 이용되고 있는 12종의 버섯 추출물을 제조하여 이들 추출물의 항산화능 검색과 함께 인간유래의 혈액암 세포주 및 정상 임파구세포의 성장에 미치는 영향에 대하여 조사하였다. 그 결과, 향버섯, 번데기동충하초, 만가닥버섯, 아가리쿠스, 영지버섯, 표고버섯 메탄올 추출물에서 $30\~60\%$정도의 DPPH radical 소거 활성을 보였고, 목이버섯, 그물버섯, 새송이버섯에서 $10\~30\%$의 활성을 보였다. 또한 chinese hamster V79 cells에서 만가닥 버섯, 번데기동충하초, 향버섯 메탄올추출물의 경우 H2O2로 유도된 세포 독성에 대한 $39\~53\%$ 정도의 유의적인 생존율을 나타내었다. 그리고 인간유래 혈액암세포인 HL6O과 U937에 대해 향버섯, 만가닥버섯, 번데기동충하초, 아가리쿠스, 영지버섯 추출물들이 높은 증식 억제 활성이 보였다. 특히 버섯 메탄올추출물 1.0 mg/mL 처리시 HL 60에 대해 향버섯이 $70.5\%$로 가장 높은 저해율을, U937에 대해서는 번데기동충하초가 $81.5\%$의 가장 높은 저해율을 나타내었다. 그리고 버섯 열수추출물들은 메탄올추출물보다 낮은 저해 활성을 보였다. 그러나 모든 버섯추출물들은 인간의 정상 임파구세포에 대해 $95\%$ 이상의 높은 생존율을 나타내어, 정상 세포에 대한 성장 저해 효과가 없음을 보여주었다. 번데기동충하초, 아가리쿠스, 만가닥버섯, 영지버섯, 향버섯 추출물은 항산화 할성 및 혈액암 세포주에 대한 증식 억제 활성이 높음을 확인할 수 있었다.

• Asian Pacific Journal of Cancer Prevention
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• 제14권12호
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• pp.7537-7542
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• 2013

Background: Terpinen-4-ol, a monoterpene, is found as the main component of essential oil extracts from many plants. In this study apoptotic and autophagic types of cell death induced by terpinen-4-ol and associated mechanisms were investigated in human leukemic HL-60 cells. Materials and Methods: The cytotoxicity of human leukemic U937 and HL-60 cells was determined by MTT assay. Cytochrome c release, expression of Bax, Bcl-2, Bcl-xl and cleaved Bid were determined by Western blotting. Cell morphology was examined under a transmission electron microscope. LC3-I/II, ATG5 and Beclin-1 levels were detected by immunoblotting. Results: Terpinen-4-ol exhibited cytotoxicity to human leukemic HL-60 but not U937 cells. The apoptotic response to terpinen-4-ol in HL-60 cells was due to induction of cytochrome c release from mitochondria and cleavage of Bid protein after the stimulation of caspase-8. There was a slightly decrease of Bcl-xl protein level. The characteristic cell morphology of autophagic cell death was demonstrated with multiple autophagosomes in the cytoplasm. At the molecular level, the results from Western blot analysis showed that terpinen-4-ol significantly induced accumulation of LC3-I/II, ATG5 and Beclin-1, regulatory proteins required for autophagy in mammalian cells. Conclusions: Terpinen-4-ol induced-human leukemic HL-60 cell death was via both autophagy and apoptosis.

• 한국발생생물학회지:발생과생식
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• 제21권2호
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• pp.139-150
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• 2017

Metformin is the most commonly prescribed anti-diabetic drug with relatively minor side effect. Substantial evidence has suggested that metformin is associated with decreased cancer risk and anticancer activity against diverse cancer cells. The tyrosine kinase inhibitor imatinib has shown powerful activity for treatment of chronic myeloid leukemia and also induces growth arrest and apoptosis in colorectal cancer cells. In this study, we tested the combination of imatinib and metformin against HCT15 colorectal cancer cells for effects on cell viability, cell cycle and autophagy. Our data show that metformin synergistically enhances the imatinib cytotoxicity in HCT15 cells as indicated by combination and drug reduction indices. We also demonstrate that the combination causes synergistic down-regulation of pERK, cell cycle arrest in S and $G_2/M$ phases via reduction of cyclin B1 level. Moreover, the combination resulted in autophagy induction as revealed by increased acidic vesicular organelles and cleaved form of LC3-II. Inhibition of autophagic process by chloroquine led to decreased cell viability, suggesting that induction of autophagy seems to play a cell protective role that may act against anticancer effects. In conclusion, our present data suggest that metformin in combination with imatinib might be a promising therapeutic option in colorectal cancer.