• Asian Pacific Journal of Cancer Prevention
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• v.15 no.20
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• pp.8715-8718
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• 2014

Background: ABVD (doxorubicin, bleomycin, vinblastine (Vb) and dacarbazine) is the standard regimen in Hodgkin's lymphoma (HL).Vincristine (O) is a mitotic spindle agent like Vb. We aimed to evaluate the efficacy and safety of O as a part of ABOD in HL. Materials and Methods: Patients who had ABOD were enrolled. Stage I-II HL were evaluated for unfavorable risk factors according to NCCN. National Cancer Institute Common Toxicity Criteria was used for toxicity. Results: Seventy-nine HL patients in our center between 2003 and 2007 were evaluated retrospectively. Median follow-up was 54 months. Most of the patients were male in their third decade. Median ABOD cycles were 6 (2-8). Primary refractory disease rate was 17.7% whereas it was 5.1% for early relapse and 5.1% for late relapse disease. Response rates were as 82.3% for complete response, 11.4% for partial response, 5.1% for stable disease and 1.3% for progressive disease. Half of relapsed patients had autologous stem cell transplantation. Estimated 5-year failure-free survival was 71% and significantly longer in early stage patients without risk factors, bulky disease or radiotherapy (RT) (p=0.05, p<0.0001, p=0.02; respectively). Estimated 5-year overall survival was 74% and significantly longer in those who had no RT (p=0.001). Dose modification rate was 5.1% and chemotherapy delay rate was 19%. There were no toxicity-related deaths. Conclusions: ABOD seems to be effective with managable toxicity in HL, even in those with poor prognostic factors.

• Archives of Pharmacal Research
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• v.21 no.1
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• pp.41-45
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• 1998

Hypericin, a photosensitizing plant pigment, was found to be a potent inducer of differentiation of human myeloid leukemia U-937 cells. At a concentration of $0.2{\mu}M$, hypericin exhibited 50% growth inhibition. An effect on cell differentiation by hypericin was assessed by its ability to induce phagocytosis of latex particles, and to reduce nitroblue tetrazolium (NBT). Approximately 51% of $0.2{\mu}M$ hypericin-treated cells were stained with NBT and 63% showed phagocytic activity. In order to establish whether hypericin induces differentiation of U-937 cells to macrophage or granulocyte, esterase activities and cell sizes were measured. When U-937 cells were treated with $0.2{\mu}M$ and $0.15{\mu}M$ of hypericin, the .alpha.-naphthyl acetate esterase activity was increased by 38.4% and 48.1%, respectively, but naphthol AS-D chloroacetate esterase activity was not influenced. The size of hypericin-treated cells in terms of cell mass was larger than that observed in untreated cells as determined by flow cytometry. Protein kinase C (PKC) inhibitor, NA-382, decreased the NBT reducing activity of hypericin, whereas a cAMP-dependent protein kinase A (PKA) inhibitor, H-89, did not show any influence on the differentiations. These results indicate that hypericin triggers differentiation toward monocyte/macrophage lineage by PKC stimulation.

• Biomolecules & Therapeutics
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• v.27 no.1
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• pp.41-47
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• 2019

The apoptotic effects of shikonin (5,8-dihydroxy-2-[(1R)-1-hydroxy-4-methylpent-3-enyl]naphthalene-1,4-dione) on the human colon cancer cell line SNU-407 were investigated in this study. Shikonin showed dose-dependent cytotoxic activity against SNU-407 cells, with an estimated $IC_{50}$ value of $3{\mu}M$ after 48 h of treatment. Shikonin induced apoptosis, as evidenced by apoptotic body formation, sub-G_1$ phase cells, and DNA fragmentation. Shikonin induced apoptotic cell death by activating mitogen-activated protein kinase family members, and the apoptotic process was mediated by the activation of endoplasmic reticulum (ER) stress, leading to activation of the $PERK/elF2{\alpha}/CHOP$ apoptotic pathway, and mitochondrial $Ca^{2+}$ accumulation. Shikonin increased mitochondrial membrane depolarization and altered the levels of apoptosis-related proteins, with a decrease in B cell lymphoma (Bcl)-2 and an increase in Bcl-2-associated X protein, and subsequently, increased expression of cleaved forms of caspase-9 and -3. Taken together, we suggest that these mechanisms, including MAPK signaling and the ER- and mitochondria-mediated pathways, may underlie shikonin-induced apoptosis related to its anticancer effect.

• Journal of Dairy Science and Biotechnology
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• v.22 no.2
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• pp.99-106
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• 2004

Tumor cell proliferation inhibitory, antioxidative activities and glutathione content were analyzed in a variety of spore forming lactic acid bacteria. Tumor cell proliferation inhibitory activity varied widely depending upon the strains of spore forming lactic acid bacteria and the types of carcinoma cell lines(0${\simn}$56.7%), Bacillus coagulans KTCC3625 has shown a marked antipro-liferative effect against the carcinoma cells and NCL-H1299 human lymphoma cell line tended to be least affected by the spore forming lactic acid bacterial cell extracts. Antioxidative activity analyzed in the lipid peroxidation occurred in all the test strains varied on the strains(5.0 to 52.0%) an extensively high degree of antioxidative activity was demonstrated by three strains of Bacillus coagulans KTCC3625, Bacillus coagulans KTCC1015 and Lactobacillus sporogens CU 815. Concentrations of glutathione were highest in a strain of Lactobacillus sporogenes CU 815 followed by Sporo-lactobacillus inulinus ATCC13538 (5.34 to 8.19 mol/g). Spearmans' rank correlation quotient between cellular GSH levels and linoleic acid peroxidation inhibitory effects of the spore forming lactic acid bacteria revealed highly significant correlation quotient of 0.78. Spearmans' rank correlation quotient between the Caski human cervix carcinoma cell proliferation inhibitory activity and the linoleic acid peroxidation inhibitory effects of the spore forming lactic acid bacteria and that between Caski carcinoma cell proliferation inhibitory activity and the cellular GSH levels were shown to be 0.29 and 0.32,respectively, which means an insignificant positive correlation however.

• Journal of the Korean Society of Food Science and Nutrition
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• v.27 no.1
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• pp.141-148
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• 1998

This study describes the effects of 1,25-dihydroxyvitamin D3[1,25(OH)2D3, calcitriol] analog, 1,25(OH)2-16ene-23yne-D3 on proliferatin and differentiatin of the human histiocytic lymphoma cell line U937. This paper also describes the effects of 1,25(OH)2-16ene-23yne-D3 on ${\gamma}$-interferon(IFN-${\gamma}$) synthesis by phytohemagglutinin-activated peripheral blood lymphocytes(PBLs). In the present investigation, 1,25(OH2)-16ene-23yne-D3 was compared to the natural metablite of vitamin D3, 1,25(OH)2D3. 1,25(OH)2-16ene-23yne-D3 was more potent than 1,25(OH)2D3 for inhibition of proliferation and induction of differentiation of U937 cells, Its effects on inhibition of proliferation was about 30-fold more potent than 1,25(OH)2D3. On induction of differentiation as measured by nonspecific esterase (NSE) activity and morphologic change, this analog morphologically and functionally differentiated U937 cells to monocyte-macrophage phenotype showing a decrease of N/C ration in Giemsa staining and the increase of adherence ability of surface. After 3 days in culture, a more significant supression of IFN-${\gamma}$ synthesis analog on supression of IFN-${\gamma}$ synthesis was a dose-dependent manner, with peak activity at 10-7M. The strong direct effects of 1,25(OH)2-16ene-23yne-D3 on cell proliferation and cell differentiation, make this compound an interesting candidate for clinical studies for several types of malignancies, and the effects on supression of IFN-${\gamma}$ synthesis provide the further evidence for a role of 1,25(OH)2-16ene-23yne-D3 in immunoregulation.

• Proceedings of the Korea Society of Environmental Toocicology Conference
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• 2003.05a
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• pp.185-185
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• 2003

To develope the novel anti-allergic drug, many sophoricoside derivatives were synthesized. Among these derivatives, JSH-II-3, JSH-Ⅵ-3, JSH-Ⅶ-3, and JSH-Ⅷ-3 were selected and subjected to high throughput toxicity screening (HTTS) because they revealed strong IL-5 inhibitory activity and limitation of quantity. Mouse lymphoma thymidine kinase (tk$\^$+/-/) gene assay (MOLY) and single cell gel electrophoresis (Comet) assay in mammalian cells were used as HTTS tool in our laboratory. In MOLY assay, JSH-Ⅶ-3 at 50 ∼ 6 $\mu\textrm{g}$/ml concentrations was not shown significant mutagenic effect in the absence and presence of S-9 metabolic activation system. However, the concentration of ISH-II-3, 38 $\mu\textrm{g}$/ml, induced increased mutation frequency (MF) in the presence of S-9 metabolic activation system. Also in comet assay, DNA damage was not observed in JSH-Ⅵ-3 and JSH-Ⅶ-3, wherase concentration of 32.8 $\mu\textrm{g}$/ml in JSH-II-3 and 13.9 $\mu\textrm{g}$/ml in JSH-Ⅶ-3 were induced DNA damage in the absence of S-9 metabolic activation system. Therefore, we suggest that JSH-Ⅵ-3 and JSH-Ⅶ-3 have no genotoxic effects but JSH-II-3 and JSH-Ⅷ-3 induce some mutagenicity and DNA strand breaks in mouse lymphoma cell line used this study.

• Korean Journal of Acupuncture
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• v.37 no.2
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• pp.97-103
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• 2020

Objectives : Parkinson's disease, a progressive neurodegenerative disease, is caused by the loss of dopaminergic neurons in the substantia nigra. There is no clear treatment or remedy for Parkinson's disease; therefore, the development of novel therapies related to anti-inflammatory and antioxidant effects is required. This study was performed to evaluate the neuroprotective effect of water extracts from Cervi Cornu (CC) in dopaminergic cells. Methods : We studied effects of CC on apoptosis, cell death and inflammation in SH-SY5Y neuroblastoma cells treated by methylpyridinium ion (MPP+). SH-SY5Y cell line was treated with CC for 24 hours and then 500 μM MPP+ for 18 hours. Results : Cervi Cornu treatment inhibited the decrease in tyrosine hydroxylase (TH) expression and decreased the activation of inflammatory factors mitochondrial cytochrome C oxidase (COX2) and inducible NO synthase (iNOS) against MPP+ neurotoxicity. Apoptosis factors BCL2 associated X, apoptosis regulator (BAX) levels were decreased and B-Cell CLL/Lymphoma 2 (BCL2) levels were increased. Conclusions : These results suggest that CC treatment had neuroprotective effects in the SH-SY5Y neuroblastoma cells against toxicity induced by MPP+. The results suggest new possibilities of CC for the treatment of Parkinson's disease.

• The Korean Journal of Mycology
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• v.27 no.4 s.91
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• pp.312-317
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• 1999

In order to study the antitumoral effect of meju extracts, which was made with a single inoculum of the microorganism, the cytotoxicity effects on several human leukemia cells such as promyelocytic leukemia cell (HL60), histiocytic lymphoma cell (U937) and acute T-cell leukemia Jurkat cell, and lymphocyte were analyzed by MTT assay. Twenty one microbes, mainly fungal genera, were isolated from Korean traditional mejus of different regions. From those collected isolates, meju was manufactured and extracted with 80% methanol, respectively. Meju methanol extracts exhibited low activites in cytotoxicity tests on HL60 cell, but high antitumoral effects of meju methanol extracts were shown on U937 and Jurkat cells. Meju methanol extracts made with a genera of Mucor, Absidia and Aspergillus showed prominant cytotoxic activities, especially. However all these extracts had no inhibitory effects on the cell growth of lymphocyte under the same conditions.

• YAKHAK HOEJI
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• v.42 no.4
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• pp.345-352
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• 1998

Praecoxin A, an ellagitannin, purified from Alnus hirsuta var.microphlla was evaluated on the antitumor activity. Praecoxin A had the significant cytotoxicity to s ix tumor cell lines: human chronic myelogenous leukemia K-562, human promyelocytic leukemia HL-60, mouse leukemia P388, mouse lymphocytic leukemia L-1210, sarcoma-l8O, mouse lymphoma L5178Y except L-1210. And the most sensitive cell line was K-562 ($ED_{50}=2.43{\mu}g/ml$). The $ED_{50} of praecoxin A against HL-60, P388, L-1210, sarcoma7l8O and L5178Y were 6.28, 8.66, 10.00, 7.01, $9.32{\mu}g/ml$, respectively. Praecoxin A showed the increasing effect in life span by 36.8% on the 1st day after treatment of 10mg/kg in mice bearing sarcoma-180 tumor cells (ascitic form) via NCI (National Cancer Institute, U.S.A.) protocol in vivo assay. As a result, praecoxin A is considered to show the antitumor activity.

• Journal of Korean Neurosurgical Society
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• v.49 no.1
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• pp.13-19
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• 2011

Objective: The purpose of this study is to investigate the combined effects of ginkgo biloba extract, ginkgolide A and B and aspirin on SK-N-MC, human neuroblastoma cell viability and mRNA expression of growth associated protein43 (GAP43), Microtubule-associated protein 2 (MAP2), B-cell lymphoma2 (Bcl2) and protein53 (p53) gene in hypoxia and reperfusion condition. Methods: SK-N-MC cells were cultured with Dulbecco's Modified Eagle's Medium (DMEM) media in $37^{\circ}C$, 5% $CO_2$ incubator. The cells were cultured for 8 hours in non-glucose media and hypoxic condition and for 12 hours in normal media and $O_2$ concentration. Cell survival rate was measured with Cell Counting Kit-8 (CCK-8) reagent assay. Reverse transcriptase polymerase chain reaction (RT-PCR) was used to estimate mRNA levels of GAP43, MAP2, Bcl2, and p53 genes. Results: The ginkgolide A and B increased viable cell number decreased in hypoxic and reperfused condition. The co-treatment of ginkgolide B with aspirin also increased the number of viable cells, however, there was no additive effect. Although there was no increase of mRNA expression of GAP43, MAP2, and Bcl2 in SK-N-MC cells with individual treatment of ginkgolide A, B or aspirin in hypoxic and reperfused condition, the co-treatment of ginkgolide A or B with aspirin significantly increased GAP43 and Bcl2 mRNA levels. In MAP2, only the co-treatment of ginkgolide A and aspirin showed increasing effect. The mRNA expression of p53 had no change in all treating conditions. Conclusion: This study suggests that the combined treatments of Ginkgo biloba extracts and aspirin increase the regeneration of neuroblastoma cells injured by hypoxia and reperfusion.