• Clinical and Experimental Pediatrics
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• v.46 no.12
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• pp.1260-1265
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• 2003

Purpose : In 1970, the Berlin-Frankfurt-Munster(BFM) group introduced an intensification therapy after remission induction to reduce relapse of acute lymphoblastic leukemia(ALL) in childhood. Delayed intensification(DI) phase has been included for treatment of ALL in our hospital since the mid-1990s. The purpose of this study is to evaluate the outcome with vs. without DI phase and the outcome with two vs. one DI phase for intermediate risk patients. Methods : One hundred and thirty nine children with ALL who were treated at the Department of Pediatrics of Wonju Christian Hospital and Yonsei University Medical Center between March, 1990 and July, 2002 were analysed retrospectively. Results : Thirty-eight patients were treated with a DI phase, and 101 patients were treated without a DI phase. Among the DI patients, seven patients were treated with a double DI phase. Five-year overall survival(OS) in the low, intermediate, and high risk groups were 68%, 66% and 58%, respectively. 5-year OS in DDI, DI, and control were 95%, 86% and 40%, respectively. In the low risk group, 5-year event free survival(EFS) in DI, and control were 94% and 58%, respectively. Conclusion : Delayed intensification improved EFS on childhood ALL in all risk groups.

• Journal of Ginseng Research
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• v.42 no.2
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• pp.165-174
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• 2018

Background: Extended endoplasmic reticulum (ER) stress may initiate apoptotic pathways in cancer cells, and ER stress has been reported to possibly increase tumor death in cancer therapy. We previously reported that caspase-8 played an important role in compound K-induced apoptosis via activation of caspase-3 directly or indirectly through Bid cleavage, cytochrome c release, and caspase-9 activation in HL-60 human leukemia cells. The mechanisms leading to apoptosis in A549 and SK-MES-1 human lung cancer cells and the role of ER stress have not yet been understood. Methods: The apoptotic effects of compound K were analyzed using flow cytometry, and the changes in protein levels were determined using Western blot analysis. The intracellular calcium levels were monitored by staining with Fura-2/AM and Fluo-3/AM. Results: Compound K-induced ER stress was confirmed through increased phosphorylation of $eIF2{\alpha}$ and protein levels of GRP78/BiP, XBP-1S, and $IRE1{\alpha}$ in human lung cancer cells. Moreover, compound-K led to the accumulation of intracellular calcium and an increase in m-calpain activities that were both significantly inhibited by pretreatment either with BAPTA-AM (an intracellular $Ca^{2+}$ chelator) or dantrolene (an RyR channel antagonist). These results were correlated with the outcome that compound K induced ER stress-related apoptosis through caspase-12, as z-ATAD-fmk (a specific inhibitor of caspase-12) partially ameliorated this effect. Interestingly, 4-PBA (ER stress inhibitor) dramatically improved the compound K-induced apoptosis. Conclusion: Cell survival and intracellular $Ca^{2+}$ homeostasis during ER stress in human lung cancer cells are important factors in the induction of the compound K-induced apoptotic pathway.

• The Korea Journal of Herbology
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• v.30 no.4
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• pp.37-44
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• 2015

Objectives : The present study was designed to evaluate the anti-inflammatory and anti-oxidative stress activities through regulation of Nrf2-mediated genes by Rhei rhizoma and Glycyrrhiza rhizoma combined extract (RGE) in reflux esophagitis.Methods : The antioxidant activity of RGE in vitro was measured in terms of radical scavenging capacity such as DPPH and ABTS. RGE was administered at 350 mg/kg body weight prior to induction of reflux esophagitis. Reflux esophagitis was induced that tied the pylorus and the transitional junction between the forestomach and the corpus in Sprague-Dawley rats.Results : RGE scavenged DPPH and ABTS effectively and IC₅₀of RGE each were 4.9 μg/ml and 45.6 μg/ml. Our results show that RGE administration markedly ameliorated mucosal damage upon histological evaluation. In serum and esophagus tissue, RGE significantly suppressed the oxidative stress biomarkers. Reflux esophagitis induced rats exhibited down-regulation of antioxidant-related proteins in the esophagus; however, the levels with treatment of RGE were significantly higher than those of vehicle reflux esophagitis rats. RGE treatment caused significant reductions in activation of NF-κB transcription factor. Thus, RGE significantly exhibited potent anti-inflammatory activities by suppressing the protein expression levels of pro-inflammatory proteins such as COX-2 and iNOS and inflammatory cytokines such as TNF-αin the esophagus tissue.Conclusions : Reflux esophagitis caused considerable levels of oxidative stress in the esophageal mucosa and the administration of RGE reduced the esophageal mucosa damage through the regulation of Nrf2 and NF-κB pathways. Our findings can considered as supplementary therapy in the prevention or treatment of reflux esophagitis.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.2
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• pp.627-633
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• 2015

Background: To study the effect of parecoxib, a novel cyclooxygenase-2 selective inhibitor, on the radiation response of colorectal cancer (CRC) cells and its underlying mechanisms. Materials and Methods: Both in vitro colony formation and apoptosis assays as well as in vivo mouse xenograft experiments were used to explore the radiosensitizing effects of parecoxib in human HCT116 and HT29 CRC cells. Results: Parecoxib sensitized CRC cells to radiation in vitro with a sensitivity enhancement ratio of 1.32 for HCT116 cells and 1.15 for HT29 cells at a surviving fraction of 0.37. This effect was partially attributable to enhanced apoptosis induction by parecoxib combined with radiation, as illustrated using an in vitro apoptosis assays. Parecoxib augmented the tumor response of HCT116 xenografts to radiation, achieving growth delay more than 20 days and an enhancement factor of 1.53. In accordance with the in vitro results, parecoxib combined with radiation resulted in less proliferation and more apoptosis in tumors than radiation alone. Radiation monotherapy decreased microvessel density (MVD) and microvessel intensity (MVI), but increased the hypoxia level in xenografts. Parecoxib did not affect MVD, but it increased MVI and attenuated hypoxia. Conclusions: Parecoxib can effectively enhance radiation sensitivity in CRC cells through direct effects on tumor cells and indirect effects on tumor vasculature.

• Journal of the Korean Society of Food Science and Nutrition
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• v.33 no.1
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• pp.1-6
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• 2004

$\beta$-Sitosterol is the major phytosterol in higher plants, including fruits and vegetables. The molecule has been shown to have the potential for prevention and therapy for human cancer. We investigated the effects of $\beta$-sitosterol on the cell proliferation of HCT116 human colon cancer cells in order to understand its anti-proliferative mechanism. $\beta$-Sitosterol treatment resulted in the inhibition of cell proliferation in a concentration-dependent manner. The anti-proliferative effect of HCT116 cells by $\beta$-sitosterol was associated with formation of apoptotic bodies and degradation of $\beta$-catenin protein. In addition, $\beta$-sitosterol-treatment induced a marked accumulation of tumor suppressor p53 and a concomitant induction of cyclin-dependent kinase (Cdk) inhibitor p21 without alteration in the levels of cyclins and Cdks. Taken together, these findings provide important new insights into the possible molecular mechanisms of the anti-cancer activity of $\beta$-sitosterol.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.15
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• pp.6651-6661
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• 2015

Breast cancer is a global health concern and is a major cause of death among women. In Oman, it is the most common cancer in women, with an incidence rate of 15.6 per 100,000 Omani females. Various anticancer remedies have been discovered from natural products in the past and the search is continuing for additional examples. Cytotoxic natural compounds may have a major role in cancer therapy either in potentiating the effect of chemotherapy or reducing its harmful effects. Recently, a few studies have reported advantages of using crude camel milk in treating some forms of cancer. However, no adequate data are available on the lyophilised camel's milk responsibility for triggering apoptosis and oxidative stress associated with human breast cancer. The present study aimed to address the role of the lyophilised camel's milk in inducing proliferation repression of BT-474 and HEp-2 cells compared with the non-cancer HCC1937 BL cell line. Lyophilized camel's milk fundamentally repressed BT-474 cells growth and proliferation through the initiation of either the intrinsic and extrinsic apoptotic pathways as indicated by both caspase-3 mRNA and its action level, and induction of death receptors in BT-474 but not the HEp-2 cell line. In addition, lyophilised camel's milk enhanced the expression of oxidative stress markers, heme-oxygenase-1 and reactive oxygen species production in BT-474 cells. Increase in caspase-3 mRNA levels by the lyophilised camel's milk was completely prevented by the actinomycin D, a transcriptional inhibitor. This suggests that lyophilized camel's milk increased newly synthesized RNA. Interestingly,it significantly (p<0.003) repressed the growth of HEp-2 cells and BT-474 cells after treatment for 72 hours while 24 hours treatment repressed BT-474 cells alone. This finding suggests that the lyophilised camel's milk might instigate apoptosis through initiation of an alternative apoptotic pathway.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.10
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• pp.6007-6012
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• 2013

ANXA2, a member of the annexin family, is overexpressed and plays important roles in tumor development. However, the significance of ANXA2 expression in gastric carcinoma has not been clarified.To elucidate its roles in growth of gastric cancer, ANXA2 expression in SGC-7901 cells was inhibited with a designated siRNA, then cell proliferation, cell cycling, apoptosis and motility were determined by MTT assay, flow cytometry, Hoechst 33342 staining and wound healing assay, respectively. To further assess the behavior of ANXA2 deleted SGC-7901 cells, changes of microstructures were observed under fluorescence microscopy, laser scanning confocal microscopy and electron microscopy. We found that inhibition of ANXA2 expression caused cell proliferation to decrease significantly with G1 arrest, motility to be reduced with changes in pseudopodia/filopodia structure and F-actin and ${\beta}$-tubulin expression, and apoptosis to be enhanced albeit without significance. At the same time, ANXA2 deletion resulted in fewer pseudopodia/filopodia, non-stained areas were increased, contact inhibition among cells reappeared, and expression of F-actin and ${\beta}$-tubulin was decreased, with induction of polymerized disassembled forms. Taken together, these data suggest that ANXA2 overexpression is important to maintain the malignancy of cancer cells, and this member of the annexin family has potential to be considered as a target for the gene therapy of gastric carcinoma.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.10
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• pp.5989-5993
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• 2013

Background: Radiation therapy is the mainstay of treatment for nasopharyngeal carcinoma. Importance of tumor coverage and challenges posed by its unique and critical location are well evident. Therefore we aimed to evaluate our radiation treatment plan through dose volume histograms (DVHs) to find planning target volume (PTV) dose coverage and factors affecting it. Materials and Methods: This retrospective study covered 45 histologically proven nasopharyngeal cancer patients who were treated with definitive 3D-CRT and chemotherapy between Feb 2006 to March 2013 at the Department of Oncology, Section Radiation Oncology, Aga Khan University Hospital, Karachi, Pakistan. DVH was evaluated to find numbers of shrinking field (phases), PTV volume in different phases and its coverage by the 95% isodose lines, along with influencing factors. Results: There were 36 males (80%) and 9 females (20%) in the age range of 12-84 years. Stage IVA (46.7%) was the most common stage followed by stage III (31.1). Eighty six point six-percent received induction, 95.5% received concurrent and 22.2% received adjuvant chemotherapy. The prescribed median radiation dose was 70Gy to primary, 60Gy to clinically positive neck nodes and 50Gy to clinically negative neck regions. Mean dose to spinal cord was 44.2Gy and to optic chiasma was 52Gy. Thirty seven point eight-percent patients completed their treatment in three phases while 62.2% required four to five phases. Mean volume for PTV3 was $247.8cm^3$ (50-644.3), PTV4 $173.8cm^3$ (26.5-345.1) and PTV5 $119.6cm^3$ (18.9-246.1) and PTV volume coverage by 95% isodose lines were 74.4%, 85.7% and 100% respectively. Advanced T stage, intracranial extension and tumor volume > $200cm^3$ were found to be important factors associated with decreased PTV coverage by 95% isodose line. Conclusions: 3D CRT results in adequate PTV dose coverage by 95% isodose line. However advanced T stage, intracranial extension and large target volume require more advanced techniques like IMRT for appropriate PTV coverage.

• Biomedical Science Letters
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• v.3 no.1
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• pp.11-20
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• 1997

A regulation of differentiation in human neuroblastoma cells remains poorly understood, although it is of great importance in the clinical therapy of neuroblastoma. This study was aimed to elucidate effects of DNA synthesis inhibitors on the differentiation of neuroblastoma cells on the basis of morphological, biochemical and molecular respects. Three DNA synthesis inhibitors, sodium butyrate, hydroxyurea, cytosine arabinoside were used to explore their effects on the cellular morphology, the expression of c-myc and the elevation of choline acetyltransferase activity. They led to the extension or neurite-like processes reflecting differentiation or IMR-32 cells. In addition, the treatment of three DNA synthesis inhibitors resulted in the remarkable increases in the expression of c-myc as well as the stimulation of choline acetyltransferase activity which is involved in the synthesis of acetylcholine in the differentiated cholinergic neurons. Taken together, these results indicate that DNA synthesis inhibitors play an important role in the induction of cellular differentiation in IMR-32 cells. Furthermore these DNA synthesis inhibitors seem to be future useful to give an important clue (for the treatment of neuroblastoma).

• Journal of Plant Biotechnology
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• v.38 no.1
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• pp.62-68
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• 2011

Calmodulin (CaM), a $Ca^{2+}$ binding protein in eukaryotes, mediates cellular $Ca^{2+}$ signals in response to a variety of biotic and abiotic external stimuli. The $Ca^{2+}$-bound CaM transduces signals by modulating the activities of numerous CaM-binding proteins. As a CaM binding protein, AtCBP63 ($\b{A}$rabidopsis thaliana $\b{C}$aM-binding protein $\underline{63}$ kD) has been known to be positively involved in plant defense signaling pathway. To investigate the pathogen resistance function of AtCBP63 in potato, we constructed transgenic potato (Solanum tuberosum L.) plants constitutively overexpressing AtCBP63 under the control of cauliflower mosaic virus (CaMV) 35S promoter. The overexpression of the AtCBP63 in potato plants resulted in the high level induction of pathogenesis-related (PR) genes such as PR-2, PR-3 and PR-5. In addition, the AtCBP63 transgenic potato showed significantly enhanced resistance against a pathogen causing bacterial soft rot, Erwinia carotovora ssp. Carotovora (ECC). These results suggest that a CaM binding protein from Arabidopsis, AtCBP63, plays a positive role in pathogen resistance in potato.