• Asian Pacific Journal of Cancer Prevention
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• v.14 no.12
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• pp.7569-7576
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• 2013

Background: The purpose of this article is to present preliminary results of simultaneous boost irradiation radiotherapy for locally advanced nasopharyngeal carcinoma (NPC). Methods: Fifty-eight patients who underwent simultaneous boost irradiation radiotherapy for NPC in Cancer Center of Sun Yat-sen University between September 2004 and December 2009 were eligible. Acute and late toxicities were scored weekly according to the Radiation Therapy Oncology Group (RTOG) acute and late radiation morbidity scoring schemes. An especial focus was on evidence of post-radiation brain injury. Also quality of life was analysed according to the EORTC (European Organisation for Research and Treatment of Cancer) recommendations. Discrete variables were compared by ${\chi}^2$ test. The Kaplan-Meier method was used to calculate the survival rates and generate survival curves. Results: A total of 58 patients with a mean follow-up time of 36 months completed clinical trials.Fifty-seven patients (98.3) achieved complete remission in the primary sites and cervical lymph nodes, with only one patient (1.7%) showing partial remission.The most frequently observed acute toxicities during the concurrent chemoradiotherapy were mucositis and leucopenia. Four patients (6.9%) had RTOG grade 3 mucositis, whereas four patients (6.9%) had grade 3 leucopenia. No patient had grade 4 acute toxicity. Three (5.17%) of the patients exhibited injury to the brain on routine MRI examination, with a median observation of 32 months (range, 25-42months). All of them were RTOG grade 0. The 3-year overall, regional-free and distant metastasis-free survival rates were 85%, 94% and 91%, respectively. Conclusion: Simultaneous boost irradiation radiotherapy is feasible in patients with locally advanced nasopharyngeal carcinoma. The results showed excellent local control and overall survival, with no significant increase the incidence of radiation brain injury or the extent of damage. A larger population of patients and a longer follow-up period are needed to evaluate ultimate tumor control and late toxicity.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.26 no.6
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• pp.581-590
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• 2000

Alterations in the cellular genome affecting the expression or function of genes controlling cell growth and differentiation are considered to be the main cause of cancer. Over 30 oncogenes can be activated by insertional mutagenesis, single point mutations, chromosomal translocations and gene amplification. The ras oncogenes have been detected in $15{\sim}20%$ of human tumors that include some of the most common forms of human neoplasia and are known to acquire their transforming properties by single point mutations in two domains of their coding sequences, most commonly in codons 12 and 61. The ras gene family consists of three functional genes, N-ras, K-ras and H-ras which encode highly similar proteins of 188 or 189 amino acid residues generically known as P21. ras proteins have been shown to bind GTP and GTP, and possess intrinsic GTPase activity. Experimental study was performed to observe the mutational change of the ras gene family and apply the results to the clinical activity. 36 Golden Syrian Hamster each weighing $60{\sim}80g$ were used and painted with 0.5% DMBA by 3 times weekly on the right buccal cheek(experimental side) for 6, 8, 10, 12, 14 and 16 weeks. Left buccal cheek (control side) was treated with mineral oil as the same manner of the right side. The hamsters were sacrificed on the 6, 8, 10, 12, 14 & 16 weeks. Normal and tumor tissues from paraffin block were completely dissected by microdissection and DNA from both tissue were isolated by proteinase K/phenol/chloroform extraction. Segments of the K-ras and H-ras gene were amplified by PCR using the oligonucleotide primers corresponding to the homologous region (codon 12 and 61) of the hamster gene, and then confirmational change of ras genes was observed by SSCP and autosequencing analysis. The results were as follows : 1. Malignant lesion could be found in the experimental side from the experimental six weeks. 2. One hamster among six showed point mutation of the H-ras codon 12($G{\rightarrow}A$ transition) at the experimental 10 and 14 weeks. 3. One of six at 6 weeks, two of six at 8 weeks and one of six at 12 weeks revealed the confirmational change of the H-ras codon 61($A{\rightarrow}T$ transversion). 4. The incidence of point mutation of H-ras codon 12 and 61 were 5.5%(2 of 36) and 11%(4 of 36) respectively. 5. Point mutation of the K-ras could not be seen during the whole experimental period. Form the above results, these findings strongly support the concept that H-ras oncogenes may have the influence of the DMBA induced carcinoma of hamster buccal pouch.

• Journal of Life Science
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• v.20 no.8
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• pp.1281-1286
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• 2010

Gaucher disease (GD) is caused by glucocerebrosidase functional deficiency and the most prevalent lysosomal storage disorder (LSD), with an incidence of about 1 in 20,000 new births. Resveratrol, one kind of phytoalexin, is a produced naturally by several plants and has anti-tumor, anti-aging, anti-inflammatory and neuro-protective effects. In this paper we provide the cellular protective effect of resveratrol in both type I and type II Gaucher disease cells. Resveratrol treatment did not show any significant change in the p21 and p53 mRNA expression level, however expression level of the p21 protein, a cell cycle arrest factor, shows significant increment in both types of Gaucher disease cells. These cell cycle arrest patterns were confirmed by both MTT assay measurement and microscopy detection. In comparison, expression level of poly ADP ribose polymerase (PARP), an apoptosis indicator protein, was significantly decreased in both type I and II Gaucher disease cells after treatment with resveratrol. This result indicates that resveratrol relievescellular apoptotic stress fromtype I and II Gaucher disease cells. Therefore, we demonstrate that resveratrol inhibits cell proliferation via p21 activity and activates cellular repair systems for Gaucher disease cells. Our results provide at least one of the molecular mechanisms of Gaucher disease and may allow the verification of potential drug targets for therapeutic trials.

• Journal of Gastric Cancer
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• v.1 no.3
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• pp.161-167
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• 2001

Purpose: Although gastric carcinomas occur throughout the world and the incidence is on the decrease, they remain the most common type of carcinoma in Korea. Significant advancements in the diagnostics and the surgical treatment of gastric carcinomas have been achieved during the last three decades. The present retrospective study was undertaken to investigate the chronological changes in the clinical features, including clinicopathological findings, operative treatment, and prognosis of gastric carcinomas. Materials and Methods: A total of 1973 patients with a primary gastric adenocarcinoma who had been treated surgically during the period from 1983 to 1998 at the Department of Surgery, Korea University College of Medicine, were divided into two groups to evaluate chronological changes: 1007 patients had been treated during the period from 1983 to 1992 (early period) and 966 patients during the period from 1993 to 1998 (late period). Chronological changes in age, sex, ratio of early gastric cancer (EGC), and resectability were analyzed in all 1973 cases. For the 1755 resected cases, we also studied the chronological changes in the clinicopathological and treatment factors between the early-period (n=894) and the late-period (n=867) groups. Results: There were significant differences between the two periods with regard to age and ratio of EGC: EGC was more frequent in the late period. Univariate analysis of resected cases showed that gross type, tumor size, depth of invasion, UICC stage, and histological type were statistically significant. The analysis of the treatment factors revealed that total gastrectomies and extended lymphadenectomies were more frequent during the late period. The number of lymph nodes dissected was $26.0\pm12.7$ in the early period and $33.4\pm14.1$ in the late period (p<0.01). The 5-year survival rate in all cases was $51.4\%$ in the early period and $55.9\%$ in the late period. The stage-related survival rates (UICC 4th Ed., 1987) in the early vs. the late periods were $92.9\%\;vs.\;95.5\%$ in stage IA, $82.1\%\;vs.\;91.1\%$ in stage IB, $76.5\%\;vs.\;73.1\%$ in stage II, $46.5\%\;vs.\;52.1\%$ in stage IIIA, $14.5\%\;vs.\;33.6\%$ in stage IIIB, and $2.8\%\;vs.\;8.8\%$ in stage IV. There was a statistically significant difference in survival between stage IIIB and IV. Conclusion: These results suggest that the differences in the clinicopathological findings are related primarily to the increased number of early gastric cancer cases in the late period and that the improved survival noted during the late period for in stage IIIB and IV cancers might be related to extended surgery.

• Clinical and Experimental Pediatrics
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• v.60 no.3
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• pp.86-93
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• 2017

Purpose: To evaluate the clinical spectrum of posttransplantation lymphoproliferative disorder (PTLD) after solid organ transplantation (SOT) in children. Methods: We retrospectively reviewed the medical records of 18 patients with PTLD who underwent liver (LT) or kidney transplantation (KT) between January 1995 and December 2014 in Seoul National University Children's Hospital. Results: Eighteen patients (3.9% of pediatric SOTs; LT:KT, 11:7; male to female, 9:9) were diagnosed as having PTLD over the last 2 decades (4.8% for LT and 2.9% for KT). PTLD usually presented with fever or gastrointestinal symptoms in a median period of 7 months after SOT. Eight cases had malignant lesions, and all the patients except one had evidence of Epstein-Barr virus (EBV) involvement, assessed by using in situ hybridization of tumor tissue or EBV viral load quantitation of blood. Remission was achieved in all patients with reduction of immunosuppression and/or rituximab therapy or chemotherapy, although 1 patient had allograft kidney loss and another died from complications of chemotherapy. The first case of PTLD was encountered after the introduction of tacrolimus for pediatric SOT in 2003. The recent increase in PTLD incidence in KT coincided with modification of clinical practice since 2012 to increase the tacrolimus trough level. Conclusion: While the outcome was favorable in that all patients achieved complete remission, some patients still had allograft loss or mortality. To prevent PTLD and improve its outcome, monitoring for EBV infection is essential, which would lead to appropriate modification of immunosuppression and enhanced surveillance for PTLD.

• Biomedical Science Letters
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• v.12 no.3
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• pp.153-160
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• 2006

Human colon cancer is the second most fatal disease among a variety of cancers to cause cancer death in U.S.A. and its incidence rate is currently increased in Korea. Recently, many studies have been being progressed on the efficacy of diverse combination treatments. But results of these studies in vitro were not similar those in vivo. This study compared the anticancer reactions between each use of arsenic trioxide and taxol against human colon cancer HT-29 cell line and combined use of two drugs. And these results compared with the results of HT-29 spheroid cells having similar characteristics to the solid tumor in vivo. The spheroid of HT-29 cells was formed by using a multicellular spheroid system and the result was observed through electron microscopy. In vitro cytotoxicity of each use of arsenic trioxide and taxol was evaluated in HT-29 monolayer cells. The $IC_{50}$ value for arsenic trioxide was to be $33{\mu}M$ and taxol was to be 18nM. The result treated with the combination of taxol and arsenic trioxide decreased the cytotoxicity on the HT-29 monolayer cells. The spheroid cells represented higher resistance against drugs than the monolayer cells. I demonstrated DNA fragmentation after incubation with concentrations more than $10{\mu}M$ arsenic trioxide and 100nM taxol for 48h, on the monolayer cells. But the results of HT-29 cell line treated with the combination of taxol and arsenic trioxide was the same as the outcome of control samples that were not treated with any drug. And I don't demonstrated DNA fragmentation on the spheroid cells. These results suggest that apoptosis was not induced in the use of the combination can be thought as that arsenic trioxide might work as an antagonist to inhibit a taxol mechanism to induce apoptosis. And the spheroid cells represented higher resistance against drugs than the monolayer cells.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.17
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• pp.7781-7784
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• 2015

Background: The commonly held view of the tumor suppressor p53 is as a regulator of cell proliferation, apoptosis and many other biological processes as well as external and internal stress responses. Mdm2 SNIP309 is a negative regulator of p 53. Therefore, this study aimed to determine the correlation between the patterns of Mdm2 SNIP 309 and the inflammation grading of Helicobacter pylori associated gastritis in a Thai population. Materials and Methods: A cross-sectional study was carried out from November 2014 through June 2015. Biopsy specimens were obtained from infected patients and infection was proved by positive histology. The gastric mucosa specimens were sent to the Molecular Genetic Unit, Institute of Medicine, Suranaree University of Technology where they were tested by molecular methods to detect the patterns of Mdm2 SNIP 309 using the real-time PCR hybridization probe method. The results were analyzed and compared with the Updated Sydney classification. Results: A total of 100 infected patients were interviewed and gastric mucosa specimens were collected. In this study the percentage of Mdm2 SNIP 309 T/T homozygous and Mdm2 SNIP309 G/T heterozygous was 78% and 19 % respectively whereas Mdm2 SNIP309 G/G homozygous was 3%. Mdm2 SNIP 309 T/T homozygous and Mdm2 SNIP309 G/T heterozygous correlated with mild to moderate inflammation (P<0.01) whereas Mdm2 SNIP309 G/G homozygous correlated with severe inflammation (P<0.01). Conclusions: Our study found the frequency of Mdm2 SNP309 G/G in our Thai population to be very low, and suggests that this can explain to some extent the low incidence of severe inflammation and gastric cancer changes in the Thai population. Mild to moderate inflammation are the most common pathologic gradings due to the unique genetic polymorphism of Mdm2 SNIP 309 in the Thai population.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.15
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• pp.6363-6367
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• 2014

Purpose: This study was conducted to assess the preventive effect of Actinidia valvata Dunn (AVD) extract on an animal model of gastrointestinal carcinogenesis on the basis of changes in tumor incidence, cell proliferation, and apoptosis. Materials and Methods: Seventy-five male Wistar rats were divided into five different treatment groups with 15 rats in each group. Group I was given normal feed, whereas Groups II to IV were treated with 10% sodium chloride in the first six weeks and 100ug/mL of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in drinking water for 24 weeks. Group II was then given normal feed, whereas Group III was given AVD extract (0.24g/kg/day) for 12 weeks. Group IV was given AVD extract from the first week to the 36th week, whereas Group V was treated with AVD extract alone for 36 weeks. All rats were sacrificed at the end of the 36-week experiment and assessed for the presence of gastrointestinal tumors. The occurrence of cancer was evaluated by histology. Bax, Bcl-2, Caspase-3, and cyclinD1 were determined by immunohistochemical staining and Western blotting. Results: The incidences of gastric cancer were 0% in Group I, 73.3% in Group II, 33.3% in Group III, 26.7% in Group IV, and 0% in Group V. Bcl-2 and cyclinD1 expression was decreased in AVD extract treated groups, whereas Bax and Caspase-3 expression was increased. Comparison with group II revealed significant differences (p<0.01). Conclusions: AVD extract exhibits an obvious preventive effect on gastrointestinal carcinogenesis induced by MNNG in rats through the regulation of cell proliferation and apoptosis.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.8
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• pp.3651-3657
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• 2014

Hepatocellular carcinoma (HCC) has a relatively higher incidence in many countries of Asia. Globally, HCC has a high fatality rate and short survival. Epirubicin, a doxorubicin analogue, may be administered alone or in combination with other agents to treat primary liver cancer and metastatic diseases. However, the toxic effects of epirubicin to normal tissues and cells have been one of the major obstacles to successful cancer chemotherapy. Here, we investigated the effects of epirubicin in combination with kappa-selenocarrageenan on mice with H22 implanted tumors and HepG-2 cell proliferation, immune organ index, morphology, cell cycle and related protein expressions in vivo and in vitro with sequential drug exposure. The inhibitory rate of tumor growth in vivo was calculated. Drug sensitivity was measured by MTT assay, and the King's principle was used to evaluate the interaction of drug combination. Morphological changes were observed by fluorescent microscopy. Cell cycle changes were analyzed by flow cytometry. Expression of cyclin A, Cdc25A and Cdk2 were detected by Western blotting. In vivo results demonstrated that the inhibitory rate of EPI combined with KSC was higher than that of KSC or EPI alone, and the Q value indicated an additive effect. In addition, KSC could significantly raise the thymus and spleen indices of mice with H22 implanted tumors. In the drug sensitivity assay in vitro, exposure to KSC and EPI simultaneously was more effective than exposure sequentially in HepG-2 cells, while exposure to KSC prior to EPI was more effective than exposure to EPI prior to KSC. Q values showed an additive effect in the simultaneous group and antagonistic effects in the sequential groups. Morphological analysis showed similar results to the drug sensitivity assay. Cell cycle analysis revealed that exposure to KSC or EPI alone arrested the cells in S phase in HepG-2 cells, exposure to KSC and EPI simultaneously caused accumulation in the S phase, an effect caused by either KSC or EPI. Expression of cyclin A, Cdc25A and Cdk2 protein was down-regulated following exposure to KSC and EPI alone or in combination, exposure to KSC and EPI simultaneously resulting in the lowest values. Taken together, our findings suggest that KSC in combination with EPI might have potential as a new therapeutic regimen against HCC.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.7
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• pp.3057-3063
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• 2014

Background: Anaplastic lymphoma kinase (ALK) gene rearrangement in non-small cell lung cancer (NSCLC) has been intensively studied. The gold standard for ALK detection is FISH, but this is not routinely conducted in clinical practice, so that the IHC method has a role. The aim of this study was to identify the incidence of ALK rearrangement and risk or prognostic factors for ALK positivity using both of IHC and FISH methods. Materials and Methods: From January 2008 to December 2012, 267 completely resected NSCLC patients in Chiang Mai University Hospital were enrolled in this study. Clinical and pathological variables and outcomes of treatment were retrospectively reviewed. IHC and FISH were used to evaluate ALK rearrangement. Sensitivity and specificity of IHC were analyzed. Multivariable analysis was used to identify clinico-pathological correlations with positive results of IHC and clinical outcomes. Results: Twenty-two (8.2%) of 267 specimens were IHC-positive for ALK with intense cytoplasmic staining, whereas only 10 (3.8%) were FISH-positive. Sensitivity, specificity and the positive likelihood ratio with IHC were 80.0%, 94.9%, and 15.8 respectively. Age less than 55 years (RR 4.4, 95%CI 1.78-10.73, p value=0.001) and presence of visceral pleural invasion (VPI) (RR 2.9, 95%CI 1.21-6.78, p value =0.017) were identified as risk factors for ALK rearrangement with FISH. There were no statistically significant differences in other clinical and pathological variables. ALK rearrangement was not a prognostic factor for tumor recurrence or overall survival. Conclusions: The incidences of ALK positivity in completely resected NSCLCs in northern Thailand were 8.2% by IHC and 3.8% by FISH. IHC with mouse monoclonal, Ventana D5F3 antibody can be used as a screening tool before FISH method because of high specificity and high positive likelihood ratio. Age less than 55 years and VPI are risk factors for ALK positivity.