• Journal of Acupuncture Research
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• 제30권1호
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• pp.43-55
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• 2013

I investigated whether snake venom toxin(SVT) from Vipera lebetina turanica enhances the apoptosis ability of tumor necrosis factor(TNF)-related apoptosis-inducing ligand(TRAIL) in cancer cells. TRAIL inhibited HCT116 cell growth in a dose-dependent manner. Consistent with cell growth inhibition, the expression of TRAIL receptors; DR4 and DR5 was significantly increased as well as apoptosis related proteins such as cleaved caspase-3, 8, 9 and Bax. However, the expression of survival proteins(eg, cFLIP, survivin, XIAP and Bcl2) was suppressed by the combination treatment of SVT and TRAIL. Pretreatment with the reactive oxygen species(ROS) scavenger N-acetylcysteine reduced the SVT and TRAIL-induced upregulation of DR4 and DR5 expression and expression of the apoptosis related protein such as caspase-3 and-9 as well as cell growth inhibitory effects. The collective results suggest that SVT facilitates TRAIL-induced apoptosis in human colorectal cancer HCT116 cells through up-regulation of the TRAIL receptors; DR4 and DR5 via ROS pathway signals.

• Asian Pacific Journal of Cancer Prevention
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• 제15권9호
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• pp.4033-4037
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• 2014

Emerging evidence has shown associations of microRNA-205 (miR-205) with crucial cell processes such as the epithelial-mesenchymal transition (EMT) and aberrant expression with tumorigenesis in many types of human malignancy. This prospective study characterized the contribution of miR-205 to the colorectal cancer (CRC) tumorigenesis. The real-time reverse transcription-polymerase chain reaction was used to examine miR-205 levels prospectively in 36 pairs of samples of CRC tissue and adjacent noncancerous tissue (>2 cm from cancer tissue). In addition, the relationship between miR-205 levels and clinicopathological features was explored. The capability of miR-205 to function as a tumor marker was also examined. miR-205 expression levels did not show significant changes overall. However, miR-205 was significantly downregulated in a group of CRC samples compared with matched noncancerous tissue samples. Moreover, decreased miR-205 correlated significantly with lymphatic metastasis. A receiver operating characteristic (ROC) curve also showed an optimum cut off point of $1.4{\times}10^{-3}$ to distinguish lymphatic metastatic CRCs from non-metastatic CRCs. Interestingly we found lymphatic metastasis in almost 80% of the depressed samples. This study suggested that miR-205 could be reduced in the majority of metastatic CRCs and the risk of CRC metastasis may be predicted by monitoring miR-205 in patient samples collected at the time of the initial diagnosis. Therefore, targeting miR-205 and its potential environmental activators might be a promising therapeutic option to prevent malignant progression toward metastasis.

• Radiation Oncology Journal
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• 제32권2호
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• pp.77-83
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• 2014

Purpose: To determine the prognostic and predictive value of liver volume in colorectal cancer patients with unresectable liver metastases. Materials and Methods: Sixteen patients received whole liver radiotherapy (WLRT) between January 1997 and June 2013. A total dose of 21 Gy was delivered in 7 fractions. Results: The median survival time after WLRT was 9 weeks. In univariate analysis, performance status, serum albumin and total bilirubin level, liver volume and extrahepatic metastases were associated with survival. The mean liver volume was significantly different between subgroups with and without pain relief (3,097 and 4,739 mL, respectively; p = 0.002). Conclusion: A larger liver volume is a poor prognostic factor for survival and also a negative predictive factor for response to WLRT. If patients who are referred for WLRT have large liver volume, they should be informed of the poor prognosis and should be closely observed during and after WLRT.

• 핵의학기술
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• 제22권1호
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• pp.76-79
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• 2018

Purpose Carcinoembryonic antigen (CEA) is cell-surface 180-200 kDa glycoprotein that is overexpressed in breast, stomach pancreas, lung, and colorectal cancers. CEA was first described in 1965 by Gold and Freedman and then serum CEA of colorectal cancer patients was first measured in 1969 by radioimmunoassay by Thomson. CEA is currently most widely used tumor marker in the clinic for management of colorectal cancer. Various CEA test kits have been developed and commercialized. CEA kits from different manufacturers might have different test results because of different reagents and protocol. The purpose of this study was to compare results of four commercial available CEA kits. Materials and Methods This study was designed to evaluate four commercially available CEA kits using serum samples acquired from 120 patients who visited our clinic. Test results were compared and analyzed according to the respective test methods. High concentration samples were diluted with saline and diluted solution. Results All of the four kits showed a significant correlation within the reference value. However, three of the four kits used for the dilution test using high concentration samples showed the hook effect. Conclusion Results of the present study showed that It is important to establish the standardized dilution standards for the high-concentration specimens to manage the error of the test result by the hook effect.

• Radiation Oncology Journal
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• 제35권3호
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• pp.281-288
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• 2017

Purpose: The serum carcinoembryonic antigen (CEA) level has been recognized as a prognostic factor in colorectal cancer, and associated with response of rectal cancer to radiotherapy. This study aimed to identify CEA-interacting proteins in colon cancer cells and observe post-irradiation changes in their expression. Materials and Methods: CEA expression in colon cancer cells was examined by Western blot analysis. Using an anti-CEA antibody or IgG as a negative control, immunoprecipitation was performed in colon cancer cell lysates. CEA and IgG immunoprecipitates were used for liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. Proteins identified in the CEA immunoprecipitates but not in the IgG immunoprecipitates were selected as CEA-interacting proteins. After radiation treatment, changes in expression of CEA-interacting proteins were monitored by Western blot analysis. Results: CEA expression was higher in SNU-81 cells compared with LoVo cells. The membrane localization of CEA limited the immunoprecipitation results and thus the number of CEA-interacting proteins identified. Only the Ras-related protein Rab-6B and lysozyme C were identified as CEA-interacting proteins in LoVo and SNU-81 cells, respectively. Lysozyme C was detected only in SNU-81, and CEA expression was differently regulated in two cell lines; it was down-regulated in LoVo but up-regulated in SNU-81 in radiation dosage-dependent manner. Conclusion: CEA-mediated radiation response appears to vary, depending on the characteristics of individual cancer cells. The lysozyme C and Rab subfamily proteins may play a role in the link between CEA and tumor response to radiation, although further studies are needed to clarify functional roles of the identified proteins.

• Asian Pacific Journal of Cancer Prevention
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• 제17권8호
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• pp.4117-4123
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• 2016

Background: Methylation of promoter 2 of the SHP1 gene is epithelial cell specific, with reported potential as a lymph node metastatic marker. Objective: To demonstrate SHP1-P2 methylation-specific quantitative PCR effectiveness in detecting colorectal cancer (CRC) DNA in lymph nodes. Materials and Methods: SHP1-P2 methylation levels were measured in lymph nodes of CRC patients and compared with pathological findings and patient prognosis. Results: Lymph nodes of CRC metastatic patients without microscopically detectable cancer cells had higher SHP1-P2 methylation levels than lymph nodes of controls (p<0.001). In addition, a higher SHP1-P2 methylation level was associated with a shorter duration until adverse disease events, metastasis, recurrence and death (r2 = 0.236 and p value = 0.048). Studying two cohorts of 74 CRC patients without microscopic lymph node metastases showed that only the cohort containing samples with high SHP1-P2 methylation levels had a significant hazard ratio of 3.8 (95%CI = 1.02 to 14.2). Conclusions: SHP1-P2 methylation PCR can detect CRC DNA in lymph nodes even if cancer cells are not visible under a microscope, confirming applicability as a potential universal lymph node metastatic marker.

• Asian Pacific Journal of Cancer Prevention
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• 제17권3호
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• pp.1175-1179
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• 2016

The results of this study demonstrate the potential prognostic and predictive values of KRAS and BRAF gene mutations in patients with colorectal cancer (CRC). It has been proven that KRAS and BRAF mutations are predictive biomarkers for resistance to anti-EGFR monoclonal antibody treatment in patients with metastatic CRC (mCRC). We demonstrated the distribution of KRAS (codons 12, 13 and 61) and BRAF (codon 600) gene mutations in 50 mCRCs using direct sequencing and compared the results with clinicopathological data. KRAS and BRAF mutations were identified in 15 (30%) and 1 (2%) patients, respectively. We identified KRAS mutations in codon 12, 13 and 61 in 73.3% (11/15), 20% (3/15) and 6.67% (1/15) of the positive patients, respectively. The KRAS mutation frequency was significantly higher in tumors located in the ascending colon (p=0.043). Thus, we found that approximately 1/3 of the patients with mCRC had KRAS mutations and the only clinicopathological factor related to this mutation was tumor location. Future studies with larger patient groups should yield more accurate data regarding the molecular mechanism of CRC and the association between KRAS and BRAF mutations and clinicopathological features.

• Asian Pacific Journal of Cancer Prevention
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• 제16권12호
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• pp.5063-5067
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• 2015

Background: Colorectal cancer (CRC) is the most common gastrointestinal malignancy and is a significant cause of mortality. Its incidence is generally increasing in Asia. Reports from the West have indicated that the incidence of rectal cancer is increasing in the younger population. This study assessed the time trend of CRC in Brunei Darussalam specifically assessing the different age groups at which the incidences start to increase. Materials and Methods: The National Cancer registry was reviewed (1991 to 2014). The age standardized rate (ASR) and the age specific incidence rates (ASIRs) for three time periods (1991-1998), (1999-2006) and (2007-2014) were calculated. Results: The mean age of diagnosis was $59.3{\pm}14.6$ years old, incidences being slightly higher amongst men (57.6%) and Malays (67.1%). The most common tumor type was adenocarcinoma (96.4%). Rectal cancers accounted for 35.2% (n=372/1,056) of all cancers of the large bowel; more men were affected than women. The proportion of rectal cancer was also high among the indigenous group. In the three time periods, the ASR for CRC increased from 16 per 100,000 (1991-1998) to 19.6 per 100,000 (1999-2006) and 24.3 per 100,000 (2007-2014). The ASIRs for CRC increased markedly between the time periods 1998-2006 and 2007-2014, beginning in the 40-44 years age group. For rectal cancers, the ASIRs started to increase in the 25-29 age group onward whereas for colon cancers, the increase was observed at a later age, starting from the 45-49 age group. Conclusions: Our study showed an increase in the incidence of CRC including in the younger age groups. The increase was seen earlier in rectal cancer compared to colon cancer. These data mirror the trends reported from the West.

• Asian Pacific Journal of Cancer Prevention
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• 제15권20호
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• pp.9015-9019
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• 2014

The study aimed to compare the 2 main types of insurance used by colorectal cancer (CRC) patients in a university hospital in Thailand: universal coverage (UC) and 'Civil Servant Medical Benefit Scheme' (CSMBS) in terms of hospital expenditure and survival outcomes. CRC cases in stages I-IV who were operated on and had completed their adjuvant therapy in Songklanagarind Hospital from 2004 through 2013 were retrospectively reviewed regarding their hospital expenditure, focusing on surgical and chemotherapy costs. Of 1,013 cases analyzed, 524 (51.7%) were in the UC group while 489 (48.3%) belonged to the CSMBS group. Cases with stage IV disease were significantly more frequent in the UC group. Average total treatment expenditure (TTE) was 143,780 Thai Baht (THB) (1 US$ =~ 30 THB). The TTE increased with tumor stage and the chemotherapy cost contributed the most to the TTE increment. TTE in the CSMBS group was significantly higher than in the UC group for stage II-III CRCs. The majority of cases in the UC group (65.5%) used deGramont or Mayo as their first line regimen, and the proportion of cases who started with a capecitabine-based regimen (XELOX or $Xeloda^{(R)}$) was significantly higher in the CSMBS group (61.0% compared to 24.5% in the UC group, p-value < 0.01). On survival analysis, overall survival (OS) and progress free survival in the CSMBS group were significantly better than in the UC group. The 5-year OS in the CSMBS and UC groups were 84.3% and 74.6%, respectively (p-value < 0.01). In conclusion, the study indicates that in Thailand, the type of insurance influences resource utilization, especially the choice of chemotherapy, in CRC cases. This disparity in treatment, in turn, results in a gap in treatment outcomes.

• Asian Pacific Journal of Cancer Prevention
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• 제15권14호
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• pp.5601-5605
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• 2014

Background: Agrocybe aegerita Lectin (AAL) has been identified to have high affinity for sulfated and ${\alpha}2$-3-linked sialic acid glycoconjugates, especially the sulfated and sialyl TF (Thomsen-Friedenreich) disaccharide. This study was conducted to investigate the clinicopathological and prognostic value of AAL in identifying aberrant glycosylation in colorectal cancer (CRC). Materials and Methods: Glycoconjugate expression in 59 CRC tissues were detected using AAL-histochemistry. Clinicopathological associates of expression were analyzed with chisquare test or Fisher's exact test. Relationships between expression and the various clinicopathological parameters was estimated using Kaplan-Meier analysis and Cox regression models. Results: AAL specific glycoconjugate expression was significantly higher in tumor than corresponding normal tissues (66.1% and 46.1%, respectively, p=0.037), correlating with depth of invasion (p=0.015) and TNM stage (p=0.024). Patients with lower expression levels had a significantly higher survival rate than those with higher expression (p=0.046 by log rank test and p=0.047 by Breslow test for overall survival; p=0.054 by log rank test and P=0.038 by Breslow test for progress free survival). A marginally significant association was found between AAL specific glycoconjugate expression and overall survival by univariate Cox regression analysis (p=0.059). Conclusions: Lower AAL specific glycoconjugate expression is a significant favorable prognostic factor for overall and progress free survival in CRC. This is the first report about the employment of AAL for histochemical analysis of cancer tissues. The binding characteristics of AAL means it has potential to become a powerful tool for the glycan investigation and clinical application.