• Asian Pacific Journal of Cancer Prevention
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• 제17권8호
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• pp.4019-4023
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• 2016

Background: Colorectal cancer (CRC) or bowel cancer is one of the most important cancer diseases, needing serious attention. The cell surface receptor gene human epidermal growth factor receptor (EGFR) may have an important role in provoking CRC. In this pharmaceutical era, it is always attempted to identify plant-based drugs for cancer, which will have less side effects for human body, unlike the chemically synthesized marketed drugs having serious side effects. So, in this study the authors tried to assess the activity of two important plant compounds, ferulic acid (FA) and p-coumaric acid (pCA), on CRC. Materials and Methods: FA and pCA were tested for their cytotoxic effects on the human CRC cell line HCT 15 and also checked for the level of gene expression of EGFR by real time PCR analysis. Positive results were confirmed by in silico molecular docking studies using Discovery Studio (DS) 4.0. The drug parallel features of the same compounds were also assessed in silico. Results: Cytotoxicity experiments revealed that both the compounds were efficient in killing CRC cells on a controlled concentration basis. In addition, EGFR expression was down-regulated in the presence of the compounds. Docking studies unveiled that both the compounds were able to inhibit EGFR at its active site. Pharmacokinetic analysis of these compounds opened up their drug like behaviour. Conclusions: The findings of this study emphasize the importance of plant compounds for targeting diseases like CRC.

• Asian Pacific Journal of Cancer Prevention
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• 제17권8호
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• pp.4025-4030
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• 2016

Background: Correlation between colorectal cancer (CRC) and abdominal obesity has been established, but there is a paucity of data on non-obese CRC patients. The aim of this study was to establish the characteristics of CRCs that occur in such patients. Materials and Methods: Consecutive CRC patients without cachexia were included. Unintended body weight loss, T4- or M1-staged CRCs, extensive lymph node involvement, or synchronous malignancy were classified as cachectic conditions. Abdominal fat volumes were measured using a multidetector CT unit with a software (Rapidia, INFINITT, Seoul, Korea). Results: Of the newly-diagnosed CRC patients, 258 non-cachectic and 88 cachectic patients were analyzed. The cancer size (p<0.001) and T stage (p<0.001) were inversely correlated with body mass index (BMI), visceral fat and subcutaneous fat volumes. Cancer size was the only independent factor related to BMI (p=0.016), visceral fat volume (p=0.002), and subcutaneous fat volume (p=0.027). In non-cachectic patients, a significant inverse correlation was found only between the cancer size and visceral fat volume (p=0.017). Conclusions: Non-obese CRC patients tend to have larger CRC lesions than their obese counterparts even under non-cachectic conditions. Such an inverse correlation between cancer size and visceral fat volume suggests that considerable CRCs are not correlated with abdominal obesity.

• 전자공학회논문지
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• 제51권5호
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• pp.20-28
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• 2014

본 논문에서는 분산 제어망에서 통신 오류가 발생한 노드를 실시간으로 탐지할 수 있는 기법을 제안한다. 기존의 분산 제어망은 노드 내 오류가 발생하는 지점을 탐지하기 위해, 노드 간 의존성의 영향을 고려해야 하며 이는 전체적인 분산 제어망의 성능 저하의 원인이 될 수 있다. 이를 해결하기 위하여, 본 논문에서 제안된 기법은 각 노드의 손상으로 인해 발생되는 고장노드들을 빠른 시간 내에 탐지하기 위해 단일 Bose-Chaudhuri-Hocquenghem (BCH) 비트를 Cyclic Redundancy Check (CRC) 코드에 삽입하여 기존의 CRC 코드 내 비트와 대체하는 방식을 택한다. 고장 노드 판정의 탐지 정확성을 높이기 위해 고장 가중치 계수를 통한 고장 판단 기법을 제안한다. 제안된 기법의 효용성을 증명하기 위해 MATLAB을 이용하여 모의실험 환경을 구축하고, 제안된 기법의 성능을 분석하였다. 이를 통하여, BCH 코드 내 비트 간 분배를 통해 수정되는 정도에 관계없이 CRC 코드의 성능이 우수하게 보존됨을 알 수 있었으며, 기존의 CRC 코드 기법보다 빠른 시간 내에 손상된 노드를 탐지할 수 있음을 보였다.

• Asian Pacific Journal of Cancer Prevention
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• 제16권9호
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• pp.4077-4080
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• 2015

The chemokine receptor 4 (CXCR4) has been widely used in diagnosis and prognosis of colorectal cancer (CRC). However, there is no current consensus on the impact of CXCR4 on CRC patients. The purpose of this study was to evaluate the prognostic and clinicopathological importance of CXCR4 in CRC patients. Databases, such as PubMed, Cochrane library, CBM and EMBASE updated to 2014 were searched to include eligible articles. We analysed correlations between CXCR4 expression and clinicopathological features and overall survival (OS). A total of 1, 055 CRC patients from twelve studies were included in the study. The pooled odds ratios (ORs) which indicated CXCR4 expression was likely to be associated with TNM stage (OR=0.43, CI=0.34-0.55, P<0.00001), lymph node status (OR=2.23, CI=1.23-4.05, P=0.008) and vascular invasion (OR=2.21, CI=1.11-4.39, P=0.02). Poor overall survival of CRC cancer was found to be significantly related to CXCR4 overexpression (hazard ratio (HR) 1.36 CI=1.17-1.59, P<0.0001), whereas combined ORs revealed that CXCR4 expression had no correlation with gender or differentiation. Based on the published studies, CXCR4 overexpression in patients w ith CRC indicates poor survival outcome and clinicopathological factors.

• Asian Pacific Journal of Cancer Prevention
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• 제17권3호
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• pp.939-944
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• 2016

Background: Cell-free DNA circulating in blood is a candidate biomarker for malignant tumors. Unlike uniformly truncated DNA released from apoptotic non diseased cells, DNA released from necrotic cancer cells varies in size. Objectives: To measure the DNA integrity index in serum and the absolute DNA concentration to assess their clinical utility as potential serum biomarkers for colorectal carcinoma (CRC) compared to CEA and CA19-9. Materials and Methods: Fifty patients with CRC, 10 with benign colonic polyps and 20 healthy sex and age matched volunteers, were investigated by real time PCR of ALU repeats (ALU q-PCR) using two sets of primers (115 and 247 bp) amplifying different lengths of DNA fragments. The DNA integrity index was calculated as the ratio of q-PCR results of ALU 247/ALU 115bp. Results: Serum DNA integrity was statistically significantly higher in CRC patients compared to the benign and control groups (p<0.001). ROC curves for differentiating CRC patients from normal controls and benign groups had areas under curves of 0.90 and 0.85 respectively. Conclusions: The DNA integrity index is superior to the absolute DNA concentration as a potential serum biomarker for screening and diagnosis of CRC. It may also serve as an indicator for monitoring the progression of CRC patients. Combining CEA and CA19-9 with either of the genetic markers studied is better than either of them alone.

• Asian Pacific Journal of Cancer Prevention
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• 제15권17호
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• pp.7091-7095
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• 2014

Background: The study aimed to evaluate the incidence of CpG island promoter methylation of BMP6, a member of the transforming growth factor beta family, in tissue samples from colorectal cancers (CRC) and look for its association with BMP6 expression and clinicopathological correlation. Materials and Methods: Methylation specific PCR for the BMP6 promoter region was performed with 85 frozen tissue samples of CRC and 45 of normal colon. Methylation status of MLH1 was also determined by the same method. Expression of BMP6 was evaluated by immunohistochemistry (IHC), using Allred's scoring system. The methylation status was analyzed against clinical and pathological parameters in CRC. Results: The study revealed BMP6 hypermethylation in 34 of 85 tumor specimens (40%), and 15 out of 45 normal tissue samples from CRC (33%). The incidence of hypermethylation was inversely correlated with IHC score. Allred's scores of 7 or more were correlated with lower frequency of BMP6 hypermethylation (29% compared to 50% in the remaining, p-value 0.049). However, there was no association between hypermethylation status and any clinicopathological parameters. The methylation status of BMP6 was not correlated with that of MLH1, a key methylation determinant in CRC. On survival analysis, there was no significant difference in progress-free survival (PFS) between the cases with and without hypermethylation (2-year PFS 74% and 76%, respectively). Conclusions: CpG island methylation of BMP6 is found in high frequency in CRC and this epigenetic event is associated with suppressed protein expression in the tumor tissue. However, the marker is not associated with tumor progression of the disease.

• Asian Pacific Journal of Cancer Prevention
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• 제14권11호
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• pp.6779-6782
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• 2013

Background: The DNA repair gene XRCC1 Arg399Gln gene polymorphism has been found to be implicated in the development of various cancers, including colorectal cancer (CRC), in different populations. We aimed to determine any association of this polymorphism with the risk of CRC in Kashmir. Materials and Methods: A total of 120 confirmed cases of CRC and 146 healthy cancer free controls from the Kashmiri population were included in this study. Genotyping was carried out by the polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP) method. Results: Genotype frequencies of XRCC1 Arg399Gln observed in controls were 34.2%, 42.5% and 23.3% for GG (Arg/Arg), GA (Arg/Gln), AA( Gln/Gln), respectively, and 28.3%, 66.7% and 5% in cases, with an odds ratio (OR)=5.7 and 95% confidence interval (CI) =2.3-14.1 (p=0.0001). No significant association of Arg399Gln SNP with any clinicopathological parameters of CRC was found. Conclusions: We found the protective role of 399Gln allele against risk to the development of CRC. The XRCC1 heterozygote status appears to be a strong risk factor for CRC development in the Kashmiri population.

• Asian Pacific Journal of Cancer Prevention
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• 제15권15호
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• pp.6421-6423
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• 2014

Background: Recent studies have revealed a prognostic impact of the MPV (mean platelet volume)/platelet count ratio in terms of survival in advanced non-small cell lung cancer. However, there has been no direct analysis of the survival impact of MPV in patients with mCRC. The aim of the study is to evaluate the pretreatment MPV of patients with metastatic and non-metastatic colorectal cancer (non-mCRC) and also the prognostic significance of pretreatment MPV to progression in mCRC patients treated with bevacizumab-combined chemotherapy. Materials and Methods: Fifty-three metastatic and ninety-five non-metastatic colorectal cancer patients were included into the study. Data on sex, age, lymph node status, MPV, platelet and platecrit (PCT) levels were obtained retrospectively from the patient medical records. Results: The MPV was significantly higher in the patients with mCRC compared to those with non-mCRC ($7.895{\pm}1.060$ versus $7.322{\pm}1.136$, p=0.013). The benefit of bevacizumab on PFS was significantly greater among the patients with low MPV than those with high MPV. The hazard ratio (HR) of disease progression was 0.41 (95%CI, 0.174-0.986; p=0.04). In conclusion, despite the retrospective design and small sample size, MPV can be considered a prognostic factor for mCRC patients treated with bevacizumab-combined chemotherapy.

• Asian Pacific Journal of Cancer Prevention
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• 제15권7호
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• pp.3287-3291
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• 2014

Background: The interesting preponderance of Chinese with colorectal carcinoma (CRC) amongst the three major ethnic groups in Malaysia prompted a study to determine DNA mismatch repair (MMR) status in our CRC and attempt correlation with patient age, gender and ethnicity as well as location, grade, histological type and stage of tumour. Histologically re-confirmed CRC, diagnosed between $1^{st} $January 2005 and $31^{st}$ December 2007 at the Department of Pathology, University of Malaya Medical Centre, were immunohistochemically stained with monoclonal antibodies to MMR proteins, MLH1, MSH2, MSH6 and PMS2 on the Ventana Benchmark XT autostainer. Of the 142 CRC cases entered into the study, there were 82 males and 60 females (M:F=1.4:1). Ethnically, 81 (57.0%) were Chinese, 32 (22.5%) Malays and 29 (20.4%) Indians. The patient ages ranged between 15-87 years (mean=62.4 years) with 21 cases <50-years and 121 ${\geq}50$-years of age. 14 (9.9%) CRC showed deficient MMR (dMMR). Concurrent loss of MLH1 and PMS2 occurred in 10, MSH2 and MSH6 in 2 with isolated loss of MSH6 in 1 and PMS2 in 1. dMMR was noted less frequently amongst the Chinese (6.2%) in comparison with their combined Malay and Indian counterparts (14.8%), and was associated with right sided and poorly differentiated tumours (p<0.05). 3 of the 5 (60.0%) dMMR CRC cases amongst the Chinese and 1 of 9 cases (11.1%) amongst the combined Malay and Indian group were <50-years of age. No significant association of dMMR was noted with patient age and gender, tumour stage or mucinous type.

• Asian Pacific Journal of Cancer Prevention
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• 제14권10호
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• pp.6069-6075
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• 2013

Background: At present, the diagnosis of colorectal cancer (CRC) requires a colorectal biopsy which is an invasive procedure. We undertook this pilot study to develop an alternative method and potential new biomarkers for diagnosis, and validated a set of well-integrated tools called ClinProt to investigate the serum peptidome in CRC patients. Methods: Fasting blood samples from 67 patients diagnosed with CRC by histological diagnosis, 55 patients diagnosed with colorectal adenoma by biopsy, and 65 healthy volunteers were collected. Division was into a model construction group and an external validation group randomly. The present work focused on serum proteomic analysis of model construction group by ClinProt Kit combined with mass spectrometry. This approach allowed construction of a peptide pattern able to differentiate the studied populations. An external validation group was used to verify the diagnostic capability of the peptidome pattern blindly. An immunoassay method was used to determine serum CEA of CRC and controls. Results: The results showed 59 differential peptide peaks in CRC, colorectal adenoma and health volunteers. A genetic algorithm was used to set up the classification models. Four of the identified peaks at m/z 797, 810, 4078 and 5343 were used to construct peptidome patterns, achieving an accuracy of 100% (> CEA, P<0.05). Furthermore, the peptidome patterns could differentiate the validation group with high accuracy close to 100%. Conclusions: Our results showed that proteomic analysis of serum with MALDI-TOF MS is a fast and reproducible approach, which may provide a novel approach to screening for CRC.