• Journal of Gastric Cancer
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• 제4권1호
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• pp.1-6
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• 2004

Purpose: Despite numorous reports on the relationship between the level of carcinoembryonic antigen (CEA) in gall bladder bile and liver metastasis in colorectal cancer, no similar studies have been carried out for gastric carcinomas. We, therefore, undertook the present study to establish the relationship between the gall bladder bile CEA and liver metastasis as well as the post-operative survival rate in gastric carcinoma patients with curative resections. Materials and Methods: In 373 gastric cancer patients (252 males, 121 females, age $21\∼76$ years) operated on at Kosin University Hospital between 1989 1996, the CEA concentration in the gall bladder bile was determined during the operation and the value was related to the rates of post-operative survival and liver metastasis during follow-up period. Results: The overall rate of patient survival decreased gradually with increase in TNM stage. The 13-year postoperative survival rates for stages Ia, Ib, II, IIIa, and IIIb were $95.7\%,\;92.5\%,\;79.9\%,\;50.9\%,\;and\;43.3\$, respectively, and the 10-year survival rate for stage IV was $22.6\%$. The patients with a high ($\geq$10 ng/ml) biliary CEA showed a significantly lower rate of survival than those with a low (<10 ng/ml) biliary CEA. The 13-year cumulative survival rate was $55.4\%$ for the high CEA group and $76.5\%$ for the low CEA group (P<0.01). Also, the patients with a high biliary CEA showed a significantly higher rate ($11.5\%$) of liver metastasis than those with a low biliary CEA ($1.9\%$) (P<0.000). In patients with TNM stages (I and II), the CEA level did not affect the post-operative survival rates ($95.4\%\;and87.7\%$ in the high and low CEA groups, P>0.10), but in those with high TNM stages (III and IV), the survival rate was significantly lower in the high CEA group ($25.9\%$) than in the low CEA group ($57.8\%$) (P<0.05). Conclusion: These result suggest that the gall bladder bile CEA level obtained in an advanced-staged gastric cancer operation may be used in predicting the post-operational survival rate and in sorting out patients with a high risk for cancer recurrence, especially in the liver area.

• Bioinformatics and Biosystems
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• 제1권1호
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• pp.67-72
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• 2006

The aim of this paper is to discuss the effect of missing values in detecting differentially expressed genes in a cDNA microarray experiment in the context of a one sample problem. We conducted a cDNA micro array experiment to detect differentially expressed genes for the metastasis of colorectal cancer based on twenty patients who underwent liver resection due to liver metastasis from colorectal cancer. Total RNAs from metastatic liver tumor and adjacent normal liver tissue from a single patient were labeled with cy5 and cy3, respectively, and competitively hybridized to a cDNA microarray with 7775 human genes. We used $M=log_2(R/G)$ for the signal evaluation, where Rand G denoted the fluorescent intensities of Cy5 and Cy3 dyes, respectively. The statistical problem comprises a one sample test of testing E(M)=0 for each gene and involves multiple tests. The twenty cDNA microarray data would comprise a matrix of dimension 7775 by 20, if there were no missing values. However, missing values occur for various reasons. For each gene, the no missing proportion (NMP) was defined to be the proportion of non-missing values out of twenty. In detecting differentially expressed (DE) genes, we used the genes whose NMP is greater than or equal to 0.4 and then sequentially increased NMP by 0.1 for investigating its effect on the detection of DE genes. For each fixed NMP, we imputed the missing values with K-nearest neighbor method (K=10) and applied the nonparametric t-test of Dudoit et al. (2002), SAM by Tusher et al. (2001) and empirical Bayes procedure by $L\ddot{o}nnstedt$ and Speed (2002) to find out the effect of missing values in the final outcome. These three procedures yielded substantially agreeable result in detecting DE genes. Of these three procedures we used SAM for exploring the acceptable NMP level. The result showed that the optimum no missing proportion (NMP) found in this data set turned out to be 80%. It is more desirable to find the optimum level of NMP for each data set by applying the method described in this note, when the plot of (NMP, Number of overlapping genes) shows a turning point.

• Molecules and Cells
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• 제43권7호
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• pp.662-670
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• 2020

We have investigated the involvement of the pre-mRNA processing factor 4B (PRP4) kinase domain in mediating drug resistance. HCT116 cells were treated with curcumin, and apoptosis was assessed based on flow cytometry and the generation of reactive oxygen species (ROS). Cells were then transfected with PRP4 or pre-mRNA-processing-splicing factor 8 (PRP8), and drug resistance was analyzed both in vitro and in vivo. Furthermore, we deleted the kinase domain in PRP4 using Gateway™ technology. Curcumin induced cell death through the production of ROS and decreased the activation of survival signals, but PRP4 overexpression reversed the curcumin-induced oxidative stress and apoptosis. PRP8 failed to reverse the curcumin-induced apoptosis in the HCT116 colon cancer cell line. In xenograft mouse model experiments, curcumin effectively reduced tumour size whereas PRP4 conferred resistance to curcumin, which was evident from increasing tumour size, while PRP8 failed to regulate the curcumin action. PRP4 overexpression altered the morphology, rearranged the actin cytoskeleton, triggered epithelial-mesenchymal transition (EMT), and decreased the invasiveness of HCT116 cells. The loss of E-cadherin, a hallmark of EMT, was observed in HCT116 cells overexpressing PRP4. Moreover, we observed that the EMT-inducing potential of PRP4 was aborted after the deletion of its kinase domain. Collectively, our investigations suggest that the PRP4 kinase domain is responsible for promoting drug resistance to curcumin by inducing EMT. Further evaluation of PRP4-induced inhibition of cell death and PRP4 kinase domain interactions with various other proteins might lead to the development of novel approaches for overcoming drug resistance in patients with colon cancer.

• Journal of Hospice and Palliative Care
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• 제12권4호
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• pp.228-233
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• 2009

목적: 본 연구는 응급실을 내원하는 암 환자의 실태를 파악하기 위한 후향적 조사연구이다. 방법: 2006년 1월부터 2006년 12월까지 C 대학교병원 응급실에 내원한 종양내과 암 환자 564명의 응급실 의료정보지를 분석하였다. 실태 조사서는 암 병동 근무경력 6년 이상의 간호사 4인과 종양내과 교수 1인 및 간호대학 교수 1인에게 내용 타당도를 검증받아 사용하였으며, 수집된 자료는 SAS (ver 9.1)를 이용하여 빈도와 백분율로 분석하였다. 결과: 대상자의 질병관련 특성은 위장관계 암이 28.9%로 가장 많았고, 병기는 4기가 66.9%로 가장 많았다. 응급실 내원 전에 최근 받은 치료는 항암화학요법이 51.6%이었고, 항암화학요법 치료 횟수는 1~5회가 82.5%로 가장 많았으며, 최근 치료받은 장소는 입원 병동이 52.4%로 가장 많았다. 대상자의 응급실 내원관련 특성은 항암화학요법 치료 후 내원까지 2주 이하인 경우가 62.9%로 가장 많았고, 증상 발현에서 내원까지의 기간이 1일 이내가 34.9%, 응급실 내원 후 입원까지 1일이내가 71.8%로 가장 많았다. 내원요일은 평일이 73.2%로 가장 많았고, 응급실 내원 후 입원한 경우가 77.2%로 가장 많았다. 응급실을 내원 시 주요증상은 통증이 34.3%로 가장 많았고, 위 장관계 증상이 30.0%, 호흡기계 증상이 21.5%, 고열이 16.3% 순이었다. 응급실에 내원한 주요증상은 위장관계 암과 췌장 간 담도암은 통증, 림프종은 고열, 폐암은 호흡기계 증상, 두경부암이나 육종, 유방암을 포함한 기타 암은 위장관계 증상이 가장 많았다. 결론: 이상의 결과를 볼 때 암 환자들이 응급실을 내원하는 주요증상은 질환에 따라 차이가 있기 때문에 대상자의 특성에 따라 맞춤형 프로그램을 개발하는 것이 필요하다. 특히 3기 이상의 진행암 환자들이 응급실을 내원하지 않고 총체적인 의료서비스를 받을 수 있는 제도를 마련하는 것이 시급하다. 또한 암 환자들이 병원과 가정에서 적극적으로 통증 관리를 연계해서 받을 수있는 체계를 마련하고, 위장관계 암과 폐암 환자들이 퇴원 후 응급증상을 효율적으로 관리할 수 있는 맞춤형 교육자료를 개발해야 할 필요가 있다고 생각한다.

• Asian Pacific Journal of Cancer Prevention
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• 제15권23호
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• pp.10193-10198
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• 2015

Background: Cancer is a major cause of mortality in developing countries and correct and valid information about the epidemiology of this disease is the first step in the planning of health care in each region. The aim of this study was to determine the relative frequency, mean age and sex ratio of the most 10 common non-skin cancers in the world and Iran, among patients referred to an oncology clinic. Materials and Methods: This descriptive study was conducted in Mashhad, north east of Iran. The data obtained from the records of patients referred to the private oncology center between the years of 1985-2012". According to the latest report of GLOBOCAN study commonest malignancies included were lung, breast, colorectal, prostate, stomach, liver, cervix, esophageal, bladder cancers and Non-Hodgkin lymphoma. Results: A total of 4,606 cases were analyzed. The mean age was $55.5{\pm}13.8years$ (male: $59.5{\pm}13.9$, female: $52.6{\pm}12.9$). Overall, breast cancer (1,264 cases, relative frequency of 27.4%) was the most prevalent cancer; however the mean ages of diagnosis were not significantly different between 5-year time period divisions (p=0.290). The most common cancer in men was esophageal cancer (26.3%).The lowest mean age was related to women diagnosed with breast cancer ($48.5{\pm}11.8$) and men with non-Hodgkins lymphoma ($48.4{\pm}17.8$). There were statistically significant differences between the mean age of men and women with gastric (p=0.003) and esophageal cancers (p<0.001). Male to female sex ratios in our study for bladder, lung and stomach cancers were 6.57, 2.60 and 2.50 respectively. Conclusions: The results showed that breast cancer tends to be found in younger female patients and bladder cancer appears more often in men. Screening in target population in addition to early diagnosis may reduce death and disability.

• Asian Pacific Journal of Cancer Prevention
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• 제16권8호
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• pp.3395-3402
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• 2015

Background: Preoperative 5-fluorouracil (5-FU)-based chemoradiotherapy is a standard treatment for locally advanced colorectal cancer (CRC). However, CRC cells often develop chemoradiation resistance (CRR). Recent studies have shown that long non-coding RNA (lncRNA) plays critical roles in a myriad of biological processes and human diseases, as well as chemotherapy resistance. Since the roles of lncRNAs in 5-FU-based CRR in human CRC cells remain unknown, they were investigated in this study. Materials and Methods: A 5-FU-based concurrent CRR cell model was established using human CRC cell line HCT116. Microarray expression profiling of lncRNAs and mRNAs was undertaken in parental HCT116 and 5-FU-based CRR cell lines. Results: In total, 2,662 differentially expressed lncRNAs and 2,398 mRNAs were identified in 5-FU-based CRR HCT116 cells when compared with those in parental HCT116. Moreover, 6 lncRNAs and 6 mRNAs found to be differentially expressed were validated by quantitative real time PCR (qRT-PCR). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis for the differentially expressed mRNAs indicated involvement of many, such as Jak-STAT, PI3K-Akt and NF-kappa B signaling pathways. To better understand the molecular basis of 5-FU-based CRR in CRC cells, correlated expression networks were constructed based on 8 intergenic lncRNAs and their nearby coding genes. Conclusions: Changes in lncRNA expression are involved in 5-FU-based CRR in CRC cells. These findings may provide novel insight for the prognosis and prediction of response to therapy in CRC patients.

• Radiation Oncology Journal
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• 제34권2호
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• pp.106-112
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• 2016

Purpose: To identify possible predictors of pathologic complete response (pCR) of rectal cancer after preoperative concurrent chemoradiotherapy (CCRT). Materials and Methods: We conducted a retrospective review of 53 patients with rectal cancer who underwent preoperative CCRT followed by radical surgery at a single center between January 2007 and December 2012. The median radiotherapy dose to the pelvis was 54.0 Gy (range, 45.0 to 63.0 Gy). Five-fluorouracil-based chemotherapy was administered via continuous infusion with leucovorin. Results: The pCR rate was 20.8%. The downstaging rate was 66%. In univariate analyses, poor and undifferentiated tumors (p = 0.020) and an interval of ${\geq}7$ weeks from finishing CCRT to surgery (p = 0.040) were significantly associated with pCR, while female gender (p = 0.070), initial carcinoembryonic antigen concentration of <5.0 ng/dL (p = 0.100), and clinical stage T2 (p = 0.100) were marginally significant factors. In multivariate analysis, an interval of ${\geq}7$ weeks from finishing CCRT to surgery (odds ratio, 0.139; 95% confidence interval, 0.022 to 0.877; p = 0.036) was significantly associated with pCR, while stage T2 (odds ratio, 5.363; 95% confidence interval, 0.963 to 29.877; p = 0.055) was a marginally significant risk factor. Conclusion: We suggest that the interval from finishing CCRT to surgery is a predictor of pCR after preoperative CCRT in patients with rectal cancer. Stage T2 cancer may also be an important predictive factor. We hope to perform a robust study by collecting data during treatment to obtain more advanced results.

• Asian Pacific Journal of Cancer Prevention
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• 제16권17호
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• pp.7831-7836
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• 2015

Background: Colorectal cancer (CRC) is one of the most common malignancies of the gastrointestinal tract. The aim of this study was to assess the general knowledge of CRC in individuals living in Rasht, Iran, using a population-based cross-sectional telephone survey. Materials and Methods: A total of 1557 participants between 18 and 80 years of age were interviewed using random sampling from the telephone directory. Knowledge of risk factors, symptoms, diagnosis, and prevention of CRC was assessed using a validated questionnaire. Results: The mean knowledge level of the 1,557 respondents (average age 46 y) was $13.5{\pm}4.29$ (maximum possible score = 26), and 46.4% (722/1,557) of the subjects achieved grades lower than the mean score. The mean scores for knowledge of symptoms and risk factors were $3.97{\pm}1.83$ (range: 0-7) and $5.17{\pm}1.65$ (range: 0-9), respectively. Older age, higher education, and employment were significantly associated with better scores for recognition of risk factors and warning symptoms. The majority of subjects correctly identified weight loss (70.2%; 1,093/1,557) and rectal bleeding (63.3%; 986/1,557) as symptoms of CRC, and that smoking (85.9%; 1,337/1,557) and a low-fiber diet (73.4%; 1,143/1,557) were risk factors. Approximately half of the subjects noted increasing age, genetic background and fried food as other risk factors. A considerable number (54.8%; 853/1,557) identified colonoscopy as a screening method for detecting CRC in asymptomatic patients. However, a third of the subjects in the target group for screening (${\geq}50y$) were not interested in undergoing screening, primarily due to a lack of symptoms. Conclusions: Our results suggest that the knowledge of CRC is poor among the public, and therefore greater attempts should be made to increase awareness. Public education emphasizing the risk factors and symptoms of CRC, as well as the importance of regular screening regardless of the presence of symptoms, may help to reduce CRC morbidity and mortality.

• Asian Pacific Journal of Cancer Prevention
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• 제17권12호
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• pp.5147-5152
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• 2016

Background: Investigations of methods for detection of mutations have uncovered major weaknesses of direct sequencing and pyrosequencing, with their high costs and low sensitivity in screening for both known and unknown mutations. High resolution melting (HRM) analysis is an alternative tool for the rapid detection of mutations. Here we describe the accuracy of HRM in screening for KRAS and BRAF mutations in metastatic colorectal cancer (mCRCs) samples. Materials and Methods: A total of 1000 mCRC patients in Mehr Hospital, Tehran, Iran, from Feb 2008 to May 2012 were examined for KRAS mutations and 242 of them were selected for further assessment of BRAF mutations by HRM analysis. In order to calculate the sensitivity and specificity, HRM results were checked by pyrosequencing as the golden standard and Dxs Therascreen as a further method. Results: In the total of 1,000 participants, there were 664 (66.4%) with wild type and 336 (33.6%) with mutant codons 12 and/or 13 of the KRAS gene. Among 242 samples randomly checked for the BRAF gene, all were wild type by HRM. Pyrosequencing and Dxs Therascreen results were in line with those of the HRM. In this regard, the sensitivity and specificity of HRM were evaluated as 100%. Conclusion: The findings suggest that the HRM, in comparison with DNA sequencing, is a more appropriate method for precise scanning of KRAS and BRAF mutations. It is also possible to state that HRM may be an attractive technique for the detection of known or unknown somatic mutations in other genes.

• Asian Pacific Journal of Cancer Prevention
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• 제15권20호
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• pp.8699-8703
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• 2014

18-fluoro-2-deoxyglucose positron emission tomography-computed tomography ($^{18}F$-FDG PET/CT) scans are commonly used for the staging and restaging of various malignancies, such as head and neck, breast, colorectal and gynecological cancers. However, the value of FDG PET/CT for detecting prostate cancer is unknown. The aim of this study was to evaluate the clinical value of incidental prostate $^{18}F$-FDG uptake on PET/CT scans. We reviewed $^{18}F$-FDG PET/CT scan reports from September 2009 to September 2013, and selected cases that reported focal/diffuse FDG uptake in the prostate. We analyzed the correlation between $^{18}F$-FDG PET/CT scan findings and data collected during evaluations such as serum prostate-specific antigen (PSA) levels, digital rectal examination (DRE), transrectal ultrasound (TRUS), and/or biopsy to confirm prostate cancer. Of a total of 18,393 cases, 106 (0.6%) exhibited abnormal hypermetabolism in the prostate. Additional evaluations were performed in 66 patients. Serum PSA levels were not significantly correlated with maximum standardized uptake values (SUVmax) in all patients (rho 0.483, p=0.132). Prostate biopsies were performed in 15 patients, and prostate cancer was confirmed in 11. The median serum PSA level was 4.8 (0.55-7.06) ng/mL and 127.4 (1.06-495) ng/mL in the benign and prostate cancer groups, respectively. The median SUVmax was higher in the prostate cancer group (mean 10.1, range 3.8-24.5) than in the benign group (mean 4.3, range 3.1-8.8), but the difference was not statistically significant (p=0.078). There was no significant correlation between SUVmax and serum PSA, prostatic volume, or Gleason score. $^{18}F$-FDG PET/CT scans did not reliably differentiate malignant or benign from abnormal uptake lesions in the prostate, and routine prostate biopsy was not usually recommended in patients with abnormal FDG uptake. Nevertheless, patients with incidental prostate uptake on $^{18}F$-FDG PET/CT scans should not be ignored and should be undergo further clinical evaluations, such as PSA and DRE.