• Asian Pacific Journal of Cancer Prevention
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• 제13권7호
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• pp.3209-3212
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• 2012

Introduction: Colorectal carcinoma (CRC) is the most common gastrointestinal malignancy in the older population, but it is also quite frequent among young adults in developing countries. The aim of this study was to update the trends of clinicopathological features of CRC in young Nepalese. Methods: A retrospective comparative study on the data retrieved from the surgical records of all patients between 20 to 39 years of age with CRC was carried out for periods of 5 years each from 1999 to 2003 (early) and 2004 to 2008 (recent), treated at Tribhuvan University Teaching Hospital, Kathmandu, Nepal. Results: The number of young adults with CRC increased from 28 to 34. However, the proportion of young patients in both groups was 28% of all CRC patients. The mean ages were $34{\pm}4.7$ and $31.8{\pm}5.1$ years in early and recent 5 years, respectively, and the male female ratio changed from 2:3 to 4:3. Abdominal pain as the most common presenting symptom was replaced by bleeding per rectum in recent years. The mean duration from onset of symptoms to seeking medical advice decreased from 7.8 months to 5.6 months in recent years. More patients (85.3%) were subjected to endoscopic examination in recent years than early years (60.7%) and right colonic cancer increased from 10.7% to 26.5%. However, the rectum was the commonest site in both early (71.4%) and recent (50%) groups. CRC was detected significantly at an earlier stage (7.1% vs 32.4%) in recent years with large proportion of modified Dukes B stage. Poorly differentiated adenocarcinoma was the predominant histology in both groups (50% vs 60.7%). Curative resection had risen in recent years (39.3% vs 73.6%). Conclusion: CRC among Nepalese young adults accounts for a high incidence (28%) of all CRC cases. Although right sided colonic cancer has been increasing, rectum is the commonest site. There is also an increasing trend for diagnosis at earlier stages of the disease which can be treated with curative intent.

• Asian Pacific Journal of Cancer Prevention
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• 제17권4호
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• pp.2119-2123
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• 2016

Background: There is an established link between obesity related metabolic derangement and colorectal cancer development. Recently, we developed a metabolic-colorectal cancer risk score. In this follow-up study, we studied its association with colorectal neoplasm by measuring two major metabolic syndrome biomarkers, leptin and adiponectin. Objectives: To evaluate the serum levels of leptin and adiponectin in patients with colorectal polyps and colorectal cancer and to determine any correlation with metabolic risk score. Results: In total, 130 individuals were studied: 30 controls without colonic pathology, 18 with colonic adenoma (CAP), and 82 with colorectal adenocarcinoma (CRC, 17 cases of T1-2 and 65 cases of T3-4). The metabolic risk scores in CAP and T1-2 CRC were higher than those in the controls and T3-4 CRC cases. There were no statistically significant differences in leptin levels among CAPs, CRCs, and controls. Both leptin and adiponectin levels reflected differences in body mass index and metabolic risk scores. Cases in the CAP group and early T-stage CRC groups had lower adiponectin levels (14.03 and 13.01 mg/ml, respectively) than the no polyps group (19.5mg/ml, p = 0.03). The average serum adiponectin level in the invasive cancer group (18.5 ng/ml) was comparable with that of the control group. Conclusions: The level of serum adiponectin was positively correlated with the metabolic risk score. Decreased serum adiponectin was significantly associated with the development of colorectal adenoma and early stage colorectal carcinoma.

• Asian Pacific Journal of Cancer Prevention
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• 제16권16호
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• pp.6923-6928
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• 2015

Background: Early detection of various kinds of cancers nowadays is needed including colorectal cancer due to the highly significant effects in improving cancer treatment. The aim of this study was to evaluate the potential value of adiponectin, visfatin and resistin as early biomarkers for colorectal cancer patients. Materials and Methods: Serum levels of adiponectin, visfatin and resistin were measured by a sandwich-enzyme-linked (ELISA) assay technique in 114 serum samples comprising 34 patients with colorectal cancer (CRC), 27 with colonic polyps (CP), 24 with inflammatory bowel disease (IBD) and 29 healthy controls. The diagnostic accuracy of each serum marker was evaluated using receiver-operating characteristic (ROC) curve analysis. Results: The mean concentration of adiponectin was significantly higher in CRC and CP groups than IBD and control groups (P-value <0.05). Also the mean concentration of serum resistin was significantly elevated in the IBD and control groups compared to CRC and CP groups (P-value = 0.014). However, no significant difference was noted in patients of the CRC and CP groups. On the other hand, the mean concentration of visfatin was significantly elevated in CRC and control groups compared to CP and IBD groups (P-value = 0.03). ROC analysis curves for the studied markers revealed that between CRC and IBD groups serum level of adiponectin had a sensitivity of 76.7% and a specificity of 76% at a cut off value of 3940, +LR being 3.2 and -LR 0.31 with AUC 0.852, while serum level of adiponectin between CP and IBD had a sensitivity of 77.8% and a specificity of 75% at a cut off value of 3300, with +LR=3.11 and -LR = 0.3 with AUC 0.852. On the other hand the serum level of visfatin between CRC and CP groups had a sensitivity of 65.5% and a specificity of 66.7 at a cut off value of 2.4, +LR being 1.67 and -LR 0.52 with AUC 0.698. Also the serum level of resistin had a sensitivity of 62.5% and a specificity of 70.3% at a cut off value of 24500, with +LR=2.1 and -LR = 0.53 with AUC 0.685 between control and other groups. On the other hand by comparing control vs CP groups resistin had a sensitivity of 81.8% and a specificity of 70.8% at a cut off value of 17700, with +LR=2.8 and -LR = 0.26 with AUC 0.763 while visfatin had a sensitivity of 68.2% and a specificity of 70.8% at a cut off value of 2.7, with +LR=2.34 and -LR = 0.0.45 with AUC 0.812. Conclusions: These findings support potential roles of adiponectin, visfatin and resistin in early detection of CRC and discrimination of different groups of CRC, CP or IBD patients from normal healthy individuals.

• Asian Pacific Journal of Cancer Prevention
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• 제15권5호
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• pp.2083-2087
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• 2014

Colorectal cancers remain to be a common cause of cancer-related death. Early-onset cases as well as those of various ethnic origins have aggressive clinical features, the basis of which requires further exploration. The aim of this work was to examine the expression patterns of $p15^{INK4b}$ and SMAD4 in colorectal carcinoma of different ethnic origins. Fifty-five sporadic colorectal carcinoma of Egyptian origin, 25 of which were early onset, and 54 cancers of Finnish origin were immunohistochemically stained with antibodies against $p15^{INK4b}$ and SMAD4 proteins. Data were compared to the methylation status of the $p15^{INK4b}$ gene promotor. $p15^{INK4b}$ was totally lost or deficient (lost in ${\geq}50%$ of tumor cell) in 47/55 (85%) tumors of Egyptian origin as compared to 6/50 (12%) tumors of Finnish origin (p=7e-15). In the Egyptian cases with $p15^{INK4b}$ loss and available $p15^{INK4b}$ promotor methylation status, 89% of cases which lost $p15^{INK4b}$ expression were associated with $p15^{INK4b}$ gene promotor hypermethylation. SMAD4 was lost or deficient in 25/54 (46%) tumors of Egyptian origin and 28/48 (58%) tumors of Finnish origin. 22/54 (41%) Egyptian tumors showed combined loss/deficiency of both $p15^{INK4b}$ and SMAD4, while $p15^{INK4b}$ was selectively lost/deficient with positive SMAD4 expression in 24/54 (44%) tumors. Loss of $p15^{INK4b}$ was associated with older age at presentation (>50 years) in the Egyptian tumors (p=0.04). These data show for the first time that $p15^{INK4b}$ loss of expression marks a subset of colorectal cancers and ethnic origin may play a role in this selection. In a substantial number of cases, the loss was independent of SMAD4 but rather associated with $p15^{INK4b}$ gene promotor hypermethylation and old age which could be related to different environmental exposures.

• Asian Pacific Journal of Cancer Prevention
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• 제14권7호
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• pp.4249-4254
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• 2013

Background: Parafibromin is a protein encoded by the HRPT2 (hyperparathyroidism 2) oncosuppressor gene and its down-regulated expression is involved in pathogenesis of parathyroid, breast, gastric and colorectal carcinomas. This study aimed to clarify the effects of parafibromin expression on the phenotypes and relevant mechanisms of DLD-1 colon carcinoma cells. Methods: DLD-1 cells transfected with a parafibromin-expressing plasmid were subjected to examination of phenotype, including proliferation, differentiation, apoptosis, migration and invasion. Phenotype-related proteins were measured by Western blot. Parafibromin and ki-67 expression was detected by immunohistochemistry on tissue microarrays. Results: The transfectants showed higher proliferation by CCK-8, better differentiation by electron microscopy and ALP activity and more apoptotic resistance to cisplatin by DNA fragmentation than controls. There was no difference in early apoptosis by annexin V, capase-3 activity, migration and invasion between DLD-1 cells and their transfectants. Ectopic parafibromin expression resulted in down-regulated expression of smad4, MEKK, GRP94, GRP78, $GSK3{\beta}$-ser9, and Caspase-9. However, no difference was detectable in caspase-12 and -8 expression. A positive relationship was noted between parafibromin and ki-67 expression in colorectal carcinoma. Conclusions: Parafibromin overexpression could promote cell proliferation, apoptotic resistance, and differentiation of DLD-1 cells.

• Asian Pacific Journal of Cancer Prevention
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• 제16권11호
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• pp.4521-4524
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• 2015

Background: Endometrial carcinoma is the most common malignant tumor of the female genital tract and the fourth most common cancer in Iranian women after breast, colorectal and lung cancers. Various genetic alterations appear to be early events in the pathogenesis of endometrial carcinoma and it seems that PTEN is the most commonly mutated gene in the endometrioid subtype. The aim of the present study was to investigate the correlation between mutations in exon 7 of PTEN gene and endometrial carcinoma. Materials and Methods: Seventy-five patients with endometrial carcinoma and 75 females whose underwent hysterectomy for non tumoral indication were selected for evaluation of PTEN mutations in exon 7 by PCR-SSCP and sequencing. Correlations between the frequency and type of mutation and the pathologic findings of the cancer (tumor subtype, stage and grade) were assessed. Results: All of the samples were obtained from Iranian patients. 60 % (45 cases) of the tumors were endometriod and 40% (30 cases) were of serous type. The grade distributions of the 75 cases according to the FIGO staging system were as follows: low grade, 20 cases; high grade 55 cases, low stage, 41 cases; high stage 34 cases. For exon 7 of the PTEN gene, the analysis showed that there were no mutations in our cases. Conclusions: Our findings in the present study suggest that exon 7 of PTEN does not play any significant role in the development of endometrial carcinoma in Iranian cases.

• Asian Pacific Journal of Cancer Prevention
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• 제14권3호
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• pp.2113-2118
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• 2013

Aim and Background: Cervical cancer remains the third most common cancer in women globally after breast and colorectal cancer. Well-characterized biomarkers are necessary for early diagnosis and to predict metastatic progression and effective therapy. MiRNAs can regulate gene expression, cell growth, differentiation and apoptosis by targeting mRNAs for translational repression or degradation in tumor cells. The present study was conducted to assess expression of miR93, miR200a, RECK, MMP2, MMP9 in invasive cervical carcinoma, and analyze their clinical significance. Method: A total of 116 patients with invasive cervical carcinoma and 100 patients undergoing hysterectomy for benign lesions were retrospectively examined. Quantitative real-time PCR was performed to determine expression of miR93 and miR200a while RECK, MMP2, MMP9 and MVD were assessed by immunohistochemical staining. Results: Cervical carcinoma patients demonstrated up-regulation of miR-93, miR-200a, MMP2 and MMP9, with down-regulation of RECK as compared to benign lesion tissues. RECK was significantly inversely related to invasion and lymphatic metastasis. The 5-year survival rate for patients with strong RECK expression was significantly higher than that with weakly expressing tumors. Conclusion: MiR-93 and miR-200a are associated with metastasis and invasion of cervical carcinoma. Thus together with RECK they are potential prognostic markers for cervical carcinoma. RECK cooperating with MMP2, MMP9 expression is a significant prognostic factor correlated with long-term survival for patients with invasive cervical carcinoma.

• Journal of Digestive Cancer Reports
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• 제8권1호
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• pp.1-50
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• 2020

Although surgery was the standard treatment for early gastrointestinal cancers, endoscopic resection is now a standard treatment for early gastrointestinal cancers without regional lymph node metastasis. High-definition white light endoscopy, chromoendoscopy, and image-enhanced endoscopy such as narrow band imaging are performed to assess the edge and depth of early gastrointestinal cancers for delineation of resection boundaries and prediction of the possibility of lymph node metastasis before the decision of endoscopic resection. Endoscopic mucosal resection and/or endoscopic submucosal dissection can be performed to remove early gastrointestinal cancers completely by en bloc fashion. Histopathological evaluation should be carefully made to investigate the presence of risk factors for lymph node metastasis such as depth of cancer invasion and lymphovascular invasion. Additional treatment such as radical surgery with regional lymphadenectomy should be considered if the endoscopically resected specimen shows risk factors for lymph node metastasis. This is the first Korean clinical practice guideline for endoscopic resection of early gastrointestinal cancer. This guideline was developed by using mainly de novo methods and encompasses endoscopic management of superficial esophageal squamous cell carcinoma, early gastric cancer, and early colorectal cancer. This guideline will be revised as new data on early gastrointestinal cancer are collected.

• Toxicological Research
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• 제35권4호
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• pp.331-341
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• 2019

Cancer is one of the common causes of death with a high degree of mortality, worldwide. In many types of cancers, if not all, sex-biased disparities have been observed. In these cancers, an individual's sex has been shown to be one of the crucial factors underlying the incidence and mortality of cancer. Accumulating evidence suggests that differentially expressed genes and proteins may contribute to sex-biased differences in male and female cancers. Therefore, identification of these molecular differences is important for early diagnosis of cancer, prediction of cancer prognosis, and determination of response to specific therapies. In the present review, we summarize the differentially expressed genes and proteins in several cancers including bladder, colorectal, liver, lung, and nonsmall cell lung cancers as well as renal clear cell carcinoma, and head and neck squamous cell carcinoma. The sex-biased molecular differences were identified via proteomics, genomics, and big data analysis. The identified molecules represent potential candidates as sex-specific cancer biomarkers. Our study provides molecular insights into the impact of sex on cancers, suggesting strategies for sex-biased therapy against certain types of cancers.

• 대한임상검사과학회지
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• 제49권4호
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• pp.470-476
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• 2017

mTOR 신호전달 단백질의 변화는 다양한 종류의 암에서 관찰 되었다. 따라서 이들 단백질은 최근에 암 치료제에 대한 새롭고 흥미로운 표적이 되고 있다. 우리는 대장암과 선종 환자의 mTOR 세포신호의 활성도를 조사하였다. 면역조직화학적 방법으로 대장암과 선종의 세포신호 단백질 성분인 mTOR, p70-S6K, S6, 4EBP1 발현을 분석하였다. 이번 연구는 모두 100개의 예를 악성(Colorectal Adenocarcinoma, CRAC) 40건, 고등급 선종(Adenoma with High grade intraepithelial neoplasms, HIN) 30건, 저등급 선종(Adenoma with Low-grade intraepithelial neoplasms, LIN) 30건으로 분류하여 진행하였다. p-mTOR의 발현률은 LIN 7%, HIN 30%, CRAC 75%였고 p-S6의 발현률 또한 LIN 10%, HIN 27%, CRAC 55%였다. p-mTOR, p-S6의 발현과 선종-선암 연속성은 중요한 상관관계 있다는 것이 발견되었다. 그리고 흥미롭게도 p-S6 발현률은 진행암보다 초기암에서 더 높았다.