• Asian Pacific Journal of Cancer Prevention
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• 제16권16호
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• pp.7161-7165
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• 2015

Background: Esophageal squamous cell carcinoma (ESCC) is a common cancer in the north east of India. The present study concerned the prevalence of human papilloma virus (HPV) in the ESCC in north eastern India and its impact on response to chemotherapy. Materials and Methods: p16 expression, a surrogate marker for HPV infection was assessed in 101 pre-treatment biopsies of locally advanced ESCC, reported from a comprehensive cancer centre in north east India, using immunohistochemistry. All patients received neo-adjuvant chemotherapy. Response was assessed clinically and histopathologically with attention to p16 expression. Results: p16 was expressed in 22% of ESCC (22 out of 101) and was more prevalent in patients who were more than 45 years of age (P=0.048). p16 positive tumors appeared more commonly in the upper 2/3 of the thoracic esophagus (18 in 22). Nine of the 22 (41%) p16 positive tumors achieved pathologic complete response following neo-adjuvant chemotherapy (P=0.008). There was a trend towards reduced mortality in this group (P=0.048). Some 9 of the 20 (45%) patients who achieved pathologic complete response were p16 positive. Conclusions: Expression of p16 in ESCC correlates with higher rate of pathologic complete remission in patients undergoing neo adjuvant chemotherapy and could be a predictive marker for response assessment.

• Asian Pacific Journal of Cancer Prevention
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• 제14권1호
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• pp.21-25
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• 2013

Background: Genetic factors and environmental factors play a role in pathogenesis of esophageal squamous cell carcinoma (ESCC). Previous studies regarding the association of folate intake and Methylenetetrahydrofolate reductase C677T polymorphism with ESCC was conflicting. We conducted a meta-analysis to investigate the association of MTHFR C677T and folate intake with esophageal cancer risk. Methods: MEDLINE, EMBASE and the Chinese Biomedical Database were searched in our study. The quality of studies were evaluated by predefined scale, and The association of polymorphisms of MTHFR C677T and folate intake and ESCC risk was estimated by Odds ratio (ORs) with 95% confidence intervals (CIs). Results: 19 studies (4239 cases and 5575 controls) were included for meta-analysis. A significant association was seen between individuals with MTHFR 677 CT [OR(95%)=1.47(1.32-1.63)] and TT [OR(95%)=1.69(1.49-1.91)] genotypes and ESCC risk (p<0.05). Low intake of folate had significantly higher risk of esophageal cancer among individuals with CT/TT genotype [OR(95%)=1.65(1.1-2.49)], while high intake of folate did not find significant high risk of esophageal cancer among individuals with CT/TT genotype [OR(95%)=1.64 (0.82-3.26)]. Conclusions: Our meta-analysis indicated the folate intake and MTHFR 677CT/TT are associated with the risk of ESCC, and folate showed a significant interaction with polymorphism of MTHFR C677T.

• Asian Pacific Journal of Cancer Prevention
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• 제14권12호
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• pp.7315-7319
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• 2013

Background: The metastasis gene osteopontin (OPN) is subject to alternative splicing, which yields three messages, osteopontin-a, osteopontin-b and osteopontin-c. Osteopontin-c is selectively expressed in invasive, but not in noninvasive tumors. In the present study, we examined the expression of OPN-c in esophageal squamous cell carcinomas (ESCCs) and assessed its value as a diagnostic biomarker. Methods: OPN-c expression was assessed by immunohistochemistry in 63 ESCC samples and correlated with clinicopathologic factors. Expression was also examined in peripheral blood mononuclear cells (PBMCs) from 120 ESCC patients and 30 healthy subjects. The role of OPN-c mRNA as a tumor marker was investigated by receiver operating characteristic curve (ROC) analysis. Results: Immunohistochemistry showed that OPN-c was expressed in 30 of 63 cancer lesions (48%)and significantly associated with pathological T stage (P=0.038) and overall stage (P=0.023). Real time PCR showed that OPN-c mRNA was expressed at higher levels in the PBMCs of ESCC patients than in those of healthy subjects (P<0.0001) with a sensitivity as an ESCC biomarker of 86.7%. Conclusion: Our findings suggest that expression of OPN-c is significantly elevated in ESCCs and this upregulation could be a potential diagnostic marker.

• Journal of Chest Surgery
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• 제40권12호
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• pp.843-850
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• 2007

배경: 흉부 식도암에서 Ivor-Lewis수술이 널리 이용되어 왔으나 최근 3구역 절제술로 보다 좋은 성적들이 보고되고 있다. 식도 편평세포암 환자에서 Ivor-Lewis수술의 유용성을 알아보고자 한다. 대상 및 방법: 1994년 9월부터 2004년 8월까지 식도암으로 절제술을 받은 273명의 환자 중 편평세포암으로 다른 원발성 암이 없고 Ivor-Lewis수술로 완전절제가 가능하였던 172명을 대상으로 술 후 합병증, 조기 및 장기성적, 재발양상을 후향적인 방법으로 분석하였다. 결과: 술 후 병기는 I기 40명(23%), IIA기 48명(27%), IIB기 18명 (10%), III기 55명(33%), IVA 5명(3%), IVB 6명(4%)이었다. 수술과 관련된 사망은 172명의 환자 중 7명(4%)에서 발생하였으며 술 후 합병증은 32명(18%)에서 발생하였고 55명(32%)에서 재발하였다. 전체 환자의 5년 생존율은 48%였는데, 병기별 5년 생존율은 I기 85.6%, IIA기 47.6%, IIB기 65%, III기 22.8%, IV기 0%였다. 종양의 위치에 따른 5년 생존율은 상흉부가 26.5%로 중흉부와 하흉부 52.4%에 비해 낮았으나 통계적 유의성은 없었다. 결론: 이상의 결과로 식도 편평세포암 환자에서 Ivor-Lewis수술의 적용은 비교적 만족할 만한 결과를 얻었으며, 상흉부 식도암인 경우에는 통계적 유의성은 없었으나 중 하 흉부식도암에 비해 낮은 5년 생존율을 보여 3구역 림프절절제술로의 전환도 고려해야 할 것으로 생각된다.

• The Korean Journal of Physiology and Pharmacology
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• 제27권5호
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• pp.493-511
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• 2023

Hippo/YAP signaling hinders cancer progression. Inactivation of this pathway contributes to the development of esophageal cancer by activation of Akt. However, the possible interaction between Akt and Hippo/YAP pathways in esophageal cancer progression is unclear. In this study, we found that ursolic acid (UA) plus 3'3-diindolylmethane (DIM) efficiently suppressed the oncogenic Akt/Gsk-3β signaling pathway while activating the Hippo tumor suppressor pathway in esophageal cancer cells. Moreover, the addition of the Akt inhibitor LY294002 and the PI3K inhibitor 3-methyladenine enhanced the inhibitory effects of UA plus DIM on Akt pathway activation and further stimulated the Hippo pathway, including the suppression of YAP nuclear translocation in esophageal cancer cells. Silencing YAP under UA plus DIM conditions significantly increased the activation of the tumor suppressor PTEN in esophageal cancer cells, while decreasing p-Akt activation, indicating that the Akt signaling pathway could be down-regulated in esophageal cancer cells by targeting PTEN. Furthermore, in a xenograft nude mice model, UA plus DIM treatment effectively diminished esophageal tumors by inactivating the Akt pathway and stimulating the Hippo signaling pathway. Thus, our study highlights a feedback loop between the PI3K/Akt and Hippo signaling pathways in esophageal cancer cells, implying that a low dose of UA plus DIM could serve as a promising chemotherapeutic combination strategy in the treatment of esophageal cancer.

• Asian Pacific Journal of Cancer Prevention
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• 제13권4호
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• pp.1261-1266
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• 2012

Introduction: HPV has been found repeatedly in esophageal squamous cell carcinoma (ESCC) tissues. However, reported detection rates of HPV DNA in these tumors have varied markedly. Differences in detection methods, sample types, and geographic regions of sample origin have been suggested as potential causes of variation. We have reported that infection of HPV DNA in ESCC tumors depends on anatomical sites of esophagus of the patients from Mazandaran, north of Iran. Materials and Methods: HPV DNA was examined in 46 upper, 69 middle and 62 lower third anatomical sites of esophageal squamous cell carcinoma specimens collected from Mazandaran province in north Iran, near the Caspian Littoral as a region with high incidence of ESCC. HPV L1 DNA was detected using Qualitative Real time PCR and MY09/MY11 primers. Results: 28.3% of upper, 29% of middle and 25.8% of lower third of ESCC samples were positive for HPV DNA. 13.6% for males and 14.1% for females were HPV positive in all samples. Conclusions: HPV infection is about one third of ESCC in this area. Findings in this study increase the possibility that HPV is involved in esophageal carcinogenesis. Further investigation with a larger sample size is necessary.

• Asian Pacific Journal of Cancer Prevention
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• 제15권7호
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• pp.3075-3079
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• 2014

Background: The relationship between body mass index(BMI) and outcomes after chemoradiotherapy(CRT) has not been systematically addressed. The purpose of this study was to evaluate the effect of BMI on survival in patients with esophageal squamous cell carcinoma (ESCC). Materials and Methods: Sixty ESCC cases were retrospectively reviewed in this study. Patient overall survival(OS) and disease-free survival (DFS) were compared between two groups (BMI< $24.00kg/m^2$ and $BMI{\geq}24.00kg/m^2$). Results: There were 41 patients in the low/normal BMI group (BMI< $24.00kg/m^2$) and 19 in the high BMI group ($BMI{\geq}24.00kg/m^2$). No significant differences were observed in patient characteristics between these. We found no difference in 2-year OS and DFS associated with BMI (p=0.763 for OS; p=0.818 for DFS) using the Kaplan-Meier method. Univariate analysis revealed that higher clinical stage was prognostic for worse 2-year OS and DFS, metastasis for 2-year OS, lymph node status for 2-year DFS, while age, gender, smoking, drinking, tumor location and BMI were not prognostic. There were no differences in the 2-year OS (hazard ratio=1.117; p=0.789) and DFS(hazard ratio=1.161; p=0.708) between BMI groups in multivariate analysis, whereas we found statistical differences in the 2-year OS and DFS associated with clinical stage, gender and tumor infiltration (p<0.04), independent of age, smoking, drinking, tumor location, the status of lymph node metastases and BMI. Conclusions: BMI was not associated with survival in patients with ESCC treated with CRT as primary therapy. BMI should not be considered a prognostic factor for patients undergoing CRT for ESCC.

• Asian Pacific Journal of Cancer Prevention
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• 제13권8호
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• pp.3713-3716
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• 2012

Objective: Transmembrane protein 166 (TMEM166) expression in esophageal squamous cell carcinoma (ESCC) and remote normal esophageal tissues was examined to assess any role in tumour biology. Methods: TMEM166 mRNA expression in 36 cases with ESCC (36 tumour samples, 36 remote normal esophageal tissue samples) was detected by RT-PCR. TMEM166 protein expression was analysed in paraffin-embedded tissue samples from the same cases by immunohistochemistry. Results: Semi-quantitative analysis showed TMEM166 mRNA expression in ESCCs to be significantly lower than in remote normal esophageal tissues ($0.759{\pm}0.713$ vs. $2.622{\pm}1.690$, P=0.014). TMEM166 protein expression was also significantly reduced (69.4% vs. 94.4%, P<0.01). Conclusion: TMEM166 mRNA and protein expression demonstrated significant reduction in ESCCs compared with remote esophageal tissues, albeit with no correlation with tumour size, differentiation, stage, and lymph node metastasis, suggesting a role in regulating autophagic and apoptotic processes in the ESCC.

• Asian Pacific Journal of Cancer Prevention
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• 제15권4호
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• pp.1563-1566
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• 2014

Background: Esophageal squamous cell carcinoma (ESCC) accounts for most esophageal cancer in Asia, and is the sixth common cause of cancer-related deaths worldwide. Previous studies indicated HOXB7 is overexpressed in ESCC tissues, but data on prognostic value are limited. Methods: A total of 76 advanced ESCC cases were investigated. Immunohistochemistry (IHC) was used to detect the expression levels of HOXB7 and Kaplan-Meier curves and Cox regression models to determine prognostic significance. Stratified analysis was also performed according to lymph node (LN) status. Results: Kaplan-Meier curve analysis indicated that HOXB7 positive patients had significantly shorter overall survival (OS) than HOXB7 negative patients. Multivariate analysis using the Cox proportional hazards model indicated only TNM stage and HOXB7 expression to be independent predictors of overall survival of advanced ESCC patients. HOXB7 indicated poor OS in both lymph node negative (LN-) and lymph node positive (LN+) patients. Conclusion: HOXB7 predicts poor prognosis of advanced ESCC patients and can be applied as an independent prognostic predictor.

• Asian Pacific Journal of Cancer Prevention
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• 제13권7호
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• pp.3299-3303
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• 2012

Objective: To investigate the association between xeroderma pigmentosum group D (XPD) Asp312Asn polymorphism and esophageal cancer (EC) susceptibility by meta-analysis. Methods: We searched PubMed up to April 9th, 2012, to identify relevant papers, and 8 published case-control studies including 2165 EC patients and 3141 healthy controls were yielded. Odds ratios (ORs) with relevant 95% confidence intervals (CIs) were applied to assess the association between XPD Asp312Asn polymorphism and EC susceptibility with the Comprehensive Meta-Analysis software, version 2.2. Results: Overall, the meta-analysis results suggested the XPD Asp312Asn polymorphism to be significantly associated with EC susceptibility [(Asn/Asn+Asp/Asn) vs. Asp/Asp: OR=1.20, 95%CI=1.05-1.36, p=0.01; and Asp/Asn vs. Asp/Asp: OR=1.15, 95%CI =1.01-1.31, p=0.04]. In the subgroup analysis by ethnicity and cancer type, significantly associations were found for Caucasian populations [(Asn/Asn+Asp/Asn) vs. Asp/Asp: OR=1.26, 95%CI =1.08-1.47, p<0.001; Asp/Asn vs. Asp/Asp: OR=1.19, 95%CI =1.02-1.40, p=0.03] and esophageal squamous cell carcinoma [(Asn/Asn+Asp/Asn) vs. Asp/Asp: OR=1.19, 95%CI=1.01-1.41, p=0.04]. There was no heterogeneity and no publication bias existed. Conclusions: This meta-analysis shows that the XPD Asp312Asn polymorphism may be a risk factor for developing EC, especially for Caucasian populations and esophageal squamous cell carcinoma.