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Qualitative and Quantitative Studies of Polygene Proteins Expression in esophageal Precancerous Lesions and esophageal carcinoma

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Chinese Journal of Cancer Research 2007年第2期19卷 100-107页

作者：李超霞吴名耀况丽平 Department of Pathology the Key Immunopathology Laboratory of Guangdong Province Shantou University Medical College

Objective： To examine the expressions of MDM2, P53 and P27 proteins in chronic esophagitis, para-cancer mucosa and esophageal carcinoma. Methods： Immunohistochemistry was used to detect the expressions of MDM2, P53 and P27 proteins in forty-seven patients suffering from chronic esophagitis and eighty-five cases of esophageal carcinoma and corresponding para-cancer mucosa. Flow cytometry（（FCM） was applied to detect the quantities of these proteins expressed in fresh tissues of 48 cases of esophageal cancer and their para-cancer tissues and 24 cases of relative normal mucosa at the surface of cutting edge. Results： Immunohistochemistry results showed that the expressions of the three studied proteins were very similar in the epithelia of chronic esophagitis and para-cancer mucosa （P〉0.05）. Both the qualitative and quantitative studies displayed that the P53 protein had no expression and its accumulations would appear only in the early stages of esophagus canceration while the MDM2 and P27 proteins had different degrees of expressions in cases of normal esophageal mucosa. MDM2 protein markedly increased in the advanced stages of esophageal canceration. A quantitative study showed that the expression of P27 protein had a linearity of decreasing tendency （F=9.132, P=0.002） in the course of esophageal canceration. Conclusion： Chronic esophagitis may be a precancerous lesion. Owing to the changes of the P53 and P27 proteins, we can also conclude that these occur in the early stages of esophagus oncogenesis, however the changes of MDM2 expression may occur in the advanced stage of esophageal canceration.

关键词： esophageal carcinoma Oncogene protein Precancerous lesion lmmunohistochemistry Flow cytometry

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Development of a nomogram for overall survival in patients with esophageal carcinoma:A prospective cohort study in China

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World Journal of Gastrointestinal Oncology 2025年第1期17卷 158-168页

作者： Shi-Shi Yu Xi Zheng Xiao-Sheng Li Qian-Jie Xu Wei Zhang Zhong-Li Liao Hai-Ke Lei Department of Gastroenterology Chongqing University Cancer HospitalChongqing 400030China Chongqing Cancer Multi-omics Big Data Application Engineering Research Center Chongqing University Cancer HospitalChongqing 400030China Department of Health Statistics School of Public HealthChongqing Medical UniversityChongqing 400016China

BACKGROUND esophageal carcinoma(EC)presents a significant public health issue in China,with its prognosis impacted by myriad *** creation of a reliable prog-nostic model for the overall survival(OS)of EC patients promises to greatly advance the customization of treatment *** To create a more systematic and practical model that incorporates clinically significant indicators to support decision-making in clinical *** This study utilized data from a prospective longitudinal cohort of 3127 EC patients treated at Chongqing University Cancer Hospital between January 1,2018,and December 12,*** the least absolute shrinkage and selection operator regression alongside multivariate Cox regression analyses helped pinpoint pertinent variables for constructing the *** efficacy was assessed by concordance index(C-index),area under the receiver operating characteristic curve(AUC),calibration curves,and decision curve analysis(DCA).RESULTS Nine variables were determined to be significant predictors of OS in EC patients:Body mass index(BMI),Karnofsky performance status,TNM stage,surgery,radiotherapy,chemotherapy,immunotherapy,platelet-to-lymphocyte ratio,and albumin-to-globulin ratio(ALB/GLB).The model demonstrated a C-index of 0.715(95%CI:0.701-0.729)in the training cohort and 0.711(95%CI:0.689-0.732)in the validation *** the training cohort,AUCs for 1-year,3-year,and 5-year OS predictions were 0.773,0.787,and 0.750,respectively;in the validation cohort,they were 0.772,0.768,and 0.723,respectively,illustrating the model's *** curves and DCA verified the model's predictive accuracy and net *** A novel prognostic model for determining the OS of EC patients was successfully developed and validated to help clinicians in devising individualized treatment schemes for EC patients.

关键词： esophageal carcinoma High-risk factors Prognosis Overall survival Prediction model

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Randomized clinical trial on seven-day-per-week continuous accelerated irradiation for patients with esophageal carcinoma: Preliminary report on tumor response and acute toxicity

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World Journal of Gastroenterology 2006年第43期12卷 7047-7050页

作者： Su-Ping Sun Ya-Zhou Liu Tao Ye Wen Zhang Wen-Bin Shen Jing-Lei Shi Hai-Ting Xu Wei-Dong Wang Department of Radiation Oncology ChangzhouSecond hospital-The Affiliated Hospital of Nanjing MedicalUniversity Changzhou 213003 Jiangsu Province China Department of Radiation Oncology Xuzhou Cancer Hospital Xuzhou 221005 Jiangsu Province China

AIM: Tumor response and normal tissue toxicity of seven-day-per-week continuous accelerated irradiation (CAIR) for patients with esophageal carcinoma were evaluated and compared to conventional irradiation (CR). METHODS: Sixty patients with squamous cell carcinoma of the esophagus were randomized into two groups: the CAIR group (30 patients) and the CR group (30 pa- tients). Patients in the CAIR group received radiotherapy (RT) with 2 Gy/fraction per day at 7 d/wk with a total dose of 50-70 Gy (average dose 64.2 Gy). The overall time of irradiation was 3.6-5.0 wk (average 4.6 wk). RT in the CR group was 2 Gy/fraction per day at 5 d/wk with a total dose of 40-70 Gy (average dose 61.7 Gy). The overall time of irradiation was 4.0-7.0 wk (average 6.4 wk). RESULTS: The data showed that the immediate tumor response to RT was better in the CAIR group than in the CR group. Efficiency rates (CR plus PR) were 82.8% (24/29) and 58.6% (17/29), respectively (P = 0.047). In both groups the incidences of esophagitis and tracheitis were insignificant (P = 0.376, 0.959), and no patient re- ceived toxicity that could not be tolerated. CONCLUSION: CAIR shortens overall treatment time and is well tolerated by patients. It may be superior to CR in enhancing the local response of tumor, but its remote effect for esophageal carcinoma awaits further follow-up.

关键词： esophageal carcinoma Continuous acceler-ated irradiation Conventional irradiation Toxicity Over-all treatment time

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Neoadjuvant chemoradiotherapy for resectable esophageal carcinoma:A meta-analysis

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World Journal of Gastroenterology 2009年第47期15卷 5983-5991页

作者： Hai-Lin Jin Hong Zhu Ting-Sheng Ling Hong-Jie Zhang Rui-Hua Shi Department of Gastroenterology the First Affiliated Hospital of Nanjing Medical University Nanjing 210029 Jiangsu Province China

AIM:To compare neoadjuvant chemoradiotherapy and surgery with surgery alone for resectable esophageal carcinoma. METHODS:We used MEDLINE and EMBASE databases to identify eligible studies and manual searches were done to ensure no studies were *** validity assessment was performed and a trial quality score was assigned. RESULTS:Eleven randomized controlled trials(RCTs) including 1308 patients were *** chemoradiotherapy significantly improved the overall survival compared with surgery *** ratio(OR) [95%confidence interval(CI),P value],expressed as neoadjuvant chemoradiotherapy and surgery vs surgery alone,was 1.28(1.01-1.64,P=0.05)for 1-year survival,1.78(1.20-2.66,P=0.004)for 3-year survival,and 1.46(1.07-1.99,P=0.02)for 5-year *** mortality increased in patients treated by neoadjuvant chemoradiotherapy(OR: 1.68,95%CI:1.03-2.73,P=0.04),but incidence of postoperative complications was similar in two groups (OR:1.14,95%CI:0.88-1.49,P=0.32).Neoadjuvant chemoradiotherapy lowered the local-regional cancer recurrence(OR:0.64,95%CI:0.41-0.99,P=0.04), but incidence of distant cancer recurrence was similar (OR:0.94,95%CI:0.68-1.31,P=0.73).Histological subgroup analysis indicated that esophageal squamous cell carcinoma did not benefit from neoadjuvantchemoradiotherapy,OR(95%CI,P value)was 1.16(0.85-1.57,P=0.34)for 1-year survival,1.34 (0.98-1.82,P=0.07)for 3-year survival and 1.41 (0.98-2.02,P=0.06)for 5-year survival. CONCLUSION:Neoadjuvant chemoradiotherapy can raise the survival rate of patients with esophageal adenocarcinoma.

关键词： esophageal carcinoma Neoadjuvant chemoradiotherapy Randomized controlled trial Metaanalysis

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Expression of Livin and vascular endothelial growth factor in different clinical stages of human esophageal carcinoma

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World Journal of Gastroenterology 2008年第37期14卷 5749-5754页

作者： Li Chen Guo-Sheng Ren Fan Li Shan-Quan Sun Department of Thoracic Surgery the First AffiliatedHospital of Chongqing Medical University Chongqing 400016China Department of General Surgery theFirst Affiliated Hospital of Chongqing Medical UniversityChongqing 400016 China Anatomy institution of Chongqing MedicalUniversity Chongqing 400016 China

AIM： To investigate the role of Livin and vascular endothelial growth factor （VEGF） in human esophageal carcinoma, and analyze its relationship to clinical stages.METHODS： Expression of Livin in fresh esophageal cancer tissues was detected by immunohistochemistry （IHC）, Western blotting and reverse transcriptasepolyrnerase chain reaction （RT-PCR）, and VEGF by Western blotting and RT-PCR. All statistical analyses were performed by SPSS version 11.0. RESULTS： Livin positivity was also significantly correlated with tumor stages, increasing with tumor progression. Expression of Livin and VEGF increased with the process of esophageal carcinoma. In the fourth clinical stage, expression of Livin and VEGF was the most significant. Expression of Livin was positively correlated with VEGF. CONCLUSION： Over-expression of Livin and VEGF contributes to the pathogenesis of esophageal carcinoma.

关键词： esophageal carcinoma Livin Vascular endothelial growth factor

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Detachment of esophageal carcinoma cells from extracellular matrix causes relocalization of death receptor 5 and apoptosis

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World Journal of Gastroenterology 2009年第7期15卷 836-844页

作者： Guang-Chao Liu Jun Zhang Shi-Gui Liu Rong Gao Zhang-Fu Long Ke Tao Yuan-Fang Ma Key Laboratory of Bio-resource and Eco-environment of China Ministry of Education College of Life Sciences of Sichuan University Chengdu 610064 Sichuan Province China Henan Provincial Key Laboratory for Natural Drug and Immune Engineering Henan University Kaifeng 475004 Henan Province China Institute of Immunology Medical College Henan University Kaifeng 475004 Henan Province China

AIM： To investigate the effect of detachment of esophageal cancer cells from extracellular matrix on the localization of death receptor 5 （DR5） and apoptosis. METHODS： Anchorage-dependent EC9706 cells of esophageal squamous cell carcinoma were pretreated or not treated with brefeldin A. Detached cells were harvested by ethylenediaminetetraacetic acid digestion. Expression and localization of DR5 in these cells were determined by immunocytochemical and immunofluorescence assays, as well as flow cytometry analysis. Apoptosis of EC9706 cells was detected by flow cytometry after stained with fluorescein isothiocyanate-labeled annexin V/propidium iodide. Activation of caspase 8 was detected by Western blot analysis. RESULTS： Immunocytochemical assay indicated that DR5 was predominantly perinuclear in adherent cells but was mainly localized in cell membrane in detached cells. In addition, immunofluorescence assay also confirmed the above-mentioned results, and further demonstrated that DR5 was present in the form of coarse granules in detached cells, but in the form of fine granules in adherent cells. Cytometry analysis revealed higher levels of DR5 expression on the surfaces of brefeldin-A-untreated cells than on the surfaces of brefeldin-A-treated cells, but brefeldin A treatment did not affect the total DR5 expression levels. Moreover, nocodazole did not influence the extracelluar DR5 expression levels in EC9706 cells. Apoptosis assay revealed that detached cells were more sensitive to DR5 antibody-induced apoptosis than adherent ceils. Western blotting showed that caspase 8 was activated in temporarily detached cells 4 h earlier than in adherent cells. CONCLUSION： Progress from adhesion to detachment of EC9706 cells causes DR5 relocalization, and promotes cytoplasmic translocation of DR5 to cell surfaces via a Golgi-dependent pathway. Moreover, it might also result in DR5 aggregation to render apoptosis of detached cells.

关键词： Translocation of death receptor 5 Celldetachment esophageal carcinoma Anoikis Apoptosis

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Expression and clinical significance of S100A2 and p63 in esophageal carcinoma

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World Journal of Gastroenterology 2009年第33期15卷 4183-4188页

作者： Li-Yu cao Yu Yin Hao Li Yan Jiang Hong-Fu Zhang Department of Pathology Anhui Medical University Hefei 230032 Anhui Province China

AIM： TO investigate the expression and clinical significance of S100A2 mRNA and protein, p63 protein in esophageal squamous cell carcinoma （ESCC） and their roles in carcinogenesis and progression of esophageal carcinoma （EC）. METHODS： Immunohistochemical staining （S-P method） for S100A2 and p63 protein were performed in 40 samples of ESCC and 40 samples of normal esophageal mucosa. In situ hybridization （ISH） was used to detect the expression of S100A2 mRNA. RESULTS： Expression of S100A2 mRNA in ESCC was positive in 77.5% of samples, which was lower than that in normal mucosa （100%） by ISH （P = 0.002）. The expression level of S100A2 mRNA was closely related to differentiation and and node-metastasis （P = 0.012, P = 0.008）. Expression of $100A2 protein was positive in 72.5% of ESCC samples and expression of p63 protein was positive in 37.5% of ESCC samples, and was lower than that in normal mucosa （100%）（P = 0.000）. The expression of S100A2 protein was correlated with the differentiation and node-metastasis （P = 0.007, P = 0.001）, but no relationship was observed between the expression of p63 protein and clinical pathological manifestations. S100A2 protein was positively correlated with the expression of S100A2 mRNA, and negatively associated with the expression of p63 protein （P = 0.000, P = 0.002）. CONCLUSION： S100A2 and p63 protein both play important roles in the carcinogenesis of ESCC. An investigation into the combined expression of S100A2 and p63 may be helpful in early diagnosis and in evaluating the prognosis of ESCC.

关键词： Immunohistochemistry In situ hybridization esophageal carcinoma p63 S100A2

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Surgical resection for esophageal carcinoma: Speaking the language

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World Journal of Gastroenterology 2005年第15期11卷 2211-2212页

作者： Robert J. Korst Division of Thoracic Surgery

The terminology used to describe esophagectomy for carcinoma can be confusing, even for specialists in gastrointestinal disease. As a result, specific terms are often used out of their intended context. To simplify the nomenclature, two points regarding procedures for surgical resection of the esophagus are critical: the extent of resection (radical vs standard) and the operative approach (choice of incisions). It is important to understand that the radicality of the resection may have little to do with the operative approach, with the exception of esophagectomy without thoracotomy (transhiatal esophagectomy), which mandates the performance of a standard or non-radical resection. Esophagectomy has emerged as the standard curative treatment option for patients with esophageal carcinoma; however, unlike the surgical resection of other types of solid tumors, many different surgical options and/or approaches exist for these patients. This heterogeneity of care may result from the fact that the esophagus is accessible through more than one body cavity (left hemithorax, right hemithorax, abdomen).In addition, and partially as a result of its accessibility,different types of surgical specialists harbor this operation in their armamentarium, including general surgeons,thoracic surgeons, and surgical oncologists. Despite this enthusiasm amongst surgeons, little consensus exists as to which option is most oncologically sound. Further, the details of the various surgical approaches and procedures for resection of the esophagus are often difficult to comprehend, even for specialists in gastrointestinal disease, with much of the relevant terminology used out of its intended context. To facilitate the understanding of the surgical options for esophageal carcinoma, it is useful to view the operation from two angles: the extent of resection (Aradical@ vs Astandard@) and the operative approach (choice of incisions).

关键词： esophageal carcinoma Terminology

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Value of endoscopic methylene blue and Lugol's iodine double staining and detection of GST-n and telomerase in the early diagnosis of esophageal carcinoma

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World Journal of Gastroenterology 2005年第39期11卷 6090-6095页

作者： Xuan Zhu Shuang-Hong Zhang Kun-He Zhang Bi-Ming Li Jiang Chen Department of Gastroenterology the First Affiliated Hospital Jiangxi Medical College Nanchang 330006 Jiangxi Province China Department of Digestive Institution the First Affiliated Hospital Jiangxi Medical College Nanchang 330006 Jiangxi Province China

AIM：To explore the expressions of GST-π and telomerase activity in esophageal carcinoma and premalignant lesions and to investigate the value of endoscopic methylene blue （MB） and Lugol＇s iodine double staining. METHODS： Seventy-two patients with esophagopathy were sprayed endoscopically with MB and Lugol＇s iodine in proper order and the areas stained blue and brown, and the area between the blue and brown stains were obtained. Depending on the pattern of mucosal staining, biopsy specimen was obtained. GST-π and telomerase activity in specimens were examined by immunohistochemistry and PCR-based silver staining telomeric repeat amplification protocol, respectively. RESULTS： After MB and Lugol＇s iodine staining, the area between both the colors was obtained in 64 of the 72 patients and the areas were stained blue and brown in all of the 72 patients. Association test of two simultaneous ordinal categorical data showed a correlation between the esophageal mucosal staining and the esophageal histology （P〈0.005）. The expression of GST-π and telomerase activity in esophageal carcinoma and premalignant lesions increased. The expression of GST-π and telomerase activity in dysplasia and carcinoma was significantly higher than that in normal epithelium （P〈0.005）. The expression in hyperplasia was slightly higher than that in normal epithelium. With the lesions progressing from low- to moderate- to high-grade dysplasia, the positive rate increased （P〈0.025）. Expression of GST-π was correlated with that of telomerase activity in dysplasia and carcinoma （φ= 0.4831, P〈0.005;φ= 0.3031, P〈0.025, respectively）; but there was no correlation between them in normal epithelium and hyperplasia. CONCLUSION： The expression of GST-π and telomerase may be an early event in the carcinogenesis of esophagus. They may play an induced and synergistic role with each other in the carcinogenesis of esophagus. Endoscopic MB and Lugol＇s iodine double staining and detection of GST-π and telomerase acti

关键词： esophageal carcinoma Endoscopy Glutathione S-transferases Telomerase

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Anti-tumor Effect and Its Mechanisms of Ursolic Acid on Human esophageal carcinoma Cell Eca-109 in Vivo

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Chinese Journal of Cancer Research 2008年第3期20卷 205-210页

作者：陈国庆沈宜段红 Department of Pathophysiology Chongqing University of Medical Sciences Chongqing 400016 China

Objective： To investigate the anti-tumor effect and possible mechanisms of ursolic acid on human esophageal carcinoma in vivo. Methods： Atransplanted tumor model by injecting Eca-109 cells into subcutaneous tissue of BALB/c nude mice was established. 40 nude mice bearing tumors were randomly divided into 4 groups and 0.2 ml saline or 0.2 ml ursolic acid （25-100 mg·kg^-1·d^-1） was injected into abdominal cavity respectively once everyday and lasted for fourteen days. The changes of tumor volume were measured continuously and tumor inhibition rate was calculated. The morphological changes of apoptosis were observed by electron microscope. The expressions of COX-2, bcl-2 and Bax protein in transplanted tumors were detected by immunohistochemistry. At last the PGE2 level of transplanted tumors was detected byradioimmunoassay. Results： Treatment of nude mice with 25, 50, or 100 mg·kg^-1·d^-1 of ursolic acid significantly inhibited the growth of the human esophageal carcinoma tumor in nude mice and induced Eca-109 cells apoptosis as demonstrated by electron microscopy analyses. The expressions of COX-2 and bcl-2 in the transplanted tumors were decreased in ursolic acid groups, while the Bax increased. The PGE2 level of transplanted tumors was decreased in ursolic acid groups with adose-relatedmanner. Conclusion： Ursolic acid has anti-tumor effects against human esophageal carcinoma cells in vivo, which are likely mediated via induction of tumor cell apoptosis and inhibition of COX-2 and PGE2.

关键词： Ursolic acid esophageal carcinoma Apoptosis COX-2 PGE2

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