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Radiotherapy combined with nimotuzumab for elderly esophageal cancer patients:A phaseⅡclinical trial

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Chinese Journal of Cancer Research 2021年第1期33卷 53-60页

作者： Xu Yang Yirui Zhai Nan Bi Tao Zhang Lei Deng Wenqing Wang Xin Wang Dongfu Chen Zongmei Zhou Luhua Wang Jun Liang Department of Radiation Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100121China

Objective:To investigate the safety and efficacy of nimotuzumab combined with radiotherapy for elderly patients with non-resectable esophageal carcinoma(EC).Methods:Eligible patients were aged 70 years or older and had treatment-naive,histologically proven inoperable locally advanced *** patients received radiotherapy with a total dose of 50-60 Gy in 25-30 fractions,concurrent with weekly infusion of *** primary end point was the rate of more than grade 3 ***:From June 2011 to July 2016,46 patients with stageⅡ-IV EC with a median age of 76.5 years were *** were 10,28 and 8 patients with stageⅡ,III and IV disease,*** common acute toxicities included esophagitis(grade 1-2,75.4%;grade 3,8.7%),pneumonitis(grade 1,4.3%;grade 2,6.5%;grade3,2.2%),leukopenia(grade 1-2,60.9%;grade 3-4,4.4%),gastrointestinal reaction(grade 1-2,17.3%;grade 3,2.2%),thrombocytopenia(grade 1-2,21.7%;grade 3,2.2%),and radiothermitis(grade 1-2,39.2%).The incidence of grade 3-4 adverse effects was 17.4%.No grade 5 toxicities were *** complete response,partial response,stable disease,and progressive disease were observed in 1(2.2%),31(67.4%),12(26.1%),and 2(4.3%)patients,*** median overall survival(OS)and progression-free survival(PFS)were 17 and 10 months,*** 2-,3-,and 5-year OS and PFS rates were 30.4%,21.7%,19.6%,and 26.1%,19.6%,19.6%,***:Nimotuzumab combined with radiotherapy is a safe and effective therapy for elderly patients who are not surgical *** studies are warranted to confirm its therapeutic effects in elderly EC patients.

关键词： Nimotuzumab esophageal neoplasm elderly radiotherapy treatment outcome

Phase Ib trial of camrelizumab combined with chemotherapy and apatinib for neoadjuvant treatment of locally advanced thoracic esophageal squamous cell carcinoma

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Journal of the National Cancer Center 2022年第2期2卷 98-105页

作者： Zhen Wang Xiankai Chen Yong Li Jianjun Qin Yuan Fang Zhaoyang Yang Yan Fang Dong Qu Ruixiang Zhang Qingfeng Zheng Xiaozheng Kang Liyan Xue Jing Huang Yin Li Jie He Department of Thoracic Surgery National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Clinical Cancer Center National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Department of Pathology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Department of Nuclear Medicine National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Department of Radiology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Department of Medical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina

Objective:This is a prospective,single-arm,phase Ib study to evaluate the safety and efficacy of camrelizumab combined with chemotherapy and apatinib as neoadjuvant therapy for locally advanced thoracic esophageal squamous cell carcinoma(ESCC).Methods:The regimen encompassed 2-4 cycles of neoadjuvant camrelizumab,nab-paclitaxel,nedaplatin,and apatinib to treatment-naive patients with resectable locally advanced *** treatment was repeated every 14 ***,six patients were planned to receive two cycles of neoadjuvant therapy as safety assessment,and then 24 patients received four cycles of neoadjuvant therapy,followed by esophagectomy after 4-8 *** primary endpoint was *** key secondary endpoints were pathologic complete response(pCR)and major pathologic response(MPR).Results:This study enrolled 30 patients,among whom,five patients received two cycles of neoadjuvant therapy,and one patient missed the second cycle of therapy due to grade 3 elevated alanine transaminase(ALT)*** remaining 24 patients received four planned cycles of neoadjuvant *** patients(36.7%)devel-oped grade 3 neoadjuvant treatment-related adverse events(TRAEs).No patient developed grade 4 or 5 ***(23.3%)was the most common grade 3 ***-nine patients underwent esophagectomy af-ter neoadjuvant *** them,15 patients(51.7%)achieved MPR,including seven patients with pCR(24.1%).Radiographic analyses established a significant correlation between maximal standardized uptake value(SUV max)reduction and pathologic regression(P=0.00095).Conclusions:Neoadjuvant camrelizumab combined with chemotherapy plus apatinib demonstrated a manageable safety profile for patients with locally advanced ESCC,and an encouraging efficacy was observed in most of the treated patients.A decrease in SUV max of the primary tumor may be a predictor of pathologic response to neoadjuvant camrelizumab combined with chemotherapy plus apatinib in ESCC.

关键词： esophageal neoplasm Immunotherapy Neoadjuvant Chemotherapy

Effect of Lentivirus-induced shRNA Silencing CXCR4 Gene on Proliferation and Apoptosis in Human esophageal Carcinoma Cell Line Eca109

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Clinical oncology and cancer researeh 2010年第3期7卷 193-199页

作者： Dao-feng WANG State Key Laboratory of Oncology in Southern China Department of ICU Cancer Center Sun Yat-sen University Department of Thoracic Surgery Cancer Center Sun Yat-sen University Guangzhou 510060 Guangdong Province. China.

OBJECTIVE To discuss the application of the slow virus-induced short-hairpin RNA （vshRNA） to silence the expression of CXCR4 in EsCa cell lines Eca109, and observe the effect of silencing CXCR4 on the proliferation and apoptosis of Eca109 cells in vitro. METHODS The expression plasmid of vshRNA targeting CXCR4 was constructed, with a concurrent construction of negative vshRNA expression plasmid, and without targeting any known mRNA. Real-time quantitative PCR and Western blot assay were used to determine the change of CXCR4 expression in the post-transfected EsCa cell Eca109, and MTT assay was conducted to detect the change of proliferation in EsCa Eca109 cell after silencing the CXCR4. The .ow cytometry was used to detect the change of the cell cycle and apoptosis in the post-silenced EsCa Eca109 cell in di. erent groups. RESULTS The transfection rate was respectively （87.3 ± 1.2）% and （90.1 ± 1.4）% in the CXCR4- RNAi-LV （silent group） and NC-GFP-RNAi-LV （negative control group） cellular plasmids. The vshRNA interference resulted in a down-regulation of the CXCR4 gene mRNA and protein expressions in Eca109 cells. CXCL12 promoted the proliferation of EsCa cell lines Eca109. The speed of EsCa cell proliferation became slower in the silencing group than in the normal control （also the control） and the negative control groups （P 〈 0.05）. However, there was no significant difference in comparison of the proliferation speeds between the negative control and the normal control groups （P 〉 0.05）. In the silencing group, the proportion of the cells in phase G0/G1, phase S and phase G2/M was respectively （69.9 ± 5.0）%, （17.1 ± 2.5）% and （13.0 ± 7.4）%, and the apoptotic rate achieved （7.27 ± 0.50）%. In the normal control group, the proportion of the cells in phase G0/G1, S and G2/M was respectively （55.9 ± 4.6）%, （30.2 ± 3.9）% and （13.8 ± 1.4）%, and the apoptotic rate was （3.30 ± 0.70）%. In the negative control group, the proportion of cells in phase G0/G1, S and G2/M was res

关键词： RNA CXCR4 esophageal neoplasm proliferation apoptosis

THE DIAGNOSIS AND TREATMENT FOR RECURRENT DYSPHAGIA OF esophageal CARCINOMA AFTER RADICAL RADIOTHERAPY

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Chinese Journal of Cancer Research 1998年第1期10卷 73-75页

作者：陈克能程邦昌师晓天马金山 The First Hospital Lanzhou Medical College Department of Thoracic and Cardiovascular Srugery The First Affiliated HospitalHubei Medical University Wuhan The First Thoracic Department Anyang Tumor Hospital Anyang

Objective: To investigate the diagnosis and treatment for recurrent dysphagia of esophageal carcinoma after radical radiotherapy. Methods: The experince of 41 cases with recurrent dysphagia of esophageal carcinoma after radical radiotherapy were retrospectively summerized. Results: All of the cases were surgically treated form July, 1989 to May, 1997 with resectability rate in 97%, operative mortality in 4.8%, postoperative morbidity in 29%. Pathological examination showed squemous cell carcinoma in 82.8%, and serious radiation reaction in 13.2% after operation. The 1, 3, 5year survival rates after operation were 72.7%, 36.3%, 18.1% respectively, and those after radiation in 100%, 60%, and 35.5% respectively. Conclusion: Most of recurrent dysphagia for these cases were due to uncontrolled/recurrent cancer, and minority of them were due to constriction after radiotherapy. It is difficult to distinguish cancer with benigh constriction before operation. Some cases have lymphatic metastasis without local cancer recurrence. For those patients with recurrent disphagia should be treated with operation as early as possible.

关键词： esophageal neoplasm Radiotherapy Surgery Pathology.

A Randomized Clinical Study on Combination of Concurrent Chemo-Radiotherapy and Thalidomide for Middle-Late esophageal Cancer

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Clinical oncology and cancer researeh 2010年第2期7卷 140-145页

作者： Ming-jin SHE Zu-sheng MA Gui-zhi LI Qin WANG Yong-li SHEN Department of Oncology the Hospital of Division of Armed Police of Anhui Province Hefei 230041 Anhui Province China.

OBJECTIVE To evaluate the response rate and tolerance of patients with middle-late esophageal carcinoma, who were treated with concurrent chemoradiotherapy （CCRT） plus *** Sixty-five eligible patients with local middle-late esophageal carcinoma were randomly assigned to the treatment group （TG） and the control group （CG）. The 33 patients from the TG were treated with CCRT plus thalidomide （a 60-70 Gy of radiation dose, and 5-FU plus cisplatin; oral administration of thalidomide at a dose of 100 mg/d on the first week and 200 mg/d on the second. Both were taken with water, at bedtime until completion of the radiotherapy. In the CG, 32 patients received CCRT only. The clinical effects and tolerance to the CCRT between the 2 groups were *** The response rates of the therapeutic combination in the TG and CG were 87.9% and 68.7%, respectively. There were no statistical differences in comparing the response rates between the 2 groups （P 〉 0.05）; the local control rates in the TG and CG were 93% and 91%, respectively, and there were no statistical differences between the 2 groups （P 〉 0.05）; the 1-year survival rates of the patients in the TG and CG were 74.0% and 63.0%, respectively, without statistical differences between the 2 groups （P 〉 0.05）. The improvement rates of KPS scoring in the TG and CG were 57.6% and 31.3%, respectively. There were significant differences in comparing the improvement rates between the 2 groups （P 〈 0.05）. The incidence rates of nausea and vomiting were lower in the TG compared to the CG, with a statistical significance between the 2 groups （P 〈 0.05）. However, the incidence rates of constipation, lethargy and fatigue were higher in the TG than in CG, showing a statistically significant difference between the 2 groups （P 〈 0.05）. CONCLUSION CCRT combined with thalidomide in treating esophageal carcinoma may improve the quality of life of the patients, the treatment may also raise patients＇ compliance to chemoradi

关键词： esophageal neoplasm thalidomide radiotherapy drug therapy.

CLINICAL　EVALUATION　OF　CERVICAL　esophageal　RECONSTRUCTION　AFTER　RESECTION　OF　THORACIC　esophageal　CARCINOMA

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Chinese Journal of Cancer Research 1996年第4期8卷 291-294页

作者：许金良邵令方高宗人卫功铨陈明耀王文光 Department of Thoracic Surgery Henan Tumor Hospital Zhengzhou

The data of 3,714 patients with thoracic esophageal carcinoma from Apr, 1979 to Dec. 1994 were analysed in purpose to estimate the value of cervical esophagogastrotomy (cervical reconstruction) in the treatment of thoracic esophageal carcinoma. The results show that while cervical esophagogastrotomy was rarely used in the early years (only 8.8% of the treated cases), it has been recently used as the routine standard procedure in our hospital (94.1 %). This technic is of great importance and useful for the radical removal of tumor, the eradication of cervical and mediastinal lymph nodes, the reduction of post-operative complications and surgical mortality, as well as to improve the life quality of the patient. The operation indications, approach and the surgical efficacy are also discussed in the article.

关键词： esophageal neoplasm Esophagectomy

Identification of human papillomavirus in esophageal squamous papillomas

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World Journal of Gastroenterology 2008年第46期14卷 7107-7111页

作者： Olga L Bohn Leticia Navarro Jesus Saldivar Sergio Sanchez-Sosa Department of Pathology UPAEP University Hospital

AIM： To investigate the presence of human papillomavirus （HPV） in esophageal squamous papilloma （ESP） and determine p16, p53 and Ki67 expression in a Mexican cohort. METHODS： Nineteen cases diagnosed as ESP, corresponding to 18 patients were reviewed; nineteen cases of normal esophageal mucosa were used as negative controls. HPV detection was performed by ,amplified chromogenic in situ hybridization （ACISH） using a wide spectrum-cocktail probe and PCR. RESULTS： The average age at presentation was 46.3 years （range 28-72 years）. Patients included four （22.22%） males and 14 （77.77%） females. The most frequent location was upper third （11 cases）, followed by middle third （3 cases） and unknown site （5 cases）. Immunohistochemistry （IHC） revealed basal and focal p53 expression in 17 cases （89%）; p16 was expressed in eight cases （42.10%） and the Ki67 index ranged from 10% to 30%. HPV was detected in 14 out of 16 cases （87.5%） by ACISH： Twelve showed diffuse nuclear patterns and two showed granular patterns. HPV DNA was identified by PCR in 12 out of 14 cases （85.7%）. Low-risk HPV types were detected in the most of the cases. CONCLUSION： This study provides identification of HPV infection in almost 80% of ESP using either ACISH or PCR; overall, all of these lesions show low expression of cell-cycle markers. We suggest ACISH as an alternative diagnostic tool for HPV detection in ESR .

关键词： Human papillomavirus esophageal papilloma Papillomatosis esophageal neoplasm Immunohistochemistry Cell cycle

Copy number changes of target genes in chromosome 3q25.3-qter of esophageal squamous cell carcinoma: TP63is amplified in early carcinogenesis but down-regulated as disease progressed

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World Journal of Gastroenterology 2005年第9期11卷 1267-1272页

作者： Chueh-ChuanYen Yann-JangChen Chin-ChenPan Kai-HsiLu PaulChih-HsuehChen Jiun-YiHsia Jung-TaChen Yu-ChungWu Wen-HuHsu Liang-ShunWang Min-HsiungHuang Biing-ShiungHuang Cheng-PoHu Po-MinChen Chi-HungLin DivisionofMedicalOncology DepartmentofMedicineTaipeiVeteransGeneralHospitalandNationalYang-MingUniversitySchoolofMedicineTaipeiTaiwanChina FacultyofLifeScience NationalYang-MingUniversityTaipeiTaiwanChina DepartmentofPathology NationalYang-MingUniversityandTaipeiVeteransGeneralHospitalTaiwanChina InstituteofMicrobiologyandImmunology NationalYang-MingUniversityTaipeiTaiwanChina DivisionofThoracicSurgery DepartmentofSurgeryTaichungVeteransGeneralHospitalTaichungTaiwanChina DepartmentofPathology.TaichungVeteransGeneralHospital andDepartmentofPathologyChung-ShanMedicalUniversityTaichungTaiwanChina DivisionofThoracicSurgery DepartmentofSurgeryTaipeiVeteransGeneralHospitalandNationalYang-MingUniversityTaipeiTaiwanChina InstituteofMicrobiologyandImmunology NationalYang-MingUniversityandDepartmentofMedicalResearchandEducationTaipeiVeteransGeneralHospitalTaipeiTaiwanChina InstituteofMicrobiologyandImmunology andInstituteofBiophotonicsNationalYang-MingUniversityTaipeiTaiwanChina

AIM: By using comparative genomic hybridization, gain of 3q was found in 45-86% cases of esophageal squamous cell carcinoma (EC-SCC). Chromosome 3q25.3-qter is the minimal common region with several oncogenes found within this region. However, amplification patterns of these genes in EC-SCC have never been reported. The possible association of copy number changes of these genes with pathologic characteristics is still not clear. METHODS: Real-time quantitative PCR (Q-PCR) was performed to analyze the copy number changes of 13 candidate genes within this region in 60 primary tumors of EC-SCC, and possible association of copy number changes with pathologic characteristics was analyzed by statistics. Immunohistochemistry (IHC) study was also performed on another set of 111 primary tumors of EC-SCC to verify the association between TP63 expression change and lymph node metastasis status. RESULTS: The average copy numbers (±SE) per haploid genome of individual genes in 60 samples were (from centromere to telomere): SSR3: 4.19 (±0.69); CCNL1: 5.24 (±0.67); SMC4L1: 2.01 (±0.16); EVI1: 2.02 (±0.12); hTERC. 5.28 (±0.54); SKIL 2.71 (±0.14); EIF5A2. 1.95 (±0.12); ECT2: 9.18 (±1.68); PIK3CA: 8.13 (±1.17); EIF4G1: 1.07 (±0.05); 557: 3.07 (±0.25); TP63: 2.51 (±0.22); TFRC. 2.42 (±0.19). Four clusters of amplification were found: SSR3 and CCLN1 at 3q25.31; hTERC and SKIL at 3q26.2; ECT2 and PIK3CA at 3q26.31-q26.32; and 55T, TP63 and TFRC at 3q27.3-q29. Patients with lymph node metastasis had significantly lower copy number of TP63 in the primary tumor than those without lymph node metastasis. IHC study on tissue arrays also showed that patients with lymph node metastasis have significantly lower TP63 staining score in the primary tumor than those without lymph node metastasis. CONCLUSION: This study showed that different amplification patterns were seen among different genes within 3q25.3-qter in EC-SCC, and several novel candidate oncogenes (SSR3, SMC4L1, ECT2, and SST) were ide

关键词： Chromosomal aberration Comparative genomic hybridization esophageal neoplasm Immunohistochemistry Quantitative real-time PCR Tissue array Tumor protein 63

Expression of G3BP and RhoC in esophageal squamous carcinoma and their effect on prognosis

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World Journal of Gastroenterology 2007年第30期13卷 4126-4130页

作者： Hui-Zhong Zhang Jin-Geng Liu Yi-Ping Wei Cheng Wu Yong-Ke Cao Mei Wang Department of Cardiothoracic Surgery The Second Affiliated Hospital Sun Yat-Sen University 107 Yan- Jiang Road Guangzhou 510120 Guangdong Province China

AIM: To investigate the expression and significance of G3BP and RhoC proteins in esophageal squamous carcinoma (ESC). METHODS: The expression of G3BP and Rhoc proteins in 80 cases of ESC was detected by immunohistochemistry. The relationship was studied between the expression of the two proteins and tumor size, differentiation degree, TNM stage, lymph node metastasis and prognosis of ESC. RESULTS: The positive expression rate of G3BP in ESC was 71.25%; and the rate in the lymph node metastasis group was significantly higher than that in the non- lymph node metastasis group (Z = -2.283, P = 0.022), but no relations were found between G3BP expression and tumor size, differentiation degree and TNM stage (P > 0.05). The group with G3BP positive expression had shorter survival time than the group with G3BP negative expression (P = 0.000). The positive expression rate of RhoC in ESC was 66.25%; and the rate in the lymph node metastasis group was significantly higher than that in the non-lymph node metastasis group (Z = -2.115, P 0.05). The RhoC positive expression group had a shorter survival time than the RhoC negative expression group (P < 0.001. The expression of G3BP protein correlated positively with the expression of RhoC in ESC tissues (rs = 0.656, P < 0.001). CONCLUSION: The expression of G3BP and RhoC protein is closely related to the lymph node metastasis and survival in ESC patients. G3BP and RhoC proteins can be considered as predictors of prognosis in ESC patients.

关键词： esophageal neoplasm G3BP RhoC Immunohistochemistry Lymph node metastasis Prognosis