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Interferon-α enhances sensitivity of human osteosarcoma U2.S cells to doxorubicin by p53-dependent apoptosis

Acta Pharmacologica Sinica 2007年第11期28卷 1835-1841页

作者： Xiang-wei YUAN~2.Xiao-feng ZHU~(3,5),Xiu-fang HUANG~4,Pu-yi SHENG~2.Ai-shan HE~2.Zi-bo YANG~2.Rong DENG~3,Gong-kanFENG~3,Wei-ming LIAO~(2.5)~2.Department of Orthopedic Surgery,The First Affiliated Hospital,Sun yat-sen {2.,guangzhou 510080,china ~3 state key laboratoryof oncology in south china,cancer center,Sun yat-sen {2.,guangzhou 510060,china ~4 Department of Pathology,The AffiliatedJiangmen Hospital,Sun yat-sen {2.,Jiangmen 52.030,china Department of Orthopedic Surgery The First Affiliated Hospital Sun Yat-sen University Guangzhou 510080 China state key Laboratory of {2. in south china Cancer Center Sun Yat-sen University Guangzhou 510060 China Department of Pathology The Affiliated Jiangmen Hospital Sun Yat-sen University Jiangmen 529030 China

Aim:To determine whether interferon-α(IFNα) can enhance doxorubicinsensitivity in osteosarcoma cells and its molecular ***:Cellviability was evaluated using 3-(4,5-dimethylthiazol-2.yl)-2.5-diphenyltetrazoliumbromide *** was studied using Flow cytometry analysis,Hoechst332.8 staining,DNA fragmentation assay,as well as the activation ofcaspase-3 and poly (ADP-ribose) *** expression was detectedby Western *** dependence of p53 was determined using ***:IFNα increased doxorubicin-induced cytotoxicity to a muchgreater degree through apoptosis in human osteosarcoma p53-wild U2.S cells,but not p53-mutant MG63 ***α markedly upregulated p53,Bax,Mdm2.andp2.,downregulated Bcl-2.and activated caspase-3 and PARP cleavage in re-sponse to doxorubicin in U2.S ***,the siRNA-mediated silencing ofp53 significantly reduced the IFNα/doxorubicin combination-induced cytotoxic-ity and PARP ***:IFNα enhances the sensitivity of humanosteosarcoma U2.S cells to doxorubicin by p53-dependent *** propercombination with IFNα and conventional chemotherapeutic agents may be a ra-tional strategy for improving the treatment of osteosarcoma with functional p53.

关键词： Interferon-α doxorubicin apoptosis p53 osteosarcoma

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Expression of calreticulin is associated with infiltration of T-cells in stage ⅢB colon cancer

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World Journal of Gastroenterology 2010年第19期16卷 2428-2434页

作者： Rui-Qing Peng, Ya Ding, Xing Zhang, Yi-Xin Zeng, Xiao- Shi Zhang, state key Laboratory of {2. in south china, Biotherapy center, cancer center, Sun yat-sen university, 651 Dongfeng R E, guangzhou 510060, Guangdong Province, china Ying-Bo Chen, Zhi-Wei Zhou, state key Laboratory of {2. in south china, Department of Gastric and Pancreatic {2., cancer center, Sun yat-sen university, 651 Dongfeng R E, guangzhou 510060, Guangdong Province, china Rong Zhang, state key Laboratory of {2. in south china, Department of Endoscopy, cancer center, Sun yat-sen university, 651 Dongfeng R E, guangzhou 510060, Guangdong Province, china Xing-Juan Yu, Yi-Xin Zeng, state key Laboratory of {2. in south china, Department of Experimental Research, cancer center, Sun yat-sen university, 651 Dongfeng R E, guangzhou 510060, Guangdong Province, china state key Laboratory of {2. in south china Biotherapy Center Sun Yat-sen University 651 Dongfeng R E Guangzhou 510060 Guangdong Province China.

AIM: To investigate the correlation between expression of calreticulin and infiltration of lymphocytes in stage ⅢB colon cancer. METHODS: Sixty-eight pathologically-confirmed speci-mens were obtained from stage ⅢB (T3N1M0) colon cancer patients who underwent radical resection between January 1999 and May 2.02.at the {2. of Sun yat-sen university, guangzhou, china. Immuno-histochemical analysis was performed to show infiltration of lymphocytes and expression of calreticulin in colon cancer. Association between calreticulin expression, infiltration of lymphocytes, and 5-year survival rate of patients was assessed. RESULTS: The expression level of calreticulin was lower in cancer nest than in its adjacent normal epithelium since 61.8% (42.68) of the samples were stained with calreticulin in colon cancer. The expression of calreticulin in colon cancer was associated with the infi ltration of CD45RO+ cells rather than with that of CD3+ cells. In addition, the stronger expression of calreticulin and the higher infiltration of CD3+ and CD45RO+ cells in colon cancer were associated with the higher 5-year survival rate of patients. CONCLUSION: Expression of calreticulin is associated with infiltration of T-cells, which implies that a low expression level of molecular marker may represent a new mechanism underlying immune escape in colon cancer.

关键词： Calreticulin Tumor-infiltrating lymphocyte Colon cancer Immune escape

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Adjuvant interferon therapy for malignant melanoma:the debate

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Chinese Journal of cancer 2010年第11期29卷 907-913页

作者： Qiang Zhou1,2. Xiao-Shi Zhang1,2.1 state key Laboratory of {2. in south china, guangzhou, Guangdong 510060, P. R. china 2.Biotherapy center, Sun yat-sen university {12., guangzhou, Guangdong 510060, P. R. china Biotherapy center Sun Yat-sen University Cancer Center State Key Laboratory of Oncology in South China Guangdong Guangzhou 510060

Based on the results of the Kirkwood high-dose interferon alpha-2. (HDI) adjuvant therapy trial of the Eastern Cooperative oncology Group 1684, the US Food and Drug Administration (FDA) approved HDI as the postoperative adjuvant therapy for high-risk melanoma. Unfortunately, controversies continue regarding the use of interferon (IFN) as adjuvant therapy for melanoma owing to the inconsistent results of subsequent trials. Numerous trials of adjuvant interferon therapy demonstrated a benefit in terms of relapse-free survival (RFS), but without confirmed significant effect on overall survival (OS). The optimal timing, dose, and type of interferon are not yet defined. Therefore, adjuvant interferon treatment is preferentially applied in the randomized clinical trials in specialized centers. Decisions about the appropriateness of adjuvant interferon alfa-2. treatment for patients should be made on an individual basis, after discussion with the patient, including an explanation of the potential benefits and side effects of interferon therapy. Moreover, we also need to use available regimens reasonably, seek feasible and predictable prognostic factors to serve patients with individualized therapy.

关键词：恶性黑色素瘤干扰素α 辅助治疗治疗试验人类发展指数美国食品临床试验合理利用

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Antiangiogenic therapy:a novel approach to overcome tumor hypoxia

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Chinese Journal of cancer 2010年第8期29卷 715-720页

作者： Fang Peng1,2. Ming Chen1,2.1 state key Laboratory of {2. in south china, guangzhou, Guangdong 510060, P. R. china 2.Department of Radiation {2., Sun yat-sen university {12., guangzhou, Guangdong 510060, P. R. china Department of Radiation oncology Sun Yat-sen University Cancer Center State Key Laboratory of Oncology in South China Guangdong Guangzhou 510060

Hypoxia is a common phenomenon in solid tumors. Resistance of hypoxic tumor cells to radiation is a significant reason of failure in the local control of tumors. The growth and metastasis of solid tumors rely on blood vessels. Antiangiogenic agents mainly target tumor blood vessels, and radiation therapy mainly targets tumor cells. Combination of antiangiogenic treatment and radiation exhibits synergistic effect, which improves the response of tumors to radiation therapy. The mechanisms of interaction between antiangiogenic agents and ionizing radiation are complex and involve interactions between tumor cells and tumor microenvironment, including tumor oxygenation, stroma, and vasculature. The original mechanism of antiangiogenesis is to induce ischemia and hypoxia in tumors, thereby, "starve" the tumors. However, recently, emerging data suggest that antiangiogenic agents could reduce the proportion of hypoxic cells through normalizing tumor vasculature, decreasing oxygen consumption, and other mechanisms. The use of antiangiogenic agents provides a new approach to overcome the hypoxia problem, and ultimately improves the efficacy of radiation therapy. In this review, we discuss tumor hypoxia, tumor angiogenesis and its regulation, mechanisms of antiangiogenic therapy combined with radiation therapy, and how antiangiogenic therapy overcomes tumor hypoxia.

关键词：抗血管生成肿瘤细胞抗缺氧疗法放射治疗电离辐射肿瘤血管生成相互作用

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Expression of hepatitis B virus surface antigen in 12. Hodgkin's lymphoma patients

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Chinese Journal of cancer 2010年第8期29卷 735-740页

作者： Miao-Zhen Qiu1,2. Dan-Yun Ruan1,2. Zhi-Qiang Wang1,2. Hui-Yan Luo1,2. Kai-Yuan Teng1,2. Zhong-Jun Xia1,3, Yue Lu1,3, Hui-Qiang Huang1,2. Wen-Qi Jiang1,2. Rui-Hua Xu1,2.1 state key Laboratory of {2. in south china, Sun yat-sen university cancer center, guangzhou, Guangdong 510060, P. R. china 2.Department of Medical {2., Sun yat-sen university cancer center, guangzhou, Guangdong 510060, P. R. china 3 Department of Hematology {2., Sun yat-sen university cancer center, guangzhou, Guangdong 510060, P. R. china Sun yat-sen {2. cancer center State Key Laboratory of Oncology in South China Guangdong Guangzhou 510060

Background and Objective: Little is known about the incidence of hepatitis B virus (HBV) infection in Hodgkin's lymphoma patients. This study was to evaluate the impact of HBV infection on the survival of Hodgkin's lymphoma patient. Methods: Clinical data of 12. Hodgkin's lymphoma patients treated at the Sun yat-sen {2. cancer center between January 2.04 and October 2.07 were collected. The impact of prognostic factors including HBV infection on survival was examined by univariate and multivariate analyses. A log-rank test was used for univariate analysis and the Cox proportional hazards regression model was used for multivariate analysis. Results: Of the 12. patients, 18 (15.0%) were hepatitis B virus surface antigen (HBsAg)-positive. The HBsAg-positive patients had lower 5-year survival rate than did the HBsAg-negative ones (66.9% vs. 91.3%, P = 0.006). When the patients were divided into early-stage (Ⅰ+Ⅱ) and advanced-stage (Ⅲ+Ⅳ) groups, the 5-year survival rate was significantly different between the HBsAg-positive and -negative patients in early-stage group (64.8% vs. 96.0%, P < 0.001), while not significantly different in advanced-stage group (75.0% vs. 84.8%, P=0.667). Both univariate and multivariate analyses showed that radiotherapy and HBV infection were independent prognosis factors for the patients with early-stage Hodgkin's lymphoma (P=0.006 and 0.014, respectively). Conclusions: The incidence of HBV infection is similar between Hodgkin's lymphoma patients and normal population. HBV infection is an independent prognosis factor for survival in the patients with early-stage Hodgkin's lymphoma.

关键词：乙肝病毒表面抗原淋巴瘤患者乙肝表面抗原多因素分析金病毒感染肝炎病毒

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The results and prognosis of different treatment modalities for solitary metastatic lung tumor from nasopharyngeal carcinoma:a retrospective study of 105 cases

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Chinese Journal of cancer 2010年第9期29卷 787-795页

作者： Jun Ma1,2. Zhe-Sheng Wen1,2. Peng Lin1,2. Xin Wang1,2. Fang-Yun Xie1,3 1 state key Laboratory of {2. in south china, guangzhou, Guangdong 510060, P.R.china 2.Department of Thoracic {2., Sun yat-sen university {12., guangzhou, Guangdong 510060, P.R.china 3 Department of Radiation {2., Sun yat-sen university {12., guangzhou, Guangdong 510060, P.R.china Department of Thoracic Surgery, Shanxi Provincial People’s Hospital, Taiyuan, Shanxi 030012. P.R.china Department of Thoracic oncology Sun Yat-sen University Cancer Center State Key Laboratory of Oncology in South China Guangdong Guangzhou 510060 Department of Radiation oncology Sun Yat-sen University Cancer Center State Key Laboratory of Oncology in South China Guangdong Guangzhou 510060

Background and Objective:Nasopharyngeal carcinoma (NPC) is known for its propensity for distant *** metastasis is one of the most important causes of death for patients with *** metastatic lung tumor from NPC is a distinctive group associated with a better *** study was to find a more effective treatment modality and prognostic factors for the ***:Clinical data of 105 cases of solitary metastatic lung tumor from NPC were retrospectively *** rate was calculated by the Kaplan-Meier *** difference of survival between the patients treated by different modalities was evaluated by the log-rank *** Cox univariate and multivariate analyses of gender, age, pathologic type, stage, adjuvant chemotherapy, evaluation of treatment for NPC, disease-free interval, size of metastatic tumor, pulmonary hilar and/or mediastinal lymph node metastasis, treatment modalities, recurrent distant metastases and/or relapse of NPC were ***:The local control rate was 53.8% in chemotherapy group, 88.0% in radiotherapy +/-chemotherapy group, and 96.4% in operation +/-chemotherapy group (P2.087, 95% CI=1.2.7-3.410, P=0.003).The T stage of NPC, size of metastatic tumor, hilar and/or mediastinal lymph node metastasis, and the treatment modality were independent prognostic ***:Operation +/-chemotherapy and radiotherapy +/-chemotherapy are better treatment of solitary metastatic lung tumor from NPC, which could improve the local control and prolong the PFS and *** is recommended for patients with higher T stage of NPC, size of metastatic tu

关键词：治疗方式鼻咽癌预后孤立全国人民代表大会肺疗效评价多因素分析

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Percutaneous radiofrequency ablation approach through the spleen:initial case report for pancreatic tail gastrinoma

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Chinese Journal of cancer 2010年第9期29卷 836-841页

作者： Pei-Hong Wu1,2. Chang-Chuan Pan1,2. Zi-Lin Huang1,2. Wang Li1,2. Ming Zhao1,2. Zhi-Wei Zhou1,3 1 state key Laboratory of {2. in south china, guangzhou, Guangdong 510060, P.R.china 2.Department of Medical Imaging & Interventional Radiology, Sun yat-sen university cancer center, guangzhou, Guangdong 510060, P.R.china 3 Department of Abdominal {2., Sun yat-sen university cancer center, guangzhou, Guangdong 510060, P.R.china Department of Medical Imaging& Interventional Radiology Sun Yat-s en University Cancer Center State Key Laboratory of Oncology in South China Guangdong Guangzhou 510060 Department of Abdominal oncology Sun Yat-sen University Cancer Center State Key Laboratory of Oncology in South China Guangdong Guangzhou 510060

Gastrinoma has a low incidence, and the pancreas-originated gastrinoma is *** gastrinoma patients with liver metastases have poor prognosis and short *** treatment to reduce the tumor burden helps to improve symptoms and slows down tumor progression for patients with unresectable *** report a case of pancreatic tail gastrinoma with unresectable liver *** patient received a comprehensive minimally invasive interventional treatment, that is, chemoembolization and radiofrequency ablation for liver metastases, and percutaneous transplenic radiofrequency ablation combined with radioactive 12.I seed implantation for pancreatic tail *** patient was followed up for more than 2. months, and showed no clear evidence of tumor *** explored the safety and feasibility of percutaneous transplenic radiofrequency ablation for unresectable pancreatic tail *** transplenic approach allow more indications for minimally invasive therapy and provides a new treatment option not only for patients with unresectable pancreatic tail tumor but also for patients refusing surgery.

关键词：射频消融胃泌素病例报告尾部局部治疗手术切除肿瘤病介入治疗

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One patient with metastastic colorectal cancer successfully treated by combination of targeted agents after failure of chemotherpay

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Chinese Journal of cancer 2010年第12期29卷 1023-1028页

作者： Liang-Ping Xia1,2, Pei-Hong Wu1,3, Jian-Chuan Xia1,4, Bei Zhang1,2, Zhong-Zhen Guan1,5, De-sen Wan1,6, Gui-Fang Guo1,2, Yi-Xin Zeng1,7 1 state key Laboratory of oncology in south china, guangzhou, Guangdong 510060, P. R. china 2 VIP Region, Sun yat-sen Universty cancer center, guangzhou, Guangdong 510060, P. R. china 3 Department of Medical Imaging and Interventional Radiology, Sun yat-sen Universty cancer center, guangzhou, Guangdong 510060, P. R. china 4 Biotherapy cancer, Sun yat-sen Universty cancer center, guangzhou, Guangdong 510060, P. R. china 5 Department of Medical oncology, Sun yat-sen Universty cancer center, guangzhou, Guangdong 510060, P. R. china 6 Department of Colorectal cancer,Sun yat-sen Universty cancer center, guangzhou, Guangdong 510060, P. R. china 7 Sun yat-sen Universty cancer center, guangzhou, Guangdong 510060, P. R. china VIP Region Sun Yat-sen Universty Cancer Center StateKey Laboratory of Oncology in South China Guangdong Guangzhou 510060 Department of Medical Imaging and Interventional Radiology Sun Yat-sen Universty Cancer Center StateKey Laboratory of Oncology in South China Guangdong Guangzhou 510060 Biotherapy cancer Sun Yat-sen Universty Cancer Center StateKey Laboratory of Oncology in South China Guangdong Guangzhou 510060 Department of Medical oncology Sun Yat-sen Universty Cancer Center StateKey Laboratory of Oncology in South China Guangdong Guangzhou 510060 Department of Colorectal cancer Sun Yat-sen Universty Cancer Center StateKey Laboratory of Oncology in South China Guangdong Guangzhou 510060 Sun yat-sen Universty {2. StateKey Laboratory of Oncology in South China Guangdong Guangzhou 510060

Either cetuximab or bevacizumab can improve the survival of patients with metastastic colorectal cancer (mCRC) if administered combided with cytotoxic agents. However, the effect of two or more target agents in combination is uncertain in these patients. Here, we reported a patient with mCRC successfully treated by a combination of target agents after the failure of chemotherapy. The patient received palliative resection of primary tumor followed by 9 cycles of postoperative XELOX regimen, cytokine-induced killer cell (CIK)-based biotherapy, traditional Chinese medicine, particle implantation in the lung metastatic lesions. The tumor progressed 2. months after the standard treatments. Then, the regimen cetuximab, bevacizumab and cefitinib was applied. During the treatment with targeted agents, grade IV acne-like rash and relatively severe parionychia of the toes occurred. Both of them recovered smoothly. The PET-CT reexamination at 40 days after the target treatment showed that the metabolism of mediastinal lymph nodes basically recovered to a normal level. The combination of multiple targeted agents obtained a progression-free survival(PFS) of 11 months and the patient with a good quality of life during this period.

关键词：药物治疗结直肠癌转移性患者大肠细胞毒性靶向药物不确定性

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Correlation analysis between loss of heterozygosity at chromosome 18q and prognosis in the stage-Ⅱ colon cancer patients

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Chinese Journal of cancer 2010年第8期29卷 761-767页

作者： Wei Wang1,2. Yuan-Fang Li1,2. Xiao-Wei Sun1,2. Gong Chen1,3, You-Qing Zhan1,2. Chun-Yu Huang1,2. De-sen Wan1,3, Zhi-Zhong Pan1,3, Zhi-Wei Zhou1,2.1 state {2. Labortary of oncology in south china, guangzhou, Guangdong 510060, P. R. china 2.Department of Gasrtic and Pancreatic Surgery, Sun yat-sen university {12., guangzhou, Guangdong 510060, P. R. china 3 Department of Colorectal Surgery, Sun yat-sen university {12., guangzhou, Guangdong 510060, P. R. china Department of Gasrtic and Pancreatic Surgery Sun Yat-sen University Cancer Center State Key Labortary of Oncology in South China Guangdong Guangzhou 510060 Department of Colorectal Surgery Sun Yat-sen University Cancer Center State Key Labortary of Oncology in South China Guangdong Guangzhou 510060

Background and Objective: Colorectal cancer is one of the most common malignant cancers in the world. Although the clinicopathologic staging is the golden criterion for the prognosis at pre{2.t, the optimum prognostic criteria for colorectal cancer should be a combination of the clinicopathologic staging and the molecular markers. However, there are currently no molecular markers available for the prognosis of colorectal cancer. Several tumor-suppressor genes associated with colorectal cancer have been mapped at the 18q2.-2. region. In this study we detected the frequency of loss of heterozygosity (LOH) at chromosome 18q and investigated the relationship between LOH and clinicopathologic features and its prognostic value for patients with stage Ⅱ colon cancer. Methods: A total of 106 samples of tumor tissues and corresponding normal mucosa from patients with sporadic stage-Ⅱ colon cancer were included in this study. All the samples were formalin-fixed and paraffin-embedded. DNA was extracted from tumor tissues and LOH of D18S474, D18S55, D18S58, D18S61 and D18S64 at chromosome 18q was analyzed using polymerase chain reaction (PCR), polyacrylamide gel-electrophoresis, and DNA sequencing method. Multivariate analysis for association between LOH and prognosis in colon cancer patients was performed with Cox proportional hazards regression model. Results: The median follow-up time was 68 months. For 106 patients, 5-year survival rate was 83.6%, which was associated with age and gross tumor type (P = 0.011 and 0.034, respectively). Among 102.patients who were eligible for LOH information, the overall frequency of LOH is 49.0% (50/102., and that of LOH at 5 microsatellite loci of D18S474, D18S55, D18S58, D18S61, and D18S64 was 30.2. (2./86), 2..4% (18/77), 2..6% (2./70), 35.0% (2./80), and 2..8%(15/72., respectively. The occurrence of LOH was significantly associated with tumor location and histopathologic grade (P = 0.02., 0.016 and 0.005, respectively). LOH was more freq

关键词：大肠癌染色体杂合性预后患者相关分析聚丙烯酰胺凝胶电泳临床病理

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Impact of KRAS mutation and PTEN expression on cetuximab-treated colorectal cancer

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World Journal of Gastroenterology 2010年第46期16卷 5881-5888页

作者： Fang-Hua Li,Zhuang-Hua Li,Hui-Yan Luo,Miao-Zhen Qiu,Yu-Hong Li,Rui-Hua Xu,state key Laboratory of {2. in southern china,Department of Medical {2.,Sun yatsen university cancer center,guangzhou 510060,Guangdong Province,china Fang-Hua Li,Department of Medical {2.,Shengli Oil Field Central Hospital,Dongying 2.7034,Shandong Province,china Lin Shen,Department of GI {2.,Peking university School of {2.,Beijing cancer Hospital and Institute,Beijing 100142.china Hui-Zhong Zhang,state key Laboratory of {2. in southern china,Department of Pathology,Sun yat-sen university cancer center,guangzhou 510060,Guangdong Province,china state key Laboratory of {2. in southern china Department of Medical Oncology Sun Yat-Sen University Cancer Center Guangzhou 510060 Guangdong Province China. xurh@***

AIM:To investigate the prognostic value of KRAS mutation,and phosphatase and tensin (PTEN) expression in Chinese metastatic colorectal cancer metastatic colorectal cancer (mCRC) patients treated with ***:Ninety Chinese mCRC patients treated with cetuximab were evaluated for KRAS mutation and PTEN protein expression by DNA sequencing of codons 12.and 13 and immunohistochemistry,*** then selected 61 patients treated with cetuximab,either in combination with chemotherapy,or alone as a second-line or third-line regimen to assess whether KRAS mutation or PTEN protein expression is associated with the response and the survival time of mCRC patients treated with ***:KRAS mutation was found in 30 (33.3%) tumor samples from the 90 patients,and positive PTEN expression was detected in 58 (64.4%) of the 90 *** the 61 patients who were treated with cetuximab as a second-line or third-line regimen,the resistance to cetuximab was found in 2. patients with KRAS mutation and in 39 patients without KRAS mutation,with a response rate of 4.5% and 46.1% respectively (P=0.001),a shorter median progression-free survival (PFS) time of 14 ± 1.3 wk and 32.± 2.5 wk respectively (P 2.mo and 19 ± 1.8 mo respectively (P 2. patients with negative PTEN expression and in 37 patients with positive PTEN expression respectively (P 2. and 48.6% respectively,a shorter median PFS survival time of 17 ± 2.0 wk and 2. ± 1.9 wk respectively (P=0.07),and a median OS time of 11 ± 1.3 mo and 18 ± 1.9 mo respectively (P=0.004).Combined KRAS mutation and PTEN expression analysis showed that the PFS and OS time of patients with two favorable prognostic factors were longer than those of patients with one favorable prognostic factor or no favorable prognostic factor (P < 0.001).CONCLUSION:KRAS mutation and PTEN protein expression are significantly corr

关键词： Cetuximab Metastatic colorectal cancer KRAS mutation Phosphatase and tensin protein expression

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