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Progress of research on predicting breast cancer prognosis based on multi-gene expression levels

Chinese Journal of Clinical Oncology.2013;(13):807-810,814. doi:10.3969/j.issn.1000-8179.2013.13.015

Breast cancer is one of the most common cancers in women. Current clinical prognostic indicators and practice guide-lines show that almost 70% of node-negative and 30% of lymph node-positive breast cancer patients can survive 5-10 years without dis-tant metastasis after surgery. Patients also unnecessarily suffer the side effects of chemotherapy. Assays on multi-gene expression levels as prognosis prediction indicators have been successfully used to predict the prognosis of breast cancer patients because of the abnor-mal expression levels of a series of metastasis-related genes in cancer cells with high metastatic potential. In this review, we highlight the progress of research on predicting breast cancer prognosis based on multi-gene expression levels detected by microarray and qRT-PCR methods.

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Effect of NF-κBp65 on Epithelial-mesenchymal Transition in Esophageal Squmous Cell Carcinoma

Hongyan ZHANG ; Xiaojun WANG ; Feng WANG ; Xinhua WANG ; Yang SUN ; Shanshan LI

Chinese Journal of Clinical Oncology.2010;37(4):187-189,193. doi:10.3969/j.issn.1000-8179.2010.04.003

Objective: To study the effect of NF-κBp65 on epithelial-mesenchymal transition (EMT) in esophageal squa-mous cell carcinoma cell line EC9706. Methods: Esophageal squamous cell carcinoma cell line EC9706 was transfected by chemically synthesized NF-κBp65-ASODN. RT-PCR, immunocytochemistry and flow cytomertry were used to detect the mRNA and protein expression of NF-κBp65, E-cedherin and Vimentin in EC9706 before and after NF-κBp65-ASODN trans-fection. The morphological alterations of EC9706 cells were observed under inverted microscope and scarification test was used to detect the mobility of EC9706 cells before and after transfection. Results: After NF-κBp65-ASODN transfection, the mRNA (0.14±0.06) and protein (immunocytochemistry: 11.33%±1.40%, flow cytomertry: 11.78%) expressions of NF-κBp65 in EC9706 were significantly lower than those before transfection (mRNA: 0.45 ± 0.05; protein: immunocytochemistry: 17.17%±1.66%, flow cytomertry: 15.76%, P<0.05), the mRNA (0.36±0.08) and protein (immunocytochemistry: 17.58%± 1.86%, flow cytomertry: 14.98%) expressions of E-cedherin in EC9706 cells were significantly higher than those before transfection (mRNA: 0.22±0.06; protein: immunocytochemistry: 14.42%±1.63%, flow cytomertry: 12.22%, P<0.05) and the mRNA (0.75±0.07) and protein (immunocytochemistry: 16.00% ± 1.41 %, flow cytomertry: 12.90%) expressions of Vimentin were significantly lower than those before transfection (mRNA: 0.89±0.09; protein: immunocytochemistry: 19.50±0.89%, flow cytomertry: 17.76%, P<0.05). After NF-κBp65-ASODN transfection, the morphological alterations of EC9706 cells oc-curred and the migration length (0.45±0.08) was significantly shorter than that before transfection (0.81±0.11, P<0.05). Con-clusion: NF-κBp65 may contribute to EMT in esophageal squamous cell carcinoma. NF-κBp65-ASODN transfection can in-hibit EMT in esophageal squamous cell carcinoma, up-regulate E-cadherin expression, down-regulate Vimentin expression and decrease cell mobility.

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Research progress in clinical presentation and management of ad-vent events associated with sorafenib in hepatocellular carcinoma

Lan ZHANG ; Zhenggang REN

Chinese Journal of Clinical Oncology.2013;(20):1268-1271. doi:10.3969/j.issn.1000-8179.20130794

Sorafenib is a novel oral multikinase inhibitor that inhibits Raf kinase because of its anti-proliferative property. Sorafenib also inhibits receptor tyrosine kinases of multiple proangiogenic factors, such as VEGFR-1/2/3 and PDGFR-β. The combina-tion of both its anti-proliferative and anti-angiogenic properties makes sorafenib an attractive agent in cancer treatment. To date, sorafenib is the only approved systemic treatment for patients with hepatocellular carcinoma. The most common adverse events of this inhibitor included hand-foot skin reactions, nausea, diarrhea, weight loss, and hypertension. These adverse events can severely affect patient compliance, which may negate the effect of therapy. Correct understanding and treatment of these adverse events can improve clinical outcome. This paper discusses the clinical aspect of sorafenib-induced adverse events and the molecular basis behind their toxic-ity. Recommendations for the management of the adverse effects are also provided.

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Function of tumor-associated macrophages in gastric cancer

Xijin ZHOU ; Guohua LI

Chinese Journal of Clinical Oncology.2013;(20):1261-1263. doi:10.3969/j.issn.1000-8179.20130232

Macrophages are a diverse phenotype that has important functions in inherent and adaptive immunity. Macrophage ac-tivation has two distinct states of polarization:the classically activated (M1) and the alternatively activated (M2) macrophage pheno-types in different micro-environments. M2 macrophages exert an immuno-regulatory activity that is associated with the induction of Th2 responses. The macrophages can infiltrate in the tumor micro-environment, and is also known as tumor-associated macrophages (TAMs). TAMs show the M2 macrophage phenotypes that have been associated with tumor neo-vascularization, infiltration, and metas-tasis. This review aims to investigate the importance of the immuno-regulatory activity of TAM in the carcinogenesis of gastric cancers.

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Effect of hypofractionated palliative thoracic radiotherapy for ad-vanced non-small cell lung cancer

Weishuai LIU ; Lujun ZHAO ; Zhiyan LIU ; Bo LI ; Zhiyong YUAN ; Ping WANG

Chinese Journal of Clinical Oncology.2013;(20):1240-1243. doi:10.3969/j.issn.1000-8179.20131579

Objective:To investigate the effect and toxicity of short-course and hypofractionated palliative thoracic radiotherapy (PTR) for advanced non-small cell lung cancer (NSCLC). Methods:A total of 25 patients with stageⅢB and stageⅣNSCLC, who underwent PTR from September 2010 to July 2006, were retrospectively analyzed. The PTR regime was 45 Gy in 15 fractions. Symptom relief, effect, and toxicity after completion of PTR were assessed. Survival was analyzed using the Kaplan-Meier method. Results:Except for one patient who completed only 36 Gy in 12 fractions, all other patients completed all plans. The thoracic symptoms of 18 patients were relieved. The response rates for the five main symptoms were:hemoptysis 87.5%(7/8), cough 70.6%(12/17), pain 73.3%(11/15), dyspnea 57.1%(8/14), and hoarseness 50%(1/2). The complete response and partial response after PTR was 28%, and no grade 3 or higher toxicities occurred. The median time of overall survival (OS) is 13 months (95%CI:6.6 months to 19.5 months), and one-year OS is 51.5%. According to the univariate analysis, KPS before PTR, the number of post-PTR was significantly related to the survival. Conclusion:For advanced NSCLC patients, the PTR regime given as 45 Gy in 15 fractions evidently relieved thoracic symptoms, improved OS, and shortened treatment time. Recent relevant adverse radiotherapy reactions are low, and more prospective clinical studies must be conducted.

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Effect of CO2 pneumoperitoneum on the expression levels of CX-CL12 and CXCR4 in nude mice xenografts from human ovarian cancer SKOV3 cells

Ying ZHANG ; Ying LIU ; Aizhen FU ; Yuanjun LI ; Bingjuan FAN ; Xin LUO

Chinese Journal of Clinical Oncology.2013;(20):1217-1220. doi:10.3969/j.issn.1000-8179.20130357

Objective:To investigate the effect of the expression levels of CXCL12 and CXCR4 of carbon dioxide (CO2) pneu-moperitoneum on nude mice xenografts from human ovarian cancer SKOV3 cells in the same pressure at different times. Methods:A total of 40 animal models of human ovarian cancer SKOV3 cell-bearing nude mice xenografts were established. The animals were ran-domly divided into four groups (n=10), namely, the simple anesthesia group, 0.5 h laparotomy group, and 0.5 and 1 h CO2 pneumoperi-toneum groups. After the aforementioned treatments in the groups, the expression levels of CXCL12 and CXCR4 mRNAs of tumor tis-sues were detected by reverse transcription-polymerase chain reaction (RT-PCR), whereas those of the CXCL12 and CXCR4 proteins were detected by Western blot. Results:The 40 animal models of human ovarian cancer SKOV3 cell-bearing nude mice were success-fully established. After the treatment, RT-PCR results reveal that the CXCL12 mRNA expression was significantly higher in the 1 h CO2 pneumoperitoneum group than that in the other three groups. However, no differences were observed in the CXCR4 mRNA expression of each group. Western blot analysis also obtained the same results. Conclusion:The expression level of CXCL12 in SKOV3 cells of the 1 h CO2 pneumoperitoneum group increased, which possibly promoted the growth of peritoneal tumors, and had a slight effect on tu-mor metastasis.

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Advances in research on adaptive radiotherapy for nasopharyn-geal carcinoma

Jinjian CHENG ; Hua YANG ; Zhiping LU ; Heming LU ; Yanrong HAO ; Jiaxin CHEN

Chinese Journal of Clinical Oncology.2013;(20):1272-1275. doi:10.3969/j.issn.1000-8179.20130149

Intensity-modulated radiotherapy (IMRT) is gradually replacing conventional radiation therapy and has become the mainstream radical treatment for patients with nasopharyngeal carcinoma (NPC). IMRT can conform and increase radiation doses to tu-mor-associated regions as well as decrease exposure doses and volumes on normal organs and tissues to avoid damage on critical or-gans. Aside from system and setup errors, other factors, such as the gradual reduction of the primary NPC lesion and the decrease in vol-ume of involved neck lymph nodes as well as body weight loss and changes in the head and neck shape during IMRT, may cause devia-tions in the radiation doses and volume delivered to the NPC targets and the organs at risk. These factors may affect the accuracy of IMRT. Several researchers have attempted to correct such deviations during IMRT for NPC patients by using adaptive radiotherapy (ART). The results indicate that ART is feasible to a certain degree and can correct the deviations, including decrease in tumor volume, body weight loss, and changes in head and neck shape of NPC patients.

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Two-tier system on the origin of epithelial ovarian carcinomas and associated molecular biological basis

Wenfeng CAO ; Ming LIU ; Baocun SUN

Chinese Journal of Clinical Oncology.2013;(20):1264-1267. doi:10.3969/j.issn.1000-8179.20130790

Ovarian epithelial carcinomas are the most common lethal gynecological malignancies. Ovarian carcinomas are divid-ed into Types I and II based on different morphologies, genetic alterations, and biomarker expression. Low-grade micropapillary serous carcinoma are Type I tumors. Type I tumors are slow growing, generally confined to the ovary at diagnosis, and with better prognosis. These tumors develop from well established precursor lesions that are termedborderlinetumors. Type 1 tumors are genetically stable and are characterized by mutations in a number of different genes including KRAS, BRAF, PTEN, and beta-catenin. Type II tumors are rapidly growing and highly aggressive neoplasms, for which well defined precursor lesions have not been described. They may arise in the fimbrial epithelium of the oviduct with advanced stage, more aggressive behavior, and worse prognosis. High-grade serous carcino-ma belongs to Type II tumors. This group of tumors has a high level of genetic instability and is characterized by TP53 mutation. Hence, ovarian cancer comprises a heterogeneous group of tumors with distinctly different histological characteristics, molecular genet-ic features, and clinical course.

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Pharmacokinetic study of palonosetron hydrochloride in healthy volunteers

Zhongling ZHU ; Zhongsheng TONG ; Duanyun SI ; Weilin DONG ; Zhao YAN

Chinese Journal of Clinical Oncology.2013;(20):1256-1260. doi:10.3969/j.issn.1000-8179.20131398

Objective: To evaluate the pharmacokinetics of palonosetron hydrochloride in healthy volunteers. Methods: Thir-ty-one healthy volunteers were grouped into three palonosetron hydrochloride dosage regimens of 0.125, 0.25, and 0.5 mg. The plasma concentrations of palonosetron were determined by ultra high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). DAS 2.1 software was applied to assess the plasma concentration-time data. Results:After intravenous injection of 0.125, 0.25, and 0.5 mg palonosetron to the subjects, the AUC0-168h values of palonosetron were (7.5±2.5), (15.2±4.0), and (34.8±9.7) μg· h·mL-1. The t1/2 values were (27.2±9.5), ( 27.2±6.5), and (31.4±5.6) h. Palonosetron exposure increased proportionally with the dose range of 0.125 mg to 0.5 mg. The correlation coefficient was 0.998. No grade 3 or grade 4 toxicity was observed during the study. Con-clusion:A rapid, sensitive, and selective UPLC-MS/MS method for palonosetron quantification in human plasma was developed and validated. All the participants indicated high tolerance throughout the study. Our data showed that palonosetron exhibits linear pharma-cokinetics over the the dose range of 0.125 mg to 0.5 mg.

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Clinical application of multi-slice computed tomography angiogra-phy in pulmonary lobectomy of patients with lung cancer

Miao LI ; Wanpeng WU ; Chao CUI ; Zhiheng XING ; Kai WANG

Chinese Journal of Clinical Oncology.2013;(20):1252-1255. doi:10.3969/j.issn.1000-8179.20130967

Objective:To explore the clinical value of chest multi-slice computed tomography angiography (MSCTA) as a preoper-ative examination for lung cancer patients undergoing pulmonary lobectomy. Methods: Sixty lung cancer patients formed the study population and were randomly divided into 2 groups of 30 cases each. In the experimental group, CTA images of the tumors and pulmo-nary artery, bronchial artery, pulmonary vein were acquired, analyzed, and post-processed using VR to determine the anatomical rela-tionship between vessels and tumors. Pulmonary lobectomy followed. Cases in the control group underwent pulmonary lobectomy with-out guidance by chest MSCTA. Operation times and amounts of operative blood loss were compared between the two groups. Results:Significant differences between groups in terms of operation time (study group vs. control group, 199±55.7 vs. 231.5±51.2(min);P=0.02) and amount of operative blood loss (study group vs. control group, 318.33±99.6 vs. 431.7±89.5(mL), P<0.01) were observed. Val-ues of operation time and amount of contrast agents in the study group were consistently lower than those in the control group. Conclu-sion:Chest MSCTA can shorten the operation time and reduce the amount of operative blood loss during pulmonary lobectomy. Thus, the technique has significant clinical value.

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