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25 February 2015, Volume 7 Issue 1 Previous Issue    Next Issue

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Role of BIM signaling in crizotinib-induced apoptosis in the EML4-ALK-positive lung adenocarcinoma cell line H2228 WEI Jiang,PENG Haiyan,SU Cuiyun,SONG Xiangqun,WANG Huilin,NING Ruiling,ZHOU Shaozhang 2015, 7 (1):  1-5.  doi: 10.3969/j.issn.1674-5671.2015.01.01 Abstract ( 320 )   PDF (1009KB) ( 533 )   Save Objective To establish a crizotinib-resistant line of the EML4-ALK-positive lung adenocarcinoma cell line H2228 and compare it with the crizotinib-sensitive parental line to examine the possible role of BIM in crizotinib-induced apoptosis. Methods H2228 human lung cells were exposed to gradually increasing doses of crizotinib（50，100，200，500，1000 nmol/L）to create a crizotinib-resistant line（H2228/CR）. Then H2228/CR and parental H2228 cells were exposed to different doses of crizotinib，and their growth was compared using the MTT assay，while levels of apoptosis were compared using flow cytometry. Western blotting was used to compare levels of ALK，p-ALK，ERK，p-ERK and BIM in the two cell lines. Results After 8 months of crizotinib selection，the resistant line H2228/CR showed an IC50 of 3，418 nmol/L compared to 335 nmol/L for the parental H2228 line. The RI for H2228/CR cells was 10.20. Crizotinib inhibited the growth of H2228/CR cells to a much smaller extent than it inhibited H2228， and it led to a much smaller proportion of apoptotic cells in H2228/CR cultures. Levels of phospho-ERK were higher in H2228/CR cells， implying down-regulation of BIM. Conclusion BIM may help mediate crizotinib-induced apoptosis in lung cancer， and its down-regulation may contribute to crizotinib resistance. Related Articles | Metrics

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Isolation， culture and characterization of portal venous tumor thrombus cells from patients with hepatocellular carcinoma （HCC） with or without portal vein tumor thrombosis PENG Yuchong,LU Shidong,XIE Zhibo,PANG Yebing,OU Chao,LI Lequn 2015, 7 (1):  6-12.  doi: 10.3969/j.issn.1674-5671.2015.01.02 Abstract ( 327 )   PDF (1180KB) ( 856 )   Save Objective To explore the stem cell-like properties of primary cultures of hepatocellular carcinoma （HCC） cells and portal vein tumor thrombus（PVTT） cells. Methods Fresh hepatocellular carcinoma（HCC） with portal vein tumor thrombosisand（PVTT）or not were used for short-term primary culture and stability batches by utilizing enzymatic digestion. We would be classify the stability of the cultured cells as HCC without PVTT, the T-primary tumor of HCC with PVTT and PVTT,called section of HCC-PVTT（-）,HCC-PVTT（+）and PVTT. Flow cytometry detect the content of CD90+ and the expressions of relative gene and protein from HCC with PVTT or not，which were tested by qRT-PCR and Western blot methods. Testing the cells of invasion by Transwell chamber. Results We successfully cultured primary HCC cells and PVTT cells. Flow cytometry revealed the presence of a CD90+ subpopulation in both types of cultures. The different cultures varied in invasiveness as follows：PVTT cells>HCC-PVTT（+） cells>HCC-PVTT（+） cells>HCC-PVTT（-）cells（P<0.05）. Conclusions Stem cell-like populations exist in HCC and PVTT tissue，and their stem cell characteristics correlate positively with tumor invasion and metastasis. Related Articles | Metrics

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Effect of metformin on HEC-1A endometrial cancer cells in the presence of LKB1 overex-pression SONG Yue,SONG Honglin,TANG Qiaoqiao,PAN Yueqiong,HE Junkui,ZHAO Ruiqi 2015, 7 (1):  12-17.  doi: 10.3969/j.issn.1674-5671.2015.01.03 Abstract ( 215 )   PDF (387KB) ( 503 )   Save Objective To investigate the effect of metformin on proliferation and cell cycle of HEC-1A endometrial cancer cells in the presence of LKB1 overexpression. Methods HEC-1A cells overexpressing LKB1 and control HEC-1A cells were treated with different concentrations of metformin. The two groups were compared in terms of proliferation rate，cell migration ability and cell cycle using a colony formation assay，transwell experiments and flow cytometry. Expression of LKB1 and mTOR mRNA was measured using RT-PCR，and levels of the corresponding proteins were measured using Western blotting. Results Treating LKB1-overexpressing HEC-1A cells with metformin inhibited colony formation，cell motility，and expression of mTOR mRNA and protein in a dose-dependent manner relative to control HEC-1A cells（P<0.05）. It also reduced the proportion of LKB1-overexpressing HEC-1A cells in S phase relative to controls（P<0.05）. Conversely，treating LKB1-overexpressing HEC-1A cells with metformin increased the proportion of cells in G0 /G1 phase and upregulated expression of LKB1 mRNA and protein in a dose-dependent manner（P<0.05）. Conclusion Metformin inhibits proliferation and cell migration of HEC-1A endometrial cancer cells overexpressing LKB1，potentially by acting on the LKB1/mTOR signaling pathway. Related Articles | Metrics

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Bioinformatic analysis of genes and signaling pathways associated with RhoGDI2-inhibited bladder cancer metastasis TANG Yong,LI Xiuning,GAO Chao,LIU Hannan,WANG Qi 2015, 7 (1):  18-22.  doi: 10.3969/j.issn.1674-5671.2015.01.04 Abstract ( 224 )   PDF (377KB) ( 674 )   Save Objective This study used bioinformatics to examine the genes and signaling pathways associated with RhoGDP dissociation inhibitor 2（RhoGDI2） inhibits bladder cancer metastasis. Methods Six datasets from genomic microarray studies of patients with metastatic bladder cancer were downloaded from the Gene Expression Omnibus database. On-line GEO2R tools were used to screen for genes differentially expressed between individuals expressing low or high levels of RhoGDI2. On-line DAVID tools were used to map differentially expressed genes to signaling pathways. Result The genes A2M，CORO1A，ENC1，and FGD3 were expressed at higher levels in patients expressing high levels of RhoGDI2. RhoGDI2 appeared to influence the RhoA-ROCK-MLC and Ras-Raf- MEK signaling pathways to the greatest extent. Conclusion RhoGDI2 may act via the RhoA-ROCK-MLC and Ras-Raf-MEK pathways to regulate cytoskeleton， cell proliferation， differentiation and metastasis in bladder cancer. Related Articles | Metrics

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Effects of different doses of ionizing radiation on DNA damage and apoptosis of breast cancer cells with and without BRCA mutations YIN Xue,ZHU Xiaodong,LIANG Xia,QU Song,LI Ye,LI Ling,ZHAO Wei 2015, 7 (1):  23-27.  doi: 10.3969/j.issn.1674-5671.2015.01.05 Abstract ( 288 )   PDF (779KB) ( 511 )   Save Objective To investigate the effects of different ionizing radiation doses on DNA damage and apoptosis of breast cancer cell lines with and without BRCA mutations. Methods BRCA mutant cells （MDA-MB-436） and non-BRCA mutant cells （MDA-MB-231） were subjected to different doses of ionizing radiation：0，2，4，6，8，or 10 Gy. The percentage of apoptotic cells was assessed by flow cytometry. After 30 min of irradiation， DNA damage was detected using an immunofluorescence-based γH2AX focus assay. Results Increasing radiation dose was associated with greater double-strand DNA damage and apoptosis in both MDA-MB-436 and MDA-MB-231 cells，with the greatest effects reached at 8 Gy. At individual doses，DNA damage and apoptosis were significantly more severe in MDA-MB-436 cells than in MDA-MB-231 cells（P＜0.05）. Conclusions Double-strand DNA damage and apoptosis vary in proportion to radiation dose， and cells containing BRCA mutations may be more radiation-sensitive than cells lacking such mutations. Related Articles | Metrics

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The value of contrast-enhanced combined routine transrectal ultrasound in the diagnosis of prostate cancer YAN Xue,LIAO Xinhong,GAO Yong,QIN Hongzhen,LU Lu,LI Zhixian,LI Ye 2015, 7 (1):  28-32.  doi: 10.3969/j.issn.1674-5671.2015.01.06 Abstract ( 235 )   PDF (584KB) ( 653 )   Save Objective To determine the value of  contrast-enhanced and routine transrectal ultrasound combination in the diagnosis of prostate cancer. Method A total of 70 men with suspected prostate cancer were examined by both routine and contrast-enhanced transrectal ultrasound at our hospital. Diagnosis was confirmed by prostate biopsy. Result The pathological positive rate was 62.9%. A total of 37 patients were diagnosed with prostate cancer by contrast-enhanced combined routine transrectal ultrasound，while 21 were diagnosed with prostate cancer by routine transrectal ultrasound. Significantly different values of diagnostic performance parameters were obtained for the contrast-enhanced combined routine technique vs. the routine technique（all P＜0.05）：sensitivity，84.1% vs 47.7%；specificity，69.2% vs 53.8%；positive predictive value，82.2% vs 63.6%；negative predictive value，72.0% vs 37.8%；and pathological coincidence rate，78.6% vs 50.0%. Conclusion Contrast-enhanced combined routine transrectal ultrasound shows higher diagnostic performance than routine transrectal ultrasound for diagnosing prostate cancer. Related Articles | Metrics

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The significance of neoadjuvant chemotherapy for inhibiting colorectal liver metastasis GAN Zhaoyi,LIN Yuan 2015, 7 (1):  32-36.  doi: 10.3969/j.issn.1674-5671.2015.01.07 Abstract ( 263 )   PDF (419KB) ( 374 )   Save Objective To investigate the efficacy of neoadjuvant chemotherapy for inhibiting colorectal liver metastasis. Methods Clinical records of 76 patients who were treated for colorectal liver cancer metastasis at the Affiliated Tumor Hospital of Guangxi Medical University were retrospectively analyzed. All patients underwent neoadjuvant chemotherapy before surgery. The following patient data were analyzed： size of the primary colorectal cancer and its liver metastases，serum CEA levels before and after neoadjuvant chemotherapy，radical resection，chemotherapy side effects， surgical complications and 2-year survival. Results The size of the primary tumor and its liver metastases decreased significantly after neoadjuvant chemotherapy in most patients， as did serum CEA levels （P＜0.05）. The objective response rate for liver metastases was 66.11%（51/76），with 0 cases of complete remission （CR），51 partial remission （PR），24 stable disease（SD），and 1 progressive disease （PD）. The objective response rate for primary tumors was 57.89%（44/76），with 0 cases of CR，44 PR，30 SD，and 2 PD. The main side effects of neoadjuvant chemotherapy were peripheral nerve toxicity，myelosup-presion and gastrointestinal reaction. The rate of radical resection was 30.26%（23/76），and the rate of surgical complications was 3.95%. The 2-year survival rate was significantly higher among patients treated by radical resection than among those who did not receive this treatment. Conclusion Neoadjuvant chemotherapy is effective and tolerable for patients with colorectal liver metastases. It may improve not only the radical resection rate but also prognosis. Related Articles | Metrics

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Nutritional risk status of patients receiving adjuvant chemotherapy after breast cancer surgery and its effects on chemotherapy MAO Liping,SHEN Fei,SUN Yajun 2015, 7 (1):  36-40.  doi: 10.3969/j.issn.1674-5671.2015.01.08 Abstract ( 254 )   PDF (381KB) ( 561 )   Save  Objective To assess the nutritional risk status of patients receiving adjuvant chemotherapy after breast cancer surgery and analyze the effects of that status on chemotherapy. Methods A total of 96 patients receiving adjuvant chemotherapy after breast cancer surgery and with Nutritional Risk Screening 2002 （NRS 2002） scores < 3 were selected. After six cycles of chemotherapy， patients were re-evaluated and divided into a group at nutritional risk（NRS 2002≥3） and a group at no nutritional risk（NRS 2002＜3）. The two groups were compared in terms of clinical data， nutritional status，adverse reactions and length of hospitalization. Results Among 96 patients who received 6 cycles of adjuvant chemotherapy after breast cancer surgery，39 had NRS 2002≥3 and the incidence of nutritional risk among these patients was 40.6%. The group at nutritional risk and the group at no risk were similar in terms of menstruation，expression of estrogen receptor/progestin receptor（ER/PR） and human epidermal growth factor receptor 2 （cerbB-2）， cell proliferation index （Ki-67），periodization and relative chemotherapy dose intensity （P>0.05）. The two groups were similar in the following indicators（P>0.05），both before and after chemotherapy：hemoglobin，blood albumin，total lymphocyte count，and triceps brachii muscle skin fold thickness. Body mass index changed significantly as a result of chemotherapy in the nutritional risk group （P<0.05），with the body mass index after therapy being similar between the risk group and no-risk group（P<0.05）. The two groups differed significantly in rates of neutropenia，hemoglobin decrease，thrombocytopenia， nausea and vomiting，oral mucositis，abnormal liver function，fatigue and other grade Ⅲ+Ⅳ adverse reactions（P<0.05）. Conclusion Early assessment of nutritional risk during adjuvant chemotherapy after breast cancer may reduce the occurrence of adverse reactions due to chemotherapy. Related Articles | Metrics

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Efficacy and safety of combined XELOX and Endostar therapy as first-line treatment for patients with advanced biliary tract carcinoma REN Tiejun，SHAN Fengxiao，HOU Jianfeng，XUE Qi 2015, 7 (1):  41-44.  doi: 10.3969/j.issn.1674-5671.2015.01.09 Abstract ( 282 )   PDF (444KB) ( 13032 )   Save Objective  To observe the efficacy and safety of the combination of Endostar therapy with capecitabine and oxaliplatin therapy as a first-line treatment for patients with advanced biliary tract carcinoma. Methods Records were retrospectively reviewed for 42 patients with stage Ⅳ primary biliary tract carcinoma confirmed by pathology and imaging，who were treated at our hospital from January 2008 to December 2013. Eighteen patients were treated with Endostar+XELOX，while 24 were treated with XELOX alone. The XELOX regimen involved capecitabine at 1.25 g/m2， po，d1-d14 and oxaliplatin at 85 mg/m2，ivgtt， d1. Endostar was given at a dose of 15 mg，ivgtt， d1-d14，on a 21-day cycle. After 2 cycles，efficacy， quality of life（QOL），safety，median  progression-free survival （mPFS） and median overall survival（mOS） were compared between the two treatment groups. Results In the XELOX group after 2 treatment cycles，no patient was in CR，6 were in PR，8 were in SD，and 10 were in PD；the response rate（RR） was 25.0%， disease control rate （DCR） was 58.3%，mPFS was 5.0 months and mOS was 9.5 months. QOL improved as a result of treatment，and 66.7% patients were in stable condition. In the Endostar+XELOX group after 2 cycles， no patient was in CR，5 were in PR，6 were in SD，and 7 were in PD；RR was 27.7%，DCR was 61.1%，mPFS was 7.5 months and mOS was 14.0 months. QOL improved as a result of therapy，and 77.8% of patients achieved a stable condition. mPFS and mOS were significantly longer for patients who received combination therapy（P<0.05）. The two therapies were associated with similar types and rates of adverse events，the most frequent of which were gastrointestinal reactions，hand-foot syndrome，myelosuppression，neurotoxicity，and stomatitis（mainly gradeⅠ-Ⅱ）. Conclusion Endostar+XELOX shows good efficacy as a first-line treatment for advanced biliary tract carcinoma，and it is well tolerated， justifying its further study and potentially wider implementation in the clinic. Related Articles | Metrics

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Expression and clinical significance of NF-κB and IκBα in gastric cancer tissue LI Yaping,LIU Zhensheng,HUANG Guannan,JIANG Xiangjun 2015, 7 (1):  45-48.  doi: 10.3969/j.issn.1674-5671.2015.01.10 Abstract ( 217 )   PDF (445KB) ( 497 )   Save Related Articles | Metrics

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Combination of Gemcitabine combined with platinum-based chemotherapy in the treatment of advanced cancer patiets ZHANG Dingqing 2015, 7 (1):  49-51.  doi: 10.3969/j.issn.1674-5671.2015.01.11 Abstract ( 222 )   PDF (351KB) ( 463 )   Save Related Articles | Metrics

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Research progress of signaling pathway in osteosarcoma WANG Xianyang，CHANG Junli，SHI Qi，WANG Yongjun，YANG Yanping 2015, 7 (1):  52-55.  doi: 10.3969/j.issn.1674-5671.2015.01.12 Abstract ( 276 )   PDF (412KB) ( 662 )   Save Related Articles | Metrics

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Safety research of oncolytic adenovirus LU Keqing,WANG Zhiping 2015, 7 (1):  56-59.  doi: 10.3969/j.issn.1674-5671.2015.01.13 Abstract ( 382 )   PDF (358KB) ( 613 )   Save Related Articles | Metrics

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Regulation of E2F3 on proliferation of tumor cells LIANG Ziji,LIU Lei,LIU Jianjun 2015, 7 (1):  60-63.  doi: 10.3969/j.issn.1674-5671.2015.01.14 Abstract ( 247 )   PDF (358KB) ( 406 )   Save Related Articles | Metrics

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Cognitive function，mood，and sleep quality in patients treated with intensity-modulated radiation therapy for nasopharyngeal cancer：a prospective study MO Yanlin,LI Ling 2015, 7 (1):  63-64.  doi: 10.3969/j.issn.1674-5671.2015.01.15 Abstract ( 191 )   PDF (288KB) ( 355 )   Save Related Articles | Metrics