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    25 April 2018, Volume 10 Issue 2 Previous Issue    Next Issue

    Application and challenges of precision medicine in disease prevention

    Zhou Zechen, Chen Dafang
    2018, 10 (2):  75-80.  doi: 10.3969/j.issn.1674-5671.2018.02.01
    Abstract ( 299 )   PDF (550KB) ( 493 )   Save
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    Tumor molecular pathology epidemiology
    Zhou Zihan, Yu Hongping
    2018, 10 (2):  85-89.  doi: 10.3969/j.issn.1674-5671.2018.02.03
    Abstract ( 315 )   PDF (449KB) ( 260 )   Save
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    Silencing of c-jun inhibits growth and angiogenesis of radioresistant human nasopharyngeal carcinoma tumors implanted in nude mice

    Lin Guoxiang, Li Ling, Qu Song, Yu Binbin, Liang Zhongguo, Sun Yongchu,Zhou Lei, Chen Kaihua, Lu Qiteng, Zhu Xiaodong
    2018, 10 (2):  90-94.  doi: 10.3969/j.issn.1674-5671.2018.02.04
    Abstract ( 234 )   PDF (586KB) ( 217 )   Save

    Objective To investigate the effect of c-jun silencing on the growth and angiogenesis of radioresistant human nasopharyngeal carcinoma CNE-2R cells implanted in nude mice. Methods Cells were infected with lentivirus expressing c-jun-targeting shRNA in CNE-2R cells  (c-jun-shRNA group) or with lentivirus expressing negative control shRNA (NC group);control cells were left uninfected. Levels of vascular endothelial growth factor (VEGF) in the three types of cells were measured using Western blotting. Positive clones were selected and transplanted in nude mice. Levels of CD34 and VEGF were analyzed using immunochemistry. Results VEGF protein levels were significantly lower in the c-jun-shRNA group than in the NC and control groups in vitro and in vivo. In the c-jun-shRNA group,tumor volume was(720.85±72.10) mm3,tumor weight was (0.42±0.04) g,and MVD was 11.69±3.30. The corresponding results in the NC group were(1,196.81±90.69)mm3,(0.80±0.08) g,and 32.56±7.33;the corresponding results in the control group were (1,203.76±100.42) mm3,(0.83±0.05) g,and 35.45±4.87. Tumor volume,tumor weight,MVD and grading differed significantly between the c- jun- shRNA group and the other groups(P<0.05). Conclusion Silencing the c- jun gene can inhibit the growth and angiogenesis of radioresistant nasopharyngeal carcinoma.

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    Detecting changes in TLR-4 and IL-6 during hepatitis B virus infection in a tree shrew model
    Fan Ni,Lu Yuxiu,Tang Yanping,Li Kezhi,He Pan,Cao Ji,Lu Yulei, Lin Youzhi, Yang Chun
    2018, 10 (2):  95-99.  doi: 10.3969/j.issn.1674-5671.2018.02.05
    Abstract ( 224 )   PDF (482KB) ( 340 )   Save

    Objective To detect changes in TLR-4 and IL-6 in tree shrews infected by hepatitis B virus. Methods A total of 25 tree shrews were inoculated with human hepatitis B virus (HBV) and then divided into an HBV-infected group,suspected HBV-infected group and control group based on detection of the HBV marker HBsAg or HBV DNA using a photochemical method or fluorescence- probe PCR. HBV-infected animals showed persistent positive results for HBsAg or HBV DNA,while the suspected HBV-infected group showed two or more positive results for HBsAg or HBV DNA. Levels of TLR-4 and IL-6 in peripheral blood and liver tissues were measured using,respectively,enzyme-linked immunosorbent assay (ELISA) and hematoxylin- eosin staining. Levels of TLR-4 and IL-6 mRNA in liver tissue of all three groups were measured using real-time fluorescence quantitative PCR. All assays were performed between post-natal weeks 8 and 24. Results Seven animals were assigned to the HBV-infected group,while five were assigned to the suspected HBV-infected group; all control animals showed negative results. Levels of TLR-4 in the peripheral blood of infected and suspected infected animals were significantly higher than in control animals (P<0.05)at weeks of 8,12,16,20,and 24. Levels were not significantly different between the infected and suspected infected groups. Similar results were observed for levels of IL-6 in peripheral blood. Levels of TLR-4 and IL-6 mRNA in liver tissue were significantly higher in the infected and suspected infected groups than in the control group(P<0.05). Conclusion Levels of TLR-4 and IL-6 are elevated in tree shrews following infection with HBV virus,and these signaling molecules may play an important role in the infection process.

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    Single nucleotide polymorphisms in DNA repair gene RAD52 miRNA target sequence and susceptibility to hepatocellular carcinoma
    Wang Jianwu, Yu Xiangyuan, Wang Qianqian, Qin Linyuan, Bei Chunhua,Tan Shengkui, He Songqing, Tang Bo, Liao Weijia, Yu Hongping
    2018, 10 (2):  99-104.  doi: 10.3969/j.issn.1674-5671.2018.02.06
    Abstract ( 355 )   PDF (476KB) ( 241 )   Save

    Objective To investigate the DNA repair gene RAD52 3'- untranslated region (3'- UTR) miRNA target sequence polymor- phisms and susceptibility to hepatocellular carcinoma(HCC) in Guangxi population. Methods A case- control study of 1,002 HCC cases and 1,013 cancer- free controls was performed.miRNA target sequence SNPs(rs1051669,rs1051672,rs7301931 and rs7310449) in the RAD52 gene 3'- UTR region were genotyped to analyze the relationship between the distribution frequency of SNP genotypes and genetic susceptibility to HCC. Results There was no significant difference in the distribution frequency of the SNP genotypes in the RAD52 between the case group and the controls(P>0.05).After adjusting for age,sex,smoking,alcohol consumption and HBV infection,no significant association was found between the SNP genotypes and HCC susceptibility. Further stratification analysis showed that,compared with the rs1051669 C allele carrying genotypes,TT genotype can significantly reduce the risk of individuals suffering from HCC(TT vs CT/CC:OR=0.03,95%CI:0.00- 0.62,P=0.03),and compared with rs1051672 G alleles carrying genotypes,the AA genotype can significantly reduced the risk of HCC(AA vs GA/GG:OR=0.03,95%CI:0.01- 0.88,P=0.04) in the female. Conclusions RAD52 gene 3'- UTR region miRNA target sequence SNPs rs1051669 and rs1051672 might be associated with HCC susceptibility in female of Guangxi area.

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    Expression of receptor-interacting protein kinase 3 in an animal model of neuropathic pain
    Hou Weinan,Zhou Yanqiong,Li Changlong,Zhu Min,Huang Donghai,Luo Lihong,Liang Rui
    2018, 10 (2):  105-109.  doi: 10.3969/j.issn.1674-5671.2018.02.07
    Abstract ( 226 )   PDF (555KB) ( 238 )   Save

    Objective To observe the expression of receptor- mediated protein kinase 3 (RIP3) in a rat model of spinal nerve ligation and explore whether it is involved in the pathogenesis of neuropathic pain. Methods Rats were randomly divided into four groups: operation,saline,inhibitor and sham operation(n=10 rats per group). In the operation,saline,and inhibitor groups,a lumbar 5 spinal nerve ligation model was established. Animals in the sham operation group underwent surgery without nerve ligation. In the inhibitor group,GSK'872 was injected intrathecally at 30 min before model establishment;in the saline group,the same volume of saline was intrathecally injected. Behavior and mechanical allodynia were recorded for each group. RIP3 expression was analyzed using immuno- histochemistry and Western blotting;TNF-α and IL-1β levels were determined using ELISA. Results The operation and saline groups showed significant behavioral differences,significantly lower mechanical allodynia,as well as significantly higher levels of RIP3 protein,TNF-α and IL-1β than the sham operation group(P<0.05). The inhibitor group showed lower mechanical pain sensitivity and protein content than the operation and saline groups (P<0.05). Expression of RIP3,TNF-α and IL-1β negatively correlated with mechanical allodynia. Conclusions RIP3 is up-regulated in this animal model of neuropathic pain,so RIP3 may be involved in the development of neuropathic pain.

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    Effect of changes in organs at risk on target volume during image-guided radiation therapy for cervical cancer
    Chen Wenjuan, Jiang Nan,Ni Xiaolei, Bai Penggang,Chen Kaiqiang
    2018, 10 (2):  109-113.  doi: 10.3969/j.issn.1674-5671.2018.02.08
    Abstract ( 283 )   PDF (515KB) ( 288 )   Save

    Objective To investigate the effect of changes in volume and position of the bladder and rectum on target volume in patients with advanced cervical cancer using intensity- modulated radiotherapy. Methods A total of 16 cases of intensity- modulated radiotherapy in patients with cervical cancer were analyzed,and CBCT imaging was performed at radiotherapy doses of 9 Gy/5f,18 Gy/10f,27 Gy/15f,36 Gy/20f and 48.6 Gy/27f. CBCT images were integrated with the original CT image,and the target volume and organs at risk (OARs) were outlined. Dose volume histograms (DVH) were used to analyze changes in volume,volume change rate and DICE similarity of rectum,bladder and other organs. Results Mean volume of bladder was 88.48-195.49 cm3;rectum,40.41-42.93 cm3;sigmoid,792.85-907.86 cm3;and intestine,38.49-49.05 cm3. Bladder volume varied significantly from 0f to 27 f (P<0.05),but the other organs did not differ significantly in volume change rate(delta V%,P>0.05) and in DICE similarity (DSC,P>0.05). Bladder volume rate and rectal volume showed a significant negative correlation with the DSC of the gross target volume (GTV- T) and the corpus (CTV- T) (P<0.05). Conclusions Volume and location of the bladder,rectum and other organs changed substantially during intensity- modulated radiation therapy of cervical cancer. Volume change rate of bladder and rectum negatively correlated with the DSC of GTV-T and CTV-T.

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    Expression and significance of CD133,CD68 and PD-L1 in human brain glioma
    Chen Hao,Mo Ligen,Deng Teng,Luan Fangkun,Yu Yanan,Yu Haiyue,Tian Min
    2018, 10 (2):  113-118.  doi: 10.3969/j.issn.1674-5671.2018.02.09
    Abstract ( 391 )   PDF (603KB) ( 338 )   Save

    Objective To investigate the expression of glioma stem cell(GSC) marker CD133,the tumor- associated macrophage (TAM) marker CD68 and the negative co- stimulatory molecule PD-L1 in different pathological grades of glioma tissue and their possible correlation. Methods Double immunofluorescence staining was used to detect co- expression of CD68 and PD-L1 protein in glioma tissues of different pathological grades. The expression of CD133,CD68 and PD-L1 genes in 30 cases of low- grade glioma tissue (grade Ⅰ and Ⅱ) and 30 cases of high- grade glioma tissue (grade Ⅲ and Ⅳ) were detected by quantitative real- time fluorescent PCR (qRT-PCR),and correlation with clinical pathological grade was analyzed. Results The majority of PD-L1-positive cells were TAMs,and as the pathological grade of gliomas increased,the co-expression of CD68 and PD-L1 increased. In glioma tissues,pathological grade positively correlated with levels of CD133 (r=0.647,P<0.001),CD68 (r=0.499,P<0.001),and PD-L1(r=0.445,P=0.001). The expression levels of CD133,CD68 and PD-L1 were significantly higher in high-grade glioma tissue than in low-grade gliomas (P<0.05). Expression of the CD133 gene positively correlated with that of the CD68 gene across all samples (r=0.525,P<0.001),in low-grade samples (r=0.518,P=0.005),and in high-grade samples(r=0.500,P=0.007). Expression of the CD133 gene also positively correlated with that of the PD-L1 gene across all samples (r=0.431,P<0.001),in low- grade samples (r=0.398,P=0.036),and in high-grade samples (r=0.417,P=0.027). Conclusion PD-L1 in glioma tissue is expressed mainly by TAMs in the tumor microenvironment. Expression of CD133,CD68 and PD-L1 relates closely to the tumor degree of malignancy.

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    Ratio of gamma-glutamyl transpeptidase to platelets for staging hepatic fibrosis in patients with hepatocellular carcinoma
    Ou'yang Gaoxiong, Zhang Zhiming,Wang Peng,Ren Yuan,Li Jiahao,Liu Yukai, Xiang Bangde, Liu Jianyong
    2018, 10 (2):  119-123.  doi: 10.3969/j.issn.1674-5671.2018.02.10
    Abstract ( 479 )   PDF (612KB) ( 339 )   Save

    Objective To assess the usefulness of the ratio of gamma-glutamyl transpeptidase to platelets (GPR)for staging hepatic fibrosis in patients with hepatocellular carcinoma(HCC). Methods Medical records were collected and analyzed for 194 patients who underwent curative liver resection from August 2015 to August 2016 at our hospital. GPR,the ratio index of aminotransferase to platelets (APRI) and the four-factor index (FIB4) were compared for their ability to stage hepatic fibrosis based on the area under the receiver operating characteristic curve. Results Liver fibrosis stage correlated positively with GPR,APRI,FIB4 and ALT,but negatively with PLT (all P<0.05). GPR,APRI,FRONS,FIB4,and PLT differed significantly in different stages of liver fibrosis (P<0.05). Among patients with liver fibrosis stage > S0,the indices GPR,APRI,FIB4 and PLT showed similar areas under the curve (P>0.05). In contrast,among patients with liver fibrosis stages > S1 and S3 ,GPR showed an area under the curve similar to that of APRI and PLT (P>0.05) but different from that of FIB4(P<0.05). The area under the GPR curve was significantly greater than the areas under the APRI and PLT curves(P<0.05). Conclusions GPR is simple to calculate from data obtained during routine clinical it can be more accurate for staging liver fibrosis than other indices. It may therefore be useful as a noninvasive index for preoperative staging of hepatic fibrosis in HCC patients.

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    Patterns of local or regional recurrence after intensity-modulated radiotherapy for nasopharyngeal carcinoma
    Li Bo, Kang Min, Lu Ying, Yu Bin, Liao Xueyin, Bin Ying, Zhou Pingting, Yang Zhendong, Liu Kang, Li Jixi, Wang Rensheng
    2018, 10 (2):  124-128.  doi: 10.3969/j.issn.1674-5671.2018.02.11
    Abstract ( 434 )   PDF (461KB) ( 465 )   Save

    Objective The aim of this study was to evaluate patterns of local or regional recurrence of nasopharyngeal carcinoma (NPC) in patients treated with intensity- modulated radiotherapy(IMRT). Methods We performed a retrospective analysis of 645 patients with NPC treated at three centers in China from January 2009 to December 2011. All patients had non-metastatic NPC that had not been treated prior to IMRT. The Kaplan-Meier method was used to calculate patient survival rates,and log-rank testing was used to compare survival differences,and explore treatment failure patterns for local or regional recurrence after radiotherapy. Results During a mean follow-up of 62 months(11-95),local recurrence rates were 0.9% at 1 year,6.5% at 3 years,and 9.0% at 5 years. Locoregional control rates were 99.1% at 1 year,93.4% at 3 years,and 90.1% at 5 years. In the 60 patients with recurrence,in-field recurrence rate was 93.3% (56/60);marginal-field recurrence,5.0% (3/60);and out-field recurrence,1.7% (1/60). Of all treatment failures,81.7%(49/60) occurred within the first three years after treatment. Conclusions IMRT resulted in excellent locoregional control in our NPC patients. Most cases of recurrence happened in the first three years after treatment. Locoregional failure most often involved in-field recurrence.

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    Relationship between clinicopathological features of primary human non-small cell lung cancer and their tumorigenicity in nude mice
    Xu Yi,Tang Shicong, Zhou xin,Xu Xiang,Huang Yaoyuan, Wang Shoufeng,Pan Hong
    2018, 10 (2):  128-132.  doi: 10.3969/j.issn.1674-5671.2018.02.12
    Abstract ( 327 )   PDF (585KB) ( 454 )   Save

    Objective To investigate the relationship between the tumorigenicity of non-small cell lung cancer (NSCLC) tissue in a nude mouse model of patient-derived xenografts(PDX) and clinicopathological features of the primary tumor in the original patients. Methods A total of 15 NSCLC tissues were implanted subcutaneously in nude mice in order to assess their tumorigenicity,which was compared with the clinicopathologic features of the primary tumor. Expression of p63,cytokeratin 5/6 (CK5/6),thyroid transcription factor-1(TTF-1) and Ki-67 was detected by immunohistochemical analysis of tumor tissue from the original patients. Results Of the 15 NSCLC tissues transplanted into nude mice,6(40%) were tumorigenic. Tumorigenicity of the PDX model was related to TNM stage and tumor differentiation in the corresponding patients(P<0.05). The rates of TTF-1 and Ki-67 expression in NSCLC tissue were significantly higher in the engrafted group than in the non-engrafted group (83% vs 22%,100% vs 22%,P<0.05),while the rate of p63 expression was significantly lower in the engrafted group (50% vs 100%,P=0.041). Conclusions Expression intensity of p63,TTF-1,and Ki-67 in human NSCLC tissue correlates with its tumorigenicity in nude mice. Poorer differentiation of the primary tumor and more advanced stage correlate with greater tumorigenicity. 

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    Clinical pathological analysis of 10 cases of ovarian sclerosingstromal tumor
    Li Haimei, Yu Jinxia, Yang Haijun
    2018, 10 (2):  132-136.  doi: 10.3969/j.issn.1674-5671.2018.02.13
    Abstract ( 423 )   PDF (723KB) ( 341 )   Save

    Objective To analyze the clinicopathological characteristics and differential diagnosis of ovarian sclerosing stromal tumor.Methods The clinicopathological characteristics of 10 cases of ovarian sclerosing  stromal tumor treated at our hospital were examined. Results Mean age of the patients was 48.7 years(17-78  years) and clinical symptoms were usually abdominal pain,shortened menstruation,postmenopausal bleeding and frequent micturition. Macroexamination revealed unilateral,glossy and coated tumors with a surface cap-sule. Optical microscopy of tumor tissue revealed a false lobular structure. All patients were positive for SMA,Vimentin,and α-inhibin. Conclusions Ovarian sclerosing stromal tumor is rare and clinical data about the disease are limited. Therefore diagnosis is difficult and usually relies on pathology and the efficacy of operation is good.

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    Correlations of RSK4 expression with Ki-67,cyclin D1,CXCR4 and E-cadherin levels in an in vivo tumor model of breast cancer
    Wang Fengfeng, Zhu Jia, Yang Huawei, Wei Wei, Jiang Yi, Ji Yinan, Liu Jianlun
    2018, 10 (2):  136-140.  doi: 10.3969/j.issn.1674-5671.2018.02.14
    Abstract ( 289 )   PDF (940KB) ( 332 )   Save

    Objective To investigate the relationship between RSK4 expression and Ki-67,cyclin D1,CXCR4 and E-cadherin levels in an in vivo tumor model of breast cancer in order to explore the mechanism of breast cancer development. Methods The experimental group of nude mice was subcutaneously injected with MCF-7 cells transfected with siRNA (RSK4-RNAi-LV),while the negative control group was subcutaneously injected with MCF-7 cells transfected with siRNA (NC-GFP-LV),and a blank control group was subcutaneously injected with MCF-7 cells alone. Expression of RSK4,Ki-67,cyclin D1,CXCR4 and E-cadherin in samples of transplanted tumors was observed by immunohistochemistry. Results Levels of RSK4 and E-cadherin protein were 3.2±0.5% and 28.2±0.7% in the experimental group,which was significantly lower than in the blank control group (36.7±3.4%,51.7±4.2%) and negative control group(61.1±5.1%,49.2±3.8%) (F=56.79 and 61.89,P<0.05). Similar,expression levels of Ki-67,cyclin D1,and CXCR4 in the experimental group were,respectively,67.8±5.8%,61.7±4.6%,and 56.3±3.9%,which were significantly higher than in the blank control group(34.5±1.4%,29.7±2.5%,30.7±3.1%) and the negative control group (29.8±1.9%,35.7±4.6%,28.5±3.7%) (F=45.24,52.16,and 61.24,P<0.05). RSK4 protein expression showed a significant negative correlation with Ki-67(r=-0.857,P<0.001),cyclin D1(r=-0.826,P<0.001) and CXCR4 (r=-0.867,P<0.001). RSK4 protein expression showed a significant positive correlation with E-cadherin(r=0.879,P<0.001). Conclusions RSK4 knockdown may affect the expression of tumor proliferation factor and invasion factor,promoting the proliferation and metastasis of breast cancer cells. RSK4 may regulate genes in a way that promotes breast cancer cell proliferation and invasion,including up-regu-lation of CXCR4,Ki-67,and CyclinD1,as well as down-regulation of E-cadherin.

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    Cancer incidence and mortality in Xintian county,Yongzhou city,Hunan province,2014
    Liu Junhong,Huang Feng, He Zhongyong, Ou'yang Le, Zhou Yuren, Xu Kekui
    2018, 10 (2):  141-145.  doi: 10.3969/j.issn.1674-5671.2018.02.15
    Abstract ( 294 )   PDF (349KB) ( 395 )   Save

    Objective To analyze cancer incidence and mortality in Xintian county,Yongzhou city,Hunan province in 2014.  Methods Based on the methods and criteria of data quality from the National Central Cancer Registry (NCCR),we checked and evaluated the data of Xintian county,yongzhou city cancer registrations in 2014. Data were stratified by gender,age and cancer site. The incidence,mortality,and 10 most common cancers were calculated. Data from the Chinese population census in 2000 and Segi's population were used to calculate age-standardized incidence/mortality rates. Results The population of cancer patients in Xintian County,Yongzhou City,Hunan Province was 430,700 in the middle of 2014. There were approximately 774 new cancer cases and 517 cancer deaths in 2014 in Xintian County. The crude incidence was 179.71/105 (male 219.13/105,female 134.91/105). Age-standardized incidence was 146.79/105 based on the Chinese standard population (ASR China) and 142.48/105 based on world standard population (ASR world),and the cumulative incidence rate (0~74 years old) was 16.47%. The 5 most common cancers were lung,liver,breast,gastric,and nasopharyngeal. Crude mortality was 120.04/105 (male 161.51/105,female 72.91/105),ASR China mortality was 95.05/105 and ASR world mortality was 94.68/105,with a cumulative mortality rate (0~74 years old) of 11.38%. The 5 most deadly cancers were lung,liver,gastric,breast,and colorectal anal. Conclusions The leading causes of malignant tumor morbidity and mortality among male residents in Xintian county are lung,liver,gastric,colorectal anal and nasopharyngeal cancer,so cancer prevention and treatment should focus on these cancers in the high-risk male population. Incidence and mortality of malignant tumors are lower in women than in men,yet intervention measures should also target women at high cancer risk.

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    Dosimetry comparison of non-coplanar and co-planar field intensity modulated radiotherapy for brain oligopotential metastases
    Lou Fengjun, Chen Liang, Ni Baihui, Ai Yuan, Xu Xiaoni
    2018, 10 (2):  146-148.  doi: 10.3969/j.issn.1674-5671.2018.02.16
    Abstract ( 253 )   PDF (369KB) ( 258 )   Save
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    Influence of different degree depression on perioperative immune function in patients with hepatocellular carcinoma
    Zhao Lingyun, Wei Jueling, You Xuemei, Zhao Xinhua, Tang Juan, Li Qiuqin, Xiang xiao, Zhong Jianhong, Li Lequn
    2018, 10 (2):  151-155.  doi: 10.3969/j.issn.1674-5671.2018.02.18
    Abstract ( 229 )   PDF (419KB) ( 335 )   Save
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    Progress of primary hepatocellular carcinoma combined with portal vein tumor thrombus
    Shang Liming, Qin Wei, Xu Jing
    2018, 10 (2):  162-166.  doi: 10.3969/j.issn.1674-5671.2018.02.21
    Abstract ( 253 )   PDF (376KB) ( 397 )   Save
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