Sorafenib, a pan-protein kinase inhibitor, inhibits the activity of various kinases (like vascular endothelial growth factor, platelet-derived growth factor, and rapidly accelerated fibrosarcoma) and clinically has been used to treat different human cancers. This study investigated its antitumor activity in ovarian cancer and the underlying molecular events. To achieve that, ovarian cancer SKOV-3 cells were treated with or without sorafenib (10 µM), transforming growth factor (TGF)-β1 (10 ng/mL), sorafenib (10 µM) + TGF-β1 (10 ng/mL), and TGF-β1 (10 ng/mL) + Ly2157299 (5 µM), followed by 8-Gy radiation. The cells were then subjected to cell viability, wound healing, Transwell, caspase-3 activity, and western blot assays. TGF-β1 treatment enhanced ovarian cancer cell epithelial-mesenchymal transition (EMT), whereas sorafenib and a selective TGF-β1 inhibitor Ly2157299 reversed tumor cell EMT, invasion, and expression of EMT markers (E-cadherin and vimentin). Sorafenib and Ly2157299 treatment also significantly reduced the tumor cell viability. Furthermore, both sorafenib and Ly2157299 significantly enhanced ovarian cancer cell radiosensitivity, as assessed by a caspase-3 activity assay. In conclusion, sorafenib inhibited ovarian cancer cell proliferation and mobility and induced tumor cell radiosensitivity. Molecularly, sorafenib could inhibit the TGF-β1-mediated EMT. Future studies will assess sorafenib anti-ovarian cancer activity plus TGF-β1 inhibitors in ovarian cancer in vivo.

目的 探讨三氧化二砷(As2O3)通过早幼粒细胞白血病(PML)基因对三阴性乳腺癌细胞增殖、侵袭迁移的影响.方法 采用慢病毒介导的短发夹核糖核酸干扰技术,观察PML对三阴性乳腺癌MDA-MB-231细胞增殖、克隆形成和侵袭迁移的影响,进一步观察As2O3联合沉默PML表达对MDA-MB-231细胞增殖、克隆形成和侵袭迁移的影响.结果 沉默PML的表达可以降低MDA-MB-231细胞的增殖活性,减少细胞的克隆数量,抑制细胞的侵袭转移能力.As2O3联合PML沉默可以显著抑制细胞增殖.As2O3联合PML沉默组的细胞克隆数最少,细胞迁移数最少.结论 沉默PML的表达可以降低三阴性乳腺癌细胞的增殖、侵袭迁移能力,As2O3可以增强PML对细胞增殖和侵袭迁移能力的抑制作用,可能作为乳腺癌新的治疗靶点,对三阴性乳腺癌具有潜在的治疗价值.

BACKGROUND:Circular RNAs (circRNAs) have been proven to function as pivotal regulators in cancer occurrence and progression. However, the function of circ_0006404 (circRNA Forkhead box O3 (circFOXO3)in prostate cancer (PCa) is poorly understood.METHODS:The enrichment of circ_0006404, FOXO3, microRNA-1299 (miR-1299) and cofilin 2 (CFL2) was measured by quantitative real-time polymerase chain reaction (qRT-PCR). The viability, metastasis and proliferation were determined by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, transwell and colony formation assays, respectively. Flow cytometry was used to assess cell cycle progression and apoptosis. Circ_0006404/miRNAs interactions were explored using Circular RNA Interactome database, while TargetScan software was used for seeking the targets of miR-1299. Dual-luciferase reporter assay, RNA-pull down and RNA immunoprecipitation (RIP) assays were conducted to verify the target interaction between miR-1299 and circ_0006404 or CFL2. CFL2 protein level was analyzed by Western blot assay. Animal experiments were performed to test the role of circ_0006404 in PCa tumor growth in vivo.RESULTS:Circ_0006404 level was notably elevated in PCa. Circ_0006404 contributed to the viability, metastasis and proliferation and impaired the apoptosis of PCa cells. Circ_0006404 directly targeted miR-1299, and miR-1299 silencing largely reversed circ_0006404 interference-induced influences in PCa cells. CFL2 directly bound to miR-1299, and miR-1299-induced effects in PCa cells were largely attenuated by CFL2 overexpression. CFL2 was regulated by circ_0006404/miR-1299 axis in PCa cells. Circ_0006404 promoted PCa progression via miR-1299/CFL2 axis in vivo.CONCLUSION:Circ_0006404 accelerated the survival, motility and proliferation while impeded the apoptosis of PCa cells via miR-1299/CFL2 axis. Circ_0006404 might be a stable potential bio-marker for PCa diagnosis and treatment.

Enhancer of zeste homolog 2 (EZH2), an oncogene, is a commonly up-regulated epigenetic factor in human cancer. Hepatocellular carcinoma deletion gene 1 (DLC1) is an antioncogene that is either expressed at low levels or not expressed in many malignant tumours. Curcumin is a promising anticancer drug that has antitumour effects in many tumours, but its mechanism of action is unclear. Our research demonstrated that EZH2 was up-regulated in breast cancer (BC) tissues and cells, whereas DLC1 was down-regulated, and the expression of EZH2 and DLC1 was negatively correlated in BC. By analysing the characteristics of clinical cases, we found that positive expression of EZH2 and negative expression of DLC1 may be predictors of poor prognosis in patients with triple-negative breast cancer (TNBC). Moreover, knockdown of EZH2 expression restored the expression of DLC1 and inhibited the migration, invasion and proliferation, promoted the apoptosis, and blocked the cell cycle of MDA-MB-231 cells. Furthermore, we found that curcumin restored the expression of DLC1 by inhibiting EZH2; it also inhibited the migration, invasion and proliferation of MDA-MB-231 cells, promoted their apoptosis and blocked the cell cycle. Finally, xenograft tumour models were used to demonstrate that curcumin restored DLC1 expression by inhibiting EZH2 and also inhibited the growth and promoted the apoptosis of TNBC cells. In conclusion, our results suggest that curcumin can inhibit the migration, invasion and proliferation, promote the apoptosis, block the cycle of TNBC cells and restore the expression of DLC1 by inhibiting the expression of EZH2.

目的 分析鼠肉瘤病毒致癌基因(KRAS)在非小细胞肺癌(NSCLC)患者中的突变状况及其与NSCLC患者的临床病理特征和预后关系,为NSCLC临床治疗提供数据支撑.方法 收集郑州大学附属肿瘤医院2015年1月至2016年12月收治的经组织病理学确诊并行二代测序技术检测(NGS)的551例NSCLC患者的临床资料,随访至2018年12月31日,排除其中随访丢失的患者数据,共计356例患者入组此研究,讨论KRAS基因突变状态及其与临床病理特征、预后的关系.结果 356例NSCLC患者中,42例患者KRAS基因突变,包括2号外显子突变的患者36例和3号外显子突变的患者6例[其中2例为合并表皮生长因子受体(EGFR)基因突变的患者],与KRAS基因野生型比较,KRAS基因突变多见于≥60岁、男性、吸烟的NSCLC患者(x2=13.199,P＜0.001;x2=12.926,P ＜0.001;x2=22.423 ,P ＜0.001),而TNM分期、病理类型则对KRAS基因突变无明显影响(x2=0.521,P=0.914;x2=1.777,P=0.183).KRAS基因突变NSCLC患者的中位疾病无进展生存时间和中位总生存时间分别为5.5个月和10.7个月,均显著低于KRAS基因野生型NSCLC患者的10.2个月和18.6个月,差异均有统计学意义(P=0.001;P=0.001).亚组分析显示:删除2例含EGFR、KRAS基因双突变的患者,KRAS基因2号外显子突变NSCLC患者与3号外显子突变NSCLC患者的中位疾病无进展生存时间比较差异无统计学意义(P=0.795).对于KRAS基因突变患者,化疗治疗组中位总生存时间为10.4个月,长于未治疗组的2.2个月,差异有统计学意义(P＜0.001).结论 NSCLC患者KRAS基因突变状态可能与患者年龄、性别、吸烟史有关,KRAS基因突变预示着NSCLC患者更差的预后,而化疗能延长其生存时间.

目的:探讨联合检测外周血B7-H2与白细胞介素22(IL-22)水平变化在直肠癌诊断及预后评估中的价值.方法:回顾性选取2016年6月—2018年6月收治的老年直肠癌患者99例为实验组,另选取同期健康体检中心的老年健康者50例为对照组.利用ELISA试剂盒检测血清中B7-H2与IL-22水平的变化,利用Pearson相关性分析血清中B7-H2与IL-22水平与直肠癌预后的相关性,并利用生存曲线分析直肠癌根治术后的预后情况.结果:99例老年直肠癌患者均获得随访,随访率为100％,不同TNM分期、淋巴转移和远处转移患者血清B7-H2和IL-22的高水平与低水平表达差异有统计学意义(P<0.05).实验组外周血淋巴细胞表面B7-H2的表达要明显低于对照组(P<0.05),IL-22的表达要明显高于对照组(P<0.05).生存曲线显示,血清中B7-H2的表达与直肠癌的预后呈正相关,IL-22的表达与直肠癌的预后呈负相关(r=0.174、-0.296,P<0.05).结论:B7-H2和IL-22的表达水平与直肠癌的发生和进展具有相关性,可以作为直肠癌筛查检测预后的分子标志物.

Objective To explore the effect and mechanism of metformin(Metf) on side population(SP) cells of human esophageal squamous cell carcinoma. Methods We detected SP ratio of different esophageal squamous cell lines and sorted of SP cells by flow cytometry. The effects of metformin on the proliferation of SP cells in vitro were detected by CCK-8 method, plate cloning and sphere assay. The effect of Metf on the expression of SP cell-associated gene protein was detected by Western blot. Results The SP ratio of the nine esophageal squamous carcinoma cell lines in this experiment was 0.2%-2%. Metf could reduce the SP ratio of KYSE 150, significantly inhibiting the cell proliferation, the number of clones and the number of spheres of SP cells. The degree of inhibition was positively correlated with Metf concentration and administration time. The difference is statistically significant (P < 0.01). In addition, Metf reduced the expression of the relevant stem genes SOX2 and OCT4 in SP cells to varying degrees. Conclusion Metf could reduce the ratio of SP cells in esophageal squamous cell carcinoma, which may provide a new approach for the treatment and prevention of esophageal cancer.

目的 通过分析癌症基因组数据库(TCGA)中基因芯片数据,挖掘人热休克蛋白B6(HSPB6)在正常膀胱组织及膀胱癌组织中的表达及其预后意义.方法 通过Oncomine及人蛋白质数据库分析HSPB6在正常膀胱组织与膀胱癌组织中的差异表达;通过基因表达谱数据动态分析HSPB6表达水平与患者预后的关联;通过String数据库分析与HSPB6相关的基因及蛋白并预测其功能.结果 膀胱癌组织中HSPB6的表达较正常膀胱组织低,差异有统计学(P＜0.05);生存分析中HSPB6与患者疾病无进展生存时间、总生存时间具有明显相关性(P＜0.05).结论 尽管HSPB6在膀胱癌组织中普遍较癌旁正常组织低表达,但其在癌组织中的高表达反而是患者不良预后因素.

NRON mediates the degradation of tat protein to participate in HIV-1 infection. Interestingly, our study observed the down-regulation of NRON in triple-negative breast cancer (TNBC) tissues compared with paired adjacent healthy tissues. In contrast, lncRNA snaR was up-regulated in TNBC tissues and was inversely correlated with NRON. Expression levels of snaR increased, while expression levels of NRON decreased along with the increase of clinical stages. The snaR overexpression resulted in promoted cancer cell proliferation but did not significantly affect NRON expression. NRON overexpression inhibited cancer cell proliferation and down-regulated snaR. The snaR overexpression reduced the effects of NRON overexpression. We therefore conclude that NRON may down-regulate lncRNA snaR to inhibit cancer cell proliferation in TNBC.

多学科综合治疗(MDT)可通过多学科之间的紧密协作为患者提供最优治疗,已逐渐成为国际上公认的肿瘤治疗模式.肿瘤学研究生的培养也需要跟上治疗模式的进步,将MDT与消化道恶性肿瘤的临床教学相结合,可提高学生的主观能动性及临床能力,虽然有一定的局限性,仍是一种值得推广的教学方式.

Emerging evidence suggests that circular RNAs (circRNAs) are linked to the development and progression of human cancers. Nevertheless, their contribution to breast cancer (BC) is still largely unknown. In the current study, we screened and identified a novel circRNA, circ-UBE2D2, which was highly expressed in BC cell lines and tissues and was closely related to aggressive clinical features and dismal prognosis. Small interfering RNA (siRNA)–mediated circ-UBE2D2 silencing notably inhibited the proliferation, migration and invasion of BC cells, whereas circ-UBE2D2 overexpression displayed opposite effects. Mechanistically, circ-UBE2D2 was able to simultaneously function as molecular sponges of miR-1236 and miR-1287 to regulate the expression of their respective target genes. Moreover, circ-UBE2D2–induced tumor-promoting effects could be effectively blocked by miR-1236 or miR-1287 in BC cells. More importantly, therapeutic delivery of cholesterol-conjugated si-circ-UBE2D2 oligonucleotides significantly delayed tumor growth in vivo. Overall, our findings indicate that circ-UBE2D2 plays an essential oncogenic role in BC, and targeting circ-UBE2D2 may be a feasible treatment for BC patients.

目的探讨Ⅳ期贲门癌组织中KRAS突变和血清糖类抗原19-9（CA19-9）水平的相关性。方法收集64例确诊的新发Ⅳ期贲门癌患者,采用限制性片段长度多态性聚合酶链反应检测癌组织中KRAS突变,采用酶联免疫吸附试验检测血清中CA19-9水平,并分析两者的相关性。结果 64例Ⅳ期贲门癌组织中KRAS突变阳性者27例（42.19%）,血清CA19-9阳性者25例（39.06%）。27例KRAS突变阳性者中23例CA19-9阳性,两者均阳性者占35.94%;37例KRAS突变阴性者中35例CA19-9阴性,两者均阴性者占54.69%。64例贲门癌中KRAS和CA19-9表达呈正相关（r s =0.808,P＜0.05）。结论Ⅳ期贲门癌组织中KRAS突变和血清CA19-9的升高呈正相关,提示患者临床预后不良,其中CA19-9检测相对方便、经济。

目的 研究四次跨膜L6家族成员1(TM4SF1)在三阴性乳腺癌干细胞中的作用及靶向抑制TM4SF1通路对三阴性乳腺癌干细胞自我更新的影响.方法 构建TM4SF1-RNA干扰质粒,转染三阴性乳腺癌MDA-MB-231细胞系,经流式细胞仪进行分选,观察乳腺癌干细胞比例,进而进行细胞生长曲线、乳腺癌干细胞的克隆形成以及裸鼠成瘤能力实验等功能检测.结果 特异性转染TM4SF1-RNA干扰质粒后,TM4SF1表达显著被抑制,乳腺癌干细胞比例降低,但细胞增殖速度无明显差异;形成的克隆数目明显降低.接种5周后三阴性乳腺癌MDA-MB-231细胞系组瘤体体积明显大于三阴性乳腺癌MDA-MB-231细胞系DsiRNA-1组.结论 通过靶向TM4SF1通路能够抑制三阴性乳腺癌干细胞自我更新,该通路有可能作为乳腺癌干细胞新的治疗靶点,对三阴性乳腺癌具有潜在的治疗价值.

目的 晚期乳腺癌患者一般体质较弱,既往治疗失败后,对化疗耐受性差、效果不明显,因此寻找疗效好、不良反应轻的新药尤为重要.本研究对阿帕替尼治疗晚期乳腺癌疗效及安全性进行分析.方法 回顾性分析2016-09-06-2018-03-10郑州大学第一附属医院收治的47例既往化疗失败或复发转移后使用阿帕替尼的晚期乳腺癌患者临床资料,分析阿帕替尼单药(17例)和联合化疗(30例)患者的无进展生存期(progression free survival,PFS)、客观有效率和疾病控制率.结果 Kaplan-Meier法分析结果显示,47例晚期乳腺癌患者的中位PFS为113 d(95.54～130.46).17例阿帕替尼单药组患者中位PFS为90 d,30例阿帕替尼联合化疗组患者中位PFS为113 d,差异无统计学意义,P=0.672.治疗后部分缓解(partial response,PR)6例,疾病稳定(stable disease,SD)31例,疾病进展(progressive disease,PD)10例,客观有效率(objective response rate,ORR)为12.77％,疾病控制率(disease control rate,DCR)为78.72％,两组ORR(P=1.000)和DCR(P=0.512)差异均无统计学意义.多因素Cox回归结果显示,雌激素受体(estrogen receptor,ER)阳性表达(HR=0.429,95 ％％CI:0.204～0.905,P=0.026)、治疗期间出现高血压(HR=0.452,95％CI:0.232～0.881,P=0.020)是影响阿帕替尼治疗晚期乳腺癌PFS的预后保护性因素;既往化疗次数≥4次(HR=2.197,95％CI:1.163～4.418,P=0.015)是其预后危险性因素.不良反应大多数为轻中度(1～2级),经处理可以好转或耐受.结论 阿帕替尼治疗晚期乳腺癌有一定疗效,不良反应可控,耐受性好,但尚需扩大样本进一步验证.

目的 探讨阿帕替尼单药治疗晚期三阴性乳腺癌的疗效和不良反应.方法 回顾性分析郑州大学第一附属医院收治的22例既往化疗失败或复发转移后接受阿帕替尼单药治疗的晚期三阴性乳腺癌患者的临床资料,观察并记录阿帕替尼治疗晚期三阴性乳腺癌的有效率、疾病控制率、疾病无进展生存时间,寻找影响患者预后的因素.结果 22例可评价疗效患者的中位疾病无进展生存时间为107(58.82 ～123.18)d.治疗后部分缓解3例,疾病稳定12例,疾病进展7例,有效率为13.64％,疾病控制率为68.18％.多因素COX回归分析结果显示:暂未发现ECOG评分(P=0.376)、治疗期间出现的高血压(P =0.338)、手足综合征(P=0.201)是影响晚期三阴性乳腺癌患者疾病无进展生存时间的独立预后因素.阿帕替尼的不良反应大多数为轻中度(1、2级),经处理可以好转或耐受.结论 阿帕替尼单药用于晚期三阴性乳腺癌的治疗有一定疗效,不良反应可控,耐受性好,值得进一步研究.

Previous studies have demonstrated that Licochalcone A possesses anti-inflammatory, anticancer, anti-bacterial, anti-malarial and anti-parasitic activities. In the present study the potential anticancer effects of Licochalcone A on MCF-7 cells were investigated. Licochalcone A significantly decreased cell viability and promoted autophagy and apoptosis, as demonstrated by an MTT assay, acridine orange staining and Annexin V-fluorescein isothiocyanate staining, respectively. Western blot analyses demonstrated that Licochalcone A treatment activated the LC3-II signaling pathway while suppressing the phosphoinositide 3-kinase (PI3K)/RAC-α serine-threonine-protein kinase (Akt)/mammalian target of rapamycin (mTOR) signaling pathway. In addition, Licochalcone A significantly increased caspase-3 activity and significantly decreased B-cell lymphoma-2 expression. The results from the present study indicate that Licochalcone A inhibits PI3K/Akt/mTOR activation, and promotes autophagy and apoptosis in MCF-7 cells.

Objective To compare the clinical effect and safety of icotinib double dose targeted therapy and pemetrexed plus cisplatin in treatment of advanced lung adenocarcinoma after targeted thera -py.Methods Forty-four patients with epidermal growth factor rectpeor ( EGFR) gene mutations ad-vanced lung adenocarcinoma after icotinib 125 mg/times, 3 times/day were randomly divided into group A ( icotinib group ) and group B ( pemetrexed group ) , and 22 cases in each group .The clinical efficacy and safety of the two groups were compared .Results The effective rate of group A was 9.1％, the dis-ease control rate was 63.6％; the effective rate of group B was 27.3％, the disease control rate was 77.3％, there were no significant differences between the two groups ( P>0.05 ) .The main toxic and side effects in group A were rash , and that in the group B was the digestive tract reaction and bone mar-row suppression , which can be tolerated .There was no significant difference in the main toxic and side effects between the two groups ( P>0.05 ) .Conclusions There is no significant difference in efficacy between ecotinib double dose group and pemetrexed group , but ecotinib double dose group has little toxic and side effects .