c-Met是酪氨酸激酶受体的一种,由MET基因编码产生.肝细胞生长因子(HGF)作为c-Met唯一的天然配体,与其结合后激活相关下游通路如PI3K、MAPK和STAT 3等,参与肿瘤的增殖、迁移、侵袭等方面.c-Met主要激活形式包括有配体依赖的自分泌或旁分泌机制和非配体依赖机制等,许多恶性肿瘤包括肺癌在内均存在c-Met的多种异常活化机制.国内外研究发现c-Met的异常激活同样参与肺癌的发生、发展及预后,c-Met信号通路在肺癌进展和侵袭中的作用已得到广泛研究,c-Met相关抑制剂在肺癌的临床前和临床试验中也显示出抗肿瘤活性.因此本文就c-Met的结构、功能和其异常活化机制与肺癌发生、发展的关系及针对该通路的相关靶向药物在肺癌治疗中的研究进展进行简单的综述.

卵巢癌是妇科恶性肿瘤中常见的类型之一,由于其早期无明显症状,患者就诊时已为晚期.目前晚期卵巢癌的标准治疗主要是以铂类为基础的化疗,但大多数患者会出现复发或耐药后进展等.因此,临床迫切需要新的治疗方法以改善晚期卵巢癌患者的预后.近年来,随着对肿瘤免疫学及分子生物学的不断深入研究,免疫治疗作为一种新兴的治疗肿瘤的方式,为晚期卵巢癌患者提供了新的治疗方向.本文将对晚期卵巢癌免疫治疗的临床研究现状进行综述.

三阴性乳腺癌作为乳腺恶性肿瘤中最具侵袭性的类型,化学治疗是其主要而有效的治疗手段,但多药耐药性的产生仍是影响疗效的主要障碍.miRNAs是一种内生型的、非编码小RNAs,它作为一种潜在的致瘤因子或抑制因子,能靶向调节其目的基因从而参与肿瘤的耐药.因此,在开拓新的三阴性乳腺癌基因治疗的策略中,miRNAs具有潜在的治疗价值.本文总结了miRNAs在三阴性乳腺癌多药耐药中的作用机制及其在治疗中的应用前景.

With the development of targeted drugs and next-generation sequencing (NGS) technology, the treatment paradigm of non–small-cell lung cancer (NSCLC) has evolved into oncogene-targeted precision medicine.1 Another revolutionary advance in treating NSCLC is biomarker profiling using liquid biopsy.2 High throughput NGS-based liquid biopsy testing overcomes spatial heterogeneity beyond a single tissue biopsy, provides us with more comprehensive genomic information, and has become a promising alternative for dynamically monitoring tumor genomic evolution and guiding decision-making for treatment strategy in a minimally invasive manner.

环状RNA(circular RNAs,circRNAs)是长链非编码RNAs,与线性RNAs不同,它是共价闭合环路,没有5'、3'极性和腺苷的尾巴.它们具有种类丰富、进化保守、在细胞质中相对稳定的特性.circRNAs的这些特性带来许多潜在的功能,如作为微小RNA(microRNA,miR-NA)的海绵,结合RNA相关蛋白质形成RNA-蛋白质复合物,然后调节基因的转录.重要的是,circRNAs突变或异常表达与各种肿瘤的发生、发展密切相关,可以作为肿瘤的分子标志物或潜在治疗靶点,为肿瘤的早期诊断、疗效评价、预后预测和肿瘤基因治疗提供一个新的靶点.

Purpose Multidrug resistance (MDR) remains a major obstacle in the treatment of triple-negative breast cancer (TNBC) with conventional chemotherapeutic agents. A previous study demonstrated that hsa-miRNA-143-3p plays a vital role in drug resistance of TNBC. Downregulation of hsa-miRNA-143-3p upregulated the expression of its target protein cytokine-induced apoptosis inhibitor 1 (CIAPIN1) in order to activate MDR, while upregulation of hsa-miRNA-143-3p effectively enhances the sensitivity of drug-resistant TNBC cells to chemotherapeutics. The present study aimed to further verify these findings in vivo. Methods We established a hypodermic tumor nude mice model using paclitaxel-resistant TNBC cells. We expressed ectopic hsa-miRNA-143-3p under the control of a breast cancer-specific human mammaglobin promoter that guided the efficient expression of exogenous hsa-miRNA-143-3p only in breast cancer cells. Thereafter, we overexpressed hsa-miRNA-143-3p in xenografts using a recombinant virus system and quantified the expression of hsa-miRNA-143-3p, CIAPIN1 protein, and proteins encoded by related functional genes by western blot. Results We successfully completed the prospective exploration of the intravenous virus injection pattern from extensive expression to targeted expression. The overexpression of hsa-miRNA-143-3p significantly alleviated chemoresistance of TNBC by inhibiting viability. In addition, we observed that the expression of CIAPIN1 as a hsa-miRNA-143-3p target protein was remarkably decreased. Conclusion We partly illustrated the mechanism underlying the hsa-miRNA-143-3p/CIAPIN1 drug resistance pathway. HsamiRNA-143-3p as a tumor suppressive microRNA may be a novel target to effectively reverse MDR of TNBC in vivo.

Background: Thymic carcinoma is prone to early metastasis and invasion, while its metastasis to the breast is particularly unique. Case Report: We describe a case of thymic epithelial tumor metastatic to the breast fulfilling clinical diagnostic criteria. A 47-year-old female patient diagnosed with stage IV thymic carcinoma and previously treated with chemoradiation was diagnosed with metastatic breast cancer during a periodic review. Color Doppler ultrasonography showed a low-echo real occupancy in the breast. Pathological examination of the breast mass confirmed the diagnosis of thymic carcinoma metastasis. Conclusion: Hematogenous metastasis of thymic carcinoma to the breast is rare but not exceptional, and long-term survival can be expected with appropriate treatment.

Cytokine-induced apoptosis inhibitor 1 (CIAPIN1), originally termed anamorsin, is an anti-apoptotic molecule that acts as a downstream effector of the receptor tyrosine kinase-Ras signaling pathway. Overexpression of CIAPIN1 contributes to multidrug resistance (MDR) and microRNA (miR)-143 is typically considered a tumor suppressor in breast cancer. The present study aimed to evaluate the therapeutic potential of miR-143 as a treatment for drug-resistant breast cancer via the downregulation of CIAPIN1 in vitro. The expression levels of miR-143 were measured using quantitative polymerase chain reaction and the expression levels of CIAPIN1 were detected via western blot analysis. Bioinformatic analyses was additionally conducted to search for miR-143, which may potentially target CIAPIN1. Luciferase reporter plasmids were created and used to verify direct targeting. In addition, Taxol-induced drug-resistant (TDR) breast cancer cell proliferation was evaluated using the Cell Counting Kit-8 assay in vitro. The present study identified an inverse association between miR-143 and CIAPIN1 protein expression levels in breast cancer MCF-7, MDA-MB-231 and MDA-MB-453 TDR cells. Specific targeting sites for miR-143 in the 3'-untranslated region of the CIAPIN1 gene were identified, which exhibit the ability to regulate CIAPIN1 expression. It was revealed that the repression of CIAPIN1 via miR-143 suppressed the proliferation of breast cancer TDR cells. The findings of the present study verified the role of miR-143 as a tumor suppressor in breast cancer MDR via inhibition of CIAPIN1 translation.

Objective To predict and select the targeting miRNA highly matched the 3'untranslated region (3'UTR) of cytokine induced apoptosis inhibitor1 (CIAPIN1) gene, and to primarily investigate the targeting correlation between CIAPIN1 and the target miRNA in parental cell lines and drug-resistant cell lines of breast cancer. Methods The miRNA potentially binding to seed side of CIAPIN1 3'-UTR was predicted by the bioinformatics software as well as screening out the target miRNA according to the literatures TargetScan, PicTarmi and miRanda. The expression of CIAPIN1 protein in parental cell lines and resistant cell lines of breast cancer was detected by using Western blot. The expression of the target miRNA in parental cell lines and resistant cell lines of breast cancer was detected by real-time quantitative PCR (qRT-PCR). Results The miRNAs binding to seed side of targeting CIAPIN1 3'-UTR were predicted including miRNA143, miRNA571, miRNA647. Compared with parental cell lines, the CIAPIN1 protein in resistant cell lines of breast cancer was high expression detected by Western blot with significant difference (MCF-7/Tax vs. MCF-7: 0.80 vs. 0.21; MDA-MB-231/Tax vs. MDA-MB-231: 0.70 vs. 0.31; MDA-MB-453/Tax vs. MDA-MB-453: 1.00 vs. 0.35, all P<0.035). Compared with parental cell lines, miRNA143, miRNA571 and miRNA647 in resistant cell lines was low expression detected by qRT-PCR, and there were statistical differences. Conclusions The miRNAs binding to seed side of CIAPIN1 3'-UTR are predicted and selected including miRNA143, miRNA571, miRNA647. Compared with in parental cell lines, these miRNAs are low expression, and the CIAPIN1 protein is high expression in resistant cell lines of breast cancer, which suggests these miRNAs may be involved in multidrug resistance in breast cancer by regulating CIAPIN1 gene.

Objective:To explore the inhibitory effect and mechanism of scutellarin on human breast cancer cell line MCF - 7. Methods:Human breast cancer cells line MCF - 7 was treated with different concentrations of scutella-rin. The proliferation on human breast cancer cells line MCF - 7 was determined by MTT colorimetric experimental. The appropriate drug concentration and incubation time were chosen to deal with human breast cancer cells line MCF- 7,and then,the RNA was extracted. The microarray gene expression and analysis technology were used to screen the differentially expression of miRNAs and the real - time fluorescence quantitative PCR technology was used to vali-date the differences expression of miRNAs. Results:In the certain concentration range,scutellarin can inhibit the pro-liferation of human breast cancer cells line MCF - 7. Scutellarin can significantly increase the expression of the miR -15a and miR - 16. Conclusion:Scutellarin can inhibit the proliferation of human breast cancer cells line MCF - 7, and the up regulate the miRNA - 15a and miRNA - 16.

Our study aimed to investigate the correlation between single nucleotide polymorphisms of ERCC1/XRCC1/XPA genes and postoperative chemotherapy efficacy and prognosis of endometrial carcinoma. Our study included 108 patients with endometrial carcinoma and 100 healthy participants. ERCC1 rs11615/XRCC1 rs25487/XPA rs1800975 gene polymorphisms were detected by polymerase chain reaction-restriction fragment length polymorphism. Then the chemotherapy efficacy and toxic effects of the patients were assessed. The genotype and allele frequency of ERCC1 rs11615/XRCC1 rs25487 in the case group were significantly different from that in the control group (all P<0.05). The patients with AA + GA in ERCC1 rs11615 had an increased risk of endometrial carcinoma than those with GG, and the risk of endometrial carcinoma for patients with AA + GA was also higher in comparison with patients with GG genotype in XRCC1 rs25487 (all P<0.05). GG on both ERCC1 rs11615/XRCC1 rs25487 had a higher effective rate of chemotherapy than GA + AA (all P<0.05). ERCC1 rs11615/XRCC1 rs25487 gene polymorphisms were linked with toxic effects in liver, kidney, and nervous system. ERCC1 rs11615/XRCC1 rs25487, muscular invasion, and tumor stage were independent risk factors for the prognosis of endometrial carcinoma (all P<0.05). However, no significant associations were observed between XPA rs1800975 polymorphism and chemotherapy efficacy and prognosis of endometrial carcinoma (all P>0.05). These results indicated that ERCC1 and XRCC1 but not XPA polymorphisms correlate with response to chemotherapy in endometrial carcinoma.

[目的]探讨TRAIL与舒尼替尼(sunitinib)体外不同用药方式下对表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKI)抵抗的NSCLC A549细胞的抗肿瘤活性及其机制.[方法]实验分为对照组、TRAIL组、舒尼替尼组、TRAIL联合舒尼替尼组(T+S)、TRAIL序贯舒尼替尼组(T→S)和舒尼替尼序贯TRAIL组(S→T).CCK8法检测TRAIL和舒尼替尼对A549细胞的生长抑制作用;流式细胞术检测TRAIL和舒尼替尼作用后细胞周期变化及诱导的细胞凋亡;Western blot检测TRAIL和舒尼替尼作用后Akt、p-Akt蛋白表达的变化.[结果]T+S组及T→S组的抗增殖作用及诱导细胞凋亡的能力明显优于TRAIL组、舒尼替尼组及S→T组(P均＜0.05).细胞周期显示,TRAIL和舒尼替尼均能使细胞周期阻滞于G0/G1期,T+S组、T→S组对G0/G1期的阻滞作用明显增强.Western blot结果显示,TRAIL单独作用于A549细胞能明显上调p-Akt的表达,而舒尼替尼能下调p-Akt的表达;T+S组、T→S组、S→T组p-Akt的表达明显减少.[结论]舒尼替尼通过抑制TRAIL诱导的PI3K/Akt通路活化,增加TRAIL诱导的A549细胞凋亡.此外,两药物对A549细胞周期的特异性阻滞作用,也是诱导凋亡增加的原因之一.

Multi-drug resistance of breast cancer remains a major obstacle for effective treatment,which involves many complicated mechanisms,including drug transport in the body,metabolism and drug targets.Recent researches find that the tradition Chinese medicine not only has good effects in improving the body resistance and general situation of patients and enhancing the effects of chemoradiotherapy,but also plays a vital roles in the muti-drug resistance reversal of breast cancer.

Multi-drug resistance (MDR) of breast cancer is a key factor of breast cancer treatment failure.MicroRNA (miRNA) is a class of endogenous expressed,small,single-stranded RNA molecules,and regulate the expression of genes at post-transcriptional level by combining with target message RNA.MiRNA participate in the mechanisms of drug resistance of breast cancer,and are feasible therapeutic targets for the treatment of drug resistance in breast cancer.Finding and studying miRNA related with drug resistance of breast cancer as well as their mechanisms have become a current research hotspot.

多药耐药性是乳腺癌化疗失败的一个重要原因.其中,MDR1基因产物P-糖蛋白(P-gp)的增多是引起多药耐药性的一个重要因素.P-gp可以利用ATP提供的能量将肿瘤细胞内的化疗药物泵出胞外,使胞内药物浓度不断下降,从而使药物的抗癌作用减弱甚至消失,肿瘤细胞出现耐药.据研究,许多机制参与调控乳腺癌MDR1基因及其产物P-gp的表达.

Objective To investigate the effect of doxorubicin and TRAIL on proliferation and the expression of TRAIL receptors in human hepatocellular carcinoma cells HepG2 and SMMC-7721.Methods Growth inhibition rate was examined respectively by MTT assay under treatment with TRAIL or doxorubicin or in combination.The change of TRAIL receptors(DR4/DR5) in mRNA and protein levels was quantified by RT-PCR and Western blotting analysis respectively.Results The growth inhibiting rates of HepG2 and SMMC-7721 cells treated by 0.86,8.6 and 86μmol/L doxorubicin after 24h were(8.84±0.44)% and(8.67±1.22)%,(24.12±1.11)% and(25.39±2.26)%,and(64.55±4.05)% and(66.2±3.74)%,which were in a concentration dependent manner.There were obvious differences between different groups treated with doxorubicin in inhibiting rates(P<0.05).The growth inhibiting rates of HepG2 and SMMC-7721 cells treated by 10,100,500,1000ng/ml TRAIL after 24h were(5.83±0.25)% and(5.66±0.56)%,(9.60±1.38)% and(8.96±1.13)%,(11.87±1.43)% and(12.11±1.84)%,and(15.12±3.84)% and(16.16±1.41)%.There were obvious differences between 10ng/ml group and other concentration groups treated with TRAIL(P<0.01).Low-concentration doxorubicin combined with TRAIL treating HepG2 and SMMC-7721 cells could enhance the sensibility of those cells to TRAIL.With time expansion and concentration increase,cell growth inhibiting rates rised with time and concentration dependent manner.The increase of TRAIL death receptors(DR4/DR5) in mRNA and protein levels was detected in HepG2 cells treated with doxorubicin,however,significant increased DR5 expression was observed in SMMC-7721 cells but not in DR4.Conclusion Low-concentration doxorubicin in combination with TRAIL presents synergistic effect,and the possible mechanism lies in doxorubicin may enhance TRAIL-induced apoptosis through up-regulating death receptors,especially DR5,indicating the potential of TRAIL to treat hepatocellular carcinoma.

<正>患者男,63岁,上腹部胀痛22个月。2011年04月07日胃镜检查示:胃角小弯侧见不规则溃疡,大小约3 cm×3 cm。病理报告:(胃角)癌,倾向低分化腺癌。血CEA及CA19-9正常,腹部CT未见明显肿大淋巴结。遂行2个周期化疗:多西他赛75 mg/m~2,第1天;顺铂75 mg/m~2,第1天;卡培他滨1 000 mg/m~2,bid,连服14d;21d为1个周期。2011年06月07日复查胃镜示:病灶明显缩小。患者于2011年06月10日在全麻下行胃癌根治术。术后病理报告:(胃)隆起型绒毛膜癌,浸及浆膜,小弯侧形成癌结节,(第8组)淋巴结及小弯侧淋巴结各有1个转移,上下切缘(-),大网膜(-)。免疫组化:HCG(+),CK8/18(+),CK7部分(+),P63少数(+),CK5/6(-),CK20(-),CEA(-)。术后继续行巩固化疗。

[Purpose] To investigate the effect of subtoxic adriamycin and TRAIL on cell proliferation and expression of TRAIL receptors in human hepatoma carcinoma cells HepG2.[Methods] Growth inhibition rates were examined by MTT assay under treatment with TRAIL or adriamycin or with combination.The changes of TRAIL receptors (DR4,DR5,DcR1 and DcR2) in mRNA and protein level were quantified by RT-PCR and Western-blot analysis respectively.[Results] Adriamycin had concentration-dependent effect on growth inhibition of HepG2 cells,which was not observed in TRAIL.The killing ability was enhanced with the combination of subtoxic adriamycin and subtoxic TRAIL.Increase of TRAIL death receptors (DR4,DR5) in mRNA and protein level was detected after treating with adriamycin,however,significant decrease was observed in decoy receptors (DcR1,DcR2).[Conclusions] Subtoxic concentration of adriamycin and TRAIL in combination presents synergistic effect,and the possible mechanism lies in that adriamycin may enhance TRAIL-induced apoptosis through upregulating death receptors,which means TRAIL has potential application value for cancer treatment.

It has been preliminarily demonstrated that CIAPIN1 plays an essential role in normal tissue and is closely related to tumor formatin and development, prognosis and multiple drug resistance. CIAPIN1-based target therapy may provide a novel thinkingpathway in cancer treatment.

Objective To study the clinical efficacy and toxicity of improved CHOP regimen combined with vinorelbine(NVB) and cisplatin(DDP) for patients with recrudescent refractory non-Hodgkin's lymphoma(NHL).Methods Thirty-six patients with recrudescent refractory NHL were recruited.The improved CHOP regimen substituted vincristine(VCR) and prednisone(PDN) with NVB and DDP.The treatment repeated in every 21 days.The clinical efficacy and toxicity were assessed after at least 2 cycles of chemotherapy.Results The overall response rate(RR) was 69.4%,complete response(CR)16.7%,patial response(PR)52.8%.Median progressive time was 15.3 months.Median survival time was 20.8 months.The most common toxic effect was myelosuppression.Conclusion CHND regimen can be used as the second choice for recrudescent refractory NHL.