Objective:To investigate the predictive value of tumor regression rate after induction chemotherapy for survival of patients with locally advanced nasopharyngeal carcinoma.Methods:A total of 161 patients with stage Ⅲ-ⅣA nasopharyngeal carcinoma newly diagnosed at the Daping Hospital of Army Medical University from January 2009 to December 2012 were selected as the research subjects. The relationships between tumor size changes before and after induction chemotherapy and survival time were analyzed. Kaplan-Meier method was used to draw the survival curve accompanied with log-rank test. Cox regression analysis was used to analyze the risk factors affecting the prognosis of patients with nasopharyngeal carcinoma.Results:There were statistically significant differences in the tumor regression rate of primary lesions between N 1and N 2-3( Z=2.177, P=0.029), T 1-2and T 3-4( Z=-4.501, P<0.001)patients after induction chemotherapy. In N 1stage patients, the 5-year overall survival (OS) rates of patients with primary lesions achieving objective response ( n=18) and those without objective response ( n=19) after induction chemotherapy were 88.89% and 57.45%, and patients with cervical lymph node metastatic lesions achieving objective response ( n=19) and those without objective response ( n=18) were 86.72% and 49.10% respectively, with statistically significant differences ( χ2=6.023, P=0.014; χ2=7.441, P=0.006). In N 2-3stage patients, the 5-year OS rates of patients with primary lesions achieving objective response ( n=81) and those without objective response ( n=43) after induction chemotherapy were 77.56% and 50.70%, and patients with cervical lymph node metastatic lesions achieving objective response ( n=85) and those without objective response ( n=39) were 75.11% and 52.04% respectively, with significant differences ( χ2=8.037, P=0.005; χ2=7.268, P=0.007). Univariate Cox regression analysis showed that in patients with stage N 1, the tumor regression rate of primary lesions ( HR=0.048, 95% CI: 0.004-0.644, P=0.022), the efficacy of primary lesions ( HR=0.174, 95% CI: 0.037-0.830, P=0.028), the efficacy of cervical lymph node metastatic lesions ( HR=0.154, 95% CI: 0.033-0.725, P=0.017) after induction chemotherapy were significantly associated with OS; in N 2-3stage patients, the tumor regression rate of primary lesions ( HR=0.178, 95% CI: 0.056-0.564, P=0.003), the tumor regression rate of cervical lymph node metastatic lesions ( HR=0.081, 95% CI: 0.020-0.324, P<0.001), the efficacy of primary lesions ( HR=0.422, 95% CI: 0.228-0.781, P=0.006), the efficacy of cervical lymph node metastatic lesions ( HR=0.439, 95% CI: 0.238-0.813, P=0.009) after induction chemotherapy were significantly associated with OS. In multivariate Cox regression including N stage and tumor regression rate, N stage and efficacy, the interaction items were not statistically significant (all P>0.05). In T 1-2stage patients, the 5-year OS rates of patients with primary lesions achieving objective response ( n=45) and those without objective response ( n=13) after induction chemotherapy were 77.55% and 84.62%, and patients with cervical lymph node metastatic lesions achieving objective response ( n=43) and those without objective response ( n=15) were 78.89% and 80.00% respectively, with no significant differences ( χ2=0.239, P=0.625; χ2=0.005, P=0.943); in T 3-4stage patients, the 5-year OS rates of patients with primary lesions achieving objective response ( n=54) and those without objective response ( n=49) after induction chemotherapy were 78.90% and 45.00%, and patients with cervical lymph node metastatic lesions achieving objective response ( n=61) and those without objective response ( n=42) were 75.10% and 42.89% respectively, with significant differences ( χ2=13.615, P<0.001; χ2=12.752, P<0.001). Univariate Cox regression analysis showed that in patients with stage T 1-2, the tumor regression rate, the efficacy of primary lesions and cervical lymph node metastatic lesions after induction chemotherapy were not related to OS (all P>0.05); in T 3-4stage patients, the tumor regression rate of primary lesions ( HR=0.121, 95% CI: 0.033-0.444, P=0.001), the tumor regression rate of cervical lymph node metastatic lesions ( HR=0.126, 95% CI: 0.036-0.442, P=0.001), the efficacy of primary lesions ( HR=0.297, 95% CI: 0.150-0.588, P<0.001), the efficacy of cervical lymph node metastatic lesions ( HR=0.329, 95% CI: 0.173-0.625, P=0.001) after induction chemotherapy were significantly associated with OS. Multivariate Cox regression analysis showed that the interaction test of T stage and the efficacy of primary lesion trended to be statistically significant ( P=0.062). Conclusion:In patients with stage Ⅲ-ⅣA nasopharyngeal carcinoma, the responsiveness to induction chemotherapy in stage T 3-4patients has important value in predicting survival prognosis.

Objective To explore the value of neutrophil lymphocyte ratio (NLR) in predicting the efficacy of neoadjuvant chemoradiotherapy for esophageal squamous cell carcinoma (ESCC). Methods Clinical data of 104 patients (92 males and 12 females) with esophageal squamous cell carcinoma undergoing preoperative neoadjuvant therapy in our center from January 2016 to June 2020 were collected and analyzed. Blood routine test was carried out in 3 d before neoadjuvant chemoradiotherapy, including neutrophil count, lymphocyte count, monocyte count and platelet count. Then NLR, platelet lymphocyte ratio (PLR) and lymphocyte monocyte ratio (LMR) were calculated respectively. Iodine water radiography and chest enhanced CT scanning were carried out before and after neoadjuvant treatment, so as to determine the regression grade of tumor. The survival status of all patients was followed up for 4~53 months. Mann Whitney U test was used to analyze the difference of continuous variables between groups. Receiver operating characteristic (ROC) curve was applied to evaluate the predictive effect and the best cut-off value of NLR. Chi-square test was performed to analyze the correlation between NLR and clinical characteristics. Logistic regression and Cox regression analyses were adopted respectively to investigate the independent predictors of neoadjuvant remission as well as the independent prognostic factors of overall survival (OS). Results Among the 104 enrolled patients, there were 0, 38, 54 and 12 cases who achieved complete remission (CR), partial remission (PR), stable disease (SD) and progression disease (PD) criteria respectively after neoadjuvant therapy. NLR before treatment was revealed to be an independent predictor of neoadjuvant chemoradiotherapy remission (OR=0.404, 95%CI: 0.208~0.787, P=0.008). ROC curve showed that NLR had a moderate predictive effect on neoadjuvant chemoradiotherapy remission (AUC=0.737, 95% CI: 0.631~0.844, P < 0.001), and the optimal cut-off value was 2.77, with the corresponding sensitivity and specificity of 0.712 and 0.737, respectively. However, multivariate Cox regression analysis showed that only surgery following neoadjuvant therapy was an independent prognostic factor for OS (HR=0.258, 95% CI: 0.068~0.983, P=0.047). Conclusion NLR before treatment may be an independent predictor of clinical remission after neoadjuvant therapy for ESCC patients, but it may not be suitable for OS prediction.

Background Inhibition of vascular endothelial growth factor receptor (VEGFR) has shown antitumour activity in advanced hepatocellular carcinoma, but few studies of VEGFR inhibitors have been done in populations with a high prevalence of hepatitis B virus infection. The aim of this study was to evaluate the efficacy and safety of apatinib in patients with pretreated advanced hepatocellular carcinoma. Methods AHELP was a randomised, double-blind, placebo-controlled, phase 3 trial done at 31 hospitals in China, in patients (aged >= 18 years) with advanced hepatocellular carcinoma who had previously been refractory or intolerant to at least one line of systemic chemotherapy or targeted therapy. Patients were randomly assigned (2:1) to receive apatinib 750 mg or placebo orally once daily in 28-day treatment cycles. Group allocation was done with a central randomisation system, with a block size of six, and was stratified by Eastern Cooperative Oncology Group performance status, previous sorafenib treatment, and presence of vascular invasion or extrahepatic metastasis. The primary endpoint was overall survival, which was defined as time from randomisation to death from any cause, and was analysed in patients who were randomly assigned and received at least one dose of the study drug. Safety analyses were done in patients who received at least one dose of the study treatment and had post-dose safety assessments. This trial is registered with ClinicalTrials.gov, NCT02329860. Findings Between April 1, 2014, and May 3, 2017, 400 eligible patients were randomly assigned to receive apatinib (n=267) or placebo (n=133). Seven patients (six in the apatinib group and one in the placebo group) did not receive study treatment and were excluded from efficacy analyses. Overall survival was significantly improved in the apatinib group compared with the placebo group (median 8.7 months [95% CI 7.5-9.8] vs 6.8 months [5.7-9.1]; hazard ratio 0.785 [95% CI 0.617-0.998], p=0.048). 387 patients (257 in the apatinib group and 130 in the placebo group) had a safety assessment after study treatment and were included in safety analyses. The most common treatment-related adverse events of grade 3 or 4 were hypertension (71 [28%] patients in the apatinib group vs three [2%] in the placebo group), hand-foot syndrome (46 [18%] vs none), and decreased platelet count (34 [13%] vs one [1%]). 24 (9%) patients in the apatinib group and 13 (10%) in the placebo group died due to adverse events, but none of these deaths were deemed to be related to treatment by investigators. Interpretation Apatinib significantly improved overall survival in patients with pretreated advanced hepatocellular carcinoma compared with placebo, with a manageable safety profile. Copyright (C) 2021 Elsevier Ltd. All rights reserved.

据2015年肿瘤统计我国肺癌的发生率在男性居第1位和女性居于第2位,并且肺癌的肿瘤相关致死率中国人群中均居于首位,肺癌中的80％患者被确诊为非小细胞肺癌(non-small cell lung cancer,NSCLC)[1].NSCLC骨转移骨痛是晚期患者最常见的症状,约有80％的晚期NSCLC骨转移患者经历骨痛[2].放射治疗是骨转移骨痛患者控制疼痛最常见的治疗方式,对于NSCLC肺癌疼痛VAS评分大于4分的患者,放疗作为最常见的干预手段[3-5].

Background:There is an urgent clinical need to select the patients with resectable gastrointestinal stromal tumors (GISTs) who can benefit from adjuvant treatment after complete resection based on disease recurrence risk stratification. We hypothesized that integrating biomarkers into available risk assessment tools may improve the precision of GIST prognostic predictions. Methods:Candidate genes that may cause GIST progression were identified using the Gene Expression Omnibus dataset GSE20708. Quantitative Real-time was used to confirm the prognostic value of the candidate genes for recurrence-free survival (RFS) in a cohort of 94 patients. Results: Thirty-seven differentially expressed genes between localized tumors and metastatic primary tumors were found; 14 (37.8%) were upregulated and 23 (62.2%) were downregulated in the latter tumors. Low-density lipoprotein receptor class A domain containing 4 (LDLRAD4) was selected for further prognostic analysis. Although LDLRAD4 mRNA expression was not associated with recurrence risk grades as determined by the revised NIH consensus criteria, multivariate Cox regression analysis showed that LDLRAD4 expression (hazard ratio [HR] = 4.403, 95% confidence interval [CI]: 1.822-10.641, P = 0.001), tumor size (HR = 1.174, 95% CI: 1.027-1.342, P = 0.019) and tumor location (HR = 6.291, 95% CI: 1.128-35.080, P = 0.036) were independent prognostic factors for RFS in patients with resectable GISTs. Moreover, the RFS model constructed by these three factors may effectively predict GIST prognosis within the first 2 postsurgical years. Conclusion: Our study identifies LDLRAD4 as a suitable prognostic marker for GISTs. The integration of biomarkers into risk assessment tools may improve the precision of GIST prognostic predictions.

Abstract BACKGROUND Cisplatin is commonly used in lung cancer therapy, but cisplatin resistance in lung cancer cells remains an unsolved problem. Here, we report that cytoplasmic APE1 contributes to cisplatin resistance, cell proliferation and migration in lung cancer cells. METHODS Immunofluorescence, western blot analysis, lentivirus transfection and scratch assays, and transwell migration and invasion assays were carried out on the cell lines A549 and Calu-1. A total of 124 samples of lung cancer tissues were evaluated to determine the clinical effects of cytoplasmic APE1 and COX-2. RESULTS We found that cytoplasmic APE1 expression was lower in cisplatin sensitive cells than in cisplatin-resistant cells, and the upregulation of cytoplasmic APE1 significantly reduced cisplatin sensitivity in lung cancer cells. Gain-of-function studies demonstrated that cytoplasmic APE1 promoted lung cancer cell proliferation, migration and invasion in vitro and tumor growth in vivo, which were inhibited after cisplatin treatment. In patient samples, cytoplasmic APE1 in lung cancer tissues was an independent indicator of overall survive (OS) for lung cancer patients (P < 0.001). Mechanistic studies revealed that cytoplasmic APE1 promotes lung cancer malignancy by activating the COX-2/Akt/β-catenin pathway. Furthermore, the mutation of the APE1-C65 site caused upregulation of cytoplasmic APE1 and inhibited cell growth, migration and invasion of lung cancer cells. CONCLUSION We suggest that modulating cytoplasmic APE1 in lung cancer is a promising novel strategy for overcoming cisplatin resistance.

Resistance to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) has become the main clinical challenge of advanced lung cancer. This research aimed to explore the role of PARP1-mediated autophagy in the progression of TKI therapy. PARP1-mediated autophagy was evaluated in vitro by CCK-8 assay, clonogenic assay, immunofluorescence, and western blot in the HCC-827, H1975, and H1299 cells treated with icotinib (Ico), rapamycin, and AZD2281 (olaparib) alone or in combination. Our results and GEO dataset analysis confirmed that PARP1 is expressed at lower levels in TKI-sensitive cells than in TKI-resistant cells. Low PARP1 expression and high p62 expression were associated with good outcomes among patients with NSCLC after TKI therapy. AZD2281 and a lysosomal inhibitor reversed resistance to Ico by decreasing PARP1 and LC3 in cells, but an mTOR inhibitor did not decrease Ico resistance. The combination of AZD2281 and Ico exerted a markedly enhanced antitumor effect by reducing PARP1 expression and autophagy in vivo. Knockdown of PARP1 expression reversed the resistance to TKI by the mTOR/Akt/autophagy pathway in HCC-827IR, H1975, and H1299 cells. PARP1-mediated autophagy is a key pathway for TKI resistance in NSCLC cells that participates in the resistance to TKIs. Olaparib may serve as a novel method to overcome the resistance to TKIs.

Background: Serum miRNA was once found as potential disease survival index,thus we investigated the role of miRNA in predicting prognosis in loco-regionally advanced NPC patients treated with CCRT. Methods: This study included two phases: (i) We enrolled 3 NPC patients with recurrence or distant metastasis (experimental group, EG) and 3 NPC patients in clinical remission (control group, CG),who were treated with CCRT within 5 years.The paired serum was collected before and after treatment and biomarkers were discovered by LNA-TaqMan Human MicroRNA Arrays. (ii) we used the bioinformatic analysis, marker selection and an independent validation by qRT-PCR to analyse the serums of 29 NPC patients with recurrent disease or distant metastasis and 19 NPC patients in clinical remission treated with CCRT. Using the Kaplan-Meier method, log-rank test and Cox regression model to estimate the accuracy of the miRNAs to predict PFS and OS, and identified factors significantly associated with prognosis, respectively. Results: Using fold change≥2.0 or ≤0.5 and p≤0.05 as cutoff levels, we identified 1 up-regulated and 6 down-regulated miRNAs, 1 up-regulated and 9 down-regulated miRNAs in EG versus CG before and after CCRT, respectively. After these down-regulated miRNAs were dealed with bioinformatics analysis and normalization, only 5 different miRNAs were significantly reduced, which there were no significant difference in the expression of miRNA-26b, miRNA-29a and miRNA-125b before CCRT, and the expression of miRNA-143 and miRNA-29b after CCRT in the serum samples of 48 NPC patients. Based on this, we calculated a risk score with the expression of miRNA-26b、miRNA-29a、miRNA-125b、miRNA-29b、miRNA-143 and then classified patients as high or low risk group. Cox regression model suggested that combining miRNA-29a and miRNA-125b before CCRT with miRNA-26b after CCRT was independent prognostic factors for PFS (HR=3.149, 95%CI:1.018-9.115, p=0.034), whereas combining the former two is independent for OS (HR=5.146, 95%CI:1.674-15.817, p=0.04). Conclusions : For loco-regionally advanced NPC patients treated with CCRT, especially high-risk patients- serum miRNAs, such as miRNA-29a, miRNA-125b and miRNA-26b etc., play an important role in predicting prognosis factors of PFS and OS, which will contribute to the strategic direction for future research.

The diagnostic and prognostic evaluation of primary central nervous system lymphoma (PCNSL) is challenging due to the lack of sensitive biomarkers. The present study aimed to evaluate the value of interleukin (IL)-10 in this context. Between October 2016 and December 2018, 91 patients with suspected intracranial neoplasms were recruited, and the concentrations of IL-10 or IL-6 in both the cerebrospinal fluid (CSF) and blood were measured and analyzed by the Kruskal-Wallis test. The correlation between CSF IL-6 or IL-10 levels and tumor size was determined by Spearman's coefficient analysis. The receiver operating characteristic curve was used to evaluate the diagnostic value of CSF IL-6 and IL-10 levels. Median progression-free survival (PFS) and overall survival time were calculated using Kaplan-Meier survival analysis. Among the 91 patients, 3 were diagnosed with PCNSL on the basis of neuroimaging data and CSF IL-10 levels. A total of 35 cases were verified to show diffuse large B-cell lymphoma on histological assessment, 17 of which were diagnosed as PCNSL by MRI. The median PFS and OS were 8.00 months [95% confidence interval (CI), 3.94-12.06) and 17.5 months (95% CI, 11.55-23.45) respectively in the 12 PNCSL cases with regular follow up. The diagnostic efficiency of serum IL-6 levels was lower than that of serum IL-10 levels (P=0.030), which, in turn, was lower than that of CSF IL-10 levels (P<0.001). The decline and increase in CSF IL-10 levels was concurrent with improvement and deterioration in manifestation, respectively, which predated the MRI variation. High CSF IL-10 levels indicated low Karnofsky performance scale scores and shortened PFS times. CSF IL-10 levels higher than 1,000 pg/ml signified disease progression. CSF IL-10 levels could be a sensitive biomarker guiding the differential diagnosis, early recurrence detection, prognostic evaluation and therapeutic strategy establishment in cases of PCNSL.

A number of novel drugs targeting the fibroblast growth factor receptor (FGFR) signaling pathway have been developed, including mostly tyrosine kinase inhibitors, selective inhibitors or monoclonal antibodies. Multiple preclinical and clinical studies have been conducted worldwide to ascertain their effects on diverse solid tumors. Drugs, such as lenvatinib, dovitinib and other non-specific FGFR inhibitors, widely used in clinical practice, have been approved by the Food and Drug Administration for cancer therapy, although the majority of drugs remain in preclinical tests or clinical research. The resistance to a single agent for FGFR inhibition with synthetic lethal action may be overcome by a combination of therapeutic approaches and FGFR inhibitors, which could also enhance the sensitivity to other therapeutics. Therefore, the aim of the present review is to describe the pharmacological characteristics of FGFR inhibitors that may be combined with other therapeutic agents and the preclinical data supporting their combination. Additionally, their clinical implications and the remaining challenges for FGFR inhibitor combination regimens are discussed.

Background To explore the efficacy and safety of Transcatheter rectal arterial chemoembolization with oxaliplatin and S-1 concurrent chemoradiotherapy as neoadjuvant therapy for locally advanced rectal cancer. Methods This s a prospective, monocentric, non-randomized clinical study, a total of 95 patients were enrolled and assigned to two groups: an investigational group ( n = 50) receiving transcatheter rectal arterial chemoembolization (TRACE) with oxaliplatin and preoperative radiotherapy plus S-1 concurrent chemotherapy (NATRACE-CRT), followed by surgery, a control group ( n = 45) receiving standard fluorouracil-based combined modality treatment, consisting of preoperative radiotherapy plus capecitabine based chemotherapy (NA-CRT), followed by surgery. The primary endpoint was postoperative pathological regression rate which evaluated by tumor regression grade (TRG) according to the 7th edition of the American Joint Committee on Cancer (AJCC) standard, and the secondary endpoints included objective response rate (ORR) and toxicity, as well as surgical complications, and postoperative tumor downstaging. Results Compared with NA-CRT group (17.78% (95% confidence interval (CI): 6.2–29.4)), the TRG0 was 30% (95% CI 16.8–43.2) in the NATRACE-CRT group ( P = 0.231). The TRG0 + 1 rate was 60% (95% CI: 45.9–74.1) and 33.33% (95% CI: 19–47.7) in NATRACE-CRT group and NA-CRT group, respectively ( P = 0.013). The ORR of the NATRACE-CRT group was 84% and that of the NA-CRT group was 66.67% ( p = 0.058). Incidence of preoperative toxic side effects and surgical complications was similar between the two groups. Conclusion TRACE with oxaliplatin plus concurrent S-1 chemoradiotherapy as a neoadjuvant therapy provided better pathological remission rate versus standard treatment with a similar safety profile. Trial registration NCT03601156 .

目的:探讨肝癌患者循环miR-203a-3p表达与SOCS1和SOCS3的关系及意义.方法:选取50例拟行手术治疗的原发性肝癌患者为研究组,术前留取血样,术中留取病理组织和癌旁组织;另取50例同期入院体检的健康志愿者为对照组,留取血样.采用荧光定量PCR实验测定血样miR-203a-3p表达水平;免疫蛋白印迹实验测定组织SOCS1和SOCS3表达;甲基化特异性PCR实验测定组织SOCS1和SOCS3的甲基化水平.结果:研究组循环miR-203a-3p水平低于对照组,差异具有统计学意义(P<0.05).研究组病理组织SOCS1和SOCS3表达水平低于癌旁组织,病理组织SOCS1和SOCS3甲基化程度高于癌旁组织,差异具有统计学意义(P<0.05).研究组循环miR-203a-3p水平与组织SOCS1和SOCS3表达呈正相关性(r=0.576和r=0.475,P<0.05),与组织SOCS1和SOCS3甲基化程度呈负相关性(r=-0.585和r=-0.579,P<0.05).结论:miR-203a-3p可能对原发性肝癌的SOCS1、SOCS3甲基化修饰有影响,有望为其临床诊治提供新靶点.

目的 观察微小RNA(miR-5047)在前列腺癌细胞株中的表达,探讨其对TIPE3基因表达的调控. 方法 采用实时定量PCR(RT-qPCR)检测miR-5047在4种前列腺癌细胞株(C4-2B、LNCaP、DU-145、PC-3)和正常前列腺滤泡细胞RWPE-1中的表达.以表达量最低的细胞为感染对象,使用慢病毒Lenti-阴性对照序列(miR-NC)和Lenti-miR-5047分别感染细胞,分别命名为对照组和实验组.RT-qPCR检测感染后细胞中miR-5047的表达.细胞划痕实验和MTT法分别检测两组细胞的迁移和增殖能力.基于microRNA. org数据库对miR-5047进行靶基因预测.双荧光素酶报告基因检测验证miR-5047的靶基因.RT-qPCR和Western blot检测两组细胞中靶基因在mRNA和蛋白水平的表达. 结果 与正常前列腺滤泡细胞RWPE-1相比,在前列腺癌细胞中miR-5047的表达明显降低(P＜0. 05),在C4-2B细胞中表达最低(P＜0. 01).与对照组相比,实验组C4-2B细胞中miR-5047的表达明显增加(P＜0. 01).与对照组相比,实验组C4-2B细胞的迁移能力降低(P＜0. 01).实验组C4-2B细胞的增殖能力从第2天开始低于对照组(P＜0. 05).microRNA. org数据库显示miR-5047的靶基因是肿瘤坏死因子α诱导蛋白8样因子3(tumor necrosis factor-α induced protein 8 like 3,TIPE3),双荧光素酶报告基因检测证实miR-5047可与TIPE3互补结合(P＜0. 01).与对照组相比,实验组细胞中TIPE3 mRNA和蛋白水平的表达明显降低(P＜0. 01). 结论miR-5047在前列腺癌细胞株中呈低表达,miR-5047可能通过下调TIPE3基因的表达,抑制前列腺癌C4-2B细胞的迁移和增殖能力.

目的 检测长链非编码RNA(long-chain non-coding RNA,lncRNA)LINC00665在膀胱癌细胞株中的表达,探讨其对膀胱癌侵袭和增殖的影响及作用机制.方法 应用实时定量PCR(qPCR)检测LINC00665在5种膀胱癌细胞株(T24、BIU-87、5637、UM-UC-3、J82)和正常膀胱上皮细胞SV-HUC-1中的表达.以表达量最高的细胞为感染对象,分别感染阴性对照慢病毒和携带LINC00665抑制序列的慢病毒,定义为对照组和实验组.qPCR检测感染效率.Transwell侵袭实验和MTT法分别检测各组细胞的侵袭和增殖能力.qPCR检测各组细胞中钙结合蛋白A13(calcium binding protein A13,S100A13)mRNA的表达.Western blot检测S100A13蛋白和P13K/AKT/mTOR信号通路蛋白的表达.结果 与正常膀胱上皮细胞相比,膀胱癌细胞中LINC00665的表达明显增加(P<0.05),其中UM-UC-3细胞中表达最高(P<0.01).与对照组相比,实验组UM-UC-3细胞中LINC00665的表达明显减少(P<0.01).与对照组相比,实验组UM-UC-3细胞的侵袭能力降低(P<0.01);实验组UM-UC-3细胞的增殖能力从第3天开始降低(P<0.05).与对照组相比,实验组细胞中S100A13 mRNA和蛋白水平的表达明显降低(P<0.01),P13K/AKT/mTOR信号通路蛋白明显降低.结论 LINC00665在膀胱癌细胞株中明显高表达,降低lncRNA LINC00665表达水平可通过调控S100A13表达,干扰P13K/AKT/mTOR信号通路转导,抑制膀胱癌UM-UC-3细胞的侵袭和增殖能力.

目的 分析微小RNA-8085(miR-8085)在膀胱癌组织中的表达及其对膀胱癌J82细胞侵袭和增殖的影响,并探究其分子机制. 方法 实时定量PCR(qPCR)检测32例膀胱癌和癌旁组织中miR-8085的表达水平.以携带miR-8085的慢病毒或阴性对照慢病毒感染J82细胞,命名为实验组和对照组,qPCR检测转染效率.Transwell侵袭实验和四甲基偶氮唑蓝(MTT)法分别检测感染后J82细胞的侵袭能力和增殖能力.生物信息学方法预测miR-8085可能的靶基因.双荧光素酶报告基因实验验证miR-8085与靶基因mRNA的结合.qPCR和Western blot检测感染后J82细胞中靶基因在mRNA和蛋白水平的表达量. 结果 膀胱癌组织和癌旁组织中miR4085的表达量分别为2.50±0.78和7.35±0.92(P＜0.01).与对照组相比,实验组J82细胞中miR-8085的表达量显著增加(P＜0.01).对照组和实验组中J82穿膜细胞数分别为82.63±7.60和35.45±11.27,实验组J82细胞的侵袭能力显著被抑制(P＜0.05).实验组J82细胞的增殖能力从第3天开始显著被抑制(P＜0.05).生物信息学方法显示,miR-8085可能的靶基因是拓扑异构酶Ⅱα(TOP2A).双荧光素酶报告基因实验显示,miR-8085可与TOP2A mRNA 3'非翻译区靶向结合.实验组J82细胞株中TOP2A基因在mRNA和蛋白水平的表达量均显著减少(P＜0.01).结论 miR-8085在膀胱癌中表达明显降低,过表达miR-8085可通过干扰TOP2A基因的表达,抑制膀胱癌J82细胞的侵袭和增殖能力,可能成为膀胱癌治疗的潜在靶点.

Objective: Objective: To develop a model for predicting response to anti-epidermal growth factor receptor ( anti-EGFR) antibody by using feature genes of cell subpopulations in the tumor microenvironment of recurrent and metastat-ic squamous cell carcinoma of the head and neck. Methods: Gene Expression Omnibus datasets with records of progression free survival after treated with anti-EGFR antibody and gene expression profiles evaluated by microarray assay were retrieved. The feature genes peculiar to each of cell subpopu-lations in the tumor microenvironment was obtained from previ- ously published articles. Differentially expressed genes were firstly identified between the long progression free survival (PFS) group and the short PFS group in the discovery set and used to calculate sensitive indexes of each cell subpopulation. Least absolute shrinkage and selection operator was used to establish the anti-EGFR antibody sensitivity score (EASS) which was further verified in the validation set. Results: The median EASS deduced from the nine cell subpopulations was 30. 73 (26. 24-41. 29) in the discovery set GSE65021. The long PFS group was significantly discriminated from the short PFS group through EASS revealed by ROC analysis (AUC: 1. 000, 95% CI: 1. 000-1. 000, P<0. 001). In the validation set GSE102995, the EASS remained an independent prognostic factor for PFS after adjusted for stage (IV vs II-III) and per-formance status score (HR=0. 647,95% CI:0. 503-0. 831,P=0. 001). The consensus index of EASS for predicting PFS was 0. 755 (95% CI: 0. 719-0. 791), which was significantly higher than that of stage 0. 542 (95% CI: 0. 336-0. 748) (P=0. 032). Conclusion: The EASS is efficient to predict the response to anti-EGFR antibody in the recurrence and metas-tasis of squamous cell carcinoma of the head and neck, which is worthy of further study and validation.

引文格式:Wang G, Xiao H, Chen C. Study on the sensitivity of neoadjuvant chemoradiotherapy for rectal cancer [J]. J Cancer Control Treat, 2019, 32 (4):295-298. [王阁,肖何,陈川. 对直肠癌新辅助放化疗敏感性研究的若干探讨[J].肿瘤预防与治疗,2019,32(4):295-298. ]

The current prognosis of thymic epithelial tumors (TETs) is according to the World Health Organization (WHO) histologic classification and the Masaoka staging system. These methods of prognosis have certain limitations in clinical application and there is a need to seek new method for determining the prognosis of patients with TETs. To date, there have been no studies done on the use of DNA methylation biomarkers for prognosis of TETs. The present study was therefore carried out to identify DNA methylation biomarkers that can determine the overall survival in patients with TETs.

Background: In daily work, pathologists often use TTF1 and GATA3 in the differential diagnosis of primary lung adenocarcinoma (TTF1+ GATA3-) and metastatic bladder cancer (or breast cancer) (TTF1- GATA3+). However, we encountered a small lung biopsy sample of TTF1+ GATA3+ (clinically suggesting both lung and bladder occupancy), and the dyeing results caused us great confusion; thus, we intended to determine the expressions of TTF1 and GATA3 in lung and bladder cancer by expanding the sample. Methods: The study included a complete case report and the tissue microarrays including pulmonary squamous cell carcinomas (n = 55), lung adenocarcinomas (n = 47), high-grade (n = 68) and low-grade (n = 43) urothelial carcinomas of the bladder. TTF1 and GATA3 immunohistochemical staining were performed on the tissue microarrays, and the relevant literature was retrieved. Results: Our staining results on tissue microarrays showed that TTF1 was expressed in pulmonary adenocarcinomas (44/47, 93.6%), squamous cell carcinomas (1/55, 1.8%), low-grade (1/43, 2.3%) and high grade (2/68, 2.9%) urothelial carcinomas; GATA3 was only expressed in urothelial carcinomas of the bladder (high-grade: 48/68, 70.6%; lowgrade: 42/43, 97.7%). Our literature search results showed that TTF1 could be expressed in a very small number of bladder urothelial carcinomas, and GATA3 could be expressed in a few primary lung squamous cell carcinomas and a very small number of primary lung adenocarcinomas. Conclusions: TTF1 and GATA3 are good markers in the differential diagnosis of primary non-small cell lung cancer (GATA3-) and metastatic urothelial carcinoma of the bladder (GATA3+). However, pathologists should pay attention to a few special cases: lung cancer may express GATA3, and urothelial carcinoma may express TTF1. In these cases, some additional immunohistochemical markers, such as napsin A and URO III, should be added to assist the diagnosis.