BACKGROUND:Lung adenocarcinoma (LUAD) is the most common form of lung cancer. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is abnormally expressed in various tumor tissues and is associated with malignant phenotypes. However, the clinical significance, function, and mechanism of LUAD invasion and metastasis remain unclear. METHODS:We retrospectively enrolled 100 patients with LUAD in this study. Initially, qRT-PCR was performed to detect PCSK9 levels in clinical tissues. Subsequently, bioinformatics analysis of scRNA-seq and The Cancer Genome Atlas Program (TCGA) datasets was performed to predict the role of PCSK9 in tumor cell malignancy and its potential downstream pathways. These predictions were validated experimentally using the CCK-8 assay, TUNEL staining, wound healing, transwell invasion assay, and an in vivo lung metastasis model. Finally, Western blotting and an AKT inhibitor (MK2206) were used to verify the underlying mechanism. RESULTS:PCSK9 was significantly upregulated in LUAD tissues compared to paracancerous tissues and was associated with poorer OS and DFS. Bioinformatics analysis of scRNA-seq data and TCGA analysis predicted that PCSK9 is highly enriched in tumor cells and is involved in EMT, and that the PI3K/AKT pathway plays a significant role in LUAD development. Experiments confirmed that PCSK9 markedly promoted LUAD cell proliferation, migration, and invasion in vitro and lung metastasis in vivo. PCSK9 overexpression significantly upregulated p-AKT, p-PI3K, and p-mTOR levels. Furthermore, the AKT inhibitor, MK2206, reversed the promoting effects of PCSK9. CONCLUSIONS:PCSK9 expression is associated with the prognosis and diagnosis of LUAD. This molecule activates the PI3K/AKT signaling pathway, thereby driving invasion, metastasis, and proliferation in LUAD.

Objective: Treatment-related toxicity following stereotactic ablative radiotherapy (SABR) in patients with central and ultracentral non-small cell lung cancer (NSCLC) is of potential concern, and the best regimens are still being explored. This study aimed to evaluate the clinical outcomes and toxicities of the patients with ultracentral and central NSCLC treated with SABR at our institution.Method: This retrospective study included patients with central and ultracentral NSCLC treated with SABR to prescription doses of 50 Gy in five fractions, 56 Gy in seven fractions, or 60 Gy in ten fractionsat Jiangsu Cancer Hospital between May 2013 and October 2018. The patients were grouped as central or ultracentral tumors.Overall survival (OS), progression-free survival (PFS), and grade >= 3 toxicities were analyzed.Results: Forty patients (31 male, nine female) were included. Median follow-up was 41 (5-81) months. The 1-, 2-, and 3-year OS rates were 90.0%, 83.6%, and 66.0%, respectively, and the 1-, 2-, and 3-year PFS rates were 82.5%, 62.9%, and 54.2%, respectively. OS in the ultracentral group was inferior compared with the central group (median, 52.0 months, 95%CI: 43.0-61.0 vs. not reached, P = 0.03).The median PFS was 38.0 months in the ultracentral group (95%CI: 19.8-56.2) vs. not reached in the central group, although this difference was not statistically significant (P = 0.06). The overall incidence of grade >= 3 toxicity was five (12.5%) patients, (5 in the ultracentralgroup vs. 0 in the central group; P = 0. 11), including one patient with grade 3 pneumonitis, two with grade 3 bronchial obstruction, one with grade 5 bronchial obstruction, and one with grade 5 esophageal perforation.Conclusion: Worse outcomes were obseverd in patients with ultracentral NSCLC than those with central tu-mors after SABR. Higher rate of treatment-related grade 3 or more toxicity was observed in the ultracentral group.(c) 2023 Elsevier Inc. All rights reserved.

Objectives:To investigate the health-related quality of life (HRQL) of long-term survivors of inoperable esophageal squamous cell carcinoma (ESCC) treated with definitive radiation therapy, the real-world trends in the use of advanced radiation techniques, and their impact on the survival outcomes of ESCC patients. Methods:In this multicenter retrospective observational study, the medical records related to demographics and treatment of ESCC patients who were treated with definitive radiation therapy at 14 provincial hospitals in China from 1 January 2015 to 31 December 2016 were analyzed. A HRQL questionnaire was completed by survivors and collected by doctors at the final follow-up. The difference in quality of life between patients with or without recurrence was compared using the Wilcoxon-Mann-Whitney test. Overall survival (OS) was estimated using the Kaplan-Meier method and the group differences were assessed by unstratified log-rank test. The Cox proportional hazards model with Efron's method of tie handling was used to calculate the risk factors for OS. Results:The data of a total of 3,308 patients were collected for this study, 248 were excluded because of missing data, and a final of 3,060 patients were included in the analysis. Most patients (2,901; 94.8%) received intensity-modulated radiotherapy (IMRT)/volumetric-modulated arc therapy (VMAT)/tomotherapy (TOMO). The 5-year OS rate was 30%. Patients who received either two-dimensional radiotherapy (2DRT; HR, 2.43 [95% CI, 1.70-3.47]; P < 0.001) or three-dimensional radiotherapy (3DRT; HR, 1.45 [95% CI, 1.14-1.84]; P = 0.003) had a significantly increased risk of death compared to those who received IMRT/VMAT/TOMO. Of the 716 (23.4%) long-term survivors who completed the HRQL questionnaire, nearly 70% patients were still able to swallow normally or almost normally, and >80% patients did not experience weight loss. Nearly 80% patients found life very enjoyable or were fairly enjoying life. Conclusions:This large, multicenter retrospective study on ESCC patients who received definitive radiation therapy found that most ESCC survivors are satisfied with their quality of life. Most patients received advanced radiation technology. Patients who received either 2DRT or 3DRT had a significantly increased risk of death compared to those who received advanced radiation technology.

目的 探讨偏侧鼻咽癌调强放疗原发灶临床靶区(CTV)的个体化优化方案的可行性.方法 回顾性分析2016年10月至2018年2月于江苏省肿瘤医院连续收治的偏侧鼻咽癌初诊患者87例.偏侧鼻咽癌定义为肿瘤浸润不超过健侧侧壁.根据鼻咽肿瘤侵犯趋势,对原发灶CTV进行如下优化:CTV2健侧包及翼腭窝根部,不包及健侧卵圆孔,咽旁间隙水平健侧仅充分包及咽后外侧淋巴结,健侧颈内静脉不常规包及.评估失败模式和5年生存率[局部控制率(LCR)、无进展生存(PFS)、总生存(OS)],采用Kaplan-Meier法计算;配对t检验和秩和检验法分析优化区域剂量变化及不良反应.结果 全组中位随访59.5个月,5年LCR、PFS、OS分别为98.9％、86.5％、92.1％.CTV优化区域内无1例局部复发.健侧风险结构的优化使腮腺、颞叶、耳蜗、中耳剂量分别降低了 13.45％、9.14％、38.83％、29.36％.观察到4例(4.6％)3级晚期听力损伤,均位于患侧.对比患侧,优化方案明显减轻了健侧的听力损伤(P＜0.001).其他3级晚期不良反应包括颅神经损伤、颈部皮下纤维化、视力损伤,各1例.结论 偏侧鼻咽癌原发灶CTV采取个体化优化方案是安全的,剂量学优势明显,不良反应发生率低,值得临床推广.

Objective: To investigate the function and mechanism of miR-1179 in the tumorigenesis of hepatocellular carcinoma (HCC). Methods: The levels of miR-1179 and NUAK2 in clinical tissues or cell lines were examined using quantitative Real-time PCR (qRT-PCR). Cell Counting Kit-8 (CCK-8), EdU assay, colony formation, wound healing, Transwell assays and flow cytometry assays were conducted to examine the impact of miR-1179 on HCC cells. The protein expression of NUAK2 was detected using Western blotting assay. Bioinformatics analysis and luciferase reporter assays were conducted to reveal the association of miR-1179 with NUAK2. Results: MiR-1179 expression was significantly downregulated in HCC specimens and cell lines compared to normal samples and cells. The miR-1179 overexpression inhibited HCC cell migration, invasion and proliferation through targeting NUAK2. Overexpression of NUAK2 can reverse the effect of miR-1179 on hepatocellular carcinoma cells. Conclusion: miR-1179 suppresses HCC developmen through targeting NUAK2. Which can be used as a potent HCC diagnostic marker.

Long noncoding RNA small nucleolar RNA host gene 10 (SNHG10) has been suggested to function as tumor promoter in various human cancer types. Herein, the role of SNHG10 in colorectal cancer (CRC) was explored. Expression levels of genes in colorectal cancer tissues and cell lines were detected by Starbase and reverse transcription quantitative PCR (RT-qPCR) Cell Counting Kit-8 (CCK-8), the BrdU incorporation assay and Transwell assays were explored to study the function of SNHG10 in HCT116 and DXH-1 cells. In addition, the interaction of SNHG10 and miR-3690 was analyzed by dual-luciferase reporter assays. SNHG10 had a high expression level in CRC tissues and cell lines. Meanwhile, knockdown of SNHG10 reduced cell viability, inhibited cell proliferation and decreased cell migration and invasion. Moreover, bioinformatics analysis revealed that one potential target gene of SNHG10 was miR-3690. Dual-luciferase reporter assay confirmed that miR-3690 directly targeted SNHG10. Importantly, SNHG10 could decrease the expression of miR-3690 in HCT116 and DXH-1 cells. More importantly, the silencing of miR-3690 reversed the effect of the SNHG10 knockdown on the cell viability, proliferation, migration and invasion of HCT116 and DXH-1 cells. The present results demonstrated that SNHG10 promotes colorectal cancer cells the malignant progression by targeting miR-3690.Abbreviations: CRC: Colorectal cancer; Lnc RNA: Long noncoding RNA; microRNAs: miRNAs/miRs; RT-qPCR: reverse transcription quantitative polymerase chain reaction; CCK-8: Cell Counting Kit-8.

Background: This study aimed to explore the relationship between zinc finger protein 488 (ZNF488) and non-small cell lung cancer (NSCLC), as well as the function and mechanism of ZNF488 involved in the invasion and metastasis. Method： TCGA and HPA databases were used to analyze NSCLC data. Quantitative Reverse transcription polymerase chain reaction (qRT-PCR) was used to detect the expression level of ZNF488 in tissues. 100 cases of NSCLC tissues were subjected to immunohistochemical staining (IHC) to evaluate the endogenous expression of ZNF488, and than analyze its correlation with clinical characteristics. After constructing ZNF488 stably overexpressing cell lines, wound healing test and transwell invasion assays were used to explore the invasion and migration ability of lung cancer cells in both ZNF488 over-expressing and the vector control cell lines. In vivo , we used ZNF488 over-expressing and the vector control cell lines to construct animal models of lung metastasis by tail vein injection. The gene chip technology was used to explore the differential genes between vector and ZNF488 over-expressing group. The DAVID database was used to analyze the differential genes by KEGG pathway MEK inhibitor AZD6244 was used to verify the potential signaling pathway. Western blot was used to detect the protein expression levels. Results： The expression of ZNF488 in NSCLC tissues was generally higher than that in normal lung tissues, and its expression level was significantly related to TNM stage, overall survival (OS), local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and progression-free survival (PFS) ( p <0.05). The results of functional and animal experiments showed that ZNF488 promoted the cell invasion and matastasis in NSCLC. In terms of mechanism, ZNF488 can induce epithelial-mesenchymal transition (EMT) in NSCLC by activating the MAPK/ERK signaling pathway, thereby promoting the invasion and metastasis. MEK inhibitor AZD6244. could partially reverse ZNF488-induced invasive ability. Conclusion: As an independent prognostic indicator, ZNF488 can promote the invasion and metastasis by activating the MAPK/ERK signaling pathway in NSCLC .

Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, Jiangsu Province 210009, People’s Republic of China Background: ZNF488 acts as an oncogene which promotes cell invasion and endows tumor cells stem cell capacity in nasopharyngeal carcinoma (NPC), but its correlation with clinicopathologic characteristics and patients’ survival in NPC remain undefined. Methods: In this study, 158 cases of confirmed NPC were subjected to immunohistochemistry staining for evaluating endogenous expression. Kaplan–Meier method and log-rank test were used to estimate the survival rates. The relationship between ZNF488 and clinicopathological characteristics was statistically calculated by chi-squared test, univariate and multivariate analysis. In addition, adhesion assay, MTT and colony formation assays were performed for measuring adhesion and proliferation capacity. Cell cycle analysis via flow cytometry was conducted to explore cell cycle distribution. Western blot was used to detect pathway protein levels, and the pFAK (Y397) kit was used for focal adhesion kinase (FAK) activation. Results: We demonstrated that high expression of ZNF488 was significantly correlated with locoregional failure (P=0.018) and distant metastasis (P=0.001). Patients with high ZNF488 expression had poorer overall survival (P<0.001), loco-regional recurrence-free survival (P<0.001), distance metastasis-free survival (P<0.001) and progression-free survival (P<0.001) than those with low ZNF488 group. Multivariate analysis showed that ZNF488 expression was an independent prognostic indicator for predicting NPC patients’ survival (HR, 3.314; 95% CI, 1.489–7.386; P=0.003). Additionally, ZNF488-induced collagen IV/ FAK/AKT to enhance adhesion ability meanwhile led to the upregulation of Cyclin D1 to facilitate cell proliferation through promoting cell cycle progression and inhibition of apoptosis through caspase-independent way. Conclusion: These results reveal that ZNF488, as an independent prognostic indicator, promotes cell adhesion and proliferation through collagen IV/FAK/AKT/Cyclin D1 pathway in NPC.

Background: ZNF488 acts as an oncogene which promotes cell invasion and endows tumor cells stem cell capacity in nasopharyngeal carcinoma (NPC), but its correlation with clinicopathologic characteristics and patients' survival in NPC remain undefined. Methods: In this study, 158 cases of confirmed NPC were subjected to immunohistochemistry staining for evaluating endogenous expression. Kaplan-Meier method and log-rank test were used to estimate the survival rates. The relationship between ZNF488 and clinicopathological characteristics was statistically calculated by chi-squared test, univariate and multivariate analysis. In addition, adhesion assay, MTT and colony formation assays were performed for measuring adhesion and proliferation capacity. Cell cycle analysis via flow cytometry was conducted to explore cell cycle distribution. Western blot was used to detect pathway protein levels, and the pFAK (Y397) kit was used for focal adhesion kinase (FAK) activation. Results: We demonstrated that high expression of ZNF488 was significantly correlated with locoregional failure (P=0.018) and distant metastasis (P=0.001). Patients with high ZNF488 expression had poorer overall survival (P<0.001), loco-regional recurrence-free survival (P<0.001), distance metastasis-free survival (P<0.001) and progression-free survival (P<0.001) than those with low ZNF488 group. Multivariate analysis showed that ZNF488 expression was an independent prognostic indicator for predicting NPC patients' survival (HR, 3.314; 95% CI, 1.489-7.386; P=0.003). Additionally, ZNF488-induced collagen IV/FAK/AKT to enhance adhesion ability meanwhile led to the upregulation of Cyclin D1 to facilitate cell proliferation through promoting cell cycle progression and inhibition of apoptosis through caspase-independent way. Conclusion: These results reveal that ZNF488, as an independent prognostic indicator, promotes cell adhesion and proliferation through collagen IV/FAK/AKT/Cyclin D1 pathway in NPC.

BACKGROUND:miR-203a-3p was reported as a tumor suppressor and disregulated in many malignancies including nasopharyngeal carcinoma (NPC). However, its function in tumor growth and metastasis in NPC has rarely been reported.METHODS:The expression level of miR-203a-3p in human NPC tissues and cell lines was detected via real-time PCR (RT-PCR). Cell proliferation, migration and invasion were assessed in vitro by MTT, colony formation and transwell assay, respectively. The function of miR-203a-3p in vivo was detected through NPC xenograft tumor growth and lung metastatic mice model. Dual-luciferase reporter assay was used to identify the direct target of miR-203a-3p.RESULTS:The expression of miR-203a-3p was decreased in NPC tissues and cell lines in comparison with normal nasopharyngeal tissues and cell line. Ectopic expression of miR-203a-3p inhibited while inhibiting miR-203a-3p expression increased NPC cell proliferation, migration and invasion in vitro. MR-203a-3p overexpression suppressed xenograft tumor growth and lung metastasis in vivo. LASP1 was identified as a direct target of miR-203a-3p, which was confirmed by real-time PCR and western blotting assay. Ectopic expression of LASP1 partially reversed miR-203a-3p-mediated inhibition on proliferation, migration and invasion in NPC cells.CONCLUSION:Collectively, miR-203a-3p suppresses tumor growth and metastasis through targeting LASP1 in NPC. The newly identified miR-203a-3p/LASP1 pathway provides further insights into the initiation and progression of NPC, which may represent a novel therapeutic target for NPC.

Objective To evaluate the treatment outcome, prognostic factors, radiation dose, and toxicities in patients with early-stage primary diffuse large B-cell lymphoma of Waldeyer's ring (WR-DLBCL) treated with intensity-modulated radiotherapy (IMRT).Methods This study included 80 patients with a confirmed diagnosis of stage Ⅰ-Ⅱ primary WR-DLBCL who were admitted to our hospital from 2008 to 2015.Only 3 patients received radiotherapy alone, and the other patients received radiotherapy and chemotherapy.After chemotherapy, 24 patients achieved complete remission (CR), and 53 patients achieved partial remission (PR).IMRT was given to the primary lesion and cervical lymphatic drainage region.Survival analysis was performed using the Kaplan-Meier method and log-rank test.The Cox model was used for analysis of prognostic factors.The toxicities were scored using the RTOG criteria.Results The median follow-up was 64 months.The 5-year locoregional control (LRC), overall survival (OS), and progression-free survival (PFS) rates were 94%, 88%, and 84%, respectively.The dose-volume histogram showed that the maximum, mean, and minimum doses to primary gross tumor volume were 54.47 Gy, 52.27 Gy, and 38.83 Gy, respectively.Prognostic analysis showed that age>60 years and increased lactate dehydrogenase (LDH) were influencing factors for OS (P=0.009 and 0.002), and that aged>60 years, IPI ≥2, and increased LDH were influencing factors for PFS (P=0.001, 0.035, and 0.007).Among all patients, 12, 53, and 8 experienced grade 1-3 radiation-induced acute oral mucositis, respectively, and 16 and 13 experienced grade 1 and 2 xerostomia as the late toxicity, respectively.Conclusions For patients with early-stage primary WR-DLBCL, IMRT results in satisfactory OS, PFS, and LRC and has tolerable early or late radiation-induced toxicities.

[目的]探讨局部晚期鼻咽癌患者治疗前血浆EBV-DNA水平与肿瘤负荷及预后的关系.[方法] 165例初治局部晚期鼻咽癌患者,均采用适形调强放射治疗(IMRT).收集患者治疗前EBV-DNA拷贝数水平及肿瘤靶区体积,并对患者生存结果进行随访总结.[结果]治疗前血浆EBV-DNA中位拷贝数3790copies/ml,鼻咽原发灶(GTV nx)、淋巴结病灶(GTVnd)及总GTV体积中位值分别为72.46、23.26、106.25cm3; EBV-DNA水平与GTVnd及总GTV体积显著相关(P＜0.01).治疗前血浆EBV-DNA表达阴性及阳性患者2年总生存率分别为100.0％和98.4％(P＞0.05),无病生存率94.4％和80.8％ (P＜0.05).[结论]局部晚期鼻咽癌患者治疗前血浆EBV-DNA水平与鼻咽癌患者颈部淋巴结转移负荷有关,治疗前血浆EBV-DNA表达阴性的患者无病生存率优于阳性患者.

This retrospective study aims to examine the association of plasma Epstein-Barr virus- (EBV-) DNA levels with the tumor volume and prognosis in patients with locally advanced nasopharyngeal carcinoma (NPC). A total of 165 patients with newly diagnosed locally advanced NPC were identified from September 2011 to July 2012. EBV-DNA was detected using fluorescence quantitative polymerase chain reaction (PCR) amplification. The tumor volume was calculated by the systematic summation method of computer software. The median copy number of plasma EBV-DNA before treatment was 3790 copies/mL. The median gross tumor volume of the primary nasopharyngeal tumor (GTVnx), the lymph node lesions (GTVnd), and the total GTV before treatment were 72.46, 23.26, and 106.25 cm(3), respectively; the EBV-DNA levels were significantly correlated with the GTVnd and the total GTV (P < 0.01). The 2-year overall survival (OS) rates in patients with positive and negative pretreatment plasma EBV-DNA were 100% and 98.4% (P = 1.000), and the disease-free survival (DFS) rates were 94.4% and 80.8% (P = 0.044), respectively. These results indicate that high pretreatment plasma EBV-DNA levels in patients with locally advanced NPC are associated with the degree of lymph node metastasis, tumor burden, and poor prognosis.

MiR-145 is downregulated and functions as a tumor suppressor in many malignancies. In this study, the biological function, molecular mechanism, and direct target genes of miR-145 in nasopharyngeal carcinoma (NPC) cells were investigated. Cell survival was detected by cell viability assay, and cell cycle was determined through flow cytometry. Invasion and migration of NPC cells were examined using cell invasion and wound healing assays, respectively. A disintegrin and metalloproteinase 17 (ADAM17) was verified as the target of miR-145 through luciferase reporter assay, qRT-PCR, and Western blot analysis. In NPC cell lines, miR-145 expression was significantly downregulated and ADAM17 protein expression was upregulated. ADAM17 was downregulated at the post-transcriptional level by miR-145 via the binding site of ADAM17-3′UTR. Transfection with miR-145 mimic suppressed cell growth and induced cell cycle arrest in the G0/G1 phase by upregulating key G0/G1 phase regulators, namely, p53 and p21. MiR-145 also inhibited cellular migration and invasion through targeting ADAM17 involving the regulation of EGFR and E-cadherin. Knockdown of ADAM17 elicited similar effects to that of miR-145 on NPC cells. This study reveals that miR-145 suppressed the invasion and migration of NPC cells by targeting ADAM17. Thus, miR-145 could be a therapeutic target for NPC.

This study aims to evaluate the radiosensitization effect of nedaplatin on nasopharyngeal carcinoma (NPC) cell lines with different Epstein-Barr virus (EBV) status. Human NPC cell lines CNE-2 (EBV-negative) and C666 (EBV-positive) were treated with 0-100 μg/mL nedaplatin, and inhibitory effects on cell viability and IC50 were calculated by MTS assay. We assessed changes in radiosensitivity of cells by MTS and colony formation assays, and detected the apoptosis index and changes in cell cycle by flow cytometry. MTS assay showed that nedaplatin caused significant cytotoxicity in CNE-2 and C666 cells in a time- and dose-dependent manner. After 24 h, nedaplatin inhibited growth of CNE-2 and C666 cells with IC50 values of 34.32 and 63.69 μg/mL, respectively. Compared with radiation alone, nedaplatin enhanced the radiation effect on both cell lines. Nedaplatin markedly increased apoptosis and cell cycle arrest in G2/M phase. Nedaplatin radiosensitized human NPC cells CNE-2 and C666, with a significantly greater effect on the former. The mechanisms of radiosensitization include induction of apoptosis and enhancement of cell cycle arrest in G2/M phase.

[目的]探讨ZNF488基因对鼻咽癌细胞HONE1生物学行为的影响.[方法]构建携带空载体、人ZNF488基因的逆转录病毒质粒pMSCV和pMSCV-ZNF488,以磷酸钙法转染293FT细胞并收集病毒液,感染鼻咽癌细胞株HONE1,经嘌呤霉素筛选及Western Blot鉴定,建立稳定表达ZNF488的HONE 1-pMSCV-ZNF488和空载体HONE 1-pMSCV的细胞株.应用噻唑盐(MTT)法、平板克隆形成实验检测ZNF488过表达对HONE1细胞生长增殖的影响,同时应用流式细胞术检测ZNF488对细胞周期增殖指数的影响.划痕实验及Transwell体外侵袭实验观察ZNF488对HONE1迁移侵袭能力的影响.Western Blot检测上皮—间质转化(EMT)相关蛋白及抑癌基因PTEN的表达情况.[结果]成功建立稳定表达ZNF488的HONE1-pMSCV-ZNF488细胞株,MTT法及平板克隆形成实验结果显示,与空载体组HONE1-pMSCV细胞相比,HONE1-pMSCV-ZNF488细胞增殖及克隆形成能力均增强.流式细胞术显示过表达ZNF488细胞S期百分比较空载体组高,增殖指数增加.划痕实验、Transwell体外侵袭实验示ZNF488能够显著增加细胞的迁移、侵袭能力.Western Blot检测发现上皮标志E-Cadherin、α-Catenin表达降低,间质性标志Fibronectin、Vimentin表达升高,同时抑癌因子PTEN表达下降.[结论]过表达ZNF488可通过诱导鼻咽癌细胞HONE1发生上皮间质转变及下调抑癌基因PTEN,促进细胞的增殖及迁移侵袭能力.

Purpose To evaluate the efficacy and toxicities of nedaplatin (NDP)-based chemotherapy concurrent with intensity-modulated radiotherapy (IMRT) in the treatment for patients with locally advanced nasopharyngeal carcinoma (NPC). Methods One hundred and sixty-six locally advanced NPC patients with stage Ⅲ to Ⅳa received IMRT concurrent with NDP-based chemotherapy.Simutaneous integrated boost (SIB) technique to a whole field encompassing nasopharyngeal carcinoma and full neck were used in IMRT. The total prescription dose according to the two processes of IMRT was 70Gy/32F to gross target volume to nasopharynx (GTVnx),66Gy/32F to positive neck lymph nodes (GTVnd),60Gy/32F to clinical target volume 1 with high risk of metastasis (CTV1),50.4Gy/28F to clinical target volume 2 with lower risk of metastasis(CTV2).Two courses of NDP-based chemotherapy were delivered during radiotherapy, each for 21 days. Concurrent NDP-based chemotherapy were divided into three groups: FP group (5-fluorouracil+NDP,n=58),TP group (taxol+NDP,n=62) and TFP group (taxol+5-fluorouracil+NDP,n=46). The efficacy and acute toxicities of each group were analyzed. Results All patients completed concurrent chemo-radiotherapy. With a median follow-up of 43 months, the 4-year overall survival rates (OS),local control (LC),regional control (RC),and distant metastasis-free survival(DMFS) were 81.5%,93.0%,98.2%,79.0% in FP group,81.7%,91.4%, 96.8%,82.0% in TP group,and 84.7%,90.8%,93.3%,81.9% in TFP group,respectively. However,no significant difference of OS (P=0.752),LC (P=0.961),RC (P=0.423) and DMFS (P=0.836) was observed in the three groups. The most common treatment-related toxicities includedmyelosuppression,gastrointestinal symptoms and oral mucositis. Those of grade Ⅲ ～ Ⅳ acute toxicities were 17.2%,22.6%,41.3% respectively,with significant difference in the three groups (P=0.016). The TFP group experienced more grade Ⅲ～Ⅳ acute toxicities in comparing to TP or FP group(P=0.037,P=0.007). Multivariate Cox regression analysis revealed that N-classification was an independent prognostic factor for OS(P=0.036) and DMFS (P=0.037).Conclusion IMRT concurrent with NDP-based chemotherapy provide favorable local control and OS with strong compliance and acceptable toxicities for locally advanced NPC. TFP regimen shows a similar efficacy with TP or FP regimens in tumor control and overall survival,but with an increasing acute toxicities incidence. N-classification is the main influencing factor of prognosis,distant metastasis remains the most difficult treatment challenge for patients with locally advanced NPC.

嗅神经母细胞瘤(ONB)是一种少见的来源于鼻腔、鼻窦嗅上皮的恶性肿瘤,局部侵袭性强,颈部淋巴结及远处转移发生率较高。由于其临床罕见性,目前尚无标准的治疗方案。手术联合放疗(和/或化疗)仍是提高ONB生存率的最有效的治疗手段。文章就嗅神经母细胞瘤的临床表现、病理及影像学特征以及诊断和治疗方面的研究进展进行综述。