熊果酸对口腔鳞状细胞癌Tca8113细胞周期及凋亡的实验研究

目的探讨熊果酸对口腔鳞状细胞癌(Tca8113)的生长抑制情况及其对细胞周期和凋亡的作用。方法用浓度0、10、20、30、40、50μmol/L的熊果酸对口腔鳞状细胞癌进行干预,MTT法检测细胞增殖活性,流式细胞仪分析细胞周期,Annexin-V-FITC/PI双染流式细胞仪定量检测细胞凋亡。结果 (1)熊果酸对Tca8113细胞的增殖抑制具有时间--剂量依赖性,各实验组细胞增殖抑制率与对照组比较差异具有统计学意义(P<0.05)。(2)各浓度组熊果酸将细胞阻滞于S期,浓度30、40、50μmol/L的熊果酸总凋亡率分别为30.76%、43.77%及70.15%,与对照组比较差异有统计学意义(P<0.05)。结论熊果酸在体外抑制口腔鳞状细胞癌生长,呈时间--剂量依赖性,并阻滞细胞周期,促进细胞凋亡。     

Twist蛋白在口腔鳞状细胞癌中的表达及意义

目的检测Twist蛋白在口腔鳞状细胞癌(oral squamous cell carcinoma,OSCC)中的表达及与其临床病理学指标的关系。方法应用免疫组织化学S-P法检测Twist蛋白在69例OSCC组织及16例正常口腔黏膜组织中的表达。检测结果采用SPSS17.0软件进行统计学分析。结果在69例OSCC中,Twist阳性表达率71.01%;在正常口腔黏膜组织中其阳性表达率为0%,二者比较差异有统计学意义;Twist在OSCC中的表达与不同肿瘤分期、有无淋巴结转移有关;而其表达与患者性别、年龄、肿瘤分化程度无关。结论 Twist蛋白表达与OSCC的不同肿瘤分期和淋巴结转移有关。     

E-钙粘蛋白在口腔鳞状细胞癌中的表达及意义

目的 观察E-钙粘蛋白在口腔鳞状细胞癌中的表达.方法 运用SP免疫组织化学法进行试验,检测E-钙粘蛋白在口腔鳞状细胞癌中的表达及与口腔鳞状细胞癌组织学分级的关系.结果 E-钙粘蛋白在正常黏膜与口腔鳞癌中的表达差异有统计学意义(P<0.05),且其表达均与鳞癌的组织学分级具有相关性(P<0.05).结论 E-钙粘蛋白的异常表达在口腔鳞状细胞癌的发生发展中起一定作用.     

Smac蛋白在口腔白斑转化为口腔鳞状细胞癌的作用

目的探究Smac蛋白在口腔白斑转化为口腔鳞状细胞癌过程中的作用。方法对所选取的标本进行Smac蛋白染色时,采用免疫组化技术SP法,同时统计其阳性率,并进行分析和比较。结果 Smac蛋白在口腔正常黏膜及不同病变的表达,经统计学分析,随着组织异常程度的增加,Smac蛋白阳性表达强度具有递减的趋势(P<0.05)。结论 Smac蛋白随着组织异常程度的增加有逐渐下降的趋势,提示Smac蛋白的低表达可能对OLK癌变的发展起重要作用。     

FXYD-3蛋白在口腔鳞状细胞癌中的表达及临床意义

目的探讨FXYD-3（Mat-8）蛋白在口腔鳞状细胞癌中的表达及其临床病理意义。方法采用免疫组化的方法检测20例正常口腔黏膜组织和57例口腔鳞状细胞癌组织中FXYD．3蛋白的表达并分析其临床意义。结果FXYD-3蛋白在口腔鳞状细胞癌中的阳性表达率为37％（21／57）,明显高于正常口腔黏膜组织中阳性表达率10％（2／20）（P〈0．05）。FXYD-3蛋白的表达与患者性别、年龄、肿瘤大小、组织学分级和淋巴结转移情况均无相关性（P〉0．05）。结论FXYD-3蛋白在口腔鳞状细胞癌中的表达上调,可能只是口腔鳞状细胞癌发生阶段的一个早期事件,与肿瘤的浸润转移可能关系不大。     

口腔鳞状细胞癌组织中的PD-L1表达及其临床意义

目的:检测口腔鳞状细胞癌(OSCC)组织中的程序性死亡分子配体1(PD-L1)的表达水平,并探讨其临床意义.方法:选取我院病理科2014-06～2015-01存档的OSCC患者病理组织石蜡标本89例(实验组)和正常口腔黏膜组织标本10例(对照组)为研究对象.采用免疫组化Sp法检测癌组织和正常组织中PD-L1的阳性表达,...     

错配修复基因hMLH1在口腔鳞状细胞癌中的表达及意义

目的 探讨错配修复基因hMLH1在口腔鳞状细胞癌组织中的表达及意义.方法 采用免疫组化法检测69例口腔鳞状细胞癌和40例正常口腔黏膜组织中hMLH1的表达情况.结果 口腔鳞状细胞癌组织中hMLH1的阳性表达率47.8％低于正常口腔黏膜组织77.5％,差异有统计学意义(P＜0.05).结论 hMLH1可能在口腔鳞状细胞癌...     

口腔鳞状细胞癌术前TPF化疗患者的护理

目的 探讨TPF化疗方案在口腔癌治疗中的临床应用及常见的毒副反应,总结TPF化疗方案治疗的护理要点及并发症的防治.方法 我科2009年4月至2010年6月期间共有14例口腔鳞状细胞癌患者术前进行TPF化疗.均严格按化疗程序进行化疗前预处理,掌握用药方法并合理安排用药时间,严密观察化疗药物的毒副反应并采取积极有效的护理措施.结果 14例患者中,其中出现食欲不振7例,恶心不适6例,呕吐5例,腹部不适5例.胸闷憋气、乏力2例.出现皮肤瘙痒、皮疹3例,无并发过敏性休克.静脉炎3例,无并发皮肤溃烂、坏死.结论 TPF化疗方案治疗口腔癌过程中,应重视患者的心理护理,合理安排用药,加强化疗药物毒副反应的观察和护理,可有效减少并发症的发生,减轻不良反应,有助于化疗的顺利完成.     

Enhancement of cisplatin induced apoptosis by suberoylanilide hydroxamic acid in human oral squamous cell carcinoma cell lines

Both the resistance of tumor cells to cisplatin and dose-related toxicity remain two of the most important problems in the chemotherapy of clinical oral squamous cell carcinoma (OSCC). Researchers have been seeking a combinative treatment regimen to improve the effect of chemotherapy. As potent new anti-cancer drugs, histone deacetylase inhibitors (HDACI(S)) have been reported to be associated with chromatin modification and display synergistic activities with some traditional chemotherapeutic agents. In this study, we evaluated the potential combinative effect of low dose cisplatin and suberoylanilide hydroxamic acid (SAHA, one of the most potent HDACI(S)) in OSCC cell lines. Cell viability and apoptotic assay were examined. Compared with either cisplatin (4 microg/ml) or SAHA (2 microM) treated alone, co-administration of both drugs synergistically induces cytotoxicity and apoptosis in both Tca8113 and KB cell lines. Furthermore, diverse apoptosis-associated proteins, including p53, BID, cytochrome C and caspase-3 were involved in the induction of apoptosis. Our results suggest that concurrent treatment with SAHA enhances tumor cell sensitivity to subtoxic doses of cisplatin. This may be regarded as a novel strategy for treatment of OSCC.     

AURKA基因在口腔鳞癌中的表达及意义

目的 检测极光激酶A(AURKA)基因在口腔鳞癌中的表达及意义.方法 收集20例口腔正常组织及42例口腔鳞状细胞癌(OSCC)组织,采用Real-Time PCR检测AURKA基因在不同口腔组织中的表达.结果 AURKA mRNA在OSCC中高表达,且不同分化程度,不同临床分期,组间差异有统计学意义.不同年龄,不同性别,组间差异无统计学意义.结论 AURKA在OSCC中高表达,AURKA作为激酶可能直接或间接地激活多种致癌蛋白或使多种抑癌蛋白失活,从而推动肿瘤的发生发展.     

口腔鳞癌预后及复发的临床病理影响因素分析

目的：探讨口腔鳞癌预后及复发的临床病理影响因素。方法口腔鳞癌患者40例,对所有患者在手术治疗后3年内进行随访,观察患者预后效果。结果所有患者均成功获得随访,除了年龄因素（χ2=2.30,P〉0.05）和病灶位置（χ2=1.22,P〉0.05）因素之外,病理分级结果（χ2=6.68,P〈0.05）、淋巴结转移情况（χ2=12.21, P〈0.05）等因素均是影响口腔鳞癌治疗预后的因素。结论低分化、术前已经出现淋巴结转移的口腔鳞癌患者具有较差的治疗预后,在治疗计划的拟定过程中需加强治疗。     

Silmitasertib-induced macropinocytosis promoting DDP intracellular uptake to enhance cell apoptosis in oral squamous cell carcinoma

Cisplatin (DDP) is a first-line chemotherapeutic drug applied for the treatment of oral squamous cell carcinoma (OSCC). The anticancer activity of DDP is tightly linked to its intracellular uptake. It is unwise to increase the DDP intake by increasing the dose or shortening the dosing interval because of the severe systemic toxicity (nephrotoxicity, ototoxicity and neurotoxicity) in DDP application. The main uptake pathways of DDP include passive diffusion and active transporter transport. Therefore, finding additional uptake pathways that can improve the effective intracellular concentration of DDP is critical. Macropinocytosis, an endocytic mechanism for extracellular material absorption, contributes to the intracellular uptake of anticancer drugs. No research has been conducted to determine whether macropinocytosis can augment the intracellular uptake of DDP in OSCC cells or not. Based on that, we proved for the first time that silmitasertib (previously CX-4945) could trigger macropinocytosis, which may increase the intracellular uptake of DDP and enhance apoptosis via in vivo and in vitro experiments. We hope that our findings will inspire a new approach for the application of DDP in cancer treatment.     

口腔鳞癌中MMP-2表达及其意义

目的 研究MMP-2蛋白在口腔正常黏膜、上皮异常增生及口腔鳞癌中的表达状况,探讨其在（squamous carcinoma,OSCC）发生发展过程中的作用及意义,为OSCC的临床诊断、治疗、预后以及生物学评估提供新的思路和理论依据。方法 选择58例口腔鳞癌组织、15例口腔粘膜上皮异常增生组织和11例正常口腔黏膜组织,应用PV-9000两步免疫组织化学染色法检测MMP-2蛋白的表达情况。结果 MMP-2在正常黏膜、上皮异常增生口腔黏膜、鳞癌三组的阳性率分别为18.18%、26.67%、100%,三组总体差异及组间差异均有统计学意义（P〈0.05）。在OSCC组,高、中、低分化三组的强阳性率分别为8.00%、47.62%、58.33%,三组间总体比较有显著性差异（P〈0.05）。在OSCC组,按年龄、性别、瘤体大小等分组间比较MMP-2表达无显著性差异（P〉0.05）;在按有无淋巴结转移、临床分期以及分化程度等分组间比较MMP-2的表达差异有显著性差异（P〈0.05）。结论 在OSCC中,MMP-2的表达随着肿瘤分化程度降低而增高,而有淋巴结转移的肿瘤,MMP-2的表达明显增高。MMP-2在口腔鳞癌中的表达与患者的年龄、性别及临床分期无明显相关性。     

环氧化酶2和Ki-67在口腔鳞状细胞癌中的表达及相关性研究

目的 研究Ki-67和环氧化物酶2(COX-2)在口腔鳞状细胞癌中的表达及相互关系.方法 采用免疫组化方法检测28例口腔扁平苔藓组织(15例单纯扁平苔藓、13例伴异常增生)、28例口腔鳞状细胞癌组织及15例正常口腔黏膜组织中Ki-67、COX-2的表达.结果 COX-2在正常口腔黏膜组织中不表达、Ki-67组织仅为低表达或不表达;口腔鳞状细胞癌组、单纯增生组和异常增生组COX-2和Ki-67的高表达率明显高于正常口腔黏膜组[COx-2分别为64.3％ (18/28)、33.3％ (5/15)、30.8％ (4/13)比0(0),67.9％(19/28)、26.7％ (4/15)、30.8％ (4/13)比0(0),均P＜0.01],口腔鳞状细胞癌组COX-2和Ki-67的高表达率明显高于单纯增生组和异常增生组(均P ＜0.01).口腔鳞状细胞癌中COX-2的表达阳性率为85.7％(24/28),Ki-67为85.7％(24/28);二者表达呈正相关(r=0.8,P＜0.05).结论 Ki-67和COX-2在口腔鳞状细胞癌发生、发展中起着重作用,二者表达呈正相关,在口腔鳞癌的发生发展中有协同作用.     

CD44v6在口腔鳞癌中的表达及其临床意义

目的观察CD44拼接变异体6（CD44 splice variant 6,CD44v6）在口腔鳞癌中的表达并探讨其临床意义。方法采用免疫组化SP法检测50例口腔鳞癌组织和10例正常口腔粘膜组织中CD44v6的表达,并根据患者的病理特征分析CD44v6的表达情况,探讨CD44v6的表达与患者临床病理特征之间的关系。结果口腔鳞癌组织中CD44v6的阳性表达率为68.00%,显著高于正常粘膜组织中CD44v6的阳性表达率（20.00%）;CD44v6蛋白的阳性表达与肿瘤对邻近组织的浸润深浅程度和组织学分级显著相关（P〈0.05）,但与患者的年龄和肿瘤的原发部位无关。结论 CD44v6的表达上调可能在口腔鳞癌的浸润过程中发挥重要作用。     

晚期肺鳞癌血清鳞癌相关抗原检测的临床意义

目的：探讨晚期肺鳞癌血清鳞癌相关抗原(SCC-Ag)检测的临床价值。方法80例肺癌患者为研究对象,其中鳞癌50例,腺癌14例,小细胞肺癌(SCLC)11例,大细胞肺癌(LCLC)5例,另选45例良性病变患者,对所有患者进行SCC-Ag检测。结果肺鳞癌阳性率为68.00%,肺腺癌阳性率14.29%, SCLC阳性率18.18%, LCLC阳性率20.00%,对照组2.22%。经手术前后动态观察显示,根治术后SCC-Ag可在3 d内转阴,与其他术式比较差异有统计学意义(P<0.05)。结论SCC-Ag为肺鳞癌特殊标记物,是对患者手术效果与远期预后进行预测的重要参考指标。     

Histone deacetylase inhibitors in oral squamous cell carcinoma treatment

Introduction: The involvement of the histone deacetylases (HDACs) family in tumor development and progression is well demonstrated. HDAC inhibitors (HDACis) constitute a novel, heterogeneous family of highly selective anticancer agents that inhibit HDACs and present significant antitumor activity in several human malignancies, including oral squamous cell carcinoma (OSCC).

Areas covered: This review summarizes the current research on the anticancer activity of HDACis against OSCC. The review also presents the molecular mechanisms of HDACis action and the existing studies evaluating their utilization in combined therapies of OSCC.

Expert opinion: The currently available data support evidence that HDACis may provide new therapeutic options against OSCC, decreasing treatment side effects and allowing a more conservative therapeutic approach. Future research should be focused on in vivo and clinical evaluation of their utilization as combined therapies or monotherapies. Before HDACis can be brought into clinical practice as treatment options for OSCC, further evaluation is needed to determine their optimal dosage, the appropriate duration of treatment and whether they should be used in combination or as stand-alone therapeutics.     

Resveratrol inhibits oral squamous cell carcinoma cells proliferation while promoting apoptosis through inhibition of CBX7 protein

As a natural compound, resveratrol (Res) is confirmed to be promising drug for the treatment of malignant tumors. Therefore, our study aimed to observe the impacts of Res on the proliferation and apoptosis of oral squamous cell carcinoma cells (HSC‐3 cells) as well as the mechanism involving chromobox protein homolog 7 (CBX7) signal transduction. HSC‐3 cells were treated with Res, Akt agonist (AL3818) and p16 inhibitor (SC79), and transfected with CBX7 mimics and inhibitor plasmids. The CCK‐8 assay was used to detect cell proliferation, flow cytometry was performed to assess cell cycle and apoptosis, and cell colonies and histone DNA level were also measured. Western blot analysis was used to determine the expression levels of related proteins. HSC‐3 cells showed decreased cell proliferation, colonies, BrdU‐counled cells and increased apoptosis, histone DNA level, the activities of caspase‐3 and caspase‐9 when treated with Res. Western blot analysis revealed elevated Cle‐PARP and Cle‐caspase 3 expression and reduced t‐PARP expression in HSC‐3 cells treated with Res compared with control. AL3818 and SC79 could decrease the inhibitory effects of Res on the growth of HSC‐3 cells. Furthermore, CBX7 overexpression could also partly reverse the roles of Res in the growth of HSC‐3 cells, and Akt and p16 signal transduction. Our results demonstrate that Res suppresses the proliferation, and induces the apoptosis of oral squamous cell carcinoma cells through the inhibition of CBX7/Akt and the activation of p16 cascades.