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.     

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.     

细胞凋亡指数在口腔鳞状细胞癌中的变化

目的 探讨细胞凋亡与口腔鳞状细胞癌(OSCC)预后之间的关系.方法 由活检或外科手术获得诊断的OSCC组织标本经末端脱氧核苷酸转移酶介导的UTP缺口标记(TUNEL)染色以鉴定凋亡细胞,并由阳性细胞百分比表示细胞凋亡指数(AI).结果 化疗后AI显著升高(P＜0.01).虽然未经治疗病例AI在活检组织和外科手术切除组织间没有发生显著变化,但AI的升高与良好预后有关(P＜0.05).结论 AI的升高有可能作为判断未经治疗OSCC患者预后的有用指标.     

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.     

CD147和MMP-2在口腔鳞状细胞癌中的表达及意义

目的:研究口腔鳞状细胞癌(OSCC)中基质金属蛋白酶诱导因子(CD147)和基质金属蛋白酶-2(MMP-2)的表达及意义.方法:采用免疫组化SP法对35例口腔鳞状细胞癌组织中CD147和MMP-2的表达及相关性进行分析.结果:CD147和MMP-2在OSCC组织中高表达,阳性表达率分别为65.71％、68.57％;二者...     

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。     

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。     

口腔鳞癌中Cyclin D1和Bcl-2蛋白表达相关性的研究

目的研究Cyc lin D1和Bc l-2在口腔鳞癌组织和正常口腔粘膜中的表达及意义。方法用免疫组织化学S-P法对62例口腔鳞癌手术切除标本和10例正常口腔粘膜标本中Cyc lin D1和Bc l-2基因蛋白的表达情况进行检测。结果口腔鳞癌组织中Cyc lin D1表达率67.7%(42/62),正常口腔粘膜组织中未见表达,两组间差异有显著性(P<0.05);Bc l-2在正常口腔粘膜组织中也未见表达,在癌组织中Bc l-2蛋白阳性表达率58.1%(36/62),两组间差异也有显著性(P<0.05)。结论Cyc lin D1和Bc l-2两种蛋白在癌组织中存在过表达,口腔鳞癌组织中Cyc lin D1与Bc l-2的表达呈正相关。过表达的Cyc lin D1与Bc l-2可作为评价口腔鳞癌组织分级的参考指标之一。     

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.     

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。     

STAT-3抑制剂WP1066增强顺铂对口腔鳞状细胞癌侵袭能力抑制作用的体外研究

目的 探讨信号转导及转录激活因子 3 （STAT-3） 调控 miR-21 增强化疗药物顺铂抑制人口腔鳞状细胞癌侵袭能力的作用。方法 实验共分 3 组： 二甲基亚砜组 （DMSO 组）、 顺铂组 （DDP 组）、 小分子抑制剂+顺铂组（WP1066+DDP 组）。实时定量 PCR 检测 miR-21 表达水平; Western blot 检测 STAT-3 及 p-STAT-3、 基质金属蛋白酶组织抑制因子 3 （TIMP-3）、 基质金属蛋白酶 2/9 （MMP-2/9） 的表达; 用 Matrigel 基质生长实验和 Transwell 体外侵袭实验检测肿瘤细胞生长形成球形克隆、 侵袭能力; 荧光素酶报告基因实验检测 miR-21 的表达水平。结果 WP1066+DDP 处理组的 STAT3/pSTAT-3 表达水平比 DDP 组低; WP1066+DDP 组 miR-21 表达比前两组低; 通过 Transwell 小室聚碳酸酯膜的细胞数 WP1066+DDP 组少于 DDP 组; WP1066+DDP 组细胞生长形成球的能力明显较 DDP 组减弱; TIMP-3 蛋白表达较前两组升高; MMP-2/9 表达水平较前两组明显下调。荧光素酶实验证明 WP1066+ DDP 组的荧光素酶活性明显低于 DDP 组和 DMSO 组。结论 通过抑制舌癌细胞中 STAT-3 活性, 下调 miR-21 表达, 可以增强化疗药物抑制口腔鳞状细胞癌的侵袭能力, 为使 WP1066 联合 DDP 化疗成为靶向治疗人口腔鳞状细胞癌提供了实验依据。     

PIK3 CA rs4975596基因多态性与口腔癌的相关性研究

目的 探讨PIK3CA rs4975596单核苷酸多态性与口腔癌发生的相关性。方法 应用聚合酶链反应检测PIK3CA rs4975596基因多态性,比较口腔癌组与健康人群PIK3CA rs4975596基因型的分布频率差异以及等位基因频率差异。结果 50例口腔癌组和50例健康人群对照组PIK3CA rs4975596基因型分布频率野生型AA分别为52%和68%,杂合型AG分别为28%和24%,突变型GG分别为20%和8%,两组比较差异有统计学意义(χ²=7.073,P=0.029);等位基因频率野生型A分别为65%和76%,突变型G分别为35%和24%,两组比较差异有统计学意义(χ²=5.360,P=0.024)。口腔癌组与健康人群对照组PIK3CA rs4975596基因型分布频率和等位基因频率差异有统计学意义。结论 口腔癌的发生可能与PIK3CA rs4975596基因型多态性具有某种关联。     

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。     

Survivin在人口腔黏膜白斑和鳞状细胞癌中表达的研究

目的　探讨Survivin在口腔黏膜白斑和鳞状细胞癌组织中的表达及意义以及与口腔鳞状细胞癌发生发展的关系。方法　采用免疫组织化学方法检测口腔正常黏膜 (10例 ) ,口腔黏膜白斑 (34例 )和鳞状细胞癌(2 7例 )中Survivin的表达。结果　正常黏膜组中未见Survivin表达 ;异常增生性白斑组和鳞状细胞癌组中发现Survivin的表达 ,但表达强度不同。三组之间差异具有显著性 (P <0 .0 5 )。在异常增生性白斑组 ,随异常增生程度的增加 ,Survivin的表达逐渐增强 (P <0 .0 5 )。鳞状细胞癌中Survivin表达随细胞分化程度降低而表达增强 (P <0 .0 5 )。结论　Survivin的表达与细胞的增殖的分化有关 ,Survivin的表达水平增高是口腔黏膜白斑恶变发生发展中的早期事件 ,在鳞状细胞癌的发生发展中起着十分重要的作用 ,可以将其作为预测口腔黏膜白斑恶变潜能的重要标志物。     

XIAP inhibitor embelin induces autophagic and apoptotic cell death in human oral squamous cell carcinoma cells

Embelin is an active ingredient of traditional herbal remedies for cancer and other diseases. Recently, it has been suggested that autophagy may play an important role in cancer therapy. However, little data are available regarding the role of autophagy in oral cancers. Therefore, we conducted this study to examine whether Embelin modulates autophagy in Ca9‐22. Our results showed that Embelin had anticancer activity against the Ca9‐22 human tongue squamous cell, and we observed that autophagic vacuoles were formed by MDC and AO. We also analyzed Embelin‐treated Ca9‐22 cells for the presence of biochemical markers and found that it directly affected the conversion of LC3‐II, the degradation of p62/SQSTM1, full‐length cleavage formation of ATG5‐ATG12 complex and Beline‐1, and caspase activation. Rescue experiments using an autophagy inhibitor showed Embelin‐induced cell death in Ca9‐22, confirming that autophagy acts as a pro‐death signal. Furthermore, Embelin exhibited anticancer activity against Ca9‐22 via both autophagy and apoptosis. These findings suggest that Embelin may potentially contribute to oral cancer treatment and provide useful information for the development of a new therapeutic agent.     

miR-29a对口腔鳞癌细胞增殖、迁移和侵袭的影响

目的 以PIK3R2为靶点,探讨miR-29a介导的PI3K/Akt信号通路对口腔鳞癌SCC-9细胞增殖、迁移和侵袭的影响.方法 以RT-PCR法检测miR-29a在SCC-9细胞中的表达.以MTT法、细胞划痕实验、Transwell法和Western blot检测SCC-9细胞的增殖、迁移、侵袭和蛋白表达水平.结果 ...     

Targeting DSG3: from pemphigus to squamous cell carcinoma

Desmosomes are specialized structures of the cell membrane that are crucial for the establishment and maintenance of cell–cell adhesion and tissue integrity. Transmembrane proteins of desmosomes, desmogleins, and desmocollins are responsible for extracellular binding and, thus, are important for interkeratinocyte cohesion. Desmoglein 3 (DSG3) is a member of the desmoglein subfamily of cadherin cell adhesion molecule superfamily. It is mainly expressed in stratified epithelia, including the basal and suprabasilar epidermal layers and throughout the oral epithelium layers. In the human autoimmune blistering disease pemphigus vulgaris, autoantibodies against DSG3 cause loss of cell–cell adhesion (acantholysis) with resultant epidermal and mucosal blisters. More recently, a potential role of desmosomes in cancer development has been hypothesized. To this regard, several investigations have focused on the possible contribution of DSG3 in carcinogenesis. In this article, the role of DSG3 in the process of squamous cell carcinogenesis and the controversies concerning this issue will be discussed.     

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.     

口腔鳞癌E-cadherin表达与淋巴结转移的相关性分析

目的: 检测粘附分子E-cadherin 的表达与口腔鳞癌淋巴结转移的关系.方法: 应用免疫组织化学方法,检测40 例口腔鳞状细胞癌标本中E-cadherin 的表达.结果: E-cadherin 在正常粘膜及口腔癌中呈不同程度表达,染色程度与淋巴结转移之间有显著的相关性.结论: 伴有淋巴结转移的口腔鳞癌中E-cadherin的表达明显低于无淋巴转移者, E-cadherin的表达可作为预测口腔鳞癌淋巴结转移、判断预后的一项指标.