Transcriptomic and Immunophenotypic Characterization of Tumor Immune Microenvironment in Squamous Cell Carcinoma of the Oral Tongue

The tumor immune microenvironment of oral tongue squamous cell carcinoma may be accountable for differences in clinical behavior, particularly between different age groups. We performed RNA expression profiling and evaluated tumor infiltrating lymphocytes (TILs) and their T-cell subsets in order to assess the functional status of oral tongue squamous cell carcinoma tumor microenvironment and detect potentially clinically useful associations. Archival surgical pathology material from sixteen oral tongue squamous cell carcinoma patients was microscopically evaluated for TIL densities. RNA was extracted from macrodissected whole tumor sections and normal controls and RNA expression profiling was performed by the NanoString PanCancer IO 360 Gene Expression Panel. Immunostains for CD4, CD8 and FOXP3 were evaluated manually and by digital image analysis. Oral tongue squamous cell carcinomas had increased TIL densities, numerically dominated by CD4 + T cells, followed by CD8 + and FOXP3 + T cells. RNA expression profiling of tumors versus normal controls showed tumor signature upregulation in inhibitory immune signaling (CTLA4, TIGIT and PD-L2), followed by inhibitory tumor mechanisms (IDO1, TGF-β, B7-H3 and PD-L1). Patients older than 44 years showed a tumor microenvironment with increased Tregs and CTLA4 expression. Immunohistochemically assessed CD8% correlated well with molecular signatures related to CD8 + cytotoxic T-cell functions. FOXP3% correlated significantly with CTLA4 upregulation. CTLA4 molecular signature could be predicted by FOXP3% assessed by immunohistochemistry (R² = 0.619, p = 0.026). Oral tongue squamous cell carcinoma hosts a complex inhibitory immune microenvironment, partially reflected in immunohistochemically quantified CD8 + and FOXP3 + T-cell subsets. Immunohistochemistry can be a useful screening tool for detecting tumors with upregulated expression of the targetable molecule CTLA4.Electronic supplementary materialThe online version of this article (10.1007/s12105-020-01229-w) contains supplementary material, which is available to authorized users.     

A comparison of the pro-inflammatory, NF-κB-dependent cytokines: TNF-alpha, IL-1-alpha, IL-6, and IL-8 in different oral fluids from oral lichen planus patients

To explore the feasibility of detection of the level of NF-κB-dependent cytokines in oral fluids from patient with oral lichen planus (OLP) for clinical application, 13 OLP subjects were enrolled in the study as were 13 age–sex-matched controls. In each subject, the whole unstimulated saliva (WUS), mixture of saliva and isotonic saline oral rinse (Saliva-NaCl), and lesion tissue transudates (TT) were collected by standard techniques. The level of cytokines, TNF-alpha, IL-1-alpha, IL-6, and IL-8 in three types of oral fluids was determined by ELISA. In the three types of oral fluids, a significantly higher level of these cytokines was detected in OLP patients than in normal controls. These results indicate that NF-κB-dependent inflammatory cytokines may be detected at increased levels in certain oral fluids which may have diagnostic and prognostic potential for monitoring disease activity and making therapeutic decisions in patients with OLP.     

正交偏光镜下人体胆汁液晶光学性质的研究

本文报导了在正交偏光镜下，对人体胆汁液晶的光学性质的研究，结果表明，胆汁液晶是一种非均质体，在正交偏光镜下，呈现出特殊的干涉图样和四次消光现象，光性符号是单轴正性的，干涉色级是一级灰白，双折射率Δｎ＝０．０１１－０．０１７。     

Copper-inhibition of the growth of oral streptococci and actinomyces

Copper ions were found to inhibit the rate of growth in broth culture of Streptococcus mitis, Streptococcus mutans, Streptococcus salivarious, Streptococcus sanguis, Actinomyces viscosus and Actinomyces naeslundii. In all cases, 10^?3 M copper inhibited the rate of growth, whereas 10^?4 M and lower concentrations had little or no effect. At the concentrations used in mouthwashes one mode of action of copper ions is to reduce the rate of growth of oral bacteria in vitro.     

口矫器治疗阻塞性睡眠呼吸暂停的机制及疗效预测

目的观察一种下颌前移性口矫器治疗阻塞性睡眠呼吸暂停(OSA)的疗效并探讨其治疗原理,探讨应用颌面结构分析法来预测口矫器的疗效。　方法70例经多导睡眠仪(PSG)检查确诊的OSA患者,男性63例,女性7例,平均年龄(50.5±11.6)岁,呼吸暂停指数(AI)(34.9±21.3)次/h,夜间最低血氧饱和度(66.3±16.5)%。经口腔科会诊后制作口矫器,治疗3个月后复查PSG检查。每例患者治疗前均在带及不带口矫器两种状态下摄头颅侧位片作颌面结构分析。　结果治疗后AI由(34.9±21.3)次/h减至(15.6±19.2)次/h(P<0.000 1),夜间最低血氧饱和度由(66.3±16.6)%升至(74.1±15.5)%(P<0.001)。共有45例患者AI减少≥50%。反应良好组患者缩颌较明显,前上面部长度较长,置入口矫器后下颌显著前突、上气道径增宽、长度缩短、上气道面积增大。　结论口矫器对部分OSA患者具有确切疗效,其治疗作用可能主要与改善睡眠期上气道周围结构关系,保持气道通畅有关。     

沙利霉素对口腔鳞癌细胞增殖和凋亡的影响

目的:探讨沙利霉素(salinomycin)对口腔鳞癌细胞增殖和凋亡的影响,并初步探讨沙利霉素对信号通路的影响。方法:培养口腔鳞状细胞癌细胞系CAL-27,将1、2、4、8、16、32 μmol/L沙利霉素和1.25、2.5、5、10、20、40、80 μmol/L顺铂与CAL-27细胞共同培养,24 h和48 h后用细胞计数试剂盒-8(cell counting kit-8,CCK-8)法检测沙利霉素和顺铂对CAL-27细胞增殖的影响;0、2、4、8 μmol/L沙利霉素和0、5、10、20 μmol/L顺铂与CAL-27细胞共培养48 h后,通过流式细胞术检测沙利霉素和顺铂对CAL-27细胞周期的影响,蛋白免疫印迹法(Western blot)检测CAL-27细胞中天冬氨酸特异性半胱氨酸蛋白酶-3(cysteine-containing aspartate-specific proteases-3,Caspase-3)、天冬氨酸特异性半胱氨酸蛋白酶-9(cysteine-containing aspartate-specific proteases-9,Caspase-9)、脱氧核糖核酸(deoxyribonucleic acid,DNA)修复酶(poly ADP-ribose polymerase,PARP)、蛋白激酶B(protein kinase B, Akt)和磷酸化蛋白激酶B (phosphorylated protein kinase B,p-Akt)的表达。结果:CCK-8实验表明沙利霉素和顺铂均能显著抑制口腔鳞状细胞癌CAL-27细胞增殖,且抑制作用呈时间依赖性和药物浓度依赖性,但是相对于临床一线化疗药物顺铂而言,沙利霉素对CAL-27细胞增殖的抑制效果更加显著(P<0.001)。细胞周期检测表明,与加入二甲基亚砜(dimethyl sulfoxide,DMSO)的对照组相比,8 μmol/L沙利霉素与CAL-27细胞共同培养48 h后,细胞休眠期/DNA合成前期的CAL-27细胞比例明显升高(40.40%±1.99% vs.64.46%±0.90%,P<0.05), DNA合成期和DNA合成后期/有丝分裂期的CAL-27细胞比例出现降低(24.32%±2.30% vs.18.73%±0.61%,P<0.05,35.01%±1.24% vs.16.54%±1.31%,P<0.05);顺铂对CAL-27细胞周期没有特异性改变。蛋白免疫印迹法结果显示,沙利霉素在上调CAL-27细胞中Caspase-3和 Caspase-9蛋白表达(P<0.05)的同时下调PARP、Akt和p-Akt蛋白的表达(P<0.05)。结论:相对于顺铂而言,沙利霉素对CAL-27细胞增殖有更强的抑制作用,并且能将口腔鳞状细胞癌CAL-27细胞周期阻滞在细胞休眠期/DNA合成前期,同时能够诱导CAL-27细胞发生凋亡,这一机制可能和Akt/p-Akt 信号通路相关。     

Mandibular invasion in oral cancers

Mandibular resection for oral cancers has significant aesthetic and functional sequelae. A reliable preoperative predictor of mandibular invasion is required to guide the need for and extent of mandibular resection. An orthopantomogram of the mandible is an accurate, reliable, cost-effective predictor of bony involvement except for central arch lesions. The feasibility of outer table rim mandibulectomy alone in patients with floor of mouth tumors needs to be examined carefully. Received: 11 December 1998 / Accepted: 7 October 1999     

口腔肿瘤恶变与唾液蔗糖酶活性的相关性研究

目的 :探讨唾液蔗糖酶活性与口腔肿瘤恶变之间的相互关系。方法 :采用邻甲苯胺测糖法 ,测定单位时间内唾液蔗糖酶水解蔗糖生成的葡萄糖量 ;在PH6 ,37℃条件下进行酶反应用双倒数作图法测出表观Km和表观Vm值 ;检测蔗糖酶活性。结果 :正常人唾液蔗糖酶活性为 1 32 2± 0 434mU/mgpro ,口腔鳞癌患者唾液蔗糖酶活性为 1 5 48± 0 6 5 7mU/mgpro ,二者之间比较无显著差异 (P >0 0 5 ) ;正常人唾液蔗糖酶的表观Km =(1 1 2± 2 4)× 1 0 -2 mol/L ,表观Vm =1 1 38± 0 35 2 (每分钟光密度值 ) ,口腔鳞癌患者唾液蔗糖酶的表观Km =(9 5±2 2 )× 1 0 -2 mol/L ,表观Vm =(1 0 89± 0 6 32 ) (每分钟光密度值 )。结论 :口腔良性肿瘤、涎腺腺瘤、口腔鳞癌患者与正常人比 ,唾液蔗糖酶活性无显著差异。     

VEGF—C mRNA在口腔鳞癌中的表达

目的：探讨血管内生长因子－Ｃ（ＶＥＧＦ－Ｃ）ｍＲＮＡ在正常口腔粘膜、白斑及鳞癌等组织中的表达。方法：ＴＲ－ＰＣＲ法检测ＶＥＧＦ－Ｃ ｍＲＮＡ的表达。结果：鳞癌组织ＶＥＧＦ－Ｃ ｍＲＮＡ表达明显高于正常口腔粘膜及白斑（Ｐ〈０．０１）;鳞癌表达与病理分级（Ｐ〈０．０１）、淋巴结转移（Ｐ〈０．０１）密切相关,与临床分期无关（Ｐ〉０．０５）。结论：ＶＥＧＦ－Ｃ对鳞癌生长及转移有促进作用,有望作为检测淋巴管