Photodynamic therapy of oral leukoplakia and orallichen planus using methylene blue:A pilot study

Premalignant lesions like oral lichen planus(OLP),oral leukoplakia(OL)has a fair probability of transforming into malignancy and they are perverse toward conventional therapies.Photody-namic therapy(PDT)has been considered as an alternative/complimentary therapeutic mo-dality for the management of premalignant lesions.In this study,methylene blue mediated photodynamic therapy(MB-PDT)was used as a possible alternative method for the treatment of OLP and OL.A total of 15 OLP lesions and 13 OL lesions were enrolled in the study.The patients were irradiated 1using metal halide lamp filtered at 630土10nm,with a light exposure dose of 120 J/cm^(2) per stting.For the OLP lesions,MB-PDT was performed once a week for four weeks and for the OL lesions,MB-PDT was performed twice a week for three weeks.Lesions were evaluated pre-and post-and at follow-u sessions by changes in sign and symptom scores,and size of lesions.We have observed a 53.3%of complete reduction in the treated OLP lesions and their decrease in size,sign and symptom score after treatment and at follow-up session was statistially signifcant.We have also observed complete response for one OL lesion of the 13 treated lesions.The result indicates that MB-PDT is an effective modality in management of OLP and OL.Among the two types of premalignancies treated with MB-PDT,OLP lesions responded much better than that of OL.

Upregulation of epidermal growth factor receptor 4 in oral leukoplakia

In the present study,we investigate the expression profile of the epidermal growth factor receptor family,which comprises EGFR/ ErbBl,HER2/ErbB2,HER3/ErbB3 and HER4/ErbB4 in oral leukoplakia(LP).The expression of four epidermal growth factor receptor (EGFR) family genes and their ligands were measured in LP tissues from 14 patients and compared with levels in 10 patients with oral lichen planus(OLP) and normal oral mucosa(NOM) from 14 healthy donors by real-time polymerase chain reaction(PCR) and immunohistochemistry.Synchronous mRNA coexpression of ErbBl,ErbB2,ErbB3and ErbB4 was detected in LP lesions.Out of the receptors,only ErbB4 mRNA and protein was more highly expressed in LP compared with NOM tissues.These were strongly expressed by epithelial keratinocytes in LP lesions,as shown by immunohistochemistry.Regarding the ligands,the mRNA of Neuregulin2 and 4 were more highly expressed in OLP compared with NOM tissues.Therefore,enhanced ErbB4 on the keratinocytes and synchronous modulation of EGFR family genes may contribute to the pathogenesis and carcinogenesis of LP.

Critical review of topical management of oral hairy leukoplakia

Oral hairy leukoplakia(OHL) is a disease associated with Epstein-Barr virus and human immunodeficiency virus infections. OHL is usually an asymptomatic lesion, but in some cases treatment is recommended to reestablish the normal characteristics of the tongue, to eliminate pathogenic microorganisms, to improve patient comfort and for cosmetic reasons. Proposed treatments for this condition include surgery, systemic antiviral treatment and topical management. Topical treatment is an inexpensive and safe therapy that is easy to apply, noninvasive, free of systemic adverse effects and effective over a long period of time. The aim of this study was to present a review of the literature for topical therapy for OHL. Gentian violet, retinoids, podophyllin, acyclovir and podophyllin associated with topical antiviral drugs were used to treat OHL. Reports with this focus are limited, and since 2010, no new studies have been published that discuss the efficacy of topical treatments for OHL. Podophyllin with acyclovircream was found to be effective, causing regression of lesions with no recurrences. Additional searches are necessary to provide clinical evidence of topical man agement effectiveness.

C-Ha-ras Oncogene in Oral Leukoplakia Tissues

The amplification and the G-T mutation at codon 12 of the C-Ha-ras oncogene in oral leukoplakia tissues were analyzed by using polymerase chain reaction (PCR) and molecular biologic technique. The results showed that these tissues had no amplification of Ha-ras oncogene. Only one case harbored G-T mutation in 11 oral leukoplakias, but this mutation was absent in 10 normal oral mucosal tissues. The possible role and significance of C-Ha-ras oncogene in oral precancerous lesions were also discussed.

光动力疗法治疗口腔白斑的研究进展

口腔白斑(oral leukoplakia, OLK)指发生于口腔黏膜上不能被擦去、也不能以临床或组织病理学方法诊断为其他可定义的疾病的白色损害,是一种口腔黏膜癌前病变。现有治疗OLK的方法中,非手术治疗如药物治疗缺乏其防止OLK恶性转化和复发的确切证据;而手术治疗则存在适应证窄、术后口腔形态及功能受损等不足;光动力疗法(photodynamic therapy, PDT)是一种现代的非侵入性疗法,可用于治疗包括口腔白斑在内的各种肿瘤及非肿瘤病变,由于其良好的组织形态及功能保存潜能,现已成为治疗口腔白斑的一种新型且前景广阔的治疗选择。该文就PDT治疗口腔白斑应用的光敏剂、光源及其辅助治疗手段作一综述。

中医药治疗口腔黏膜白斑的研究进展

口腔黏膜白斑(Oral leukoplakia,OLK)是一种主要发生于颊、舌部黏膜的非传染性慢性疾病,外形多为白色或灰白色斑块状损害,也可表现为红白间杂。上皮异常增生是OLK主要的病理改变特点,因此其具有潜在的癌变风险。OLK的病因及发病机制尚不明确,目前尚无特效治疗方法。中医药在治疗OLK中具有独特优势,充分结合中西医优势,对于OLK的治疗具有极大意义。文章对中医药及中医药联合西药治疗OLK的现状及研究进展加以综述。

OLK、EK和OSCC 3p微卫星改变及其与病理的关系

目的探讨口腔白斑、红斑及鳞状细胞癌染色体3p上3个微卫星位点杂合性缺失(LOH)、微卫星不稳定(MSI)改变状况及其与病理的关系。方法选择3p上3个微卫星位点,应用聚合酶链式反应-变性聚丙烯酰胺凝胶电泳-银染方法,研究39例口腔白斑,12例红斑,32例口腔鳞状细胞癌染色体3p上D3S1266、D3S643、D3S966的LOH、MSI的状况及其与病理的关系。结果口腔癌前病变及鳞状细胞癌组织中3p上3个位点均出现LOH和/或MSI。不同病理分级组间单个位点LOH或/和MSI发生率无显着性差异(P>0.05)。当综合3p上3个位点的LOH及MSI总的检出率进行统计学分析,LOH检出率在不同临床病理组别之间差异显著(P<0.01)。MSI检出率在不同临床病理组别之间差异无显著性(P>0.05)。MSI在口腔癌前病变癌变早期即已发生,LOH发生频率则随口腔癌前病变癌变的发生发展逐渐增高。结论3p区域的基因异常是口腔鳞状细胞癌发生和发展过程高频分子事件,该区域可能存在抑癌基因。3p上的微卫星改变状况在口腔癌的发生、发展中扮演重要的角色。

OLK患者与OSCC癌患者的原癌基因蛋白差异及相关性研究

目的探讨原癌基因蛋白在口腔鳞状细胞癌(oral squamous cell carcinoma,OSCC)及口腔白斑中(oral leukoplakia,OLK)的意义。方法选取唐山工人医院口腔科已确诊为口腔白斑的患者40例作为OLK组,确诊为口腔鳞状细胞癌患者40例作为OSCC组,同时期体检正常志愿者40例作为对照组,取病变组织、正常口腔粘膜作为样本,研磨后取上清液,采用酶联免疫法检测3组研究对象样本中MDM2蛋白,p53蛋白,Ki-67蛋白的含量情况,并分析3者的相关性。结果 3组间MDM2、p53表达水平比较均为OSCC组>OLK组>对照组;3组间Ki-67表达水平比较,OSCC组>OLK组>对照组(P<0.05);MDM2,p53,Ki-67在口腔白斑及口腔鳞状细胞癌中表达呈正相关(P<0.05),在正常粘膜中表达无相关。结论口腔白斑发展成为口腔鳞状细胞癌与MDM2,p53,Ki-67的高表达有关,MDM2、p53、Ki-67 3者之间呈正相关。

口腔白斑研究前沿和热点分析

目的 对口腔白斑(oral leukoplakia,OL)研究的前沿和热点进行分析。方法 计算机检索Web of Science数据库核心合集,检索时间1995年1月1日至2021年12月31日。利用CiteSpace软件进行文献计量学分析。结果 OL相关研究发表数量稳步增长,相关研究得到全社会越来越多的支持及关注。在国家维度中,美国是发文数量最多的国家;在研究机构中,我国位居前20的机构最多,上海交通大学是发表论文数量最多的机构。因OL致病因素不明确,研究者期望通过多个学科的研究获得突破性进展。通过文献关键词分析癌变、相关病变和随访研究是目前的科研热点;基于关键词的突现强度分析,潜在的恶性疾病、分类和发育异常是研究前沿。结论 文献可视化分析直观展现OL研究的热点和前沿,为今后研究提供参考。

Expression and significance of p53 and mdm2 in patients with leukoplakia cancer

Objective:To study the relationship of the expressions of p53 and mdm2 in leukoplakia cancer.Methods:RT-PCR was used to detect the mRNA of p53,mdm2 in patients with leukoplakia cancer.The frequencies of p53,mdm2 in peripheral blood were detected by flow cytometric analysis.Results:The expression of p53mRNA in normal oral mucosa,simple oral leukoplakia,no-simple oral leukoplakia and leukoplakia cancer were 7.7%,27.3%,33.3%,56.8%,respectively.The frequencies of p53 in normal oral mucosa,simple oral leukoplakia,no-simple oral leukoplakia and leukoplakia cancer were(0.3±0.1)%,(l.6±0.9)%,(1.9±1.1)%,(3.4±1.8)%.The expression of mdm2 mRNA in normal oral mucosa,simple oral leukoplakia,no-simple oral leukoplakia and leukoplakia cancer were 0.0%,6.8%,11.1%,37.8%,respectively.The frequencies of mdm2 in normal oral mucosa,simple oral leukoplakia,no-simple oral leukoplakia and leukoplakia cancer were(0.1±0.1)%,(0.8±0.6)%,(1.2±0.8)%,(1.2±0.8)%.There was a positively correlation between p53 mRNA and mdm2 mRNA.Conclusions:The positive rate of p53 and mdm2 cells in the peripheral blood increases in patients with leukoplakia cancer tissue and has positive correlation with the severity of leukoplakia cancer.

Role of angiogenesis in oral squamous cell carcinoma development and metastasis: an immunohistochemical study

Although a few studies have shown that vascularity is increased from normal mucosa to dysplasia to carcinoma suggesting that disease progression in the oral mucosa is accompanied by angiogenesis. The role in lymph node metastasis in oral squamous cell carcinoma （OSCC） is equivocal. Role of angiogenesis in OSCC development and metastasis is evaluated in this study. This retrospective study of 50 samples consisted of 9 normal buccal mucosa, 22 leukoplakias, and 19 OSCC. Polyclonal antibodies to von-Willebrand factor were used to highlight the microvessels. Images were captured and morphometric image analysis was done for microvessel density （MVD）, area, and perimeter. Highest, as well as mean values of these three parameters were compared. MVD and perimeter, but not area, are significantly different between normal mucosa and OSCC, and leukoplakia and OSCC. There were no differences between normal mucosa and leukoplakia. MVD, area, and perimeter were not significantly different between the OSCC with and without lymph node metastasis. The highest and mean values of MVD are significantly correlated. In the development of OSCC, angiogenic phenotypic change occurs in carcinomas rather than in the pre-cancerous stage, and quantification of angiogenesis in OSCC does not predict the risk of lymph node metastasis.

Quality of life and oral potentially malignant disorders: Critical appraisal and prospects

Quality of life(QoL) is a vital and often required health outcome measure that is relevant to patient care. A healthy oral cavity enables person to perform daily activities without any limitations. However, any disturbance may result in impaired QoL. The oral health-remains an essential element of people's health and well-being. In recent years, the tradition of clinical practice and research has been changed by incorporating QoL assessment, as it helps in assessment of patients' needs and monitoring treatment responses. Oral potentially malignant disorders(OPMDs) are a group of chronic disorders including oral leukoplakia(OL), oral lichen planus and oral submucous fibrosis(OSF). It is evident that patients with OPMDs experience significant health-related symptoms, functional limitations and psycho-social impairment, compromising their Qo L. Moreover, the worsening of Qo L has been associated with advanced stages of OPMDs. Despite of increasing number of OPMD cases in recent decades, limited literature is available regarding QoL in this population. Although, there is higher prevalence of habit-related OPMDs, particularly OSF and OL in Southern Asian countries, only a few studies have been performed in these populations. Moreover, these studies administered generic Qo L instruments, which offer less sensitivity to clinical changes. However, condition-specific instruments are more sensitive and allows better measurement of QoL. As the impacts of different conditions on OHRQoL may vary, the development and validation of a QoL instrument specific to each clinical entity of OPMDs is currently needed.

Analysis of clinical symptoms and signs in cases of oral submucous fibrosis which have transformed into squamous cell carcinoma

To analyze the clinical symptoms and signs in cases of oral submucous fibrosis which has transformed into squamous cell carcinoma, twenty-nine patients with squamous cell carcinoma correlated with oral submucous fibrosis, leukoplakia, lichen planus were taken biopsy for positive diagnosis. The clinical and pathological diagnosis of oral submucous fibrosis depended on clinical and pathological diagnostic standards. The oral submucous fibrosis involving different portions and size in the mouth was observed and recorded. The portions of oral cancer, clinical findings and symptoms, cancerous size, the conditions of the local lymphatic nodes and of oral submucous fibrosis correlated with squamous cell carcinoma in the mouth, oral leukoplakia, lichen planus were also observed and recorded. In twenty-nine patients with oral squamous cell carcinoma, duration from oral submucous fibrosis transformed into oral cancer ranged from 2 to 15 years with an average year of 6.69. The serious degrees of oral submucous fibrosis in the patients with oral cancer were that the moderately advanced stage was found in 3 cases (10.34%) and the advanced stage was found in 26 cases (89.65%). The cancerous portion was that the buccal mucosa was found in 9 cases (31.03%);the tongue was found in 14 cases (48.27%);the other portion was found in the rest 6 cases (20.68%). Among the twenty-nine patients twenty-three patients with squamous cell carcinoma were associated with leukoplakia (79.31%), five patients were associated with lichen planus (17.24%). Twenty-seven patients (93.1%) had habits of betel quid chewing, smoked cigarette and drank alcohol, the rest two patients had habits of betel quid chewing and cigarette smoking. The present study demonstrates that oral submucous fibrosis is a real precancerous lesion and may transform into squamous cell carcinoma in the mouth.

Precancerous lesions of oral mucosa

Precancerous lesions of oral mucosa, known as potentially malignant disorders in recent years, are consists of a group of diseases, which should be diagnosed in the early stage. Oral leukoplakia, oral submucous fibrosis, and oral erythroplakia are the most common oral mucosal diseases that have a very high malignant transformation rate. Oral lichen planus is one of the potentially malignant disorders that may be seen in six different subtypes including papular, reticular, plaquelike, atrophic, erosive, and bullous type, clinically. Atrophic and erosive subtypes have the greater increased malignant transformation risk compared to another subtypes. Although there are various etiological studies, the etiology of almost all these diseases is not fully understood. Geographically, etiologic factors may vary.The most frequently reported possible factors are tobacco use, alcohol drinking, chewing of betel quid containing areca nut, and solar rays. Early diagnosis is very important and can be lifesaving, because in late stages, they may be progressed to severe dysplasia and even carcinoma in situ and/or squamous cell carcinoma. For most diseases, treatment results are not satisfactory in spite of miscellaneous therapies. While at the forefront of surgical intervention, topical and systemic treatment alternatives such as corticosteroids, calcineurin inhibitors, and retinoids are widely used.

OSCC和OLK患者口腔黏膜组织中IL-12p35和Ebi3的表达及意义

目的探讨口腔鳞状细胞癌(OSCC)和口腔白斑(OLK)患者口腔黏膜组织中白细胞介素35(IL-35)α链p35亚基(IL-12p35)和β链EB病毒诱导基因3亚基(Ebi3)的表达及意义。方法选取OSCC患者34例、OLK患者32例及正颌手术、良性非炎症性肿瘤切除术患者15例分别作为OSCC组、OLK组及正常组,取3组患者口腔黏膜组织,采用苏木精-伊红染色法(HE)染色进行形态学观察和病理学诊断,采用免疫组织化学超敏二步法(IHC)检测IL-12p35和Ebi3蛋白的表达。结果OSCC、OLK组患者口腔黏膜组织Ebi3、IL-12p35蛋白阳性表达率均高于正常组(P<0.001),且OSCC与OLK组间Ebi3蛋白的阳性表达率差异有统计学意义(P<0.001);IL-12p35、Ebi3蛋白阳性表达分别与上皮异常增生程度呈正相关关系(r IL-12p35=0.370,P=0.001;r Ebi3=0.380,P<0.001);OSCC组中Ebi3、IL-12p35蛋白表达与患者淋巴结转移有关(P<0.05),但与其性别、年龄、分化程度及TNM分期无关(P>0.05)。结论IL-12p35和Ebi3在OSCC及OLK患者口腔黏膜组织中表达上调,IL-35可能在口腔黏膜癌变发展过程中起重要作用。

A portable illumination device for photodynamic therapy of the oral cavity

Photodynamic therapy(PDT)is a minimally invasive method for treating oral leukoplakia In this paper,we propose a portable PDT device consisting of a flexible circuit board with a liquid flow cooling module on the back.The light source size was 17 mm×11 mm×4 mm,and the iradiation area of the light source was up to 100mm'.The iradiance range of this device was from 10mW/cm^(2)to 100mW/cm^(2).Simulation and experimental results showed that the irradiance cofficient variation for a treatment area of 81 mm was less than 7%.At an irradiance of 100 mW/cm a device surface temperature of lower than 42℃ can be achieved to satisfy the safety requirements under the con-ditions that the temperature of cooling liquid is 10℃ and the liquid flow speed is above 12 mL/min.

FTIR-ATR and FT-Raman Spectroscopy for Biochemical Changes in Oral Tissue

Nowadays, biomedicine development is caused by the necessity of fast premalignant and malignant diagnosis. In the case of cancer, it is important to identify degree of tumor’s malice. We investigated the differences of Fourier Transform Infrared-Attenuated Total Reflection (FTIR-ATR) and FT-Raman spectroscopy between leukoplakia, oral cancer and normal tissues. Human tissue contains many compounds with known absorption spectra in the range of Near Infrared (NIR) spectroscopy. These compounds have a fingerprint region, which permits their characterization. FTIR spectroscopy is a promising diagnostic tool. There is ability to detect skin, cervix, prostate, breast, esophagus, stomach, bladder and oral cancers [1]. Imaging using FTIR microscope allows analysis of biochemical compounds in microregions of biological materials. FTIR microspectroscopy is the perfect technique for tissues and individual cells analysis [1]. It delivers information about biochemistry of cell or tissue samples and has been applied in many areas of medical research [2]. IR absorption spectra of abnormal tissues and normal tissues are compared by lipid (2800 - 3000 cm–1), protein (1500 - 1700 cm–1), and nucleic acids (1000 - 1250 cm–1) regions [2]. One of the mucous membrane lesions of the mouth is leukoplakia. This change has a “fingerprint region” in the range of 900 - 1800 cm–1 [3]. Raman spectroscopy has high potential of medical diagnosis. This method is a molecular specific technique that can be used to develop a fundamental biochemical understanding of tissue physiology and pathology. Both methods are dedicated to screening of preneoplastic and neoplastic tissues and have a potential to reduce morbidity of leucoplakia and oral cancers. Obtained data suggested that these infrared techniques are applicable to biomedical and clinical diagnostics.

口腔黏膜脱落细胞数量对口腔癌风险指数预测准确性的影响

目的 探讨不同口腔黏膜脱落细胞数量对预测口腔癌风险指数准确性的影响,为口腔黏膜脱落细胞检查刷取样本的标准提供依据。方法 纳入口腔白斑患者、口腔癌患者各12例,正常对照组12例,刷取病损或正常部位口腔黏膜脱落细胞,Feulgen染色,获取DNA指数,随机抽取500、1000、2000、4000、6000、8000、10000个细胞,每例样本重复随机抽取7次,分别计算口腔癌风险指数。结果 正常对照组中,各组口腔癌风险指数均在0.1附近,无统计学差异。口腔白斑组中,有8例样本细胞数量对口腔癌风险指数结果没有影响,4例样本出现轻度影响。12例样本中500~8000个细胞数各组的口腔癌风险指数与10000个细胞数组比较,均无统计学差异。在口腔癌组中,细胞数量对口腔癌风险指数影响较大,具有显著统计学差异(P <0.01),其中4000、6000及8000个细胞数组口腔癌风险指数与变异系数10000个细胞数组比较没有统计学差异。结论 口腔白斑伴异常增生样本,脱落细胞数量对口腔癌风险指数有一定影响。对于口腔癌样本,至少需要刷取4000个脱落细胞才能获得准确的口腔癌风险指数。

基于网络药理学及体外细胞学探讨野黄芩苷抑制口腔白斑癌变的作用机制

目的:利用网络药理学分析野黄芩苷抑制口腔白斑(oral leukoplakia,OLK)癌变的分子机制,采用细胞学进一步验证。方法:通过网络药理学挖掘野黄芩苷作用于OLK的分子靶点,构建蛋白互作网络,通过GO、KEGG富集分析预测野黄芩苷可能的作用靶点及相关通路。利用CCK-8实验、Transwell实验验证野黄芩苷对口腔白斑细胞(Leuk-1)、舌癌细胞(Cal-27)增殖、迁移、侵袭的作用;Western印迹法检测相关分子的表达。采用GraphPad Prism 9软件包进行统计学分析。结果:野黄芩苷作用于OLK的潜在作用靶点共29个,HIF-1α为其中关键靶点。GO、KEGG分析结果显示,野黄芩苷高度参与细胞及组织对缺氧的反应并作用于组织缺氧相关的HIF-1信号通路。细胞学结果表明,野黄芩苷能显著抑制Leuk-1、Cal-27增殖(IC50:2 mmol/L)、迁移和侵袭(P<0.05)。Western印迹法进一步验证了关键分子靶点,1 mmol/L野黄芩苷能明显抑制Leuk-1和Cal-27细胞内HIF-1α蛋白的表达。结论:野黄芩苷可能通过抑制HIF-1信号通路表达,对OLK癌变起到抑制作用。

环状RNA在口腔白斑和口腔扁平苔藓中的共同表达

目的 探讨环状RNA在口腔白斑(oral leukoplakia,OLK)和口腔扁平苔藓(oral lichen planus,OLP)疾病发生发展中的共同表达,为研究OLK与OLP的发病机制及癌变机制提供基础。方法 本研究获得医院伦理审批。采用高通量测序技术检测OLK、OLP、口腔鳞状细胞癌和正常口腔黏膜组织中差异表达的circRNA,采用qRTPCR、酶耐受实验和sanger测序筛选并验证OLK与OLP中共同显著差异表达circRNA,并对关键circRNA扩大样本量验证;采用GO和KEGG富集分析差异circRNA可能涉及的生物学过程及信号通路;采用TargetScan与MiRanda预测circRNA下游的miRNA并绘制ceRNA网络。结果 OLK与OLP共同差异表达的circRNA共49个,包括30个上调和19个下调的circRNA;经验证,筛选的3个上调circRNA(circHLA-C,circTTN,circRNF13)和2个下调circRNA(circSEPN2,circALDH3A2)表达趋势与测序结果一致。其中circHLA-C是具有反式剪接位点的关键circRNA,经扩大样本量验证,circHLA-C在OLK与OLP中显著上调。ROC曲线分析显示,OLK中circHLA-C曲线下面积为0.955,OLP中circHLA-C曲线下面积为0.988。GO功能富集显示与免疫功能生物学过程密切相关,KEGG通路分析中富集分数最高的信号通路是“自然杀伤细胞介导的细胞毒性”,HLA-C在这些通路中显著富集,ceRNA网络分析表明circHLA-C可能与多种癌症相关miRNA相互作用,如hsa-miR-26a-5p、hsa-miR-129-5p和hsa-miR-29a-3p。结论 OLK与OLP存在相同差异表达的circRNA,circHLA-C是OLK与OLP共有的最显著上调的circRNA;circHLA-C可能会成为OLP与OLK诊断和预后的潜在生物标志物。