Regulatory T cells and M2-polarized tumour-associated macrophages are associated with the oncogenesis and progression of oral squamous cell carcinoma

Regulatory T cells (Tregs) and tumour-associated macrophages (TAMs) contribute to the tumour microenvironment by inhibiting anti-tumour immune responses. This study was performed to investigate the roles of Tregs and TAMs in oral squamous cell carcinoma (OSCC) and oral epithelial precursor lesions (OEPL). The expression of Treg markers CD25 and FoxP3 and TAM markers CD163 and CD204 was investigated in 82 OSCC and 45 OEPL specimens, and their associations with clinicopathological parameters were analyzed. Correlations were found among CD25, FoxP3, CD163, and CD204 levels (P < 0.001), and these targets were up-regulated in OSCC compared to OEPL (P < 0.001). In OSCC, infiltration of Tregs and/or M2 TAMs was associated with sex and clinicopathological features, such as tumour size, nodal metastasis, tissue differentiation, stromal reaction, invasive behaviour, and invasive depth. In OEPL, CD25, FoxP3, CD163, and CD204 immunoreactivities were significantly associated with sex, postoperative recurrence, and cancerization to OSCC. This study is novel in showing that the infiltration of Tregs and M2 TAMs is significantly associated with the progression of premalignant lesions to OSCC. This suggests that these cells represent prognostic biomarkers for premalignant lesion progression and that immunotherapeutic approaches to control Treg/M2 TAM numbers could protect against progression to malignancy.     

The role of cyclin‐dependent kinases in oral potentially malignant disorders and oral squamous cell carcinoma

Oral squamous cell carcinoma (OSCC) is a major global health problem with a relatively low‐moderate 5‐year survival rate. OSCC is often preceded by lesions and conditions known as oral potentially malignant disorders (OPMDs) that have an increased risk of malignant transformation. Despite advances in diagnostic technology and cancer research, the prognosis of OSCC remains poor as it is frequently detected a late stage. Understanding the molecular pathways involved in oral carcinogenesis provides a platform to identify biomarkers that may allow the early detection of OSCC and accurate prediction of the malignant potential of OPMDs. In addition, specific molecular inhibitors can be developed to target these important pathways and allow advanced therapeutic management to improve the prognosis of this malignancy. A common feature across a number of different cancers is the dysfunction of cell cycle moderator proteins known as cyclin‐dependent kinases. This review summarises the current literature regarding the role of cyclin‐dependent kinases in oral carcinogenesis with a particular focus on cyclin‐dependent kinases 4 (CDK4) and 6 (CDK6). This is of particular relevance as CDK4 and CDK6 inhibitors have shown some promising results in other cancer types and are interesting potential treatments for OSCC.     

Expression of p16 in oral cancer and premalignant lesions

Background:  Expression of p16 has been proposed as a marker for malignant transformation. This study aimed to evaluate p16 expression in oral squamous cell carcinoma (OSCC) and premalignant lesions including oral leukoplakia (OL) with and without dysplasia.
Methods:  Expression of p16 was investigated in 56 samples including OSCC, OL with and without dysplasia, and normal oral mucosa. Expression of p16 was identified by immunohistochemistry, using the CINtecTM p16INK4a Histology Kit. Both nuclear and/or cytoplasmic staining of the keratinocytes were considered to be positive and the percentage of positive cells was calculated.
Results:  Expression of p16 was detected in 3/16 (18.75%) cases of OSCC, in 4/15 (26.7%) cases of OL without dysplasia, and in none of OL with dysplasia and normal mucosa. No significant differences in p16 expression prevalence were found among OSCC, OL with and without dysplasia and normal mucosa. The percentages of positive cells in OSCC and OL without dysplasia were 0.89 and 0.17, respectively. No significant difference in the percentage of positive keratinocytes was found.
Conclusion:  As a marker, p16 is not reliable for oral mucosal dysplasia and malignant transformation.     

口腔黏膜癌变过程中Fas与FasL表达的相互关系

目的　初步探讨Fas和Fas L蛋白在口腔黏膜癌前损害发生发展过程中的作用及变化规律。方法　分别选出正常口腔黏膜、上皮单纯增生、上皮轻度异常增生、上皮中度异常增生、上皮重度异常增生与原位癌、鳞状细胞癌标本,共64例,采用免疫组织化学染色技术---酶标链亲和素生物素法(LsAB)染色并进行光镜下观察。结果　多数口腔鳞癌显示Fas表达的下调和Fas L表达的上调,同样的结果见于口腔癌前损害黏膜组织。结论　Fas 和Fas L的表达参与了口腔癌变过程,且可能是癌细胞逃避宿主免疫攻击的机制。Fas/Fas L系统有望成为判定口腔癌前损害预后的生物标志。     

Alteration in the expression of cdk4 and cdk6 proteins in oral cancer and premalignant lesions

J Oral Pathol Med (2010) 39 : 793–799 Background: Cdk4 and cdk6, key players in G1 phase, have been shown to play an important role in the development of oral squamous cell carcinoma (OSCC). This study investigated the expression of these two proteins in OSCC and premalignant lesions including oral leukoplakia (OL) with and without dysplasia and determined if alterations in the expression of these two proteins could be used as markers of malignant transformation. Methods: Expressions of cdk4 and cdk6 were evaluated in 61 samples including OSCC, OL with and without dysplasia and normal oral mucosa using immunohistochemistry method. Nuclear staining of the keratinocytes was considered positive and the percentage of positive cells was calculated. Results: Expression of cdk4 was found in 11/15 (73.33%) OSCC, 13/14 (92.85%) OL with dysplasia, 13/20 (65%) OL without dysplasia and 3/12 (25%) normal mucosa. Expression of cdk6 was detected in 9/15 (60%) OSCC, 3/14 (21.43%) OL with dysplasia, 5/20 (25%) OL without dysplasia and 1/12 (8.33%) normal mucosa. In cdk4 stained specimens, the frequency of positive cases and the percentage of positive cells in normal mucosa was significantly lower than OL with dysplasia and OSCC. For cdk6 staining, the prevalence of positive cases and the percentage of positive cells in normal mucosa were significantly lower than OSCC. Conclusions: Overexpressions of cdk4 and cdk6 were observed in OSCC, indicating that these two proteins play a crucial role in OSCC. The aberrant expression of cdk4 was found in OL with dysplasia, suggesting that cdk4 may be involved in the early event of carcinogenesis.     

Expression of p63 and CD44 in oral squamous cell carcinoma and correlation with clinicopathological parameters

Squamous cell carcinoma (SCC) is the sixth most frequent malignant tumor of the head and neck region. Despite advances in therapeutic options over the last decades, the rate of mortality and morbidity has not been improved markedly. A small subset of cells, cancer stem cells (CSCs), with self-renewal properties have become a major focus of current cancer research. CD44 and p63 are identified as candidate stem cell markers in normal squamous epithelium and SCC. The role of these markers in oral squamous cell carcinoma (OSCC) is still debatable. The aim of this study was to evaluate immunohistochemical expression of these markers in OSCC samples and also correlates the expression of these markers with some clinicopathological parameters of prognostic significance including histological grading, TNM staging, overall survival (OS) rate as well as patients’ age, gender, and tumor location. CD44 and p63 were expressed in all studied lesions with different degrees. Statistically significant difference was observed between CD44 and p63 expression with tumor grade and stage with higher expression in high grade and advanced OSCCs. No significant relationship was detected between markers immunoreactivity and patients age, gender, tumor location as well as OS. These markers can possibly advance our understanding of the initiating mechanisms and pathogenesis of OSCC and also result in novel therapeutic target in cancer treatment.     

Markedly increased Oct4 and Nanog expression correlates with cisplatin resistance in oral squamous cell carcinoma

J Oral Pathol Med (2011) 40 : 621–628 Background: Oral squamous cell carcinoma (OSCC) is the sixth most prevalent cancer worldwide. Cancer stem cells (CSC) model theoretically contribute to tumor growth, metastasis, and chemo‐radioresistance. Cisplatin is a widely used chemotherapeutic agent for OSCC treatment. The aim of this study was to compare stemness genes expression in chemo‐sensitive and chemo‐resistant specimens and further explore the potential markers that may lead to induce chemo‐resistance in OSCC. Methods: The study method is the treatment of OC2 cells with cisplatin select cisplatin‐resistant OC2 cells. Self‐renewal ability was evaluated by cultivating parental and cisplatin‐resistant OC2 cells within sphere‐forming assay after serial passages. Differential expression profile of stemness markers between parental and cisplatin‐resistant OC2 cells was elucidated. The parental and cisplatin‐resistant OC2 cells were assessed for migration/invasion/clonogenicity tumorigenic properties in vitro. Expression of stemness markers in chemo‐sensitive and chemo‐resistant patients with OSCC was performed by immunohistochemistry staining in vivo. Results: Sphere‐forming/self‐renewal capability was increased in cisplatin‐resistant OC2 cells. Cisplatin‐resistant OC2 cells highly expressed the stemness markers (Nanog, Oct4, Bmi1, CD117, CD133, and ABCG2). Furthermore, cisplatin‐resistant OC2 cells increased migration/invasion/clonogenicity ability. Notably, up‐regulation of Oct4 and Nanog expression was significantly observed in cisplatin‐resistant patients with OSCC (**P < 0.01). Conclusions: These data indicate that cancer stem‐like properties were expanded during the acquisition of cisplatin resistance in OSCC. Clinically, oral cancer stemness markers (Oct4 and Nanog) overexpression may promote the OSCC’s recurrence to resist cisplatin.     

CXCR-4 knockdown by small interfering RNA inhibits cell proliferation and invasion of oral squamous cell carcinoma cells

Background:  Oral squamous cell carcinomas (OSCCs) are characterized by a high degree of local invasion and a high rate of metastases to cervical lymph nodes. Downregulation of CXCR-4 by siRNA inhibits invasion and growth of breast and colon cancer cells. However, there have been no reports on the downregulation of CXCR-4 by small interfering RNA (siRNA) in oral cancer cells.
Methods:  We generated two stable CXCR-4-knockdown clones (KBsi and KOSCC-25Bsi) from the KB and KOSCC-25B OSCC cell lines by lentiviral delivery. In vitro invasion and cell proliferation assays were used to investigate the effect of CXCR-4 downregulation on cell proliferation and invasiveness in KBsi and KOSCC-25Bsi. Immunohistochemistry was performed to evaluate the correlation between CXCR-4 expression and proliferation in 26 OSCC tissue samples.
Results:  CXCR4-knockdown OSCC cells showed reduced invasiveness. The invasiveness of KBsi decreased to 29.5% of the vector-infected controls, and KOSCC-25Bsi decreased to 38.1% of the control vector-infected cells ( P  <   0.05). The CXCR4-knockdown OSCC cells grew significantly slower than the vector-infected control cells. KBsi and KOSCC-25Bsi cells proliferated at 69.5% and 71.7%, respectively, of the rate of control vector-infected cells ( P  <   0.05). CXCR-4-positive group had significantly higher PCNA labeling index than CXCR-4-negative group in OSCC tissue samples.
Conclusion:  These results suggest that the downregulation of CXCR-4 induces anti-proliferative and anti-invasive effects in OSCC and that CXCR-4 might be a useful target molecule for the treatment of OSCC.     

肿瘤相关巨噬细胞在口腔癌中作用的研究进展

肿瘤相关巨噬细胞（tumor associated macrophages, TAMs）是肿瘤微环境中重要的免疫细胞和炎症细胞，在肿瘤的发生、增殖、侵袭和转移中发挥重要作用。该文从口腔癌中TAMs的来源及分化、促口腔癌前病损进展、致口腔癌侵袭转移等方面对TAMs在口腔癌发生发展中的作用进行综述，以期为针对TAMs的口腔癌研究及靶向治疗提供新思路。     

Reduced expression of the CD44 variant exons in oral squamous cell carcinoma and its relationship to metastasis

In the present study, we examined the expression of CD44 variant exons in human oral squamous cell carcinoma (OSCC). Of ten cell lines from OSCCs, two (KB and H357), as well as the HeLa cell line, failed to express CD44 variant exons. In surgical specimens, all normal mucosa expressed CD44v9 (both mRNA and protein). Of 40 primary OSCCs, 19 (47.5%) showed downregulation of CD44v9, which correlated with tumor cell differentiation, primary metastasis to lymph nodes and secondary metastasis to lymph nodes. The results suggest that the downregulation of CD44v9 may play a role in lymphatic metastasis of OSCC and changes in its expression may be a useful diagnostic tool to determine the metastatic potential of OSCC to lymph nodes. Moreover, three cell lines that failed to express CD44 variant exons might become a useful experimental model to study the role of variant exons in the progression of OSCC.     

口腔鳞癌VEGF诱导树突状细胞致免疫耐受的机制研究

目的 探讨口腔鳞状细胞癌(oral squamous cell carcinoma, OSCC)中血管内皮细胞生长因子(vascular endothelial growth factor, VEGF)诱导树突状细胞(dendritic cells, DCs)向免疫耐受型转化的作用及机制。方法 将树突状细胞分为4组：对照组(DC)、VEGF组(DC中加入外源性VEGF)、共培养组(DC与SCC7细胞共培养)及抗VEGF组(DC与SCC7细胞共培养后加入VEGF抗体),采用流式细胞术(flow cytometry, FCM)检测DC表面标记分子的表达情况;为了检测DC对T细胞增殖的影响,将实验分为5组：空白组(T细胞)、对照组(T细胞+DC)、VEGF组(T细胞+DC+VEGF)、共培养组(T细胞+DC+SCC7细胞上清)及抗VEGF组(T细胞+DC+SCC7上清+VEGF抗体),采用混合淋巴细胞反应(mixed lymphocyte reaction, MLR)检测;分别应用Western blot、real time PCR及FCM检测各组DC中吲哚胺-2,3-双加氧酶(indole...     

Phospholipase C‐γ1 expression correlated with cancer progression of potentially malignant oral lesions

Background: Phospholipase C‐γ1 (PLCγ1) is required for cellular migration during tumor progression and invasion of oral squamous cell carcinoma (OSCC) cells. The objective of the current study was to determine immunoexpression pattern of PLCγ1 in oral potentially malignant lesions (OPLs) and evaluate PLCγ1 usefulness as a biomarker for predicting clinical behavior in the carcinogenesis of OPL. Methods: In a retrospective follow‐up study, the expression pattern of PLCγ1 protein was determined using immunohistochemistry in samples from 68 patients, including untransformed cases (n = 38) and malignant‐transformed cases (n = 30). The corresponding post‐malignant lesions (OSCCs) were also performed. Results: We observed that elevated expression of PLCγ1 in 40 of 68 (59%) general OPLs and 23 of 30 (77%) OSCCs compared with that in normal oral mucosa. Kaplan–Meier analysis revealed that patients with PLCγ1 positivity had a significantly higher incidence of OSCC than those with PLCγ1 negativity. Cox regression analysis revealed that PLCγ1 expression patterns were significantly associated with increased risk of malignant progression. In addition, the correlation between PLCγ1 expression in pre‐malignant OPL and that in post‐malignant OSCC was significant (P = 0.004). Conclusion: These data indicate that PLCγ1 expression in OPL correlated with oral cancer progression, and PLCγ1 may serve as a useful marker for the identification of high‐risk OPL into OSCC.     

新疆部分维族、汉族口腔黏膜癌前病变及口腔鳞状细胞癌P16蛋白表达的研究

目的 探讨新疆维吾尔族、汉族口腔黏膜癌前病变及口腔鳞状上皮细胞癌的发生与发展过程中P16蛋白表达的意义。方法 采用免疫组化LSAB法对40例口腔扁平苔藓（维吾尔族20例，汉族20例），43例口腔白斑（维吾尔族23例，汉族20例）和60例口腔鳞状上皮细胞癌（维吾尔族24例，汉族41例）分别进行检测。结果口腔鳞状上皮细胞癌组织中P16蛋白阳性率为32．3％，明显低于口腔白斑（55．8％）和口腔扁平苔藓（72．5％），P＜0．005，维族与汉族之间的的差异均无统计学意义（P＞0．05）。结论 P16蛋白表达缺失在口腔鳞状上皮细胞癌的发生与发展过程中起重要作用；据本研究资料，尚不能认为P16蛋白的表达在维族与汉族之间的差异有显著性。     

Repression of G protein–coupled receptor family C group 5 member A is associated with pathologic differentiation grade of oral squamous cell carcinoma

Background

G protein–coupled receptor family C group 5 member A (GPRC5A), a member of G protein–coupled receptor family, has been shown to function as a tumor suppressor in lung tissue. The biological functions of GPRC5A have therefore been linked to lung tissue. However, the biological significance of this gene product remains obscure. In this study, we investigated the expression of GPRC5A proteins in normal oral tissue and oral squamous cell carcinoma (OSCC), and we characterized its biological activity in OSCC cell lines.

Methods

Western blot analysis and immunohistochemical staining were used to investigate the expression of GPRC5A in both OSCC cell lines and clinical samples. GPRC5A stable transfectants and their parental OSCC cells were characterized for their biological activities in anchorage‐independent growth.

Results

High levels of immunohistochemical GPRC5A expression were detected in normal oral tissue, especially differentiated area. In contrast, GPRC5A expression was dramatically repressed in OSCCs (P < 0.01). The immunohistochemical GPRC5A expression was moderately well differentiated, but greatly repressed in moderately differentiated OSCCs and completely repressed in poorly differentiated OSCCs. Overexpression of GPRC5A in OSCC CAL27 cells resulted in a suppressed anchorage‐independent growth activity, a transforming phenotype.

Conclusions

GPRC5A is expressed in normal oral epithelium. Repression of GPRC5A is associated with poorly differential grade of OSCCs. Overexpression of GPRC5A in OSCC cell line reversed the malignant phenotype. Thus, GPRC5A is important for homeostasis in oral tissue, and deletion or repression of this gene may involve in tumorigenesis of OSCCs and may serve as a prognostic marker for malignant type of OSCCs.     

Expression of hepatocyte growth factor and c-met protein is significantly associated with the progression of oral squamous cell carcinoma in Taiwan

BACKGROUND: Hepatocyte growth factor (HGF) is a pleotropic growth factor that regulates cell proliferation, migration, survival, tumor angiogenesis, and tumor cell invasion and metastasis. Its diverse biological effects are mediated through its interaction with its receptor, c-met protein. METHODS: In this study, we examined the expression of HGF and c-met protein in 93 specimens of oral squamous cell carcinoma (OSCC), 10 specimens of oral epithelial dysplasia (OED), 14 specimens of oral epithelial hyperkeratosis (OEH), and 16 specimens of normal oral mucosa (NOM) by immunohistochemistry. The HGF and c-met labeling indices (LIs) in OSCC, OED, OEH, and NOM groups were calculated and compared between groups. The correlation between the expression of HGF or c-met in OSCCs and clinicopathological parameters, or survival of OSCC patients was analyzed statistically to investigate the possible influence of HGF or c-met on the progression and prognosis of OSCCs in Taiwan. RESULTS: Positive HGF or c-met staining was mainly cytoplasmic. The mean HGF LI increased significantly from NOM (3.1 +/- 5.1%) through OEH (32.5 +/- 19.8%) and OED (52.0 +/- 19.3%) to OSCC (71.9 +/- 28.6%; P = 0.000). The mean c-met LI also increased significantly from NOM (25.8 +/- 30.8%) and OEH (34.4 +/- 19.3%) through OED (53.0 +/- 20.0%) to OSCC (73.0 +/- 29.4%; P = 0.000). Statistical analysis showed that the c-met LI in either the tumor center or invasion front was significantly associated with T status, N status, and clinical staging of OSCC. However, only the HGF LI in the tumor invasion front was significantly correlated with N status and clinical staging of OSCC. CONCLUSION: Our results suggest that the expression of HGF and c-met protein is an early event in oral carcinogenesis in Taiwan. The HGF LI in the tumor invasion front and the c-met LI in either the tumor center or invasion front can predict the progression of OSCCs in Taiwan.     

口腔黏膜癌变过程中中心体的扩增及其意义

目的　了解口腔黏膜癌变过程中中心体的状况,探讨中心体的异常在口腔鳞状细胞癌(OSCC)发生发展中的作用及其在口腔黏膜癌变过程中的意义。方法　选取正常口腔黏膜(12例)、轻度上皮异常增生(2例)、中度上皮异常增生(8例)、重度上皮异常增生(12例),口腔高分化鳞癌(10例)、中分化鳞癌(15例)、低分化鳞癌(7例)的石蜡包埋组织,采用间接免疫荧光双重染色(γ-微管蛋白单克隆抗体及细胞角蛋白多克隆抗体)显示上皮细胞中的中心体,分析其在口腔黏膜癌变过程中的变化趋势及在各组间的差异。结果　正常口腔黏膜上皮表现为大小数目正常的中心体,但在72·73%(16/22)的上皮异常增生及84·38%(27/32)OSCC组织中观察到部分上皮或肿瘤细胞中出现异常中心体,表现为中心体直径的增加或数目的增多。具有异常中心体的细胞数目随上皮异常增生程度的增加及肿瘤分化程度的降低而增加,二者存在明显的正相关关系(P<0·01)。结论　中心体的扩增是口腔黏膜癌变过程中的早期事件并与口腔癌发生发展进程有关,口腔黏膜癌变过程中的细胞形态学改变与中心体扩增之间可能存在直接机制上的联系。从调控中心体循环入手治疗口腔癌前病损及OSCC,有可能成为口腔癌预防和治疗的新途径。     

Organotypic culture of normal,dysplastic and squamous cell carcinoma‐derived oral cell lines reveals loss of spatial regulation of CD44 and p75NTR in malignancy

Oral squamous cell carcinomas (OSCC) often arise from dysplastic lesions. The role of cancer stem cells in tumour initiation is widely accepted, yet the potential existence of pre‐cancerous stem cells in dysplastic tissue has received little attention. Cell lines from oral diseases ranging in severity from dysplasia to malignancy provide opportunity to investigate the involvement of stem cells in malignant progression from dysplasia. Stem cells are functionally defined by their ability to generate hierarchical tissue structures in consortium with spatial regulation. Organotypic cultures readily display tissue hierarchy in vitro; hence, in this study, we compared hierarchical expression of stem cell‐associated markers in dermis‐based organotypic cultures of oral epithelial cells from normal tissue (OKF6‐TERT2), mild dysplasia (DOK), severe dysplasia (POE‐9n) and OSCC (PE/CA P J15). Expression of CD44, p75^NTR, CD24 and ALDH was studied in monolayers by flow cytometry and in organotypic cultures by immunohistochemistry. Spatial regulation of CD44 and p75^NTR was evident for organotypic cultures of normal (OKF6‐TERT2) and dysplasia (DOK and POE‐9n) but was lacking for OSCC (PE/CA PJ15)‐derived cells. Spatial regulation of CD24 was not evident. All monolayer cultures exhibited CD44, p75^NTR, CD24 antigens and ALDH activity (ALDEFLUOR^® assay), with a trend towards loss of population heterogeneity that mirrored disease severity. In monolayer, increased FOXA1 and decreased FOXA2 expression correlated with disease severity, but OCT3/4, Sox2 and NANOG did not. We conclude that dermis‐based organotypic cultures give opportunity to investigate the mechanisms that underlie loss of spatial regulation of stem cell markers seen with OSCC‐derived cells.     

Serum vitamin D levels of patients with oral squamous cell carcinoma (OSCC) and expression of vitamin D receptor in oral precancerous lesions and OSCC

Background: Resistance to programmed cell death (apoptosis) is a crucial factor for the carcinogenesis of oral squamous cell carcinoma (OSCC). Vitamin D (calcitriol) may overcome apoptosis resistance in tumor cells of OSCC. Vitamin D receptor (VDR) expression in oral precancerous lesions of OSCC has not been analyzed and serum vitamin D level seems to be a predictor of cancer development. Material and Methods: Expression of VDR was analyzed in normal oral mucosa (n=5), oral precursor lesions (simple hyperplasia, n=11; squamous intraepithelial neoplasia, SIN I-III, n=35), and OSCC specimen (n=42) by immunohistochemistry (IHC). Moreover, serum vitamin D levels were measured by 25(OH)D3 (calcidiol) in patients with OSCC (n=42) and correlated with IHC results. Results: Expression of VDR was significantly increased in precancerous and OSCC compared with normal tissue. Compared with SIN I-III lesions VDR expression significantly decreased in OSCC. Severe vitamin D deficiency was detected in our OSCC patient cohort but there was no significant correlation analyzed between serum vitamin D levels and corresponding immunohistochemically detected VDR expression in OSCC. Conclusions: Our survey provides the first evidence of VDR expression in precancerous lesions of OSCC. Apoptosis induction of VDR+ cells in oral precancerous lesions and OSCC by natural vitamin D or synthetic vitamin D compounds could be useful for chemoprevention. Moreover, systemically and/or locally applied, these compounds may act as sensitizers for apoptosis mediated by radio-, and chemotherapy treatment in OSCC. Key words:Oral cancer, oral precancer, lichen planus, leukoplakia, apoptosis, serum 25(OH)D3, vitamin D receptor, chemoprevention, multistep carcinogenesis.     

姜黄素单独及联合防治口腔鳞癌机制的研究进展

口腔鳞状细胞癌(OSCC)是一种发病率极高的口腔上皮来源恶性肿瘤,其发病机制尚未完全明确。OSCC具有早期颈淋巴结转移倾向,预后不佳,加上其特殊解剖位置,是导致复发的重要因素。姜黄素是从姜科植物根茎部中提取的活性成分,具有抗氧化、抗炎、抗凝、抗癌等多重药理功效,且少见不良反应,使其在医学领域具有潜在的应用前景。多项研究证明姜黄素可以通过调节多种信号通路中特定效应因子,诱导恶性肿瘤细胞凋亡、抑制肿瘤细胞的增殖和侵袭、调节肿瘤细胞细胞周期、缓解肿瘤耐药以及提高抗癌药物敏感性。近年来口腔医学各个分支学科对姜黄素的应用日渐增加,例如在防治牙周炎、颞下颌关节炎、黏膜癌前病损等方面。本文针对近年来姜黄素单独及联合其他天然药物在口腔鳞癌防治方面的作用机制及研究进展作一综述,以期为更深层次的研究提供参考。     

Clinical features of microinvasive stage I oral carcinoma

Oral Diseases (2011) 17 , 298–303 Background: This study aimed to analyse a case series of microinvasive (tumour thickness <4 mm) stage I oral squamous cell carcinoma (OSCC), with an emphasis on the clinical features of the tumours. Methods: In total, 32 microinvasive and 67 non‐microinvasive stage I lesions, which had been surgically treated, were retrospectively studied and compared. The data analysed included gender, age, risk habits, clinical appearance, lesion site, symptoms, nodal involvement and outcome. Results: The clinical features of microinvasive lesions meant that, more often than not, they resembled premalignant lesions (P = 0.008), and diagnosis was mainly based on accurate clinical examination rather than the presence of symptoms (P = 0.029). During a median follow‐up of 4.5 years, one nodal involvement and one cancer‐related death were observed in patients with microinvasive lesions. A significantly higher (P = 0.044) level of nodal involvement was observed in the non‐microinvasive lesion group. Conclusions: Stage I OSCC has a favourable prognosis overall, but nodal recurrence is more common in non‐microinvasive cancers. As microinvasive lesions tend to present clinically as premalignant lesions, accurate clinical examination is essential if misdiagnosis of early lesions is to be avoided.