口腔鳞癌组织中CIAP1表达水平与PTP化疗方案疗效及预后的关系

目的:探究口腔鳞癌细胞CIAP1的表达水平与临床PTP(顺铂+替尼泊甙+平阳霉素/博莱霉素)方案化疗效果及患者预后之间的关系。初步评价其表达水平是否可以指导临床个体化化疗方案的制定。方法:采用回顾性研究的方法检测了42例原发晚期口腔鳞癌标本化疗前后CIAP1的表达情况,评价其化疗前表达水平与化疗效果及临床预后之间的相关性。同时,对比分析化疗前后CIAP1的表达变化情况。结果:42例口腔鳞癌标本中CIAP1在胞质及胞核均有不同程度的表达,其胞质表达水平与化疗效果及预后显著相关。化疗前后口腔鳞癌标本中CIAP1的表达没有相关性。结论:胞质CIAP1表达水平是临床PTP方案化疗疗效及患者预后的一个有效预测因子。     

Ursolic acid induces apoptosis and autophagy in oral cancer cells

Oral squamous cell carcinoma (OSCC) is the fifth common cause of cancer mortality in Taiwan with high incidence and recurrence and needs new therapeutic strategies. In this study, ursolic acid (UA), a triterpenoid, was examined the antitumor potency in OSCC cells. Our results showed that UA inhibited the proliferation of OSCC cells in a dose‐ and time‐dependent manner in both Ca922 and SCC2095 oral cancer cells. UA induced caspase‐dependent apoptosis accompanied with the modulation of various biological biomarkers including downregulating Akt/mTOR/NF‐κB signaling, ERK, and p38. In addition, UA inhibited angiogenesis as evidenced by abrogation of migration/invasion and blocking MMP‐2 secretion in Ca922 cells. Interestingly, UA induced autophagy in OSCC cells, as manifested by LC3B‐II conversion and increased p62 expression and accumulation of autophagosomes. Inhibition by autophagy inhibitor enhanced UA‐mediated apoptosis in Ca922 cells. The experiment provides a rationale for using triterpenoid in the treatment of OSCC.     

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目的探讨水通道蛋白-3（AQP-3）在口腔鳞状细胞癌（OSCC）组织中的表达及其意义。方法应用免疫组化Envosion法,检测山西省人民医院病理科2009年9月至2013年7月存档的60例OSCC病理组织石蜡标本和10例正常口腔黏膜上皮组织q-AQP-3蛋白的表达水平并进行比较分析。结果在60例OSCC的病理标本中AQP-3主要表达在细胞的胞膜上,也有少量表达在胞浆中。AQP-3在OSCC标本中的阳性表达率（81．7％）明显高于在正常口腔黏膜组织中的阳性表达率（20．0％）,差异有统计学意义（P〈0．05）。OSCC组织中AQP-3的表达在不同年龄（X2=0．032）、性别（X2=O．045）、病变部位（X2=1-313）方面的差异均无统计学意义（均P〉O．05）,在不同组织分化程度（X2=8．626）、临床分期（X2=21．59）以及是否有颈淋巴结转移（X2=3．90）方面的差异有统计学意义（均P〈0．05）。结论AQP-3的异常表达与OSCC的发生、发展有密切关系,可作为OSCC治疗和预后的辅助性指标。     

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??Abstract?? Objective To investigate the expression of PTTG1 and its promoting effect for epithelial mesenchymal transition ??EMT?? in oral squamous cell carcinoma?? OSCC. Methods Quantitative RT-PCR ??qRT-PCR?? was carried out to detect the mRNA expression level of PTTG1 for 58 pairs of OSCC and normal control tissues. RNAi was used to knockdown PTTG1 expression in SCC9 cell line. E-cadherin level was detected before and after RNAi?? using western blot. Results The relative expression of PTTG1 in OSCC tissues??3.046±1.137??was significantly higher than that of normal tissues ??0.975±0.434????P < 0.05??. Overexpression was closely related to the lymph node metastasis and clinical stage ??P < 0.05??. E-cadherin level decreased remarkably after the knockdown of PTTG1 in SCC9 cell ??P < 0.05??. Conclusion The overexpression of PTTG1 in OSCC patients is closely related to OSCC clinical stage and lymph node metastasis?? which promotes EMT progress.     

口腔鳞癌中乙酰肝素酶的促血管生成作用及临床意义

目的：研究口腔鳞癌（OSCC）中乙酰肝素酶（Heparanase,Hpa）mRNA的表达,探索其与微血管密度（microvessel density,MVD）的关系,从而了解OSCC中Hpa在肿瘤血管生成中的作用,为OSCC的研究及治疗提供理论依据。方法：选择手术切除及活检的人OSCC标本64例,口腔正常黏膜10例,采用原位杂交技术检测HpamRNA的表达,用CD31抗体进行血管内皮的免疫组化染色,计数微血管密度。结果：HpamRNA在OSCC中的表达显著高于其在正常组织中的表达（P〈0．05）,HpamRNA阳性表达的OSCC组织中MVD显著高于阴性表达组（P〈0．05）,HpamRNA表达与淋巴结转移显著相关（P〈0．05）。结论：Hpa能够促进OSCC的血管生成,参与了肿瘤淋巴结转移,可望成为口腔鳞癌抗血管生成治疗中的靶向因子。     

Circulating Vimentin Over-Expression in Patients with Oral Sub Mucosal Fibrosis and Oral Squamous Cell Carcinoma

Oral squamous cell carcinoma (OSCC) is one of the most common (90%) types of oral carcinomas in the world. It is the 2nd most common and 3rd deadliest cancer in India. The lack of early detection marker is one of the major causes of worst prognosis. The vimentin belongs to intermediate filament family proteins which plays significant role in maintaining cellular integrity. Over-expression of vimentin has been widely reported in many epithelial cancers however the information regarding its prevalence in the oral cancers still needs further scientific intervention. The expression level of circulating vimentin protein in serum samples (n = 30) of oral submucous fibrosis (OSMF), OSCC patients and healthy controls were measured by performing ELISA. The serum level of vimentin was significantly higher in OSMF (p < 0.01) and OSCC (p < 0.003) patients as compared to healthy subjects. The circulating vimentin levels showed a gradual increase with increasing disease status (normal < OSMF < OSCC). Circulatory levels of vimentin may ba useful indicator of disease progression and as a suitable target for therapeutic intervention of oral submucous fibrosis and oral carcinoma.     

Association of PD-L1 and ZEB-1 expression patterns with clinicopathological characteristics and prognosis in oral squamous cell carcinoma

Programmed cell death-1 (PD-1) and its ligand programmed cell death 1 ligand 1 (PD-L1) are immune checkpoint inhibitors that play an important role in the host immune avoidance mechanism of tumors. The relationship between PD-L1 expression and malignancy has been reported in various types of cancer, such as lung and gastric cancer. In addition, epithelial-mesenchymal transition (EMT) of cancer cells is deeply involved in the invasion and metastasis of cancer. It has been reported that zinc finger E-box binding homeobox 1 (ZEB-1), an EMT inducer, contributes to metastasis in pancreatic and colon cancer. The present study aimed to investigate the relationship between the expression patterns of two markers, PD-L1 and ZEB-1, and clinicopathological characteristics and prognosis of oral squamous cell carcinoma (OSCC). Biopsy or surgical excision specimens from 169 patients with OSCC were used in the present study. Immunohistochemical staining with monoclonal anti-PD-L1 antibody and anti-ZEB-1 antibody was conducted. Cases with >1% tumor cells positive for PD-L1 and those with >10% tumor cells positive for ZEB-1 were considered positive, respectively. The findings revealed that individual expression of PD-L1 and ZEB-1 in OSCC was not associated with tumor size, degree of differentiation or Yamamoto-Kohama invasion pattern classification. However, co-expression of PD-L1 and ZEB-1 was associated with higher cervical lymph node metastasis and a lower survival rate. In conclusion, the results of the present study indicated that co-expression of PD-L1 and ZEB-1 could serve as a potential marker for the prognosis of patients with OSCC.     

Prx1调控PINK1/Parkin介导的线粒体自噬在实验性口腔黏膜癌变中的作用

目的 检测口腔黏膜癌变过程中线粒体自噬相关蛋白PINK1、Parkin表达变化及抗氧化蛋白Prx1对其调控作用,探讨Prx1在口腔黏膜癌变中的作用机制.方法 利用4NQO化学诱导Prx1+/+和Prx1+/-小鼠舌黏膜癌变模型,采用免疫组织化学染色及Q-PCR方法 ,检测PINK1、Parkin在小鼠舌正常黏膜、白斑、...     

Role of TP53 in the progression of pre-malignant and malignant oral mucosal lesions. A follow-up study of 144 patients

Background:  Prediction of progression from pre-malignant oral mucosal lesions to malignancy, or recurrence of an existing oral squamous cell carcinoma (OSCC), is an important clinical problem in oral medicine.
Methods:  This study presents a follow-up of a study published in 2002. Samples from 54 patients with OSCC, 45 with oral lichen planus (OLP) and 45 with hyperkeratosis (clinically leukoplakia), diagnosed between 1987 and 1996, were analysed for TP53 protein expression and TP53 mutation. Follow-up was 11–17 years for OSCC (mean 13.3), 12–22 years for OLP (mean 15.9) and 12–17 years for hyperkeratosis (mean 14.5).
Results:  Of the 54 OSCC patients, 28 experienced recurrent disease, 21 died of OSCC, 22 died of other causes. Of the 14 OSCC patients with mutated TP53 ( n  = 11), the cancer recurred in eight (57%) and in 20/39 (51%) without mutation. Expression of TP53 protein was significantly associated with reduced overall survival. Among OLP patients, nine were TP53- mutated out of 31 tested. One TP53- mutated OLP patient developed OSCC in a different site. Of the hyperkeratosis patients, three were mutated of 22 tested. One hyperkeratosis patient (non-mutated) developed OSCC in the same site.
Conclusion:  TP53 mutations can exist in benign oral mucosal lesions for many years without progression to malignancy. No association was found between TP53 protein expression or TP53 mutation and recurrence of OSCC or disease-related survival. Overall survival was reduced in patients with positive TP53 protein expression.