人头颈鳞癌细胞中CDH13的表达及其甲基化状态研究

目的 研究抑癌基因H-钙黏素(CDH13)在人头颈部鳞癌细胞系SCC10A和PCI-37B中的表达水平及其启动子区域的甲基化状态。 方法 定量 PCR和Western blotting检测CDH13在头颈鳞癌细胞系SCC10A和PCI-37B及两种正常组织中的mRNA和蛋白表达变化,并通过甲基化特异性PCR和硫化测序检测CDH13基因启动子区域的甲基化情况。 结果 与正常组织比较,头颈鳞癌细胞SCC10A和PCI-37B中CDH13的mRNA和蛋白表达水平均降低。SCC10A和PCI-37B细胞中CDH13基因甲基化水平高于口腔黏膜正常组织,人头颈鳞癌细胞系中CDH13基因启动子区域呈高甲基化状态。 结论 CDH13启动子区域高甲基化可能是导致人头颈鳞癌中CDH13表达沉默的重要因素,但其影响肿瘤发生发展的具体机制仍需进一步探究。     

头颈部鳞癌颈淋巴结转移诸因素对预后的影响

对382例头颈部原发鳞癌病人颈清扫标本连续切片病理观察结果和临床资料进行回顾性分析，探讨淋巴结转移的各项临床和病理学因素与病人预后的关系。发现总体5年生存率为46.1％，口腔癌、口咽癌、下咽癌和喉癌的5年生存率分别为49．7％，39．7％，35．0％和60．3％。表明颈淋巴结的临床分期、触诊淋巴结大小、病理转移淋巴结情况、颈淋巴解剖分区受累数和最低受累平面与病人5年生存率有密切关系（均P＜0．01），而阳性淋巴的个数对病人预后无明显影响。提示针对影响预后的淋巴结因素应采取相应的治疗措施，以提高病人的5年生存率。     

P73基因在喉鳞癌中的表达及其临床意义

目的 探讨P73基因在喉鳞癌中的表达。方法用原位杂交方法检测49例喉鳞癌组织、19例声带息肉、12例癌旁组织及8例非典型增生组织中P73的表达。结果喉鳞癌组织P73阳性表达26例定位于胞浆，9例定位于腺体，5例定位于胞核，9例未表达。P73阳性表达率在喉鳞癌组织、声带息肉、癌旁组织及非典型增生组织中分别为53．06％(26／49)，36．84％(7／19)，41．67％(5／12)，37．5％(3／8)，P73与喉鳞癌的临床分型、分期无相关性。结论P73基因可能并非喉癌癌变过程中的靶基因，在喉癌的发生发展中可能不发挥重要作用。     

喉鳞癌组织中p15蛋白表达的研究

1994年 ,美国 Beach研究小组克隆了 p1 5基因。它定位于 9号染色体 p2 1 ,是一种能抑制细胞过度增殖的细胞周期调节基因 ,在白血病、神经胶质瘤、肺癌、黑色素瘤、骨肉瘤、非霍奇金淋巴瘤等多种肿瘤中 ,发现 p1 5基因的纯合子缺失或过度甲基化导致该基因的失活。本研究采用 LSAB免疫组化方法 ,检测了 p1 5基因在喉鳞癌组织和声带息肉良性组织中的蛋白表达情况。1　材料和方法1 .1 　 研究对象55例喉鳞癌标本及 1 0例声带息肉标本均取自华西医科大学第一临床医学院病理科 1 988～1 995年手术切除喉鳞癌组织石蜡标本 ,均有完整临床病理资料…     

喉癌组织中CHFR基因mRNA表达水平及启动子区甲基化的研究

目的:探讨CHFR基因表达水平及启动子区CpG岛过甲基化与喉癌发生发展的关系.方法:采用荧光定量PCR技术和甲基化特异性PCR技术检测50例喉癌组织(喉癌组)和15例正常喉组织(对照组)CHFR基因mRNA表达情况及启动子区CpG岛过甲基化情况.结果:①CHFR基因在对照组mRNA全部表达,在喉癌组mRNA有2例(4%)表达缺失,48例表达量明显下调(相对表达量为0.50±0.12),其中Ⅰ和Ⅱ期相对表达量(0.30±0.04),Ⅲ期和Ⅳ期相对表达量(0.70±0.21),与对照组比较,差异有统计学意义(P<0.01).②在对照组中未发现CHFR基因启动子区甲基化,在喉癌组中CHFR基因启动子区甲基化率为22%(11/50),其中Ⅰ期和Ⅱ期患者共10例,Ⅲ期1例,Ⅳ期未发现甲基化,与对照组比较,差异均有统计学意义(P<0.01).③甲基化的喉癌标本mRNA相对表达量为0.11±0.05,2例mRNA表达缺失.未甲基化的喉癌标本mRNA相对表达量为0.75±0.13.甲基化和mRNA表达相关,γ=0.387(P<0.05).结论:喉癌组织中CHFR基因mRNA表达缺失或下调,CHFR基因启动子区CpG岛过甲基化在喉癌组织中是频发事件,二者密切相关,可能与喉癌的发生发展有关,有望能成为喉癌的早期诊断及治疗靶点基因之一.     

蛋白激酶CK2及其抑制剂与头颈部鳞癌的关系

蛋白激酶CK2是真核细胞中普遍存在的第二信使非依赖性丝/苏氨酸蛋白激酶,目前蛋白激酶CK2已成为抗肿瘤的重要靶点之一,其抑制剂具有抗肿瘤作用.本文简介了蛋白激酶CK2的分子结构、主要功能及其作用机制,蛋白激酶CK2抑制剂的分类及其作用机制,蛋白激酶CK2及其抑制剂与头颈部鳞癌的关系.     

喉癌组织中IGFBP-rP1基因的甲基化及表达

目的：探讨喉癌中胰岛素样生长因子结合蛋白一相关蛋白1（IGFBP—rP1）基因启动子区甲基化与蛋白表达之间的关系。方法：采用甲基化特异性PCR方法和免疫组织化学的方法分别检测45例喉癌组织及18例癌旁组织中IGFBP-rP1基因的甲基化状态和蛋白表达情况。结果：喉癌组织IGFBP—rP1启动子区甲基化率为33．3％（15／45）,相应癌旁组织甲基化率为5．6％（1／18）,喉癌组织中IGFBP—rP1基因甲基化率明显高于癌旁组织（P〈0．05）。喉癌组织中IGFBP—rP1蛋白表达显著低于癌旁正常组织（P％0．05）,且与其启动子区甲基化状态呈负相关。结论：IGFBP—rP1基因启动子区甲基化导致基因沉默可能是喉癌发生的机制之一。     

CHFR基因在鼻咽癌中异常甲基化的研究

目的:检测鼻咽癌中CHFR基因的转录表达及其启动子区甲基化状态,探讨其在鼻咽癌中的转录失活机制及其意义;评价鼻咽拭子检测CHFR基因甲基化状态在鼻咽癌诊断和治疗中的意义。方法:RT-PCR检测鼻咽癌细胞株中CHFR基因的转录表达水平。甲基化特异性PCR检测鼻咽癌细胞株、鼻咽癌活检组织、正常鼻咽组织及配套的鼻咽拭子样本中CHFR基因的甲基化状态。亚硫酸氢盐测序分析鼻咽癌细胞株和鼻咽癌组织、正常鼻咽组织中CHFR基因启动子区的具体甲基化状态。5-氮杂-2'-脱氧胞苷(5-aza-dC)处理鼻咽癌细胞株后观察CHFR基因转录表达水平的改变情况。结果:CHFR基因在鼻咽癌细胞株中转录表达下调或沉默;CHFR基因在鼻咽癌细胞株和鼻咽癌组织中均呈高频率、肿瘤特异性的甲基化。鼻咽癌患者鼻咽癌组织和配套鼻咽拭子样本中CHFR基因的甲基化频率分别为65.5%和63.8%,两者符合率达86.2%。鼻咽癌组织和细胞株中CHFR基因启动子区大部分的CpG位点为甲基化,而正常组织全为非甲基化;5-aza-dC可显著恢复鼻咽癌细胞株中CHFR基因的转录表达。结论:鼻咽癌中CHFR基因由于启动子区CpG岛的DNA甲基化而转录表达下调。鼻咽...     

通过生物信息学筛选头颈部鳞状细胞癌差异表达基因及相关生物学特性分析

目的　利用生物信息学方法,筛选出与头颈鳞状细胞癌发生发展相关的差异表达基因（differentially expressed genes,DEGs）,进而寻找出有助于头颈鳞状细胞癌早期诊断和预后的分子生物标志物。方法　整合3个GEO数据库,筛选DEGs,进行GO（gene ontology）功能注释及KEGG（the Kyoto Encyclopedia of Gene and Genomes）通路富集分析,构建蛋白质-蛋白质作用网络（protein-protein interaction,PPI）,提取关键基因,验证其差异表达水平及与预后的关系。结果　从数据集中共筛选出39个上调基因和44个下调基因;GO分析发现上调的DEGs生物学功能主要是细胞外基质结构活性、结构分子活性等,下调的DEGs主要与代谢、结构分子活性等有关。KEGG分析表明上调的DEGs主要在PI3k-Akt信号通路、粘着斑;下调的DEGs主要集中在化学致癌、药物代谢-细胞色素P450途径。通过PPI筛选出4个关键基因MMP1、PLAU、RBP1、SEMA3C与头颈鳞状细胞癌的无病生存期显著相关,且高表达组的预后显著差于低表达组。结论　本研究筛选出MMP1、PLAU、RBP1、SEMA3C与头颈鳞状细胞癌的发生发展和预后相关,为临床诊断和治疗提供了新的靶点。     

Basaloid squamous cell carcinoma of the head and neck

OBJECTIVE/HYPOTHESIS: Basaloid squamous cell carcinoma (BSCC), an uncommon tumor with predilection for the upper aerodigestive tract, is a distinct variant of squamous carcinoma, because of its unique histological features and ominous clinical behavior. This study reviews the experience in treating BSCC from two institutions. STUDY DESIGN: Retrospective. METHODS: H&E-stained sections from 20 patients with BSCC of the head and neck were reviewed and clinical follow-up was obtained for all patients. RESULTS: The study group consisted of 14 male and 6 female patients. Their ages ranged from 43 to 85 years, with a mean age of 62 years. Sites of origin included the larynx (4), tongue (3), pyriform sinus (3), nose (2), floor of mouth (2), mastoid (1), tonsil (1), epiglottis (1), nasopharynx (1), trachea (1), and palate (1). Pain was the most common presenting symptom (5 cases), followed by hoarseness and bleeding (3 cases each). Tobacco and alcohol abuse was noted in 17 patients. Treatment modalities included surgery with or without chemotherapy or radiotherapy in 13 patients, chemotherapy with irradiation in 2, chemotherapy alone in 2, and radiotherapy alone in 3. Clinical follow-up revealed no evidence of disease in 11 patients. Four were alive with disease at the time of writing and five died of disease. CONCLUSION: BSCC is a highly aggressive malignant tumor that presents in elderly patients who have a history of abuse of tobacco or alcohol, or both. Greater number of patients must be studied and compared with age-matched and stage-matched controls of conventional squamous cell carcinoma to determine whether the poor clinical outcome is related more to high-stage presentation or to the tumor's high-grade malignant cytological features.     

头颈鳞状细胞癌相关致病基因的筛选和临床分析

目的筛选头颈鳞状细胞癌（head and neck squamous cell carcinoma, HNSCC）差异表达基因（differentially expressed genes, DEGs）,进一步探究其潜在分子机制。方法从Gene Expression Omnibus（GEO）数据库下载HNSCC基因芯片数据集,通过GEO2R鉴定HNSCC与正常样本间的DEGs,并对DEGs进行基因本体(gene ontology, GO)功能注释和京都基因与基因组百科全书（kyoto encyclopedia of genes and genomes, KEGG）通路分析,应用Cytoscape进行蛋白质-蛋白质相互作用（protein protein interaction, PPI）网络构建,最后通过UALCAN数据库进行生存分析。结果筛选出143个DEGs,其中上调基因50个,下调基因93个。GO分析显著富集在胶原分解代谢过程、细胞粘附及蛋白水解等生物过程,KEGG通路分析显著富集在药物代谢、核因子 κB（muclear factor κB,NF κB）信号通路、ECM 受体相互作用、补体和凝血级联等通路。PPI网络构建筛选出15个HNSCC相关核心基因,其中PLAU、SPP1、TIMP1被鉴定为临床相关基因。结论SPP1是抗癌治疗的良好靶标,也是指导放射治疗的标志物。PLAU和TIMP1可能是HNSCC的关键基因,有望成为分子靶向治疗的新靶点,PLAU和SPP1可能通过NF κB信号通路调节HNSCC发展。     

Whole-body MRI for staging patients with head and neck squamous cell carcinoma

Conclusions. Whole-body MRI is feasible for the tumor staging of patients with malignant head and neck tumors and appears to be a quick, reliable and proven alternative in general and for patients with contraindications to CT. This examination minimizes the logistical effort required compared to multimodality strategies. Its economic impact remains to be determined. Objective. To assess the performance of whole-body MRI for staging patients with squamous cell carcinoma of the head and neck region. Material and methods. This was a randomized, prospective clinical study. For tumor staging, 21 patients (mean age 56.7 years; range 43–80 years) with advanced malignant head and neck tumors underwent whole-body MRI in addition to routinely performed imaging investigations, including sonography, chest X-ray, CT of the head, neck and thorax and endoscopy. All investigations were accomplished within a period of 10±3 days in a random order. A randomized, blinded, consensus assessment of all the whole-body MRI examinations was performed by two radiologists. The localization and extent of the primary tumor and metastases were documented for whole-body MRI and compared to the standard of reference (all other imaging modalities as well as histology). Point estimates of the diagnostic accuracy of whole-body MRI were calculated. Results. In accordance with the standard of reference, the overall TNM category was correctly determined with whole-body MRI in all 21 patients. However, four patients were classified as having carcinoma of unknown primary, as the primary tumor was not found with any imaging modality. Two patients had mediastinal, pulmonary and hepatic metastases.     

Control of neck nodes in squamous cell carcinoma of the head and neck by radiotherapy: prognostic factors

313 patients with cervical metastases from a squamous carcinoma of the head and neck treated with radiotherapy, were studied by means of a multivariant analysis in order to determine the prognostic factors for cure. These were: lymph node response to irradiation (P= 0.0000), size of node (P= 0.0000), radiotherapy dose (P= 0.0037), condition of the primary (controlled vs non-controlled) (P= 0.0015), recurrent cervical metastases post-surgery (P= 0.0286).     

头颈部鳞状细胞癌的靶向治疗研究进展

头颈部肿瘤是常见肿瘤之一,超过95%的病理类型是鳞状细胞癌,手术与放化疗结合的综合治疗方案是头颈部鳞状细胞癌(HNSCC)的主要治疗方案,但是总体生存率并不高,主要原因是肿瘤复发和/或转移;同时复发性或转移性HNSCC常无法进行手术治疗,放化疗效果也差。靶向治疗的发现为HNSCC、特别是复发性或转移性HNSCC的治疗提供了新的方法。为了进一步认识靶向治疗的临床治疗作用,就HNSCC的靶向治疗研究进展做一综述。     

Soft tissue cervical metastases of squamous carcinoma of the head and neck

Some 497 of 3085 patients with squamous cell carcinoma of the head and neck treated between 1963 and 1990 had a later radical neck dissection at some time after initial treatment. The histological slides were all reviewed, firstly to confirm the presence of squamous cell carcinoma within the neck, and secondly to ascertain whether the metastasis was to soft tissue, to a lymph node or to both. The presence of extracapsular rupture in lymph node deposits was also assessed. Of the 497 patients, 138 had soft tissue deposits only, and 359 had nodal deposits only. Of the patients with nodal deposits 165 had extracapsular rupture and 194 did not. The 5-year survival of the 138 patients with soft tissue metastases was 27% compared with 33% for patients with extracapsular rupture and 50% for patients with no extracapsular rupture. Weighted logistic regression showed that soft tissue deposits were significantly more common in patients in poor general condition, plus poorly differentiated squamous cell carcinoma plus T₄ tumours (P < 0.005), and in patients with poorly differentiated squamous cell carcinoma plus T₄ tumours (P < 0.025). Cox's multivariate analysis with backward elimination showed that gender, histological differentiation, site of primary tumour and age of patient had no statistically significant effect on survival. The number of nodes (P < 0.0001), the presence of extracapsular rupture (P < 0.0001) and the presence of soft tissue free metastases (P < 0.001) were all highly significant. The N-status at recurrence also reached statistical significance (P < 0.0001).