MTDH促进头颈鳞癌细胞放疗抵抗的实验研究

目的探讨星形胶质细胞上调基因1（astrocyte elevated gene 1,AEG 1,又称MTDH）对头颈部鳞状细胞癌（简称头颈鳞癌）放疗抵抗的影响。方法Western blotting检测放射线照射后头颈鳞癌细胞MTDH蛋白表达的改变。通过脂质体转染的MTDH cDNA和慢病毒介导的MTDH shRNA,分别在不同头颈鳞癌细胞中过表达和抑制MTDH,平板集落形成实验检测头颈鳞癌细胞放疗抵抗能力的改变,细胞免疫荧光染色检测DNA双链损伤指标γH2AX的表达。结果MTDH在头颈鳞癌细胞中的表达随着放射性照射剂量的增加和时间的延长逐渐升高。在CNE 2细胞中过表达MTDH,其体外集落形成能力增强;相反,在Tu686细胞中抑制MTDH的表达,其体外集落形成能力减弱。同时,细胞免疫荧光显示Tu686细胞在MTDH抑制后,其DNA双链损伤指标γH2AX的表达增加,表明DNA双链损伤修复过程受阻。结论MTDH能促进头颈鳞癌细胞放疗抵抗的形成,与其对DNA双链损伤修复的调控作用相关。     

Beclin1调控鼻咽癌细胞放疗抵抗的体外研究

目的探讨Beclin1基因对鼻咽癌细胞放疗抵抗的影响。方法Western blotting法检测CNE2、6 10B及其放疗抵抗细胞CNE2 Rs、6 10BRs中Beclin1蛋白的表达,CNE2细胞经不同条件放射线照射后Beclin1蛋白的表达改变;通过脂质体转染Beclin1 cDNA和慢病毒介导的Beclin1 shRNA,在6 10B细胞和CNE2 Rs细胞中分别过表达及沉默Beclin1基因,平板克隆集落形成实验检测鼻咽癌细胞的放疗抵抗能力的改变;细胞免疫荧光法检测DNA双链损伤相关指标γ H2AX表达的改变。结果Beclin1蛋白在放疗抵抗细胞中表达增加,同时随着放疗时间的延长及放疗剂量的增加,Beclin1蛋白表达迅速升高,随后趋于基础水平;Beclin1过表达后6 10B细胞克隆集落形成能力增强,生存分数增加,γ H2AX焦点数量减少;相反,Beclin1沉默后,CNE2 Rs细胞克隆集落形成能力下降,生存分数下降,γ H2AX焦点数量增加。结论Beclin1能促进鼻咽癌细胞的放疗抵抗性,其与放疗后DNA双链损伤修复调控可能相关。     

miR-18a促进自噬增强人鼻咽癌细胞株放疗敏感性的研究

目的:探索miR-18a过表达和抑制表达对人鼻咽癌细胞株CNE1和CNE2放疗敏感性的影响及可能的机制。方法:采用miR-18a过表达质粒miR-18a模拟物和抑制表达质粒miR-18a遏制物及空白对照质粒转染人鼻咽癌细胞株CNE1和CNE2细胞,实时荧光定量反转录聚合酶链反应（qRT-PCR）和蛋白免疫印迹法（WB）...     

自噬相关基因Atg3、Ambra1与慢性单纯性鼻窦炎、鼻息肉及鼻息肉伴发哮喘的相关性研究

目的 自噬是机体的一种重要的保护和防御机制.研究拟通过对自噬相关基因Atg3、Ambra1表达的观察,探讨自噬与慢性鼻窦炎(CRS)及哮喘之间的关联性及可能的作用机制.方法收集24例鼻中隔偏曲患者的下鼻甲黏膜作为正常对照组,选取21例慢性单纯性鼻窦炎患者(CRSsNP组)、22例慢性鼻窦炎鼻息肉患者(CRSwNP组)及18例慢性鼻窦炎鼻息肉伴发哮喘患者(CRSwNP伴哮喘组)的鼻腔黏膜组织为实验组.采用免疫组织化学染色技术检测Atg3、Ambra1在各组中的表达强度及分布,分析自噬相关基因在各组间表达的差异,并分析各组中两基因之间的相关性.结果 ①自噬相关基因Atg3在对照组、CRSsNP组、CRSwNP组、CRSwNP伴哮喘组中表达逐渐增强,在各组间表达差异有统计学意义(x2=31.080,P＜0.001);进一步两两比较,在对照组与CRSsNP组之间(P=0.002)、对照组与CRSwNP组之间(P＜0.001)、对照组与CRSwNP伴哮喘组之间(P＜0.001)、CRSsNP组与CRSwNP伴哮喘组之间(P =0.002)、CRSwNP组与CRSwNP伴哮喘组之间(P =0.024)表达差异均有统计学意义,在CRSsNP组与CRSwNP组之间(P=0.304)表达差异无统计学意义.②自噬相关基因Ambra1在对照组、CRSsNP组、CRSwNP组、CRSwNP伴哮喘组中表达逐渐增强,在各组间表达差异有统计学意义(x2=33.000,P＜0.001);进一步两两比较,在对照组与CRSsNP组之间(P=0.009)、对照组与CRSwNP组之间(P＜0.001)、对照组与CRSwNP伴哮喘组之间(P ＜0.001)、CRSsNP组与CRSwNP伴哮喘组之间(P ＜0.001)、CRSwNP组与CRSwNP伴哮喘组之间(P=0.009)表达差异均有统计学意义,在CRSsNP组与CRSwNP组之间(P =0.205)表达差异无统计学意义.③8.Atg3与Ambra1在CRSsNP组(r=0.619,P=0.003)、CRSwNP组(r=0.392,P=0.022)和CRSwNP伴哮喘组(r =0.552,P=0.033)中表达呈正相关性,在对照组中无相关性(r=0.316,P=0.133).结论 细胞自噬与CRS疾病的发生发展密切相关,可能参与了CRSwNP伴哮喘的发生,且自噬相关基因Atg3与Ambra1在CRS的发生发展过程中可能存在协同作用,自噬可成为CRS诊疗新的研究方向.     

Angiogenesis in head and neck squamous cell carcinoma

Tumour angiogenesis has recently attracted a great deal of attention as a critical part of oncogenesis and a necessary prerequisite for a malignant phenotype. Research into this process not only offers new insights into tumour biology but is also leading to the development of realistic novel and minimally toxic anti-tumour therapies. Various pro-angiogenic and anti-angiogenic cytokines and pathways have been characterized and their interrelationships are becoming increasingly complex as new findings are made. This article reviews the current understanding of tumour angiogenesis, the basic mechanisms involved and the more important and investigated pathways and proteins involved.     

Hyercalcaemia in head and neck squamous cell carcinoma

PURPOSE OF REVIEW: Patients with advanced head and neck cancer are being treated with chemo-radiotherapy, and life is being prolonged, with or without persistent disease, for longer than was previously. Hypercalcaemia may present in patients with advanced or disseminated head and neck cancer, and, as such, these patients may present to a larger variety of clinicians for advice concerning their symptoms and illness. Modes of presentation of hypercalcaemia and treatment strategies are reviewed. RECENT FINDINGS: There were previously few large series of head and neck cancer patients diagnosed with hypercalcaemia, which may or may not have been related to their cancer being treated. Investigations, by way of blood/serum calcium level, may identify such patients. Patients with cancer-related hypercalcaemia have a poor prognosis, but many may respond temporarily to treatment when offered, with an improvement of their quality of life and death. SUMMARY: Hypercalcaemia should and must be considered in all patients who have or possibly have a diagnosis of a head and neck cancer and who present unwell with symptoms of fatigue, lethargy and somnolence. Investigation must include serum calcium (corrected for serum albumin binding) and parathyroid hormone level. Patients may be treated by a combination of rehydration and bisulphonate therapy until the serum calcium is reduced to a level below 3 mmol/l. The majority of patients diagnosed with hypercalcaemia due to head and neck malignancy die of their diseases in the short term, but some may enjoy a prolongation of life with reasonable quality if diagnosed and treated aggressively.     

Papillary squamous cell carcinoma versus verrucous squamous cell carcinoma of the head and neck

Papillary squamous cell carcinoma and verrucous squamous cell carcinoma of the head and neck may be confused. The clinicopathological profile of the two neoplasms is presented and the differential diagnosis is discussed. A correct diagnosis is imperative in order to institute the most appropriate treatment.     

Basaloid squamous cell carcinoma of the head and neck

PURPOSE OF REVIEW: Basaloid squamous cell carcinoma is an uncommon variant of squamous cell carcinoma and was first described as a distinct entity in 1986. Basaloid squamous cell carcinoma seems to have a poorer survival rate than classical squamous cell carcinoma. On the basis of a critical literature survey, we attempt to evaluate if basaloid squamous cell carcinoma is really more aggressive and presents a poorer outcome than squamous cell carcinoma. RECENT FINDINGS: All papers are retrospective, and most include small numbers of cases, which are further diminished when subdivided according to specific sites. Only in three studies was basaloid squamous cell carcinoma of the head and neck region compared with matched squamous cell carcinoma controls. These studies did not show a uniform tendency regarding the aggressiveness and outcome of basaloid squamous cell carcinoma. In addition, several recent papers confirmed the presumed greater aggressiveness and worse outcome, and other recent papers questioned these characteristics. SUMMARY: The presented literature survey does not permit conclusions regarding the aggressiveness and outcome of basaloid squamous cell carcinoma compared with squamous cell carcinoma. Greater numbers of basaloid squamous cell carcinoma should be studied and compared with site-matched, stage-matched, and age-matched controls of conventional squamous cell carcinoma.     

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.     

Antisense inhibition of cyclin D1 in human head and neck squamous cell carcinoma

OBJECTIVE: To study the role of cyclin D1 in regulating the biological behavior of head and neck cancer. DESIGN: Squamous cell carcinoma of the head and neck (SCCHN) cells were stably transfected with an antisense cyclin D1 using lipofectin-mediated transfection. In vitro growth assays, cell cycle analyses, cytotoxicity assays, and in vivo tumorigenicity assays were performed. MATERIALS: Human SCCHN cell lines TU138, TU167, TU177, TU182, MDA183, and MDA1386 and athymic nude mice were used for this study. RESULTS: The antisense cyclin D1 transfected cells revealed decreased growth rates in vitro and decreased tumorigenicity in athymic nude mice. Furthermore, antisense cyclin D1 transfection enhanced the chemosensitivity against cisplatin. CONCLUSIONS: These studies provided evidence that overexpression of cyclin D1 may play an important role in growth rates and biological behavior of human head and neck cancer. Additionally, expression of cyclin D1 may make human head and neck cancer cells resistant to platinum-based chemotherapeutic approaches. The ability to suppress the malignant phenotype by down-regulating cyclin D1 expression may provide a new gene therapy approach for patients with head and neck cancer.     

Mononuclear phagocytes in head and neck squamous cell carcinoma

The head and neck squamous cell carcinoma microenvironments contain many immune cells and their secretory products. Many of these cells belong to the mononuclear phagocyte system. The aim of this review is to study the interactions between mononuclear phagocytes and head and neck squamous cell carcinoma tissue. The role of inflammation in tumours and the cytokine interleukin-6 will be highlighted. Future therapy strategies in the treatment of head and neck cancer might be directed towards mononuclear phagocytes and their cytokine production.