β-连环蛋白表达在鼻咽癌癌变过程中作用的研究

目的研究β-连环蛋白(β-catenin)在鼻咽癌(nasopharyngeal carcinoma,NPC)癌变过程中的作用。方法免疫组化结合组织微阵列检测β-catenin蛋白在174例NPC、71例异型增生鼻咽黏膜上皮、48例单纯增生鼻咽黏膜上皮及63例正常鼻咽黏膜上皮组织中的阳性表达及其阳性信号的定位。结果β-catenin在NPC组织细胞浆/细胞核中高表达(71.3%),但其细胞膜呈低阳性表达(19.0%);β-catenin在NPC组织中的细胞浆/细胞核阳性表达率显著高于异型增生鼻咽黏膜上皮、增生鼻咽黏膜上皮和正常鼻咽黏膜上皮(P<0.01)。非角化性鼻咽癌和未分化癌组织的β-catenin蛋白细胞浆/细胞核异常阳性表达率显著高于角化性鼻咽癌(P<0.01)。临床Ⅲ和Ⅳ期NPC组织中β-catenin蛋白的细胞浆/细胞核阳性表达率显著高于临床Ⅰ和Ⅱ期(P<0.01),有淋巴结转移的NPC组织中β-catenin蛋白的细胞浆/细胞核阳性表达率显著高于无淋巴结转移NPC(P<0.01)。结论β-catenin蛋白在癌细胞细胞浆/细胞核中的过表达在NPC发生、发展过程中起重要作用;β-catenin蛋白细胞浆/细胞核阳性可作为预测鼻咽癌临床进展和侵袭、转移的分子标志。     

人核迁移蛋白C 在鼻咽癌组织中的表达及临床意义

目的:明确鼻咽癌(NPC)组织中人核迁移蛋白C(hNudC)的表达及其临床意义.方法:应用免疫组织化学方法和Western blot方法检测80例NPC和30例鼻咽黏膜慢性炎组织中hNudC的表达情况,并应用条带密度分析软件半定量分析Western blot条带密度.结果:在 NPC中,hNudC阳性表达率为83.75%(67/80),明显高于鼻咽部黏膜慢性炎症组织23.33%(7/30)(P<0.05), hNudC蛋白的阳性表达率随着NPC临床分期的进展而增加(P<0.05).结论:hNudC基因表达与NPC细胞恶性增殖密切相关,检测其表达对研究NPC的发生、发展具有一定临床意义.     

增殖细胞核抗原和p53基因在鼻咽癌中的表达及相关性研究

目的:通过免疫组织化学方法检测鼻咽癌(NPC)患者增殖细胞核抗原(PCNA)、p53基因表达,分析其与主要临床指标间的关系。方法:免疫组织化学检测鼻咽活检组织中PCNA、p53蛋白表达,并比较与分析两者和NPC临床分期及颈淋巴结转移的关系。结果:鼻咽部慢性炎性组织中p53阳性率为9.5%,明显低于NPC组织中的阳性率(76.3%)(P<0.01)。NPC伴颈淋巴结转移组p53阳性率(90.9%)明显高于无颈淋巴结转移组(57.7%)(P<0.01),临床Ⅱ、Ⅲ和Ⅳ期p53阳性率(分别为93.3%、80.0%和100.0%)均明显高于临床Ⅰ期(40.0%)(均P<0.01),且表达强度有增加的趋势。随着临床分期的增高,PCNA增殖指数(PI)分级有增高的趋势,NPC伴颈淋巴结转移组中PCNAPI之Ⅰ级所占比例较无颈淋巴结转移组下降,而Ⅱ、Ⅲ、Ⅳ级所占比例增加,但无统计学意义,NPC组织中PCNA表达与p53表达显著相关(P<0.01)。结论:p53蛋白可作为NPC较好的肿瘤标记物,p53阳性的NPC患者较易发生颈淋巴结转移,随着NPC病程的发展,p53表达率及表达强度均增加,PCNAPI可反映NPC的增殖状况,可能与预后相关。     

鼻咽癌组织中程序性死亡配体-1的表达及其临床意义

目的:探讨程序性死亡配体-1(PD-L1)在鼻咽癌(NPC)中的表达及其临床意义.方法:采用免疫组织化学染色法检测59例NPC患者的癌组织和10例正常鼻咽黏膜组织中PD-L1的表达,RT-PCR技术检测30例NPC患者的癌组织及其中10例距离肿瘤组织3 cm以外的正常鼻咽黏膜组织中PD-L1mRNA的表达,并对其表达水平与临床病理组织学参数之间的关系进行相关性分析.结果:正常鼻咽黏膜组织中不表达PD-L1分子,而NPC癌组织中免疫组织化学PD-L1阳性表达率为67.8%(40/59),RT-PCR检测PD-L1mRNA的阳性表达率为66.7%(20/30).PD-L1的表达与肿瘤分期及淋巴结转移明显相关(P<0.05),但与患者的年龄、性别无明显相关(P>0.05).结论:PD-L1 NPC组织中的高表达,可能在肿瘤的发生、发展中起到一定的作用,有希望成为NPC免疫治疗的一个新靶点.     

TrKB与VEGF在鼻咽癌组织中的表达及临床意义

目的探讨血管内皮生长因子(VEGF)、酪氨酸激酶B(TrKB)在鼻咽癌(NPC)组织中的表达并比较两者表达的相关性及分析与肿瘤临床特征的关系。方法采用免疫组化方法检测经活检确诊为NPC的患者55例及鼻咽炎组织30例中VEGF、TrKB蛋白表达水平，比较二两者表达差异。根据患者年龄和性别、肿瘤临床分型、原发灶大小、淋巴结转移和有无远处转移将病例分组，应用双变量相关Pearson检验分析研究VEGF、TrKB表达与肿瘤临床病理特征之间的关系。结果①VEGF蛋白于肿瘤细胞浆及血管内皮细胞浆中均表达，TrKB蛋白阳性表达绝大多数位于细胞浆内。在55例NPC患者中，45例TrKB阳性表达，阳性表达率为81.8%；47例VEGF阳性表达，阳性表达率为85.4%。30例鼻咽炎中，只有3例TrKB阳性表达，阳性表达率为10.0%；5例VEGF阳性表达，阳性表达率为16.7%。肿瘤组织中TrKB、VEGF阳性表达率明显高于鼻咽炎组织（P<0.05），NPC组织中VEGF与TrKB表达有明显相关性（R=0.716,P<0.01）；②VEGF蛋白表达与NPC的临床分期(P=0.002)、肿瘤的直径大小(P=0.009)及有无淋巴结转移(P=0.001)明显相关，与患者性别、年龄、有无远处转移无关（P＞0.05）。TrKB蛋白表达与临床分期(P=0.00)、肿瘤的直径大小(P=0.00)、有无淋巴结转移（P=0.006）明显相关，与患者性别、年龄、有无远处转移无关（P＞0.05）。结论VEGF、TrKB在NPC组织中表达增加，可能与NPC的发生发展有关。TrKB可能与NPC血管形成有关。 （     

LMP2A、E-Cadherin和fibronectin在鼻咽癌中的表达及其临床意义

目的:探讨EBV编码的潜伏膜蛋白2A(LMP2A)与上皮-间质转化(EMT)标志物E-钙粘素(E-Cadherin)和纤维连接蛋白在鼻咽癌(NPC)中的表达及与临床病理学参数的关系。方法:采用免疫组织化学SP法检测LMP2A、E-Cadherin和fibronectin蛋白在32例鼻咽黏膜慢性炎、56例NPC和18例NPC淋巴结转移灶中的表达。结果:1LMP2A在NPC及其淋巴结转移灶中的阳性表达率分别为89.3%(50/56)和77.8%(14/18),均明显高于鼻咽黏膜慢性炎(37.5%,12/32)(均P<0.01);E-Cadherin在NPC及其淋巴结转移灶中的正常表达率分别为33.9%(19/56)和5.6%(1/18),均明显低于鼻咽黏膜慢性炎(90.6%,29/32)(均P<0.01);fibronectin在NPC及其淋巴结转移灶中的阳性表达率分别为83.9%(47/56)和72.2%(13/18),均明显高于鼻咽黏膜慢性炎(28.1%,9/32)(均P<0.01)。2NPC中LMP2A与E-Cadherin正常表达呈负相关(r=-0.387,P<0.01)、与fibronectin表达呈正相关(r=0.421,P<0.01)。3LMP2A、E-Cadherin和fibronectin表达与NPC患者N分期和临床分期密切相关(均P<0.05),与M分期无相关性(P>0.05);LMP2A、E-Cadherin表达与T分期也密切相关(均P<0.01)。结论:LMP2A、fibronectin在NPC中表达升高,而E-Cadherin正常表达则降低;LMP2A可能通过下调E-Cadherin和上调fibronectin表达来介导EMT促进NPC淋巴结转移和恶性进展。     

鼻咽癌组织中nm23-H1蛋白的表达及其临床意义

目的了解抑癌基因nm23-H1蛋白在鼻咽癌组织中的表达,探讨其与鼻咽癌发生发展及转移的关系。方法采用免疫组化法检测43例鼻咽癌患者鼻咽部组织中nm23-H1蛋白的表达,分析鼻咽癌患者不同临床分期及鼻咽癌是否伴有淋巴转移组织中nm23-H1蛋白表达的差异;同期选取17例慢性鼻咽炎患者鼻咽部组织作为对照。结果鼻咽癌组织中nm23-H1蛋白阳性表达率为53.4%,慢性鼻咽炎组织中nm-23H1阳性率为88.2%,两者比较有统计学意义（P〈0.05）;鼻咽癌Ⅰ-Ⅱ期组织中阳性率为88.2%,Ⅲ-Ⅳ期组织中阳性率为30.8%,两者比较有统计学意义（P〈0.05）;鼻咽癌伴有淋巴结转移组和不伴有淋巴转移组阳性率分别为38.5%、76.5%,两者比较有统计学意义（P〈0.05）。结论抑癌基因nm23-H1蛋白表达下调,可能与鼻咽癌发生发展、侵袭转移有关。     

鼻咽癌组织中环氧合酶-2和基质金属蛋白酶-2的表达及与淋巴结转移的关系

目的:研究环氧合酶-2(COX-2)和基质金属蛋白酶-2(MMP-2)在鼻咽癌(NPC)组织中的表达及其与淋巴结转移的关系.方法:应用免疫组织化学SP法检测86例NPC组织中COX-2和MMP-2蛋白的表达,并与淋巴结转移的临床资料进行对比分析.结果:COX-2和MMP-2在NPC组织中的阳性率分别为75.58%和66.28%,显著高于正常鼻咽黏膜组织(均P<0.01);它们的表达与淋巴结转移呈正相关(均P<0.01),2种蛋白的表达之间呈正相关(P<0.01).结论:NPC组织中COX-2和MMP-2的表达均增高;二者在肿瘤淋巴结转移的过程中可能起协调作用.     

EB病毒LMP2A在鼻咽癌患者肿瘤组织中的表达及意义

目的:观察EB病毒(EBV)潜伏膜蛋白2A(LMP2A)在鼻咽癌(NPC)患者肿瘤组织中的表达,探讨采用LMP2A作为靶抗原进行NPC免疫治疗的可行性。方法:采用SP免疫组织化学方法,检测40例NPC组织及38例鼻咽黏膜慢性炎症组织标本LMP2A的表达。结果:40例NPC 标本中36例LMP2A表达阳性(90．0％);LMP2A的表达与NPC病理分化程度无明显相关性。38例鼻咽黏膜慢性炎症组织标本中33例 LMP2A阴性反应,5例阳性反应。鼻咽黏膜慢性炎组织与NPC组织中LMP2A阳性表达率间差异存在统计学意义。结论:在不同病理分化程度的NPC肿瘤组织中LMP2A均可广泛表达,在正常鼻咽组织细胞中基本不表达。采用LMP2A作为靶抗原诱导机体特异性细胞免疫反应杀伤NPC肿瘤细胞具一定可行性。图2表1参15     

EB病毒LMP2A在鼻咽癌患者肿瘤组织中的表达及意义

目的：观察EB病毒(EBV)潜伏膜蛋白2A(LMP2A)在鼻咽癌(NPC)患者肿瘤组织中的表达,探讨采用LMP2A作为靶抗原进行NPC免疫治疗的可行性。方法：采用SP免疫组织化学方法,检测40例NPC组织及38例鼻咽黏膜慢性炎症组织标本LMP2A的表达。结果：40例NPC标本中36例LMP2A表达阳性(90．0％);LMP2A的表达与NPC病理分化程度无明显相关性。38例鼻咽黏膜慢性炎症组织标本中33例LMP2A阴性反应,5例阳性反应。鼻咽黏膜慢性炎组织与NPC组织中LMP2A阳性表达率间差异存在统计学意义。结论：在不同病理分化程度的NPC肿瘤组织中LMP2A均可广泛表达,在正常鼻咽组织细胞中基本不表达。采用LMP2A作为靶抗原诱导机体特异性细胞免疫反应杀伤NPC肿瘤细胞具一定可行性。     

A Decrease in Maxillary Sinus Pressure,as Seen in Upper Airway Allergy or Infection,Results in an Increase in Upper Airway Nitric Oxide Levels

The paranasal sinuses are connected to the nasal cavity via small osties. Ostial occlusion, caused by mucosal swelling, will result in a slowly increasing negative pressure inside the sinus cavity. In parallel, the oxygen content in the sinus will decrease, resulting in the development of relative hypoxia. Hypoxia is a powerful inducer of nitric oxide (NO) synthase, and inducible NO synthase has been shown to be present in considerable amounts in the upper airways, including the sinuses. The present study was designed to investigate whether a reduction in sinus pressure would affect upper airway NO production. Thirteen healthy volunteers were investigated. A pressure chamber was used to lower the ambient pressure to-4.9 kPa. NO was sampled from one nostril or via a drainage tube inserted into the maxillary sinus before, during and after the hypobaric exposure. When the pressure was decreased, NO levels increased from 256 &#45 15 to 316 &#45 19 ppb ( n =13, p <0.001). The NO levels remained elevated (282 &#45 21 ppb; p <0.05) when measurements were repeated 20 min after leaving the chamber. The nasal airway resistance (V2 tot ) also increased as a result of the chamber session (from 16 &#45 2° before to 21 &#45 3° after; p <0.05). An increase in NO levels was also found when the experiments were repeated with NO sampled directly from the maxillary sinus (225 &#45 6 before and 265 &#45 9 ppb after; n =6, p <0.001). For control purposes the nasal analyses were repeated again, this time under hyperbaric conditions (+4.9 kPa). This resulted in a slight decrease in the NO levels (from 273 &#45 22 to 241 &#45 17 ppb; n =10, p <0.001), but there was no change in the nasal airway resistance. We conclude that a reduction in sinus pressure, as seen in upper airway allergy or infection, may result in an increase in upper airway NO production.     

One‐stop neck lump clinic: phase 2 of audit. How are we doing?

One‐stop neck lump clinic: phase 2 of audit. How are we doing? Regular monitoring and audit of a service are integral to ensuring maintenance of efficiency and standards. This is particularly important where the quality of the service is operator dependent, as is the case in the clinical diagnosis of neck lumps and fine needle aspiration cytology. The one‐stop neck lump clinic has now been running in the department for more than 20 months. A previous article described the results of the first phase audit carried out at 6 months and had identified a waiting time to be seen that was longer than that recommended by the British Association of Otorhinolaryngologists, Head and Neck Surgeons. Measures were implemented to reduce this waiting time and a second audit was carried out after another 10 months with the aims of assessing if modification of the means of referral reduces waiting time and if the outcomes of clinical performance in phase 1 could be maintained or improved. We discuss the results of phase 2 in the audit spiral.     

The expression of vascular endothelial growth factor (VEGF) and VEGF‐C in early laryngeal cancer: relationship with radioresistance

The expression of vascular endothelial growth factor (VEGF) and VEGF‐C in early laryngeal cancer: relationship with radioresistance Angiogenesis is essential for tumour growth and invasion. Vascular endothelial growth factor (VEGF) is a prime mediator of tumour angiogenesis. VEGF‐C is a closely related protein that effects lymphatic endothelial cells and may be important in the process of lymphatic metastasis. The purpose of this study was to evaluate the expression of these cytokines in patients with T1 and T2a glottic, squamous cell carcinoma, in comparison with normal epithelial control tissue, to ascertain any association with radioresistance. Twenty‐two tumours treated by radiotherapy (13 radiosensitive, nine radioresistant) and seven normal control tissues were studied. The minimum follow‐up was 2 years after radiotherapy. Expression of VEGF and VEGF‐C was evaluated by immunohistochemistry of formalin‐fixed, paraffin‐embedded biopsy specimens. Analysis was carried out using a quantitative computer image analyser. Both VEGF and VEGF‐C were detectable in tumour and normal control specimens. There was increased expression in tumour specimens of both VEGF (P = 0.03) and VEGF‐C (P < 0.001). In addition, the expression of VEGF‐C was associated with tumours of higher histological grade (P = 0.021). There was, however, no difference in VEGF and VEGF‐C expression between radioresistant and radiosensitive tumours. The expression of VEGF and VEGF‐C is increased in early laryngeal squamous cell carcinoma (SCC). However, measuring the expression of these proteins cannot predict radioresistance in this tumour group.     

Treatment of Maxillary Sinus Carcinoma: Clinical Results Using the Kitasato Modality

The conventional therapeutic regimen for maxillary sinus carcinoma consists of dissection of the maxilla, full-dose irradiation and extensive chemotherapy. However, the results obtained with this treatment are often poor. Even when patients recover, their quality of life is significantly reduced as a result of deformity of facial structures and swallowing and articulation dysfunctions. A retrospective analysis of 68 patients with maxillary sinus carcinoma treated with the Kitasato modality between 1975 and 1999 was conducted. All patients underwent pergingival maxillary sinus surgery combined with pre- and postoperative irradiation therapy with standardized total doses of 16 Gy; the postoperative irradiation was given in combination with regional intra-arterial infusion chemotherapy administered via the superficial temporal artery. All visible tumor lesions were removed where possible in order to preserve or facilitate cellular immunity after surgery. The cumulative 5-year survival rates were 85.7% for Stage II patients, 88.1% for Stage III, 76.6% for Stage IVA and 75.0% for Stage IVB.     

Cervical Reflex Induced by Click Stimuli in Cats

We studied click-evoked potentials in the anterior horn of the spinal cord in 17 cats. A concentric needle electrode was inserted into the anterior horn of the spinal cord at levels C3-C6. Potentials evoked with 105 dB SPL clicks were recorded with a peak latency of 4.89-5.10 ms only at the C3 level. These responses were observed 45-60 dB SPL above the auditory brainstem response (ABR) threshold, and no potentials were evoked by stimulation of the contralateral ear. Average was performed 100 times with changes in stimulation frequency of 1-20 Hz. The amplitude of the potentials decreased with increasing stimulus frequency, but there were no changes in ABRs. The responses disappeared after destruction of the medial vestibulospinal tract at the obex level, but ABRs were still recorded. The spinal nucleus of the accessory nerves was located in the anterior horn of the spinal cord at levels C1-C6, and the sternocleidomastoid muscle motoneurons were found at levels C1-C3. The click-evoked potentials recorded in this study reflect responses of the spinal nucleus of accessory nerves through the vestibulospinal tract to click stimulation. The responses have the same characteristics as vestibular-evoked myogenic potentials that can be recorded using surface electrodes over the sternocleidomastoid muscles of humans.     

A simple objective evaluation and grading for facial paralysis outcomes

Matrix metalloproteinase (MMP)-2 and -9 degrade type IV collagen, which is one of the major components of the basement membrane in normal tissue and expressed in the surroundings of the cancer nest in squamous cell carinoma. The degeneration of type IV collagen is an essential step in the metastasis to lymph nodes and distant organs. In this study, we examined MMP-2 and -9 levels of cancer tissue and serum obtained from patients with head and neck squamous cell carcinoma (HNSCC) in order to evaluate the relationship between the clinicopathologic features and MMPs. We examined the production of MMP-2 and -9 in cancer tissue homogenates of 73 patients who had HNSCC and the serum MMP levels of 16 patients with HNSCC and 8 healthy volunteers. We also studied the localization of MMP-2 in the carcinoma using an immunohistochemical approach. The concentrations of MMP-2 and -9 in the tissue homogenates and serum were measured by means of a sandwich enzyme immunoassay using a monoclonal antibody. Immunohistochemical analyses were performed with monoclonal antibody to MMP-2. The concentration of MMP-2 in the tumor tissue homogenates was unrelated to tumor size, but that in patients with lymph node metastases was significantly higher than in those without lymph node metastases. The concentration of MMP-9 was unrelated to lymph node metastasis and tumor size. The levels of both MMP-2 and -9 in serum were unrelated to lymph node metastasis. Immunohistochemistry indicated that MMP-2 was mainly expressed in cancer cells. Because MMP-2 degrades type IV collagen, the level of MMP-2 in carcinomas may be a useful indicator of the degree of invasion and metastasis.     

A case of cortical deafness and anarthria

The nasal epithelium protects the underlying tissue from damage. Epithelial cell growth is controlled by epidermal growth factor (EGF) and is possibly affected by toxic proteins, e.g. eosinophil cationic protein (ECP). The aims of this study were to examine nasal fluid epithelial cell counts and their relations to EGF, eosinophils and ECP in 23 patients with seasonal allergic rhinitis and 20 healthy controls. Nasal fluid epithelial cell counts were lower in patients than in controls. EGF levels did not differ between patients and controls, and correlated with epithelial cell counts in controls but not in patients. Eosinophils and ECP were higher in patients than in controls, but did not correlate with epithelial cell counts. The role of growth factors, such as EGF, in regulating epithelial cells merits further study.     

Tongue Base Reduction with Temperature-controlled Radiofrequency Volumetric Tissue Reduction for Treatment of Obstructive Sleep Apnea Syndrome

In recent years a considerable effort has been made to establish the use of different surgical techniques for the treatment of obstructive sleep apnea syndrome (OSAS). Nevertheless, treatment of hypopharyngeal obstruction due to tongue base hypertrophy remains in many ways an unsolved problem. The aim of this study was to evaluate the safety and efficacy of tongue base reduction with temperature-controlled radiofrequency volumetric tissue reduction in the treatment of OSAS. Twenty patients with OSAS and tongue base hypertrophy were treated with radiofrequency tissue ablation. An intensified treatment protocol was used, delivering 2,800 J per treatment session under local anesthesia. Two nights of polysomnography testing were performed before and after treatment. Daytime sleepiness, snoring and postoperative morbidity were assessed using questionnaires. Mean respiratory disturbance index (RDI) was reduced from 32.1 to 24.9/h after a mean of 3.4 treatment sessions. Six patients (33%) were cured after the procedure (reduction in RDI of &#83 50% and a postoperative RDI of <15/h) and ten (55%) showed an improvement of >20% in their RDI. Daytime sleepiness and snoring improved significantly. Peri- and postoperative morbidity was low; one severe complication occurred (tongue base abscess). We were able to achieve similar cure and responder rates to those reported in a recently published pilot study but with a reduced number of treatment sessions. We believe that this technique may improve patient acceptance and have beneficial cost implications.     

Bilateral versus unilateral cochlear implantation in young children

Objectives

To compare the preverbal communication skills of two groups of young implanted children: those with unilateral implantation and those with bilateral implantation.

Material and methods

The study assessed 69 children: 42 unilaterally and 27 bilaterally implanted with age at implantation less than 3 years. The preverbal skills of these children were measured before and 1 year after implantation, using Tait Video Analysis that has been found able to predict later speech outcomes in young implanted children.

Results

Before implantation there was no significant difference between the unilateral group and the bilateral group. There was still no difference at 12 months following implantation where vocal autonomy is concerned, but a strongly significant difference between the groups for vocal turn-taking and non-looking vocal turns, the bilateral group outperforming the unilateral group. Regarding gestural turn-taking and gestural autonomy, there was a strongly significant difference between the two groups at the 12 month interval, and also a difference before implantation for gestural autonomy, the unilateral group having the higher scores. Multiple regression of non-looking vocal turns revealed that 1 year following implantation, bilateral implantation contributed to 51% of the variance (p < 0.0001), after controlling for the influence of age at implantation and length of deafness which did not reach statistical significance.

Conclusions

Profoundly deaf bilaterally implanted children are significantly more likely to use vocalisation to communicate, and to use audition when interacting vocally with an adult, compared with unilaterally implanted children. These results are independent of age at implantation and length of deafness.