酪氨酸激酶受体B与脑源性神经营养因子mRNA在鼻咽癌中的定量表达

目的研究酪氨酸激酶受体B（tyrosine kinase receptors B,TrkB）及其配体脑源性神经营养因子（brain derived neurotrophin factor,BDNF）在鼻咽癌中的表达及其与鼻咽癌生物学行为的关系。方法采用实时荧光PCR的方法对57例鼻咽癌组织、20例鼻咽炎性黏膜组织中的TrkB、BDNF进行检测。结果实时荧光PCR结果为TrkB、BDNF在鼻咽癌组织中表达显著高于鼻咽炎性黏膜组织（P〈0．05）。TrkB表达随鼻咽癌临床浸润程度的升高,淋巴结转移的发生而上调（P〈0．05）。BDNF在有淋巴结转移者显著高于无淋巴结转移者（P〈0．05）。TrkB的表达强度与BDNF有正相关的关系（rs=0．281,P〈0．05）。结论表明TrkB和BDNF在鼻咽癌的浸润和转移机制中起着重要作用,特异性阻断TrkB／BDNF信号传导通路,将为临床治疗鼻咽癌找到新的突破点。     

乙酰肝素酶、蛋白激酶CK2β与缺氧诱导因子-1α仪在鼻咽癌组织中的表达及其相关性研究

目的：检测乙酰肝素酶（HPA）、蛋白激酶CK2β（CK2β）、缺氧诱导因子-α（HIF-1α）在鼻咽癌（NPC）组织中的表达及其与临床特征之间的关系;并分析三者在NPC组织中表达的相关性。方法：采用免疫组织化学染色技术Super-Vision法检测49例NPC组织标本及15例慢性鼻咽炎（CNT）组织标本中HPA、CK2β及HIF-1α的表达水平。结果：HPA、CK2β与HIF-1α在NPC组织中的表达水平均高于CNT组织中的表达,差异均有统计学意义（P〈O．05）;HPA、CK2β与HIF-β的表达与NPC临床分期、治疗后有无复发或转移相关（P〈0．05）,与患者的性别无关（P〉0．05）;HIF-1α的表达水平与NPC患者的年龄密切相关（P％0．01）,而HPA、CK2β的表达水平则与NPC患者的年龄无关（P〉0．05）;HPA、CK2β与HIF-1α任意两者间在NPC组织中的表达均呈正相关性（P〈O．05）。结论：HPA、CK2β和HIF-1α参与了NPC的发生和发展、浸润及转移;在NPC的发生发展过程中,HPA、CK2β和HIF-1α之间可能存在协同作用。     

喉癌中血管生成素-2和基质金属蛋白酶-7的表达及临床意义

目的：研究喉癌组织中血管生成素-2（Ang-2）和基质金属蛋白酶-7（MMP-7）的表达情况及临床意义。方法：应用免疫组织化学SP法检测65例喉癌及34例癌旁喉黏膜组织中Ang-2和MMP-7的表达,分析Ang-2和MMP-7表达与喉癌浸润、转移和预后的关系。结果：喉癌组织中Ang-2和MMP-7表达的阳性率均明显高于癌旁喉黏膜组织（均P〈0．05）,且Ang-2表达与肿瘤T分期及临床分期相关（均P〈0．05）,MMP-7表达与肿瘤T分期、淋巴结转移以及临床分期相关（均P〈0．05）,而二者表达与患者年龄、病程、吸烟、饮酒、病理分化程度及临床分型无关（均P〉0．05）。喉癌组织中Ang-2和MMP-7表达存在正相关性（P〈0．05）。Kaplan—Meier生存分析显示Ang2表达与患者总生存率有密切关系（P〈0．05）,而与无瘤生存率未见明显关系（P〉0．05）;MMP-7表达与总生存率及无瘤生存率均未见明显关系（P〉0．05）。Cox回归分析显示Ang-2和MMP-7阳性表达为喉癌独立的预后因素。结论：喉癌组织中存在Ang-2和MMP-7的高表达,两者可作为临床上判断喉癌生物学行为、评估预后的客观指标。     

喉及下咽部鳞状细胞癌中血管内皮生长因子-c及其受体FLT-4表达与淋巴结转移的相关研究

目的：研究喉及下咽部鳞状细胞癌组织中血管内皮生长因子-C（VEGF-C）及其受体VEGFR-3（FLT-4）的表达情况,以及它们在肿瘤淋巴转移、微转移中的作用和意义。方法：采用免疫组织化学SP法及图像分析技术,检测49例喉及下咽部痛组织中VEGFC、FLT-4及淋巴结中VEGF-C蛋白表达和相对含量。结果：喉及下咽部癌组织中VEGF-C的表达与病理分级密切相关（均P〈0．05）,与淋巴结转移之间存在相关关系（均P〈0．05）,与临床T分期无关。FLT-4表达与VEGF-C阳性表达呈同向性改变,与淋巴结转移相关（均P〈0．05）;喉及下咽部癌组织中,FLT-4阳性脉管数与病理分级及临床T分期差异无统计学意义（均P〉0．05）。喉及下咽部癌组织中淋巴结微转移组,VEGFC、FLT-4表达与无转移组之间的差异无统计学意义（P〉0．05）。结论：VEGFC在喉及下咽部癌组织中,通过其特异性受体FLT-4导致淋巴管增生,促进肿瘤淋巴转移,从而影响患者的预后;检测VEGF-C、FLT-4,对肿瘤诊断、判断患者预后具有重要临床价值。     

CD105与喉鳞状细胞癌血管生成及生物学行为的关系

目的：研究CD105在喉鳞状细胞癌血管中的表达,及其喉鳞状细胞癌生物学行为的意义。方法：采用双重免疫组织化学染色技术分别检测CD34／Ki67、CD105／Ki67在30例喉鳞状细胞癌和10例正常喉黏膜石蜡标本中的表达,分别以抗CD34和抗CD105单克隆抗体标记量化新生微血管（MVD）,以抗Ki67单克隆抗体标记增殖的内皮细胞,并结合临床资料进行分析。结果：正常组和喉鳞状细胞癌组比较,MVDCD105差异有统计学意义（P〈0．05）;喉鳞状细胞癌组CD105标记的微血管增殖指数（PI）高于CD34标记组（P〈0．01）;MVDCD34与MVDCD105在喉鳞状细胞癌高分化组和低分化组的差异均有统计学意义（P〈0．05）;MVDCD34与MVDCD105均与淋巴结转移无关（P〉0．05）;MVDCD34与肿瘤的浸润范围无关（P〉0．05）,与喉鳞状细胞癌的临床分期也无关（P〉0．05）;MVDCD105则随肿瘤浸润范围的增大而增加（P〈0．01）,且随临床分期升高而增加（P〈0．01）。结论：CD105是新生血管的特异性标志物,新生血管密度与肿瘤的大小、临床分期相关,但与喉鳞状细胞癌的淋巴结转移无关。     

淋巴管内皮透明质酸受体-1标记的喉鳞状细胞癌组织淋巴管密度测定及其临床意义

目的：探讨喉鳞状细胞癌组织中微淋巴管密度、位置及增殖情况与喉癌生物学行为和临床病理因素的关系。方法：利用LSAB免疫组化三步法研究淋巴管内皮特异性标记物淋巴管内皮透明质酸受体-1（LYVE-1）在喉鳞状细胞癌组织中的表达，光镜和图像分析观察微淋巴管密度并对淋巴管进行定位；EnVision免疫组化二步法研究Ki67在LYVE-1（＋）管腔的表达，评价淋巴管增殖情况。结果：①颈淋巴结转移组瘤巢内LYVE-1（＋）管腔密度高于非转移组，差异有统计学意义（P〈0．01）；T1组瘤巢内LYVE-1（＋）管腔密度低于T2、T3、T4组，差异具有统计学意义（均P〈0．01），T2组瘤巢内LYVE-1（＋）管腔密度低于T3、T4组，差异有统计学意义（均P〈0．05），T3组与T4组瘤巢内LYVE-1（＋）管腔密度相比差异无统计学意义（P=0．582）；瘤巢内LYVE-1（＋）管腔密度在声门型组与声门上型组、鳞癌Ⅰ级组与鳞癌Ⅱ级组之间差异无统计学意义（均P〉0．05）。②颈淋巴结转移组瘤巢周LYVE-1（＋）管腔密度高于非转移组，差异无统计学意义（P〉0．05）。⑧瘤巢内LYVE-1（＋）管腔存在Ki67核棕黄色着色，瘤巢周LYVE-1（＋）管腔未见这一现象。结论：喉鳞状细胞癌组织LYVE-1标记的瘤巢内淋巴管密度与肿瘤浸润、淋巴结转移正相关；喉鳞状细胞癌肿瘤淋巴管生成主要在瘤巢内，瘤巢内淋巴管在肿瘤的浸润、转移过程中发挥更为重要的作用。     

喉癌组织中DcR3蛋白的表达及临床意义

目的：探讨诱捕受体3（DcR3）在喉癌组织中的表达及其与各临床病理因素的关系。方法：采用流式细胞术检测41例喉癌组织和41例相应癌旁组织中的DcR3的表达,并以15例非喉癌患者喉部正常黏膜组织作对照。结果：①喉癌组织中DcR3蛋白的表达量及阳性表达率均明显高于癌旁组织及正常喉黏膜组织（P〈0．01或P〈0．05）,癌旁组织及正常喉黏膜组织的表达差异无统计学意义（P〉0．05）;②DcR3蛋白的表达与喉癌组织中的淋巴结转移、临床分期、分化程度有相关性（均P〈0．05）;与临床分型、肿瘤大小、吸烟量、年龄和性别无相关性（均P〉0．05）。结论：DcR3蛋白的高表达可促进喉癌的发生、发展,其蛋白检测可作为判断喉癌分化、浸润、转移、分期的重要指标。     

RECK基因在鼻咽癌中的表达及其临床意义

目的检测伴有Kazal域的富含半胱氨酸的逆转诱导蛋白（reversion-inducing cysteine-rich protein with Kazal motif,RECK）基因在鼻咽癌（nasopharyngeal carcinoma,NPC）组织中的表达及其与临床病理因素的关系。方法采用原位杂交技术检测60例原发性NPC（颈淋巴结转移组和无颈淋巴结转移组各30例）、10例NPC颈部转移淋巴结（metastastic lymph node,MLN）和20例鼻咽黏膜慢性炎症组织（chronic nasopharyngitis tissue,CNT）中RECK mRNA的表达,并对NPC各临床病理参数进行分析。结果 CNT、NPC和MLN中RECK的阳性表达率分别为85.0%（17/20）、26.7%（16/60）和30.0%（3/10）。与CNT比较,NPC和MLN中RECK表达下调,差异均有统计学意义（P均〈0.05）。NPC有淋巴结转移组与无淋巴结转移组RECK阳性表达率分别为13.3%（4/30）和40.0%（12/30）,两者比较,差异有显著性（P〈0.05）。NPC原发灶中RECK低表达与患者性别、年龄、T分级和临床分期无关（P均〉0.05）,与颈淋巴结转移、复发和治疗后5年生存期有关（P均〈0.05）。结论 RECK基因低表达可能与NPC的进展有关,它可作为评估NPC颈淋巴转移、复发及预后的生物学参考指标。     

膜联蛋白A5在喉癌组织中的表达及临床意义

目的通过观察膜联蛋白A5（annexinA5，ANXA5）在喉癌组织中的表达，探讨ANXA5在喉癌中的作用。方法采用免疫组化SP法及RT-PCR法检测53例不同临床分期、病理学分级及颈部淋巴结转移的喉癌组织与25例癌旁组织标本中ANXA5及其基因的表达情况。结果喉癌组织中ANXA5水平高于癌旁组织中ANXA5的水平（P〈0．05）；ANXA5的表达与临床分期、病理学分级及颈部淋巴结转移密切相关（P〈0．05），与患者年龄、性别及临床分型无关（P〉0．05）。结论ANXA5可能在喉癌的发生、发展中发挥重要作用。     

肝细胞生长因子和乙酰肝素酶在喉鳞状细胞癌组织中的表达及其临床意义

目的：研究喉鳞状细胞癌（LSCC）组织中肝细胞生长因子（hypatocyte cell growth factor HGF）和乙酰肝素酶（heparanase,Hpa）的表达及其临床意义,分析不同病理分级（高、中、低分化）LSCC组织中HGF和Hpa表达的差异,为临床治疗及防治喉癌转移、复发提供理论依据和新的思路。方法：采用免疫组织化学SP法检测40例接受手术治疗并经病理证实为原发性LSCC的病理组织石蜡标本,同期40例接受手术治疗并经病理证实为成人喉原发性乳头状瘤病理组织石蜡标本和12例癌旁正常喉黏膜组织石蜡标本中的HGF和Hpa表达,并结合临床资料进行分析。结果：HGF、Hpa在LSCC组中阳性表达率分别为77．5％、72．5％,与喉乳头状瘤组和癌旁正常喉黏膜组比较,均差异有统计学意义（均P〈0．01）。且两者的表达与LSCC原发部位无明显的相关性（P〉0．05）,而与T分期呈正相关（P〈0．05）;有局部淋巴结转移组显著高于无局部淋巴结转移组,其比较差异有统计学意义（P〈0．05）;与细胞分化程度呈负相关（P〈0．05）。在40例LSCC中,HGF和Hpa表达呈正相关关系（P〈0．01）。结论：LSCC中存在HGF和Hpa的高表达,与良性组织差别显著,肿瘤组织中的表达水平与与淋巴结转移、病理分级、临床分期、T分级等有关,与肿瘤原发部位无关。HGF和Hpa在LSCC的表达呈正相关,可作为评估LSCC进展的有价值的指标。     

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.     

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.     

Lack of significant estrogen and progesterone receptor expression in nasal telangiectasias in hereditary hemorrhagic telangiectasia: an immunohistochemical analysis

Obstructive sleep apnea syndrome (OSAS) is characterized by snoring and apnea during sleep leading to decreased oxygen saturation and disturbed sleep, excessive daytime sleepiness and neuropsychological disturbances. This study investigates cognitive neuropsychological abilities in a group of 53 OSAS patients before and after treatment with uvulopalatopharyngoplasty. General intellectual ability, verbal learning and memory as well as executive functioning were measured at baseline and 6 months postoperatively. After surgery there were significant improvements in verbal learning and memory (mean change - 39, SD 57.3, p <0.001), recall (mean change - 24.3, SD 39.3, p <0.001) and executive functioning (as assessed by percentage of errors on the Wisconsin Card Sorting Test; mean change-9.1, SD 15.7, p <0.001). These improvements were in accordance with improvements in the degree of sleep apnea, the oxygen desaturation index (mean change -9.7, SD 15.9, p <0.001) and arterial minimum oxygen saturation (mean change 4.5%, SD 10.2%, p <0.01). Surgical treatment seems to improve verbal learning, memory and recall and executive functions in parallel with better oxygenation in OSAS.     

Measurement of chemosensory function

Although hundreds of thousands of patients seek medical help annually for disorders of taste and smell, relatively few medical practitioners quantitatively test their patients' chemosensory function, taking their complaints at face value. This is clearly not the approach paid to patients complaining of visual, hearing, or balance problems. Accurate chemosensory testing is essential to establish the nature, degree, and veracity of a patient's complaint, as well as to aid in counseling and in monitoring the effectiveness of treatment strategies and decisions. In many cases, patients perseverate on chemosensory loss that objective assessment demonstrates has resolved. In other cases, patients are malingering. Olfactory testing is critical for not only establishing the validity and degree of the chemosensory dysfunction, but for helping patients place their dysfunction into perspective relative to the function of their peer group. It is well established, for example, that olfactory dysfunction is the rule, rather than the exception, in members of the older population. Moreover, it is now apparent that such dysfunction can be an early sign of neurodegenerative diseases such as Alzheimer's and Parkinson's. Importantly, older anosmics are three times more likely to die over the course of an ensuring five-year period than their normosmic peers, a situation that may be averted in some cases by appropriate nutritional and safety counseling. This review provides the clinician, as well as the academic and industrial researcher, with an overview of the available means for accurately assessing smell and taste function, including up-to-date information and normative data for advances in this field.