鼻咽癌的血管生成及其临床意义

目的　探讨血管内皮生长因子 (vascularendothelialgrowthfactor,VEGF)的表达和微血管密度 (mi crouesseldensity ,MVD)在鼻咽癌中的临床意义。方法　采用免疫组织化学S -P法 ,研究 4 0例鼻咽癌组织和10例正常鼻咽黏膜组织切片中的血管内皮生长因子的表达和微血管密度。结果　血管内皮生长因子主要定位于肿瘤细胞的胞浆和胞膜 ,鼻咽癌组织中血管内皮生长因子的表达阳性率为 92 .5 % (37/ 4 0 ) ,明显高于正常鼻咽黏膜组织 (P <0 .0 5 ) ,微血管密度也明显高于正常鼻咽黏膜组织 (P <0 .0 5 ) ,且二者具有相关性 (相关系数为 0 .80 9,P <0 .0 5 ) ,并与鼻咽癌病人分期、淋巴结转移和骨、肺、肝等远处转移有关。结论　鼻咽癌血管内皮生长因子的表达和微血管密度与肿瘤淋巴结转移和远处转移有关 ,血管生成在鼻咽癌生长、浸润、转移中起着重要的作用。血管内皮生长因子的表达和微血管密度可以作为鼻咽癌病人有意义的预后指标。     

不同家族史鼻咽癌患者癌组织Prohibitin的表达

目的对比Prohibitin(PMB)在不同家族史的鼻咽癌患者癌组织中的表达,以探究鼻咽组织中Prohibitin是否可以作为鼻咽癌潜在标记物。方法收集高癌家系气虚质鼻咽癌患者、鼻咽黏膜慢性炎症患者的鼻咽组织各9例,散发气虚质鼻咽癌患者的鼻咽组织12例,应用实时定量PCR方法检测Prohibitin在各组鼻咽组织中的表达。利用Western-blotting蛋白免疫印迹方法检测Prohibitin在各组患者鼻咽组织中的表达。结果 PHB m RNA在鼻咽黏膜慢性炎症鼻咽组织、散发气虚质鼻咽癌组织、高癌家系气虚质鼻咽癌组织中的2-△△Ct值分别为1.00±0.72、1.08±0.49、0.97±0.41(P0.05)。PHB蛋白相对表达依次为0.33±0.21、0.59±0.25、1.72±0.96(P0.05)。分析各组间对比PHB基因表达量无明显变化,但蛋白表达量鼻咽癌患者明显高于正常人,高癌家系鼻咽癌患者蛋白表达量高于散发患者,考虑与级联放大反应有关,有望成为高癌家系气虚质鼻咽癌患者早期诊断及筛查的标志物。     

鼻咽癌中环氧化酶-2的表达及其与Survivin和Caspase-3的相关性研究

目的探讨环氧化酶-2(COX-2)在低分化鼻咽癌中的表达及其与Survivin和Caspase-3的关系。方法采用免疫组织化学方法对56例低分化鼻咽癌患者肿瘤组织及20例鼻咽黏膜组织的COX-2和Survivin及Caspase-3蛋白表达进行检测。结果鼻咽癌标本中COX-2的表达阳性率为76.8%,鼻咽黏膜表达阳性率为15.0%,两组之间差异有统计学意义(P<0.01)。鼻咽癌中COX-2和Survivin的表达具有相关性(P<0.05),COX-2和Caspase-3的表达无相关性(P>0.05)。结论COX-2在低分化鼻咽癌致病中起着重要作用,其凋亡抑制作用可能通过调控Survivin途径来实现。     

鼻咽癌间质微血管密度与MMP-2表达和肿瘤转移的关系

目的 研究鼻咽癌组织中微血管密度的分布以及与基质金属蛋白酶2(matrix metalloproteinase2,MMP-2)的表达关系,探讨其与肿瘤淋巴结转移的关系.方法 应用免疫组化Elivision Plus二步法,检测50例鼻咽癌和15例炎性鼻咽部黏膜组织间质微血管密度(microvascular density,MVD)的分布,并检测MMP-2的表达.结果 鼻咽癌组织MVD为21.92±7.80,明显高于炎性鼻咽黏膜组织(9.23±1.84),两者之间差异有显著性(P＜0.01);MMP-2阳性组MVD均值为25.46±6.79,高于MMP-2阴性组17.40±6.69,MMP-2的表达与MVD有关(P＜0.01).此外,鼻咽癌MVD与临床分期及淋巴结转移密切相关(P＜0.01).结论 MMP-2可能促进鼻咽癌间质血管生成,促进肿瘤的侵袭和转移,MMP-2和MVD有可能成为判定鼻咽癌生物学行为和预后的重要指标.     

Survivin和MRP表达的相关性及与鼻咽癌耐药的关系研究

目的:探讨Survivin、多药耐药蛋白(MRP)表达相关性及与鼻咽癌耐药之间的关系。方法:本研究首先采用免疫组织化学法检测Survivin和MRP在45例鼻咽癌和24例正常鼻咽黏膜上皮组织中的表达,分析其表达与鼻咽癌临床病理特征之间的关系;其次,检测Survivin和MRP在31例鼻咽癌紫杉醇耐药患者与20例紫杉醇非耐药患者中的表达,分析它们的表达相关性及其与鼻咽癌耐药的关系;最后采用浓度递增法持续诱导建立鼻咽癌化疗耐药细胞株5-8F-PTX(+),Western blot检测Survivin和MRP在5-8F-PTX(+)和5-8F中的表达情况。结果:Survivin在鼻咽癌组织中的阳性率为71.1%(32/45),明显高于正常鼻咽黏膜组织8.33%(2/24)(P<0.05);Survivin表达与鼻咽癌的分化程度、淋巴结和远处转移以及临床分期有关,与年龄、性别无关;低分化鼻咽癌中Survivin表达阳性率为79.5%(31/39),明显高于中分化鼻咽癌的16.7%(1/6),二者比较差异有统计学意义(P<0.05);Survivin在鼻咽癌化疗耐药患者中表达阳性率为83.9%(26/31),明显高于非耐药患者45.0%(9/20),二者比较差异有统计学意义(P<0.05);MRP在鼻咽癌化疗耐药患者中表达阳性率为87.1%(27/31),明显高于非耐药患者40.0%(8/20),二者比较差异有统计学意义(P<0.05);31例鼻咽癌化疗耐药患者中Survivin和MRP的表达呈正相关;Survivin和MRP在5-8F-PTX(+)中表达水平明显高于非耐药的5-8F;5-8FPTX(+)耐药细胞株中,紫杉醇、顺铂、5-FU、长春新碱耐药的IC50值均明显高于亲本5-8F组。结论:Survivin表达与鼻咽癌的分化、转移和临床分期有关,可作为鼻咽癌发生、发展的分子标记物;Survivin和MRP高表达与鼻咽癌细胞的耐药性增加有关。     

EB病毒基因BARF1在鼻咽癌中的表达及其意义

目的 EB病毒与鼻咽癌(特别是低分化鳞癌)密切相关。BARF1基因是EBV裂解期中的早期基因，本研究通过检测BARF1基因在鼻咽癌组织中的表达，希望能进一步揭示EB病毒与鼻咽癌的关系及致癌的可能机制。方法 对经病理确诊的47例鼻咽低分化鳞癌病人分别取癌组织、癌旁组织及相对正常鼻咽黏膜和13例其他头颈部恶性肿瘤癌组织及8例正常人鼻咽黏膜组织(均证实有EB病毒潜伏感染)，采用巢式-PCR技术检测BARF1在这些组织中的表达情况。结果 鼻咽癌组织BARF1基因表达率为91．5％(43／47)，其中39例相对强表达，4例弱表达；癌旁组织BARF1基因表达率为46．8％(22／47)，其中儿例相对强表达，儿例弱表达；相对正常黏膜BARF1基因表达率为6．4％(3／47)，3例均为弱表达；携带EB病毒的其他头颈部恶性肿瘤组织、正常人鼻咽黏膜组织均未检测到：BARY1基因表达。结论 从相对正常鼻咽黏膜到癌旁组织再到鼻咽癌组织BARF1基因的表达趋势为从不表达到表达，从弱表达到强表达。说明EB病毒与鼻咽癌的发生确实存在密切相关性；提示启动BARF1基因的表达有可能是EB病毒致鼻咽癌的重要条件之一。     

组织微阵列研究eIF4E在鼻咽癌中的表达及其临床意义

目的　研究eIF4E在鼻咽癌及其癌旁组织和鼻咽上皮组织的表达及其临床意义。方法　应用自行研制的组织微阵列 ,结合免疫组化技术 ,检测eIF4E在鼻咽癌及其癌旁上皮组织和鼻咽上皮组织的表达情况。结果　eIF4E在鼻咽上皮组织、癌旁上皮组织和鼻咽癌组织中阳性表达率分别为 6 1 .0 %(5 8/ 95 )、84 .6 %(77/ 91 )和87.3%(1 99/ 2 2 8) ,鼻咽癌和癌旁上皮组织的阳性表达率均高于鼻咽上皮组织 (P <0 .0 1 ) ,鼻咽癌和癌旁上皮组织两者阳性表达率比较无统计学意义 (P >0 .0 5 )。eIF 4E的表达与鼻咽癌的转移和临床分期无显著相关性(P >0 .0 5 ) ,而与放疗是否耐受有显著相关 (P <0 .0 5 )。结论　eIF4E在鼻咽癌的发生过程中可能起重要作用 ;eIF4E可作为预测鼻咽癌放疗是否耐受的分子指标之一。     

人类鼻咽癌端粒酶活性的研究及其临床意义

目的　探讨端粒酶在鼻咽癌中的表达及其临床意义。方法　采用TRAP 银染法对 42例鼻咽部低分化鳞状细胞癌、10例鼻咽部正常粘膜和 8例鼻咽纤维血管瘤进行端粒酶活性检测及血清VCA/IgA检测 ,并分析其与临床病理的关系。结果　鼻咽部正常粘膜和鼻咽癌端粒酶阳性率分别为 2 0 %和 88.1% ,8例鼻咽纤维血管瘤均未检测到端粒酶活性。鼻咽癌伴颈部淋巴结转移者端粒酶阳性率高于无颈部淋巴结转移者 (P =0 .0 35 ) ,临床晚期 (III、IV)端粒酶阳性率高于临床早期 (I、II) (P=0 .0 48) ,而端粒酶与鼻咽癌患者的年龄、性别及远处转移均无明显相关性 (P >0 .0 5 )。鼻咽癌患者血清EB病毒VCA/IgA阳性率明显高于鼻咽粘膜正常者 (P <0 .0 0 1)。结论　端粒酶活性表达在鼻咽癌发病机制中起着重要作用。端粒酶活性结合血清EB病毒抗体的检测有利于鼻咽癌的早期诊断。     

凋亡抑制基因Survivin与鼻咽癌预后关系的研究

目的　探讨凋亡抑制基因Survivin蛋白产物在鼻咽癌 (NPC)组织中的表达情况与凋亡指数 (AI)、临床特征及预后之间的关系。方法　应用免疫组化技术S P法及TUNEL法 ,对 5 1例鼻咽癌组织标本进行凋亡抑制基因Survivin蛋白产物及凋亡指数检测。结果　在鼻咽癌组织中Survivin蛋白产物表达阳性率为 82 .4 % ,其中高表达占 5 1% ,AI平均为 2 .6 % ,Survivin的表达与AI存在相关性且与NPC病人的预后密切相关 (P <0 .0 5 )。结论Survivin的过度表达是导致NPC凋亡减少的一个重要原因 ,对NPC发生、发展起一定作用 ,而且对NPC的预后有重要的价值     

基质金属蛋白酶2及其组织抑制物在鼻咽癌中的表达

目的 研究基质金属蛋白酶2(matrix metalloproteinase 2,MMP-2)及其组织抑制物(tissue inhibitor of metalloproteinases 2,TIMP-2)在鼻咽癌中的表达及其与鼻咽癌生物学行为的关系.方法 采用免疫组化Elivision Plus二步法对50例鼻咽癌组织、15例炎性鼻咽黏膜组织MMP-2、TIMP-2进行检测,并进行x2检验.结果 免疫组化结果显示MMP-2、TIMP-2在鼻咽癌组织中表达显著高于炎性鼻咽黏膜组织(P＜0.05).MMP-2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,有显著性差异(P＜0.01).TIMP-2在有淋巴结转移者极显著高于无淋巴结转移者(P＜0.01).TIMP-2随临床浸润程度升高其表达上调,但无显著性差异(P＞0.05).结论 表明MM P2和TIMP-2在鼻咽癌细胞突破基底膜向外扩散及转移中起着重要作用,MMP-2/TIMP-2比率失衡在判断鼻咽癌侵袭性、估计其预后中有一定意义.     

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.     

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.     

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.     

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.