喉癌肿瘤组织HIF-1α与COX-2蛋白和mRNA的表达及意义

目的:探讨喉鳞状细胞癌组织中缺氧诱导因子-1α(HIF-1α)、环氧合酶-2(COX-2)蛋白质和mRNA的表达,以期有助于喉鳞状细胞癌发生、发展和转移机制的进一步阐明。方法:用免疫组织化学和RT-PCR方法检测76例喉鳞状细胞癌组织和9例癌旁正常组织中HIF-1α、COX-2蛋白和mRNA的表达,并按T分期、病理分级分别探讨HIF-1α、COX-2蛋白和mRNA的表达与各临床病理参数的关系。结果:①HIF-1α、COX-2蛋白表达在喉癌标本的表达量明显高于癌旁正常组织(P<0.05),随T分期的增加而增高;中、低分化的喉癌组织中HIF-1α表达显著高于高分化喉癌;COX-2蛋白表达与病理分级无关。②HIF-1α与COX-2mRNA在喉癌组织中的阳性表达率分别是67.11%和75.00%,明显高于癌旁正常组织(P<0.05),癌旁正常组织未检测到COX-2mRNA表达。HIF-1α与COX-2mRNA在喉癌组织中的阳性表达率与T分期有关(P<0.05),标本的表达量随T分期的增加而增高,但是与病理分级无关(P>0.05)。③HIF-1α蛋白表达阳性病例中,COX-2的阳性率为78.72%。结论:HIF-1α与COX-2在喉鳞状细胞癌组织的表达增高并密切相关,可能是喉癌发生发展的原因之一。     

Stat3及其靶基因Cyclin D1在喉鳞状细胞癌组织中的表达及临床意义

目的:研究喉鳞状细胞癌组织中信号转导和转录激活因子3(Stat3)及其靶基因细胞周期蛋白D1(Cyclin D1)的表达情况并探讨其临床意义。方法:应用Western blot和RT-PCR方法,研究喉鳞状细胞癌组织中Stat3、Cyclin D1蛋白和mRNA的表达情况以及与喉鳞状细胞癌临床病理因素的关系。结果:喉鳞状细胞癌组织中Stat3、Cyclin D1蛋白和mRNA的表达水平明显高于正常喉黏膜组织(P<0.01)。Stat3、Cyclin D1蛋白表达水平与喉鳞状细胞癌临床分期、分化程度及淋巴结转移有关(P<0.01);在喉鳞状细胞癌组织中Stat3蛋白、mRMA与CyclinD蛋白、mRNA的表达均呈正相关(r=0.564、0.552,均P<0.01)。结论:Stat3信号转导通路在喉鳞状细胞癌的发生、发展过程中起重要作用,检测喉鳞状细胞癌组织中Stat3及其靶基因Cyclin D1的表达可以反映肿瘤的恶性程度。     

信号转导和转录激活因子3及其靶基因c-myc在喉鳞状细胞癌中的表达与意义

目的:检测喉鳞状细胞癌中信号转导和转录激活因子3(STAT3)基因及其靶基因c-myc的表达,探讨其临床意义及相关性.方法:采用原位杂交技术和免疫组织化学技术,在mRNA和蛋白2个水平检测STAT3和c-myc基因在56例喉鳞状细胞癌和30例喉全(或近全)切除者癌旁(>2.0 cm)正常黏膜中的表达,应用显微图像分析系统测定阳性表达的平均吸收度值,并进行统计分析.结果:在喉鳞状细胞癌组织中存在STAT3和c-myc基因的mRNA和蛋白高表达;STAT3和c-myc基因的mRNA表达与喉鳞状细胞癌的临床分期、分化程度和淋巴结转移有关(P<0.05或P<0.01);STAT3和c-myc基因的蛋白表达与喉鳞状细胞癌的临床分期和淋巴结转移有关(P<0.05或P<0.01);在喉鳞状细胞癌组织中STAT3和c-myc基因的高表达呈正相关(r=0.622 4、0.7012,均P<0.01).结论:STAT3基因及其靶基因c-myc的表达与喉鳞状细胞癌的发生、发展和转移等生物学行为有关,两者的表达呈正相关.     

喉癌组织中程序性细胞死亡因子4的表达及临床意义

目的:探讨程序性细胞死亡因子4(PDCD4)基因在喉鳞状细胞癌中的表达情况及PDCD4蛋白表达水平与喉癌临床病理学特征的关系。方法:应用Westernblot检测8例喉鳞状细胞癌患者喉癌组织及癌旁正常鳞状上皮组织中PDCD4蛋白的表达水平。应用免疫组织化学SP法检测PDCD4蛋白在54例喉癌组织及部分癌旁正常组织中的表达情况及PDCD4蛋白在这些组织中的细胞定位,观察PDCD4蛋白表达情况与喉癌临床病理学参数之间的关系。结果:PDCD4蛋白在癌旁正常组织中呈高表达,在喉癌中呈低表达或缺失(P<0.05)。PDCD4蛋白在喉正常鳞状上皮细胞核、细胞质表达,在喉癌组织中呈细胞质表达甚至缺失。PDCD4蛋白表达水平在喉癌病理分级各组间不相等(P<0.05),肿瘤分化程度越高,PDCD4蛋白表达越高(P<0.05)。结论:PDCD4基因是抑癌基因,其表达和缺失与喉癌的发生、肿瘤细胞的分化有关,有望成为喉癌基因治疗的新靶点。     

KAI1基因在喉癌及转移淋巴结中的表达

目的 通过研究KAI1基因在人类喉鳞状细胞癌及转移淋巴结中的蛋白表达情况,试图阐明KAI1基因蛋白的表达与喉癌转移之间的关系。方法 取喉鳞状细胞癌组织标本蜡块40例及转移的淋巴结13例,以癌旁正常组织标本蜡块30例作为对照,采用免疫组织化学SP法,检测KAI1单克隆抗体在喉鳞状细胞癌、转移淋巴结及癌旁正常组织标本中蛋白的表达,并结合患者临床病理资料进行统计学分析。结果 KAI1基因在癌旁正常组织、喉鳞状细胞癌及转移淋巴结中的表达率分别为93.33%（28/30）、62.50%（25/40）、30.77%（4/13）,且各组之间差异均有统计学意义（P＜0.05）。KAI1基因的蛋白表达与喉鳞状细胞癌的临床分期差异有统计学意义（P＜0.05）,与性别、年龄、原发部位、病理学分级及有无淋巴结转移无关(P＞0.05)。 结论 KAI1基因在喉鳞状细胞癌转移淋巴结中的表达较在喉鳞状细胞癌中的表达呈显著性下降,该基因可能在喉癌转移过程中起一定作用。     

Stathmin基因在喉鳞状细胞癌中的表达及临床意义

目的 观察stathmin基因和蛋白质在喉鳞状细胞癌(简称鳞癌)中的表达情况,探讨stathmin基因与喉鳞癌生物学行为的关系及临床意义,进一步认识喉鳞癌发生和发展的分子机制.方法选取2005年3月至2006年4月的38例喉鳞癌患者,术中从肿瘤中心部位取癌组织(实验组),在肿瘤边缘外1.0cm部位取癌旁正常组织(对照组).应用半定量逆转录-聚合酶链反应(RT-PCR)分析38例患者的喉鳞癌组织和癌旁正常组织中stathmin基因mRNA的表达水平,冰冻切片免疫组织化学方法检测喉鳞癌组织和癌旁正常组织中stathmin蛋白的表达情况.结果 RT-PCR结果显示,stathmin基因mRNA在38例喉癌患者的喉癌组织和癌旁正常组织均呈阳性表达;经半定量分析,stathmin mRNA在喉癌组织中的表达水平明显高于在癌旁正常组织的表达水平(t=9.655,P＜0.05).免疫组织化学发现,stathmin蛋白在26例(26/38,68.4%)患者的喉癌组织呈阳性表达,在13例(13/38,34.2%)患者的癌旁正常组织呈弱阳性表达;stathmin蛋白在喉癌组织中的阳性表达率明显高于在癌旁正常组织的阳性表达率(x2=8.901,P＜0.05).同时发现,stathmin mRNA的表达水平和stathmin蛋白的阳性表达率在Ⅲ期和Ⅳ期喉癌组明显高于Ⅰ期和Ⅱ期病例组(t=6.284,x2=5.810,P＜0.05),有颈部淋巴转移组明显高于无转移组(t=9.350,x2=6.923,P＜0.05).结论 stathmin基因和蛋白在喉鳞癌中的表达明显高于癌旁正常组织,在中晚期喉鳞癌中的表达明显高于早期喉鳞癌,并且与颈淋巴转移有关.stathmin基因与喉鳞癌的发生和发展均有密切关系,并可能与喉癌的预后有关.     

Jab1和p27kip1基因在喉鳞状细胞癌组织和喉癌Hep-2细胞中的表达及意义

目的:探讨Jab1和p27kip1基因在喉鳞状细胞癌组织和喉癌Hep-2细胞中的表达及意义。方法:采用免疫组织化学方法检测50例喉鳞状细胞癌组织和10例癌旁正常组织中Jab1和p27kip1的表达。采用人工合成Jab1siRNAⅡ用脂质体2000包裹后转染Hep-2细胞,用RT-PCR方法分析转染后喉癌细胞中Jab1和p27kip1基因的表达情况。结果:Jab1和p27kip1蛋白的阳性表达定位为细胞核中,Jab1在人喉鳞状细胞癌组织中高表达,正常喉黏膜中不表达或弱表达;p27kip1在人喉癌组织中弱表达,正常喉黏膜中强表达;两者呈负相关。Jab1siRNAⅡ可降低Jab1mRNA表达,并且随着时间的延长,Jab1mRNAⅡ在Hep-2细胞中的表达逐渐减弱,而p27kip1 mRNA的表达则无明显变化。结论:Jab1在人喉鳞状细胞癌组织中表达增强,正常喉黏膜中不表达或弱表达;p27kip1则正好相反。两者在喉癌中的表达呈负相关。Jab1siRNAⅡ可以特异性降低Jab1mRNA在喉癌Hep-2细胞中的表达,为进一步研究Jab1基因在喉癌中的作用奠定了基础。     

程序性细胞死亡因子5在喉鳞状细胞癌组织中的表达及临床意义

目的 探讨程序性细胞死亡因子5（PDCD5）在喉鳞状细胞癌组织中的表达及与临床病理指标的相关性。方法 采用逆转录多聚酶链式反应（RT PCR）技术和Western blot免疫印记技术检测41例喉鳞状细胞癌及29例癌旁正常黏膜组织中PDCD5mRNA和蛋白的表达情况,进一步应用免疫组化方法验证其在喉鳞状细胞癌组织中的定位表达。结果 PDCD5 mRNA喉鳞状细胞癌组织中较癌旁正常组织的表达明显降低,表达差异有统计学意义（P=0.006）;Western blot结果显示PDCD5 蛋白在喉鳞状细胞癌组织中较癌旁正常组织的表达明显降低,表达差异有统计学意义（P=0.012）。肿瘤组织中PDCD5 mRNA表达缺失与PDCD5蛋白表达缺失之间存在明显的相关性（Pearson r= 0.695, P<0.01）。免疫组化进一步证实PDCD5在肿瘤组织中的高频率缺失。χ2检验分析发现PDCD5蛋白表达缺失与喉鳞状细胞癌患者的年龄、性别、肿瘤原发部位和有无淋巴结转移无相关性,但是与肿瘤TNM分期以及组织学分级之间相关(mRNA P=0.032, P=0.021;蛋白 P=0.027, P=0.016)。结论 PDCD5在喉癌中多呈低表达,在喉鳞状细胞癌的发生、发展过程中可能起重要作用。     

整联蛋白亚基在喉鳞状上皮细胞癌组织中的表达及意义

目的:探讨整联蛋白亚基在喉鳞状上皮细胞癌(LSCC)中的表达情况及其意义.方法:采用基因芯片检测4例LSCC及对应癌旁正常组织中整联蛋白亚基的表达.采用RT-PCR检测24例LSCC及对应癌旁正常组织中基因芯片筛选出的4例均有明显差异表达的Integrins subunits.结果:基因芯片检测出IntegrinαV、Integrinβ8、Integrinα8,在LSCC组织及对应癌旁正常组织中均有明显差异表达,其中IntegrinαV、Integrinβ8 表达上调,Integrinα8表达下调.RT-PCR检测IntegrinaV在LSCC中的相对表达量为1.0131±0.478 0,与在对应癌旁正常组织中的相对表达量(0.7591±0.467 8)比较差异有统计学意义(P<0.05);Integrinβ8在LSCC中的相对表达量为1.736 2±1.384 9,与在对应癌旁正常组织中的相对表达量(1.226 7±0.936 3)比较差异有统计学意义(P<0.05);Integrinα8在LSCC中的相对表达量为(0.264 6±0.262 2),与对应癌旁正常组织中的相对表达量(0.545 7±0.382 7)比较差异也有统计学意义(P<0.05).结论:IntegrinαV、Integrinβ8及Integrinα8可能与LSCC的发生、发展相关.     

唐氏综合征侯选区域1基因在喉咽鳞状细胞癌与癌旁组织中的表达及意义

目的:通过研究喉咽鳞状细胞癌组织与癌旁组织中唐氏综合征侯选区域1(DSCR1)基因的表达,了解其表达与肿瘤临床特征的关系,探讨DSCR1基因对喉咽鳞状细胞癌的生物学行为的影响。方法:免疫组织化学p-V9000法,使用兔抗DSCR1抗体DCT3,检测DSCR1基因蛋白在喉咽鳞状细胞癌与正常癌旁组织中的表达,并将其与临床资料之间进行统计学分析。结果:肿瘤组织中DSCR1基因表达阳性率94.9%,癌旁组织中表达阳性率35.9%,差异有统计学意义(t=23.69,P<0.01);DSCR1基因的表达在不同的病理分化程度、TNM分期差异有统计学意义(P<0.05);DSCR1基因的表达在不同的肿瘤发病年龄、性别、部位、生长方式、淋巴结转移以及吸烟史组均差异无统计学意义。结论:DSCR1基因在喉咽鳞状细胞癌的发生、发展过程中有重要作用,可以影响肿瘤的生物学行为。     

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.