Evidence for a possible anatomical subsite–mediated effect of tobacco in oral potentially malignant disorders and carcinoma

J Oral Pathol Med (2011) 40 : 214–217 Purpose: To test the hypothesis that cigarette smokers develop oral potentially malignant disorders or carcinomas in preferential anatomical subsites. Methods: The association of smoking habit with the presence of oral lesions in specific anatomical subsites was assessed in 123 patients using the odds ratio analysis. Results: When compared to all the other subsites, the relative frequency of smokers with lesions was higher in the buccal mucosa and in the floor of the mouth (FOM) (P = 0.002 and P = 0.005), while it was lower in the tongue (P < 0.0005). Smokers were about 7 years younger than non‐smokers (P = 0.008). Conclusions: The association of smoking and age suggests that smoking may contribute to generate a field of injury that leads to lesions in shorter periods than other causes. The stronger relationship of smoking with lesions in the buccal mucosa and FOM than in the tongue suggests that tissue characteristics mediate the effects of tobacco.     

Glioma Pathophysiology: Insights Emerging from Proteomics

Proteomics is increasingly employed in both neurological and oncological research to provide insight into the molecular basis of disease but rarely has a coherent, novel pathophysiological insight emerged. Gliomas account for >50% of adult primary intracranial tumors, with malignant gliomas (anaplastic astrocytomas and glioblastoma multiforme) being the most common. In glioma, the application of proteomic technology has identified altered protein expression but without consistency of these alterations or their biological significance being established. A systematic review of multiple independent proteomic analyses of glioma has demonstrated alterations of 99 different proteins. Importantly 10 of the 99 proteins found differentially expressed in glioma [PHB, Hsp20, serum albumin, epidermal growth factor receptor (EGFR), EA-15, RhoGDI, APOA1, GFAP, HSP70, PDIA3] were identified in multiple publications. An assessment of protein–protein interactions between these proteins compiled using novel web-based technology, revealed a robust and cohesive network for glioblastoma. The protein network discovered (containing TP53 and RB1 at its core) compliments recent findings in genomic studies of malignant glioma. The novel perspective provided by network analysis indicates that the potential of this technology to explore crucial aspects of glioma pathophysiology can now be realized but only if the conceptual and technical limitations highlighted in this review are addressed.     

微创置管引流术联合甘露聚糖肽腔内灌注治疗恶性胸腹水的临床研究

目的探索中心静脉导管微创置管引流术联合甘露聚糖肽局部灌注治疗在机体状况差的晚期恶性胸腹水患者中应用的安全性和临床疗效。方法从2003年10月到2007年12月间,共对51例机体机能状况差(中位KPS评分40分)的晚期恶性胸腹水患者进行了中心静脉导管微创置管引流术联合甘露聚糖肽局部灌注治疗。在胸腹水引流完全后,经导管进行甘露聚糖肽的生物灌注治疗,甘露聚糖肽的剂量从20mg/次逐渐增加到50mg/次,每周灌注2次。结果经导管置管引流后,100%的患者与胸腹水压迫相关的临床症状得到明显缓解,胸腹水控制CR25例(49.0%,PR19例(37.3%),NC4例(7.8%),PC3例(5.9%),总有效率为86.2%(44/51)。中位带管时间63d(25～107d),中位积液无进展时间71d(0～248d),中位生存时间92d(25～265d)。37例患者(72.5%)经引流灌注后胸腹水得到控制而拔管,11例患者(21.6%)带管死亡。无置管相关死亡病例,与置管相关的并发症轻微,灌注药物后不良反应较轻,所有患者均能耐受治疗。生活质量改善明显,KPS评分改善者41例(80.4%),稳定者10例(19.6%),中位KPS评分提高到60分。结论中心静脉导管微创置管引流术联合甘露聚糖肽局部灌注治疗应用于机体状况差的晚期恶性胸腹水患者安全、有效,值得临床推广。     

力比泰联合顺铂治疗30例恶性胸膜间皮瘤的疗效观察

目的：探讨力比泰（培美曲塞）联合顺铂治疗恶性胸膜间皮瘤（MPM）的疗效和毒副作用。方法：30例恶性胸膜间皮瘤患者采用力比泰联合顺铂全身化疗，其中力比泰500mg／m^2第一天静脉点滴，顺铂20mg／m^2，第1—5天静脉点滴，21天为1周期，一般3—4周期。观察近期疗效、远期疗效、毒副作用、中位缓解期和中位生存期。结果：30例患者中，CR4例，PR13例，SD7例，NC6例。总有效率56．7％（17／30），中位缓解期6．8个月，中位生存期11．9个月，毒副作用：白细胞减少发生率为30％（9／30），Ⅲ度-Ⅳ度10％（3／30），血小板减少发生率10％（3／30），皮疹发生率30％（9／30），低热发生率20％（6／30），口腔炎发生率为20％（6／30），其它尚包括恶心、呕吐、疲劳、嗜睡和厌食等。所有毒副作用经对症处理和支持治疗后均恢复正常。结论：力比泰联合顺铂治疗恶性胸膜间皮瘤疗效较好，毒副作用较轻，值得临床推广。     

18F]2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG PET) as a diagnostic tool for neurofibromatosis 1 (NF1) associated malignant peripheral nerve sheath tumours (MPNSTs): a long-term clinical study.

BACKGROUND: Malignant peripheral nerve sheath tumours (MPNSTs) are difficult to detect in neurofibromatosis 1 (NF1) individuals. The purpose was to evaluate [(18)F]2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG PET) and PET computed tomography (CT) as a diagnostic tool for MPNST in NF1 patients with symptomatic plexiform neurofibromas and to verify the diagnosis by pathology and clinical follow-up. PATIENTS AND METHODS: NF1 individuals with symptomatic plexiform neurofibromas underwent clinical evaluation and magnetic resonance imaging. Qualitative FDG PET and PET CT associated with semi-quantitative maximum standard uptake value (SUVmax) assessed possible malignant change. Excision/biopsy verified the diagnosis when possible and clinical follow-up was undertaken in all patients. RESULTS: In all, 116 lesions were detected in 105 patients aged 5-71 years, including 80 plexiform neurofibromas, five atypical neurofibromas, 29 MPNST and two other cancers. Biopsy confirmed the findings in 59 tumours and no MPNST was diagnosed on clinical follow-up of 23 lesions diagnosed as benign on FDG PET and PET CT. FDG PET and PET CT diagnosed NF1-associated tumours with a sensitivity of 0.89 [95% confidence interval (CI) 0.76-0.96] and a specificity of 0.95 (CI 0.88-0.98), but the SUVmax level did not predict tumour grade. CONCLUSION: FDG PET and PET CT is a sensitive and specific diagnostic tool for NF1-associated MPNST. Other PET tracers will be required to solve the problem of predicting tumour grade.     

STK15在恶性肿瘤中的研究进展

中心体这一微小的细胞器，在有丝分裂中对维持细胞的极性及染色体分离具有重要的调节作用。目前的研究表明中心体异常在人类恶性肿瘤中普遍存在。作为一种中心体相关激酶，STK15与恶性肿瘤的发生之间存在着极其密切的联系，其活性的改变会引起中心体扩增、染色体不稳定及细胞的转化。本文主要介绍目前STK15在部分人类恶性肿瘤中的研究进展。     

Up-to-date survival estimates and historical trends of cutaneous malignant melanoma in the south-east of The Netherlands.

BACKGROUND: We present survival outcomes of patients registered in the Dutch population-based Eindhoven Cancer Registry (ECR). PATIENTS AND METHODS: Data on patients diagnosed with a melanoma between 1980 and 2002 were obtained from the ECR. Data on vital status up to 1 January 2005 were obtained, up-to-date survival rates were calculated using period analysis. Multivariate analyses were carried out using Cox proportional hazards model. RESULTS: Ten-year crude survival rates were 82% for women and 60% for men (P < 0.05). Thin melanomas (Breslow thickness 74%, for melanomas >4.0 mm these rates were <65% (P < 0.05). In the early 1980s, 5-year relative survival rates were 84% and 62% for young (<60 years) women and men, and 66% and 69%, respectively, for the elderly (aged 60+). In the period 2000-2002, these rates had improved to >90% for females and to >72% for males. Multivariate analyses showed increased hazard ratios with increasing age and Breslow thickness, being male, having a melanoma on the trunk or unknown sites and having a nodular melanoma. CONCLUSIONS: Despite the absence of improvements in treatment options for melanoma, survival improved significantly, except for elderly males.     

替莫唑胺治疗复发性脑胶质瘤的疗效观察

目的 观察单独使用新型口服烷化剂替莫唑胺（Temozolomide TMZ）治疗复发性恶性脑胶质瘤的疗效及安全性。方法 选择38例年龄为18～65a，通过立体定向活检技术进行组织学检查确诊为复发性脑恶性胶质瘤（Ⅲ、Ⅳ级）复发前2mo内未接受放疗或化疗的病人，给予替莫唑胺每天150～2mg/m^2，连续空腹口服5d，28d为1个周期。本组病人接受化疗2～6个周期。每1个周期均随访检查病人的临床表现、血常规及肝、肾功能，以判断病人能否耐受。替莫唑胺治疗第2、3及6个周期末施行相应的增强CT或MR检查，与化疗前的影像学资料进行比较，判断肿瘤实体变化情况。结果 有效率52．6％：CR1例，PR6例，SD13例，PD18例；平均无进展存活时间和总存活时间分别为2．2mo和4．1mo，生存最长者已达10．2mo；化疗期间病人的不良反应及骨髓毒性较轻微。结论 替莫唑胺治疗复发性脑胶质瘤安全而有效，病人耐受较好，是一有良好前景的化疗药物。     

人脑胶质瘤组织HIF-1α和COX-2及CD105蛋白表达与临床病理学关系的研究

目的:探讨缺氧诱导因子-1α(HIF-1α)、环氧化酶-2(COX-2)及CD105在人脑胶质瘤组织中的表达及与临床病理特征的关系。方法:应用免疫组化SP法检测70例胶质瘤和10位正常人脑组织中HIF-1α、COX-2和CD105的表达,并测定CD105标记的MVD。结果:1)胶质瘤组织中HIF-1α、COX-2和CD105蛋白的阳性表达率分别为64.3%、61.4%和74.3%,明显高于正常人脑组织。2)HIF-1α、COX-2表达和MVD与胶质瘤病理分级密切相关。3)胶质瘤组织中HIF-1α和COX-2蛋白表达的一致符合率为70.35%,且两者表达呈正相关,r=0.5837,P=0.004。4)HIF-1α和COX-2阳性表达组的MVD(35.87±4.55和36.00±4.57)均高于阴性表达组(29.19±4.69和29.48±4.71),P值均为0.0000;两者均为阳性表达时的MVD(36.22±4.62)最大,明显高于其他各组(33.75±3.59和28.29±4.33),P=0.0001;两者表达均与MVD呈正相关,r值分别为0.5405和0.4652,P值分别为0.005和0.014。结论:HIF-1α、COX-2和CD105过表达可能在胶质瘤的恶性进展中发挥重要作用,并与肿瘤血管形成密切相关,三者的联合检测可更准确地揭示胶质瘤的生物学特性。     

胶质瘤的神经分子病理学检测指标及其意义

脑胶质瘤是比较常见的脑肿瘤,侵袭性强,治疗的敏感性差,预后不好。随着分子生物学的不断发展,临床对肿瘤细胞的增殖动力学及耐药机制认识逐渐深入。神经分子病理是近年来在传统组织病理学的基础上结合分子生物学及分子遗传学的研究成果,能够在基因和蛋白水平上检测肿瘤细胞的受体、生长因子、染色体、抑癌基因及癌基因等的变化,并根据以上检查了解肿瘤细胞的分化、生长速度、转移侵袭性及对抗化疗和放疗的可能性等相关信息,较传统病理客观,且简便易行,在分析和判断胶质瘤的生长,分化程度,指导治疗方案的选择及预后的判断等方面有着重要的实用价值。