hTERT启动子调控hNIS基因介导肺癌细胞碘摄取和131I治疗的实验研究

目的 构建含人端粒酶反转录酶(hTERT)核心启动子调控的人钠/碘同向转运体(hNIS)基因重组腺病毒,并靶向转染至肺癌A549细胞中特异性表达.探讨hTERT启动子调控的hNIS基因介导放射性碘治疗肿瘤的可能性.方法 应用AdEasy系统构建重组腺病毒Ad-hTERT-hNIS,同时构建巨细胞病毒(CMV)启动子调控的hNIS重组腺病毒Ad-CMV.hNIS作为阳性对照,不含hNIS的重组腺病毒Ad-CMV作为阴性对照.应用反转录.聚合酶链反应(RT-PCR)方法验证hTERT在转染肿瘤细胞中的转录活性,摄碘实验检测表达的hNIS蛋白功能,细胞克隆形成实验评价131I对转染肿瘤细胞的毒性作用.结果 成功构建重组腺病毒Ad-hTERT-hNIS、Ad-CMV-hNIS及Ad-CMV,并经PCR验证正确.RT-PCR证实hNIS cDNA能从Ad-hTERT-hNIS转染的细胞中扩增出来.Ad-hTERT-hNIS和Ad-CMV-hNIS转染的肺癌A549细胞摄碘能力比阴性对照组Ad-CMV转染的细胞分别提高了23和31倍,且摄碘能力可以被NaClO4抑制.Ad-hTERT-hNIS和Ad-CMV-hNIS转染的肺癌A549细胞均可被131I杀死,2组细胞成活率分别为(31.2±1.45)%和(23.6±4.08)%,而阴性对照组和未转染病毒组分别为(89.0 ±2.99)%和(91.2 ±4.63)%.结论 hTERT启动子调控的hNIS重组腺病毒转染肿瘤细胞后,应用131I治疗有望成为一种新的基因靶向治疗手段.     

肺灌注显像在Ⅲ期非小细胞肺癌调强放疗中对功能肺的保护

目的 探讨肺灌注显像在Ⅲ期非小细胞肺癌(NSCLC)调强放疗(IMRT)保护功能肺的可行性。方法 选择拟行放疗的Ⅲ期NSCLC患者24例,分别行PET-CT和SPECT定位,图像传至治疗计划系统进行图像融合。根据SPECT图像确定功能肺(FL)和非功能肺(NFL),FL是指放射性计数为最大放射性计数的30%以上(包括30%)的区域,其他区域为NFL。肺灌注受损分为4级:0级,无灌注受损;1级,肿瘤及其周围局部肺灌注受损;2级,达1叶肺灌注受损;3级,超过1叶肺灌注受损。根据SPECT图像提供的肺功能信息制定IMRT计划进行优化,尽可能降低FL的照射体积剂量。采用配对t检验统计分析优化前后的IMRT计划的肺组织剂量参数变化。结果 患者均有不同程度的肺灌注缺损,其中肺灌注受损1级8例,2级6例,3级10例。根据SPECT提供的肺功能信息优化IMRT计划后WLV和FLV均有不同程度降低,而FLV降低程度更加明显。优化后WLV₁₀、WLV₁₅、WLV₂₀、WLV₂₅、WLV₃₀和FLV₁₀、FLV₁₅、FLV₂₀、FLV₂₅、FLV₃₀差异有统计学意义。结论 根据SPECT图像提供的肺功能信息优化IMRT计划以保护Ⅲ期NSCLC功能肺是可行的。     

Mathematical modelling of the spatio-temporal response of cytotoxic T-lymphocytes to a solid tumour.

In this paper a mathematical model describing the growth of a solid tumour in the presence of an immune system response is presented. In particular, attention is focused upon the attack of tumour cells by so-called tumour-infiltrating cytotoxic lymphocytes (TICLs), in a small, multicellular tumour, without necrosis and at some stage prior to (tumour-induced) angiogenesis. At this stage the immune cells and the tumour cells are considered to be in a state of dynamic equilibrium--cancer dormancy--a phenomenon which has been observed in primary tumours, micrometastases and residual disease after ablation of the primary tumour. Nonetheless, the precise biochemical and cellular mechanisms by which TICLs control cancer dormancy are still poorly understood from a biological and immunological point of view. Therefore we focus on the analysis of the spatio-temporal dynamics of tumour cells, immune cells and chemokines in an immunogenic tumour. The lymphocytes are assumed to migrate into the growing solid tumour and interact with the tumour cells in such a way that lymphocyte-tumour cell complexes are formed. These complexes result in either the death of the tumour cells (the normal situation) or the inactivation (sometimes even the death) of the lymphocytes. The migration of the TICLs is determined by a combination of random motility and chemotaxis in response to the presence of chemokines. The resulting system of four nonlinear partial differential equations (TICLs, tumour cells, complexes and chemokines) is analysed and numerical simulations are presented. We consider two different tumour geometries--multi-layered cell growth and multi-cellular spheroid growth. The numerical simulations demonstrate the existence of cell distributions that are quasi-stationary in time and heterogeneous in space. A linear stability analysis of the underlying (spatially homogeneous) ordinary differential equation (ODE) kinetics coupled with a numerical investigation of the ODE system reveals the existence of a stable limit cycle. This is verified further when a subsequent bifurcation analysis is undertaken using a numerical continuation package. These results then explain the complex heterogeneous spatio-temporal dynamics observed in the partial differential equation (PDE) system. Our approach may lead to a deeper understanding of the phenomenon of cancer dormancy and may be helpful in the future development of more effective anti-cancer vaccines.     

p53基因(今又生~)联合支气管动脉化疗治疗肺癌15例近期疗效观察

目的探讨瘤内注射或经支气管动脉灌注p53基因联合支气管动脉灌注化疗(BAI)治疗肺癌的安全性、疗效和给药途径。方法经病理证实的15例肺癌,首先在CT引导下经皮穿刺瘤内注射或经支气管动脉灌注p53基因(今又生~),2～5天后,行BAI灌注化疗药物;然后根据病情变化再次进行基因治疗和/或BAI。治疗后常规使用螺旋CT定期复查,评价治疗效果。结果全部15例患者均完成上述治疗,并接受随访2～11个月。有效率(CR+PR)46.7%(7/15),1例肺部肿块消失,6例肺部肿块缩小,3例纵隔淋巴结缩小,1例胸水减少,仅1例观察到肿瘤长大,14例临床症状有不同程度缓解93.3%(14/15)。p53治疗后6例出现发热(38℃～40℃),未观察到基因药物的其它严重副作用,无严重操作有关并发症出现。结论本研究结果初步显示,作为肿瘤综合治疗的一部分,p53基因治疗与BAI联合应用,是一种治疗肺癌安全、有效的方法,提高了BAI的治疗效果。经皮瘤内注射p53是否为一种较好的给药途径值得进一步探讨。     

肺内源性和肺外源性呼吸衰竭机械通气的临床对比研究

目的探讨肺内源性和肺外源性呼吸衰竭机械通气时的肺保护性策略。方法通过25例呼吸衰竭中12例肺内源性和13例肺外源性机械通气临床资料的回顾性分析,对比研究两组呼吸力学差异时对通气模式选择、参数设置和调节的影响,以及肺保护的实施方法。结果在两组APACHE-Ⅱ评分、平均年龄和Vt设置无差异的条件(P>005)下,肺内源性组PEEP/CPAP、PSV、f的需设值均明显高于肺外源性组(P<001)。肺内源性组Pplat、PIP、Raw的监测结果大于肺外源性组,而Crs小于肺外源性组(P<001)。肺内源性组417%和肺外源性组154%因MOF而死亡(APACHE-Ⅱ评分均>20分),组间比较有显著差异(P<001)。结论肺内源性和肺外源性呼吸衰竭机械通气时,实施肺保护的方法不同。前者应首选压力预置通气模式,后者可首选容量预置通气模式。以设置中、小Vt为原则,按个体化的通气需求而设置f和加用恰当的PSV、CPAP/PEEP对减少VILI、病死率可能有益。     

多层螺旋CT肺密度测定对结缔组织病肺问质病变的早期诊断

目的探讨多层螺旋CT(MSCT)肺密度测定对结缔组织病(CTD)肺间质病变(ILL)早期诊断的临床意义。方法对222例CTD患者及50名正常对照者，应用MSCT附带的Pulmo自动评估软件进行上、中、下肺区的密度测定，并同时进行肺高分辨扫描(}-IR(_1、)，分析二者的变化与CTD伴ILL的关系。结果222例cm患者中197例平均肺密度有不同程度的增高，25例平均肺密度正常。157例HRCT有不同程度的肺间质病变，65例HRCT正常。50名正常对照者HRCT均正常，8名平均肺密度有不同程度的增高，42名平均肺密度正常。结论采用MSCT与HRCT对CTD伴ILL的检测结果差异有统计学意义，P=0．000(双侧)，因此MSCT平均肺密度测定对早期诊断CTD伴ILL比HRCT更敏感，更有临床意义。     

The value of MCA, CA 15-3, CEA and CA-125 for discrimination between metastatic breast cancer and adenocarcinoma of other primary sites

MCA, CA 15-3, CEA and CA 125 were determined in the serum of 49 patients with metastatic breast cancer and 38 patients with metastatic adenocarcinoma of other primary sites. By using the 99th percentile of the normal value distribution as the cut-off point, the positive predictive value (PV+) was found to be 85% (95% CI 76-94) for MCA, and 71% (95% CI 61-81) for CA 15-3. When receiver-operating-characteristic (ROC) curves were constructed, the PV+ for CA 15-3 was increased to 82% (95% CI 72-92), using 60 U ml-1 as the cut-off point. With the exception of two patients who had a slightly elevated MCA, MCA and CA 15-3 identified the same patients with breast cancer. By combining a positive MCA or CA 15-3 with a negative CEA and CA 125, further improvement of the PV+ could be achieved; 100% (95% CI 91-100). We conclude that MCA and CA 15-3 may play a useful role in discrimination between patients with metastatic breast cancer and those with adenocarcinoma of other primary sites.