5—单硝酸异山梨酯控释片的研究

研究了5-单硝酸异山梨醣控释片的处方组成和制备工艺,并对不同处方进行了体外溶出试验,证实体外释药可维持10 h以上。体外释药速率与HPMC的粘度及其在处方中的比例有关,与溶出介质的pH值无关,体外释药过程,符合Higuchi方程,经稳定性实验考察,证实本制剂在37℃、RH 75%的条件下保存三个月后,其含量、溶出度、外观、硬度、脆碎度均无变化。     

鼻咽癌放疗前行介入灌注化疗的临床疗效分析

目的探讨在鼻咽癌放疗前行经导管动脉灌注化疗的临床应用价值.方法 43例鼻咽癌患者经颌内动脉和咽升动脉灌注化疗药物进行治疗,主要药物为顺铂、5-Fu和平阳霉素.术后一周常规放疗.以同期行单纯放疗的65例鼻咽癌患者作为对照组.结果治疗组与对照组完全缓解率分别为74.41%和60.0%.结论鼻咽癌放疗前行经导管动脉灌注化疗的安全、有效.     

鼻咽癌调强放疗中解剖及剂量学改变再次计划必要性研究

目的 探讨鼻咽癌调强放疗(IMRT)中解剖学动态变化规律,以及这些变化对剂量学分布的影响,客观评价放疗重新修改物理计划的必要性.方法搜集12例Ⅲ～Ⅳ期鼻咽癌患者进行相关临床前瞻性研究,所有患者均接受同步放化疗.疗前常规螺旋CT扫描,由临床医生进行靶区及危及器官勾画.IMRT计划完成后再次螺旋CT扫描校正治疗中心,开始治疗后的每周按治疗中心重复进行螺旋CT扫描,然后将获取的CT图像和原计划CT图像融合.首先在系统融合界面就变化的PTV1及正常器官(腮腺、轮廓)进行重新修改,并计算出靶区及正常器官体积变化范围,从中寻找再次计划的最佳时间段.其次按照首次计划条件在重新修改的靶区上再次计算,得出靶区及正常器官剂量学参数后与首次计划对比观察其变化.结果 IMRT治疗中头颈部外轮廓、腮腺体积逐步缩小,放疗至5周左右腮腺及轮廓体积变化达顶峰,因而选择第5周CT和首次CT作为剂量学研究对象.再次计算及配对设计比较发现治疗中和治疗前PTV1,D99、D95,脊髓Dmax、Dmean,脑干Dmax、Dmean,下颌骨Dmax、Dmean相似(P值均＞0.05),而双侧腮腺D50不同(P左=0.03,P右=0.01).结论 IMRT治疗过程中鼻咽癌患者出现腮腺缩小、轮廓改变和PTV缩小.放疗至5周左右相关体积变化达顶峰.第5周再次计划与原计划相比脊髓、脑干、下颌骨、PTV1各项剂量学参数值变化不大,但腮腺剂量增加较为明显.     

三种阈值下勾画非小细胞肺癌PET图像靶区及影响的研究

目的 比较不同阈值对18FDG PET-CT图像中非小细胞肺癌靶区勾画及放疗计划可能产生的影响.方法 选择CT图像上原发灶边界清楚的、呼吸动度≤5 mm的非小细胞肺癌8例,注射18FDG后1 h行PET扫描并以CT图像作衰减校正.以CT图像勾画的大体肿瘤体积(GTVCT)为标准,比较PET图像上用3种阈值条件[即肿瘤内最大像素值的42%(42%Imax(total))、本底平均像素值+肿瘤内最大像素值与本底平均像素值的差值的20%(Iback+20%Imax-back(max))和本底平均像素值+肿瘤内每层最大像素值与本底平均像素值的差值的20%(Iback+20%Imax-back(slice))]勾画的GTV(计为GTV42%、GTV20%max和GTV20%slice)与GTVCT差异及对GTVCT覆盖率的差异.以GTVCT、GTV42%、GTV20%max、GTV20%slice三维外放1 cm为计划靶体积,分别计为PTVCT、PTV42%、PTV20%max、PTV20%slice.对不同PTV设计三维适形放疗计划,并均给予靶区剂量66 Gy分33次6.6周完成.比较以不同PTV设计的计划中,PTVCT内接受＜95%处方剂量的体积(VPTV)及肺V20,并推算可能产生的TCP和肺NTCP的差异.结果 GTV42%、GTV20%max、GTV20%slice与GTVCT的中位体积差分别为-54.1%,-21.5%和5.3%,三者对GTVCT的覆盖率中位数分别为45.9%、78.0%和95.3%(F=57.50,P＜0.01).以不同PTV设计放疗计划时,PTV42%的中位VPTV为7.5%,由此可能导致TCP中位下降1%.PTV20%max和PTV20%slice的中位VPTV分别为1.3%和0.0%,其TCP与PTVCT的相似,与PTV42%的不同.三者的肺V20和肺NTCP与PTVCT的相似.结论 层面化阈值条件Iback+20%Imax-back(slice)可能是PET图像用于肺癌靶区勾画的较准确阈值,该阈值不依赖于预先由CT提供的肿瘤体积信息,可望用于伴有肺不张的非小细胞肺癌的靶区勾画.     

Selection and their antitumor activity of antisense oligonucleotides targeting messenger RNA of vascular endothelial growth factor receptor 2

Objective： To select the antisense oligonucleotides （asONs） which hybridize with the mRNA of vascular endothelial growth factor receptor2 （VEGFR2, also named as kinase insert domain-containing receptor：KDR） in an effective and specific way, and to investigate their antitumor activity in MCF-7 cells. Methods： The effective antisense oligonucleotides were chosen by computer prediction combined with oligonucleotide microarrays. The inhibition effect on MCF-7 cells proliferation was measured by MTT; and VEGFR2 expression was surveyed by Western-blotting and RT- PCR. Results： Using predicting secondary structure of VEGFR2 mRNA with RNA folding program, computer prediction designed 30 antisense oligonucleotide probes that were directed to local loose regions of RNA structure. In 30 probes, 4（4/30, 13.33%） antisense oligonucleotides showed strong hybridization intensities in oligonucleotide microarrays test and were selected. All these antisense oligonucleotides targeting 4 different sites of VEGFR2 mRNA lowered the level of VEGFR2 mRNA and protein present in MCF-7 cells. Proliferation of MCF-7 cells was reduced by 4 antisense oligonucleotides, respectively, in which asON1 was the most effective, with the inhibitory rates being 53.06% at 0.8 I.tmol/L. Conclusion： Combination of computer prediction with oligonucleotide microarrays is an effective way in selecting optimal antisense oligonucleotides. The antisense oligonucleotides showed good correlation between their antitumor activity and the hybridization intensities. The antisense oligonucleotides targeting VEGFR2 mRNA demonstrated prominent antitumor role in vitro.     

Magnitude of residual internal anatomy motion on heavy charged particle dose distribution in respiratory gated lung therapy

PURPOSE: To assess the variation in carbon beam dose distribution due to residual motion in lung cancer patients undergoing respiratory-gated radiotherapy. METHODS AND MATERIALS: A total of 11 lung cancer patients underwent four-dimensional computed tomography with a 256-multislice computed tomography scanner under free-breathing conditions. A compensating bolus was designed to cover the treatment beam for all planning target volumes during a 30% duty cycle centered on exhalation (gating window). This bolus was applied to the four-dimensional computed tomography data for one respiratory cycle, and then the carbon beam dose distribution was calculated. RESULTS: A water equivalent pathlength variation of <5 mm was observed in the gating window, but this increased to 95% volume irradiation is dependent on the respiratory phase but not the gating window. However, the dose for >95% volume irradiation correlated well with the tumor displacement distance. More than 90% of the dose for >95% volume irradiation could be delivered in the gating window with <4-mm tumor displacement resulting from exhalation. CONCLUSION: The results of our study have shown that even when the treatment beam delivery occurs outside the gating window, the prescribed dose to the target is not affected in patients with a tumor displacement of <4 mm. Thus, respiratory gating is not required in radiotherapy for patients with <4-mm tumor displacement in a respiratory cycle.     

Incidentally simultaneous occurrence of RET/PTC, H4-PTEN and BRAF mutation in papillary thyroid carcinoma

Because interaction existed between PTEN and RET-RAS-RAF-MAPK pathway, H4-PTEN (a newly identified gene rearrangement), RET/PTC and BRAF mutation were scanned in 125 Chinese patients with papillary thyroid carcinoma (PTC). H4-PTEN were detected in 9.6% of PTC and the frequency of the occurrence of BRAF mutation and/or RET/PTC in H4-PTEN positive tumors was extremely high (75%). On the other hand, age has an important effect on the aberration formation and young age renders more prone to multi-genetic events. A combinational scanning of these involved changes will improve the predictive value of molecular aberrations in the treatment of PTC.     

Selective promotion by phenylmethanesulfonyl fluoride of peripheral and spinal cord neuropathies initiated by diisopropyl phosphorofluoridate in the hen

This paper reports studies in hens showing that diisopropyl phosphorofluoridate (DFP) neuropathy is promoted by PMSF when initiated either in central (spinal cord) or peripheral nervous system. Moreover, the critical site for promotion is in peripheral nerve axons rather than in their cell bodies. Selective promotion in peripheral nerves was achieved by giving PMSF into sciatic artery monolaterally (7 mg/kg) to birds where neuropathy was initiated by DFP, either systemically (0.3 mg/kg s.c.) or intra-arterially (0.04 mg/kg in the same artery). Birds developed monolateral neuropathy in the leg where PMSF was delivered. Promotion of spinal cord neuropathy was achieved by giving PMSF (120 mg/kg s.c.) to birds where neuropathy was initiated selectively in spinal cord. This was obtained by protecting peripheral axons with intra-arterial bilateral injections of PMSF (0.55 × 2 mg/kg) followed by DFP (0.3, 0.4 or 0.7 mg/kg s.c.). The resulting syndrome was characterized by spastic ataxia.     

肝动脉插管化疗加栓塞术治疗中晚期肝癌

15例无手术指征的中晚期肝癌患者,经肝动脉插管灌注化疗加栓塞治疗效果观察。临床症状明显改善者占80％,瘤体缩小占73％。灌注加栓塞治疗较单纯灌注好。多次灌注栓塞治疗较一次好,患者的生存期延长,部分病人可获得二期手术切除的机会。