Experiment research of cisplatin implants inhibiting transplantation tumor growth and regulating the expression of KLK7 and E-cad of tumor-bearing mice with gastric cancer

Objective: To study the influence of cisplatin implants on transplantation tumor growth and the expression of tissue kallikrein-7(KLK7) and E-cadherin(E-cad) in tumor-bearing mice with gastric cancer. Methods: BALB/c nude mice were collected as experimental animal and were randomly divided into model control group(Group A), tail intravenous injection of cisplatin group(Group B), intratumor injection of cisplatin group(Group C) and cisplatin implants treatment group(Group D). After the drugs intervening, the weight and volume of transplantation tumors were measured on Day 20, Day 30 and Day 40 and serum and KLK7 and E-cad contents in transplanted tumor tissue were examined. Results: On Day 20, Day 30 and Day 40 after treatment, the weight and volume of transplantation tumors of tumorbearing mice in four groups were different(Group A > Group B > Group C > Group D). The contents of KLK-7 and E-cad in tumor tissue and serum of tumor-bearing mice in four groups were different(Group A > Group B > Group C > Group D in KLK-7) and(Group A < Group B < Group C < Group D in E-cad). The weight and volume, and KLK7 and E-cad contents of transplantation tumors in four groups were significant difference(P<0.05). Conclusion: Cisplatin implants can inhibit the growth of transplanted tumor tissue and down-regulated KLK7 expression and up-regulated E-cad expression of tumor-bearing mice with gastric

Global Protein Expression Analysis of Molecular Markers of DS-1-47,a Component of Implantation-promoting Traditional Chinese Medicine

This study investigated the molecular markers of DS-1-47,a component of an implantation-promoting traditional Chinese medicine consisting of Astragalus mongholicus,Atractylodes macrocephala,Scutellaria baicalensis and Dipsacales,in an attempt to clarify the molecular mechanism and action targets of DS-1-47.Controlled ovarian stimulation（COS） method was used to establish the implantation dysfunction models of mice.Animals were divided into normal pregnant group,COS model group and DS-1-47 group.Laser capture microdissection-double dimensional electrophoresis-mass spectrum（LCM-DE-MS） was used to analyze the uterine protein molecules that were possibly involved in the promotion of implantation.Twenty-three proteins in DS-1-47 group were significantly changed as compared to those in COS model group,with 7 proteins down-regulated and 16 proteins up-regulated.Except for some constituent proteins,the down-regulated proteins included collagen α-1（Ⅵ） chain,keratin 7,keratin 14,myosin regulatory light chain 12 B,myosin light polypeptide 9,heat shock protein β-7,and C-U-editing enzyme APOBEC-2;the up-regulated proteins included apolipoprotein A-I,calcium regulated protein-3,proliferating cell nuclear antigen,L-xylulose reductase,and calcium binding protein.These 23 proteins that were regulated by DS-1-47 represented a broad diversity of molecule functions.The down-regulated proteins were associated with stress and immune response,and those up-regulated proteins were related to proliferation.It was suggested that these proteins were important in regulating the uterine environment for the blastocyst implantation.By identification of DS-1-47 markers,proteomic analysis coupled with functional assays is demonstrated to be a promising approach to better understand the molecular mechanism of traditional Chinese medicine.

Relationship between miR-7-5p expression and ^(125)I seed implantation efficacy in pancreatic cancer and functional analysis of target genes

Objective The aim of this study was to investigate the relationship between miR-7-5p expression and intertissue-^(125)I irradiation sensitivity in pancreatic cancer tissues and to analyze the function of target genes.Methods Thirty-seven patients with unresectable pancreatic ductal adenocarcinoma(PDAC)treated with radioactive ^(125)I seed implantation were enrolled.RT-PCR was used to detect the expression level of miR-7-5p in cancer tissues and analyze the relationship between miR-7-5p expression and ^(125)I radiation sensitivity.Bioinformatic software and online tools were used to predict the miR-7-5p target genes and analyze their functional annotation and pathway enrichment.Results Radioactive ^(125)I seed implantation was followed up for 2 months.The objective response rate of the miR-7-5p high expression group was 65.0%(13/20),whereas the objective response rate of the miR-7-5p low expression group was 5.88%(1/17),and the difference between the two groups was statistically significant(χ^(2)=13.654,P<0.001).A total of 187 target genes were predicted using three databases.GO functional annotation showed that target genes were mainly involved in cellular response to insulin stimulus,regulation of gene expression by genetic imprinting,cytosol,peptidyl-serine phosphorylation,bHLH transcription factor binding,cargo loading into vesicles,cellular response to epinephrine stimulus,and nucleoplasm.KEGG pathway enrichment analysis showed that target genes were mainly involved in the ErbB signaling pathway,HIF-1 signaling pathway,axon guidance,longevity regulatory pathway,endocrine resistance,glioma,choline metabolism in cancer,and EGFR tyrosine kinase inhibitor drug resistance.Molecular complex detection analysis by Cytoscape revealed that PIGH,RAF1,EGFR,NXT2,PIK3CD,PIK3R3,ERBB4,TRMT13,and C5orf22 were the key modules of miR-7-5p target gene clustering.Conclusion The expression of miR-7-5p in pancreatic cancer tissues positively correlated with the radiosensitivity of ^(125)I seeds.Via targeted gene regulation,miR-7-5p acts on the network of multiple signaling pathways in PDAC and participates in its occurrence and development.Thus,miR-7-5p may become a predictive index of ^(125)I seed implantation therapy sensitivity in PDAC patients.

Effect of Chemical Doping and Ion Implantation on Cond uctivity of Poly(p-phenylene vinylene) Derivatives

The surface conductivity of poly [ 2-methoxy-5-（3＇-methyl） butoxy]-p-phenylene vinylene （PMOMBOPV） films doped with FeCl3 and H2SO4 by chemical method and implanted by N^＋ ions was studied and the comparison of environmental stability of conductive behavior was also investigated. The energy and dose of N^＋ ions were in the rang 15～35 keV and 3. 8×10^15～9. 6×10^16 ions/cm^2, respectively. The conductivity of PMOMBOPV film was enhanced remarkably with the increases of the energy and dose of N^＋ ions. For example, the conductivity of PMOMBOPV film was 3. 2×10^-2S/cm when ion implantation was performed with an energy of 35 keV at a dose of 9. 6 × 10^14 ions/cm^2 , which was almost seven orders of magnitude higher than that of film unimplanted. The environmental stability of conductive behavior for ionimplanted film was much better than that of chemical doped films. Moreover, the conductive activation energy of ion-implanted films was measured to be about 0.17 eV.

A COMPUTER SIMULATION OF HIGH-DOSE ION IMPLANTATION INTO AMORPHOUS MATERIALS

A computer program MACA was developed for simulating high-dose ion implantation into amorphous solids. The topology of amorphous solids was modelled by adjusting the free flight path distribution between collisions, so that the radial distribution function will characterize the short - range order and long - range disorder of amorphous targets. A simulation example is given.

Differential Expression of Retrotransposon WIS 2-1A Response to Vacuum, Low-Energy N^+ Implantation and ^(60)Coγ-ray Irradiation in Wheat

Mutagenesis and retrotransposons have a close relationship, but little attention has been paid yet to the activity of retrotransposons produced by physical mutagens. The variation of retrotransposon WIS 2-1A activity in wheat （Triticum aestivum L.） embryos at three different growth times （30 h, 45 h and 60 h） was investigated after they had been treated with N^＋ implantation in a vacuum of 5× 10^-2 Pa and irradiation by ^60Coγ-ray respectively. For each of the three growth times the expression of WIS 2-1A showed almost entirely a same trend of downregulation, upregulation, then downregulation, and upregulation again with the increase in dose of N^＋ implantation, but the expression appeared irregular with the increase in irradiation of ^60Coγ-ray. In conclusion, the acutely activating effect of WIS 2-1A stimulated by vacuum and high dose N^＋ implantation within a shorter incubation time may provide a convenient tool to advance the research on mutagenic breeding and function genes.

The Role for AVE0991 (MAS-Receptor Angiotensin II (1-7) Agonist) in Reducing Cisplatin-Induced Acute Kidney Injury on C57BL/6 Mice

Acute Kidney Injury (AKI) is a condition that causes nephrotoxicity in kidney tissues due to cisplatin-induced cancer treatments. Hence, it is proposed in this review that AVE0991 (a MAS-receptor Angiotensin II (1-7) agonist) may reduce cisplatin-induced acute kidney injury by promoting nitric oxide production.

I-123 metaiodobenzylguanidine imaging for predicting ventricular arrhythmia in heart failure patients

Compared to antiarrhythmic drugs, implantable cardioverter defibrillator （ICD） leads to a more significant im- provement in preventing ventricular arrhythmia in heart failure patients. However, an important question has been raised that how to select appropriate patients for ICD therapy. 1-123 metaiodobenzylguanidine （MIBG） planar and SPECT imaging have shown great potentials to predict ventricular arrhythmia in heart failure patients by as- sessing the abnormalities of the sympathetic nervous system. Clinical trials demonstrated that several parameters measured from 1-123 MIBG planar and SPECT imaging, such as heart-to-mediastinum ratio, washout rate, defect score, and innervation/perfusion mismatch, predicted ventricular arrhythmias in heart failure patients. This paper introduces the current practice of ICD therapy and reviews the technical background of 1-123 MIBG planar and SPECT imaging and their clinical data in predicting ventricular arrhythmia.

The Breeding of a Pigment Mutant Strain of Steroid Hydroxylation Aspergillus Flavus by Low Energy Ion Implantation

In the process of the fermentation of steroid C11α-hydroxylgenation strain Aspergillus flavus AF-ANo208, a red pigment is derived, which will affect the isolation and purification of the target product. Low energy ion beam implantation is a new tool for breeding excellent mutant strains. In this study, the ion beam implantation experiments were performed by infusing two different ions： argon ion （Ar^＋） and nitrogen ion （N^＋）. The results showed that the optimal ion implantation was N^＋ with an optimum dose of 2.08- 1015 ions/cm^2, with which the mutant strain AF-ANm16 that produced no red pigment was obtained. The strain had high genetic stability and kept the strong capacity of C11α-hydroxylgenation, which could be utilized in industrial fermentation. The differences between the original strain and the mutant strain at a molecular level were analyzed by randomly amplified polymorphic DNA （RAPD）. The results indicated that the frequency of variation was 7.00%, which would establish the basis of application investigation into the breeding of pigment mutant strains by low energy ion implantation.

Implant Compositional Disordering on InGaAs/InP MQW Structures

Some new results of implant disordering on InP based MQW structures by implanted compositional disordering are presented. The energy shift of PL peak depends on ion species, ion dose, annealing conditions and target temperature. The results indicate that the nonactive ions such as F+ and Ne+ are the best candidates for IICD, the ion dose which caused biggest blue shift is around 1 × 10 14 cm-2 for room temperature implantation and 5 × 10 14 cm-2 for an elevated implanted temperature of 200 ℃ and the optimum annealing condition is approximately 750 ℃ for 30 s. AES and TEM characterization suggests that ion bombardment by nonelectrically active ions such as F+, Ne+ induced same amount of layer interdiffusion which results in the band gap blue shift due to the compositional changes.

顺铂植入剂兔舌内植入药动学研究

目的研究顺铂植入剂在兔舌内植入的药动学。方法兔12只随机均分实验组、对照组,实验组舌内植入顺铂植入剂,对照组静注顺铂,用原子吸收法测不同时间血浆中顺铂浓度,求算药动学参数并比较。结果实验组达峰时、峰浓度、清除率、平均驻留时间和AUC分别是对照组的650、0.06、0.32、4.45和2.07倍。结论顺铂植入剂兔舌内植入作用时间长、舌内作用强度大、全身作用强度微小、药物利用率高,有利于舌癌治疗。

“植入用缓释顺铂”内镜下植入治疗晚期食管癌的Ⅱ_a期临床研究

目的:观察植入用缓释顺铂治疗晚期食管癌的安全性和有效性,并探索其合适给药剂量。方法:本研究为前瞻性、多中心、单臂Ⅱa期临床研究,计划入组病例24~32例。西京医院消化内科为本试验的分中心之一,共15例患者,其中60mg组2例,80mg组4例,100mg组9例。受试者于植药前、植药后1周、4周进行血生化、肝肾功能检查,观察与药物相关的不良反应。入组前进行内镜、CT、食道钡餐检查,4周再进行内镜、CT和食道钡餐复查,参照WHO实体肿瘤疗效评估标准,对比检验判断近期疗效。结果:本中心入组的15例中13例完成全部实验流程,可进行耐受性和不良反应评价。该试验未出现Ⅲ-Ⅳ度不良反应,已发生的实验室及症状性不良事件≤Ⅱ度,100mg组受试者有62.5%发生胸骨后疼痛。可进行肿瘤体积评估的10例病例CT显示疾病控制率(DCR)为90%(9例/10例)。根据疗效、不良反应及并发症分析结果,结合给药方法及剂量,拟定Ⅲ期临床研究以每厘米为一个层面,每一层面植药20mg作为临床试验用药单位剂量强度。结论:内镜引导下在食管肿瘤边缘区域和瘤内植入"植入用缓释顺铂粒子",对治疗晚期食管癌有一定的疗效,且临床耐受性较好,对于不能手术或者放弃手术的有吞咽困难的食管癌患者,可改善其食管梗阻症状。

顺铂植入剂在蛋白变性剂醋酸中的行为研究

目的:研究顺铂植入剂与蛋白变性剂70%醋酸共存时的相容性以及顺铂植入剂的释药规律。方法:在显微镜下观察顺铂植入剂在蛋白变性剂70%醋酸中的形态变化。用HPLC法测定顺铂植入剂体外释药规律;测定顺铂植入剂植入小鼠体内后的释药规律。结果:顺铂植入剂在70%醋酸中仅发生表面隆起、龟裂,植入剂的辅料被腐蚀。顺铂植入剂在70%醋酸中的释药和植入小鼠体内的释药均符合一级释药方程,但在体外释药较快。结论:顺铂植入剂与70%醋酸具有相容性,可以配伍使用。

皮下埋植式动脉灌注顺铂及咖啡因治疗骨盆恶性肿瘤的近期报告

目的 :探讨动脉灌注基因毒性抗癌剂顺铂及促凋亡剂咖啡因对骨盆恶性肿瘤治疗的效果。方法 :2 2例患者 ,应用顺铂 10 0～ 12 0 m g/m2 ,咖啡因 1～ 1.5 g/m2 /2 4h× 3,经皮下埋植式给药装置行动脉导向性灌注 3～ 5次 ,然后按 1981年 WHO观察指标进行疗效评价。结果 :骨痛完全缓解者 13例 (6 0 % ) ,部分缓解者 6例 (2 7% ) ,轻度缓解者 3例 (13% ) ,止痛总有效率 87%。骨病变完全缓解 1例 (5 % ) ,部分缓解 15例 (6 8% ) ,无效 6例 (2 7% ) ,总有效率73%。结论 :本疗法对原、继发性骨盆恶性肿瘤止痛疗效确切 ,骨病变疗效满意 ,对传统化疗不敏感的骨盆恶性肿瘤(如软骨肉瘤、滑膜肉瘤 )亦有较好疗效。

高效液相色谱法测定皮下植入顺铂的血浆及肾脏浓度

目的建立高效液相色谱测定皮下植入顺铂血浆和肾脏中顺铂(DDP)浓度的方法。方法采用高效液相色谱法测定血浆和组织中的顺铂经二乙基二硫代氨基甲酸钠(DDTC)络合衍生化后用乙醚提取的产物Pt(DDTC)2。采用岛津LC-2010A高效液相色谱仪,流动相水-甲醇(25:75),流速1.0ml/min,在254nm处测定药物浓度。结果顺铂的线性范围为0.1～10μg/ml,r=0.9998(血浆),r=0.9993(肾脏),日内RSD和日间RSD均小于10%,最低检测限为50ng。结论本法是一种准确有效的检测方法,适用于皮下植入顺铂的血药浓度监测和药动学研究。

兔舌内植入顺铂植入剂体内药物分布研究

目的研究兔舌内植入顺铂植入剂体内药物分布特征。方法将顺铂植入剂4mg植入兔舌内,于植药后不同时间点取血和组织样,用原子吸收法测定血和组织样的顺铂浓度,求算药动学参数并与静脉给药比较。结果舌体、颈淋巴结、肾、血液顺铂的峰浓度分别是静脉给药的3.24、6.85、0.57和0.05倍;舌体、颈淋巴结维持有效浓度时间均是静脉给药的720倍以上。结论舌体植入顺铂植入剂舌体和颈淋巴结药物浓度高、有效作用时间长、作用强度大;肾内药物浓度低,血药浓度极低,有利于舌癌治疗。进一步的顺铂植入剂实验室和临床试验值得开展。

TACE联合^(125)碘粒子植入治疗原发性肝癌的疗效观察

目的探讨经皮导管动脉化疗栓塞术(TACE)联合CT导向下125碘粒子植入与TACE联合125碘粒子植入联合顺铂瘤内注射治疗肝癌的疗效。方法选择100例原发肝癌患者,随机分成2组,50例TACE+125碘粒子植入术为对照组,与治疗组50例TACE+125碘粒子植入+顺铂瘤内注射术,术后行肿瘤体积、血AFP值、T淋巴细胞亚群CD3、CD4、CD8,血常规、肝肾功能指标、种植性转移、随访生存期对比。结果所有患者均于术后1、2、6、12个月后复查,结果显示对照组50例肿瘤体积平均缩小27.4%,治疗组肿瘤体积平均缩小38.6%;两组血AFP值均下降,治疗组下降明显;对照组发现7例远处转移,治疗组3例远处转移;肝肾功能及T淋巴细胞亚群检测,对照组与治疗组无显著差异;术后一年死于远处转移者,对照组8例,治疗组2例,对照组与治疗组对比差异有统计学意义(P<0.05)。结论 TACE+125碘粒子植入+顺铂瘤内注射治疗肝癌的疗效观察证明,TACE联合粒子植入及顺铂瘤内注射治疗肝癌较TACE联合粒子植入方法治疗更为有效。

缓释粒子内镜植入在胃肠道肿瘤化疗中应用观察

目的:初步评价化疗缓释粒子肿瘤部位植入治疗胃肠恶性肿瘤的临床疗效和不良反应。方法:选择隆起型胃肠道恶性肿瘤患者31例,在消化内镜直视下将5-FU、顺铂的缓释粒子植入到肿瘤间质。结果:完全缓释10例,部分缓释12例,病情稳定6例,3例无缓解,平均有效率为70.9%。患者疼痛缓解率为70.9%,体重增加21例,占67.7%。不良反应除因术中操作出血外,仅见WBC轻度下降、轻度恶性、腹泻,无发生肝肾功能损害。结论:胃肠道恶性肿瘤化疗缓释粒子内镜植入突出了局部靶向治疗,具有微创、安全、有效及并发症发生率低的特点,是综合治疗胃肠道恶性肿瘤新的有效手段之一。

^(125)I粒子植入联合DP方案治疗中晚期肺鳞癌的临床疗效

目的分析^(125)I粒子植入联合多西他赛和顺铂(DP)方案对治疗中晚期肺鳞癌的临床疗效。方法选取84例中晚期肺鳞癌患者为研究对象,随机将患者分为实验组和对照组,每组各42例,实验组患者给予^(125)I粒子植入联合多西他赛和顺铂(DP)方案治疗,对照组患者给予DP方案化疗,分析比较两组患者的临床疗效及临床不良反应。结果实验组患者的临床治疗有效率为73.81%,明显较高对照组的47.62%(P<0.05);实验组患者的1年生存率(85.71%)及中位无进展生存期[(6.3±1.4)个月]明显高于对照组[54.76%,(3.8±1.1)个月](P<0.05);两组患者临床不良反应主要为白细胞及血小板数目减少、恶心呕吐等症状,但程度均较轻(P>0.05)。结论^(125)I粒子植入联合多西他赛和顺铂(DP)方案治疗中晚期肺鳞癌的临床疗效肯定,患者生存期可得到延长,毒副作用较小,该化疗方案可为临床治疗中晚期肺鳞癌提供参考价值。

植入用缓释顺铂联合^(125)I粒子治疗晚期肺癌短期效果的探讨

目的:探讨CT引导下经皮穿刺种植植入用缓释顺铂粒子联合放射性125I粒子治疗晚期非小细胞肺癌(NSCLC)的短期疗效。方法:治疗前临床检查或活检证实为NSCLC 75例,分为植入用缓释顺铂联合125I粒子组(A组),植入用缓释顺铂组(B组)和接受诺维本加顺铂方案化疗组(C组),3组在治疗前和治疗后6个月根据胸CT检查,测量肿瘤体积,按国际标准判定疗效,随访1年。结果:A组有效率为92.9%,1年生存率92.8%。B组有效率为18.2%,1年生存率81.8%。C组有效率为20.0%,1年生存率80.0%。A组与另两组间疗效有显著性差异(P<0.005),B组与C组间疗效无显著性差异(P﹥0.05)。结论:植入用缓释顺铂联合125I粒子治疗晚期NSCLC短期效果显著。