靶向性双自杀基因混合碘油对兔肝癌的介入治疗研究

目的评价携带血管内皮生长因子（VEGF）启动子调控的TK及CD融合双自杀基因重组腺病毒系统（AdVEGF-CDglyTK）与超液化碘油混合栓塞兔肝癌的治疗效果.方法 36只荷VX2瘤兔随机分4组,LP组（单纯超液化碘油栓塞组）;LP＋AdVEGF-CDglyTK组（超液化碘油＋AdVEGF-CDglyTK混合栓塞,介入术后腹腔注射GCV ＋5-FC治疗组）;AdVEGF-CDglyTK组（单纯灌注AdVEGF-CDglyTK,介入术后腹腔注射GCV ＋5-FC治疗组）;NS组（生理盐水治疗组）.于术前及术后第10、15天行CT检查观察肿瘤的体积,免疫组织化学法检测肿瘤组织VEGF的表达及微血管密度（MVD）.结果 4组兔术前肿瘤体积在统计学无显著性差异（P〉0.05）;介入治疗后10天、15天的各组之间肿瘤增长率均有显著性差异（P〈0.05）,LP＋AdVEGF-CDglyTK肿瘤增长率最小,而LP组肿瘤增长率小于AdVEGF-CDglyTK组,三个治疗组疗效均优于生理盐水对照组.VEGF表达方面：LP组表达最高,与其它三组相比有显著性差异（P〈0.05）,其它三组之间未见显著性差异.MVD表达：LP组最高,LP＋AdVEGF-CDglyTK组最低,与其它各组相比有显著性差异（P〈0.05）,而AdVEGF-CDglyTK组MVD表达也低于NS组,有显著性差异（P〈0.05）.结论在对兔肝癌的治疗中,与单纯碘油栓塞以及单纯灌注AdVEGF-CDglyTK相比,AdVEGF-CDglyTK与碘油混合肝动脉栓塞可以明显降低肿瘤的生长率,减少肿瘤组织VEGF的表达及减少肿瘤新生血管生成.     

纳米材料栓塞对肿瘤组织表达CD147影响的研究

目的探讨应用羟基磷灰石纳米材料和超液化碘油混悬液栓塞治疗,对肝癌组织表达CD147的影响。方法30只接种VX2肿瘤系的荷瘤兔随机分为3个治疗组:对照组;超液化碘油组;纳米材料和超液化碘油组。通过超选插管胃十二指肠动脉分别给予生理盐水(1mL/只),超液化碘油(0.3mL/kg),纳米材料和超液化碘油混悬液(0.3mL/kg)。术后3dCT检查确认插管成功。2周后,应用免疫组织化学法(S-P)和westernblot方法,来检测3组肿瘤组织CD147的表达。结果免疫组化显示,CD147在3组的肿瘤组织细胞膜均有表达,阳性率分别为(31.33±5.88)%,(75.63±4.44)%,(80.03±5.59)%,对照组与碘油组,纳米碘油组在CD147的表达差异有统计学意义(P<0.01),后两组差异则无统计学意义(P>0.05)。Westernblot半定量检测,碘油组和纳米碘油组CD147的表达量升高,与对照组对比有统计学意义(P<0.05)。结论应用超液化碘油,或羟基磷灰石纳米材料和超液化碘油混悬液栓塞治疗后,肿瘤组织表达CD147有上升趋势,可能是造成栓塞治疗后肿瘤复发率高的因素之一。     

纳米局部治疗介导的P53联合Rb基因对兔xVX2肝转移灶血管新生的影响及分子机制

【摘要】 目的 本研究旨在联合P53及Rb两种抗癌基因,通过纳米基因靶向治疗技术,探索其对肝转移癌灶血管新生的影响及其分子机制。方法〓以超液化碘油及Pll修饰的nHAP乳剂为载体,将含有野生型P53、Rb基因的重组表达质粒经肝动脉共同或者分别转运至兔VX2肝转移癌灶局部,采用蛋白印迹法及原位共焦激光显微镜确定P53及Rb共表达蛋白在转移灶的表达。然后病理观察肿瘤组织微血管密度(MVD)变化。最后应用Realtime RT-PCR级ECL蛋白杂交技术检测CD31、CD34及VEGF的表达差异。结果〓CD31标记的MVD显示:与其他组相比,nanoplex-p53/lipiodol及nanoplex-(p53+Rb)/lipiodol组肿瘤MVD均降低;CD34标记的MVD显示:与其他组相比,nanoplex- Rb/lipiodol及nanoplex-(p53+Rb)/lipiodol组MVD均降低。nanoplex- p53/lipiodol及nanoplex-(p53+Rb)/lipiodol组CD31 mRNA和蛋白表达降低;nanoplex- Rb/lipiodol及nanoplex-(p53+Rb)/lipiodol组CD34 mRNA和蛋白表达降低;nanoplex- p53/lipiodol、nanoplex- Rb/lipiodol及nanoplex-(p53+Rb)/lipiodol组VEGF mRNA和蛋白表达降低。结论〓以Pll-nHAP为载体的Rb基因协同P53基因纳米靶向治疗通过降低CD31、CD34及VEGF的表达减少新生血管生成,增强其抗肿瘤效应。P53基因联合Rb基因的纳米基因靶向治疗有可能成为抑制消化道癌肝转移灶血管新生的有效治疗方法。     

纳米局部治疗介导的P53联合Rb基因对兔VX2肝转移灶血管新生的影响及分子机制

目的本研究旨在联合P53及Rb两种抗癌基因,通过纳米基因靶向治疗技术,探索其对肝转移癌灶血管新生的影响及其分子机制。方法以超液化碘油及Pll修饰的nHAP乳剂为载体,将含有野生型P53、Rb基因的重组表达质粒经肝动脉共同或者分别转运至兔VX2肝转移癌灶局部,采用蛋白印迹法及原位共焦激光显微镜确定P53及Rb共表达蛋白在转移灶的表达。然后病理观察肿瘤组织微血管密度(MVD)变化。最后应用Realtime RT-PCR级ECL蛋白杂交技术检测CD31、CD34及VEGF的表达差异。结果CD31标记的MVD显示:与其他组相比,nanoplex-p53/lipiodol及nanoplex-(p53+Rb)/lipiodol组肿瘤MVD均降低;CD34标记的MVD显示:与其他组相比,nanoplex-Rb/lipiodol及nanoplex-(p53+Rb)/lipiodol组MVD均降低。nanoplex-p53/lipiodol及nanoplex-(p53+Rb)/lipiodol组CD31 mRNA和蛋白表达降低;nanoplexRb/lipiodol及nanoplex-(p53+Rb)/lipiodol组CD34 mRNA和蛋白表达降低;nanoplex-p53/lipiodol、nanoplex-Rb/lipiodol及nanoplex-(p53+Rb)/lipiodol组VEGF mRNA和蛋白表达降低。结论以Pll-nHAP为载体的Rb基因协同P53基因纳米靶向治疗通过降低CD31、CD34及VEGF的表达减少新生血管生成,增强其抗肿瘤效应。P53基因联合Rb基因的纳米基因靶向治疗有可能成为抑制消化道癌肝转移灶血管新生的有效治疗方法。     

纳米材料碘油混悬液栓塞后兔VX2肿瘤组织MT1-MMP表达改变的意义

目的 观察应用羟基磷灰石纳米粒子和超液化碘油混悬液栓塞后,兔VX2肿瘤组织膜型基质金属蛋白酶-1(MT1-MMP)表达变化的意义.方法 60只接种VX2肿瘤细胞的荷瘤兔随机分为3组:肿瘤组、超液化碘油组、羟基磷灰石纳米超液化碘油混悬液组.通过胃十二指肠动脉插管分别给予:生理盐水(1 ml/只)、超液化碘油(0.3 ml/kg)、纳米超液化碘油混悬液(0.3 ml/kg).术后3 d CT检查确认插管成功.两周后,应用免疫组织化学三步法(S-P)测定肿瘤组织MT1-MMP的表达定位,以及治疗干预后表达量的改变.RT-PCR检测MT1-MMP mRNA的表达差异,Western blot法分析MT1-MMP蛋白表达变化.结果 MT1-MMP在肿瘤细胞膜和肿瘤组织间质都有表达.肿瘤组与碘油组、纳米碘油组的阳性表达相比,差异有统计学意义(P＜0.05),而碘油组和纳米碘油组则无明显差异(P＞0.05).Western blot法检测各组蛋白量的表达也支持此结果.RT-PCR检测3组mRNA表达值的对比无明显差异(P＞0.05).结论 MT1-MMP主要表达于肿瘤细胞膜和间质.超液化碘油和(或)羟基磷灰石纳米粒子栓塞后,肿瘤组织及间质的MT1-MMP的表达上调,可能是造成栓塞后肿瘤转移复发率高的分子机制之一.     

单纯疱疹病毒胸苷激酶基因、野生型p53基因联合治疗裸鼠肝癌

目的：观察阳离子脂质体介导的单纯疱疹病毒胸苷激酶基因（HSV－TK）、野生型P53基因（wt-p53）联合治疗裸鼠肝癌的作用。方法：用6μl Dosper脂质体介导将1．5μgHSV－TK基因、1．5μg野生型p53基因转染人肝癌细胞系SMMC－7721，逆转录聚合酶链反应（RT－PCR）检测基因表达，四唑蓝比色（MTT）法测定其对肝癌细胞的杀伤作用。在0．8cm裸鼠肝癌模型单独或联合导入5μg基因后，结合应用前药无氧鸟苷（GCV）100mg/kg体重7－10d，分别观察肿瘤的生长情况。结果：单独导入wt-p53对肝癌细胞的抑制率为15％，与HSV－TK基因联用后，在GCV10μmol/L时，杀伤效率明显强于单用HSV－TK，但在GCV1000μmol/L时，两者间杀伤效率差异无显著性（P＞0．05）。在鼠实验性肝癌，导入wt-p53后，肿瘤的生长受到抑制；wt-p53与HSV－TK／GCV联用后，在治疗的第8天就有4只（80％）裸鼠肿瘤完全消退，与HSV－TK／GCV组相比差异有显著性（P＜0．05）。结论：HSV－TK基因、wt-p53基因联合应用对裸鼠肝癌有显著杀伤作用。     

肝段性栓塞化疗在肝癌介入治疗中的应用

目的 评价肝段性栓塞化疗在肝癌介入治疗中的的疗效、不良反应和应用价值。方法超选择肝段性栓塞化疗和非超选择常规插管栓塞化疗各20例，前者以超选择技术进入肿瘤血管进行栓塞化疗，后者以插管进入肝固有动脉或肝左右动脉进行栓塞化疗。以碘油填充效果、介入术后第7天肝功能恢复情况、生活质量评分及平均住院花费为观察终点指标。结果两组碘油填充效果、生存质量评分具有统计学显著性差异；两组介入术后第7天肝功能恢复情况无统计学差异；治疗组花费较对照组高，但患者能耐受。结论肝段性栓塞化疗在肝癌介入治疗中有明显的应用价值。     

兔肝肿瘤介入栓塞后血清VEGF早期改变的实验研究

目的：探讨对兔VX2肝肿瘤模型进行胃十二指肠动脉介入栓塞术,早期血清VEGF的改变及意义。方法：将40只接种VX2肿瘤组织2周的荷瘤兔随机分为两组：碘油组（n=20）和对照组（n=20）,通过超选择插管胃十二指肠动脉分别给予超液化碘油（0．3mL／只）、生理盐水（1mL／只）。1周后,应用酶联免疫吸附法（ELISA）测定兔血清VEGF的变化,免疫组织化学法（ABC）检测残余肿瘤组织的蛋白表达,定量PCR检测VEGFmRNA的表达改变。结果：介入栓塞后,碘油组血清VEGF1．42±0．29ng／mL,对照组1．12±0．21ng／mL,二者相比差异有统计学意义（P〈0．01）。碘油组残余肿瘤细胞VEGF的表达明显高于对照组（P〈0．01）,VEGFmRNA表达也高于对照组（P〈0.05）。结论：应用碘油介入栓塞兔VX2肝肿瘤术后,残余肿瘤组织表达VEGF明显升高,可作为预测残余肿瘤细胞转移复发的有效指标之一。     

WTp53基因联合TK/GCV、CD/5-Fc系统治疗人结肠癌的实验研究

目的：观察WTp53基因联合TK／GCV、CD／5-Fc系统对人结肠癌的治疗效果，并探讨其作用机理。方法：采用培养细胞移植法，将人结肠癌细胞系SW480接种于裸鼠背部皮下，建立裸鼠人结肠癌移植瘤模型，将32只裸鼠随机分为4组：对照组、WTp53组、TK、CD组、WTp53与TK、CD组，每组8只，WTp53采用脂质体介导，TK、CD采用逆转录病毒介导。将WTp53、TK、CD注入移植瘤体内，瘤内注射TK、CD的裸鼠同时腹腔注射GCV、5-Fc治疗，观察各组小鼠的生存状况及肿瘤体积、瘤重、肿瘤生长抑制率、常规病理、生存期等指标，比较观察各治疗组的治疗效果及对荷瘤裸鼠存活的影响。结果：各治疗组裸鼠人结肠癌移植瘤的生长均受到显著抑制，裸鼠存活期显著延长，联合基因治疗组效果更好，WTp53、与TK、CD有交互协同作用。结论：WTp53、TK／GCV、CD／5-Fc对人结肠癌SW480细胞有明显抑制作用，WTp53基因联合TK／GCV、CD／5-Fc系统效果更强。     

WTp53基因联合TK/GCV、CD/5-FC系统抑制结肠癌肝转移的实验研究

目的研究WTp53基因联合TK／GCV、CD／5-FC系统对结肠癌肝转移的抑制作用。方法32只裸鼠随机分为4组，每组8只。脾内注射法建立结肠癌肝转移动物模型。第1组：脾内注射SW480细胞（对照组）；第2组：脾内注射SW480／p53细胞；第3组：脾内注射SW480／TK-CD细胞，腹腔注射GCV、5-FC；第4组：脾内注射SW480／p53与SW480／TK-CD等比例混合细胞，腹腔注射GCV、5-FC。观察各组裸小鼠的肝转移率、肝转移瘤数目、肿瘤细胞凋亡指数（AI）、生存期等指标。结果各治疗组裸鼠肝转移的发生率下降，平均肝转移瘤数减少，其动物的生存期延长，肝转移瘤内的癌细胞凋亡率增高。联合基因治疗组效果最好，且WTp53与TK／GCV、CD／5-FC有交互协同作用。结论WTp53基因与TK／GCV、CD／5-FC系统联合应用具有协同效应，可有效地抑制结肠癌肝转移的形成。     

Combined effects of hematoporphyrin derivative phototherapy and adriamycin in a murine tumor model

Hematoporphyrin derivative phototherapy (HpD-PT) is currently being used experimentally in the treatment of various malignancies. The effectiveness of HpD-PT appears to be limited to superficial malignancies because of its inability to penetrate more than 0.5-1 cm. The mechanism of action has been demonstrated to result from the formation of toxic singlet oxygen and other oxygen radicals. Preliminary work suggested that the addition of other chemical agents known to produce toxic oxygen radicals may enhance the effect of HpD-PT. To test this hypothesis, we examined the effectiveness of HpD-PT in the Walker 256 carcinosarcoma with and without Adriamycin. Tumor kill was estimated by calculating the area of necrosis on photomicrographic sections. From this area, a radius of tumor necrosis was determined and compared among various control and experimental groups. HpD-PT was effective in this model when compared to control groups (radius of necrosis 3.79 +/- 0.97 mm vs. 2.60 +/- 1.26 mm, P less than .05). The addition of Adriamycin significantly increased the radius of necrosis when compared to HpD-PT (4.57 +/- 1.70 mm vs. 3.69 +/- 0.97 mm, P less than .01). From this work we conclude that HpD-PT demonstrates effective tumor killing in this murine model. The addition of Adriamycin significantly increased tumor kill.     

Facing the Reality: The World Cannot Afford Uremia Therapy at the Start of the 21st Century

Abstract: Although remarkably successful in prolonging useful life, there is minimal probability that the majority of the world's population will benefit from contemporary therapy for irreversible renal failure because of its inordinately high cost in light of available resources. While affluent nations establish priorities for allocation of slots for maintenance dialysis or recipients of organ transplants, poor and developing countries must await the development of inexpensive, low technology treatments to substitute for absent kidney function. One attractive potential alternative to contemporary uremia therapy is the use of the intestine as a giant substitute and somewhat displaced nephron. Possible means of extracting wastes via the gut include ingestion of a mixed oral sorbent, instillation of bacterial crystallized enzymes to transform nitrogenous wastes to essential amino acids, or administration of high osmolality laxatives to promote diarrhea containing nitrogenous wastes. Any of these approaches may extract sufficient solute and water to sustain anephric life. An optimistic view of evolving uremia therapy is that within the next decade pills and purges for the poor may supplant more effective though expensive high technology approaches now encompassed in so-called modern nephrology.     

胆囊切除术后胆瘘的处理体会

本文报告７例胆囊切除术后胆瘘，根据具体情况选择治疗方法：其中保守治疗４例，治愈２例，失败２例；再手术治疗４例均治愈；内镜乳头括约肌切开术治疗１例治愈。作者认为；保守治疗治愈率不高，时间长；再手术治疗愈较高，但手术较困难、危险性高，易导致副损伤的发生；内镜治疗具有创伤小侵入外科并发症少，治愈率高等优点，可作为术后胆瘘的首选治疗方法，值得进一步推广应用。     

Focal therapy for primary and salvage prostate cancer treatment: a narrative review

Despite innovations in surgical technology and advancements in radiation therapy, radical treatments for clinically localized prostate cancer are associated with significant patient morbidity, including both urinary and sexual dysfunction. This has created a vital need for therapies and management strategies that provide an acceptable degree of oncologic efficacy while mitigating these undesirable side effects. Successful developments in screening approaches and advances in prostate imaging have allowed clinicians to identify, localize, and more precisely target early cancers. This has afforded urologists with an important opportunity to develop and employ focal ablation techniques that selectively destroy tumors while preserving the remainder of the gland, thus avoiding detrimental treatment effects to surrounding sensitive structures. A lack of high-level evidence supporting such an approach had previously hindered widespread adoption of focal treatments, but there are now numerous published clinical trials which have sought to establish benchmarks for safety and efficacy. As the clinical evidence supporting a potential role in prostate cancer treatment begins to accumulate, there has been a growing acceptance of focal therapy in the urologic oncology community. In this narrative review article, we describe the techniques, advantages, and side effect profiles of the most commonly utilized focal ablative techniques and analyze published clinical trial data supporting their evolving role in the prostate cancer treatment paradigm.     

系统治疗在肝癌术前新辅助治疗中应用进展

近年来，肝癌的系统治疗进展迅速，新的免疫治疗药物、靶向药物不断涌现，新的治疗理念和治疗方案不断创新。但关于系统治疗应用于肝癌术前的方案选择和疗效分析，探讨相对较少。肝癌的新辅助系统治疗按其目的和后续手术方式可分为可切除性肝癌的新辅助系统治疗、不可切除肝癌的转化治疗和肝移植术前的降期或桥接治疗。新辅助系统治疗策略的制定需基于术前诊断特别是病理学诊断、多学科讨论及分子肿瘤学委员会讨论、系统的疗效评估、科学的终点选择及术中术后的全过程管理。由于肝癌肝移植涉及系统免疫调节和免疫微环境重塑，其综合治疗的方案、方式都处于探讨阶段。新辅助治疗用于肝癌肝移植的术前降期或术前桥接在免疫治疗时代，是亟需探讨的重要问题。     

靶向治疗在肿瘤新辅助治疗中的应用

<正>靶向治疗是除手术、放疗、化疗外治疗肿瘤的一种新方法,是在无创或微创条件下以肿瘤为目标,采用有选择、针对性较强、病人易于接受、反应小的局部或全身治疗,最终达到有效控制肿瘤、减少肿瘤周围正常组织损伤目的的各种手段的总称。肿瘤的靶向治疗凭借其特异性与靶向性,     

A multicomponent behavioural and drug intervention for nocturia in elderly men: rationale and pilot results

OBJECTIVES

To evaluate the number of medical and urological conditions associated with nocturia in a cohort of older men who were primary‐care enrolees, and to assess the feasibility and efficacy of using a multicomponent intervention to reduce nocturia and its bother.

SUBJECTS AND METHODS

Men aged ≥50 years and with two or more episodes of nocturia were recruited from the primary‐care clinics at one Veterans Affairs Medical Center to participate in a 4‐week, open‐label, prospective pilot study. A multicomponent intervention composed of behavioural therapy and targeted drug therapy was administered according to a specified protocol based upon identified risk factors for nocturia. Outcome measures included self‐reported nocturia and bother on the American Urological Association (AUA)‐7 Symptom Index, 3‐day bladder diaries and self‐reported sleep‐related measures recorded using 7‐day sleep diaries.

RESULTS

Fifty‐five men completed the protocol (mean age 67 years, sd 8.3); they had a mean of 4.5 of nine defined conditions potentially related to nocturia. Highly prevalent conditions included moderate‐to‐severe benign prostatic hyperplasia (87%), hypertension (86%) and urinary frequency (71%). The mean diary‐recorded nocturia decreased from 2.6 to 1.9 (P < 0.001), and bother score reduced from 3.1 to 1.1, representing a change from a ‘medium’ to a ‘very small’ problem (on a 5‐point scale). Sleep diary‐derived measures also improved significantly (time to initiate sleep, time to return to sleep after awakening, quality of sleep).

CONCLUSIONS

Given that individual older patients often have multiple coexistent risk factors for nocturia, identifying a principal cause of nocturia, a concept emphasized in treatment guidelines, proved to be difficult. Implementing a multicomponent behavioural intervention combined with drug(s) was feasible in older men and reduced nocturia frequency, bother from nocturia, and time to initiate sleep, within 4 weeks. These promising results merit repeating using a randomized, controlled trial.     

单剂疗法和10天疗法治疗尿路感染疗效对比分析

对比治疗尿路感染的疗法的疗效。方法 将女性尿路感染患者进行随机双盲分组,使用复方新诺明单剂治疗与10天治疗。同时测定两组各期阴道,肠道大肠杆菌感染情况。结果 开始治疗两周内,10天治疗治愈率明显高于单剂治疗组(P<0.05)。6周后后治愈率相近。在根绝阴道和肠道细菌方面,单剂治疗效果较差,导致治疗两周内同种菌株复发率增高。10天治疗副作用高于单剂治疗组(P<0.05)。结论 单剂及10天疗法各有优缺点。     

原发性肝癌综合治疗的进展和热点

原发性肝癌（本文特指肝细胞癌,以下简称肝癌）的治疗原则是以手术为主的综合治疗。围绕提高根治性手术切除率和降低术后复发率等难题,肝癌的转化治疗、新辅助治疗和术后辅助治疗应运而生,极大地丰富了综合治疗的内涵,也成为研究热点。肝癌侵袭转移性强且常合并肝硬化等,综合治疗必不可少,但因手术适应证仍存在争议、个体间异质性大等原因,...