Intravenous RNA interference gene therapy targeting the human epidermal growth factor receptor prolongs survival in intracranial brain cancer.

PURPOSE: The human epidermal growth factor receptor (EGFR) plays an oncogenic role in solid cancer, including brain cancer. The present study was designed to prolong survival in mice with intracranial human brain cancer with the weekly i.v. injection of nonviral gene therapy causing RNA interference (RNAi) of EGFR gene expression. EXPERIMENTAL DESIGN: Human U87 gliomas were implanted in the brain of adult scid mice, and weekly i.v. gene therapy was started at day 5 after implantation of 500000 cells. An expression plasmid encoding a short hairpin RNA directed at nucleotides 2529-2557 within the human EGFR mRNA was encapsulated in pegylated immunoliposomes. The pegylated immunoliposome was targeted to brain cancer with 2 receptor-specific monoclonal antibodies (MAb), the murine 83-14 MAb to the human insulin receptor and the rat 8D3 MAb to the mouse transferrin receptor. RESULTS: In cultured glioma cells, the delivery of the RNAi expression plasmid resulted in a 95% suppression of EGFR function, based on measurement of thymidine incorporation or intracellular calcium signaling. Weekly i.v. RNAi gene therapy caused reduced tumor expression of immunoreactive EGFR and an 88% increase in survival time of mice with advanced intracranial brain cancer. CONCLUSIONS: Weekly i.v. nonviral RNAi gene therapy directed against the human EGFR is a new therapeutic approach to silencing oncogenic genes in solid cancers. This is enabled with a nonviral gene transfer technology that delivers liposome-encapsulated plasmid DNA across cellular barriers with receptor-specific targeting ligands.     

Clinical analysis of 276 cases of non-palpable TO breast cancer

Objective Discussion of diagnosis, treatment and prognosis of non-palpable TO breast cancer. Methods Between 1978 and 1997, 9,980 female patients with operable breast cancer were treated surgically, of which 276 were determined to have TO breast cancer. Most TO breast cancers could be detected promptly with careful examination of presenting symptoms, such as nipple discharge, local thickening of the breast, nipple erosion, nipple retraction and postmenopausal mastalgia, while 12 cases were detected by routine mammography of the contralateral breast. Results All patients were treated surgically and their tissue subjected to histopathological examination. Most cases (73.0%) were noninvasive or early invasive carcinoma. Axillary lymph nodes metastases were found in 7.69% of 234 mastectomy cases. Conclusion The survival rate was significantly increased if the tumor was in an early stage. The 5-, 10-, 15-years survival rates were 98.1%, 94.6% and 90.3%, respectively.     

Hematospermia as the presenting symptom of metastatic malignant melanoma of unknown primary origin

The presence of blood in the ejaculate is alarming to patients and may arise from many sources in the genitourinary tract. Fortunately, hematospermia is rarely due to underlying malignancy and only necessitates further evaluation with continued symptoms. We report a case of persistent hematospermia in a man with human immunodeficiency virus caused by metastatic malignant melanoma to both seminal vesicles. The evaluation included pelvic magnetic resonance imaging and transrectal ultrasound-guided biopsy. Metastases to the brain were subsequently discovered, but a primary source for the melanoma could not be identified. This is the first reported case of isolated involvement of the seminal vesicles with malignant melanoma and underscores the potential for serious disease presenting as hematospermia.     

放疗增敏剂甘氨双唑钠的Ⅱ期临床研究

目的 :按二期临床研究要求观察注射用甘氨双唑钠 (简称CMNa)的有效性和安全性。方法 :采用平行对照、随机分组的设计方法 ,将 2 8例经病理组织学确诊的需接受放射治疗的头颈部、食管和肺部肿瘤患者 ,按 2∶1的比例分设实验组(CMNa +常规放疗 )和对照组 (单纯常规放疗 ) ,观察其有效性和安全性的相关指标。结果 :治疗前后血常规、肝肾功能的实验室检查 ,治疗中和治疗后不良反应、严重程度的观察比较及不良反应率的结果比较。两组均无显著性差异。肿瘤原发灶和转移灶的CR率和CR +PR率两组未见显著性差异。但转移灶达PR时所需的照射剂量明显低于对照组 (P <0 0 5 )。结论 :安全性与前期研究结果相符 ,在临床推荐剂量内未观察到明显消化道和神经系统等的不良反应 ,有效率未见显著性差异可能与样本数较少有关。据后期汇总的大样本统计显示两组的显著性差异表现在CMNa可提高CR率和总有效率 ,并降低达到CR和PR时的照射剂量     

一种新的细胞凋亡相关基因——高同型半胱氨酸诱导基因HCY-2的功能初探

目的　探讨高同型半胱氨酸 (HCY)血症引起心血管病和出生性缺陷的作用机制。方法　采用诱导筛选方法克隆高同型半胱氨酸诱导基因 HCY- 2 ,以 Northern印迹分析检测 HCY- 2基因在大鼠不同组织中的表达 ,以免疫组化方法验证 HCY- 2蛋白在大鼠不同组织中的表达。结果　以诱导筛选方法从大鼠血管平滑肌细胞内克隆到一个新的全长 c DNA,即高同型半胱氨酸诱导基因 HCY- 2 ,它编码 142个氨基酸。Northern印迹分析和免疫组化检测表明 ,HCY- 2基因可在大鼠心、肾、脑、肝、肺等组织中广泛表达。在体外 ,将重组 HCY- 2基因转移至内皮细胞中 ,能够引起细胞凋亡和 DNA损伤 ;在体内 ,将 HCY- 2基因转移至鸡胚内 ,则诱发鸡胚细胞凋亡 ,并引起畸形。结论　 HCY- 2基因可能是一种新的凋亡基因 ,高同型半胱氨酸血症可能通过 HCY- 2基因诱发心血管病和出生性畸形。     

电针刺激对外伤性脊髓损伤患者功能独立性评定影响的临床研究

目的:通过观察电针刺激疗法对外伤性脊髓损伤患者的生活独立功能的影响,为脊髓损伤患者寻求一条有效的康复治疗途径。方法:62例外伤性脊髓损伤患者被随机分成治疗组32例,接受电针刺激加运动治疗、作业治疗;对照组30例,接受单纯性运动治疗、作业治疗。在治疗前后进行功能独立性评定。结果:治疗组与对照组的功能独立性积分均明显高于治疗前(P<0.01),而治疗组治疗后的分值97.78±19.55明显高于对照组的分值87.53±16.67(P<0.05)。同样,治疗组的住院效率明显高于对照组(P<0.05)。结论:电针刺激加运动与作业治疗的综合康复手段能明显改善外伤性脊髓损伤患者的生活独立能力,且能科学地提高住院效率。     

液相色谱-质谱测定鸦胆子油脂肪乳注射液在癌症患者体内的血药浓度

目的 建立液相色谱-质谱(LC-MS)法测定癌症患者单剂量滴注鸦胆 子油脂肪乳后体内油酸浓度。方法 用自身对照试验设计,7名癌症患者,第3 天不给药,抽取不同时间点空白血浆样品;第5天,单剂量滴注鸦胆子油脂肪乳 注射液100 mL,滴注开始后,抽取不同时间点血浆样品,60 min滴完,用LC- MS法测定血药浓度。结果 线性范围为2．44-156 mg·L-1;日内、日间变异 系数均<14％;7名癌症患者单剂量滴注鸦胆子油脂肪乳注射液100 mL后,主 要药代动力学参数:tmax=(1．08±0．19)h,Cmax(95．20±29．10)mg·L-1, AUC0-7h=(265．67±59．32)mg·h·L-1,t1／2=(12．14±6．42)h。结论 本法 适用临床测定血浆中油酸浓度。     

螺旋CT三维重建在鼻骨骨折中的临床应用价值

目的：探讨螺旋CT三维成像对鼻骨骨折的诊断价值。方法：应用GE Lightspeed Plus多排螺旋机扫描仪，对46例鼻外伤患者进行鼻骨横断面扫描和三维重建成像，并对检查结果进行分析。结果：46例鼻外伤患者中，9例普通X线侧位平片未发现骨折(19．6％)；CT图像均能清晰显示骨折线，其中单纯鼻骨骨折32例(69.6％)，并发上颌骨额突骨折11例(23．9%)，上颌窦骨折1例，筛窦纸样板骨折3例，鼻中隔断裂1例。结论：螺旋CT三维成像对于诊断鼻骨骨折具有重要的诊断价值。     

眼灌注压对人视乳头微循环的影响

目的 了解眼外负压吸引诱导的眼灌注压改变的条件下，正常人、原发性开角性青光眼(POAG)患者和正常眼压性青光眼患者(NTG)的视乳头微循环的变化，探讨视乳头局部自身调节的幅度。方法正常人8例，POAG患者10例和NTG患者7例，采用眼外负压杯吸引诱导眼压升高，负压增加的幅度为30s50mmHg，同时测量眼压。采用HRF测量视乳头处血流量。将基础状态下视乳头血流值作为基础值，当眼压升高到30mmHg和40mmHg时，分别测量这两点视乳头微循环的血流值，在40mmHg后解除负压吸引，测量负压吸引解除后1min、5min时视乳头微循环的血流值。结果 三组视乳头的基础血流量无明显差异。当眼压升高到30mmHg时，正常组的血流量仍维持稳定，但POAG组和NTG组明显下降，POAG组下降幅度超过25％，NTG组下降幅度超过45％。当眼压升高到40mmHg，正常组视乳头血流量也出现明显下降，其中0NHF下降约30％，POAG组和NTG组下降更明显，POAG组下降幅度超过50％，NTG组下降幅度超过65％。在解除负压吸引后1min，正常组血流量增加的幅度约为31％，POAG组增加约19％，NTG组无明显增加。在负压解除后5min，三组视乳头血流基本恢复到基础状态。结论 正常组视乳头微循环有一定范围的自身调节幅度，可以耐受眼灌注压一定程度的改变，POAG组和NTG组自身调节能力均有不同程度的损害。