A neutralizing anti-fibroblast growth factor (FGF) 8 monoclonal antibody shows anti-tumor activity against FGF8b-expressing LNCaP xenografts in androgen-dependent and -independent conditions

BACKGROUNDS: Fibroblast growth factor 8-isoform b (FGF8b) has been detected in human clinical sex-organ related cancers including hormone-refractory prostate cancer. There are, however, few relevant experimental models. A murine monoclonal anti-FGF8 antibody, KM1334, has been shown to neutralize FGF8b and inhibit the growth of androgen-dependent mouse mammary SC-3 cells in vitro and in vivo. In the present study, we evaluated the anti-tumor activity of KM1334 against androgen-dependent and -independent progression of FGF8b-expressing human prostate cancer xenografts. METHODS: FGF8b cDNA was transfected into androgen-dependent human prostate cancer cell line LNCaP, and its xenograft tumors were established subcutaneously in SCID mice with or without castration. KM1334 at the dose of 400 microg/head was injected twice weekly. RESULTS: FGF8b-expressing LNCaP cells secreted FGF8b, showed enhanced level of Erk1/2 phosphorylation, and showed more potent growth properties than mock-expressing cells in vitro and in vivo. KM1334 reduced these properties in vitro, inhibited tumorigenecity in vivo (T/C=0.33), and showed anti-tumor activity against established tumors (T/C=0.47) of FGF8b-expressing cells. FGF8b-expressing LNCaP tumors were androgen-dependent. However, they recurred as androgen-independent FGF8b positive tumors after castration. KM1334 also inhibited the growth of established FGF8b-expressing tumors in the androgen-independent states (T/C=0.47). CONCLUSIONS: These results indicate that humanized monoclonal antibodies, conserving the paratope of KM1334, are a promising candidate for therapy of FGF8b-expressing clinical prostate cancers. Follow-up studies using xenograft models with clinical FGF8b-expressing tumors are required to validate these early findings.     

Clipless and sutureless laparoscopic surgery for adrenal and extra-adrenal tumors

BACKGROUND: Newer, energy-based devices like the ultrasonic coagulator (Harmonic Scalpel, Ethicon Endo-Surgery, Inc., Cincinnati, OH) and the LigaSure vessel-sealing system (Valleylab, Boulder, CO) are increasingly being used in advanced laparoscopic procedures. Use of these devices has resulted in shorter operative time, less blood loss, and lower conversion rates. We present our experience with these devices for laparoscopic removal of adrenal and extra-adrenal tumors. METHODS: Ten patients with adrenal tumors and 4 with extra-adrenal tumors were operated on laparoscopically with the ultrasonic shears and LigaSure vessel-sealing system. The entire surgery was carried out using these energy-based devices without using any clips or sutures. RESULTS: No conversions were necessary. None of the patients experienced any major intraoperative or postoperative bleeding. The mean size of the tumor was 6.2 cm (range, 3 to 8). The mean operative time was 123 minutes (range, 80 to 210), and the mean blood loss was 70 mL (range, 10 to 150). Histopathology revealed pheochromocytomas in 7 patients. CONCLUSIONS: Use of the LigaSure vessel-sealing device along with ultrasonic shears for laparoscopic removal of adrenal and extra-adrenal tumors is safe and effective.     

纳洛酮对颅脑肿瘤显微手术后血β-内啡肽和内皮素的影响

目的探讨纳洛酮对颅脑肿瘤显微手术后血β-内啡肽（β-erdorphin,β-EP）和内皮素（Endothelin,ET）的影响。方法对颅脑肿瘤显微手术后的100例患者按手术次序分治疗组和对照组各50例。两组病例术后均进行常规治疗,治疗组术后加用纳洛酮。采用放射免疫法测定两组患者血β-EP和ET。结果治疗组和对照组术后即刻血βEP、ET值均较术前有所上升,两组相比较差别无统计学意义（P〉0．05）,之后血β-EP、ET均渐下降,但治疗组下降程度较快,术后第二天即接近术前水平,与对照组比较差别有统计学意义（P〈0．001）。结论颅脑肿瘤显微手术后早期大剂量应用纳洛酮能明显降低患者术后血β-EP、ET的值,从而减轻了由于内源性阿片肽及ET异常升高所致的继发性脑损害。     

原发性输尿管癌的磁共振诊断

目的分析输尿管癌的磁共振成像（MRI）表现，评价MRI对原发性输尿管癌的诊断价值。方珐用1．5T磁共振扫描仪，采用T2加权成像（T2WI）快速自旋回波序列（FSE）、脂肪抑制技术和MR尿路造影（MRU）检查，观察分析21例原发性输尿管癌的MRI表现。结果21例原发性输尿管癌中，5例表现为输尿管上端结节状病灶，4例表现为输尿管中段结节或条状病灶，12例表现为输尿管下段或下端结节或条状病灶。T1WI为等、略低信号，T2WI为等、高信号，增强扫描有轻、中度强化。MRU显示输尿管截然中断13例，鼠尾状狭窄中断4例，管壁不规则狭窄僵硬4例，与术中所见梗阻部位及程度完全相符。结论MRI结合MRU能清晰显示输尿管肿瘤的梗阻部位、梗阻程度以及累及范围、周围结构情况，选择合理的检查序列加做增强扫描，是诊断输尿管肿瘤的理想方法。     

重楼总皂苷对多发骨折-脂多糖两次打击模型大鼠血清细胞因子水平的影响

目的：探讨重楼总皂苷（RPTS）对多发骨折-脂多糖两次打击模型大鼠血清TNF-α、IL-1β及IL-6水平的影响。方法：68只Wistar大鼠随机分成5组,除空白对照组外,其余各组按多发骨折-脂多糖两次打击模型标准制模。制模成功后1h,除空白对照组和模型对照组外各组予以不同浓度的RPTS灌胃,干预后6h采血,以ELISA法检测血清中TNF-α、IL-1β及IL-6浓度。结果：大鼠血清TNF-α、IL-1β及IL-6浓度,模型对照组与空白对照组相比较明显升高（P〈0.001）,而RPTS各干预组与模型对照组相比较却明显下降（P〈0.001）,差异均有统计学意义。结论：重楼总皂苷可以降低多发骨折-脂多糖两次打击模型大鼠血清中的TNF-α、IL-1β及IL-6水平。     

带血管骨移植治疗股骨头无菌性坏死进展

股骨头无菌性坏死是骨科临床较常见的疾病，如能早期做出诊断（股骨头塌陷前），可采用钻芯减压（植骨或不植骨）、截骨、以及带或不带血管的骨移植治疗，尽力保存髋关节功能。局部带蒂骨移植与和游离带血管的骨移植能将带血运的骨组织植入股骨头骨坏死区，除用健康骨组织替代坏死骨外，还重建了股骨头新的血供来源。经5年观察，对各期患者治疗成功率为80％。应用游离带血管的骨移植治疗股骨头无菌性坏死，可获得较高的成功率。     

小鼠全层皮肤创伤愈合过程中基质细胞衍生因子-1及其受体CXCR4基因表达的研究

目的：研究小鼠全层皮肤创伤愈合过程中创面基质细胞衍生因子-1（stroma-cell derived factor-1,SDF-1）及其受体CXCR4的基因表达情况。方法：建立小鼠背部皮肤正中近颈侧1.5cm×1.5cm的正方形皮肤全层缺损模型,分别于伤后1、2、3、4、5、7、10和14d获取创缘组织,应用半定量逆转录-聚合酶链反应检测损伤后各时间点创面SDF-1及CXCR4的mRNA表达,并观察组织病理学变化。结果：伤后1～3d创面有大量炎症细胞浸润,4d时有肉芽组织形成,5d可见上皮细胞覆盖创面,7d时创面周围明显上皮化,14d创面基本完全愈合。SDF-1及CXCR4在创面愈合过程均呈双峰表达,SDF-1基因表达于伤后1d明显增高（P〈0.01）,随后下降,于伤后3d达最低,随后再次升高,于伤后5d达峰值（P〈0.01）,然后下降,14d时接近伤前值。CXCR4基因表达于伤后1d升高,然后继续升高,至伤后5d达峰值,随后下降,于伤后10d表达最少（P〈0.01）,伤后14d表达再次增加（P〈0.01）。结论：SDF-1/CXCR4轴参与了创伤愈合的炎症反应期和增殖期的愈合过程,在皮肤组织创伤愈合过程中起着重要作用。     

E-cadherin和nm23-H1的表达及其临床意义在胰腺癌

目的探讨上皮细胞钙黏蛋白（E-cadherin）和转移抑制基因（nm23-H1）表达与胰腺癌侵袭转移的关系。方法应用免疫组织化学技术SP法，检测31例癌组织中E-cadherin和nm23-H1的表达水平。结合肿瘤的侵袭转移能力、分化程度和分期等进行分析。结果31例胰腺癌组织中E-cadherin和nm23-H1的表达强度均低于对照的胰腺组织；E-cadherin和nm23-H1的表达强度与胰腺癌的远处转移能力密切相关；胰腺癌中E-cadherin和nm23-H1的表达具有明显正相关。结论E-cadherin和nm23-H1的表达水平能反映胰腺癌的侵袭转移能力。两种蛋白的表达水平之间呈明显正相关。联合检测两种蛋白在胰腺癌组织中的表达，对临床判断胰腺癌的预后可能有一定的意义。     

肝细胞癌门静脉癌栓中肝细胞生长因子及其受体的表达

目的研究肝细胞生长因子（HGF）及其受体C-Met在肝细胞癌门静脉癌栓中的表达,探讨HGF及C-Met的表达与门静脉癌栓形成与发展的关系。方法用半定量逆转录-聚合酶链反应（RT-PCR）技术检测HGFmRNA及C-MetmRNA在20例肝细胞癌门静脉癌栓及其癌旁组织、10例无门静脉癌栓形成的肝细胞癌和癌旁组织及10例正常肝组织中的表达。结果HGF及C-Met在肝癌及癌栓中的阳性表达率均显著高于正常肝组织及癌旁组织,差异有统计学意义（P〈0．05）,HGF及C—Met在癌栓中及肝癌中表达的阳性率比较差异无统计学意义（P〉0．05）,HGF与C—Met在各组织中的表达阳性率高低差异无统计学意义（P〉0．05）。HGF及C—Met在肝癌及癌栓中的表达量均显著高于正常肝组织及癌旁组织,差异有统计学意义（P〈0．05）,HGF及C-Met在癌栓中表达量显著高于其在肝癌中表达量（P〈0．05）,HGF与C-Met在各组织中的表达量差异无统计学意义（P〉0．05）。结论HGF及C-Met参与了肝癌的形成,而肝癌患者HGF及C-Met量的升高可能是肝癌发展形成门静脉癌栓的原因之一,HGF及C—Met可作为门静脉癌栓形成的监测指标。