多柔比星葡聚糖纳米粒联合YH-16对SKOV3的杀伤作用

目的初步探讨载多柔比星葡聚糖纳米粒（DOX/DEX-PLA）联合YH-16（重组内皮抑素）对卵巢癌细胞的体内外的杀伤作用。方法以双乳化剂蒸发法制备DOX/DEX-PLA载药纳米粒,透射电镜观察纳米粒形态,分光光度法计算载药率,体外药物释放实验考察纳米粒对DOX的缓释作用。MTT法观察对卵巢癌细胞的体外杀伤作用,动物实验观察其体内抑瘤效应。结果DOX/DEX-g-PLA纳米微粒呈球形,粒径约83nm,药物包封率约67.1%。体外释放实验提示,纳米制剂中约50%的药物持续缓慢释放,可持续达7d;体内抑瘤实验显示,纳米缓释制剂联合YH-16间隔给药疗效优于未包载药物每日给药的疗效。结论DOX/DEX-PLA纳米粒联合YH-16可有效抑制卵巢癌细胞的生长。     

硬脂酸聚乙二醇阿霉素纳米粒的制备及其对人肝癌细胞的杀伤作用

目的合成硬脂酸聚乙二醇阿霉素纳米微粒(DOX鄄SLNs鄄PEG)并检测其相关参数,观察其对人肝癌细胞杀伤作用。方法以“乳化蒸发鄄低温固化”法合成DOX鄄SLNs鄄PEG纳米粒。透射电镜计算粒径,分光光度法计算载药率,噻唑蓝法(MTT法)观察对肝癌细胞的体外杀伤效应及观察体内抑瘤效应。结果DOX鄄SLNs鄄PEG纳米粒平均粒径120±4.84mm,包封率68.6%,体外释放实验提示,7d可释放所载60%左右的药物。体内抑瘤实验表明:控释制剂间隔给药疗效已优于未包载药物每日给药的疗效,量效关系明显。结论DOX鄄SLNs鄄PEG纳米粒可有效抑制肝癌细胞的生长。     

携带小鼠白介素12基因的增殖型腺病毒对胃癌细胞株化疗敏感性影响的研究

目的研究携带白介素12(mIL-12)基因的增殖型腺病毒CNHK200-mIL-12对胃癌细胞株化疗敏感性的影响。方法扩增增殖型腺病毒Onyx-015及携带小鼠mIL-12基因的增殖型腺病毒CNHK200-mIL-12,利用MTT法测定同一病毒滴度下联合应用不同浓度化疗药物及同一化疗药物浓度下联合应用不同滴度病毒对胃癌细胞株杀伤作用,并观察增殖型腺病毒联合化疗药物对裸鼠腹腔种植瘤的抑制作用。结果当不同感染复数(MOI)=0.5时,增殖型病毒Onyx-015、CNHK200-mIL-12对胃癌细胞SGC-7901无明显的杀伤作用。加入化疗药物阿霉素(ADM)、氟尿嘧啶(5-Fu)和卡铂(CAP)后,两者对SGC-7901的杀伤率随着药物浓度增加都有不同程度的升高,与单纯使用化疗药物组比较,差异有统计学意义(P<0.05)。浓度为10μg/ml的5-Fu对SGC-7901的杀伤作用不明显,单用增殖型腺病毒对SGC-7901的杀伤作用也较弱,两者联合应用杀伤活性明显提高,与未加5-Fu组比较,差异有统计学意义(P<0.05)。动物试验证明:经Onyx-015联合5-Fu治疗后,裸鼠腹腔内肿瘤形成率为1/6,而CNHK200-mIL-12联合5-Fu组未见腹腔内肿瘤生长,与单用增殖型腺病毒或单用化疗者比较,差异有统计学意义(P<0.05)。结论携带mIL-12基因的增殖型腺病毒能够提高胃癌细胞株对化疗药物的敏感性,在杀伤胃癌细胞株的作用中     

氟尿嘧啶免疫聚乳酸纳米微粒抗肿瘤效应的研究

目的利用载氟尿嘧啶（5-FU）免疫聚乳酸（PEA）纳米微粒（NPs），观察其对严重联合免疫缺陷病（SCID）鼠人胃癌移植模型的治疗效应。方法超声乳化法合成的载5-FU的抗血管内皮生长因子（VEGF）单克隆抗体纳米微粒，建立SCID鼠人胃癌移植肿瘤模型，观察药物对高表达VEGF胃癌移植肿瘤模型的治疗效应及其不良反应。结果空白对照组、未载药空纳米微粒组、5-FU组（20mg／kg）、抗VEGF单克隆抗体-未载药空纳米微粒组、抗VEGF单克隆抗体组、载5-FU纳米微粒组、5-FU（20mg／kg）加抗VEGF单克隆抗体组及抗VEGF单克隆抗体-载5-FU纳米微粒组（20mg／kg）的抑瘤率分别为0、6．61％、24．26％、27．94％、35．29％、37．50％、39．71％和52．21％，且载5-FU的抗VEGF单克隆抗体纳米微粒组和未载药纳米微粒组的血白细胞数量及肝肾功能与空白对照组相比，差异无统计学意义（P〈0.05）；而含5-FU原药组血白细胞数量较空白对照组和抗VEGF单克隆抗体-载5-FU纳米微粒组下降34．43％和37．38％（P〈0.05）：而肝转氨酶升高93．17％和66．56％。治疗组与对照组癌细胞凋亡指数相比，以抗VEGF单克隆抗体．载5-FU纳米微粒组更为明显，差异有统计学意义（P〈0.05）；含抗VEGF抗体的实验组微血管密度明显低于含5-FU药组和对照组（P〈0.05）。结论载5-FU抗VEGF单克隆抗体纳米微粒可提高5-FU的抑瘤率，并通过抑制肿瘤的血管生成，诱导肿瘤细胞凋亡，增加疗效，有效降低5-FU的骨髓抑制和肝肾功能损害作用．是一种安全的新型药物纳米级靶向制剂。     

聚酰胺-氨纳米微粒介导5-氟尿嘧啶联合小RNA-21抑制乳腺癌细胞生长的研究

目的 观察聚酰胺-氨(PAMAM)纳米微粒介导5-氟尿嘧啶(5-Fu)联合小RNA-21抑制乳腺癌细胞MCF-7生长的效果.方法 透析法制备5-Fu/PAMAM,孵育法同载miR-21抑制剂;透射电镜观察形貌;紫外分光光度计检测载药率和包封率;流式细胞仪检测转染效率及细胞凋亡;噻唑蓝(MTT)比色法检测细胞增殖;Transwell检测细胞侵袭能力变化.结果 5-Fu/PAMAM形貌规整,包封率为(66.21±4.11)%,载药率为(31.77±0.73)%,转染效率为(60.54±6.97)%;联合治疗组肿瘤细胞生长缓慢,在观察截止期时生存率(55.85±3.71)%;联合治疗组细胞凋亡率(18.32±2.42)%,与对照组比较明显增多(F=58.326,P<0.01);联合治疗组视野内细胞数目仅为(18.96±3.14)个,侵袭能力显著降低(F=16.409,P<0.01).结论 PAMAM可以实现5-Fu和miR-21的同载,并有效抑制乳腺癌细胞的体外生长.     

载5-氟尿嘧啶聚乳酸纳米微粒瘤内注射治疗胃癌

目的观察生物可降解5-氟尿嘧啶聚乳酸纳米微粒（5-Fu-NPs）注射缓释剂用于肿瘤内局部给药的抗肿瘤活性。方法36只（SCID）小鼠随机分为6组，分别瘤内注射生理盐水的对照组、瘤内注射5．Fu．NPs（包括5-Fu20mg／kg体重和5-Fu30mg／kg体重）、无载药NPs、5-Fu注射液及腹腔注射5-Fu注射液，每3d瘤内给药1次共3次。观察荷瘤鼠肿瘤生长、荷瘤鼠给药前、后血象及给药后肿瘤组织凋亡指数。结果瘤内注射5-Fu-NPs缓释剂组小鼠肿瘤生长缓慢，瘤体明显小于5-Fu（含5-Fu20mg／kg体重）腹腔注射给药组，相应的抑瘤率分别为2．93％、22．87％、27．57％、41．64％和50．43％，其中以瘤内注射5-Fu-NPs对小鼠胃癌有较高抑瘤率，呈现良好的量效关系，且对骨髓的副作用为最小。结论瘤内应用5-Fu-NPs缓释剂的抗肿瘤效果优于局部和全身单纯5-Fu给药。     

5-氟尿嘧啶和柳氮磺胺吡啶对胰腺癌细胞株BxPC-3的抗增殖作用

目的探讨5-氟尿嘧啶(5-Fu)联合柳氮磺胺吡啶(sulfasalazine)对细胞株BxPC-3抗增殖作用。方法噻唑蓝(MTT)比色法、流式细胞仪、相差显微镜分别检测不同浓度(12.5、25.0、50.0、100.0)mg/L5-Fu联合0.5mmol/Lsulfasalazine作用细胞株BxPC-3生长抑制率、细胞周期、凋亡率及细胞形态变化。结果不同浓度5-Fu联合0.5mmol/Lsulfasalazine作用细胞株BxPC-3生长抑制率呈时间、剂量依赖性;100mg/L5-Fu联合0.5mmol/Lsulfasalazine作用细胞株BxPC-3凋亡率从63%(12h)增加到93%(48h),与对照组比较[t=48.87(12h),263.15(48h),P<0.01];G0/G1期细胞从80%(12h)到97%(48h),与对照组比较[t=5.97(12h),10.39(48h),P<0.01];相差显微镜观察两者联合作用12h大量细胞固缩变圆,随时间延长胞体萎缩裂解。结论两者联合作用细胞株BxPC-3有协同抑制作用,与细胞周期、凋亡率及形态变化相关。     

增殖性腺病毒CNHK600-p53的构建及对肝癌细胞抑制的体外实验研究

目的研究携带p53基因的新型增殖性腺病毒CNHK600-p53的导入是否增加肝癌细胞株PLC／PRF5对化疗药物的敏感性。方法采用四甲基偶氮唑盐(methylthiazolyl tetrazolium assay,MTT)法,观察化疗药物5-氟尿嘧啶(Fluorouracil,5-Fu)、丝裂霉素(Mitomycin,MMC)和表阿霉素(Epirubicin,EPI)单独及与CNHK600-p53联合对肝癌细胞株PLC／PRF5的杀伤效应。结果PLC／PRF5在5-Fu浓度为400μg／ml时细胞抑制率为(65±4．2)％,MMC浓度为1μg／ml细胞抑制率为(41±1．9)％,EPI浓度为10μg／ml细胞抑制率为(65±1．8)％。转入CNHK600-p53(MOI= 0．625)后再使用上述浓度的化疗药物,细胞抑制率分别为(89±5．3)％、(60±2．3)％和(75±1．5)％。当MOI值为0．3125,0．625,1．25时,CNHK600-p53组和Ad-p53组的细胞抑制率分别为(27±2．5)％、(30±3．7)％、(61±4．3)％和(4±2．7)％、(5±3．5)％、(16±4．5)％。结论单用CNHK600-p53效果优于Ad-p53,携带p53基因的CNHK600-p53能提高肝癌细胞株PLC／PRF5对化疗药物的敏感性。     

硬脂酸阿霉素纳米粒的制备及在抗肝癌中的应用

目的　合成硬脂酸聚乙二醇阿霉素纳米微粒(doxorubicin solid lipid nanoparticles polyethylene glycol, DOX SLNs PEG)并检测其相关参数,观察其对人肝癌细胞杀伤作用。方法　以“乳化蒸发 低温固化”法合成 DOX SLNs PEG 纳米粒,透射电镜计算粒径,分光光度法计算载药率,MTT法观察对肝癌细胞的体外杀伤作用。结果　DOX SLNs PEG 纳米粒平均粒径( 120±4 84) mm,包封率68 6%,体外释放实验提示,7 d可释放所载60%左右的药物;体内抑瘤实验表明:控释制剂间隔给药疗效已优于未包载药物每日给药的疗效,量效关系明显。结论　DOX SLNs PEG纳米粒可有效抑制肝癌细胞的生长。     

载氟尿嘧啶聚乳酸碳纳米管复合材料对胃癌细胞株的体外杀伤效应

目的制备荷载氟尿嘧啶（5-Fu）的聚乳酸（PLLA）碳纳米管（CNT）复合材料（5-FU-PLLA-CNTs）,并探讨其对人胃癌细胞株（MGC803和MNK45）的体外杀伤效应。方法以PLLA—CNTs为原料,采用超声乳化法荷载5．FU;通过扫描电子显微镜观察5-FU—PLLA—CNTs形态和结构;用紫外可见光光度仪测定不同时间5-FU．PLLA．CNTs的5-FU释放量及累计释放量,并绘制体外释放曲线;设计实验组（不同浓度的5-Fu—PuA—CNTs）及阳性（相应浓度的5-FU）和阴性对照组（不加任何药物）,用CCK8法检测不同浓度的5-Fu．PLLA-CNTs对MGC803和MNK45的增殖抑制作用;流式细胞术检测5-FU—PuIA—CNTs作用前后细胞凋亡的变化。结果成功制备5-FU．PLLA．CNTs药物深层薄膜,薄膜载药率为（4．54±0．43）％,包封率（21．56±2．36）％。体外释放实验显示,5-FU-PLLA-CNTs在24h内释放率为23．9％,呈缓慢上升趋势,至31d体外累计释放率达85．3％。CCK8实验显示,与对照组比较,5．Fu—PLLA．CNTs对两株胃癌细胞具有明显抑制作用（P〈0．01）,随着药物浓度的增加,抑制作用增强;随着作用时间的延长,呈持续抑制状态。流式细胞仪显示,经1mg／孔5-Fu-PuJA。CNTs处理的实验组MGC803和MNK45细胞凋亡率与阴性对照组比较,差异具有统计学意义（均P〈0．05）;与阳性对照组比较,差异无统计学意义（均P〉0．05）。结论5-FU-PLLA-CNTs具有良好的药物缓释性能,对胃癌细胞株具有明显的杀伤和抑制增殖作用,其最佳浓度为1mg／孔。     

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目的　总结原发性胆囊鳞癌、腺鳞癌的诊治经验。方法　回顾性分析了浙江大学医学院附属第二医院 1994～ 2 0 0 3年收治的少见胆囊癌 9例 (鳞癌 1例 ,腺鳞癌 8例 )。结果　行根治性手术 4例 ,姑息性手术 5例。9例中有 8例得到随访 ,均在术后半年内死亡 ,术后中位生存期 5 1d。结论　胆囊鳞癌腺鳞癌恶性程度较高 ,但淋巴结转移相对较晚。对于合适病例应尽可能行根治性胆囊切除 ,必要时行扩大根治性切除 ,术后放疗可能是一个较好的治疗方式。     

Mucoepidermoid carcinoma of the esophagus —A case report

We treated a 66-year old woman with mucoepidermoid carcinoma of the esophagus. The histologic features of this tumor seemed to originate from esophageal glands and their ducts. This deduction was based on the subepithelial growth pattern and the presence of in-situ carcinoma showing a glandular or squamous pattern at the location of the esophageal gland duct. Although the biological nature of this tumor was not elucidated, the prognosis is similar to that seen with the ordinary type of esophageal squamous carcinoma.     

The surgical management of synchronous hepatocellular carcinoma and thoracic esophageal carcinoma

A 73-year-old man was hospitalized with pathologically documented hepatocellular carcinoma and cirrhosis, and a 5.0-cm tumor located in the left lobe was resected by a left lateral segmentectomy. At the same time, metastatic squamous cell carcinoma was identified by frozen section in a perigastric lymph node in the lesser omentum. Intraoperative endoscopy revealed a 1.0-cm erosive lesion in the thoracic esophagus that was subsequently found to be primary squamous cell carcinoma. Seven weeks later, a transthoracic subtotal esophagectomy with substernal, cervical esophagogastrostomy was performed. Twenty-two months after these resections there has been no recurrence of either the hepatocellular or esophageal carcinomas.     

胆囊鳞癌和腺鳞癌12例临床分析

目的总结原发性胆囊鳞癌和腺鳞癌的诊治经验。方法回顾性分析了解放军总医院肝胆外科1994—2004年收治的胆囊癌12例（鳞癌4例，腺鳞癌8例），男女各6例。结果行根治性手术9例，姑息性手术3例。12例中有11例得到随访，其中2例在1年后死亡，1例在半年后死亡，其余均在半年内死亡。术后中位生存期108d。结论胆囊鳞癌和腺鳞癌恶性程度高，但远处转移较少，有利于手术切除。术后放疗有可能是一个有效的方法。     

Molecular Diagnosis in Head and Neck: What a Surgical Pathologist Must Know

Molecular alterations in tumors have become interesting targets both for diagnostic and for therapeutic and prognostic applications in tumor pathology. In the head and neck, there are a variety of different alterations, encompassing all the different types of genetic events associated with carcinogenesis. This paper reviews three different types of tumors that display a spectrum of genetic alterations: the translocation in Mucoepidermoid carcinoma, Epstein Barr virus association in nasopharyngeal carcinoma, and the HRPT2 tumor suppressor gene in parathyroid carcinoma. Basic histology is reviewed and the genetic alterations are discussed, along with a brief discussion of potential diagnostic implications.     

肝脏黏液表皮样癌1例报告

肝脏黏液表皮样癌(mucoepidermoid carcinoma of liver)是肝脏肿瘤中一种罕见的病理类型,在组织学上被认为是胆管细胞癌(intrahepatic cholangiocarcinoma,ICC)的变体,病理学上与肝内胆管细胞癌相互鉴别。目前,国内外文献报道十余例。皖南医学院弋矶山医院肝胆外科收治1例肝脏黏液表皮样癌。现报告如下。     

Mucoepidermoid carcinoma of the thymus

Mucoepidermoid carcinoma of the thymus is a rare carcinoma and there is little agreement about the treatment of this tumor. According to the analysis of previously reported tumors, biologic behavior of the tumor correlated with the spread of the lesion and degree of differentiation. We report a case of this tumor in a 31-year-old man. Resection of the tumor included the left upper lobe of the lung the phrenic nerve, pericardium and disseminations in the pleura. The clinicopathological feature of this case was high-stage disease and low-grade histology. Postoperative chemotherapy and radiotherapy were performed, and the patient is alive without recurrence 14 months after surgery.     

胆囊鳞癌和腺鳞癌12例临床分析

目的总结原发性胆囊鳞癌和腺鳞癌的诊治经验。方法回顾性分析了解放军总医院肝胆外科1994-2004年收治的胆囊癌12例(鳞癌4例,腺鳞癌8例),男女各6例。结果行根治性手术9例,姑息性手术3例。12例中有11例得到随访,其中2例在1年后死亡,1例在半年后死亡,其余均在半年内死亡。术后中位生存期108d。结论胆囊鳞癌和腺鳞癌恶性程度高,但远处转移较少,有利于手术切除。术后放疗有可能是一个有效的方法。     

Apocrine carcinoma of the breast —A case report

A case of apocrine carcinoma of the breast is reported herein. Apocrine carcinoma is a rare tumor characteristically composed of large cells with eosinophilic cytoplasm. This case involves a 34-year old woman who underwent a modified radical mastectomy and is now doing well with no evidence of recurrence, 10 months after her surgery.     

Presence of a micropapillary pattern in mucinous carcinomas of the breast and its impact on the clinical behavior

Infiltrating micropapillary carcinomas (IMPC) of breast are highly angioinvasive tumors with poor prognosis. This study is based on the observation that a similar micropapillary pattern is also observed in mucinous carcinomas of breast. About 102 mucinous carcinomas were evaluated for the presence and impact of this micropapillary pattern on the clinical behavior. Of these, 68 were mucinous carcinomas with a micropapillary pattern (MUMPC), 20 had MUMPC mixed with an infiltrating duct carcinoma component, two were solid variants of papillary carcinoma with mucin (SVPCMU), five had collision of the MUMPC and SVPCMU patterns and seven were mucinous carcinomas with signet ring cells (MUS). The factors negatively affecting overall survival (OAS) and disease-free survival (DFS) included the histological type of mucinous carcinoma, nodal metastases, an irregular tumor border, <50% mucin and an IMPC type of local recurrence or metastases. In the multivariate analysis, the histologic type of mucinous carcinoma and an irregular tumor border were most significant for OAS and DFS. Thus, 86% of mucinous carcinomas in this study were mucinous variants of the angioinvasive infiltrating micropapillary carcinomas. These tumors can produce IMPC type of metastases and thus should be treated aggressively.