Targeted delivery of doxorubicin by CSA-binding nanoparticles for choriocarcinoma treatment

Gestational trophoblastic neoplasia (GTN) can result from the over-proliferation of trophoblasts. Treatment of choriocarcinoma, the most aggressive GTN, currently requires high doses of systemic chemotherapeutic agents, which result in indiscriminate drug distribution and severe toxicity. To overcome these disadvantages and enhance the chemotherapeutic efficacy, chondroitin sulfate A (CSA)-binding nanoparticles were developed for the targeted delivery of doxorubicin (DOX) to choriocarcinoma cells using a synthetic CSA-binding peptide (CSA-BP), derived from malarial protein, which specifically binds to the CSA exclusively expressed in the placental trophoblast. CSA-BP-conjugated nanoparticles rapidly bonded to choriocarcinoma (JEG3) cells and were efficiently internalized into the lysosomes. Moreover, CSA-BP modification significantly increased the anti-cancer activity of the DOX-loaded nanoparticles in vitro. Intravenous injections of CSA-BP-conjugated nanoparticles loaded with indocyanine green (CSA-INPs) were rapidly localized to the tumor. The CSA-targeted nanoparticles loaded with DOX (CSA-DNPs) strongly inhibited primary tumor growth and, more importantly, significantly suppressed metastasis in vivo. Collectively, our results highlight the potential of the CSA-BP-decorated nanoparticles as an alternative targeted delivery system of chemotherapeutic agents for treating choriocarcinoma and for developing new GTN therapies based on drug targeting.     

Sonographic and Doppler imaging in the diagnosis and treatment of gestational trophoblastic disease: a 12-year experience.

OBJECTIVE: To evaluate the clinical utility of sonography with Doppler examination in the diagnosis and treatment of gestational trophoblastic disease (GTD). METHODS: A retrospective analysis of 355 cases of GTD seen over a 12-year period in 2 large university referral hospitals in China was performed. Clinical appearances, sonographic findings, Doppler waveforms, and patient outcomes were reviewed. Sonographic and Doppler examinations were performed to diagnose the presence of molar tissue, detect invasive disease, assess disease recurrence, and monitor the efficacy of chemotherapy. Doppler waveforms of 13 patients with normal early pregnancies were also examined for comparison. RESULTS: Of the 355 patients with GTD, 106 had a classic hydatidiform mole (CHM), 33 had a partial hydatidiform mole (PHM), 184 had an invasive hydatidiform mole (IHM), and 32 had choriocarcinoma. Sonography showed abnormal molar tissue confined to the endometrial cavity in all cases of CHM. In cases of IHM and choriocarcinoma, soft tissue invasion and cystic vascular spaces within the myometrium were shown. Cases of PHM had a thickened, hydropic placenta with a concomitant fetus. Doppler waveforms showed resistive indices of 0.55 (SD, 0.06) for CHM, 0.56 (SD, 0.04) for PHM, 0.28 (SD, 0.06) for IHM, 0.25 (SD, 0.05) for choriocarcinoma, and 0.66 (SD, 0.04) for normal pregnancies. The abnormal sonographic and Doppler findings in invasive disease resolved when chemotherapy was successful. CONCLUSIONS: Sonography and Doppler imaging were helpful in diagnosing GTD, in determining whether invasive disease was present, in detecting recurrence of disease, and in following the effectiveness of chemotherapy.     

男性原发绒癌13例临床分析并文献回顾

目的探讨男性原发绒癌的诊断、治疗及预后因素。方法回顾性分析北京协和医院1990年至2012年收治的男性绒癌患者的临床资料,并复习同期文献报道的男性绒癌患者临床资料。结果本院13例患者的中位生存期54个月,包括7个原发部位。所有患者均经手术治疗,12例患者同时加用了联合化疗或放疗。随访至2013年3月,6例患者存活,疾病无复发(随访时间21~138月)。复习文献100例病例,连同我院病例共113例,总的中位生存期10个月,肿瘤最常见的原发部位为睾丸(41/113),大部分伴有转移(80/113)。年龄≤34岁、绒癌合并其他组织成分、联合化疗的患者中位生存期较长。结论男性原发绒癌预后较女性妊娠绒癌明显差,经积极的化疗可延长生存期,年轻(≤34岁)、肿瘤合并其他组织成分者,预后相对偏好。     

不同分期绒癌化疗的回顾性临床疗效对比分析

目的：探讨绒癌临床各期综合治疗的预后及毒副作用发病率的差异。方法：收集2002-01-01-2009-12-31山东医学高等专科学校附属医院收治绒癌患者116例，回顾性分析不同期别经化疗等综合治疗后的临床转归。结果：绒癌总完全缓解率72．4％（84／116），其中I和Ⅱ期均为100．0％（23／23，25／25），Ⅲ期为66．7％（30／45），IV期为26．1％（6／23）。4种期别化疗毒副作用的发病率比较结果显示，伪膜性肠炎发生率差异有统计学意义，P〈0．001；骨髓抑制、口腔溃疡和肝功异常的发生率差异无统计学意义，P值分别为0．692、0．999和0．634。II和Ⅳ期患者总生存比较差异有统计学意义，P=0．009。Ⅲ期患者单纯化疗与手术联合化疗的总生存期比较差异无统计学意义，P=0．781；IV期患者单纯化疗与手术联合化疗的总生存期比较差异无统计学意义，P=0．615。结论：绒癌对化学治疗敏感，但≥Ⅱ期患者经多药物联合化疗其完全缓解率较早期患者明显降低。不同期别患者化疗药物的毒副作用发病率差异无统计学意义。Ⅲ期患者5年总生存期明显高于Ⅳ期患者。手术联合化疗不能提高绒癌的总生存期。     

紫草素对人绒癌耐药细胞株增殖的抑制及凋亡的作用

目的 研究紫草素对体外培养的人绒癌耐药细胞株(JAR/MTX)抑制增殖、促进凋亡及诱导细胞周期停滞的作用.方法 经不同浓度的紫草素分别作用24 h、48 h、72 h后,应用cck-8试剂盒检测其细胞毒性,应用流式细胞仪分析细胞周期分布及凋亡率变化,应用荧光显微镜观察凋亡现象.结果 当紫草素浓度从0.1875 μg/ml增加到3μg/ml时,其48h抑制率从46.48±12.0%升高到92.05±9.2%,0.75μg/ml紫草素分别作用24 h、48 h、72 h,其抑制率分别为43.94±10.1%、68.56±10.2%、84.97 ±18.63%,与对照组相比差异具有显著性(P＜0.05或P＜0.01),可见随着紫草素剂量的增加和作用时间的延长,对绒癌耐药细胞生长的抑制率也明显增加.当紫草素浓度从0.1875 μg/ml增加到3μg/ml时,与细胞作用48h后,凋亡率由12.13±5.67%升高到30.08±7.85%(P＜0.05或P＜0.01),随着药物浓度增加凋亡率亦增加,并可见典型的凋亡细胞核形态学变化.细胞周期分布也呈浓度依赖性改变,一方面增高C,0/G1期细胞比例(P＜0.05),另一方面降低S期和G2/M期细胞比例(P＜0.05).结论 紫草素对JAR/MTX具有明确的抗增殖、促凋亡、阻滞细胞周期进程的作用,值得进一步深入研究与探讨.     

月经紊乱1年余腹胀3个月发现子宫内膜癌2个月

向阳(主持人,妇产科主任医师):合并生殖细胞肿瘤成分的子宫内膜癌非常罕见,我们对这样一例疑难病例进行回顾性分析,和大家分享诊治过程中的经验,共同提高诊疗水平。首先请住院医师介绍病例。吕嬿(妇产科住院医师):患者,28岁,已婚。因月经紊乱1年余,腹胀3个月,发现子宫内膜癌2个月于2010-12-05收入我院。患者从2009年10月起出现经期延长、经量增多、经间期少量出血,未就诊。2010年9月起出     

男性肺原发性绒毛膜癌1例并文献复习

回顾性分析南京医科大学第一附属医院通过手术切除病理确诊的1例男性肺原发性绒毛膜癌(primary choriocarcinoma,PCC)的临床资料、影像学及组织病理学等特征,结合国内外文献复习,总结肺PCC的诊断及治疗进展.男性肺PCC是一种较为罕见高度恶性生殖细胞肿瘤,病因不明,临床表现多样,咯血最常见.早期诊断困难,易误诊为常见病,预后差,致死率高.手术联合化疗是目前较为提倡的治疗方案.男性肺PCC的诊断较难,需结合临床、影像学等综合分析,确诊需依赖组织病理学.