药液稀释容量对长春新碱致兔血管损伤的影响

[目的]探讨抗肿瘤药物长春新碱不同药液稀释容量对血管损伤的影响.[方法]采用兔耳自身对照法进行低容量(实验组)和高容量(对照组)静脉穿刺,48 h后光学显微镜下观察兔耳缘静脉局部病理改变.[结果]实验组内皮细胞增生、血管周围水肿、管腔出血显著重于对照组,差异有统计学意义(P<0.05或P<0.01).[结论]静脉输注的药液稀释容量过低,增加了药液浓度及刺激性,亦增加了化疗药物对静脉损伤的危险性,临床实践中应根据药物性质选择合理的稀释容量,以减少对静脉血管的损伤.     

Differential tumor cell targeting of anti-HER2 (Herceptin) and anti-CD20 (Mabthera) coupled nanoparticles

Two types of antibody-labeled nanoparticles (mAb-NPs) were prepared with the aim to achieve specific tumor targeting. Anti-HER2 and anti-CD20 monoclonal antibodies (mAb) were used as model ligands. Small poly(dl-lactic acid) nanoparticles (PLA NPs) with a mean size of about 170 nm were prepared by the salting out method. Thereafter, the coating of PLA NPs with mAbs was performed in two steps. First, thiol groups (-SH) were introduced on the surface of PLA-NPs by a two-step carbodiimide reaction. The number of -SH groups on the surface of NPs increased from 150 to 400 mmol-SH/mol PLA when cystamine concentrations of 25-1518 mol cystamine/mol PLA were used during the thiolation reaction. In the second step, covalent coupling of antibodies to thiolated NPs (NPs-SH) was obtained via a bifunctional cross-linker, m-maleimidobenzoyl-N-hydroxy-sulfosuccinimide ester (sulfo-MBS). For both mAbs anti-HER2 and anti-CD20, respectively, the number of -SH functions on the NPs had no influence on the amount of mAb coupled to the NPs. Approximately, 295 anti-HER2 and 557 anti-CD20 molecules, respectively, were covalently coupled per nanoparticle. The NPs size after the coupling reactions was about 250 nm. The specific interaction between tumor cells and mAb-NPs was determined by confocal microscopy using two cell lines: SKOV-3 human ovarian cancer cells (overexpressing HER2) and Daudi lymphoma cells (overexpressing CD20). The results showed the selective targeting of mAb-NPs to tumor cells overexpressing the specific antigen. While anti-CD20 labeled NPs (anti-CD20 NPs) bound to and remained at the cellular surface, anti-HER2 labeled NPs (anti-HER2 NPs) were efficiently internalized. The mAb-NPs represent a promising approach to improve the efficacy of NPs in active targeting for cancer therapy while the choice of the antibody-target system defines the fate of the mAb-NPs after their binding to the cells.     

肠胃清对人大肠癌细胞HCT8／V皮下移植瘤长春新碱耐药的逆转作用

目的：观察中药复方肠胃清口服液逆转大肠癌长春新碱耐药的作用,初步探讨其逆转耐药的作用机制。方法：建立人大肠癌耐长春新碱（VCR）细胞株HCT8／V裸鼠皮下移植瘤模型,随机分为正常对照组、VCR组、肠胃清组、肠胃清高剂量＋VCR组、肠胃清低剂量＋VCR组。治疗结束后计算瘤体抑制率;高效液相色谱法检测瘤内VCR药物浓度;流式细胞技术检测瘤内细胞周期和凋亡改变。结果：肠胃清高低剂量联合VCR的瘤体抑制率为47．47％、69．62％,明显高于单用肠胃清或VCR组;对照组VCR的含量为0．1745μg／g瘤重,而肠胃清高剂量联合VCR组的浓度为12．2236μg／g瘤重,是对照组的70．05倍;与对照组比较,药物干预后,G1期细胞明显增加,S期细胞明显低于对照组,细胞凋亡率明显增加,以肠胃清联合VCR组作用最强。结论：肠胃清逆转大肠癌移植瘤对VCR的耐药与通过增加瘤体内药物浓度、诱导细晌凋亡有关。     

Crocetin induces cytotoxicity and enhances vincristine-induced cancer cell death via p53-dependent and -independent mechanisms

Aim:

To investigate the anticancer effect of crocetin, a major ingredient in saffron, and its underlying mechanisms.

Methods:

Cervical cancer cell line HeLa, non-small cell lung cancer cell line A549 and ovarian cancer cell line SKOV3 were treated with crocetin alone or in combination with vincristine. Cell proliferation was examined using MTT assay. Cell cycle distribution and sub-G₁ fraction were analyzed using flow cytometric analysis after propidium iodide staining. Apoptosis was detected using the Annexin V-FITC Apoptosis Detection Kit with flow cytometry. Cell death was measured based on the release of lactate dehydrogenase (LDH). The expression levels of p53 and p21^WAF1/Cip1 as well as caspase activation were examined using Western blot analysis.

Results:

Treatment of the 3 types of cancer cells with crocetin (60-240 μmol/L) for 48 h significantly inhibited their proliferation in a concentration-dependent manner. Crocetin (240 μmol/L) significantly induced cell cycle arrest through p53-dependent and -independent mechanisms accompanied with p21^WAF1/Cip1 induction. Crocetin (120-240 μmol/L) caused cytotoxicity in the 3 types of cancer cells by enhancing apoptosis in a time-dependent manner. In the 3 types of cancer cells, crocetin (60 μmol/L) significantly enhanced the cytotoxicity induced by vincristine (1 μmol/L). Furthermore, this synergistic effect was also detected in the vincristine-resistant breast cancer cell line MCF-7/VCR.

Conclusion:

Ccrocetin is a potential anticancer agent, which may be used as a chemotherapeutic drug or as a chemosensitizer for vincristine.     

VMP方案治疗Ⅲ期妊娠滋养细胞肿瘤疗效分析

目的探讨甲氨蝶呤、顺铂联合长春新碱(VMP)方案治疗Ⅲ期妊娠滋养细胞肿瘤的疗效及安全性。方法 2007年1月—2011年5月,在安徽省立医院接受VMP方案化疗的Ⅲ期妊娠滋养细胞肿瘤患者共52例,回顾性分析这些患者的临床资料,观察该方案治疗的疗效及安全性。结果 52例Ⅲ期妊娠滋养细胞肿瘤患者共接受244个疗程的VMP方案化疗(其中包括86个疗程的巩固治疗),平均疗程4.69个;低危者完全缓解率达100%,高危者达81.8%;主要毒副反应包括骨髓抑制、消化道反应和口腔溃疡等,无严重毒副反应发生。结论 VMP方案用于Ⅲ期妊娠滋养细胞肿瘤治疗,是一种安全有效的方案。     

Acute deterioration of Charcot-Marie-Tooth disease IA (CMT IA) following 2 mg of vincristine chemotherapy.

Background:Severe up to life-threatening neuropathy has beenobserved in patients with hereditary neuropathies receiving vincristine. Case report:A 52-year-old female painter suffering fromhigh-grade non-Hodgkin's lymphoma (stage IVB) was treated with a total of 4mg of vincristine during two courses of CHOP chemotherapy (cyclophosphamide,vincristine, adriamycin, prednisone). At onset of treatment no neurologicalproblems were reported. There was good lymphoma response to chemotherapy. Atthe same time, however, the patient gradually developed dysphagia, dysarthria,muscular weakness of both lower and upper extremities, areflexia, paraesthesiaof the fingertips and bilateral sensory impairment of feet and lower legs.These symptoms continually worsened over a period of seven weeks until she wasunable to walk or to perform her work. Electrophysiological studies showedperipheral axonal and demyelinative sensorimotor neuropathy in correlation tohistological findings. Molecular analysis revealed 17p11.2 duplication typicalfor Charcot–Marie–Tooth disease IA. While continuing chemotherapywithout the use of vincristine the patient's neurologic symptoms slowlyrecovered within six months. Conclusion:Prior to administration of vincristine family andpatient history as well as physical examination should be performed carefullyto look for underlying hereditary neuropathy. For those patients with aclinical history or symptoms suggestive for CMT nerve conduction velocitystudies and on an individual base even molecular genetic analysis areneccessary to prevent serious neurologic complications.     

口腔颌面部肿瘤CPV方案短疗程术前诱导化疗的临床研究

目的观察31例Ⅲ~Ⅳ期口腔颌面部肿瘤患者应用CPV方案短疗程术前诱导化疗的可行性。方法对化疗前后实验室检查及术后感染率和3、5年生存率进行观察研究。结果术后感染率为18%,3、5年生存率分别为61.3%、35.5%。结论在经济欠发达的地区该方案具有一定的可行性。     

Thrombotic thrombocytopenic purpura associated with HIV and visceral Kaposi's sarcoma treated with plasmapheresis and chemotherapy

We present a case of a patient who is HIV positive and developed both thrombotic thrombocytopenia purpura and visceral Kaposi's sarcoma (KS) with hemorrhage. This case presents a difficult management problem in that the patient's bleeding originated from KS lesions and did not quickly abate with plasmapheresis therapy despite both clinical and laboratory improvement after 2–4 days. Chemotherapy was initiated on day 13 and the patient's condition improved markedly afterward. We believe the addition of chemotherapy to plasmapheresis hastened the improvement of our patient's thrombotic thrombocytopenic purpura (TTP) and KS-related bleeding. Therefore, under similar conditions, we recommend combining plasmapheresis and chemotherapy at the onset of therapy. Am. J. Hematol. 58:148–149, 1998. Published 1998 Wiley-Liss, Inc.

1 This article is a U.S. Government work and, as such, is in the public domain in the United States of America.