Chaklader M, Das P, Pereira J A, Chatterjee S, Basak P, Law A, Banerjee T, Chauhan S, Law S
Stem Cell Research and Application Unit, Department of Biochemistry and Medical Biotechnology, Calcutta School of Tropical Medicine, Kolkata-700073, West Bengal, India.
Exp Oncol. 2011 Jun;33(2):83-9.
To evaluate the efficacy of intraperitoneal vincristine administration into ascitic sarcoma-180 bearing mice as a model of human malignant ascites regarding various peritoneal/retroperitoneal sarcomatosis, and to evaluate the flowcytometric telomerase reverse transcriptase expression for the diagnostic and prognostic purposes.
Present study included disease induction by intraperitoneal homologous ascitic sarcoma-180 transplantation followed by in vivo intraperitoneal drug administration to study mitotic index, flowcytometric cell cycle and telomerase reverse transcriptase expression pattern, erythrosin-B dye exclusion study for malignant cell viability assessment. Besides, in vitro malignant ascite culture in presence and absence of vincristine sulfate and survival study were also taken into consideration.
Intraperitoneal vincristine administration (concentration 0.5 mg/kg body weight) significantly diminished the mitotic index in diseased subjects in comparison to untreated control subjects. Treated group of animals showed increased life span and median survival time. Cell viability assessment during the course of drug administration also revealed gradual depression on cell viability over time. Flowcytometric cell cycle analysis showed a good prognostic feature of chemotherapeutic administration schedule by representing high G2/M phase blocked cells along with reduced telomerase reverse transcriptase positive cells in treated animals.
We conclude that long term administration of vincristine sulfate in small doses could be a good pharmacological intervention in case of malignant peritoneal ascites due to sarcomatosis as it indirectly reduced the level of telomerase reverse transcriptase expression in malignant cells by directly regulating cell cycle and simultaneously increased the life expectancy of the diseased subjects.
以携带腹水型肉瘤-180的小鼠作为人类恶性腹水模型，评估腹腔注射长春新碱对各种腹膜/腹膜后肉瘤病的疗效，并评估流式细胞术检测端粒酶逆转录酶表达用于诊断和预后判断的价值。
本研究包括通过腹腔内同种异体腹水型肉瘤-180移植诱导疾病，随后进行体内腹腔内给药，以研究有丝分裂指数、流式细胞术细胞周期和端粒酶逆转录酶表达模式，采用伊红-B染料排斥试验评估恶性细胞活力。此外，还考虑了在有和没有硫酸长春新碱存在的情况下进行体外恶性腹水培养以及生存研究。
与未治疗的对照小鼠相比，腹腔注射长春新碱（浓度0.5mg/kg体重）显著降低了患病小鼠的有丝分裂指数。治疗组动物的寿命和中位生存时间增加。给药过程中的细胞活力评估还显示，随着时间的推移，细胞活力逐渐下降。流式细胞术细胞周期分析显示，化疗给药方案具有良好的预后特征，表现为治疗动物中高比例的G2/M期阻滞细胞以及端粒酶逆转录酶阳性细胞减少。
我们得出结论，小剂量长期给予硫酸长春新碱可能是治疗肉瘤病所致恶性腹腔腹水的一种良好的药理学干预措施，因为它通过直接调节细胞周期间接降低了恶性细胞中端粒酶逆转录酶的表达水平，同时延长了患病小鼠的预期寿命。
Zotero 插件