Comparison of biochemical and biological methods in the evaluation of new anthracycline drugs.

Comparison of biochemical and biological methods in the evaluation of new anthracycline drugs.
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生化法与生物学法评价蒽环类新药的比较

DOI:
10.1159/000401466
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发表时间:
1978
期刊:
Antibiotics and chemotherapy
影响因子:
--
通讯作者:
A. Casazza
A. Casazza
中科院分区:
--
文献类型:
--
作者:
A. Di Marco;F. Zunino;A. Casazza

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评价候选药物抗肿瘤活性的主要问题是区分药物对肿瘤细胞和正常细胞的作用。出于这个原因,大多数用于评价抗肿瘤药物的实验系统以动物实验肿瘤为代表,其中在没有明显毒性的情况下抑制肿瘤生长或延长寿命可以很容易地归因于相对于正常细胞对肿瘤的某种特异性或更高的作用。近年来,主要在小鼠中进行的实验性肿瘤的巨大发展,研究人员现在有可能研究药物对具有不同组织学特征、在动物体内的定位、抗原性、病因学等的各种肿瘤的活性。肿瘤也可以用于评估根据不同时间表施用的药物的效果,单独或与其它化疗剂或免疫刺激剂联合,与放疗或手术联合,以及在正常或免疫抑制小鼠中等。(for综述,参见VENDITTI [16]和以下论文)。体外系统已被广泛考虑,但遗憾的是,到目前为止,它们不能取代体内系统用于临床抗肿瘤活性的可预测性[9]。然而,不应低估新药活性的体外表征的重要性,同时也要记住,在这里可以更容易地研究作用机制。在我们对蒽环类抗生素的抗肿瘤活性和作用机制进行广泛研究的经验中,
The main problem in the evaluation of the antitumor activity of a candidate drug is the differentiation between the effects of the drug against tumor cells and normal cells. For this reason, the majority of experimental systems for the evaluation of antitumor drugs are represented by animal experimental tumors, where the inhibition of tumor growth or the increase of life span in absence of evident toxicity can be easily ascribed to a somewhat specific or higher effect against tumor versus normal cells. In recent years, a great development of experimental tumors, mainly in mice, has been undertaken, and the researcher has now the possibility to investigate the activity of the drug against a variety of tumors with different histological features, localization in the animal body, antigenicity, etiology, etc. The tumors may also be employed for evaluation of the effect of the drug administered according to different schedules, alone or in combination with other chemotherapeutic or immunostimulating agents, with radiotherapy or surgery, and in normal or immunodepressed mice, etc.(for a review, see VENDITTI [16] and following papers).In vitro systems have been considered extensively, but unfortunately, up to now, they could not replace in vivo systems for predictability of clinical antitumor activity [9]. However, the importance of in vitro characterization of new drug activity should not be underestimated, keeping in mind also that the mechanism of action can be here more easily studied. In our experience relative to an extensive investigation on the antitumor activity and mechanism of action of anthracycline antibiotics, we have tried