Selective cancer therapeutics最新文献

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Rapid remission of a large pleomorphic rhabdomyosarcoma with radiation and a novel schedule of simultaneous high-dose cisplatin. 大多形性横纹肌肉瘤的快速缓解与放疗和同时高剂量顺铂的新计划。

Selective cancer therapeutics

Pub Date : 1989-01-01 DOI: 10.1089/sct.1989.5.205

W J Uphouse, Y T Lee, A P Ronquillo, K Fleet

引用次数: 1

Effects of physiological oxygen environment on drug-induced cell lethality of multicellular tumor spheroids from human lung cancer. 生理氧环境对人肺癌多细胞肿瘤球体药物致死性的影响。

Selective cancer therapeutics

Pub Date : 1989-01-01 DOI: 10.1089/sct.1989.5.13

S Inoue, T Ohnuma

Advanced malignant tumors of certain histological types contain a hypoxic and necrotic core. Multicellular tumor spheroids (MTS) have the characteristics of chronically hypoxic cells in the center. We studied the effects of physiological oxygen environment on MTS growth and the cell lethality produced by doxorubicin (DXR) and cisplatin (DDP). MTS were made from 2 human lung cancer cell lines; PC-6 small cell and PC-10 squamous cell carcinoma, and grown for 2, 3 or 4 weeks; either in 5% CO2/air or 5% 02/5% CO2/90% N2. They were exposed to graded concentrations of DXR for 1 hr and cell lethality was determined by clonogenic assay. In the physiological oxygen environment MTS growth was retarded for both cell lines. PC-6 MTS grown in physiological oxygen environment were more sensitive to DXR than those developed in air. The differential sensitivity was most pronounced with the 2 week old MTS and gradually narrowed with increasing MTS size. In contrast, PC-10 MTS developed in the physiological oxygen environment were more resistant to DXR than those in air; the differences were again most pronounced in 2 week old MTS. There were little differences in cell kill effects of DDP, irrespective of cells being in monolayer or in MTS and growing in air or in physiological oxygen environment. These observations are consistent with the interpretation that cells in PC-6 MTS are scarcely affected by the physiological oxygen environment but easily affected by DXR, whereas cells in PC-10 MTS responded vice versa.

某些组织学类型的晚期恶性肿瘤包含缺氧和坏死的核心。多细胞球状肿瘤(MTS)具有中心慢性缺氧细胞的特征。我们研究了生理氧环境对多柔比星(DXR)和顺铂(DDP)对MTS生长及细胞致死率的影响。2种人肺癌细胞系制备MTS;PC-6小细胞癌和PC-10鳞状细胞癌，分别生长2、3、4周;在5% CO2/空气或5% 02/5% CO2/90% N2中均可。将小鼠暴露于不同浓度的DXR中1小时，通过克隆致死性试验测定细胞的致死率。在生理氧环境下，两种细胞系的MTS生长均受到抑制。生理氧环境下生长的PC-6 MTS对DXR的敏感性高于空气环境下生长的PC-6 MTS。敏感性差异在2周大的MTS时最为明显，随着MTS大小的增加而逐渐缩小。生理氧环境下生长的PC-10 MTS比空气环境下生长的PC-10 MTS更耐DXR;在2周龄的MTS中，差异再次最为明显。无论细胞处于单层或MTS中，生长在空气中或生理氧环境中，DDP的细胞杀伤效果几乎没有差异。这些观察结果与PC-6 MTS细胞几乎不受生理氧环境的影响，但容易受到DXR的影响的解释一致，而PC-10 MTS细胞则相反。

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引用次数: 4

Biocompatibility of a biodegradable, controlled-release polymer in the rabbit brain. 一种可生物降解、控释聚合物在兔脑中的生物相容性。

Selective cancer therapeutics

Pub Date : 1989-01-01 DOI: 10.1089/sct.1989.5.55

H Brem, A Kader, J I Epstein, R J Tamargo, A Domb, R Langer, K W Leong

The biodegradable polyanhydrides are a new class of controlled release polymers developed for the interstitial delivery of drugs to their target site in the brain or other organs over periods ranging from days to years. These polymers can release molecules of any size in a predictable fashion. Their degradation products are non-cytotoxic and biocompatible. The biocompatibility of a biodegradable polyanhydride, the copolymer of poly[bis(p-carboxyphenoxy)propane] anhydride and sebacic acid (PCPP-SA) in a 50:50 formulation, was studied in the rabbit brain. Twenty adult New Zealand White male rabbits underwent implantation of PCPP-SA in a frontal lobe and absorbable gelatin sponge (Gelfoam) in the other frontal lobe. The animals were evaluated daily until the time of sacrifice. Groups of four animals were sacrificed sequentially on post-operative days 1, 3, 7, 21, and 60, and the brains processed for histological evaluation. None of the animals showed behavioral changes or neurological deficits suggestive of toxicity and all that received implants survived to their date of sacrifice. The histological examination showed no significant differences between the tissue reaction from PCPP-SA compared to Gelfoam. The polymers were also tested in the rabbit cornea bioassay and did not induce an inflammatory response. We conclude that PCPP-SA (50:50), a new biodegradable polymeric matrix that can be surgically implanted for the interstitial delivery of drugs in the brain, is biocompatible in the rabbit brain.

可生物降解的聚酸酐是一种新型的缓释聚合物，用于将药物在几天到几年的时间内输送到大脑或其他器官的靶部位。这些聚合物可以以可预测的方式释放任何大小的分子。它们的降解产物无细胞毒性和生物相容性。研究了一种可生物降解聚酸酐(聚双(对羧基苯氧基)丙烷)与癸二酸(PCPP-SA)以50:50配比的共聚物)在兔脑内的生物相容性。在20只成年新西兰白兔的一只额叶植入pppp - sa，另一只额叶植入可吸收明胶海绵(Gelfoam)。这些动物每天都被评估，直到献祭的时候。各组4只动物分别于术后第1、3、7、21、60天依次处死，并对脑组织进行组织学评价。没有一只动物表现出行为变化或神经缺陷，表明它们中毒了，所有接受植入物的动物都活到了祭祀日期。组织学检查显示，与明胶泡沫相比，pppp - sa的组织反应无显著差异。这些聚合物也在兔角膜生物测定中进行了测试，没有引起炎症反应。我们得出结论，pppp - sa(50:50)是一种新的可生物降解聚合物基质，可以通过手术植入用于脑内药物的间质传递，在兔脑中具有生物相容性。

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