Cancer drug delivery最新文献_第2页

Ultrastructural and freeze fracture localization of multilamellar liposomes containing a lipophilic cisplatin analogue in normal tissues and liver metastases of M5076 reticulosarcoma. M5076网状肉瘤正常组织和肝转移灶中含有亲脂顺铂类似物的多层脂质体的超微结构和冷冻骨折定位

Cancer drug delivery Pub Date : 1987-01-01 DOI: 10.1089/cdd.1987.4.75

R Perez-Soler, A R Khokhar, J Lautersztain, P A Mitchell, K L Schmidt

{"title":"Ultrastructural and freeze fracture localization of multilamellar liposomes containing a lipophilic cisplatin analogue in normal tissues and liver metastases of M5076 reticulosarcoma.","authors":"R Perez-Soler, A R Khokhar, J Lautersztain, P A Mitchell, K L Schmidt","doi":"10.1089/cdd.1987.4.75","DOIUrl":"https://doi.org/10.1089/cdd.1987.4.75","url":null,"abstract":"The tissue localization of multilamellar vesicles (MLV) (size 0.5-5.0 microns) composed of dimyristoylphosphatidyl choline (DMPC) and dimyristoylphosphatidyl glycerol (DMPG) (molar ratio 7:3) containing a lipophilic cisplatin analogue (NDDP) was studied in mice by freeze fracture (FF) and transmission electron microscopy (TEM). Liposomes were observed within cytoplasmic vacuoles of hepatocytes and Kupffer cells in normal mice as early as 5 minutes after intravenous (iv) administration of MLV-NDDP. Liposomes within hepatocytes were more numerous but smaller in diameter (0.5-2.0 microns) than those within Kupffer cells (2.0-4.0 microns). In normal lung examined by FF or TEM at 5 minutes after MLV-NDDP administration, liposomes were only observed in the intravascular space. Liposomes could not be identified within Type I or II pneumocytes nor within the alveolar space. Two hours after iv administration, the distribution within the liver showed an increased number of liposomes in the hepatocytes with some evidence of liposome decomposition. The distribution in the lung was virtually identical to that observed at 5 minutes. The pattern of tissue localization within lung and liver of empty MLV 5 minutes and 2 hours after iv administration was identical to that of MLV-NDDP. In mice bearing gross liver metastases of M5076 reticulosarcoma, liposomes were present in the cytoplasm of tumor cells as well as normal cells 5 minutes and 2 hours after the iv administration of MLV-NDDP. These studies suggest that MLV composed of DMPC and DMPG containing NDDP are able to cross the liver sinusoidal capillaries and gain access to both hepatocytes from normal liver and malignant cells of M5076 reticulosarcoma from liver metastases.","PeriodicalId":77686,"journal":{"name":"Cancer drug delivery","volume":"4 2","pages":"75-88"},"PeriodicalIF":0.0,"publicationDate":"1987-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cdd.1987.4.75","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14449477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 11

Continuous infusion or intravenous bolus: what is the rationale for doxorubicin administration? 持续输注或静脉注射:阿霉素给药的理由是什么?

Cancer drug delivery Pub Date : 1987-01-01 DOI: 10.1089/cdd.1987.4.191

J Robert

引用次数: 18

Levels of dihydrofolate reductase in livers of birds, animals, primates, and man. 鸟类、动物、灵长类动物和人类肝脏中二氢叶酸还原酶的水平。

Cancer drug delivery Pub Date : 1987-01-01 DOI: 10.1089/cdd.1987.4.185

V M Whitehead, B A Kamen, D Beaulieu

引用次数: 19

Kinetics of methotrexate and its metabolites in red blood cells. 甲氨蝶呤及其代谢产物在红细胞中的动力学。

Cancer drug delivery Pub Date : 1987-01-01 DOI: 10.1089/cdd.1987.4.119

N Lena, A M Imbert, P Brunet, J P Cano, Y Carcassonne

引用次数: 13

Characterization of liposomes containing the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP) and their interaction with mouse macrophages. 含趋化肽n -甲酰基-蛋氨酸-亮基-苯丙氨酸(FMLP)脂质体的表征及其与小鼠巨噬细胞的相互作用。

Cancer drug delivery Pub Date : 1987-01-01 DOI: 10.1089/cdd.1987.4.233

R Nayar, K Morikawa, I J Fidler

{"title":"Characterization of liposomes containing the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP) and their interaction with mouse macrophages.","authors":"R Nayar, K Morikawa, I J Fidler","doi":"10.1089/cdd.1987.4.233","DOIUrl":"https://doi.org/10.1089/cdd.1987.4.233","url":null,"abstract":"The purpose of these studies was to characterize liposomes containing the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP) and to examine their interaction with mouse peritoneal macrophages. Because of its hydrophobic properties, FMLP can be readily incorporated into both phosphatidylcholine (PC) and PC/phosphatidylserine (PS) (7:3, mol ratio) multilamellar vesicles (MLV). The association of FMLP with the MLVs is stable in medium with or without serum. The size distribution and aqueous trap volume of MLV consisting of PC or PC/PS that contain FMLP at a 10:1 molar ratio do not differ from that of MLV without FMLP. MLV containing equimolar phospholipid-to-FMLP ratios are smaller but have larger aqueous trap volumes. MLV consisting of PC and FMLP (10:1 molar ratio) are phagocytosed more efficiently than PC MLV, and their phagocytosis is mediated via the FMLP receptors on macrophages. In contrast, MLV consisting of PC/PS or PC/PS with FMLP (7:3:1 molar ratios) are phagocytosed to the same extent, and so the FMLP receptors on macrophage surface do not influence this process. The delivery of FMLP in liposomes to macrophages is very efficient: up to 25-fold more FMLP delivered by MLV is internalized into macrophages than when it is in free form. Once associated with the macrophages in either free form or via liposomes, some FMLP is degraded and released into the medium, but the majority of FMLP molecules remain with the macrophages to be degraded at a steady rate. The present findings may explain how liposome-FMLP produces tumoricidal properties in macrophages.","PeriodicalId":77686,"journal":{"name":"Cancer drug delivery","volume":"4 4","pages":"233-44"},"PeriodicalIF":0.0,"publicationDate":"1987-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cdd.1987.4.233","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14578498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 7

Treatment of astrocytoma with a 5-day cisplatin infusion. 顺铂输注5天治疗星形细胞瘤。

Cancer drug delivery Pub Date : 1987-01-01 DOI: 10.1089/cdd.1987.4.47

S M Grunberg, J H Bertram, J E McDermed, M L Apuzzo

{"title":"Treatment of astrocytoma with a 5-day cisplatin infusion.","authors":"S M Grunberg, J H Bertram, J E McDermed, M L Apuzzo","doi":"10.1089/cdd.1987.4.47","DOIUrl":"https://doi.org/10.1089/cdd.1987.4.47","url":null,"abstract":"Although cisplatin may have intrinsic activity against astrocytoma, limited penetration into the central nervous system may severely curtail delivery of adequate amounts of drug to the tumor. In an attempt to increase the dose of delivered drug without markedly increasing toxicity, cisplatin was administered by 5-day continuous intravenous infusion at a dose of 28 mg/m2/day (total dose 140 mg/m2) to 15 evaluable patients (5 with astrocytoma Grade III and 10 with astrocytoma Grade IV). Median age was 39 years, median Karnofsky Performance Status was 80%, and all patients had been previously treated with other modalities. One patient (7%) achieved Partial Response as demonstrated by increased strength of paretic extremities, increased Karnofsky Performance Status, and decrease of enhancing tumor mass on CT scan. Although nephrotoxicity was minimal, nausea and vomiting (usually mild) was seen in 14 patients. Myelosuppression was also common (anemia in 7 patients, leukopenia in 4 patients and thrombocytopenia in 3 patients). Ototoxicity was seen in 5 patients and may represent a combined modality toxicity with prior cranial radiotherapy. Routes and schedules which allow a higher peak serum concentration of cisplatin (such as subselective intracerebral artery infusion) may be necessary to achieve greater central nervous system drug penetration and to maximally exploit cisplatin in the treatment of astrocytoma.","PeriodicalId":77686,"journal":{"name":"Cancer drug delivery","volume":"4 1","pages":"47-53"},"PeriodicalIF":0.0,"publicationDate":"1987-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cdd.1987.4.47","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14728476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 10

Prevention of adriamycin-induced cardiotoxicity by prenylamine: a pilot double blind study. 丙烯胺预防阿霉素引起的心脏毒性:一项先导双盲研究。

Cancer drug delivery Pub Date : 1987-01-01 DOI: 10.1089/cdd.1987.4.129

J Milei, A Marantz, J Alé, A Vazquez, J E Buceta

{"title":"Prevention of adriamycin-induced cardiotoxicity by prenylamine: a pilot double blind study.","authors":"J Milei, A Marantz, J Alé, A Vazquez, J E Buceta","doi":"10.1089/cdd.1987.4.129","DOIUrl":"https://doi.org/10.1089/cdd.1987.4.129","url":null,"abstract":"Adriamycin (ADM) is an effective antineoplastic drug. However, the amount of ADM that can be administered must be limited because of the risk of developing a severe dose-dependent myocardiopathy. Prenylamine (PNL), a calcium antagonistic drug, provided partial protection against ADM-induced cardiotoxicity in mice and in the rabbit. Thus, it was considered important to evaluate the cardioprotective potential of PNL in patients given ordinary doses of ADM. Twenty-six patients were selected and randomized in two groups, and a double-blind trial was begun. Group A (n = 13): patients received ADM, i.v. at standard oncological doses up to 550 mg/m2, plus placebo, orally. Group B (n = 13): ADM was administered as in Group A, but PNL 200 mg/day was given instead of placebo. Standard ECG and chest radiographs were performed at the beginning of treatment and every two months. Mode-M echocardiograms and 24-hour ambulatory ECGs were obtained previously to the beginning of the ADM treatment and two months after the administration of the last dose of the drug. In Group A, three patients died from oncological causes, total ADM dose was 359 +/- 100 mg/m2, and the mean age was 59.7 years. One patient in this group developed a congestive myocardiopathy while another patient developed a severe supraventricular arrhythmia. In Group B, four patients died from oncological causes, total ADM dose was 367 +/- 132 mg/m2, and the mean age was 63.8 years. No myocardiopathy was found in this group. These findings suggest that simultaneous administration of PNL may mitigate ADM cardiotoxicity, but larger trials are needed to draw definite conclusions.","PeriodicalId":77686,"journal":{"name":"Cancer drug delivery","volume":"4 2","pages":"129-36"},"PeriodicalIF":0.0,"publicationDate":"1987-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cdd.1987.4.129","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14552914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 22

The pharmacology of hepatic regional administration of cisplatin in a rabbit model. 兔肝区给药顺铂的药理作用。

Cancer drug delivery Pub Date : 1987-01-01 DOI: 10.1089/cdd.1987.4.225

R Kar, R W Opfell, A G Wile

{"title":"The pharmacology of hepatic regional administration of cisplatin in a rabbit model.","authors":"R Kar, R W Opfell, A G Wile","doi":"10.1089/cdd.1987.4.225","DOIUrl":"https://doi.org/10.1089/cdd.1987.4.225","url":null,"abstract":"The pharmacology of hepatic regional administration of CisplatinR (DDP) was examined in a rabbit model. Routes and modes of administration were: IV, hepatic arterial infusion (HAI), HAI with stopflow, HAI with microembolic material [collagen for embolization (CFE)], and portal vein (PV). DDP was rapidly administered, blood samples were drawn over 45 minutes, and hepatic tissue was obtained. Filterable plasma DDP levels were measured by HPLC. Hepatic DDP levels were determined by atomic absorption spectroscopy. All modes of regional administration yielded significantly higher hepatic DDP levels when compared to tissue levels following IV administration. Only the PV and HACFE routes resulted in significantly less systemic drug exposure (AUC) when compared to IV administration. These data indicate a relative pharmacologic advantage of 1.8 for HAI, 3.4 for PV, 1.8 for HAI stopflow, and 4.3 for HACFE compared to IV DDP administration. This pre-clinical study demonstrates substantial pharmacologic advantage for PV and HACFE routes of DDP administration and suggests that clinical trials based on this information be considered.","PeriodicalId":77686,"journal":{"name":"Cancer drug delivery","volume":"4 4","pages":"225-32"},"PeriodicalIF":0.0,"publicationDate":"1987-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cdd.1987.4.225","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14578497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Conjugates of ara-AMP with lactosaminated albumin: a study on their immunogenicity in mouse and rat. ara-AMP与乳胺化白蛋白结合物的小鼠和大鼠免疫原性研究。

Cancer drug delivery Pub Date : 1987-01-01 DOI: 10.1089/cdd.1987.4.145

L Fiume, C Busi, P Preti, G Spinosa

{"title":"Conjugates of ara-AMP with lactosaminated albumin: a study on their immunogenicity in mouse and rat.","authors":"L Fiume, C Busi, P Preti, G Spinosa","doi":"10.1089/cdd.1987.4.145","DOIUrl":"https://doi.org/10.1089/cdd.1987.4.145","url":null,"abstract":"Complexes of albumin with oligosaccharides have been successfully employed in experimental chemotherapy as hepatotropic carriers of antiviral drugs or as vectors of anticancer-agents, but their clinical use is hampered by an immune response they might evoke. In the present experiments we have studied the humoral immunogenicity of conjugates of 9-beta-D-arabinofuranosyl adenine 5'-monophosphate (ara-AMP) with lactosaminated albumin (L-SA), in mice and rats. These complexes were prepared with the aim of increasing the chemotherapeutic index of ara-AMP in the treatment of chronic hepatitis B virus (HBV) infection. L-SA-ara-AMP conjugates prepared with heterologous albumin produced antibodies in mice and rats when repeatedly injected intraperitoneally. The same conjugates prepared with homologous albumin induced only low amounts of antibodies, when given by repeated intraperitoneal injection, whereas they did not evoke antibodies in mice and were tolerogenic in rats when administered repeatedly by the intravenous route. These results suggest that in a clinical use of drug conjugates prepared with oligosaccharide-albumin complexes the risk of an immune response can be reduced by employing human albumin and by injecting the conjugates by the intravenous route.","PeriodicalId":77686,"journal":{"name":"Cancer drug delivery","volume":"4 3","pages":"145-50"},"PeriodicalIF":0.0,"publicationDate":"1987-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/cdd.1987.4.145","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13599268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 30

Biological activities of 5-fluorouracil and its prodrug 5'-deoxy-5-fluorouridine in rats. 5-氟尿嘧啶及其前药5'-脱氧-5-氟吡啶在大鼠体内的生物活性。

Cancer drug delivery Pub Date : 1987-01-01 DOI: 10.1089/cdd.1987.4.137

J L Au, Y M Rustum, H K Slocum

引用次数: 3