Selective cancer therapeutics最新文献_第4页

Forbeck forum on improved drug delivery to brain tumors. 关于改善脑肿瘤药物输送的福贝克论坛。

Selective cancer therapeutics Pub Date : 1990-01-01 DOI: 10.1089/sct.1990.6.109

A I Freeman, J Fenstermacher, W Shapiro, J Kemshead, M Chasin, O M Colvin, M Diksic, J Finley, A Hertler, V Levin

引用次数: 0

A pharmacologic approach to dosage intensification. 剂量强化的药理学方法。

Selective cancer therapeutics Pub Date : 1990-01-01 DOI: 10.1089/sct.1990.6.129

A J Weiss

引用次数: 0

Therapy of murine liver metastases by administration of MDP encapsulated in liposomes. 脂质体包封MDP治疗小鼠肝转移瘤。

Selective cancer therapeutics Pub Date : 1990-01-01 DOI: 10.1089/sct.1990.6.63

T Daemen, B H Dontje, A Veninga, G L Scherphof, W L Oosterhuis

{"title":"Therapy of murine liver metastases by administration of MDP encapsulated in liposomes.","authors":"T Daemen, B H Dontje, A Veninga, G L Scherphof, W L Oosterhuis","doi":"10.1089/sct.1990.6.63","DOIUrl":"https://doi.org/10.1089/sct.1990.6.63","url":null,"abstract":"In a reproducible murine model of liver metastases, it was demonstrated that liposomal muramyl dipeptide (MDP) as an adjuvant therapy reduces and prevents the development of metastases. C26 colon adenocarcinoma cells were injected into the spleen (5 x 10(4) cells per mouse) of syngeneic BALB/c mice. On day 3, the spleen was removed to prevent a large tumor burden in the spleen. On day 17, 100% of the mice had developed tumor foci in the liver. Liposomal MDP treatment consisted of the i.v. or i.p. administration of 1 mumol of liposomal lipid containing 5 micrograms of MDP per mouse for ten consecutive days. When therapy was initiated two days after tumor cell inoculation, the number of metastases that had developed on day 17 was strongly reduced compared to control mice. Approximately 20% of the mice were free of liver metastases. Initiation of therapy two days prior to tumor cell inoculation enhanced the effect significantly: about 45% of the mice were free of metastases on day 17. The treatment protocol for survival studies was slightly different; liposomal MDP was administered on the first six consecutive days followed by administration twice weekly, through day 24. Control mice died between day 21 and 33 after tumor cell inoculation, whereas liposomal MDP treated mice died between day 26 and 46 with 1 out of 25 mice surviving for more than 120 days. The mortality of the liposomal MDP treated mice that were free of liver metastases was caused by a local tumor at the site of operation.(ABSTRACT TRUNCATED AT 250 WORDS)","PeriodicalId":21792,"journal":{"name":"Selective cancer therapeutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1990-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/sct.1990.6.63","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13516733","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

Studies on age-dependent plasma platinum pharmacokinetics and ototoxicity of cisplatin. 顺铂年龄依赖性血浆铂药代动力学及耳毒性研究。

Selective cancer therapeutics Pub Date : 1990-01-01 DOI: 10.1089/sct.1990.6.145

T Murakami, S Inoue, K Sasaki, T Fujimoto

{"title":"Studies on age-dependent plasma platinum pharmacokinetics and ototoxicity of cisplatin.","authors":"T Murakami, S Inoue, K Sasaki, T Fujimoto","doi":"10.1089/sct.1990.6.145","DOIUrl":"https://doi.org/10.1089/sct.1990.6.145","url":null,"abstract":"The age-related difference of cisplatin (CDDP) pharmacokinetics and ototoxicity were studied in 6 children with solid tumors who received CDDP infusion. CDDP was administered intravenously for 6 hours at a dosage of 30-120 mg/m2 and plasma-free platinum concentrations were determined by atomic absorption spectrophotometry. Plasma-free platinum concentrations ranged from 1.0 to 2.1 micrograms/ml at the end of infusions and declined rapidly with T1/2 of 0.6-1.5 hours. Pharmacokinetic parameters of plasma-free platinum were analyzed in 13 CDDP infusions by the one-compartment open model method. Parameters (Ke, Cl, T1/2 and Vd) of free platinum pharmacokinetics were 0.66 hr-1, 7.71l/hr, 1.35 hr and 15.71l in the younger group (age: 1.7-6.5 years old) and 1.44 hr-1, 11.41l/hr, 0.61 hr and 8.99l in the older group (age: 12.2-15.7 years old), respectively. Up to 600 mg/m2 of the cumulative dosage of CDDP caused minimal ototoxicity in the older group; however, in the younger group, hearing loss at a high frequency zone (6000 and 8000 Hz) began to appear at a cumulative dosage of 200 mg/m2 and progressed to middle zone (3000 Hz) when dosages surpassed 400 mg/m2. These data indicate that the pharmacokinetic difference in age possesses a large distribution volume (Vd) and that slower elimination of the drug in a younger age group is an important factor for age-dependent ototoxicity.","PeriodicalId":21792,"journal":{"name":"Selective cancer therapeutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1990-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/sct.1990.6.145","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13431657","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: 26

Free and liposomal doxorubicin treatment of intraperitoneal colon 26 tumor: therapeutic and pharmacologic studies. 游离和脂质体阿霉素治疗腹腔内结肠肿瘤:治疗和药理学研究。

Selective cancer therapeutics Pub Date : 1990-01-01 DOI: 10.1089/sct.1990.6.193

E Mayhew, M Cimino, J Klemperer, R Lazo, J Wiernikowski, S Arbuck

{"title":"Free and liposomal doxorubicin treatment of intraperitoneal colon 26 tumor: therapeutic and pharmacologic studies.","authors":"E Mayhew, M Cimino, J Klemperer, R Lazo, J Wiernikowski, S Arbuck","doi":"10.1089/sct.1990.6.193","DOIUrl":"https://doi.org/10.1089/sct.1990.6.193","url":null,"abstract":"Intraperitoneal (i.p.) chemotherapy is being investigated as an adjunct to surgery to kill residual cancer cells, inhibit cancer cell seeding, local recurrence, and metastases for ovarian, gastric, and colon cancers. In this report, the therapeutic effects of Doxorubicin (Dox) and liposome-entrapped Dox (Dox-Lip) against i.p. mouse colon 26 (C26) tumor were compared. It was found that Dox-Lip was less toxic than Dox after i.p. administration in non-tumor bearing animals. I.P. Dox and Dox-Lip significantly inhibited the growth of C26 tumor when the treatment was initiated 1 day after tumor cell inoculation, but both administration forms were ineffective against well-established (8-day) tumors. Multiple dose schedules did not improve the therapeutic response. Dox-Lip was not therapeutically superior to Dox at equal doses or at approximately equi-toxic doses. In addition, the relative retention of Dox and Dox-Lip in the peritoneal cavity and their plasma pharmacokinetics were investigated. It was found that Dox levels in the peritoneal cavity were maintained for longer periods after i.p. Dox-Lip was administered. However, the results show that maintenance of elevated drug levels in the peritoneal cavity does not necessarily lead to increased therapeutic effects.","PeriodicalId":21792,"journal":{"name":"Selective cancer therapeutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1990-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/sct.1990.6.193","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13250422","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: 16

Reversal of doxorubicin and cisplatin resistance in vivo in murine leukemias by the calcium antagonist RO 11-2933. 钙拮抗剂ro11 -2933逆转小鼠白血病体内阿霉素和顺铂耐药

Selective cancer therapeutics Pub Date : 1990-01-01 DOI: 10.1089/sct.1990.6.167

A Mazzoni, G Canti

引用次数: 2

5-iodo-2'-deoxyuridine-protein conjugates: synthesis and enzymatic degradation. 5-碘-2'-脱氧尿苷蛋白缀合物:合成和酶降解。

Selective cancer therapeutics Pub Date : 1990-01-01 DOI: 10.1089/sct.1990.6.1

J Baranowska-Kortylewicz, S J Adelstein, A I Kassis

{"title":"5-iodo-2'-deoxyuridine-protein conjugates: synthesis and enzymatic degradation.","authors":"J Baranowska-Kortylewicz, S J Adelstein, A I Kassis","doi":"10.1089/sct.1990.6.1","DOIUrl":"https://doi.org/10.1089/sct.1990.6.1","url":null,"abstract":"Several halogenated analogs of thymidine and cytidine possess antineoplastic and antiviral activity. They are also powerful sensitizers of bacterial and mammalian cells to lethal effects of x-irradiation. An important factor limiting the effectiveness of these agents in therapy is their extremely short half-life in circulation due to rapid hepatic dehalogenation. An approach to this problem is to deliver the drug directly to its target using monoclonal antibodies. This study evaluates the lysosomotropic delivery systems of halogenated pyrimidines using 5-iodo-2'-deoxyuridine [IUdR] as a model. IUdR, derivatized and activated at either the 3'- or the 5'-position forms covalent adducts with the epsilon-amino groups of the lysine residues in proteins (bovine serum albumin [BSA], and immunoglobulins [IgG]). Two methods suitable for conjugation of IUdR to proteins involving either the formation of acyl-imidazoles in the reaction of IUdR succinates with N,N'-carbonyldiimidazole or the preparation of N-succinimidyl esters of IUdR succinates were established. Both derivatives express comparable reactivity toward proteins. The degree of IUdR incorporation is easily controlled by the ratio of reagents. The succinate \"arm\" linking IUdR to protein is susceptible to lysosomal hydrolysis in vitro releasing intact IUdR. The half-life of the IUdR-IgG conjugate in the presence of the lysosomal enzymes was shown to be approximately twice that of the IUdR-BSA conjugate.","PeriodicalId":21792,"journal":{"name":"Selective cancer therapeutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1990-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/sct.1990.6.1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13494387","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

Liposome-incorporated 3',5'-O-dipalmitoyl-5-fluoro-2'-deoxyuridine as a slow-release anti-tumor drug depot in rat liver macrophages. 脂质体结合3'，5'- o-双棕榈酰基-5-氟-2'-脱氧尿苷作为大鼠肝巨噬细胞的缓释抗肿瘤药物库。

Selective cancer therapeutics Pub Date : 1990-01-01 DOI: 10.1089/sct.1990.6.15

M Van Borssum Waalkes, G L Scherphof

{"title":"Liposome-incorporated 3',5'-O-dipalmitoyl-5-fluoro-2'-deoxyuridine as a slow-release anti-tumor drug depot in rat liver macrophages.","authors":"M Van Borssum Waalkes, G L Scherphof","doi":"10.1089/sct.1990.6.15","DOIUrl":"https://doi.org/10.1089/sct.1990.6.15","url":null,"abstract":"We synthesized the 3',5'-O-dipalmitoyl derivative of 5-fluoro-6-[3H]-2'-deoxyuridine and incorporated it into the bilayers of multilamellar liposomes (400 nm diameter) of various lipid compositions. The prodrug-containing liposomes were incubated with rat liver macrophages (Kupffer cells) in monolayer culture and with lysosomal fractions from whole rat liver homogenates. The release of water-soluble radioactive degradation products from the cells was measured and we found the rate of release strongly dependent on the lipid composition of the liposomes. After 4 hours of incubation the release of radioactivity was 9-fold higher from egg-phosphatidylcholine/phosphatidylserine/cholesterol liposomes than from distearoylphosphatidylcholine/dipalmitoylphosphatidylglycerol/cholest ero l or dioctadecyl-sn-glycero-phosphorylcholine/dipalmitoylphosphatidylg lycerol/ cholesterol liposomes. A somewhat less pronounced difference in rate of prodrug degradation was found when the liposomes were incubated with lysosomal fractions. The water-soluble products that were formed showed anti-tumor activity against C26-adenocarcinoma tumor cells in vitro. Preliminary evidence suggests this activity to be caused by 5-fluoro-2'-deoxyuridine. We conclude that incubation of liposomes of varied composition containing diacylated 5-fluoro-2' deoxyuridine derivatives with Kupffer cells in culture, results in the formation of an intracellular prodrug depot in these cells from which compounds with anti-tumor activity are released with controllable rates.","PeriodicalId":21792,"journal":{"name":"Selective cancer therapeutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1990-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/sct.1990.6.15","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13294775","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: 16

Reduction of vinblastine neurotoxicity in mice utilizing a collagen matrix carrier. 利用胶原基质载体降低长春碱对小鼠的神经毒性。

Selective cancer therapeutics Pub Date : 1990-01-01 DOI: 10.1089/sct.1990.6.35

R Sutton, N Yu, E Luck, D Brown, F Conley

引用次数: 14

Evaluation of quinidine effect on the antitumor activity of adriamycin and mitoxantrone in adriamycin-sensitive and -resistant P388 leukemia cells. 奎尼丁对阿霉素敏感耐药P388白血病细胞阿霉素和米托蒽醌抗肿瘤活性的影响。

Selective cancer therapeutics Pub Date : 1990-01-01 DOI: 10.1089/sct.1990.6.93

H Parekh, M Chitnis

{"title":"Evaluation of quinidine effect on the antitumor activity of adriamycin and mitoxantrone in adriamycin-sensitive and -resistant P388 leukemia cells.","authors":"H Parekh, M Chitnis","doi":"10.1089/sct.1990.6.93","DOIUrl":"https://doi.org/10.1089/sct.1990.6.93","url":null,"abstract":"Utilizing the P388 murine leukemia cells sensitive (P388/S) and resistant (P388/ADR) to Adriamycin (ADR), we evaluated the effect of quinidine, an anti-arrhythmic agent, on the cytotoxic activity of ADR and Mitoxantrone (MITO), both in vitro as well as in vivo. Quinidine enhanced the cytotoxicity of both ADR and MITO in P388/S and P388/ADR cells, as assessed by the decrease in color intensity of formazan crystal in the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay. A dose dependent inhibition of 3H-thymidine and 3H-uridine incorporation was observed when the P388/S and P388/ADR cells were exposed to quinidine alone. A non-toxic concentration of quinidine (5 microM) enhanced the DNA biosynthesis inhibition induced by ADR (55 to 65%) and MITO (37 to 44%) in P388/ADR cells, indicating reversal of resistance, while in P388/S cells only a minimal increase in DNA biosynthesis inhibition was observed. The combination of quinidine at doses of 50 to 100 mg/kg significantly potentiated the antitumor activity of ADR and MITO in P388/ADR bearing mice, whereas the potentiation of ADR and MITO antitumor response was lower in P388/S bearing mice. Quinidine increased the cellular levels of ADR by 53 to 126% in P388/ADR cells in vitro, but failed to indicate such elevated levels of cellular ADR in P388/S cells. This enhanced intracellular accumulation of ADR in P388/ADR cells, explains the therapeutic efficacy of ADR and MITO in P388/ADR, both in vitro as well as in vivo. Results suggest the efficacy of quinidine to ameliorate the antitumor effects of ADR and MITO in drug resistant tumor cells.","PeriodicalId":21792,"journal":{"name":"Selective cancer therapeutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1990-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/sct.1990.6.93","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13516735","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: 8