Selective cancer therapeutics最新文献_第3页

Anti-tumor effect of cisplatin, carboplatin, mitoxantrone, and doxorubicin on peritoneal tumor growth after intraperitoneal and intravenous chemotherapy: a comparative study. 顺铂、卡铂、米托蒽醌和阿霉素对腹腔和静脉化疗后腹膜肿瘤生长的抑制作用比较研究。

Selective cancer therapeutics Pub Date : 1990-01-01 DOI: 10.1089/sct.1990.6.73

G Los, J D Nagel, J G McVie

{"title":"Anti-tumor effect of cisplatin, carboplatin, mitoxantrone, and doxorubicin on peritoneal tumor growth after intraperitoneal and intravenous chemotherapy: a comparative study.","authors":"G Los, J D Nagel, J G McVie","doi":"10.1089/sct.1990.6.73","DOIUrl":"https://doi.org/10.1089/sct.1990.6.73","url":null,"abstract":"Tumor growth was studied in a peritoneal tumor model in the rat after intravenous and intraperitoneal administration of doxorubicin (4 mg/kg), mitoxantrone (2.5 mg/kg) and cisplatin (4 mg/kg) and after intraperitoneal administration of carboplatin (20 mg/kg). All treatments delayed tumor growth and intraperitoneal treatment was more effective initially than intravenous treatment for all drugs tested. Regrowth occurred between 2 and 7 weeks after treatment and was less pronounced after intravenous treatment. Tumor sizes in cisplatin treated rats 7 weeks after treatment were comparable after intraperitoneal and intravenous treatments. Intraperitoneal carboplatin even with a dose 5 times higher than cisplatin resulted in a less tumor growth delay in all stages of the treatment, compared to cisplatin. All cytostatic drugs, except carboplatin, induced loss of body weight. Weight loss was similar for intraperitoneal and intravenous treatment with both cisplatin and mitoxantrone while for doxorubicin the weight loss was significantly higher after intravenous treatment than after intraperitoneal therapy. Considering the \"therapeutic index\", defined as the ratio of tumor growth delay to weight loss, cisplatin had the highest \"therapeutic index\", 1.5 (intraperitoneal) and 1.7 (intravenous) compared to 0.3 (intraperitoneal) and 0.6 (intravenous) for Mitoxantrone and 0.4 (intraperitoneal) and 0.5 (intravenous) for doxorubicin. This indicated that cisplatin was the most favorable drug to use in this peritoneal tumor model for both intraperitoneal and intravenous treatment. The tumor growth delay was initially more pronounced after intraperitoneal cisplatin compared with intravenous.","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.1990.6.73","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13347743","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: 13

Phase I trial and biochemical evaluation of tiazofurin administered on a weekly schedule. 每周一次给药噻唑呋林的一期试验和生化评价。

Selective cancer therapeutics Pub Date : 1990-01-01 DOI: 10.1089/sct.1990.6.51

T J Melink, G Sarosy, A R Hanauske, J L Phillips, J H Bayne, M R Grever, H N Jayaram, D D Von Hoff

{"title":"Phase I trial and biochemical evaluation of tiazofurin administered on a weekly schedule.","authors":"T J Melink, G Sarosy, A R Hanauske, J L Phillips, J H Bayne, M R Grever, H N Jayaram, D D Von Hoff","doi":"10.1089/sct.1990.6.51","DOIUrl":"https://doi.org/10.1089/sct.1990.6.51","url":null,"abstract":"Tiazofurin (2-B-D-Ribofuranosylthiazole-4-Carboxamide: NSC 286193) is a nucleoside antimetabolite that acts as a potent inhibitor of IMP dehydrogenase resulting in a guanine nucleotide deprivation. Recent in vivo biochemical observations in rats bearing hepatoma suggested a correlation between depletion of guanine nucleotides and antitumor effect. The present phase I trial utilized a weekly x 3 bolus infusion schedule, repeated every 5 weeks. Biochemical measurements of GTP and dGTP were performed in patients at each dose level. Twelve patients received 16 courses of the drug in doses ranging from 1100 to 2050 mg/m2 weekly x 3. The dose limiting toxicities were pericarditis and clinical symptoms suggestive of a more generalized serositis (chest and abdominal pain). Other toxicities included reversible elevations in CPK (MM band only) and SGOT, nausea, vomiting, and arthralgias. Neurotoxic effects were generally mild, including headaches, anxiety, and malaise. Only 1 of 6 patients evaluated for tiazofurin's biochemical activity showed a sustained depletion of guanine nucleotide pools. No antitumor activity was observed. The maximally tolerated dose of tiazofurin on this intermittent weekly x 3 schedule was 1650 mg/m2. Toxicity and the overall lack of biochemical and biologic effect at clinically achievable doses may preclude further clinical evaluation of this drug on a weekly schedule. The toxicities observed in our study were similar to those reported for phase I investigations using a considerably higher dose intensity with daily x 5 schedules.","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.1990.6.51","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13492166","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: 4

Enhanced effect of adriamycin on a rat liver adenocarcinoma after hepatic artery injection with degradable starch microspheres. 肝动脉注射可降解淀粉微球后阿霉素对大鼠肝腺癌的增强作用。

Selective cancer therapeutics Pub Date : 1990-01-01 DOI: 10.1089/sct.1990.6.23

I A el Hag, H Teder, G Roos, P I Christensson, U Stenram

引用次数: 10

Targeting behavior of hepatic artery injected temperature sensitive liposomal adriamycin on tumor-bearing rats. 肝动脉注射温敏脂质体阿霉素对荷瘤大鼠的靶向作用。

Selective cancer therapeutics Pub Date : 1990-01-01 DOI: 10.1089/sct.1990.6.119

Y Y Zou, M Ueno, M Yamagishi, I Horikoshi, I Yamashita, K Tazawa, X Q Gu

{"title":"Targeting behavior of hepatic artery injected temperature sensitive liposomal adriamycin on tumor-bearing rats.","authors":"Y Y Zou, M Ueno, M Yamagishi, I Horikoshi, I Yamashita, K Tazawa, X Q Gu","doi":"10.1089/sct.1990.6.119","DOIUrl":"https://doi.org/10.1089/sct.1990.6.119","url":null,"abstract":"Temperature sensitive liposomal Adriamycin (LADM) was injected into the hepatic artery of rats bearing implanted hepatic tumors. Two hours after the injection, the liver was heated at 42 degrees C and maintained for six minutes at that temperature using local hyperthermia. Blood samples were taken at regular intervals until 8 hours after injection, at which time the animals were sacrificed and the drug distribution in the tissues was examined. Results indicate that the Adriamycin was released from the liposome, with the drug concentration in circulation peaking at 30 minutes after heating. High drug levels (25.2 micrograms/g of wet tissue) in the tumor and high tumor/liver Adriamycin level ratios (TLAR; 4.1) were found. The drug levels and the TLAR of the liposomal Adriamycin injection combined with heating (LADM H) were significantly different from those of the same dose of aqueous Adriamycin with heating (ADM H) or aqueous Adriamycin (ADM) and LADM without heating. The experiment shows that the LADM is cleared from the liver slowly, and when hyperthermia treatment at phase-transition temperature of the liposome is performed, the drug level in an implanted hepatic tumor is increased, and in the parenchyma is decreased. The results imply that targeting the hepatic tumor in this way may be an effective therapeutic method, and the drug release from the liposome may be controlled externally. This method appears promising for clinical practice.","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.1990.6.119","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13431652","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: 23

Decrease of liver energy charge, ATP and glutathione at concomitant intraarterial administration of adriamycin and degradable starch microspheres in rat. 阿霉素和可降解淀粉微球同时动脉给药对大鼠肝脏能量电荷、ATP和谷胱甘肽的影响。

Selective cancer therapeutics Pub Date : 1990-01-01 DOI: 10.1089/sct.1990.6.135

I A el Hag, G Roos, U Stenram

引用次数: 4

Extravasation of doxorubicin from vascular access devices. 阿霉素从血管通路装置外渗。

Selective cancer therapeutics Pub Date : 1990-01-01 DOI: 10.1089/sct.1990.6.103

C F Curran, J K Luce

引用次数: 7

The uptake and metabolism of cyclophosphamide by the ovary. 卵巢对环磷酰胺的摄取和代谢。

Selective cancer therapeutics Pub Date : 1990-01-01 DOI: 10.1089/sct.1990.6.83

K Ataya, E Pydyn, J Young, R Struck

{"title":"The uptake and metabolism of cyclophosphamide by the ovary.","authors":"K Ataya, E Pydyn, J Young, R Struck","doi":"10.1089/sct.1990.6.83","DOIUrl":"https://doi.org/10.1089/sct.1990.6.83","url":null,"abstract":"The uptake of cyclophosphamide (CTX) and its metabolites was evaluated by injecting adult female rats with 14C-CTX on the morning of metestrous or proestrus. Rats were sacrificed 1 and 5 hours after 14C-CTX injection. The ovary, uterus, spleen, thymus, liver, kidney, anterior pituitary, duodenum, skeletal muscle and whole blood were isolated from each rat. Samples were combusted using a biological material oxidizer and the resulting CO2 was absorbed and counted. Liver and kidney had the highest uptake of 14C-radioactivity. The ovary appears to have 14C uptake comparable to the thymus and other tissues. Metabolism of CTX by the ovary was investigated by incubating 14C-CTX with human and rat granulosa cells and other ovarian cells obtained from pregnant mares' serum gonadotropin (PMSG)-primed immature rats, in separate experiments. The conversion of CTX to two marker metabolites, 4-ketocyclophosphamide and 4-hydroxycyclophosphamide was negligible and did not change in the presence of luteinizing hormone (LH). It is concluded that 1) following 14C-CTX injection, the ovary takes up a proportion of 14C-radioactivity comparable to other target tissues (e.g. thymus) and 2) the ovary is not capable of activating CTX in vitro in our system.","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.1990.6.83","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13516734","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: 12

Low-dose systemic doxorubicin in combination with regional hepatic hyperthermia. 低剂量全身性阿霉素联合局部肝热疗。

Selective cancer therapeutics Pub Date : 1990-01-01 DOI: 10.1089/sct.1990.6.177

M A Burton, D K Kelleher, J P Codde, B N Gray

引用次数: 1

Bepridil enhances adriamycin-induced DNA biosynthesis inhibition in human myeloid leukemia cells. 贝必地尔增强阿霉素诱导的人髓性白血病细胞DNA生物合成抑制作用。

Selective cancer therapeutics Pub Date : 1990-01-01 DOI: 10.1089/sct.1990.6.183

H Parekh, S Advani, M Chitnis

{"title":"Bepridil enhances adriamycin-induced DNA biosynthesis inhibition in human myeloid leukemia cells.","authors":"H Parekh, S Advani, M Chitnis","doi":"10.1089/sct.1990.6.183","DOIUrl":"https://doi.org/10.1089/sct.1990.6.183","url":null,"abstract":"The utilization of drug response modulators, based on their physico-chemical properties to augment the cytotoxic response of anticancer drugs is now gaining importance. We present in this communication, investigations performed to assess the antitumor activity of Adriamycin (ADR), on chronic myeloid leukemia (CML) cells, and the effect of bepridil, a calcium channel blocker on the ADR cytotoxicity. Inhibition of 3H-thymidine incorporation into DNA was used as an index of the cytotoxic effects of drugs when utilised alone or in combination. The combination of bepridil (1 and 5 micrograms/ml) and ADR (5 and 10 micrograms/ml) indicated a significant (P less than 0.001) enhancement in the DNA biosynthesis inhibition in CML cells, as compared to those samples exposed to ADR alone. The observed inhibition of DNA biosynthesis was found to be totally reversible, partially reversible and completely irreversible when the CML cells were exposed to bepridil alone, ADR alone and ADR plus bepridil, respectively. Bepridil was found to be highly lipid soluble at physiological pH, and this property could be responsible for the modulation of the ADR activity observed in this study. Results obtained, though preliminary due to the small sample size, clearly indicate a necessity for a detailed evaluation of bepridil effects, which would lead to higher therapeutic gains in anticancer chemotherapy in the clinic.","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.1990.6.183","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13250421","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

HPLC and flow cytometric analyses of uptake of adriamycin and menogaril by monolayers and multicell spheroids. 高效液相色谱和流式细胞术分析单层细胞和多细胞球体对阿霉素和甲诺加瑞的摄取。

Selective cancer therapeutics Pub Date : 1990-01-01 DOI: 10.1089/sct.1990.6.153

T J Bichay, E G Adams, W R Inch, W J Adams, J E Brewer, B K Bhuyan

{"title":"HPLC and flow cytometric analyses of uptake of adriamycin and menogaril by monolayers and multicell spheroids.","authors":"T J Bichay, E G Adams, W R Inch, W J Adams, J E Brewer, B K Bhuyan","doi":"10.1089/sct.1990.6.153","DOIUrl":"https://doi.org/10.1089/sct.1990.6.153","url":null,"abstract":"We have used both HPLC and flow cytometry to measure and compare the uptake of two anthracyclines, menogaril (MEN) and Adriamycin (ADR), in V79 Chinese hamster lung fibroblasts grown as monolayers and as 650 microns multicell spheroids. In order to compare intracellular drug accumulation in spheroid cells measured by the two methods, we converted mean channel fluorescence of the flow cytometer to drug uptake expressed as ng/10(6) cells by using a standard curve. The standard curve related the flow cytometric mean channel fluorescence, of monolayer cells exposed to either drug, to the intracellular drug accumulation determined by HPLC. This standard curve was then used to convert the mean channel fluorescence of cells from drug-exposed spheroids to ng/10(6) cells. Our results show that equal intracellular drug accumulation (determined by HPLC) in spheroids and monolayers does not result in equal cellular fluorescence emission (determined by flow cytometry) by these 2 cell populations. For example, monolayer cells with an intracellular MEN accumulation of 650 ng/10(6) cells, emit 40 units of fluorescence as measured by flow cytometry. However, spheroid cells with the same intracellular accumulation emit about 80 units of fluorescence. This results in the intracellular MEN uptake in spheroids measured by flow cytometry being as much as 2- to 3-fold higher than that measured by HPLC. Intracellular ADR accumulation measured by flow cytometry was also higher than that obtained by HPLC. In spite of the quantitative difference between the two methods, qualitatively both methods gave similar results. Thus, both techniques showed that at equal drug concentration in medium drug uptake in monolayers was much greater than in spheroids.(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.1990.6.153","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13305771","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: 5