Regional pharmacokinetics of 5-bromo-2'-deoxyuridine and 5-fluorouracil in dogs: hepatic arterial versus portal venous infusions.

Abstract:

:The purpose of this study was to determine the effect of route of hepatic administration of drug on the regional pharmacokinetics and systemic exposure of 5-fluorouracil (FUra) and 5-bromo-2-deoxyuridine (BrdUrd). A total of 13 mixed-breed male and female dogs were used in these acute studies. Each dog was administered hepatic arterial and portal venous infusions of a single drug, in a cross-over fashion, at two dose rates for a total of four sequential infusions. BrdUrd was studied at 0.250 and 0.500 micromol/min/kg, and FUra was studied at 0.125 and 0.500 micromol/min/ kg. Each infusion lasted 2 h, at which time steady-state plasma concentrations were obtained (ie., gastroduodenal artery, portal vein, hepatic vein, and femoral artery), perfusion rates in hepatic artery and portal vein were measured, and hepatic extraction (as opposed to extraction across the splanchnic region) was directly assessed. BrdUrd and FUra were found to be highly extracted across the liver (E(H) > or = 0.65) at the regional dose rates studied, resulting in low values for the fraction of drug escaping presystemic hepatic elimination (F(H) < or = 0.35). In addition, the regional kinetics (ie., hepatic extraction, fraction escaping first-pass elimination in the liver, and hepatic clearance) and systemic exposure (i.e., CFA) of FUra and BrdUrd were not significantly different following hepatic arterial versus portal venous infusions of drug. Thus, it appears that regional chemotherapy may be applied to halogenated pyrimidines following hepatic arterial, portal venous, and alternating regional dosing routes with no additional risk of systemic toxicity.

journal_name

Cancer Res

journal_title

Cancer research

authors

Kuan HY,Smith DE,Ensmiger WD,Knol JA,DeRemer SJ,Yang Z,Stetson PL

subject

Has Abstract

pub_date

1996-10-15 00:00:00

pages

4724-7

issue

20

eissn

0008-5472

issn

1538-7445

journal_volume

56

pub_type

杂志文章
  • Effect of alpha-difluoromethylornithine on L-phenylalanine mustard-induced cytotoxicity and DNA interstrand cross-linking in a human cell line in vitro.

    abstract::We compared L-phenylalanine mustard (L-PAM)-induced cytotoxicity and DNA cross-linking with and without a 42-h preincubation with the ornithine decarboxylase inhibitor alpha-difluoromethylornithine (DFMO, 1 mM) in a human lymphoma cell line. The combination showed increased toxicity with a Do ratio of 1.6. L-PAM-induc...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Ducore JM,McNamara L

    更新日期:1986-03-01 00:00:00

  • Coordinate loss of MAP3K7 and CHD1 promotes aggressive prostate cancer.

    abstract::Prostate cancer subtypes are poorly defined and functional validation of drivers of ETS rearrangement-negative prostate cancer has not been conducted. Here, we identified an ETS(-) subtype of aggressive prostate cancer (ERG(-)MAP3K7(del)CHD1(del)) and used a novel developmental model and a cell line xenograft model to...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-14-1596

    authors: Rodrigues LU,Rider L,Nieto C,Romero L,Karimpour-Fard A,Loda M,Lucia MS,Wu M,Shi L,Cimic A,Sirintrapun SJ,Nolley R,Pac C,Chen H,Peehl DM,Xu J,Liu W,Costello JC,Cramer SD

    更新日期:2015-03-15 00:00:00

  • Staphylococcal Protein A column: correlation of mitogenicity of perfused plasma with clinical response.

    abstract::Eleven patients with advanced breast cancer and four with astrocytoma were treated with plasma perfused over columns containing staphylococcal Protein A (SPA). Doses of 5 to 20 mg of SPA were bound to collodion charcoal particles, and this treatment resulted in partial remissions in one patient with astrocytoma and in...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Bertram JH,Grunberg SM,Shulman I,Apuzzo ML,Boquiren D,Kunkel L,Hengst JC,Nelson J,Waugh WJ,Plotkin D

    更新日期:1985-09-01 00:00:00

  • Effects of phenylethyl isothiocyanate on early molecular events in N-nitrosomethylbenzylamine-induced cytotoxicity in rat esophagus.

    abstract::There is little information on early molecular events in the development of N-nitrosomethylbenzylamine (NMBA)-induced rat esophageal tumorigenesis and of the effects of chemopreventive agents on these events. In this study, we identified genes in rat esophagus that were differentially expressed in response to short-te...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-06-4531

    authors: Reen RK,Dombkowski AA,Kresty LA,Cukovic D,Mele JM,Salagrama S,Nines R,Stoner GD

    更新日期:2007-07-01 00:00:00

  • Long-term XPC silencing reduces DNA double-strand break repair.

    abstract::To study the relationships between different DNA repair pathways, we established a set of clones in which one specific DNA repair gene was silenced using long-term RNA interference in HeLa cell line. We focus here on genes involved in either nucleotide excision repair (XPA and XPC) or nonhomologous end joining (NHEJ; ...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-06-3371

    authors: Despras E,Pfeiffer P,Salles B,Calsou P,Kuhfittig-Kulle S,Angulo JF,Biard DS

    更新日期:2007-03-15 00:00:00

  • Experimental antitumor activity against murine tumor model systems of 8-carbamoyl-3-(2-chloroethyl)imidazo[5,1-d]-1,2,3,5-tetrazin-4(3 H)-one (mitozolomide), a novel broad-spectrum agent.

    abstract::8-Carbamoyl-3-(2-chloroethyl)imidazo[5,1-d]-1,2,3,5-tetrazin-4(3H) -one (mitozolomide) demonstrates curative action against a range of murine tumor model systems. At single doses of between 20 and 40 mg/kg, the latter of which approximates the 10% lethal dose value in mice, the compound elicited cures against the L121...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Hickman JA,Stevens MF,Gibson NW,Langdon SP,Fizames C,Lavelle F,Atassi G,Lunt E,Tilson RM

    更新日期:1985-07-01 00:00:00

  • Relocalized p27Kip1 tumor suppressor functions as a cytoplasmic metastatic oncogene in melanoma.

    abstract::The p27 tumor suppressor negatively regulates G1 cell cycle progression. However, human malignancies rarely select for deletion/inactivation of p27, a hallmark of tumor suppressor genes. Instead, p27 is degraded or relocalized to the cytoplasm in aggressive malignancies, supporting the notion that p27 sequestration fr...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-07-1375

    authors: Denicourt C,Saenz CC,Datnow B,Cui XS,Dowdy SF

    更新日期:2007-10-01 00:00:00

  • The synthetic compound CC-5079 is a potent inhibitor of tubulin polymerization and tumor necrosis factor-alpha production with antitumor activity.

    abstract::We have found that the synthetic compound CC-5079 potently inhibits cancer cell growth in vitro and in vivo by a novel combination of molecular mechanisms. CC-5079 inhibits proliferation of cancer cell lines from various organs and tissues at nanomolar concentrations. Its IC(50) value ranges from 4.1 to 50 nmol/L. The...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-05-2083

    authors: Zhang LH,Wu L,Raymon HK,Chen RS,Corral L,Shirley MA,Narla RK,Gamez J,Muller GW,Stirling DI,Bartlett JB,Schafer PH,Payvandi F

    更新日期:2006-01-15 00:00:00

  • The role of growth factor receptor pathways in human breast cancer cells adapted to long-term estrogen deprivation.

    abstract::To study the long-term effects of estrogen deprivation on breast cancer, MCF-7Ca human estrogen receptor-positive breast cancer cells stably transfected with human aromatase gene were cultured in the steroid-depleted medium for 6 to 8 months until they had acquired the ability to grow. Proliferation of these cells (UM...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-04-4092

    authors: Sabnis GJ,Jelovac D,Long B,Brodie A

    更新日期:2005-05-01 00:00:00

  • Aromatase localization in human breast cancer tissues: possible interactions between intratumoral stromal and parenchymal cells.

    abstract::Aromatase is a key enzyme in intratumoral estrogen production required for the production of estrogens through the conversion of serum androgens in postmenopausal breast cancer patients. There have been, however, controversies regarding the intratumoral localization of aromatase in human breast carcinoma tissues. Ther...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-06-3105

    authors: Miki Y,Suzuki T,Tazawa C,Yamaguchi Y,Kitada K,Honma S,Moriya T,Hirakawa H,Evans DB,Hayashi S,Ohuchi N,Sasano H

    更新日期:2007-04-15 00:00:00

  • Tumor susceptibility and apoptosis defect in a mouse strain expressing a human p53 transgene.

    abstract::Activation of apoptosis is believed to be critical for the role of p53 as a tumor suppressor. Here, we report a new mouse strain carrying a human p53 transgene in the mouse p53-null background. Expression of human p53 in these mice was comparable with wild-type murine p53; however, transactivation, induction of apopto...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-05-2063

    authors: Dudgeon C,Kek C,Demidov ON,Saito S,Fernandes K,Diot A,Bourdon JC,Lane DP,Appella E,Fornace AJ Jr,Bulavin DV

    更新日期:2006-03-15 00:00:00

  • Topoisomerase II-mediated DNA breaks and cytotoxicity in relation to cell proliferation and the cell cycle in NIH 3T3 fibroblasts and L1210 leukemia cells.

    abstract::The DNA intercalator, 4'-(9-acridinylamino)methanesulfon-m-anisidide (m-AMSA) and the nonintercalator, etoposide (VP-16) produce topoisomerase II-mediated protein-linked DNA strand breaks. This function of topoisomerase II was investigated in relation to cell proliferation and cell cycle. Mouse fibroblasts NIH 3T3 and...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Markovits J,Pommier Y,Kerrigan D,Covey JM,Tilchen EJ,Kohn KW

    更新日期:1987-04-15 00:00:00

  • Pulmonary radiation injury: identification of risk factors associated with regional hypersensitivity.

    abstract::Effective radiation treatment of thoracic tumors is often limited by radiosensitivity of surrounding tissues. Several experimental studies have suggested variations in radiosensitivity of different pulmonary regions. Mice and rat studies in part contradict each other and urge for a more detailed analysis. This study w...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-04-3466

    authors: Novakova-Jiresova A,van Luijk P,van Goor H,Kampinga HH,Coppes RP

    更新日期:2005-05-01 00:00:00

  • A CD44 survival pathway triggers chemoresistance via lyn kinase and phosphoinositide 3-kinase/Akt in colon carcinoma cells.

    abstract::A major obstacle to successful treatment of colorectal cancer is chemotherapy resistance. Enhanced expression of variant CD44 isoforms has been associated with aggressive tumor behavior, prompting the question of whether signaling from this receptor might modulate drug sensitivity. Activation of variant CD44 in colon ...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Bates RC,Edwards NS,Burns GF,Fisher DE

    更新日期:2001-07-01 00:00:00

  • Tropomyosins of human mammary epithelial cells: consistent defects of expression in mammary carcinoma cell lines.

    abstract::Suppression of synthesis of specific tropomyosin (TM) isoforms occurs commonly in human, murine, and avian fibroblasts transformed by retroviral oncogenes or other modalities. The resulting deficiency or altered distribution of TMs may predispose the cells to microfilament instability and contribute to expression of t...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Bhattacharya B,Prasad GL,Valverius EM,Salomon DS,Cooper HL

    更新日期:1990-04-01 00:00:00

  • Imaging active urokinase plasminogen activator in prostate cancer.

    abstract::The increased proteolytic activity of membrane-bound and secreted proteases on the surface of cancer cells and in the transformed stroma is a common characteristic of aggressive metastatic prostate cancer. We describe here the development of an active site-specific probe for detecting a secreted peritumoral protease e...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-14-2185

    authors: LeBeau AM,Sevillano N,Markham K,Winter MB,Murphy ST,Hostetter DR,West J,Lowman H,Craik CS,VanBrocklin HF

    更新日期:2015-04-01 00:00:00

  • Histochemical localization of aldehyde dehydrogenase during rat hepatocarcinogenesis.

    abstract::Significant changes in aldehyde dehydrogenase (ALDH) activity occur during chemically induced rat hepatocarcinogenesis. We have developed a procedure for the histochemical localization of hepatic ALDH which has proven extremely useful as an additional probe for studying changes in this enzyme during hepatocarcinogenes...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Lindahl R,Clark R,Evces S

    更新日期:1983-12-01 00:00:00

  • An unexpected biotransformation pathway for tetrachloro-(d,l-trans)-1,2-diaminocyclohexaneplatinum(IV) (tetraplatin) in the L1210 cell line.

    abstract::Tetrachloro(d,l-trans)-1,2-diaminocyclohexaneplatinum(IV) (tetraplatin) has been considered a prodrug which would be converted rapidly to dichloro(d,l-trans)-1,2-diaminocyclohexaneplatinum(II) [PtCl2(dach)] under physiological conditions. However, the biotransformations of tetraplatin have not been studied in detail. ...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Chaney SG,Gibbons GR,Wyrick SD,Podhasky P

    更新日期:1991-02-01 00:00:00

  • Human monocytes, but not dendritic cells derived from them, are defective in base excision repair and hypersensitive to methylating agents.

    abstract::Monocytes and dendritic cells are key players in the immune response. Because dendritic cells drive the tumor host defense, it is important that monocytes and dendritic cells survive cytotoxic tumor therapy. Although most of the anticancer drugs target DNA, the DNA repair capacity of monocytes and dendritic cells has ...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-06-3712

    authors: Briegert M,Kaina B

    更新日期:2007-01-01 00:00:00

  • Carcinogenicity of mutagens: predictive capability of the Salmonella mutagenesis assay for rodent carcinogenicity.

    abstract::A total of 224 chemicals that have been tested in long-term studies for carcinogenicity in rats and mice by the National Cancer Institute and the National Toxicology Program were tested for mutagenicity in Salmonella typhimurium. Correlations between mutagenicity and carcinogenicity were examined. The influences of ch...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Zeiger E

    更新日期:1987-03-01 00:00:00

  • Synergy between methionine stress and chemotherapy in the treatment of brain tumor xenografts in athymic mice.

    abstract::This study describes a novel approach to the treatment of brain tumors with the combination of recombinant L-methionine-alpha-deamino-gamma-lyase and chemotherapeutic regimens that are currently used against such tumors. The growth of Daoy, SWB77, and D-54 xenografts in athymic mice was arrested after the depletion of...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Kokkinakis DM,Hoffman RM,Frenkel EP,Wick JB,Han Q,Xu M,Tan Y,Schold SC

    更新日期:2001-05-15 00:00:00

  • A Novel MIF Signaling Pathway Drives the Malignant Character of Pancreatic Cancer by Targeting NR3C2.

    abstract::Pancreatic cancers with aberrant expression of macrophage migration inhibitory factor (MIF) are particularly aggressive. To identify key signaling pathways that drive disease aggressiveness in tumors with high MIF expression, we analyzed the expression of coding and noncoding genes in high and low MIF-expressing tumor...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-15-2841

    authors: Yang S,He P,Wang J,Schetter A,Tang W,Funamizu N,Yanaga K,Uwagawa T,Satoskar AR,Gaedcke J,Bernhardt M,Ghadimi BM,Gaida MM,Bergmann F,Werner J,Ried T,Hanna N,Alexander HR,Hussain SP

    更新日期:2016-07-01 00:00:00

  • New chimeric anti-pancarcinoma monoclonal antibody with superior cytotoxicity-mediating potency.

    abstract::The monoclonal antibodies (MAbs) 323/A3 and 17-1A both recognize a 40-kDa carcinoma-associated epithelial glycoprotein (EGP40). MAb 17-1A has been used in many therapeutic trials as an immunotherapeutic agent to combat advanced colorectal cancer, and about 5-10% overall responses have been observed. It has been shown ...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Velders MP,Litvinov SV,Warnaar SO,Gorter A,Fleuren GJ,Zurawski VR Jr,Coney LR

    更新日期:1994-04-01 00:00:00

  • Seasonal and geographical changes of spontaneous skin papillomas in the Japanese newt Cynops pyrrhogaster.

    abstract::The occurrence of spontaneous skin papillomas in Japanese newts (Cynops pyrrhogaster) from Niigata prefecture in Northern Japan was monitored over four seasons covering a period of 2 years. Of 13,613 newts, 249 were found to possess papillomas. The percentage of newts with papillomas was highest in autumn, ranging fro...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Asashima M,Komazaki S,Satou C,Oinuma T

    更新日期:1982-09-01 00:00:00

  • Concomitant tumor and minor histocompatibility antigen-specific immunity initiate rejection and maintain remission from established spontaneous solid tumors.

    abstract::Nonmyeloablative hematopoietic cell transplantation can cure patients with hematologic malignancies but has reported limited success against solid tumors. This is possibly because of profound peripheral tolerance mechanisms and/or suboptimal tumor recognition by effector T lymphocytes. We report that in mice developin...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-09-4253

    authors: Hess Michelini R,Freschi M,Manzo T,Jachetti E,Degl'Innocenti E,Grioni M,Basso V,Bonini C,Simpson E,Mondino A,Bellone M

    更新日期:2010-05-01 00:00:00

  • Development, Function, and Clinical Significance of Plasmacytoid Dendritic Cells in Chronic Myeloid Leukemia.

    abstract::Plasmacytoid dendritic cells (pDC) are the main producers of a key T-cell-stimulatory cytokine, IFNα, and critical regulators of antiviral immunity. Chronic myeloid leukemia (CML) is caused by BCR-ABL, which is an oncogenic tyrosine kinase that can be effectively inhibited with ABL-selective tyrosine kinase inhibitors...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-18-1477

    authors: Inselmann S,Wang Y,Saussele S,Fritz L,Schütz C,Huber M,Liebler S,Ernst T,Cai D,Botschek S,Brendel C,Calogero RA,Pavlinic D,Benes V,Liu ET,Neubauer A,Hochhaus A,Burchert A

    更新日期:2018-11-01 00:00:00

  • Inflammatory, proliferative, and neoplastic lesions at the site of metallic identification ear tags in Wistar [Crl:(WI)BR] rats.

    abstract::During a 2-yr study of carcinogenesis by CdCl2 in male Wistar [Crl:(WI)BR] rats, weekly clinical observations during the last 6 mo of the study revealed many cases of persistent tumor-like masses at the site of the metal identification tags in the ears of the animals. A total of 14 tumors (mostly compound osteosarcoma...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Waalkes MP,Rehm S,Kasprzak KS,Issaq HJ

    更新日期:1987-05-01 00:00:00

  • Increased expression and processing of the Alzheimer amyloid precursor protein in pancreatic cancer may influence cellular proliferation.

    abstract::Abnormal cleavage of amyloid precursor protein (APP) in the central nervous system has been linked to the development of Alzheimer's disease. Recent work has identified additional roles for APP in peripheral tissue, such as cellular proliferation and motility. APP undergoes proteolytic processing to release a soluble ...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Hansel DE,Rahman A,Wehner S,Herzog V,Yeo CJ,Maitra A

    更新日期:2003-11-01 00:00:00

  • Cardiac glycosides inhibit p53 synthesis by a mechanism relieved by Src or MAPK inhibition.

    abstract::p53 is regulated at multiple levels. We report here that p53, in multiple lines of human cancer cells, is down-regulated by cardiac glycoside drugs digoxin and ouabain, potent inhibitors of Na(+)/K(+)-ATPase. These drugs reduced the basal levels of p53 protein at nanomolar concentrations in a dose-, time-, and cancer ...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-09-0891

    authors: Wang Z,Zheng M,Li Z,Li R,Jia L,Xiong X,Southall N,Wang S,Xia M,Austin CP,Zheng W,Xie Z,Sun Y

    更新日期:2009-08-15 00:00:00

  • Pharmacokinetic and phase I evaluation of esorubicin (4'-deoxydoxorubicin) by continuous infusion over forty-eight hours in patients with leukemia.

    abstract::Sixteen patients with previously treated acute nonlymphocytic leukemia or chronic myelogenous leukemia in blast crisis were given one to three courses of esorubicin by continuous infusion over 48 h. Dosage levels extended from 35 to 85 mg/m2. Four patients showed partial responses of short duration. Nonhematological t...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Kreis W,Rottach C,Budman DR,Chan K,Schulman P,Allen SL,Weiselberg L,Vinciguerra V

    更新日期:1988-10-01 00:00:00