Abstract:
OBJECTIVE:To study the pharmacokinetics of neamine in rats and to evaluate its anti-cervical cancer activity. METHODS:The plasma level of neamine was determined by HPLC-ELSD. Pharmacokinetic parameters were calculated using DAS 2.0 software. Tissue microarray analysis was conducted to examine angiogenin (ANG) expression in normal and cancerous cervical tissues and to determine its correlation with clinical and pathologic presentations of cervical cancers. The anti-cervical cancer activity of neamine was assessed both in vitro and in vivo. RESULTS:After intravenous (i.v.) administration of 15, 30, and 60 mg kg(-1) neamine, the pharmacokinetic parameters were as follows: AUC(0-t), 9,398.0 ± 653.4, 19,235.2 ± 2,939.0, and 35,437.7 ± 3,772.2 mg L(-1) min; C max, 170.8 ± 13.1, 353.3 ± 15.8, and 464.0 ± 33.1 mg L(-1); T 1/2, 34.9 ± 4.1, 46.8 ± 5.1, and 58.0 ± 12.5 min, respectively. The bioavailability of neamine administered through intramuscular, subcutaneous, intraperitoneal and intragastric route was 14.0 ± 3.0, 8.4 ± 0.6, 6.5 ± 3.3, and 3.1 ± 0.2 %, respectively. Up-regulated ANG expression and increased nuclear translocation were observed in cervical cancers as compared to normal cervical tissues. Moreover, upregulation of ANG was positively correlated with primary tumor invasion. Neamine inhibited ANG-induced HUVEC and HeLa cell proliferation as well as nuclear translocation of ANG. Consistently, neamine inhibited both the establishment and progression of xenograft human cervical cancers in athymic mice. CONCLUSIONS:The bioavailability of neamine administered through extravascular routes was low. The half-life of neamine through i.v. administration was short. This suggests that a higher dosing frequency in order to maintain a therapeutic effect. Neamine holds potential against cervical cancer. The mechanisms of neamine inhibition are through blocking nuclear translocation of ANG thereby inhibiting both angiogenesis and cancer cell proliferation.
journal_name
Cancer Chemother Pharmacoljournal_title
Cancer chemotherapy and pharmacologyauthors
Liu Y,Zhang X,An S,Wu Y,Hu G,Wu Ydoi
10.1007/s00280-014-2658-7subject
Has Abstractpub_date
2015-03-01 00:00:00pages
465-74issue
3eissn
0344-5704issn
1432-0843journal_volume
75pub_type
杂志文章abstract:PURPOSE:To explore the safety and tolerability of combining two epigenetic drugs: decitabine (a DNA methyltransferase inhibitor) and panobinostat (a histone deacetylase inhibitor), with chemotherapy with temozolomide (an alkylating agent). The purpose of such combination is to evaluate the use of epigenetic priming to ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-014-2501-1
更新日期:2014-10-01 00:00:00
abstract:PURPOSE:Sonidegib (Odomzo) selectively inhibits smoothened and suppresses the growth of hedgehog pathway-dependent tumors. A population pharmacokinetic (PK) analysis of sonidegib in healthy subjects and patients with advanced solid tumors was conducted to characterize PK, determine variability, and estimate covariate e...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-016-2982-1
更新日期:2016-04-01 00:00:00
abstract:PURPOSE:The ErbB family members are protein tyrosine kinases, which play a crucial role in the signal transduction pathways that regulate key cellular functions. Overexpression of the ErbB family members is associated with oncogenicity, metastatic potential, cell proliferation, apoptosis, angiogenesis, and prognosis in...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,评审
doi:10.1007/s00280-011-1748-z
更新日期:2011-12-01 00:00:00
abstract::The selective Aurora-A kinase inhibitor MLN8237 is in clinical trials for hematologic malignancies, ovarian cancer and other solid tumors. We previously showed that MLN8237 is potently antiproliferative toward standard monolayer-cultured glioblastoma cells. We have now investigated the effect of MLN8237 with and witho...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-014-2430-z
更新日期:2014-05-01 00:00:00
abstract:OBJECTIVE:To characterize the population pharmacokinetics of plitidepsin (Aplidin) in cancer patients. METHODS:A total of 283 patients (552 cycles) receiving intravenous plitidepsin as monotherapy at doses ranging from 0.13 to 8.0 mg/m(2) and given as 1- or 24-h infusions every week; 3- or 24-h infusion biweekly; or 1...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,meta分析
doi:10.1007/s00280-008-0841-4
更新日期:2009-06-01 00:00:00
abstract::We compared the safety and efficacy in mice with peritoneal carcinomatosis of two etoposide formulations: an aqueous solution (Etp-sol) and particles suspended in oil (the addition products of iodine and the ethyl esters of the fatty acids obtained from poppy-seed oil (Lipiodol) or sesame oil; Etp-oil). We also invest...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00685848
更新日期:1995-01-01 00:00:00
abstract::The interaction between cisplatin (cDDP) and tamoxifen (TAM) was evaluated in the human head and neck squamous-carcinoma cell lines UM-SCC-10B and UM-SCC-5. Synergy between cDDP and TAM was demonstrated in the UM-SCC-10B cell line. Concordant with the synergistic effect between cDDP and TAM, the rate of development of...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00686837
更新日期:1995-01-01 00:00:00
abstract:OBJECTIVE:SDX-101 is the non-cyclooxygenase 2-inhibiting R-enantiomer of the non-steroid anti-inflammatory drug etodolac, and has anti-tumour activity in chronic lymphocytic leukaemia (CLL). SDX-308 and SDX-309 are more potent, structurally related indole-pyran analogues of SDX-101. The current study was performed to i...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-006-0400-9
更新日期:2007-09-01 00:00:00
abstract:PURPOSE:This study aimed to determine the correlation between DNA repair enzyme O6-methylguanine DNA methyltransferase (MGMT) status and the response to streptozocin in advanced well-differentiated pancreatic neuroendocrine tumors (WD panNETs). METHODS:To test the hypothesis that MGMT deficiency was required for an al...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-018-3700-y
更新日期:2019-01-01 00:00:00
abstract:PURPOSE:Imatinib mesylate (Imatinib), clinically employed for chronic myeloid leukemia and gastrointestinal stromal tumors, is a selective inhibitor of the tyrosine kinases, c-abl, c-kit and PDGFRs. Due to the frequent expression of these genes in breast cancer cells, the clinical efficacy of Imatinib has recently been...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-010-1394-x
更新日期:2011-04-01 00:00:00
abstract:PURPOSE:The potential use of combined therapy is under intensive study including the association between classical cytotoxic and genes encoding toxic proteins which enhanced the antitumour activity. The main aim of this work was to evaluate whether the gef gene, a suicide gene which has a demonstrated antiproliferative...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-009-1135-1
更新日期:2010-05-01 00:00:00
abstract:BACKGROUND:Recently, melatonin has been associated with cancer both in vitro and in vivo. However, the value of melatonin in the treatment of cancer remains disputable. Hence, we performed a systematic review of randomized controlled trials (RCTs) of melatonin in solid tumor cancer patients and observed its effect on t...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,meta分析,评审
doi:10.1007/s00280-012-1828-8
更新日期:2012-05-01 00:00:00
abstract:PURPOSE:Olaratumab is a recombinant human IgG1 monoclonal antibody against PGDFRα. Olaratumab plus doxorubicin improved survivalversus doxorubicin in an open-label, randomised phase 2 soft tissue sarcoma (STS) trial. We characterised the olaratumab exposure-response relationship for progression-free survival (PFS), ove...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1007/s00280-018-3723-4
更新日期:2019-01-01 00:00:00
abstract:PURPOSE:The plasma and cerebrospinal fluid (CSF) pharmacokinetics of the camptothecin analogs, 9-aminocamptothecin (9-AC) and irinotecan, were studied in a nonhuman primate model to determine their CSF penetration. METHODS:9-AC, 0.2 mg/kg (4 mg/m2) or 0.5 mg/kg (10 mg/m2), was infused intravenously over 15 min and iri...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s002800050768
更新日期:1998-01-01 00:00:00
abstract:BACKGROUND:Cancer has become one of the global health issues and it is the life-threatening disease characterized by unrestrained growth of cells. Despite various advances being adopted by chemotherapeutic management, the use of the current anticancer drugs such as Doxorubicin, Asparginase, Methotrexate, Vincristine re...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-017-3414-6
更新日期:2017-11-01 00:00:00
abstract::A sensitive solid-phase-extraction and high-performance liquid chromatography (HPLC) method has been developed to investigate the pharmacokinetics and metabolism of the hypoxic-cell cytotoxic agent tirapazamine (1,2,4-benzotriazine-3-amine 1,4-di-N-oxide; WIN 59075, SR 4233), currently in phase I/II studies in the Uni...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00685859
更新日期:1995-01-01 00:00:00
abstract:PURPOSE:Metronomic chemotherapy, at a minimally toxic dose and with a frequent schedule, is a potentially novel approach to the control of advanced cancer disease via a different mechanism from maximum tolerable doses chemotherapy. Taking advantage of the potential effectiveness of metronomic therapy, tegafur/uracil (U...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s00280-006-0377-4
更新日期:2007-08-01 00:00:00
abstract::Carmustine (BCNU) has proved to be of value against a variety of primary brain tumors. This agent exhibits a steep dose-response curve in in vitro and animal tumor models and has been proposed for use in high-dose chemotherapy as a single agent or in combination. We conducted a phase II study to assess high-dose BCNU ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s002800050586
更新日期:1997-01-01 00:00:00
abstract::In the original article, corresponding author's given name and family name are flipped. It should be "Siqing Fu" rather than "Fu Siqing". ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 已发布勘误
doi:10.1007/s00280-016-3002-1
更新日期:2016-04-01 00:00:00
abstract::Both the capacity of healthy human, cancer patient, and mouse plasma proteins to bind flavone acetic acid (FAA) and the qualitative differences in the plasma protein-binding site were studied. The binding capacity of plasma proteins for FAA was saturated within the therapeutic range in both species. The binding of FAA...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00689272
更新日期:1990-01-01 00:00:00
abstract:PURPOSE:Patupilone (EPO906) is a novel potent microtubule stabilizer, which has been evaluated for cancer treatment. A novel physiologically based pharmacokinetics (PBPK) model was developed based on nonclinical data to predict the disposition of patupilone in cancer patients. METHODS:After a single intravenous dose (...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-012-1863-5
更新日期:2012-06-01 00:00:00
abstract::A phase I trial of indicine-N-oxide was carried out in 12 children with solid tumors and in 16 with leukemia. Doses of 5, 6, and 7.5 g/m2 were given parenterally as a 15-min infusion every 3 weeks. The maximum tolerated dose in patients with solid tumors was 7.5 g/m2 and the dose-limiting toxicity was myelosuppression...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF02897298
更新日期:1990-01-01 00:00:00
abstract::The dextromethorphan-O-demethylase activity determined in human liver microsomes was used to screen various anticancer drugs for their ability to inhibit this cytochrome CYP2D6-dependent activity. Competitive inhibition indicates that the drug binds the enzyme and is potentially subjected to a polymorphic metabolism. ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00685896
更新日期:1993-01-01 00:00:00
abstract::We evaluated the antiproliferative and the proapoptotic ability of gemcitabine in three non-small-cell lung cancer (NSCLC) cell lines. NCI-H292 (mucoepidermoid carcinoma), NCI-CorL23 (large-cell carcinoma) and NCI-Colo699 (adenocarcinoma) cells were cultured with and without 0.5, 0.05 and 0.005 microM gemcitabine for ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s002800000183
更新日期:2000-01-01 00:00:00
abstract::Cancer is a major health issue worldwide and the global burden of cancer is expected to reduce the costs of treatment as well as prolong the survival time. One of the promising approaches is drug repurposing, because it reduces costs and shortens the production cycle of research and development. Disulfiram (DSF), whic...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,评审
doi:10.1007/s00280-020-04216-8
更新日期:2021-01-10 00:00:00
abstract:PURPOSE:Several studies have identified amino acid residues located on the hydrophobic side of the helix that forms transmembrane domain 6 (TM6) of the ABC transporter P-glycoprotein (Pgp) as being important for function. The purpose of this study was to determine if alterations to residues on the hydrophilic side coul...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s002800100354
更新日期:2001-11-01 00:00:00
abstract:PURPOSE:Although treatment of melanoma with BRAF inhibitors and immune checkpoint inhibitors achieves a high response rate, a subset of melanoma patients with intrinsic and acquired resistance are insensitive to these therapeutics, so to improve melanoma therapy other target molecules need to be found. Here, we screene...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-017-3317-6
更新日期:2017-06-01 00:00:00
abstract::A new synthetic tripeptide (p-F-Phe-m-bis-(2-chloroethyl)amino-Phe-Met ethoxy HCl), PTT.119, was demonstrated to have significant cancericidal activity against seven in vitro tumor cell lines of different origins and etiologies and against primary human AMML, ALL, and hairy cell leukemias. Viabilities of each murine t...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00254592
更新日期:1984-01-01 00:00:00
abstract:PURPOSE:We have previously reported that intra-arterial chemotherapy prolongs the survival of patients with advanced HCC (aHCC); however, whether the response to intra-arterial chemotherapy depends on the etiology of underlying liver cirrhosis (LC) is still unknown. AIM:The aim of this study was to assess any influenc...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-008-0851-2
更新日期:2009-06-01 00:00:00
abstract::Any approach applied to drug discovery and development by the medical community and pharmaceutical industry has a direct impact on the future availability of improved, novel, and curative therapies for patients with cancer. By definition, drug discovery is a complex learning process whereby research efforts are direct...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,评审
doi:10.1007/s00280-003-0653-5
更新日期:2003-07-01 00:00:00