Abstract:
:Alpha-tocopheryloxy acetic acid (α-TEA) is an ether derivative of vitamin E and has been shown to suppress tumor growth in various murine and human xenograft tumor models, including melanoma, breast, lung, prostate, and ovarian cancers. The purpose of this study was to assess its safety and pharmacokinetics after repeat dosing in a preclinical murine model. Male and female mice received α-TEA doses of 100, 300, or 1500 mg/kg/day by daily oral gavage for 28 days. α-TEA serum levels were determined weekly by high-performance liquid chromatography with mass spectrometric detection. After 28 days of dosing, complete blood counts were taken, blood chemistry was analyzed, and histology was performed. Pharmacokinetic parameters were determined after single dosing. There was no mortality, and we found no clinical signs of toxicity in any of the α-TEA doses tested. Histopathological evaluation of major organs (heart, lung, kidney, liver, spleen, jejunum, ileum, and cecum) revealed no significant α-TEA treatment-related lesions. Blood counts revealed low-grade anemia but no other significant differences between treatment and control groups. Blood chemistry revealed moderate liver toxicity that was dose dependent and was absent in the lowest dose group. There were no significant sex-specific differences in the toxicity profile. The half-life of orally administered α-TEA was determined to be 52 h. This is the first report comprehensively evaluating the toxicity profile of this novel anticancer drug and will facilitate the design of clinical trials to evaluate the safety and antitumor efficacy of α-TEA in patients with cancer.
journal_name
Anticancer Drugsjournal_title
Anti-cancer drugsauthors
Hahn T,Akporiaye ETdoi
10.1097/CAD.0b013e32834f6271subject
Has Abstractpub_date
2012-04-01 00:00:00pages
455-64issue
4eissn
0959-4973issn
1473-5741journal_volume
23pub_type
杂志文章abstract::The therapeutic effects of the new anti-angiogenesis factor TNP-470 were examined against carcinomatous peritonitis in mice. In the first experiment using carcinomatous peritonitis caused by i.p. inoculation of 10(6) M5076 tumor cells, TNP-470 solution was injected i.p. in a bolus of 50 mg/kg body weight into two grou...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-199506000-00012
更新日期:1995-06-01 00:00:00
abstract::We have previously shown that L-methionine inhibits proliferation of breast, prostate, and colon cancer cells. This study extends these findings to BXPC-3 (mutated p53) and HPAC (wild-type p53) pancreatic cancer cells and explores the reversibility of these effects. Cells were exposed to L-methionine (5 mg/ml) for 7 d...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0000000000000038
更新日期:2014-02-01 00:00:00
abstract::In a recent study we demonstrated that recombinant human growth hormone (r-hGH; Saizen) delayed tumor-induced cachexia in human tumor xenografts in vivo. Such a therapeutic effect could have a great impact in the supportive care of advanced cancer patients. Before large clinical studies are initiated possible growth s...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-200009000-00011
更新日期:2000-09-01 00:00:00
abstract::In the present study we investigated the enhancement of cytotoxicity of peritoneal macrophages induced by OK-432. Rats received an i.p. injection of OK-432 at doses of 0.1, 0.5 or 1.0 KE/rat. Two days later, rats were sacrificed and peritoneal macrophages were isolated. Then the number of macrophages was counted, and ...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-200110000-00010
更新日期:2001-10-01 00:00:00
abstract::Overexpression of the multidrug resistance MDR1 gene product P-glycoprotein and/or the multidrug resistance-associated protein MRP confers multidrug resistance to cancer cells. The pipecolinate derivative VX-710 has previously been demonstrated to reverse MDR1-mediated multidrug resistance at concentrations of 0.5-2.5...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-199702000-00005
更新日期:1997-02-01 00:00:00
abstract::A combined treatment with conventional chemotherapies can enhance the effectiveness of chemotherapeutic agents against cancers. Here, we have shown that the naturally occurring triterpenoids synergistically enhance the response of cervical cancer cells to taxol. Of the triterpenoid compounds, pristimerin enhanced the ...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0b013e328347181a
更新日期:2011-09-01 00:00:00
abstract::In the past decade, tumour flare reaction (TFR) was considered as a new side effect associated with immunomodulatory agents (IMiDs) and as a condition of chronic lymphocytic leukaemia (CLL). However, this phenomenon is also observed with immune checkpoint inhibitors in solid tumours. It is still poorly understood and ...
journal_title:Anti-cancer drugs
pub_type: 杂志文章,评审
doi:10.1097/CAD.0000000000000814
更新日期:2019-10-01 00:00:00
abstract::Methoxymorpholinyl doxorubicin (PNU 152243) is a morpholinyl analog possessing a methoxymorpholinyl group at the 3' position of the sugar moiety, which, compared with doxorubicin, appears to be less cardiotoxic and more cytotoxic against multidrug-resistant tumor cells. In this study, we report the anticancer activity...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/01.cad.0000132238.23050.f5
更新日期:2004-07-01 00:00:00
abstract::A new dosage form (ACR-CH) comprising aclarubicin adsorbed on activated carbon particles was designed to sustain release of aclarubicin. ACR-CH or aclarubicin aqueous solution (ACR-sol) was injected subcutaneously into the fore foot-pads of rats. ACR-CH distributed a statistically significantly higher level of aclarub...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-199106000-00006
更新日期:1991-06-01 00:00:00
abstract::The mechanism of action of a synthetic compound--2,2'-bipyridyl-6-carbothioamide--was investigated by developing tumor lines resistant to it (P388-R1.5 and P388-R4). P388-R4 is resistant to inhibitors of ribonucleotide reductase (RR) while no resistance was observed to antitumor drugs having other targets (except to b...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-199012000-00009
更新日期:1990-12-01 00:00:00
abstract::A lack of cross-resistance between the aromatase inhibitors (AIs) provides evidence to suggest that there are clinical differences between these agents. Available data from clinical trials indicate that patients exposed to nonsteroidal AIs may benefit from a steroidal compound of similar biochemical potency, and durab...
journal_title:Anti-cancer drugs
pub_type: 杂志文章,评审
doi:10.1097/01.cad.0000277875.81122.25
更新日期:2008-03-01 00:00:00
abstract::Verapamil, cyclosporin A (CsA), the cyclosporin derivative SDZ PSC 833 and the novel cyclopeptolide SDZ 280-446 were tested for their capacity to chemosensitize a P-glycoprotein (Pgp)-expressing multi-drug resistant (MDR) variant of the CEM human T lymphoblastoid cell subline (CCRF ACTD 400+). That MDR-CEM cell sublin...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:
更新日期:1993-12-01 00:00:00
abstract::Treatment of mammalian cells with chemotherapeutic drugs can result in perturbations of nucleotide pools. Monitoring these perturbations in cultured tumor cells from human sources is useful for assessment of the effect of drug therapy and a better understanding of the mechanism of action of these drugs. In this study,...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0000000000000096
更新日期:2014-07-01 00:00:00
abstract::We have synthesized and characterized doxorubicin (DOX)-loaded galactosylated gelatin nanovectors using in vitro and in vivo for targeting liver cells including hepatocarcinoma cells. Galactosylated and nongalactosylated gelatin nanovectors (GL-GN-DOX and GN-DOX) were spherical in shape and had mean sizes of about 95....
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0b013e328351424f
更新日期:2012-09-01 00:00:00
abstract::We recently established that NCPMF-60, a newly synthesized flavonoid, is an active cytotoxic component. The molecular mechanisms by which NCPMF-60 exerts its cytotoxic activity are currently unknown. In this study, we show that NCPMF-60 induces G2/M phase arrest and apoptosis in human hepatocellular carcinoma HepG2 ce...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0b013e3283405801
更新日期:2011-01-01 00:00:00
abstract::Cyclophosphamide, an alkylating agent, is currently being used for the treatment of various types of cancer, either alone or in combination with other cytostatic drugs. However, cyclophosphamide has a detrimental effect on lipid metabolism and causes hyperlipidemia in patients. Since alpha-tocopherol is known to reduc...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-199512000-00009
更新日期:1995-12-01 00:00:00
abstract::Telomerase is an enzyme responsible for telomere maintenance in almost all human cancer cells, but generally not expressed in somatic ones. Therefore, antitelomerase therapy is a potentially revolutionary therapeutic strategy, and the antitumor activity of telomerase inhibitors (TI) has been studied extensively recent...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0000000000000508
更新日期:2017-08-01 00:00:00
abstract::Esophageal cancer is one of the fatal cancers around the world. Dexmedetomidine (DEX) is widely used during anesthesia of esophageal cancer surgery. Nevertheless, the role of DEX in the progression of esophageal cancer remains barely known. The proliferation, apoptosis and metastasis of esophageal cancer cells were de...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0000000000000934
更新日期:2020-08-01 00:00:00
abstract::1,4-Anthraquinone (AQ) was synthesized and shown to prevent L1210 leukemic cells from synthesizing macromolecules and growing in vitro. In contrast, its dihydroxy-9,10anthraquinone precursor, quinizarin, was inactive. The antitumor activity of AQ was compared to that of daunorubicin (DAU), which is structurally differ...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-200006000-00004
更新日期:2000-06-01 00:00:00
abstract::The present study aimed to entrap and characterize the morphology and antitumor effects of a dermaseptin (DStomo01) peptide in chitosan nanoparticles, in vitro. DStomo01 nanoparticles showed moderate polydispersivity, excellent colloidal stability, and slow release. It was noted that free DStomo01 induced DNA fragment...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0000000000000052
更新日期:2014-03-01 00:00:00
abstract::In a previous study, we showed that a combination of an oral fluoropyrimidine anticancer agent (S-1) and gemcitabine (GEM) had synergistic effects on cell growth and cell cycle arrest in the pancreatic cancer cell line MIA PaCa-2. Therefore, we conducted further mechanistic studies using the pancreatic cancer cell lin...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0b013e328350e8c7
更新日期:2012-06-01 00:00:00
abstract::The effects of vitamin C on the oxidative stress in blood platelets induced by cisplatin were studied. In the presence of vitamin C we measured in blood platelets the production of thiobarbituric acid reactive substances (TBARS), the generation of superoxide radicals (O2*-), other reactive oxygen species (H2O2, single...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-200007000-00010
更新日期:2000-07-01 00:00:00
abstract::We investigated whether Ukrain modulates the malignant phenotype of clear cell renal cell carcinoma (ccRCC) cells Caki-1, Caki-2, and ACHN treated with four doses (5, 10, 20, and 40 μmol/l) for 24 and 48 h. The epithelial-to-mesenchymal transition markers E-cadherin, β-catenin, and vimentin were analyzed by immunofluo...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0b013e328346c7f7
更新日期:2011-09-01 00:00:00
abstract::Imexon is an investigational anti-cancer agent, pharmaceutically formulated as a lyophilized solid for i.v. infusion requiring reconstitution and subsequent dilution in infusion fluid before infusion. Imexon contains a highly reactive aziridine ring in its structure, which limits its stability in aqueous solutions. In...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/01.cad.0000172833.70444.ba
更新日期:2005-08-01 00:00:00
abstract::Our previous studies have demonstrated the in-vitro and in-vivo targeting of a generation-5 (G5) dendrimer-based multifunctional conjugate, which used folic acid (FA) as the targeting agent and methotrexate (MTX) as the chemotherapeutic drug. For the synthesized G5-FA-MTX nanodevice conjugate to be clinically applicab...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0b013e3282f28842
更新日期:2008-02-01 00:00:00
abstract::We have reported a 33% partial response rate with acceptable toxicity using weekly 24-h infusion of high-dose 5-fluorouracil (5-FU) and leucovorin (LV) in patients with far advanced biliary tract cancers (BTC). In this study, we added mitomycin (MMC) to 5-FU and LV in an attempt to improve the response rate and surviv...
journal_title:Anti-cancer drugs
pub_type: 临床试验,杂志文章
doi:10.1097/00001813-200104000-00006
更新日期:2001-04-01 00:00:00
abstract::Colorectal cancer occurs throughout the world but is most common in developed countries. Cancer progression is believed to be driven by genetic mutations in this complex condition. Risk factors for developing colorectal cancer include a genetic family history, long-term ulcerative colitis, and colonic polyps. The use ...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0000000000000708
更新日期:2019-02-01 00:00:00
abstract::Gallbladder carcinoma is the most common malignancy of the biliary tract and is associated with a very poor outcome. The aim of the present study was to investigate the effects of oxymatrine (OM) on gallbladder cancer cells and the possible mechanism of its effects. The effects of OM on the proliferation of gallbladde...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0000000000000124
更新日期:2014-10-01 00:00:00
abstract::Previous in vitro biochemical studies have revealed that the antitumor drug leinamycin causes oxidative DNA damage and DNA alkylation. However, it is still not clear whether the same mechanism(s) of action operate in cultured human tumor cells. Here, we evaluated the effects of leinamycin in the human pancreatic carci...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/01.cad.0000136886.72917.6f
更新日期:2004-08-01 00:00:00
abstract::One hundred and thirty-one children with a median age of 5 years were administered Navoban (tropisetron), a selective antagonist of the serotonin receptor (5-HT3), dosed once daily at 0.2 mg/kg (with a maximum of 5 mg daily) in a study aimed at evaluating the prevention of nausea and vomiting induced by anti-cancer ch...
journal_title:Anti-cancer drugs
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1097/00001813-199502001-00003
更新日期:1995-02-01 00:00:00