Abstract:
:Targeting oncogenic signaling pathways by small molecules has emerged as a potential treatment strategy for cancer. reactivation of p53 and induction of tumor cell apoptosis (RITA) is a promising anticancer small molecule that reactivates p53 and induces exclusive apoptosis in tumor cells. Less well appreciated was the possible effect of small molecule RITA on p53-null leukemia cells. In this study, we demonstrated that RITA has potent antileukemic properties against p53-null chronic myeloid leukemia (CML)-derived K562 cells. RITA triggered apoptosis through caspase-9 and caspase-3 activation and poly (ADP-ribose) polymerase cleavage. RITA decreased STAT5 tyrosine phosphorylation, although it did not inhibit phosphorylation of the direct BCR-ABL substrate CrkL. Real-time PCR analysis showed that RITA downregulates antiapoptotic STAT5 target genes Bcl-xL and MCL-1. The downregulation of nuclear factor-κB (NF-κB), as evidenced by inhibition of IκB-α phosphorylation and its degradation, was associated with inhibition of Akt phosphorylation in RITA-treated cells. Furthermore, consistent with the decrease of mRNA levels, protein levels of the nuclear factor-κB-regulated antiapoptotic (cIAP1, XIAP, and Bcl-2) and proliferative (c-Myc) genes were downregulated by RITA in K562 cells. In conclusion, the ability of RITA to inhibit prosurvival signaling pathways in CML cells suggests a potential application of RITA in CML therapeutic protocols.
journal_name
Anticancer Drugsjournal_title
Anti-cancer drugsauthors
Mobaraki RN,Karimi M,Alikarami F,Farhadi E,Amini A,Bashash D,Paridar M,Kokhaei P,Rezvani MR,Kazemi A,Safa Mdoi
10.1097/CAD.0000000000000651subject
Has Abstractpub_date
2018-10-01 00:00:00pages
847-853issue
9eissn
0959-4973issn
1473-5741journal_volume
29pub_type
杂志文章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::Low doses of drugs delivered at close, regular intervals are increasingly being used to manage patients with different neoplasms. Despite the good tolerability, treatment-related adverse events still occur following metronomic protocols. The aim of this study was to retrospectively investigate whether polymorphisms of...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0000000000000429
更新日期:2016-11-01 00:00:00
abstract::Bevacizumab has been shown to be effective combined with chemotherapy for first-line treatment of advanced colorectal cancer, but little information is available about its efficacy and safety in patients who may be candidates for surgery at any time during the disease. The case history of a female patient with colorec...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/01.cad.0000349778.09614.54
更新日期:2009-04-01 00:00:00
abstract:UNLABELLED:Thirty-two evaluable patients with squamous cell cancer of the cervix were treated with i.v. paclitaxel 250 mg/m2 over 3 h every 21 days. They received standard premedications and granulocyte colony stimulating factor (G-CSF) support (5 micrograms/kg/day). Median (range) age was 49 (29-81) years and performa...
journal_title:Anti-cancer drugs
pub_type: 临床试验,杂志文章
doi:10.1097/00001813-199708000-00002
更新日期:1997-08-01 00:00:00
abstract::A new dosage formulation of 5-fluorouracil incorporated in microspheres (5-FU-MS) was developed for the treatment of peritoneal carcinomatosis. We studied the acute toxicity and side effects of i.p. 5-FU-MS in mice. The 50% lethal dose value for 5-FU-MS was 535.4 mg/kg of 5-FU, which was 2.22 times that of the aqueous...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-199609000-00010
更新日期:1996-09-01 00:00:00
abstract::Vinblastine at doses ranging from 0.2 to 6 mg/kg body weight was administered i.p. to mice in the absence or presence of the drugs PSC 833, cyclosporin A, mefloquine, quinidine and dipyridamole, all compounds that modulate the multidrug resistance pump and thus increase the accumulation of this cytotoxin in drug-resis...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-199601000-00007
更新日期:1996-01-01 00:00:00
abstract::Two young adults that presented with intra-abdominal desmoplastic small cell tumors (DSCT) without any evidence of a primary site are described. Both cases share the clinical characteristic features of this rare tumor which include predominant intra-abdominal location as initial presentation, nesting pattern of growth...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:
更新日期:1996-02-01 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::We conducted a phase I study to determine the maximum tolerated dose, the recommended dose and the safety profile of S-1 and carboplatin combination regimen in the treatment of patients with advanced non-small-cell lung cancer. Chemotherapy-naive patients with advanced non-small-cell lung cancer were treated with S-1 ...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0b013e32801265eb
更新日期:2007-04-01 00:00:00
abstract::The immunotherapy significantly improved survival of non-small cell lung cancer patients, but it may cause immune-related adverse events, which are severe in less than 10% of cases. We report the case of one patient who developed myositis and myasthenia during nivolumab treatment for metastatic lung squamous carcinoma...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0000000000000903
更新日期:2020-06-01 00:00:00
abstract::Results are summarized for two phase II studies of docetaxel as first-line therapy for advanced squamous cell carcinoma of the head and neck (SCCHN) and one study of docetaxel as second-line therapy for advanced soft tissue sarcomas. In all three studies, docetaxel was administered at a dose of 100 mg/m2 by intravenou...
journal_title:Anti-cancer drugs
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1097/00001813-199507004-00004
更新日期:1995-07-01 00:00:00
abstract::Substitutions in thiophene structure give rise to new derivatives with different biological and pharmacological activities. The present study investigated the cytotoxicity activity of some thiophene derivatives in breast cancer cells maintained in two-dimensional (2D) or in three-dimensional (3D) culture and evaluated...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0000000000000581
更新日期:2018-02-01 00:00:00
abstract::Uterine sarcomas are rare tumors constituting 1-3% of all uterine malignancies. These tumors are characterized by aggressive growth and by poor overall prognosis. There is much controversy concerning diagnostic criteria and the great variation in histology, as well as the role of radiotherapy and chemotherapy in the m...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-199102000-00004
更新日期:1991-02-01 00:00:00
abstract::The delivery formulation 5-FU-MS [5-fluorouracil (5-FU) incorporated in microspheres composed of a poly(glycolide-co-lactide) matrix] slowly releases 5-FU over 3 weeks. 5-FU-MS delivers higher concentrations of the drug to the i.p. tissues for a longer period of time with lower blood plasma concentrations than does an...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-199803000-00012
更新日期:1998-03-01 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::Docetaxel has shown promise for the treatment of hormone-refractory prostate cancer and has become the standard of care. The flare phenomenon is a known entity in androgen-deprivation therapy of advanced prostate cancer and it has also been described in palliative chemotherapy of hormone-refractory prostate cancer. Th...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/01.cad.0000231468.69535.97
更新日期:2006-09-01 00:00:00
abstract::The results of several preclinical and clinical studies were reported by oncology professionals at the 43rd American Society of Clinical Oncology (ASCO) meeting, the largest international forum in which the latest achievements in cancer research are annually presented. The central theme this year was 'Translating Rese...
journal_title:Anti-cancer drugs
pub_type:
doi:10.1097/CAD.0b013e3282f2c938
更新日期:2008-02-01 00:00:00
abstract::The antitumor action of bestatin is considered to be an indirect action mediated by T-cells. Therefore, we investigated the effects of bestatin on the differentiation and proliferation of human precursor T-cells using a colony formation technique. Bestatin did not increase the overall number of T-cell colonies, but it...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-199102000-00005
更新日期:1991-02-01 00:00:00
abstract::Combretastatin A4 phosphate (CA4P) is a prodrug that selectively destroys tumor blood vessels, and has shown efficacy as a targeted anticancer drug in both animal models and clinical trials. The aims of this single-center, open label, phase I clinical trial were to investigate the safety and tolerability of CA4P admin...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0000000000000070
更新日期:2014-04-01 00:00:00
abstract::Clinical empiricism has recognized resistant breast cancer as a privileged target for docetaxel (Taxotere). This worldwide registration will offer medical oncologists the opportunity to develop new indications for docetaxel. Pharmacokinetics, preclinical optimal combination and clinical practice will constitute the ra...
journal_title:Anti-cancer drugs
pub_type: 杂志文章,评审
doi:
更新日期:1996-08-01 00:00:00
abstract::The in-vitro growth inhibition of cancer and normal cell lines caused by mixed or covalently linked antimetabolites should clarify whether the conjugation of antimetabolites influences cell sensitivity and growth inhibition in a manner that differs from an equimolar mixture of the same antimetabolites or not. Growth i...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0b013e32835e5996
更新日期:2013-04-01 00:00:00
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journal_title:Anti-cancer drugs
pub_type: 杂志文章,评审
doi:10.1097/CAD.0b013e32833dad91
更新日期:2010-10-01 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::Large (>6 microm) rigid microparticles (MPs) become passively entrapped within the lungs after intravenous (i.v.) injection making them an attractive and highly efficient alternative to inhalation for pulmonary delivery. In this study, PEGylated 6 microm polystyrene MPs with multiple copies of the norvaline (Nva) alph...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0b013e328332a322
更新日期:2010-01-01 00:00:00
abstract::There is growing interest in the discovery of bioactive metabolites from endophytes as an alternative source of therapeutics. Identification of their therapeutic targets is essential in understanding the underlying mechanisms and enhancing the resultant therapeutic effects. As such, bioactive compounds produced by end...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0b013e3283635a47
更新日期:2013-09-01 00:00:00
abstract::The aim of this review is to summarize currently available information on the rapid screening and initial characterization of the different mechanisms of resistance to hydrophilic [e.g. methotrexate (MTX)] and lipophilic antifolates [e.g. trimetrexate (TMTX)] in cultured mammalian cells using fluorescein-methotrexate ...
journal_title:Anti-cancer drugs
pub_type: 杂志文章,评审
doi:10.1097/00001813-199310000-00002
更新日期:1993-10-01 00:00:00
abstract::Dihydroartemisinin (DHA), a semisynthetic derivative of artemisinin, has recently shown antitumor activity in various cancer cells. Its effect on pancreatic cancer is, however, unknown and the mechanism is unclear. The study aims to investigate its antitumor activity and underlying mechanisms in human pancreatic cance...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0b013e3283212ade
更新日期:2009-02-01 00:00:00
abstract::Management of gastric cancer in older adults is challenging. Perioperative treatment with epirubicin, cisplatin, and 5-fluorouracil combination chemotherapy and surgery is considered the standard treatment of locally advanced gastric adenocarcinoma. However, this chemotherapy regimen is not well tolerated in older adu...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0b013e32834a2c16
更新日期:2011-11-01 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::Interleukin-12 (IL-12) has important immunomodulatory effects on T and natural killer (NK) cells that might be exploited in anticancer treatment. Murine IL-12 models have shown antimetastatic and antitumor effects against murine tumors in vivo. Data on the effects of human IL-12 on human tumors are confined to 51Cr-re...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-199605000-00006
更新日期:1996-05-01 00:00:00