Biochemical and molecular effects of UCN-01 in combination with 5-fluorodeoxyuridine in A431 human epidermoid cancer cells.

Abstract:

:Concurrent and pre-exposure of A431 human epidermoid cancer cells to UCN-01, an investigational anticancer drug, with 5-fluoro--2'-deoxyuridine (FdUrd), which targets thymidylate synthase, produced more than additive cytotoxicty. A 24-h exposure to 10 nM FdUrd led to inhibition of TS, a 2.5-fold increase in total thymidylate synthase protein content, profound dTTP depletion and a 6.3-fold increase in the ratio of dATP to dTTP, but did not cause single-strand breaks in DNA. However, FdUrd enhanced UCN-01-associated DNA strand breaks. Concurrent thymidine exposure led to repletion of dTTP pools, and cytoprotection against FdUrd alone and with UCN-01. UCN-01 arrested cells in G1, decreased the percentage of FdUrd-treated cells in S phase and reduced FdUrd-DNA incorporation, suggesting the latter was not important for cytotoxicity. Delayed induction of high molecular mass DNA fragmentation and poly(ADP-ribose) polymerase cleavage was observed with the combination of UCN-01 and FdUrd. These findings suggest that while FdUrd-mediated deoxynucleotide imbalance alone was insufficient to induce apoptosis in this p53-mutant cell line, it magnified UCN-01's effects, most likely by interfering with DNA repair. The clinical evaluation of UCN-01 combined with 5-fluoropyrimidines may be of interest.

journal_name

Anticancer Drugs

journal_title

Anti-cancer drugs

authors

Grem JL,Danenberg KD,Kao V,Danenberg PV,Nguyen D

doi

10.1097/00001813-200203000-00008

subject

Has Abstract

pub_date

2002-03-01 00:00:00

pages

259-70

issue

3

eissn

0959-4973

issn

1473-5741

journal_volume

13

pub_type

杂志文章
  • A suramin derivative induces enterocyte-like differentiation of human colon cancer cells without lysosomal storage disorder.

    abstract::Suramin is a polysulfonated naphthylurea currently investigated for the treatment of advanced malignancy. We have previously reported that suramin was a potent inducer of the differentiation of the human colic adenocarcinoma cell clone HT29-D4 (Fantini et al., J Biol Chem, 1989; 264: 10282-10286). In this report, we s...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/00001813-199010000-00011

    authors: Baghdiguian S,Nickel P,Marvaldi J,Fantini J

    更新日期:1990-10-01 00:00:00

  • Cisplatin microcrystals suspended in oil--toxicity in mice.

    abstract::A new dosage format, cisplatin microcrystals suspended in oil (CDDP-oil), was developed for the treatment of peritoneal carcinomatoses. We studied the acute toxicity of CDDP-oil injected intraperitoneally in mice. The 50% lethal dose was 30.3 mg/kg (27.1-33.7 mg/kg at the 95% confidence level), which was 1.79 times th...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/00001813-199306000-00015

    authors: Tsujimoto H,Hagiwara A,Sakakura C,Sasaki S,Osaki K,Ohyama T,Sakakibara T,Takahashi T

    更新日期:1993-06-01 00:00:00

  • A prolonged complete response in a patient with BRAF-mutated melanoma stage IV treated with the MEK1/2 inhibitor selumetinib (AZD6244).

    abstract::In melanoma, the RAS/RAF/MEK/ERK pathway is frequently activated by mutations in BRAF and NRAS. Selumetinib (AZD6244) is an oral, selective, non-ATP-competitive inhibitor of MEK1/2. Here, we describe a patient with metastatic melanoma (T1N2cM1a) with a BRAF V600E mutation. She is currently being treated with selumetin...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/CAD.0b013e328350737d

    authors: Boers-Sonderen MJ,Desar IM,Blokx W,Timmer-Bonte JN,van Herpen CM

    更新日期:2012-08-01 00:00:00

  • Survival response of a human glioma cell line to hyperthermia associated with rhein.

    abstract::The effect of association of hyperthermia with the anti-inflammatory drug rhein (RH), 4,5-dihydroxyanthraquinone-2-carboxylic acid, on the clonogenic activity of human glioma cells has been examined. RH inhibits neoplastic growth mainly through an ATP depletion, but thermal cell killing is not mediated by the drug-ind...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/00001813-199208000-00015

    authors: Floridi A,Gentile PF,Bruno T,Delpino A,Iacobini C,Benassi M

    更新日期:1992-08-01 00:00:00

  • Exploring the lack of cross-resistance between aromatase inhibitors: evidence for a difference?

    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

    authors: Lønning PE

    更新日期:2008-03-01 00:00:00

  • An update of a phase II study of paclitaxel in advanced or recurrent squamous cell cancer of the cervix.

    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

    authors: Kudelka AP,Winn R,Edwards CL,Downey G,Greenberg H,Dakhil SR,Freedman RS,LoCoco S,Umbreit J,Delmore JE,Arbuck S,Loyer E,Gacrama P,Fueger R,Kavanagh JJ

    更新日期:1997-08-01 00:00:00

  • Response to immunotherapy rechallenge after interval chemotherapy in a patient with head and neck cancer.

    abstract::Patients with metastatic squamous cell cancer of the head and neck (SCCHN) have a poor prognosis, with most patients surviving less than a year. Immunotherapy (IO) is changing the natural history of the disease and programmed death-ligand 1 (PD-L1) inhibitors are showing notable improvements in survival with a more fa...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/CAD.0000000000000706

    authors: Cabezas-Camarero S,Cabrera-Martín MN,Pérez-Segura P

    更新日期:2019-02-01 00:00:00

  • Special pharmacokinetics of dipetarudin suggests a potential antitumor activity of this thrombin inhibitor.

    abstract::Thrombin is a potent mitogen for many tumor cells, suggesting that this enzyme may be involved in tumor genesis and metastasis. Inhibition of thrombin expressed on the surface of tumor cells may improve outcomes in some tumor cases. For this reason, a thrombin inhibitor to be applied in antitumor therapy must have fav...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/00001813-200402000-00007

    authors: López ML,Nowak G

    更新日期:2004-02-01 00:00:00

  • A randomized trial of two schedules of trimetrexate versus 5-fluorouracil in advanced colorectal cancer: a Southwest Oncology Group study.

    abstract::Trimetrexate (TMQ), a non-classical folate antagonist, was studied in a randomized controlled trial in patients with advanced colorectal cancer and without prior chemotherapy. Patients were randomly assigned to one of three treatments: TMQ at 200 mg/m2 i.v. q 2 weeks, TMQ at 12 mg/m2 i.v. daily x 5 or 5-fluorouracil (...

    journal_title:Anti-cancer drugs

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1097/00001813-199504000-00004

    authors: Brown TD,Fleming TR,Goodman PJ,Macdonald JS,Pugh RP,O'Rourke T

    更新日期:1995-04-01 00:00:00

  • Non-allergic nature of docetaxel-induced acute hypersensitivity reactions.

    abstract::Based on observations of a discrepancy between 'hypersensitivity' reactions to docetaxel (DT) and the clinical features of allergic reactions, we explored the hypothesis that DT-induced acute hypersensitivity reactions (AHRs) have a non-allergic origin. Forty cancer patients receiving DT and 16 patients receiving othe...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/01.cad.0000131685.06390.b7

    authors: Ardavanis A,Tryfonopoulos D,Yiotis I,Gerasimidis G,Baziotis N,Rigatos G

    更新日期:2004-07-01 00:00:00

  • Primary chemotherapy with gemcitabine, liposomal doxorubicin and docetaxel in patients with locally advanced breast cancer: results of a phase I trial.

    abstract::The primary objective was to determine the optimal doses for gemcitabine (prolonged infusion), liposomal doxorubicin (Myocet) and docetaxel as primary (neoadjuvant) chemotherapy for locally advanced breast cancer. Secondary objectives included evaluation of the safety and efficacy of the regimen. Patients (n=19) with ...

    journal_title:Anti-cancer drugs

    pub_type: 临床试验,杂志文章,多中心研究

    doi:10.1097/00001813-200501000-00003

    authors: Schmid P,Krocker J,Schulz CO,Michniewicz K,Dieing A,Eggemann H,Heilmann V,Blohmer JU,Sezer O,Elling D,Possinger K

    更新日期:2005-01-01 00:00:00

  • 8-Farnesyloxycoumarin induces apoptosis in PC-3 prostate cancer cells by inhibition of 15-lipoxygenase-1 enzymatic activity.

    abstract::Prostate cancer is the second most common cancer in men worldwide. Overexpression of 15-lipoxygenase-1 (15-LOX-1) has been reported in prostate cancer patients. This study aimed to investigate the cytotoxic and anticancer effects of 8-farnesyloxycoumarin (8f), a prenylated coumarin, by inhibition of 15-LOX-1 activity,...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/CAD.0000000000000399

    authors: Hosseinymehr M,Matin MM,Sadeghian H,Bahrami AR,Kaseb-Mojaver N

    更新日期:2016-10-01 00:00:00

  • A prospective randomized controlled trial of tumour chemosensitivity assay directed chemotherapy versus physician's choice in patients with recurrent platinum-resistant ovarian cancer.

    abstract::The primary aim of this randomized trial was to determine response rate and progression-free survival following chemotherapy in patients with platinum-resistant recurrent ovarian cancer, who had been treated according to an ATP-based tumour chemosensitivity assay in comparison with physician's choice. A total of 180 p...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章,随机对照试验

    doi:10.1097/CAD.0b013e3281de727e

    authors: Cree IA,Kurbacher CM,Lamont A,Hindley AC,Love S,TCA Ovarian Cancer Trial Group.

    更新日期:2007-10-01 00:00:00

  • RITA induces apoptosis in p53-null K562 leukemia cells by inhibiting STAT5, Akt, and NF-κB signaling pathways.

    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 th...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/CAD.0000000000000651

    authors: Mobaraki RN,Karimi M,Alikarami F,Farhadi E,Amini A,Bashash D,Paridar M,Kokhaei P,Rezvani MR,Kazemi A,Safa M

    更新日期:2018-10-01 00:00:00

  • 2-Deoxy-D-glucose suppresses the migration and reverses the drug resistance of colon cancer cells through ADAM expression regulation.

    abstract::Cancer cell resistance to chemotherapy is associated with a poor prognosis. The compound 2-deoxy-D-glucose (2-DG) enhances the effect of chemotherapy against cancer cells lines in vitro and in vivo. However, its effect on the epithelial to mesenchymal transition (EMT) in drug-resistant cancer cells has not been fully ...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/CAD.0000000000000472

    authors: Park GB,Chung YH,Kim D

    更新日期:2017-04-01 00:00:00

  • Evaluation of certain ureas and nitrosoureas of 2,3-dihydro-1,4-benzothiazines against Sarcoma-180 solid tumors in vivo.

    abstract::Different derivatives of nitrosoureas were synthesized by a long sequence of reactions and were evaluated for their anticancer activities against female Swiss albino mice, 6-8 weeks old, weighing 18-24 g and bearing Sarcoma-180 (S-180) ascitic tumor. Experimental protocols include injecting a total of 2 x 10(5) S-180 ...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/00001813-199510000-00009

    authors: Nyati MK,Rajoria CM,Gupta RR,Dev PK

    更新日期:1995-10-01 00:00:00

  • Chemotherapy for recurrent/metastatic head and neck cancers.

    abstract::Chemotherapy is the only option of treatment for most patients presenting with a recurrent and/or metastatic head and neck squamous cell carcinoma. The triple association of cisplatin, 5-fluorouracile, and cetuximab is still the current standard for fit patients. Other schemes are currently being compared with this pr...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章,评审

    doi:10.1097/CAD.0000000000000473

    authors: Karabajakian A,Toussaint P,Neidhardt EM,Paulus V,Saintigny P,Fayette J

    更新日期:2017-04-01 00:00:00

  • A cost--utility analysis comparing second-line chemotherapy schemes in patients with metastatic breast cancer.

    abstract::A cost-utility analysis has been performed comparing taxanes, vinorelbine and standard therapy for metastatic breast cancer considering clinical efficacy, quality-adjusted-life-years (QALYs) and costs. A decision model has been built. Clinical efficacy data were collected by literature review. Utility data and cost da...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/00001813-200107000-00007

    authors: Li N,van Agthoven M,Willemse P,Uyl-de Groot C

    更新日期:2001-07-01 00:00:00

  • Effect of modulators of the multidrug resistance pump on the distribution of vinblastine in tissues of the mouse.

    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

    authors: Lyubimov E,Lan LB,Pashinsky I,Stein WD

    更新日期:1996-01-01 00:00:00

  • Response by Choi criteria to sunitinib plus octreotide LAR in a functional heavily pretreated advanced pancreatic neuroendocrine tumor.

    abstract::Pancreatic neuroendocrine tumors (PNETs) are rare malignancies that arise from the islets of Langerhans. The role of standard chemotherapy in advanced well-differentiated PNETs remains to be defined. Sunitinib is an oral multitargeted inhibitor with antiangiogenic and antitumor properties that has shown significant im...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/CAD.0b013e328344484b

    authors: Grande E,José Díez J,Pachón V,Angeles Vaz M,Longo F,Guillén C,García de Paredes ML,Carrato A

    更新日期:2011-06-01 00:00:00

  • Vitamin C suppresses the cisplatin toxicity on blood platelets.

    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

    authors: Olas B,Wachowicz B,Buczyński A

    更新日期:2000-07-01 00:00:00

  • RNA interference targeting the R2 subunit of ribonucleotide reductase inhibits growth of tumor cells in vitro and in vivo.

    abstract::RNA interference, a posttranscriptional gene-silencing mechanism, has received considerable attention for its potential as a new therapeutic strategy to treat human diseases and conditions including cancer. Various studies have supported a role for the R2 subunit of ribonucleotide reductase in cancer progression and m...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/CAD.0b013e328013c04f

    authors: Avolio TM,Lee Y,Feng N,Xiong K,Jin H,Wang M,Vassilakos A,Wright J,Young A

    更新日期:2007-04-01 00:00:00

  • Galloyl cyclic-imide derivative CH1104I inhibits tumor invasion through suppressing matrix metalloproteinase activity.

    abstract::Matrix metalloproteinase (MMP)-2 and MMP-9 have been associated with the ability of tumor cells to metastasize because of their capacity to degrade type IV collagen, the main component of basement membrane, and to their elevated expression in malignant tumors. (S)-methyl 6-(benzyloxycarbonylamino)-2-(2-((S)-2,6-dioxo-...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/CAD.0b013e328313e15b

    authors: Chen MH,Cui SX,Cheng YN,Sun LR,Li QB,Xu WF,Ward SG,Tang W,Qu XJ

    更新日期:2008-11-01 00:00:00

  • DNA topoisomerase-targeting antitumor agents and drug resistance.

    abstract::A review of the chemotherapeutic agents which have been developed by targeting DNA topoisomerase I and II is presented. Camptothecins as topoisomerase I-targeting agents and newly developed topoisomerase II-targeting agents with unique properties are expected to be promising anticancer agents in the near future. An im...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章,评审

    doi:10.1097/00001813-199208000-00002

    authors: Takano H,Kohno K,Matsuo K,Matsuda T,Kuwano M

    更新日期:1992-08-01 00:00:00

  • Determinants of trifluorothymidine sensitivity and metabolism in colon and lung cancer cells.

    abstract::Trifluorothymidine (TFT) is a fluorinated thymidine analog that after conversion to its monophosphate derivative can inhibit thymidylate synthase (TS) and be incorporated into DNA. TFT is a good substrate for thymidine phosphorylase (TP), and the combination of TFT and a TP inhibitor (TPI), called TAS-102, has been de...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/00001813-200503000-00007

    authors: Temmink OH,de Bruin M,Comijn EM,Fukushima M,Peters GJ

    更新日期:2005-03-01 00:00:00

  • In vitro chemosensitivity to gemcitabine, oxaliplatin and zoledronic acid predicts treatment response in metastatic gastric cancer.

    abstract::Individual response of disseminated cancer to chemotherapy is unpredictable. In vitro chemotherapy-induced apoptosis can be measured and might be a method to evaluate in vivo activity of tested drugs. In this report, tumor cells of a patient with signet cell carcinoma of the stomach and diffuse bone marrow infiltratio...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/00001813-200501000-00013

    authors: Trojan J,Kim SZ,Engels K,Kriener S,Mitrou PS,Chow KU

    更新日期:2005-01-01 00:00:00

  • Evidence of extended (>7 years) activity of bevacizumab and metronomic cyclophosphamide in a patient with platinum-resistant low-grade serous ovarian carcinoma.

    abstract::A patient with platinum resistant low-grade serous ovarian carcinoma had an objective response to therapy with bevacizumab and evidence of extended activity (>7 years). This case report adds to the growing literature regarding the use of bevacizumab in low-grade serous ovarian carcinoma. ...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/CAD.0b013e328363b64e

    authors: Rose PG,Roma A

    更新日期:2013-10-01 00:00:00

  • Inhibition of breast and ovarian carcinoma cell growth by 1,25-dihydroxyvitamin D3 combined with retinoic acid or dexamethasone.

    abstract::This study examined the growth inhibitory effects of combining 1,25-dihydroxyvitamin D3 (calcitriol) with retinoic acid or dexamethasone against cultured breast and ovarian carcinoma cells. Retinoic acid (12.5-50 nM) increased the effectiveness of calcitriol (12.5-50 nM) against MCF-7 and NIH:OVCAR3 cells, with synerg...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章

    doi:10.1097/00001813-199508000-00009

    authors: Saunders DE,Christensen C,Williams JR,Wappler NL,Lawrence WD,Malone JM,Malviya VK,Deppe G

    更新日期:1995-08-01 00:00:00

  • Molecular basis of hypertension side effects induced by sunitinib.

    abstract::Over the past decade a number of vascular complications have emerged, such as newly developed or worsened hypertension, in patients who were administered with new cancer treatments for several types of cancer that were untreatable earlier. Hypertension is emerging as one of the most common adverse effects of therapy w...

    journal_title:Anti-cancer drugs

    pub_type: 杂志文章,评审

    doi:10.1097/CAD.0b013e3283403806

    authors: Aparicio-Gallego G,Afonso-Afonso FJ,León-Mateos L,Fírvida-Pérez JL,Vázquez-Estévez S,Lázaro-Quintela M,Ramos-Vázquez M,Fernández-Calvo O,Campos-Balea B,Antón-Aparicio LM

    更新日期:2011-01-01 00:00:00

  • Pulmonary targeting microparticulate camptothecin delivery system: anticancer evaluation in a rat orthotopic lung cancer model.

    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

    authors: Chao P,Deshmukh M,Kutscher HL,Gao D,Rajan SS,Hu P,Laskin DL,Stein S,Sinko PJ

    更新日期:2010-01-01 00:00:00