Abstract:
PURPOSE:Aldehyde dehydrogenases class-1A1 (ALDH1A1) and class-3A1 (ALDH3A1) have been associated with resistance to cyclophosphamide (CP) and its derivatives. We have previously reported the downregulation of these enzymes by all-trans retinoic acid (ATRA). METHODS:In this study, we used siRNA duplexes as well as retrovirally expressed siRNA to knockdown one or both enzymes together in A549 lung cancer cell line in order to investigate the role of each one in mediating the resistance and the effect of the addition of ATRA. RESULTS:The results show that significant and specific knockdown of each enzyme can be achieved and that each one contributes similarly to cell resistance to 4-hydroperoxycyclophosphamide (4-HC), an active derivative of CP. Added effects were seen when both enzymes were inhibited. The addition of ATRA also exhibited additional inhibitory effects on ALDH activity and increased 4-HC toxicity when added to single siRNA aimed at one of the enzymes. On the other hand, ATRA had minimal and insignificant additional inhibitory effects on ALDH enzyme activity when added to a combination of siRNAs against both enzymes, but still increased 4-HC toxicity beyond that seen with RNAi-mediated inhibition of both enzymes together. CONCLUSIONS:We conclude that both enzymes, ALDH1A1 and ALDH3A1 will need to be blocked in order to achieve the highest sensitivity to 4-HC. Furthermore, ATRA increases 4-HC toxicity even when added to a combination of siRNAs against both enzymes, thus suggesting additional mechanisms by which ATRA can increase drug toxicity.
journal_name
Cancer Chemother Pharmacoljournal_title
Cancer chemotherapy and pharmacologyauthors
Moreb JS,Mohuczy D,Ostmark B,Zucali JRdoi
10.1007/s00280-006-0233-6subject
Has Abstractpub_date
2007-01-01 00:00:00pages
127-36issue
1eissn
0344-5704issn
1432-0843journal_volume
59pub_type
杂志文章abstract::A major side effect of cisplatin treatment is peripheral neuropathy. In the past few years we have provided evidence that the ACTH4-9 analogue ORG 2766 provides protection against this neuropathy in rats and man. In this study we investigated the development of a cisplatin-induced neuropathy and the protective and the...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00685621
更新日期:1993-01-01 00:00:00
abstract::The initial results from the Children's Cancer Study Group (CCSG) study on vindesine are the subject of this report. Vindesine was shown to be active in the treatment of acute lymphocytic leukemia (ALL) in children in a phase-II clinical trial conducted by the CCSG. A phase-II trial is now in progress. The aim of this...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00257193
更新日期:1979-01-01 00:00:00
abstract:PURPOSE:The objectives of this phase I dose-finding study of erlotinib were to investigate the toxicity profile, to confirm the acceptable toxicity of doses up to 150 mg/day, and to assess the pharmacokinetic (PK) profile and antitumor activity in Japanese patients with solid tumors. PATIENTS AND METHODS:Patients with...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-007-0494-8
更新日期:2008-03-01 00:00:00
abstract::In an attempt to establish a relationship between the pharmacokinetics in mouse heart of new anthracycline derivatives and their potential chronic cardiotoxicity and on this way to provide a useful and economical test for screening of new analogs, we followed the accumulation and metabolism of six anthracyclines in th...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00255483
更新日期:1982-01-01 00:00:00
abstract:PURPOSE:Since the hypothesis that solid tumors cause angiogenesis by secreting pro-angiogenic factors was introduced, research on angiogenesis has proceeded continuously. Development of inhibitors targeting the angiogenic tyrosine kinases, to block downstream signal transduction pathways, has become an important approa...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,评审
doi:10.1007/s00280-016-2961-6
更新日期:2016-05-01 00:00:00
abstract:PURPOSE:The histone deacetylase inhibitor, suberoylanilide hydroxamic acid (SAHA), enhances cisplatin [cis-diammine dichloroplatinum (II)] (CDDP)-induced apoptosis in the oral squamous cell carcinoma (OSCC) cell line by complex, multifunctional mechanisms. We investigated the role of endoplasmic reticulum (ER) stress i...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-009-0969-x
更新日期:2009-11-01 00:00:00
abstract::The novel isocoumarin 2-(8-hydroxy-6-methoxy-1-oxo-1 H-2-benzopyran-3-yl) propionic acid (NM-3) has completed phase I clinical evaluation as an orally bioavailable angiogenesis inhibitor. NM-3 directly kills both endothelial and tumor cells in vitro at low mM concentrations and is effective in the treatment of diverse...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-005-1013-4
更新日期:2005-12-01 00:00:00
abstract:PURPOSE:To assess the activity and safety of combined folinic acid (FA), 5-fluorouracil (5-FU) and mitomycin C (MMC) in metastatic breast cancer patients previously treated with at least two chemotherapy regimens. PATIENTS AND METHODS:A total of 104 consecutive patients were enrolled for treatment with FA 100 mg/m(2) ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s00280-002-0495-6
更新日期:2002-10-01 00:00:00
abstract::Thirty-two evaluable patients with advanced measurable gastric adenocarcinoma were treated with a combination of 5-fluorouracil, adriamycin, and BCNU (FAB). Two complete and fourteen partial responses were observed, with an overall response rate of 50%. The median duration of response was 10 months, and the median sur...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/BF00256545
更新日期:1984-01-01 00:00:00
abstract:UNLABELLED:Hypericin, a polycyclic aromatic dianthroquinone, is a natural pigment derived from the plant Hypericum perforatum (St John's Wort). The compound has been synthesized and shown to inhibit the growth of malignant glioma cell lines in vitro via inhibition of protein kinase C. Oral hypericin has entered clinica...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s002800000188
更新日期:2001-01-01 00:00:00
abstract::DDMP, a diaminopyrimidine folate antagonist, was given to 26 tumor patients in a dosage of 50 mg/m2 per week orally, simultaneously with 3 mg CF i.m. or i.v. The CF dose was increased to 30 mg in patients showing evidence of toxicity, and withdrawn in the absence of toxicity. The dose-limiting toxicity was seen in mye...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/BF00254043
更新日期:1978-01-01 00:00:00
abstract:BACKGROUND:The pharmacokinetics and tissue distribution of photofrin II (PF) and its efficacy in sonodynamic therapy were studied in rats bearing AH130 solid tumors. MATERIALS AND METHODS:In order to find the optimum timing of the ultrasound exposure after administration of PF, the PF concentrations in plasma, skin, m...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-002-0523-6
更新日期:2003-02-01 00:00:00
abstract::A novel antitumor compound, N-beta-dimethyl-aminoethyl 9-carboxy-5-hydroxy-10-methoxybenzo[a]-phenazine-6-carboxamide sodium salt (NC-190) was evaluated for its antitumor activity in experimental murine tumor systems. In the initial studies with P388 leukemia (i.p.-i.p.), NC-190 led to an increase of greater than 200%...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00267943
更新日期:1989-01-01 00:00:00
abstract:PURPOSE:A standard chemotherapy regimen for neuroendocrine carcinoma of the gastrointestinal tract (GI-NEC) has not been established. Treatment usually consists of platinum doublets, consistent with the standard treatment for small-cell lung cancer (SCLC), with which it shares clinicopathological similarities. Here, we...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-011-1619-7
更新日期:2011-11-01 00:00:00
abstract:PURPOSE:To characterize cobimetinib pharmacokinetics and evaluate impact of clinically relevant covariates on cobimetinib pharmacokinetics. METHODS:Plasma samples (N = 4886) were collected from 487 patients with various solid tumors (mainly melanoma) in three clinical studies (MEK4592g, NO25395, GO28141). Cobimetinib ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-015-2862-0
更新日期:2015-11-01 00:00:00
abstract:PURPOSE:An isolated pelvic perfusion technique using multiple agents was used both in patients with unresectable recurrent pelvic neoplasms and as a preoperative therapy for advanced pelvic malignancy. METHODS:The technique consisted of vascular occlusion via transfemoral balloon catheters, circulation and drug infusi...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s002800050918
更新日期:1999-01-01 00:00:00
abstract:PURPOSE:To confirm the efficacy and toxicity of gemcitabine and S-1 combination chemotherapy when used as a first-line therapy in patients with unresectable pancreatic cancer. METHODS:Patients with locally advanced or metastatic or recurrent pancreatic adenocarcinoma, which was histologically or cytologically proven, ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,多中心研究
doi:10.1007/s00280-009-1059-9
更新日期:2010-02-01 00:00:00
abstract::Dianhydrogalactitol (DAG) increased the life span of both BCNU-sensitive and -resistant L1210 tumor-bearing mice. However, the BCNU-resistant strain showed slightly lower sensitivity against DAG, which could be overcome by an increase in drug dose of ca. 20%. The somewhat lower sensitivity was proportional to a slight...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00304764
更新日期:1989-01-01 00:00:00
abstract::Between December 1982 and November 1990, 31 patients with advanced urothelial carcinoma were treated with one of two combination chemotherapy regimens. A total of 20 patients were treated with 3 mg/m2 mitomycin C and 300 mg/m2 cyclophosphamide given intravenously every 10-14 days and with 180 mg/m2 5-fluorouracil (5-F...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/BF00686944
更新日期:1992-01-01 00:00:00
abstract:PURPOSE:Pegylated liposomal doxorubicin (PLD) is used to treat patients with breast and gynecological cancers. In order to optimize treatment with PLD, we assessed the prognostic and predictive factors for efficacy of PLD. METHODS:Seventeen patients treated with PLD 30 or 40 mg/m(2) underwent pharmacokinetic sampling ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-014-2514-9
更新日期:2014-09-01 00:00:00
abstract:PURPOSE:Artemisinins are now established drugs for treatment of malaria. These agents have been shown to possess impressive anti-cancer properties. We have investigated the role of artemisone (ATM), a novel derivative of artemisinin (ART) in a cancer setting both alone and in combination with established chemotherapeut...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-010-1355-4
更新日期:2011-03-01 00:00:00
abstract:PURPOSE:Nasopharyngeal carcinoma (NPC) is one of the most commonly diagnosed cancers worldwide with significantly high prevalence in Southern China. Chemoprevention of cancer with alkylating agent compounds could potentially reverse, suppress, or prevent cancer progression. Cisplatin (CIS) is an antineoplastic or cytot...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-018-3536-5
更新日期:2018-05-01 00:00:00
abstract:PURPOSE:The established treatment for small-cell lung cancer has been a cisplatin-etoposide combination, as the most effective chemotherapy regimen. Paclitaxel has also been used in combination with cisplatin and etoposide but this has been unacceptable due to the toxicity. This toxicity could be attributed to the thre...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,多中心研究
doi:10.1007/s00280-012-2022-8
更新日期:2013-02-01 00:00:00
abstract:BACKGROUND:The docetaxel/cisplatin (DC) combination is an active regimen against advanced/metastatic non-small-cell lung cancer (NSCLC), and bevacizumab (B) improves the efficacy of frontline chemotherapy. This phase II study was designed in order to explore the efficacy and safety of DCB regiment in this setting. MET...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,多中心研究
doi:10.1007/s00280-012-2037-1
更新日期:2013-03-01 00:00:00
abstract::A total of 23 patients were treated at five dose escalations with high-dose combination cyclophosphamide, cisplatin, and melphalan with autologous bone marrow support. The maximum tolerated doses of cyclophosphamide, cisplatin, and melphalan were 5,625, 180, and 80 mg/m2, respectively. The dose-limiting toxicity was c...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00435840
更新日期:1989-01-01 00:00:00
abstract::Anthracyclines are important antitumor agents used in the treatment of solid tumors, lymphomas, and acute lymphoblastic as well as myelocytic leukemias. The clinical utility of agents such as doxorubicin and daunorubicin and their well-characterized cardiotoxicity have prompted many efforts to develop analogs that ret...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00686485
更新日期:1992-01-01 00:00:00
abstract::OSI-7836 (4'-thio-beta-D-arabinofuranosylcytosine) is a novel nucleoside analog in phase I clinical development for the treatment of cancer. As with other nucleoside analogs, the proposed mechanism of action involves phosphorylation to the triphosphate form followed by incorporation into cellular DNA, leading to cell ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-004-0844-8
更新日期:2005-03-01 00:00:00
abstract::Trastuzumab has deeply and radically changed the course of HER2-positive breast cancer disease. The recent development of a subcutaneous (SC) formulation of trastuzumab is an important step towards improved patients' care. SC trastuzumab at a fixed dose of 600 mg administered every 3 weeks for about 5 min provides a v...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-013-2289-4
更新日期:2013-12-01 00:00:00
abstract::Methylene blue (MB) is a phenothiazine with radio and photosensitizing properties and anti-tumoral activity. Our group has shown that MB was capable of inhibiting the in vitro growth of erythroleukemic cells with multidrug resistance (MDR). However, there are no studies comparing the cytotoxicity of this molecule for ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-005-1014-3
更新日期:2005-12-01 00:00:00
abstract:PURPOSE:To investigate the activity of combination chemotherapy with ifosfamide, 5-fluorouracil, etoposide and cisplatin in patients with metastatic urothelial cancer. METHODS:A group of 29 patients were treated with 2000 mg/m2 ifosfamide, 750 mg/m2 5-fluorouracil, 100 mg/m2 etoposide and 20 mg/m2 cisplatin. All four ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s002800100320
更新日期:2001-07-01 00:00:00