Abstract:
PURPOSE:Malignant rhabdoid tumors (MRT), although rare, are one of the most aggressive pediatric malignancies. Loss of INI1, a tumor suppressor gene and member of the SWI/SNF chromatin remodeling complex, is a recurrent genetic characteristic of these tumors and an important diagnostic marker. We have previously demonstrated a novel interaction between the serine/threonine kinase Akt and INI1, as well as other SWI/SNF subunits. This, coupled with experiments in the literature suggesting that the PI3K/Akt pathway is dysregulated in MRT cells, caused us to investigate the activation and importance of this pathway in this tumor type. METHODS:In this study, we used MTT assays to evaluate the sensitivity of MRT cell lines to PI3K inhibition. Western blot analysis and Raf pulldown assays were used to examine potential mechanisms of PI3K/Akt dysregulation. RESULTS:Inhibition of the PI3K/Akt pathway caused a significant reduction in the survival of the four MRT cell lines tested, and three cell lines demonstrated constitutively active Akt. Two of these constitutively active Akt cell lines abundantly expressed IGF-1R and an inhibitor of IGF-1R, NVP-AEW541, reduced Akt phosphorylation in one of them. The third constitutively active Akt cell line appeared to express a mutant IGF-1R. CONCLUSIONS:Our data suggests that the PI3K/Akt pathway is a crucial means of maintaining the survival and growth of MRT cells. The cells therefore employ various mechanisms to stimulate this pathway, and growth factor receptor dysregulation appears to be a common method. Drugs that inhibit the PI3K pathway or interfere with IGF autocrine loops may be of great value in treating MRT, which is largely resistant to conventional chemotherapeutic approaches.
journal_name
Cancer Chemother Pharmacoljournal_title
Cancer chemotherapy and pharmacologyauthors
Foster K,Wang Y,Zhou D,Wright Cdoi
10.1007/s00280-008-0796-5subject
Has Abstractpub_date
2009-04-01 00:00:00pages
783-91issue
5eissn
0344-5704issn
1432-0843journal_volume
63pub_type
杂志文章abstract:PURPOSE:The study mainly aimed to determine the biological function of a novelly synthesized phenanthroimidazole derivative, named L233, and to explore its potential mechanisms. METHODS:Cell survival was examined using the MTT assays, and the DNA-damaging role of L233 was explored using the comet assay. Moreover, the ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-015-2894-5
更新日期:2016-01-01 00:00:00
abstract:OBJECTIVE:We evaluated the efficacy and safety of M-VAC chemotherapy combined with mild hyperthermia, a new therapeutic strategy for advanced metastatic transitional cell carcinoma of the urothelium. SUBJECTS AND METHODS:The subjects were 12 patients diagnosed with advanced metastatic transitional cell carcinoma of th...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-009-0964-2
更新日期:2009-11-01 00:00:00
abstract::Chemobrain refers to a common sequela experienced by a substantial subset of cancer patients exposed to chemotherapeutic treatment, a phenomenon that dramatically deteriorates the survivors' quality of life and prevents them from restoring their pre-cancer life. This review is intended to address the current knowledge...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,评审
doi:10.1007/s00280-019-03827-0
更新日期:2019-07-01 00:00:00
abstract:PURPOSE:The objectives of these analyses were to (1) develop a semimechanistic-physiologic population pharmacokinetic/pharmacodynamic (PK/PD) model to describe neutropenic response to pemetrexed and to (2) identify influential covariates with respect to pharmacodynamic response. PATIENTS AND METHODS:Data from 279 pati...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-005-0077-5
更新日期:2006-04-01 00:00:00
abstract:PURPOSE:This study evaluated mechanistic differences of pralatrexate, methotrexate, and pemetrexed. METHODS:Inhibition of dihydrofolate reductase (DHFR) was quantified using recombinant human DHFR. Cellular uptake and folylpolyglutamate synthetase (FPGS) activity were determined using radiolabeled pralatrexate, methot...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-009-0954-4
更新日期:2009-10-01 00:00:00
abstract:PURPOSE:We evaluated the efficacy and safety of capecitabine and temozolomide (CAPTEM) in patients with metastatic neuroendocrine tumors (NETs) to the liver. This regimen was based on our studies with carcinoid cell lines that showed synergistic cytotoxicity with sequence-specific dosing of 5-fluorouracil preceding tem...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-012-2055-z
更新日期:2013-03-01 00:00:00
abstract:PURPOSE:Triple-negative breast cancers (TNBCs) do not derive benefit from molecular-targeted treatments such as endocrine therapy or anti-HER2 therapy because they lack those molecular targets. On the other hand, TNBCs have been shown to respond to neoadjuvant chemotherapy (NAC). In this study, we analyzed TNBC patient...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-010-1371-4
更新日期:2011-04-01 00:00:00
abstract::Leukemic cells from seven patients with acute nonlymphoblastic leukemia and granulocytes, and mononuclear cells from three healthy controls were isolated by centrifugation on metrozoate-dextran. The intracellular accumulation of both the free and DNA-bound forms of daunorubicin and doxorubicin was studied in vitro. Th...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00253105
更新日期:1979-01-01 00:00:00
abstract::Nine children with poor-prognosis malignancies--seven with advanced neuroblastoma and two with metastatic Ewing's sarcoma--were given high doses of melphalan (HDM), 150 mg/m2 (3 patients) and 180 mg/m2 (6 patients), as a 'late intensification' agent combined with noncryopreserved autologous bone marrow transplants. Me...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00263898
更新日期:1985-01-01 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:To investigate the synergistic cytotoxicity of TRAIL in combination with chemotherapeutic agents in A549 cell lines, we systematically evaluated the cytotoxicity of TRAIL alone and TRAIL in combination with cisplatin, paclitaxel (Taxol) or actinomycin D in A549 cell lines in vitro and in vivo, and whether the s...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-004-0867-1
更新日期:2005-02-01 00:00:00
abstract::To determine whether dimethylsulfoxide (DMSO) can potentiate antitumor activity of cyclophosphamide (CYC) in patients with squamous cell carcinoma of the lung, 14 patients were treated with 5 l of a 5% or 6% DMSO solution PO over 3 days and 1,500 mg CYC/m2 IV as a 60-min infusion on the third day of treatment. Serial ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00262327
更新日期:1981-01-01 00:00:00
abstract:PURPOSE:By a scaffold shortening strategy, a small series of retinoidal amides fenretinide (4-HPR) analogs have been synthesized from α, β-ionones and tested for their antiproliferative and differentiating activities, and antioxidant effect. METHODS:The antiproliferative activity and triggering of apoptosis of our sho...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-017-3265-1
更新日期:2017-04-01 00:00:00
abstract::To obtain a clearer definition of the relationship between the structure of BCNU and CCNU and their antitumor activity, we determined the uptake, distribution, and tissue/plasma partition ratios of both compounds in normal organs and intracerebral (ic) 9L tumors in rats. Greater uptake, distribution, and tissue/plasma...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00257156
更新日期:1978-01-01 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::Nanoparticulate carriers of anthracyclines are being developed with the aim of improving the pharmacokinetic or pharmacodynamic behavior of these drugs. To understand how the drug reaches its nuclear targets, we have developed two methods that allow the quantification of the interaction between an anthracycline and ce...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00686835
更新日期:1995-01-01 00:00:00
abstract:PURPOSE:To assess the safety of the association of radiotherapy (RT) and systemic treatments for patients with metastatic malignant melanoma (mMM). METHODS:A retrospective analysis included consecutive patients treated with palliative RT, and at least one line of systemic therapy for mMM between 2001 and 2016. Treatme...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-019-03806-5
更新日期:2019-05-01 00:00:00
abstract::Male Sprague-Dawley rats were given single i.p. injections of 1,3-bis(2-chloroethyl)-1-Nitrosourea (BCNU) to investigate changes in hepatic microsomal cytochrome P-450 content and metabolic activity. On day 14 after treatment (20 mg/kg), cytochrome P-450 content had decreased by approximately 25% and ethylmorphine N-d...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00684877
更新日期:1990-01-01 00:00:00
abstract:PURPOSE:P-glycoprotein is a 170-kDa plasma membrane multidrug transporter that actively exports cytotoxic substances from cells. Overexpression of P-glycoprotein by tumor cells is associated with a multidrug-resistant phenotype. Immunosuppressive agents such as cyclosporins and macrolides, have been shown to attenuate ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s002800050960
更新日期:1999-01-01 00:00:00
abstract::Forty-one previously treated patients with advanced Hodgkin's disease were treated with a combination chemotherapy regimen -- ABVD (adriamycin, bleomycin, velbe/vincristine, imidazole carboxamide). Complete remission was achieved in three patients (7%), partial remission in 23 (56%), and no response in 15 patients (37...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00258297
更新日期:1979-01-01 00:00:00
abstract:PURPOSE:Polyamines are biologic cations necessary for normal cell growth. Polyamine analogues have been shown to be effective inhibitors of tumor growth. We tested the effect of the polyamine analogues 1,1 9-bis(ethylamino)-5,10,15-triazanonadecane (BE-4-4-4-4), N1,N11-bis(ethyl)norspermine (BE-3-3-3) and 1,15-bis(ethy...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s002800050643
更新日期:1997-01-01 00:00:00
abstract:PURPOSE:The present study aims to establish a method that provides fast, precise and reproducible pharmacokinetic (PK) parameters of antibody-calicheamicin conjugates. The method should discriminate between PK of the antibody moiety and PK of the conjugated calicheamicin (CM). METHODS:The conjugates gemtuzumab ozogami...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-007-0560-2
更新日期:2008-05-01 00:00:00
abstract::The effects of intravesical chemoimmunotherapy with epirubicin and bacillus Calmette-Guérin (BCG) for prophylaxis of recurrence of superficial bladder cancer (pTa, pT1) were investigated in 29 patients aged a median of 70 years between January of 1991 and May of 1993. The patients received intravesical instillation of...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/BF00686923
更新日期:1994-01-01 00:00:00
abstract::Mitoxantrone, 1,4-dihydroxy-5,8-bis(((2-[(2-hydroxyethyl)amino]ethyl) amino))-9,10-anthracenedione dihydrochloride, a new antitumor agent was evaluated in nine cancer patients as part of a phase I trial. In general, the drug was well tolerated. Leukopenia was the dose-limiting toxic effect. Mild to moderate leukopenia...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00578556
更新日期:1980-01-01 00:00:00
abstract:PURPOSE:In patients with epidermal growth factor receptor (EGFR)-mutated, advanced, non-small cell lung cancer (NSCLC), common gefitinib-sensitive EGFR mutations that predict a greater response to therapy include the exon 19 deletion and L858R point mutation. The objective of this study was to evaluate whether body sur...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-016-3232-2
更新日期:2017-03-01 00:00:00
abstract:PURPOSE:Our aim was to develop an optimal sampling strategy for the description of the pharmacokinetics of rubitecan and its active metabolite 9-aminocamptothecin (9-AC) for use in phase II/III studies with oral rubitecan administered in a daily times five schedule. METHODS:Concentration-time data of rubitecan and 9-A...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/s00280-002-0516-5
更新日期:2002-12-01 00:00:00
abstract::Exposure of cells of the K-562 erythroleukemia cell line to 4-hydroperoxycyclophosphamide (4-HC), an analog of activated cyclophosphamide, causes a concentration-dependent inhibition of in vitro colony formation by these cells. For investigation of the role of glutathione (GSH) in the metabolism of 4-HC, GSH levels of...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF02994088
更新日期:1990-01-01 00:00:00
abstract::Macroautophagy is widely accepted as a cytoprotective mechanism against various environmental stresses. While inhibition of autophagy is generally considered to increase the susceptibility of cancer cells to therapeutic agents, whether it also plays a similar role in tumor stem cells is unclear and still controversial...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,评审
doi:10.1007/s00280-014-2634-2
更新日期:2015-05-01 00:00:00
abstract:PURPOSE:Following a previously published pre-clinical validation, this phase I study evaluated the safety, maximum tolerated dose, anti-tumour activity and immune status of a gemcitabine-chloroquine combination as a first- or late-line treatment in patients with metastatic or unresectable pancreatic cancer. METHODS:In...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-017-3446-y
更新日期:2017-11-01 00:00:00
abstract::Previous studies have demonstrated that treatment with fludarabine 4 h prior to arabinosylcytosine (ara-C) potentiates the accumulation of the active triphosphate of ara-C (ara-CTP) in leukemic lymphocytes. The clinical efficacy of this combination was evaluated in 15 patients with chronic lymphocytic leukemia (CLL) t...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00686108
更新日期:1994-01-01 00:00:00