Abstract:
PURPOSE:The observation that the orphan drug dichloroacetate (DCA) selectively promotes mitochondria-regulated apoptosis and inhibits tumour growth in preclinical models by shifting the glucose metabolism in cancer cells from anaerobic to aerobic glycolysis attracted not only scientists', clinicians' but also patients' interests and prompted us to further evaluate DCA effects against paediatric malignancies. METHODS:The effects of DCA on mitochondrial membrane potential (ΔΨm), cell viability and induction of apoptosis were evaluated in paediatric tumour cell lines and the non-malignant cell line HEK293. In addition, combinations of DCA with the standard anticancer drugs cisplatin, doxorubicin, and temozolomide were tested and intra- and extra-cellular platinum species analysed. RESULTS:DCA selectively induced phosphatidylserine externalisation and reduced ΔΨm in paediatric tumour cells compared to HEK293 cells, but DCA concentrations ≤ 10 mmol/L only moderately inhibited the growth of 18 paediatric tumour cell lines. DCA neither influenced the in vitro stability of cisplatin nor the cellular cisplatin uptake, but it abrogated the cytotoxicity of cisplatin in 7 out of 10 cell lines. DCA also affected the cytotoxicity of doxorubicin but did not influence the cytotoxicity of temozolomide. Despite phosphatidylserine externalisation, DCA failed to activate caspase 3/7 and, moreover, suppressed caspase 3/7 activation by cisplatin and doxorubicin. CONCLUSIONS:Our results indicate that apart from the intriguing effects of DCA on the glucose metabolism of cancer cells, the use of DCA for cancer treatment has to be evaluated carefully. Moreover, compassionate use of the orally available drug by patients with cancer themselves without medical supervision is strongly discouraged at present.
journal_name
Cancer Chemother Pharmacoljournal_title
Cancer chemotherapy and pharmacologyauthors
Heshe D,Hoogestraat S,Brauckmann C,Karst U,Boos J,Lanvers-Kaminsky Cdoi
10.1007/s00280-010-1361-6subject
Has Abstractpub_date
2011-03-01 00:00:00pages
647-55issue
3eissn
0344-5704issn
1432-0843journal_volume
67pub_type
杂志文章abstract::We have developed and validated a selective analytical procedure, based on ion-exchange normal-phase liquid chromatography with fluorescence detection and liquid-liquid extraction, for the analysis of vinblastine (VBL) in biological matrices. The assay is suitable for the determination of the parent compound and its m...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00686174
更新日期:1993-01-01 00:00:00
abstract:OBJECTIVE:To characterize the population pharmacokinetics of plitidepsin (Aplidin) in cancer patients. METHODS:A total of 283 patients (552 cycles) receiving intravenous plitidepsin as monotherapy at doses ranging from 0.13 to 8.0 mg/m(2) and given as 1- or 24-h infusions every week; 3- or 24-h infusion biweekly; or 1...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,meta分析
doi:10.1007/s00280-008-0841-4
更新日期:2009-06-01 00:00:00
abstract:PURPOSE:BMS-310705, a novel semisynthetic derivative of epothilone B, is a tubulin-polymerization agent currently in phase I clinical trials for anticancer therapy. The in vitro and in vivo pharmacokinetics and oral bioavailability of BMS-310705 were investigated in mice, rats, and dogs. In addition, comparison of the ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-004-0928-5
更新日期:2005-08-01 00:00:00
abstract::All-trans-retinoic acid (ATRA) has been incorporated in front-line therapy for newly diagnosed acute promyelocytic leukemia (APL). We conducted a multicenter study of differentiation therapy with ATRA alone or in combination with chemotherapy followed by intensive postremission chemotherapy in patients with APL (the J...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1007/s002800100308
更新日期:2001-08-01 00:00:00
abstract:PURPOSE:To differentiate the antagonistic and agonistic effect of toremifene at the level of the hypothalamus-hypophysis axis a leutinizing hormone-releasing hormone (LHRH) test was performed during a phase II clinical trial. METHODS:In 15 postmenopausal patients with advanced breast cancer, follicle-stimulating hormo...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s002800050811
更新日期:1998-01-01 00:00:00
abstract::The development of more effective treatment strategies currently provides the only realistic hope of reducing breast cancer mortality. Among such treatments, high-dose chemotherapy (HDC) has been proposed to be a potentially curative strategy. Consideration of the factors involved in the successful treatment of human ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,评审
doi:10.1007/s002800051067
更新日期:1997-01-01 00:00:00
abstract:PURPOSE:6-Gingerol, a major biochemical and pharmacological active ingredient of ginger, has shown anti-inflammatory and antitumor activities against various cancers. Searching for natural products with fewer side effects for developing adjunctive therapeutic options is necessary. METHODS:The effects of 6-gingerol on ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-019-03999-9
更新日期:2020-02-01 00:00:00
abstract::We investigated the effect of pretreatment with difluoromethylornithine (DFMO), an ornithine decarboxylase inhibitor, on the cytocidal responses of four human adenocarcinoma cell lines to two alkylating and crosslinking agents: chlorambucil and N,N',N"-triethylenethiophosphoramide (thiotepa). The cell lines studied in...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00299860
更新日期:1986-01-01 00:00:00
abstract:PURPOSE:Phosphatidylinositol (PtdIns) 3-kinase is an important mediator of many cellular functions. The study of PtdIns 3-kinase has been facilitated by the existence of the potent irreversible inhibitor of p110 PtdIns 3-kinase, wortmannin. The purpose of the study was to investigate the relationship between the cell g...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s002800051123
更新日期:1999-01-01 00:00:00
abstract::Plasma and tissue levels of doxorubicin (DXR) and doxorubicinol (DXR-OL) were measured fluorometrically after high-pressure liquid chromatography at 1, 3, and 24 h following one, nine, and 24 doses of 1.0 mg DXR/kg or one and eight doses of 4.0 mg DXR/kg, IP, to rats. Comparison of plasma levels of DXR found following...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00258216
更新日期:1981-01-01 00:00:00
abstract::In recent years significant progress in the understanding of the immune biology of melanoma has evolved from the identification of melanoma antigens (MAs) recognized by T cells. MAs consist of intracellular proteins that are expressed on the surface of cancer cells in association with human leukocyte antigen (HLA) cla...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,评审
doi:10.1007/pl00014052
更新日期:2000-01-01 00:00:00
abstract::Tumor-tissue and plasma concentrations of platinum were studied prospectively in two groups of eight patients who were suffering from advanced non-small-cell lung cancer. Treatments including two different schedules of cisplatin administration (25 vs 100 mg/m2 on day 1) were compared. At 30 min after the beginning of ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00689280
更新日期:1990-01-01 00:00:00
abstract::Reduced drug accumulation may be one reason for intrinsic drug resistance in chronic lymphatic leukemia of the B-cell type (B-CLL). Immunophenotyped leukemic human B-cells from 38 cases of B-CLL were characterized for P-glycoprotein (PGP) content. In all, 30 cases of B-CLL were additionally analyzed for further parame...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00686038
更新日期:1994-01-01 00:00:00
abstract:PURPOSE:The present study was designed to determine pharmacological and biochemical properties of 2-methoxyantimycin A analogs (OMe-A1, OMe-A2, OMe-A3, and OMe-A5), which are novel antitumor compounds, and provide a basis for future pharmaceutical development, preclinical evaluation, and clinical trials. METHODS:A hig...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-004-0978-8
更新日期:2005-09-01 00:00:00
abstract:PURPOSE:Imatinib mesylate (Imatinib), clinically employed for chronic myeloid leukemia and gastrointestinal stromal tumors, is a selective inhibitor of the tyrosine kinases, c-abl, c-kit and PDGFRs. Due to the frequent expression of these genes in breast cancer cells, the clinical efficacy of Imatinib has recently been...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-010-1394-x
更新日期:2011-04-01 00:00:00
abstract::Cisplatin produces good responses in solid tumours including small cell lung cancer (SCLC) but this is limited by the development of resistance. Oxaliplatin is reported to show activity against some cisplatin-resistant cancers but there is little known about oxaliplatin in SCLC and there are no reports of oxaliplatin ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-005-0148-7
更新日期:2006-08-01 00:00:00
abstract::The toxic effect of 3'-deoxyadenosine N1-oxide (3'-dANO) on mice, on their different organs, and on Ehrlich ascites tumor cells was studied. In both healthy and tumour-bearing animals, the lethal dose for 10% of the mice receiving i.p. injections (LD10) of 3'-dANO was estimated to be about 300 mg/kg x 4 days in one mo...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00686398
更新日期:1992-01-01 00:00:00
abstract:PURPOSE:A metronomic schedule of chemotherapy (resulting in a greater frequency of drug delivery) has shown efficacy in head and neck cancer. Our aim was to investigate the overall survival in tongue cancer patients with metronomic neoadjuvant chemotherapy with bleomycin compared to those with surgery alone. METHODS:I...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-016-3141-4
更新日期:2016-10-01 00:00:00
abstract::Nine children with soft tissue sarcomas, five of them rhabdomyosarcomas with initial metastatic disease, (one patient, partial response, one patient), refractory primary, (two patients, relapse, five patients) were treated with a combination of high-dose VP16 (100 mg/m2 daily for 5 days) and cisplatin (40 mg/m2 daily ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00685912
更新日期:1994-01-01 00:00:00
abstract::The full-scale commercial appearance of antibiotics in the 1950s caused a shift in the nature of lethal diseases from infectious and acute to noninfectious and chronic. In this situation, biological response modifiers (BRMs), which are not based on selective toxicity, could be expected to be useful. Several types of B...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,评审
doi:10.1007/s00280-003-0590-3
更新日期:2003-07-01 00:00:00
abstract:PURPOSE:Temozolomide (TMZ) is a widely used oral alkylating agent that has been associated with the development of severe hematologic adverse events (HAEs). Limited clinical information about HAEs is available. METHODS:We searched the FDA MedWatch database for TMZ and obtained all MedWatch reports on TMZ submitted to ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-011-1679-8
更新日期:2012-01-01 00:00:00
abstract:PURPOSE:5-Fluorouracil (5-FU), an anti-cancer drug, has been used for hepatoblastoma (HB) chemotherapy in children, who may have impaired ovarian follicle pool reserve with lasting effects to reproduction. Therefore, this study aimed to investigate 5-FU effects on survival, growth, and morphology of ovarian preantral ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-020-04217-7
更新日期:2021-01-20 00:00:00
abstract:PURPOSE:The purpose of this article is to report the first case of markedly increased anticoagulant activity of warfarin when used in combination with doxifluridine, given as a replacement for capecitabine. METHODS:International normalized ratio (INR) of a 73-year-old female patient receiving warfarin was increased af...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-010-1249-5
更新日期:2010-10-01 00:00:00
abstract:PURPOSE:Malignant gliomas display aggressive local behavior and are not cured by existing therapy. Etoposide, a topoisomerase-II-inhibitor agent, is one of the most active and useful antineoplastic agents. However, etoposide is not usually used on these tumors. We undertook an in vitro study to prove that etoposide is ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s002800050713
更新日期:1998-01-01 00:00:00
abstract:PURPOSE:The safety and efficacy of oral metronomic low-dose treosulfan chemotherapy in combination with the cyclooxygenase-2 (COX-2) inhibitor rofecoxib as a compound with antiangiogenic potential, a therapeutic regimen optimally targeting endothelial cells instead of tumor cells, were assessed in pretreated advanced m...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s00280-003-0678-9
更新日期:2003-11-01 00:00:00
abstract::Recent advances in cDNA microarray techniques have enabled us to study the expression of many genes simultaneously. As gastric cancer remains one of the most common cancers in Japan, we studied gene expression profiles in gastric cancer by cDNA microarray analysis to determine if it would be clinically useful. We demo...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-004-0882-2
更新日期:2004-09-01 00:00:00
abstract::Over the last decade, metronomic chemotherapy has been increasingly considered as an attractive strategy for treating cancer in a variety of settings. Beside pharmaco-economic considerations making metronomics a unique opportunity in low- or middle-income countries, revisiting dosing schedules using continuous low dos...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,评审
doi:10.1007/s00280-014-2546-1
更新日期:2014-09-01 00:00:00
abstract:PURPOSE:There is a need for effective chemotherapy protocols for gall bladder cancer (GBC). Gemcitabine has antitumor activity in pancreatic cancer. Oxaliplatin is effective in GI cancers. Based on evidence of synergy between these two, we designed this study to evaluate efficacy of this combination in unresectable GBC...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-009-1055-0
更新日期:2010-02-01 00:00:00
abstract::The value of estrogen receptor (ER) status in the prediction of tumor response to combination chemotherapy was retrospectively analyzed in breast cancer patients selected for prospective controlled trials of chemotherapy (85 with advanced disease and 256 with operable tumors). All patients were previously untreated wi...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/BF00255456
更新日期:1980-01-01 00:00:00
abstract:BACKGROUND:As tumors evolve, they upregulate glucose metabolism while also encountering intermittent periods of glucose deprivation. Here, we investigate mechanisms by which pancreatic cancer cells respond to therapeutic (2-deoxy-D-glucose, 2-DG) and physiologic (glucose starvation, GS) forms of glucose restriction. M...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-013-2358-8
更新日期:2014-02-01 00:00:00