Abstract:
:The mechanisms of cytotoxicity, cellular drug uptake, intracellular drug distribution, cellular pharmacokinetics, formation of arabinofuranosylcytosine triphosphate (ara-CTP), and DNA incorporation of N4-hexadecyl-1-beta-D-arabinofuranosylcytosine (NHAC), a new lipophilic derivative of arabinofuranosylcytosine (ara-C) formulated in small unilamellar liposomes, were determined in vitro in the human leukemic cell lines K-562 and U-937. Furthermore, the induction of erythroid differentiation by NHAC was tested in K-562 cells. The cytotoxicity of NHAC in both cell lines was not influenced by the deoxycytidine (dCyd) concentration or the presence of the nucleoside-transport-blocking agent dipyridamole as demonstrated in coincubations with dCyd and/or dipyridamole, whereas in contrast, the cytotoxicity of ara-C was decreased additively by both drugs. As compared with ara-C, the uptake of NHAC displayed up to 16- and 5-fold increases in K-562 and U-937 cells, respectively, depending on the drug concentration. Studies of the drug distribution and pharmacokinetics of NHAC revealed a depot effect for NHAC in the cell membranes, resulting in half-lives 2.6 and 1.4 times longer than those of ara-C in the two cell lines. The ara-CTP concentrations derived from NHAC were 150- and 75-fold lower at a drug concentration of 1 microM in K-562 and U-937 cells, respectively. The DNA incorporation of the drugs observed after incubation with 2 microM NHAC was 60- and 30-fold lower as compared with that seen at 2 microM ara-C in the two cell lines. Furthermore, NHAC was capable of inducing irreversible erythroid differentiation to a maximum of only 22% of K-562 cells, whereas ara-C induced differentiation at a drug concentration 100-fold lower in 50% of the cells. These results indicate a mechanism of cytotoxicity for NHAC that is independent of the nucleoside transport mechanism and the phosphorylation pathway and suggest that the mechanisms of action of NHAC are significantly different from those of ara-C. Therefore, NHAC might be used for the treatment of ara-C-resistant malignancies.
journal_name
Cancer Chemother Pharmacoljournal_title
Cancer chemotherapy and pharmacologyauthors
Horber DH,Schott H,Schwendener RAdoi
10.1007/BF00685798subject
Has Abstractpub_date
1995-01-01 00:00:00pages
483-92issue
6eissn
0344-5704issn
1432-0843journal_volume
36pub_type
杂志文章abstract::Sodium cyanate (NaOCN) at a dose of 250 mg/kg was shown to decrease protein synthesis in P388 leukemia tumor cells to approximately 52% of control values at 2 h and 32% at 5 h after NaOCN administration, without a corresponding decrease in various normal tissues of the tumor-bearing CD2Fl mice. CD2Fl mice that had rec...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00254597
更新日期:1984-01-01 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
abstract::A total of 40 patients with metastatic breast cancer were treated with 120 mg/m2 i.v. epirubicin every 3 weeks for a maximum of 10 cycles. Nine achieved a complete response and 17 showed a partial response, for an objective response rate of 65% (95% confidence interval, 47%-83%); the median duration of response was 7 ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/BF00688864
更新日期:1991-01-01 00:00:00
abstract::A total of 51 patients with large, primary, high-grade soft-tissue sarcomas of the extremities were treated at our institute with two preoperative and three postoperative cycles of doxorubicin plus ifosfamide/mesna. Preoperative doxorubicin was given intra-arterially for lesions of the lower extremities. Of 47 evaluab...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章,多中心研究
doi:
更新日期:1993-01-01 00:00:00
abstract::Fourteen new agents of natural products origin which are under development as antitumor agents at the National Cancer Institute are discussed with reference to their sources, structures, antitumor activity, current status, and future prospects as clinically effective agents. ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00254042
更新日期:1978-01-01 00:00:00
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:PURPOSE:The combination of capecitabine and paclitaxel (XP) has demonstrated synergistic antitumor activity in preclinical models. The purpose of this phase II study was to evaluate the efficacy and safety of a monthly XP regimen in patients with metastatic breast cancer (MBC). METHODS:Eligible patients had received o...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,多中心研究
doi:10.1007/s00280-012-2068-7
更新日期:2013-03-01 00:00:00
abstract:BACKGROUND:Statins have potential antineoplastic properties via arrest of cell-cycle progression and induction of apoptosis. A previous study demonstrated in vitro and in vivo antineoplastic synergism between statins and gemcitabine. The present randomized, double-blinded, phase II trial compared the efficacy and safet...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1007/s00280-013-2328-1
更新日期:2014-01-01 00:00:00
abstract::AspCNU and SarCNU are two amino acid amide congeners (L-asparaginamide and sarcosinamide congeners) of chloroethylnitrosoureas. The in vitro myelotoxicity of these agents compared with BCNU at 1-8 micrograms/ml was determined in bone marrow cells from normal volunteers in the CFU-C assay. AspCNU and SarCNU were signif...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00434356
更新日期:1985-01-01 00:00:00
abstract::Unidirectional blood-brain barrier transfer of the lipophilic anticancer agents vincristine and vinblastine was studied in anesthetized rats, using an isolated, in situ brain perfusion technique. Drug binding to plasma constituents was also measured. Despite the high lipophilicity of these agents (the log octanol/phys...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF02897227
更新日期:1990-01-01 00:00:00
abstract:PURPOSE:Decitabine is a nucleoside analog used in the treatment for myelodysplastic syndrome. The compound requires intracellular conversion to its triphosphate to become active. Decitabine triphosphate has, however, never been quantified in peripheral blood mononuclear cells (PBMCs) from patients. METHOD:This article...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-012-1850-x
更新日期:2012-06-01 00:00:00
abstract:PURPOSE:Anti-angiogenic agents combined with histone deacetylase inhibitors act synergistically in vitro and in vivo. We conducted a phase I study of the combination of the anti-VEGF monoclonal antibody bevacizumab and histone deacetylase inhibitor valproic acid in patients with advanced cancers. METHODS:Bevacizumab w...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-014-2384-1
更新日期:2014-03-01 00:00:00
abstract::A total of 26 evaluable patients with previously untreated, non-resectable adenocarcinoma of the lung were given 80 mg/m2 i.v. teniposide daily for 5 days every 3 weeks. Three partial responses (11%) were obtained that lasted for 12, 11 and 32 weeks, respectively. Leucopenia was the dose-limiting side effect, with WBC...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00685166
更新日期:1991-01-01 00:00:00
abstract:PURPOSE:The safety of S-1 in recurrent colorectal cancer patients with chronic myeloid leukemia (CML) treated with dasatinib has not been established. We evaluated the safety and pharmacokinetics of S-1 in a recurrent colon cancer patient with CML treated with dasatinib. PATIENT:A 70-year-old man had undergone surgery...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-014-2620-8
更新日期:2014-12-01 00:00:00
abstract::Dose fractionation is known to reduce the toxicity of ifosfamide and also results in an increased production of alkylating metabolites. Administration by slow infusion using the convenience of ambulatory pumps is therefore of interest. We used HPLC to investigate the stability of ifosfamide in aqueous solution (either...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF02897261
更新日期:1990-01-01 00:00:00
abstract:PURPOSE:Arsenic compounds have been found to be effective in the treatment of acute promyelocytic leukemia through the downregulation of bcl-2 expression. Resistant ovarian cancer cells often overexpress bcl-2 or p53 proteins or both. We hypothesized that arsenic compounds, such as As2O3 and As2S3, could also be active...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s002800100278
更新日期:2001-06-01 00:00:00
abstract:PURPOSE:Many patients with non-small cell lung cancer (NSCLC) are eligible only for palliative radiation (RT) at presentation. This study was designed to assess the feasibility of adding the anti-EGFR monoclonal antibody nimotuzumab to palliative thoracic RT. METHODS:Patients with stage IIB, III or IV NSCLC considered...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-010-1379-9
更新日期:2011-04-01 00:00:00
abstract:PURPOSE:Glutathione S-transferases (GSTs) family of enzymes is best known for their cytoprotective role and their involvement in the development of anticancer drug resistance. Recently, emergence of non-detoxifying properties of GSTs has provided them with significant biological importance. Addressing the complex inter...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,评审
doi:10.1007/s00280-014-2566-x
更新日期:2015-01-01 00:00:00
abstract:PURPOSE:Folate receptor (FR) targeted drug conjugates were prepared by covalently attaching the vitamin folate, to the potent anticancer drug, mitomycin C (MMC). One such conjugate, called EC72, was synthesized with an intramolecular disulfide bond, and it was found to exhibit efficacious anti-tumor activity against FR...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-005-0151-z
更新日期:2006-08-01 00:00:00
abstract::A total of 2,238 new cancer patients were treated in our institution in 1988; among the 423 (18.9%) who were greater than 70 years old, 51 underwent chemotherapy. The median age was 75.8 years, and the Karnofsky performance status (KPS) was greater than or equal to 70% for 40 patients. Malignancies were hematopoietic ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00687328
更新日期:1991-01-01 00:00:00
abstract:PURPOSE:The ErbB family members are protein tyrosine kinases, which play a crucial role in the signal transduction pathways that regulate key cellular functions. Overexpression of the ErbB family members is associated with oncogenicity, metastatic potential, cell proliferation, apoptosis, angiogenesis, and prognosis in...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,评审
doi:10.1007/s00280-011-1748-z
更新日期:2011-12-01 00:00:00
abstract:PURPOSE:To characterize and compare pharmacokinetic parameters in children and adults treated with temozolomide (TMZ) administered for 5 days in three doses daily, and to evaluate the possible relationship between AUC values and hematologic toxicity. METHODS:TMZ pharmacokinetic parameters were characterized in pediatr...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1007/s00280-003-0677-x
更新日期:2003-12-01 00:00:00
abstract:OBJECTIVE:The aim of this study was to evaluate the efficacy and toxicities of liposome-paclitaxel and carboplatin concurrent with radiotherapy for locally advanced lung squamous cell carcinoma (LSCC). METHODS:The clinical data of 38 patients with locally advanced LSCC treated with liposome-paclitaxel based concurrent...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-018-3640-6
更新日期:2018-09-01 00:00:00
abstract:PURPOSE:D-Limonene is a natural monoterpene with pronounced chemotherapeutic activity and minimal toxicity in preclinical studies. A phase I clinical trial to assess toxicity, the maximum tolerated dose (MTD) and pharmacokinetics in patients with advanced cancer was followed by a limited phase II evaluation in breast c...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s002800050793
更新日期:1998-01-01 00:00:00
abstract::Intravesical instillation of adriamycin (ADM) or mitomycin C (MMC) was carried out for the purpose of preventing the recurrence of superficial bladder cancers (Ta and T1) after transurethral resection or transurethral coagulation. First, eligible patients were divided into two groups (solitary and multiple) and then t...
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/BF00262491
更新日期:1987-01-01 00:00:00
abstract:PURPOSE:We report the unexpected absence of early relapse (before 30 months) in 24 consecutive patients with isolated limb primary Ewing sarcoma treated with an intensified pilot protocol, SCMCIE94. METHODS:Clinical data for the study were collected retrospectively from the patient files. The protocol included 6 cours...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-019-03789-3
更新日期:2019-05-01 00:00:00
abstract:PURPOSE:The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor gefitinib (ZD1839, Iressa) is approved for cancer treatment. We investigated whether gefitinib treatment can enhance human EGF (hEGF) uptake in vitro, thereby increasing the potential of hEGF as a vehicle for EGFR-targeted therapy. METHODS:W...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-013-2198-6
更新日期:2013-08-01 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:PURPOSE:Angiotensin (1-7) [A(1-7)] is a bioactive peptide of the renin angiotensin system that stimulates the number of bone marrow progenitors and hematopoietic recovery after myelosuppression. We evaluated the combination of A(1-7) with colony-stimulating factors, Neupogen and Epogen, on bone marrow progenitors and t...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-013-2312-9
更新日期:2013-12-01 00:00:00
abstract::Doxifluridine (5'-deoxy-5-fluorouridine, 5'-dFUR) metabolism has been reported to be saturable and associated with a fall in clearance of the drug as the dose is increased. The aim of the present study was to determine the disposition of 5'-dFUR and 5-fluorouracil (5-FU) when 5'-dFUR was given as a 5-day infusion, wit...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00684885
更新日期:1990-01-01 00:00:00