Abstract:
:The aim of the present studies was to elucidate the effects and optimal modulatory conditions of 5-ethyl-2'-deoxyuridine (EtdUrd) on the antitumour efficacy, pharmacokinetics and catabolism of 5-fluorouracil (5-FU) on Colon-26 and Colon-38 murine tumours. HPLC and GC-MS techniques were used to measure the concentrations of 5-FU, dihydro-5-fluorouracil, EtdUrd, 5-ethyluracil and uridine in the plasma and that of 5-FU and 5-fluoro-2'-deoxyuridine monophosphate (FdUMP) in the tumours. It was shown that EtdUrd, given 1 h before 5-FU, selectively enhanced the antitumour action of 5-FU, without significantly increasing its toxic side-effects, thus resulting in an approximately three times higher therapeutic index. Pharmacokinetic studies revealed that 1 h after 400 mg/kg EtdUrd administration - i.e. at the time of 5-FU treatment - the plasma concentration of EtdUrd was 269 microM, and that of 5-ethyluracil, as the major metabolite of EtdUrd, was 421 microM. It is of interest that EtdUrd pretreatment did not change the maximal plasma concentration of 5-FU; however, the half-life of the terminal elimination increased from 114.5 min to 171.2 min and thus the mean residence time of 5-FU rose significantly (P < 0.05). After the combined treatment, the maximal concentration of dihydro-5-fluorouracil in the plasma decreased from 61.06 microM to 29.70 microM (P < 0.01). The intratumoral concentrations of 5-FU were 34%-158% higher 6-96 h after the combined treatment than after the single 5-FU treatment. EtdUrd also caused a moderate increase in the intratumoral level of FdUMP. It is noteworthy, that EtdUrd increased the endogenous uridine concentration in the plasma from 18 microM to a maximum of 249 microM, and the level remained high for longer than 6 h. The present studies indicate that EtdUrd enhances the therapeutic index of 5-FU by reducing the catabolism, prolonging the plasma and intratumoral concentrations of 5-FU and, at the same time, offering protection to normal organs by increasing the endogenous uridine level.
journal_name
J Cancer Res Clin Oncoljournal_title
Journal of cancer research and clinical oncologyauthors
Kralovánszky J,Katona C,Jeney A,Pandi E,Noordhuis P,Erdélyi-Tóth V,Otvös L,Kovács P,Van der Wilt CL,Peters GJdoi
10.1007/s004320050333subject
Has Abstractpub_date
1999-12-01 00:00:00pages
675-84issue
12eissn
0171-5216issn
1432-1335pii
91250675.432journal_volume
125pub_type
杂志文章abstract:PURPOSE:Individuals affected by rheumatoid arthritis (RA) occasionally develop lymphoproliferative disorders (RA-LPD). To study the molecular changes underscoring the RA-LPD, mutations of p53 and Bak gene were analyzed in RA-LPD with (MTX-LPD) or without methotrexate treatment for RA (non-MTX-LPD). METHODS:Histology a...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/s00432-006-0152-2
更新日期:2007-02-01 00:00:00
abstract::Irritant diterpene ester toxins were isolated from Euphorbia nubica and E. helioscopia, which are contaminants of the green fodder of livestock in Egypt. Fractionations of methanol extracts of aerial parts of both plants were monitored by the irritation unit on the mouse ear. Plant extracts were subjected to multiplic...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/s004320000214
更新日期:2001-01-01 00:00:00
abstract::Tissue sections of frozen biopsy specimens obtained from normal and hyperplastic human lymphoid tissues as well as 40 cases of non-Hodgkin's lymphomas were analysed in immunofluorescence tests (using red TRITC and green FITC double-labeling). A panel of antisera including well-characterized conventional reagents to im...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/BF00405058
更新日期:1981-01-01 00:00:00
abstract::For therapeutic purposes, two chimeric DNA/RNA hammerhead ribozymes were synthesized to cleave AML1/MTG8, the t(8;21)-associated fusion mRNA of acute myeloid leukemia. One ribozyme, A/MRZ-1, recognizes the area adjacent to the fusion point between AML1 and MTG8, and cleaves six bases downstream from this point. The ot...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/BF01209655
更新日期:1996-01-01 00:00:00
abstract::Elevated glutamate concentrations are commonly observed in tumor patients, and glutamate was recently found to competitively inhibit the membrane transport of cystine. We therefore investigated the possibility that elevated plasma glutamate levels may damage the immune system. The experiments in this report demonstrat...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/BF00417824
更新日期:1988-01-01 00:00:00
abstract:BACKGROUND:Acute kidney injury (AKI) is gaining worldwide attention recently, emerging as a major public health threat. However, the association between the development of AKI and subsequent malignancy has not been studied before. METHODS:We conducted a population study based on the Taiwan National Health Insurance da...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/s00432-014-1600-z
更新日期:2014-04-01 00:00:00
abstract:BACKGROUND:Proteins involved in the aberrant regulation of signaling pathways and their downstream effectors are promising targets for cancer therapy. Survivin is an anti-apoptotic and cell cycle-promoting protein, which is consistently overexpressed in cancer cells. In normal cells, its expression is tightly controlle...
journal_title:Journal of cancer research and clinical oncology
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doi:10.1007/s00432-012-1195-1
更新日期:2012-07-01 00:00:00
abstract:PURPOSE:To evaluate prognostic factors in estrogen receptor (ER)-positive, operable breast cancer focusing on the progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). PATIENTS AND METHODS:A total of 819 patients with ER-positive, operable breast cancer were enrolled. All patients received up...
journal_title:Journal of cancer research and clinical oncology
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doi:10.1007/s00432-011-0976-2
更新日期:2011-07-01 00:00:00
abstract:OBJECTIVE:Brain metastasis as the first symptom of lung cancer is a unique clinical entity. We conducted a retrospective study to investigate the clinical characteristics and survival of patients with lung cancer whose first symptom was brain metastases in an Asian population. METHODS:A retrospective study of 186 such...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/s00432-012-1344-6
更新日期:2013-03-01 00:00:00
abstract::Three thousand Yoshida sarcoma cells were inoculated into the wall of the descending colon of each of 120 male Sprague-Dawley rats. On day 8 after the tumor implantation, the animals were at random divided into four groups of 30 rats each. The effect of cyclophosphamide (70 mg/kg), BCNU (25 mg/kg), and methyl-CCNU (45...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/BF00405350
更新日期:1979-05-14 00:00:00
abstract:PURPOSE:Putative tumor suppressor genes LATS1 and LATS2 are implicated in the regulation of the cell cycle at the G2/M and G1/S phase, respectively. This study investigated possible correlations of intra-tumoral LATS1 and LATS2 mRNA levels with response to epirubicin plus cyclophosphamide (EC) or docetaxel (DOC) treatm...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/s00432-007-0194-0
更新日期:2007-08-01 00:00:00
abstract:PURPOSE AND METHODS:Loss of heterozygosity (LOH) in a chromosomal location indicates the presence of an inactivated tumor suppressor gene (TSG). Inactivation of TSG has a functional role in the tumorigenesis of head and neck squamous cell carcinoma (HNSCC). Based on the recent evidences of a putative TSG on chromosome ...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/s00432-008-0423-1
更新日期:2008-12-01 00:00:00
abstract::A transplantable non-immunogenic murine carcinoma of spontaneous origin, WHT Carcinoma N-C (Hewitt), was used to assess the effectiveness of melphalan (Ml) and/or methotrexate (Mx) for treatment of occult metastatic disease following surgical excision of primary tumors. Early surgical excision alone cured 66% of mice;...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/BF00410790
更新日期:1980-01-01 00:00:00
abstract::Targeted therapy refers to anticancer treatment which specifically targets key molecules of cancer cells and/or neovascular cells, aiming to thus interfere with processes of tumorigenesis, cancer progression and metastasis. The epidermal growth factor receptor (EGFR) was the first receptor to be proposed for targeted ...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章,评审
doi:10.1007/s00432-009-0622-4
更新日期:2009-09-01 00:00:00
abstract:PURPOSE:PARP inhibitors (PARPi) are used in a wide range of human solid tumours but a limited evidence is reported in rhabdomyosarcoma (RMS), the most frequent childhood soft-tissue sarcoma. The cellular and molecular effects of Olaparib, a specific PARP1/2 inhibitor, and AZD2461, a newly synthesized PARP1/2/3 inhibito...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/s00432-018-2774-6
更新日期:2019-01-01 00:00:00
abstract::Bleomycin was injected i.p. in rats, and the amount of expired ethane which indicates lipid peroxidation was followed up for 78 h. Compared to controls neither 1 x 30 mg/kg and 2 x 30 mg/kg nor 1 x 70 mg/kg bleomycin led to increased ethane expiration, although body weight loss indicated toxicity. That pulmonary toxic...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/BF00409644
更新日期:1982-01-01 00:00:00
abstract::The antitumor and anti-metastatic effects of a potent angiogenesis inhibitor, O-(chloroacetyl-carbamoyl)fumagillol (TNP-470), was investigated in a highly metastatic model of human hepatocellular carcinoma-LCI-D20. Small pieces of LCI-D20 tumor tissue were implanted subcutaneously into the right axillary region of 24 ...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/BF01240121
更新日期:1997-01-01 00:00:00
abstract::Multicellular tumor spheroids (MCTS) grown from the bladder cancer cell line RT112 and from the prostate cancer cell line PCA were exposed to 200 or 800 electromagnetically generated focused ultrasound shock waves. RT112 cells showed a distinct but transient decrease in proliferation whereas the effect of PCA cells wa...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/BF01240146
更新日期:1994-01-01 00:00:00
abstract::A previous cohort-study in a cardboard factory demonstrated that high and prolonged occupational exposure to trichloroethene (C2HCl3) is associated with an increased incidence of renal cell cancer. The present hospital-based case/control study investigates occupational exposure in 58 patients with renal cell cancer wi...
journal_title:Journal of cancer research and clinical oncology
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doi:10.1007/s004320050186
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abstract::The genetically engineered chimeric cB72.3m4 and cB72.3m12 antibodies recognize the same tumor-associated TAG72 antigen. The high-affinity cB72.3m4 antibody had an approximately 18-fold higher affinity constant for the TAG72 antigen than the low-affinity cB72.3m12 antibody. The relationship between antibody affinity a...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/BF01200725
更新日期:1993-01-01 00:00:00
abstract:PURPOSE:B-cell translocation gene 3 (BTG3) has been identified as a candidate driver gene for various cancers, but its specific role in colorectal cancer (CRC) is poorly understood. We aimed to investigate the relationship between expression of BTG3 and clinicopathological features and prognosis, as well as to explore ...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/s00432-017-2561-9
更新日期:2018-02-01 00:00:00
abstract::Twenty-five surgical specimens of malignant human prostate, 3 lymph nodes with metastatic prostate carcinoma, 11 normal human prostates, as well as 3 human prostate cell lines (DU-145, PC3 and LNCaP) were examined for the expression of the human matrix metalloproteinase-7 gene (MMP-7) from the human collagenase family...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/BF01613138
更新日期:1991-01-01 00:00:00
abstract:PURPOSE:The study aim was to compare the disease control in two groups of patients affected by liver metastases from CRC treated with microwave ablation (MWA) or stereotactic body radiation therapy (SBRT). METHODS:We extracted data of patients treated between 2009 and 2016. Inclusion criteria were: (1) maximum diamete...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/s00432-018-2692-7
更新日期:2018-09-01 00:00:00
abstract:PURPOSE:The TNM classification is used to assess cancers of the oral cavity, and advancements in imaging techniques have revealed clear variations in tumor volume at presentation. This study therefore aimed to clarify whether preoperative imaging, with exact measurements of the tumor, could affect post-surgery survival...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/s00432-014-1881-2
更新日期:2015-06-01 00:00:00
abstract:PURPOSE:MicroRNAs (miRs) have been frequently reported dysregulating in tumors and playing a crucial role in tumor development and progression. However, the expression of miR-155 and its role in gastric cancer (GC) are still obscure. METHODS:qRT-PCR was applied to detect miR-155 expression in 60 matched GC samples and...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/s00432-016-2139-y
更新日期:2016-06-01 00:00:00
abstract::The laboratory findings in patients receiving high-dose vitamin A as adjuvant treatment for stage I lung cancer are here reported. A group of 283 patients were randomized to either treatment with retinyl palmitate (300,000 IU daily for 12 months) or standard follow-up, and are now evaluable after a median observation ...
journal_title:Journal of cancer research and clinical oncology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/BF01613140
更新日期:1991-01-01 00:00:00
abstract:INTRODUCTION:Aberrant expression of RNA-binding motif protein 3 (RBM3) has been suggested as a prognostic biomarker in several malignancies. MATERIALS AND METHODS:This study was performed to analyse the prevalence and clinical significance of RBM3 immunostaining in non-small cell lung cancers (NSCLCs). Therefore, we t...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/s00432-019-02850-1
更新日期:2019-04-01 00:00:00
abstract:PURPOSE:The aim of this study was to combine clinical pathologic variables that are associated with pathologic completer response (pCR) and relapse-free survival (RFS) after neoadjuvant chemotherapy into prediction nomograms. METHODS:A total of 370 stage II or III breast cancer patients who received neoadjuvant doceta...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/s00432-011-0991-3
更新日期:2011-09-01 00:00:00
abstract:BACKGROUND:Long noncoding RNAs (LncRNAs) have been demonstrated as playing important roles in diverse biological processes including tumorigenesis. However, the clinical significance and biological function of LncRNA nuclear-enriched abundant transcript 1 (NEAT1) in gastric cancer are still unknown. The aim of this stu...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/s00432-016-2152-1
更新日期:2016-07-01 00:00:00
abstract:PURPOSE:Investigation of cell migration and proliferation of human glioma cell line spheroids (CLS) and evaluation of morphology, apoptosis, and immunohistochemical expression of MIB-1, p53, and p21 of organotypic muticellular spheroids (OMS) following cisplatin (CDDP) and irradiation (RT). MATERIAL AND METHODS:Sphero...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/s00432-005-0014-3
更新日期:2005-11-01 00:00:00