Abstract:
PURPOSE:The aim of this study was to investigate the relationship between changes in IL-1β expression and intestinal apoptosis after chemotherapy. And we further determine whether interleukin-1 receptor antagonist (IL-1Ra) reduces apoptosis in vivo after 5-fluorouracil (5-FU) chemotherapy in the small intestine. METHODS:Intestinal mucositis was induced in mice by intraperitoneal injection of a single dose of 5-FU (200 mg/kg). IL-1Ra (1 mg/kg) was injected subcutaneously twice daily after 5-FU injection. 5-FU-induced intestinal apoptosis was detected by TUNEL assay. The expression of IL-1β induced by 5-FU in local intestinal tissue was examined by RT-PCR and immunohistochemistry. Assessment of 5-FU-induced mucositis (histology, diarrhea scores, bowel weight) was performed. The apoptosis-related proteins were investigated by western blotting analysis. The proliferation of intestine was examined by immunohistological staining of PCNA. Viability of IEC-6 cells was determined using the CCK-8 assay. The apoptosis of IEC-6 cells was examined by Hoechst 33342 staining. RESULTS:The variation of IL-1β expression induced by 5-FU was in accordance with the changes in intestinal apoptosis. Administration of IL-1Ra could block the destructive effect of IL-1β and reduce apoptosis in the small intestinal crypt after chemotherapy. The protection against apoptosis was in accordance with the reduction of the up-regulation of Bax and caspase 3 and the elimination of the down-regulation of Bcl-2 and Bcl-xL. Moreover, IL-1Ra attenuated the severity of intestinal mucositis induced by 5-FU and enhanced intestinal crypt proliferation. In vitro experiments showed that IL-1Ra suppressed apoptosis and increased cell viability in enterocyte IEC-6 cells treated with 5-FU. Additionally, IL-1Ra did not affect the chemotherapeutic effect of 5-FU in tumor CT-26 xenograft mice. CONCLUSIONS:Our studies elucidate that IL-1β is quite possibly involved in and mediated the course of intestinal apoptosis after 5-FU chemotherapy. Administered with IL-1Ra protects mice against intestinal apoptosis induced by 5-FU, relieves mucosal impairment of the small intestine, and facilitates the recovery of the intestinal mucosa. IL-1Ra treatment offers a novel promising strategy for the prevention and cure of chemotherapy-induced intestinal mucositis in clinical practice.
journal_name
Cancer Chemother Pharmacoljournal_title
Cancer chemotherapy and pharmacologyauthors
Wu ZQ,Han XD,Wang Y,Yuan KL,Jin ZM,Di JZ,Yan J,Pan Y,Zhang P,Huang XY,Wang ZG,Zheng Qdoi
10.1007/s00280-010-1451-5subject
Has Abstractpub_date
2011-07-01 00:00:00pages
87-96issue
1eissn
0344-5704issn
1432-0843journal_volume
68pub_type
杂志文章abstract:PURPOSE:Inhibitors of DNA (cytosine-5)-methyltransferases (DNMT) are active antineoplastic agents. We conducted the first-in-human phase I trial of 5-fluoro-2'-deoxycytidine (FdCyd), a DNMT inhibitor stable in aqueous solution, in patients with advanced solid tumors. Objectives were to establish the safety, maximum tol...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,多中心研究
doi:10.1007/s00280-014-2674-7
更新日期:2015-03-01 00:00:00
abstract::Thymidine (dThd) concentrations have been measured in the sera of normal subjects and solid tumor cancer patients by means of a sensitive high-pressure liquid chromatographic assay to determine whether natural and methotrexate (MTX)-induced fluctuations were large enough to alter the toxicity of MTX to marrow. The mea...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00434388
更新日期:1981-01-01 00:00:00
abstract::The aim of the present study was to investigate whether cisplatin would enhance the radioresponse of a human tumour xenograft when given in different schedules combined with accelerated fractionated radiation therapy. A human squamous carcinoma of the hypopharynx, FaDu, was grown in the thigh of athymic nude mice. Tum...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s002800050699
更新日期:1997-01-01 00:00:00
abstract:BACKGROUND:Ovarian cancer is one of the most frequently fatal gynecological cancers because most cases are diagnosed at an advanced stage. Loss of growth control and a marked resistance to apoptosis are considered major mechanisms driving tumor progression. Little is known about the effect of various treatment regimens...
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/s00280-004-0993-9
更新日期:2005-10-01 00:00:00
abstract::Long-term results were analyzed in terms of tumor progression and survival in patients with superficial bladder cancer who were enrolled in the second intravesical chemoprophylactic study of the Japanese Urological Cancer Research Group for Adriamycin, which was started in July 1982. This study was a prospective, rand...
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/BF00686935
更新日期:1992-01-01 00:00:00
abstract::Our previous randomised trial in patients with advanced ovarian cancer indicated a significant response and survival advantage for those receiving high-dose (100 mg/m2) as compared with low-dose (50 mg/m2) cisplatin in combination with cyclophosphamide (750 mg/m2). However, this was accompanied by more toxicity; perip...
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/s002800050723
更新日期:1998-01-01 00:00:00
abstract:PURPOSE:Pemetrexed, a multi-targeted antifolate that disrupts synthesis of both purines and pyrimidines, is approved for use in malignant pleural mesothelioma and non-small cell lung cancer. Pemetrexed is currently being evaluated for anti-tumor activity in a variety of solid and central nervous system tumors. We studi...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-006-0285-7
更新日期:2007-03-01 00:00:00
abstract::Cyclophosphamide demonstrates enhanced tumoricidal activity with decreased bone marrow toxicity when given on a divided-dose schedule in certain animal models. A total of 22 patients presenting with refractory metastatic cancer were treated in a phase I trial of continuous infusion of cyclophosphamide over 96 h. Granu...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00686337
更新日期:1991-01-01 00:00:00
abstract:PURPOSE:To determine the growth inhibitory effects of mifepristone on endometrial cancer cell growth and evaluate its effect on apoptosis using HEC-1-A and Ishikawa human endometrial cancer cell lines. METHODS:The human endometrial cancer cell lines, HEC-1-A and Ishikawa, were cultured in vitro. MTT assays were comple...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-007-0628-z
更新日期:2008-08-01 00:00:00
abstract::Peripheral blood stem and progenitor cells (PBSC and PBPC), which circulate at very low levels during steady-state hematopoiesis, show a transient but marked increase during hematologic recovery from marrow-suppressive chemotherapy. To ensure rapid and sustained hematologic engraftment after autologous PBSC transplant...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s002800051051
更新日期:1996-01-01 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::In this review of the management of invasive carcinoma of the bladder the results of primary and systemic therapies are evaluated in the light of the natural history of the disease. The clinical and pathological causes of treatment failure are assessed in an attempt to identify new approaches that may be used in the f...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,评审
doi:10.1007/BF00254978
更新日期:1979-01-01 00:00:00
abstract:PURPOSE:To investigate the antitumor effects of tyroserleutide (tyrosyl-seryl-leucine, YSL) on human Bel7402 hepatocarcinoma in vitro and in vivo, with preliminary exploration of its antitumor mechanism. METHODS:MTT was used to observe the anticarcinogenic effects of YSL on human hepatocarcinoma Bel7402 cells in vitro...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-005-0046-z
更新日期:2006-01-01 00:00:00
abstract:PURPOSE:Acid ceramidase (AC) occupies an important place in the control of cancer cell proliferation. We tested the influence of AC inhibition on the effects of PSC 833, a P-glycoprotein antagonist with potent ceramide-generating capacity, to determine whether AC could be a therapeutic target in pancreatic cancer. MET...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-012-2050-4
更新日期:2013-03-01 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::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:PURPOSE:Inhibition of the mammalian target of rapamycin (mTOR), a regulator of hypoxia inducible factor (HIF), is an established therapy for advanced renal cell cancer (RCC). Inhibition of mTOR results in compensatory AKT activation, a likely resistance mechanism. We evaluated whether addition of the Akt inhibitor peri...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-011-1684-y
更新日期:2012-01-01 00:00:00
abstract::The purpose of this study was to assess the efficacy of verapamil (20 microM) and hyperthermia (42 degrees C) as modifiers of mitomycin C (MMC), used at different concentrations, in inhibiting the growth of human gastric adenocarcinoma (AGS) cells. Combined verapamil and hyperthermia treatment resulted in a significan...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00685086
更新日期:1994-01-01 00:00:00
abstract::S-1 is an oral formulation of ftorafur (FT), oxonic acid and 5-chloro-2,4-dihydroxypyridine (CDHP) at a molar ratio of 1:0.4:1. FT is a 5-fluorouracil (5-FU) prodrug, CDHP is a dihydropyrimidine dehydrogenase (DPD) inhibitor and oxonic acid is an inhibitor of 5-FU phosphoribosylation in the gastrointestinal mucosa and...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s00280-003-0617-9
更新日期:2003-07-01 00:00:00
abstract:INTRODUCTION:Despite the extensive clinical experience with irinotecan, significant concerns remain regarding its toxicity. In a phase I trial, we modulated irinotecan pharmacokinetics by inhibiting biliary excretion of SN-38, the active metabolite of irinotecan, using cyclosporine. The modulation appeared to decrease ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1007/s00280-005-1020-5
更新日期:2005-10-01 00:00:00
abstract:PURPOSE:Plitidepsin absorption, distribution, metabolism and excretion characteristics were investigated in a mass balance study, in which six patients received a 3-h intravenous infusion containing 7 mg 14C-plitidepsin with a maximum radioactivity of 100 µCi. METHODS:Blood samples were drawn and excreta were collecte...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-018-3637-1
更新日期:2018-09-01 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::Methotrexate and methotrexate polyglutamates were quantitatively determined in red blood cells from 12 children with acute lymphoblastic leukemia who were treated with MTX (15-20 mg/m2 per week) and daily 6-mercaptopurine orally during the steady-state period of erythrocyte MTX concentration (ery-MTX). The terminal de...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00257362
更新日期:1988-01-01 00:00:00
abstract:BACKGROUND:Inhibitors of heat shock protein (Hsp) 90 induce apoptosis in multiple myeloma (MM) cells, but the molecular mechanisms underlying this cytotoxic outcome are not clear. Here, we investigate the effect of IPI-504, a novel and highly soluble inhibitor of the Hsp90 ATPase activity, on the unfolded protein respo...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-007-0546-0
更新日期:2008-05-01 00:00:00
abstract::Taxol is the prototype of a class of antineoplastic drugs that target microtubules. It enhances tubulin-monomer polymerization and stabilizes tubulin polymers, increasing the fraction of cells in the G2 or M phase of the cell cycle. We report that treatment of HL-60 and U937 myeloid cell lines with 1-10 microM taxol i...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00686187
更新日期:1995-01-01 00:00:00
abstract:PURPOSE:The interindividual variability of vincristine pharmacokinetics is quite large, but the origins of this variability are not properly understood. The aim of this study was to develop a population pharmacokinetic model of vincristine in a paediatric population treated for solid tumour disease and evaluate the imp...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-010-1541-4
更新日期:2011-11-01 00:00:00
abstract:PURPOSE:HER2-targeted therapy with trastuzumab and (CF/X) prolonged overall survival (OS) in metastatic HER2neu+ gastric carcinoma (GC). Lapatinib inhibits both EGFR and HER2neu. We investigated the efficacy and safety of lapatinib with epirubicin (E) + CF/X in GC according to HER2neu and EGFR status. METHODS:Tumors f...
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/s00280-018-3667-8
更新日期:2018-10-01 00:00:00
abstract:PURPOSE:This phase I clinical trial evaluated the safety, tolerability, and pharmacokinetics of high-dose intravenous (i.v.) ascorbic acid as a monotherapy in patients with advanced solid tumors refractory to standard therapy. METHODS:Five cohorts of three patients received i.v. ascorbic acid administered at 1 g/min f...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-013-2179-9
更新日期:2013-07-01 00:00:00
abstract:PURPOSE:Following promising responses to the DNA methyltransferase (DNMT) inhibitor 5-fluoro-2'-deoxycytidine (FdCyd) combined with tetrahydrouridine (THU) in phase 1 testing, we initiated a non-randomized phase 2 study to assess response to this combination in patients with advanced solid tumor types for which tumor s...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-020-04073-5
更新日期:2020-05-01 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