Abstract:
:KRN 8602 (MX2) is a novel morpholino anthracycline derivative having the chemical structure 3'-deamino-3'-morpholino-13-deoxo-10-hydroxycarminomycin hydrochloride. To investigate the mechanisms of resistance to MX2, we established an MX2-resistant phenotype (K562/MX2) of the human myelogeneous leukaemia cell line (K562/P), by continuously exposing a suspension culture to increasing concentrations of MX2. K562/MX2 cells were more resistant to MX2 than the parent cells, and also showed cross-resistance to etoposide and doxorubicin. Topoisomerase (Topo) IIalpha protein levels in K562/MX2 cells were lower of those in K562/P cells on immunoblot analysis and decreased expression of Topo IIalpha mRNA was seen in K562/MX2 cells. Topoisomerase II catalytic activity was also reduced in the nuclear extracts from K562/MX2 cells when compared with K562/P cells. Aberrant methylated CpG of Topo IIalpha gene was observed in K562/MX2 cells when compared with the parent line on methylation-specific restriction enzyme analysis. To overcome the drug resistance to MX2 and etoposide, we investigated treatment with 5-Aza-2'-deoxycytidine (5AZ), which is a demethylating agent, in K562/MX2 cells. 5-Aza-2'-deoxycytidine treatment increased Topo IIalpha mRNA expression in K562/MX2 cells, but not in K562/P cells, and increased the cytotoxicity of MX2 and etoposide. Methylated CpG was decreased in K562/MX2 cells after 5AZ treatment. We concluded that the mechanism of drug resistance to MX2 and etoposide in K562/MX2 cells might be the combination of decreased expression of Topo IIalpha gene and increased methylation, and that 5AZ could prove to be a novel treatment for etoposide-resistant cell lines, such as K562/MX2.
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
Asano T,Nakamura K,Fujii H,Horichi N,Ohmori T,Hasegawa K,Isoe T,Adachi M,Otake N,Fukunaga Ydoi
10.1038/sj.bjc.6602498subject
Has Abstractpub_date
2005-04-25 00:00:00pages
1486-92issue
8eissn
0007-0920issn
1532-1827pii
6602498journal_volume
92pub_type
杂志文章abstract:BACKGROUND:Laminin-5 (Ln5), a heterotrimer composed of three chains (α3, β3, and γ2), is a major component of the basement membrane in most adult tissues. One of the chains, Ln5-γ2, is a marker of invasive tumours because it is frequently expressed as a monomer in malignant tumours. Recent studies from our laboratories...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2011.283
更新日期:2011-09-06 00:00:00
abstract::Colorectal tumours from MYH polyposis patients display an excess of somatic G : C --> T : A transversions in the adenomatous polyposis coli gene. Here, we identify k-ras mutations in nine out of 54 (16.7%) MYH polyposis tumours. Their presence was associated with increased dysplasia and tubulovillous morphology (P=0.0...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6601747
更新日期:2004-04-19 00:00:00
abstract::Immunoreactive and bioassayable plasma fibronectin (opsonic α(2) surface-binding (SB) glycoprotein) was measured during experimental Sarcoma-180 tumour growth in mice. Male C57BL/6 mice were challenged s.c. with 2 × 10(6) viable Sarcoma-180 tumour cells and evaluated sequentially in parallel with saline-injected contr...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1980.174
更新日期:1980-06-01 00:00:00
abstract::We studied 5555 seminoma patients and 3733 patients with nonseminomatous testicular cancers diagnosed in Southeast England between 1960 and 2004. For both groups survival improved over time: 10-year relative survival increased from 78% in 1960-1969 to 99% in 1990-2004 for seminomas, and from 55 to 95% for nonseminomas...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6603589
更新日期:2007-02-12 00:00:00
abstract::The objective of the study was to investigate the predictive value of various clinical, biochemical, and histopathological parameters, with special emphasis on the expression of the retinoblastoma protein (pRB), on the radiation response in bladder cancer. In order to obtain a truly objective response measure, patient...
journal_title:British journal of cancer
pub_type: 临床试验,杂志文章
doi:10.1038/sj.bjc.6601063
更新日期:2003-07-21 00:00:00
abstract:BACKGROUND:Prostate cancer is the most common cancer in British men but its aetiology is not well understood. We aimed to identify risk factors for prostate cancer in British males. METHODS:We studied 219 335 men from the UK Biobank study who were free from cancer at baseline. Exposure data were collected at recruitme...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2017.312
更新日期:2017-11-07 00:00:00
abstract::Human papillomavirus (HPV) is thought to cause some vulval squamous cell carcinomas (VSCC) by degrading p53 product. Evidence on whether HPV-negative VSCC results from p53 mutation is conflicting. We performed immunohistochemistry for p53 product on 52 cases of lone vulval intraepithelial neoplasia (VIN), 21 cases of ...
journal_title:British journal of cancer
pub_type: 杂志文章,meta分析,多中心研究
doi:10.1038/sj.bjc.6600677
更新日期:2003-01-27 00:00:00
abstract::We have established a novel ascites tumour model (MDA435/LCC6) from the oestrogen receptor-negative, invasive and metastatic MDA-MB-435 human breast cancer cell line. MDA435/LCC6 cells grow as both malignant ascites and solid tumours in vivo in nude mice and nude rats, with a tumour incidence of approximately 100%. Un...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1996.29
更新日期:1996-01-01 00:00:00
abstract::Because the focus of nasopharyngeal carcinoma (NPC) is very close to intracranial organs, it often makes incursions into cranial cavity. Identification of intracranial invasion-associated indicators will provide potential therapeutic targets for NPC patients with intracranial invasion. In this regard, Human Xpro HC-pl...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6604167
更新日期:2008-01-29 00:00:00
abstract::To design hybrid tumour necrosis factor-alpha (TNF-alpha) applicable to systemic anti-tumour therapeutic use, we assessed the relationships among the molecular size of hybrid TNF-alpha, in vitro bioactivity and in vivo anti-tumour potency. Natural human TNF-alpha was covalently modified with polyethylene glycol (PEG) ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1996.495
更新日期:1996-10-01 00:00:00
abstract::The treatment of breast cancer patients has changed rapidly in the past decade, but empirical data at local and national level are scarce. Predicting the consequences of screening for primary treatment is consequently difficult. The aim of this analysis of records on admissions to hospital of women with breast cancer ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1994.466
更新日期:1994-12-01 00:00:00
abstract::Nuclear polyploidization in the livers of CF-1 mice, exposed to dieldrin (0, 1, 5 and 10 ppm in the diet), was studied up to the median time of liver tumour development (ranging from 15 to 27 months) in the respective treatment groups. In untreated controls nuclear polyploidization is characterized by a linear increas...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1988.160
更新日期:1988-07-01 00:00:00
abstract::The modulating effect of 43 degrees C hyperthermia on the induction of oncogenic transformation by the antineoplastic agents, actinomycin D, mitomycin C, and 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) was examined using the C3H 10T1/2 cell line. For any given level of cytotoxicity, cells exposed to the three chemothe...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1988.9
更新日期:1988-01-01 00:00:00
abstract::Electrochemotherapy is an anti-tumour treatment that utilizes locally delivered electric pulses to increase cytotoxicity of chemotherapeutic drugs. The aim of our study was to determine whether anti-tumour effectiveness of electrochemotherapy with cisplatin is a consequence of increased plasma membrane permeability ca...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6690222
更新日期:1999-03-01 00:00:00
abstract::We investigated expression of a human p53-inducible gene, P2XM, a member of the P2X-receptor family of ATP-gated ion channels, in 56 human primary soft-tissue tumours including 47 sarcomas and nine benign tumors. Among the 47 sarcomas examined by reverse transcription polymerase chain reaction, 12 had lost expression ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6690484
更新日期:1999-06-01 00:00:00
abstract:BACKGROUND:Emergence of drug-resistant cancer phenotypes is a challenge for anti-cancer therapy. Cancer stem cells are identified as one of the ways by which chemoresistance develops. METHOD:We investigated the anti-inflammatory combinatorial treatment (DA) of doxorubicin and aspirin using a preclinical microfluidic m...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/s41416-018-0301-9
更新日期:2019-02-01 00:00:00
abstract::The association between chromosomal radiosensitivity and genetic predisposition to head and neck cancer was investigated in this study. In all, 101 head and neck cancer patients and 75 healthy control individuals were included in the study. The G(2) assay was used to measure chromosomal radiosensitivity. The results d...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6604345
更新日期:2008-05-20 00:00:00
abstract:BACKGROUND:Nonsteroidal anti-inflammatory drugs (NSAIDs) have been associated with improved survival in some cancers, but evidence for ovarian cancer is limited. METHODS:Pooling individual-level data from 12 Ovarian Cancer Association Consortium studies, we evaluated the association between self-reported, pre-diagnosi...
journal_title:British journal of cancer
pub_type: 杂志文章,meta分析
doi:10.1038/bjc.2017.68
更新日期:2017-04-25 00:00:00
abstract::The management of older patients with aggressive non-Hodgkin's lymphoma presents a challenge to the physician. Age is a poor prognostic indicator, due to reduced ability to tolerate and maintain dose-intensive chemotherapy. Generally, older patients demonstrate a lower response rate, reduced survival and increased tox...
journal_title:British journal of cancer
pub_type: 杂志文章,随机对照试验
doi:10.1038/sj.bjc.6602975
更新日期:2006-03-27 00:00:00
abstract::Hypomethylation has been reported to be responsible for the activation of several oncogenes. The possibility that hypomethylation is involved in the regulation of MET transcription was investigated through the analysis of the methylation status of one CpG island containing 43 CpGs in six cases of papillary carcinoma, ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6601988
更新日期:2004-08-16 00:00:00
abstract::We report here a case of a patient affected by endometrial cancer and treated primarily with leuprolide, the surgical approach being unfeasible due to her compromised conditions. The therapy was continued for more than 6 years, and no progression of the disease was observed. During this period, some histological and i...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1054/bjoc.2001.1900
更新日期:2001-08-03 00:00:00
abstract::We assayed methyl-p-hydroxyphenyllactate esterase (MeHPLAase) activity in 63 cases of primary laryngeal squamous cell carcinoma. MeHPLAase activity did not show any correlation with oestrogen, progesterone and epidermal growth factor (EGF) receptor levels. No significant relationship was found between MeHPLAase activi...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1998.210
更新日期:1998-04-01 00:00:00
abstract:BACKGROUND:Combined oral contraceptive (COC) use reduces epithelial ovarian cancer (EOC) risk. However, little is known about risk with COC use before the first full-term pregnancy (FFTP). METHODS:This Canadian population-based case-control study (2001-2012) included 854 invasive cases/2139 controls aged ⩾40 years who...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2016.400
更新日期:2017-01-17 00:00:00
abstract::In the BUPA Study, a prospective study of 22,000 men attending a screening centre in London, serum samples were collected and stored. The concentration of beta-carotene was measured in the stored serum samples from 271 men who were subsequently notified as having cancer and from 533 unaffected controls, matched for ag...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1988.97
更新日期:1988-04-01 00:00:00
abstract::The relation between pretreatment night-time urinary catecholamine excretion and chemotherapy-induced nausea and vomiting was studied. The first cohort included 17 women and three men with various cancer forms receiving low or moderately emetogenic chemotherapy. The second cohort included 42 women receiving cisplatinu...
journal_title:British journal of cancer
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1038/bjc.1994.364
更新日期:1994-10-01 00:00:00
abstract::Immunoglobulins (Ig) and some complement components (C) were quantified in sera from patients with gastric carcinoma before surgery and at regular intervals during a 5-year follow-up. The preoperative concentrations of C1-INH and C4 were higher (P < 0.0005 and P < 0.005) and IgG lower (P < 0.0005) in 50 patients with ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1992.376
更新日期:1992-11-01 00:00:00
abstract:BACKGROUND:The host immune reaction is represented by immune/inflammatory cell infiltrates. Here we systematically analysed tumour-infiltrating immune/inflammatory cells in pancreatic ductal carcinoma (PDC) and evaluated their clinicopathological impact. METHODS:Using immunohistochemistry, we examined tumour-infiltrat...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2013.32
更新日期:2013-03-05 00:00:00
abstract::Preclinical studies have demonstrated the synergistic anti-tumour activity of combination therapy with the oral cytostatics, 5'-deoxy-5-fluorouridine (5'-DFUR) and cyclophosphamide (CPA), in human breast cancer xenograft models. This study was performed to evaluate the efficacy and safety of this oral combination chem...
journal_title:British journal of cancer
pub_type: 临床试验,杂志文章
doi:10.1038/sj.bjc.6601350
更新日期:2003-11-03 00:00:00
abstract::Aminoglutethimide without glucocorticoid has been shown to be a clinically effective treatment for postmenopausal breast cancer in low dosage (250 mg day-1). The mechanism of action of this approach is thought to be the inhibition of peripheral aromatase, the enzyme which converts androstenedione to oestrone. The acti...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1985.144
更新日期:1985-07-01 00:00:00
abstract::In recent years, large discrepancies were described in the success rate of the tyrosinase reverse transcription polymerase chain reaction (RT-PCR) for detecting melanoma cells in the peripheral blood of melanoma patients. We present a quality control study in which we analysed the reproducibility of detection of tyros...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6690436
更新日期:1999-05-01 00:00:00