Abstract：
BACKGROUND:Tumours consist of heterogeneous cancer cells and are likely to contain drug-tolerant cell subpopulations, causing early relapse. However, treatment strategies to eliminate these cells have not been established. METHODS:We established gastric cancer patient-derived cells (PDCs) to examine the contribution of CD44 splicing variant 9 (CD44v9)-positive cells in gastric cancer drug tolerance. We performed gene expression signature-based in silico screening using JFCR_LinCAGE, our anticancer compound gene expression database and subsequent validation in BALB/c-nu/nu mouse xenograft to identify agents targeting the drug-tolerant cancer cells. RESULTS:CD44v9-positive cancer cells were enriched among residual cancer cells after treatment with SN-38, an active metabolic of irinotecan. CD44v9 protein was responsible for this drug resistance. We identified epidermal growth factor receptor (EGFR) inhibitors as agents that can target CD44v9-positive cell populations in gastric cancer PDCs. CD44v9 promoted cell proliferation, and EGFR inhibition attenuated CD44v9 protein expression through downregulation of the AKT and the ERK signalling pathways, leading to preferential suppression of CD44v9-positive cells. Importantly, EGFR inhibitors significantly reduced the number of residual cancer cells after cytotoxic anticancer drug treatment and enhanced the antitumor effect of irinotecan in vivo. CONCLUSIONS:EGFR inhibitors could be potential agents to eradicate cytotoxic anticancer drug-tolerant gastric cancer cell populations.
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
Mashima T,Iwasaki R,Kawata N,Kawakami R,Kumagai K,Migita T,Sano T,Yamaguchi K,Seimiya Hdoi
10.1038/s41416-019-0600-9subject
Has Abstractpub_date
2019-11-01 00:00:00pages
846-856issue
10eissn
0007-0920issn
1532-1827pii
10.1038/s41416-019-0600-9journal_volume
121pub_type
杂志文章abstract：BACKGROUND:Prevalence of (pre)cancerous colorectal lesions are higher in men than in women, although transition rates from advanced lesions to cancer is similar in both sexes. Our aim was to investigate whether the sex-specific difference in incidence of premalignant colorectal lesions might be explained by the impact ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2016.324
更新日期：2016-11-22 00:00:00
abstract：:In this study, the role of parity in conferring protection of the mammary gland against chemical carcinogenesis induced by 7,12-dimethylbenz(a)anthracene (DMBA) was investigated. Experiments were also carried out to determine if an 'interrupted' pregnancy was capable of reducing the incidence of mammary tumour inducti...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1988.88
更新日期：1988-04-01 00:00:00
abstract：:To examine whether weight loss at presentation influences outcome in patients who received chemotherapy for lung cancer or mesothelioma. Multivariate analysis of prospectively collected data 1994-2001. Data were available for age, gender, performance status, histology, stage, response, toxicity, progression-free and o...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6601781
更新日期：2004-05-17 00:00:00
abstract：:Lymph node pathologic status is the most important prognostic factor in vulvar cancer; however, complete inguinofemoral node dissection is associated with significant morbidity. Lymphoscintigraphy associated with gamma-probe guided surgery reliably detects sentinel nodes in melanoma and breast cancer patients. This st...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1054/bjoc.1999.0918
更新日期：2000-01-01 00:00:00
abstract：:The aim of this study was to assess the prognostic value of pretreatment clinical and laboratory parameters in refractory or relapsed multiple myeloma (MM) patients who have a long-term response to thalidomide (THAL), lasting at least 18 months. The study was carried out on 234 patients who received THAL for relapsed/...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6602225
更新日期：2004-11-29 00:00:00
abstract：:The prodrug N-[4-(daunorubicin-N-carbonyl-oxymethyl)phenyl] O-beta-glucuronyl carbamate (DNR-GA3) was synthesized for specific activation by human beta-glucuronidase, released in necrotic areas of tumour lesions. In vitro, DNR-GA3 was 18 times less toxic than daunorubicin (DNR) and the prodrug was completely activated...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1998.729
更新日期：1998-12-01 00:00:00
abstract：BACKGROUND:Multiple myeloma is a plasma cell disorder that is characterised by clonal proliferation of malignant plasma cells in the bone marrow, monoclonal paraprotein in the blood or urine and associated organ dysfunction. It accounts for approximately 1% of cancers and 13% of haematological cancers. Myeloma arises f...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2012.525
更新日期：2012-12-04 00:00:00
abstract：:The expression of peroxisome proliferator-activated receptor (PPAR)gamma in thyroid neoplasias and in normal thyroid (NT) tissues has not been fully investigated. The objectives of the present work were: to study and compare the relative expression of PPARgamma in normal, benign and malignant thyroid tissues and to co...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6601989
更新日期：2004-08-16 00:00:00
abstract：BACKGROUND:Administration of interleukin-2 (IL-2) has shown some effects on malignant pleural mesothelioma (MPM) tumour regression. The purpose of this study was to investigate the ability of IL-2 to modify immunological effector cells and angiogenesis in MPM patients and their prognostic value. METHODS:Tumour-infiltr...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6605438
更新日期：2009-12-01 00:00:00
abstract：BACKGROUND:The aim was to evaluate whether this gastric cancer-screening programme was effective in reducing oesophageal cancer mortality. METHODS:A population-based retrospective cohort study was conducted using the Korean National Cancer Screening Programme (NCSP) database. The study cohort comprised 16,969 oesophag...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/s41416-020-0883-x
更新日期：2020-08-01 00:00:00
abstract：:Classification of lymphoid malignancy has changed markedly in recent years and advances have been made in therapy. This study investigated the variations in treatment and survival of 1622 patients in a population-based registry. A total of 1009 cases of malignant lymphoma (ML) were classified according to the Kiel cla...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1995.406
更新日期：1995-09-01 00:00:00
abstract：:Choriocarcinoma can be imaged by external scintigraphy after intravenous administration of radiolabelled antibody directed against human chorionic gonadotrophin (HCG). The purpose of this study was to investigate whether antibody imaging was sufficiently sensitive and specific to improve the selection of patients for ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1987.134
更新日期：1987-06-01 00:00:00
abstract：:Expression of both P-glycoprotein (P-gp) and mutant p53 have recently been reported to be associated with poor prognosis of breast cancer. The expression of P-gp is associated in vitro and in vivo with cross-resistance to several anti-cancer drugs. p53 plays a regulatory role in apoptosis, and mutant p53 has been sugg...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1996.316
更新日期：1996-07-01 00:00:00
abstract：:Bleomycin is a chemotherapuetic drug used primarily in the treatment of squamous-cell carcinoma, while misonidazole is an effective radiosensitizer and potent cytotoxic agent selectively affecting hypoxic cells. V79 Chinese hamster cells were used to investigate the cytotoxicity of bleomycin (BLM) under aerated and hy...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1978.34
更新日期：1978-02-01 00:00:00
abstract：:The present study was designed in order to evaluate the response rate and the toxicity of continuous infusion of Interleukin 2 (IL2) in patients over 65 with metastatic renal cell carcinoma. Twenty-five patients, median age 69 (range 65-77), without any prior systemic anticancer therapy received a continuous infusion ...
journal_title：British journal of cancer
pub_type： 临床试验,杂志文章
doi：10.1038/bjc.1992.152
更新日期：1992-05-01 00:00:00
abstract：:Exposure to the fibrous mineral erionite is known to induce mesothelioma in man and laboratory animals. Previous studies demonstrated the presence of a trypsin-like protease associated with tumour cells. This protease could be demonstrated by the use of fluorescent probes which located cells possessing this enzyme. We...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1988.269
更新日期：1988-11-01 00:00:00
abstract：:The vaso-active drug hydralazine causes a considerable increase in the cytotoxic effect of melphalan towards the KHT tumour in mice. The enhancement in response, measured as the concentration of melphalan required to achieve a given tumour response, is 3.0 and 2.35 when determined using the regrowth delay assay and th...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1988.177
更新日期：1988-08-01 00:00:00
abstract：:The influence of vascular endothelial growth factor (VEGF) expression and microvessel density (MVD) on prognosis and the relationship between VEGF expression and MVD in ovarian carcinoma are not well defined. We studied VEGF expression in parallel with MVD by immunohistochemistry in 94 ovarian tumours (64 malignant, 1...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1054/bjoc.2000.1228
更新日期：2000-07-01 00:00:00
abstract：:Evidence in the literature suggests that hyperthermia (HT) or inhibitors of calmodulin can increase the sensitivity of rodent cells to bleomycin (BLM) by interfering with DNA repair functions. In an attempt to explore methods of improving the efficacy of thermochemotherapy we have investigated the individual and combi...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1986.14
更新日期：1986-01-01 00:00:00
abstract：BACKGROUND:A decade ago it was reported that childhood cancer incidence was higher in boys than girls in many countries, particularly those with low gross domestic product (GDP) and high infant mortality rate. Research suggests that socio-economic and cultural factors are likely to be responsible. This study aimed to i...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2012.191
更新日期：2012-06-26 00:00:00
abstract：:Plasma concentrations of certain hormones linked to breast cancer risk were measured in age-pooled samples from 3,250 rural Chinese women in 65 counties, and 300 British women, all aged 35-64. In age-groups 35-44, 45-54 and 55-64 respectively, mean oestradiol concentrations were 36% (P = 0.043), 90% (P less than 0.001...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1990.344
更新日期：1990-10-01 00:00:00
abstract：BACKGROUND:Previous studies on the effects of different prostate cancer treatments on quality of life, were confounded because patients were not comparable. This study examined treatment effects in more comparable groups. METHODS:From 2008-2011, 240 patients with localised prostate cancer were selected to be eligible ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2013.181
更新日期：2013-05-14 00:00:00
abstract：:A score based on the combination of the systemic inflammatory response and albumin hazards ratio (HR) 1.70, 95% CI 1.23 - 2.35, P=0.001) was comparable in prognostic value to that based on stage and performance status (HR 1.48, 95% CI 1.12 - 1.95, P=0.006) in patients with inoperable non-small-cell lung cancer. The fo...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6601242
更新日期：2003-09-15 00:00:00
abstract：BACKGROUND:Based on the microRNA (miRNA) signature of bladder cancer (BC) by deep sequencing, we recently found that several double-stranded mature miRNAs derived from the same pre-miRNAs were sufficiently expressed and acted as tumour suppressors by regulating common target genes in BC. Our deep-sequencing signature o...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2017.43
更新日期：2017-04-11 00:00:00
abstract：:The effect on cell-cycle progression in various phases of the cell cycle caused by an acute exposure to hypoxia in absence and presence of misonidazole (MISO) was investigated. Exponentially growing and synchronized cells of the human line NHIK 3025 were exposed to different degrees of hypoxia for a short period (1.5 ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1983.271
更新日期：1983-12-01 00:00:00
abstract：BACKGROUND:The small stress heat shock protein 27 (Hsp27) has recently turned as a promising target for cancer treatment. Hsp27 upregulation is associated with tumour growth and resistance to chemo- and radio-therapeutic treatments, and several ongoing drugs inhibiting Hsp27 expression are under clinical trial. Hsp27 i...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2012.188
更新日期：2012-06-26 00:00:00
abstract：:Human monocytes can be induced to synthesize a cytotoxin which affects certain tumour cell lines. The interaction of monocyte cytotoxin with a susceptible cell line (L929) has been studied to obtain clues to the mode of action of the cytotoxin. The cytotoxin acts directly on the cells rather than on the culture medium...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1983.205
更新日期：1983-09-01 00:00:00
abstract：:Targeting growth-regulatory pathways is a promising approach in cancer treatment. A prerequisite to the development of such therapies is characterisation of tumour growth regulation in the particular tumour cell type of interest. In order to gain insight into molecular mechanisms underlying proliferative responses in ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6602535
更新日期：2005-04-25 00:00:00
abstract：:We evaluated animal food intake and cooking methods in relation to endometrial cancer risk in a population-based case-control study in Shanghai, China. A validated food frequency questionnaire was used to collect the usual dietary habits of 1204 cases and 1212 controls aged 30-69 years between 1997 and 2003. Statistic...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6603458
更新日期：2006-12-04 00:00:00
abstract：:Up to 60% of gastro-oesophageal junction (GEJ) adenocarcinomas show nuclear beta-catenin expression, pointing to activated T-cell factor (TCF)/beta-catenin-driven gene transcription. We demonstrate in five human GEJ adenocarcinoma cell lines that nuclear beta-catenin expression indeed correlates with enhanced TCF-medi...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6601589
更新日期：2004-02-23 00:00:00
