Abstract：
BACKGROUND:Enzastaurin, an oral serine-threonine kinase inhibitor, was initially developed as an ATP-competitive selective inhibitor against protein kinase Cβ. However, the mechanism by which enzastaurin contributes to tumourigenesis remains unclear. METHODS:We analysed the anti-tumour effects of enzastaurin in 22 lung cancer cell lines to ascertain the potential for enzastaurin-based treatment of lung cancer. To identify molecules or signalling pathways associated with this sensitivity, we conducted a gene, receptor tyrosine kinases phosphorylation and microRNA expression profiling study on the same set of cell lines. RESULTS:We identified eight genes by pathway analysis of molecules having gene-drug sensitivity correlation, and used them to build a support vector machine algorithm model by which sensitive cell lines were distinguished from resistant cell lines. Pathway analysis revealed that the JAK/STAT signalling pathway was one of the main ones involved in sensitivity to enzastaurin. Overexpression of JAK1 was observed in the sensitive cells by western blotting. Simultaneous administration of enzastaurin and JAK inhibitor inhibited enzastaurin-induced cell growth-inhibitory effect. Furthermore, lentiviral-mediated JAK1-overexpressing cells were more sensitive to enzastaurin than control cells. CONCLUSION:Our results suggested that the JAK1 pathway may be used as a single predictive biomarker for enzastaurin treatment. The anti-tumour effect of enzastaurin should be evaluated in lung cancer with overexpressed JAK pathway molecules.
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
Shimokawa T,Seike M,Soeno C,Uesaka H,Miyanaga A,Mizutani H,Kitamura K,Minegishi Y,Noro R,Okano T,Yoshimura A,Gemma Adoi
10.1038/bjc.2012.7subject
Has Abstractpub_date
2012-02-28 00:00:00pages
867-75issue
5eissn
0007-0920issn
1532-1827pii
bjc20127journal_volume
106pub_type
杂志文章abstract：:Findings in humans and animal models suggest that in utero hormonal and dietary exposures increase later breast cancer risk. Since alcohol intake by adult women consistently increases their breast cancer risk, we wondered whether maternal alcohol consumption during pregnancy increases female offspring's mammary tumori...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6601793
更新日期：2004-06-01 00:00:00
abstract：:Various procedures for immunoprotection in the A-SW mouse SEWA tumour system were compared. Four types of protector agents were used: polyoma virus, allogeneic S724 cells, A9/SEWA hybrid cells and xenogeneic ST(py) cells. Several injection schedules were also employed. On the whole, reasonable immunoprotection was obt...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1974.70
更新日期：1974-04-01 00:00:00
abstract：:A long term follow-up study has been undertaken in 33 patients with acute non-lymphoblastic leukaemia (ANLL) in order to establish whether a correlation exists between the clinical course and the immunologic pattern of lymphoid subpopulations. Peripheral blood lymphoid cells have been investigated longitudinally (each...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1988.221
更新日期：1988-09-01 00:00:00
abstract：BACKGROUND:To enhance the success rate of nanocarrier-mediated chemotherapy combined with an anti-angiogenic agent, it is crucial to identify parameters for tumour vasculature that can predict a response to the treatment of the anti-angiogenic agent. METHODS:To apply transforming growth factor (TGF)-beta type I recept...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6605367
更新日期：2009-12-01 00:00:00
abstract：:Fine-needle aspiration cytology, which is well established to be accurate for the diagnosis of thyroid cancer, may be inconclusive for the follicular thyroid neoplasms. As galectin-3 was suggested to be a marker of malignant thyrocytes, we investigated whether this protein might be helpful in the diagnosis of aspirate...
journal_title：British journal of cancer
pub_type： 临床试验,杂志文章
doi：10.1038/sj.bjc.6602822
更新日期：2005-11-14 00:00:00
abstract：:Cancer Research UK has recently sponsored a meeting, organized by the UK Medical Research Council, on cancer drug resistance. Several of the molecular mechanisms responsible for this clinical outcome, such as DNA interstrand crosslink repair, apoptosis evasion, cytochrome P450 and P-glycoprotein, were discussed. There...
journal_title：British journal of cancer
pub_type：
doi：10.1038/sj.bjc.6602821
更新日期：2005-10-31 00:00:00
abstract：:Oestrogen (RE) and progesterone (RP) cytosolic receptors have been studied in 59 clinically inflammatory tumours of the human breast. The results were compared to those obtained in a series of 496 operable tumours. A single saturating dose of oestradiol for RE and R 5020 for RP was used and the cut-off between negativ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1981.291
更新日期：1981-12-01 00:00:00
abstract：:Animal tumour models using orthotopic tumours for the evaluation of cancer therapies are of greater clinical relevance than subcutaneous models, but they also pose greater difficulties for measuring tumour size and quantifying response to treatment. In this study, we used noninvasive bioluminescence imaging to monitor...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6601637
更新日期：2004-03-22 00:00:00
abstract：:This paper describes the results of a study set up to investigate factors associated with the high proportions of 'death certificate only' registrations (DCOs) for all cancers registered in south-east England between 1987 and 1989 and to identify those which might be subject to registry intervention. DCOs as a proport...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1995.125
更新日期：1995-03-01 00:00:00
abstract：:Broad-spectrum neuropeptide growth factor antagonists, such as [D-Arg1, D-Phe5, D-Trp7,9, Leu11]substance P (antagonist D) and [Arg6, D-Trp7,9, NmePhe8]substance P(6-11) (antagonist G), are currently being investigated as possible anti-tumour agents. These compounds are hoped to be effective against neuropeptide-drive...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1996.126
更新日期：1996-03-01 00:00:00
abstract：BACKGROUND:Although salt intake is considered a probable risk factor for gastric cancer, relevant studies have provided heterogeneous results, and the magnitude of the association has not been accurately quantified. METHODS:To quantify gastric cancer risk in relation to dietary salt exposure according to Helicobacter ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6605993
更新日期：2011-01-04 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：:Diagnosis of hereditary non-polyposis colorectal cancer (HNPCC) is currently based on phenotypical analysis of an expanded pedigree. Diagnostic guidelines ('Amsterdam criteria') proposed by the International Collaborative Group on HNPCC are often too stringent for use with small families. There is also the possibility...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1995.508
更新日期：1995-11-01 00:00:00
abstract：BACKGROUND:We assessed the sensitivity to adjuvant chemotherapy in cell cycle checkpoint kinase 2 (CHEK2) vs non-CHEK2 breast cancer patients by comparing the contralateral breast cancer incidence and distant disease-free and breast cancer-specific survival between both groups, stratified for adjuvant chemotherapy. ME...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2014.306
更新日期：2014-08-26 00:00:00
abstract：:A substantial excess risk of lymphomas and nonmelanoma skin cancer has been demonstrated following organ transplantation. Large sample size and long follow-up time may, however, allow more accurate risk estimates and detailed understanding of long-term cancer risk. The objective of the study was to assess the risk of ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6601219
更新日期：2003-10-06 00:00:00
abstract：:The effect of 10(-6) M tamoxifen on MCF-7 cells adapted to growth in 0.5% foetal calf serum has been studied. The growth inhibitory effect of this tamoxifen concentration was abolished by simultaneous addition of 10(-8) M oestradiol, indicating that tamoxifen may exert its effect via binding to the oestrogen receptor....
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1984.113
更新日期：1984-06-01 00:00:00
abstract：:Our purpose was to determine the response rate and median and overall survival of gemcitabine as monotherapy versus gemcitabine plus irinotecan in advanced or metastatic pancreatic cancer. Patients with histologically or cytologically confirmed adenocarcinoma who were chemotherapy and radiotherapy naive were enrolled....
journal_title：British journal of cancer
pub_type： 杂志文章,多中心研究,随机对照试验
doi：10.1038/sj.bjc.6603301
更新日期：2006-09-04 00:00:00
abstract：:It has been postulated that paternal gonadal exposure would increase the sex ratio by inducing X-chromosomal dominant lethals but that maternal gonadal exposure would decrease the sex ratio by inducing recessive sex-linked lethals. We therefore evaluated the sex ratio (male-to-female ratio) of children born to survivo...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6600748
更新日期：2003-02-10 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：:The continuous cell line UCRU BL 17CL was derived from a human invasive bladder cancer and expresses elements of transitional, squamous and glandular differentiation. Nine clones of this line were established by limit dilution and have been extensively characterised. Only six of these clones grew subcutaneously in nud...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1990.81
更新日期：1990-03-01 00:00:00
abstract：:Laminin promotes the malignant phenotype, and the expression of certain laminin receptors is increased in malignancy. Previously, we demonstrated that a laminin-adhesive subclone of a human colon cancer cell line showed increased tumorigenicity in nude mice and increased affinity of the beta1 integrin for laminin rela...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1998.3
更新日期：1998-01-01 00:00:00
abstract：:Thirty patients with previously treated metastatic breast cancer were entered in a phase II study with oral lonidamine. Twenty-eight patients are evaluable for toxicity and 25 for response. A partial remission was obtained in four patients (16%) and disease stability in 11 (44%): 10 patients progressed (40%). Toxicity...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1989.51
更新日期：1989-02-01 00:00:00
abstract：:Adriamycin and cyclophosphamide are active agents in human and experimental tumours. Using the L1210 murine leukaemia, their effectiveness alone and in combination was studied. The combination is highly synergistic in this tumour, resulting in a greater than 50% survival rate when the agents used alone at optimal dose...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1975.150
更新日期：1975-08-01 00:00:00
abstract：:Docetaxel has been reported to show promising anti-tumour activity in pancreatic ductal cancer (PC). This study was conducted to evaluate the activity and toxicity of moderate-dose (60 mg m(-2)) docetaxel in Japanese chemo-naive patients with measurable metastatic PC. The patients had a performance status of 0-2. They...
journal_title：British journal of cancer
pub_type： 临床试验,杂志文章,多中心研究
doi：10.1038/sj.bjc.6690375
更新日期：1999-05-01 00:00:00
abstract：:A Phase I study of oral daily misonidazole (MISO) with conventional pelvic irradiation, has been conducted in patients with carcinoma of the cervix Stages IB, IIB, IIIB and IVA. MISO was administered in daily dosages to sequential groups of patients at doses of 0.15 g/m2, 0.30 g/m2 or 0.45 g/m2 for 22 days over 5 week...
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.1982.138
更新日期：1982-06-01 00:00:00
abstract：BACKGROUND:Eukaryotic translation elongation factor 1A2 (eEF1A2) is a known proto-oncogene. We proposed that stimulation of the eEF1A2 expression in cancer tissues is caused by the loss of miRNA-mediated control. METHODS:Impact of miRNAs on eEF1A2 at the mRNA and protein levels was examined by qPCR and western blot, r...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2013.243
更新日期：2013-06-11 00:00:00
abstract：:Disseminating disease is a predictive and prognostic indicator of poor outcome in children with neuroblastoma. Its accurate and sensitive assessment can facilitate optimal treatment decisions. The International Neuroblastoma Risk Group (INRG) Task Force has defined standardised methods for the determination of minimal...
journal_title：British journal of cancer
pub_type： 杂志文章,多中心研究,实务指引
doi：10.1038/sj.bjc.6605029
更新日期：2009-05-19 00:00:00
abstract：BACKGROUND:The role of different subtypes of tumour infiltrating lymphocytes (TILs) in breast ductal carcinoma in situ (DCIS) is still poorly defined. This study aimed to assess the prognostic significance of B and T lymphocytes and immune checkpoint proteins expression in DCIS. METHODS:A well characterised DCIS cohor...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/s41416-020-0797-7
更新日期：2020-05-01 00:00:00
abstract：:Early detection of relapse has been advocated to improve survival in children with recurrent medulloblastoma. However, the prognostic factors and the longer term outcome of these patients remains unclear. Pattern of recurrences were analysed in three consecutive protocols of the Société Française d'Oncologie Pédiatriq...
journal_title：British journal of cancer
pub_type： 临床试验,杂志文章,多中心研究
doi：10.1038/bjc.1998.220
更新日期：1998-04-01 00:00:00
abstract：:Previous studies have shown that multidrug resistance (MDR) in the doxorubicin-selected lung tumour cell lines COR-L23/R, GLC4/ADR and MOR/R is associated with overexpression of the MRP gene. In this study we report that resistance to daunorubicin, vincristine and rhodamine 123 can be partially reversed in these cell ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1995.281
更新日期：1995-07-01 00:00:00
