Abstract:
PURPOSE:Lysine-specific demethylase 1 (LSD1) was highly expressed in several malignancies and had been implicated in pathological processes of cancer cells. However, the role of LSD1 in colorectal cancer (CRC) carcinogenesis, prognosis and treatment remains uncharacterized. METHODS:In this study, we examined LSD1 expression in paraffin-embedded CRC specimens from 295 patients, including 65 patients with paired samples of colorectal carcinoma, adjacent adenoma and normal colorectal tissues. Using an LSD1 inhibitor, CBB1003, as a probe, we studied the association between LSD1 and leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5), a CRC stem cell marker involved in carcinogenesis. The anti-tumor effects of CBB1003 on CRC cells were also examined. RESULTS:LSD1 expression was significantly elevated in colorectal tumor tissues compared with adjacent adenoma and normal colorectal tissues (P < 0.001), and LSD1 levels were significantly correlated with an advanced AJCC T stage (P = 0.012) and distant metastasis (P = 0.004). CBB1003 inhibited CRC cell proliferation and colony formation. In cultured CRC cells, inhibiting LSD1 activity by CBB1003 caused a decrease in LGR5 levels while overexpression of LGR5 reduced CBB1003-induced cell death. We also observed the inactivation of β-catenin/TCF signaling after CBB1003 treatment, consistent with the positive correlations among LSD1, LGR5, β-catenin and c-Myc expression in human colon tumor and adenoma tissues. CONCLUSION:Our result suggested that LSD1 overexpression promotes CRC development and that the LSD1 inhibitor inhibits CRC cell growth by down-regulating LGR5 levels and inactivates the Wnt/β-catenin pathway. Thus, LSD1 and its inhibitor might provide a new target or a useful strategy for therapy of CRC.
journal_name
J Cancer Res Clin Oncoljournal_title
Journal of cancer research and clinical oncologyauthors
Hsu HC,Liu YS,Tseng KC,Yang TS,Yeh CY,You JF,Hung HY,Chen SJ,Chen HCdoi
10.1007/s00432-014-1782-4subject
Has Abstractpub_date
2015-01-01 00:00:00pages
11-21issue
1eissn
0171-5216issn
1432-1335journal_volume
141pub_type
杂志文章abstract:BACKGROUND:Targeted treatment of chronic myelogenous leukemia using imatinib has dramatically improved patient outcome. However, residual disease can be detected in the majority of patients treated with imatinib. Compensatory activation of MAP kinases (MAPK1/2) in response to BCR-ABL-inhibitors has been reported as a p...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/s00432-011-1086-x
更新日期:2012-02-01 00:00:00
abstract:AIM:To examine the expressions of focal adhesion kinase (FAK) and its clinical significance in hepatocellular carcinoma (HCC). METHODS:We determined the expression levels of FAK on both steady-state mRNA and protein levels in 50 HCC samples by quantitative real-time PCR and immunohistochemistry, respectively. The corr...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/s00432-010-0806-y
更新日期:2010-10-01 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:PURPOSE:The oncogenic roles of sphingosine kinase 1 (SphK1) in various cancers, including thyroid cancer, have been well demonstrated. However, the microRNAs (miRNAs) associated with the oncogenic roles of SphK1 remain largely unknown. METHODS:Global gene and miRNA expression in TPC1-Vector and TPC1-SphK1 cells was an...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/s00432-016-2315-0
更新日期:2017-04-01 00:00:00
abstract::The effects of four barbiturates with or without liver-tumor-promoting activity were examined on survival and deoxyribonucleic acid (DNA) synthesis of suckling and adult rat hepatocytes in serum-free primary culture: Of the four barbiturates, two promoters, phenobarbital and barbital, enhanced DNA synthesis of sucklin...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/BF01629426
更新日期:1992-01-01 00:00:00
abstract::The relation between the intracellular glutathione (GSH) concentration and hydrogen-peroxide(H2O2)-induced cytotoxicity was investigated. The intracellular GSH concentration in human glioblastoma (T98G, U87MG) and glioma (KG1C) cell lines was one or two orders of magnitude higher than that in a human myelogenous leuke...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/s004320050115
更新日期:1997-01-01 00:00:00
abstract::In supporting the human-tumor cloning effort of the Southwest Oncology Group, we conducted an independent retrospective study to evaluate the clinical correlations of the soft-agar colony-forming assay developed by Hamburger and Salmon (1977). This study was made with the cooperation of 76 clinicians and 11 hospitals ...
journal_title:Journal of cancer research and clinical oncology
pub_type: 临床试验,杂志文章
doi:10.1007/BF01884250
更新日期:1985-01-01 00:00:00
abstract:PURPOSE:The orphan, membrane-bound estrogen receptor (GPER) is expressed at high levels in a large fraction of breast cancer patients, and its expression is favorable for patients' survival. We investigated the role of GPER as a potential tumor suppressor in MCF-7 and SK-BR-3 breast cancer cells. METHODS:The effect of...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/s00432-014-1598-2
更新日期:2014-04-01 00:00:00
abstract:PURPOSE:In stomach adenocarcinoma, the role of the hormonal receptor, estrogen receptor (ER), has been controversial. Recently, a new estrogen receptor, called estrogen receptor beta (ER beta), was found to be expressed in various tissues including normal gastrointestinal tract. In this paper, the expression of ER beta...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/s00432-002-0336-3
更新日期:2002-06-01 00:00:00
abstract::In the present study, we report that the betel quid ingredient catechu, its extract and pure principle catechin were nonmutagenic in Salmonella typhimurium TA 100, TA 1535, TA 98, and TA 1538 assays with or without metabolic activation. They also exhibited dose-dependent decreases in mutagenicity of benzo(a)pyrene [B(...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/BF00417833
更新日期:1988-01-01 00:00:00
abstract:PURPOSE:Molecular mechanisms of response to hypomethylating agents in patients with myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML) still remain largely unknown. Therefore, the effects of 5-Azacytidine (Aza) on clonal architecture and DNA methylation were investigated in this study. METHODS:...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/s00432-019-03016-9
更新日期:2019-11-01 00:00:00
abstract:PURPOSE:Bone marrow adherent cells contain conventional bone marrow stromal cells and mesenchymal stem cells and these cells constitute the hematopoietic microenvironment. Mesenchymal stem cells have the capacity to give rise to multiple mesenchymal lineage cells and even ectodermal lineage cells. In the present study,...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/s00432-009-0723-0
更新日期:2010-06-01 00:00:00
abstract::Bis-beta-diketonato complexes of titanium, zirconium, and hafnium were tested against autochthonous colorectal tumors in rats. The model was found to reflect the clinical situation most closely. Of the compounds tested, budotitane was the most effective in terms of decrease in tumor weight and number and in increasing...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/BF00390038
更新日期:1987-01-01 00:00:00
abstract::Sarcoma 180 tumor tissue from C57 mice was processed in a soft agar clonogenic assay immediately after removal from the animal and after various methods of storage. The sensitivity to the antineoplastic drug cis-platinum was not affected by different storage methods. The highest yield of colony forming cells per 100 m...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/BF00417832
更新日期:1988-01-01 00:00:00
abstract:BACKGROUND:Despite of the introduction of novel treatment modalities for multiple myeloma, high-dose chemotherapy with hematopoietic stem-cell rescue is still considered the standard of care for eligible patients <65 years of age. As we have previously reported, stem-cell grafts regularly contain quantities of plasma c...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/s00432-008-0499-7
更新日期:2009-04-01 00:00:00
abstract:BACKGROUND:The role of somatic BRCA1/2 gene mutations in breast cancer is getting increasing attention in view of hereditary disease. The medullary phenotype and triple negative intrinsic subtypes are often, but not exclusively encountered in BRCA1 germline mutated breast cancer, whilst for BRCA2, no association to spe...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/s00432-018-2609-5
更新日期:2018-05-01 00:00:00
abstract:PURPOSE:The Wnt pathway plays an important role in embryonic development, and defects in this pathway have been implicated in the tumorigenesis. The Dickkopf 3 (DKK3) is a putative Wnt signaling inhibitor that is frequently inactivated in human cancers. However, the expression of DKK3 in ovarian cancer remains unknown....
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/s00432-010-0916-6
更新日期:2011-04-01 00:00:00
abstract::The inducibility of cytotoxic T lymphocytes (CTL) that react with carcinoembryonic antigen (CEA) was tested in cancer patients with elevated (more than 5 ng/ml) serum CEA levels when antigen presentation was carried out with paraformaldehyde-fixed adhesive peripheral blood mononuclear cells (PBMC) from the patient tha...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/pl00008486
更新日期:2000-07-01 00:00:00
abstract::A total of 30 inbred Wistar rats were orally administered 70 microgram/ml solution of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) for 35 weeks and then tap water for the following 20 to 30 weeks. Four of the 20 females and two of ten males developed carcinoids in the glandular stomach, but no metastasis could be found...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/BF00405896
更新日期:1981-01-01 00:00:00
abstract:PURPOSE:The disappointing results of chemotherapy in glioblastoma might be caused by the choices of agents, which mostly include nitrosurea. We compared the in vitro efficacy of chemotherapeutic agents, developing a method to summarize published data. METHOD:Between 1966 and 1995 chemotherapy in glioma cells was repor...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章,meta分析
doi:10.1007/s004320050305
更新日期:1999-08-01 00:00:00
abstract::Several investigators have discussed the possible combination of tamoxifen and interferon (IFN) in the treatment of breast cancer patients. The rationale in combining these drugs is that IFN induces the expression of estrogen receptors and therefore increases the sensitivity of breast cancer cells toward the growth-in...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/BF00393339
更新日期:1989-01-01 00:00:00
abstract::The role of L-tyrosine, L-phenylalanine, L-dihydroxyphenylalanine (dopa) and L-tryptophan in melanin biosynthesis in melanotic hamster melanoma IC-Sofia was investigated with the aid of 14C-aminoacids. Tyrosine and phenylalanine were found to be the main melanin precursors: about 64.5% of total melanin labeling was du...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/BF00390476
更新日期:1984-01-01 00:00:00
abstract:PURPOSE:Long interspersed nuclear element 1 (LINE-1 or L1) is a dominant non-long terminal repeat (non-LTR) retrotransposon in the human genome that has been implicated in the overexpression of MET. Both the canonical MET and L1-MET transcripts are considered to play a role in hepatocellular carcinoma (HCC) development...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/s00432-020-03395-4
更新日期:2021-01-01 00:00:00
abstract:PURPOSE:Natural killer (NK) cells can kill transformed cells and represent anti-tumor activities for improving the immunotherapy of cancer. In previous works, we established human interleukin-15 (hIL-15) gene-modified NKL cells (NKL-IL15) and demonstrated their efficiency against human hepatocarcinoma cells (HCCs) in v...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/s00432-018-2654-0
更新日期:2018-07-01 00:00:00
abstract::The role of different cytogenetic changes has been extensively evaluated in patients with acute myeloid leukemia (AML), and cytogenetic analysis of AML blasts is essential to form prognostic subgroups in order to stratify for the extent of therapy. Nevertheless, 40-45% of AML patients lack such cytogenetic markers, i....
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章,评审
doi:10.1007/s00432-008-0524-x
更新日期:2009-04-01 00:00:00
abstract:PURPOSE:The aim of this study was to assess the frequency of second primary non-breast cancer after breast cancer diagnosis and treatment, and its correlation with clinicopathological features. METHODS:Data from 21,527 patients with primary breast cancer were collected retrospectively in a single cancer centre; 4.1% o...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/s00432-018-2621-9
更新日期:2018-05-01 00:00:00
abstract::Telomerase, a ribonucleoprotein enzyme, is expected to be a new marker for cancer diagnosis. TRAP (the telomeric-repeat amplification protocol) developed by Kim et al. is a sensitive method to detect telomerase activity. Telomerase activity is detected by TRAP in most malignant cells in vivo and in vitro, but it is no...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/BF01438310
更新日期:1997-01-01 00:00:00
abstract::Carboplatin and interferon beta (IFN beta) were tested alone and in combination for their antiproliferative activity on the human melanoma cell line SK-MEL 28 in vitro. Cells were incubated for 4 days in the presence of carboplatin (0.1 mM and 0.1 microM) and interferon beta (5 pM and 5 nM) and cell growth inhibition ...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/BF01202218
更新日期:1995-01-01 00:00:00
abstract::Osteosarcoma cells derived from patients have been isolated and subsequently cultured for the past 35 years. To date though, there have been no major breakthroughs in the development of a model for osteosarcoma that uses orthotopic implantation of human osteosarcoma cells and that closely emulates the clinical progres...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章,评审
doi:10.1007/s00432-006-0157-x
更新日期:2007-03-01 00:00:00
abstract::Seventy-three evaluable patients with advanced measurable solid tumors were given cisdichlorodiammineplatinum (II) (DDP) at a dose of 20 mg/M2 IV for 1-5 days every 3 weeks, and 19 patients who failed on this low dose DDP protocol received a single high dose of 100 mg/M2 IV once every 3 weeks. Forty-six patients had r...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/BF00395492
更新日期:1984-01-01 00:00:00