Abstract:
:Antisense oligonucleotides have been investigated as anticancer agents administered alone or in combination with conventional chemotherapeutics. In the present study, we demonstrated synergistic effects between anti-MDM2 antisense oligonucleotides and the clinically used anticancer agent irinotecan, using nude mouse models of human colon cancers (LS174T and DLD-1). Surprisingly, a 5-base mismatch oligonucleotide also showed similar effects. To elucidate the underlying mechanisms, in vitro and in vivo pharmacokinetic and pharmacodynamic studies were performed. In LS174T cells, the antisense oligonucleotide, but not the mismatch oligonucleotide, specifically inhibited MDM2 expression, resulting in a significant increase in irinotecan-associated p53 activation and p21 induction. In DLD-1 cells, the antisense oligonucleotide specifically inhibited MDM2 expression, resulting in a significant increase in irinotecan-associated p21 induction although mutant p53 levels remained unchanged. Both oligonucleotides increased tissue uptake of irinotecan and the conversion of irinotecan to its active metabolite SN-38. These results suggest that oligonucleotides have a role in irinotecan metabolism and action, providing a basis for future development of antisense oligonucleotides as a sensitizer for irinotecan-based therapy.
journal_name
Int J Oncoljournal_title
International journal of oncologyauthors
Wang H,Wang S,Nan L,Yu D,Agrawal S,Zhang Rkeywords:
subject
Has Abstractpub_date
2002-04-01 00:00:00pages
745-52issue
4eissn
1019-6439issn
1791-2423journal_volume
20pub_type
杂志文章abstract::Tumor cell (TC) metastasis is initiated by selective adhesion of TCs to target structures such as basement membrane and endotheliaI cells (ECs), followed by transvascular migration of TCs. Variants of murine B16 melanoma having different metastatic potentials (in the order BL6 greater than or equal to F10>F1>WA4) have...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.6.2.319
更新日期:1995-02-01 00:00:00
abstract::miRNA‑223 (miR‑223) has been reported to function not only as a tumor suppressor, but also as an oncogenic microRNA (miRNA or miR) in various cancer cells. Therefore, the functional role of miR‑223 has not been elucidated to date, at least to the best of our knowledge. We previously performed the deep sequencing analy...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2019.4762
更新日期:2019-06-01 00:00:00
abstract::CA IX is a tumor-associated transmembrane isoform of the carbonic anhydrase with a high enzyme activity and a functional involvement in the pH regulation and cell adhesion. Expression of CA9 gene in tumor cells is principally regulated by the high cell density and the hypoxia-related VHL-HIF pathway. In renal cell car...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2005-04-01 00:00:00
abstract::Hedgehog (HH) pathway Smoothened (Smo) inhibitors are active against Gorlin syndrome-associated basal cell carcinoma (BCC) and medulloblastoma where Patched (Ptch) mutations occur. We interrogated 705 epithelial cancer cell lines for growth response to the Smo inhibitor cyclopamine ...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2012.1599
更新日期:2012-11-01 00:00:00
abstract::The presence of arachidonate 12-lipoxygenase (12-LOX) potentiates prostate cancer (PCa) progression and therefore may be a good therapeutic target and/or a potential diagnostic predictor for PCa. In this study, we examined the expression of 12-LOX in PCa stem cells (PCa SCs) to test if it can serve as a unique marker ...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2011.901
更新日期:2011-04-01 00:00:00
abstract::High lactate production in cells during growth under oxygen-rich conditions (aerobic glycolysis) is a hallmark of tumor cells, indicating the role of mitochondrial function in tumorigenesis. In fact, enhanced mitochondrial biogenesis and impaired quality control are frequently observed in cancer cells. Mitochondrial D...
journal_title:International journal of oncology
pub_type: 杂志文章,评审
doi:10.3892/ijo.2018.4468
更新日期:2018-09-01 00:00:00
abstract::A murine B16 melanoma parental line (B16) and two clones either pigmented (B16P) or non-pigmented (B16NP) were cocultured as aggregates with mouse 3T3 fibroblasts. In vivo, these mixed aggregates developed more aggressive tumors in the mouse than corresponding pure aggregates. In vitro, the three pure cell lines secre...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.5.5.1125
更新日期:1994-11-01 00:00:00
abstract::Metastasis or progression of ovarian cancer cells is known to be due to the action of various angiogenic factors. We determined the expression of thymidine phosphorylase/platelet-derived endothelial cell growth factor (TP/PD-ECGF) and vascular endothelial growth factor (VEGF) in cell lines established from 3 serous ad...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2003-05-01 00:00:00
abstract::Retinoids, which include vitamin A (retinol) and its derivatives, have previously been investigated as potential chemopreventive and chemotherapeutic agents in bladder cancer. We examined mRNA expression of the retinoid receptors RARalpha, RARbeta2, RARgamma and RXRalpha, as well as two putative RARbeta2 target genes,...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2005-04-01 00:00:00
abstract::Two mouse HPV16-transformed cell lines, viz. MK16 cells, which induce metastasizing tumors, and TC-1 cells, which induce non-metastasizing tumors were transduced with the gene for mouse endostatin. Two clones constitutively expressing endostatin were isolated from each of them. They were denoted ME3 and ME9, and TE2 a...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo_00000331
更新日期:2009-07-01 00:00:00
abstract::The aim of this study was to investigate STK15 amplification in histologically benign urothelium and invasive tumor tissue of urothelial bladder cancer patients in relation to clinicopathologic and molecular characteristics, and to analyze a hypothesized association between the STK15 single nucleotide polymorphism at ...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2007-10-01 00:00:00
abstract::Structural maintenance of chromosome 1 alpha (SMC1A) gene has been reported to be related to tumor development in some types of human cancers. However, the misregulation of SMC1A and its functions in castration-resistant prostate cancer (CRPC) have not been well understood. In the present study, we found that SMC1A wa...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2016.3697
更新日期:2016-11-01 00:00:00
abstract::Five retinoblastoma tumours from patients treated in the King Khaled Eye Specialist Hospital in Riyadh were analysed for mutations in the RB1 gene using single strand conformation polymorphism analysis and mutations were found in all of them. In one tumour the mutation in exon 11 was homozygous demonstrating the role ...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.6.3.687
更新日期:1995-03-01 00:00:00
abstract::Endometrial cancer is the most common gynecological cancer. We identified interleukin 11 (IL11) as a critical mediator of endometrial tumourigenesis and demonstrated that IL11 regulates chondroitin sulfate proteoglycan (CSPG4) in human placental trophoblasts. CSPG4 is a cell membrane protein overexpressed in numerous ...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2017.3848
更新日期:2017-03-01 00:00:00
abstract::Telomerase activity and its subunits (hTERC, hTERT mRNA) were evaluated in ovarian tumours in relation to the expression of p53, c-Myc and estrogen receptor (ER). Furthermore, relations between telomerase activity, hTERC and hTERT with known clinicopathologic prognostic factors and survival in patients with malignant ...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.23.5.1451
更新日期:2003-11-01 00:00:00
abstract::Intrinsic resistance of glioma cells to radiation and chemotherapy is currently hypothesized to be partially attributed to the existence of cancer stem cells. Emerging studies suggest that mesenchymal stem cells may serve as a potential carrier for delivery of therapeutic genes to disseminated glioma cells. However, t...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2014.2284
更新日期:2014-04-01 00:00:00
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journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.12.2.421
更新日期:1998-02-01 00:00:00
abstract::Hepatitis B X-interacting protein (HBXIP) is a novel oncoprotein. We have previously reported that HBXIP promotes the proliferation and migration of breast cancer cells. S-phase kinase-associated protein 2 (Skp2) is another oncoprotein which is important for migration. In this study, we investigated whether Skp2 is in...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2014.2411
更新日期:2014-07-01 00:00:00
abstract::Cancer represents a severe challenge to healthcare systems and individuals worldwide. The development of multiple drug resistance is a major issue regarding cancer therapy, which can result in the progression of disease. Cholesterol is a major constituent of cell membranes and participates in the regulation of several...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2020.5124
更新日期:2020-09-22 00:00:00
abstract::Retroviral reverse transcriptase (RT) plays a definite role in retroviral life cycle and is essential for the process of retrotransposition. We investigated the RNA expression of endogenous reverse transcriptases (enRTs) in the NIH3T3 mouse genome using, as a probe, a mixture of RT-PCR generated reverse transcriptase ...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2003-10-01 00:00:00
abstract::Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related mortality worldwide. We have previously reported that LASP-1 is a downstream protein of the urokinase type plasminogen activator (uPA). Here we investigated the role of LASP-1 in HCC by a molecular and biological characterization of LASP-1...
journal_title:International journal of oncology
pub_type: 杂志文章
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journal_title:International journal of oncology
pub_type: 杂志文章
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更新日期:2019-03-01 00:00:00
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journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo_00000609
更新日期:2010-05-01 00:00:00
abstract::Collagen type I is an abundant component of the extracellular matrix and due to its longevity, constitutes a prominent target of non-enzymatic post-translational in vivo modifications such as carbamylation and glycation. These protein modifications involved in aging, renal diseases and diabetes, are linked to elevated...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2012.1393
更新日期:2012-06-01 00:00:00
abstract::The prognosis of non-small cell lung cancer (NSCLC) patients who failed two or more treatment regimens remains very poor. We conducted a phase II study to explore the feasibility of personalized peptide vaccination (PPV), in which peptides are selected and administered based on the pre-existing host immunity before va...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2014.2699
更新日期:2015-01-01 00:00:00
abstract::Insulin-like growth factor-binding protein-2 (IGFBP-2) is considered to be a human tumor antigen, and the tumor-specific immunity of IGFBP-2 has been reported in several types of cancer. The purpose of this study was to evaluate whether autoantibodies to IGFBP-2 can be used as diagnostic markers in lung cancer. The re...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2012.1699
更新日期:2013-01-01 00:00:00
abstract::The aim of this study was to determine the prevalence of human papillomavirus (HPV) in patients with laryngeal benign lesions (LBLs) and laryngeal squamous cell carcinomas (LSCCs) using a sensitive E6/E7 type-specific PCR. Paraffin-embedded samples from LBL (n=39) and LSCC patients (n=67) were evaluated for the presen...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2011.1031
更新日期:2011-07-01 00:00:00
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journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2016.3724
更新日期:2016-12-01 00:00:00
abstract::Erucylphosphocholine (ErPC) is a promising antineoplastic drug for the treatment of malignant brain tumors. It exerts strong anticancer activity and induces apoptosis even in chemoresistant glioma cells. In the present study, A172 and U373MG glioma cells were treated with ErPC to explore the contribution of MAP kinase...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2004-12-01 00:00:00
abstract::A multi stage extraction procedure which gives the possibility to analyze both water soluble and lipid components stemming from the same specimen has been developed in our laboratory. Metabolites from brain cancer biopsies have been compared to metabolites in normal human brain, developing mouse brain and primary mous...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2.4.545
更新日期:1993-04-01 00:00:00