Abstract:
:Chemotherapy (CT) resistance in ovarian cancer is related to multiple factors, and assessment of these factors is necessary for the development of new drugs and therapeutic regimens. In an effort to identify such determinants, we evaluated the expression of approximately 21,000 genes using DNA microarray screening in paired tumor samples taken prior to and after CT treatment from 6 patients with predominantly advanced stage, high-grade epithelial ovarian cancer. A subset of differentially expressed genes was selected from all microarray data by initial filtering on confidence at p=0.05, followed by filtering on expression level (>or=2-fold). Using these selection criteria, we found 121 genes to be commonly up-regulated and 54 genes to be down-regulated in the post-CT tumors, compared to primary tumors. Up-regulated genes in post-CT tumors included substantial number of genes with previously known implication in mechanisms of chemoresistance (TOP2A, ETV4, ABCF2, PRDX2, COX2, COX7B, MUC1, MT3, MT2A), and tumorigenesis (SCGB2A2, S100A9, YWHAE, SFN, ATP6AP1, MGC5528, ASS, TACC3, ARHGAP4, SRA1; MGC35136, PSAP, SPTAN1, LGALS3BP, TUBA4, AMY2B, PPIA, COX1, GRB2, CTSL). Down-regulated genes in post-CT samples mostly included genes implicated in chemosensitivity (GRP, TRA1, ADPRTL1, TRF4-2), cell proliferation and cell cycle control (NGFRAP1, TPD52L1, TAX1BP1) and tumor suppression and apoptosis (SMOC2, TIMP3, AXIN1, CASP4, P53SCV). Additionally, gene clustering analysis revealed the existence of two distinct expression signatures of chemoresistant tumors, which was further confirmed by assessment of some genetic (p53 gene mutation status) and clinical parameters (CT regimens). Our data suggest that intrinsic and acquired chemoresistant phenotypes of post-CT tumors may be attributed to the combined action of different factors implicated in mechanisms of chemoresistance, tumor invasion/progression and control of cell proliferation. This type of molecular profiling could have important clinical implications in resolving chemoresistance and the development of novel treatment strategies designed to prevent its emergence.
journal_name
Int J Oncoljournal_title
International journal of oncologyauthors
L'Espérance S,Popa I,Bachvarova M,Plante M,Patten N,Wu L,Têtu B,Bachvarov Dsubject
Has Abstractpub_date
2006-07-01 00:00:00pages
5-24issue
1eissn
1019-6439issn
1791-2423journal_volume
29pub_type
杂志文章abstract::The Raf/MEK/ERK signaling cascade has been extensively studied for its roles in growth and differentiation of a variety of cell types. Confliciting evidence exists regarding the function of classical MAPK signaling with regards to the development of chemotherapeutic drug resistance; some reports describe an pro-surviv...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2005-06-01 00:00:00
abstract::In order to optimize the management of patients with renal cell carcinoma (RCC) it is important to define the genetic risk for metastatic disease. In this study we performed comparative genomic hybridization (CGH) on metastatic tumors aiming at the identification of genetic alterations associated with metastatic disea...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.17.5.903
更新日期:2000-11-01 00:00:00
abstract::Acquired drug resistance to chemotherapy is a major problem in the treatment of cancer. After primary surgical intervention, followed by chemotherapy treatments, the majority of patients develop disease recurrence. This is due to tumor cell heterogeneity and genetic instability. In contrast to tumor cells, proliferati...
journal_title:International journal of oncology
pub_type: 杂志文章,评审
doi:
更新日期:2005-08-01 00:00:00
abstract::Ganoderma lucidum (Curt.:Fr.) P. Karst, a medicinal fungus, has been widely used in Asian countries for centuries to prevent or treat a variety of diseases, including cancer. However, the mechanisms responsible for the effects of G. lucidum on cancer cells remain to be elucidated. We have previously shown that ethyl a...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2007-10-01 00:00:00
abstract::The positron-emitting radiohalogens 18F, 75Br, 76Br, and 124I are reviewed regarding their relevance for positron emission tomography (PET) in oncology. Relevant production routes of these cyclotron-generated isotopes are given, followed by publications that deal with applications of these radiohalogens. This article ...
journal_title:International journal of oncology
pub_type: 杂志文章,评审
doi:
更新日期:2003-02-01 00:00:00
abstract::Point mutations in the K-ras gene are observed at a high incidence in human pancreatic carcinomas. These alterations can be used as potential targets for specific ribozyme-mediated reversal of the malignant phenotype. We designed an anti-K-ras ribozyme against codon 12 of the mutant K-ras gene transcripts (GGT right c...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2004-03-01 00:00:00
abstract::Experimental studies have established that the sulfated glycosaminoglycans heparan sulfate and chondroitin sulfate act as co-receptors of cytokines and growth factors that drive the malignant cell phenotype and the remodelling of the surrounding tumor stroma. However, the clinical relevance of these studies remains il...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2011.1164
更新日期:2011-12-01 00:00:00
abstract::The objective of the present study was to establish the individual and combined chemopreventive potential of a widely used non-steroidal anti-inflammatory drug, ibuprofen (IBU), encapsulated in solid lipid nanoparticles (SLNs) for the chemoprevention of pancreatic cancer. The IBU SLNs were optimized using various lipi...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2015.2879
更新日期:2015-04-01 00:00:00
abstract::We have isolated a new -ene, named BAC, which is the human equivalent of the murine H19 gene and is highly expressed in most fetal tissues and in a variety of fresh tumors. BAC was analyzed in 130 untreated invasive carcinomas of different types. The frequency of BAC-expressing cancers as well as the level of expressi...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2.5.753
更新日期:1993-05-01 00:00:00
abstract::Human malignant neuroblastoma is characterized by poor differentiation and uncontrolled proliferation of immature neuroblasts. Retinoids such as all-trans-retinoic acid (ATRA), 13-cis-retinoic acid (13-CRA), and N-(4-hydroxyphenyl) retinamide (4-HPR) at low doses are capable of inducing differentiation, while flavonoi...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo_00000201
更新日期:2009-03-01 00:00:00
abstract::Accumulating evidence indicates that microRNAs (miRNAs) have a critical role in cell proliferation and metastasis in hepatocellular carcinoma (HCC). However, the effect of miR‑300 on the development and progression of HCC remains unclear. In the present study, it was observed that miRNA (miR)‑300 expression was signif...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2019.4715
更新日期:2019-04-01 00:00:00
abstract::Nitric oxide (NO) shows tumoricidal activity. We had previously reported that NO downregulates the phosphatidylinositol-3-kinase/Akt pathway, but upregulates the MEK/ERK pathway downstream of growth factor signaling. We hypothesized that NO donor and MEK inhibitor in combination syn...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2011.1243
更新日期:2012-03-01 00:00:00
abstract::The effects of different substrate stiffness were investigated on epithelial-mesenchymal transition (EMT) of cervical cancer cell lines and the role of miR-106b and its target protein DAB2 therein. Cervical cancer cell lines HeLa and SiHa were cultured on artificial substrates with different stiffness prepared using d...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2017.3978
更新日期:2017-06-01 00:00:00
abstract::Although most hepatocellular carcinoma (HCC) is related to viral infection, there is a substantial population of HCC patients (5-20%) who are negative for both markers of hepatitis B virus and hepatitis C virus infection [non-B, non-C (NBNC) hepatitis] in Japan and the incidence of NBNC-HCC has recently tended to incr...
journal_title:International journal of oncology
pub_type: 杂志文章,评审
doi:10.3892/ijo.2013.2061
更新日期:2013-11-01 00:00:00
abstract::The cell-adhesion properties of cancer cells can be targeted to block cancer metastasis. Although cytosolic lysyl-tRNA synthetase (KRS) functions in protein synthesis, KRS on the plasma membrane is involved in cancer metastasis. We hypothesized that KRS is involved in cell adhesion-related signal transduction for cell...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2016.3381
更新日期:2016-04-01 00:00:00
abstract::Malignant gliomas are diffuse infiltrative growing tumors with a poor prognosis despite treatment with a combination of surgery, radiotherapy and chemotherapy. It has been shown recently that complete tumor resection improves the survival time significantly. Hypericin, a component of St. Johns Wort, is one of the most...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2011.968
更新日期:2011-05-01 00:00:00
abstract::Hepatocyte growth factor (HGF), the ligand for the c-met proto-oncogene product, is a multifunctional protein that enhances tumor cell motility, extracellular matrix invasion, and mitogenic or morphogenic activities of various cell types. In this study we examined the expression of the c-Met receptor in human oral squ...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2004-10-01 00:00:00
abstract::One of the early events of apoptosis is proteolysis. The enzyme(s) involved in this event appear to be the serine protease(s), inasmuch as the reversible or irreversible inhibitors of serine proteases prevent DNA degradation and abrogate other signs of apoptosis in several cell systems (Gorczyca et al, Int J Oncol 1: ...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.3.4.627
更新日期:1993-10-01 00:00:00
abstract::The p53-induced wig-1 gene encodes an unusual nuclear zinc finger protein with high sequence similarity between human, rat and mouse. Wig-1 belongs to a group of proteins with widely spaced zinc fingers that bind double stranded (ds) RNA. We show here that wig-1 is present in Gallus gallus (chicken), Silurana tropical...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2004-06-01 00:00:00
abstract::Voltage-gated potassium (Kv) channels play important roles in differentiation and growth of non-excitable cells. Inhibition of these channels is also known to suppress proliferation of various cancer cells. Here we examine expression of K+ channel subunit genes in various uterine cancer cells and their roles in cell p...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2004-07-01 00:00:00
abstract::Whether elderly patients with metastatic esophageal, gastroesophageal, and gastric cancer do as well with chemotherapy as their younger counterparts was investigated in this pooled analysis. In total, 367 patients from 8 consecutive, first-line trials were included: i) etoposide + cisplatin; ii) 5-fluorourucil + leuco...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo_00000535
更新日期:2010-03-01 00:00:00
abstract::MicroRNAs (miRNAs) were reported to be involved in the development of clear cell renal cell carcinoma (ccRCC). However, the study on miRNAs in ccRCC is far from complete. The present study identified miRNAs which could act as potential novel prognostic markers for ccRCC, and analyzed its possible mechanism. We found t...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2016.3746
更新日期:2016-12-01 00:00:00
abstract::Esophageal squamous cell carcinoma (ESCC), the most common esophageal cancer in East Asia, is among the six cancers with the highest fatality rates worldwide. Unfortunately, multidisciplinary treatment strategies have not achieved satisfactory outcomes. Therefore, novel insights into the molecular biology of ESCC are ...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2015.3167
更新日期:2015-11-01 00:00:00
abstract::Cell lines established from the TH-MYCN transgenic murine model of neuroblastoma are a valuable preclinical, immunocompetent, syngeneic model of neuroblastoma, for which knowledge of their p53 pathway status is important. In this study, the Trp53 status and functional response to Nutlin-3 and ionising radiation (IR) w...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2018.4261
更新日期:2018-03-01 00:00:00
abstract::After the publication of the article, the authors noted that they had made the following errors. In Fig. 5B, total PDK1 is incorrect in the published paper. The corrected version of Fig. 5B is shown below. Also in Fig. 6B, the DMSO-treated group and the brassinin (400 µM)-treated group are incorrect, and the corrected...
journal_title:International journal of oncology
pub_type: 已发布勘误
doi:10.3892/ijo.2015.3315
更新日期:2016-03-01 00:00:00
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 m...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2002-04-01 00:00:00
abstract::Hepatocellular carcinoma (HCC) is one of the most malignant types of cancer, and is associated with high recurrence rates and a poor response to chemotherapy. Immune signatures in the microenvironment of HCC have not been well explored systematically. The aim of the present study was to identify prognostic immune sign...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2020.4998
更新日期:2020-05-01 00:00:00
abstract::Knowledge of intrinsic tumor heterogeneity is vital for understanding of tumor progression mechanisms as well as for providing efficient treatments. In situ proteomic profiling of tumors is a powerful technology with potential to enhance our understanding of tumor biology, but sources of variability due to patient and...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2007-07-01 00:00:00
abstract::Alternative polyadenylation and microRNA regulation are both mechanisms of post-transcriptional regulation of gene expression. Alternative polyadenylation often results in mRNA isoforms with the same coding sequence but different lengths of 3' UTRs, while microRNAs regulate gene expression by binding to specific mRNA ...
journal_title:International journal of oncology
pub_type: 杂志文章,评审
doi:10.3892/ijo.2013.2047
更新日期:2013-10-01 00:00:00
abstract::To elucidate the involvement of proteasome inhibition in apoptosis induced by anthracycline anticancer agents, we investigated the interaction between the proteasome and anthracycline anticancer agents, and the function of the proteasome in apoptosis. Exposure of L1210 mouse lymphocytic leukemia cells to adriamycin (A...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2002-06-01 00:00:00