Abstract:
:We investigated the clinical significance of the expression levels of matrix metalloproteinase 9 (MMP-9) in renal cell carcinoma (RCC). In addition, we validated the efficacy of pyrrole imidazole polyamide (PIP) targeting MMP-9 on inhibiting proliferation and invasion of RCC. We evaluated the expression levels of MMP-9 in 249 RCC specimens by immunostaining and analyzed the association between MMP-9 expression levels and cancer-specific survival. Furthermore, in a human RCC cell line, Caki-2, we tested the effect of a couple of PIPs targeting MMP-9 one recognizing an NF-κB binding site (MMP-9-NF-κB PIP) and another for the AP-1 binding site (MMP-9-AP-1 PIP) in the MMP-9 promoter. The expression levels of MMP-9, proliferative activity and invasive capability were tested by quantitative PCR, WST8 assay and Matrigel invasion assay, respectively. By immunostaining of the clinical specimens, strong MMP-9 staining was proven to be a significant predictor of poor prognosis for cancer-specific survival (P<0.01). In Caki-2 cells, MMP-9-NF-κB PIP significantly reduced the expression levels of MMP-9 mRNA and inhibited cell invasion, but did not affect the cell proliferation activity. On the other hand, no effect was found in MMP-9-AP-1 PIP on MMP-9 mRNA expression, cell proliferation and invasion. We confirmed the inhibitory effects of MMP-9-NF-κB PIP on the expression of MMP-9 and subsequent invasion of Caki-2 cells. Since it was clearly shown that high MMP-9 expression levels were associated with poor prognosis of RCC, MMP-9 is a potential candidate target for RCC treatment. Transcription therapy using a minor groove binder, such as NF-κB PIP, may be a potential therapeutic agent for RCC, although further investigation is required.
journal_name
Int J Oncoljournal_title
International journal of oncologyauthors
Sato A,Nagase H,Obinata D,Fujiwara K,Fukuda N,Soma M,Yamaguchi K,Kawata N,Takahashi Sdoi
10.3892/ijo.2013.2073subject
Has Abstractpub_date
2013-11-01 00:00:00pages
1441-6issue
5eissn
1019-6439issn
1791-2423journal_volume
43pub_type
杂志文章abstract::5-Fluorouracil (5-FU), a fluoropyrimidine analogue, is one of the most commonly used anticancer drugs for the treatment of gastrointestinal malignancies. Some studies reported that the cytotoxicity of fluoropyrimidines is mediated, in large part, by inhibition of the thymidylate synthase (TS), an essential DNA synthet...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2004-01-01 00:00:00
abstract::We report a retrospective study of all patients with localised non-Hodgkin's lymphoma referred to the Sheffield Lymphoma Group (1970-1995). A total of 1,979 patients with non-Hodgkin's lymphoma were seen: 553 (28%) presented with stage I or II disease, 411 (21%) extranodal, 142 (7%) nodal. The commonest extranodal sit...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.13.6.1313
更新日期:1998-12-01 00:00:00
abstract::Thymidylate synthase (TS) is an essential enzyme for DNA biosynthesis that is an important target of fluoropyrimidine anti-cancer drugs such as 5-fluorouracil (5-FU), which is frequently used against human colon adenocarcinomas. Because levels of TS in such tumors may be predictive of chemotherapeutic response to 5-FU...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:1993-02-01 00:00:00
abstract::We have previously isolated a drug-resistant, [PC3(R)], variant of human prostate PC3 cell line, which showed significant resistance (>10-fold) to adriamycin. No known mechanisms of drug resistance were found; however, resistant cells expressed more bcl2, c-myc, and ms oncogenes compared to the sensitive cells. In thi...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.11.4.819
更新日期:1997-10-01 00:00:00
abstract::Thirty patients who underwent hepatectomy for the treatment of hepatocellular carcinoma (HCC) were examined for expression of HLA class I antigens on HCC cells by flow cytometry. The expression was found significantly lower in cases of stage IV compared with those of stage I or stage II (p<0.05), and in cases of intra...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.8.6.1243
更新日期:1996-06-01 00:00:00
abstract::Bovine lactoferricin (LfcinB) is a cationic antimicrobial peptide that selectively induces apoptosis in several different types of human cancer cells. However, the potential use of LfcinB as an anticancer agent is presently limited by the need for relatively high concentrations of the peptide to trigger apoptosis. Cer...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2008-03-01 00:00:00
abstract::To overcome the poor tumor transduction efficiency of adenovirus serotype 5 (Ad5) observed in several types of cancer, the fiber region of Ad5, apart from its tail, was replaced by adenovirus serotype 35 (Ad35). The chimeric Ad5/F35 adenoviral vector did not exhibit any significant enhancement of transduction efficien...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2013.1812
更新日期:2013-04-01 00:00:00
abstract::B7-H4 is a transmembrane protein which is a member of the B7 superfamily. It is overexpressed in various types of cancer, including gastric cancer. However, the effects of B7-H4 on the tumorigenicity of gastric cancer and the underlying mechanisms have not yet been fully explored. Thus, the aim of this study was to ex...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2018.4274
更新日期:2018-04-01 00:00:00
abstract::Tamoxifen (Tam), a selective estrogen receptor modulator, is in wide clinical use for the treatment and prevention of breast cancer. However, extended TAM administration for breast cancer induces increased VEGF levels in patients, promoting new blood vessel formation and thereby limiting its efficacy and highlighting ...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2014.2299
更新日期:2014-04-01 00:00:00
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 ...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2006-07-01 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::Due to the central role in predicting response to herceptin and possibly also other anticancer drugs, accurate and reproducible detection of the HER2 status is important. Fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) are the most commonly used methods for HER2 analysis. It is a disadvantage ...
journal_title:International journal of oncology
pub_type: 临床试验,杂志文章
doi:
更新日期:2004-12-01 00:00:00
abstract::CXC chemokines have a major influence on the angiogenesis, growth and metastatic potential of pancreatic ductal adenocarcinoma. CXCL16 is a unique transmembrane CXC chemokine, which is shed by members of the disintegrins and metalloproteases (ADAMs), in particular by ADAM10 and ADAM17. In our study, we evaluated expre...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2008-08-01 00:00:00
abstract::The deregulation of the epidermal growth factor receptor (EGFR) pathway plays a major role in the pathogenesis of prostate cancer (PCa). However, therapies targeting EGFR have demonstrated limited effectiveness in PCa. A potential mechanism to overcome EGFR blockade in cancer cells is the autocrine activation of alter...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2012.1509
更新日期:2012-09-01 00:00:00
abstract::Most malignant tumors have a defect in the Rb pathway that allows them to proliferate autonomously, unrestricted by the availability of mitogens and growth factors. This defect preconditions tumor cells to be less sensitive to inhibitors of growth factor receptors and/or signal transduction pathways that arrest normal...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.19.4.811
更新日期:2001-10-01 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::Macrophages activated by lipopolysaccharide or interferon-gamma have been shown to be cytotoxic to tumor cells by releasing nitric oxide. Here, we report that unstimulated rat alveolar macrophages cultured with certain tumor cells produce nitric oxide and are cytotoxic to these tumor cells. Alveolar macrophages were t...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2.6.1053
更新日期:1993-06-01 00:00:00
abstract::We have previously shown that the combination of allogeneic intra-bone marrow-bone marrow transplantation (IBM-BMT) and donor lymphocyte infusion (DLI) using CD4+ cell-depleted spleen cells is effective in suppressing tumor growth, but that this does not induce graft-versus-host disease (GVHD) in mice. In this report,...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2007-06-01 00:00:00
abstract::Advanced metastatic melanoma is a malignant tumor for which there is currently no effective treatment due to resistance development. Ginsenoside Rg3, a saponin component extracted from ginseng roots, has been shown to reduce melanoma cell proliferation by decreasing histone deacetylase 3 and increasing p53 acetylation...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2019.4787
更新日期:2019-06-01 00:00:00
abstract::Shc protein is known to be related to cell proliferation and carcinogenesis. However, the involvement of Shc in hepatocellular carcinoma (HCC) remains unknown. In the present study, we report that p46 Shc is probably expressed in the nuclei of hepatocytes and/or cancer cells during the development of HCC in Long-Evans...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2004-10-01 00:00:00
abstract::We report here that lysocellin, a polyether antibiotic from a streptomycete, induces G1 phase arrest in human osteosarcoma MG63 cells. Lysocellin up-regulates p21WAF1/Cip1 and down-regulates cyclin D1 at the mRNA level. In addition, cyclin D1 is down-regulated by the proteasome-dependent signal pathway in MG63 cells. ...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2006-04-01 00:00:00
abstract::Colorectal cancer (CRC) is the third most common type of cancer; however, the molecular mechanisms underlying colorectal tumor metastasis and growth remain elusive. Recently, accumulating evidence has indicated that long non‑coding RNAs (lncRNAs) play a critical role in CRC progression and metastasis; however, the bio...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2018.4451
更新日期:2018-09-01 00:00:00
abstract::Lamins are the major components of the nuclear lamina and play important roles in many cellular processes. The role of lamins in cancer development and progression is still unclear but it is known that reduced expression of lamin B1 has been observed in colon cancer. Thus, the aim of the present study was to elucidate...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2017.4182
更新日期:2018-01-01 00:00:00
abstract::Hepatocellular carcinoma is the most frequent liver cancer and hepatitis B virus is included among the risk factors for the development of this type of neoplasia. Direct detection of this virus is difficult due to the lack of a simple tissue culture system for growing the virus. Amplification of HBV nucleic acid seque...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:1992-07-01 00:00:00
abstract::Colorectal cancer (CRC) is one of the most common cancers; however, the development of drugs to treat the condition has reached a plateau. Bortezomib (PS-341, Velcade®) is a proteasome inhibitor approved for the treatment of hematological malignancies, including multiple myeloma. A few trials of bortezomib, alone or i...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2012.1448
更新日期:2012-07-01 00:00:00
abstract::Seven ovarian and one cervical human cancer cell lines were examined far their sensitivity or resistance to tumor necrosis factor, to three topoisomerase II inhibitors and to cisplatin. Only one line exhibited the multidrug-resistance phenotype and another one an 'atypical'-MDR phenotype. The combination of TNF and to...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:1995-09-01 00:00:00
abstract::The enzyme poly(ADP-ribose)polymerase (PARP) has been implicated in several cellular processes by the demonstration of ADP-ribosylation of proteins which play a role in cellular repair of DNA damage, response to ionizing radiation and apoptosis. In addition, ADP-ribosylation has been shown to play a role in cell cycle...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.8.4.803
更新日期:1996-04-01 00:00:00
abstract::Extrahepatic cholangiocarcinoma (CC) is an aggressive malignancy with dismal prognosis and characterized by early invasion, metastasis and postoperative recurrence. Therefore, understanding the main molecular mechanisms of this malignancy is the key for the development of novel and effective therapeutic strategies for...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2015.2957
更新日期:2015-01-01 00:00:00
abstract::We have assessed the prognostic significance of mutations in the p53 tumor suppressor gene in patients with small non-cleaved cell lymphomas. In this retrospective pilot study we have, been able to evaluate the response to therapy of 21 previously untreated patients. Seven of these patients (33%) had tumors which cont...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.4.3.567
更新日期:1994-03-01 00:00:00
abstract::The in situ formation of cytotoxic metabolites by an enzyme-catalyzed reaction is a recent approach in cancer therapy. The present results show that multidrug-resistant human colon adenocarcinoma cells (LoVo) are significantly more sensitive than corresponding wild-type cells to hydrogen peroxide and aldehydes, the pr...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2006-10-01 00:00:00