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  • American Association for Cancer Research (AACR)  (9)
  • 1
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    Online Resource
    Abstract 4993: IFI27 and NOV , downstream regulated genes by S100A4, are playing important roles in pancreatic carcinogenesis
    American Association for Cancer Research (AACR) ; 2014
    In:  Cancer Research Vol. 74, No. 19_Supplement ( 2014-10-01), p. 4993-4993
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 74, No. 19_Supplement ( 2014-10-01), p. 4993-4993
    Abstract: S100A4 is a member of the Ca2+-dependent S100 protein family, and positive association between S100A4-upregulation andmetastasis/invasion was reported. We reported a significant association between upregulation of S100A4 and perineural invasion in pancreatic cancer. Furthermore, siRNA-mediated knockdown of S100A4 promoted cell death mainly mediated by induction of apoptosis only in cancer cells with high expression of S100A4, and forced expression of S100A4 induced accelerated cell motility only in cancer cells with low expression. To explore the molecular mechanisms of cell motility after the forced expression of S100A4, we analyzed gene expression profiles and identified some candidate genes including IFI27 and NOV (CCN3) that are regulated by S100A4-upregulation, and we further focused on IFI27 and NOV. IFI27 showed significant upregulation after the forced expression of S100A4 and downregulation after siRNA mediated knockdown of S100A4, while NOV seemed to show an inverse relationship with S100A4. Using 93 primary resected tumors, we performed immunohistochemical analyses and identified significant positive association between S100A4 and IFI27 expressions. Although NOV did not show significant inverse-association, siRNA-mediated knockdown in high level expressing cells showed significant acceleration of cell motility. Clinicopathologic characteristics demonstrated positive associations between IFI27 expression and intrapancreatic neural invasion (P=0.0023) and negative associations between NOV expression and invasion pattern (P=0.017) were observed. Our present study suggests that IFI27 and NOV may be downstream regulated genes of S100A4 and that expressional changes may play important roles in invasion of pancreatic cancer. Citation Format: Na Chen, Yuriko Saiki, Hitoshi Sekine, Makoto Sunamura, Shinichi Fukushige, Fuyuhiko Motoi, Shinichi Egawa, Michiaki Unno, Akira Horii. IFI27 and NOV, downstream regulated genes by S100A4, are playing important roles in pancreatic carcinogenesis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4993. doi:10.1158/1538-7445.AM2014-4993
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2014-4993
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2014
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    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 2
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    Synchronous Alterations of Wnt and Epidermal Growth Factor Receptor Signaling Pathways through Aberrant Methylation and Mutation in Non–Small Cell Lung Cancer
    American Association for Cancer Research (AACR) ; 2007
    In:  Clinical Cancer Research Vol. 13, No. 20 ( 2007-10-15), p. 6087-6092
    Details
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 13, No. 20 ( 2007-10-15), p. 6087-6092
    Abstract: Purpose: The Wnt and epidermal growth factor receptor (EGFR) signaling pathways play crucial roles in the pathogenesis of a variety of malignant tumors. Although the details of each cascade are understood, very little is known about their collective effects in non–small cell lung cancer (NSCLC). Experimental Design: A total of 238 NSCLC samples were examined for methylation of Wnt antagonists [secreted frizzled-related protein (sFRP)-1, sFRP-2, sFRP-5, Wnt inhibitory factor-1, and Dickkopf-3] and for EGFR and KRAS mutations. Protein expression levels of β-catenin were assayed in 91 of the 238 NSCLCs. Results: We found that (a) aberrant methylation of Wnt antagonists is common in NSCLCs; (b) methylation of sFRP-2 is more prevalent in females, nonsmokers, and adenocarcinoma cases; (c) Dickkopf-3 methylation is significantly associated with a poor prognosis in adenocarcinomas; (d) there is a positive correlation between activated EGFR mutation and nuclear accumulation of β-catenin; (e) KRAS mutation and aberrant methylation of Wnt antagonists are positively correlated; and (f) EGFR mutation is significantly associated with a good prognosis in tumors lacking methylated Wnt antagonist genes. Conclusions: These results contribute to a better understanding of the cross-talk between the Wnt and EGFR signaling pathways and help foster development of chemotherapeutic treatments in NSCLCs.
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    URL: Article
    DOI: 10.1158/1078-0432.CCR-07-0591
    RVK:
    XA 36791
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2007
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  • 3
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    Abstract 5295: S100A4 regulates tumor growth, motility, and invasion in pancreatic cancer
    American Association for Cancer Research (AACR) ; 2010
    In:  Cancer Research Vol. 70, No. 8_Supplement ( 2010-04-15), p. 5295-5295
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 70, No. 8_Supplement ( 2010-04-15), p. 5295-5295
    Abstract: S100A4 protein belongs to the S100 subfamily, which has grown to be one of the large subfamilies of the EF-hand Ca2+-binding proteins, and overexpression of S100A4 is suggested to associate with cell proliferation, invasion, and metastasis. We observed frequent overexpression of S100A4 in pancreatic cancer cell lines by quantitative real-time RT-PCR and Western blotting. Tissue microarray analysis validated S100A4 overexpression in primary pancreatic cancer tissues, and overexpression of S100A4 associated with perineural invasion. We further analyzed RNAi-mediated knockdown to address the possibility of its use as a therapeutic target for pancreatic cancer. The specific knockdown of S100A4 strongly suppressed cell growth, induced G2 arrest and eventual apoptosis, and decreased cell migration. Furthermore, microarray analyses revealed that knockdown of S100A4 induced expression of the tumor suppressor genes PRDM2 and VASH1. We further established stably S100A4-expressing cell lines using two pancreatic cancer cell lines with low level of S100A4 expression; remarkable accelerated cell growth and motility was observed after induction of S100A4, whereas no change was observed in the control cells. Comparison of the expressional profiles after siRNA-mediated knockdown and expression vector-mediated induction is underway, and the results will also be demonstrated and discussed. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5295.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM10-5295
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2010
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    detail.hit.zdb_id: 410466-3
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  • 4
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    Abstract 4184: Expression analysis of iPS inductive gene in gastrointestinal cancer by tissue microarray
    American Association for Cancer Research (AACR) ; 2011
    In:  Cancer Research Vol. 71, No. 8_Supplement ( 2011-04-15), p. 4184-4184
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 71, No. 8_Supplement ( 2011-04-15), p. 4184-4184
    Abstract: Background: Recent progress is enabling us to induce iPS cells using somatic differentiated cells. We are now establishing iPS cells from normal gastrointestinal epithelial cells. However, the risks associated with transfection of iPS inductive genes (Sox2, Oct 3/4, klf4 and c-Myc) to somatic differentiated cells has not been well examined. Thus, in order to understand the role of iPS inductive genes in gastrointestinal cancer, we examined the expression of Sox2, Oct3/4, klf4, c-Myc and Nanog by cancer tissue microarray. Methods: We examined gene expression in 86 esophageal cancers, 50 gastric cancers, 80 colorectal cancers, 37 biliary tract cancers and 34 pancreatic cancers. Immunohistochemical expression levels of 5 genes were evaluated by the combination of their intensity and distribution. The expression level was compared to the clinico-pathological data of the patients. Results: Klf4 reduction was associated with lymph node metastasis of colorectal cancer which resulted in a poor prognosis for the patients (p=0.02). Klf4 reduction also tended to indicate a poor prognosis in esophageal cancer (P=0.06). Furthermore, Sox2 reduction was an independent prognostic factor in gastric cancer (p=0.03) and a high expression of OCT3/4 tended to indicate a poor prognosis in esophageal cancer (p=0.07). Nanog reduction was associated with poor prognosis in biliary tract and pancreatic cancer(p=0.02). On the other hand, c-Myc did not have any association with clinico-pathological factors of gastrointestinal cancer. Clustering analysis revealed that prognosis of the subgroup of simultaneous positive expressions of iPS inductive genes was better than that of other subgroups in colon cancer, however there was no difference among subtypes in esophageal cancer. Conclusions: The role of iPS inductive genes may differ in various gastroenterological cancer patients. However, further large-scale analysis is needed to elucidate this issue. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4184. doi:10.1158/1538-7445.AM2011-4184
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2011-4184
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2011
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    detail.hit.zdb_id: 410466-3
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  • 5
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    Abstract 2720: Newly established Barrett's adenocarcinoma cell line (TYAE-1).
    American Association for Cancer Research (AACR) ; 2013
    In:  Cancer Research Vol. 73, No. 8_Supplement ( 2013-04-15), p. 2720-2720
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 73, No. 8_Supplement ( 2013-04-15), p. 2720-2720
    Abstract: Although 10 esophageal adenocarcinoma cell lines have been reported, only 5 were Barrett's adenocarcinoma cell lines. Furthermore, there was only one mouse-inoculated esophageal adenocarcinoma cell line. In this paper, we present a newly established Barrett's esophageal adenocarcinoma cell line (TYAE-1). Material and Method: The Barrett's esophageal adenocarcinoma cells were obtained from the resected tumor of a patient (74 years-old male). The resected tumor was confirmed as well-differentiated intraepithelial Barrett's adenocarcinoma without lymphnode metastasis. The tumor was too small (T1a) for a primary culture, so we transplanted the tumor in the back of a nude mouse. Results: One month later, the tumor grew rapidly and was able to be re-transplanted to other mice. Up to the writing of this report, the tumor (TYAE-1m) was able to be re-transplanted 10 times every month. The histology of the transplanted tumor was slightly different from the primary tumor. The majority of the tumor was cribriform type and there were a few tubular-trabecular type cells. The expression of beta-Catenin was cytoplasmic in the cribriform part and membranous in the tubular part. Both cell types did express VEGF slightly however they did not express HER-2. We also started to perform in vitro cultures from the mice transplanted tumor and established TYAE-1c cell. TYAE-1c cells were able to be transplanted in nude mice and transplanted tumor showed the same histological features as TYAE-1m. TYAE-1m and TYAE-1c cells were sensitive to Gemcitabine treatment. On the other hand, both tumors did not show sensitivity for Docetaxel treatment. In conclusion: Although the tumor was small and had no invasive characteristics by clinicopathological examination, this tumor has aggressive behavior. This in vitro and in vivo Barrett's adenocarcinoma model may useful for understanding the behavior of Barrett's adenocarcinoma. Citation Format: Yutaka Shimada, Makoto Moriyama, Tomoyuki Okumura, Shinichi Sekine, Shigeaki Sawada, Koshi Matsui, Shozo Hojo, Kazuto Shibuya, Isaku Yoshioka, Toru Yoshida, Takuya Nagata, Kazuhiro Tsukada. Newly established Barrett's adenocarcinoma cell line (TYAE-1). [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2720. doi:10.1158/1538-7445.AM2013-2720
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2013-2720
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2013
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  • 6
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    Overexpression of Collagen XVIII Is Associated with Poor Outcome and Elevated Levels of Circulating Serum Endostatin in Non–Small Cell Lung Cancer
    American Association for Cancer Research (AACR) ; 2004
    In:  Clinical Cancer Research Vol. 10, No. 16 ( 2004-08-15), p. 5361-5366
    Details
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 10, No. 16 ( 2004-08-15), p. 5361-5366
    Abstract: Purpose: The aim of this study was to determine whether collagen XVIII expression is correlated with circulating serum endostatin and whether this has any prognostic value in patients with non–small cell lung cancer (NSCLC). Experimental Design: Serum endostatin levels were measured quantitatively by a competitive enzyme immunoassay, and collagen XVIII expression in tumor tissue was investigated with an immunohistochemical method in a series of 94 patients who underwent surgery for NSCLC. Results: Sixty cases (63.8%) had positive immunohistochemical staining with anticollagen XVIII polyclonal antibodies, including strongly positive staining in 11 (11.7%) cases. The mean (± SD) serum endostatin level was 41.6 ± 34.4 ng/ml in the patient group and 16.3 ± 10.3 ng/ml in the control group (P & lt; 0.0001). The 11 cases who were strongly collagen XVIII-positive had significantly higher serum endostatin levels than the cases who were negative or weakly positive (P = 0.0297). The 5-year survival rates of negative, weakly positive, and strongly positive patients were 77.8%, 56.9%, and 43.8%, respectively. The cases with strongly positive collagen XVIII expression had a significantly poorer outcome than cases with negative expression (P = 0.0027). A multivariate analysis with Cox proportional hazards model for disease-specific survival revealed that expression of collagen XVIII (strongly positive versus negative; weakly positive versus negative), tumor classification, and regional lymph node classification were independent prognostic factors. Conclusions: Our results suggest that expression of collagen XVIII in tumor tissue is strongly associated with a poorer outcome in NSCLC and correlates with elevated levels of circulating serum endostatin.
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    URL: Article
    DOI: 10.1158/1078-0432.CCR-04-0443
    RVK:
    XA 36791
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2004
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  • 7
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    Abstract B131: Chemical array screen identifies a novel MMP inhibitor NPDK-18 that suppresses tumor cell migration
    American Association for Cancer Research (AACR) ; 2015
    In:  Molecular Cancer Therapeutics Vol. 14, No. 12_Supplement_2 ( 2015-12-01), p. B131-B131
    Details
    In: Molecular Cancer Therapeutics, American Association for Cancer Research (AACR), Vol. 14, No. 12_Supplement_2 ( 2015-12-01), p. B131-B131
    Abstract: Background and Purpose: Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases that degrade extracellular matrix components and that have been implicated in a wide range of pathological processes including tumor metastasis. Although many small-molecule MMP inhibitors have been developed, there are some problems related to specificity and side effects. In addition, recent studies have shown that several MMPs have nonproteolytic and tumor-suppressing functions depending upon the stage of cancer progression. Thus, much work remains for the elucidation of each MMP function and the development of new MMP inhibitors. Small-molecule microarrays represent a powerful new platform for facilitating target-based screens. Thousands of small molecules are arrayed on a slide glass and used to screen for protein-small molecule interactions in a high-throughput manner. We have developed unique photo-cross-linked chemical arrays, which enable the immobilization of a variety of small molecules on a solid support in a functional group-independent manner using a photoaffinity reaction. In this study, we screened MMP-9 inhibitors using the photo-cross-linked chemical arrays. Methods and Results: The array slides with compounds of the RIKEN NPDepo chemical library were probed sequentially with His-Myc-tagged human recombinant MMP-9, anti-His antibody, and a Cy5-labeled secondary antibody, and then scanned with a microarray scanner. The fluorescence signals from two slides treated with and without His-Myc-tagged MMP-9 were quantified. We obtained 27 hit compounds among 24,275 compounds; 2 of the identified compounds (isoxazole compound NPDK-1 and naphthofluorescein) inhibited MMP-9 enzyme activity in vitro. We further explored 17 analogs of NPDK-1 and found that NPDK-18 showed the strongest inhibitory activity against MMP-9, with an IC50 value of 3.8 μM. NPDK-18 inhibited the enzyme activities of MMP-2, MMP-12 and MMP-13, as well as MMP-9 and MMP-9/ΔHemopexin, with almost identical potency, but showed no inhibition against MMP-1 and MMP-7. The biological potency of NPDK-18 was confirmed in a wound-healing scratch assay, where NPDK-18 significantly inhibited cell migration of human fibrosarcoma HT1080 cells with no cell toxicity at 10 μM. Conclusion: These results suggest that NPDK-18 is a broad-spectrum MMP inhibitor. Our study has shown that the photo-cross-linked chemical arrays are useful for high-throughput drug screening. Citation Format: Makoto Kawatani, Yasumitsu Kondoh, Kaori Honda, Tomomi Sekine, Hiroyuki Osada. Chemical array screen identifies a novel MMP inhibitor NPDK-18 that suppresses tumor cell migration. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr B131.
    Type of Medium: Online Resource
    ISSN: 1535-7163 , 1538-8514
    URL: Article
    DOI: 10.1158/1535-7163.TARG-15-B131
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2015
    detail.hit.zdb_id: 2062135-8
    SSG: 12
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  • 8
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    Abstract 2377: New micro-fluidic devices with polymeric materials for isolation of circulating tumor cells
    American Association for Cancer Research (AACR) ; 2012
    In:  Cancer Research Vol. 72, No. 8_Supplement ( 2012-04-15), p. 2377-2377
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 72, No. 8_Supplement ( 2012-04-15), p. 2377-2377
    Abstract: Introduction: Circulating tumor cells (CTCs) have been isolated from peripheral blood of cancer patients using cell detection and capture system, however the machine itself and the running costs are expensive. Thus a low cost device has been desired. Recently, a micro-fluidic device has been introduced. In this study, we would like to present a new micro-fluidic device with polymeric materials for isolation of circulating tumor cells. The IRB approval number was #21-88. Materials & Methods: We prepared a micro-fluidic device with the structures imprinted using a mold on the resin followed by UV-light curing in a couple of minutes. The resin contained a monomer having an epoxy group which enabled the device surface to react with other functional groups for immobilization of antibodies. The antibodies were immobilized not directly but with polymers to the surface. Polyacrylic acid (Mw:5,000) was grafted to the device surface by the reaction of the carboxyl group and the surface epoxy group, then IgG antibodies were covalently bonded to the polymer with the condensation agent for amino and carboxyl groups. Finally, EpCAM antibodies were attached to the IgG antibodies in the polymer. Results: Esophageal cancer cells KYSE220 dispersed in phosphate buffered saline (PBS) at a concentration of 1000 cells/ml were flowed through the CTC capture device described above at a rate of 1ml/hour. After cells passed, we observed many cells captured on the microstructure of the device, whereas no cells were seen without EpCAM antibodies on the device surface. We could evaluate the trapped cells by a quick cell stain method or fluorescent staining. We also detected KYSE220 cells in the healthy whole blood or selected nuclear cell separation. We have just started to evaluate this for detection of CTC in cancer patients. The cost of the new device was 10 dollar for each chip excluding the cost of the antibody. Conclusion: We developed a new micro-fluidic device with polymeric materials for isolation of circulating tumor cells. This new chip may be useful for isolation of CTC at a low cost. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2377. doi:1538-7445.AM2012-2377
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2012-2377
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2012
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    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 9
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    Abstract 3039: microRNA profiling of gastric cancer patients from formalin-fixed paraffin-embedded (FFPE) samples
    American Association for Cancer Research (AACR) ; 2010
    In:  Cancer Research Vol. 70, No. 8_Supplement ( 2010-04-15), p. 3039-3039
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 70, No. 8_Supplement ( 2010-04-15), p. 3039-3039
    Abstract: InIntroduction: microRNA (miRNA) are small non-coding RNAs which target specific mRNA. Recent progression of RNA extraction technology from formalin-fixed paraffin-embedded (FFPE) tissues enables us to access miRNA profiling using world wide stored specimens. Here, we present miRNA profiling of gastric cancer patients from FFPE specimens. Method: First, we examined the level of cross-linking caused by formalin and degradation of mRNA and miRNA from day to year levels. Then, we established the criteria of evaluable RNA from FFPE specimens. The miRNA profiling was obtained from 47 gastric cancer patients who received operations from 1997 to 2007 using 3D-Gene human miRNA chip (Toray) which contains 885 miRNA species. Results: Out of 47 paired samples, 37 pairs (78.8%) were determined evaluable with our criteria. As results, we showed that 30 miRNAs were significantly down-regulated and that 15 miRNAs were up-regulated in gastric cancer in comparison to normal gastric tissue. Of these, 18 miRNAs, including mir-21 and mir-34a, were identified as a prognostic factor of gastric cancer patients. Furthermore, we found 25 miRNAs have association with the recurrence of adjuvant oral Tegaful treatment and 5 miRNAs have association with lymph node metastasis. Conclusion: We have discovered miRNAs that are associated with prognosis, chemosensitivity and lymph node metastasis in gastric cancer patients. miRNA profiling using FFPE specimens is a useful and promising method of evaluation of world wide stored specimens that accompany may valuable clinical data. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3039.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM10-3039
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2010
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    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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