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  • American Association for Cancer Research (AACR)  (98)
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  • American Association for Cancer Research (AACR)  (98)
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  • 1
    Online Resource
    Online Resource
    NR1D1 Stimulates Antitumor Immune Responses in Breast Cancer by Activating cGAS-STING Signaling
    American Association for Cancer Research (AACR) ; 2023
    In:  Cancer Research Vol. 83, No. 18 ( 2023-09-15), p. 3045-3058
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 83, No. 18 ( 2023-09-15), p. 3045-3058
    Abstract: Potentiating antitumor immunity is a promising therapeutic approach for treating a variety of cancers, including breast cancer. One potential strategy to promote antitumor immunity is targeting DNA damage response. Given that the nuclear receptor NR1D1 (also known as REV-ERBα) inhibits DNA repair in breast cancer cells, we explored the role of NR1D1 in antitumor CD8+ T-cell responses. First, deletion of Nr1d1 in MMTV-PyMT transgenic mice resulted in increased tumor growth and lung metastasis. Orthotopic allograft experiments suggested that loss of Nr1d1 in tumor cells rather than in stromal cells played a prominent role in increasing tumor progression. Comprehensive transcriptome analyses revealed that biological processes including type I IFN signaling and T cell–mediated immune responses were associated with NR1D1. Indeed, the expression of type I IFNs and infiltration of CD8+ T cells and natural killer cells in tumors were suppressed in Nr1d1−/−;MMTV-PyMT mice. Mechanistically, NR1D1 promoted DNA damage–induced accumulation of cytosolic DNA fragments and activated cGAS-STING signaling, which increased the production of type I IFNs and downstream chemokines CCL5 and CXCL10. Pharmacologic activation of NR1D1 by its ligand, SR9009, enhanced type I IFN–mediated antitumor immunity accompanied by the suppression of tumor progression and lung metastasis. Taken together, these findings reveal the critical role of NR1D1 in enhancing antitumor CD8+ T-cell responses, suggesting that NR1D1 may be a good therapeutic target for breast cancer. Significance: NR1D1 suppresses breast cancer progression and lung metastasis by enhancing antitumor immunity via cGAS-STING pathway activation, which provides potential immunotherapeutic strategies for breast cancer.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/0008-5472.CAN-23-0329
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2023
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 2
    Online Resource
    Online Resource
    RhoGDI2 Expression Is Associated with Tumor Growth and Malignant Progression of Gastric Cancer
    American Association for Cancer Research (AACR) ; 2009
    In:  Clinical Cancer Research Vol. 15, No. 8 ( 2009-04-15), p. 2612-2619
    Details
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 15, No. 8 ( 2009-04-15), p. 2612-2619
    Abstract: Purpose: Rho GDP dissociation inhibitor 2 (RhoGDI2) has been identified as a regulator of Rho family GTPase. However, there is currently no direct evidence suggesting whether RhoGDI2 activates or inhibits Rho family GTPase in vivo (and which type), and the role of RhoGDI2 in tumor remains controversial. Here, we assessed the effects of RhoGDI2 expression on gastric tumor growth and metastasis progression. Experimental Design: Proteomic analysis was done to investigate the tumor-specific protein expression in gastric cancer and RhoGDI2 was selected for further study. Immunohistochemistry was used to detect RhoGDI2 expression in clinical samples of primary gastric tumor tissues which have different pathologic stages. Gain-of-function and loss-of-function approaches were done to examine the malignant phenotypes of the RhoGDI2-expressing or RhoGDI2-depleting cells. Results: RhoGDI2 expression was correlated positively with tumor progression and metastasis potential in human gastric tumor tissues, as well as cell lines. The forced expression of RhoGDI2 caused a significant increase in gastric cancer cell invasion in vitro, and tumor growth, angiogenesis, and metastasis in vivo, whereas RhoGDI2 depletion evidenced opposite effects. Conclusion: Our findings indicate that RhoGDI2 is involved in gastric tumor growth and metastasis, and that RhoGDI2 may be a useful marker for tumor progression of human gastric cancer.
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    URL: Article
    DOI: 10.1158/1078-0432.CCR-08-2192
    RVK:
    XA 36791
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2009
    detail.hit.zdb_id: 1225457-5
    detail.hit.zdb_id: 2036787-9
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  • 3
    Online Resource
    Online Resource
    Inhibition of 15-Hydroxyprostaglandin Dehydrogenase by Helicobacter pylori in Human Gastric Carcinogenesis
    American Association for Cancer Research (AACR) ; 2013
    In:  Cancer Prevention Research Vol. 6, No. 4 ( 2013-04-01), p. 349-359
    Details
    In: Cancer Prevention Research, American Association for Cancer Research (AACR), Vol. 6, No. 4 ( 2013-04-01), p. 349-359
    Abstract: Helicobacter pylori (H. pylori) infection induces a chronic inflammatory response, which promotes gastric carcinogenesis. 15-Hydroxyprostaglandin dehydrogenase (15-PGDH) plays a key role as a tumor suppressor in gastrointestinal cancers. The aim of this study was to elucidate the role of 15-PGDH in gastric carcinogenesis associated with H. pylori. 15-PGDH expression in gastric biopsies from H. pylori–infected (n = 25) and noninfected (n = 15) subjects was analyzed by quantitative real-time PCR, Western blot analysis, and immunohistochemistry. 15-PGDH DNA methylation was evaluated by methylation-specific PCR and pyrosequencing. The expression of 15-PGDH, Snail, extracellular signal–regulated kinase (ERK)1/2, TLR4, and MyD88 in response to H. pylori infection was assessed by immunoblot analysis. Compared with negative specimens, H. pylori–positive specimens had 2-fold lower 15-PGDH mRNA levels and significantly less 15-PGDH protein. In four H. pylori–infected subjects with longitudinal follow-up, the suppression of 15-PGDH expression was reversed by H. pylori eradication therapy. In parallel with suppressing 15-PGDH expression, H. pylori infection activated expression of TLR4 and MyD88 expression, increased levels of phospho-ERK1/2, and increased expression of EGF receptor (EGFR)-Snail. Inhibition of Snail and MyD88 reversed suppression of 15-PGDH expression, and siMyD88 reduced phosphorylated ERK1/2. Similarly, treatment with an ERK1/2 and EGFR inhibitor also restored 15-PGDH expression. H. pylori appeared to promote gastric carcinogenesis by suppressing15-PGDH. This process is mediated by the TLR4/MyD88 pathway via ERK1/2 or EGFR-Snail transcriptional regulation. 15-PGDH may be a useful marker and a potential therapeutic target in H. pylori–induced gastric carcinogenesis. Cancer Prev Res; 6(4); 349–59. ©2013 AACR.
    Type of Medium: Online Resource
    ISSN: 1940-6207 , 1940-6215
    URL: Article
    DOI: 10.1158/1940-6207.CAPR-12-0389
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2013
    detail.hit.zdb_id: 2422346-3
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  • 4
    Online Resource
    Online Resource
    Abstract 265: Epi-magnolin suppresses EGF-induced neoplastic cell transformation by inhibition of Akt/mTOR signaling pathway in JBC Cl41 cells
    American Association for Cancer Research (AACR) ; 2018
    In:  Cancer Research Vol. 78, No. 13_Supplement ( 2018-07-01), p. 265-265
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 78, No. 13_Supplement ( 2018-07-01), p. 265-265
    Abstract: The phosphatidylinositol-3-kinase (PI3K)/Akt/the mammalian target of rapamycin (mTOR) signaling pathway is frequently activated in human cancer and plays a pivotal role in cell proliferation and transformation. In this study, we reveal epi-magnolin, a phytochemical found in Magnolia flos, as an inhibitor of Akt/mTOR signaling pathway. Epi-magnolin inhibits EGF-induced Akt phosphorylation at Thr308 and Ser473, but not extracellular signal-regulated kinases (ERKs)/ribosomal S6 kinase 2 (RSK2) signaling pathway. Moreover, we demonstrate that epi-magnolin suppresses JB6 cell proliferation by impairing EGF-induced G1/S cell cycle transition in a dose-dependent manner. Notably, epi-magnolin abrogates phosphorylation of c-Jun at Ser63 and 73 as well as total c-Jun protein level, which leads to downregulation of AP-1 transactivation activity. The inhibition effect of Akt/mTOR signaling pathway and AP-1 transactivation activity by epi-magnolin suppressed EGF-induced anchorage-independent cell transformation. Based on these results, epi-magnolin might be a chemopreventive agent by targeting Akt/mTOR signaling pathway. Key words: chemoprevention, cell transformation, Akt/mTOR signaling pathway Citation Format: Cheol-Jung Lee, Sun-Mi Yoo, Seung-Min Kim, Seon-Yeon Cho, Juhee Park, Yu-Mi Shin, Yong-Yeon Cho, Hye Suk Lee. Epi-magnolin suppresses EGF-induced neoplastic cell transformation by inhibition of Akt/mTOR signaling pathway in JBC Cl41 cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 265.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2018-265
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2018
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    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 5
    Online Resource
    Online Resource
    Abstract 5378: Inhibition of 15-hydroxyprostaglandin dehydrogenase by Helicobacter pylori in human gastric carcinogenesis.
    American Association for Cancer Research (AACR) ; 2013
    In:  Cancer Research Vol. 73, No. 8_Supplement ( 2013-04-15), p. 5378-5378
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 73, No. 8_Supplement ( 2013-04-15), p. 5378-5378
    Abstract: Helicobacter pylori (H pylori) infection induces a chronic inflammatory response, which promotes gastric carcinogenesis. 15-hydroxyprostaglandin dehydrogenase (15-PGDH) plays a key role as a tumor suppressor in gastrointestinal cancers. The aim of this study was to elucidate the role of 15-PGDH in gastric carcinogenesis associated with H pylori. 15-PGDH expression in gastric biopsies from H pylori-infected (n=25) and non-infected (n=15) subjects was analyzed by quantitative real-time PCR, western blot analysis, and immunohistochemisty. 15-PGDH DNA methylation was evaluated by methylation specific PCR and pyrosequencing. The expression of 15-PGDH, Snail, ERK1/2, TLR4 and MyD88 in response to H pylori infection was assessed by immunoblot analysis. Compared to negative specimens, H pylori positive specimens had 2-fold lower 15-PGDH mRNA levels and significantly less 15-PGDH protein. In four H pylori infected subjects with longitudinal follow-up, the suppression of 15-PGDH expression was reversed by H pylori eradication therapy. In parallel with suppressing 15-PGDH expression, H pylori infection activated expression of TLR4 and MyD88 expression, increased levels of phospho-ERK1/2, and increased expression of Snail. Inhibition of MyD88 reversed suppression of 15-PGDH expression and reduced phosphorylated ERK1/2. Similarly, treatment with an ERK1/2 inhibitor also restored 15-PGDH expression. Heliocobacter pylori appeared to promote gastric carcinogenesis by suppressing15-PGDH. This process is mediated by the TLR4/MyD88 pathway via ERK1/2 and Snail transcriptional regulation. 15-PGDH may be a useful marker and a potential therapeutic target in H pylori-induced gastric carcinogenesis. Citation Format: Yeon Mi Ryu, Seung-Jae Myung, Young Soo Park3, Ho June Song, Dong-Hoon Yang, Jin-Yong Jeong, Sun Mi Lee, Miyeoun Song, Do Hoon Kim, Hyo-Jeong Lee, Stephen P. Fink, Sandy D. Markowitz, Kee Wook Jung, Kyung-Jo Kim, Byong Duk Ye, Jung-Sik Byeon, Hwoon-Yong Jung, Suk-Kyun Yang, Jin-Ho Kim. Inhibition of 15-hydroxyprostaglandin dehydrogenase by Helicobacter pylori in human gastric carcinogenesis. [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 5378. doi:10.1158/1538-7445.AM2013-5378
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2013-5378
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2013
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 6
    Online Resource
    Online Resource
    Abstract C73: Anticancer effects of a novel phosphoinositol 3-kinase inhibitor in human hepatocellular carcinoma.
    American Association for Cancer Research (AACR) ; 2011
    In:  Molecular Cancer Therapeutics Vol. 10, No. 11_Supplement ( 2011-11-12), p. C73-C73
    Details
    In: Molecular Cancer Therapeutics, American Association for Cancer Research (AACR), Vol. 10, No. 11_Supplement ( 2011-11-12), p. C73-C73
    Abstract: The phosphatidylinositol 3-kinase (PI3K) is one of the most important regulators of cancer cell growth, survival, motility, and metabolism. As PI3K is activated in a wide variety of human malignancies, it is emerging as an attractive target for cancer treatment. Recently, we have designed and synthesized a new series of imidazo [1,2-a] pyridine derivatives as PI3Ka inhibitors. In this study, we investigated the effect of HS-196 [ethyl 6-(5-(2,4-difluorophenylsulfonamido) pyridin-3-yl) imidazo [1,2-a] pyridine-3-carboxylate] in human hepatocellular carcinoma (HCC) cells. HS-196 inhibited phosphorylation of signaling components downstream from PI3K, such as Akt, mTOR, p70S6K and glycogen synthase kinase 3b (GSK3b) by western blotting and immunofluorescence staining. And HS-196 showed anti-proliferative effects in variety of HCC cells in a dose-dependent manner. Interestingly, HS-196 didn't affect the normal liver cell line (HL-7702), while sorafenib and doxorubicin showed cytotoxicity at the same concentration. Also, HS-196 induced apoptosis by increasing the proportion of sub-G1 apoptotic cells, and caused cell cycle arrest at G0/G1 phase. HS-196 increased the expression of p27 and p21 and decreased that of cyclin D1 associated with cell cycle arrest. The induction of apoptosis by HS-196 was confirmed by DAPI and TUNEL staining, and the increases of the cleaved PARP, caspase-3, caspase-9 were observed. Furthermore, HS-196 decreased the expression of hypoxia-inducible factor-1a(HIF-1a) and vascular endothelial growth factor (VEGF) and inhibited the tube formation and migration of human umbilical vein endothelial cells (HUVECs), which were confirmed by Matrigel plug assay performed in BALB/c nude mouse. Taken together, these results demonstrated that HS-196 exhibited its anticancer activity through disrupting the PI3K/Akt pathway, causing cell cycle arrest and consequently inducing apoptosis, and inhibiting angiogenesis in human HCC ce lls. We suggest that HS-196 may be a potential new candidate for targeted HCC therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr C73.
    Type of Medium: Online Resource
    ISSN: 1535-7163 , 1538-8514
    URL: Article
    DOI: 10.1158/1535-7163.TARG-11-C73
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2011
    detail.hit.zdb_id: 2062135-8
    SSG: 12
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  • 7
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    Abstract 4963: Tanshinone IIA induces JNK-dependent intrinsic apoptosis via suppressing astrocyte-elevated gene 1 expression in chronic myelogenous leukemia KBM-5 cells
    American Association for Cancer Research (AACR) ; 2012
    In:  Cancer Research Vol. 72, No. 8_Supplement ( 2012-04-15), p. 4963-4963
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 72, No. 8_Supplement ( 2012-04-15), p. 4963-4963
    Abstract: Tanshinone IIA (Tan IIA) is a phytochemical isolated from the root of Salviae miltiorrhizae (Danshen) and has been reported to have various biological activities such as anti-inflammation, anti-oxidation and anti-cancer. However, the underlying molecular mechanisms to control anti-cancer effect of Tan IIA in chronic myelogenous leukemia (CML) have not been fully understood yet. In the present study, we investigated whether Tan IIA has the anti-cancer potential by inducing apoptosis in CML cells. Tan IIA significantly decreased the viability of human CML KBM-5 cells, but not normal peripheral blood lymphocytes. Tan IIA induced apoptotic cell death by increasing the sub-G1 cell populations and stimulating atypical shrunken of nucleus and DNA fragmentation. Also, Tan IIA significantly reduced the mitochondrial membrane potential, stimulated the release of cytochrome C from mitochondria into the cytosol and activated intrinsic caspase cascade. Furthermore, Tan IIA enhanced phosphorylation of JNK and suppressed the expression of astrocyte-elevated gene-1 (AEG-1). In contrast, blocking JNK activity using JNK inhibitor SP600125 reversed Tan IIA-induced apoptosis and AEG-1 expression. Taken together, our findings suggest that Tan IIA induces JNK-dependent intrinsic apoptosis via suppressing AEG-1 expression in KBM-5 cells as a valuable candidate agent for CML therapy. 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 4963. doi:1538-7445.AM2012-4963
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2012-4963
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2012
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 8
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    Abstract 2047: Betulinic acid exerts anti-angiogenic activity via regulation of HIF-1 alpha and STAT3 in PC-3 prostate cancer cells under hypoxia
    American Association for Cancer Research (AACR) ; 2011
    In:  Cancer Research Vol. 71, No. 8_Supplement ( 2011-04-15), p. 2047-2047
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 71, No. 8_Supplement ( 2011-04-15), p. 2047-2047
    Abstract: Signal transducer and activator of transcription 3 (STAT3) is a transcription factor constitutively overexpressed in several human cancer cells and related to various cellular processes such as cell survival, angiogenesis and proliferation. In the present study, we examined whether betulinic acid (BA), a triterpene from the bark of white birch, could inhibit hypoxia-mediated activation of STAT3 and HIF-1 alpha in androgen independent human prostate cancer PC-3 cells. Our results show that BA inhibited the transcriptional activities and nuclear accumulation of both HIF-1 alpha and STAT3 under hypoxia. In addition, BA significantly reduced cellular and secreted levels of hypoxia-induced vascular endothelial growth factor (VEGF), a critical angiogenic factor, in PC-3 cells. BA prevented in vitro capillary tube formation in human umbilical vein endothelial cells (HUVECs) maintained in conditioned medium of hypoxia-induced PC-3 cells. Moreover, silencing HIF 1 alpha and STAT3 by siRNA transfection augmented the suppression of VEGF expression by BA under hypoxia. Mechanistically, BA inhibited the recruitment of HIF-1 alpha and STAT3 on the VEGF promoter. Taken together, these findings suggest that BA may exert angio-prevention via inactivation of hypoxia-induced STAT3 and HIF-1 alpha in PC-3 cells. The in vivo anti-angiogenic and anti-PCa efficacy are being evaluated. 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 2047. doi:10.1158/1538-7445.AM2011-2047
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2011-2047
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2011
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 9
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    Abstract 2063: Synergistic anticancer activity of Sorafenib in combination with HS-173, a novel PI3K inhibitor against pancreatic cancer cells.
    American Association for Cancer Research (AACR) ; 2013
    In:  Cancer Research Vol. 73, No. 8_Supplement ( 2013-04-15), p. 2063-2063
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 73, No. 8_Supplement ( 2013-04-15), p. 2063-2063
    Abstract: The K-RAS mutation, resulting in activation of the Raf/MEK/ERK pathway, has been implicated in pancreatic cancer development. And the PI3K/Akt pathway is highly activated in pancreatic cancer and considered to be a cancer hallmark. The principal objective of this study was to assess the synergic effect between Sorafenib (a Raf inhibitor) and HS-173 (a novel PI3K inhibitor) along with the underlying mechanism to gain insight into novel therapeutic strategies for treating pancreatic cancer. We first investigated the cytotoxic effect of co-treatment with Sorafenib and HS-173 using the Calcusyn program. Combined treatment with the two drugs synergistically inhibited the viability of Panc-1 cells (combination index & lt; 1). Concomitantly, co-treatment with Sorafenib and HS-173 induced G2/M arrest and increased apoptosis with the loss of mitochondria potential. Apoptosis resulting from co-treatment with Sorafenib and HS-173 was accompanied by increased levels of cleaved caspase-3 and PARP as well as greater numbers of TUNEL-positive apoptotic cells compared to treatment with either drug alone. Furthermore, combined treatment with these drugs decreased the expression HIF-1α and VEGF, two factors that play an important role in angiogenesis. The anti-angiogenic effect of simultaneous treatment with Sorafenib and HS-173 was confirmed by observing the suppressed tube formation of VEGF-induced human umbilical vein endothelial cells and inhibition of blood vessel formation in a Matrigel plug assay in mice. Taken together, our study demonstrated that combined treatment with Sorafenib and HS-173 has a synergistic anticancer effect on pancreatic cancer cells, indicating that simultaneously targeting the Raf/MEK and PI3K/Akt pathways can induce a synergistic inhibitory effect on pancreatic cancers in which both pathways are activated. Based on the observations from our study, we suggest that the combined administration of these two drugs may be considered to be a new therapeutic regimen for treating pancreatic cancer. Citation Format: Sun-Mi Yun, Kyung Hee Jung, Hyunseung Lee, Byung Hee Park, Hong Hua Yan, Soon-Sun Hong. Synergistic anticancer activity of Sorafenib in combination with HS-173, a novel PI3K inhibitor against pancreatic cancer cells. [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 2063. doi:10.1158/1538-7445.AM2013-2063
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2013-2063
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2013
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 10
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    Abstract 39: Fibroblast growth factor induces neoplastic cell transformation through a non-canonical signaling pathway
    American Association for Cancer Research (AACR) ; 2015
    In:  Cancer Research Vol. 75, No. 15_Supplement ( 2015-08-01), p. 39-39
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 75, No. 15_Supplement ( 2015-08-01), p. 39-39
    Abstract: Induction of cell proliferation is closely related with the cellular signaling pathway activation by stimulation of diverse growth factors such as epidermal growth factor (EGF) and fibroblast growth factor. The stimulation of growth factors induces activation of extracellular signal-regulated kinases (ERKs)/p90 ribosomal S6 kinases (p90RSK), resulting in induction of cell proliferation and cell transformation. Although fibroblast growth factor (FGF) is a well-known growth factor and acts as a ligand of FGF receptor (FGFR), a receptor tyrosine kinase, in cytoplasmic membrane, the tumor promoter potential has not been clearly understood. Here, we provided the evidences that FGF acted as a tumor promoter. We found that FGF-induced cell proliferation and anchorage-independent cell transformation were correlated with the induction of G1/S cell cycle transition. Importantly, we found that kaempferol targeted and inhibited FGFR phosphorylation by in vitro and ex vivo. Interestingly, FGF stimulation utilized a non-canonical signaling pathway to activate RSK2 and ATF-1, which was not transduced by EGF stimulation. We confirmed that kaempferol inhibited tyrosine phosphorylation of FGFR, resulted in nuclear accumulation of phospho-ATF-1 at Ser63. Importantly, kaempferol, PKC412, PD98059 and U0126 inhibited EGF-induced anchorage-independent cell transformation in JB6 Cl41 cells. In contrast, FGF-induced cell transformation in soft agar was not inhibited by PD98059 and U0126. Taken together, these results demonstrate that FGF acts as a tumor promoter and dual inhibition of kaempferol on the kinase activities of FGFR and RSK2 suppresses the FGF-induced neoplastic cell transformation through a non-canonical signaling pathway which is not utilized by EGF stimulation. Citation Format: Sun-Mi Yoo, Cheol-Jung Lee, Mee-Hyun Lee, Yong-Yeon Cho. Fibroblast growth factor induces neoplastic cell transformation through a non-canonical signaling pathway. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 39. doi:10.1158/1538-7445.AM2015-39
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2015-39
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2015
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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