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  • American Association for Cancer Research (AACR)  (50)
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  • 1
    Online Resource
    Online Resource
    Abstract 6219: WM-S1, the novel small molecule inhibitor of mutant RTK/receptor tyrosine kinase, for the treatment of cancer
    American Association for Cancer Research (AACR) ; 2022
    In:  Cancer Research Vol. 82, No. 12_Supplement ( 2022-06-15), p. 6219-6219
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 82, No. 12_Supplement ( 2022-06-15), p. 6219-6219
    Abstract: As the representative targeted anticancer drug for colon cancer patients, cetuximab is the EGFR targeted therapeutic antibody and used for treatment of KRAS wild type cancers. Even some patient with KRAS wt gene did not respond cetuximab. However, there is no treatment available for cetuximab-resistant patient group, which is almost 50% of KRAS WT gene holders. Recently, our team identified cetuximab primary resistant related proteins named as mtRTK (mutant receptor tyrosine kinase) by array analysis based cetuximab responder or non-responder colon cancer patient tissues. We investigated mtRTK’s oncogenic potential as a novel anti-cancer target. A large proportion of colon cancer patients (36.2% Caucasian, 56.9% Korean) expressed the mtRTK was identified, using the sequencing analysis of patient samples. Based on these results, our efforts have led to the discovery of WM-S1, mtRTK inhibitor, which is the first mtRTK inhibitor in clinical development. The potent enzyme inhibitor showed a high anticancer activity confirmed in Patient-Derived Cells (PDC) and Patient-Derived Xenograft (PDX) animal models expressing the mutation. In preclinical studies demonstrate that WM-S1 is well tolerated in rats and dogs. Furthermore, WM-S1 has potent anticancer activities for various solid tumor (NSCLC, cholangiocarcinoma, etc.) including activated mtKRAS colon cancer expressing the mtRTK. Currently we are investigating WM-S1 in a phase 1a trial in AUS, which is the first mtRTK inhibitor in clinical development. Meanwhile, the mtRTK inhibitor WM-S1 drives antitumor immunity (with anti-PD-L1) in NSCLC. Combinational approaches with immunotherapy showed that synergistic effect of WM-S1 and anti-PD1 monoclonal antibody, suppressing tumor growth by 75% in anti-PD1 resistance NSCLC-derived humanized mouse model. A phase 1b trial is expected to develop WM-S1 through not only indication expansion but also combination therapy with immuno-checkpoint inhibitors in the USA, AUS and KOR from Q2 2022. In conclusion, mtRTK is a potential oncogenic driver mutation in various solid tumor. A first-in-class anticancer agent WM-S1 targeting mtRTK can be promising therapeutic agents for cetuximab-resistant colon cancer patients regardless of KRAS mutation status and other cancers. Citation Format: Joseph Kim, Jai-Hee Moon, Kyung-Mi Lee, Hyun Ryu, Eun Hye Park, Sang Hee Kim, Jeong Seok Kim, Young Ok Ko, Yong Seok Kim, Hyo Jin Kim, Tae Young Kim Kim, Moon Seong Yoo, Soll Jin, Seongrak Kim, Yoon Sun Park, Min Ki Lee, Mi So Lee, Ji Hyun Go, Yu Geun Ji, Jun Hyung Lee, Haneul Lee, Min Hwa Kim, Eun Hee Ko, Yeo Jin Lee, Seung-Mi Kim, Joon-yee Jeong, Yeon-seoung Choi, Seung-geon Bae, Jinwoo Lee, Won Jun Lee, Min-Kyeong Kim, Ji min Shin, Dong-in Koh, Sun-Chul Hur, Chun-Ho Park, Hyun Ho Lee, Dong-Hoon Jin. WM-S1, the novel small molecule inhibitor of mutant RTK/receptor tyrosine kinase, for the treatment of cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6219.
    Type of Medium: Online Resource
    ISSN: 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2022-6219
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2022
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  • 2
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    Abstract 2669: Identification of a novel small-molecule inhibitor for treatment of human colon cancer patients
    American Association for Cancer Research (AACR) ; 2018
    In:  Cancer Research Vol. 78, No. 13_Supplement ( 2018-07-01), p. 2669-2669
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 78, No. 13_Supplement ( 2018-07-01), p. 2669-2669
    Abstract: As the representative targeted anticancer drug for colon cancer patients, Erbitux is the EGFR targeted therapeutic antibody and used for treatment of KRAS wild-type colon cancer patients. Even some patients with KRas wt gene did not respond to Erbitux. However, there is no treatment available for Erbitux-resistant patient group with KRAS WT gene, which is almost 50% of KRAS WT gene holders. Recently, our team identified Erbitux primary resistant related proteins named as CRG (Cetuximab-Resistant Gene) by array analysis based Erbitux responder or nonresponder colon cancer patients derived tissues and confirmed by in vitro and in vivo assay system. Based on these results, we synthesized a novel series of CRG targeted inhibitor. CRG inhibitor (CRG i;WM compound) is a lead compound for treating colon cancer patients who do not respond to Erbitux and have KRAS wild-type gene. CRG i has potent in vitro enzyme activity and high anticancer activity against various colon cancer cell lines with good selectivity in in vitro and in vivo system. Furthermore, the compound has good potent ADME/Tox. profiles for optimized lead. CRG i also displays strong anticancer effect in in vivo xenograft models and patient-derived xenograft (PDX) models. In addition, CRG i shows promising signs of overcoming Erbitux resistance in CRG knockout cells-derived xenograft model. We continue to discover improved preclinical candidates with better selectivity and ADME/Tox. profiles and validate predictive biomarker in colon cancer patients. In these efforts, we found some compounds with better profiles than CRG i. We are also trying to develop small molecules having highly potent activity against mutant CRG. In conclusion, active CRG is a promising biomarker and target for Erbitux-resistant KRAS wt colon cancer patients. Our compounds can be promising therapeutic agents for Erbitux-resistant KRAS wt colon cancer patients. Citation Format: Chun-Ho Park, Sun-Chul Hur, Joseph Kim, Dae Hee Lee, Yoon Sun Park, Jae-Sik Shin, Seung-Woo Hong, Jai-Hee Moon, Hyojin Kim, So Hee Lee, Hyebin Park, Joonyee Jung, Mi Jin Kim, Sang Soo Park, Jun Ki Hong, Ji Hee Gong, Jieun Kim, Il-Whea Ku, Hyun Ho Lee, Dong-Hoon Jin. Identification of a novel small-molecule inhibitor for treatment of human colon cancer patients [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 2669.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2018-2669
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2018
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  • 3
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    Abstract 2909: Development of new mechanism based therapeutic antibodies in non-small cell lung cancer
    American Association for Cancer Research (AACR) ; 2018
    In:  Cancer Research Vol. 78, No. 13_Supplement ( 2018-07-01), p. 2909-2909
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 78, No. 13_Supplement ( 2018-07-01), p. 2909-2909
    Abstract: Lung cancer is second most common cancer in the world. Non Small Cell Lung Cancer (NSCLC) accounts approximately 80-85% of all lung cancer diagnosis. Traditional therapies of this disease were surgical resection, chemotherapy, and radiotherapy, alone or in combination. In addition, targeted therapeutic approach was based on the concept of discovering genetic alterations and the signaling pathways in cancer. Recently, to overcome the critical points for standard therapies, many groups were studied immunotherapeutic approaches, such as programed cell-death protein 1 (PD-1) antibody. However, rational use of these agents has been limited by the lack of a definitive predictive biomarker. Therefore, we identified new target, cancer immunotherapy related gene, CMG by shRNA libraries screening analysis on chemo-agents & target therapy resistant non-small cell lung cancer cells. First of all, we investigated CMG expression by immunohistochemistry in various tissue microarray (TMA). These results show that CMG highly expressed in Lung cancer, Liver cancer, and gastric cancer. We investigated target potentials on lung cancer, liver cancer, and gastric cancer cell lines using in vitro and in vivo assay system. Knockdown of CMG by CMG shRNA was induced cell death in various cancer cell lines. In addition, suppression of CMG was induced tumor size regression in CMG shRNA stable cell lines-derived xenograft model. Based on these results, we synthesized a novel series of CMG therapeutic antibody. CMG therapeutic antibody is a lead antibody for treating Lung cancer patients who express CMG gene. These antibodies have anti-cancer effects and immunotherapeutic effects in lung cancer (NSCLC), liver cancer, and gastric cancer. In addition, the in vivo efficacy of CMG antibody was assessed in mouse lung cancer derived syngeneic mouse model. The CMG antibody was tri-daily i.p. injected and the tumor volume was measured and compared between groups. Dramatic tumor regression was observed in CMG antibody treated group. These results were shown that these antibodies have immunotherapeutic potentials. In conclusion, CMG is a promising target for Lung cancer patients (chemo-agents resistant or PD-1 resistant Lung cancer patienrts). Our antibodies can be promising therapeutic agents for lung cancer, Liver cancer, and gastric cancer. Citation Format: Jai-hee Moon, Dae Hee Lee, Jae-Sik Shin, Joseph Kim, Yoon Sun Park, Seung-Woo Hong, So Hee Lee, Mi Jin Kim, Joonyee Jung, Chun-Ho Park, Sun-Chul Hur, Hyojin Kim, Hyebin Park, Sang Soo Park, Jun Ki Hong, Ji Hee Gong, Jieun Kim, Hyun Ho Lee, Il-Whea Ku, Dong-Hoon Jin. Development of new mechanism based therapeutic antibodies in non-small cell lung cancer [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 2909.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2018-2909
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2018
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  • 4
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    Abstract 1216: New therapeutic antibody ("WM-A1") for treatment of low or no PD-L1 NSCLC patients
    American Association for Cancer Research (AACR) ; 2021
    In:  Cancer Research Vol. 81, No. 13_Supplement ( 2021-07-01), p. 1216-1216
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 81, No. 13_Supplement ( 2021-07-01), p. 1216-1216
    Abstract: The number of lung cancer patients is increasing every year worldwide. For these patients' treatment, not only anticancer drugs but also immune anticancer drugs are rapidly being developed. So far, the PD-1 antibody is widely used in treating NSCLC patients, and various pharmaceutical companies are continuously developing it. However, in PD-L1 low or negative patients, new drugs are required because there are no appropriate drugs. Of course, the PD-1 antibody is sometimes used, but the response rate is low, so new therapeutic drugs are needed.We identified a new target for PD-L1 low or negative patients using PD-L1 negative or positive lung cancer tissues. The new target's code name is "Target protein A." Target protein A expressed higher in tumor than normal. As a result of analyzing caucasian lung cancer patients' tissues by immunohistochemistry, 36% of cases expressed "Target protein A". Moreover, we also confirmed that target protein A was higher in tumors than normal through the TCGA database. Based on these results, we developed an immune anticancer drug (WM-A1) targeting Target protein A and demonstrated that it induces cancer cell death by inhibiting the binding with the binding partner protein B. Meanwhile, to clarify the relationship between PD-L1 and Target protein A, we analyzed the expression between the two proteins in lung cancer cell lines and proved that they exhibit reverse correlation. Among PD-L1 low or negative lung cancer patient tissues, about 32.75% of tissues expressed Target protein A. Conversely, among the patient samples expressing Target protein A, the PD-L1 low or negative population was 63%. We checked a similar trend through the TCGA database. For the efficacy of WM-A1, we confirmed that WM-A1 induced T cell-mediated cell death in a co-culture system with human PBMC and secreted major cytokines. In addition, we revealed that the group transplanted with a cell line expressing Target protein A in the PBMC humanized model showed high immuno-anticancer efficacy. Furthermore, we demonstrated that WM-A1 increased T cell activation and related cytokine expression. However, there was no reactivity to the PD-1 antibody because it expressed Target protein A and did not express PD-L1.Therefore, we suggest that WM-A1 is a new therapeutic antibody for the PD-L1 low or negative patient population. Based on these findings, we are planning a preclinical study (GLP-Tox) in 2021. #Corresponding author: Dong-Hoon Jin*These authors (Hye jin Son and Minki Lee) contributed equally to this work. Citation Format: Hye jin Son, Minki Lee, Seongrak Kim, Jai-Hee Moon, Hana Kim, Wonhwa Shin, Joseph Kim, Mi So Lee, Daeun Kim, Seunggeon Bae, Joonyee Jeong, Seung-Woo Hong, Chun-Ho Park, Hyun Ho Lee, Dong-Hoon Jin. New therapeutic antibody ("WM-A1") for treatment of low or no PD-L1 NSCLC patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1216.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2021-1216
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2021
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  • 5
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    Clinical Validation of Colorectal Cancer Biomarkers Identified from Bioinformatics Analysis of Public Expression Data
    American Association for Cancer Research (AACR) ; 2011
    In:  Clinical Cancer Research Vol. 17, No. 4 ( 2011-02-15), p. 700-709
    Details
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 17, No. 4 ( 2011-02-15), p. 700-709
    Abstract: Purpose: Identification of novel biomarkers of cancer is important for improved diagnosis, prognosis, and therapeutic intervention. This study aimed to identify marker genes of colorectal cancer (CRC) by combining bioinformatics analysis of gene expression data and validation experiments using patient samples and to examine the potential connection between validated markers and the established oncogenes such as c-Myc and K-ras. Experimental Design: Publicly available data from GenBank and Oncomine were meta-analyzed leading to 34 candidate marker genes of CRC. Multiple case-matched normal and tumor tissues were examined by RT-PCR for differential expression, and 9 genes were validated as CRC biomarkers. Statistical analyses for correlation with major clinical parameters were carried out, and RNA interference was used to examine connection with major oncogenes. Results: We show with high confidence that 9 (ECT2, ETV4, DDX21, RAN, S100A11, RPS4X, HSPD1, CKS2, and C9orf140) of the 34 candidate genes are expressed at significantly elevated levels in CRC tissues compared to normal tissues. Furthermore, high-level expression of RPS4X was associated with nonmucinous cancer cell type and that of ECT2 with lack of lymphatic invasion while upregulation of CKS2 was correlated with early tumor stage and lack of family history of CRC. We also demonstrate that RPS4X and DDX21 are regulatory targets of c-Myc and ETV4 is downstream to K-ras signaling. Conclusions: We have identified multiple novel biomarkers of CRC. Further analyses of their function and connection to signaling pathways may reveal potential value of these biomarkers in diagnosis, prognosis, and treatment of CRC. Clin Cancer Res; 17(4); 700–9. ©2011 AACR.
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    URL: Article
    DOI: 10.1158/1078-0432.CCR-10-1300
    RVK:
    XA 36791
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2011
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  • 6
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    Abstract 395: Chemokine ligand 7 expression in liver metastasis of colorectal cancer
    American Association for Cancer Research (AACR) ; 2011
    In:  Cancer Research Vol. 71, No. 8_Supplement ( 2011-04-15), p. 395-395
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 71, No. 8_Supplement ( 2011-04-15), p. 395-395
    Abstract: The main cause of death for colorectal cancer (CRC) patients is the development of metastatic lesions at sites distant from the primary tumor. Therefore, it is important to find biomarkers that are related to the metastasis and to study the possible mechanism. Recent data have shown that soluble attractant molecules called chemokines support the metastasis of certain cancers to certain organs. To identify molecular regulators that are differentially expressed in liver metastasis of CRC, PCR array was performed and CCL7 showed remarkable overexpression in liver metastatic tumor tissues. To validate the result of PCR array, 30 patients with primary CRC and liver metastases were selected. Immunohistochemistry and real-time PCR analysis showed that CCL7 was expressed in normal colonic epithelium and the expression was higher in liver metastases than in primary CRC. CCR1, CCR2, and CCR3, receptors of CCL7, were not expressed in normal colonic epithelium nor colon and metastatic cancer, but expressed in normal hepatocytes and stroma by immunohistochemical staining. Real-time PCR showed that the expressions of CCR1, CCR2, and CCR3 were also higher in liver metastases than in primary CRC. There would be chemokine/chemokine receptors interactions between CCL7 and its receptors in liver, which supply the environment for metastatic colon cancer cells to survive and proliferate in liver. 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 395. doi:10.1158/1538-7445.AM2011-395
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2011-395
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2011
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  • 7
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    Abstract 502: Cytokeratin staining for complete remission in rectal cancer after chemoradiation
    American Association for Cancer Research (AACR) ; 2010
    In:  Cancer Research Vol. 70, No. 8_Supplement ( 2010-04-15), p. 502-502
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 70, No. 8_Supplement ( 2010-04-15), p. 502-502
    Abstract: Purpose: Generally, pathologic complete remission (CR) of rectal cancer after neoadjuvant chemoradiation therapy (CRT) is confirmed by routine hematoxylin and eosin (H & E) staining. The aim of this study was to identify residual rectal cancer cells in primary lesions in patients with pathologic CR by staining immunohistochemically for cytokeratin. Methods: The medical records of 358 rectal cancer patients that underwent neoadjuvant CRT prior to radical surgery between October 2002 and August 2007 were reviewed. The authors stained sections of resected specimens of the 58 (15.9%) patients (42 males; mean age 54 years) that achieved pathologic CR (as determined originally by H & E staining) with H & E and performed IHC using monoclonal cytokeratin antibody. These stained sections were then reviewed by a pathologist for residual rectal cancer cells. Results: Of the 58 patients that achieved CR by initial pathologic examinations, 8 (13.8%) were found to contain tumor by cytokeratin IHC. Our H & E study in these 8, revealed that 6 were positive for cancer cells, but that the remaining 2, were negative for residual rectal cancer cells. Conclusion: By better enabling the identification of residual rectal cancer cells cytokeratin IHC offers a means of improving staging accuracy, and thus, would be use to provide information for actual prognosis and treatment decision making of patients who had clinically CR in rectal cancer after CRT. 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 502.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM10-502
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2010
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  • 8
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    Combination treatment with arsenic trioxide and phytosphingosine enhances apoptotic cell death in arsenic trioxide–resistant cancer cells
    American Association for Cancer Research (AACR) ; 2007
    In:  Molecular Cancer Therapeutics Vol. 6, No. 1 ( 2007-01-01), p. 82-92
    Details
    In: Molecular Cancer Therapeutics, American Association for Cancer Research (AACR), Vol. 6, No. 1 ( 2007-01-01), p. 82-92
    Abstract: Resistance to anticancer drugs can sometimes be overcome by combination treatment with other therapeutic drugs. Here, we showed that phytosphingosine treatment in combination with arsenic trioxide (As2O3) enhanced cell death of naturally As2O3-resistant human myeloid leukemia cells. The combination treatment induced an increase in intracellular reactive oxygen species level, mitochondrial relocalization of Bax, poly(ADP-ribose) polymerase-1 (PARP-1) activation, and cytochrome c release from the mitochondria. N-acetyl-l-cysteine, a thiol-containing antioxidant, completely blocked Bax relocalization, PARP-1 activation, and cytochrome c release. Pretreatment of 3,4-dihydro-5-[4-(1-piperidinyl)butoxy]-1(2H)-isoquinolinone, a PARP-1 inhibitor, or PARP-1/small interfering RNA partially attenuated cytochrome c release, whereas the same treatment did not affect Bax relocalization. The combination treatment induced selective activation of p38 mitogen-activated protein kinase (MAPK). Inhibition of p38 MAPK by treatment of SB203580 or expression of domi nant-negative forms of p38 MAPK suppressed the combination treatment–induced Bax relocalization but did not affect PARP-1 activation. In addition, antioxidant N-acetyl-l-cysteine completely blocked p38 MAPK activation. These results indicate that phytosphingosine in combination with As2O3 induces synergistic apoptosis in As2O3-resistant leukemia cells through the p38 MAPK–mediated mitochondrial translocation of Bax and the PARP-1 activation, and that p38 MAPK and PARP-1 activations are reactive oxygen species dependent. The molecular mechanism that we elucidated in this study may provide insight into the design of future combination cancer therapies to cells intrinsically less sensitive to As2O3 treatment. [Mol Cancer Ther 2007;6(1):82–92]
    Type of Medium: Online Resource
    ISSN: 1535-7163 , 1538-8514
    URL: Article
    DOI: 10.1158/1535-7163.MCT-06-0349
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2007
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  • 9
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    Inhibiting DX2-p14/ARF Interaction Exerts Antitumor Effects in Lung Cancer and Delays Tumor Progression
    American Association for Cancer Research (AACR) ; 2016
    In:  Cancer Research Vol. 76, No. 16 ( 2016-08-15), p. 4791-4804
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 76, No. 16 ( 2016-08-15), p. 4791-4804
    Abstract: The aminoacyl tRNA synthetase complex-interacting multifunctional protein 2 (AIMP2) splice variant designated DX2 is induced by cigarette smoke carcinogens and is often detected in human lung cancer specimens. However, the function of DX2 in lung carcinogenesis is obscure. In this study, we found that DX2 expression was induced by oncogenes in human lung cancer tissues and cells. DX2 prevented oncogene-induced apoptosis and senescence and promoted drug resistance by directly binding to and inhibiting p14/ARF. Through chemical screening, we identified SLCB050, a novel compound that blocks the interaction between DX2 and p14/ARF in vitro and in vivo. SLCB050 reduced the viability of human lung cancer cells, especially small cell lung cancer cells, in a p14/ARF-dependent manner. Moreover, in a mouse model of K-Ras–driven lung tumorigenesis, ectopic expression of DX2 induced small cell and non–small cell lung cancers, both of which could be suppressed by SLCB050 treatment. Taken together, our findings show how DX2 promotes lung cancer progression and how its activity may be thwarted as a strategy to treat patients with lung cancers exhibiting elevated DX2 levels. Cancer Res; 76(16); 4791–804. ©2016 AACR.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/0008-5472.CAN-15-1025
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2016
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  • 10
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    Aberrant Methylation of APC, MGMT, RASSF2A , and Wif-1 Genes in Plasma as a Biomarker for Early Detection of Colorectal Cancer
    American Association for Cancer Research (AACR) ; 2009
    In:  Clinical Cancer Research Vol. 15, No. 19 ( 2009-10-01), p. 6185-6191
    Details
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 15, No. 19 ( 2009-10-01), p. 6185-6191
    Abstract: Purpose: To identify epigenetic molecular makers in plasma for the early detection of colorectal cancer. Experimental Design: We retrospectively analyzed the methylation status of 10 genes in fresh-frozen tissues and corresponding plasma samples from 243 patients with stage I and II sporadic colorectal cancer, 276 healthy individuals, and plasma from 64 colorectal adenoma patients using methylation-specific PCR. The methylation score (Mscore) was used to find molecular markers with high sensitivity and specificity. Results: Of the 243 colorectal cancer tissues, methylation was detected in 18% for p14, 34% for p16, 27% for APC, 34% for DAPK, 32% for HLTF, 21% for hMLH1, 39% for MGMT, 24% for RARβ2, 58% for RASSF2A, and 74% for Wif-1. Receiver operator characteristic curve analysis in plasma from 243 patients with cancer and 276 healthy individuals showed that the M score of any single gene had a sensitivity of & lt;40% after controlling for age, sex, and tumor location. The specificity of the M score was not different between multigene and single gene analyses, but the sensitivity of the M score was significantly increased by multigene analysis. For all patients, the M score in a model including APC, MGMT, RASSF2A, and Wif-1 genes had a sensitivity of 86.5% and a specificity of 92.1% when 1.6 was used as a cutoff. In this model, the M score had a positive predictive value of 90.6% and a negative predictive value of 88.8%. Conclusion: The present study suggests that tumor-specific methylation of APC, MGMT, RASSF2A, and Wif-1 genes might be a valuable biomarker in plasma for the early detection of colorectal cancer. (Clin Cancer Res 2009;15(19):6185–91)
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    URL: Article
    DOI: 10.1158/1078-0432.CCR-09-0111
    RVK:
    XA 36791
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2009
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