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  • American Association for Cancer Research (AACR)  (9)
  • 1
    Online Resource
    Online Resource
    Abstract P5-16-03: Phase II study of trastuzumab biosimilar (Herzuma®) plus gedatolisib in patients with HER-2 positive metastatic breast cancer who progressed after 2 or more HER-2 directed chemotherapy (BR 18-13, KM-10A): Interim analysis
    American Association for Cancer Research (AACR) ; 2022
    In:  Cancer Research Vol. 82, No. 4_Supplement ( 2022-02-15), p. P5-16-03-P5-16-03
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 82, No. 4_Supplement ( 2022-02-15), p. P5-16-03-P5-16-03
    Abstract: Background: Prognosis of patients with HER-2 positive metastatic breast cancer (MBC) has been revolutionized with the development of monoclonal antibodies targeting HER-2 and antibody-drug conjugate, but resistance to anti-HER-2 therapy is inevitable ultimately. PI3K-AKT-mTOR pathway aberration is known to be one of the key resistance mechanisms. BR18-13(KM-10A) study is a phase 2 clinical trial evaluating efficacy and safety of Herzuma® (trastuzumab biosimilar) plus Gedatolisib (dual PI3K/mTORC inhibitor) in patients with HER-2 positive MBC who progressed after multiple lines of therapy. Methods: Patients with HER-2 positive MBC with known PIK3CA pathologic mutation or amplification whose disease progressed after more than 2 HER-2 directed therapy were enrolled in the study. They received Herzuma® (8mg/kg IV for 1st cycle loading dose, and then 6mg/kg IV every 3 weeks) plus Gedatolisib (180mg on D1, 8, 15 of every 21 days). We evaluated efficacy of the combination treatment as interim analysis. The data cutoff of this interim analysis was June 8, 2021. Results: 17 patients were enrolled and followed for a median of 6.2 months. At data cutoff, 17 patients were eligible for response assessment. All patients were confirmed to have pathologic PIK3CA aberrations: 9 kinase mutations (H1047X), 5 helical mutations (E545X), 2 other point mutations, and 1 amplification. Overall, response rate was 64.7% and disease control rate was 82.4%. Eleven patients reached partial response (PR) as their best response, three were stable disease (SD), and three had progressive disease (PD). Two patients who have reached PR remain on investigational treatment until the data cutoff point, and the longest one is on treatment for 12.0 months. The median progression-free survival assessed in data cutoff time was 5.9 months. One patient ended treatment due to CNS disease progression, but her visceral metastatic lesions were decreased with experimental treatment. No fatal adverse events related to trial medication were reported. Conclusion: In this phase 2 study, Trastuzumab biosimilar plus Gedatolisib presented 64.7% of response rate with manageable toxicity in patients with HER-2 positive MBC with PIK3CA mutation. Clinical trial information: NCT03698383 Acknowledgement: this research was supported by a grant of the Korea Health Technology R & D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (Grant number: HI17C2206). Citation Format: Ju Won Kim, Hee Kyung Ahn, Jong Gwon Choi, Yee Soo Chae, Gyeong-Won Lee, Keon Uk Park, Eunmi Lee, Sung Hoon Sim, Jee Hyun Kim, Yeon Hee Park, Miso Kim, Jin Hyun Park, Jeong Eun Kim, Han Jo Kim, Mi Sun Ahn, So Yeon Oh, Min Hwan Kim, Su-Jin Koh, Kyoung Eun Lee, Myoung Joo Kang, Jae Ho Byun, Joo Young Ha, Jung Hye Kwon, Joo Young Jung, Su Ee Lee, Inhae Park, Kyong Hwa Park. Phase II study of trastuzumab biosimilar (Herzuma®) plus gedatolisib in patients with HER-2 positive metastatic breast cancer who progressed after 2 or more HER-2 directed chemotherapy (BR 18-13, KM-10A): Interim analysis [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-16-03.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.SABCS21-P5-16-03
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2022
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  • 2
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    Suicide Rates and Risk Factors among Korean Cancer Patients, 1993-2005
    American Association for Cancer Research (AACR) ; 2010
    In:  Cancer Epidemiology, Biomarkers & Prevention Vol. 19, No. 8 ( 2010-08-01), p. 2097-2105
    Details
    In: Cancer Epidemiology, Biomarkers & Prevention, American Association for Cancer Research (AACR), Vol. 19, No. 8 ( 2010-08-01), p. 2097-2105
    Abstract: Background: As the number of cancer survivors increases, suicide risk approaches that of the general population. We therefore investigated suicide rates and risk factors among Korean cancer patients. Methods: We observed 816,295 cancer patients for 3,007,294 person-years from 1993 to 2005 through a nationwide cancer registry. We calculated their sex- and age-standardized mortality ratios (SMR) and studied suicide risk factors using rate ratios (RR) based on a log-linear Poisson regression model. Results: Compared with the Korean general population, the suicide rate among cancer patients was high [SMR, 2.00; 95% confidence interval (95% CI), 1.91-2.08]. The rates were highest in the year following the cancer diagnosis (SMR, 3.45; 95% CI, 3.19-3.73) and were still elevated 5 years later (SMR, 1.23; 95% CI, 1.12-1.36). The clinical groups at highest risk were male pancreas cancer patients (SMR, 6.01; 95% CI, 4.33-8.33) and female lung cancer patients (SMR, 3.55; 95% CI, 2.55-4.94). The sociodemographic groups at highest risk were those who had no spouse versus those who were married (RR, 1.50; 95% CI, 1.35-1.68), those who were not employed versus those who were (RR, 1.39; 95% CI, 1.26-1.54), and those who did not have high school education versus those who had (RR, 1.52; 95% CI, 1.30-1.79). Conclusions: Korean cancer patients are at increased risk of suicide. Both clinical and sociodemographic factors play a role. Impact: There is a need for social support and suicide prevention strategies for cancer survivors in Korea. Cancer Epidemiol Biomarkers Prev; 19(8); 2097–105. ©2010 AACR.
    Type of Medium: Online Resource
    ISSN: 1055-9965 , 1538-7755
    URL: Article
    DOI: 10.1158/1055-9965.EPI-10-0261
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2010
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  • 3
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    Small-Molecule Inhibitors of USP1 Target ID1 Degradation in Leukemic Cells
    American Association for Cancer Research (AACR) ; 2013
    In:  Molecular Cancer Therapeutics Vol. 12, No. 12 ( 2013-12-01), p. 2651-2662
    Details
    In: Molecular Cancer Therapeutics, American Association for Cancer Research (AACR), Vol. 12, No. 12 ( 2013-12-01), p. 2651-2662
    Abstract: Inhibitor of DNA binding 1 (ID1) transcription factor is essential for the proliferation and progression of many cancer types, including leukemia. However, the ID1 protein has not yet been therapeutically targeted in leukemia. ID1 is normally polyubiquitinated and degraded by the proteasome. Recently, it has been shown that USP1, a ubiquitin-specific protease, deubiquitinates ID1 and rescues it from proteasome degradation. Inhibition of USP1 therefore offers a new avenue to target ID1 in cancer. Here, using a ubiquitin-rhodamine–based high-throughput screening, we identified small-molecule inhibitors of USP1 and investigated their therapeutic potential for leukemia. These inhibitors blocked the deubiquitinating enzyme activity of USP1 in vitro in a dose-dependent manner with an IC50 in the high nanomolar range. USP1 inhibitors promoted the degradation of ID1 and, concurrently, inhibited the growth of leukemic cell lines in a dose-dependent manner. A known USP1 inhibitor, pimozide, also promoted ID1 degradation and inhibited growth of leukemic cells. In addition, the growth of primary acute myelogenous leukemia (AML) patient-derived leukemic cells was inhibited by a USP1 inhibitor. Collectively, these results indicate that the novel small-molecule inhibitors of USP1 promote ID1 degradation and are cytotoxic to leukemic cells. The identification of USP1 inhibitors therefore opens up a new approach for leukemia therapy. Mol Cancer Ther; 12(12); 2651–62. ©2013 AACR.
    Type of Medium: Online Resource
    ISSN: 1535-7163 , 1538-8514
    URL: Article
    DOI: 10.1158/1535-7163.MCT-13-0103-T
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2013
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  • 4
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    Abstract 702: A novel small molecule inhibitor of ENPP1 promotes T and NK cell activation and enhances anti-tumor efficacy in combination with immune checkpoint blockade therapy
    American Association for Cancer Research (AACR) ; 2023
    In:  Cancer Research Vol. 83, No. 7_Supplement ( 2023-04-04), p. 702-702
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 83, No. 7_Supplement ( 2023-04-04), p. 702-702
    Abstract: Background: The cGAS-STING signaling pathway has led to significant anti-cancer innate immune responses in cancer immunotherapy. 2’3’-cGAMP binds to STING and promotes the production of various pro-inflammatory cytokines such as type I interferon, which changes cold tumors to hot tumors through modulating tumor microenvironment. Therefore, activation of STING pathway has been considered as an important target for cancer immunotherapy. Ecto-Nucleotide Pyrophosphatase/Phosphodiesterases 1 (ENPP1), highly expressed membrane-bound enzyme in cancer cells, modulates cGAMP levels by hydrolyzing 2’,3’-cGAMP to alter the inflammatory mileu. In this study, we show that targeting ENPP1 is a promising strategy for STING regulation in cancer immunotherapy through indirect activation of the STING pathway. Methods: The ENPP1 inhibitory activities were measured by ENPP1 enzyme assay using both pNP-TMP and cGAMP as substrates. Cell-based activities were assessed by measuring IFN-beta release using THP-1 dual reporter assay. To validate biological functions, we evaluated cancer-cell killing effects of immune cells in co-culture spheroid system and T cell proliferation assay. The in vivo anti-tumor efficacy of our compound was assessed by monitoring tumor growth in CT-26 syngeneic mouse model. Results: LCB33 ENPP1 inhibitor shows excellent ENPP1 inhibitory activity at an IC50 of 0.9pM and 1nM in enzyme assay using pNP-TMP and cGAMP as substrates, respectively. Our compound showed extensive ENPP1 selectivity in the PDE and kinase panel assays and favorable in vivo pharmacokinetic properties. The results from THP-1 dual reporter assay demonstrated the potency and efficacy of our compound which induce STING-mediated type I IFN release. In co-culture spheroids, our compounds induced immune cell penetration into spheroids, which indicates that immune-cell mediated tumor cell death via ENPP1 inhibition. Furthermore, LCB33 compound stimulated cytokine production without affecting to the proliferation of human T cells. Finally, in the CT-26 colorectal syngeneic mouse model, oral administration at 5 mg/kg demonstrated a TGI of 39% as monotherapy and a TGI of 72% in combination with anti-PD-L1, which describes our compound enhance anti-cancer effect of immune checkpoint blockade. Conclusions: Taken together, we report a novel and potent small molecule ENPP1 inhibitor in this study. Our ENPP1 inhibitor showed immune-cell mediated anti-cancer effects without affecting T cell proliferation. Additionally, we confirmed that our compounds showed synergistic anti-cancer effect with immune checkpoint blocker, anti-PD-L1, in colon-cancer mouse model. Further, we are going to perform Pharmacodynamic analysis in tumor infiltrating lymphocytes and tumor associated macrophages to verify immune-modulatory function of our ENPP1 inhibitors. Citation Format: Pyoung Oh Yoon, Juhyeon Kim, A-Ram Lee, Eunji Son, Young cheol Lee, Eunmi Jung, HyeongRae Kim, YeonHee Lee, SoEun Park, Dae-Yon Lee, Chul-Woong Chung. A novel small molecule inhibitor of ENPP1 promotes T and NK cell activation and enhances anti-tumor efficacy in combination with immune checkpoint blockade therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 702.
    Type of Medium: Online Resource
    ISSN: 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2023-702
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2023
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  • 5
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    Abstract LB-276: Effect of lay health worker intervention on complinace of hepatitis B vaccinations in Asian Americans: Randomizd control trial
    American Association for Cancer Research (AACR) ; 2015
    In:  Cancer Research Vol. 75, No. 15_Supplement ( 2015-08-01), p. LB-276-LB-276
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 75, No. 15_Supplement ( 2015-08-01), p. LB-276-LB-276
    Abstract: Background/Context: Asian Americans are at high risk with contracting the Hepatitis B virus (HBV). There are preventive measures with vaccinations that could be administered. However, there are several barriers that preclude Asian Americans from receiving the proper care. Purpose: To implement lay health worker (LHW) telephone intervention using randomized control trial. Setting: Asian American community-based organizations in the Baltimore-Washington Metropolitan area from April 2013 to March 2014. Participants: 232 Asian American adults who were unprotected and 18 years of age or older. Intervention: Calling those in the intervention group to remind to receive a 3-shot series for HBV vaccinations at month 1, 2, and 5. Data collection/analysis: In a parent study, 600 Asian Americans participated in study by completing pretest, reading photo novel, and doing free Hepatitis B screening. A week later, participants received the results (i.e., protected, unprotected, and infected). In this study, those unprotected was assigned to either intervention or control group. The intervention group received the LHW intervention. Seven months after the pretest, those unprotected (n = 187) were followed by phone. The outcome measure was whether they had received a series of vaccines over 6 months with 3 groups (none, 1 or 2 vaccines, and completed). Multinomial logistic regressions were used. Results: We found that those in the intervention group were more likely to have 1 or more vaccines than the control group, compared to no vaccination group (OR = 3.04, 95% CI, 1.16, 8.00). Also, those in the intervention group were more likely to complete a series of vaccinations than the control group, compared to no vaccination group (OR = 7.29, 95% CI 3.39, 5.67). We also found that time is the most important barriers preventing them from seeking hepatitis B vaccinations. Conclusion: The LHW intervention was successful in increasing the chances to protect them from HBV infection in high risk group of Asian Americans. This study suggests that it is very critical to implement this culturally integrated LHW intervention program to reduce liver cancer health disparities among Asian Americans. Mulitivariate mulitinomial logistic regression model for having hepatitis B vaccinations (n = 187)None vs. 1or 2 vaccinesNone vs completedOR (95% CI)OR (95% CI)Control1.001.00Intervention3.04 (1.16, 8.00)7.29 (3.39, 5.67) Citation Format: Hee-Soon Juon, Frederic Kim, Carol Strong, Eunmi Park. Effect of lay health worker intervention on complinace of hepatitis B vaccinations in Asian Americans: Randomizd control trial. [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 LB-276. doi:10.1158/1538-7445.AM2015-LB-276
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2015-LB-276
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2015
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  • 6
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    Abstract 1338: Ferulic acid as a natural bioactive compound enhances PARP inhibitor sensitivity in breast cancer cells
    American Association for Cancer Research (AACR) ; 2016
    In:  Cancer Research Vol. 76, No. 14_Supplement ( 2016-07-15), p. 1338-1338
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 76, No. 14_Supplement ( 2016-07-15), p. 1338-1338
    Abstract: Homologous-recombination (HR)-dependent repair defective cells are hypersensitive to poly (ADP-ribose) polymerase (PARP) inhibitors. Combinations of defective HR pathway and PARP inhibitors have been an effective chemotherapy strategy. We previously showed that knockdown of the WD40-repeat containing protein, Uaf1, is HR repair defect in mouse embryo fibroblast cells and is sensitive to ABT-888, a chemotherapy drug commonly used for inhibiting PARP. Consistent with the HR defective mouse genetic study, here, we show that ferulic acid inhibits Rad 51 foci formation and accumulates γ-H2AX in breast cancer cells. Ferulic acid treatment reduces HR repair and causes breast cancer cells to become hypersensitive to ABT-888 treatment. Our study indicates that ferulic acid with PARP inhibitor treatment may be useful for the combination chemotherapy as a natural bioactive compound. Citation Format: Eunmi Park, Hyuna Lee. Ferulic acid as a natural bioactive compound enhances PARP inhibitor sensitivity in breast cancer cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1338.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2016-1338
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2016
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 7
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    Reduction in IκB Kinase α Expression Promotes the Development of Skin Papillomas and Carcinomas
    American Association for Cancer Research (AACR) ; 2007
    In:  Cancer Research Vol. 67, No. 19 ( 2007-10-01), p. 9158-9168
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 67, No. 19 ( 2007-10-01), p. 9158-9168
    Abstract: We reported recently a marked reduction in IκB kinase α (IKKα) expression in a large proportion of human poorly differentiated squamous cell carcinomas (SCC) and the occurrence of Ikkα mutations in human SCCs. In addition, overexpression of IKKα in the epidermis inhibited the development of skin carcinomas and metastases in mice. However, whether a reduction in IKKα expression promotes skin tumor development is currently unknown. Here, we assessed the susceptibility of Ikkα hemizygotes to chemical carcinogen-induced skin carcinogenesis. Ikkα+/− mice developed 2 times more papillomas and 11 times more carcinomas than did Ikkα+/+ mice. The tumors were larger in Ikkα+/− than in Ikkα+/+ mice, but tumor latency was shorter in Ikkα+/− than in Ikkα+/+ mice. Some of the Ikkα+/− papillomas and most Ikkα+/− carcinomas lost the remaining Ikkα wild-type allele. Somatic Ikkα mutations were detected in carcinomas and papillomas. The chemical carcinogen-induced H-Ras mutations were detected in all the tumors. The phorbol ester tumor promoter induced higher mitogenic and angiogenic activities in Ikkα+/− than in Ikkα+/+ skin. These elevated activities were intrinsic to keratinocytes, suggesting that a reduction in IKKα expression provided a selective growth advantage, which cooperated with H-Ras mutations to promote papilloma formation. Furthermore, excessive extracellular signal-regulated kinase and IKK kinase activities were observed in carcinomas compared with those in papillomas. Thus, the combined mitogenic, angiogenic, and IKK activities might contribute to malignant conversion. Our findings provide evidence that a reduction in IKKα expression promotes the development of papillomas and carcinomas and that the integrity of the Ikkα gene is required for suppressing skin carcinogenesis. [Cancer Res 2007;67(19):9158–68]
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/0008-5472.CAN-07-0590
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2007
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  • 8
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    Inhibition of the Nedd8 System Sensitizes Cells to DNA Interstrand Cross-linking Agents
    American Association for Cancer Research (AACR) ; 2012
    In:  Molecular Cancer Research Vol. 10, No. 3 ( 2012-03-01), p. 369-377
    Details
    In: Molecular Cancer Research, American Association for Cancer Research (AACR), Vol. 10, No. 3 ( 2012-03-01), p. 369-377
    Abstract: The Fanconi anemia pathway is required for repair of DNA interstrand cross-links (ICL). Fanconi anemia pathway–deficient cells are hypersensitive to DNA ICL–inducing drugs such as cisplatin. Conversely, hyperactivation of the Fanconi anemia pathway is a mechanism that may underlie cellular resistance to DNA ICL agents. Modulating FANCD2 monoubiquitination, a key step in the Fanconi anemia pathway, may be an effective therapeutic approach to conferring cellular sensitivity to ICL agents. Here, we show that inhibition of the Nedd8 conjugation system increases cellular sensitivity to DNA ICL–inducing agents. Mechanistically, the Nedd8 inhibition, either by siRNA-mediated knockdown of Nedd8-conjugating enzymes or treatment with a Nedd8-activating enzyme inhibitor MLN4924, suppressed DNA damage–induced FANCD2 monoubiquitination and CHK1 phosphorylation. Our data indicate that inhibition of the Fanconi anemia pathway is largely responsible for the heightened cellular sensitivity to DNA ICLs upon Nedd8 inhibition. These results suggest that a combination of Nedd8 inhibition with ICL-inducing agents may be an effective strategy for sensitizing a subset of drug-resistant cancer cells. Mol Cancer Res; 10(3); 369–77. ©2012 AACR.
    Type of Medium: Online Resource
    ISSN: 1541-7786 , 1557-3125
    URL: Article
    DOI: 10.1158/1541-7786.MCR-11-0497
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2012
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  • 9
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    PARI Overexpression Promotes Genomic Instability and Pancreatic Tumorigenesis
    American Association for Cancer Research (AACR) ; 2013
    In:  Cancer Research Vol. 73, No. 8 ( 2013-04-15), p. 2529-2539
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 73, No. 8 ( 2013-04-15), p. 2529-2539
    Abstract: Treatment options for patients with pancreatic ductal adenocarcinoma (PDAC) remain limited. Therapeutic targets of interest include mutated molecules that predispose to pancreatic cancer such as KRAS and TP53. Here, we show that an element of the homologous recombination pathway of DNA repair, the PARP-binding protein C12orf48/PARI (PARPBP), is overexpressed specifically in pancreatic cancer cells where it is an appealing candidate for targeted therapy. PARI upregulation in pancreatic cancer cells or avian DT40 cells conferred DNA repair deficiency and genomic instability. Significantly, PARI silencing compromised cancer cell proliferation in vitro, leading to cell-cycle alterations associated with S-phase delay, perturbed DNA replication, and activation of the DNA damage response pathway in the absence of DNA damage stimuli. Conversely, PARI overexpression produced tolerance to DNA damage by promoting replication of damaged DNA. In a mouse xenograft model of pancreatic cancer, PARI silencing was sufficient to reduce pancreatic tumor growth in vivo. Taken together, our findings offered a preclinical proof-of-concept for PARI as candidate therapeutic target to treat PDAC. Cancer Res; 73(8); 2529–39. ©2013 AACR.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/0008-5472.CAN-12-3313
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2013
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    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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