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  • 1
    Online Resource
    Online Resource
    A Phase I Study of Oral Paclitaxel with a Novel P-Glycoprotein Inhibitor, HM30181A, in Patients with Advanced Solid Cancer
    Korean Cancer Association ; 2014
    In:  Cancer Research and Treatment Vol. 46, No. 3 ( 2014-07-15), p. 234-242
    Details
    In: Cancer Research and Treatment, Korean Cancer Association, Vol. 46, No. 3 ( 2014-07-15), p. 234-242
    Type of Medium: Online Resource
    ISSN: 1598-2998 , 2005-9256
    URL: Article
    DOI: 10.4143/crt.2014.46.3.234
    Language: English
    Publisher: Korean Cancer Association
    Publication Date: 2014
    detail.hit.zdb_id: 2514151-X
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  • 2
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    Abstract 2975: Rad21, as a high order chromatin architecture molecule, regulates global gene transcription.
    American Association for Cancer Research (AACR) ; 2013
    In:  Cancer Research Vol. 73, No. 8_Supplement ( 2013-04-15), p. 2975-2975
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 73, No. 8_Supplement ( 2013-04-15), p. 2975-2975
    Abstract: Rad21 is a subunit of cohesin complex, which is well known to be involved in sister chromatid cohesion at mitotic phase. In recent studies, Rad21 has been also known to be associated with long-range chromosome interaction to dynamically regulate gene transcription. However, Very little is known about Rad21-mediated high order chromatin structure and global changes in gene transcription in human cancer. In this study, we silenced Rad21 gene using Lenti-virus knockdown system and performed transcriptome analysis to verify the changes in gene transcription by knockdown of Rad21. Among genes showing significant transcription changes by the reduction of Rad21, we chose several target genes decreasing its transcription and checked the transcriptional change with passaging over a 60 day period. Interestingly, the change in transcription level of some genes appeared by the earliest passage time point, whereas those of other genes arose during the course of long-term passage. Consistent with gene transcription changes, results from a ChIP assay demonstrated that Rad21-knockdown cells showed low level of Rad21 occupancy and active histone marks (H3K4me3 and Pol2) on the target genes, indicating that dynamic histone modifications also contribute to regulation of the target genes. To figure out whether the reduction of Rad21 binding directly affects the chromatin loops, we applied Chromosome Conformation Capture (3C) -qPCR in Rad21-knockdown cells. The results demonstrated that the decreased Rad21 expression cause overal reduction of locus interaction on the target genes, indicating that Rad21 binding was directly required for long-range interactions at the target gene regions and gene transcription regulation. Taken together, the results of our study demonstrated that long-range chromosome interaction mediated by Rad21 can dynamically regulate global gene transcription in human cancer cells, indicating that it may be important for cancer development. Citation Format: Jiyeon Yun, Sang-Hyun Song, Jee-Youn Kang, Hwang-Phill Kim, Sae-Won Han, Do-Youn Oh, Seock-Ah Im, Yung-Jue Bang, Tae-You Kim. Rad21, as a high order chromatin architecture molecule, regulates global gene transcription. [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 2975. doi:10.1158/1538-7445.AM2013-2975 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2013-2975
    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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  • 3
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    Online Resource
    A multicenter phase II study of everolimus in patients with progressive unresectable adenoid cystic carcinoma
    Springer Science and Business Media LLC ; 2014
    In:  BMC Cancer Vol. 14, No. 1 ( 2014-12)
    Details
    In: BMC Cancer, Springer Science and Business Media LLC, Vol. 14, No. 1 ( 2014-12)
    Type of Medium: Online Resource
    ISSN: 1471-2407
    URL: Article
    DOI: 10.1186/1471-2407-14-795
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2014
    detail.hit.zdb_id: 2041352-X
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  • 4
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    Online Resource
    Is There Any Role of Adjuvant Chemotherapy for T3N0M0 or T1N2M0 Gastric Cancer Patients in Stage II in the 7th TNM but Stage I in the 6th TNM System?
    Springer Science and Business Media LLC ; 2016
    In:  Annals of Surgical Oncology Vol. 23, No. 4 ( 2016-4), p. 1234-1243
    Details
    In: Annals of Surgical Oncology, Springer Science and Business Media LLC, Vol. 23, No. 4 ( 2016-4), p. 1234-1243
    Type of Medium: Online Resource
    ISSN: 1068-9265 , 1534-4681
    URL: Article
    DOI: 10.1245/s10434-015-4980-7
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2016
    detail.hit.zdb_id: 2074021-9
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  • 5
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    Gemcitabine and Vinorelbine Combination Chemotherapy in Anthracycline- and Taxane-pretreated Advanced Breast Cancer
    Korean Cancer Association ; 2008
    In:  Cancer Research and Treatment Vol. 40, No. 2 ( 2008), p. 81-
    Details
    In: Cancer Research and Treatment, Korean Cancer Association, Vol. 40, No. 2 ( 2008), p. 81-
    Type of Medium: Online Resource
    ISSN: 1598-2998
    URL: Article
    DOI: 10.4143/crt.2008.40.2.81
    Language: English
    Publisher: Korean Cancer Association
    Publication Date: 2008
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  • 6
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    Online Resource
    Prognostic value of serum soluble programmed death-ligand 1 (sPDL1) and dynamics during chemotherapy in advanced gastric cancer patients.
    American Society of Clinical Oncology (ASCO) ; 2019
    In:  Journal of Clinical Oncology Vol. 37, No. 15_suppl ( 2019-05-20), p. 4034-4034
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 15_suppl ( 2019-05-20), p. 4034-4034
    Abstract: 4034 Background: The soluble form Programmed Death-Ligand 1(sPDL1) is suggested to have immunosuppressive activity and under investigation as candidate biomarker for immuno-oncology drug development. In this study, we measured the serum sPDL1 at pre-and post-chemotherapy and evaluated its prognostic implication and dynamics during chemotherapy in advanced gastric cancer (GC). Methods: We prospectively enrolled 68 GC patients who were candidates for palliative standard 1 st -line chemotherapy, and blood was serially collected at pre-and post-one cycle of chemotherapy, at best response and disease progression. sPDL1 was measured using an enzyme-linked immunosorbent assay. Response to chemotherapy, overall survival (OS), progression-free survival (PFS) and other prognostic factors including neutrophil-lymphocyte ratio (NLR) were obtained. The cut-off values of sPDL1 levels and changes for survivals were found using C-statistics. Results: The median baseline sPDL1 was 0.8ng/mL(range, 0.06 - 6.06ng/mL). The median OS and PFS were 14.9 months (95% CI: 7.33-22.47) and 8.0 months (95% CI: 5.96-10.0), respectively. sPDL1 and NLR showed a positive correlation. Patients with low levels of sPD-L1 at diagnosis ( 〈 1.92 ng/mL) showed a better OS and PFS than the patients with a high sPDL1 (OS: 18.3 vs. 95 months, P = 0.057, PFS: 8.9 vs. 6.0 months, P = 0.04). The baseline sPDL1 before treatment were higher in the PD group than in the SD and PR groups (mean:2.91, 1.17, 1.19, P = 0.019). Patients whose sPDL1 increased after 1 st cycle of chemotherapy showed the tendency of worse PFS and OS. When disease progressed, sPDL1 increased compared with baseline (mean:1.31, 1.45, P = 0.029). Conclusions: sPDL1 at pre-chemotherapy confers the prognostic value for PFS and OS in GC patients under palliative 1 st -line chemotherapy. The dynamics of sPDL1 during chemotherapy correlates with disease courses.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2019.37.15_suppl.4034
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
    detail.hit.zdb_id: 2005181-5
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  • 7
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    Online Resource
    The prognostic role of soluble transforming growth factor-β related with soluble programmed death-ligand 1 in biliary tract cancer.
    American Society of Clinical Oncology (ASCO) ; 2019
    In:  Journal of Clinical Oncology Vol. 37, No. 15_suppl ( 2019-05-20), p. 4094-4094
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 15_suppl ( 2019-05-20), p. 4094-4094
    Abstract: 4094 Background: We previously reported that soluble programmed death-Ligand 1 (sPD-L1) at pre-chemotherapy indicated the prognostic value for overall survival (OS) and the dynamics of sPD-L1 during palliative chemotherapy correlated with disease burden in biliary tract cancer (BTC). Transforming growth factor (TGF) -β attenuates tumor response to PD1/PD-L1 inhibitors. Strategy of dual targeting of PD1/PD-L1 and TGF-β is now under investigation. This study aimed to evaluate the association between soluble TGF-β (sTGF-β) and sPD-L1, dynamics during chemotherapy and its prognostic role in BTC. Methods: Study population consisted of 90 BTC patients treated with first line chemotherapy. Blood samples at pre-and post-chemotherapy and at disease progression (PD) were prospectively collected. Plasma sTGF-β and sPD-L1 levels were measured by using an enzyme-linked immunosorbent assay. Results: The median progression free survival (PFS) and OS of all patients was 6.9 months (m) (95% CI, 5.2-8.6) and 11.5 m (95% CI, 9.4-13.6). The best response was CR in 7 (7.8%), PR in 20 (22.2%), SD in 52 (57.8%), and PD in 11 patients (12.2%). The mean baseline sTGF-β and sPD-L1 were 16.4 ng/ml and 1.3 ng/ml. There was a positive association between sTGF-β and sPD-L1 in terms of baseline levels and changes after chemotherapy (at pre-chemo, Pearson correlation = 0.578, p 〈 0.001; change after chemotherapy, Pearson correlation = 0.542, p 〈 0.001). Patients with higher pre-chemotherapy sPD-L1 ( 〉 1.3 ng/ml) showed worse OS (9.2 vs 16.2 m, p 〈 0.001). Both sPD-L1 (1.8 vs 1.0 ng/ml, p 〈 0.001) and sTGF-β (20.5 vs 11.6 ng/ml, p 〈 0.001) were increased significantly at the time of PD compared with pre-chemotherapy. Regarding changes after chemotherapy, increased sTGF-β after chemotherapy (Δ 〉 3.2 ng/ml) had worse prognosis (PFS: 5.1 vs 7.3 m, p = 0.024; OS: 9.2 vs 12.3 m, p = 0.028). This prognostic value of change of sTGF-β after chemotherapy was also significant in multivariable analysis with other clinical factors (PFS: HR = 1.78, p = 0.022; OS: HR = 1.86, p = 0.018). Conclusions: In BTC, there is a positive association between sTGF-β and sPD-L1 value in terms of baseline levels and changes after chemotherapy. sTGF-β could be associated with the survival, particularly, increased value after chemotherapy indicates worse prognosis.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2019.37.15_suppl.4094
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
    detail.hit.zdb_id: 2005181-5
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  • 8
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    Online Resource
    Inhibition of ATR Increases the Sensitivity to WEE1 Inhibitor in Biliary Tract Cancer
    Korean Cancer Association ; 2020
    In:  Cancer Research and Treatment Vol. 52, No. 3 ( 2020-07-15), p. 945-956
    Details
    In: Cancer Research and Treatment, Korean Cancer Association, Vol. 52, No. 3 ( 2020-07-15), p. 945-956
    Abstract: PurposeCurrently, the DNA damage response (DDR) pathway represents a key target for new cancer drug development. Advanced biliary tract cancer (BTC) has a poor prognosis because of the lack of efficacious treatment options. Although DNA repair pathway alterations have been reported in many patients with BTC, little is known regarding the effects of DDR-targeted agents against BTC.Materials and MethodsIn this study, nine BTC cell lines were exposed to the WEE1 inhibitor (AZD1775). In vitro, MTT assay, colony-forming assay, cell cycle analysis, phospho-histone H3 staining assay, Transwell migration assay, and western blot were performed. Then, to enhance the antitumor effect of AZD1775, the combination treatment of WEE1 inhibitor and ataxia telangiectasia mutated and Rad3 related (ATR) inhibitor (AZD6738) was conducted using MTT assay and comet assay. Finally, HuCCT-1 and SNU2670 xenograft models were established to confirm the anti-tumor effect of AZD1775 alone. Furthermore, the combination treatment was also evaluated in SNU2670 xenograft models.ResultsAZD1775 blocked the phosphorylation of CDC2 and CDC25C in all cell lines, but significantly increased apoptosis and S phase arrest in sensitive cells. However, increased p-ATR and phosphorylated ataxia telangiectasia mutated levels were observed in less sensitive cells. In addition, in vitro and in vivo data illustrated that AZD1775 combined with AZD6738 exerted more potent anti-tumor effects than either drug alone. Although WEE1 inhibition has promising anti-tumor effects in some BTC cells, the addition of ATR inhibitors could enhance its efficacy.ConclusionTaken together, this study supports further clinical development of DDR-targeted strategies as monotherapy or combination regimens for BTC.
    Type of Medium: Online Resource
    ISSN: 1598-2998 , 2005-9256
    URL: Article
    DOI: 10.4143/crt.2020.080
    Language: English
    Publisher: Korean Cancer Association
    Publication Date: 2020
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  • 9
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    Online Resource
    Phase I Pharmacokinetic Study of Nivolumab in Korean Patients with Advanced Solid Tumors
    Oxford University Press (OUP) ; 2018
    In:  The Oncologist Vol. 23, No. 2 ( 2018-02-01), p. 155-e17
    Details
    In: The Oncologist, Oxford University Press (OUP), Vol. 23, No. 2 ( 2018-02-01), p. 155-e17
    Abstract: This pharmacokinetic study of nivolumab showed that there is little ethnic difference in the handling of nivolumab. Nivolumab was well tolerated in Korean patients. Background This phase I study of nivolumab, an anti-programmed cell death-1 (anti-PD-1) monoclonal antibody, investigated the pharmacokinetics and safety of nivolumab in Korean patients with advanced solid tumors. Findings were compared with results from Japan and the U.S. Materials and Methods In this two-part study, patients received a single dose of nivolumab (1, 3, and 10 mg/kg; ONO-4538-13) and were followed up for 3 weeks. Those who met the required criteria proceeded to the second part (ONO-4538-14), and received the same dose as in part one every 2 weeks. Results Six patients per dose level were enrolled (n = 18). The mean elimination half-life of nivolumab among the groups ranged from 15.0 to 19.1 days. The maximum serum concentration and area under serum concentration–time curve increased almost dose-proportionally at doses from 1 to 10 mg/kg. Adverse drug reactions (ADRs; mostly grade ≤2) were reported in seven patients (38.9%). ADRs grade ≥3 occurred in one patient (5.6%; pneumonitis). Three patients (16.7%) developed ADRs related to thyroid dysfunction. Conclusion The pharmacokinetic parameters of nivolumab were similar among patients from Korea, Japan, and the U.S. The safety profile was consistent with findings from previous studies.
    Type of Medium: Online Resource
    ISSN: 1083-7159 , 1549-490X
    URL: Article
    DOI: 10.1634/theoncologist.2017-0528
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2018
    detail.hit.zdb_id: 2023829-0
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  • 10
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    Abstract 2110: WEE1 inhibition could reverse trastuzumab resistance by downregulation of PD-L1 in HER2-positive cancers
    American Association for Cancer Research (AACR) ; 2019
    In:  Cancer Research Vol. 79, No. 13_Supplement ( 2019-07-01), p. 2110-2110
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 79, No. 13_Supplement ( 2019-07-01), p. 2110-2110
    Abstract: Background: Trastuzumab in combination with chemotherapy is a standard of care for patients with HER2-positive breast and gastric cancer. Resistance mechanism to trastuzumab, anti-HER2 therapy, includes multiple pathways. Cancer cells could evade immune surveillance through high expression of programmed cell death ligand 1 (PD-L1) on cancer or immune cells. Among resistance mechanisms to trastuzumab, the role of PD-L1 modulation has not yet been discovered in HER2-positive cancers. WEE1 is involved in cell cycle progression and DNA damage response (DDR), and, interestingly, beyond DDR, it could modulate immunes. We aimed to evaluate the role of PD-L1 in trastuzumab resistance in HER2-positive cancers with/without immune cells and to explore WEE1 inhibitor as a trastuzumab resistance overcoming strategy by modulation of PD-L1. Methods: Four trastuzumab-resistant (HR) cells (SNU216HR, N87HR, SNU2670HR, SNU2773HR) were established from 2 HER2-amplified gastric cancer cells (SNU216, NCI-N87) and 2 HER2-amplified biliary tract cancer cells (SNU2670, SNU2773). For WEE1 inhibition, AZD1775 was used. MTT assay, colony formation assay, cell cycle analysis by FACS Calibur flow cytometer, and western blot were done. Results: All four HR cells showed PD-L1 upregulation compared with parental cells. When PD-L1 was knocked-down by transfection with si-PD-L1, anti-growth/proliferation effects were observed in MTT assay and colony forming assay. PD-L1 itself may promote cancer cell growth without interacting with immune cells. AZD1775 downregulated PD-L1 expression and induced cell cycle arrest at sub-G1 and G2/M phases in all 4 HR cells. The synergistic anti-proliferative effects were found in all 4 HR cells with co-treatment of trastuzumab and AZD1775. Conclusion: PD-L1 upregulation may contribute to trastuzumab resistance in HER2-positive cancer cells. Targeting WEE1-PD-L1 pathway might be a candidate strategy to overcome trastuzumab resistance in HER2-positive cancers. Citation Format: Meihua Jin, Ah-Rong Nam, Ji-Eun Park, Ju-Hee Bang, Kyoung-Seok Oh, Do-Youn Oh, Yung-Jue Bang. WEE1 inhibition could reverse trastuzumab resistance by downregulation of PD-L1 in HER2-positive cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2110.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2019-2110
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2019
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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