GLORIA

GEOMAR Library Ocean Research Information Access

X

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Online Resource
    Online Resource
    Abstract 1295: SJP1901, a small molecule inhibitor targeting hippo pathway by directly inhibiting TEAD palmitoylation in hippo pathway-dependent cancer
    American Association for Cancer Research (AACR) ; 2021
    In:  Cancer Research Vol. 81, No. 13_Supplement ( 2021-07-01), p. 1295-1295
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 81, No. 13_Supplement ( 2021-07-01), p. 1295-1295
    Abstract: The hippo pathway is a critical transcriptional regulator of cell growth, proliferation, and migration in cancer, furthermore,YAP-TEAD complexes act as a major role in the pathway. S-palmitoylation of cysteine residues in TEAD proteins is required for their stability and function in hippo pathway signaling. Recently, it has become manifested that the dysregulation of hippo pathway effectors (MST1/2 and LATS1/2) is involved in oncogenesis. These effectors inactivate translocation of YAP and TAZ into the nucleus. The translocation of YAP/TAZ is responsible for acting as transcriptional coactivators by binding to the transcription factor, TEADs resulting in the transcription of cancer-related genes that drive tumor growth. Since YAP/TAZ are considered to be natively unfolded and can be difficult to handle as a drug target, TEAD is regarded as an excellent therapeutic target for intervention of the hippo pathway. SJP1901 is a small molecule of TEAD inhibitor with potential as drug candidates in malignant mesothelioma and other types of cancer. Based on the results of structure-based drug design, hit compounds were synthesized and their efficacy was evaluated.The compounds effectively inhibited palmitoylation of TEAD proteins and showed remarkable efficacy in reporter gene assay using TEAD responsive element (TRE)-integrated MCF7 with nano molar IC50 concentrations. The excellent anti-tumor effect of SJP1901 was revealed via cell proliferation inhibition assay (nano molar IC50 concentrations) andanalysis of inhibited transcription activity for target genes (CTGF and CYR61) usingmalignant mesothelia cell lines (NCI-H226, NCI-H2052 and MSTO-211H) known to display hippo pathway-dependent cell growth. In addition, these compounds showed lower toxicities in normal cells such as Fa2N4, CCD-18co and WI38 (IC50 & gt;10 μM). In conclusion, we obtained potent small molecules which inactivate TEAD proteins by directly inhibiting their palmitoylation. SJP1901 showed outstanding anti-cancer effects through regulating hippo pathway-mediated target genes and lower toxicitiy in normal cells. In vivo efficacy study and research to expand the indications are currently ongoing. Citation Format: Jihyun Um, Janghyun Lee, Kwangwoo Hwang, Sujin Park, Jooyoung Hyun, Dohyeong Lee, Jeongmin Lee, Li-Kyung Kim, Moon Jung Back, Seong Jun Park, Hwan Jung Lim, You-Keun Shin, Hei-Cheul Jeung, Jaewoong Lee, Hyun Tae Kim, Yongbin Park, Hoseok Kwon, Min-Hyo Ki. SJP1901, a small molecule inhibitor targeting hippo pathway by directly inhibiting TEAD palmitoylation in hippo pathway-dependent cancer [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 1295.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2021-1295
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2021
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 2
    Online Resource
    Online Resource
    Abstract TP126: Diffusion Weighted Image Lesion Dynamics in Acute Ischemic Stroke and Functional Recovery: Application of an Automated Software to 7000 Cases
    Ovid Technologies (Wolters Kluwer Health) ; 2024
    In:  Stroke Vol. 55, No. Suppl_1 ( 2024-02)
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 55, No. Suppl_1 ( 2024-02)
    Abstract: Introduction: The change in DWI lesion volume in acute ischemic stroke has not been investigated in detail. We aimed to investigate the effect of DWI lesion growth or regression within seven days of onset on functional recovery after ischemic stroke. Methods: From a prospective stroke registry, we retrieved acute ischemic stroke cases who had more than two DWIs during in-hospital care between 2005 and 2022. The DWI lesion volume was automatically measured using JBS-01K (JLK Inc., South Korea), a fully automated and validated deep learning algorithm using 3D U-net. The association between categorized DWI lesion volume change (10, 25, 50, and 75 percentiles corresponding to -45%, 0%, 57%, and 220% of volume change) and functional recovery was assessed using multivariable ordinal logistic regression analysis taking lower modified Rankin scale (mRS) as a dependent variable, adjusting for relevant covariates. Results: A total of 7308 patients with ischemic stroke who underwent follow-up DWIs were included. A male was 62%, mean age of 67.5±13.5, and a median of initial NIHSS 4 [IQR 1-7]. The median of interval between the initial and follow-up DWI was 90 hours [IQR 68.25 - 112.20] . The median of the initial DW lesion volume was 1.00 ml [IQR 0.27-5.98], and the median of the follow-up DW lesion volume was 2.05 ml [IQR 0.27-5.98] . DWI lesion volume was regressed in 1844 cases (25%); 136 cases (13%) of EVT and 1708 cases (27%) of non-EVT cases. Compared with patients with 25-50 percentile strata, the adjusted odds ratios (OR) of having favorable functional recovery for 〈 10th, 10-25th, 50-75th, and ≥75th percentile were 1.25 [95% CI 1.05 - 1.48], 0.96 [0.83 - 1.11] , 0.67 [0.59 - 0.76], and 0.63 [0.55 - 0.72] , respectively (Figure). Conclusions: We found that approximately a quarter of patients with ischemic stroke had an interval regression of infarct volume on DWI, which is independently associated with favorable functional recovery.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/str.55.suppl_1.TP126
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2024
    detail.hit.zdb_id: 1467823-8
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 3
    Online Resource
    Online Resource
    Abstract TMP44: Widening Sex Disparity in Thrombolysis Amid Worsening Stroke Care Quality in Korea
    Ovid Technologies (Wolters Kluwer Health) ; 2024
    In:  Stroke Vol. 55, No. Suppl_1 ( 2024-02)
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 55, No. Suppl_1 ( 2024-02)
    Abstract: Introduction: The difference in the use of intravenous thrombolysis (IVT) between females and males has been recognized. Nevertheless, there has been a lack of comprehensive investigation into the sex disparity in South Korea, where the stroke care system has experienced a government-initiated reform recently. Method: A prospective, multicenter, nationwide stroke registry (CRCS-K) was utilized to analyze acute stroke admissions during the years 2008 to 2022. IVT candidates were defined as patients with an NIHSS score of 4 or greater and who arrived at the hospital within 4.5 hours from the time last known well. The stroke care quality was measured by the 90th percentile of door-to-needle (DTN) time for IVT. The joinpoint regression model was applied to detect changes in trends of IVT utilization among the candidates. Results: A total of 96,855 admissions, of which 43% were female, were recorded during the period. IVT candidates were identified to be 15,732 (16%). The proportion of IVT among the candidates showed an increasing trend after 2008 (Phase 1), followed by a notable decline from 2013 to 2016 (Phase 2) and no significant change afterward (Phase 3, Panel A). During Phase 2, a significant decrease in IVT utilization was observed with an annual percent change (APC) of -5.40, with a greater downward trend in females (APC, -8.71) compared to males (APC, -1.99, Panel B). The 90th percentile of DTN time improved during Phase 1 (APC, -10.28), and worsened after the year 2013 (APC, 4.82, Panel C). IVT utilization was comparable between sexes in Phase 1 (adjusted OR [95% CI], 0.88 [0.76 - 1.03] ), but a significant difference was noted in Phase 2 (0.77 [0.66 - 0.91]) and in Phase 3 (0.82 [0.30 - 0.91] ), after the year 2013. Conclusion: A sex disparity in the use of IVT for ischemic stroke was documented in South Korea. In line with the deterioration in the hyperacute stroke care quality, the gender disparities in the utilization of IVT were also worsening.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/str.55.suppl_1.TMP44
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2024
    detail.hit.zdb_id: 1467823-8
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 4
    Online Resource
    Online Resource
    Molecular characteristics of incidental lower-grade glioma for treatment decision-making
    Journal of Neurosurgery Publishing Group (JNSPG) ; 2023
    In:  Journal of Neurosurgery Vol. 138, No. 3 ( 2023-03-01), p. 629-638
    Details
    In: Journal of Neurosurgery, Journal of Neurosurgery Publishing Group (JNSPG), Vol. 138, No. 3 ( 2023-03-01), p. 629-638
    Abstract: Several limitations are associated with the early diagnosis and treatment of incidental lower-grade glioma (iLGG), and due to its unknown molecular features, its management is categorized as either the “wait-and-see” strategy or immediate treatment. Therefore, in this study the authors explored iLGG’s clinical and molecular landscape to improve its management. METHODS The authors retrospectively assessed the differences between the molecular and clinical characteristics of iLGG and symptomatic lower-grade glioma (sLGG) samples filtered based on symptom data corresponding to The Cancer Genome Atlas cohort with mutations. Thereafter, genomic and transcriptomic analysis was performed. RESULTS There was no significant difference between iLGG and sLGG with respect to mutation status; however, there was an increase in the interaction between major mutations in sLGG, depending on the histological subtype and the IDH1 mutation status. Furthermore, the IDH1 mutation characteristics corresponding to wild-type glioma were much more obvious in sLGG than in iLGG. Additionally, in sLGG, genes associated with malignancy, including cell proliferation–related, cell migration–related, epithelial-to-mesenchymal transition–related, and negative regulation of cell death–related genes, were significantly upregulated, and groups showing higher expression levels of these genes were associated with worse prognosis. Also, 8 of the 75 identified upregulated genes showed positive correlation with resistance to the drugs that are normally used for glioma treatment, including procarbazine, carmustine, vincristine, and temozolomide. CONCLUSIONS The new insights regarding the different molecular features of iLGG and sLGG indicated that the immediate management of iLGG could result in better prognosis than the wait-and-see strategy.
    Type of Medium: Online Resource
    ISSN: 0022-3085 , 1933-0693
    URL: Article
    DOI: 10.3171/2022.6.JNS22967
    RVK:
    XA 10000
    RVK:
    XA 55270
    Language: Unknown
    Publisher: Journal of Neurosurgery Publishing Group (JNSPG)
    Publication Date: 2023
    detail.hit.zdb_id: 2026156-1
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 5
    Online Resource
    Online Resource
    Abstract 38: Temporal Changes in Intracranial Arterial Diseases: A Longitudinal High-Resolution Vessel Wall Imaging Analysis
    Ovid Technologies (Wolters Kluwer Health) ; 2024
    In:  Stroke Vol. 55, No. Suppl_1 ( 2024-02)
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 55, No. Suppl_1 ( 2024-02)
    Abstract: Introduction: Temporal changes of intracranial arterial disease (ICAD) in patients with ischemic stroke in high-resolution vessel wall imaging (HR-VWI) have not been elucidated. Methods: We recruited consecutive ICAD-related ischemic stroke patients admitted between June 2016 and June 2019 and had subsequent HR-VWI follow-ups. On HR-VWI, we manually segmented the lumen area (LA), total vessel area (TVA), and enhancing area (EA) of the culprit lesion's most stenotic part in the perpendicular section on T1-weighted, proton density, and post-contrast T1-weighted sequences. We defined the area stenosis as [1-LA/TVA]х100 (%) and the enhancing proportion as EA/TVAх100 (%). Enhancement ratio of the enhancing lesion was also quantified. Three raters independently quantified the imaging using ITK-SNAP with acceptable inter-rater reliability. Results: A total of 208 patients (age 57±14, male 58%) with 469 HR-VWIs (2-6 scans per patient) were included. The causes of ICAD were atherosclerosis (69%), dissection (24%), vasculitis (3%), moyamoya disease (1%), and other causes (2%). The median follow-up duration was 9.0 months (interquartile range: 3.9-13.2 months), and the maximum follow-up duration was 41.3 months. Among patients with atherosclerosis, area stenosis aggravated, stable, and improved in 7%, 77%, and 16%, respectively, with an overall rate of 0.23 ± 0.07% improvement per month. Among patients with dissection, area stenosis aggravated, stable, and improved in 2%, 49%, and 49%, respectively, with an overall rate of 2.11 ± 0.26% improvement per month (Figure, P -for-difference 〈 0.01). The temporal changes of the enhancing proportion and enhancement ratio were different between atherosclerosis and dissection (Figure, P 〈 0.01). Conclusions: ICAD lesions had dynamic changes over time; the temporal changes of atherosclerosis and dissection are distinct. Serial HR-VWI can offer insights for a more accurate diagnosis of the underlying pathologies of ICADs.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/str.55.suppl_1.38
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2024
    detail.hit.zdb_id: 1467823-8
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...