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  • 11
    Online Resource
    Online Resource
    p21-Activated kinase 3 promotes cancer stem cell phenotypes through activating the Akt-GSK3β-β-catenin signaling pathway in pancreatic cancer cells
    Elsevier BV ; 2019
    In:  Cancer Letters Vol. 456 ( 2019-08), p. 13-22
    Details
    In: Cancer Letters, Elsevier BV, Vol. 456 ( 2019-08), p. 13-22
    Type of Medium: Online Resource
    ISSN: 0304-3835
    URL: Article
    DOI: 10.1016/j.canlet.2019.04.026
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2019
    detail.hit.zdb_id: 195674-7
    detail.hit.zdb_id: 2004212-7
    SSG: 12
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  • 12
    Online Resource
    Online Resource
    Abstract 1360: Novel function of p21-activated kinase 3 (PAK3) in regulating Akt phosphorylation and pancreatic cancer stem cell phenotypes
    American Association for Cancer Research (AACR) ; 2017
    In:  Cancer Research Vol. 77, No. 13_Supplement ( 2017-07-01), p. 1360-1360
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 77, No. 13_Supplement ( 2017-07-01), p. 1360-1360
    Abstract: p21-activated kinases (PAKs) are important effectors of the Rho family GTPases and has been implicated in cytoskelestal remodeling, cell proliferation, apoptosis, and transformation. Based on the sequence, structure homology, and activation mechanism, six PAKs are classified into two groups, PAK 1-3 (group I) and PAK 4-6 (group II). PAK kinases are frequently overexpressed in various human tumors and represent therapeutically relevant targets for cancer treatments. Previous studies have shown that PAK1 and PAK4 are upregulated and/or hyperactivated in pancreatic cancer, and promotes pancreatic cancer cell motility and invasion. In our study, we showed that knockdown of PAK3, but not that of PAK1 or PAK2, inhibited pancreatic cancer cell proliferation in vitro, and tumor growth in vivo. In addition, our data showed that PAK3 regulated the protein stability of β-catenin via Akt/GSK-3β signaling pathway in pancreatic cancer cells. The role of PAK3 in regulating Akt/GSK-3β phosphorylation was further confirmed by the ectopic expression of wild-type versus kinase-dead (K297L) PAK3. Equally important, the mammosphere formation, aldehyde dehydrogenase (ALDH) activity and cancer stem cell-associated markers, were also down-regulated in PAK3 knockdown cells, suggesting the involvement of PAK3 in regulating cancer stem cell-like properties in pancreatic cancer cells. Together, these findings suggested that PAK3 as a primary regulator of Akt/GSK-3β/β-catenin signaling for maintaining cancer stem cell phenotypes and promoting tumor growth, which underlies the potential of targeting PAK3 in fostering new therapeutic strategies for pancreatic cancer. Citation Format: Hsing-Yu Wu, Ming-Chen Yang, Po-Chen Chu, Samuel K. Kulp, Ching-Shih Chen. Novel function of p21-activated kinase 3 (PAK3) in regulating Akt phosphorylation and pancreatic cancer stem cell phenotypes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1360. doi:10.1158/1538-7445.AM2017-1360
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2017-1360
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2017
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 13
    Online Resource
    Online Resource
    Current screening practice in patients under long-term hydroxychloroquine medication in Taiwan : A nationwide population-based cohort study
    Ovid Technologies (Wolters Kluwer Health) ; 2019
    In:  Medicine Vol. 98, No. 14 ( 2019-04), p. e15122-
    Details
    In: Medicine, Ovid Technologies (Wolters Kluwer Health), Vol. 98, No. 14 ( 2019-04), p. e15122-
    Abstract: Hydroxychloroquine (HCQ), an analog of chloroquine, is widely used in various rheumatologic and dermatologic disorders. However, it may cause severe retinopathy with long-term use. The guidelines proposed by the American Academy of Ophthalmology suggested a baseline fundus examination and an annual screening after 5 years by using automated visual fields (VF) plus spectral-domain optical coherence tomography (SD-OCT). Both multifocal electroretinogram (mfERG) and fundus autofluorescence (FAF) can also be used to improve the accuracy of diagnosis. The purpose of this study was to examine if the current HCQ screening practice in Taiwan was sufficient according to the guidelines to prevent severe macular complications. This study could remind every doctor to explain visual side effects thoroughly to every patient using HCQ, and refer patients for the ophthalmologic survey to eliminate potential visual impairment caused by this medicine. This nationwide population-based cohort study included all patients who started taking HCQ (n = 5826) from January 1, 1997, to December 31, 2007, in the Longitudinal Health Insurance Database 2000. The ICD codes used for HCQ retinopathy were 362.10, 362.55, 362.89, and 362.9. Patients previously diagnosed these retinal disorders were excluded. Demographic data including sex, age, diagnostic tools used, and the date of the initial diagnosis of the subsequent HCQ-related retinal disorder were collected. Patients were divided into 2 groups. The patients taking HCQ 〈 5 years were defined as group 1, and 〉 5 years as group 2. The risk of developing retinal diseases between these 2 groups was compared with a 2-sample t -test for continuous variables, and Fisher's exact test for discrete variables. Multiple logistic regressions were used for odds ratio calculation. The baseline examination ratio of the automated VF, SD-OCT scans, and multifocal electroretinograms (mfERGs) in the first 3 months were only 0.2% in both groups. The screening ratio of the 3 examination tools after 5 years were 1.1% in group 1 and 1.2% in group 2. 2.5% and 3.9% of patients developed a retinal disorder after HCQ use in group 1 and 2, respectively. The risk of developing retinal disorder was significantly higher in group 2 (relative risk = 1.53, P =  .006). The odds ratio (OR) was also significantly higher in group 2 (1.67 with 95% cumulative incidence 1.20–2.30) The examination ratio according to the guidelines was very low in Taiwan. Thus, it is very important for doctors who prescribe HCQ to schedule both baseline and annual ophthalmology screening tests and inform patients of possible severe ocular complications, even in the patient taking HCQ 〈 5 years. It is also important for ophthalmologists to review medical history carefully to find out the causes of retinotoxicity. Medications should be stopped, if possible when toxicity is recognized or strongly suspected.
    Type of Medium: Online Resource
    ISSN: 0025-7974 , 1536-5964
    URL: Article
    DOI: 10.1097/MD.0000000000015122
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2019
    detail.hit.zdb_id: 2049818-4
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  • 14
    Online Resource
    Online Resource
    Role of pilocarpine use following laser peripheral iridotomy in eyes with refractory acute angle closure glaucoma: A case report and literature review
    Ovid Technologies (Wolters Kluwer Health) ; 2022
    In:  Medicine Vol. 101, No. 27 ( 2022-07-8), p. e29245-
    Details
    In: Medicine, Ovid Technologies (Wolters Kluwer Health), Vol. 101, No. 27 ( 2022-07-8), p. e29245-
    Abstract: Angle closure glaucoma (ACG) is one of the most emergent types of glaucoma in clinical practice. Laser peripheral iridotomy (LPI) could minimize pupillary block and prevent ACG from an acute attack. However, recurrent increase in intraocular pressure (IOP) may still occur despite successful LPI. The aim of this study is to highlight the importance of postLPI pilocarpine use and larger LPI size as well as to share some experiences of cataract surgery in patients with ACG. Patient concerns: A 63-year-old female was referred to our hospital for headache, and poor control of IOP in the right eye for 3 hours. Diagnoses: The patient was diagnosed ACG in the right eye. Recurrence of ACG in the right eye and new-onset and recurrent ACG in the left eye were noted during follow-up, despite successful LPI. The diagnosis was confirmed through slit lamp and gonioscope examination. Interventions: The LPI size was enlarged and pilocarpine use was maintained at 2% (1 drop 4 times a day) in both the eyes. Finally, cataract surgery was performed in both the eyes. Outcomes: No recurrence of ACG was noted during postLPI pilocarpine use in both the eyes. The postoperative IOP was stable for 〉 6 months after cataract surgery without any surgical intervention or antiglaucoma medication use. No discomfort or major complication was observed. Conclusion: This report highlights the importance of postLPI pilocarpine use and larger LPI size in patients with refractory ACG.
    Type of Medium: Online Resource
    ISSN: 1536-5964
    URL: Article
    DOI: 10.1097/MD.0000000000029245
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
    detail.hit.zdb_id: 2049818-4
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  • 15
    Online Resource
    Online Resource
    Assessment of Expert-Level Automated Detection of Plasmodium falciparum in Digitized Thin Blood Smear Images
    American Medical Association (AMA) ; 2020
    In:  JAMA Network Open Vol. 3, No. 2 ( 2020-02-28), p. e200206-
    Details
    In: JAMA Network Open, American Medical Association (AMA), Vol. 3, No. 2 ( 2020-02-28), p. e200206-
    Type of Medium: Online Resource
    ISSN: 2574-3805
    URL: Article
    DOI: 10.1001/jamanetworkopen.2020.0206
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2020
    detail.hit.zdb_id: 2931249-8
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  • 16
    Online Resource
    Online Resource
    A Simple Dithieno[3,2‐b:2′,3′‐d]pyrrol‐Rhodanine Molecular Third Component Enables Over 16.7% Efficiency and Stable Organic Solar Cells
    Wiley ; 2021
    In:  Small Vol. 17, No. 18 ( 2021-05)
    Details
    In: Small, Wiley, Vol. 17, No. 18 ( 2021-05)
    Abstract: Organic solar cells (OSCs) can achieve greatly improved power conversion efficiency (PCE) by incorporating suitable additives in active layers. Their structure design often faces the challenge of operation generality for more binary blends. Herein, a simple dithieno[3,2‐b:2′,3′‐d]pyrrole‐rhodanine molecule (DR8) featuring high compatibility with polymer donor PM6 is developed as a cost‐effective third component. By employing classic ITIC‐like ITC6‐4Cl and Y6 as model nonfullerene acceptors (NFAs) in PM6‐based binary blends, DR8 added PM6:ITC6‐4Cl blends exhibit significantly promoted energy transfer and exciton dissociation. The PM6:ITC6‐4Cl:DR8 (1:1:0.1, weight ratio) OSCs contribute an exciting PCE of 14.94% in comparison to host binary devices (13.52%), while PM6:Y6:DR8 (1:1.2:0.1) blends enable 16.73% PCE with all simultaneously improved photovoltaic parameters. To the best of the knowledge, this performance is among the best for ternary OSCs with simple small molecular third components in the literature. More importantly, DR8‐added ternary OSCs exhibit much improved device stability against thermal aging and light soaking over binary ones. This work provides new insight on the design of efficient third components for OSCs.
    Type of Medium: Online Resource
    ISSN: 1613-6810 , 1613-6829
    URL: Issue
    URL: Article
    DOI: 10.1002/smll.v17.18
    DOI: 10.1002/smll.202007746
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2168935-0
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  • 17
    Online Resource
    Online Resource
    Silencing of p29 Affects DNA Damage Responses with UV Irradiation
    American Association for Cancer Research (AACR) ; 2006
    In:  Cancer Research Vol. 66, No. 17 ( 2006-09-01), p. 8484-8491
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 66, No. 17 ( 2006-09-01), p. 8484-8491
    Abstract: Human p29 is a newly identified nuclear protein whose function is largely undetermined. We found that p29 associated with chromatin, interacted with MCM3, and localized with proliferating cell nuclear antigen foci in the S phase. Silencing of p29 using small interfering RNA duplexes reduced DNA synthesis and increased the expression of p107, a member of the RB family, and of cyclin-dependent kinase inhibitor p21, accompanied with a decreased expression of DNA polymerase α. Lethal events consisting of premature chromatin condensation with a reduced Chk1 phosphorylation were observed in p29-depleted cells in response to UV irradiation. Intriguingly, the phosphorylation of ataxia telangectasia-mutated kinases at S1981 was suppressed in p29-depleted HeLa cells with UV irradiation, but not in hydroxyurea- and ionizing radiation-treated cells. Taken together, these results reveal a novel function of p29 in the regulation of DNA replication checkpoint responses. (Cancer Res 2006; 66(17): 8484-91)
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/0008-5472.CAN-05-3229
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2006
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 18
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    Online Resource
    Retraction: Non-epigenetic function of HDAC8 in regulating breast cancer stem cells by maintaining Notch1 protein stability
    Impact Journals, LLC ; 2020
    In:  Oncotarget Vol. 11, No. 12 ( 2020-03-24), p. 1096-1096
    Details
    In: Oncotarget, Impact Journals, LLC, Vol. 11, No. 12 ( 2020-03-24), p. 1096-1096
    Type of Medium: Online Resource
    ISSN: 1949-2553
    URL: Issue
    URL: Article
    DOI: 10.18632/oncotarget.v11i12
    DOI: 10.18632/oncotarget.27533
    Language: English
    Publisher: Impact Journals, LLC
    Publication Date: 2020
    detail.hit.zdb_id: 2560162-3
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  • 19
    Online Resource
    Online Resource
    Development of Novel Rhodacyanine-Based Heat Shock Protein 70 Inhibitors
    Bentham Science Publishers Ltd. ; 2021
    In:  Current Medicinal Chemistry Vol. 28, No. 26 ( 2021-09-08), p. 5431-5446
    Details
    In: Current Medicinal Chemistry, Bentham Science Publishers Ltd., Vol. 28, No. 26 ( 2021-09-08), p. 5431-5446
    Abstract: A growing body of evidence suggests that Hsp70, which is overexpressed in human breast tumors, plays a role in tumorigenesis and tumor progression in breast cancer as well as in its aggressive phenotypes. Hsp70 constitutes a potential therapeutic target in the treatment of this disease. Methods: We developed a new series of rhodacyanine-based Hsp70 inhibitors, represented by compounds 1 and 6, in which the cationic pyridin-1-ium or thiazol-3-ium ring of existing Hsp70 inhibitors (e.g., JG-40 and JG-98) was replaced by a corresponding benzo- fused N-heterocycle. Results: Several lines of evidence suggest that these benzo-fused derivatives may exert their antitumor activities, in part, by targeting Hsp70. These putative inhibitors displayed differential antiproliferative efficacy against breast cancer cells (IC 50 as low as 0.25 μM) versus nontumorigenic MCF-10A breast epithelial cells (IC 50 ≥ 5 μM). This was correlated with the corresponding Hsp70 expression levels. Using a protein refolding assay, we confirmed that these agents effectively inhibited the chaperone activity of Hsp70. Moreover, these inhibitors effectively suppressed the expression of well-known oncogenic client proteins of Hsp70’s, including FoxM1, HuR, and Akt, which paralleled their antiproliferative efficacy. Supporting the established role of Hsp70 in regulating protein refolding, these derivatives induced autophagy, as manifested by the conversion of LC3B-I to LC3B-II. Notably, these putative Hsp70 inhibitors did not cause a compensatory elevation in Hsp90 expression, contrasting with the previously reported effects of Hsp90 inhibitors on Hsp70 upregulation. Conclusion: Together with the finding that compounds 1 and 6 showed improved microsomal stability, these results suggest the translational potential of these putative Hsp70 inhibitors to foster new strategies for cancer therapy. However, whether these benzo-fused rhodacyanines act on kinases or other targets remains unclear. It is currently under investigation.
    Type of Medium: Online Resource
    ISSN: 0929-8673
    URL: Article
    DOI: 10.2174/0929867328666210203204254
    Language: English
    Publisher: Bentham Science Publishers Ltd.
    Publication Date: 2021
    SSG: 15,3
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  • 20
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    Pharmacological exploitation of the phenothiazine antipsychotics to develop novel antitumor agents–A drug repurposing strategy
    Springer Science and Business Media LLC ; 2016
    In:  Scientific Reports Vol. 6, No. 1 ( 2016-06-09)
    Details
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 6, No. 1 ( 2016-06-09)
    Abstract: Phenothiazines (PTZs) have been used for the antipsychotic drugs for centuries. However, some of these PTZs have been reported to exhibit antitumor effects by targeting various signaling pathways in vitro and in vivo . Thus, this study was aimed at exploiting trifluoperazine, one of PTZs, to develop potent antitumor agents. This effort culminated in A4 [10-(3-(piperazin-1-yl)propyl)-2-(trifluoromethyl)-10 H -phenothiazine] which exhibited multi-fold higher apoptosis-inducing activity than the parent compound in oral cancer cells. Compared to trifluoperazine, A4 demonstrated similar regulation on the phosphorylation or expression of multiple molecular targets including Akt, p38 and ERK. In addition, A4 induced autophagy, as evidenced by increased expression of the autophagy biomarkers LC3B-II and Atg5 and autophagosomes formation. The antitumor activity of A4 also related to production of reactive oxygen species and adenosine monophosphate-activated protein kinase. Importantly, the antitumor utility of A4 was extended in vivo as it, administrated at 10 and 20 mg/kg intraperitoneally, suppressed the growth of Ca922 xenograft tumors. In conclusion, the ability of A4 to target diverse aspects of cancer cell growth suggests its value in oral cancer therapy.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    URL: Article
    DOI: 10.1038/srep27540
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2016
    detail.hit.zdb_id: 2615211-3
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