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  • 1
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 11, No. 1 ( 2021-05-24)
    Abstract: The success of cancer chemotherapy is limited by multidrug resistance (MDR), which is mainly caused by P-glycoprotein (P-gp) overexpression. In the present study , we describe a novel microtubule inhibitor, 5-( N -methylmaleimid-3-yl)-chromone (SPC-160002), that can be used to overcome MDR. A synthetic chromone derivative, SPC-160002, showed a broad spectrum of anti-proliferative effects on various human cancer cells without affecting P-gp expression and its drug efflux function. Treatment with SPC-160002 arrested the cell cycle at the M phase, as evidenced using fluorescence-activated cell sorting analysis, and increased the levels of mitotic marker proteins, including cyclin B, pS10-H3, and chromosomal passenger complex. This mitotic arrest by SPC-160002 was mediated by promoting and stabilizing microtubule polymerization, similar to the mechanism observed in case of taxane-based drugs. Furthermore, SPC-160002 suppressed the growth and sphere-forming activity of cancer stem cells. Our data herein strongly suggest that SPC-160002, a novel microtubule inhibitor, can be used to overcome MDR and can serve as an attractive candidate for anticancer drugs.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2615211-3
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  • 2
    In: Cells, MDPI AG, Vol. 10, No. 1 ( 2021-01-08), p. 106-
    Abstract: The elimination of the cancer stem cell (CSC) population may be required to achieve better outcomes of cancer therapy. We evaluated stearoyl-CoA desaturase 1 (SCD1) as a novel target for CSC-selective elimination in colon cancer. CSCs expressed more SCD1 than bulk cultured cells (BCCs), and blocking SCD1 expression or function revealed an essential role for SCD1 in the survival of CSCs, but not BCCs. The CSC potential selectively decreased after treatment with the SCD1 inhibitor in vitro and in vivo. The CSC-selective suppression was mediated through the induction of apoptosis. The mechanism leading to selective CSC death was investigated by performing a quantitative RT-PCR analysis of 14 CSC-specific signaling and marker genes after 24 and 48 h of treatment with two concentrations of an inhibitor. The decrease in the expression of Notch1 and AXIN2 preceded changes in the expression of all other genes, at 24 h of treatment in a dose-dependent manner, followed by the downregulation of most Wnt- and NOTCH-signaling genes. Collectively, we showed that not only Wnt but also NOTCH signaling is a primary target of suppression by SCD1 inhibition in CSCs, suggesting the possibility of targeting SCD1 against colon cancer in clinical settings.
    Type of Medium: Online Resource
    ISSN: 2073-4409
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2661518-6
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  • 3
    In: Magnetic Resonance Imaging, Elsevier BV, Vol. 102 ( 2023-10), p. 229-234
    Type of Medium: Online Resource
    ISSN: 0730-725X
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2023
    detail.hit.zdb_id: 1500646-3
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  • 4
    Online Resource
    Online Resource
    MDPI AG ; 2021
    In:  Viruses Vol. 13, No. 12 ( 2021-11-23), p. 2340-
    In: Viruses, MDPI AG, Vol. 13, No. 12 ( 2021-11-23), p. 2340-
    Abstract: Immune responses induced by natural infection and vaccination are known to be initiated by the recognition of microbial patterns by cognate receptors, since microbes and most vaccine components contain pathogen-associated molecular patterns. Recent discoveries on the roles of damage-associated molecular patterns (DAMPs) and cell death in immunogenicity have improved our understanding of the mechanism underlying vaccine-induced immunity. DAMPs are usually immunologically inert, but can transform into alarming signals to activate the resting immune system in response to pathogenic infection, cellular stress and death, or tissue damage. The activation of DAMPs and cell death pathways can trigger local inflammation, occasionally mediating adaptive immunity, including antibody- and cell-mediated immune responses. Emerging evidence indicates that the components of vaccines and adjuvants induce immunogenicity via the stimulation of DAMP/cell death pathways. Furthermore, strategies for targeting this pathway to enhance immunogenicity are being investigated actively. In this review, we describe various DAMPs and focus on the roles of DAMP/cell death pathways in the context of vaccines for infectious diseases and cancer.
    Type of Medium: Online Resource
    ISSN: 1999-4915
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2516098-9
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  • 5
    Online Resource
    Online Resource
    Wiley ; 2022
    In:  Journal of Neuroimaging Vol. 32, No. 5 ( 2022-09), p. 941-946
    In: Journal of Neuroimaging, Wiley, Vol. 32, No. 5 ( 2022-09), p. 941-946
    Abstract: Diffusion kurtosis imaging (DKI) is an advanced technique more specific to irreversible ischemic injury than conventional diffusion‐weighted imaging (DWI). However, its clinical translation has been limited by a long acquisition time and complex postprocessing. Methods A fast DKI sequence (3 minutes) was implemented on a 3T MRI (Siemens Trio) and piloted as part of an inpatient brain MRI protocol. Mean kurtosis (MK) and mean diffusivity (MD) maps were postprocessed automatically at the scanner console and sent to the Picture Archiving and Communications System. We retrospectively reviewed consecutive patients in a 5‐month period with acute ischemic stroke due to large vessel occlusion. MK and MD of the ischemic infarcts and contralateral normal brain were measured, and lesion volumes were measured in large infarcts using semiautomated segmentation. Results Twenty‐two patients were included in the study (median age 66). The median time from last known well to MRI was 37 hours. MD and MK maps were successfully processed and demonstrated acute infarction in concordance with DWI in all cases. Infarcted regions had higher MK and lower MD compared to contralateral normal‐appearing regions. MK lesion volume was significantly smaller than MD volume. Conclusion In this pilot study, we demonstrated the feasibility of incorporating a fast DKI sequence into a clinical MRI protocol. Acute infarcts were depicted on kurtosis maps, and MK lesion volumes were smaller than MD, in accordance with prior works. Future studies are needed to determine the role of DKI in acute stroke treatment selection and prognostication.
    Type of Medium: Online Resource
    ISSN: 1051-2284 , 1552-6569
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 2035400-9
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  • 6
    Online Resource
    Online Resource
    American Chemical Society (ACS) ; 2021
    In:  Journal of Natural Products Vol. 84, No. 2 ( 2021-02-26), p. 298-309
    In: Journal of Natural Products, American Chemical Society (ACS), Vol. 84, No. 2 ( 2021-02-26), p. 298-309
    Type of Medium: Online Resource
    ISSN: 0163-3864 , 1520-6025
    RVK:
    Language: English
    Publisher: American Chemical Society (ACS)
    Publication Date: 2021
    detail.hit.zdb_id: 1491522-4
    SSG: 12
    SSG: 15,3
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  • 7
    In: Molecules, MDPI AG, Vol. 24, No. 24 ( 2019-12-10), p. 4520-
    Abstract: Evodiamine, an alkaloid contained in traditional Asian herbal medicines that have been used for hundreds years, is interesting due to its cytotoxic effects against many cancers. We examined the effect of evodiamine on the cancer stem cell (CSC) population and the bulk cultured cancer cells (BCC) of colon cancers to examine the double targeting effect. We found that three colon cancer cell lines’ BCC and CSC are effectively targeted by evodiamine. Evodiamine was able to suppress BCC proliferation and induce apoptosis of the cells captured in G2/M phase, as previously reported. However, evodiamine did not cause the accumulation of CSCs at a certain stage of the cell cycle, resulting in the elimination of stemness through an unknown mechanism. By analyzing the expression of 84 genes related to CSCs in two colon cancer cell lines’ CSC, as well as performing further informatics analyses, and quantitative RT-PCR analyses of 24 CSC genes, we found that evodiamine suppressed the expression of the genes that control key signaling pathways of CSC, namely, WNT and NOTCH signaling, to lead CSC elimination. These results suggest that evodiamine should be further developed for targeting both BCCs and CSCs in colon cancers.
    Type of Medium: Online Resource
    ISSN: 1420-3049
    Language: English
    Publisher: MDPI AG
    Publication Date: 2019
    detail.hit.zdb_id: 2008644-1
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  • 8
    Online Resource
    Online Resource
    Future Medicine Ltd ; 2022
    In:  CNS Oncology Vol. 11, No. 4 ( 2022-12-01)
    In: CNS Oncology, Future Medicine Ltd, Vol. 11, No. 4 ( 2022-12-01)
    Abstract: Glioblastoma (GBM) is the most common malignant adult brain and has a poor prognosis. Routine post-treatment MRI evaluations are required to assess treatment response and disease progression. We present a case of an 83-year-old female who underwent MRI assessment of post-treatment GBM after intravenous iron replacement therapy, ferumoxytol. The brain MRI revealed unintended alteration of MRI signal characteristics from the iron containing agent which confounded diagnostic interpretation and subsequently, the treatment planning. Ferumoxytol injection prior to contrast enhanced MRI must be screened in post-treatment GBM patients to accurately evaluate tumor activity.
    Type of Medium: Online Resource
    ISSN: 2045-0907 , 2045-0915
    Language: English
    Publisher: Future Medicine Ltd
    Publication Date: 2022
    detail.hit.zdb_id: 2692808-5
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  • 9
    Online Resource
    Online Resource
    Wiley ; 2015
    In:  Contrast Media & Molecular Imaging Vol. 10, No. 3 ( 2015-05), p. 163-178
    In: Contrast Media & Molecular Imaging, Wiley, Vol. 10, No. 3 ( 2015-05), p. 163-178
    Abstract: Chemical exchange saturation transfer (CEST) MRI is a versatile imaging method that probes the chemical exchange between bulk water and exchangeable protons. CEST imaging indirectly detects dilute labile protons via bulk water signal changes following selective saturation of exchangeable protons, which offers substantial sensitivity enhancement and has sparked numerous biomedical applications. Over the past decade, CEST imaging techniques have rapidly evolved owing to contributions from multiple domains, including the development of CEST mathematical models, innovative contrast agent designs, sensitive data acquisition schemes, efficient field inhomogeneity correction algorithms, and quantitative CEST (qCEST) analysis. The CEST system that underlies the apparent CEST‐weighted effect, however, is complex. The experimentally measurable CEST effect depends not only on parameters such as CEST agent concentration, pH and temperature, but also on relaxation rate, magnetic field strength and more importantly, experimental parameters including repetition time, RF irradiation amplitude and scheme, and image readout. Thorough understanding of the underlying CEST system using qCEST analysis may augment the diagnostic capability of conventional imaging. In this review, we provide a concise explanation of CEST acquisition methods and processing algorithms, including their advantages and limitations, for optimization and quantification of CEST MRI experiments. Copyright © 2015 John Wiley & Sons, Ltd.
    Type of Medium: Online Resource
    ISSN: 1555-4309 , 1555-4317
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2015
    detail.hit.zdb_id: 2222967-X
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  • 10
    In: NMR in Biomedicine, Wiley, Vol. 29, No. 5 ( 2016-05), p. 625-630
    Abstract: Diffusion kurtosis imaging (DKI) can offer a useful complementary tool to routine diffusion MRI for improved stratification of heterogeneous tissue damage in acute ischemic stroke. However, its relatively long imaging time has hampered its clinical application in the emergency setting. A recently proposed fast DKI approach substantially shortens the imaging time, which may help to overcome the scan time limitation. However, to date, the sensitivity of the fast DKI protocol for the imaging of acute stroke has not been fully described. In this study, we performed routine and fast DKI scans in a rodent model of acute stroke, and compared the sensitivity of diffusivity and kurtosis indices (i.e. axial, radial and mean) in depicting acute ischemic lesions. In addition, we analyzed the contrast‐to‐noise ratio (CNR) between the ipsilateral ischemic and contralateral normal regions using both conventional and fast DKI methods. We found that the mean kurtosis shows a relative change of 47.1 ± 7.3% between the ischemic and contralateral normal regions, being the most sensitive parameter in revealing acute ischemic injury. The two DKI methods yielded highly correlated diffusivity and kurtosis measures and lesion volumes ( R 2  ⩾ 0.90, p   〈  0.01). Importantly, the fast DKI method exhibited significantly higher CNR of mean kurtosis (1.6 ± 0.2) compared with the routine tensor protocol (1.3 ± 0.2, p   〈  0.05), with its CNR per unit time (CNR efficiency) approximately doubled when the scan time was taken into account. In conclusion, the fast DKI method provides excellent sensitivity and efficiency to image acute ischemic tissue damage, which is essential for image‐guided and individualized stroke treatment. Copyright © 2016 John Wiley & Sons, Ltd.
    Type of Medium: Online Resource
    ISSN: 0952-3480 , 1099-1492
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2016
    detail.hit.zdb_id: 2002003-X
    detail.hit.zdb_id: 1000976-0
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