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  • 1
    In: Cells, MDPI AG, Vol. 12, No. 16 ( 2023-08-14), p. 2059-
    Abstract: Chimeric-antigen-receptor (CAR) T-cell therapy for CD19-expressing B-cell malignancies is already widely adopted in clinical practice. On the other hand, the development of CAR-T-cell therapy for T-cell malignancies is in its nascent stage. One of the potential targets is CD26, to which we have developed and evaluated the efficacy and safety of the humanized monoclonal antibody YS110. We generated second (CD28) and third (CD28/4-1BB) generation CD26-targeted CAR-T-cells (CD26-2G/3G) using YS110 as the single-chain variable fragment. When co-cultured with CD26-overexpressing target cells, CD26-2G/3G strongly expressed the activation marker CD69 and secreted IFNgamma. In vitro studies targeting the T-cell leukemia cell line HSB2 showed that CD26-2G/3G exhibited significant anti-leukemia effects with the secretion of granzymeB, TNFα, and IL-8, with 3G being superior to 2G. CD26-2G/3G was also highly effective against T-cell lymphoma cells derived from patients. In an in vivo mouse model in which a T-cell lymphoma cell line, KARPAS299, was transplanted subcutaneously, CD26-3G inhibited tumor growth, whereas 2G had no effect. Furthermore, in a systemic dissemination model in which HSB2 was administered intravenously, CD26-3G inhibited tumor growth more potently than 2G, resulting in greater survival benefit. The third-generation CD26-targeted CAR-T-cell therapy may be a promising treatment modality for T-cell malignancies.
    Type of Medium: Online Resource
    ISSN: 2073-4409
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2661518-6
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  • 2
    Online Resource
    Online Resource
    MDPI AG ; 2021
    In:  International Journal of Environmental Research and Public Health Vol. 18, No. 13 ( 2021-07-04), p. 7154-
    In: International Journal of Environmental Research and Public Health, MDPI AG, Vol. 18, No. 13 ( 2021-07-04), p. 7154-
    Abstract: (1) Background: Near-miss incidents are the foundation of major injuries. They are warning signs that loss is imminent. Long working hours are a risk factor for near-misses along with sleep problems, job-related stress, and depressive symptoms. This study aimed to evaluate the indirect effects of long working hours via mediating variables on near-miss occurrences among Japanese healthcare professionals. (2) Methods: 1490 Japanese healthcare professionals’ reports from a web-based survey of workers in October 2018 were analyzed to evaluate total, direct, and indirect effects of long working hours on near-misses. We applied a generalized structural equation model with three mediating variables: sleep problems, job-related stress, and depressive symptoms. (3) Results: The total effect and direct effect of the categories of working hours longer than 41 h per week (h/w) for occurrence of near-misses were not significantly higher than that of 35–40 h/w. However, for indirect effects on occurrence of near-misses that first passed through job-related stress, there were higher reports for each category compared to 35–40 h/w, with odds ratios (OR) and 95% confidence intervals (95% CI) of OR = 1.12, 95% CI (1.07, 1.21) for 41–50 h/w; 1.25, (1.14, 1.41) for 51–60 h/w; and 1.31, (1.18, 1.51) for ≥ 61 h/w. (4) Conclusion: The results suggest that reducing working hours might improve job-related stress, which could reduce near-misses and prevent injuries.
    Type of Medium: Online Resource
    ISSN: 1660-4601
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2175195-X
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  • 3
    In: Cells, MDPI AG, Vol. 12, No. 7 ( 2023-04-06), p. 1100-
    Abstract: DPP8/9 inhibition induces either pyroptotic or apoptotic cell death in hematological malignancies. We previously reported that treatment with the DPP8/9 inhibitor 1G244 resulted in apoptotic cell death in myeloma, and our current study further evaluates the mechanism of action of 1G244 in different blood cancer cell lines. Specifically, 1G244 inhibited DPP9 to induce GSDMD-mediated-pyroptosis at low concentrations and inhibited DPP8 to cause caspase-3-mediated-apoptosis at high concentrations. HCK expression is necessary to induce susceptibility to pyroptosis but does not participate in the induction of apoptosis. To further characterize this DPP8-dependent broad-spectrum apoptosis induction effect, we evaluated the potential antineoplastic role for an analog of 1G244 with higher DPP8 selectivity, tominostat (also known as 12 m). In vitro studies demonstrated that the cytotoxic effect of 1G244 at high concentrations was enhanced in tominostat. Meanwhile, in vivo work showed tominostat exhibited antitumor activity that was more effective on a cell line sensitive to 1G244, and at higher doses, it was also effective on a cell line resistant to 1G244. Importantly, the weight loss morbidity associated with increasing doses of 1G244 was not observed with tominostat. These results suggest the possible development of novel drugs with antineoplastic activity against selected hematological malignancies by refining and increasing the DPP8 selectivity of tominostat.
    Type of Medium: Online Resource
    ISSN: 2073-4409
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2661518-6
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  • 4
    In: Current Oncology, MDPI AG, Vol. 28, No. 2 ( 2021-03-22), p. 1294-1301
    Abstract: This study aimed to determine the predictive value of the Prostate Imaging Reporting and Data System version 2 (PI-RADS v2) based on biparametric magnetic resonance imaging (bpMRI) with combined target biopsy (TBx) and systematic biopsy (SBx) in patients with suspicion of having clinically significant prostate cancer (csPCa). In this retrospective study, we reviewed the clinical and pathological records of 184 consecutive patients who underwent bpMRI before prostate biopsy. We focused on patients with PI-RADS v2 scores ≥ 3. MRI was performed using a 3-Tesla clinical scanner with a 32-channel phased-array receiver coil. PI-RADS v2 was used to describe bpMRI findings based on T2-weighted imaging and diffusion-weighted imaging scores. The primary endpoint was the diagnostic accuracy rate of PI-RADS v2 based on bpMRI for patients with prostate cancer (PCa) who underwent combined TBx and SBx. A total of 104 patients were enrolled in this study. Combined TBx and SBx was significantly superior to either method alone for PCa detection in patients with suspicious lesions according to PI-RADS v2. TBx and SBx detected concordant csPCa in only 24.1% of the patients. In addition, the rate of increase in the Gleason score was similar between SBx (41.5%) and TBx (34.1%). The diagnostic accuracy of bpMRI is comparable to that of standard multiparametric MRI for the detection of csPCa. Moreover, combined TBx and SBx may be optimal for the accurate determination of csPCa diagnosis, the International Society of Urological Pathology grade, and risk classification.
    Type of Medium: Online Resource
    ISSN: 1718-7729
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2270777-3
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