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  • MDPI AG  (30)
  • 1
    Online-Ressource
    Online-Ressource
    Safety and Efficacy of Allogeneic Natural Killer Cells in Combination with Pembrolizumab in Patients with Chemotherapy-Refractory Biliary Tract Cancer: A Multicenter Open-Label Phase 1/2a Trial
    MDPI AG ; 2022
    In:  Cancers Vol. 14, No. 17 ( 2022-08-30), p. 4229-
    Details
    In: Cancers, MDPI AG, Vol. 14, No. 17 ( 2022-08-30), p. 4229-
    Kurzfassung: Background and Aim: This study investigated the administration of combination therapy, allogeneic natural killer (NK) cells and pembrolizumab in the treatment of advanced biliary tract cancer to determine the safety and tolerability (phase 1) and the efficacy and safety (phase 2a). Methods: Forty patients (phase 1, n = 6; phase 2a, n = 34) were enrolled between December 2019 and June 2021. The patients received highly activated allogeneic NK cells (“SMT-NK”) on weeks 1 and 2 and pembrolizumab on week 1. This 3-week schedule (one cycle) was repeated until confirmed disease progression, intolerable adverse events (AEs), patient withdrawal, or finishing the maximum treatment schedule. The tumor response was evaluated after every three cycles. Results: In phase 1, four patients (66.7%) experienced seven AEs, but no severe AE was observed. In phase 2a, 126 AEs occurred in 29 patients (85.3%). Severe AEs (≥grade 3) were reported in 16 patients (47.1%). The overall response rate (ORR) was 17.4% in the full analysis set and 50.0% in the per-protocol set. Conclusions: SMT-NKs plus pembrolizumab resulted in no severe AEs directly related to the drug combination. The combination therapy also exerted antitumor activity with improved efficacy compared to the recent monotherapy with pembrolizumab in patients with advanced biliary tract cancer.
    Materialart: Online-Ressource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers14174229
    Sprache: Englisch
    Verlag: MDPI AG
    Publikationsdatum: 2022
    ZDB Id: 2527080-1
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 2
    Online-Ressource
    Online-Ressource
    Demonstration of Two-Dimensional Beam Steering through Wavelength Tuning with One-Dimensional Silicon Optical Phased Array
    MDPI AG ; 2022
    In:  Photonics Vol. 9, No. 11 ( 2022-10-28), p. 812-
    Details
    In: Photonics, MDPI AG, Vol. 9, No. 11 ( 2022-10-28), p. 812-
    Kurzfassung: We demonstrate two-dimensional beam steering through wavelength control using a one-dimensional optical phased array (OPA) in which a path difference is built up in each channel to allocate a phase delay sequentially. Prior to the beam steering through wavelength tuning, phase initialization was performed to form a single beam using electro-optic p-i-n phase shifters to compensate for the phase error due to fabrication imperfections. With a 79.6 μm path difference in the phase-feeding lines and a 2 μm pitch in the grating radiators, we achieved a continuous transversal steering of about 46° through a wavelength tuning of about 7 nm. By extending the wavelength tuning range to 90 nm, longitudinal steering was attained near 13° with a discrete interval of about 1°. The beam was maintained during full two-dimensional steering and experienced only a small degree of degradation in the beam divergences and in the side lobe level. We analyzed the parameters to be able to induce the degradation of beam quality considering the fabrication errors of the geometric parameters of the OPA. The results indicated that the scanning scheme employing wavelength tuning after initialization with phase shifters can greatly reduce the realignment process of the beam pattern, even in the presence of some effective index perturbation during the fabrication.
    Materialart: Online-Ressource
    ISSN: 2304-6732
    URL: Article
    DOI: 10.3390/photonics9110812
    Sprache: Englisch
    Verlag: MDPI AG
    Publikationsdatum: 2022
    ZDB Id: 2770002-1
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 3
    Online-Ressource
    Online-Ressource
    Liver Transplant Patients with High Preoperative Serum Bilirubin Levels Are at Increased Risk of Postoperative Delirium: A Retrospective Study
    MDPI AG ; 2020
    In:  Journal of Clinical Medicine Vol. 9, No. 5 ( 2020-05-24), p. 1591-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 9, No. 5 ( 2020-05-24), p. 1591-
    Kurzfassung: Postoperative delirium is a common complication after liver transplantation (LT). A high model for end-stage liver disease (MELD) score is an independent risk factor for postoperative delirium, but it is unclear which of the components of this score are risk indicators. The aim of this study was to analyze the incidence of postoperative delirium according to the preoperative serum bilirubin level, a component of the MELD score, in patients who underwent LT. The medical records of 325 patients who underwent LT from January 2010 to February 2019 at a single university hospital were retrospectively reviewed. The patients were divided into two groups: those who experienced postoperative delirium (Delirium group, n = 69) and those who did not (Control group, n = 256). Data on the patients’ demographic characteristics, perioperative management, and postoperative complications were collected. Mean preoperative bilirubin level was higher in the Delirium group than in the Control group (p 〈 0.0001). In the Delirium group, 54 (78.26%) patients had preoperative bilirubin levels above 3.5 mg/dL. In the multivariate analysis, preoperative bilirubin above 3.5 mg/dL was associated with postoperative delirium (p = 0.002). Therefore, preoperative hyperbilirubinemia is an independent risk factor for postoperative delirium.
    Materialart: Online-Ressource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm9051591
    Sprache: Englisch
    Verlag: MDPI AG
    Publikationsdatum: 2020
    ZDB Id: 2662592-1
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 4
    Online-Ressource
    Online-Ressource
    Aberrantly Expressed MicroRNAs in Cancer-Associated Fibroblasts and Their Target Oncogenic Signatures in Hepatocellular Carcinoma
    MDPI AG ; 2023
    In:  International Journal of Molecular Sciences Vol. 24, No. 5 ( 2023-02-21), p. 4272-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 24, No. 5 ( 2023-02-21), p. 4272-
    Kurzfassung: Cancer-associated fibroblasts (CAFs) contribute to tumor progression, and microRNAs (miRs) play an important role in regulating the tumor-promoting properties of CAFs. The objectives of this study were to clarify the specific miR expression profile in CAFs of hepatocellular carcinoma (HCC) and identify its target gene signatures. Small-RNA-sequencing data were generated from nine pairs of CAFs and para-cancer fibroblasts isolated from human HCC and para-tumor tissues, respectively. Bioinformatic analyses were performed to identify the HCC-CAF-specific miR expression profile and the target gene signatures of the deregulated miRs in CAFs. Clinical and immunological implications of the target gene signatures were evaluated in The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA_LIHC) database using Cox regression and TIMER analysis. The expressions of hsa-miR-101-3p and hsa-miR-490-3p were significantly downregulated in HCC-CAFs. Their expression in HCC tissue gradually decreased as HCC stage progressed in the clinical staging analysis. Bioinformatic network analysis using miRWalks, miRDB, and miRTarBase databases pointed to TGFBR1 as a common target gene of hsa-miR-101-3p and hsa-miR-490-3p. TGFBR1 expression was negatively correlated with miR-101-3p and miR-490-3p expression in HCC tissues and was also decreased by ectopic miR-101-3p and miR-490-3p expression. HCC patients with TGFBR1 overexpression and downregulated hsa-miR-101-3p and hsa-miR-490-3p demonstrated a significantly poorer prognosis in TCGA_LIHC. TGFBR1 expression was positively correlated with the infiltration of myeloid-derived suppressor cells, regulatory T cells, and M2 macrophages in a TIMER analysis. In conclusion, hsa-miR-101-3p and hsa-miR-490-3p were substantially downregulated miRs in CAFs of HCC, and their common target gene was TGFBR1. The downregulation of hsa-miR-101-3p and hsa-miR-490-3p, as well as high TGFBR1 expression, was associated with poor clinical outcome in HCC patients. In addition, TGFBR1 expression was correlated with the infiltration of immunosuppressive immune cells.
    Materialart: Online-Ressource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms24054272
    Sprache: Englisch
    Verlag: MDPI AG
    Publikationsdatum: 2023
    ZDB Id: 2019364-6
    SSG: 12
    Standort Signatur Einschränkungen Verfügbarkeit
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    Online-Ressource
  • 5
    Online-Ressource
    Online-Ressource
    Novel Gene Signatures as Prognostic Biomarkers for Predicting the Recurrence of Hepatocellular Carcinoma
    MDPI AG ; 2022
    In:  Cancers Vol. 14, No. 4 ( 2022-02-09), p. 865-
    Details
    In: Cancers, MDPI AG, Vol. 14, No. 4 ( 2022-02-09), p. 865-
    Kurzfassung: Hepatocellular carcinoma (HCC) has a high rate of cancer recurrence (up to 70%) in patients who undergo surgical resection. We investigated prognostic gene signatures for predicting HCC recurrence using in silico gene expression analysis. Recurrence-associated gene candidates were chosen by a comparative analysis of gene expression profiles from two independent whole-transcriptome datasets in patients with HCC who underwent surgical resection. Five promising candidate genes, CETN2, HMGA1, MPZL1, RACGAP1, and SNRPB were identified, and the expression of these genes was evaluated using quantitative reverse transcription PCR in the validation set (n = 57). The genes CETN2, HMGA1, RACGAP1, and SNRPB, but not MPZL1, were upregulated in patients with recurrent HCC. In addition, the combination of HMGA1 and MPZL1 demonstrated the best area under the curve (0.807, 95% confidence interval [CI] = 0.681–0.899) for predicting HCC recurrence. In terms of clinicopathological correlation, CETN2, MPZL1, RACGAP1, and SNRPB were upregulated in patients with microvascular invasion, and the expression of MPZL1 and SNRPB was increased in proportion to the Edmonson tumor differentiation grade. Additionally, overexpression of CETN2, HMGA1, and RACGAP1 correlated with poor overall survival (OS) and disease-free survival (DFS) in the validation set. Finally, Cox regression analysis showed that the expression of serum alpha-fetoprotein and RACGAP1 significantly affected OS, whereas platelet count, microvascular invasion, and HMGA1 expression significantly affected DFS. In conclusion, HMGA1 and RACGAP1 may be potential prognostic biomarkers for predicting the recurrence of HCC after surgical resection.
    Materialart: Online-Ressource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers14040865
    Sprache: Englisch
    Verlag: MDPI AG
    Publikationsdatum: 2022
    ZDB Id: 2527080-1
    Standort Signatur Einschränkungen Verfügbarkeit
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    Online-Ressource
  • 6
    Online-Ressource
    Online-Ressource
    Evaluation of Semen Quality of Jeju Black Cattle (JBC) to Select Bulls Optimal for Breeding and Establish Freezing Conditions Suitable for JBC Sperm
    MDPI AG ; 2022
    In:  Animals Vol. 12, No. 5 ( 2022-02-22), p. 535-
    Details
    In: Animals, MDPI AG, Vol. 12, No. 5 ( 2022-02-22), p. 535-
    Kurzfassung: To optimize the reproduction of Jeju black cattle (JBC), freezing conditions for sperm were established and sperm motility, vitality, morphology, and fertility were evaluated to select the optimal bull for breeding. Semen samples from five JBC bulls were individually mixed with freezing medium at a final concentration of 1 × 108 sperm/mL and frozen in liquid nitrogen vapor at a height of 3 or 7 cm (referred to as 3 cm sperm and 7 cm sperm, respectively). When the freezing conditions were compared, the motility of 7 cm sperm was significantly higher than that of 3 cm sperm for the JBC-A bull. The motility, curvilinear velocity, straight-line velocity, and average path velocity of fresh and frozen–thawed sperm were the highest for the JBC-A bull. The vitalities of fresh and frozen–thawed sperm were the highest for the JBC-A/E and JBC-A bulls, respectively. The percentage of normal cells in fresh sperm was the highest for the JBC-D bull. The rates of the normal formation of two pronuclei and total sperm penetration were the highest in zygotes fertilized with sperm from the JBC-A bull. The sperm from the JBC-A bull had superior qualities and are thus the most appropriate choice for the preservation and reproduction of these endangered cattle.
    Materialart: Online-Ressource
    ISSN: 2076-2615
    URL: Article
    DOI: 10.3390/ani12050535
    Sprache: Englisch
    Verlag: MDPI AG
    Publikationsdatum: 2022
    ZDB Id: 2606558-7
    SSG: 23
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 7
    Online-Ressource
    Online-Ressource
    Upregulation of Peroxiredoxin-2 in Well-Differentiated Pancreatic Neuroendocrine Tumors and Its Utility as a Biomarker for Predicting the Response to Everolimus
    MDPI AG ; 2020
    In:  Antioxidants Vol. 9, No. 11 ( 2020-11-09), p. 1104-
    Details
    In: Antioxidants, MDPI AG, Vol. 9, No. 11 ( 2020-11-09), p. 1104-
    Kurzfassung: Pancreatic neuroendocrine neoplasms (pNENs) account for 2–3% of pancreatic malignancies. Peroxiredoxins (Prdxs), which are major cellular antioxidants, are involved in multiple oncogenic signaling pathways. We investigated the role of peroxiredoxin-2 in QGP-1 human pNEN cell line and patient-derived pNEN tissue. To validate the cancer stem cell-like cell characteristics of QGP-1 cells in spheroid culture, in vitro analyses and xenografting were performed. Furthermore, immunohistochemical staining was conducted to verify the overexpression of Prdx2 in pNEN tissue. Prdx2 expression was high at the mRNA and protein levels in QGP-1 cells. Prdx2 was also overexpressed in patient-derived pNEN tissue. Silencing of Prdx2 using siRNA induced overexpression and phosphorylation of ERK and AKT in QGP-1. Cell proliferation was increased by treating QGP-1 cells with siPrdx2, and the IC50 of everolimus increased suggesting resistance to everolimus. Interestingly, QGP-1 spheroid cells, which exhibited cancer stem cell-like features, exhibited lower expression of Prdx2 and mTOR. The results suggest that Prdx2 expression level and its activity may be a potential predictive biomarker for therapeutic response or resistance to everolimus in pNEN.
    Materialart: Online-Ressource
    ISSN: 2076-3921
    URL: Article
    DOI: 10.3390/antiox9111104
    Sprache: Englisch
    Verlag: MDPI AG
    Publikationsdatum: 2020
    ZDB Id: 2704216-9
    SSG: 15,3
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 8
    Online-Ressource
    Online-Ressource
    NRF2 Knockdown Resensitizes 5-Fluorouracil-Resistant Pancreatic Cancer Cells by Suppressing HO-1 and ABCG2 Expression
    MDPI AG ; 2020
    In:  International Journal of Molecular Sciences Vol. 21, No. 13 ( 2020-06-30), p. 4646-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 21, No. 13 ( 2020-06-30), p. 4646-
    Kurzfassung: Chemoresistance is a leading cause of morbidity and mortality in patients with pancreatic cancer and remains an obstacle to successful treatment. The antioxidant transcription factor nuclear factor (erythroid-derived 2)-related factor 2 (NRF2), which plays important roles in tumor angiogenesis and invasiveness, is upregulated in pancreatic ductal adenocarcinoma (PDAC), where it correlates with poor survival. Here, we investigated the role of NRF2 in two 5-Fluourouracil-resistant (5-FUR) PDAC cell lines: BxPC-3 and CFPAC-1. Levels of NRF2 and antioxidants, such as heme oxygenase 1 (HO-1), NAD(P)H quinone dehydrogenase 1 (NQO1), and superoxide dismutase 2 (SOD2), were higher in the chemoresistant cells than in their chemosensitive counterparts. Expression of epithelial mesenchymal transition (EMT) markers, stemness markers, including Nanog, Oct4, and CD133, and that of the drug transporter ATP binding cassette, subfamily G, member A2 (ABCG2) was also upregulated in 5-FUR PDAC cells. NRF2 knockdown reversed 5-FU resistance of PDAC cells via suppression of ABCG2 and HO-1. In summary, these data indicate that NRF2 is a potential target for resensitizing 5-FUR PDAC cells to 5-FU to improve treatment outcomes in patients with pancreatic cancer.
    Materialart: Online-Ressource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms21134646
    Sprache: Englisch
    Verlag: MDPI AG
    Publikationsdatum: 2020
    ZDB Id: 2019364-6
    SSG: 12
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 9
    Online-Ressource
    Online-Ressource
    Tumor Endothelial Cells-Associated Integrin Alpha-6 as a Promising Biomarker for Early Detection and Prognosis of Hepatocellular Carcinoma
    MDPI AG ; 2023
    In:  Cancers Vol. 15, No. 16 ( 2023-08-17), p. 4156-
    Details
    In: Cancers, MDPI AG, Vol. 15, No. 16 ( 2023-08-17), p. 4156-
    Kurzfassung: HCC remains a lethal cancer type, with early detection being critical for improved patient outcomes. This study introduces a comprehensive methodological approach to identify the ITGA6 gene as a potential blood marker for early HCC (eHCC) detection. We initially analyzed the GSE114564 dataset encompassing various stages of liver disease, identifying 972 differentially expressed genes in HCC. A refined analysis yielded 59 genes specifically differentially expressed in early HCC, including ITGA6. Subsequent validation in multiple datasets confirmed the consistent upregulation of ITGA6 in HCC. In addition, when analyzing progression-free survival (PFS) within the entire patient cohort and overall survival (OS) specifically among patients classified as tumor grade G1, the group of patients characterized by high expression levels of ITGA6 displayed an elevated risk ratio in relation to prognosis. Further analyses demonstrated the predominant expression of ITGA6 in TECs and its enrichment in angiogenesis-related pathways. Additionally, positive correlations were found between ITGA6 expression and pro-tumorigenic immune cells, but not with anti-tumorigenic immune cells. Our study elucidates the potential of ITGA6 as a blood-based marker for HCC early detection and diagnosis and its complex interplay with the tumor microenvironment. Further research may lead to novel strategies for HCC management and patient care.
    Materialart: Online-Ressource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers15164156
    Sprache: Englisch
    Verlag: MDPI AG
    Publikationsdatum: 2023
    ZDB Id: 2527080-1
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 10
    Online-Ressource
    Online-Ressource
    Differential Factors for Predicting Outcomes in Left Main versus Non-Left Main Coronary Bifurcation Stenting
    MDPI AG ; 2021
    In:  Journal of Clinical Medicine Vol. 10, No. 14 ( 2021-07-07), p. 3024-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 10, No. 14 ( 2021-07-07), p. 3024-
    Kurzfassung: Background: No large-scale study has compared the clinical and angiographic predictors of cardiovascular events in patients with left main bifurcation (LMB) and non-LMB stenting after second-generation DES implantation. Herein, we investigated differential clinical and angiographic factors for predicting outcomes in LMB versus non-LMB stenting. Methods: A total of 2648 patients with bifurcation lesions treated with second-generation DESs from the retrospective patient cohort were divided into an LMB group (n = 935) and a non-LMB group (n = 1713). The primary outcome was the 7-year incidence of target lesion failure (TLF), defined as the composite of cardiac death, myocardial infarction, and target lesion revascularization. Results: The incidence of TLF was 9.8%. Those in the LMB group were associated with a higher risk of TLF (14.2% versus 7.5%, p 〈 0.001) than those in the non-LMB group. Regarding the LMB group, independent predictors of TLF were chronic kidney disease (CKD), reduced left ventricular ejection fraction (LVEF), and two-stenting. Regarding the non-LMB group, CKD, reduced LVEF, old age, diabetes, and small diameter of the main vessel stent were independent predictors of TLF. Conclusions: The two-stent strategy could potentially increase TLF for the LMB lesions, and achieving the maximal diameter of the main vessel stent could result in better clinical outcomes for non-LMB lesions.
    Materialart: Online-Ressource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm10143024
    Sprache: Englisch
    Verlag: MDPI AG
    Publikationsdatum: 2021
    ZDB Id: 2662592-1
    Standort Signatur Einschränkungen Verfügbarkeit
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    Online-Ressource
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