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  • Online Resource  (15)
  • MDPI AG  (15)
  • 1
    Online Resource
    Online Resource
    Discovery of Proteins Responsible for Resistance to Three Chemotherapy Drugs in Breast Cancer Cells Using Proteomics and Bioinformatics Analysis
    MDPI AG ; 2022
    In:  Molecules Vol. 27, No. 6 ( 2022-03-08), p. 1762-
    Details
    In: Molecules, MDPI AG, Vol. 27, No. 6 ( 2022-03-08), p. 1762-
    Abstract: Chemoresistance is a daunting obstacle to the effective treatment of breast cancer patients receiving chemotherapy. Although the mechanism of chemotherapy drug resistance has been explored broadly, the precise mechanism at the proteome level remains unclear. Especially, comparative studies between widely used anticancer drugs in breast cancer are very limited. In this study, we employed proteomics and bioinformatics approaches on chemoresistant breast cancer cell lines to understand the underlying resistance mechanisms that resulted from doxorubicin (DR), paclitaxel (PR), and tamoxifen (TAR). In total, 10,385 proteins were identified and quantified from three TMT 6-plex and one TMT 10-plex experiments. Bioinformatics analysis showed that Notch signaling, immune response, and protein re-localization processes were uniquely associated with DR, PR, and TAR resistance, respectively. In addition, proteomic signatures related to drug resistance were identified as potential targets of many FDA-approved drugs. Furthermore, we identified potential prognostic proteins with significant effects on overall survival. Representatively, PLXNB2 expression was associated with a highly significant increase in risk, and downregulation of ACOX3 was correlated with a worse overall survival rate. Consequently, our study provides new insights into the proteomic aspects of the distinct mechanisms underlying chemoresistance in breast cancer.
    Type of Medium: Online Resource
    ISSN: 1420-3049
    URL: Article
    DOI: 10.3390/molecules27061762
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2008644-1
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  • 2
    Online Resource
    Online Resource
    Moesin (MSN) as a Novel Proteome-Based Diagnostic Marker for Early Detection of Invasive Bladder Urothelial Carcinoma in Liquid-Based Cytology
    MDPI AG ; 2020
    In:  Cancers Vol. 12, No. 4 ( 2020-04-21), p. 1018-
    Details
    In: Cancers, MDPI AG, Vol. 12, No. 4 ( 2020-04-21), p. 1018-
    Abstract: Bladder urothelial carcinoma (BUC) is the most lethal malignancy of the urinary tract. Treatment for the disease highly depends on the invasiveness of cancer cells. Therefore, a predictive biomarker needs to be identified for invasive BUC. In this study, we employed proteomics methods on urine liquid-based cytology (LBC) samples and a BUC cell line library to determine a novel predictive biomarker for invasive BUC. Furthermore, an in vitro three-dimensional (3D) invasion study for biological significance and diagnostic validation through immunocytochemistry (ICC) were also performed. The proteomic analysis suggested moesin (MSN) as a potential biomarker to predict the invasiveness of BUC. The in vitro 3D invasion study showed that inhibition of MSN significantly decreased invasiveness in BUC cell lines. Further validation using ICC ultimately confirmed moesin (MSN) as a potential biomarker to predict the invasiveness of BUC (p = 0.023). In conclusion, we suggest moesin as a potential diagnostic marker for early detection of BUC with invasion in LBC and as a potential therapeutic target.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers12041018
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2527080-1
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  • 3
    Online Resource
    Online Resource
    Dual Oxidase 2 (DUOX2) as a Proteomic Biomarker for Predicting Treatment Response to Chemoradiation Therapy for Locally Advanced Rectal Cancer: Using High-Throughput Proteomic Analysis and Machine Learning Algorithm
    MDPI AG ; 2022
    In:  International Journal of Molecular Sciences Vol. 23, No. 21 ( 2022-10-26), p. 12923-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 23, No. 21 ( 2022-10-26), p. 12923-
    Abstract: High-throughput mass-spectrometry-based quantitative proteomic analysis was performed using formalin-fixed, paraffin-embedded (FFPE) biopsy samples obtained before treatment from 13 patients with locally advanced rectal cancer (LARC), who were treated with concurrent chemoradiation therapy (CCRT) followed by surgery. Patients were divided into complete responder (CR) and non-complete responder (nCR) groups. Immunohistochemical (IHC) staining of 79 independent FFPE tissue samples was performed to validate the predictive ability of proteomic biomarker candidates. A total of 3637 proteins were identified, and the expression of 498 proteins was confirmed at significantly different levels (differentially expressed proteins—DEPs) between two groups. In Gene Ontology enrichment analyses, DEPs enriched in biological processes in the CR group included proteins linked to cytoskeletal organization, immune response processes, and vesicle-associated protein transport processes, whereas DEPs in the nCR group were associated with biosynthesis, transcription, and translation processes. Dual oxidase 2 (DUOX2) was selected as the most predictive biomarker in machine learning algorithm analysis. Further IHC validation ultimately confirmed DUOX2 as a potential biomarker for predicting the response of nCR to CCRT. In conclusion, this study suggests that the treatment response to RT may be affected by the pre-treatment tumor microenvironment. DUOX2 is a potential biomarker for the early prediction of nCR after CCRT.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms232112923
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 4
    Online Resource
    Online Resource
    The Role of Nicotinamide in Cancer Chemoprevention and Therapy
    MDPI AG ; 2020
    In:  Biomolecules Vol. 10, No. 3 ( 2020-03-20), p. 477-
    Details
    In: Biomolecules, MDPI AG, Vol. 10, No. 3 ( 2020-03-20), p. 477-
    Abstract: Nicotinamide (NAM) is a water-soluble form of Vitamin B3 (niacin) and a precursor of nicotinamide-adenine dinucleotide (NAD+) which regulates cellular energy metabolism. Except for its role in the production of adenosine triphosphate (ATP), NAD+ acts as a substrate for several enzymes including sirtuin 1 (SIRT1) and poly ADP-ribose polymerase 1 (PARP1). Notably, NAM is an inhibitor of both SIRT1 and PARP1. Accumulating evidence suggests that NAM plays a role in cancer prevention and therapy. Phase III clinical trials have confirmed its clinical efficacy for non-melanoma skin cancer chemoprevention or as an adjunct to radiotherapy against head and neck, laryngeal, and urinary bladder cancers. Evidence for other cancers has mostly been collected through preclinical research and, in its majority, is not yet evidence-based. NAM has potential as a safe, well-tolerated, and cost-effective agent to be used in cancer chemoprevention and therapy. However, more preclinical studies and clinical trials are needed to fully unravel its value.
    Type of Medium: Online Resource
    ISSN: 2218-273X
    URL: Article
    DOI: 10.3390/biom10030477
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2701262-1
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  • 5
    Online Resource
    Online Resource
    Automated Gleason Scoring and Tumor Quantification in Prostate Core Needle Biopsy Images Using Deep Neural Networks and Its Comparison with Pathologist-Based Assessment
    MDPI AG ; 2019
    In:  Cancers Vol. 11, No. 12 ( 2019-11-25), p. 1860-
    Details
    In: Cancers, MDPI AG, Vol. 11, No. 12 ( 2019-11-25), p. 1860-
    Abstract: The Gleason grading system, currently the most powerful prognostic predictor of prostate cancer, is based solely on the tumor’s histological architecture and has high inter-observer variability. We propose an automated Gleason scoring system based on deep neural networks for diagnosis of prostate core needle biopsy samples. To verify its efficacy, the system was trained using 1133 cases of prostate core needle biopsy samples and validated on 700 cases. Further, system-based diagnosis results were compared with reference standards derived from three certified pathologists. In addition, the system’s ability to quantify cancer in terms of tumor length was also evaluated via comparison with pathologist-based measurements. The results showed a substantial diagnostic concordance between the system-grade group classification and the reference standard (0.907 quadratic-weighted Cohen’s kappa coefficient). The system tumor length measurements were also notably closer to the reference standard (correlation coefficient, R = 0.97) than the original hospital diagnoses (R = 0.90). We expect this system to assist pathologists to reduce the probability of over- or under-diagnosis by providing pathologist-level second opinions on the Gleason score when diagnosing prostate biopsy, and to support research on prostate cancer treatment and prognosis by providing reproducible diagnosis based on the consistent standards.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers11121860
    Language: English
    Publisher: MDPI AG
    Publication Date: 2019
    detail.hit.zdb_id: 2527080-1
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  • 6
    Online Resource
    Online Resource
    Molecular Profiling of Malignant Pleural Effusions with Next Generation Sequencing (NGS): Evidence that Supports Its Role in Cancer Management
    MDPI AG ; 2020
    In:  Journal of Personalized Medicine Vol. 10, No. 4 ( 2020-11-01), p. 206-
    Details
    In: Journal of Personalized Medicine, MDPI AG, Vol. 10, No. 4 ( 2020-11-01), p. 206-
    Abstract: Malignant pleural effusions (MPEs) often develop in advanced cancer patients and confer significant morbidity and mortality. In this review, we evaluated whether molecular profiling of MPEs with next generation sequencing (NGS) could have a role in cancer management, focusing on lung cancer. We reviewed and compared the diagnostic performance of pleural fluid liquid biopsy with other types of samples. When applied in MPEs, NGS may have comparable performance with corresponding tissue biopsies, yield higher DNA amount, and detect more genetic aberrations than blood-derived liquid biopsies. NGS in MPEs may also be preferable to plasma liquid biopsy in advanced cancer patients with a MPE and a paucicellular or difficult to obtain tissue/fine-needle aspiration biopsy. Of interest, post-centrifuge supernatant NGS may exhibit superior results compared to cell pellet, cell block or other materials. NGS in MPEs can also guide clinicians in tailoring established therapies and identifying therapy resistance. Evidence is still premature regarding the role of NGS in MPEs from patients with cancers other than lung. We concluded that MPE processing could provide useful prognostic and theranostic information, besides its diagnostic role.
    Type of Medium: Online Resource
    ISSN: 2075-4426
    URL: Article
    DOI: 10.3390/jpm10040206
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2662248-8
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  • 7
    Online Resource
    Online Resource
    Serine-Arginine Protein Kinase 1 (SRPK1) as a Prognostic Factor and Potential Therapeutic Target in Cancer: Current Evidence and Future Perspectives
    MDPI AG ; 2019
    In:  Cells Vol. 9, No. 1 ( 2019-12-19), p. 19-
    Details
    In: Cells, MDPI AG, Vol. 9, No. 1 ( 2019-12-19), p. 19-
    Abstract: Cancer, a heterogeneous disease composed of tumor cells and microenvironment, is driven by deregulated processes such as increased proliferation, invasion, metastasis, angiogenesis, and evasion of apoptosis. Alternative splicing, a mechanism led by splicing factors, is implicated in carcinogenesis by affecting any of the processes above. Accumulating evidence suggests that serine-arginine protein kinase 1 (SRPK1), an enzyme that phosphorylates splicing factors rich in serine/arginine domains, has a prognostic and potential predictive role in various cancers. Its upregulation is correlated with higher tumor staging, grading, and shorter survival. SRPK1 is also highly expressed in the premalignant changes of some cancers, showing a potential role in the early steps of carcinogenesis. Of interest, its downregulation in preclinical models has mostly been tumor-suppressive and affected diverse processes heterogeneously, depending on the oncogenic context. In addition, targeting SRPK1 has enhanced sensitivity to platinum-based chemotherapy in some cancers. Lastly, its aberrant function has been noted not only in cancer cells but also in the endothelial cells of the microenvironment. Although the aforementioned evidence seems promising, more studies are needed to reinforce the use of SRPK1 inhibitors in clinical trials.
    Type of Medium: Online Resource
    ISSN: 2073-4409
    URL: Article
    DOI: 10.3390/cells9010019
    Language: English
    Publisher: MDPI AG
    Publication Date: 2019
    detail.hit.zdb_id: 2661518-6
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  • 8
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    Online Resource
    Effects of Decomplexation Rates on Ternary Gene Complex Transfection with α-Poly(l-Lysine) or ε-Poly(l-Lysine) as a Decomplexation Controller in An Easy-To-Transfect Cell or A Hard-To-Transfect Cell
    MDPI AG ; 2020
    In:  Pharmaceutics Vol. 12, No. 6 ( 2020-05-28), p. 490-
    Details
    In: Pharmaceutics, MDPI AG, Vol. 12, No. 6 ( 2020-05-28), p. 490-
    Abstract: The tight binding of pDNA with a cationic polymer is the crucial requirement that prevents DNA degradation from undesired DNase attack to safely deliver the pDNA to its target site. However, cationic polymer-mediated strong gene holding limits pDNA dissociation from the gene complex, resulting in a reduction in transfection efficiency. In this study, to control the decomplexation rate of pDNA from the gene complex in a hard-to-transfect cell or an easy-to-transfect cell, either α-poly(l-lysine) (APL) or ε-poly(l-lysine) (EPL) was incorporated into branched polyethylenimine (bPEI)-based nanocomplexes (NCs). Compared to bPEI/pDNA NCs, the addition of APL or EPL formed smaller bPEI-APL/pDNA NCs with similar zeta potentials or larger bPEI-EPL/pDNA NCs with reduced zeta potentials, respectively, due to the different characteristics of the primary amines in the two poly(l-lysine)s (PLs). Interestingly, although both bPEI-APL/pDNA NCs and bPEI-EPL/pDNA NCs showed similar pDNA compactness to bPEI/pDNA NCs, the addition of APL or EPL resulted in slower or faster pDNA release, respectively, from the bPEI-PL/pDNA NCs than from the bPEI/pDNA NCs. bPEI-EPL/pDNA NCs with a decomplexation enhancer (i.e., EPL) improved the transfection efficiency (TE) in both a hard-to-transfect HepG2 cell and an easy-to-transfect HEK293 cell. However, although a decomplexation inhibitor (i.e., APL) reduced the TE of bPEI-APL/pDNA NCs in both cells, the degree of reduction in the TE could be compensated by PL-mediated enhanced nuclear delivery, particularly in HepG2 cells but not HEK293 cells, because both PLs facilitate nuclear localization of the gene complex per its cellular uptake. In conclusion, a decomplexation rate controller could be a potential factor to establish a high TE and design clinically available gene complex systems.
    Type of Medium: Online Resource
    ISSN: 1999-4923
    URL: Article
    DOI: 10.3390/pharmaceutics12060490
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2527217-2
    SSG: 15,3
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  • 9
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    Online Resource
    Outcomes of Pediatric Liver Transplantation in Korea Using Two National Registries
    MDPI AG ; 2020
    In:  Journal of Clinical Medicine Vol. 9, No. 11 ( 2020-10-26), p. 3435-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 9, No. 11 ( 2020-10-26), p. 3435-
    Abstract: Background: This retrospective study aimed to evaluate overall survival and the risk factors for mortality among Korean pediatric liver transplantation (LT) patients using data from two national registries: the Korean Network Organ Sharing (KONOS) of the Korea Centers for Disease Control and Prevention and the Korean Organ Transplantation Registry (KOTRY). Methods: Prospectively collected data of 755 pediatric patients who underwent primary LT (KONOS, February 2000 to December 2015; KOTRY, May 2014 to December 2017) were retrospectively reviewed. Results: The 1-, 5-, 10-, and 15-year survival rates were 90.6%, 86.7%, 85.8%, and 85.5%, respectively, in KONOS, and the 1-month, 3-month, 1-year, and 2-year survival rates were 92.1%, 89.4%, 89.4%, and 87.2%, respectively, in KOTRY. There was no significant difference in survival between the two registries. Multivariate analysis identified that body weight ≥6 kg (p 〈 0.001), biliary atresia as underlying liver disease (p = 0.001), and high-volume center (p 〈 0.001) were associated with better survival according to the KONOS database, while hepatic artery complication (p 〈 0.001) was associated with poorer overall survival rates according to the KOTRY database. Conclusion: Long-term pediatric patient survival after LT was satisfactory in this Korean national registry analysis. However, children with risk factors for poor outcomes should be carefully managed after LT.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm9113435
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2662592-1
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  • 10
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    Online Resource
    The High-Sensitivity C-Reactive Protein/Albumin Ratio Predicts Long-Term Oncologic Outcomes after Curative Resection for Hepatocellular Carcinoma
    MDPI AG ; 2018
    In:  Journal of Clinical Medicine Vol. 7, No. 6 ( 2018-06-07), p. 139-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 7, No. 6 ( 2018-06-07), p. 139-
    Abstract: High-sensitivity C-reactive protein (hsCRP) is a prognostic factor for hepatocellular carcinoma (HCC), while albumin is known to be a disease severity index of the malnutrition status in HCC patients. The present study investigated the association between postoperative hsCRP/albumin ratio and both overall survival (OS) and recurrence-free survival (RFS) following HCC surgery. This retrospective observational study examined the medical records of 389 patients who underwent resection for HCC between 2004 and 2013. Postoperative day 0–1 hsCRP/albumin ratio was collected, and the optimal postoperative mortality cut-off point was derived using receiver operating characteristics (ROC) analysis. A postoperative hsCRP/albumin ratio increase of 1.0 was associated with a 1.171-fold increase in mortality (hazard ratio (HR): 1.171, 95% confidence interval (CI): 1.072–1.278, p 〈 0.001) and a 1.19-fold increase in recurrence (HR: 1.190, 95% CI: 1.108–1.278, p 〈 0.001). The hsCRP/albumin ratio cut-off point was found to be 0.625 and 0.500. When patients were grouped by this cut-off point, the 〉 0.625 group showed a 2.257-fold increase in mortality (HR: 2.257, 95% CI: 1.470–3.466, p 〈 0.001), and the 〉 0.500 group showed a 1.518-fold increase in recurrence (HR: 1.518, 95% CI: 1.125–2.050, p = 0.006).
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm7060139
    Language: English
    Publisher: MDPI AG
    Publication Date: 2018
    detail.hit.zdb_id: 2662592-1
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