The Tohoku journal of experimental medicine
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Tohoku J. Exp. Med. · May 2023
Clinical Implication of Keratin-15 Quantification for Renal Cell Carcinoma Management: Its Dysregulation and Association with Clinicopathologic Characteristics and Prognostication.
Keratin-15 (KRT15) participates in the tumorigenesis of several cancers, especially in urinary tract carcinomas by regulating basal urothelial cell malignant proliferation and differentiation. This study intended to explore the association of KRT15 with tumor features and survival in renal cell carcinoma (RCC) patients. Totally, 210 RCC patients receiving surgical resection were retrospectively enrolled, and then, KRT15 was detected by immunohistochemistry (IHC) assay in the tumor and adjacent tissues. ⋯ In addition, multivariate regression analysis revealed that high KRT15 [hazard ratio (HR) = 1.719, P = 0.023], higher pathological grade (HR = 1.847, P < 0.001), and higher N stage (HR = 3.447, P < 0.001) were independently related to poor DFS; high KRT15 (HR = 1.796, P = 0.034), eastern cooperative oncology group performance status score (1 vs. 0) (HR = 1.734, P = 0.037), higher pathological grade (HR = 2.045, P < 0.001), and higher N stage (HR = 3.966, P < 0.001) were independently linked to unsatisfactory OS. Furthermore, data from Gene Expression Profiling Interactive Analysis suggested that KRT15 was linked to poor DFS (P = 0.037) and OS (P < 0.001); data from THE HUMAN PROTEIN ATLAS revealed that KRT15 was associated with shorter OS (P < 0.001) in RCC patients. In conclusion, KRT15 is increased in tumor tissues, and correlates with higher tumor stage and larger tumor size, along with poor prognosis for RCC.
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Tohoku J. Exp. Med. · May 2023
Differential Expressions of ADAM28 and ADAMTSL3 in Gingival Tissue of Patients with Periodontitis.
The modulation of gene expression via DNA methylation modifications is relevant to the pathogenesis of periodontitis. This study aimed at identifying novel biomarkers in gingival tissues from periodontitis by integrally analyzing methylation profiles and gene expression data. Differential gene expressions (DGEs) of dataset GSE106090 were obtained from the Gene Expression Omnibus (GEO) database for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. ⋯ There was one up-regulated mRNA with hypo-methylated gene [ADAM28 (a disintegrin and metalloproteinase 28)] and one down-regulated mRNA with hyper-methylated gene [ADAMTSL3 (a disintegrin-like and metalloprotease domain with thrombospondin type I motifs-like-3)] after integrating GSE106090 and GSE173082 datasets. Increased ADAM28 expression was validated in gingival tissues from periodontitis patients as compared to the healthy controls with decreased ADAMTSL3 expression, which were correlated with disease stage. ADAM28 and ADAMTSL3 may act as novel biomarkers in gingival tissues from periodontitis by a comprehensive analysis of bioinformatics methods and executed validation.
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Tohoku J. Exp. Med. · May 2023
Rhamnazin Enhanced Anti-Tumor Efficacy of Anti-PD-1 Therapy for Lung Cancer in Mice through Inhibition of PD-L1 Expression.
Emerging studies suggest the significance of broadening the benefit of anti-programmed cell death 1 (PD-1) therapy for lung cancer. The anti-angiogenic agents have been reported to alter the tumor microenvironment and contributes to efficiency of anti-PD-1 therapy. This study aims to investigate whether the anti-angiogenic agent rhamnazin enhances the efficacy of anti-PD-1 therapy in lung cancer. ⋯ T cell proliferation and cytotoxic factor production were evaluated after co-culturing with non-small cell lung cancer (NSCLC) H1975 cells. Rhamnazin promotes T cell proliferation and up-regulated IFN-γ, TNF-α and granzyme B in the co-culture system, while VEGFR2 overexpression abrogated these changes. These data suggest that rhamnazin enhances anti-tumor effect of anti-PD-1 therapy for lung cancer in mice via inhibition of PD-L1 expression.
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Tohoku J. Exp. Med. · May 2023
Case ReportsEffects of Low-Dose Tadalafil in a Patient with Biventricular Heart Failure: A Case Report.
Phosphodiesterase type 5 (PDE5) inhibitors such as tadalafil, can improve cardiac output by increasing left ventricular preload; however, there are concerns that this can increase the risk of heart failure due to pulmonary congestion in patients with elevated left ventricular end-diastolic pressure. We encountered a case in which low dose tadalafil improved the hemodynamics of a 66-year-old male patient with dilated cardiomyopathy (DCM) with congestion and low cardiac output due to biventricular dysfunction. The patient received a cardiac resynchronization therapy defibrillator (CRT-D) and appropriate medical therapy for heart failure. ⋯ However, the administration of a low dose of tadalafil for the patient's benign prostatic hyperplasia allowed for the increase in the dose of RAAS inhibitors and markedly improved his subjective symptoms and hemodynamics. Because of the biventricular dysfunction in severe cases, we often experience further promotion of low cardiac output by standard treatments such as RAAS inhibitors, in which low doses of PDE5 inhibitors may be effective in maintaining biventricular linkage. PDE5 inhibitors may be effective in patients, who are not able to increase the dose of RAAS inhibitors due to low cardiac output.
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Tohoku J. Exp. Med. · May 2023
Berberine Reverses the Tumorigenic Function of Colon Cancer Cell-Derived Exosomes.
Exosomes derived from colon cancer cells has been found to elevate viability and metastasis of recipient cells. Berberine is a plant-derived natural compound that has shown anti-colon cancer potential. However, berberine's impacts on the tumorigenic functions of tumor exosomes have yet to be evaluated. ⋯ The treatment with 100, 150, and 200 µg/ml of berberine-primed exosomes could dose-dependently decrease the viability [by -35.4% (p < 0.0001), -47% (p < 0.0001), and -65.5% (p < 0.0001), respectively], migration [by -24% (p = 0.0001), -43.5% (p = 0.0001), and -65.2% (p = 0.0001), respectively], and invasion [by -29% (p < 0.0001), -58.8% (p < 0.0001), and -69.7% (p < 0.0001), respectively] of HCT116 cells compared to the control. However, non-primed exosomes exerted significant inducing effects on the viability and metastatic ability of HCT116 cells. In conclusion, berberine can reverse the tumorigenic function of colon cancer exosomes and, thus, exert a remarkable suppressive impact against the survival and metastatic ability of colon cancer cells.