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  • 1
    Online Resource
    Online Resource
    Expression of Phospho-ELK1 and Its Prognostic Significance in Urothelial Carcinoma of the Upper Urinary Tract
    MDPI AG ; 2018
    In:  International Journal of Molecular Sciences Vol. 19, No. 3 ( 2018-03-08), p. 777-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 19, No. 3 ( 2018-03-08), p. 777-
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms19030777
    Language: English
    Publisher: MDPI AG
    Publication Date: 2018
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 2
    Online Resource
    Online Resource
    Identification of BXDC2 as a Key Downstream Effector of the Androgen Receptor in Modulating Cisplatin Sensitivity in Bladder Cancer
    MDPI AG ; 2021
    In:  Cancers Vol. 13, No. 5 ( 2021-02-26), p. 975-
    Details
    In: Cancers, MDPI AG, Vol. 13, No. 5 ( 2021-02-26), p. 975-
    Abstract: Underlying mechanisms for resistance to cisplatin-based chemotherapy in bladder cancer patients are largely unknown, although androgen receptor (AR) activity, as well as extracellular signal-regulated kinase (ERK) signaling, has been indicated to correlate with chemosensitivity. We also previously showed ERK activation by androgen treatment in AR-positive bladder cancer cells. Because our DNA microarray analysis in control vs. AR-knockdown bladder cancer lines identified BXDC2 as a potential downstream target of AR, we herein assessed its functional role in cisplatin sensitivity, using bladder cancer lines and surgical specimens. BXDC2 protein expression was considerably downregulated in AR-positive or cisplatin-resistant cells. BXDC2-knockdown sublines were significantly more resistant to cisplatin, compared with respective controls. Without cisplatin treatment, BXDC2-knockdown resulted in significant increases/decreases in cell proliferation/apoptosis, respectively. An ERK activator was also found to reduce BXDC2 expression. Immunohistochemistry showed downregulation of BXDC2 expression in tumor (vs. non-neoplastic urothelium), higher grade/stage tumor (vs. lower grade/stage), and AR-positive tumor (vs. AR-negative). Patients with BXDC2-positive/AR-negative muscle-invasive bladder cancer had a significantly lower risk of disease-specific mortality, compared to those with a BXDC2-negative/AR-positive tumor. Additionally, in those undergoing cisplatin-based chemotherapy, BXDC2 positivity alone (p = 0.083) or together with AR negativity (p = 0.047) was associated with favorable response. We identified BXDC2 as a key molecule in enhancing cisplatin sensitivity. AR-ERK activation may thus be associated with chemoresistance via downregulating BXDC2 expression in bladder cancer.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers13050975
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2527080-1
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  • 3
    Online Resource
    Online Resource
    The Role of Glucocorticoid Receptor Signaling in Bladder Cancer Progression
    MDPI AG ; 2018
    In:  Cancers Vol. 10, No. 12 ( 2018-12-04), p. 484-
    Details
    In: Cancers, MDPI AG, Vol. 10, No. 12 ( 2018-12-04), p. 484-
    Abstract: Previous preclinical studies have indicated that the activation of glucocorticoid receptor signaling results in inhibition of the growth of various types of tumors. Indeed, several glucocorticoids, such as dexamethasone and prednisone, have been prescribed for the treatment of, for example, hematological malignancies and castration-resistant prostate cancer. By contrast, the role of glucocorticoid-mediated glucocorticoid receptor signaling in the progression of bladder cancer remains far from being fully understood. Nonetheless, emerging evidence implies its unique functions in urothelial cancer cells. Moreover, the levels of glucocorticoid receptor expression have been documented to significantly associate with the prognosis of patients with bladder cancer. This review summarizes the available data suggesting the involvement of glucocorticoid-mediated glucocorticoid receptor signaling in urothelial tumor outgrowth and highlights the potential underlying molecular mechanisms. The molecules/pathways that contribute to modulating glucocorticoid receptor activity and function in bladder cancer cells are also discussed.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers10120484
    Language: English
    Publisher: MDPI AG
    Publication Date: 2018
    detail.hit.zdb_id: 2527080-1
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  • 4
    Online Resource
    Online Resource
    Relationship between Dislocation Density and Oxygen Concentration in Silicon Crystals during Directional Solidification
    MDPI AG ; 2018
    In:  Crystals Vol. 8, No. 6 ( 2018-06-07), p. 244-
    Details
    In: Crystals, MDPI AG, Vol. 8, No. 6 ( 2018-06-07), p. 244-
    Abstract: This paper reports the relationship between oxygen concentration and dislocation multiplication in silicon crystals during directional solidification using numerical analysis. Based on the Alexander–Haasen–Sumino model, this analysis involved oxygen diffusion from the bulk to dislocation cores during crystal growth and annealing processes in a furnace. The results showed that the dislocation density mainly increased during cooling process, rather than crystal growth, when the effect of oxygen diffusion to dislocation cores was ignored. On the contrary, the dislocation density increased during both crystal growth and cooling processes when the effect of interstitial oxygen diffusion was considered. At a dislocation density larger than 1.0 × 105 cm−2, the interstitial oxygen concentration in bulk decreased due to the diffusion process, if interstitial oxygen atoms were between dislocations, whereas the concentration at dislocation cores increases.
    Type of Medium: Online Resource
    ISSN: 2073-4352
    URL: Article
    DOI: 10.3390/cryst8060244
    Language: English
    Publisher: MDPI AG
    Publication Date: 2018
    detail.hit.zdb_id: 2661516-2
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  • 5
    Online Resource
    Online Resource
    Clinical Differentiation of Severe Fever with Thrombocytopenia Syndrome from Japanese Spotted Fever
    MDPI AG ; 2022
    In:  Viruses Vol. 14, No. 8 ( 2022-08-18), p. 1807-
    Details
    In: Viruses, MDPI AG, Vol. 14, No. 8 ( 2022-08-18), p. 1807-
    Abstract: Severe fever with thrombocytopenia syndrome (SFTS) and Japanese spotted fever (JSF; a spotted fever group rickettsiosis) are tick-borne zoonoses that are becoming a significant public health threat in Japan and East Asia. Strategies for treatment and infection control differ between the two; therefore, initial differential diagnosis is important. We aimed to compare the clinical characteristics of SFTS and JSF based on symptomology, physical examination, laboratory data, and radiography findings at admission. This retrospective study included patients with SFTS and JSF treated at five hospitals in Nagasaki Prefecture, western Japan, between 2013 and 2020. Data from 23 patients with SFTS and 38 patients with JSF were examined for differentiating factors and were divided by 7:3 into a training cohort and a validation cohort. Decision tree analysis revealed leukopenia (white blood cell [WBC] 〈 4000/μL) and altered mental status as the best differentiating factors (AUC 1.000) with 100% sensitivity and 100% specificity. Using only physical examination factors, absence of skin rash and altered mental status resulted in the best differentiating factors with AUC 0.871, 71.4% sensitivity, and 90.0% specificity. When treating patients with suspected tick-borne infection, WBC 〈 4000/µL, absence of skin rash, and altered mental status are very useful to differentiate SFTS from JSF.
    Type of Medium: Online Resource
    ISSN: 1999-4915
    URL: Article
    DOI: 10.3390/v14081807
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2516098-9
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  • 6
    Online Resource
    Online Resource
    Elevated Alpha 1(I) to Alpha 2(I) Collagen Ratio in Dermal Fibroblasts Possibly Contributes to Fibrosis in Systemic Sclerosis
    MDPI AG ; 2022
    In:  International Journal of Molecular Sciences Vol. 23, No. 12 ( 2022-06-18), p. 6811-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 23, No. 12 ( 2022-06-18), p. 6811-
    Abstract: Systemic sclerosis (SSc) is characterized by excessive collagen deposition in the skin and internal organs. Activated fibroblasts are the key effector cells for the overproduction of type I collagen, which comprises the α1(I) and α2(I) chains encoded by COL1A1 and COL1A2, respectively. In this study, we examined the expression patterns of α1(I) and α2(I) collagen in SSc fibroblasts, as well as their co-regulation with each other. The relative expression ratio of COL1A1 to COL1A2 in SSc fibroblasts was significantly higher than that in control fibroblasts. The same result was observed for type I collagen protein levels, indicating that α2(I) collagen is more elevated than α2(I) collagen. Inhibition or overexpression of α1(I) collagen in control fibroblasts affected the α2(I) collagen levels, suggesting that α1(I) collagen might act as an upstream regulator of α2(I) collagen. The local injection of COL1A1 small interfering RNA in a bleomycin-induced SSc mouse model was found to attenuate skin fibrosis. Overall, our data indicate that α2(I) collagen is a potent regulator of type I collagen in SSc; further investigations of the overall regulatory mechanisms of type I collagen may help understand the aberrant collagen metabolism in SSc.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms23126811
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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