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  • 1
    Online Resource
    Online Resource
    Changes in Serum Growth Factors during Resistance to Atezolizumab Plus Bevacizumab Treatment in Patients with Unresectable Hepatocellular Carcinoma
    MDPI AG ; 2023
    In:  Cancers Vol. 15, No. 3 ( 2023-01-18), p. 593-
    Details
    In: Cancers, MDPI AG, Vol. 15, No. 3 ( 2023-01-18), p. 593-
    Abstract: The possible mechanisms of resistance to atezolizumab/bevacizumab for unresectable HCC, and the subsequent response to these therapies, remain underexplored. The sequential changes in serum growth factors, including VEGF-A, VEGF-C, VEGF-D, ANG-2, FGF-19, HGF, and EGF during atezolizumab/bevacizumab for unresectable HCC were evaluated in 46 patients. Patients who experienced PD after CR, PR, or SD to atezolizumab/bevacizumab were evaluated. A total of 4, 9, 19, and 14 patients showed CR, PR, SD, and PD, respectively. Of 32 patients with disease control, 28 experienced PD after CR, PR, or SD with atezolizumab/bevacizumab. Baseline growth factor levels were similar between patients with or without disease control and those with or without an objective response. Growth factor changes between the baseline and the best overall response points (BOR) for patients with disease control showed that FGF-19 significantly increased and ANG2 significantly decreased at the BOR. Growth factor changes between the BOR and the PD point in 28 patients who experienced PD after disease control showed that VEGF-D and ANG2 significantly increased at the PD point compared with that at the BOR. Summarily, increased serum VEGF-D and ANG-2 levels might contribute to developing resistance to atezolizumab/bevacizumab for unresectable HCC and might be target molecules in subsequent salvage therapies.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers15030593
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2527080-1
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  • 2
    Online Resource
    Online Resource
    Frequency and Characteristics of Overestimated Renal Function in Japanese Patients with Chronic Liver Disease and Its Relation to Sarcopenia
    MDPI AG ; 2021
    In:  Nutrients Vol. 13, No. 7 ( 2021-07-14), p. 2415-
    Details
    In: Nutrients, MDPI AG, Vol. 13, No. 7 ( 2021-07-14), p. 2415-
    Abstract: Renal dysfunction and sarcopenia are important prognostic factors in patients with chronic liver disease (CLD). Muscle atrophy can cause the overestimation of renal function based on serum creatinine. However, the frequency of overestimated renal function in Japanese patients with CLD and its relationship with sarcopenia are unclear. In present study, we evaluated the frequency of overestimated renal function, defined as a 〉 20% higher eGFR using creatinine than using cystatin C, in 307 patients with CLD as well as its relationship with indicators of sarcopenia. In total, 24.8% of patients had overestimated renal function. In a multivariate regression analysis, liver cirrhosis (p = 0.004) and psoas muscle mass index (p = 0.049) were significantly associated with overestimated renal function. Loss of skeletal muscle mass was significantly more frequent in both male and female patients with overestimated renal function than without. In males, the loss of muscle strength and rate of sarcopenia, defined as loss of muscle mass and strength, were significantly higher in patients with than without overestimated renal function. The high frequency of overestimated renal function in Japanese patients suggests that indicators of renal function should be carefully considered; furthermore, monitoring and interventions for both renal function and sarcopenia are needed in patients with CLD.
    Type of Medium: Online Resource
    ISSN: 2072-6643
    URL: Article
    DOI: 10.3390/nu13072415
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2518386-2
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  • 3
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    Online Resource
    Association of Social Capital and Locus of Control with Perceived Health during the COVID-19 Pandemic in Japan
    MDPI AG ; 2022
    In:  International Journal of Environmental Research and Public Health Vol. 19, No. 15 ( 2022-08-01), p. 9415-
    Details
    In: International Journal of Environmental Research and Public Health, MDPI AG, Vol. 19, No. 15 ( 2022-08-01), p. 9415-
    Abstract: Previous studies have indicated that social capital and locus of control influence mental health. Accordingly, we investigated the effect of social capital and locus of control on perceived physical and mental health in the general Japanese population during the COVID-19 pandemic. In order to conduct a cross-sectional study, in 2021, three thousand citizens were randomly selected from the Chitose City Resident Register according to ten strata of sex and age classes between 30 years and 79 years. Because thirteen persons moved away from the city, the survey was conducted for the remaining 2987 citizens. A total of 1430 citizens (712 males, 718 females) responded to the survey with their written informed consent (response rate, 47.9%). As a result, social capital measured three dimensions, namely social support, social participation, and trust and reciprocity, and internal locus of control was significantly inversely associated with it, but external locus of control was significantly positively associated with impaired physical and mental health in male and female subjects after adjustment of lifestyle habits and lifestyle change affected by the pandemic. Strengthening social capital and internal locus of control, and weakening external locus of control, may improve physical and mental health, even if the pandemic would bring about distress. Further longitudinal study is needed to examine the causal relationship among them.
    Type of Medium: Online Resource
    ISSN: 1660-4601
    URL: Article
    DOI: 10.3390/ijerph19159415
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2175195-X
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  • 4
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    Online Resource
    Changes in Serum Growth Factors during Lenvatinib Predict the Post Progressive Survival in Patients with Unresectable Hepatocellular Carcinoma
    MDPI AG ; 2022
    In:  Cancers Vol. 14, No. 1 ( 2022-01-04), p. 232-
    Details
    In: Cancers, MDPI AG, Vol. 14, No. 1 ( 2022-01-04), p. 232-
    Abstract: Serum growth factor changes and their effect on prognosis during lenvatinib for unresectable hepatocellular carcinoma (HCC) remain underexplored. The sequential changes in serum growth factors during lenvatinib for unresectable HCC were evaluated in 58 patients using complete clinical data, and preserved serum was used to investigate changes in FGF-19, ANG-2, HGF, VEGF, and EGF. Patients with a complete response (CR), partial response (PR), and stable disease (SD) were evaluated for growth factor changes between the best response and progressive disease (PD) points, classified based on these changes, and evaluated by post progression survival (PPS). A total of 8, 24, 18, and 8 patients showed CR, PR, SD, and PD, respectively. Multivariate analysis revealed that age, relative dose intensity, and baseline ANG-2 were significantly associated with treatment response. Growth factor changes between the best response and PD points revealed that patients could be classified into four groups based on the EGF, ANG-2, and HGF changes. Although patient characteristics at baseline and PD, their response to lenvatinib, and PFS were similar among those groups, patients with an increase in all growth factors had significantly shorter PPS (median PPS was 553, 323, and 316 versus 173 days in groups 1–4 p = 0.032). We revealed that the evaluation of the changes in growth factors during lenvatinib could predict PPS.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers14010232
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2527080-1
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  • 5
    Online Resource
    Online Resource
    Noninvasive Assessment of Liver Fibrosis: Current and Future Clinical and Molecular Perspectives
    MDPI AG ; 2020
    In:  International Journal of Molecular Sciences Vol. 21, No. 14 ( 2020-07-11), p. 4906-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 21, No. 14 ( 2020-07-11), p. 4906-
    Abstract: Liver fibrosis is one of the risk factors for hepatocellular carcinoma (HCC) development. The staging of liver fibrosis can be evaluated only via a liver biopsy, which is an invasive procedure. Noninvasive methods for the diagnosis of liver fibrosis can be divided into morphological tests such as elastography and serum biochemical tests. Transient elastography is reported to have excellent performance in the diagnosis of liver fibrosis and has been accepted as a useful tool for the prediction of HCC development and other clinical outcomes. Two-dimensional shear wave elastography is a new technique and provides a real-time stiffness image. Serum fibrosis markers have been studied based on the mechanism of fibrogenesis and fibrolysis. In the healthy liver, homeostasis of the extracellular matrix is maintained directly by enzymes called matrix metalloproteinases (MMPs) and their specific inhibitors, tissue inhibitors of metalloproteinases (TIMPs). MMPs and TIMPs could be useful serum biomarkers for liver fibrosis and promising candidates for the treatment of liver fibrosis. Further studies are required to establish liver fibrosis-specific markers based on further clinical and molecular research. In this review, we summarize noninvasive fibrosis tests and molecular mechanism of liver fibrosis in current daily clinical practice.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms21144906
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 6
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    Online Resource
    Potential Correlation between Changes in Serum FGF21 Levels and Lenvatinib-Induced Appetite Loss in Patients with Unresectable Hepatocellular Carcinoma
    MDPI AG ; 2023
    In:  Cancers Vol. 15, No. 12 ( 2023-06-20), p. 3257-
    Details
    In: Cancers, MDPI AG, Vol. 15, No. 12 ( 2023-06-20), p. 3257-
    Abstract: Lenvatinib, used for unresectable hepatocellular carcinoma (HCC), causes appetite loss, but the underlying mechanisms, clinical impact, and predictive factors have been unclear. The endocrine factor FGF21 modulates appetite and is involved in cachexia. We evaluated the association between FGF21 level changes during lenvatinib treatment for unresectable HCC and appetite loss. Sixty-three eligible unresectable HCC patients who started lenvatinib treatment between 2018 and 2021 were included. We analyzed FGF21 levels at baseline; 1, 2, and 4 weeks after lenvatinib initiation, and before the onset of appetite loss. Grade ≥ 2 lenvatinib-induced appetite loss led to liver functional reserve deterioration at disease progression and a poor prognosis. Baseline characteristics and serum FGF21 levels were similar between patients with and without appetite loss. However, the serum FGF21 change rate increased significantly at 4 weeks post-lenvatinib initiation in patients with grade ≥ 2 appetite loss, as compared to those without appetite loss. Similar significant increases in the serum FGF21 level change rate were observed prior to grade ≥ 2 appetite loss onset. This suggests that changes in FGF21 levels can be used to predict patients with a greater risk of marked appetite loss and provides insights into the mechanisms underlying lenvatinib-induced appetite loss in patients with HCC.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers15123257
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2527080-1
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  • 7
    Online Resource
    Online Resource
    Serum Angiopoietin-2 Predicts the Occurrence and Recurrence of Hepatocellular Carcinoma after Direct-Acting Antiviral Therapy for Hepatitis C
    MDPI AG ; 2023
    In:  Viruses Vol. 15, No. 1 ( 2023-01-07), p. 181-
    Details
    In: Viruses, MDPI AG, Vol. 15, No. 1 ( 2023-01-07), p. 181-
    Abstract: Progressive liver fibrosis after anti-HCV treatment is a risk factor for HCC. Angiopoietin-2 (Ang2) is associated with non-regression of liver fibrosis after direct-acting antiviral (DAA). This study evaluated the predictive value of serum Ang2 levels for HCC occurrence or recurrence after DAA administration. In this retrospective study, 310 HCV-infected patients treated with DAAs in 2014–2020 were screened and evaluated for HCC occurrence or recurrence every three–six months. Multivariate Cox regression analysis revealed that age ≥ 75 years (HR: 2.92, 95% CI: 1.34–6.33; p = 0.007) and baseline Ang2 level ≥ 464 pg/mL (HR: 2.75, 95% CI: 1.18–6.37; p = 0.019) were significantly associated with HCC occurrence after DAA therapy. A high or low risk of HCC after DAA therapy could be distinguished by the combination of age and baseline Ang2 level. The cumulative incidences of de-novo HCC at two and four years were 0.8% and 3.8% in the low-risk group and 22.6% and 27.1% in the high-risk group, respectively. Baseline Ang2 level ≥ 402 pg/mL was significantly associated with HCC recurrence in patients who achieved sustained virological response with DAAs (HR: 3.68). In conclusion, serum Ang2 levels can predict HCC occurrence and recurrence after successful HCV eradication by DAAs.
    Type of Medium: Online Resource
    ISSN: 1999-4915
    URL: Article
    DOI: 10.3390/v15010181
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2516098-9
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  • 8
    Online Resource
    Online Resource
    Walking Speed Is Better Than Hand Grip Strength as an Indicator of Early Decline in Physical Function with Age in Japanese Women Over 65: A Longitudinal Analysis of the Tanno-Sobetsu Study Using Linear Mixed-Effects Models
    MDPI AG ; 2022
    In:  International Journal of Environmental Research and Public Health Vol. 19, No. 23 ( 2022-11-27), p. 15769-
    Details
    In: International Journal of Environmental Research and Public Health, MDPI AG, Vol. 19, No. 23 ( 2022-11-27), p. 15769-
    Abstract: The decline in physical function with age is a major contributor to the need for long-term care. Age-related changes in hand grip strength, knee extension, and walking speed have been reported in cross-sectional studies, but longitudinal data are needed. This longitudinal study measured changes in these three measures among community-dwelling adults aged 65–89 years who participated in general health examinations between 2017 and 2019. Analyses were stratified by sex. Linear mixed-effects models adjusted for confounding factors were used to examine the interaction of different patterns of change with age of the three measures. A total of 284 participants were included in the analysis. The interaction term of age × walking speed, with age × handgrip strength as the reference, was statistically significant in women and showed different patterns in walking speed and hand grip strength. In men, none of the age × physical function interaction terms were significant in any model. For early recognition of the onset of physical function decline in older adults, any of the three measures may be used in men, but walking speed may be more suitable than hand grip strength in women. These findings may be useful in devising sex-specific screening strategies.
    Type of Medium: Online Resource
    ISSN: 1660-4601
    URL: Article
    DOI: 10.3390/ijerph192315769
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
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  • 9
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    Online Resource
    Different Mechanisms of Action of Regorafenib and Lenvatinib on Toll-Like Receptor-Signaling Pathways in Human Hepatoma Cell Lines
    MDPI AG ; 2020
    In:  International Journal of Molecular Sciences Vol. 21, No. 9 ( 2020-05-09), p. 3349-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 21, No. 9 ( 2020-05-09), p. 3349-
    Abstract: Multiple kinase inhibitors are available for patients with advanced hepatocellular carcinoma (HCC). It is largely unknown whether regorafenib or lenvatinib modulates innate immunity including Toll-like receptor (TLR)-signaling pathways in HCC. We performed real-time RT-PCR to investigate 84 TLR-associated gene expression levels and compared these gene expression levels in each hepatoma cells treated with or without regorafenib or lenvatinib. In response to regorafenib, nine and 10 genes were upregulated in Huh7 and HepG2 cells, respectively, and only C-X-C motif chemokine ligand 10 was upregulated in both cell lines. A total of 14 and 12 genes were downregulated in Huh7 and HepG2 cells, respectively, and two genes (Fos proto-oncogene, AP-1 transcription factor subunit, and ubiquitin conjugating enzyme E2 N) were downregulated in both cell lines. In response to lenvatinib, four and 16 genes were upregulated in Huh7 and HepG2 cells, respectively, and two genes (interleukin 1 alpha and TLR4) were upregulated in both cells. Six and one genes were downregulated in Huh7 and HepG2, respectively, and no genes were downregulated in both cell lines. In summary, regorafenib and lenvatinib affect TLR signaling pathways in human hepatoma cell lines. Modulation of TLR signaling pathway may improve the treatment of HCC patients with refractory disease.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms21093349
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 10
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    Prognosis of Coronary Artery Bypass Grafting in Preschool-Aged Patients with Myocardial Ischemia Due to Giant Aneurysm of Kawasaki Disease
    MDPI AG ; 2022
    In:  Journal of Clinical Medicine Vol. 11, No. 5 ( 2022-03-04), p. 1421-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 11, No. 5 ( 2022-03-04), p. 1421-
    Abstract: Coronary artery bypass grafting (CABG) for severe cardiac sequelae of Kawasaki disease (KD) complicated by myocardial ischemia is feasible even in childhood. However, no report has summarized the prognosis of CABG in preschool-aged children. Therefore, we evaluated the outcomes of seven preschool-aged children who underwent CABG for the cardiac sequelae of KD in our hospital. The median age at KD onset and CABG was 36 and 59 months, respectively. The median period from KD onset to CABG was 12 months. The median post-operative observation period was 108 months. CABG between the left internal thoracic artery and left anterior descending artery was performed in all patients. In all patients, postoperative cardiac catheter examination revealed good graft patency and no anastomotic stenosis. Further, pre-operative abnormality of coronary flow reserve returned to normal after CABG. Currently, only one patient is taking warfarin. Regarding school–life management, no patient has exercise limitations, except for one patient who had acute myocardial infarction before CABG. Further, the risk of graft stenosis or occlusion was evaluated in the included patients. However, no accidents have been reported to date, and myocardial ischemia and school–life management have improved. Thus, CABG is an effective treatment in preschool-aged children.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm11051421
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2662592-1
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