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  • Frontiers Media SA  (168)
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  • Frontiers Media SA  (168)
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  • 1
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 10 ( 2021-1-8)
    Abstract: Previous meta-analysis had evaluated the effect of induction chemotherapy in nasopharyngeal carcinoma. But two trials with opposite findings were not included and the long-term result of another trial significantly differed from the preliminary report. This updated meta-analysis was thus warranted. Methods Literature search was conducted to identify randomized controlled trials focusing on the additional efficacy of induction chemotherapy in nasopharyngeal carcinoma. Trial-level pooled analysis of hazard ratio (HR) for progression free survival and overall survival and risk ratio (RR) for locoregional control rate and distant control rate were performed. Results Twelve trials were eligible. The addition of induction chemotherapy significantly prolonged both progression free survival (HR=0.68, 95% confidence interval [CI] 0.60–0.76, p & lt;0.001) and overall survival (HR=0.67, 95% CI 0.54–0.80, p & lt;0.001), with 5-year absolute benefit of 11.31% and 8.95%, respectively. Locoregional (RR=0.80, 95% CI 0.70–0.92, p=0.002) and distant control (RR=0.70, 95% CI 0.62–0.80) rates were significantly improved as well. The incidence of grade 3–4 adverse events during the concurrent chemoradiotherapy was higher in leukopenia (p=0.028), thrombocytopenia (p & lt;0.001), and fatigue (p=0.038) in the induction chemotherapy group. Conclusions This meta-analysis supported that induction chemotherapy could benefit patients with nasopharyngeal carcinoma in progression free survival, overall survival, locoregional, and distant control rate.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2649216-7
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  • 2
    Online Resource
    Online Resource
    Frontiers Media SA ; 2021
    In:  Frontiers in Endocrinology Vol. 12 ( 2021-12-30)
    In: Frontiers in Endocrinology, Frontiers Media SA, Vol. 12 ( 2021-12-30)
    Abstract: The gut microbiota is a newly identified contributor to the development of non-alcoholic fatty liver disease (NAFLD). Previous studies of Bifidobacterium adolescentis ( B. adolescentis ), a species of Bifidobacterium that is common in the human intestinal tract, have demonstrated that it can alleviate liver steatosis and steatohepatitis. Fibroblast growth factor 21 (FGF21) has long been considered as a biomarker of NAFLD, and recent studies have shown the protective effect of FGF21 analogs on NAFLD. We wondered whether B. adolescentis treatment would alleviate NAFLD via the interaction with FGF21. To this end, male C57BL/6J mice on a choline-deficient high-fat diet (CDHFD) were treated with drinking water supplemented with B. adolescentis for 8 weeks, followed by the acute administration of recombinant mouse FGF21 protein (rmFGF21) to conduct the FGF21 response test. Consistent with previous studies, B. adolescentis supplementation reversed the CDHFD-induced liver steatosis and steatohepatitis. This was evaluated on the NAFLD activity score (NAS), reduced liver enzymes, and lipid accumulation. Further studies demonstrated that B. adolescentis supplementation preserved the gut barrier, reduced the gut microbiota-derived lipopolysaccharide (LPS), and inhibited the hepatic TLR4/NF-κB pathway. This was accompanied by the elevated expressions of the receptors of FGF21, fibroblast growth factor receptor 1 (FGFR1) and β-klotho (KLB), in the liver and the decreased expression of FGF21. The results of FGF21 response test showed that B. adolescentis supplementation alleviated the CDHFD-induced FGF21 resistance. In vivo experiments suggested that LPS could suppress the expression of FGF21 and KLB in a dose-dependent manner. Collectively, this study showed that B. adolescentis supplementation could alleviate NAFLD by increasing FGF21 sensitivity.
    Type of Medium: Online Resource
    ISSN: 1664-2392
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2592084-4
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  • 3
    Online Resource
    Online Resource
    Frontiers Media SA ; 2023
    In:  Frontiers in Pharmacology Vol. 14 ( 2023-6-30)
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 14 ( 2023-6-30)
    Abstract: Numerous chemical compounds used in cancer treatment have been isolated from natural herbs to address the ever-increasing cancer incidence worldwide. Therein is icariin, which has been extensively studied for its therapeutic potential due to its anti-inflammatory, antioxidant, antidepressant, and aphrodisiac properties. However, there is a lack of comprehensive and detailed review of studies on icariin in cancer treatment. Given this, this study reviews and examines the relevant literature on the chemopreventive and therapeutic potentials of icariin in cancer treatment and describes its mechanism of action. The review shows that icariin has the property of inhibiting cancer progression and reversing drug resistance. Therefore, icariin may be a valuable potential agent for the prevention and treatment of various cancers due to its natural origin, safety, and low cost compared to conventional anticancer drugs, while further research on this natural agent is needed.
    Type of Medium: Online Resource
    ISSN: 1663-9812
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2587355-6
    SSG: 15,3
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  • 4
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 12 ( 2022-6-28)
    Abstract: To assess the prognostic significance of different nodal parameters [i.e., number of pathologically positive nodes, log odds of positive lymph nodes, lymph node ratio (LNR), and extra-nodal extension (ENE)] in Taiwanese patients with oral cavity squamous cell carcinoma (OCSCC), and to devise an optimized pN classification system for predicting survival in OCSCC. Methods A total of 4287 Taiwanese patients with first primary OCSCC and nodal metastases were enrolled. Cox proportional hazards regression analysis with the spline method was applied to identify the optimal cut-off values for LNR, log odds of positive lymph nodes, and number of pathologically positive nodes. Results On multivariable analysis, we identified a LNR ≥0.078/0.079, the presence of at least three pathologically positive nodes, and ENE as independent prognosticators for 5-year disease-specific survival (DSS) and overall survival (OS) rates. We therefore devised a four-point prognostic scoring system according to the presence or absence of each variable. The 5-year DSS and OS rates of patients with scores of 0−3 were 70%/62%/50%/36% ( p & lt; 0.0001) and 61%/52%/40%25%, respectively ( p & lt; 0.0001). On analyzing the AJCC 2017 pN classification, patients with pN3a displayed better survival rates than those with pN2 disease. The 5-year DSS and OS rates of patients with pN1/pN2/pN3a/pN3b disease were 72%/60%/67%/43% ( p & lt; 0.0001) and 63%/51%/67%/33%, respectively ( p & lt; 0.0001). Conclusions Three nodal parameters (i.e., a LNR ≥0.078/0.079, the presence of at least three pathologically positive nodes, and ENE) assessed in combination provided a better prognostic stratification than the traditional AJCC pN classification.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2649216-7
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  • 5
    Online Resource
    Online Resource
    Frontiers Media SA ; 2021
    In:  Frontiers in Immunology Vol. 12 ( 2021-2-2)
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 12 ( 2021-2-2)
    Abstract: The high infection rate and rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) make it a world-wide pandemic. Individuals infected by the virus exhibited different degrees of symptoms, and most convalescent individuals have been shown to develop both cellular and humoral immune responses. However, virus-specific adaptive immune responses in severe patients during acute phase have not been thoroughly studied. Here, we found that in a group of COVID-19 patients with acute respiratory distress syndrome (ARDS) during hospitalization, most of them mounted SARS-CoV-2-specific antibody responses, including neutralizing antibodies. However, compared to healthy controls, the percentages and absolute numbers of both NK cells and CD8 + T cells were significantly reduced, with decreased IFNγ expression in CD4 + T cells in peripheral blood from severe patients. Most notably, their peripheral blood lymphocytes failed in producing IFNγ against viral proteins. Thus, severe COVID-19 patients at acute infection stage developed SARS-CoV-2-specific antibody responses but were impaired in cellular immunity, which emphasizes on the role of cellular immunity in COVID-19.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2606827-8
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  • 6
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 12 ( 2022-11-14)
    Abstract: In the treatment of oral cavity squamous cell carcinoma (OCSCC), surgical quality measures which are expected to affect outcomes, including the achievement of a clear margin, are surgeon-dependent but might not be invariably associated with hospital volume. Our objective was to explore surgical margin variations and survival differences of OCSCC between two highest-volume hospitals in Taiwan. Materials and methods A total of 2009 and 1019 patients with OCSCC who were treated at the two highest-volume Taiwanese hospitals (termed Hospital 1 and Hospital 2, respectively) were included. We examined how a pathological margin & lt;5 mm impacted patient outcomes before and after propensity score (PS) matching. Results The prevalence of margins & lt;5 mm was markedly lower in Hospital 1 than in Hospital 2 (34.5%/65.2%, p & lt;0.0001). Compared with Hospital 2, tumor severity was higher in Hospital 1. On univariable analysis, being treated in Hospital 2 (versus Hospital 1; hazard ratio [HR] for 5-year disease-specific survival [DSS] = 1.34, p =0.0002; HR for 5-year overall survival [OS] = 1.17, p =0.0271) and margins & lt;5 mm (versus ≥5 mm; HR for 5-year DSS = 1.63, p & lt;0.0001; HR for 5-year OS = 1.48, p & lt;0.0001) were identified as adverse factors. The associations of treatment in Hospital 2 and margins & lt;5 mm with less favorable outcomes remained significant after adjustment for potential confounders in multivariable analyses, as well as in the PS-matched cohort. The 5-year survival differences between patients operated in Hospital 1 and Hospital 2 were even more pronounced in the PS-matched cohort (before PS matching: DSS, 79%/74%, p =0.0002; OS, 71%/68%, p =0.0269; after PS matching: DSS, 84%/72%, p & lt;0.0001; OS, 75%/66%, p & lt;0.0001). In the entire cohort, the rate of adjuvant therapy was found to be lower in patients with margins ≥5 mm than in those with margins & lt;5 mm (42.7% / 57.0%, p & lt;0.0001). Conclusions Within the two highest-volume hospitals in Taiwan, patients with OCSCC with a clear margin status (≥5 mm) achieved more favorable outcomes. These results have clinical implications and show how initiatives aimed at improving the margin quality can translate in better outcomes. A clear margin status can reduce the need for adjuvant therapy, ultimately improving quality of life.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
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  • 7
    Online Resource
    Online Resource
    Frontiers Media SA ; 2021
    In:  Frontiers in Immunology Vol. 12 ( 2021-5-10)
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 12 ( 2021-5-10)
    Abstract: Vγ2Vδ2 T cell-based immunotherapy has benefited some patients in clinical trials, but the overall efficacy is low for solid tumor patients. In this study, a bispecific antibody against both PD-L1 and CD3 (PD-L1 x CD3), Y111, could efficiently bridge T cells and PD-L1 expressing tumor cells. The Y111 prompted fresh CD8+ T cell-mediated lysis of H358 cells, but spared this effect on the fresh Vδ2+ T cells enriched from the same donors, which suggested that Y111 could bypass the anti-tumor capacity of the fresh Vγ2Vδ2 T cells. As the adoptive transfer of the expanded Vγ2Vδ2 T cells was approved to be safe and well-tolerated in clinical trials, we hypothesized that the combination of the expanded Vγ2Vδ2 T cells with the Y111 would provide an alternative approach of immunotherapy. Y111 induced the activation of the expanded Vγ2Vδ2 T cells in a dose-dependent fashion in the presence of PD-L1 positive tumor cells. Moreover, Y111 increased the cytotoxicity of the expanded Vγ2Vδ2 T cells against various NSCLC-derived tumor cell lines with the releases of granzyme B, IFNγ, and TNFα in vitro . Meanwhile, the adoptive transferred Vγ2Vδ2 T cells together with the Y111 inhibited the growth of the established xenografts in NPG mice. Taken together, our data suggested a clinical potential for the adoptive transferring the Vγ2Vδ2 T cells with the Y111 to treat PD-L1 positive solid tumors.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2606827-8
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  • 8
    In: Frontiers in Endocrinology, Frontiers Media SA, Vol. 14 ( 2023-6-2)
    Abstract: A potential association between epilepsy and subsequent type 2 diabetes mellitus (T2DM) has emerged in recent studies. However, the association between epilepsy, anti-epileptic drugs (AEDs), and the risk of T2DM development remains controversial. We aimed to conduct a nationwide, population-based, retrospective, cohort study to evaluate this relationship. Methods We extracted data from the Taiwan Longitudinal Generation Tracking Database of patients with new-onset epilepsy and compared it with that of a comparison cohort of patients without epilepsy. A Cox proportional hazards regression model was used to analyze the difference in the risk of developing T2DM between the two cohorts. Next-generation RNA sequencing was used to characterize T2DM-related molecularchanges induced by AEDs and the T2DM-associated pathways they alter. The potential of AEDs to induce peroxisome proliferator-activated receptor γ (PPARγ) transactivation was also evaluated. Results After adjusting for comorbidities and confounding factors, the case group (N = 14,089) had a higher risk for T2DM than the control group (N = 14,089) [adjusted hazards ratio (aHR), 1.27]. Patients with epilepsy not treated with AEDs exhibited a significantly higher risk of T2DM (aHR, 1.70) than non-epileptic controls. In those treated with AEDs, the risk of developing T2DM was significantly lower than in those not treated (all aHR ≤ 0.60). However, an increase in the defined daily dose of phenytoin (PHE), but not of valproate (VPA), increased the risk of T2DM development (aHR, 2.28). Functional enrichment analysis of differentially expressed genes showed that compared to PHE, VPA induced multiple beneficial genes associated with glucose homeostasis. Among AEDs, VPA induced the specific transactivation of PPARγ. Discussion Our study shows epilepsy increases the risk of T2DM development, however, some AEDs such as VPA might yield a protective effect against it. Thus, screening blood glucose levels in patients with epilepsy is required to explore the specific role and impact of AEDs in the development of T2DM. Future in depth research on the possibility to repurpose VPA for the treatment of T2DM, will offer valuable insight regarding the relationship between epilepsy and T2DM.
    Type of Medium: Online Resource
    ISSN: 1664-2392
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2592084-4
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  • 9
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Immunology Vol. 13 ( 2022-6-17)
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 13 ( 2022-6-17)
    Abstract: The potent cytotoxic property of Vγ2Vδ2 T cells makes them attractive for adoptive T cell transfer therapy. The transfusing of the expanded Vγ2Vδ2 T cells into cancer patients shows well-tolerated, but the clinical response rates are required to be improved, implying that there is still an unmet efficacy with low toxicity for this novel anti-tumor therapy. In this study, we test the anti-tumor efficacy of a Y-body-based bispecific antibody (bsAb) Vγ2 x PD-L1 that preferentially redirects Vγ2Vδ2 T cells to combat PD-L1 positive tumor cells. With nanomolar affinity levels to Vγ2Vδ2 T cells and PD-L1+ tumor cells, Vγ2 x PD-L1 bridges a Vγ2Vδ2 T cell with a SKOV3 tumor cell to form a cell-to-cell conjugation. In a PD-L1-dependent manner, the bsAb elicits effective activation (CD25+CD69+), IFNγ releasing, degranulation (CD107a+), and cytokine production (IFNγ+ and TNFα+) of expanded Vγ2Vδ2 T cells. The activations of the Vγ2Vδ2 T cells eliminate PD-L1-expressing human cancer cell lines, including H1975, SKOV3, A375, H1299, and H2228 cells, but not PD-L1 negative cells including HEK-293 (293) cells and healthy PBMCs. Finally, we show that combining Vγ2 x PD-L1 with adoptively transferring Vγ2Vδ2 T cells inhibits the growth of existing tumor xenografts and increases the number of Vγ2Vδ2 T cells into the tumor bed. Vγ2 x PD-L1 represents a promising reagent for increasing the efficacy of adoptively transferred Vγ2Vδ2 T cells in the treatment of PD-L1 positive malignant tumors.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2606827-8
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  • 10
    In: Frontiers in Molecular Biosciences, Frontiers Media SA, Vol. 8 ( 2021-5-28)
    Abstract: Objectives: To investigate the predictive value of inflammatory biomarkers in patients with unresectable hepatocellular carcinoma (HCC) for outcomes following the combination treatment of transarterial chemoembolization (TACE) plus sorafenib. Materials and Methods: A total of 314 (270 male and 44 female) treatment-naïve patients with unresectable HCC treated by TACE plus sorafenib between January 2011 and December 2018 were enrolled in the retrospective study. The primary outcome was overall survival (OS). The secondary outcome was progression-free survival (PFS). Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were obtained within 3–7 days before the initial TACE and the median value of the NLR and PLR was considered as the cut-off value. Results: The median value of NLR and PLR was 2.42 and 100, respectively. The median OS and PFS of the entire cohort were 18.7 months (95% CI: 16.8–20.6) and 9.1 months (95% CI: 8.5–9.8), respectively. The low NLR and PLR group showed improved OS and PFS compared with the high NLR and PLR group [21.8 months (95% CI: 15.2–28.5) vs. 15.4 months (95% CI: 12.4–18.3), p & lt; 0.0001; 21.6 months (95% CI: 15.8–27.5) vs. 14.9 months (95% CI: 11.9–17.8), p = 0.00027, respectively]. In addition, the low NLR and PLR group also provided a longer PFS than the high NLR and PLR group [10.4 months (95% CI: 8.9–12.0) vs. 8.1 months (95% CI: 7.1–9.2), p = 0.00022; 10.3 months (95% CI: 8.6–11.9) vs. 8.2 months (95% CI: 7.2–9.2), p & lt; 0.0001, respectively]. High NLR and PLR at baseline were predictive factors of poor OS ( p = 0.02 and p = 0.004) and PFS ( p = 0.045 and p = 0.005). Conclusion: This study showed the prognostic value of quantitative inflammatory biomarkers in correlation with OS and PFS in unresectable HCC patients undergoing TACE plus sorafenib treatment.
    Type of Medium: Online Resource
    ISSN: 2296-889X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2814330-9
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