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  • Frontiers Media SA  (33)
  • 1
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    DataSheet_1.docx
    Frontiers Media SA ; 2022
    In:  Frontiers in Immunology Vol. 13 ( 2022-8-22)
    Details
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 13 ( 2022-8-22)
    Abstract: Early identification of patients who will benefit from immune checkpoint inhibitors (ICIs) has recently become a hot issue in cancer immunotherapy. Peripheral cytokines are key regulators in the immune system that can induce the expression of immune checkpoint molecules; however, the association between peripheral cytokines and the efficiency of ICIs remains unclear. Methods A systematic review was conducted in several public databases from inception through 3 February 2022 to identify studies investigating the association between peripheral cytokines (i.e., IL-1β, IL-2, IL-2RA, IL-2R, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-15, IL-17, TNF-α, IFN-γ, and TGF-β) and ICI treatment. Survival data, including overall survival (OS) and/or progression-free survival (PFS), were extracted, and meta-analyses were performed. Results Twenty-four studies were included in this analysis. The pooled results demonstrated that the pretreatment peripheral levels of IL-6 (univariate analysis: HR = 2.53, 95% CI = 2.21–2.89, p & lt; 0.00001; multivariate analysis: HR = 2.21, 95% CI = 1.67–2.93, p & lt; 0.00001) and IL-8 (univariate analysis: HR = 2.17, 95% CI = 1.98–2.38, p & lt; 0.00001; multivariate analysis: HR = 1.88, 95% CI= 1.70–2.07, p & lt; 0.00001) were significantly associated with worse OS of cancer patients receiving ICI treatment in both univariate and multivariate analysis. However, high heterogeneity was found for IL-6, which might be attributed to region, cancer type, treatment method, sample source, and detection method. Conclusion The peripheral level of IL-8 may be used as a prognostic marker to identify patients with inferior response to ICIs. More high-quality prospective studies are warranted to assess the predictive value of peripheral cytokines for ICI treatment.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    URL: Article
    URL: Article
    DOI: 10.3389/fimmu.2022.884592
    DOI: 10.3389/fimmu.2022.884592.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2606827-8
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  • 2
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    DataSheet_1.pdf
    Frontiers Media SA ; 2022
    In:  Frontiers in Immunology Vol. 13 ( 2022-4-7)
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    In: Frontiers in Immunology, Frontiers Media SA, Vol. 13 ( 2022-4-7)
    Abstract: Natural killer (NK) cells play major roles in eliminating tumor cells. Preliminary studies have shown that NK cells and their receptors/ligands have prognostic value in malignant tumors. However, the relevance of NK cells and their receptors/ligands level to the prognosis of hepatocellular carcinoma (HCC) remains unclear. Methods Several electronic databases were searched from database inception to November 8, 2021. Random effects were introduced to this meta-analysis. The relevance of NK cells and their receptors/ligands level to the prognosis of HCC was evaluated using hazard ratios (HRs) with 95% confidence interval (95%CI). Results 26 studies were included in the analysis. The pooled results showed that high NK cells levels were associated with better overall survival (HR=0.70, 95%CI 0.57–0.86, P=0.001) and disease-free survival (HR=0.61, 95%CI 0.40-0.93, P=0.022) of HCC patients. In subgroup analysis for overall survival, CD57 + NK cells (HR=0.70, 95%CI 0.55-0.89, P=0.004) had better prognostic value over CD56 + NK cells (HR=0.69, 95%CI 0.38-1.25, P=0.224), and intratumor NK cells had better prognostic value (HR=0.71, 95%CI 0.55-0.90, P=0.005) over peripheral NK cells (HR=0.66, 95%CI 0.41-1.06, P=0.088). In addition, high level of NK cell inhibitory receptors predicted increased recurrence of HCC, while the prognostic role of NK cell activating receptors remained unclear. Conclusion NK cells and their inhibitory receptors have prognostic value for HCC. The prognostic role of NK cell activating receptors is unclear and more high-quality prospective studies are essential to evaluate the prognostic value of NK cells and their receptors/ligands for HCC.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    URL: Article
    URL: Article
    DOI: 10.3389/fimmu.2022.872353
    DOI: 10.3389/fimmu.2022.872353.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2606827-8
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  • 3
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    Image_2.tif
    Frontiers Media SA ; 2021
    In:  Frontiers in Oncology Vol. 11 ( 2021-11-4)
    Details
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 11 ( 2021-11-4)
    Abstract: Castration-resistant prostate cancer (CRPC) continues to be a major clinical problem and its underlying mechanisms are still not fully understood. The epidermal growth factor receptor (EGFR) activation is an important event that regulates mitogenic signaling. EGFR signaling plays an important role in the transition from androgen dependence to castration-resistant state in prostate cancer (PCa). Kinesin family member 15 (KIF15) has been suggested to be overexpressed in multiple malignancies. Here, we demonstrate that KIF15 expression is elevated in CRPC. We show that KIF15 contributes to CRPC progression by enhancing the EGFR signaling pathway, which includes complex network intermediates such as mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K)/AKT pathways. In CRPC tumors, increased expression of KIF15 is positively correlated with EGFR protein level. KIF15 binds to EGFR, and prevents EGFR proteins from degradation in a Cdc42-dependent manner. These findings highlight the key role of KIF15 in the development of CRPC and rationalize KIF15 as a potential therapeutic target.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fonc.2021.679173
    DOI: 10.3389/fonc.2021.679173.s001
    DOI: 10.3389/fonc.2021.679173.s002
    DOI: 10.3389/fonc.2021.679173.s003
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2649216-7
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  • 4
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    Clinical Benefit of Antiviral Agents for Hepatocellular Carcinoma Patients With Low Preoperative HBV-DNA Loads Undergoing Curative Resection: A Meta-Analysis
    Frontiers Media SA ; 2021
    In:  Frontiers in Oncology Vol. 11 ( 2021-2-19)
    Details
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 11 ( 2021-2-19)
    Abstract: The clinical benefit of adjuvant antiviral therapy after curative therapy for HCC in patients with high preoperative HBV-DNA loads has been studied widely but that in patients with low preoperative HBV-DNA loads remains controversial. The purpose of this study was to determine the effect of antiviral treatment prophylaxis on HBV reactivation, overall survival (OS), and postoperative liver function in patients with low preoperative HBV-DNA levels undergoing curative resection. Methods A meta-analysis was conducted by searching Web of Science, PubMed, Embase, and Cochrane Library until May 2020. We used REVMAN for data analysis and completed the study under the PRISMA guidelines. Results Three randomized trials and seven cohort studies, comprising of 1,131 individuals, were included in the meta-analysis. Antiviral treatment significantly reduced the rate of HBV reactivation after curative treatment of HCC, with a pooled risk ratio of 0.12 (95% c.i. 0.07 to 0.21; P & lt; 0.00001). The trials were consistently favorable for the antiviral group, with a pooled hazard ratio of 0.52 (95% c.i. 0.37 to 0.74; P = 0.0002) in respect of OS rate. However, by pooling the data from studies that reported ALT on the 30th day postoperatively, the result didn’t reach statistical significance (mean difference −4.38, 95% c.i. −13.83 to 5.07; P = 0.36). The I² values of the heterogeneity test for the above three comparisons are zero. Conclusion Antiviral therapy during curative resection is effective in reducing HBV reactivation and improving OS rate in HCC patients with low viral load.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    URL: Article
    DOI: 10.3389/fonc.2021.605648
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
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  • 5
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    DataSheet_1.pdf
    Frontiers Media SA ; 2021
    In:  Frontiers in Oncology Vol. 11 ( 2021-9-23)
    Details
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 11 ( 2021-9-23)
    Abstract: The lung immune prognostic index (LIPI) is recently developed to predict immune checkpoint inhibitors (ICIs) treatment outcomes for non-small cell lung cancer. However, its predictive value for other types of cancer remained unclear. This meta-analysis aimed to evaluate the association between pretreatment LIPI score and therapeutic outcomes in cancer patients treated with ICIs. Methods We searched PubMed, Cochrane Library literature databases and EMBASE for abstracts and full-text articles published from the inception of the database until 16th, Nov 2020. Meta-analyses were performed separately for progression-free survival (PFS) and overall survival (OS) by using the random-effects model. Results A total of 12 studies involving 4883 patients receiving ICIs treatment were identified for the primary analysis. The pooled results implied that compared with good LIPI score groups, patients with poor or intermediate LIPI score were significantly associated with worse OS (HR=3.33, 95%CI 2.64-4.21, P & lt; 0.001, I 2 = 64.2%; HR=1.71, 95%CI 1.43-2.04, P & lt; 0.001, I 2 = 43.6%, respectively) and PFS (HR=2.73,95%CI 2.00-3.73, P & lt; 0.001, I 2 = 78.2%; HR=1.43, 95%CI 1.28-1.61, P & lt; 0.001, I 2 = 16.3%, respectively). Also, for 1873 patients receiving chemotherapy, a poor LIPI score was significantly associated with worse OS (HR=2.30, 95%CI 1.73-3.07, P & lt; 0.001; I 2 = 56.2%) and PFS (HR=1.92,95%CI 1.69-2.17; P & lt; 0.001; I 2 = 0.0%) compared with good LIPI score groups. Conclusions A good LIPI score was significantly correlated with improved OS and PFS in cancer patients receiving ICIs or chemotherapy, regardless of the types of cancer.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    URL: Article
    URL: Article
    DOI: 10.3389/fonc.2021.691002
    DOI: 10.3389/fonc.2021.691002.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
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  • 6
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    Table_6.docx
    Frontiers Media SA ; 2022
    In:  Frontiers in Immunology Vol. 13 ( 2022-2-8)
    Details
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 13 ( 2022-2-8)
    Abstract: The relationship between baseline C-reactive protein (CRP) level and the prognosis of cancer patients receiving immune checkpoint inhibitor (ICI) treatment remains controversial. The aim of this meta-analysis was to clarify whether baseline CRP level can serve as a biomarker to predict the efficiency of ICI therapy. Methods All associated articles published in the Cochrane Library, EMBASE, and PubMed databases from the inception of the database to December 30, 2021, were retrieved. Progression-free survival (PFS) and overall survival (OS) outcomes were meta-analyzed using the random-effects model and adjusted using the trim-and-fill method because of publication bias. Results Thirty-three studies (6,124 patients) conducted between 2013 and 2021 were identified. The pooled outcomes implied that high baseline CRP level patients had significantly worse OS (adjusted pooled value for univariate and multivariate analysis outcomes: HR = 1.48, 95% CI = 1.41–1.56; HR = 1.46, 95% CI = 1.34–1.59) and PFS (adjusted pooled value for univariate and multivariate analysis outcomes: HR = 1.29, 95% CI = 1.15–1.45; HR = 1.20, 95% CI = 1.02–1.40) than low baseline CRP level patients, irrespective of cancer or ICI type. Further analysis indicated that 1 mg/dl was appropriate as a cutoff value for determining the low or high level of baseline CRP to predict the OS or PFS of cancer patients receiving ICI treatment (univariate analysis: HR = 1.56, 95% CI = 1.24–1.97, P = 0.909; multivariate analysis: HR = 1.58, 95% CI = 1.23–2.03, P = 0.521). Conclusions High baseline CRP level ( & gt;1 mg/dl) may be an indicator for worse OS and PFS of cancer patients treated with ICIs. More high-quality prospective studies are warranted to assess the predictive value of CRP for ICI treatment.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    URL: Article
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    DOI: 10.3389/fimmu.2022.827788
    DOI: 10.3389/fimmu.2022.827788.s001
    DOI: 10.3389/fimmu.2022.827788.s002
    DOI: 10.3389/fimmu.2022.827788.s003
    DOI: 10.3389/fimmu.2022.827788.s004
    DOI: 10.3389/fimmu.2022.827788.s005
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    DOI: 10.3389/fimmu.2022.827788.s019
    DOI: 10.3389/fimmu.2022.827788.s020
    DOI: 10.3389/fimmu.2022.827788.s021
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
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  • 7
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    Tear-derived exosomal biomarkers of Graves’ ophthalmopathy
    Frontiers Media SA ; 2022
    In:  Frontiers in Immunology Vol. 13 ( 2022-12-6)
    Details
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 13 ( 2022-12-6)
    Abstract: Graves’ ophthalmopathy (GO), the most frequent extrathyroidal manifestation of Graves’ disease (GD), can lead to a significant decline in the quality of life in patients. Exosomes, which contain proteins, lipids and DNA, play important roles in the pathological processes of various diseases. However, their roles in Graves’ ophthalmopathy are still unclear. We aimed to isolate exosomes and analyze the different exosomal proteins. Tear fluids were collected from twenty-four GO patients, twenty-four GD patients and sixteen control subjects. The numbers of tear exosomes were assayed using nanoparticle tracking analysis. A Luminex 200 kit and ELISA kit were used to confirm the different cytokine concentrations in serum. Extraocular muscle from GO patients and controls was extracted, and western blotting was used to assay the levels of Caspase-3 and complement C4A. Our study demonstrated that the number of tear exosomes differ from GD patients and control. The expression levels of cytokines, including IL-1 and IL-18, were significantly increased in the tear exosomes and serum from GO patients compared with GD patients and controls. The levels of the exosomal proteins Caspase-3, complement C4A and APOA-IV were significantly increased in GO patients compared to GD patients and controls. Orbital fibroblasts from GO patients showed significantly higher levels of Caspase-3 and complement C4A than those from controls. The levels of serum APOA-IV in GO patients were significantly higher than those in GD patients and controls. Specific proteins showed elevated expression in tear exosomes from GO patients, indicating that they may play important roles in GO pathogenesis.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    URL: Article
    DOI: 10.3389/fimmu.2022.1088606
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
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  • 8
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    Table_1.pdf
    Frontiers Media SA ; 2021
    In:  Frontiers in Physiology Vol. 12 ( 2021-9-13)
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    In: Frontiers in Physiology, Frontiers Media SA, Vol. 12 ( 2021-9-13)
    Abstract: Maintenance of telomere length is essential to delay replicative cellular senescence. It is controversial on whether growth differentiation factor 11 (GDF11) can reverse cellular senescence, and this work aims to establish the causality between GDF11 and the telomere maintenance unequivocally. Using CRISPR/Cas9 technique and a long-term in vitro culture model of cellular senescence, we show here that in vitro genetic deletion of GDF11 causes shortening of telomere length, downregulation of telomeric reverse transcriptase (TERT) and telomeric RNA component (TERC), the key enzyme and the RNA component for extension of the telomere, and reduction of telomerase activity. In contrast, both recombinant and overexpressed GDF11 restore the transcription of TERT in GDF11 KO cells to the wild-type level. Furthermore, loss of GDF11-induced telomere shortening is likely caused by enhancing the nuclear entry of SMAD2 which inhibits the transcription of TERT and TERC. Our results provide the first proof-of-cause-and-effect evidence that endogenous GDF11 plays a causal role for proliferative cells to maintain telomere length, paving the way for potential rejuvenation of the proliferative cells, tissues, and organs.
    Type of Medium: Online Resource
    ISSN: 1664-042X
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fphys.2021.726345
    DOI: 10.3389/fphys.2021.726345.s001
    DOI: 10.3389/fphys.2021.726345.s002
    DOI: 10.3389/fphys.2021.726345.s003
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2564217-0
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  • 9
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    Image_2.tif
    Frontiers Media SA ; 2022
    In:  Frontiers in Microbiology Vol. 13 ( 2022-7-29)
    Details
    In: Frontiers in Microbiology, Frontiers Media SA, Vol. 13 ( 2022-7-29)
    Abstract: Human bocavirus 1 (HBoV1), first discovered in 2005, was positive in symptomatic and healthy children and co-detected with other respiratory viruses. It is a long journey to decisively demonstrate the unique viral pathogenic function of acute respiratory tract infection (ARTI) in pediatric patients. Methods Respiratory specimens collected from pediatric patients with ARTI from January 2017 to December 2021 were screened by a capillary electrophoresis-based multiplex PCR (CEMP) assay, then genotyped by PCR and sequencing for HBoV1. For the antigen test, a part of HBoV1 DNA positive nasopharyngeal aspirates (NPAs) was used as an antigen, while a rabbit anti-HBoV1 DR2 specific to HBoV1 was used as an antibody in the indirect-immunofluorescence assay (IFA). Finally, the levels of IgG specific to HBoV1 in acute and convalescent sera selected retrospectively from only HBoV1 DNA-positive patients were evaluated by IFA. Results Among 9,899 specimens, 681 were positive for HBoV1 DNA (6.88%, 681/9899), which included 336 positives only for HBoV1 (49.34%, 336/681) and 345 (50.66%, 345/681) positives also for other pathogens. In the antigen test, there were 37 among 47 NPAs determined as HBoV1 antigen-positive (78.72%, 37/47), including 18 (48.65%, 18/37) positives solely for HBoV1 DNA. Among 4 pediatric patients with both acute and convalescent sera, there was one positive for HBoV1 antigen (D8873) and 2 lack the antigen results (D1474 and D10792), which showed seroconversion with a ≥ 4-fold increase in IgG levels. Conclusions The combination results of nucleic acid, antigen, and serology tests answered that HBoV1 is a genuine pathogen for ARTI in pediatric patients.
    Type of Medium: Online Resource
    ISSN: 1664-302X
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fmicb.2022.932858
    DOI: 10.3389/fmicb.2022.932858.s001
    DOI: 10.3389/fmicb.2022.932858.s002
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2587354-4
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  • 10
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    DataSheet2.docx
    Frontiers Media SA ; 2021
    In:  Frontiers in Pharmacology Vol. 12 ( 2021-7-15)
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    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 12 ( 2021-7-15)
    Abstract: Background: Hepatocellular carcinoma (HCC) is a lethal malignancy lacking effective treatment. The Cyclin-dependent kinases 4/6 (CDK4/6) and PI3K/AKT signal pathways play pivotal roles in carcinogenesis and are promising therapeutic targets for HCC. Here we identified a new CDK4/6 and PI3K/AKT multi-kinase inhibitor for the treatment of HCC. Methods: Using a repurposing and ensemble docking methodology, we screened a library of worldwide approved drugs to identify candidate CDK4/6 inhibitors. By MTT, apoptosis, and flow cytometry analysis, we investigated the effects of candidate drug in reducing cell-viability,inducing apoptosis, and causing cell-cycle arrest. The drug combination and thermal proteomic profiling (TPP) method were used to investigate whether the candidate drug produced antagonistic effect. The in vivo anti-cancer effect was performed in BALB/C nude mice subcutaneously xenografted with Huh7 cells. Results: We demonstrated for the first time that the anti-plasmodium drug aminoquinol is a new CDK4/6 and PI3K/AKT inhibitor. Aminoquinol significantly decreased cell viability, induced apoptosis, increased the percentage of cells in G1 phase. Drug combination screening indicated that aminoquinol could produce antagonistic effect with the PI3K inhibitor LY294002. TPP analysis confirmed that aminoquinol significantly stabilized CDK4, CDK6, PI3K and AKT proteins. Finally, in vivo study in Huh7 cells xenografted nude mice demonstrated that aminoquinol exhibited strong anti-tumor activity, comparable to that of the leading cancer drug 5-fluorouracil with the combination treatment showed the highest therapeutic effect. Conclusion: The present study indicates for the first time the discovery of a new CDK4/6 and PI3K/AKT multi-kinase inhibitor aminoquinol. It could be used alone or as a combination therapeutic strategy for the treatment of HCC.
    Type of Medium: Online Resource
    ISSN: 1663-9812
    URL: Article
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    URL: Article
    DOI: 10.3389/fphar.2021.691769
    DOI: 10.3389/fphar.2021.691769.s001
    DOI: 10.3389/fphar.2021.691769.s002
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2587355-6
    SSG: 15,3
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