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  • Online Resource  (5)
  • Frontiers Media SA  (5)
  • Wang, Shao-Gang  (5)
  • Zeng, Na  (5)
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  • Online Resource  (5)
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  • Frontiers Media SA  (5)
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  • 1
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Immunology Vol. 13 ( 2022-7-11)
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 13 ( 2022-7-11)
    Abstract: Bladder cancer (BCa) is the 10th most commonly diagnosed cancer worldwide, and cellular senescence is defined as a state of permanent cell cycle arrest and considered to play important roles in the development and progression of tumor. However, the comprehensive effect of senescence in BCa has not ever been systematically evaluated. Using the genome-wide CRISPR screening data acquired from DepMap (Cancer Dependency Map), senescence genes from the CellAge database, and gene expression data from The Cancer Genome Atlas (TCGA), we screened out 12 senescence genes which might play critical roles in BCa. A four-cell-senescence-regulator-gene prognostic index was constructed using the least absolute shrinkage and selection operator (LASSO) and multivariate COX regression model. The transcriptomic data and clinical information of BCa patients were downloaded from TCGA and Gene Expression Omnibus (GEO). We randomly divided the patients in TCGA cohort into training and testing cohorts and calculated the risk score according to the expression of the four senescence genes. The validity of this risk score was validated in the testing cohort (TCGA) and validation cohort (GSE13507). The Kaplan–Meier curves revealed a significant difference in the survival outcome between the high- and low-risk score groups. A nomogram including the risk score and other clinical factors (age, gender, stage, and grade) was established with better predictive capacity of OS in 1, 3, and 5 years. Besides, we found that patients in the high-risk group had higher tumor mutation burden (TMB); lower immune, stroma, and ESTIMATE scores; higher tumor purity; aberrant immune functions; and lower expression of immune checkpoints. We also performed gene set variation analysis (GSVA) and gene set enrichment analysis (GSEA) to investigate the interaction between risk score and hallmark pathways and found that a high risk score was connected with activation of senescence-related pathways. Furthermore, we found that a high risk score was related to better response to immunotherapy and chemotherapy. In conclusion, we identified a four-cell-senescence-regulator-gene prognostic index in BCa and investigated its relationship with TMB, the immune landscape of tumor microenvironment (TME), and response to immunotherapy and chemotherapy, and we also established a nomogram to predict the prognosis of patients with BCa.
    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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  • 2
    Online Resource
    Online Resource
    Frontiers Media SA ; 2023
    In:  Frontiers in Oncology Vol. 13 ( 2023-8-30)
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 13 ( 2023-8-30)
    Abstract: This meta-analysis and systematic review aim to analyze the association between BT and oncological outcomes of patients undergoing RC for bladder cancer, and tries to find out whether the timing of blood transfusion could also have an effect on this relationship. A total of 20 retrospective studies from online databases and other sources are identified and enrolled in this study. The results show that BT administration during RC operation or perioperative period is significantly associated with worse oncological outcomes including ACM, CSM and DR. Background Bladder cancer is one of the most common urological malignancies. Radical cystectomy (RC) remains the main treatment for localized muscle-invasive bladder cancer (MIBC) or high-grade non-muscle-invasive bladder cancer (NMIBC). In the process of RC, the administration of blood transfusion (BT) is sometimes needed, however, it may cause transfusion-related complications or lead to worse oncological outcomes. This meta-analysis and systematic review aims to give a comprehensive insight into the association between BT and oncological outcomes of patients undergoing RC, and tries to find out whether the timing of blood transfusion could also have an impact on this association. Methods This systematic review and meta-analysis were carried out according to the PRISMA 2020 reporting guideline. We have searched four bibliographic databases including PubMed (Medline), EMBASE, Cochrane Library, and Web of Science with no language limitation. Studies investigating the association between BT and oncological outcomes of patients undergoing RC are identified and included in this research from inception through March 20, 2023. This research calculates the pooled hazard ratios (pHR) and 95% confidence intervals (95% CI) of all-cause mortality (ACM), cancer-specific mortality (CSM) and disease recurrence (DR) using Random Effects models or Fixed Effects models. Subgroup analyses stratified by parameters such as timing of transfusion are also conducted. This meta-analysis was registered with PROSPERO, CRD42022381656. Results A total of 20 retrospective studies from online databases and other sources are identified and enrolled in this study. Results show that blood transfusion significantly increased the risks for ACM (HR = 1.33, 95% CI: 1.23-1.44), CSM (HR = 1.25, 95% CI: 1.15 – 1.35) and DR (HR = 1.26, 95% CI: 1.15 – 1.38). However, when stratified by the timing of BT, we find that only intraoperative and perioperative transfusion significantly increased in risks for worse prognosis, while postoperative transfusion raised none of the risks of ACM (HR = 1.26, 95% CI: 0.92-1.73), CSM (HR = 1.08, 95% CI: 0.93-1.26) nor DR (HR = 1.08, 95% CI: 0.90-1.29) significantly. Conclusion BT administration during RC operation or perioperative period is significantly associated with worse oncological outcomes including ACM, CSM and DR. Clinicians should consider carefully when deciding to administrate BT to patients undergoing RC and carry out according to current guidelines.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2649216-7
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  • 3
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 13 ( 2023-3-24)
    Abstract: T cell immunoglobulin and ITIM domain (TIGIT) is a widely concerned immune checkpoint, which plays an essential role in immunosuppression and immune evasion. However, the role of TIGIT in normal organ tissues and renal clear cell carcinoma is unclear. We aim to identify the critical role of TIGIT in renal clear cell carcinoma and find potential targeted TIGIT drugs. Materials and methods Data retrieved from the GTEX database and TCGA database was used to investigate the expression of TIGIT in normal whole-body tissues and abnormal pan-cancer, then the transcriptome atlas of patients with kidney renal clear cell carcinoma (KIRC) in the TCGA database were applied to distinguish the TIGIT related features, including differential expression status, prognostic value, immune infiltration, co-expression, and drug response of sunitinib an anti-PD1/CTLA4 immunotherapy in KIRC. Furthermore, we constructed a gene-drug network to discover a potential drug targeting TIGIT and verified it by performing molecular docking. Finally, we conducted real-time polymerase chain reaction (PCR) and assays for Transwell migration and CCK-8 to explore the potential roles of TIGIT. Results TIGIT showed a moderate expression in normal kidney tissues and was confirmed as an essential prognostic factor that was significantly higher expressed in KIRC tissues, and high expression of TIGIT is associated with poor OS, PFS, and DSS in KIRC. Also, the expression of TIGIT was closely associated with the pathological characteristics of the tumor, high expression of TIGIT in KIRC was observed with several critical functions or pathways such as apoptosis, BCR signaling, TCR signaling et al. Moreover, the expression of TIGIT showed a strong positive correlation with infiltration of CD8+ T cells and Tregs and a positive correlation with the drug sensitivity of sunitinib simultaneously. Further Tide ips score analysis and submap analysis reveal that patients with high TIGIT expression significantly show a better response to anti-PD1 immunotherapy. Following this, we discovered Selumetinib and PD0325901 as potential drugs targeting TIGIT and verified the interaction between these two drugs and TIGIT protein by molecular docking. Finally, we verified the essential role of TIGIT in the proliferation and migration functions by using KIRC cell lines. Conclusions TIGIT plays an essential role in tumorigenesis and progression in KIRC. High expression of TIGIT results in poor survival of KIRC and high drug sensitivity to sunitinib. Besides, Selumetinib and PD0325901 may be potential drugs targeting TIGIT, and combined therapy of anti-TIGIT and other treatments show great potential in treating KIRC.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2649216-7
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  • 4
    Online Resource
    Online Resource
    Frontiers Media SA ; 2023
    In:  Frontiers in Oncology Vol. 13 ( 2023-5-12)
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 13 ( 2023-5-12)
    Abstract: With the shortage of bacillus Calmette–Guérin (BCG) vaccine, it is important to find an alternative to BCG instillation, which is the most commonly used adjuvant treatment for non-muscle-invasive bladder cancer (NMIBC) patients after transurethral resection of bladder tumor treatment (TURBt) to delay tumor recurrence. Hyperthermia intravesical chemotherapy (HIVEC) with mitomycin C (MMC) is a potential treatment choice. We aim to compare HIVEC with BCG instillation for the preventive efficacy of bladder tumor recurrence and progression. Methods A network meta-analysis (NMA) was taken with MMC instillation and TURBt as the attached comparators. Randomized controlled trials (RCTs) with NIMBC patients after TURBt were included. Articles with pure BCG unresponsive patients and combined therapies were excluded. The study protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO, CRD42023390363). Results It was found that HIVEC had a non-significant 22% relative reduction in bladder tumor recurrence compared with BCG instillation [HIVEC vs. BCG: HR 0.78, 95% credible interval (CrI) 0.55–1.08] and a nonsignificant higher risk of bladder tumor progression (BCG vs. HIVEC: HR 0.77, 95% CrI 0.22–3.03). Discussion HIVEC is a potential alternative to BCG, and it is expected to be the standard therapy for NMIBC patients after TURBt during the global shortage of BCG. Systematic Review Registration PROSPERO identifier, CRD42023390363
    Type of Medium: Online Resource
    ISSN: 2234-943X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2649216-7
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  • 5
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 15 ( 2024-4-17)
    Abstract: The emergence of resistance to prostate cancer (PCa) treatment, particularly to androgen deprivation therapy (ADT), has posed a significant challenge in the field of PCa management. Among the therapeutic options for PCa, radiotherapy, chemotherapy, and hormone therapy are commonly used modalities. However, these therapeutic approaches, while inducing apoptosis in tumor cells, may also trigger stress-induced premature senescence (SIPS). Cellular senescence, an entropy-driven transition from an ordered to a disordered state, ultimately leading to cell growth arrest, exhibits a dual role in PCa treatment. On one hand, senescent tumor cells may withdraw from the cell cycle, thereby reducing tumor growth rate and exerting a positive effect on treatment. On the other hand, senescent tumor cells may secrete a plethora of cytokines, growth factors and proteases that can affect neighboring tumor cells, thereby exerting a negative impact on treatment. This review explores how radiotherapy, chemotherapy, and hormone therapy trigger SIPS and the nuanced impact of senescent tumor cells on PCa treatment. Additionally, we aim to identify novel therapeutic strategies to overcome resistance in PCa treatment, thereby enhancing patient outcomes.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2024
    detail.hit.zdb_id: 2606827-8
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