Synergistic Antitumor Effect on Bladder Cancer by Rational Combination of Programmed Cell Death 1 Blockade and CRISPR-Cas9-Mediated Long Non-Coding RNA Urothelial Carcinoma Associated 1 Knockout

2018 ◽  
Vol 29 (12) ◽  
pp. 1352-1363 ◽  
Author(s):  
Shuai Zhen ◽  
Jiaojiao Lu ◽  
Wei Chen ◽  
Le Zhao ◽  
Xu Li
Keyword(s):  
Bladder Cancer ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Urothelial Carcinoma ◽  
Antitumor Effect ◽  
Synergistic Antitumor Effect ◽  
Non Coding Rna ◽  
Programmed Cell Death 1 ◽  
Rational Combination ◽  
Long Non Coding Rna

scholarly journals PD-L1 Expression in Muscle-Invasive Urinary Bladder Urothelial Carcinoma According to Basal/Squamous-Like Phenotype

2020 ◽  
Vol 10 ◽  
Author(s):  
Bohyun Kim ◽  
Cheol Lee ◽  
Young A. Kim ◽  
Kyung Chul Moon
Keyword(s):  
Bladder Cancer ◽  
Cell Death ◽  
Urinary Bladder ◽  
Programmed Cell Death ◽  
Urothelial Carcinoma ◽  
Urinary Bladder Cancer ◽  
Programmed Cell Death 1 ◽  
Positive Rate ◽  
Muscle Invasive ◽  
Expression Classification

Urothelial carcinoma (UC) is the most common histologic type of urinary bladder cancer, and muscle-invasive UC shows aggressive behaviors. Programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) blockades have been approved as standard treatments for patients with advanced stage UC. A total of 166 muscle-invasive urinary bladder cancer (MIBC) patients, who underwent transurethral resection of the bladder or cystectomy from 2004 to 2010 were included. We evaluated PD-L1 expression by the SP142 and SP263 assays and classified the cases “positive” or “negative” according to the manufacturer’s recommendations. We performed immunohistochemistry (IHC) for cytokeratin (CK) 5/6, CK14, GATA3, FOXA1, and CK20 and classified samples as Basal-Squamous-like (BASQ) or non-BASQ subtype. The overall concordance rate for PD-L1 expression is 91.6% (152/166) (kappa = 0.732). The SP142 assay showed 15.1% positivity; the SP263 assay showed 23.5%. The high positivity in the SP142 and SP263 assay was significantly correlated with positive CK5/6, CK14 expression, negative GATA3, FOXA1, and CK20 expression. Classification according to IHC expression resulted in 12.0% (20/166) of samples being classified as BASQ subtype and 88.0% (146/166) of samples being classified as non-BASQ subtype. High positivity in the SP142 and SP263 assay was significantly correlated with the BASQ subtype (p < 0.001, both). Our study is the first to analyze the association of immunohistochemically defined BASQ and non-BASQ subtypes with two PD-L1 assays in MIBC. In conclusion, we revealed that a high PD-L1 positive rate in all PD-L1 assays was significantly associated with the BASQ-subtype, and these results suggest that the BASQ classification may be important to apply the PD-1/PD-L1 blockades in MIBC.

scholarly journals Ferroptosis-Related Long Non-Coding RNA Signature Contributes to the Prediction of Prognosis Outcomes in Head and Neck Squamous Cell Carcinomas

2021 ◽  
Vol 12 ◽  
Author(s):  
Wenru Jiang ◽  
Yingtao Song ◽  
Zhaowei Zhong ◽  
Jili Gao ◽  
Xiaofei Meng
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Head And Neck ◽  
Squamous Cell ◽  
Risk Group ◽  
External Validation ◽  
Low Risk ◽  
Survival Prediction ◽  
Non Coding Rna ◽  
Long Non Coding Rna

Background: Head and neck squamous cell carcinoma (HNSCC) is a malignant tumor, which makes the prognosis prediction challenging. Ferroptosis is an iron-dependent form of non-apoptotic regulated cell death, which could affect cancer development. However, the prognostic value of ferroptosis-related long non-coding RNA (lncRNA) in HNSCC is still limited.Methods: In the current study, we employed the DESeq2 method to characterize the differentially expressed ferroptosis-related genes (FEGs) between cancer and normal samples. Next, the FEG-related lncRNAs (FElncRNAs) were identified using Spearman’s correlation analysis and multiple permutation hypotheses. Subsequently, LASSO and stepwise multivariate Cox regression analyses were undertaken to recognize the prognosis-related FElncRNA signature (PFLS) and risk scores.Results: Herein, we first identified 60 dysregulated FEGs and their co-expressed FElncRNAs in HNSCC. Then, we recognized a set of six FElncRNAs PFLS (SLCO4A1-AS1, C1RL-AS1, PCED1B-AS1, HOXB-AS3, MIR9-3HG, and SFTA1P) for predicting patients’ prognostic risks and survival outcomes. We also assessed the efficiency of PFLS in the test set and an external validation cohort. Further parsing of the tumor immune microenvironment showed the PFLS was closely associated with immune cell infiltration abundances. Notably, the low-risk group of the PFLS showed a higher MHC score and cytolytic activity (CYT) score than the high-risk group, implying the low-risk group may have greater tumor surveillance and killing ability. In addition, we observed that the expression levels of two immune checkpoints (ICPs), i.e., programmed cell death protein 1 (PD-1) and programmed cell death 1 ligand 1 (PD-L1), showed significant associations with patients’ risk score, prompting the role of the PFLS in ICP blockade therapy. Finally, we also constructed a drug–PFLS network to reinforce the clinical utilities of the PFLS.Conclusion: In summary, our study indicated that FElncRNAs played an important role in HNSCC survival prediction. Identification of PFLS will contribute to the development of novel anticancer therapeutic strategies.

scholarly journals Combination of anti-angiogenic therapy Apatinib and immune therapy potentiate tumor microenvironment

2021 ◽  
Vol 5 (2.1) ◽  
pp. 79
Author(s):  
Chunyi Gao ◽  
Tianhui Hu
Keyword(s):  
Cell Death ◽  
Tumor Microenvironment ◽  
Programmed Cell Death ◽  
Antitumor Effect ◽  
Overall Response Rate ◽  
Response Rate ◽  
Immune Therapy ◽  
Antiangiogenic Agents ◽  
Angiogenic Therapy ◽  
Programmed Cell Death 1

Tumor immune therapy, especially anti-programmed cell death ligand-1/programmed cell death-1 (PD-L1/PD-1) treatment, is currently the focus of substantial attention. However, despite its enormous successes, the overall response rate of cancer immunotherapy remains suboptimal. There is an increased interest in combining PD-L1/PD-1 treatment with anti-angiogenic drug Apatinib to enhance antitumor effect. Presently available data seem to suggest that Apatinib may exert immune suppressive effects to make the PD-L1/PD-1 treatment works. Here, we review the extensive tumor microenvironment immune modulatory effects from antiangiogenic agents Apatinib in order to supporting VEGFR2 targettherapies in clinical trials are existing.

scholarly journals Long non-coding RNA urothelial carcinoma–associated 1 as a tumor biomarker for the diagnosis of urinary bladder cancer

Tumor Biology ◽  
2017 ◽  
Vol 39 (6) ◽  
pp. 101042831770999 ◽  
Author(s):  
Zichun Wang ◽  
Xiaoxiong Wang ◽  
Daming Zhang ◽  
Yongchun Yu ◽  
Licheng Cai ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Urinary Bladder ◽  
Urothelial Carcinoma ◽  
Urinary Bladder Cancer ◽  
Tumor Biomarker ◽  
Non Coding Rna ◽  
Long Non Coding Rna
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