Apoptosis-related gene expression can predict the response of ovarian cancer cell lines to treatment with recombinant human TRAIL alone or combined with cisplatin

Braga, Letícia da Conceição; Gonçales, Nikole Gontijo; Furtado, Rafaela de Souza; Andrade, Warne Pedro de; Silva, Luciana Maria; Filho, Agnaldo Lopes da Silva

doi:10.6061/clinics/2020/e1492

Cited by 5 publications

(3 citation statements)

References 33 publications

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“…The combination of cisplatin with rhTRAIL significantly increased apoptosis as compared to cisplatin or rhTRAIL monotherapy [29]. The same effect has been demonstrated in the SKOV-3 and TOV-21G cell lines by Braga et al [30]. Caspase-8 seems to be a good prediction marker for therapy response, which can be used to predict chemoresistance.…”

Section: Apoptotic and Non-apoptotic Functions Of Caspase-8supporting

confidence: 53%

The role of caspase-8 in the tumor microenvironment of ovarian cancer

Kostova

Mandal

Becker

et al. 2020

Cancer Metastasis Rev

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Caspase-8 is an aspartate-specific cysteine protease, which is best known for its apoptotic functions. Caspase-8 is placed at central nodes of multiple signal pathways, regulating not only the cell cycle but also the invasive and metastatic cell behavior, the immune cell homeostasis and cytokine production, which are the two major components of the tumor microenvironment (TME). Ovarian cancer often has dysregulated caspase-8 expression, leading to imbalance between its apoptotic and non-apoptotic functions within the tumor and the surrounding milieu. The downregulation of caspase-8 in ovarian cancer seems to be linked to high aggressiveness with chronic inflammation, immunoediting, and immune resistance. Caspase-8 plays therefore an essential role not only in the primary tumor cells but also in the TME by regulating the immune response, B and T lymphocyte activation, and macrophage differentiation and polarization. The switch between M1 and M2 macrophages is possibly associated with changes in the caspase-8 expression. In this review, we are discussing the non-apoptotic functions of caspase-8, highlighting this protein as a modulator of the immune response and the cytokine composition in the TME. Considering the low survival rate among ovarian cancer patients, it is urgently necessary to develop new therapeutic strategies to optimize the response to the standard treatment. The TME is highly heterogenous and provides a variety of opportunities for new drug targets. Given the variety of roles of caspase-8 in the TME, we should focus on this protein in the development of new therapeutic strategies against the TME of ovarian cancer.

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Section: Apoptotic and Non-apoptotic Functions Of Caspase-8supporting

confidence: 53%

The role of caspase-8 in the tumor microenvironment of ovarian cancer

Kostova

Mandal

Becker

et al. 2020

Cancer Metastasis Rev

View full text Add to dashboard Cite

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“…Furthermore, cisplatin can induce TRAIL apoptotic pathway in glioblastoma cells neurospheres by DR5 up-regulation and c-FLIP downregulation ( 92 ), and also in ovarian cancer SKOV-3 and TOV-21G cells through up-regulating Bax and caspase 3 expression and down-regulating Bcl-2 expression ( 93 ). Moreover, for enhancing the efficacy of TRAIL receptor agonists, the proteasome inhibitor bortezomib is considered one of the most effective sensitizers.…”

Section: Overcoming Trail Resistance Using Combination Therapymentioning

confidence: 99%

RETRACTED: Harnessing TRAIL-Induced Apoptosis Pathway for Cancer Immunotherapy and Associated Challenges

et al. 2021

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The immune cytokine tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has attracted rapidly evolving attention as a cancer treatment modality because of its competence to selectively eliminate tumor cells without instigating toxicity in vivo. TRAIL has revealed encouraging promise in preclinical reports in animal models as a cancer treatment option; however, the foremost constraint of the TRAIL therapy is the advancement of TRAIL resistance through a myriad of mechanisms in tumor cells. Investigations have documented that improvement of the expression of anti-apoptotic proteins and survival or proliferation involved signaling pathways concurrently suppressing the expression of pro-apoptotic proteins along with down-regulation of expression of TRAILR1 and TRAILR2, also known as death receptor 4 and 5 (DR4/5) are reliable for tumor cells resistance to TRAIL. Therefore, it seems that the development of a therapeutic approach for overcoming TRAIL resistance is of paramount importance. Studies currently have shown that combined treatment with anti-tumor agents, ranging from synthetic agents to natural products, and TRAIL could result in induction of apoptosis in TRAIL-resistant cells. Also, human mesenchymal stem/stromal cells (MSCs) engineered to generate and deliver TRAIL can provide both targeted and continued delivery of this apoptosis-inducing cytokine. Similarly, nanoparticle (NPs)-based TRAIL delivery offers novel platforms to defeat barricades to TRAIL therapeutic delivery. In the current review, we will focus on underlying mechanisms contributed to inducing resistance to TRAIL in tumor cells, and also discuss recent findings concerning the therapeutic efficacy of combined treatment of TRAIL with other antitumor compounds, and also TRAIL-delivery using human MSCs and NPs to overcome tumor cells resistance to TRAIL.

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“…The loss of TNFRSF10C makes cells susceptible to apoptosis induced by TNF-related apoptosis-inducing ligand 29 . TNFRSF10C methylation can predict the overall survival of cancer patients 30 , while the expression of TNFRSF10B can serve as a good predictor for the response of cancer cells to drug treatment 31 . In the present study, bioinformatics-based functional enrichment analysis revealed that TNF could serve as the central gene of the cytokine-cytokine receptor interaction pathway 32 .…”

Section: Discussionmentioning

confidence: 99%

CNV Analysis of the Correlation between Preoperative Lymph Node Metastasis and Prognosis of Early Tongue Cancer

2021

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Objective: To investigate the relationship between preoperative concealed lymph node metastasis (LNM) and prognosis in patients with early tongue cancer. Methods: According to preoperative lymph node dissection, 41 patients with tongue cancer were divided into the LNM group (n=19) and the non-LNM group (n=22). Analysis of single nucleotide variation (SNV), tumor mutation burden (TMB), mutant allele tumor heterogeneity (MATH), aneuploidy and copy number variation (CNV) was performed to identify differentially expressed genes (DEGs) related to LNM. While KEGG analysis was conducted to reveal the CNV differentially expressed genes and main enriched pathways, the correlation between pathways and genes was analyzed by hierarchical clustering. The clinical information of LNM and data on overall survival (OS) rate were obtained from The Cancer Genome Atlas (TCGA), and survival analysis was performed based on combined LNM information. Results: We observed significant correlations for the mTOR signaling pathway, Hippo signaling pathway and Wnt signaling pathway with the LNM group, while leukocyte transendothelial migration and cytokine-cytokine receptor interaction were markedly correlated with the non-LNM group. Moreover, TNFRSF10C was identified as the main DEG in the leukocyte transendothelial migration pathway. TCGA-based validation revealed that the disease-free survival (DFS) of the non-LNM group was significantly higher than that of the LNM group (P<0.005) when TNFRSF10C CNV was set to a log2 ratio>-0.163. Conclusion:The differential expression of TNFRSF10C in leukocyte transendothelial migration, an immune-related pathway, is associated with LNM and DFS. The TNFRSF10C CNV log2 ratio could potentially serve as an indicator of good prognosis for tongue cancer patients with non-LNM after neck dissection.

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Apoptosis-related gene expression can predict the response of ovarian cancer cell lines to treatment with recombinant human TRAIL alone or combined with cisplatin

Cited by 5 publications

References 33 publications

The role of caspase-8 in the tumor microenvironment of ovarian cancer

The role of caspase-8 in the tumor microenvironment of ovarian cancer

RETRACTED: Harnessing TRAIL-Induced Apoptosis Pathway for Cancer Immunotherapy and Associated Challenges

CNV Analysis of the Correlation between Preoperative Lymph Node Metastasis and Prognosis of Early Tongue Cancer

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