scholarly journals Prognostic impact of programmed cell death ligand 1 (PD-L1) expression and its association with epithelial-mesenchymal transition in extrahepatic cholangiocarcinoma

Oncotarget ◽  
2018 ◽  
Vol 9 (28) ◽  
pp. 20034-20047 ◽  
Author(s):  
Takashi Ueno ◽  
Takahiro Tsuchikawa ◽  
Kanako C. Hatanaka ◽  
Yutaka Hatanaka ◽  
Tomoko Mitsuhashi ◽  
...  
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Epithelial Mesenchymal Transition ◽  
Prognostic Impact ◽  
Extrahepatic Cholangiocarcinoma ◽  
Mesenchymal Transition

scholarly journals The Great Escape: The Power of Cancer Stem Cells to Evade Programmed Cell Death

Cancers ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 328
Author(s):  
Vanessa Castelli ◽  
Antonio Giordano ◽  
Elisabetta Benedetti ◽  
Francesco Giansanti ◽  
Massimiliano Quintiliani ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Death ◽  
Cancer Stem Cells ◽  
Programmed Cell Death ◽  
Epithelial Mesenchymal Transition ◽  
Therapeutic Approaches ◽  
Mesenchymal Transition ◽  
Programmed Death ◽  
Current Therapies ◽  
Metastasis Development

Cancer is one of the primary causes of death worldwide. Tumour malignancy is related to tumor heterogeneity, which has been suggested to be due to a small subpopulation of tumor cells named cancer stem cells (CSCs). CSCs exert a key role in metastasis development, tumor recurrence, and also epithelial–mesenchymal transition, apoptotic resistance, self-renewal, tumorigenesis, differentiation, and drug resistance. Several current therapies fail to eradicate tumors due to the ability of CSCs to escape different programmed cell deaths. Thus, developing CSC-selective and programmed death-inducing therapeutic approaches appears to be of primary importance. In this review, we discuss the main programmed cell death occurring in cancer and the promising CSC-targeting agents developed in recent years. Even if the reported studies are encouraging, further investigations are necessary to establish a combination of agents able to eradicate CSCs or inhibit their growth and proliferation.

scholarly journals Survival Impact of Aggressive Treatment and PD-L1 Expression in Oligometastatic NSCLC

2021 ◽  
Vol 28 (1) ◽  
pp. 593-605
Author(s):  
Camille Gauvin ◽  
Vimal Krishnan ◽  
Imane Kaci ◽  
Danh Tran-Thanh ◽  
Karine Bédard ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Death ◽  
Treatment Group ◽  
Programmed Cell Death ◽  
Prognostic Impact ◽  
Aggressive Treatment ◽  
Palliative Approach ◽  
Oligometastatic Disease ◽  
Group A ◽  
Group B

Background: Studies have shown that aggressive treatment of non-small cell lung cancer (NSCLC) with oligometastatic disease improves the overall survival (OS) compared to a palliative approach and some immunotherapy checkpoint inhibitors, such as anti-programmed cell death ligand 1 (PD-L1), anti-programmed cell death protein 1 (PD-1), and T-Lymphocyte-associated antigen 4 (CTLA-4) inhibitors are now part of the standard of care for advanced NSCLC. However, the prognostic impact of PD-L1 expression in the oligometastatic setting remains unknown. Methods: Patients with oligometastatic NSCLC were identified from the patient database of the Centre hospitalier de l’Université de Montréal (CHUM). “Oligometastatic disease” definition chosen is one synchronous metastasis based on the M1b staging of the eight IASLC (The International Association for the Study of Lung Cancer) Classification (within sixth months of diagnosis) or up to three cerebral metastasis based on the methodology of the previous major phase II randomized study of Gomez et al. We compared the OS between patients receiving aggressive treatment at both metastatic and primary sites (Group A) and patients receiving non-aggressive treatment (Group B). Subgroup analysis was performed using tumor PD-L1 expression. Results: Among 643 metastatic NSCLC patients, we identified 67 patients with oligometastasis (10%). Median follow-up was 13.3 months. Twenty-nine patients (43%) received radical treatment at metastatic and primary sites (Group A), and 38 patients (57%) received non-aggressive treatment (Group B). The median OS (mOS) of Group A was significantly longer than for Group B (26 months vs. 5 months, p = 0.0001). Median progression-free survival (mPFS) of Group A was superior than Group B (17.5 months vs. 3.4 months, p = 0.0001). This difference was still significant when controlled for primary tumor staging: stage I (p = 0.316), stage II (p = 0.024), and stage III (p = 0.001). In the cohort of patients who were not treated with PD-L1 inhibitors, PD-L1 expression negatively correlated with mOS. Conclusions: Aggressive treatments of oligometastatic NSCLC significantly improve mOS and mPFS compared to a more palliative approach. PD-L1 expression is a negative prognostic factor which suggests a possible role for immunotherapy in this setting.

scholarly journals A radiosensitizer, gallotannin-rich extract from Bouea macrophylla seeds, inhibits radiation-induced epithelial-mesenchymal transition in breast cancer cells

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jiraporn Kantapan ◽  
Siwaphon Paksee ◽  
Aphidet Duangya ◽  
Padchanee Sangthong ◽  
Sittiruk Roytrakul ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dna Damage ◽  
Cell Death ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Breast Cancer Cell Lines ◽  
Mesenchymal Transition ◽  
Mammosphere Formation ◽  
Radiation Induced

Abstract Background Radioresistance can pose a significant obstacle to the effective treatment of breast cancers. Epithelial–mesenchymal transition (EMT) is a critical step in the acquisition of stem cell traits and radioresistance. Here, we investigated whether Maprang seed extract (MPSE), a gallotannin-rich extract of seed from Bouea macrophylla Griffith, could inhibit the radiation-induced EMT process and enhance the radiosensitivity of breast cancer cells. Methods Breast cancer cells were pre-treated with MPSE before irradiation (IR), the radiosensitizing activity of MPSE was assessed using the colony formation assay. Radiation-induced EMT and stemness phenotype were identified using breast cancer stem cells (CSCs) marker (CD24−/low/CD44+) and mammosphere formation assay. Cell motility was determined via the wound healing assay and transwell migration. Radiation-induced cell death was assessed via the apoptosis assay and SA-β-galactosidase staining for cellular senescence. CSCs- and EMT-related genes were confirmed by real-time PCR (qPCR) and Western blotting. Results Pre-treated with MPSE before irradiation could reduce the clonogenic activity and enhance radiosensitivity of breast cancer cell lines with sensitization enhancement ratios (SERs) of 2.33 and 1.35 for MCF7 and MDA-MB231cells, respectively. Pretreatment of breast cancer cells followed by IR resulted in an increased level of DNA damage maker (γ-H2A histone family member) and enhanced radiation-induced cell death. Irradiation induced EMT process, which displayed a significant EMT phenotype with a down-regulated epithelial marker E-cadherin and up-regulated mesenchymal marker vimentin in comparison with untreated breast cancer cells. Notably, we observed that pretreatment with MPSE attenuated the radiation-induced EMT process and decrease some stemness-like properties characterized by mammosphere formation and the CSC marker. Furthermore, pretreatment with MPSE attenuated the radiation-induced activation of the pro-survival pathway by decrease the expression of phosphorylation of ERK and AKT and sensitized breast cancer cells to radiation. Conclusion MPSE enhanced the radiosensitivity of breast cancer cells by enhancing IR-induced DNA damage and cell death, and attenuating the IR-induced EMT process and stemness phenotype via targeting survival pathways PI3K/AKT and MAPK in irradiated breast cancer cells. Our findings describe a novel strategy for increasing the efficacy of radiotherapy for breast cancer patients using a safer and low-cost natural product, MPSE.

scholarly journals Epithelial-Mesenchymal Transition Induces GSDME Transcriptional Activation for Inflammatory Pyroptosis

2021 ◽  
Vol 9 ◽  
Author(s):  
Chenqiang Jia ◽  
Zhuqing Zhang ◽  
Jun Tang ◽  
Mei-Chun Cai ◽  
Jingyu Zang ◽  
...  
Keyword(s):  
Cell Death ◽  
Transcriptional Activation ◽  
Promoter Region ◽  
Drug Exposure ◽  
Epithelial Mesenchymal Transition ◽  
Experimental Models ◽  
Cytokine Release ◽  
Functional Importance ◽  
Bioinformatics Analyses ◽  
Mesenchymal Transition

GSDME is a newly recognized executor of cellular pyroptosis, and has been recently implicated in tumor growth and immunity. However, knowledge about the molecular regulators underlying GSDME abundance remains limited. Here, we performed integrative bioinformatics analyses and identified that epithelial-mesenchymal transition (EMT) gene signatures exhibited positive correlation with GSDME levels across human cancers. A causal role was supported by the observation that EMT dictated GSDME reversible upregulation in multiple experimental models. Mechanistically, transcriptional activation of GSDME was directly driven by core EMT-activating transcription factors ZEB1/2, which bound to the GSDME promoter region. Of functional importance, elevated GSDME in mesenchymally transdifferentiated derivatives underwent proteolytic cleavage upon antineoplastic drug exposure, leading to pyroptotic cell death and consequent cytokine release. Taken together, our findings pinpointed a key transcriptional machinery controlling GSDME expression and indicated potential therapeutic avenues to exploit GSDME-mediated inflammatory pyroptosis for the treatment of mesenchymal malignancies.

Sign in / Sign up

Export Citation Format

Share Document