scholarly journals PD-L1 Status in Gastric Cancers, Association with the Transcriptional, Growth Factors, AKT/mTOR Components Change, and Autophagy Initiation

2021 ◽  
Vol 22 (20) ◽  
pp. 11176
Author(s):  
Liudmila Spirina ◽  
Alexandra Avgustinovich ◽  
Sergei Afanas’ev ◽  
Maxim Volkov ◽  
Alexey Dobrodeev ◽  
...  
Keyword(s):  
Molecular Markers ◽  
Cancer Progression ◽  
Combined Treatment ◽  
Death Receptor ◽  
Autophagic Flux ◽  
Gastric Cancers ◽  
Autophagy Induction ◽  
Programmed Death ◽  
Death Receptor Ligand ◽  
Main Regulator

Introduction: The programmed death receptor ligand 1 (PD-L1) immunohistochemistry (IHC) assay is a widely used selection method for pembrolizumab treatment in gastric cancer (GC) patients. PD-L1 is the main regulator of immunity in oncogenesis. Material and methods: The study included 38 patients with GC. The combined treatment consisted of neoadjuvant FOLFOX6, or FLOT, chemotherapy and surgery. PD-L1 + tumor status was recorded in 12 patients (CPS > 5), with a negative status recorded in 26 patients. RT-PCR determined the expression of molecular markers. The level of LC3B protein was detected by Western Blotting analysis. Results: An overexpression of PD-1, PD-L2 in the tumor is associated with AKT/mTOR mRNA profile change and autophagy initiation in IHC PD-L1 positive GCs. NACT influences these biological features, modifying the expression of AKT/mTOR components and autophagic flux. In PD-L1 positive cancers, the effect of NACT and molecular markers rearrangements are essential compared to the PD-L1 negative cancers. Conclusion: The IHC PD-L1 status in gastric cancers is the significant marker of cancer progression, recovering the multiple inner mechanisms of cancer spreading and leading to ineffective therapy. Autophagy induction and angiogenesis are found in PD-L1 positive gastric cancers.

scholarly journals Increased Expression of Death Receptors 4 and 5 Synergizes the Apoptosis Response to Combined Treatment with Etoposide and TRAIL

2000 ◽  
Vol 20 (1) ◽  
pp. 205-212 ◽  
Author(s):  
Spencer B. Gibson ◽  
Ryan Oyer ◽  
Aaron C. Spalding ◽  
Steven M. Anderson ◽  
Gary L. Johnson
Keyword(s):  
Epithelial Cell ◽  
Cancer Cells ◽  
Topoisomerase Ii ◽  
Combined Treatment ◽  
Death Receptor ◽  
Death Receptors ◽  
Dominant Negative ◽  
Dependent Manner ◽  
Death Receptor Ligand ◽  
Induced Apoptosis

ABSTRACT Chemotherapeutic genotoxins induce apoptosis in epithelial-cell-derived cancer cells. The death receptor ligand TRAIL also induces apoptosis in epithelial-cell-derived cancer cells but generally fails to induce apoptosis in nontransformed cells. We show here that the treatment of four different epithelial cell lines with the topoisomerase II inhibitor etoposide in combination with TRAIL (tumor necrosis factor [TNF]-related apoptosis-inducing ligand) induces a synergistic apoptotic response. The mechanism of the synergistic effect results from the etoposide-mediated increase in the expression of the death receptors 4 (DR4) and 5 (DR5). Inhibition of NF-κB activation by expression of kinase-inactive MEK kinase 1(MEKK1) or dominant-negative IκB (ΔIκB) blocked the increase in DR4 and DR5 expression following etoposide treatment. Addition of a soluble decoy DR4 fusion protein (DR4:Fc) to cell cultures reduced the amount of etoposide-induced apoptosis in a dose-dependent manner. The addition of a soluble TNF decoy receptor (TNFR:Fc) was without effect, demonstrating the specificity of DR4 binding ligands in the etoposide-induced apoptosis response. Thus, genotoxin treatment in combination with TRAIL is an effective inducer of epithelial-cell-derived tumor cell apoptosis relative to either treatment alone.

scholarly journals Programmed Death Receptor-1/Programmed Death Receptor Ligand-1 Blockade after Transient Lymphodepletion To Treat Myeloma

2013 ◽  
Vol 190 (11) ◽  
pp. 5620-5628 ◽  
Author(s):  
Tyce J. Kearl ◽  
Weiqing Jing ◽  
Jill A. Gershan ◽  
Bryon D. Johnson
Keyword(s):  
Death Receptor ◽  
Receptor Ligand ◽  
Programmed Death ◽  
Death Receptor Ligand

scholarly journals Targeting the PD-1/PD-L1 Pathway in Renal Cell Carcinoma

2019 ◽  
Vol 20 (7) ◽  
pp. 1692 ◽  
Author(s):  
Solène-Florence Kammerer-Jacquet ◽  
Antoine Deleuze ◽  
Judikaël Saout ◽  
Romain Mathieu ◽  
Brigitte Laguerre ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Checkpoint Inhibitors ◽  
Death Receptor ◽  
Programmed Death ◽  
Pathologic Features ◽  
Death Receptor Ligand ◽  
Antiangiogenic Drugs

Renal cell carcinoma encompass distinct diseases with different pathologic features and distinct molecular pathways. Immune checkpoint inhibitors targeting the programmed death receptor ligand 1 (PD-L1) / programmed death receptor 1 (PD-1) pathway alone or in combination have greatly changed clinical management of metastatic renal cell carcinoma, now competing with antiangiogenic drugs in monotherapy for first-line treatment. However, long-term response rates are low, and biomarkers are needed to predict treatment response. Quantification of PD-L1 expression by immunohistochemistry was developed as a promising biomarker in clinical trials, but with many limitations (different antibodies, tumour heterogeneity, specimens, and different thresholds of positivity). Other biomarkers, including tumour mutational burden and molecular signatures, are also developed and discussed in this review.

Costs comparison of the immune check point inhibitors versus survival ratio in first-line non-small lung cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21050-e21050
Author(s):  
Helmy M. Guirgis
Keyword(s):  
Lung Cancer ◽  
Death Receptor ◽  
Survival Ratio ◽  
Check Point ◽  
First Line ◽  
Unresectable Stage ◽  
Programmed Death ◽  
Check Point Inhibitors ◽  
Death Receptor Ligand ◽  
One Year

e21050 Background: Five-year overall survival (OS) was reported in 20% of patients treated by Pembrolizumab (Pembro) in 1st-line advanced/metastatic (a/m)-non-small lung cancer (nsLC). Costs of the immune check point inhibitors (ICI) are relatively high and bound to increase with extended use. We purposed to weigh and compare costs of ICI vs outcome. Methods: OS, hazard ratio (HR) and survival ratio (SR) defined as (1.0-HR) were used. Chemo-drug excluded; costs were calculated in US$. Results: Adjuvant Durv one-year costs in unresectable stage III were $130,956, OS gain 363 days and SR 0.47. Pembro one-year costs were $134,778. OS were 474 and SR 0.37 in programmed death receptor-ligand-1 > 50%. At 5 years, costs were $673,890. Costs of 35-cycle Pembro combination were $336,945, OS 339 and SR 0.51. Costs increased with extended use. Atezolizumab/Bevacizumab-combination (Atezo/Bev) costs x 2-years were $492,114, OS 135 and SR 0.22. Using Biosimilar Bev costs dropped to $429,744. Ipilimumab/Nivolumab (Ipi/Nivo) costs x 2 were $544,696, OS 141 and SR 0.34. Costs of both Atezo/Bev and Ipi/Nivo increased by 50% with one year of extended use. Costs of Pembro-combination were 0.78 lower than Atezo/Bev and 0.62 than Ipi/Nivo. Pembro SR were 2.32 higher than Atezo/Bev and 1.65 than Ipi/Nivo. Absence of direct comparison, however, cast doubts on Pembro advantage. Conclusions: Costs of one-year adjuvant Durv, 3-year Pembro and 35-cycle Pembro-combination were considered fair and equitable with their corresponding SR. Pembro-combination costs were cheaper than Atezo/Bev and Nivo/Ipi. Costs of all drugs and combinations multiplied with extended use.

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