Loss of programmed cell death 10 activates tumor cells and leads to temozolomide-resistance in glioblastoma

2018 ◽  
Vol 141 (1) ◽  
pp. 31-41 ◽  
Author(s):  
Ann-Christin Nickel ◽  
Xue-Yan Wan ◽  
Dino-Vitali Saban ◽  
Yin-Lun Weng ◽  
Shu Zhang ◽  
...  
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Tumor Cells

Clinical relevance of transmembrane drug efflux as a mechanism of multidrug resistance.

1998 ◽  
Vol 16 (11) ◽  
pp. 3674-3690 ◽  
Author(s):  
D M Bradshaw ◽  
R J Arceci
Keyword(s):  
Drug Resistance ◽  
Cell Death ◽  
Multidrug Resistance ◽  
Programmed Cell Death ◽  
Tumor Cells ◽  
Efflux Pump ◽  
Active Form ◽  
Cytotoxic Agents ◽  
Transport Systems ◽  
Drug Efflux

For cytotoxic agents to have an effect on tumor cells, drugs must first be transported into the cell, potentially be metabolized to an active form, and interact appropriately with target molecules. A final common pathway of cytotoxic agents is usually the initiation of programmed cell death, or apoptosis. Tumor cells overcome the effects of cytotoxic agents at one or more of these levels. The classic multidrug-resistance (MDR) phenotype, as mediated by the drug efflux pump, P-glycoprotein, is one of the most extensively studied mechanisms of drug resistance. Additional drug transporters, such as the multidrug resistance-associated proteins (MRPs), have also been identified and can convey drug-resistance phenotypes. Important questions remain as to how and whether such transport systems can be specifically measured and effectively targeted to improve therapeutic outcomes. Furthermore, alterations in drug targets, drug metabolism, repair of DNA damage caused by drugs, and the inability to initiate programmed cell death can all contribute to drug resistance and must be ultimately considered in the explanation of tumor-cell resistance to therapy. Continued exploration of the pharmacologic methods to circumvent drug resistance, as well as strategies that involve targeted therapy and immunomodulation, should increase the specificity and efficacy of treatments for patients with cancer.

scholarly journals Association of Lung Adenocarcinoma Subtypes According to the IASLC/ATS/ERS Classification and Programmed Cell Death Ligand 1 (PD-L1) Expression in Tumor Cells

2021 ◽  
Vol 27 ◽  
Author(s):  
Graciela Cruz-Rico ◽  
Alejandro Avilés-Salas ◽  
Xitlally Popa-Navarro ◽  
Luis Lara-Mejía ◽  
Rodrigo Catalán ◽  
...  
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Lung Adenocarcinoma ◽  
Tumor Cells ◽  
Clinical Features ◽  
Final Analysis ◽  
Small Cell Lung ◽  
Entire Cohort ◽  
C 50 ◽  
L1 Protein

Background: Programmed cell death-ligand 1 (PD-L1) protein expression is one of the most extensively studied biomarkers in patients with non-small cell lung cancer (NSCLC). However, there is scarce information regarding its association with distinct adenocarcinoma subtypes. This study evaluated the frequency of PD-L1 expression according to the IASLC/ATS/ERS classification and other relevant histological and clinical features.Patients and Methods: PD-L1 expression was assessed by immunohistochemistry (IHC). According to its positivity in tumor cells membrane, we stratified patients in three different tumor proportions score (TPS) cut-off points: a) <1% (negative), b) between 1 and 49%, and c) ≥50%; afterward, we analyzed the association among PD-L1 expression and lung adenocarcinoma (LADC) predominant subtypes, as well as other clinical features. As an exploratory outcome we evaluated if a PD-L1 TPS score ≥15% was useful as a biomarker for determining survival.Results: A total of 240 patients were included to our final analysis. Median age at diagnosis was 65 years (range 23–94 years). A PD-L1 TPS ≥1% was observed in 52.5% of the entire cohort; regarding specific predominant histological patterns, a PD-L1 TPS ≥1 was documented in 31.2% of patients with predominant-lepidic pattern, 46.2% of patients with predominant-acinar pattern, 42.8% of patients with a predominant-papillary pattern, and 68.7% of patients with predominant-solid pattern (p = 0.002). On the other hand, proportion of tumors with PD-L1 TPS ≥50% was not significantly different among adenocarcinoma subtypes. At the univariate survival analysis, a PD-L1 TPS cut-off value of ≥15% was associated with a worse PFS and OS.Conclusion: According to IASLC/ATS/ERS lung adenocarcinoma classification, the predominant-solid pattern is associated with a higher proportion of PD-L1 positive samples, no subtype was identified to be associated with a high (≥50%) TPS PD-L1.

scholarly journals Predictive Values of Programmed Cell Death-Ligand 1 Expression for Prognosis, Clinicopathological Factors, and Response to Programmed Cell Death-1/Programmed Cell Death-Ligand 1 Inhibitors in Patients With Gynecological Cancers: A Meta-Analysis

2021 ◽  
Vol 10 ◽  
Author(s):  
Chen Zhang ◽  
Qing Yang
Keyword(s):  
Cell Death ◽  
Endometrial Cancer ◽  
Programmed Cell Death ◽  
Tumor Cells ◽  
Subgroup Analysis ◽  
Meta Analysis ◽  
Figo Stage ◽  
Infiltration Depth ◽  
Gynecological Cancers ◽  
Free Survival

BackgroundThe prognostic value of programmed cell death-ligand 1 (PD-L1) in gynecological cancers has been explored previously, but the conclusion remains controversial due to limited evidence. This study aimed to conduct an updated meta-analysis to re-investigate the predictive significance of PD-L1 expression.MethodsPubMed, EMBASE and Cochrane Library databases were searched. The associations between PD-L1 expression status and prognosis [overall survival (OS), progression-free survival (PFS), recurrence-free survival (RFS), cancer-specific survival (CSS) or disease-free survival (DFS)], clinical parameters [FIGO stage, lymph node metastasis (LNM), tumor size, infiltration depth, lymphovascular space invasion (LVSI) or grade] and response to anti-PD-1/PD-L1 treatment [objective response rate (ORR)] were analyzed by hazard ratios (HR) or relative risks (RR).ResultsFifty-five studies were enrolled. Overall, high PD-L1 expression was not significantly associated with OS, PFS, RFS, CSS and DFS of gynecological cancers. However, subgroup analysis of studies with reported HR (HR = 1.27) and a cut-off value of 5% (HR = 2.10) suggested that high PD-L1 expression was correlated with a shorter OS of gynecological cancer patients. Further sub-subgroup analysis revealed that high PD-L1 expressed on tumor-infiltrating immune cells (TICs) predicted a favorable OS for ovarian (HR = 0.72), but a poor OS for cervical cancer (HR = 3.44). PD-L1 overexpression was also correlated with a lower OS rate in non-Asian endometrial cancer (HR = 1.60). High level of PD-L1 was only clinically correlated with a shorter PFS in Asian endometrial cancer (HR = 1.59). Furthermore, PD-L1-positivity was correlated with LNM (for overall, ovarian and endometrial cancer expressed on tumor cells), advanced FIGO stage (for overall, ovarian cancer expressed on tumor cells, endometrial cancer expressed on tumor cells and TICs), LVSI (for overall and endometrial cancer expressed on tumor cells and TICs), and increasing infiltration depth/high grade (only for endometrial cancer expressed on TICs). Patients with PD-L1-positivity may obtain more benefit from anti-PD-1/PD-L1 treatment than the negative group, showing a higher ORR (RR = 1.98), longer OS (HR = 0.34) and PFS (HR = 0.61).ConclusionOur findings suggest high PD-L1 expression may be a suitable biomarker for predicting the clinical outcomes in patients with gynecological cancers.

scholarly journals The Prognostic Roles of Pretreatment Circulating Tumor Cells, Circulating Cancer Stem-Like Cells, and Programmed Cell Death-1 Expression on Peripheral Lymphocytes in Patients with Initially Unresectable, Recurrent or Metastatic Head and Neck Cancer: An Exploratory Study of Three Biomarkers in One-time Blood Drawing

Cancers ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 540 ◽  
Author(s):  
Pei-Hung Chang ◽  
Min-Hsien Wu ◽  
Sen-Yu Liu ◽  
Hung-Ming Wang ◽  
Wen-Kuan Huang ◽  
...  
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Head And Neck ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Progression Free Survival ◽  
Cancer Prognosis ◽  
Peripheral Lymphocytes ◽  
Blood Drawing ◽  
Programmed Cell Death 1

Circulating tumor cells (CTCs) and immune status are strongly related to cancer prognosis, although few studies have examined both factors. This prospective observational study (ClinicalTrials.gov: NCT02420600) evaluated whether CTCs, circulating cancer stem-like cells (cCSCs), and peripheral lymphocytes with/without Programmed cell death protein 1 (PD-1) expression were associated with prognosis among patients receiving palliative chemotherapy for initially unresectable, recurrent/metastatic head and neck squamous cell carcinoma (rmHNSCC). Thirty-four patients were enrolled between January 2015 and June 2016. Overall survival (OS) was associated with a higher CTC number (hazard ratio [HR]: 1.01, p = 0.0004) and cCSC ratio (HR: 29.903, p < 0.0001). Progression-free survival (PFS) was also associated with CTC number (HR: 1.013, p = 0.002) and cCSC ratio (HR: 10.92, p = 0.003). A CD8+ proportion of ≥ 17% was associated with improved OS (HR: 0.242, p = 0.004). A CD4: CD8 ratio of >1.2 was associated with poorer trend of PFS (HR: 2.12, p = 0.064). PD-1 expression was not associated with survival outcomes. Baseline CTCs, cCSC ratio, and CD8+ ratio may predict prognosis in rmHNSCC.

scholarly journals Evaluation of PD-L1 Expression in Tumor Tissue of Patients with Lung Carcinoma and Correlation with Clinical and Demographic Data

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Gustavo Dix Junqueira Pinto ◽  
Luciano de Souza Viana ◽  
Cristovam Scapulatempo Neto ◽  
Sérgio Vicente Serrano
Keyword(s):  
Lung Cancer ◽  
Cell Death ◽  
Tumor Microenvironment ◽  
Programmed Cell Death ◽  
Tumor Cells ◽  
Past History ◽  
Demographic Data ◽  
Immune Checkpoints ◽  
Programmed Cell Death 1 ◽  
History Of

Lung cancer is the leading world cause of cancer-related death, in both genders, and smoking is the main etiological factor. The discovery of immune checkpoints corroborates the hypothesis that ligands presented in tumors modulate the mechanisms of carcinogenesis and the immune activity of tumor microenvironment. Among the most studied coregulatory molecules, PD-1(programmed cell death 1)and its ligand PD-L1(programmed cell death 1 ligand 1)are noteworthy. The present study aims to enhance the understanding of the tumor microenvironment of lung cancer patients who underwent surgery, by means of analysis of PD-L1 expression in tumor cells and in intratumoral immune cells (IICs). It was found that PD-L1 expression was more frequent in tumor cells than in IICs. Collective analysis by Tissue Microarray Assay (TMA) for PD-L1 expression in tumor cells and IICs did not reproduce the findings for separate individual analysis of tumor tissues. Patients with past history of smoking were more likely to express PD-L1 in tumor cells than those who never smoked. Patients with past history of smoking were less likely to have PD-L1 positive IICs compared to those who had never smoked. The immunohistochemical expression of PD-L1 in tumor cells and IICs did not correlate with survival.

scholarly journals Macrophages eat cancer cells using their own calreticulin as a guide: Roles of TLR and Btk

2015 ◽  
Vol 112 (7) ◽  
pp. 2145-2150 ◽  
Author(s):  
Mingye Feng ◽  
James Y. Chen ◽  
Rachel Weissman-Tsukamoto ◽  
Jens-Peter Volkmer ◽  
Po Yi Ho ◽  
...  
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Cell Surface ◽  
Tyrosine Kinase ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Regulatory Protein ◽  
Toll Like Receptor ◽  
Tlr Signaling ◽  
Target Cancer

Macrophage-mediated programmed cell removal (PrCR) is an important mechanism of eliminating diseased and damaged cells before programmed cell death. The induction of PrCR by eat-me signals on tumor cells is countered by don’t-eat-me signals such as CD47, which binds macrophage signal-regulatory protein α to inhibit phagocytosis. Blockade of CD47 on tumor cells leads to phagocytosis by macrophages. Here we demonstrate that the activation of Toll-like receptor (TLR) signaling pathways in macrophages synergizes with blocking CD47 on tumor cells to enhance PrCR. Bruton’s tyrosine kinase (Btk) mediates TLR signaling in macrophages. Calreticulin, previously shown to be an eat-me signal on cancer cells, is activated in macrophages for secretion and cell-surface exposure by TLR and Btk to target cancer cells for phagocytosis, even if the cancer cells themselves do not express calreticulin.

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