Early stage diagnosis of programmed cell death (apoptosis) using electroanalysis: Nanomaterial and methods overview

Endometrial cancer is the only gynecological cancer that is rising in incidence and associated mortality worldwide. Although most cases are diagnosed as early stage disease, with chances of cure after primary surgical treatment, those with advanced or metastatic disease have a poor prognosis because of the quality of treatment options that are currently available. Mismatch repair (MMR)-deficient cancers are susceptible to programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 inhibitors. The US Food and Drug Administration granted accelerated approval to pembrolizumab for MMR-deficient tumors, the first tumor-agnostic approval for a drug. We present a case of stage IV endometrioid endometrial carcinoma with isolated PMS2 protein loss, in which treatment with first-line pembrolizumab therapy achieved a complete clinical and pathological response of tumor.

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The Prognostic Significance of PD1 and PDL1 Gene Expression in Lung Cancer: A Meta-Analysis

Frontiers in Oncology ◽

10.3389/fonc.2021.759497 ◽

2021 ◽

Vol 11 ◽

Author(s):

Chih-Hao Chang ◽

Arthur Chun-Chieh Shih ◽

Ya-Hsuan Chang ◽

Hsuan‐Yu Chen ◽

Ying-Ting Chao ◽

...

Keyword(s):

Gene Expression ◽

Lung Cancer ◽

Cell Death ◽

Programmed Cell Death ◽

Immune Checkpoint ◽

Late Stage ◽

Early Stage ◽

Meta Analysis ◽

Risk Of Relapse ◽

Stage Lung Cancer

BackgroundImmune checkpoint blockade therapy represents an extraordinary advance in lung cancer treatment. It is important to determine the expression of immune checkpoint genes, such as programmed cell death 1 (PD1) and programmed cell death-ligand 1 (PDL1), to develop immunotherapeutic strategies. The aim of this study was to explore the association between PD1 and PDL1 gene expression and prognoses and outcomes in lung cancer.MethodsThis meta-analysis analyzed 1,251 patients from eight different microarray gene expression datasets and were evaluated for their prognostic implications and verified using another independent research.ResultsThe mean expression levels of PDL1 in adenocarcinoma (AD) and squamous cell carcinoma (SC) were significantly higher in patients who died than in patients who did not. There was a trend toward incremental increases in PD1 and PDL1 expression significantly decreasing the risk of relapse and death among AD patients (HR = 0.69; 95% CI = 0.53 ~ 0.91; HR = 0.68; 95% CI = 0.54 ~ 0.84, respectively) and SC patients (HR = 0.53; 95% CI = 0.32 ~ 0.89; HR = 0.78; 95% CI = 0.57 ~ 1.00 respectively), as early-stage patients in this study were more likely to have high expression of both PD1 and PDL1 than late-stage patients (P-trend < 0.05). In contrast, late-stage SC patients expressing one or more of the genes at a high level had a significantly elevated risk of relapse (HR = 1.51; 95% CI = 1.07 ~ 2.11) and death (HR = 1.41; 95% CI = 1.08 ~ 1.84). This result was consistent with the validation data set.ConclusionThese findings indicate that high expression of PD1 and PDL1 is associated with superior outcome in early-stage lung cancer but an adverse outcome in late-stage lung cancer. The expression levels of PD1 and PDL1 individually or jointly are potential prognostic factors for predicting patient outcomes in lung cancer.

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Vacuolar processing enzyme translocates to the vacuole through the autophagy pathway to induce programmed cell death

10.1101/831982 ◽

2019 ◽

Author(s):

Paula Teper-Bamnolker ◽

Raz Danieli ◽

Hadas Peled-Zehavi ◽

Eduard Belausov ◽

Mohamad Abu-Abied ◽

...

Keyword(s):

Cell Death ◽

Programmed Cell Death ◽

Stress Responses ◽

Early Stage ◽

Carbon Starvation ◽

Activity Levels ◽

Vacuolar Processing Enzyme ◽

Concanamycin A ◽

Processing Enzyme ◽

Autophagy Pathway

AbstractThe caspase-like vacuolar processing enzyme (VPE) is a key factor in programmed cell death (PCD) associated with plant stress responses. Growth medium lacking a carbon source and dark conditions caused punctate labeling of 35S::VPE1-GFP (StVPE1-GFP) in potato leaves. Carbon starvation of BY-2 cells induced higher VPE activity and PCD symptoms. Growing VPE-RNAi BY-2 cells without sucrose reduced VPE activity and prevented PCD symptoms. During extended exposure to carbon starvation, VPE expression and activity levels peaked, with a gradual increase in BY-2 cell death. Histological analysis of StVPE1-GFP in BY-2 cells showed that carbon starvation induces its translocation from the endoplasmic reticulum to the central vacuole, through tonoplast engulfment. Exposure of BY-2 culture to the autophagy inhibitor concanamycin A caused autophagic bodies accumulation in the cell vacuole. Such accumulation did not occur in the presence of 3-methyladenine, an inhibitor of early-stage autophagy. BY-2 cells constitutively expressing StATG8IL-RFP, an autophagosome marker, showed colocalization with the StVPE1-GFP protein in the cytoplasm and vacuole. RNAi silencing of the core autophagy component ATG4 in BY-2 cells reduced VPE activity and cell death. These results are the first to suggest that VPE translocates to the cell vacuole through the autophagy pathway, leading to PCD.One sentence summaryCarbon starvation induced programmed cell death by trafficking vacuolar processing enzyme through the autophagy pathway to the vacuole.

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Prognostic value of programmed death-ligand 1 in solid tumors: A meta-analysis.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e19121 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e19121-e19121

Author(s):

Jordan L Scott ◽

Michelle Nadler ◽

Alexandra Desnoyers ◽

Fahad Almugbel ◽

Rouhi Fazelzad ◽

...

Keyword(s):

Cell Death ◽

Programmed Cell Death ◽

Solid Tumors ◽

Early Stage ◽

Meta Analysis ◽

Progression Free Survival ◽

Significant Heterogeneity ◽

Prognostic Impact ◽

Stage Of Disease ◽

Programmed Cell Death 1

e19121 Background: The programmed cell death 1 (PD-1)/programmed cell death 1 ligand 1 (PD-L1) pathway plays a crucial role in cancer immuno-surveillance and is the target of approved immunotherapeutic drugs. Available data suggest a variable prognostic impact of PD-L1 expression in solid tumors. Methods: A systematic literature search of electronic databases identified publications exploring the effect of PD-L1 on overall survival (OS) and/or progression-free survival (PFS). Hazard ratios (HR) were pooled in a meta-analysis using generic inverse-variance and random effects modeling. Subgroup analyses were conducted based on disease site, stage of disease, and method of PD-L1 quantification using the Deeks method. Results: One hundred eighty-eight studies comprised of 212,748 patients met the inclusion criteria. PD-L1 expression was associated with worse OS (HR 1.32, 95% confidence interval (CI) 1.25 - 1.38; P < 0.001). There was significant heterogeneity between disease sites (subgroup P = 0.002) with pancreatic, hepatocellular and genitourinary cancers being associated with the highest magnitude of adverse outcome (Table). PD-L1 was also associated with worse overall PFS (HR 1.19, 95% CI 1.09 - 1.30; P < 0.001). Stage of disease did not significantly affect the results (subgroup P = 0.52), nor did the method of quantification (immunohistochemistry or mRNA) (subgroup P = 0.70). Conclusions: High expression of PD-L1 is associated with worse cancer outcomes albeit with significant heterogeneity between disease sites. The effect seems consistent in early stage and metastatic disease and is not sensitive to method of PD-L1 quantification. [Table: see text]

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Autophagic Survival Precedes Programmed Cell Death in Wheat Seedlings Exposed to Drought Stress

International Journal of Molecular Sciences ◽

10.3390/ijms20225777 ◽

2019 ◽

Vol 20 (22) ◽

pp. 5777 ◽

Cited By ~ 1

Author(s):

Li ◽

Cui ◽

Sui ◽

Huang ◽

...

Keyword(s):

Cell Death ◽

Drought Stress ◽

Programmed Cell Death ◽

Wheat Cultivar ◽

Early Stage ◽

Severe Drought ◽

Wheat Seedlings ◽

The Relationship ◽

Peg 8000 ◽

Mild Drought

Although studies have shown the concomitant occurrence of autophagic and programmed cell death (PCD) in plants, the relationship between autophagy and PCD and the factors determining this relationship remain unclear. In this study, seedlings of the wheat cultivar Jimai 22 were used to examine the occurrence of autophagy and PCD during polyethylene glycol (PEG)-8000-induced drought stress. Autophagy and PCD occurred sequentially, with autophagy at a relatively early stage and PCD at a much later stage. These findings suggest that the duration of drought stress determines the occurrence of PCD following autophagy. Furthermore, the addition of 3-methyladenine (3-MA, an autophagy inhibitor) and the knockdown of autophagy-related gene 6 (ATG6) accelerated PEG-8000-induced PCD, respectively, suggesting that inhibition of autophagy also results in PCD under drought stress. Overall, these findings confirm that wheat seedlings undergo autophagic survival under mild drought stress, with subsequent PCD only under severe drought.

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9p24.1 alterations and programmed cell death 1 ligand 1 expression in early stage unfavourable classical Hodgkin lymphoma: an analysis from the German Hodgkin Study Group NIVAHL trial

British Journal of Haematology ◽

10.1111/bjh.17793 ◽

2021 ◽

Author(s):

Elena Gerhard‐Hartmann ◽

Helen Goergen ◽

Paul J. Bröckelmann ◽

Anja Mottok ◽

Tabea Steinmüller ◽

...

Keyword(s):

Cell Death ◽

Programmed Cell Death ◽

Hodgkin Lymphoma ◽

Early Stage ◽

Study Group ◽

Classical Hodgkin Lymphoma ◽

German Hodgkin Study Group ◽

Programmed Cell Death 1

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Immune Checkpoint Inhibition for Triple-Negative Breast Cancer: Current Landscape and Future Perspectives

Frontiers in Oncology ◽

10.3389/fonc.2021.648139 ◽

2021 ◽

Vol 11 ◽

Author(s):

Huimei Yi ◽

Ying Li ◽

Yuan Tan ◽

Shujun Fu ◽

Faqing Tang ◽

...

Keyword(s):

Breast Cancer ◽

Cell Death ◽

Programmed Cell Death ◽

Triple Negative Breast Cancer ◽

Immune Checkpoint ◽

Triple Negative ◽

Early Stage ◽

Checkpoint Inhibition ◽

Immune Checkpoint Inhibition ◽

Durable Response

Triple-negative breast cancer (TNBC) is characterized by the lack of clinically significant levels of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). Owing to the aggressive nature and the emergence of resistance to chemotherapeutic drugs, patients with TNBC have a worse prognosis than other subtypes of breast cancer. Currently, immunotherapy using checkpoint blockade has been shown to produce unprecedented rates of long-lasting responses in patients with a variety of cancers. Although breast tumors, in general, are not highly immunogenic, TNBC has a higher level of lymphocyte infiltration, suggesting that TNBC patients may be more responsive to immunotherapy. The identification/characterization of immune checkpoint molecules, i.e., programmed cell death protein 1 (PD1), programmed cell death ligand 1 (PDL1), and cytotoxic T lymphocyte-associated antigen 4 (CTLA4), represents a major advancement in the field of cancer immunotherapy. These molecules function to suppress signals downstream of T cell receptor (TCR) activation, leading to elimination of cytotoxic T lymphocytes (CTLs) and suppression of anti-tumor immunity. For TNBC, which has not seen substantial advances in clinical management for decades, immune checkpoint inhibition offers the opportunity of durable response and potential long-term benefit. In clinical investigations, immune checkpoint inhibition has yielded promising results in patients with early-stage as well as advanced TNBC. This review summarizes the recent development of immune checkpoint inhibition in TNBC, focusing on humanized antibodies targeting the PD1/PDL1 and the CTLA4 pathways.

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