Programmed cell death

The inhibition of the programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) pathway with small molecules is a promising approach for cancer immunotherapy. Herein, novel small molecules compounds bearing various scaffolds including thiophene, thiazole, tetrahydroquinoline, benzimidazole and indazole were designed, synthesized and evaluated for their inhibitory activity against the PD-1/PD-L1 interaction. Among them, compound Z13 exhibited the most potent activity with IC50 of 189.6 nM in the homogeneous time-resolved fluorescence (HTRF) binding assay...

Pseudoprogression encapsulates a process of temporary radiographic growth followed by subsequent regression of metastatic melanoma lesions in response to immune checkpoint blockade (ICB), such as the combination of anti-programmed cell death protein 1 (PD-1) and anticytotoxic T-lymphocyte-associated antigen 4 therapy. This occurs in approximately 5-10% of ICB-treated patients, but has not yet been described in the context of novel combination therapies. Here, we report a case of an 89-year-old patient with metastatic melanoma to the liver, lung and lymph nodes, who underwent treatment with Opdualag (combining anti-PD-1 nivolumab and anti-lymphocyte-activation gene 3 relatlimab ICBs), and developed pseudoprogression after two cycles of therapy...

Immune checkpoint inhibitor pneumonitis (ICIP) is thought to be a self-limiting disease; however, an effective treatment option does not currently exist. This study aimed to determine the clinical efficacy of combination therapy with glucocorticoids and pirfenidone for ICIP related to programmed cell death protein-1 (PD-1) inhibitors. We conducted a retrospective analysis of 45 patients with advanced non-small cell lung cancer who developed ICIP following PD-1 inhibitor and albumin-bound paclitaxel or carboplatin treatment at our hospital...

Differential expression of 128 known and 111 novel miRNAs in the panicle of Nagina 22 under terminal drought stress targeting transcription factors, stress-associated genes, etc., enhances drought tolerance and helps sustain agronomic performance under terminal drought stress. Drought tolerance is a complex multigenic trait, wherein the genes are fine-tuned by coding and non-coding components in mitigating deleterious effects. MicroRNA (miRNA) controls gene expression at post-transcriptional level either by cleaving mRNA (transcript) or by suppressing its translation...

Effective antitumor immunotherapy depends on evoking a cascade of cancer-immune cycles with lymph nodes (LNs) as the initial sites for activating antitumor immunity, making drug administration through the lymphatic system highly attractive. Here, we describe a nanomedicine with dual responsiveness to pH and enzyme for a programmed activation of antitumor immune through the lymphatic system. The proposed nanomedicine can release the STING agonist diABZI-C2-NH2 in the LNs' acidic environment to activate dendritic cells (DCs) and T cells...

CONTEXT: Procollagen C-endopeptidase enhancer 2 (PCOLCE2) is associated with the degradation of the extracellular matrix and collagen-chain trimerization, playing a yet unexplored role in tumor prognosis. OBJECTIVE: The study intended to characterize PCOLCE2's influence on colorectal cancer (CRC) using expression analysis and to investigate its prognostic potential. DESIGN: The research team performed a genetic analysis using genetic databases, including The Cancer Genome Atlas (TCGA), Gene Expression Profiling Interactive Analysis (GEPIA), the Tumor IMmune Estimation Resource (TIMER), and LinkedOmics...

INTRODUCTION: In the era of personalized medicine and treatment optimization, use of immune biomarkers holds promise for estimating the prognosis of patients with head and neck squamous cell carcinoma (HNSCC) undergoing definitive treatment. METHODS: To evaluate the prognostic potential of immune biomarkers, we conducted a prospective monocentric cohort study with loco-regionally advanced HNSCC patients indicated for definitive radiotherapy/radiochemotherapy at the Department of Oncology, Ostrava University Hospital, Czech Republic, between June 2020 and August 2023...

Sarcoma is derived from mesenchymal neoplasms and has numerous subtypes, accounting for 1% of all adult malignancies and 15% of childhood malignancies. The prognosis of metastatic or recurrent sarcoma remains poor. The current study presents two cases of sarcoma enrolled in a phase I dose escalation trial for solid tumor, who had previously failed all standard therapies. These patients were treated with VG161, an immune-stimulating herpes simplex virus type 1 oncolytic virus with payloads of IL-12, IL-15 and IL-15 receptor α unit, and a programmed cell death 1 (PD-1)/PD-1 ligand 1 blocking peptide...

Immunotherapy has been developed, which harnesses and enhances the innate powers of the immune system to fight disease, particularly cancer. PD-1 (programmed death-1) and PD-L1 (programmed death ligand-1) are key components in the regulation of the immune system, particularly in the context of cancer immunotherapy. PD-1 and PD-L1 are regulated by PTMs, including phosphorylation, ubiquitination, deubiquitination, acetylation, palmitoylation and glycosylation. PROTACs (Proteolysis Targeting Chimeras) are a type of new drug design technology...

Hepatocellular carcinoma (HCC) is a common cancer, and the body's immune responses greatly affect its progression and the prognosis of patients. Immunological suppression and the maintenance of self-tolerance in the tumor microenvironment are essential responses, and these form part of the theoretical foundations of immunotherapy. In this review, we first discuss the tumor microenvironment of HCC, describe immunosuppression in HCC, and review the major biomarkers used to track HCC progression and response to treatment...

Biliary tract cancer (BTC) is a highly aggressive malignancy with limited second-line therapy. We conducted this phase 2 trial to evaluate the efficacy and safety of second-line nab-paclitaxel plus sintilimab in advanced BTC. Histologically confirmed advanced BTC patients with documented disease progression after first-line chemotherapy were enrolled. Subjects received nab-paclitaxel 125 mg/m2 on days 1 and 8 plus sintilimab 200 mg on day 1, administered every 3 weeks. The primary end point was the objective response rate (ORR)...

INTRODUCTION: Breast cancer (BRCA) is one of the leading causes of cancer-related death in women. The improvement of the BRCA risk assessment method is of positive clinical significance. Although many clues showed the potential role of disulfidptosis in BRCA as a novel type of programmed cell death, whether disulfidptosis is involved in BRCA tumorigenesis remains unclear. METHOD: We used LASSO-univariate Cox analysis and multivariate Cox analysis to identify six disulfidptosis-related lncRNAs (DPLs) that correlated with BRCA clinical outcome and confirmed that these DPLs were independent prognostic factors for BRCA (YTHDF3-AS1, AC002398...

Ferroptosis is an iron dependent cell death driven by lipid peroxidation. Over the past decade, increasing evidence has confirmed that ferroptosis plays an irreplaceable role in the occurrence and development of many diseases, including various cancers, neurodegenerative diseases, cardiovascular diseases and autoimmune diseases. Autoimmune disease is an inflammatory disease characterized by the breakdown of immune tolerance. Nowadays, accumulating evidence indicates that ferroptosis is closely related to the pathogenesis of autoimmune diseases...

Many studies have focused on the prognostic role of soluble programmed death ligand 1 (sPD-L1) in non-small cell lung cancer (NSCLC), but outcomes are ambiguous and further investigations are needed. We addressed the matter by studying sPD-L1 in baseline samples and in longitudinal samples taken prior to three subsequent cycles of anti-PD-1/anti-PD-L1 treatments. Eighty patients with NSCLC were enrolled. Median sPD-L1 level at baseline was 52 pg/mL [95% confidence interval (CI) 49-57]. In patients treated with pembrolizumab and nivolumab, the concentration of sPD-L1 remained rather stable throughout treatment...

Myelodysplastic syndromes (MDS) are a heterogeneous group of pre-leukemic hematopoietic disorders characterized by cytopenia in peripheral blood due to ineffective hematopoiesis and normo- or hypercellularity and morphologic dysplasia in bone marrow (BM). An inflammatory BM microenvironment and programmed cell death of hematopoietic stem/progenitor cells (HSPCs) are thought to be the major causes of ineffective hematopoiesis in MDS. Pyroptosis, apoptosis and necroptosis (collectively, PANoptosis) are observed in BM tissues of MDS patients, suggesting an important role of PANoptosis in MDS pathogenesis...

During the development of the vertebrate nervous system, 50% of the nerve cells undergo apoptosis shortly after formation. This process is important for sculpting tissue during morphogenesis and removing transiently functional cells that are no longer needed, ensuring the appropriate number of neurons in each region. Dysregulation of neuronal apoptosis can lead to neurodegenerative diseases. However, the molecular events involved in activating and regulating the neuronal apoptosis program are not fully understood...

Immune checkpoint inhibitors targeting the programmed cell death-1 (PD-1) protein significantly improve survival in patients with advanced non-small-cell lung cancer (NSCLC), but its impact on early-stage ground-glass opacity (GGO) lesions remains unclear. This is a single-arm, phase II trial (NCT04026841) using Simon's optimal two-stage design, of which 4 doses of sintilimab (200 mg per 3 weeks) were administrated in 36 enrolled multiple primary lung cancer (MPLC) patients with persistent high-risk (Lung-RADS category 4 or had progressed within 6 months) GGOs...

PURPOSE: Colorectal cancer (CRC) is a very common malignancy of the digestive system. Despite a variety of treatments including surgery, chemotherapeutic and targeted drugs, the prognosis for patients with CRC is still unsatisfactory and the mortality remains high. Protein phosphorylation plays an essential role in tumorigenesis and progression and is also crucial for protein to act with proper functions. Ferroptosis is found widely involved in various diseases especially tumors as a newly identified programmed cell death...

OBJECTIVE: To investigate the associations between apparent diffusion coefficient (ADC) values extracted from three different region of interest (ROI) position approaches and programmed cell death ligand-1 (PD-L1) expression, and evaluate the performance of the nomogram established based on ADC values and clinicopathological parameters in predicting PD-L1 expression in cervical cancer (CC) patients. METHODS: Through retrospective recruitment, a training cohort of 683 CC patients was created, and a validation cohort of 332 CC patients was prospectively recruited...

Seed deterioration during storage is a major problem in agricultural and forestry production and for germplasm conservation. Our previous studies have shown that a mitochondrial outer membrane protein VOLTAGE-DEPENDENT ANION CHANNEL (VDAC) is involved in programmed cell death (PCD)-like viability loss during the controlled deterioration treatment (CDT) of elm (Ulmus pumila L.) seeds, but its underlying mechanism remains unclear. In this study, we demonstrate that the oxidative modification of GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE (GAPDH) is functioned in the gate regulation of VDAC during the CDT of elm seeds...