Programmed Cell Death Research Articles

Transcriptome analysis to identify genes related to programmed cell death resulted from manipulating of BnaFAH ortholog by CRISPR/Cas9 in Brassica napus

Fumarylacetoacetate hydrolase (FAH) catalyzes the final step of the tyrosine degradation pathway. In this study, we isolated and characterized two homologous BnaFAH genes in Brassica napus L. variant Westar, and then used CRISPR/Cas9-mediated targeted mutagenesis to generate a series of transgene-free mutant lines either with single or double-null bnafah alleles. Among these mutant lines, the aacc (bnafah) double-null mutant line, rather than the aaCC (bnaa06fah) mutant line, exhibited programmed cell death (PCD) under short days (SD). Histochemical staining and content measurement confirmed that the accumulation of reactive oxygen species (ROS) in bnafah was significantly higher than that in bnaa06fah. To further elucidate the mechanism of PCD, we performed transcriptomic analyses of bnaa06fah and bnafah at different SD stages. A heatmap cluster of differentially expressed genes (DEGs) revealed that PCD may be related to various redox regulatory genes involved in antioxidant activity, ROS-responsive regulation and calcium signaling. Combined with the results of previous studies, our work revealed that the expression levels of BnaC04CAT2, BnaA09/C09SAL1, BnaA08/C08ACO2, BnaA07/C06ERO1, BnaA08ACA1, BnaC04BIK1, BnaA09CRK36 and BnaA03CPK4 were significantly different and that these genes might be candidate hub genes for PCD. Together, our results underscore the ability of different PCD phenotypes to alter BnaFAH orthologs through gene editing and further elucidated the molecular mechanisms of oxidative stress-induced PCD in plants.

The influence of biophysical niche on tumor-associated macrophages in liver cancer.

HCC, the most common type of primary liver cancer, is a leading cause of cancer-related mortality worldwide. Although the advancement of immunotherapies by immune checkpoint inhibitors (ICIs) that target programmed cell death 1 or programmed cell death 1-ligand 1 has revolutionized the treatment for HCC, the majority is still not beneficial. Accumulating evidence has pointed out that the potent immunosuppressive tumor microenvironment in HCC poses a great challenge to ICI therapeutic efficacy. As a key component in tumor microenvironment, tumor-associated macrophages (TAMs) play vital roles in HCC development, progression, and ICI low responsiveness. Mechanistically, TAM can promote cancer invasion and metastasis, angiogenesis, epithelial-mesenchymal transition, maintenance of stemness, and most importantly, immunosuppression. Targeting TAMs, therefore, represents an opportunity to enhance the ICI therapeutic efficacy in patients with HCC. While previous research has primarily focused on biochemical cues influencing macrophages, emerging evidence highlights the critical role of biophysical signals, such as substrate stiffness, topography, and external forces. In this review, we summarize the influence of biophysical characteristics within the tumor microenvironment that regulate the phenotype and function of TAMs in HCC pathogenesis and progression. We also explore the possible mechanisms and discuss the potential of manipulating biophysical cues in regulating TAM for HCC therapy. By gaining a deeper understanding of how macrophages sense and respond to mechanical forces, we may potentially usher in a path toward a curative approach for combinatory cancer immunotherapies.

Unveiling the efficacy and mechanism of Danggui-Shaoyao-San in treating nephrotic syndrome: A meta-analysis and network pharmacology study

Aim of the studyThe purpose of this study was to investigate the efficacy and mechanism of DSS in treating nephrotic syndrome through meta-analysis and network pharmacology methods. Materials and methodsTo conduct a comprehensive search for randomized controlled trials on the efficacy of Danggui Shaoyao San (DSS) in the treatment of nephrotic syndrome, we searched across eight electronic databases from their establishment to May 1, 2023. The Cochrane Collaboration's Risk of Bias 2 tool was used to evaluate the quality of evidence regarding bias risk and outcomes. Statistical analysis was performed using RevMan software (version 5.4). Furthermore, network pharmacology was employed to validate the underlying mechanism. ResultsThis study included 14 articles that involved 1256 patients with nephrotic syndrome. The clinical efficacy of DSS against nephrotic syndrome was significantly higher than that of Western medical treatment alone. In comparison with the control groups, which were administered Western medicines alone, the use of DSS significantly increased plasma albumin levels (mean difference [MD] = 4.32, 95 % confidence interval [CI] [2.37, 6.24], p < 0.00001) and reduced 24 h urinary protein excretion (MD = −0.92, 95 % CI [−1.11, −0.73], p < 0.00001), total cholesterol levels (MD = −1.23, 95 % CI [−1.76, −0.70], p < 0.00001), triglyceride levels (MD = −0.37, 95 % CI [−0.54, −0.20], p < 0.00001). Furthermore, the combination of DSS with Western medicines achieved better control of adverse reactions in comparison with the control groups (relative risk = 0.37, 95 % CI [0.29, 0.49], p < 0.00001). Network pharmacology analysis identified 39 important active compounds and 18 core target genes involved in the treatment of primary nephrotic syndrome by DSS. Gene Ontology enrichment analysis identified 2126 biological processes, 64 cellular components, and 115 molecular functions, while Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis identified 149 signaling pathways. Key active compounds include ginsenoside Rg5, ginsenoside Rg1, schisandrin A, berberine, gallic acid, quercetin, and β-sitosterol, while potential core target genes include IL6, AKT1, TNF, VEGFA, IL1B, and TP53. KEGG pathway analysis indicated that DSS is involved in multiple mechanisms, such as neural development, synaptic plasticity, programmed cell death, inflammation, and immunity. ConclusionsDSS has higher efficacy and safety in the treatment of nephrotic syndrome and acts on nephrotic syndrome via mechanisms that involve multiple targets, components, and pathways.

Resveratrol inhibits Cell Cycle Dynamics, Caspase Activation, and Programmed Cell Death: Implications for Cancer Treatment in MCF-7 Cells"

Resveratrol inhibits Cell Cycle Dynamics, Caspase Activation, and Programmed Cell Death: Implications for Cancer Treatment in MCF-7 Cells"

NCAPD3 is a prognostic biomarker and is correlated with immune infiltrates in glioma.

Non-SMC Condensin II Complex Subunit D3 (NCAPD3) has been linked with the genesis and progression of multiple human cancers. Nevertheless, the scientific value and molecular process of NCAPD3 in glioma remain unclear. We explored the level of NCAPD3 expression in pan-cancer by multiple online databases. And we focused on the level and prognostic value of NCAPD3 expression in glioma by immunohistochemistry (IHC) and survival analysis. Meanwhile, we verified the relationship between NCAPD3, biological function and immune infiltration in glioma by Linkedomics and SangerBox databases. The expression of NCAPD3 was increased in a variety of cancers, including glioma. Its high expression was strongly related to WHO grade (P=0.002) and programmed cell death ligand 1 (PD-L1) expression of glioma (P=0.001). Patients with a high level of NCAPD3 expression had a lower overall survival (OS) in glioma than patients with a low level of NCAPD3 expression. Multivariate statistical analyses showed NCAPD3 expression (P=0.040), WHO grade (P<0.001), 1p/19q codeletion (P<0.001), recurrence (P<0.001), age (P=0.023), and chemotherapy status (P=0.001) were meaningful independent prognostic factors in patients with glioma. Furthermore, bioinformatics analysis proved that NCAPD3 has been linked to immune infiltration in glioma. High level of NCAPD3 expression may serve as a promising prognostic biomarker and correlate with dendritic cell infiltration, representing a potential immunotherapy target in glioma.

Tumor microenvironment activated MXene-protected Cu2O heterojunctions induce tumor-specific cuproptosis for enhanced sono-immunotherapy

The utilization of a copper ionophore to induce programmed cell death, known as cuproptosis, shows potential in augmenting the efficacy of traditional anticancer treatments and eliciting robust adaptive immune responses. Nevertheless, the non-tumor-specific release of Cu ions may initiate cuproptosis and cause irreversible damage to normal tissues. Herein, this work reports for the first time the regulation of degradation behaviors of Cu-based nanomaterials using Ti3C2Tx nanosheets as a protection layer to maximize the therapeutic effects of tumor-specific cuproptosis. A Z-scheme heterojunction termed Cu2O/Ti3C2Tx is facilely constructed by coating Ti3C2Tx nanosheets on the surface of Cu2O nanocubes. The fabrication of heterojunctions not only improves the sonodynamic and chemodynamic activities of Cu2O nanocubes owing to the manipulation of electron-hole transfer process, but also avoids the degradation of Cu2O nanocubes under normal physiological conditions. The tumor-specific released Cu ions not only realized the cascade amplification of ROS generation through Cu+-mediated Fenton-like reaction and Cu2+-facilitated GSH depletion, but also triggered cuproptosis through Cu+-induced DLAT oligomerization and mitochondrial dysfunction. More importantly, the immunosuppressive TME could be reversed by the greatly enhanced ROS levels and high-efficiency cuproptosis, ultimately inducing immunogenic cell death that promotes robust systemic immune responses for the eradication of primary tumors and suppression of distant tumors. This work provides a promising perspective for potential cancer treatment based on tumor-specific cuproptosis by controlling the degradation behaviors of Cu-based nanomaterials.

Emerging Therapeutic Approaches Targeting Ferroptosis in Cancer: Focus on Immunotherapy and Nanotechnology.

Ferroptosis is a newly discovered form of programmed cell death characterized by iron overload, ROS accumulation, and lipid peroxidation. It is distinguished by unique morphological, biochemical, and genetic features and stands apart from other known regulated cell death mechanisms. Studies have demonstrated a close association between ferroptosis and various cancers, including liver cancer, lung cancer, renal cell carcinoma, colorectal cancer, pancreatic cancer, and ovarian cancer. Inducing ferroptosis has shown promising results in inhibiting tumor growth and reversing tumor progression. However, the challenge lies in regulating ferroptosis in vivo due to the scarcity of potent compounds that can activate it. Integrating emerging biomedical discoveries and technological innovations with conventional therapies is imperative. Notably, considerable progress has been made in cancer treatment by leveraging immunotherapy and nanotechnology to trigger ferroptosis. This review explores the relationship between ferroptosis and emerging immunotherapies and nanotechnologies, along with their potential underlying mechanisms, offering valuable insights for developing novel cancer treatment strategies.

Activation of autophagy, paraptosis, and ferroptosis by micheliolide through modulation of the MAPK signaling pathway in pancreatic and colon tumor cells

Micheliolide (MCL), a naturally occurring sesquiterpene lactone, has demonstrated significant anticancer properties through the induction of various programmed cell death mechanisms. This study aimed to explore MCL's effects on autophagy, paraptosis, and ferroptosis in pancreatic and colon cancer cells, along with its modulation of the MAPK signaling pathway. MCL was found to substantially suppress cell viability in these cancer cells, particularly in MIA PaCa-2 and HT-29 cell lines. The study identified that MCL induced autophagy by enhancing the levels of autophagy markers such as Atg7, p-Beclin-1, and Beclin-1, which was attenuated by the autophagy inhibitor 3-MA. Furthermore, MCL was found to facilitate paraptosis, indicated by decreased Alix and in-creased ATF4 and CHOP levels. It also promoted ferroptosis, as demonstrated by the reduced expression of SLC7A11, elevated TFRC levels, and increased intracellular iron. Additionally, MCL activated the MAPK signaling pathway, marked by the phosphorylation of JNK, p38, and ERK, linked with an increase in ROS production that is vital in regulating these cell death mechanisms. These findings propose that MCL is a versatile anticancer agent, capable of activating various cell death pathways by modulating MAPK signaling and ROS levels. These results emphasize the therapeutic promise of MCL in treating cancer, pointing to the necessity of further in vivo investigations to confirm these effects and determine its potential clinical uses.

Thymol as adjuvant in oncology: molecular mechanisms, therapeutic potentials, and prospects for integration in cancer management.

Cancer remains a global health challenge, prompting a search for effective treatments with fewer side effects. Thymol, a natural monoterpenoid phenol derived primarily from thyme (Thymus vulgaris) and other plants in the Lamiaceae family, is known for its diverse biological activities. It emerges as a promising candidate in cancer prevention and therapy. This study aims to consolidate current research on thymol's anticancer effects, elucidating its mechanisms and potential to enhance standard chemotherapy, and to identify gaps for future research. A comprehensive review was conducted using databases like PubMed/MedLine, Google Scholar, and ScienceDirect, focusing on studies from the last 6years. All cancer types were included, assessing thymol's impact in both cell-based (in vitro) and animal (in vivo) studies. Thymol has been shown to induce programmed cell death (apoptosis), halt the cell division cycle (cell cycle arrest), and inhibit cancer spread (metastasis) through modulation of critical signaling pathways, including phosphoinositide 3-kinase (PI3K), protein kinase B (AKT), extracellular signal-regulated kinase (ERK), mechanistic target of rapamycin (mTOR), and Wnt/β-catenin. It also enhances the efficacy of 5-fluorouracil (5-FU) in colorectal cancer treatments. Thymol's broad-spectrum anticancer activities and non-toxic profile to normal cells underscore its potential as an adjunct in cancer therapy. Further clinical trials are essential to fully understand its therapeutic benefits and integration into existing treatment protocols.

Targeting programmed cell death via active ingredients from natural plants: a promising approach to cancer therapy

Targeting programmed cell death via active ingredients from natural plants: a promising approach to cancer therapy

Comprehensive Advanced Physicochemical Characterization and In Vitro Human Cell Culture Assessment of BMS-202: A Novel Inhibitor of Programmed Cell Death Ligand

Background/Objectives: BMS-202, is a potent small molecule with demonstrated antitumor activity. The study aimed to comprehensively characterize the physical and chemical properties of BMS-202 and evaluate its suitability for topical formulation, focusing on uniformity, stability and safety profiles. Methods: A range of analytical techniques were employed to characterize BMS-202. Scanning Electron Microscopy (SEM) was used to assess morphology, Differential Scanning Calorimetry (DSC) provided insights of thermal behavior, and Hot-Stage Microscopy (HSM) corroborated these thermal behaviors. Molecular fingerprinting was conducted using Raman spectroscopy and Fourier Transform Infrared (FTIR) spectroscopy, with chemical uniformity of the batch further validated by mapping through FTIR and Raman microscopies. The residual water content was measured using Karl Fisher Coulometric titration, and vapor sorption isotherms examined moisture uptake across varying relative humidity levels. In vitro safety assessments involved testing with skin epithelial cell lines, such as HaCaT and NHEK, and Transepithelial Electrical Resistance (TEER) to evaluate barrier integrity. Results: SEM revealed a distinctive needle-like morphology, while DSC indicated a sharp melting point at 110.90 ± 0.54 ℃ with a high enthalpy of 84.41 ± 0.38 J/g. HSM confirmed the crystalline-to-amorphous transition at the melting point. Raman and FTIR spectroscopy, alongside chemical imaging, confirmed chemical uniformity as well as validated the batch consistency. A residual water content of 2.76 ± 1.37 % (w/w) and minimal moisture uptake across relative humidity levels demonstrated its low hygroscopicity and suitability for topical formulations. Cytotoxicity testing showed dose-dependent reduction in skin epithelial cell viability at high concentrations (100 µM and 500 µM), with lower doses (0.1 µM to 10 µM) demonstrating acceptable safety. TEER studies indicated that BMS-202 does not disrupt the HaCaT cell barrier function. Conclusions: The findings from this study establish that BMS-202 has promising physicochemical and in vitro characteristics at therapeutic concentrations for topical applications, providing a foundation for future formulation development focused on skin-related cancers or localized immune modulation.

A Preliminary Study on the Correlation Between TILs and CTCs and Clinical Value in Lung Cancer Patients Analyzed by Lipid Magnetic Microspheres

The purpose of this study was to analyze the advantages of TCR gene and its relationship with tumor infiltrating lymphocytes (til) and circulating tumor cells (CTCs). The properties of EpCAM and EGFR lipid magnetic microspheres were analyzed. The levels of Programmed cell death 1 ligand 1, B7-H3 and B7-H4 in peripheral blood were measured by quantitative immunofluorescence (QIF). T cell receptor expression profile and clone proliferation were detected. The prepared EpCAM and EGFR lipid magnetic microspheres showed good stability and specificity. The therapeutic method proposed in this study is expected to be applied.

Clinical outcomes of conversion surgery after induction immunochemotherapy for borderline resectable T4 esophageal squamous cell carcinoma

BackgroundThe current treatment strategies for borderline resectable esophageal squamous cell carcinoma remain controversial. This study aimed to evaluate the efficacy and safety of programmed cell death 1 inhibitors combined with chemotherapy, followed by conversion surgery, for borderline resectable esophageal squamous cell carcinoma.MethodsPatients with borderline resectable esophageal squamous cell carcinoma treated with induction immunochemotherapy from January 1, 2020 to July 1, 2023 at our hospital were retrospectively analyzed. The primary study outcome was the R0 resection rate. Secondary study outcomes included progression-free survival (PFS), overall survival (OS), pathological complete remission (pCR) rate, and safety.ResultsForty patients with borderline resectable esophageal squamous cell carcinoma were included in the analysis. The R0 resection rate was 23/40 (57.5%); the conversion success rate was 27/40 (67.5%), and the pCR rate was 11/40 (27.5%). The median follow-up was 23.6 months (95% CI, 19.1–28.2). One-year OS and PFS rates were 77.7% and 71.8%, respectively. The incidence rate of Grade 3–4 adverse events was 10%. There was a significant difference in PFS between patients who underwent surgery and those who did not (P = 0.008, HR: 0.144 95%CI: 0.034–0.606). However, the difference in OS was not significant (P = 0.128, HR: 0.299 95%CI: 0.063–1.416). Patients who achieved clinical downstaging after induction therapy had significantly better OS (P = 0.004 h: 0.110 95%CI: 0.025–0.495) and PFS (P = 0.0016, HR: 0.106 95%CI: 0.026–0.426) compared to those who did not.ConclusionsConversion surgery after induction immunochemotherapy is a promising new strategy with a high conversion rate, inspiring R0 resection rate, significant pathological remission rate, and mild toxicity for borderline resectable esophageal squamous cell carcinoma.

PANoptosis in autoimmune diseases interplay between apoptosis, necrosis, and pyroptosis

PANoptosis is a newly identified inflammatory programmed cell death (PCD) that involves the interplay of apoptosis, necrosis, and pyroptosis. However, its overall biological effects cannot be attributed to any one type of PCD alone. PANoptosis is regulated by a signaling cascade triggered by the recognition of pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) by various sensors. This triggers the assembly of the PANoptosome, which integrates key components from other PCD pathways via adapters and ultimately activates downstream execution molecules, resulting in cell death with necrotic, apoptotic, and pyroptotic features. Autoimmune diseases are characterized by reduced immune tolerance to self-antigens, leading to abnormal immune responses, often accompanied by systemic chronic inflammation. Consequently, PANoptosis, as a unique innate immune-inflammatory PCD pathway, has significant pathophysiological relevance to inflammation and autoimmunity. However, most previous research on PANoptosis has focused on tumors and infectious diseases, leaving its activation and role in autoimmune diseases unclear. This review briefly outlines the characteristics of PANoptosis and summarizes several newly identified PANoptosome complexes, their activation mechanisms, and key components. We also explored the dual role of PANoptosis in diseases and potential therapeutic approaches targeting PANoptosis. Additionally, we review the existing evidence for PANoptosis in several autoimmune diseases and explore the potential regulatory mechanisms involved.

The role and mechanism of extracellular traps in chronic rhinosinusitis.

Chronic rhinosinusitis (CRS) is a common inflammatory disease of the nose that affects millions of individuals worldwide. Recent research has introduced the concept of an immunologic endotype based on the pathological characteristics of CRS and the types of inflammatory cell infiltration. This endotype concept is conducive to understanding CRS pathology and guiding further targeted therapy. Eosinophils and neutrophils infiltrate different proportions in different CRS endotypes and release extracellular traps (ETs) as a response to the extracellular immune response. The mechanisms of formation and biological roles of ETs are complex. ETs can trap extracellular microorganisms and limit the range of inflammation to some extent; however, excessive and long-term ETs may be related to disease severity. This review summarises and explores the mechanism of ETs and the advances in CRS research and proposes new insights into the interaction between ETs and programmed cell death (including autophagy, pyroptosis, and necroptosis) in CRS, providing new ideas for the targeted therapy of CRS.

Understanding the molecular regulatory mechanisms of autophagy in lung disease pathogenesis

Lung disease development involves multiple cellular processes, including inflammation, cell death, and proliferation. Research increasingly indicates that autophagy and its regulatory proteins can influence inflammation, programmed cell death, cell proliferation, and innate immune responses. Autophagy plays a vital role in the maintenance of homeostasis and the adaptation of eukaryotic cells to stress by enabling the chelation, transport, and degradation of subcellular components, including proteins and organelles. This process is essential for sustaining cellular balance and ensuring the health of the mitochondrial population. Recent studies have begun to explore the connection between autophagy and the development of different lung diseases. This article reviews the latest findings on the molecular regulatory mechanisms of autophagy in lung diseases, with an emphasis on potential targeted therapies for autophagy.

Unveiling the Complexities: Exploring Mechanisms of Anthracycline-Induced Cardiotoxicity.

The coexistence of cancer and heart disease, both prominent causes of illness and death, is further exacerbated by the detrimental impact of chemotherapy. Anthracycline-induced cardiotoxicity is an unfortunate side effect of highly effective therapy in treating different types of cancer; it presents a significant challenge for both clinicians and patients due to the considerable risk of cardiotoxicity. Despite significant progress in understanding these mechanisms, challenges persist in identifying effective preventive and therapeutic strategies, rendering it a subject of continued research even after three decades of intensive global investigation. The molecular targets and signaling pathways explored provide insights for developing targeted therapies, emphasizing the need for continued research to bridge the gap between preclinical understanding and clinical applications. This review provides a comprehensive exploration of the intricate mechanisms underlying anthracycline-induced cardiotoxicity, elucidating the interplay of various signaling pathways leading to adverse cellular events, including cardiotoxicity and death. It highlights the extensive involvement of pathways associated with oxidative stress, inflammation, apoptosis, and cellular stress responses, offering insights into potential and unexplored targets for therapeutic intervention in mitigating anthracycline-induced cardiac complications. A comprehensive understanding of the interplay between anthracyclines and these complexes signaling pathways is crucial for developing strategies to prevent or mitigate the associated cardiotoxicity. Further research is needed to outline the specific contributions of these pathways and identify potential therapeutic targets to improve the safety and efficacy of anthracycline-based cancer treatment. Ultimately, advancements in understanding anthracycline-induced cardiotoxicity mechanisms will facilitate the development of more efficacious preventive and treatment approaches, thereby improving outcomes for cancer patients undergoing anthracycline-based chemotherapy.

Unveiling the nexus: pyroptosis and its crucial implications in liver diseases.

Pyroptosis, a distinctive form of programmed cell death orchestrated by gasdermin proteins, manifests as cellular rupture, accompanied by the release of inflammatory factors. While pyroptosis is integral to anti-infection immunity, its aberrant activation has been implicated in tumorigenesis. The liver, as the body's largest metabolic organ, is rich in various enzymes and governs metabolism. It is also the primary site for protein synthesis. Recent years have witnessed the emergence of pyroptosis as a significant player in the pathogenesis of specific liver diseases, exerting a pivotal role in both physiological and pathological processes. A comprehensive exploration of pyroptosis can unveil its contributions to the development and regression of conditions such as hepatitis, cirrhosis, and hepatocellular carcinoma, offering innovative perspectives for clinical prevention and treatment. This review consolidates current knowledge on key molecules involved in cellular pyroptosis and delineates their roles in liver diseases. Furthermore, we discuss the potential of leveraging pyroptosis as a novel or existing anti-cancer strategy.

Avelumab reduces STAT3 expression with effects on IL-17RA and CD15.

Avelumab is a human antibody that targets the programmed cell death ligand-1 (PD-L1) protein in cancer cells. Novel anticancer therapies for renal cell carcinoma (RCC) consider cluster of differentiation 15 (CD15) and interleukin 17 receptor A (IL-17RA) as potential targets. Notably, the expression of PD-L1, CD15 and IL-17RA is dependent on signal transducer and activator of transcription 3 (STAT3). The aim of the study was to investigate whether targeting PD-L1 with avelumab alters the expression levels of CD15 and IL-17RA, and to assess the STAT3-mediated regulation of CD15 and IL-17RA. We applied immunocytochemistry (ICC) and confocal laser scanning (CLS) microscopy to assess the expression and localization of the immunotherapy targets in 3 renal cancer cell lines and 1 healthy renal cell line. After treatment with 20 ng/mL avelumab, renal cancer cells showed a reduction in STAT3 expression. The expression of CD15 increased in cancer cells that exhibited a high level of IL-17RA, and the membrane signal of CD15 was reduced. In other renal cancer cell lines, the expression of CD15 decreased. Conversely, the level of IL-17RA changed only in healthy renal cells after treatment with avelumab, with no impact on renal cancer cells. Our study suggests that the targeting of PD-L1 with avelumab alters the expression of CD15 and IL-17RA, which play an important prognostic and therapeutic role in novel anticancer therapy.

Microbiological aspects of cancer progression: A systematic review conducted according to the PRISMA 2020 guidelines and the Cochrane Handbook for Systematic Reviews of Interventions.

The complex interplay between the gut microbiota, cancer treatments and patient characteristics has emerged as a significant area of research. This study sought to examine these relationships in the context of colorectal cancer (CRC).A comprehensive search of relevant studies was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines and the Cochrane Handbook for Systematic Reviews of Interventions. The studies included a variety of treatment modalities and microbiological parameters. A data extraction form, designed specifically for this review, was used to assess a range of variables across all studies.The analysis revealed a multifaceted interaction between the gut microbiota, genetic factors and treatment outcomes. Elderly patients with CRC frequently received single-agent chemotherapy, with outcomes that were comparable to those of younger patients. The presence of tumorigenic bacteria, including Escherichia coli and Bacteroides fragilis, was associated with early colon neoplasia. Additionally, an abundance of Fusobacterium spp. was observed in colonic adenomas, contributing to a pro-inflammatory environment. Although the FcγRIIIa-158 V/V genotype was associated with higher cetuximab-mediated antibodydependent cellular cytotoxicity (ADCC), no direct influence of FcγR polymorphisms on treatment response was noted. Furthermore, the combination of programmed cell death protein-1 (PD-1), BRAF and MEK inhibition showed favorable response rates. The gut microbiome, especially the presence of Fusobacterium spp., had a notable influence on the therapeutic response in CRC.These findings underscore the role of the gut microbiota and genetic factors in cancer treatment outcomes, emphasizing the potential of a holistic approach to cancer management. Future research should exploit these findings in order to develop microbiota-modulating strategies and personalized medicine approaches for the purpose of improving the efficacy of cancer treatment.