Efficacy and Immune Mechanisms of Cetuximab for the Treatment of Metastatic Colorectal Cancer

Cetuximab is a chimeric immunoglobulin G1 mono-clonal antibody that targets the ligand-binding domain of the epidermal growth factor receptor and inhibits downstream intra-cellular signals. Research has shown that cetuximab can stimulate the autoimmune system and produce antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity reactions, which can recruit cytotoxic lymphocytes to attack and kill cancer cells. Cetuximab is mainly indicated for patients with epidermal growth factor receptor-positive metastatic colorectal cancer who fail to respond to both irinotecan-and oxaliplatin-based regimens. The efficacy and safety of cetuximab as monotherapy or in combination with other treatment options were evaluated in a series of phase II and phase III trials. Identifying the clinical and molecular markers that can predict which patient groups may best benefit from cetuximab treatment is key to improving patient outcomes and avoiding unnecessary toxicities and costs. Herein, we discuss the mechanisms of action by which cetuximab exerts its antitumor effects, as well as the possible clinical and molecular markers that may help predict therapeutic benefits for patients with metastatic colorectal cancer.

Transcriptome analysis reveals immune-related genes in tissues of Vibrio anguillarum-infected turbot Scophthalmus maximus

Turbot Scophthalmus maximus is an important mariculture fish species with high economic value.However,the bacterial diseases caused by Vibrio anguillarum infection bring huge economic losses to the turbot aquaculture industry.To understand the immune response of the turbot against V.anguillarum infection and to explore novel immune-related genes,the transcriptome analysis of turbot spleen and gills were conducted after V.anguillarum infection.Differentially expressed genes(DEGs)were identified in spleen and gill of the turbot amounted to 17261 and 16436,respectively.A large number of immunerelated DEGs were enriched in cytokine-cytokine receptor interaction signaling pathway,and the others by the kyoto encyclopedia of genes and genomes(KEGG)enrichment.The gene ontology(GO)classification analysis revealed that V.anguillarum infection had the greatest effect on biological processes and cellular components.Twelve immune-related DEGs were identified in the spleen(cstl.1,egfl6,lamb21,v2rx4,calcr,and gpr78a)and gills(ghra,sh3gl2a,cst12,inhbaa,cxcl8,and il-1b)by heat map.The proteinprotein interaction(PPI)networks were constructed to analyze the immune mechanism.The results demonstrate that the maturation and antigen processing of major histocompatibility complex(MHC)class II molecule,and calcitonin-or adrenomedullin-regulated physiological activity were important events in the immunity of turbot against V.anguillarum infection.In the gills,the protein interactions in TGF-βsignaling pathway,production of inflammatory factors,and endocytosis regulation were most significant.Our research laid a foundation for discovering novel immune-related genes and enriching the knowledge of immune mechanisms of turbot against V.anguillarum infection.

Research Hotspot and Application Status of Immune Evasion Mechanism in Ovarian Cancer

Ovarian cancer is one of the three major malignant tumors in gynecology, with increasing incidence and mortality rates. Currently, the main treatment methods remain surgical intervention in combination with chemotherapy. However, due to its high recurrence rate and the risk of drug resistance, the overall prognosis is poor. Ovarian cancer has been identified as an immunegenic tumor, and in recent years, with the continued advancement of research into immune evasion mechanisms, immunotherapy has emerged as a groundbreaking treatment modality. This article will focus on the immune escape mechanisms and their application in ovarian cancer, providing a comprehensive overview of its current status and the challenges it faces.

Event-driven Dynamic and Intelligent Scheduling for Agile Manufacturing Based on Immune Mechanism and Expert System

Based on the biological immune concept, immune response mechanism and expert system, a dynamic and intelligent scheduling model toward the disturbance of the production such as machine fault,task insert and cancel etc. Is proposed. The antibody generation method based on the sequence constraints and the coding rule of antibody for the machining procedure is also presented. Using the heuristic antibody generation method based on the physiology immune mechanism, the validity of the scheduling optimization is improved, and based on the immune and expert system under the event-driven constraints, not only Job-shop scheduling problem with multi-objective can be solved, but also the disturbance of the production be handled rapidly. A case of the job-shop scheduling is studied and dynamic optimal solutions with multi-objective function for agile manufacturing are obtained in this paper. And the event-driven dynamic rescheduling result is compared with right-shift rescheduling and total rescheduling.

Mechanisms of immunization of rice seedlings-the change of anti-pathogen substance content

The damage caused by rice damping-off diseasecould be controlled efficiently by planting vig-orous seedlings. By adjusting the environ-ment, immunization of rice nursery (IRN)could raise seedlings with well developed rootsand high physiological activity. These

Acquired pure red cell aplasia:unraveling the immune pathogenesis

Acquired pure red cell aplasia(aPRCA)is a rare hematological disorder characterized by normochromic,normocytic anemia,reticulocytopenia,and the absence of erythroblasts.The pathogenesis of aPRCA has remained elusive.This review delves into the intricate web of immune mechanisms underlying the development of this enigmatic condition.By exploring immune responses,cytotoxic effects,and antibody-mediated processes,we dissect the immune-driven assault on erythroid progenitors.The classification of aPRCA,including its primary and secondary forms,is elucidated,with a particular emphasis on etiological factors such as viruses,drugs,thymoma,and large granular lymphocytic leukemia.Furthermore,we discuss the implications of cytogenetic changes in erythroid progenitors and immune cells in the pathophysiology of aPRCA.This comprehensive overview aims to shed light on the complex interplay between immune dysregulation and erythroid failure in aPRCA,offering insights that will be crucial for better understanding and treating this disease.

Current immune therapeutic strategies in advanced or metastatic non-small cell lung cancer

Immune escape mechanisms in non-small cell lung cancer(NSCLC)can disrupt every step of the anti-cancer immune response.In recent years,an increased understanding of the specific mechanisms fueling immune escape has allowed for the development of numerous immunotherapeutic treatments that have been introduced into the clinical practice.The advent of immunotherapy has dramatically changed the current treatment landscape of advanced or metastatic NSCLC because of its durable efficacy and manageable toxicity.In this review,we will first present a brief overview of recent evidence on immune escape mechanisms in NSCLC.We will then discuss the current promising immunotherapeutic strategies in advanced or metastatic NSCLC tumors.

STUDY ON THE ANTI-TUMOR EFFICACY INDUCED BY HEAT SHOCK PROTEIN 70-PEPTIDE COMPLEXES DERIVED FROM TUMOR CELLS

OBJECTIVE: To study the efficacy and explore the mechanism of the anti-tumor immunity elicited by heat shock protein 70-peptide complexes (HSP70-PC) derived from tumor cells. METHODS: Cells culture, flow cytometric analysis, affinity chromatography for protein purification, SDS-PAGE, Western-blotting and animal experiment were used. RESULTS: HSP70-PC immunization rendered protective effect to both naive tumorl-bearing mice. All of the naive mice obtained complete resistance to Hcaf cell attack; 40% of the tumor-bearing mice survived for over 90 days, whereas the mice of control group died within 2 weeks (P

Decoding cancer's camouflage: epithelial-mesenchymal plasticity in resistance to immune checkpoint blockade

Epithelial-mesenchymal plasticity(EMP)of cancer cells contributes to cancer cell heterogeneity,and it is well established that EMP is a critical determinant of acquired resistance to cancer treatment modalities including radiation therapy,chemotherapy,and targeted therapies.Here,we aimed to explore how EMP contributes to cancer cell camouflage,allowing an ever-changing population of cancer cells to pass under the radar of our immune system and consequently compromise the effect of immune checkpoint blockade therapies.The ultimate clinical benefit of any combination regimen is evidenced by the sum of the drug-induced alterations observed in the variety of cellular populations composing the tumor immune microenvironment.The finely-tuned molecular crosstalk between cancer and immune cells remains to be fully elucidated,particularly for the spectrum of malignant cells along the epithelial to mesenchymal axis.High-dimensional single cell analyses of specimens collected in ongoing clinical studies is becoming a key contributor to our understanding of these interactions.This review will explore to what extent targeting EMP in combination with immune checkpoint inhibition represents a promising therapeutic avenue within the overarching strategy to reactivate a halting cancer-immunity cycle and establish a robust host immune response against cancer cells.Therapeutic strategies currently in clinical development will be discussed.

A dual role of inflammation in acetaminophen-induced liver injury

In many affluent nations,acetaminophen(APAP)overdose is the leading cause of drug-induced acute liver failure.The process of APAP-induced liver injury(AILI)is intimately tied to inflammation,including hepatocyte necrosis-caused initiation of inflammation,inflammation amplification that exacerbates liver injury,and the resolution of inflammation that triggers liver regeneration and repair.Excessive APAP metabolism in the liver eventually leads to hepatocyte necrosis and inflammation.Innate immune cells,such as neutrophils,eosinophils,monocytes,and gammadelta T cells,are recruited into the injured liver and release various cytokines.These immune cells and cytokines have been found to serve two purposes in AILI.In this review,we highlighted the dual role of inflammation,including inflammatory cytokines and inflammatory immune cells in AILI,and discussed possible explanations for contradictory findings.

Co-localization of the heat shock protein and human immunoglobulin G in hepatocellular carcinoma

Elevated levels of serum immunoglobulin observed in patients with cancers of epithelial origin, including carcinomas of breast, colon, and liver have been interpreted as humoral responses of host to cancer growth. Recently, Qiu et al described in detail that human cancers of epithelial origin, including carcinomas of breast, colon, liver, lung, established epithelial cancer lines, produce immunoglobulin G （IgG） in their cytoplasm. Under normal conditions, heat shock proteins （HSPs） have multiple cellular functions, such as folding and translocating newly synthesized proteins. When a cell is injured or under stress, HSPs refold damaged protein or facilitate degradation of proteins. In most cancers, heat shock proteins can capture tumour specific peptide to inhibit the growth of cancer. This study demonstrated that human IgG and HSPs are co-localized in hepatocellular carcinoma.

Interaction Between the Neglected Tropical Disease Human Schistosomiasis and HCV Infection in Egypt:a Puzzling Relationship

Egypt has the highest prevalence of chronic hepatitis C virus (HCV) infection and seropositivity worldwide, and it has been proposed that this enhanced susceptibility to HCV is related to coinfection with schistosomiasis. Although currently, there are no studies regarding the actual prevalence of both human schistosomiasis and schistosomiasis/HCV coinfection evi-dences strongly support that eliminating human schistoso-miasis from Egypt is necessary to reduce both HCV prevalence and liver pathology. The present review highlights the significant impact of the neglected tropical disease human schistosomiasis on both susceptibility of Egyptians to HCV coinfection, severity of the resulting liver pathology, and poor response to antiviral therapy. The immune evasion mechan-isms exerted by the HCV-NS3/4A protease domain, and the possible impact of immune evasion mechanisms exerted by proteases of larval, worm and egg stages of the parasite Schistosoma on human susceptibility to HCV infection are discussed. In addition, schistosome immune evasion mechanisms may include immunosuppression that in turn prevents clearance of HCV viremia and leads to relapsing HCV infection and severe liver pathology. I propose the generation of a replicon system from the most prevailing genotype (HCV-4a) in Egypt and establishing its replication on hepatoplas-toma or immune cells in presence of bilharzial antigens. Finally, the use of a humanized small animal model that can acquire both HCV and S. mansoni infections will be important to further understand in real time the impact of coinfection on both the immune system and liver pathology.