Network pharmacology study and in vitro experimental validation of Xiaojianzhong decoction against gastric cancer

BACKGROUND Cancer is one of the most serious threats to human health worldwide.Conventional treatments such as surgery and chemotherapy are associated with some drawbacks.In recent years,traditional Chinese medicine treatment has been increasingly advocated by patients and attracted attention from clinicians,and has become an indispensable part of the comprehensive treatment for gastric cancer.AIM To investigate the mechanism of Xiaojianzhong decoction(XJZ)in the treatment of gastric cancer(GC)by utilizing network pharmacology and experimental validation,so as to provide a theoretical basis for later experimental research.METHODS We analyzed the mechanism and targets of XJZ in the treatment of GC through network pharmacology and bioinformatics.Subsequently,we verified the impact of XJZ treatment on the proliferative ability of GC cells through CCK-8,apoptosis,cell cycle,and clone formation assays.Additionally,we performed Western blot analysis and real-time quantitative PCR to assess the protein and mRNA expression of the core proteins.RESULTS XJZ mainly regulates IL6,PTGS2,CCL2,MMP9,MMP2,HMOX1,and other target genes and pathways in cancer to treat GC.The inhibition of cell viability,the increase of apoptosis,the blockage of the cell cycle at the G0/G1 phase,and the inhibition of the ability of cell clone formation were observed in AGS and HGC-27 cells after XJZ treatment.In addition,XJZ induced a decrease in the mRNA expression of IL6,PTGS2,MMP9,MMP2,and CCL2,and an increase in the mRNA expression of HOMX1.XJZ significantly inhibited the expression of IL6,PTGS2,MMP9,MMP2,and CCL2 proteins and promoted the expression of the heme oxygenase-1 protein.CONCLUSION XJZ exerts therapeutic effects against GC through multiple components,multiple targets,and multiple pathways.Our findings provide a new idea and scientific basis for further research on the molecular mechanisms underlying the therapeutic effects of XJZ in the treatment of GC.

Metabologenomics and network pharmacology to understand the molecular mechanism of cancer research

In this editorial I comment on the article“Network pharmacological and molecular docking study of the effect of Liu-Wei-Bu-Qi capsule on lung cancer”published in the recent issue of the World Journal of Clinical Cases 2023 November 6;11(31):7593-7609.Almost all living forms are able to manufacture particular chemicals-metabolites that enable them to differentiate themselves from one another and to overcome the unique obstacles they encounter in their natural habitats.Numerous methods for chemical warfare,communication,nutrition acquisition,and stress prevention are made possible by these specialized metabolites.Metabolomics is a popular technique for collecting direct mea-surements of metabolic activity from many biological systems.However,con-fusing metabolite identification is a typical issue,and biochemical interpretation is frequently constrained by imprecise and erroneous genome-based estimates of enzyme activity.Metabolite annotation and gene integration uses a biochemical reaction network to obtain a metabolite-gene association so called metabologe-nomics.This network uses an approach that emphasizes metabolite-gene consensus via biochemical processes.Combining metabolomics and genomics data is beneficial.Furthermore,computer networking proposes that using meta-bolomics data may improve annotations in sequenced species and provide testable hypotheses for specific biochemical processes.CONCLUSION The genome and metabolites of biological organisms are not fully characterized with current technologies.However,increasing high-throughput metabolomics and genomics data provide promising generation of paired data sets to understand the molecular mechanism of biochemical processes as well as determining targets for pharmaceutical drug design.Contemporary network infrastructures to integrate omics analysis can provide molecular mechanism of biochemical pathways.Furthermore,clinical data may be integrated to gene expression–metabolite expression by system genetics approach.Calculating pair-wise correlations and weighted correlation network analysis provide the basis of this integration[11-13].The occurrence of strong correlations between classified metabolites and co-expression transcripts implies either various roles of metabolites or linkages between metabolic pathways and the immune system.

Neoantigen cancer vaccines:a new star on the horizon

Immunotherapy represents a promising strategy for cancer treatment that utilizes immune cells or drugs to activate the patient's own immune system and eliminate cancer cells.One of the most exciting advances within this field is the targeting of neoantigens,which are peptides derived from non-synonymous somatic mutations that are found exclusively within cancer cells and absent in normal cells.Although neoantigen-based therapeutic vaccines have not received approval for standard cancer treatment,early clinical trials have yielded encouraging outcomes as standalone monotherapy or when combined with checkpoint inhibitors.Progress made in high-throughput sequencing and bioinformatics have greatly facilitated the precise and efficient identification of neoantigens.Consequently,personalized neoantigen-based vaccines tailored to each patient have been developed that are capable of eliciting a robust and long-lasting immune response which effectively eliminates tumors and prevents recurrences.This review provides a concise overview consolidating the latest clinical advances in neoantigen-based therapeutic vaccines,and also discusses challenges and future perspectives for this innovative approach,particularly emphasizing the potential of neoantigen-based therapeutic vaccines to enhance clinical efficacy against advanced solid tumors.

Identification of anti-gastric cancer effects and molecular mechanisms of resveratrol: From network pharmacology and bioinformatics to experimental validation

BACKGROUND Gastric cancer(GC)is one of the most aggressive malignancies with limited therapeutic options and a poor prognosis.Resveratrol,a non-flavonoid poly-phenolic compound found in a variety of Chinese medicinal materials,has shown excellent anti-GC effect.However,its exact mechanisms of action in GC have not been clarified.AIM To identify the effects of resveratrol on GC progression and explore the related molecular mechanisms.METHODS Action targets of resveratrol and GC-related targets were screened from public databases.The overlapping targets between the two were confirmed using a Venn diagram,and a“Resveratrol-Target-GC”network was constructed using Cyto-scape software version 3.9.1.The protein-protein interaction(PPI)network was constructed using STRING database and core targets were identified by PPI network analysis.The Database for Annotation,Visualization and Integrated A total of 378 resveratrol action targets and 2154 GC disease targets were obtained from public databases,and 181 intersection targets between the two were screened by Venn diagram.The top 20 core targets were identified by PPI network analysis of the overlapping targets.GO function analysis mainly involved protein binding,identical protein binding,cytoplasm,nucleus,negative regulation of apoptotic process and response to xenobiotic stimulus.KEGG enrichment analysis suggested that the involved signaling pathways mainly included PI3K-AKT signaling pathway,MAPK signaling pathway,IL-17 signaling pathway,TNF signaling pathway,ErbB signaling pathway,etc.FBJ murine osteosarcoma viral oncogene homolog(FOS)and matrix metallopeptidase 9(MMP9)were selected by differential expression analysis,and they were closely associated with immune infiltration.Molecular docking results showed that resveratrol docked well with these two targets.Resveratrol treatment arrested the cell cycle at the S phase,induced apoptosis,and weakened viability,migration and invasion in a dose-dependent manner.Furthermore,resveratrol could exhibit anti-GC effect by regulating FOS and MMP9 expression.CONCLUSION The anti-GC effects of resveratrol are related to the inhibition of cell proliferation,migration,invasion and induction of cell cycle arrest and apoptosis by targeting FOS and MMP9.

Curcumin for gastric cancer:Mechanism prediction via network pharmacology,docking,and in vitro experiments

BACKGROUND Curcumin originates from the natural herb turmeric,and its antitumor effects have been known about for a long time.However,the mechanism by which curcumin affects gastric cancer(GC)has not been elucidated.AIM To elucidate the potential mechanisms of curcumin in the treatment of GC.METHODS Network pharmacological approaches were used to perform network analysis of Curcumin.We first analyzed Lipinski’s Rule of Five for the use of Curcumin.Curcumin latent targets were predicted using the PharmMapper,SwissTargetPrediction and DrugBank network databases.GC disease targets were mined through the GeneCard,OMIM,DrugBank and TTD network databases.Then,GO enrichment,KEGG enrichment,protein-protein interaction(PPI),and overall survival analyses were performed.The results were further verified through molecular docking,differential expression analysis and cell experiments.RESULTS We identified a total of 48 curcumin-related genes with 31 overlapping GC-related targets.The intersection targets between curcumin and GC have been enriched in 81 GO biological processes and 22 significant pathways.Following PPI analysis,6 hub targets were identified,namely,estrogen receptor 1(ESR1),epidermal growth factor receptor(EGFR),cytochrome P450 family 3 subfamily A member 4(CYP3A4),mitogen-activated protein kinase 14(MAPK-14),cytochrome P450 family 1 subfamily A member 2(CYP1A2),and cytochrome p450 family 2 subfamily B member 6(CYP2B6).These factors are correlated with decreased survival rates among patients diagnosed with GC.Molecular docking analysis further substantiated the strong binding interactions between Curcumin and the hub target genes.The experimental findings demonstrated that curcumin not only effectively inhibits the growth of BGC-823 cells but also suppresses their proliferation.mRNA levels of hub targets CYP3A4,MAPK14,CYP1A2,and CYP2B6 in BGC-823 cells were significantly increased in each dose group.CONCLUSION Curcumin can play an anti-GC role through a variety of targets,pathways and biological processes.

Overcoming neutrophil-induced immunosuppression in postoperative cancer therapy: Combined sialic acid-modified liposomes with scaffold-based vaccines

Immunotherapy is a promising approach for preventing postoperative tumor recurrence and metastasis. However, inflammatory neutrophils, recruited to the postoperative tumor site, have been shown to exacerbate tumor regeneration and limit the efficacy of cancer vaccines. Consequently, addressing postoperative immunosuppression caused by neutrophils is crucial for improving treatment outcomes. This study presents a combined chemoimmunotherapeutic strategy that employs a biocompatible macroporous scaffold-based cancer vaccine (S-CV) and a sialic acid (SA)-modified, doxorubicin (DOX)-loaded liposomal platform (DOX@SAL). The S-CV contains whole tumor lysates as antigens and imiquimod (R837, Toll-like receptor 7 activator)-loaded PLGA nanoparticles as immune adjuvants for cancer, which enhance dendritic cell activation and cytotoxic T cell proliferation upon localized implantation. When administered intravenously, DOX@SAL specifically targets and delivers drugs to activated neutrophils in vivo, mitigating neutrophil infiltration and suppressing postoperative inflammatory responses. In vivo and vitro experiments have demonstrated that S-CV plus DOX@SAL, a combined chemo-immunotherapeutic strategy, has a remarkable potential to inhibit postoperative local tumor recurrence and distant tumor progression, with minimal systemic toxicity, providing a new concept for postoperative treatment of tumors.

Network pharmacology and experimental validation to reveal the pharmacological mechanisms of Qizhu prescription for treating breast cancer

Objective:To investigate the mechanism underlying the effects exerted by the Qizhu prescription(QZP)in breast cancer(BC),and the respective targets.Methods: Expression data from the ArrayExpress and The Cancer Genome Atlas(TCGA)were used to identify differentially expressed genes(DEGs)in BC.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were performed on the DEGs to identify genes involved in protein–protein interactions.Molecular docking was used to explore the dynamic relationship between active molecules and targets.Cell function experiments and animal studies were conducted to evaluate the effects of hub genes and active QZP compounds on BC cell behavior.Results: Among the 25 evaluated BC-related targets of QZP,matrix metalloproteinase-1(MMP1)and epidermal growth factor receptor(EGFR)exhibited the highest degrees of dysregulation.GO and KEGG enrichment analyses revealed that the anti-BC targets of QZP primarily affected drug responses and pathways in cancer cells.Molecular docking analysis suggested potential interactions between EGFR and quercetin/luteolin,as well as between MMP1 and luteolin/kaempferol/quercetin.Quercetin significantly reduced BC cell proliferation,migration,invasion,and tumor development in vivo.Treatment of BC cells with quercetin decreased the expression or activation of several associated proteins.Conclusion: The findings of our study provide new insights into the therapeutic potential of traditional Chinese medicine against BC,with particular reference to QZP.

Mechanism of pachymic acid in the treatment of gastric cancer based on network pharmacology and experimental verification

BACKGROUND Pachymic acid(PA)is derived from Poria cocos.PA has a variety of pharmacological and inhibitory effects on various tumors.However,the mechanism of action of PA in gastric cancer(GC)remains unclear.AIM To investigate the mechanism of PA in treating GC via the combination of network pharmacology and experimental verification.METHODS The GeneCards and OMIM databases were used to derive the GC targets,while the Pharm Mapper database provided the PA targets.Utilizing the STRING database,a protein-protein interaction network was constructed and core targets were screened.The analyses of Gene Ontology,Kyoto Encyclopedia of Genes and Genomes(KEGG),and gene set enrichment analysis were conducted,and molecular docking and clinical correlation analyses were performed on the core targets.Ultimately,the network pharmacology findings were validated through in vitro cell assays,encompassing assessments of cell viability,apoptosis,cell cycle,cloning,and western blot analysis.RESULTS According to network pharmacology analysis,the core targets were screened,and the PI3K/AKT signaling pathway is likely to be the mechanism by which PA effectively treats GC,according to KEGG enrichment analysis.The experimental findings showed that PA could control PI3K/AKT signaling to prevent GC cell proliferation,induce apoptosis,and pause the cell cycle.CONCLUSION Network pharmacology demonstrated that PA could treat GC by controlling a variety of signaling pathways and acting on a variety of targets.This has also been supported by in vitro cell studies,which serve as benchmarks for further research.

Network pharmacology combined with molecular docking revealed the potential targets of Coridius chinensis in prostate cancer treatment

BACKGROUND Prostate cancer(PCa)has high morbidity and mortality rates in elderly men.With a history of thousands of years,traditional Chinese medicine derived from insects could be an important source for developing cancer-targeted drugs to prevent tumorigenesis,enhance therapeutic effects,and reduce the risk of recurrence and metastasis.Multiple studies have shown that Coridius chinensis(Cc)has anticancer effects.AIM To elucidate the mechanism of action of Cc against PCa via network pharma-cology and molecular docking.METHODS Potential targets for Cc and PCa were predicted using ChemDraw 19.0 software,the PharmMapper database and the GeneCards database.Then,the STRING database was used to construct the protein–protein interaction network.Gene Ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment and molecular docking analyses were subsequently conducted to identify the key targets,active ingredients and pathways involved.RESULTS GO and KEGG analyses indicated that the PI3K-Akt signalling pathway was the critical pathway(P value<1.0×10-8).Multiple targeting ingredients that can affect multiple pathways in PCa have been identified in Cc.Seven active compounds(asponguanosines A,asponguanine B,asponguanine C,aspong-pyrazine A,N-acetyldopamine,aspongadenine B and aspongpyrazine B)were selected for molecular docking with 9 potential targets,and the results revealed that aspongpyrazine A and asponguanosine A are the main components by which Cc affects PCa(affinity<-5 kcal/mol,hydrogen bonding),but more studies are needed.CONCLUSION We used network pharmacology to predict the bioactive components and important targets of Cc for the treatment of PCa,supporting the development of Cc as a natural anticancer agent.

Targeting colorectal cancer with Herba Patriniae and Coix seed:Network pharmacology,molecular docking,and in vitro validation

BACKGROUND Herba Patriniae and Coix seed(HC)constitute a widely utilized drug combination in the clinical management of colorectal cancer(CRC)that is known for its diuretic,anti-inflammatory,and swelling-reducing properties.Although its efficacy has been demonstrated in a clinical setting,the active compounds and their mechanisms of action in CRC treatment remain to be fully elucidated.AIM To identify the active,CRC-targeting components of HC and to elucidate the mechanisms of action involved.METHODS Active HC components were identified and screened using databases.Targets for each component were predicted.CRC-related targets were obtained from human gene databases.Interaction targets between HC and CRC were identified.A“drug-ingredient-target”network was created to identify the core components and targets involved.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analyses were conducted to elucidate the key pathways involved.Molecular docking between core targets and key components was executed.In vitro experiments validated core monomers.RESULTS Nineteen active components of HC were identified,with acacetin as the primary active compound.The predictive analysis identified 454 targets of the active compounds in HC.Intersection mapping with 2685 CRC-related targets yielded 171 intervention targets,including 30 core targets.GO and KEGG analyses indicated that HC may influence the phosphoinositide 3-kinase(PI3K)/Akt signaling pathway.Molecular docking showed that acacetin exhibited an optimal interaction with AKT1,identifying PI3K,AKT,and P53 as key genes likely targeted by HC during CRC treatment.Acacetin inhibited HT-29 cell proliferation and migration,as well as promoted apoptosis,in vitro.Western blotting analysis revealed increased p53 and cleaved caspase-3 expression and decreased levels of p-PI3K,p-Akt,and survivin,which likely contributed to CRC apoptosis.CONCLUSION Acacetin,the principal active compound in the HC pair,inhibited the proliferation and migration of HT-29 cells and promoted apoptosis through the PI3K/Akt/p53 signaling pathway.

Investigating the molecular mechanism of Chelidonii Herba against liver cancer using network pharmacology and molecular docking validation

Background:The molecular mechanism of Chelidonii Herba in treating hepatocellular carcinoma was investigated using network pharmacology and molecular docking validation.Methods:The main active components of Chelidonii Herba were screened using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform database,and the targets of these active ingredients were identified using the SwissTargetPrediction platform.Targets related to liver cancer were sourced from GeneCards,Therapeutic Targets Database,and Online Mendelian Inheritance in Man databases.Intersection targets between the active components of Chelidonii Herba and liver cancer were determined using the jvenn online platform.The protein interaction network was analyzed via STRING database and visualized using Cytoscape 3.9.1.Core targets were identified and further analyzed within the protein interaction network.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were conducted for the intersection targets using the DAVID database to correlate gene functions.Sankey bubble diagrams for Gene Ontology enrichment analysis and circular diagrams for Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were generated using CNSknowall and SangerBox online platforms.Molecular docking and visualization were performed using AutoDockTools 1.5.7 and PyMOL 2.5.7 software,respectively.Overall survival and pan-cancer analysis of core targets were conducted using the GEPIA2 online platform.Results:Twelve active components of Chelidonii Herba were identified through screening.A total of 103 intersection targets and 12 core targets were found between these active constituents of Chelidonii Herba and liver cancer.Chelidonii Herba may exert its effects on liver cancer through these 12 core targets.Several signaling pathways are implicated,including chemical carcinogen-receptor activation,endocrine resistance,HIF-1 signaling pathway,and proteoglycans in cancer.Conclusion:Chelidonii Herba potentially intervenes in cancer-related signaling pathways for treating liver cancer by targeting AKT1,EGFR,and ERBB2.This action is facilitated by active ingredients such as(S)-chrysocorydaline,dihydrochelidonorubin,cryptopine,and oxysanguinarine.Chelidonii Herba may address liver cancer through a mechanism involving multiple components,targets,and pathways.

Exploring the molecular mechanism of Baoyuan decoction in the treatment of lung cancer based on network pharmacology and molecular docking

Background:Baoyuan decoction is used clinically as an adjuvant treatment for lung cancer.However,the underlying mechanism remains unclear.Therefore,this study aimed to explore the mechanism of action of Baoyuan decoction in lung cancer treatment using network pharmacology and molecular docking technology.Methods:The Traditional Chinese Medicines Systems Pharmacology Database and Analysis Platform and SwissTargetPrediction databases were used to screen the active ingredients of Baoyuan decoction and their relevant targets.Lung cancer-related targets were obtained from the GeneCards,Online Mendelian Inheritance in Man,and DrugBank databases.Protein-protein interaction network of the common targets was constructed using the STRING database and analyzed using Cytoscape software 3.10.1.Furthermore,Gene Ontology enrichment,Kyoto Encyclopedia of Genes and Genomes pathway analyses and visualization of common genes were performed using the R software.Finally,molecular docking of the selected key ingredients and targets was performed,and the results were verified using AutoDock Vina software.Results:We identified 142 potential active ingredients,3624 potential lung cancer-related targets,and 341 common drug targets.A total of 72 core targets were identified,of which AKT1,TP53,interleukin-6,epithelial growth factor receptor,and signal transducer and activator of transcription 3 were key.A total of 4116 items were obtained via Gene Ontology enrichment analyses.Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses revealed 189 related signaling pathways,including the PI3K-Akt,AGE-RAGE signaling pathways in diabetic complications,FOXO,and TH signaling pathways,which are involved in cell proliferation,autophagy,metastasis,invasion,radiation resistance,and chemotherapy resistance in the lung cancer microenvironment.The molecular docking results suggested that the key ingredients had a strong affinity for key targets.Conclusion:This study demonstrates that Baoyuan decoction plays a key therapeutic role in a complex manner involving multiple ingredients,targets,and pathways in lung cancer.Our findings are anticipated to provide new ideas for follow-up experimental research and clinical application.

Unraveling the therapeutic mechanisms of myristic acid and luteolin 7-rutinoside in oral cancer: insights from network pharmacology and molecular docking analysis

Background:The compound Luteolin-7-rutinoside(L7R)is a flavone derivative of luteolin,predominantly identified in plant species belonging to the families Asteraceae.Conversely,Myristic acid is characterized by its structure as a 14-carbon,unsaturated fatty acid.In this investigation,we endeavor to elucidate the putative mechanisms underlying the therapeutic effects of Myristic Acid and Luteolin 7-rutinoside in the context of oral cancer treatment,employing network pharmacology coupled with molecular docking methodologies.Methods:The protein targets of Myristic Acid and Luteolin 7-rutinoside were identified through a search on the Swiss Target Database.Subsequently,a compound-target network was constructed using Cytoscape 3.9.1.Targets associated with OC were retrieved from the OMIM and GeneCards databases.The overlap between compound targets and OC-related targets was determined,and the resulting shared targets were subjected to protein-protein interaction(PPI)network analysis using the STRING database.Additionally,gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were conducted on the identified targets.Molecular docking were performed to investigate the interactions between the core target and the active compound.Results:The component target network comprises 103 nodes and 102 edges.Among the proteins in the protein-protein interaction(PPI)network,those with higher degrees are TNF,PPARG,and TP53.Analysis through Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathways indicates that the treatment of OC with Myristic Acid and Luteolin 7-rutinoside primarily involves the regulation of miRNA transcription and inflammatory response.The identified signaling pathways include Pathways in cancer,PPAR signaling pathway,EGFR signaling pathway,and TNF signaling pathway.Molecular docking studies reveal that Luteolin 7-rutinoside and Myristic acid exhibit higher affinity towards TNF,PPARG,TP53,and EGFR.Conclusion:This study reveals the potential molecular mechanism of Myristic Acid and Luteolin 7-rutinoside in the treatment of oral cancer,and provides a reference for subsequent basic research.

Exploring the mechanism of action of herb pair Pinellia Ternata-Magnolia Officinalis in the treatment of liver cancer based on network pharmacology and molecular docking

Background:Explore the anti-tumor mechanism of herb pair Pinellia ternate-Magnolia officinalis(BX-HP)in liver cancer through network pharmacology using molecular docking methods.Method:The active ingredients and corresponding targets of the herb pair Pinellia ternate-Magnolia officinalis were obtained from the HERB database.The relevant targets for liver cancer were obtained from GeneCards,DisGeNET,TTD,and Drugbank databases.Obtain common targets between herb pair Pinellia ternate-Magnolia officinalis and liver cancer through the Bioinformatics platform,establish a PPI network diagram using STRING software,and perform GO functional enrichment and KEGG pathway enrichment analysis on the DAVID platform.AutoDockTools 1.5.7 software and molecular dynamics simulation analysis are used to evaluate the binding of components to target proteins.HERB database,SwissTargetPrediction database,SwissADME database,UniProt database,GeneCards database,TTD database,DRUGBANK database,DisGeNET database,String,DAVID.Bioinformatics platform,PDB database,PubChem and TCMSP database.Result:A total of 22 active ingredients with a Probability>0.1 targets in Magnolia officinalis were screened,26 active ingredients with a Probability>0.1 targets in Pinellia ternata,ten vital active ingredients,corresponding to 979 and 803 targets with a Probability>0.1 targets,2536 liver cancer-related targets,and 279 targets in the herb pair Pinellia ternata-Magnolia officinalis.The GO functional enrichment analysis resulted in 1297 entries,namely 971 biological process entries,118 cell localization entries,and 208 molecular function entries.Three signaling pathways were annotated through the KEGG pathway.Based on molecular docking,ten vital active ingredients and five target proteins were validated to exhibit an excellent binding affinity.The above data indicates that combining the herb pair Pinellia ternata-Magnolia officinalis may treat liver cancer through specific targets and signaling pathways.Conclusion:Herb pair Pinellia ternata-Magnolia officinalis has a synergistic effect on treating liver cancer through multicomponent,multitarget,and multi-pathway approaches.This study provides a sufficient theoretical basis for subsequent research.

Colorectal cancer vaccines: Tumor-associated antigens vs neoantigens

Therapeutic options for the treatment of colorectal cancer(CRC) are diverse but still not always satisfying. Recent success of immune checkpoint inhibition treatment for the subgroup of CRC patients suffering from hypermutated tumors suggests a permanent role of immune therapy in the clinical management of CRC. Substantial improvement in treatment outcome could be achieved by development of efficient patient-individual CRC vaccination strategies. This mini-review summarizes the current knowledge on the two general classes of targets: tumor-associated antigens(TAAs) and tumorspecific antigens. TAAs like carcinoembryonic antigen and melanoma associated antigen are present in and shared by a subgroup of patients and a variety of clinical studies examined the efficacy of different TAA-derived peptide vaccines. Combinations of several TAAs as the next step and the development of personalized TAA-based peptide vaccines are discussed. Improvements of peptidebased vaccines achievable by adjuvants and immunestimulatory chemotherapeutics are highlighted. Finally, we sum up clinical studies using tumor-specific antigens-in CRC almost exclusively neoantigens-which revealed promising results; particularly no severe adverse events were reported so far. Critical progress for clinical outcomes can be expected by individualizing neoantigen-based peptide vaccines and combining them with immunestimulatory chemotherapeutics and immune checkpoint inhibitors. In light of these data and latest developments, truly personalized neoantigen-based peptide vaccines can be expected to fulfill modern precision medicine's requirements and will manifest as treatment pillar for routine clinical management of CRC.

Immunotherapy and therapeutic vaccines in prostate cancer： an update on current strategies and clinical implications

In recent years, immunotherapy has emerged as a viable and attractive strategy for the treatment of prostate cancer. While there are multiple ways to target the immune system, therapeutic cancer vaccines and immune checkpoint inhibitors have been most successful in late-stage clinical trials. The landmark Food and Drug Administration approval of sipuleuceI-T for asymptomatic or minimally symptomatic metastatic prostate cancer set the stage for ongoing phase III trials with the cancer vaccine PSA-TRICOM and the immune checkpoint inhibitor ipilimumab. A common feature of these immune-based therapies is the appearance of improved overall survival without short-term changes in disease progression. This class effect appears to be due to modulation of tumor growth rate kinetics, in which the activated immune system exerts constant immunologic pressure that slows net tumor growth. Emerging data suggest that the ideal population for clinical trials of cancer vaccines is patients with lower tumor volume and less aggressive disease. Combination strategies that combine immunotherapy with standard therapies have been shown to augment both immune response and clinical benefit.

Recent advances in heat shock protein-based cancer vaccines

BACKGROUND: Active immunotherapy has been successful in preventing many infectious diseases, and is being explored for its anti-tumor use. Purified antigens, peptides, gene-based systems and antigens contained in whole cells or cell lysates are used in specific active immunotherapy for cancer, known as cancer vaccines. Cancer vaccines do not directly kill tumor cells, but prime a specific humoral and/or cellular immune response against the tumor. Up to date, many kinds of cancer vaccines have been tested in the world and have shown their own advantages. Heat shock protein (HSP)-based cancer vaccine is one of the outstanding representatives. In this paper, we review recent advances in HSP-based cancer vaccines. DATA SOURCES: An English-language literature search was conducted using MEDLINE (1990-2005) on HSP, cancer vaccines and other related subjects. RESULTS: Several kinds of HSP-based cancer vaccines which have been explored worldwide, include tumor derived HSP-pepdde complex cancer vaccines, artificially reconstituted HSP-peptide complex cancer vaccines, HSPpeptide fusion protein cancer vaccines and HSP-based DNA cancer vaccines, etc. Many HSP-based cancer vaccines are being tested in clinical trials, and some are being tested in phase Ⅲ clinical trials at present. CONCLUSION: The available results in preclinical tests and clinical trials indicate that HSP-based cancer vaccines are promising in cancer therapy.

Advances in inducing adaptive immunity using cell-based cancer vaccines: clinical applications in pancreatic cancer

The incidence of pancreatic ductal adenocarcinoma(PDA) is on the rise, and the prognosis is extremely poor because PDA is highly aggressive and notoriously difficult to treat. Although gemcitabine- or 5-fluorouracil-based chemotherapy is typically offered as a standard of care, most patients do not survive longer than 1 year. Therefore, the development of alternative therapeutic approaches for patients with PDA is imperative. As PDA cells express numerous tumor-associated antigens that are suitable vaccine targets, one promising treatment approach is cancer vaccines. During the last few decades, cell-based cancer vaccines have offered encouraging results in preclinical studies. Cell-based cancer vaccines are mainly generated by presenting whole tumor cells or dendritic cells to cells of the immune system. In particular, several clinical trials have explored cell-based cancer vaccines as a promising therapeutic approach for patients with PDA. Moreover, chemotherapy and cancer vaccines can synergize to result in increased efficacies in patients with PDA. In this review, we will discuss both the effect of cell-based cancer vaccines and advances in terms of future strategies of cancer vaccines for the treatment of PDA patients.

mRNA vaccines:a new era in vaccine development

The advent of RNA therapy,particularly through the development of mRNA cancer vaccines,has ushered in a new era in the field of oncology.This article provides a concise overview of the key principles,recent advancements,and potential implications of mRNA cancer vaccines as a groundbreaking modality in cancer treatment.mRNA cancer vaccines represent a revolutionary approach to combatting cancer by leveraging the body’s innate immune system.These vaccines are designed to deliver specific mRNA sequences encoding cancer-associated antigens,prompting the immune system to recognize and mount a targeted response against malignant cells.This personalized and adaptive nature of mRNA vaccines holds immense potential for addressing the heterogeneity of cancer and tailoring treatments to individual patients.Recent breakthroughs in the development of mRNA vaccines,exemplified by the success of COVID-19 vaccines,have accelerated their application in oncology.The mRNA platform’s versatility allows for the rapid adaptation of vaccine candidates to various cancer types,presenting an agile and promising avenue for therapeutic intervention.Clinical trials of mRNA cancer vaccines have demonstrated encouraging results in terms of safety,immunogenicity,and efficacy.Pioneering candidates,such as BioNTech’s BNT111 and Moderna’s mRNA-4157,have exhibited promising outcomes in targeting melanoma and solid tumors,respectively.These successes underscore the potential of mRNA vaccines to elicit robust and durable anti-cancer immune responses.While the field holds great promise,challenges such as manufacturing complexities and cost considerations need to be addressed for widespread adoption.The development of scalable and cost-effective manufacturing processes,along with ongoing clinical research,will be pivotal in realizing the full potential of mRNA cancer vaccines.Overall,mRNA cancer vaccines represent a cutting-edge therapeutic approach that holds the promise of transforming cancer treatment.As research progresses,addressing challenges and refining manufacturing processes will be crucial in advancing these vaccines from clinical trials to mainstream oncology practice,offering new hope for patients in the fight against cancer.

Study on biological characters of SGC7901 gastric cancer cell-dendritic cell fusion vaccines

AIM： To detect the biological characters of the SGC7901 gastric cancer cell-dendritic cell fusion vaccines.METHODS： The suspending living SGC7901 gastric cancer cells and dendritic cells were induced to be fusioned by polyethylene glycol. Pure fusion cells were obtained by selective culture with the HAT/HT culture systems. The fusion cells were counted at different time points of culture and their growth curves were drawn to reflect their proliferative activities. The fusion cells were also cultured in culture medium to investigate whether they could grow into cell clones. MTT method was used to test the stimulating abilities of the fusion cells on T lymphocytes＇ proliferations. Moreover, the fusion cells were planted into nude mice to observe whether they could grow into new planted tumors in this kind of immunodeficiency animals.RESULTS： The fusion cells had weaker proliferative activity and clone abilities than their parental cells. When they were cultured, the counts of cells did not increase remarkably, nor could they grow into cell clones in culture medium. The fusion cells could not grow into new planted tumors after planted into nude mice. The stimulating abilities of the fusion cells on T lymphocytes＇ proliferations were remarkably increased than their parental dendritic cells. CONCLUSION： The SGC7901 gastric cancer cell-dendritic cell fusion vaccines have much weaker proliferative abilities than their parental cells, but they keep strong abilities to irritate the T lymphocytes and have no abilities to grow into new planted tumors in immunodeficiency animals. These are the biological basis for their antitumor biotherapies.