查看更多>>摘要：A pre-metastatic niche(PMN)is a protective microenvironment that facilitates the colonization of disseminating tumor cells in future metastatic organs.Extracellular vesicles(EVs)play a role in intercellular communication by delivering cargoes,such as noncoding RNAs(ncRNAs).The pivotal role of extracellular vesicle-derived noncoding RNAs(EV-ncRNAs)in the PMN has attracted increasing attention.In this review,we summarized the effects of EV-ncRNAs on the PMN in terms of immunosuppression,vascular permeability and angiogenesis,inflammation,metabolic reprogramming,and fibroblast alterations.In particular,we provided a comprehensive overview of the effects of EV-ncRNAs on the PMN in different cancers.Finally,we discussed the promising clinical applications of EV-ncRNAs,including their potential as diagnostic and prognostic markers and therapeutic targets.
查看更多>>摘要：Intra-tumor heterogeneity is now arguably one of the most-studied topics in tumor biology,as it represents a major obstacle to effective cancer treatment.Since tumor cells are highly diverse at genetic,epigenetic,and phenotypic levels,intra-tumor heterogeneity can be assumed as an important contributing factor to the nullification of chemotherapeutic effects,and recurrence of the tumor.Based on the role of heterogeneous subpopulations of cancer cells with varying cell-cycle dynamics and behavior during cancer progression and treatment;herein,we aim to establish a comprehensive definition for adaptation of neoplastic cells against therapy.We discuss two parallel and yet distinct subpopulations of tumor cells that play pivotal roles in reducing the effects of chemotherapy:"resistant"and"tolerant"popula-tions.Furthermore,this review also highlights the impact of the quiescent phase of the cell cycle as a survival mechanism for cancer cells.Beyond understanding the mechanisms under-lying the quiescence,it provides an insightful perspective on cancer stem cells(CSCs)and their dual and intertwined functions based on their cell cycle state in response to treatment.More-over,CSCs,epithelial-mesenchymal transformed cells,circulating tumor cells(CTCs),and disseminated tumor cells(DTCs),which are mostly in a quiescent state of the cell cycle are proved to have multiple biological links and can be implicated in our viewpoint of cell cycle heterogeneity in tumors.Overall,increasing our knowledge of cell cycle heterogeneity is a key to identifying new therapeutic solutions,and this emerging concept may provide us with new opportunities to prevent the dreadful cancer recurrence.
查看更多>>摘要：The interaction between cluster of differentiation 47(CD47)and signal regulatory protein α(SIRPα)protects healthy cells from macrophage attack,which is crucial for maintain-ing immune homeostasis.Overexpression of CD47 occurs widely across various tumor cell types and transmits the"don't eat me"signal to macrophages to avoid phagocytosis through binding to SIRPα.Blockade of the CD47-SIRPα axis is therefore a promising approach for cancer treat-ment.Lymphoma is the most common hematological malignancy and is an area of unmet clin-ical need.This review mainly described the current strategies targeting the CD47-SIRPα axis,including antibodies,SIRPα Fc fusion proteins,small molecule inhibitors,and peptides both in preclinical studies and clinical trials with Hodgkin lymphoma and non-Hodgkin lymphoma.
查看更多>>摘要：Ribonucleotide reductase M2(RRM2)is a small subunit in ribonucleotide reduc-tases,which participate in nucleotide metabolism and catalyze the conversion of nucleotides to deoxynucleotides,maintaining the dNTP pools for DNA biosynthesis,repair,and replication.RRM2 performs a critical role in the malignant biological behaviors of cancers.The structure,regulation,and function of RRM2 and its inhibitors were discussed.RRM2 gene can produce two transcripts encoding the same ORF.RRM2 expression is regulated at multiple levels during the processes from transcription to translation.Moreover,this gene is associated with resistance,regulated cell death,and tumor immunity.In order to develop and design inhibitors of RRM2,appropriate strategies can be adopted based on different mechanisms.Thus,a greater appre-ciation of the characteristics of RRM2 is a benefit for understanding tumorigenesis,resistance in cancer,and tumor microenvironment.Moreover,RRM2-targeted therapy will be more atten-tion in future therapeutic approaches for enhancement of treatment effects and amelioration of the dismal prognosis.
查看更多>>摘要：The hypoxic microenvironment is an essential characteristic of most malignant tu-mors.Notably,hypoxia-inducible factor-1 alpha(HIF-1α)is a key regulatory factor of cellular adaptation to hypoxia,and many critical pathways are correlated with the biological activity of organisms via HIF-1α.In the intra-tumoral hypoxic environment,HIF-1α is highly expressed and contributes to the malignant progression of tumors,which in turn results in a poor prog-nosis in patients.Recently,it has been indicated that HIF-1α involves in various critical pro-cesses of life events and tumor development via regulating the expression of HIF-1α target genes,such as cell proliferation and apoptosis,angiogenesis,glucose metabolism,immune response,therapeutic resistance,etc.Apart from solid tumors,accumulating evidence has re-vealed that HIF-1α is also closely associated with the development and progression of hemato-logical malignancies,such as leukemia,lymphoma,and multiple myeloma.Targeted inhibition of HIF-1α can facilitate an increased sensitivity of patients with malignancies to relevant ther-apeutic agents.In the review,we elaborated on the basic structure and biological functions of HIF-1α and summarized their current role in various malignancies.It is expected that they will have future potential for targeted therapy.
查看更多>>摘要：N6-methyladenosine(m6A)modifications,as one of the most common forms of in-ternal RNA chemical modifications in eukaryotic cells,have gained increasing attention in recent years.The m6A RNA modifications exert various crucial roles in various biological pro-cesses,such as embryonic development,neurogenesis,circadian rhythms,and tumorigenesis.Recent advances have highlighted that m6A RNA modification plays an important role in im-mune response,especially in the initiation and progression of autoimmune diseases.In this re-view,we summarized the regulatory mechanisms of m6A methylation and its biological functions in the immune system and mainly focused on recent progress in research on the po-tential role of m6A RNA methylation in the pathogenesis of autoimmune diseases,thus providing possible biomarkers and potential targets for the prevention and treatment of auto-immune diseases.
Mohadeseh KhoshandamHossein SoltaninejadMarziyeh MousazadehAmir Ali Hamidieh...
268-282页
查看更多>>摘要：CRISPR/Cas9 is an effective gene editing tool with broad applications for the pre-vention or treatment of numerous diseases.It depends on CRISPR(clustered regularly inter-spaced short palindromic repeats)as a bacterial immune system and plays as a gene editing tool.Due to the higher specificity and efficiency of CRISPR/Cas9 compared to other editing ap-proaches,it has been broadly investigated to treat numerous hereditary and acquired ill-nesses,including cancers,hemolytic diseases,immunodeficiency disorders,cardiovascular diseases,visual maladies,neurodegenerative conditions,and a few X-linked disorders.CRISPR/Cas9 system has been used to treat cancers through a variety of approaches,with sta-ble gene editing techniques.Here,the applications and clinical trials of CRISPR/Cas9 in various illnesses are described.Due to its high precision and efficiency,CRISPR/Cas9 strategies may treat gene-related illnesses by deleting,inserting,modifying,or blocking the expression of specific genes.The most challenging barrier to the in vivo use of CRISPR/Cas9 like off-target effects will be discussed.The use of transfection vehicles for CRISPR/Cas9,including viral vec-tors(such as an Adeno-associated virus(AAV)),and the development of non-viral vectors is also considered.
查看更多>>摘要：In recent years,significant breakthroughs have been made in the field of gene ther-apy.Adeno-associated virus(AAV)is one of the most promising gene therapy vectors and a powerful tool for delivering the gene of interest.Among the AAV vectors,AAV serotype 8(AAV8)has attracted much attention for its efficient and stable gene transfection into specific tissues.Currently,recombinant AAV8 has been widely used in gene therapy research on a va-riety of diseases,including genetic diseases,cancers,autoimmune diseases,and viral diseases.This paper reviewed the applications and challenges of using AAV8 as a vector for gene ther-apy,with the aim of providing a valuable resource for those pursuing the application of viral vectors in gene therapy.
查看更多>>摘要：Adhesion G protein-coupled receptors(aGPCRs)are the second largest diverse group within the GPCR superfamily,which play critical roles in many physiological and patho-logical processes through cell-cell and cell-extracellular matrix interactions.The adhesion GPCR Adgrg6,also known as GPR126,is one of the better-characterized aGPCRs.GPR126 was previously found to have critical developmental roles in Schwann cell maturation and its mediated myelination in the peripheral nervous system in both zebrafish and mammals.Current studies have extended our understanding of GPR126-mediated roles during develop-ment and in human diseases.In this review,we highlighted these recent advances in GPR126 in expression profile,molecular structure,ligand-receptor interactions,and associ-ated physiological and pathological functions in development and diseases.
查看更多>>摘要：PARP inhibitors(PARPi)are a kind of cancer therapy that targets poly(ADP-ribose)polymerase.PARPi is the first clinically approved drug to exert synthetic lethality by obstruct-ing the DNA single-strand break repair process.Despite the significant therapeutic effect in pa-tients with homologous recombination(HR)repair deficiency,innate and acquired resistance to PARPi is a main challenge in the clinic.In this review,we mainly discussed the underlying mechanisms of PARPi resistance and summarized the promising solutions to overcome PARPi resistance,aiming at extending PARPi application and improving patient outcomes.
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