Tumor immunotherapy has revolutionized the treatment prospects for various malignant tumors. Immune checkpoint inhibitors (ICIs) and chimeric antigen receptor T-cell therapy (CAR-T) , as representative of tumor immunotherapy, have achieved tremendous success in clinical practice and have become the first-line clinical treatment options for certain tumors. This article summarizes the progress and challenges of immune checkpoint inhibitors and CAR-T therapy in tumor treatment, and discusses the future direction of tumor therapeutic vaccines development. Identifying novel therapeutic targets within the realm of tumor immunology, engineering innovative drug delivery systems, and employing combinatorial therapeutic strategies are poised to enhance therapeutic efficacy and patient outcomes in oncology, thereby extending benefits to a broader patient population.
Humans ; Neoplasms/immunology* ; Immune Checkpoint Inhibitors/therapeutic use* ; Receptors, Chimeric Antigen/genetics* ; Immunotherapy/methods* ; Immunotherapy, Adoptive/methods* ; Animals ; Cancer Vaccines/therapeutic use*

Usnic acid,a secondary metabolite derived from lichens,has been extensively utilized in pharmaceuticals,dietary supplements,and various daily chemical products,including feed,dye,food,perfume and cosmetics,due to its notable pharmacological effects,including anti-tumor,antibacterial,antiviral,and anti-inflammatory properties.Recent studies have shown that usnic acid can inhibit the occurrence and progression of various tumors through inducing apoptosis and autophagy,arresting cell cycle progression,inhibiting cell migration and invasion,and regulating the expression of microRNAs(miRNAs).Furthermore,usnic acid can be combined with clinical anticancer drugs to achieve synergistic anti-cancer effects.Additionally,modified usnic acid analogues also exhibit significant anti-tumor activity.This article will focus on the current research status of usnic acid,examining its physical and chemical properties,the mechanisms underlying its anti-tumor effects,and the anti-tumor activity of its analogues.

Usnic acid,a secondary metabolite derived from lichens,has been extensively utilized in pharmaceuticals,dietary supplements,and various daily chemical products,including feed,dye,food,perfume and cosmetics,due to its notable pharmacological effects,including anti-tumor,antibacterial,antiviral,and anti-inflammatory properties.Recent studies have shown that usnic acid can inhibit the occurrence and progression of various tumors through inducing apoptosis and autophagy,arresting cell cycle progression,inhibiting cell migration and invasion,and regulating the expression of microRNAs(miRNAs).Furthermore,usnic acid can be combined with clinical anticancer drugs to achieve synergistic anti-cancer effects.Additionally,modified usnic acid analogues also exhibit significant anti-tumor activity.This article will focus on the current research status of usnic acid,examining its physical and chemical properties,the mechanisms underlying its anti-tumor effects,and the anti-tumor activity of its analogues.

Objective·To explore the role and molecular mechanism of GPR87 in regulating the invasion and migration of non-small cell lung cancer(NSCLC).Methods·Bioinformatics methods,including GEO,UALCAN,KM Plotter and other public database analysis platforms,were used to screen candidate genes related to NSCLC invasion and predict their clinical relevance to NSCLC.Eighty NSCLC clinical patient samples and corresponding clinical pathological data were collected from Yichang Central People's Hospital from January 2018 to August 2020.Immunohistochemistry was used to analyze the expression of GPR87 in tumor tissues and the clinical relevance of GPR87 was analyzed.siRNA-GPR87 and pCMV-GPR87-his were transfected into the human lung adenocarcinoma cell line A549 and the human lung squamous cell carcinoma cell line SK-MES-1,to construct cell lines with low and high expression of GPR87.Transwell assay was used to investigate the effect of GPR87 expression on the migration and invasion ability of NSCLC cells.ELISA was used to detect the secretion of MMP7 in the culture supernatant.RT-qPCR was used to detect the mRNA expression levels of GPR87,MMP2,MMP7,MMP9,E-cadherin,N-cadherin,vimentin,snail,twist,RHOA,RHOC,and ROCK1.ELISA was used to detect the secreted protein MMP7.Western blotting was used to detect the protein expression levels of GPR87,MMP9,E-cadherin,vimentin,RHOA,and ROCK1.Results·Bioinformatics analysis of clinical sample data showed that GPR87 was highly expressed in NSCLC.Patients with higher expression of GPR87 had worse clinical stage and were more prone to lymph node metastasis,suggesting that GPR87 might be a key gene for the high invasiveness of NSCLC.Downregulation of GPR87 expression significantly reduced the invasion and migration ability of A549 and SK-MES-1 cells,while overexpression of GPR87 enhanced the invasion and migration ability of A549 and SK-MES-1 cells.Further detection revealed that downregulation of GPR87 led to decreased mRNA expression levels of MMP2,MMP7,MMP9,RHOA,RHOC,and ROCK1,as well as a reduction in the secretion of MMP7 and the protein expression levels of MMP9,RHOA,and ROCK1 in A549 and SK-MES-1 cells.Overexpression of GPR87 increased the mRNA expression levels of MMP2,MMP7,MMP9,RHOA,RHOC,and ROCK1,as well as the secretion of MMP7 and the protein expression levels of MMP9,RHOA,and ROCK1.Regardless of GPR87 knockdown or overexpression,the expression of genes and proteins related to epithelial-mesenchymal transition(EMT)in the cells did not change significantly.Conclusion·High expression of GPR87 is closely related to the high invasiveness of NSCLC.In SK-MES-1 and A549 cells,GPR87 can activate the RHOA/ROCK1 signaling pathway,promote the expression of MMPs,and ultimately promote the invasion and migration of NSCLC.

Objective·To explore the role and molecular mechanism of GPR87 in regulating the invasion and migration of non-small cell lung cancer(NSCLC).Methods·Bioinformatics methods,including GEO,UALCAN,KM Plotter and other public database analysis platforms,were used to screen candidate genes related to NSCLC invasion and predict their clinical relevance to NSCLC.Eighty NSCLC clinical patient samples and corresponding clinical pathological data were collected from Yichang Central People's Hospital from January 2018 to August 2020.Immunohistochemistry was used to analyze the expression of GPR87 in tumor tissues and the clinical relevance of GPR87 was analyzed.siRNA-GPR87 and pCMV-GPR87-his were transfected into the human lung adenocarcinoma cell line A549 and the human lung squamous cell carcinoma cell line SK-MES-1,to construct cell lines with low and high expression of GPR87.Transwell assay was used to investigate the effect of GPR87 expression on the migration and invasion ability of NSCLC cells.ELISA was used to detect the secretion of MMP7 in the culture supernatant.RT-qPCR was used to detect the mRNA expression levels of GPR87,MMP2,MMP7,MMP9,E-cadherin,N-cadherin,vimentin,snail,twist,RHOA,RHOC,and ROCK1.ELISA was used to detect the secreted protein MMP7.Western blotting was used to detect the protein expression levels of GPR87,MMP9,E-cadherin,vimentin,RHOA,and ROCK1.Results·Bioinformatics analysis of clinical sample data showed that GPR87 was highly expressed in NSCLC.Patients with higher expression of GPR87 had worse clinical stage and were more prone to lymph node metastasis,suggesting that GPR87 might be a key gene for the high invasiveness of NSCLC.Downregulation of GPR87 expression significantly reduced the invasion and migration ability of A549 and SK-MES-1 cells,while overexpression of GPR87 enhanced the invasion and migration ability of A549 and SK-MES-1 cells.Further detection revealed that downregulation of GPR87 led to decreased mRNA expression levels of MMP2,MMP7,MMP9,RHOA,RHOC,and ROCK1,as well as a reduction in the secretion of MMP7 and the protein expression levels of MMP9,RHOA,and ROCK1 in A549 and SK-MES-1 cells.Overexpression of GPR87 increased the mRNA expression levels of MMP2,MMP7,MMP9,RHOA,RHOC,and ROCK1,as well as the secretion of MMP7 and the protein expression levels of MMP9,RHOA,and ROCK1.Regardless of GPR87 knockdown or overexpression,the expression of genes and proteins related to epithelial-mesenchymal transition(EMT)in the cells did not change significantly.Conclusion·High expression of GPR87 is closely related to the high invasiveness of NSCLC.In SK-MES-1 and A549 cells,GPR87 can activate the RHOA/ROCK1 signaling pathway,promote the expression of MMPs,and ultimately promote the invasion and migration of NSCLC.

Squalene monooxygenase (SQLE) is the rate-limiting enzyme of cholesterol biosynthesis. It plays a crucial role in regulating cholesterol homeostasis. Increasing evidence shows that SQLE is closely related to the occurrence, development, metastasis, and poor prognosis of various cancers. SQLE can not only promote the proliferation of cancer cells and epithelial-mesenchymal transformation but also play an important role in maintaining the stemness of cancer stem cells and regulating cholesterol homeostasis. SQLE may be a potential molecular target for cancer therapy. In this review, the role of SQLE in regulating cholesterol homeostasis in vivo; its function in the occurrence, development, and metastasis of various cancers; and its molecular mechanism were summarized. Screening new SQLE inhibitors may provide new ideas for targeted cancer therapy.

Type 2 diabetes mellitus and malignant tumors are two kinds of chronic diseases with tremendous impact on human health. Numerous epidemiological and clinical studies have shown that type 2 diabetes mellitus increases the risk of liver, pancreatic, endometrial, gallbladder, colorectal and breast cancers. Hyperglycemia can promote cancer cell proliferation, migration, invasion and immune escape through a variety of direct and indirect mechanisms. Insulin resistance and hyperinsulinemia can activate multiple signal transduction pathways through insulin/IGF-I signaling axis and promote tumorigenesis. Sustained chronic inflammatory responses can promote the development of cancer through DNA damage and pro-inflammatory factors. Gut microbiome dysbiosis is closely related to the occurrence of several gastrointestinal tumors. This paper reviews the progress on the correlation between type 2 diabetes mellitus and the progression of malignant tumors and the possible mechanisms.