In the process of solid tumor transformation, the expression of claudins is often dysregulated. Claudins are involved in almost all aspects of tumor biology and steps of tumor development, suggesting that they have the potential to be diagnostics, and prognostic biomarkers and therapeutic targets. Current studies have found that Claudin18.2 is overexpressed in gastric cancer, pancreatic cancer, ovarian cancer and other diseases. Targeted anti-tumor therapy based on Claudin 18.2 has become a research hotspot recently. Therefore, this article reviews the basic structural characteristics of Claudin18.2, its expression in various malignant solid tumors, the progress of research and application, and prospect.
ObjectiveThis study is aimed to determine the expression of ubiquitin-specific peptidase 39 (USP39) protein in the colorectal cancer (CRC) tissues, and the effect of silencing USP39 gene on the cell growth and cell cycle distribution of CRC cells.Methods① The expressions of USP39 protein in CRC tissues and its paracancerous tissues were determined by immunohistochemical staining method. ② By lentiviral infection, Lv-shUSP39 (KD-1 and KD-2 group) and Lv-shCon (shCon group) were transferred into SW1116 and HCT116 cells, and cells of blank control group did not received any treatment (Con group). To determine the role of USP39 gene in cell growth, MTT assay was performed to draw growth curve, and cell cycle distribution of CRC cells in the 4 groups were determined by flow cytometer.Results① The expression of USP39 protein was higher in CRC tissues compared to adjacent tissues (P=0.007). ② For SW1116 and HCT116 cells, the cell proliferation ability of KD-1 and KD-2 groups were remarkably decreased than those in corresponding shCon and Con groups on 3, 4, and 5-day (P<0.05). ③ Flow cytometry assay showed that, the percentage of G0/G1 phase cells were decreased obviously (P<0.05), while increased significantly in percentage of G2/M phase and number of sub-G1 phase cells in KD-1 group compared with that in the Con group and shCon group of SW1116 and HCT116 cells (P<0.05).ConclusionsThe expression of USP39 protein is highly expressed in CRC tissues. Knockdowning of USP39 gene can inhibit cell proliferation and promote cell apoptosis.
Objective To summarize the advance in targeted therapy for radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC). Method The literatures relevant to the targeted therapy for RAIR-DTC were reviewed and summarized. Results Targeted therapy for RAIR-DTC mainly included multi-kinase inhibitors suppressing angiogenesis and mutation-specific kinase inhibitors targeting specific mutations. Representative multi-kinase inhibitors such as sorafenib and lenvatinib, which significantly prolonged progression-free survival, had been approved to put into clinical use, though there were shortcomings such as adverse effects and resistance. Mutation-specific kinase inhibitors acted on targets such as RET, mitogen-activated protein kinase pathway, phosphoinositide 3-kinase pathway respectively, with relatively small side effects, most of which had only been applied in clinical trials up to now. Conclusions Targeted therapy for RAIR-DTC has made rapid progress in recent years, filling the gap in treatment for RAIR-DTC. Further explorations and investigations are needed to establish a more effect and safer treatment mode.
ObjectiveThis study aims to systematically review the dynamic evolution mechanisms of the tumor microenvironment (TME) in colorectal cancer liver metastasis (CRLM), to provide a theoretical basis for developing early diagnostic biomarkers and novel therapeutic targets for CRLM. MethodsBy integrating existing research, this review focuses on the key multi-step processes involved in CRLM-TME formation. It elaborates on the complex interactions among tumor cells, stromal cells, immune components, and key signaling pathways during this process, with an emphasis on their multi-factorial interplay. ResultsThe formation of the CRLM-TME involves several key steps: remote regulation by the primary tumor, specific recruitment of immune cells, adaptive remodeling of the liver microenvironment, and final colonization of the metastatic sites. This process is collectively driven by various factors such as tumor-derived metabolites, specific immune cell subsets, stromal components, and neovascularization, ultimately acts on the entire cascade of colorectal cancer cell invasion, migration, and colonization into the liver. ConclusionsThe CRLM-TME plays a critical role in the development, progression, treatment and drug resistance of CRLM. In-depth exploration of its mechanisms can provide direction for the development of early diagnostic biomarkers and therapies targeting the CRLM-TME, thereby aiming to improve the prognosis of CRLM patients.
Objective To summarize functions and mechanisms of fibroblast activation protein (FAP) and its application in targeted therapy. Method Literatures about FAP in recent years were collected to make a review. Results Thereis an important relationship between the FAP and the dipeptidyl peptidase-Ⅳ. FAP has a serine protease activity and is an important immunosuppressive component in the tumor microenvironment. FAP participate in the pathological process of the neoplastic and the non-neoplastic diseases. In the targeted therapy, the enzyme inhibitors, antibodies, vaccines, and prodrugs of FAP had been extensively studied. Conclusion FAP have various functions and participates in pathological process of many diseases, and it is of great significance to research of tumor targeted therapy.
In recent years, target temperature management (TTM) has been increasingly applied to cardiac arrest patients, and programs and strategies for TTM are in a constant state of update and refinement. This paper analyzes and proposes relevant strategies from the concept of TTM, its clinical application status for cardiac arrest patients in domestic and international medical institutions, its deficiencies in the clinical practice, and factors affecting the development of TTM, with a view to providing a realistic basis for the development of high-quality TTM in medical institutions.
ObjectiveTo construct a cationic microbubble (CMB), and investigate the enhancement of gene transfection efficiency and therapeutic effect of ultrasound-targeted microbubble destruction (UTMD) in vivo with CMB compared to definity MB (DMB).Methods In vitro, the CMB was prepared by the method of thin film hydration. The morphology, size, zeta potential, and gene-carrying capacity of CMB were compared with the DMB. In vivo, the firefly luciferase gene which was used as a reporter gene was targeted transfected into myocardium of 16 rats with CMB and DMB, respectively. The gene transfection efficiency and targeting were observed dynamically. Then, ischemia-reperfusion (I/R) model was performed on 64 rats. The models of 60 rats were successfully confirmed by using ultrasonography at 5 days after I/R. The rats were divided into 3 groups (n=20) randomly. The control group received DMB carrying empty plasmid for transfection; DMB group received DMB carrying AKT plasmid for transfection; and CMB group received CMB carrying AKT plasmid for transfection. The cardiac perfusion, cardiac function, infarct size, and infarct thickness were measured by ultrasonography and histological observations after treatment. In addition, the capillary and arteriolar densities were measured with immunohistochemical staining. The myocyte apoptosis was measured with TUNEL staining. The protein expressions of AKT, phospho-AKT (P-AKT), Survivin, and phospho-BAD (P-BAD) were measured by Western blot.ResultsThe size of CMB was uniformly. The zeta potential of CMB was significantly higher than that of DMB (t=28.680, P=0.000). The CMB bound more plasmid DNA than the DMB (P<0.05). The luciferase activity of myocardium were higher in CMB group than in DMB group bothin vitro and in vivo measurements (P<0.05). There was no significant difference between groups in the ratio of signal intensity in anterior wall to posterior wall, ejection fraction (EF), and fractional shortening (FS) at 5 days after I/R (P>0.05), but the above indexes were significant higher in CMB and DMB groups than in control group at 21 days after I/R (P<0.05). Besides, the above indexes were significant higher in CMB group than in DMB group at 21 days after I/R (P<0.05). The infarct size was the smallest and infarct thickness was the thickest in the CMB group, followed by DMB group, control group at 21 days after I/R. The capillary and arteriolar densities of CMB and DMB groups were significant higher than those of control group at 21 days after I/R (P<0.05). Besides, the capillary and arteriolar densities of CMB group were significant higher than those of DMB group (P<0.05). The apoptotic cells were the most in the control group, followed by DMB group, CMB group at 3 days after gene transfection, showing significant differences between groups (P<0.05). The protein expressions of AKT, P-AKT, Survivin, and P-BAD were significant higher in CMB and DMB groups than those in control group at 3 days after gene transfection (P<0.05). Besides, these protein expressions were significant higher in CMB group than those in DMB group (P<0.05).ConclusionThe DNA-carrying capacity and gene transfection efficiency are elevated by CMB, although its physicochemical property is the same as DMB. When ultrasound-targeted AKT gene transfection is used to treat myocardial I/R injury in rats, delivery of AKT with the CMB can result in higher transfection efficiency and greater cardiac functional improvements compared to the DMB.
Objective To explore the effect and mechanism of rapamycin and deferoxamin on wound healing after ischemia and hypoxia. Methods The model of ischemia and hypoxia wound was made on the back of 40 SPF male adult Sprague Dawley rats, weight (300±20) g; they were randomly divided into 4 groups (n=10): the control group (group A), deferoxamine intervention group (group B), rapamycin intervention group (group C), and deferoxamine+rapamycin intervention group (group D). At 3, 6, and 9 days after model preparation, rats of groups A, B, C, and D were intra-peritoneally injected with normal saline, deferoxamin (10 mg/kg), rapamycin (3 mg/kg), deferoxamin (10 mg/kg)+rapamycin (3 mg/kg) respectively. The wound healing was observed and the healing time was recorded in each group; the wound healing tissue was harvested to test the mRNA and protein expressions of mammalian target of rapamycin (mTOR), hypoxia inducible factor 1α (HIF-1α), and vascular endothelial growth factor (VEGF) by real-time fluorescence quantitative PCR and Western blot at 2 days after wound healing. Results All rats survived to the end of the experiment, and wounds healed; the healing time of groups A, B, and D was significantly shorter than that of group C (P<0.05), but there was no significant difference between groups A, B, and D (P>0.05). Real-time fluorescence quantitative PCR showed that the expression of mTOR mRNA in groups C and D was significantly decreased when compared with the expressions in groups A and B (P<0.05); there was significant difference between groups A and B (P<0.05), but no significant difference between groups C and D (P>0.05). The expressions of HIF-1α mRNA and VEGF mRNA were signi-ficantly higher in groups B and D than groups A and C, and in group A than group C (P<0.05), but there was no signifi-cant difference between groups B and D (P>0.05). Western blot showed that the relative expressions of mTOR protein in groups C and D were significantly decreased when compared with the expressions in groups A and B (P<0.05), but there was no significant difference between groups C and D (P>0.05). The relative expressions of HIF-1α protein in groups A, B, and C were significantly increased when compared with expression in group D (P<0.05), but there was no significant difference between groups A, B, and C (P>0.05). The relative expression of VEGF protein were significantly lower in groups B, C, and D than group A, in group D than groups B and C, and in group C than group B (P<0.05). Conclusion Defe-roxamin can promote the wound healing of rats after ischemia and hypoxia, and the effect of rapamycin is opposite. It may be related to the existence of mTOR and HIF-1 signaling pathway in chronic ischemia-hypoxia wound.
ObjectiveTo summarize the latest research of long non-coding RNA (lncRNA) as competitive endogenous RNA (ceRNA) and its targeting technology in pancreatic cancer, so as to provide new ideas for lncRNA targeted intervention or as an early diagnostic marker of pancreatic cancer. MethodThe domestic and foreign literature on researches of lncRNA as ceRNA and its targeting technology in the pancreatic cancer was searched and reviewed. ResultsAt present, the growing number of evidences showed that in pathological states such as tumors, the abundance of intracellular lncRNAs was sufficient to trigger ceRNA crosstalk. The lncRNA played a role like “sponge” through the complementary binding of incomplete base of miRNA with miRNA response elements, then adsorbed miRNA, and thus changed the activity and effectiveness of miRNA. It also regulated the expression of downstream target genes. Moreover, a large number of studies had identified that the lncRNA-mediated ceRNA regulatory network, namely lncRNA/miRNA/mRNA axis, played a role in promoting or inhibiting the occurrence and progression of pancreatic cancer through a variety of cellular functions. In addition, many technologies targeting lncRNA, such as small interfering RNA, antisense oligonucleotides, clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9, and small molecule inhibitors, etc. had been widely studied and acquired important results in preclinical research. ConclusionsThe ceRNA hypothesis is a functional complex composed by non-coding RNAs and mRNAs with non-coding properties, forming a ceRNA network of multi-level and cross-regulatory on the transcriptome. Epigenetic modification and key post-transcriptional regulation of lncRNA have been achieved through ceRNA network mechanism, which has become a successful paradigm for exploring the function of lncRNA. The tumor suppressive and promoting effects and mechanisms of many lncRNAs in the occurrence and development of pancreatic cancer are explored in many studies. Moreover, the continuous progress of targeted lncRNA technology provides conditions for study of lncRNA. LncRNA has a potential to be used as a biomarker for precancerous diagnosis and prognosis of pancreatic cancer.
ObjectiveTo summarize the research progress of KRAS mutation in pancreatic tumorigenesis and therapy.MethodThe research progress of KRAS mutation in pancreatic tumorigenesis and therapy were summarized by reading the domestic and international literatures published in recent years.ResultsPancreatic cancer had the title of " king of cancer”. More than 90% of pancreatic cancer patients had KRAS mutation. KRAS had a complex relationship with pancreatic cancer through downstream signaling pathways, including Raf (rapidly accelerated fibrosarcoma)-mitogen-activated protein kinase kinase (MEK)-extracellular signal-regulated kinase (ERK), phosphatidylinositol-4, 5-bisphosphate 3-kinase (PI3K)-protein kinase B (AKT), and RalGDS-Ral. Although basic research on pancreatic cancer was deepening, there was still a lack of effective molecular targeted drugs.ConclusionsKRASgene plays an important role in the occurrence of pancreatic cancer. The treatment associated with KRAS mutation provides a more effective prognostic possibility for pancreatic cancer patients.