Diabetes has become a global epidemic disease now. Its chronic progressive deterioration and the acute and chronic complications affect the quality of the patients' lives seriously. The prevention and treatment of diabetes has become one of the research focuses in recent years. NLRP3 (NOD-like receptor family, pyrin domain containing 3) inflammasome can recognize the metabolic stress signals, and cause caspase-1 activation and interleukin-1β (IL-1β) production, and is closely related to diabetes development. The latest studies have shown that NLRP3 inflammasome will be a new potential target for the treatment of diabetes. This article reviews the activation and regulation of NLRP3 inflammasome, and the effect of NLRP3 inflammasome on glucose metabolism and its targeted therapy in diabetes.
Human tumor necrosis factor-related apoptosis-inducing ligand (hTRAIL) might be developed as a novel anti-tumor drug due to its selective cytotoxicity in tumor cells. The predicted Macaca mulatta TRAIL (mmTRAIL) is highly homologous to hTRAIL in nucleotide acid as well as amino acid sequence, suggesting that mmTRAIL might induce apoptosis of human cancer cells. However, the cytotoxicity of mmTRAIL in human cancer cells has not been investigated. In this paper, it is reported that the gene encoding mmTRAIL has been cloned by using reverse-transcriptase polymerase chain reaction (RT-PCR) from monkey peripheral blood mononuclear cells (PBMCs) in our laboratory. Subsequently, an expression plasmid was constructed by inserting mmTRAIL gene into pQE30 plasmid. After induction by addition of Isopropylβ-D-1-Thiogalactopyranoside (IPTG), mmTRAIL was expressed. MmTRAIL was recovered from supernatant of sonicated bacteria by Ni-NTA agarose affinity chromatography. SDS-PAGE and gel filtration chromatography demonstrated that mmTRAIL forms trimer in solution. In vitro assays indicated that mmTRAIL was cytotoxic to human COLO205 tumor cells but not to normal cells at low concentration of nanomole. In addition, antitumor effect of mmTRAIL was evaluated in mice bearing human COLO205 tumor xenografts. Intratumorally injected mmTRAIL significantly inhibited growth of tumor grafts. These results suggested that mmTRAIL was valuable as candidate drug for cancer-targeted therapy.
ObjectiveTo understand the latest progress of transcatheter arterial chemoembolization (TACE)-based combination therapies for unresectable liver metastasis from colorectal carcinoma, and to explore the safe and effective combination therapies in order to controlling the rapid progress of disease and improving the quality of life of patients. MethodsThe literatures about TACE-based combination therapies of liver metastasis from colorectal carcinoma and the latest advance in researches of this field at home and abroad were collected, and the application of combination therapies, the advantages and features of the combined treatments were reviewed. ResultsTACE was a safe and effective therapeutic modality in treating primary liver cancer or secondary liver cancer.Compared with a single treatment, TACE-based combination therapies had distinct advantages to patients with liver metastasis from colorectal carcinoma not only improved the quality of life but also prolonged the survival time.With the emerging of various kinds of new drugs and the rapid development of a variety of interventional treatments, it could bring long-term survival benifit for patients with liver metastasis from colorectal carcinoma. ConclusionsDoctors should pay attention to the combined treatments of patients with liver metastasis from colorectal carcinoma, improve the knowledge of personalized medication about advanced tumors and actively promote more usage of combination therapies.
ObjectiveTo review the recent progress of the molecular targeted therapy for thyroid cancer. MethodsThe literatures of molecular etiology for thyroid cancer, mechanism and evaluation of targeted therapy via Medline and CHKD database were reviewed. ResultsSo far, four molecular targeted drugs (Sorafenib, Lenvatinib, Vandetanib, and Cabozantinib) have been approved for treatment of advanced thyroid cancer by FDA. They can mainly improve the patient's progression-free survival. Besides, several new molecular targeted drugs have accomplishedⅠphase or Ⅱ phase clinical trials. These drugs may be new options for treatment of advanced thyroid cancer in the future. ConclusionsMolecular targeted drugs have been the main therapeutic method for advanced thyroid cancer. However, we should invent more effective new drugs and investigate the drug combination to improve the therapeutic effect.
Objective To understand breast cancer 1 (BRCA1) gene and relationship between BRCA1 gene and breast cancer, and analyze its effect on clinical comprehensive therapy of breast cancer. Method The domestic and international studies relevant BRCA1 and breast cancer in recent years were reviewed and summarized. Results BRCA1, a tumor suppressor gene, its mutations caused structural changes and functional abnormalities, which were closely related to breast cancer. And the expression situation and mutation of BRCA1 were associated with the therapeutic effect. Conclusions Mutation of BRCA1 is closely related to occurrence and development of breast cancer in female. Comprehensive therapy ideas should be found in clinical therapy according to expression or mutation of BRCA1. Further research on BTCA1 is beneficial to explore gold standard for treatment of breast cancer.
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.
The application of precision medicine in the field of tuberculosis is still in its infancy. The precision medicine of tuberculosis cannot be separated from the rapid and accurate diagnosis, the effective anti-tuberculosis drugs, and the comprehensive application of new cutting-edge technologies. In recent years, the precision medicine of tuberculosis has focused on drug-resistant tuberculosis, host-directed therapy and nano-targeted therapy, which has achieved certain results, providing an important mean for the treatment of tuberculosis, especially for the drug-resistant tuberculosis. In the future, the development of new drugs and the application of emerging technologies are the focus of precision medicine of tuberculosis. It is necessary to gradually carry out relevant clinical trial research and objectively evaluate its application value and prospects.
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.
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.
ObjectiveThis review has summarized in detail the advances in computed tomography (CT) and magnetic resonance imaging (MRI) imaging in evaluating the efficacy of targeted therapy for gastrointestinal stromal tumor (GIST).MethodsTo summarize the image-related guidelines, consensus, international conference reports, and relevant knowledge of clinical research on the evaluation of the efficacy of GIST targeted therapy in recent years.ResultsThe CT and MRI manifestation after targeted treatment of GIST was closely related to pathological changes, including necrosis, cystic degeneration, and bleeding. CT was the preferred imaging method. Functional magnetic resonance imaging, such as diffusion weighted imaging (DWI), had made some progress. The main criteria for evaluating the efficacy of GIST targeted therapy were RECIST 1.1 and Choi criteria.ConclusionCT and MRI play an important role in evaluating the efficacy of targeted therapy for GIST.