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.
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.
The morbidity and mortality of gallbladder cancer were rising. At present, there was no effective chemotherapy regimen, so it was of great practical significance to explore new therapy target. Ferroptosis is a non-apoptotic form of cell death characterized by iron-dependent lipid peroxidation and metabolic constraints. In recent years, it had become a research hotspot. Many studies had been carried out on the relevant biological mechanisms such as liver cancer, breast cancer, pancreatic cancer, and other cancer. At present, there are still few studies on ferroptosis in gallbladder cancer, and its relevant mechanisms need further in-depth analysis, which opens up a new research direction for exploring the treatment of gallbladder cancer.
Objective To summarize the progress in related basic research of molecular targeted therapy in pancreatic cancer. Method The relevant literatures on oncogenes, epigenome, tumour microenvironment and immunotherapy in recent years at home and abroad were reviewed. ResultsIn basic research, molecularly targeted drugs had shown some efficacy in the treatment of progression of pancreatic cancer, however, in clinical trials, more satisfactory results were not achieved. Conclusion Molecularly targeted therapies for pancreatic cancer are still at a preliminary stage of exploration, and basic research has not yet been effectively translated clinically, which requires further exploration efforts in subsequent studies to provide a more solid and reliable basis for precise treatment of pancreatic cancer and achieve better clinical benefits.
ObjectiveTo summarize the remodeling of cholesterol metabolism in the occurrence and progression of pancreatic ductal adenocarcinoma (PDAC), and to review the research progress on targeted cholesterol metabolism in the treatment of PDAC. MethodRelevant literatures on cholesterol metabolism in the occurrence, development, and diagnosis and treatment of PDAC in recent years were searched and reviewed. ResultsMetabolites of PDAC tumor cells affected the expression of oncogenes or tumor suppressor genes. Signaling regulation within tumor cells affects cholesterol metabolism, characterized by increased de novo cholesterol synthesis and esterification, and reduced efflux. Tumor cells also regulated tumor immune microenvironment or tumor stroma formation through cholesterol metabolism. Inhibiting cholesterol metabolism could suppress the proliferation, invasion and migration of PDAC tumor cells, and combination therapy targeting cholesterol metabolism had a synergistic anti-PDAC effect. ConclusionsRemodeling of cholesterol metabolism occurs in both PDAC tumor cells and the tumor microenvironment, and is closely related to the occurrence, development, invasion, metastasis, and treatment response of PDAC. Targeting cholesterol metabolism or combined application with chemotherapy drugs can have anticancer effects. However, more research is needed to support the translation of cholesterol metabolism regulation into clinical treatment applications.
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.
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 systematically review the role and potential clinical value of nicotinamide N-methyltransferase (NNMT) in gastric cancer, aiming to provide new insights for diagnosis, treatment, and prognosis of gastric cancer. MethodsRelevant literature from recent years on the involvement of NNMT in gastric cancer was thoroughly analyzed. The review focuses on the mechanisms by which NNMT influences cell proliferation, invasion, migration, and metabolic reprogramming in gastric cancer. Additionally, the study explores the potential of NNMT as a diagnostic and therapeutic target. ResultsNNMT was significantly overexpressed in gastric cancer tissues and was closely associated with tumor progression. It promoted malignant behaviors through various pathways, including metabolic regulation, enhancement of cancer cell proliferation and invasion, and alteration of the tumor microenvironment. Furthermore, NNMT played a crucial role in modulating host immune responses, which might impact the clinical prognosis of gastric cancer patients. ConclusionsNNMT exhibits significant biological functions in the development and progression of gastric cancer. As a potential biomarker and therapeutic target, it holds promising clinical value in the diagnosis and targeted treatment of gastric cancer, providing new strategies and evidence for precision therapy and prognosis assessment.
ObjectiveTo understand the current progress of surgical treatment, radiotherapy, chemical drug therapy, endocrine therapy, targeted therapy, and immunotherapy of metaplastic breast cancer (MBC), so as to provide reference for the clinical therapy selection of MBC. MethodThe literature relevant to MBC therapy research in recent years was comprehensively reviewed. ResultsAt present, the pathogenesis of MBC was not clear. The histopathology of MBC was more complex and the prognosis was poor. Compared with the invasive ductal carcinoma, the MBC patients had older age of onset, larger tumor diameter, faster growth and stronger invasiveness. The simple mastectomy was currently used in surgical treatment. The axillary lymph node involvement rate of MBC patients was lower, so the sentinel lymph node biopsy was widely used. The chemical drug therapy, endocrine therapy, and targeted therapy had limited effects on MBC patients. However, with its unique molecular expression by the genomic analysis of MBC and rise of precision medicine, targeted therapy and immunotherapy had become current research hotspots, providing potential therapeutic strategies for MBC patients. ConclusionsDue to the complex histopathology and poor prognosis of MBC, and most research on MBC is retrospective studies, lacking sufficient prospective studies with sufficient sample size, so there is currently no clear consensus on the optimal treatment method for MBC. In order to better improve prognosis of MBC patients, further in-depth research on MBC histopathology, prospective studies with sufficient sample size, and development of targeted and effective therapeutic drugs are needed in the future.
ObjectiveTo explore the adjuvant treatment options for elderly patients or those with low cardiopulmonary function who cannot tolerate lobectomy for peripheral solid pathological stage ⅠA (pⅠA) non-small cell lung cancer (NSCLC). MethodsA retrospective analysis was conducted on the clinical data of patients with peripheral solid pⅠA stage NSCLC treated with lobectomy and compromised sublobar resection (CSR) in our center from 2018 to 2019. The incidence of postoperative complications and independent predictors of postoperative recurrence were analyzed. Patients in the CSR group were divided into a targeted therapy group, a chemotherapy group, and an observation group based on postoperative treatment measures. The 3-year recurrence-free survival (RFS) rate and 5-year overall survival (OS) rate of the three subgroups before and after propensity score matching (PSM) were compared. ResultsA total of 586 patients were included, including 288 males (49.15%) and 298 females (50.85%), with a median age of 64.00 years. There were 335 patients of lobectomy and 251 patients of compromised sublobar resection. There was no statistically significant difference in the incidence of postoperative complications between the lobectomy group and CSR group [RR=0.987, 95%CI (0.898, 1.085), P=0.789). Multivariate analysis showed that gender, tumor location, and size were independent risk factors for recurrence after CSR. After PSM, 17 patients were enrolled in each of the three subgroups of CSR. Kaplan-Meier survival curve analysis showed that there was no statistically significant difference in the 3-year RFS rate (P=0.115) and 5-year OS rate (P=0.101) between the targeted therapy group and the chemotherapy group after PSM, but both were significantly better than those in the observation group (P=0.041, P=0.009). Compared with lobectomy, there was no statistically significant difference in the 3-year RFS rate (P=0.069) and 5-year OS rate (P=0.540) in the targeted therapy group, while the chemotherapy group and observation group were significantly inferior to the lobectomy group (P<0.05). ConclusionCSR for treating elderly patients or those with low cardiopulmonary function with peripheral solid pⅠA stage NSCLC does not increase the incidence of postoperative complications. Gender, tumor location, and size are independent risk factors for postoperative recurrence. In terms of 3-year RFS rate and 5-year OS rate, adjuvant targeted therapy after CSR is not only superior to chemotherapy or observation but is also not inferior to lobectomy.
