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 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.
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.
Vaccines and antibodies are currently effective intervention strategies for preventing and treating COVID-19. Angiotensin-converting enzyme 2 (ACE2), a primary binding receptor for SARS-CoV-2, is a potential target for the prevention and treatment of COVID-19. At present, therapeutics based on the strategies that block the binding of SARS-CoV-2 Spike protein to the ACE2 receptor have entered clinical trials. On December 5, 2022, the journal Nature published the results of a pharmacological intervention to downregulate ACE2 expression for prevention of SARS-CoV-2 infections. The study found that a nuclear receptor, farnesoid X receptor for bile acids, regulated ACE2 expression. The clinical drug ursodeoxycholic acid that was used to treat liver diseases could downregulate ACE2 expression and prevent SARS-CoV-2 infections, showing a new potential pathway in managing COVID-19.
Objective To understand the latest research progress of chemotherapy, targeted therapy and immunotherapy drugs in the treatment of metastatic colorectal cancer. Method The literature on the efficacy of different treatment drugs for metastatic colorectal cancer in recent years both domestically and internationally was retrieved and reviewed. Results There had been many clinical research progress in the treatment of metastatic colorectal cancer, new drugs had emerged, targeted drugs were particularly prominent, and more trials of therapeutic drugs and drug combination treatment regimens were also being carried out. Different treatment methods were applied to patients according to the mutation status of RAS/RAF and the expression of mismatch repair protein, the survival benefit varied greatly. Conclusion Precision medicine is becoming increasingly important, screening patients to choose appropriate treatment modality can further improve survival benefit.
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.
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.
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.
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.