ABSTRACT
BACKGROUND: Lung cancer is currently the second most common cancer, and non-small cell lung cancer accounts for about 85% of cases. NSCLC has not been studied for pseudouridine synthase 7 (PUS), a member of the PUS family that is associated with cancer development. Here, we focused on the role and clinical significance of PUS7 in non-small cell lung cancer. AIM: To explore the role of PUS7 in NSCLC and its clinical significance. METHODS: We downloaded datasets from the TCGA database and CPTAC database. In normal bronchial epithelial cells as well as NSCLC cell lines, RT-PCR and Western blot were used to quantify PUS7 expression. The role of PUS7 in NSCLC has been investigated by CCK8, migration assay, migration assay, and flow cytometry. PUS7 expression in tumor tissues was detected by immunohistochemical staining, and we evaluated the influence of PUS7 expression on the prognosis of NSCLC patients after surgery using Cox regression analysis, both univariate and multivariate. RESULTS: NSCLC cell lines and tissues expressed high levels of PUS7, and PUS7 was found to influence the proliferation, migration, and invasion of cancer cells without affecting their apoptosis. There was a worse prognosis for NSCLC patients who have higher PUS7 expression, suggesting that PUS7 was an independent indicator of prognosis (P = .05).
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/surgery , Carcinoma, Non-Small-Cell Lung/metabolism , Lung Neoplasms/pathology , Cell Proliferation , Prognosis , Cell Line, Tumor , Cell Movement , Gene Expression Regulation, NeoplasticABSTRACT
BACKGROUND: We used the SIVmne model to examine the relative immunogenicity and protective efficacy of vaccines derived from temporal isolates of lentivirus infection. SIVmne170 is a molecular clone isolated from a pig-tailed macaque 170 weeks after inoculation with SIVmneCL8. METHODS: We immunized pig-tailed macaques with Gag/Pol/Env vaccines derived from CL8 or 170 and examined their protective efficacy against CL8, 170, or chimeras 8/170 and 170/8, containing the 5' or 3' half of the respective parental genomes. RESULTS: As expected, CL8 vaccines protected animals against the CL8, but not the 170 virus. Surprisingly, 170 vaccines not only failed to protect against the 170 virus, but also the less pathogenic CL8. Chimeric virus challenges revealed that the envelope antigen of CL8 represents an important target for protective immunity. CONCLUSIONS: These results underscore the potential importance of targeting transmitted viruses through judicious choice of immunogens from early isolates for vaccine development.
Subject(s)
Macaca nemestrina , Retroviridae Proteins/immunology , SAIDS Vaccines/immunology , Simian Acquired Immunodeficiency Syndrome/immunology , Simian Immunodeficiency Virus/immunology , Animals , Antibodies, Viral/blood , Disease Models, Animal , Enzyme-Linked Immunosorbent Assay , Flow Cytometry , Gene Products, env/immunology , Gene Products, gag/immunology , Gene Products, pol/immunology , Immunophenotyping , Interferon-gamma/blood , RNA, Viral/chemistry , RNA, Viral/genetics , Retroviridae Proteins/genetics , Reverse Transcriptase Polymerase Chain Reaction , Simian Acquired Immunodeficiency Syndrome/prevention & control , Simian Acquired Immunodeficiency Syndrome/virology , Simian Immunodeficiency Virus/genetics , Vaccines, Synthetic/immunology , Viral LoadABSTRACT
We assessed four prime-boost vaccine regimens with a Gene Gun component for SHIV89.6P in Macaca nemestrina. A dosing experiment using beta-galactosidase plasmid showed that 30 or 45 shots per dose elicited higher titer antibody than smaller doses. For SHIV89.6P, we administered a six-plasmid vaccine capable of producing non-infectious virions in vivo in combination with either vaccinia recombinants or inactivated virus. DNA prime/vaccinia boost, or the reverse, elicited strong immune responses. The SHIV89.6P challenge virus was grown in M. nemestrina peripheral blood mononuclear cells and titered in vivo intrarectally. As has been observed for SHIV89.6P in M. mulatta, the infected M. nemestrina experienced rapid and severe loss of circulating CD4+ T cells. Vaccinated macaques were challenged three weeks after the last boost. DNA prime/vaccina boost or vaccina prime/DNA boost protected 11/12 animals from acute CD4+ T cell depletion and disease, while other regimens were not effective.
