ABSTRACT
BACKGROUND: Recent clinical trials have reported improved disease-free survival rates of patients with stage pT3-4/ypT2-4 or pN + upper tract urothelial carcinoma (UTUC) on adjuvant nivolumab therapy. However, the appropriateness of the patient selection criteria used in clinical practice remains uncertain. METHODS: We retrospectively analyzed 895 patients who underwent nephroureterectomy to treat UTUC. The patients were divided into two groups: grade pT3-4 and/or pN + without neoadjuvant chemotherapy (NAC) or grade ypT2-4 and/or ypN + on NAC (adjuvant immunotherapy candidates) and others (not candidates for adjuvant immunotherapy). Kaplan-Meier curves were drawn to assess the oncological outcomes, including recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS). Cox proportional hazards models were used to identify significant prognostic factors for oncological outcomes. RESULTS: The Kaplan-Meier curves revealed notably inferior RFS, CSS, and OS of patients who were candidates for adjuvant immunotherapy. Multivariate analysis revealed that pathological T and N grade and lymphovascular invasion (LVI) status were independent risk factors for poor RFS, CSS, and OS. CONCLUSION: In total, 44.8% of patients were candidates for adjuvant immunotherapy. In addition to pathological T and N status, LVI was a significant predictor of survival, and may thus play a pivotal role in the selection of patients eligible for adjuvant immunotherapy.
Subject(s)
Carcinoma, Transitional Cell , Urinary Bladder Neoplasms , Urologic Neoplasms , Humans , Carcinoma, Transitional Cell/drug therapy , Carcinoma, Transitional Cell/pathology , Urologic Neoplasms/drug therapy , Urologic Neoplasms/surgery , Urinary Bladder Neoplasms/drug therapy , Retrospective Studies , Nephroureterectomy/methods , Prognosis , Chemotherapy, Adjuvant/methodsABSTRACT
BACKGROUND: Flagellin is the main structural protein of the ï¬agella of many pathogens including Salmonella typhimurium. It is a potent trigger of innate immune responses that enhance adaptive immune responses to a variety of protein antigens. Flagellin has intrinsic adjuvant activity mediated through toll-like receptor (TLR) 5 and is an attractive candidate for highly effective vaccine adjuvant conferring enhanced antibody and cellular immune responses to proteins or peptides. In the present study, we cloned the fliC gene from S. enterica typhimurium in eukaryote vector pVAX1 and evaluated its expression in eukaryotic cells. OBJECTIVES: The main aim of the present study was to construct a DNA vaccine expressing fliC as an adjuvant. MATERIALS AND METHODS: The fliC gene of S. typhimurium (ATCC 14028) was amplified by PCR with specific primers and cloned into the pPrime cloning vector and successfully subcloned into expression vector pVAX1. The recombinant plasmid pVAX-fliC was finally expressed in eukaryotic cells. RESULTS: Cloning and subcloning of the fliC gene were confirmed by colony PCR, restriction enzymes digestion and DNA sequencing of the recombinant plasmids pPrime-fliC and pVAX-fliC. The expression of flagellin protein in eukaryotic cells was approved by immunoï¬uorescence assay (IFA), western blotting analysis and the reverse transcriptase polymerase chain reaction (RT-PCR) method. CONCLUSIONS: The results of this study demonstrated that the fliC gene in recombinant plasmid pVAX-fliC was successfully expressed in eukaryotic cells and produced flagellin protein, which could be used as an effective adjuvant for DNA vaccine research.