Targeting Tumor Associated Antigens For The Development of Hepatocellular Carcinoma Treatment.

DBN possess the ability to induce bladder tumor as well as in the liver, and oesophagus when it is administered in the body.Exposure to DBN can happen by different modes such as by ingestion,inhalation as well through dermal contact.In the present investigation an attempt has been done to identify ,isolate as well to purify he TAA from the liver mitochondria of the mice which was exposed to DBN. It was found that mitochondrial membrane surface protein of DBN-exposed animals exhibited differential expression when compared with the control animals. A low molecular weight (~14 kDa) protein was found to be over expressed on liver mitochondrial membrane upon DBN exposure in mice as compared with the normal control and identified as TAA, showing the sign that some of the proteins could be used as TAA for further study.These identification and molecular characterization of TAAs will provide the basis for the development of cancer vaccines targeting TAAs.

Comprehensive Analysis of N6-methyladenosine Modification Patterns Associated With Multiomic Characteristics of Bladder Cancer

Purpose: To comprehensively analyze N6-methyladenosine modification patterns in bladder tumors and to further systematically explore the inherent relationships between these modification patterns and multiomic tumor characteristics.Materials and Methods: A total of 901 bladder tumor samples, including 405 samples from TCGA database, 188 samples from GSE13507 and 308 samples from GSE32894, were included in this systematic analysis. The N6-methyladenosine modification patterns were identified utilizing unsupervised clustering analysis. To quantify N6-methyladenosine modification patterns, the m6Ascore of individual sample was developed using principal component analysis algorithms. Relationships among immune infiltration, tumor mutation burden, various clinical characteristics, molecular subtypes, and the m6Ascore were systematically analyzed. The guiding value of m6Ascore in immunotherapy was further validated in an external trial cohort. Genomics of Drug Sensitivity in Cancer expression references were also utilized to perform drug sensitivity analysis for patients with distinct m6A modification patterns.Results: We determined three different N6-methyladenosine modification patterns for 901 bladder tumors. The quantitative m6Ascore of individual sample derived from N6-methyladenosine modification patterns could play a significant role in predicting overall survival, immune cell infiltration, and classic oncogene mutations. A low m6Ascore combined with high tumor mutation burden indicated better survival outcomes (p < 0.001). A higher m6Ascore also indicated a higher grade, higher T and N stage, elder ages, higher death rate, and higher PD1/PDL1/CTLA4 expressions (p < 0.01). The Basal type tended to exhibit significantly higher m6Ascores than the Luminal and Neuronal subtypes. External immunotherapy cohorts demonstrated that no difference in therapeutic effects was noted between the high and low m6Ascore groups when anti-PD1 immunotherapy was exclusively administered. When anti-PD1 and anti-CTLA4 immunotherapy were simultaneously administered, the high m6Ascore group had a significantly better prognosis than the low m6Ascore group (p < 0.001). High m6A groups were potentially sensitive to various medical treatments including Bleomycin, Bortezomib, Cisplatin, Cyclopamine, Dasatinib, Docetaxe, Rapamycin, and Vinblastine in this study.Conclusions: This study systematically revealed the important roles of m6A methylation modification patterns in bladder tumors. Detailed quantification of m6A modification patterns could improve our understanding of the bladder tumor microenvironments and could provide guidance for future immunotherapy strategies.

A high-fidelity, virtual reality, transurethral resection of bladder tumor simulator: Validation as a tool for training

Introduction: Simulation-based training is used to help trainees learn surgical procedures in a safe environment. The objective of our study was to test the face, content, and construct validity of the transurethral resection of bladder tumor (TURBT) module built on the Simbionix TURP Mentor simulator. Methods: Participants performed five standardized cases on the simulator. Domains of the simulator were evaluated on a five-point Likert scale to establish face and content validity. Construct validity was assessed through the simulator's built-in scoring metrics, as well as video recordings of the simulator screen and an anonymized view of participants' hands and feet, which were evaluated using an objective structured assessment of technical skills (OSATS) tool. Results: Ten experienced operators and 15 novices participated. Face validity was somewhat acceptable (mean realism 3.8/5±1.03 standard deviation [SD]; mean appearance 4.1/5±0.57), as was content validity, represented by simulation of key steps (mean 3.9±0.57). The simulator failed to achieve construct validity. There was no difference in mean simulator scores or OSATS scoring between experienced operators and novices. Novices significantly improved their mean simulator scores (305.9 vs. 332.4, p=0.006) and OSATS scoring (15.8 vs. 18.1, p=0.001), while 87% felt their confidence to perform TURBT improved. Overall, 92% of participants agreed that the simulator should be incorporated into residency training. Conclusions: Our study suggests a role for the TURBT module of the Simbionix TURP Mentor simulator as an introduction to TURBT for urology trainees. Strong support was found from both experienced operators and novices for its formal inclusion in resident education.

A Systematic Review and Meta-Analysis Protocol of Chemoablation vs. Transurethral Resection of Bladder Tumor in Patients With Non-Muscle-Invasive Bladder Cancer

Background: Bladder cancer is the second-ranked tumor of the genitourinary system. Transurethral resection of bladder tumor (TURBT) is currently the most important diagnosis and treatment method for non-muscular invasive bladder cancer (NMIBC). However, due to its high recurrence and progression rate, as well as high cost and inapplicability to some patients, intravesical chemoablation as an alternative to TURBT may be promising for NMIBC patients. However, there are very little data comparing its effectiveness, safety, best effective drug type, dosage selection, and cost with TURBT at present, which deserves further evaluation. The present study was designed in order to discuss which treatment is superior to another between chemoablation and TURBT in patients with NMIBC.Methods and Analysis: Databases including PubMed, MEDLINE, EMBASE, and Cochrane Library databases, as well as Chinese databases including CNKI (China national knowledge infrastructure), Wan Fang database, and Chinese Clinical Trial Registry, from August 1994 to the time when the official submission of this review was published was included in this review and screened by two reviewers (XS and DCF) independently. There were no language limitations. The study was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Data was analyzed using RevMan and Stata software. The primary aims were the clinical effectiveness, including response rate, complete response OS, CSM, recurrence rate, time to recurrent, progression rate, and time to progression, among others. The secondary aims mainly included safety and tolerability, including costs, operation time, hospital stay, bleeding volume, and complications, among others.Study Registration: This study is registered as PROSPERO CRD42021271124.

Pre-operative pyuria predicts tumor recurrence in patients undergoing transurethral resection of bladder tumor with post-operative instillation of BCG

BACKGROUND & OBJECTIVE: In Pakistan, urinary bladder cancer is one of the top ten malignancies. The most important concern after its treatment is tumor recurrence. Recent literature claimed that pre-operative pyuria in patients undergoing transurethral resection of bladder tumor was associated with significantly higher frequency of recurrence. However, there was controversy in existing literature and no such local published material was available which necessitated the present study. To determine the frequency of pre-operative pyuria in patients undergoing transurethral resection of bladder tumor for non-muscle invasive bladder cancer (NMIBC) with post-operative instillation of Bacillus Calmette Guerin (BCG) and to compare the frequency of tumor recurrence in patients with and without pre-operative pyuria. METHODOLOGY: It was a comparative study. This study involved 280 patients of both genders aged between 20-80 years. Pre-operative pyuria was diagnosed if early morning midstream urine specimen showed ≥10 white blood cells/HPF. Outcome variable was frequency of recurrence after 12 weeks of treatment on check cystoscopy. RESULTS: The mean age of the patients was 57.1±8.5 years. There were 236 (84.3%) male and 44 (15.7%) female patients in the study. 155 (55.4%) patients were tobacco smoker. Pre-operative pyuria was diagnosed in 127 (45.4%) patients while tumor recurrence was observed in 183 (65.4%) patients. The frequency of tumor recurrence was significantly higher in patients with pre-operative pyuria (85.8% vs. 48.4%; p<0.001). CONCLUSION: Pre-operative pyuria was a frequent finding in patients with non-muscle invasive bladder tumor and was associated with higher frequency of tumor recurrence which warrants routine screening of such patients for pyuria and increased frequency of tumor recurrence.

A Novel CpG Oligodeoxynucleotide Enhanced the Therapeutic Effect of Epirubicin on Bladder Tumors in Rats

Background CpG oligodeoxynucleotides, which boast anti-inflammatory, anti-infectious, and chemotherapeutic activities, are promising immunomodulators. Recently, some preclinical studies have highlighted the potent immunostimulatory and anti-tumor effects of CpG oligodeoxynucleotides, which has aroused interest in their potential clinical effects on human cancers. Methods In this study, we evaluated the therapeutic effect of a new type of CpG oligodeoxynucleotide whose sequence (5’-AACGTTGTCGTCGACGTCGTCGTCAGGCCTGACGTTATCGATGGCGTTGTCGTCAACGTTGTCGTTAACGTT-3’) was designed by our laboratory in combination with epirubicin in a bladder tumor rat model induced by N-methyl-N-nitrosourea instillation. Moreover, we explored the safety of the novel CpG oligodeoxynucleotide for bladder tumor therapy by observing the degree of cystolith in the bladder and comparing the results against those of Bacillus Calmette–Guérin therapy, which is a gold-standard treatment for bladder tumor. Results All results showed that CpG oligodeoxynucleotide combined with epirubicin significantly inhibited the growth of bladder tumors and reduced the pathological grading. As compared with bladder cells or cytokines observed under the positive control or epirubicin-alone treatment conditions, all indexes including histopathological grading, Mutation P53 gene protein expression, and Interleukin-2 (IL-2) level were significantly optimized by instillation of CpG oligodeoxynucleotide. Immunohistochemical examination indicated that CpG oligodeoxynucleotide reduced the expression of Mutation P53 gene protein in the bladder tumor rat model. Specifically, the level of IL-2 in rat serum was increased by more than 30% CpG oligodeoxynucleotide treatment combined with epirubicin. Also, in comparison with the degree of cystolith observed in the Bacillus Calmette–Guérin group, no obvious side effects were caused by CpG oligodeoxynucleotide. Conclusions CpG oligodeoxynucleotide as an immunomodulator can enhance the efficacy of epirubicin and presents higher safety than Bacillus Calmette–Guérin in treating bladder cancer.