New drug cuts the risk of death in bladder cancer by 30% compared with chemotherapy, study suggests

2021 ◽  
Keyword(s):  
Bladder Cancer ◽  
Risk Of Death ◽  
New Drug ◽  
Chemotherapy Study

scholarly journals Combination of GP88 Expression in Tumor Cells and Tumor-Infiltrating Immune Cells Is an Independent Prognostic Factor for Bladder Cancer Patients

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1796
Author(s):  
Markus Eckstein ◽  
Verena Lieb ◽  
Rudolf Jung ◽  
Danijel Sikic ◽  
Katrin Weigelt ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Prognostic Factor ◽  
Tumor Cells ◽  
Immune Cells ◽  
Potential Candidate ◽  
Poor Prognostic Factor ◽  
Risk Of Death ◽  
Increased Risk ◽  
Muscle Invasive ◽  
Disease Specific

Urothelial bladder cancer (BCa) is the ninth most commonly diagnosed cancer worldwide and accounts for approximately 3% of global cancer diagnoses. We are interested in prognostic markers that may characterize tumor cells (TCs) and immune cells (ICs) and their relationship in BCa. A potential candidate marker that meets these criteria is progranulin (GP88), which is expressed separately in TCs and ICs. We analyzed GP88 expression by immunohistochemistry (IHC) in 196 muscle-invasive BCa samples using a tissue microarray. The immunoreactive score for GP88 staining in TCs and the percentage of GP88-positive ICs was determined. An easy cutoff for the staining status of TCs (positive vs. negative) and ICs (0% vs. >0%) and, more generally, negative vs. positive GP88 staining could be applied. We detected 93 patients (47.4%) and 92 patients (46.9%) with GP88-positive TCs or ICs, respectively. The IHC results were correlated with clinicopathological and survival data. Positive GP88 staining in TCs appeared to be an independent poor prognostic factor for disease-specific survival (DSS) (RR (relative risk) = 1.74; p = 0.009) and recurrence-free survival (RFS) (RR = 1.92; p = 0.002). In contrast, negative GP88 staining in ICs was an independent negative predictor for overall survival (OS) (RR = 2.18; p < 0.001), DSS (RR = 2.84; p < 0.001) and RFS (RR = 2.91; p < 0.001) in multivariate Cox’s regression analysis. When combining GP88 staining in TCs and ICs, a specific combination of GP88-positive TCs and GP88-negative ICs was associated with a 2.54-fold increased risk of death, a 4.21-fold increased risk of disease-specific death and a 4.81-fold increased risk of recurrence compared to GP88-negative TCs and GP88-positive ICs. In summary, GP88 positivity in TCs is a negative prognostic factor for DSS and RFS. In addition, GP88 positivity can mark ICs that are associated with a good prognosis (OS, DSS and RFS). The combination of GP88 staining in TCs and ICs appears to be a significant independent prognostic biomarker in muscle-invasive BCa.

Pan cancer analysis of the intra-tumoral microbiome’s correlation with racial disparities.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 2519-2519
Author(s):  
Wei Tse Li ◽  
Matthew Uzelac ◽  
Jaideep Chakladar ◽  
Lindsay M. Wong ◽  
Aditi Gnanasekar ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
African Americans ◽  
Racial Disparities ◽  
Racial Differences ◽  
Asian Americans ◽  
Environmental Influence ◽  
Microbial Abundance ◽  
Risk Of Death ◽  
Incidence And Mortality ◽  
Starting Point

2519 Background: Microbiome composition can influence cancer development and is moderated by diet, hygiene, sanitation, and other environmental variables. For example, a Mediterranean diet could increase breast Lactobacillus abundance, while the gut microbiome changes dramatically with fructose intake. Recent studies have revealed correlations between microbial abundance and racial disparities in cancer. Given these reports, it is critical to examine whether environmental influences on the microbiome contribute to racial disparities in cancer incidence and prognosis. Methods: We examined the intra-tumoral microbiome in the lungs, breasts, bladder, colon, rectum, cervix, head and neck, prostate, and pancreas (n = 4,169). Raw tumor RNA sequencing data were downloaded from The Cancer Genome Atlas (TCGA) and aligned to bacterial genomes. Microbial abundance was correlated to race, ethnicity, and prognostic variables (Kruskal-Wallis test or Cox regression, p< 0.05). Results: We identified several microbes correlated with racial disparities for breast and bladder cancer, two microbes for lung squamous cell carcinoma, and one microbe for colon cancer. For breast cancer, African Americans have the highest mortality rate, followed by white Americans and Asian Americans. We found that four microbes, all under the order Burkholderiales, were positively correlated with poor prognosis and were most abundant in African Americans and least abundant in Asian Americans. Therefore, increased abundance of these microbes may contribute to the observed mortality differences between races. For bladder cancer, Asian Americans have the lowest incidence and mortality rates. Seven microbes, including two Geobacillus, two Pseudomonas, and two Burkholderiales, positively correlate with good prognosis and are upregulated in Asian Americans. High Pseudomonas fluorescens abundance is positively correlated with decreased risk of death (HR: 0.57, 95% CI: 0.38-0.85). High abundance of the Burkholderiales R. pickettii (HR: 0.62, 95% CI: 0.42-0.92) and V. paradoxus (HR: 0.59, 95% CI: 0.36-0.98) also exhibit the same trend. Geobacillus and Pseudomonas are both present in food, while Burkholderiales can cause nosocomial infections and are altered by diet. Conclusions: Our study is the most comprehensive to date investigating racial differences in the intra-tumoral microbiome. Our data serve as a starting point for exploring whether environmental influence of microbial abundance contributes to racial disparities in cancer.

scholarly journals Identification of Survival and Therapeutic Response-Related Ferroptosis Regulators in Bladder Cancer through Data Mining and Experimental Validation

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 6069
Author(s):  
Pu Zhang ◽  
Zijian Liu ◽  
Decai Wang ◽  
Yunxue Li ◽  
Yuan Zhang ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Risk Score ◽  
Immune Cell ◽  
Predictive Accuracy ◽  
Chemotherapy Sensitivity ◽  
Real Time Quantitative Pcr ◽  
Risk Of Death ◽  
Prediction Function ◽  
Mutation Burden ◽  
Selection Operator

Ferroptosis has been reported to regulate tumorigenesis, metastasis, drug resistance and the immune response. However, the potential roles of ferroptosis regulators in the advancement of bladder cancer remain to be explored. We systematically evaluated the multidimensional alteration landscape of ferroptosis regulators in bladder cancer and checked if their expression correlated with the ferroptosis index. We used least absolute shrinkage and selection operator regression to form a signature consisting of seven ferroptosis regulator. We confirmed the signature’s prognostic and predictive accuracy with five independent datasets. A nomogram was built to predict the overall survival and risk of death of patients. The relative expression of the genes involved in the signature was also clarified by real-time quantitative PCR. We found the risk score was related to tumor progression and antitumor immunity-related pathways. Moreover, there existed negative association between the relative antitumor immune cell infiltration level and the risk score, and higher tumor mutation burden was found in the group of lower risk score. We used The Tumor Immune Dysfunction and Exclusion database and IMvigor210 cohort having immunotherapy efficacy results to confirm the prediction function of the risk score. Furthermore, the ferroptosis regulator signature could also reflect the chemotherapy sensitivity of bladder cancer.

Relationship between high microRNA-200C expression and the risk of death from disease in muscle-invasive urothelial carcinoma of the bladder.

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 279-279 ◽  
Author(s):  
Neema Navai ◽  
Michael Brandon Williams ◽  
Sijin Wen ◽  
Arlene O. Siefker-Radtke ◽  
David James McConkey ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Urothelial Carcinoma ◽  
Multivariable Analysis ◽  
Surrogate Marker ◽  
Rank Test ◽  
P Value ◽  
Fisher Exact Test ◽  
Mesenchymal Transition ◽  
Risk Of Death ◽  
Muscle Invasive

279 Background: Bladder cancer represents both a common and highly morbid disease with limited tools for prognostication. Recently molecular studies have led to promising targets to inform disease behavior, including microRNAs (miRNA). miRNAs are non-coding RNAs, with widespread effects on cellular function. Our group has demonstrated that the miR200 family members play an integral role in epithelial to mesenchymal transition (EMT) via an inverse relationship with ZEB1 and a direct relationship with E-cadherin. EMT is seen as a necessary step for invasion and metastasis, however, studies have indicated a significant role for mesenchymal to epithelial transition (MET) to drive proliferation after cells have reached metastatic locations. Members of the miR200 family have been shown to induce MET and we hypothesize that miR200c, as a surrogate marker for MET, and will predict disease survival in muscle invasive urothelial carcinoma (MIUC). Methods: A clinically diverse sample set was obtained consisting of 101 unique specimens upon which real-time PCR miRNA analysis was performed. Regression tree analysis and best-fit modeling was used to establish the most discriminating relative miR200c expression level to predict disease specific survival. Fisher exact test was carried out to compare clinical variables, Kaplan-Meier estimate of survival distribution based on miR200c expression and univariate log-rank test was used to compare survival distributions between groups. Multivariate analysis was done via the proportional hazards model. A p-value of <0.05 was considered significant for all statistical analyses. Results: Patients with high miRNA200c had significantly more deaths (69 vs. 47%). In multivariable analysis of patients with MIUC miR200c expression was associated with the highest risk of death (RR 2.7). Lymph node involvement (RR 2.0) and age > 65yrs (RR 2.4) were also strong predictors of survival. High miR200c had lower median survival for all patients (59 vs 16 months; p = 0.039) and those with MIUC (41 vs 8 months; p = 0.0004). Conclusions: High miR200c expression is associated with a higher risk of death from bladder cancer in patients with muscle invasive disease.

MP55-13 INTRAOPERATIVE BLOOD TRANSFUSION DURING RADICAL CYSTECTOMY INCREASES THE RISK OF DEATH FROM BLADDER CANCER COMPARED TO POSTOPERATIVE TRANSFUSION

2014 ◽  
Vol 191 (4S) ◽  
Author(s):  
E. Jason Abel ◽  
Brian J. Linder ◽  
Tracy M. Downs ◽  
Tyler M. Bauman ◽  
R. Houston Thompson ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Blood Transfusion ◽  
Radical Cystectomy ◽  
Risk Of Death

Use of Preclinical Models to Assess the Therapeutic Potential of New Drug Candidates for Bladder Cancer

2012 ◽  
Vol 39 (5) ◽  
pp. 534-542 ◽  
Author(s):  
Doron Amit ◽  
Ofer N. Gofrit ◽  
Imad Matouk ◽  
Tatiana Birman ◽  
Abraham Hochberg
Keyword(s):  
Bladder Cancer ◽  
Therapeutic Potential ◽  
Preclinical Models ◽  
Drug Candidates ◽  
New Drug

scholarly journals Eight-gene risk score predicts progression and prognosis in bladder cancer

2021 ◽  
Author(s):  
Ruiliang Wang ◽  
Zongtai Zheng ◽  
Shiyu Mao ◽  
Wentao Zhang ◽  
Ji Liu ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Protein Expression ◽  
Cell Lines ◽  
Risk Score ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Risk Of Death ◽  
Mrna And Protein Expression ◽  
Muscle Invasive ◽  
Prognostic Prediction

Abstract Background: The progression from non-muscle-invasive bladder cancer (NMIBC) to muscle-invasive bladder cancer (MIBC) increases the risk of death. It is therefore important to find new relevant molecular models that will allow for effective prediction of the progression and prognosis of bladder cancer (BC).Methods: Using RNA-Sequence data of 49 BC patients in our center and weighted gene co-expression network analysis methods, a co-expression network of genes was developed and three key modules associated with malignant progression were selected. Based on the genes in three key modules, an eight-gene risk score was established using univariate Cox regression and the Least absolute shrinkage and selection operator Cox model in The Cancer Genome Atlas Program (TCGA) and validated in validation sets. Subsequently, a nomogram based on the risk score was constructed for prognostic prediction. The mRNA and protein expression levels of eight genes in cell lines and tissues were further investigated.Results: A novel eight-gene risk score was closely related to the malignant clinical features of BC and could predict the prognosis of patients in the training dataset (TCGA) and three validation sets (GSE3289 , GSE13507 and IMvigor210 trial). The nomogram showed good prognostic prediction and calibration. The mRNA and protein expression level of the eight genes were differentially expressed in cell lines and tissues.Conclusions: In our study, we established a novel eight-gene risk score which could predict the progression and prognoses of BC patients.

Standard of care for MIBC is becoming more standard.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e16011-e16011
Author(s):  
Kelly LR Miller ◽  
Heidar Albandar ◽  
David Key ◽  
John J. Haluschak
Keyword(s):  
Bladder Cancer ◽  
Barriers To Care ◽  
Statistical Tests ◽  
Standard Of Care ◽  
Standards Of Care ◽  
Group Practice ◽  
Pathology Report ◽  
Community Group ◽  
Male Predominance ◽  
Risk Of Death

e16011 Background: Despite consensus guideline recommendations, the management of muscle invasive bladder cancer (MIBC) varies dependent on institution setting. The risk of recurrence of localized bladder cancer after cystectomy is substantial and associated with stage. The current standard of care for possibly T2 and certainly T3-T4 MIBC is neoadjuvant cisplatin (NAC) based chemotherapy followed by cystectomy. As recent as 2011, only 12% of patients in this category actually received NAC (Feifer et al. 2011). Similar statistics have been confirmed in the US and Canada. Given there is a 13% reduction in risk of death with use of NAC, the adherence to this recommendation needs to improve. We hypothesize that in a multispecialty community practice where barriers to care are reduced that the percentage of eligible patients receiving NAC is significantly higher than previously reported. Methods: After IRB exemption obtained, patients from 2012-2015 with MIBC who underwent cystectomy were examined. Data collection included age, sex, date of consultation, dates and type of chemotherapy received, eGFR, date of surgery and surgical pathology report staging. Data were analyzed using Kolmogorov-Smirnov, Shapiro-Wilk, Mann-Whittney and Kruskal-Wallis statistical tests. Results: The average patient age was 69 years old with a male predominance. Approximately 54% of patients received neoadjuvant chemotherapy; however, three of those patients did not receive the recommended cisplatin based regimen. Fifty percent of patients received NAC and 57% of cisplatin eligible (age < 80, eGFR > 30) patients received NAC. The average time to cystectomy was 171 days among those receiving NAC, with a decrease in time to cystectomy correlating with age. Conclusions: In a community group practice, adherence to standard of care recommendations for higher stage MIBC patients to receive NAC are significantly higher than recently reported values, 50% vs 12%, respectfully. This was achieved while maintaining acceptable time to cystectomy. This supports our hypothesis that when barriers to care are decreased in a community group practice, high quality standards of care can be effectively delivered. In the future, 5 year overall survival will also be important to evaluate in this population.

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