scholarly journals Expression of p53 Protein Associates with Anti-PD-L1 Treatment Response on Human-Derived Xenograft Model of GATA3/CR5/6-Negative Recurrent Nonmuscular Invasive Bladder Urothelial Carcinoma

2021 ◽  
Vol 22 (18) ◽  
pp. 9856
Author(s):  
Ekaterina Blinova ◽  
Elena Samishina ◽  
Olga Deryabina ◽  
Dmitry Blinov ◽  
Dmitry Roshchin ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Treatment Response ◽  
P53 Protein ◽  
Xenograft Model ◽  
Low Grade ◽  
Double Negative ◽  
High Grade ◽  
Tumor Doubling Time ◽  
P53 Expression ◽  
Fgfr3 Mutation

Background: The possible involvement of p53 signaling, FGFR3 expression, and FGFR3 mutation rates in the prediction of the NMIBC anti-PD-L1 treatment response needs to be clarified. The main aim of our study was to explore predictive value of p53 expression, FGFR3 expression, and its gene mutation status for the therapeutic success of anti-PD-L1 treatment in the patient-derived murine model of recurrent high-PD-L1(+) GATA3(-)/CR5/6(-) high-grade and low-grade NMIBC. Methods: twenty lines of patient-derived xenografts (PDXs) of relapsed high-PD-L1(+) double-negative NMIBC were developed, of which 10 lines represented high-grade tumors and the other ones—low-grade bladder cancer. Acceptors of each grade-related branch received specific anti-PD-L1 antibodies. Animals’ survival, tumor-doubling time, and remote metastasis were followed during the post-interventional period. PD-L1, GATA3, CR5/6, and p53 protein expressions in engrafted tumors were assessed by immunohistochemistry. The FGFR3 expression and FGFR3 mutations in codons 248 and 249 were detected by real-time polymerase chain reaction. Results: The expression of p53 protein is an independent factor affecting the animals’ survival time [HR = 0.036, p = 0.031] of anti-PD-L1-treated mice with low-grade high-PD-L1(+) double-negative NMIBC PDX. The FGFR3 expression and FGFR3 mutation rate have no impact on the anti-PD-L1 treatment response in the interventional groups. Conclusions: p53 expression may be considered as a prognostic factor for the anti-PD-L1 treatment efficacy of low-grade high-PD-L1-positive GATA3(-)/CR5/6(-)-relapsed noninvasive bladder cancer.

scholarly journals PD-1 and PD-L1 are more highly expressed in high-grade bladder cancer than in low-grade cases: PD-L1 might function as a mediator of stage progression in bladder cancer

BMC Urology ◽  
2018 ◽  
Vol 18 (1) ◽  
Author(s):  
Takashi Kawahara ◽  
Yukari Ishiguro ◽  
Shinji Ohtake ◽  
Ikuma Kato ◽  
Yusuke Ito ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Low Grade ◽  
High Grade ◽  
Stage Progression

scholarly journals Effectiveness of contrast-enhanced ultrasound for detecting the staging and grading of bladder cancer: a systematic review and meta-analysis

2020 ◽  
Author(s):  
Xinyue Ge ◽  
Zhong-Kai Lan ◽  
Jing Chen ◽  
Shang-Yong Zhu
Keyword(s):  
Bladder Cancer ◽  
Diagnostic Accuracy ◽  
Likelihood Ratio ◽  
Positive Likelihood Ratio ◽  
Cochrane Library ◽  
Forest Plot ◽  
Low Grade ◽  
High Grade ◽  
Contrast Enhanced Ultrasound ◽  
Contrast Enhanced

Aim: The study retrospectively analysed the accuracy of preoperative contrast-enhanced ultrasound (CEUS) in differenti-ating stage Ta-T1 or low-grade bladder cancer (BC) from stage T2 or high-grade bladder cancer. Material and methods: We systematically searched the literature indexed in PubMed, Embase, and the Cochrane Library for original diagnostic articles of bladder cancer. The diagnostic accuracy of CEUS was compared with cystoscopy and/or transurethral resection of bladder tumors (TURBT). The bivariate logistic regression model was used for data pooling, couple forest plot, diagnostic odds ratio (DOR) and summary receiver operating characteristic (SROC). Results: Five studies met the selection criteria; the overall number of reported bladder cancers patients were 436. The pooled-sensitivity (P-SEN), pooled-specificity (P-SPE), pooled-positive likelihood ratio (PLR+), pooled-negative likelihood ratio (PLR−), DOR, and area under the SROC curve were 94.0% (95%CI: 85%–98%), 90% (95%CI: 83%–95%), 9.5 (95%CI: 5.1–17.6), 0.06 (95%CI: 0.02–0.17), 147 (95%CI: 35–612) and 97% (95% CI: 95%–98%) respectively. Conclusion: CEUS reaches a high efficiency in discriminating Ta-T1 or low-grade bladder cancer from stage T2 or high-grade bladder cancer. It can be a promising method in patients to distinguish T staging and grading of bladder cancer because of its high sensitivity, specificity and diagnostic accuracy.

scholarly journals Three serum metabolite signatures for diagnosing low-grade and high-grade bladder cancer

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Guangguo Tan ◽  
Haibo Wang ◽  
Jianlin Yuan ◽  
Weijun Qin ◽  
Xin Dong ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Low Grade ◽  
High Grade

Risk factors for bladder cancer recurrence survival in patients with upper-tract urothelial carcinoma

2018 ◽  
Vol 104 (6) ◽  
pp. 451-458 ◽  
Author(s):  
Yu-Peng Wu ◽  
Yun-Zhi Lin ◽  
Min-Yi Lin ◽  
Ting-Ting Lin ◽  
Shao-Hao Chen ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Urothelial Carcinoma ◽  
Cancer Recurrence ◽  
Cox Proportional Hazards Model ◽  
Upper Tract Urothelial Carcinoma ◽  
Intravesical Therapy ◽  
Low Grade ◽  
High Grade ◽  
Upper Tract ◽  
Bladder Cancer Recurrence

Purpose: The aim of this work was to investigate the predictive factors for bladder cancer recurrence survival (BCRS) in patients with upper-tract urothelial carcinoma (UTUC). Methods: We selected patients with UTUC who underwent segmental ureterectomy (Su) or nephroureterectomy (Nu) from 2004 to 2013 from the Surveillance, Epidemiology, and End Results (SEER) database. Patients with a history of intravesical therapy for bladder cancer and bladder cancer prior to the diagnosis of UTUC were excluded. We used Kaplan-Meier analysis, log-rank tests, and Cox proportional hazards model to compare overall survival, cancer-specific survival, and BCRS. Results: In a cohort of 1,454 patients, 169 (11.6%) had low-grade tumors and 1,285 (88.4%) had high-grade tumors; 239 (16.4%) underwent Su and 1,215 (83.6%) underwent Nu. We found that T4 grade (hazard ratio [HR] = 6.216; 95% confidence interval [CI], 3.197-12.087) and ureteral tumors (HR = 1.764; 95% CI, 1.173-2.652) were predictors of shorter BCRS, whereas Nu (HR = 0.608; 95% CI, 0.388-0.953) predicted longer BCRS. Five-year BCRS rates were low-grade tumors: 94.1%, high-grade tumors: 85.4% (p = 0.038); plus Su: 82.9%, and Nu: 87.6% (p = 0.016). Conclusions: Use of Su should be more selective for high-grade tumors, as it correlates with shorter BCRS. Tumors located in the ureter are associated with shorter BCRS than those located in the renal pelvis.

scholarly journals Exosome-Derived LINC00960 and LINC02470 Promote the Epithelial-Mesenchymal Transition and Aggressiveness of Bladder Cancer Cells

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1419
Author(s):  
Cheng-Shuo Huang ◽  
Jar-Yi Ho ◽  
Jung-Hwa Chiang ◽  
Cheng-Ping Yu ◽  
Dah-Shyong Yu
Keyword(s):  
Bladder Cancer ◽  
Notch Signaling ◽  
Cancer Cells ◽  
Signaling Pathways ◽  
Cancer Progression ◽  
Epithelial Mesenchymal Transition ◽  
Low Grade ◽  
High Grade ◽  
Mesenchymal Transition ◽  
Bladder Cancer Cells

Exosomes are essential for several tumor progression-related processes, including the epithelial–mesenchymal transition (EMT). Long non-coding RNAs (lncRNAs) comprise a major group of exosomal components and regulate the neoplastic development of several cancer types; however, the progressive role of exosomal lncRNAs in bladder cancer have rarely been addressed. In this study, we identified two potential aggressiveness-promoting exosomal lncRNAs, LINC00960 and LINC02470. Exosomes derived from high-grade bladder cancer cells enhanced the viability, migration, invasion and clonogenicity of recipient low-grade bladder cancer cells and activated major EMT-upstream signaling pathways, including β-catenin signaling, Notch signaling, and Smad2/3 signaling pathways. Nevertheless, LINC00960 and LINC02470 were expressed at significantly higher levels in T24 and J82 cells and their secreted exosomes than in TSGH-8301 cells. Moreover, exosomes derived from LINC00960 knockdown or LINC02470 knockdown T24 cells significantly attenuated the ability of exosomes to promote cell aggressiveness and activate EMT-related signaling pathways in recipient TSGH-8301 cells. Our findings indicate that exosome-derived LINC00960 and LINC02470 from high-grade bladder cancer cells promote the malignant behaviors of recipient low-grade bladder cancer cells and induce EMT by upregulating β-catenin signaling, Notch signaling, and Smad2/3 signaling. Both lncRNAs may serve as potential liquid biomarkers for the prognostic surveillance of bladder cancer progression.

Adaptive genetic algorithms combined with high sensitivity single cell-based technology derived urine-based score to differentiate between high-grade and low-grade transitional cell carcinoma of the bladder.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 572-572
Author(s):  
Shaheen Riadh Alanee ◽  
Zade Roumayah ◽  
Musatafa Deebajah ◽  
James O. Peabody ◽  
Rodrigo Mora ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Bladder Cancer ◽  
Single Cell ◽  
Transitional Cell ◽  
Low Grade ◽  
High Grade ◽  
Median Score ◽  
Adaptive Genetic Algorithms ◽  
Cell Flow Cytometry ◽  
Carcinoma Of The Bladder

572 Background: We previously showed that adaptive genetic algorithms (AGA), in combination with single-cell flow cytometry technology, can be used to develop a noninvasive urine-based score to detect bladder cancer with high accuracy. Our aim in this analysis was to investigate if that same score can differentiate between high grade (HG) and low grade (LG) transitional cell carcinoma of the bladder (BC). Methods: We collected urine samples from cystoscopy confirmed HG and LG superficial bladder cancer patients and healthy donors in an optimized urine collection media. We then examined these samples using an assay developed from AGA in combination with single-cell flow cytometry technology. Results: We examined 50 BC and 15 healthy donor urine samples. Patients were majorly White (59.2%), males (61.2%), and had HG BC (66.7%). AGA derived score of 1.1 differentiated between BCa and healthy patients with high precision (AUC 0.92). The median score was 2.8 for LG BC and 6 for LG BC. Mann-Whitney Rank Sum Test indicated that the difference between the median score of HG and LG BC was significant at P value = 0.003. The score performed well independent of patients’ sex or smoking history. Conclusions: Using single-cell technology and machine learning, we developed a new urine-based score that can potentially differentiate between HG and LG bladder cancer. Future studies are planned to validate this score.

scholarly journals Combined cytotoxic effect of UV-irradiation and TiO2microbeads in normal urothelial cells, low-grade and high-grade urothelial cancer cells

2015 ◽  
Vol 14 (3) ◽  
pp. 583-590 ◽  
Author(s):  
Roghayeh Imani ◽  
Peter Veranič ◽  
Aleš Iglič ◽  
Mateja Erdani Kreft ◽  
Meysam Pazoki ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Cells ◽  
Uv Irradiation ◽  
Cytotoxic Effect ◽  
Urothelial Cancer ◽  
Low Grade ◽  
High Grade ◽  
Urothelial Cells ◽  
Efficient Approach

Paper shows that internalization of the TiO2microbeads followed by the UV-irradiation is an efficient approach for killing cancer urothelial cells. Additionally, differentiation dependent differences in the sensitivity of the cells to the UV-irradiation are shown, and a model of photocatalytic treatment of thein vivobladder cancer is presented.

scholarly journals A Single-Institutional Study of Human Immunodeficiency Virus-Related Bladder Cancer

2021 ◽  
Author(s):  
Mengmeng Zhang ◽  
Yanyan Zhang ◽  
Zhiqiang Zhu ◽  
Yu Zhang
Keyword(s):  
Bladder Cancer ◽  
Cancer Patients ◽  
Clinical Characteristics ◽  
Transitional Cell ◽  
Invasive Bladder Cancer ◽  
Low Grade ◽  
High Grade ◽  
Muscle Invasive Bladder Cancer ◽  
Tumor Pathology ◽  
Muscle Invasive

Abstract Purpose: We wished to investigate the clinical characteristics, treatments for tumor, pathology and outcomes of bladder cancer patients with HIV-infected.Patients and methods: We identified 10 cases of bladder cancer with HIV-infected from 2015 to 2020.We retrospectively investigated the clinical characteristics of the cases including demographic information, clinical presentation, TNM stage and so on. We investigated treatments for tumor, pathology, outcomes and HIV-relevant parameters during patients’ hospitalization course as well. Results: In our study, it was astonished to find that bladder cancer patients with HIV-infected were males at the median age of 51 years old, and no females were diagnosed on the contrary. Nine (90%)patients presented with painless gross hematuria, while one patient with incidental findings on ultrasonic examination. Six(60%) patients co-infected with another kind of infectious disease, four with syphilis, and two with HBV respectively. The median CD4+ T-lymphocyte cell count was 493/ul withthin 2 weeks prior to the diagnosis bladder cancer. Cystoscope examination manifested that the lesions were located in the trigonum of the bladder in four(40%)patients. All patients underwent surgeries successfully, six underwent transurethral resection of bladder tumor(TURBT),two of whom relapsed once, and one underwent TURBT twice due to recurrence and then RC and urethrectomy because of urethral invasion. All non muscle-invasive bladder cancer(NMIBC)patients received intravesical chemotherapy with pirarubicin 30mg for at least half year conventionally, and only one patient occurred mild adverse reaction of irritative symptoms of bladder. Pathologic analysis documented that all patients(100%) had transitional cell carcinoma(TCC). Tumor grade classification showed that three cases were identified with low grade TCC, and six cases with high grade or invasive TCC, two of whom occurred recurrence for once or twice respectively. One patient was identified with low grade TCC of primary tumor and high grade TCC of recurrent focal(Figure 2).Five cases(50%) were ascertained as (NMIBC) with pT1N0M0, while the rest five patients(50%) were muscle-invasive bladder cancer(MIBC) with at least pT2N0M0. During the median follow-up of 56 months (range from 5 months to 68 months) six cases(five were MIBC patients )died due to distant metastases. No patients acceptted adjuvent immunotherapy mainly due to the role of PD-1+ T cells in HIV transcription in treated aviremic individuals, concerns of unknown adverse effects and economic factors.Conclusions: It seemed like that bladder caner patients had higher tumor stage and more aggressive pathology. we did not find any evidence on the relationship between immunodeficiency and cancer progression because of relatively stable HIV status of this crew in our study. MIBC patients with HIV-infected really have worse outcomes, and more attention is warranted to pay to this special population in this situation when they present with hematuria extraordinarily.

Role of MCM as an adjuvant to urine cytology in the diagnosis of bladder cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e15011-e15011
Author(s):  
Nadira Narine ◽  
Bensita M.V Thottakam ◽  
Alessia Donnini ◽  
Sushant Dhanvijay ◽  
Kasra Saeb-Parsy ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Positive Outcome ◽  
Urine Cytology ◽  
Low Grade ◽  
High Grade ◽  
Minichromosome Maintenance ◽  
Molecular Tests ◽  
In Vitro Diagnostic ◽  
Mcm Proteins

e15011 Background: Urine cytology, a cheap non invasive first line test (PAP) has traditionally been used for the diagnosis of urothelial carcinoma (UC) as it has excellent sensitivity for the detection of high grade and in situ lesions. However, sensitivity for low grade carcinoma is rather varied as this is a problematic area with various mimics leading to both over and under diagnoses. To overcome this dilemma, a number of biomarkers and molecular tests have been employed with mixed results and varied financial implications. We report on a relatively cheap and easily adopted in vitro diagnostic test, Minichromosome maintenance (MCM) proteins, as an adjuvant to cytology in the diagnosis of both low and high grade bladder cancer (BC). MCM proteins play an important regulatory role in eukaryotic DNA replication and is expressed only as normal cells progress from G0 into G1/S phase of the cell cycle. However, over expression has been demonstrated in neoplasia in a range of sites including urothelium. Methods: 106 patients from gross haematuria (GH, 39) and cystoscopic surveillance (CS, 67) clinics were investigated for newly diagnosed and recurrent BC respectively by MCM and cytology with histological outcome being used as the gold standard. Results: Using biopsy positive outcome, MCM and cytology had a sensitivity of 91.7%, specificity of 86.6%, PPV of 66.7% and NPV of 97.3%. There was noticeably improved correlation of MCM and cytology with increasing grade of BC (Table). Conclusions: We showed the combination of MCM and cytology to be highly sensitive and specific for the determination of CIS, G2, and G3 BC with improved detection of G1 bladder cancer. The combination of MCM and cytology suggests that this offers promise as a novel diagnostic biomarker in GH and CS patients. [Table: see text]

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