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 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.

Feasibility of finding circulating tumors cells and assigning PD-L1 receptor status using single-cell technology combined with Celsee Genesis system.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 567-567
Author(s):  
Shaheen Riadh Alanee ◽  
Vishal Sharma ◽  
William Chow ◽  
Bruce Kendrick Patterson
Keyword(s):  
Bladder Cancer ◽  
Single Cell ◽  
Tumor Cells ◽  
Microfluidic Chip ◽  
High Sensitivity ◽  
Low Grade ◽  
High Grade ◽  
Blood Samples ◽  
Sensitivity Level ◽  
Bladder Pathology

567 Background: enumerating circulating tumor cells (CTC) may improve our ability to differentiate between localized and metastatic bladder cancer (BC) and predict response to systemic therapies. However, previously used CTC identification platforms had limited utility in managing patients diagnosed with this disease because they lacked the appropriate sensitivity level. Also, they did not report on the PD-L1 receptor status, which is becoming an essential component of modern immunotherapy of BC. Methods: We used a novel device to enrich and retrieve CTCs from blood samples of patients with high grade and low-grade BC, as well as benign conditions, treated with cystectomy by using a microfluidic chip. The Celsee Genesis (Celsee Inc) captures CTCs with high sensitivity and allows the captured CTCs to be retrieved for molecular analysis. It uses the microfluidic chip, which has approximately 56,320 capture chambers. Based on differences in cell size and deformability, each chamber ensures that small blood cells escape while larger CTCs of varying sizes are trapped and isolated in the chambers. PD-L1 expression on the isolated tumor cells was then evaluated using 4-color single-cell technology (IncellDX Inc.) directly on the chip. Results: Ten bladder cancer (5 low grade (LG) and 5 high grade (HG) disease) and two benign bladder pathology patients provided blood samples before their cystectomy. Circulating tumor cells were found in 3 patients (two LG and one HG disease). CTCs were four times higher in the HG sample than in the LG samples. PD-L1 expression was high on CTCs isolated from the HG patient’s blood sample and lower in the two LG blood samples. No CTCs were detected in patients with benign bladder pathology. Conclusions: Our results show the feasibility of using novel, high sensitivity CTC detection and PD-L1 single cell measuring technology in patients with BC. We also show that this technology has a potentially high sensitivity level for detecting CTC in patients with bladder malignancies by detecting low levels of CTCs in low-grade disease. More extensive studies are planned to validate our findings.

scholarly journals Disseminated BCG: Complications of Intravesical Bladder Cancer Treatment

2014 ◽  
Vol 2014 ◽  
pp. 1-3 ◽  
Author(s):  
Uyen To ◽  
Joyce Kim ◽  
David Chia
Keyword(s):  
Bladder Cancer ◽  
Hypersensitivity Pneumonitis ◽  
Superficial Bladder Cancer ◽  
Transitional Cell ◽  
Low Grade ◽  
Newly Diagnosed ◽  
Insidious Onset ◽  
Initial Symptoms ◽  
Intravesical Bcg ◽  
Carcinoma Of The Bladder

Intravesical bacillus Calmette-Guerin (BCG) has been established as an effective treatment of superficial bladder cancer (Parker and Kommu, 2013). However, major side effects, including pneumonitis, sepsis, and even death, may occur in <5% of patients (Gonzalez et al., 2003). Here we present a case of severe disseminatedMycobacterium bovisfollowing intravesical BCG administration. Our patient is a 76-year-old gentleman with newly diagnosed superficial transitional cell carcinoma of the bladder who recently received his first intravesical BCG treatment. He initially presented with hemoptysis and was found to have extensive patchy infiltrates bilaterally. He was treated for pneumonia with antibiotics and then with steroids for hypersensitivity pneumonitis but continued to deteriorate. Due to the temporal proximity of his exposure to BCG, we administered treatment for presumed disseminated BCG infection with rifampin, isoniazid, and ethambutol. Within a 48-hour period, the patient improved dramatically. The reported cases of infection from intravesical BCG illustrate an insidious onset with initial symptoms of low-grade fevers and cystitis but may progress to pneumonitis. If the symptoms persist for more than 7 days or if there is clinical deterioration, RIPE therapy (with rifampin, isoniazid, pyridoxine, and ethambutol) and a fluoroquinolone should be administered for a 6–9-month course along with steroids for 4–6 weeks (Naudžiunas et al., 2012).

scholarly journals ANALYSIS OF THE EXPRESSION OF FAS/CD95 AND HSP70 IN LOW AND HIGH GRADE UROTHELIAL CELL CARCINOMA OF THE BLADDER

2017 ◽  
Vol 53 (4) ◽  
pp. 247
Author(s):  
Heryanto Heryanto ◽  
Etty Hary Kusumastuti ◽  
Anny Setijo Rahaju
Keyword(s):  
Cell Carcinoma ◽  
Transitional Cell ◽  
Urothelial Cell ◽  
Hsp70 Expression ◽  
Low Grade ◽  
High Grade ◽  
Urothelial Cell Carcinoma ◽  
Cross Sectional ◽  
Carcinoma Of The Bladder ◽  
Spearman Test

Urothelial Cell Carcinoma (UCC), also called transitional cell carcinoma of the bladder, is the most common malignancy in urinary tract. The prognosis of this disease is highly dependent on the histological grading at diagnosis. Fas/CD95 has a role in apoptotic process, whereas HSP70 has an antiapoptotic role. This study aimed to analyze the expression of Fas/CD95 and HSP70 in low grade and high grade urothelial cell carcinoma in the bladder. This was an analytic observational study with cross sectional approach. Population and sample were paraffin blocks of urothelial cell carcinoma in the Laboratory of Anatomic Pathology, Dr. Soetomo Hospital, Surabaya in the period of January 2011-December 2016. Each grading of urothelial cell carcinoma was randomly sampled. Immunohistochemystry with Fas/CD95 and HSP70 were performed. Expression of Fas/CD95 and HSP70 were assessed semiquantitatively. Expression of Fas/CD95 and HSP70  were analyzed using Mann-Whitney test and Spearman test. The results showed there was significant different in expression of Fas/CD95 and HSP70 in low and high grades in urothelial cell carcinoma. There was no significant correlation between the expression of Fas/CD95 and HSP70 in urothelial cell carcinoma.  As a conclusion, the role of CD95 and HSP70 expression can be useful as marker for the diagnosis, especially in the determination of the grade of differentiation.

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 Single-cell RNA Sequencing Reveals Immunosuppressive Myeloid Cell Diversity and Restricted Cytotoxic Effector Cell Trafficking and Activation During Malignant Progression in Glioma

2021 ◽  
Author(s):  
Sakthi Rajendran ◽  
Clayton Peterson ◽  
Alessandro Canella ◽  
Yang Hu ◽  
Amy Gross ◽  
...  
Keyword(s):  
T Cells ◽  
Tumor Microenvironment ◽  
Single Cell ◽  
Immune Cell ◽  
Myeloid Cell ◽  
Malignant Progression ◽  
Low Grade ◽  
Cell Trafficking ◽  
High Grade ◽  
Single Cell Rna Sequencing

Low grade gliomas (LGG) account for about two-thirds of all glioma diagnoses in adolescents and young adults (AYA) and malignant progression of these patients leads to dismal outcomes. Recent studies have shown the importance of the dynamic tumor microenvironment in high-grade gliomas (HGG), yet its role is still poorly understood in low-grade glioma malignant progression. Here, we investigated the heterogeneity of the immune microenvironment using a platelet-derived growth factor (PDGF)-driven RCAS (replication-competent ASLV long terminal repeat with a splice acceptor) glioma model that recapitulates the malignant progression of low to high-grade glioma in humans and also provides a model system to characterize immune cell trafficking and evolution. To illuminate changes in the immune cell landscape during tumor progression, we performed single-cell RNA sequencing on immune cells isolated from animals bearing no tumor (NT), LGG and HGG, with a particular focus on the myeloid cell compartment, which is known to mediate glioma immunosuppression. LGGs demonstrated significantly increased infiltrating T cells, CD4 T cells, CD8 T cells, B cells, and natural killer cells in the tumor microenvironment, whereas HGGs significantly abrogated this infiltration. Our study identified two distinct macrophage clusters in the tumor microenvironment; one cluster appeared to be bone marrow-derived while another was defined by overexpression of Trem2, a marker of tumor associated macrophages. Our data demonstrates that these two distinct macrophage clusters show an immune-activated phenotype (Stat1, Tnf, Cxcl9 and Cxcl10) in LGG which evolves to an immunosuppressive state (Lgals3, Apoc1 and Id2) in HGG that restricts T cell recruitment and activation. We identified CD74 and macrophage migration inhibition factor (MIF) as potential targets for these distinct macrophage populations. Interestingly, these results were mirrored by our analysis of the TCGA dataset, which demonstrated a statistically significant association between CD74 overexpression and decreased overall survival in AYA patients with grade II gliomas. Targeting immunosuppressive myeloid cells and intra-tumoral macrophages within this therapeutic window may ameliorate mechanisms associated with immunosuppression before and during malignant progression.

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