Predominance of M2-polarized macrophages in bladder cancer affects angiogenesis, tumor grade and invasiveness

Bladder cancer is a major cause of morbidity and mortality. At initial diagnosis, 75% of patients present with nonmuscle-invasive disease and 25% of patients have muscle-invasive or metastatic disease.Patients with noninvasive disease suffer from a high rate of recurrence and 10–30% will have disease progression. Patients with muscle-invasive disease are primarily treated with radical cystectomy, but frequently succumb to their disease despite improvements in surgical technique. In non–muscle-invasive disease, multiplicity, tumor size, and prior recurrence rates are the most important predictors for recurrence, while tumor grade, stage, and carcinomain situare the most important predictors for progression. The most common tool that clinicians use to predict outcomes after radical cystectomy is still the tumor-node-metastasis (TNM) staging system, with lymph node involvement representing the most important prognostic factor. However, the predictive accuracy of staging and grading systems are limited, and nomograms incorporating clinical and pathologic factors can improve prediction of bladder cancer outcomes. One limitation of current staging is the fact that tumors of a similar stage and grade can have significantly different biology. The integration of molecular markers, especially in a panel approach, has the potential to further improve the accuracy of predictive models and may also identify targets for therapeutic intervention or patients who will respond to systemic therapies.

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Microfluidic Assaying of Circulating Tumor Cells and its Correlation with Muscle Invasiveness and Tumor Grade of Urothelial Bladder Cancer

10.21203/rs.3.rs-267304/v1 ◽

2021 ◽

Author(s):

Guanghou Fu ◽

Kok Suen Cheng ◽

Anqi Chen ◽

Zhijie Xu ◽

Xiaoyi Chen ◽

...

Keyword(s):

Bladder Cancer ◽

Risk Stratification ◽

Cancer Patients ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Tumor Grade ◽

Invasive Bladder Cancer ◽

Low Grade ◽

Muscle Invasive Bladder Cancer ◽

Muscle Invasive

Abstract Background: Bladder cancer is characterized by its frequent recurrence and progression. Effective treatment strategies need to be based on an accurate risk stratification, in which muscle invasiveness and tumor grade represent the two most important factors. Traditional imaging techniques provide preliminary information about muscle invasiveness but are lacking in terms of accuracy. Although as the gold standard, pathological biopsy is only available after the surgery and cannot be performed longitudinally for long-term surveillance. Methods: In this work, we developed a microfluidic approach that interrogates circulating tumor cells (CTCs) in the peripheral blood of bladder cancer patients to reflect the risk stratification of the disease. Results：In a cohort of 48 bladder cancer patients comprising 33 non-muscle invasive bladder cancer (NMIBC) cases and 15 muscle invasive bladder cancer (MIBC) cases, the CTC count was found to be considerably higher in the MIBC group compared with the NMIBC group (4.67 vs. 1.88 CTCs/3 mL, P=0.019), and was significantly higher in high-grade bladder cancer patients verses low-grade bladder cancer patients (3.69 vs. 1.18 CTCs/3mL, P=0.024). Conclusions: This microfluidic assay of CTCs is believed to be a promising complementary tool for the risk stratification of bladder cancer.Trial registration: This research was conducted under the approval of the Ethics Committee of the First Affiliated Hospital at Zhejiang University School of Medicine with the Registration No. 2015-218.

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DEPDC1B is a tumor promotor in development of bladder cancer through targeting SHC1

Cell Death and Disease ◽

10.1038/s41419-020-03190-6 ◽

2020 ◽

Vol 11 (11) ◽

Author(s):

Chin-Hui Lai ◽

Kexin Xu ◽

Jianhua Zhou ◽

Mingrui Wang ◽

Weiyu Zhang ◽

...

Keyword(s):

Bladder Cancer ◽

Cancer Cells ◽

Malignant Tumors ◽

Tumor Grade ◽

In Vivo Studies ◽

Mechanistic Study ◽

Tumor Promotor ◽

Bladder Cancer Cells

AbstractBladder cancer is one of the most commonly diagnosed malignant tumors in the urinary system and causes a massive cancer-related death. DEPDC1B is a DEP domain-containing protein that has been found to be associated with a variety of human cancers. This study aimed to explore the role and mechanism of DEPDC1B in the development of bladder cancer. The analysis of clinical specimens revealed the upregulated expression of DEPDC1B in bladder cancer, which was positively related to tumor grade. In vitro and in vivo studies showed that DEPDC1B knockdown could inhibit the growth of bladder cancer cells or xenografts in mice. The suppression of bladder cancer by DEPDC1B was executed through inhibiting cell proliferation, cell migration, and promoting cell apoptosis. Moreover, a mechanistic study found that SHC1 may be an important route through which DEPDC1B regulates the development of bladder cancer. Knockdown of SHC1 in DEPDC1B-overexpressed cancer cells could abolish the promotion effects induced by DEPDC1B. In conclusion, DEPDC1B was identified as a key regulator in the development of bladder cancer, which may be used as a potential therapeutic target in the treatment of bladder cancer.

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Urinary Bladder Cancer in Egypt: Are There Gender Differences in Its Histopathological Presentation?

Advances in Urology ◽

10.1155/2018/3453808 ◽

2018 ◽

Vol 2018 ◽

pp. 1-7 ◽

Cited By ~ 2

Author(s):

Fiorina Kyritsi ◽

Christopher A. Loffredo ◽

Yun-Ling Zheng ◽

George Philips ◽

Sania Amr

Keyword(s):

Gender Differences ◽

Bladder Cancer ◽

Cell Carcinoma ◽

Urinary Bladder Cancer ◽

Tumor Grade ◽

Pelvic Lymphadenectomy ◽

Cancer Type ◽

Bladder Tissue ◽

Primary Bladder ◽

Tissue Specimens

We investigated gender differences in the histopathologic presentation of bladder cancer cases in Egypt, where both urothelial cell carcinoma (UC) and squamous cell carcinoma (SCC) types are highly prevalent. We used logistic regression to estimate the unadjusted (OR) and adjusted odds ratio (AOR) and 95% confidence interval (CI) of the associations between gender and different histopathologic and sociodemographic parameters of 2,186 confirmed cases of primary bladder cancer (1,775 males and 411 females; 784 SCC and 1,402 UC). There were no statistically significant gender differences in tumor grade, stage, mucosal ulcer, or inflammatory cystitis, regardless of the cancer type, but men were less likely than women to have undergone cystectomy with pelvic lymphadenectomy. Having Schistosoma haematobium (SH) ova in the bladder tissue was significantly associated with male gender in the fully adjusted model of either SCC (AOR (95% CI) = 2.12 (1.15–3.89)) or UC cases (3.78 (1.89–7.55)). Compared to females, male cases were significantly older at time of diagnosis and smokers. In Egypt, regardless of the type of bladder cancer (SCC or UC), male more than female cases had evidence of SH infection, but not other histopathologic differences, in bladder tissue specimens.

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Correlation of Allelic Loss of the P53 Gene and Tumor Grade, Stage, and Malignant Progression in Bladder Cancer

International Journal of Urology ◽

10.1111/j.1442-2042.1997.tb00144.x ◽

1997 ◽

Vol 4 (1) ◽

pp. 74-78 ◽

Cited By ~ 12

Author(s):

Masakazu Tsutsumi ◽

Kokichi Sugano ◽

Kensei Yamaguchi ◽

Tadao Kakizoe ◽

Hideyuki Akaza

Keyword(s):

Bladder Cancer ◽

P53 Gene ◽

Tumor Grade ◽

Malignant Progression ◽

Allelic Loss

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Correlation of abnormal upper tract cytology and tumor histology in patients who have undergone a nephroureterectomy for urothelial carcinoma with disease recurrence in the bladder.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.6_suppl.288 ◽

2013 ◽

Vol 31 (6_suppl) ◽

pp. 288-288

Author(s):

Einar Freyr Sverrisson ◽

Timothy Kim ◽

Patrick Espiritu ◽

Wade Jeffers Sexton ◽

Julio Pow-Sang ◽

...

Keyword(s):

Bladder Cancer ◽

Previous History ◽

Tumor Grade ◽

Disease Recurrence ◽

Intravesical Therapy ◽

Prior History ◽

Upper Tract ◽

History Of ◽

One Year ◽

Bladder Recurrence

288 Background: 15-50% of patients with upper tract urothelial carcinomas (UTUC) will have a bladder recurrence. Abnormal upper tract cytology (UTC) is an indicator of higher grade tumors but has not been associated with bladder recurrence. We were interested in investigating the role of UTC as a predictor of bladder cancer recurrences in patients with no prior history of bladder cancer presenting with UTUC. Methods: Of 67 patients who had an UTC collected prior to their nephroureterectomy (NU) in 2004-2012, we identified 17 patients with a recurrent disease in the bladder who met the criteria of having no previous history of bladder cancer at the time of their NU. UTC and histology were reviewed and analyzed with the bladder pathology data. Positive or suspicious cytology was defined as abnormal and atypical or reactive as benign. Results: 15 (88%) of 17 patients (11 men and 6 women) who met our criteria were diagnosed with bladder cancer within one year after their NU (average 7.5 months (range 2-26)). 10 (59%) of 17 patients had abnormal UTC with a calculated sensitivity and specificity of 59% and 22%, respectively. 7 (70%) of 10 patients with abnormal UTC compared to 5 (71%) of 7 patients with benign cytology had high grade (HG) bladder cancer (p=1.0). Muscle invasive tumors were found in 5 (29%) of 17 patients and 3 (60%) of those had abnormal UTC. All six women had HG bladder cancer compared to 6 of 10 men (p=0.23). HG tumors were slightly more common in the bladder compared to the upper tract (75% vs 65%, p=0.70) and 14 (87.5%) of 16 bladder tumors had the same tumor grade in the upper tract. Conclusions: Abnormal UTC is a poor predictor of bladder recurrence in patients with a history of UTUC. The majority of patients who developed bladder recurrence presented within one year from NU with HG disease which underscores the importance of aggressive surveillance and the consideration of prophylactic intravesical therapy at the time of NU in this patient cohort.

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Evaluation of clinical and laboratory characteristics of patients with bladder cancer in Ardabil province, 2016

International Journal of Community Medicine and Public Health ◽

10.18203/2394-6040.ijcmph20180742 ◽

2018 ◽

Vol 5 (3) ◽

pp. 885

Author(s):

Ali Hoseinkhani ◽

Firouz Amani ◽

Yasamin Torabi

Keyword(s):

Bladder Cancer ◽

Urban Areas ◽

Tumor Grade ◽

Tumor Stage ◽

Cross Sectional Study ◽

Common Type ◽

Blood Type ◽

High Grade ◽

Cross Sectional ◽

Urethral Carcinoma

Background: Bladder cancer is the most common cancer of the urethra and genital tract and is ranked ninth in terms of its incidence. The aim of this study was to investigate the clinical and laboratory characteristics of patients with bladder cancer in Ardabil province.Methods: This is a cross-sectional study that has been done on 81 patients with bladder cancer. Necessary information such as age, sex, blood type, RH, family history of bladder cancer, smoking, drug use, tumor stage and grade and type of tumor were collected from the patient's hospital record or by telephone interview.Results: Sixty seven patients (82.7%) were male. The mean age of patients was 66.9±15.02 years. The blood group A, was the most common type of blood. (39.5%) of all patients, 54.3% had cigarette smoking and 47(58%) live in city. The most common type of tumor grade was high-grade papillary urethral carcinoma (48.1%).The most common stages of the tumor was Ta (40.7%) and the most common clinical manifestation was hematuria (90.1%). 27 patients (33.3%) had a delay of more than 3 months between observation of hematuria and cystoscopy.Conclusions: The findings showed that the most common grade and stage of the tumor in patients were high-grade papillary urethral carcinoma and Ta; the most prevalent clinical presentation was hematuria; the prevalence of the disease was higher among males, at ages older than 70 years old, in people with a blood type A, and among people living in urban areas; a study with bigger sample size should be done in future in the country Iran.

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Downregulation of Urinary microRNA-200c acts as a Promising Novel Bio-marker in the Diagnosis of Patients With Bladder Cancer

10.21203/rs.3.rs-91603/v1 ◽

2020 ◽

Author(s):

Hao Zi ◽

Wen-Lin Tao ◽

Lei Gao ◽

Zhao-Hua Yu ◽

Xiao-Dong Bai ◽

...

Keyword(s):

Bladder Cancer ◽

Cancer Patients ◽

Roc Curve ◽

Area Under The Curve ◽

Tumor Grade ◽

Healthy Controls ◽

Strongly Correlated ◽

Operating Characteristics ◽

Diagnostic Capacity ◽

Pcr Method

Abstract BackgroundMicroRANs (miRNAs) have been reported to be involved in various human cancers. The aim of this study was to explore the diagnostic performance of urine miR-200c in bladder cancer. MethodsQuantitative real-time polymerase chain reaction (qRT-PCR) method was applied to measure the relative expression of urine miR-200c in bladder cancer patients. The relationship between urine miR-200c level and clinicopathological factors was analyzed using χ2 test. The diagnostic capacity of urine miR-200c was calculated using the receiver operating characteristics (ROC) curve analysis.ResultsUrinary level of miR-200c was significantly reduced in bladder cancer patients compared with healthy controls (P=0.000). Furthermore, urine miR-200c expression was strongly correlated with histologic grade (P=0.019), tumor grade (P=0.003), and lymph node metastasis (P=0.001). ROC curve showed that urine miR-200c could distinguish bladder cancer patients from healthy controls with an area under the curve of 0.844. The cutoff value of 1.235, with the sensitivity of 89.0% and the specificity of 70.7% respectively.ConclusionUrine miR-200c may act as a noninvasive diagnostic biomarker for bladder cancer.

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TSPAN7 Exerts Anti-Tumor Effects in Bladder Cancer Through the PTEN/PI3K/AKT Pathway

Frontiers in Oncology ◽

10.3389/fonc.2020.613869 ◽

2021 ◽

Vol 10 ◽

Author(s):

Xi Yu ◽

Shenglan Li ◽

Mingrui Pang ◽

Yang Du ◽

Tao Xu ◽

...

Keyword(s):

Bladder Cancer ◽

Cell Lines ◽

Therapeutic Potential ◽

Tumor Grade ◽

Biological Properties ◽

Akt Pathway ◽

Dynamic Regulation ◽

Potential Marker

The tetraspanin protein superfamily participate in the dynamic regulation of cellular membrane compartments expressed in a variety of tumor types, which may alter the biological properties of cancer cells such as cell development, activation, growth and motility. The role of tetraspanin 7 (TSPAN7) has never been investigated in bladder cancer (BCa). In this study, we aimed to investigate the biological function of TSPAN7 and its therapeutic potential in human BCa. First, via reverse transcription and quantitative real-time PCR (qRT-PCR), we observed downregulation of TSPAN7 in BCa tissues samples and cell lines and found that this downregulation was associated with a relatively high tumor stage and tumor grade. Low expression of TSPAN7 was significantly correlated with a much poorer prognosis for BCa patients than was high expression. Immunohistochemistry (IHC) showed that low TSPAN7 expression was a high-risk predictor of BCa patient overall survival. Furthermore, the inhibitory effects of TSPAN7 on the proliferation and migration of BCa cell lines were detected by CCK-8, wound-healing, colony formation and transwell assays in vitro. Flow cytometry analysis revealed that TSPAN7 induced BCa cell lines apoptosis and cell cycle arrest. In vivo, tumor growth in nude mice bearing tumor xenografts could be obviously affected by overexpression of TSPAN7. Western blotting showed that overexpression of TSPAN7 activated Bax, cleaved caspase-3 and PTEN but inactivated Bcl-2, p-PI3K, and p-AKT to inhibit BCa cell growth via the PTEN/PI3K/AKT pathway. Taken together, our study will help identify a potential marker for BCa diagnosis and supply a target molecule for BCa treatment.

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