Low Frequency of Intratumor Heterogeneity in Bladder Cancer Tissue Microarrays

PIK3CA is a key component of phosphatidylinositol 3-kinase (PI3K) pathway that its involvement in tumorigenesis has been revealed by previous research. However, its functions and potential mechanisms in bladder cancer are still largely undiscovered. Tissue microarray (TMA) with 66 bladder cancer patients was surveyed via immunohistochemistry to evaluate the level of PIK3CA and CUX1 and we found upregulation of PIK3CA in bladder cancer tissue and patients with higher level of PIK3CA presented with poorer prognosis. Overly expressed PIK3CA promoted growth, migration, invasion, and metastasis of bladder cancer cells and knockdown of PIK3CA had the opposite effect. Gain-of-function and loss-of-function studies showed that PIK3CA expression was facilitated by CUX1, leading to activation of epithelial-mesenchymal transition (EMT), accompanied by upregulated expression of Snail, β-catenin, Vimentin and downregulated expression of E-cadherin in the bladder cancer cell lines. Besides, over-expressed CUX1 could restore the expression of downregulated Snail, β-catenin, Vimentin and E-cadherin which was induced by PIK3CA knockdown. These results revealed that PIK3CA overexpression in bladder cancer was regulated by the transcription factor CUX1, and PIK3CA exerted its biological effects by activating EMT.

Download Full-text

Development of a novel immunotherapy for muscle invasive bladder cancer (MIBC).

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.6_suppl.402 ◽

2017 ◽

Vol 35 (6_suppl) ◽

pp. 402-402

Author(s):

Irina Y. Tcherepanova ◽

Bradley C. Leibovich ◽

Jacoba Slagter-Jager ◽

Patrick Dillon ◽

Shawn Michael Leland ◽

...

Keyword(s):

Bladder Cancer ◽

Rna Extraction ◽

Rna Degradation ◽

Invasive Bladder Cancer ◽

Cancer Tissue ◽

Autologous Tumor ◽

Muscle Invasive Bladder Cancer ◽

Bladder Tissue ◽

Bladder Cancer Tissue ◽

Muscle Invasive

402 Background: AGS-003 is an autologous tumor RNA-loaded dendritic cell-based immunotherapy being tested in advanced renal cell carcinoma (RCC) patients. The immunologic specificity for the patient’s own tumor is achieved using amplified tumor RNA electroporated into monocyte derived dendritic cells. To produce AGS-003 for RCC patients the RNA is amplified from a 100 mg primary tumor sample obtained via nephrectomy. In this non treatment study we evaluated the feasibility of RNA amplification from MIBC tissue acquired by transurethral resection of bladder tumor (TURBT). Methods: MIBC tissue was obtained via TURBT. Following draining of the irrigant used during the TURBT procedure, tissue was placed into an RNA preservative solution to prevent RNA degradation until processing. Methods developed for the amplification of RCC tumor RNA and RNA quality testing were applied to the RNA extracted from the MIBC specimens. Results: This work demonstrated that the methods developed for the amplification and testing of RNA from RCC can be successfully employed for the amplification of RNA from MIBC specimens collected by TURBT. Results demonstrated that the total RNA yields obtained from bladder tissue exceed that of similar masses of primary RCC tumors. This finding enabled the reduction in the amount of starting material from 100 mg to 50 mg of bladder tissue. The amount of amplified RNA produced from the lower bladder cancer masses were sufficient to support the production of immunotherapy at full scale (17 doses average). Conclusions: These data demonstrate the feasibility of RNA extraction and amplification from muscle invasive bladder cancer tissue and supports our planned phase II clinical study. [Table: see text]

Download Full-text

MP-20.03: Prognostic Significance of Epidermal Growth Factor Receptor (EGFR) and Survivin Expression in Bladder Cancer Tissue and Urine Cytology Sediment of Patients with Transitional Cell Carcinoma of the Urinary Bladder

Urology ◽

10.1016/j.urology.2009.07.764 ◽

2009 ◽

Vol 74 (4) ◽

pp. S141-S142

Author(s):

E.O. Kehinde ◽

J.T. Anim ◽

K. Kapila ◽

A. Prasad ◽

V. Jerin ◽

...

Keyword(s):

Bladder Cancer ◽

Epidermal Growth Factor Receptor ◽

Growth Factor ◽

Transitional Cell ◽

Prognostic Significance ◽

Growth Factor Receptor ◽

Survivin Expression ◽

Cancer Tissue ◽

Bladder Cancer Tissue ◽

Epidermal Growth

Download Full-text

Telomerase activity in bladder cancer tissue

Experimental and Therapeutic Medicine ◽

10.3892/etm_00000015 ◽

2010 ◽

Vol 1 (1) ◽

pp. 85-88 ◽

Cited By ~ 2

Author(s):

AKIHIRO MORII ◽

AKIRA KOMIYA ◽

AKIOU OKUMURA ◽

HIDEKI FUSE

Keyword(s):

Bladder Cancer ◽

Telomerase Activity ◽

Cancer Tissue ◽

Bladder Cancer Tissue

Download Full-text

Therapy-relevant aberrant expression of MRP3 and BCRP mRNA in TCC-/SCC-bladder cancer tissue of untreated patients

Oncology Reports ◽

10.3892/or.2017.5695 ◽

2017 ◽

Vol 38 (1) ◽

pp. 551-560 ◽

Cited By ~ 1

Author(s):

Mona Rady ◽

Marwa Mostageer ◽

Jan Rohde ◽

Ashraf Zaghloul ◽

Ruth Knüchel-Clarke ◽

...

Keyword(s):

Bladder Cancer ◽

Cancer Tissue ◽

Aberrant Expression ◽

Bladder Cancer Tissue

Download Full-text

Expression of MMP28 in bladder cancer tissue microarray and its clinical significance

10.21203/rs.2.12805/v1 ◽

2019 ◽

Author(s):

Wang Heng ◽

Wu Junxiu ◽

Chen Xinpeng ◽

Zhang Qi ◽

Zhao Tingxiao ◽

...

Keyword(s):

Bladder Cancer ◽

Disease Progression ◽

Clinical Significance ◽

Histological Grade ◽

Expression Patterns ◽

Lymphatic Invasion ◽

Cancer Tissue ◽

Cancer Specific Survival ◽

Stage Disease ◽

Bladder Cancer Tissue

Abstract Background: The aim of this study was to explore the expression pattern and prognostic value of MMP-28 for bladder cancer and analyze its relationship with the clinicopathological features of human bladder cancer. Methods: Immunohistochemical staining for MMP28 was performed in 491 archived radical bladder cancer resection and 80 normal specimens. The immunoreactivity of these proteins was correlated to evaluate their clinical significance as prognostic factors. Results: Protein level of MMP-28 was up-regulated in bladder cancer compared with adjacent non-tumor tissues. The increased expression of MMP-28 was significantly associated with high histological grade, lymph node metastasis, lymphatic invasion and distant metastasis (P<0.05). High expression of MMP-28 was also associated with greater risk of disease progression and decreased chance of cancer-specific survival. Further analysis suggested that MMP-28 was related with decreased overall survival. Conclusions: MMP-28 could be used as an effective marker for tumor diagnosis and predict tumor progression in bladder cancer. The expression patterns of MMP-28 interaction correlated well with the pathological stage, disease progression and tumor-specific survival. The finding may help identify more biologically aggressive carcinomas which could aid in patients who benefit from more intensive adjuvant therapy.

Download Full-text

Identification of Hyal2-expressing tumor-associated myeloid cells in cancer: implications for cancer-related inflammation through enhanced hyaluronan degradation

10.1101/2020.09.14.296475 ◽

2020 ◽

Author(s):

Paul R. Dominguez Gutierrez ◽

Elizabeth P. Kwenda ◽

William Donelan ◽

Padraic O’Malley ◽

Paul L. Crispen ◽

...

Keyword(s):

Bladder Cancer ◽

Tumor Microenvironment ◽

Tumor Tissue ◽

Myeloid Cells ◽

Suppressor Cells ◽

Major Constituent ◽

Cancer Tissue ◽

Myeloid Derived Suppressor Cells ◽

Bladder Cancer Tissue ◽

Tumor Infiltrate

AbstractIncreased presence of myeloid derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs) in tumor tissue has been extensively reported. These cells represent a major constituent of tumor infiltrate and exhibit a distinct phenotype with immunosuppressive and tolerogenic functions. However, their role in the regulation of hyaluronan (HA) metabolism in the tumor microenvironment has not been established. Here we describe a novel function of tumor-associated myeloid cells related to the enhanced breakdown of extracellular HA in human bladder cancer tissue leading to accumulation of small HA fragments with MW <20 kDa. Increased fragmentation of extracellular HA and accumulation of low molecular weight HA (LMW-HA) in tumor tissue was associated with elevated production of multiple inflammatory cytokines, chemokines, and angiogenic factors. The fragmentation of HA by myeloid cells was mediated by the membrane-bound enzyme hyaluronidase 2 (Hyal2). The increased numbers of Hyal2+CD11b+ myeloid cells were detected in the tumor tissue as well as in the peripheral blood of bladder cancer patients. Co-expression of CD33 suggests that these cells belong to monocytic myeloid-derived suppressor cells. HA-degrading function of Hyal2-expressing MDSCs could be enhanced by exposure to tumor-conditioned medium, and IL-1β was identified as one of factors involved in the stimulation of Hyal2 activity. CD44-mediated signaling plays an important role in the regulation of HA-degrading activity of Hyal2-expressing myeloid cells, since engagement of CD44 receptor with specific monoclonal antibody triggered translocation of Hyal2 enzyme to the cellular surface and also stimulated secretion of IL-1β. Taken together, this work identifies the Hyal2-expressing tumor-associated myeloid cells, and links these cells to the accumulation of LMW-HA in the tumor microenvironment and cancer-related inflammation and angiogenesis.

Download Full-text