602: COX-2 Inhibition: A Mechanism for Increasing the Efficacy of BCG Immunotherapy for Urothelial Carcinoma

In spite of the fact that inflammation has been regarded as a localized orgeneralized defensive component of the body to different types harmful stimuli, there hasbeen becoming confirmation of its strong part in initiation or progression of different ailmentsparticularly related with cancer. Objectives: Aim of this study was to recognize the pattern ofexpression and level of intensity of COX-2 in different grades of papillary urothelial carcinomaof urinary bladder along with significance of COX 2 in tumerogenesis of urothelial carcinoma ofurinary bladder. Setting: Department of Pathology, BMSI, JPMC. Period: 1.1.2009 to 31.12.2012.Methods: The marker of COX-2 was investigated by using Immuno- histochemistry. Results:COX 2 was not detected in normal urothelium, but its intensity was expressed as 68% in lowgrade, 72 % in high grade and 80 % in invasive urothelial carcinoma. Conclusion: Results ofthe present study indicate that COX-2 as a component of inflammation play an important rolein progression of urinary bladder tumor and encourage use of COX 2 inhibitors as potentialantitumor agent.

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Identification of different miRNAs and their relevant miRNA targeted genes involved in sister chromatid cohesion and segregation (SCCS)/chromatin remodeling pathway on T1G3 urothelial carcinoma (UC) response to BCG immunotherapy

Clinical Genitourinary Cancer ◽

10.1016/j.clgc.2021.12.001 ◽

2021 ◽

Author(s):

Amira Awadalla ◽

Mohamed H Zahran ◽

Hassan Abol-Enein ◽

Abdel-Rahman N Zekri ◽

Mohamed Abd Elbaset ◽

...

Keyword(s):

Urothelial Carcinoma ◽

Chromatin Remodeling ◽

Sister Chromatid ◽

Sister Chromatid Cohesion ◽

Bcg Immunotherapy ◽

Chromatid Cohesion

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309 THE EXPRESSION OF KI-67 AND COX-2 IN PATIENTS WITH UROTHELIAL CARCINOMA OF THE UPPER URINARY TRACT

European Urology Supplements ◽

10.1016/s1569-9056(09)60314-6 ◽

2009 ◽

Vol 8 (4) ◽

pp. 198

Author(s):

J. Bae ◽

H.G. Jeon ◽

H.H. Kim ◽

S.E. Lee ◽

E. Lee

Keyword(s):

Urinary Tract ◽

Urothelial Carcinoma ◽

Upper Urinary Tract ◽

Ki 67 ◽

Cox 2

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The role of neutrophils and TNF-related apoptosis-inducing ligand (TRAIL) in bacillus Calmette–Guérin (BCG) immunotherapy for urothelial carcinoma of the bladder

Cancer and Metastasis Reviews ◽

10.1007/s10555-009-9195-6 ◽

2009 ◽

Vol 28 (3-4) ◽

pp. 345-353 ◽

Cited By ~ 34

Author(s):

Henry M. Rosevear ◽

Andrew J. Lightfoot ◽

Michael A. O’Donnell ◽

Thomas S. Griffith

Keyword(s):

Urothelial Carcinoma ◽

Bacillus Calmette Guerin ◽

Bcg Immunotherapy ◽

Carcinoma Of The Bladder

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Cox-2 gene overexpression in ureteral stump urothelial carcinoma following nephrectomy for renal cell carcinoma: a case report

Journal of Medical Case Reports ◽

10.1186/1752-1947-6-44 ◽

2012 ◽

Vol 6 (1) ◽

Cited By ~ 1

Author(s):

Wei-Pin Chang ◽

Tsu-Ming Chien ◽

Yu-Shiuan Wang ◽

Siou-Jin Chiu ◽

Mei-Hui Lee ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Case Report ◽

Urothelial Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Gene Overexpression ◽

Cox 2

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Increased COX-2 Immunostaining in Urothelial Carcinoma of the Urinary Bladder Is Associated with Invasiveness and Poor Prognosis

Analytical Cellular Pathology ◽

10.1155/2019/5026939 ◽

2019 ◽

Vol 2019 ◽

pp. 1-8

Author(s):

Basim Al-Maghrabi ◽

Wafaey Gomaa ◽

Mohammed Abdelwahed ◽

Jaudah Al-Maghrabi

Keyword(s):

Urinary Bladder ◽

Urothelial Carcinoma ◽

Distant Metastasis ◽

Immunohistochemical Staining ◽

Lymphovascular Invasion ◽

Tumor Grade ◽

Tissue Microarrays ◽

Clinicopathological Parameters ◽

Cox 2 ◽

Muscle Invasion

Background. Urothelial carcinoma of the urinary bladder (UCB) is the commonest bladder tumor. Cyclooxygenase-2 (COX-2) mediates angiogenesis, cell survival/proliferation, and apoptosis. This study investigates the relation of COX-2 immunostaining in UCB to clinicopathological parameters in Saudi Arabia. Methods. The study population includes 123 UCB and 25 urothelial mucosae adjacent to UCB. UCB samples were collected before any local or systemic therapy. Tissue microarrays were designed and constructed, and TMA blocks were sliced for further immunohistochemical staining. Immunohistochemical staining was done using a mouse anti-human COX-2 monoclonal antibody. A cutoff point of 10% was chosen as the threshold to determine low and high COX-2 immunostaining. Results. COX-2 immunostaining is higher in UCB than in the adjacent urothelium (p=0.033). High COX-2 immunostaining is associated with high-grade UCB (p=0.013), distant metastasis (p=0.031), lymphovascular invasion (p=0.008), positive muscle invasion (p=0.017), pT2 and above (p=0.003), and high anatomical stages (stage II and above). High COX-2 immunostaining is an independent predictor of higher tumor grade (p<0.001), muscle invasion (p=0.015), advanced pathological T (p=0.014), lymphovascular invasion (p=0.011), and distant metastasis (p=0.039). High COX-2 immunostaining is associated with lower overall survival rate (p=0.019). Conclusion. COX-2 immunostaining is associated with the invasiveness of UCB which may be used as an independent prognostic marker. COX-2 may be a significant molecule in the initiation and progression of UCB. Molecular and clinical investigations are required to explore the molecular downstream of COX-2 in UCB and effectiveness of COX-2 inhibitors as adjuvant therapy along with traditional chemotherapy.

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The Factors Affecting Expansion of Reactive Tumor Infiltrating Lymphocytes (TIL) From Bladder Cancer and Potential Therapeutic Applications

Frontiers in Immunology ◽

10.3389/fimmu.2021.628063 ◽

2021 ◽

Vol 12 ◽

Author(s):

Ahmet Murat Aydin ◽

Brittany L. Bunch ◽

Matthew Beatty ◽

Ali Hajiran ◽

Jasreman Dhillon ◽

...

Keyword(s):

Bladder Cancer ◽

Urothelial Carcinoma ◽

Tumor Infiltrating Lymphocytes ◽

Cell Phenotype ◽

Primary Tumors ◽

Bcg Immunotherapy ◽

Bcg Therapy ◽

Significant Difference ◽

Previously Treated ◽

Infiltrating Lymphocytes

Tumor infiltrating lymphocytes (TIL) therapy was shown to provide durable objective response in patients with metastatic melanoma. As a fundamental first step to bring TIL therapy to clinical use, identification of patients whose tumors yield optimal numbers of reactive TIL is indispensable. We have previously shown that expansion of tumor reactive TIL from primary bladder tumors and lymph node metastases is feasible. Here, we performed TIL harvesting from additional surgical specimens (additional 31 primary tumors and 10 lymph nodes) to generate a heterogenous cohort of 53 patients with bladder cancer (BC) to evaluate the tumor characteristics that lead to tumor-reactive TIL expansion. Among a total of 53 patients, overall TIL growth from tumor samples were 37/53 (69.8%) and overall anti-tumor reactive TIL were 26/35 (74.3%). Mixed urothelial carcinoma is associated with higher anti-tumor reactivity of expanded TIL than pure urothelial carcinoma (89.5% vs. 56.3%, p=0.049). The anti-tumor reactivity of expanded TIL from primary tumors previously treated with BCG immunotherapy were lower (33.3% vs. 82.6%, p=0.027) although T-cell phenotype (CD3+, CD4+, CD8+, and CD56+) was similar regardless prior of BCG therapy. Addition of agonistic 4-1BB antibody in culture media with IL-2 improved the number of expanded TIL from primary tumors previously treated with BCG immunotherapy. There was no significant difference between basal and luminal subtype tumors in terms of viable and reactive TIL growth. Our study demonstrates that TIL expansion is feasible across all BC patients and BC subtypes, and we suggest that TIL therapy can be a reasonable treatment strategy for various manifestations of BC.

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