Antibacterial Therapy by Ag+ Ions Complexed with Titan Yellow/Congo Red and Albumin during Anticancer Therapy of Urinary Bladder Cancer

According to the World Health Organization report, the increasing antibiotic resistance of microorganisms is one of the biggest global health problems. The percentage of bacterial strains showing multidrug resistance (MDR) to commonly used antibiotics is growing rapidly. Therefore, the search for alternative solutions to antibiotic therapy has become critical to combat this phenomenon. It is especially important as frequent and recurring infections can cause cancer. One example of this phenomenon is urinary tract infections that can contribute to the development of human urinary bladder carcinoma. This tumor is one of the most common malignant neoplasms in humans. It occurs almost three times more often in men than in women, and in terms of the number of cases, it is the fifth malignant neoplasm after prostate, lung, colon, and stomach cancer. The risk of developing the disease increases with age. Despite the improvement of its treatment methods, the current outcome in the advanced stages of this tumor is not satisfactory. Hence, there is an urgent need to introduce innovative solutions that will prove effective even in the advanced stage of the disease. In our study, a nanosystem based on ionic silver (Ag+) bound to a carrier—Titan yellow (TY) was analyzed. The possibility of binding the thus formed TY-Ag system to Congo red (CR) and albumin (BSA) was determined. TY-Ag binding to CR provides for better nanosystem solubility and enables its targeted intracellular transport and binding to immune complexes. The binding of TY-Ag or CR-TY-Ag to albumin also protects the system against the uncontrolled release of silver ions. It will also allow the delivery of silver in a targeted manner directly to the desired site in the case of intravenous administration of such a system. In this study, the MIC (Minimum Inhibitory Concentration) and MBC (Minimum Bactericidal Concentration) values of the TY-Ag or BSA-TY-Ag systems were determined in two reference strains (Escherichia coli and Staphylococcus aureus). The paper presents nanosystems with a size of about 40–50 nm, with an intense antibacterial effect obtained at concentrations of 0.019 mM. We have also discovered that TY-Ag free or complexed with BSA (with a minimal Ag+ dose of 15–20 mM) inhibited cancer cells proliferation. TY-Ag complex diminished migration and effectively inhibited the T24 cell viability and induced apoptosis. On the basis of the obtained results, it has been shown that the presented systems may have anti-inflammatory and antitumor properties at the same time. TY-Ag or BSA-TY-Ag are new potential drugs and may become in future important therapeutic compounds in human urinary bladder carcinoma treatment and/or potent antimicrobial factors as an alternative to antibiotics.

TEX10 Promotes the Tumorigenesis and Radiotherapy Resistance of Urinary Bladder Carcinoma by Stabilizing XRCC6

Urinary bladder carcinoma refers to the commonest carcinoma with weak prognostic result for the patient as impacted by the limited treatment possibilities and challenging diagnosing process. Nevertheless, the molecular underpinning of bladder carcinoma malignant progression is still not clear. As a novel core part of pluripotency circuitry, testicular expression 10 (TEX10) plays an actively noticeable effect on reprogramming, early embryo development, and embryonic stem cell self-renewal. Nevertheless, TEX10 expressions and functions within bladder carcinoma are still not known. The present work is aimed at revealing TEX10 expression and biological function within urinary bladder carcinoma and elucidating the potential mechanisms. Results showed that TEX10 is abundant in urinary bladder carcinoma, and its protein level was related to poor disease-free survival in a positive manner. Reduced TEX10 level inhibited urinary bladder carcinoma cell proliferating process and metastasis in vitro and xenograft tumorigenicity in vivo. Notably, TEX10 might regulate carcinoma cell proliferating process and metastasis via XRCC6, thereby controlling the signaling of Wnt/β-catenin and DNA repair channel. Moreover, TEX10 gene knockout reduced the radiotherapy resistance of urinary bladder carcinoma. In brief, this work revealed that TEX10 could exert a significant carcinogenic effect on urinary bladder carcinoma tumorigenesis and radiotherapy resistance through the activation of XRCC6-related channels. Accordingly, targeting TEX10 is likely to offer a novel and feasible therapeutically related strategy for inhibiting urinary bladder carcinoma tumorigenicity.

Association of BRCA1 and BRCA2 genes in arsenic-induced urinary bladder carcinoma

Objective: Study was performed to determine content of arsenic in urinary bladder tumour tissue and association of BRCA1 and BRCA2 protein expression with urinary bladder carcinoma development. Materials and methods: This study was performed in a tertiary care hospital of Eastern India. Post-operative tumour tissue was analysed for arsenic content as well as BRCA1 and BRCA2 expression. Statistical analysis was done and association between stage, grade and BRCA1 and BRCA2 expression with arsenic level in tumour tissue was done. Results: Total 50 patients were included in study. Out of which 26 were arsenic positive as well as 24 were arsenic negative. Maximum patients in arsenic positive group were from arsenic endemic zones of West Bengal, India. There was significant correlation between higher stage and grade of tumour and arsenic positivity. BRCA1 correlation was significant with arsenic positive group whereas BRCA2 correlation was not significant with arsenic positive group. Conclusion: Bladder carcinomas are more common in arsenic endemic zones of our country. This association can help in future to develop drugs which act on selected mutation of genes such as BRCA1, especially in arsenic-associated bladder cancers.

Endobronchial metastasis of urinary bladder carcinoma

Introduction: Bladder cancer is the 12th most common cancer type worldwide. The most common symptom is painless hematuria. The most common sites of distant metastasis are liver (47%), lung (45%) and bone (32%), respectively. Case report: 73-year-old male patient was admitted with the complaint of hematuria. With a preliminary diagnosis of bladder cancer transurethral resection of tumour (TUR-B) was performed and pathology reported invasive urothelial carcinoma. The patient applied to the pulmonary diseases outpatient clinic with the complaint of cough and wheezing. Bronchoscopy was performed with a pre-diagnosis of bladder cancer metastasis. Multiple biopsies from EBL reported in accordance with urothelial carcinoma metastasis. Result: Urothelial carcinoma of the bladder may present with different pulmonary involvement. Although endobronchial metastasis is a rare condition; it should always be kept in mind in patients with respiratory system complaints. Keywords: endobronchial metastasis; bladder carcinoma; urothelial carcinoma; pulmonary involvement.

Expression of GATA3 and Cytokeratin 14 in Urinary Bladder Carcinoma (Histopathological and Immunohistochemical Study)

BACKGROUND: Urothelial carcinoma (UC) with squamous differentiation (SD) is the most common histologic variant of bladder carcinoma and its presence is associated with poor prognosis which may need early radical cystectomy to avoid progression and recurrence. It is difficult to detect few foci of SD, especially nonkeratinizing or early switch from urothelial to squamous epithelium on only morphological basis. Combination of GATA3 and Cytokeratin 14 (CK14) could be helpful in differentiating pure UC, UC with SD and pure squamous cell carcinoma (SCC). AIM: Assessment of GATA3 and CK14 expression in urinary bladder carcinoma and correlation with clinical and histopathological variables, for both diagnostic and prognostic purposes. MATERIALS AND METHODS: Sixty cases of archived paraffin blocks of urinary bladder carcinoma were tested for GATA3 and CK14 expression by immunohistochemistry using a rabbit monoclonal antibody against human CK 14 and mouse monoclonal antibody against GATA3, respectively. RESULTS: There is a significant correlation between GATA3 immunohistochemical expression and histological tumor subtypes of bladder carcinoma (p < 0.001), i.e. the GATA3 is a useful marker for urothelial origin especially in papillary UC. There is a significant correlation between GATA3 immunohistochemical expression and UC grade (p < 0.001). CK14 showed positive cytoplasmic staining in 9/14 (64.3%) cases of UC with SD and (13/13) (100%) cases of pure SCC and negative in 33/33(100%) cases of UC other than UC with SD. CK14 had sensitivity (64.3%) and specificity (100%) for areas of SD. CONCLUSION: GATA3 is a specific immunohistochemical marker for urothelial origin. CK14 is a highly specific and sensitive immunohistochemical marker of squamous cell carcinoma.

A HISTOPATHOLOGICAL STUDY OF BLADDER TUMORS

Background: The bladder is a common site for urinary tract malignancy. Urinary bladder carcinoma is of global concern and the histopathological types and variants are of relevance for their management. This study was carried out to assess the histopathological characteristics of bladder tumors. Materials and methods: The data was collected retrospectively and prospectively to include a total of 140 urinary bladder tumor specimens. Detailed medical records of these subjects were collected, and histopathological examination was performed on the prospective samples. Results: The most common symptom of bladder tumor was hematuria. Cystoscopy results found grossly visible tumor growths in about 76% subjects. Of the total sample, 84% patients underwent transurethral resection of bladder tumor (TURBT) surgery and the rest of them underwent cystectomy. Furthermore, the commonest histopathological type of urinary bladder carcinoma was invasive urothelial carcinoma. About 68.6% patients had high grade tumor. Most tumor growths were present on the lateral side (46.43%). In 52.86% specimens, deep muscles were involved in the tumor. Node involvement was positive in 11 (47.83%) patients. As per TNM classication, majority of the specimens were pT2bN2Mx (26.09%) and pT2bN0Mx (5, 21.74%). Tumors were detected in stage 2 (26.09%), stage 3 (30.43%) and stage 4 (39.13%). Conclusions: The most common symptom observed in patients with urinary bladder carcinoma was hematuria. Cystoscopy results found 75.71% subjects to have grossly visible tumor growths. The major histopathological type of bladder carcinoma was invasive. In 52.86% specimens, deep muscles were involved in the tumor. About 68.6% patients had high grade tumor.

Enhanced Expression but Decreased Specific Activity of Matrix Metalloproteinase 10 (MMP-10) in Comparison with Matrix Metalloproteinase 3 (MMP-3) in Human Urinary Bladder Carcinoma

Human urinary bladder cancer is a huge worldwide oncological problem causing many deaths every year. The degradation of extracellular matrix (ECM) induced by molecules such as matrix metalloproteinases (MMPs) is one of the main factors influencing the process of metastasis origination. The MMP expression is tied to tumor aggressiveness, stage, and patient prognosis. The cleavage of constituent proteins is initiated and prolonged by matrix metalloproteinases, such as MMP-3 and MMP-10. The aim of this study was to evaluate the expression and activity of both MMPs in human urinary bladder cancer occurring at various stages of the disease. Tissue samples from patients with urinary bladder cancer were analyzed. Samples were collected from patients with a low- and high-grade cancer. Control tissue was collected from the site opposite to the tumor. DNA content, MMPs content, and activity of MMP-3 and MMP-10 were measured using ELISA and Western blot techniques. MMP-3 and MMP-10 occur in high molecular complexes in human urinary bladder in healthy and cancerous tissues. Particularly, in high-grade tumors, the content of MMP-10 prevails over MMP-3. The actual and specific activities vary in both grades of urinary bladder cancer; however, the highest activity for MMP-3 and MMP-10 was found in low-grade tissues. In conclusion, MMP-10 had a higher content, but a lower activity in all investigated tissues compared to MMP-3. Generally, obtained results demonstrated a contrary participation of MMP-3 and MMP-10 in ECM remodeling what may be crucial in the pathogenesis of human urinary bladder carcinoma.