Browsing by Subject "Bladder cancer"

Now showing 1 - 12 of 12
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    Cytokeratin expression patterns in normal and malignant urothelium, a review of the biological and diagnostic implications
    (Murcia : F. Hernández, 1999) Southgate, J.; Harnden, P.; Trejdosiewicz, L.K.
    The cytokeratins are the intermediate filament proteins characteristic of epithelial cells. In human cells, some 20 different cytokeratin isotypes have been identified. Epithelia1 cells express between two and ten cytokeratin isotypes and the consequent profile which reflects both epithelial type and differentiation status may be useful in tumour diagnosis. The transitional epithelium or urothelium of the urinary tract shows alterations in the expression and configuration of cytokeratin isotypes related to stratification and differentiation. In transitional cell carcinoma, changes in cytokeratin profile may provide information of potential diagnostic and prognostic significance. The intensification of immunolabelling with some CK8 and CK18 antibodies may underly an active role in tumour invasion and foci of CK17-positive cells may represent proliferating populations. Loss of CK13 is a marker of grade and stage and de novo expression of CK14 is indicative of squamous differentiation and an unfavourable prognosis. However, perhaps the most important recent finding is the demonstration that a normal CK20 expression pattern is predictive of tumour non-recurrence and can be used to make an objective differential diagnosis between transitional cell papilloma and carcinoma. This review will consider cytokeratin expression in urothelium and discuss the application of cytokeratin typing to the diagnosis and prognosis of patients with TCC.
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    DNA-Ploidy, morphometric-stereological and P-Glycoprotein study of superficial bladder carcinomas
    (S. Karger AG, 1992) Sánchez Fernández de Sevilla, M. C.; Gil Salom, M.; Pérez Bacete, M.; Morell Cuadreny, L.; Martínez Díaz, F.; Iborra Juan, I.; Fenollosa Entrena, B.; Llombart Bosch, A.; Oftalmología, Optometría, Otorrinolaringología y Anatomía Patológica
    We carried out a DNA-ploidy, morphometri􀀜stereolcgic and P-glycoprotein study on 40 newly diagnosed superficial bladder cancer patients (G l-G2), cor­relating the results with histological grade and clinical outcome. Variations in the number of patients who present recurrences, progression or remain tumor-free during the whole follow-up period (at least 5 years) were not signif­icant when related to nuclear size, proliferative diploid index, presl!nce of aneuploidy and expression of P-glycoprotein. lt is striking how the majority of disease-free subjects showed a proliferative diploid index higher than 10%. Moreoyer .. 3 of them presented a11 aneuploid cell population. In our study, only histological grade showed a significant discriminatory level in terms of progression versus no progression in patients with superficial bladder cancer.
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    Gene products involved in metastasis of bladder cancer
    (Murcia : F. Hernández, 2003) Davies, B.R.
    Metastasis is usually responsible for mortality in patients suffering from muscle invasive bladder cancer. Whilst expression of a great number of genes and their protein products have been associated with metastasis and/or poor prognosis in bladder cancer, evidence that they actively drive the metastatic process, and hence make potentially good therapeutic targets, is often lacking. This is due to the limited number and application of effective animal models which reflect the pathogenesis of the human disease. In this review I will discuss the processes involved in metastasis, consider the established animal models of bladder cancer progression and metastasis, and review the evidence for a role of various gene products in this process. Consideration of clinical studies in conjunction with evidence from experimental animal models reveals that the tyrosine kinase receptor erbB1/EGFR, the calcium binding protein S100A4 and the the cell cycle arrest/apoptosis-inducing p53 protein are amongst the most promising targets for therapy against metastatic disease in patients with bladder cancer.
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    Knockdown of ZNF280A inhibits cell proliferation and promotes cell apoptosis of bladder cancer
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2024) He, Long; Wang, Xialu; Chen, Peng; Du, Cheng; Li, Jinjiang
    Objective. ZNF280A is a member of the zinc finger protein family, whose role in human cancers is little known and rarely reported. This study aimed to investigate the role of ZNF280A in bladder cancer. Methods. Immunohistochemical analysis was performed to detect the expression of ZNF280A in clinical samples. ZNF280A knockdown cell models were constructed by transfection of shRNA-expressing lentivirus. MTT assay and flow cytometry were performed for detecting cell proliferation, apoptosis and cycle. Wound healing and Transwell assays were operated to detect cell migration. Western blotting and Human Apoptosis Antibody Microarray were used to measure expression of related proteins. A mouse xenograft model was constructed for in vivo study. Results. Our study demonstrated that ZNF280A was up-regulated in bladder cancer tissues compared with normal tissues, whose high expression was significantly correlated with advanced malignant grade. Knockdown of ZNF280A inhibited cell proliferation and cell migration, promoted cell apoptosis and G1/G2 phase arrest. The tumor growth in vivo was also proved to be inhibited by ZNF280A. Moreover, ZNF280A may promote bladder cancer through regulation of MAPK9, Cyclin D1 and the Akt pathway. Conclusions. In this study, ZNF280A was shown as a potential tumor promoter and prognosis indicator for bladder cancer. Targeting ZNF280A may be a promising strategy for the development of novel bladder cancer treatment.
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    lmmunohistochemical expression of Retinoblastoma gene product (Rb), p53 protein, MDM2, c-erbB-2, HLA-DR and proliferation indices in human urinary bladder carcinoma
    (Murcia : F. Hernández, 2000) Loachim, E.; Charchanti, A.; Stavropoulos, N.E.; Skopelitou, A.; Athanassiou, E.D.; Agnantis, N.J.
    Archival biopsy specimens from transitional cell bladder cancers (n=88) were analysed immunohistochemically for the expression of the retinoblastoma (Rb) gene protein, p53, mdm2, c-erbB-2, HLA-DR antigen and proliferation indices. An altered nuclear expression of Rb, p53 and mdm2 was observed in 55.2%, 33.3% and 18.2% of tumors respectively. Cytoplasmic membrane immunoreactivity (>25% tumor cells) for c-erbB-2 was detected in 14.1% of tumors and aberrant HLA-DR antigen cytoplasmic staining (>5% of tumor cells) in 22.2% of the cases. P53 overexpression was associated with higher tumor grade and stage. Aberrant HLA-DR antigen expression and PCNA were also correlated with the grade of differentiation and tumor stage. MIBl was statistically correlated with stage. pRb scores and HLADR antigen expression were correlated with proliferation activity as determined by PCNA and MIBl immunostaining. p53 protein was also strongly correlated with the proliferation index PCNA. A strong correlation between PCNA and MIBl (pc0.0001) was also found. In addition a statistically positive correlation between p53 and HLA-DR antigen expression was observed. Our data show that, although pRb and p53 protein expressions are not associated between them, they may contribute to the growth fraction of the bladder cancer. In addition, p53 and HLA-DR antigen expression could be indicators of aggressive behavior of bladder cancer.
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    microRNA expression profiles as decision-making biomarkers in the management of bladder cancer
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2017) Amir, Sharon; Mabjeesh, Nicola J.
    Bladder cancer (BC) is generally divided into non-muscle-invasive BC (NMIBC) and muscle-invasive BC (MIBC). The standard treatment protocol for MIBC patients is radical cystectomy preceded by neoadjuvant chemotherapy (NAC). About one-half of the MIBC patients show a priori resistance to chemotherapy, and are therefore exposed to the risks of disease progression and toxicity from ineffective NAC. The discovery of microRNA (miRNA) regulation in tumorigenesis has provided new directions for the development of a new type of BC biomarkers. In this review, we describe the emerging miRNAs as BC biomarkers for different purposes, including diagnosis, prognosis and therapeutic response. miRNA expression profile changes with alteration of the tissue phenotype. This phenomenon is utilized to predict tumor diagnosis, cancer subclass, disease stage, prognosis and therapeutic response. We classified the miRNAs which are involved in bladder cancer according to malignant potential, chemoresistance, discrimination between normal to cancerous and clinical outcome. Focusing on the major obstacle regarding MIBC patient's NAC response, we summarized the miRNAs that are deregulated and have the potential to identify the patients resistant to NAC, such as miR-34, miR-100, miR-146b and miR-9 and miR-193a-3p. In conclusion, miRNAs expression profile of bladder cancer patient is a promising tool that can serve as biomarker for different aims. Based on this profile we propose upfront radical cystectomy instead of standard NAC to those MIBC patients who are at higher risk for chemoresistance and poor response.
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    Molecular pathogenesis of urothelial bladder cancer
    (Murcia : F. Hernández, 2003) Theodorescu, D.
    Carcinoma of the urinary bladder is the second most common urologic malignancy. In addition, these tumors are one of the best understood genitourinary neoplasms with a well defined etiology, natural history, tumor biology, treatment options and outcome. This level of understanding arises as a consequence of multiple factors and represents a convergence of knowledge from diverse scientific disciplines. Insight provided by these disciplines, coupled with unique features of this neoplasm which make it assessable for detection, monitoring and treatment, combine to make this disease a model system for modern oncology. The intent of this review is to provide the reader an overview of our current understanding of this tumor from the standpoint of its molecular biology as related to tumor development and progression.
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    Molecular pathology of low malignant bladder transitional cell carcinoma: a current perspective
    (Murcia : F. Hernández, 2005) Wang, H.T.; Chang, J.W.
    Bladder transitional cell carcinoma (BTCC) actually has two phenotypes: low malignant and aggressive. Most previous molecular and cytogenetic analyses of bladder cancer were focused on aggressive BTCC. Little is known about the events that lead to the development of low malignant BTCC. This review mainly introduces the concept of two types of bladder tumors and then focuses on the molecular pathology of low malignant BTCC in particular. It is hoped that further understanding of the molecular pathology of low malignant BTCC may provide novel therapies and many other clinical benefits in patients with this disease.
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    RFWD3 acts as a tumor promotor in the development and progression of bladder cancer
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Jiang, Peng; Xu, Zhijie; Wu, Shan; Sun, Junjie; Tian, Junjie
    Background. Bladder cancer is one of the most commonly diagnosed malignancies of the urinary system with relatively poor prognosis and insufficient treatment strategies. RFWD3 is an E3 ligase whose function is rarely investigated in malignant tumors. Methods. A tissue microarray was used for evaluating RFWD3 expression in clinical samples and its correlation with tumor characteristics and patients’ prognosis. RFWD3 knockdown and overexpression cell models were constructed for conducting loss-of-function and gain-of-function assays. qPCR and western blotting were used for detecting mRNA and protein levels of RFWD3, respectively. MTT assay, colony formation assay, flow cytometry, wound-healing assay and transwell assay were carried out to demonstrate the change of cell phenotypes upon RFWD3 knockdown. Results. RFWD3 expression was relatively higher in bladder cancer tissues than in normal tissues, which is correlated with higher N stage and poorer prognosis of patients. Knockdown of RFWD3 in bladder cancer cells significantly inhibited cell proliferation, colony formation, promote cell apoptosis and restrained cell migration. Overexpression of RFWD3 induced the opposite effects. Conclusions. It was illustrated that RFWD3 possesses excellent tumor-promoting ability in bladder cancer. Accordingly, RFWD3 may be a promising therapeutic target in the targeted therapy of bladder cancer, which is worth further research.
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    The S100 proteins for screening and prognostic grading of bladder cancer
    (Murcia : F. Hernández, 2007) Yao, R.; Davidson, D.D.; López Beltrán, A.; MacLennan, G.T.; Montironi, R.; Cheng, L.
    The S100 gene family, which is composed of at least 24 members carrying the Ca2+ binding EF-hand motif, has been implicated in both intracellular and extracellular functions, including enzyme activities, immune responses, cytoskeleton dynamics, Ca2+ homeostasis, cell growth and cell differentiation. Altered S100 protein levels are associated with a broad range of diseases, including cardiomyopathy, inflammatory and immune disorders, neurodegenerative disorders and cancer. Although the precise role of S100 protein in carcinogenesis is poorly understood, it seems that formation of homo- and hetero-dimers, binding of Ca2+ and interaction with effector molecules are essential for the development and progression of many cancers. Several studies have suggested that S100 proteins promote cancer progression and metastasis through cell survival and apoptosis pathways. In animal models of bladder cancer, several S100 proteins are differentially expressed in bladder tumors relative to normal urothelium. In human bladder cancer, overexpression of S100A4, S100A8 or S100A11 are associated with stage progression, invasion, metastasis and poor survival. This review summarizes these findings and evaluates their implications for human bladder cancer management
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    The suppressive effects of miR-1180-5p on the proliferation and tumorigenicity of bladder cancer cells
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2017) Ge, Qiangqiang; Wang, Chenghe; Chen, Zhong; Li, Fan; Hu, Jia; Ye, Zhangqun
    In our previous research, we have reported that a candidate microRNA (miR-1180-5p) has the capacity to induce overexpression of tumor suppressor gene p21 and inhibit the growth of human bladder cancer (BCa) cell lines in vitro. However, the exact mechanism as to how miR-1180-5p suppresses BCa cell proliferation remains unknown, and the inhibitory effect of miR-1180-5p in vivo also need to be investigated. In the present study, we found that the expression level of miR-1180-5p was lower in BCa cells than in normal human urothelial cells. Furthermore, we found that overexpression of p21, activated by miR-1180-5p, interfered with cell cycle progress by inhibiting the cell cycle related proteins (CDK4, CDK6, Cyclin D1 and Cyclin A2), and thereby suppressed BCa cell proliferation. In addition, miR-1180-5p also suppressed the tumor growth in vivo significantly. Taken together, our study provides evidence that up-regulation of p21 is mainly responsible for the suppressive effect of miR1180-5p on BCa cells and miR-1180-5p can significantly inhibit tumorigenicity in vivo.
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    WTAP enhances the instability of SYTL1 mRNA caused by YTHDF2 in bladder cancer
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2024) Wang, Jiansong; Luo, Jianjun; Wu, Xuecheng; Li, Zhuo
    Background. Bladder cancer (BCa) is the most frequent type of cancer in humans. The association between m6A modification and the anti-tumor effects of natural killer (NK) cells has been described in BCa. This study intended to investigate the implications of m6A regulators in modulating SYTL1 expression in BCa and the association with the anti-tumor effects of NK cells. Methods. The prognostic role of SYTL1 in BCa was investigated using bioinformatics analysis, and the correlation between SYTL1 expression and NK cells was analyzed. The effects of SYTL1 on the anti-tumor response of NK-92 cells were examined by RT-qPCR, cytotoxicity, western blot, and ELISA assays. The relationships among WTAP, YTHDF2, and SYTL1 were investigated by RT-qPCR, RIP-qPCR, ELISA, and actinomycin D treatment. Finally, the effects of WTAP and SYTL1 on BCa tumor growth and the anti-tumor response of NK cells were verified in vivo. Results. SYTL1 was reduced in BCa tissues and had a prognostic significance, which was related to NK cell-mediated anti-tumor responses. NK-92 cells produced toxicity to BCa cells, which was further enhanced by SYTL1 overexpression in BCa cells through prompting LDH, NKG2D, NKp30, and NKp44 and IFN-γ levels. WTAP enhanced the degradation of the SYTL1 mRNA by YTHDF2. WTAP and YTHDF2 impaired the anti-tumor response of NK cells in BCa. SYTL1 inhibited the BCa progression in mice while enhancing the anti-tumor response of NK cells. Conclusions. WTAP inhibited the anti-tumor response of NK cells to BCa cells by promoting the degradation of SYTL1 mRNA through YTHDF2-mediated m6A methylation.