Progress in the Research and Targeted Therapy of ErbB/HER Receptors in Urothelial Bladder Cancer

Bladder cancer is a lethal malignancy and a majority of bladder cancer arise from urothelial cells. Infiltration and metastasis are barriers for the radical cystectomy to achieve favored outcome and are the main cause of death. Systemic therapy, including chemotherapy, targeted therapy, and immunotherapy, is fundamental for these patients. erbB/HER receptors are found to be overexpressed in a subgroup of urothelial carcinoma, targeting erbB/HER receptors in these patients was found to be an efficient way in the era of genetic testing. To evaluate the role of erbB/HER receptors in bladder cancer, we reviewed the literature and ongoing clinical trials as regards to this topic to unveil the context of erbB/HER receptors in bladder cancer, which probably help to solidate the theoretical basis and might instruct further research.

Proteomics analysis in urinary bladder cancer patients identifies urinary SOD2 as a predictive marker of recurrence

Early non-invasive detection of tumor is an urgent clinical need for managing urothelial bladder cancer. Cystoscopy and cytology are the current standards for diagnosis of recurrence, but are limited by low sensitivity. Quantitative proteomics tool was employed to identify important deregulated molecules in bladder cancer tissues and validated using Western blot and immunohistochemistry analysis. A set of 1137 proteins were identified in four paired bladder cancer patients. Among these, 64 proteins were deregulated in all cases among which 9 were commonly up-regulated. The Ingenuity Pathway Analysis (IPA) generated top 11 Networks in which three commonly upregulated (SERPING1, SOD2 and HSPB6) proteins were involved and selected for further validation. Tissue expression of SOD2, SERPING1 and HSPB6 monitored in an independent sample set (n=18) by immuno-histochemical analysis showed similar profile. Western blot analysis of these proteins in urine of bladder cancer (n=26) and healthy subjects (n=10) showed a specificity and sensitivity of >80% for SOD2 and selected for further validation in a separate set (n=150) by ELISA. Significant elevation in urinary SOD2 level was found in urothelial bladder cancer patients compared to healthy controls and in recurrent cases compared to primary (p-value<0.001). Kaplan Meier survival analysis showed urinary SOD2 concentration >2,100 pg/ml was significantly associated with poorer survival and cumulative survival of patient with low SOD2 concentration was 34.4% compared to 18.9% in patient with high SOD2 at 24 months (p=0.025). The study identifies SOD2 as a non-invasive biomarker which may help to extend the period between cystoscopies during follow-up.

Identification of prognostic and therapeutic value of CC chemokines in Urothelial bladder cancer: evidence from comprehensive bioinformatic analysis

Background Urothelial bladder cancer (BC) is one of the most prevalent malignancies with high mortality and high recurrence rate. Angiogenesis, tumor growth and metastasis of multiple cancers are partly modulated by CC chemokines. However, we know little about the function of distinct CC chemokines in BC. Methods ONCOMINE, Gene Expression Profiling Interactive Analysis (GEPIA), Kaplan–Meier plotter, cBioPortal, GeneMANIA, and TIMER were used for analyzing differential expression, prognostic value, protein–protein interaction, genetic alteration and immune cell infiltration of CC chemokines in BC patients based on bioinformatics. Results The results showed that transcriptional levels of CCL2/3/4/5/14/19/21/23 in BC patients were significantly reduced. A significant relation was observed between the expression of CCL2/11/14/18/19/21/23/24/26 and the pathological stage of BC patients. BC patients with high expression levels of CCL1, CCL2, CCL3, CCL4, CCL5, CCL8, CCL13, CCL15, CCL17, CCL18, CCL19, CCL22, CCL25, CCL27 were associated with a significantly better prognosis. Moreover, we found that differentially expressed CC chemokines are primarily correlated with cytokine activity, chemokines receptor binding, chemotaxis, immune cell migration. Further, there were significant correlations among the expression of CC chemokines and the infiltration of several types of immune cells (B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells). Conclusions This study is an analysis to the potential role of CC chemokines in the therapeutic targets and prognostic biomarkers of BC, which gives a novel insight into the relationship between CC chemokines and BC.

Gender Differences in Urothelial Bladder Cancer: Effects of Natural Killer Lymphocyte Immunity

Men are more likely to develop cancer than women. In fact, male predominance is one of the most consistent cancer epidemiology findings. Additionally, men have a poorer prognosis and an increased risk of secondary malignancies compared to women. These differences have been investigated in order to better understand cancer and to better treat both men and women. In this review, we discuss factors that may cause this gender difference, focusing on urothelial bladder cancer (UBC) pathogenesis. We consider physiological factors that may cause higher male cancer rates, including differences in X chromosome gene expression. We discuss how androgens may promote bladder cancer development directly by stimulating bladder urothelium and indirectly by suppressing immunity. We are particularly interested in the role of natural killer (NK) cells in anti-cancer immunity.

Study Results of the 2,3-Diphosphoglycerate Content in Erythrocytes of Patients with Malignant Neoplasm Anemia in Genitourinary Organs Cancer

Every year, more than 6 million people are diagnosed with and more than 4 million people die from cancer all over the world, which is approximately 10% of the total mortality. The incidence of cancer in Ukraine shows a gradual increase, with the number of newly diagnosed patients 304-308 per 100 thousand people. Bladder cancer ranks second in the world among oncological diseases of the urinary system after prostate cancer. In the later stages of diseases, their course may be associated with malignant neoplasm anemia. The purpose of the study was to study the content of 2,3-diphosphoglycerate in erythrocytes of peripheral venous blood of patients with malignant neoplasm anemia with urothelial bladder cancer and prostate cancer, depending on the severity of anemia; to evaluate the possible diagnostic and prognostic value of the studied indicator. Materials and methods. 96 patients (64 men and 32 women) with urothelial bladder cancer were examined. There were 39 patients (28 men and 11 women) among them, the course of their underlying disease was not accompanied by the presence of anemia (first (I) observation group) and 57 patients (36 men and 21 women), the course of their underlying disease was aggravated by malignant neoplasm anemia (second (II) observation group). Also, 48 men with prostate cancer whose course of the disease was not aggravated by malignant neoplasm anemia (19 men) (third (III) observation group) and 29 men (fourth (IV) observation group) were diagnosed with malignant neoplasm anemia. The age of the patients under the survey was from 22 to 79 years old. All patients were examined after verifying the diagnosis and before starting any treatment. The content of 2,3-diphosphoglycerate in erythrocytes of peripheral venous blood was determined by the method of I. S. Luganova, M. N. Blinov (1975). Results and discussion. The content of 2,3-diphosphoglycerate in peripheral venous erythrocytes of patients with malignant neoplasm anemia due to urothelial bladder cancer and prostate cancer has been studied. It was found that malignant neoplasm anemia in patients with urothelial bladder cancer and prostate cancer is associated with an increase in the studied indicator (p<0.05). The article discusses the possible causes and pathogenetic mechanisms of the identified changes. Conclusion. Patients with urothelial bladder cancer and prostate cancer have an imbalance of energy metabolism that occurs in erythrocytes. This process is manifested by an increase in the amount of 2,3-diphosphoglycerate