Schistosoma-associated Bladder Cancer Research Articles

Molecular Docking and Dynamics Simulation Revealed Ivermectin as Potential Drug against Schistosoma-Associated Bladder Cancer Targeting Protein Signaling: Computational Drug Repositioning Approach.

Urogenital schistosomiasis is caused by Schistosoma haematobium (S. haematobium) infection, which has been linked to the development of bladder cancer. In this study, three repurposing drugs, ivermectin, arteether and praziquantel, were screened to find the potent drug-repurposing candidate against the Schistosoma-associated bladder cancer (SABC) in humans by using computational methods. The biology of most glutathione S-transferases (GSTs) proteins and vascular endothelial growth factor (VEGF) is complex and multifaceted, according to recent evidence, and these proteins actively participate in many tumorigenic processes such as cell proliferation, cell survival and drug resistance. The VEGF and GSTs are now widely acknowledged as an important target for antitumor therapy. Thus, in this present study, ivermectin displayed promising inhibition of bladder cancer cells via targeting VEGF and GSTs signaling. Moreover, molecular docking and molecular dynamics (MD) simulation analysis revealed that ivermectin efficiently targeted the binding pockets of VEGF receptor proteins and possessed stable dynamics behavior at binding sites. Therefore, we proposed here that these compounds must be tested experimentally against VEGF and GST signaling in order to control SABC. Our study lies within the idea of discovering repurposing drugs as inhibitors against the different types of human cancers by targeting essential pathways in order to accelerate the drug development cycle.

Protocols for Preparation and Mass Spectrometry Analysis of Clinical Urine Samples to Identify Candidate Biomarkers of Schistosoma-Associated Bladder Cancer.

Advances in mass spectrometry instrumentation have revolutionized analytical capability in clinical proteomics. In parallel, various sample preparation methods have been developed to try to address the inherent complexity and dynamic range of clinical samples, typically involving a combination of depletion of abundant proteins followed by extensive prefractionation. However, the depth of coverage routinely achieved in discovery proteomics experiments on peripheral fluids such as serum, still leaves something to be desired, especially if no depletion or prefractionation is done in order to increase the throughput of clinical samples. Remarkably, despite being an easily accessible, typically sterile and diagnostically rich clinical sample, urine is often overlooked and as such has received less development effort. As an ultrafiltrate of blood, urine contains proteins and protein fragments originating from all parts of the body which may have diagnostic or prognostic potential if accurately and reproducibly quantified. Here, we describe an efficient and simple method for the concentration of urine samples by methanol-chloroform precipitation and subsequent in-solution tryptic digestion prior to discovery or targeted mass spectrometry analysis. We exemplify this method by reference to the discovery of novel candidate urinary biomarkers of schistosomiasis. Importantly, the methods described here have been used to identify >1900 protein groups in human urine by label-free discovery proteomics, without requiring any prior depletion or prefractionation, making this approach amenable to high throughput clinical biomarker studies in many diseases.

New Horizons for Observation of Patients with the Bladder Cancer Associated with Schistosoma haematobium Invasion

Background and Purpose: The aim of the study was to improve the diagnostic and treatment approach for the medical care for patients with Schistosoma-associated bladder cancer (SA-BC). Material and Methods: The survey results the study of 56 patients with gross hematuria in medical institutions of the Province Benguela (Angola) since 2007 to 2012. Group A (n=35) included patients before applying the standardized diagnostic algorithm. Group B (n=21) included patients using the new organizational format, in hospital outpatient’s. Results: The progression to locally advanced stage of SA-BC was verified at significantly higher rate (80%). In patients from group A, while verified locally advanced SA-BC stays at low level (66,7%) in group B. Conclusion: The combined usage of urine cytology test, ultrasonography and cystoscopy at the increased proliferative process caused by Schistosoma haematobium (SH) allows to reveal diagnose SA-BC in early stages, subject to on condition of patient’s admission in hospital outpatient care structures of specialized medical institutions.

Patterns of schistosoma-associated bladder cancer in Egypt: A retrospective study

Patterns of schistosoma-associated bladder cancer in Egypt: A retrospective study

Schistosomiasis and bladder cancer: similarities and differences from urothelial cancer

Through the years, schistosoma-associated bladder cancer was believed to be a unique entity of disease, different from urothelial cancer. As carcinogenesis is a highly complex process resulting from the accumulation of many genetic and epigenetic changes leading to alterations in the cell proliferation and regulation process, confirmation of their minute differences or similarities are extremely difficult. In bladder cancer, many of these carcinogenic cascades were not fully documented in spite of the efforts undertaken. The control of schistosomiasis and the subsequent decrease in the intensity of infestation showed feature changes approaching that of urothelial tumors. However, schistosoma-associated bladder cancer still presents in more advanced stages than schistosoma-non-associated urothelial cancer. Furthermore, many data were collected proving that, upon applying the same treatment protocol and management care, stage-by-stage comparison of the treatment end results were found to be similar in bladder cancer patients with the different etiologies.

Cytogenetic profile of locally advanced and metastatic schistosoma-related bladder cancer and response to chemotherapy

Bladder cancer is a common malignancy in developing countries in which bladder infection with the parasite Schistosoma haematobium is prevalent. Several epidemiological, histopathological, and clinical characteristics of schistosoma-associated bladder cancer suggest that it is distinct from bladder cancer seen in other places in the world. The aim of this study was to extend establishing the cytogenetic profile of this type of malignancy in advanced and metastatic cases, and to demonstrate its relation to the end results of systemic therapy. Fluorescence in situ hybridization was applied to interphase nuclei to detect numerical chromosome changes in 41 patients with bladder cancer. Numerical chromosome aberrations were detected in 27 of 41 cases (66%). In 17 (41%) cases, a gain of chromosome 7 was observed, while losses in chromosomes 9 and 17 were detected in 20 (49%) and 18 (44%) cases, respectively. Loss of chromosome Y was detected in 7 of the 32 male patients included in this study (22%). There was a statistically significant association between stage of the disease and overall survival; Bajorin score and time to disease progression and overall survival; and between response to systemic therapy and time to disease progression and overall survival. The only chromosomal abnormality that had a significant relationship with overall survival was the gain of chromosome 4. When the genetic basis of schistosoma-associated bladder cancer is fully understood, new diagnostic and therapeutic strategies could be developed, which in turn may promote better clinical management and survival.

Changing Patterns (Age, Incidence, and Pathologic Types) of Schistosoma-associated Bladder Cancer in Egypt in the Past Decade

To assess the patterns of schistosomiasis-associated bladder cancer in Egypt from 2001 to 2010 in a retrospective study. Bilharzial bladder carcinoma is the most common cancer, particularly in Egyptian men. Classically, carcinoma in a bilharzial bladder is most commonly of the squamous cell type. During the past decade, certain changes have occurred in the features in Schistosomiasis-associated carcinoma in Egypt with a decline in the frequency of squamous cell carcinoma and increase in the frequency of transitional cell carcinoma. This was a retrospective study of 1932 patients treated at Kasr Al Aini Hospital, Cairo University, from 2001 to 2010. Two groups were selected: group 1 included 1002 patients from 2001 to 2005 and group 2 included 930 patients from 2006 to 2010. The mean patient age increased from 41±11.2 years to 52±8.6 years, and the male/female ratio changed from 5.6:1 to 4.2:1. The incidence of associated bilharziasis decreased from 80% to 50%. A significant increased occurred in transitional cell carcinoma from 20% to 66%, with a significant decrease in squamous cell carcinoma from 73% to 25%. No difference was observed in the tumor stage or grade or incidence of lymph node metastases between the 2 groups. The pattern of incidence of the various histologic types of bladder cancer have changed, with most cases now transitional cell carcinoma, in contrast to the findings in the earlier Egyptian series. Additional studies are encouraged to explain the factors explaining these changes.

Prognostic Value of Cyclooxygenase-2 Expression in Squamous Cell Carcinoma of the Bladder

Inflammation is associated with the pathogenesis of carcinoma, including squamous cell carcinoma of the bladder. Cyclooxygenase-2 is an enzyme that is induced at inflammation sites. We assessed the expression pattern of cyclooxygenase-2 in patients with squamous cell carcinoma of the bladder and determined whether cyclooxygenase-2 expression is associated with clinical outcomes after radical cystectomy. Immunohistochemical staining for cyclooxygenase-2 was done on archival bladder specimens from 152 patients treated with radical cystectomy for squamous cell carcinoma on the Autostainer (DakoCytomation, Carpinteria, California). Bright field microscopy imaging coupled with advanced color detection software was used. Cyclooxygenase-2 was defined as over expressed when greater than 20% cells were positive. We assessed the relationship of cyclooxygenase-2 expression with pathological parameters and clinical outcome. The study included 99 male and 53 female patients with a mean age of 52 years who had squamous cell carcinoma, including 80.9% with bilharziasis. Presenting stage was T2 or greater and presenting grade was GII or less in 93.4% of patients. Median followup was 63.2 months. Cyclooxygenase-2 was over expressed in 74 cystectomy specimens (48.7%) and associated with higher pathological stage (p=0.003) and grade (p=0.049). On multivariate Cox proportional hazards regression analysis cyclooxygenase-2 over expression was associated with disease recurrence (p=0.031) and bladder cancer specific mortality (p=0.046). Cyclooxygenase-2 over expression is associated with pathological stage, grade and worse outcomes after radical cystectomy, suggesting a role in bladder squamous cell carcinoma progression. Our findings support the need for further evaluation of cyclooxygenase-2 and inflammatory signaling pathways, and cyclooxygenase-2 targeted prevention or therapy in patients with bladder squamous cell carcinoma.

Cyclooxygenase-2: a possible target in schistosoma-associated bladder cancer.

To analyse and compare the expression of cyclooxygenase (COX) enzymes in schistosoma-associated bladder cancer, and to determine any association with tumour grade or stage. Sixty paired samples of tumour and adjacent nonmalignant urothelium were identified. There were 25 squamous and 28 transitional cell carcinomas, and seven adenocarcinomas. Serial sections were obtained and a standard three-layer immunohistochemistry protocol, using COX-1- and COX-2-specific mouse monoclonal antibodies, applied. COX-1 was expressed mostly in nonvascular smooth muscle with weak reactivity in malignant and nonmalignant urothelium. Nonmalignant urothelium expressed COX-2 weakly, notably in areas of dysplasia and squamous metaplasia whereas there was a significant increase in COX-2 (P < 0.001) with moderate to strong granular cytoplasmic expression in all three malignant histological types. The COX-2 reactivity was higher in transitional and adenocarcinomas than in squamous cell carcinoma (P < 0.001). Areas of carcinoma in situ showed COX-2 reactivity comparable with that in invasive areas and more intense than that detected in dysplastic or metaplastic urothelium (P < 0.001). There was a statistically significant positive correlation between COX-2 expression and tumour grade (P = 0.0052). COX-2 is over-expressed in schistosoma-associated bladder cancer, consistent with a potential role for COX-2 inhibitors in the prevention and management of this disease.

DNA Copy Number Changes in Schistosoma-Associated and Non- Schistosoma-Associated Bladder Cancer

DNA copy number changes were investigated in 69 samples of schistosoma-associated (SA) and non-schistosoma-associated (NSA) squamous cell carcinoma (SCC) and transitional cell carcinoma (TCC) of the bladder by comparative genomic hybridization (CGH). DNA copy number changes were detected in 47 tumors. SA tumors had more changes than NSA tumors (mean, 7 vs. 4), whereas the number of changes in SCC and TCC tumors was similar. SA tumors displayed more gains than losses (1.7:1), whereas NSA tumors showed an equal number of gains and losses. Changes that were observed at similar frequencies in SCC and TCC, irrespective of the schistosomal status, included gains and high-level amplifications at 1q, 8q, and 20q and losses in 9p and 13q. These changes may be involved in a common pathway for bladder tumor development and progression independent of schistosomal status or histological subtype. Losses in 3p and gains at 5p were seen only in SCC (P < 0.01) and losses in 5q were more frequent in SA-SCC than in other tumors (P < 0.05). However, changes that were more frequent in TCC than those in SCC included gains at 17q (P < 0.01) and losses in 4q (P < 0.05) and 6q (P < 0.01). Gains and high-level amplifications at 5p were seen only in SA-SCC (P < 0. 01), whereas gains and high-level amplifications with minimal common overlapping regions at 11q13 were more frequently seen both in SA-SCC and SA-TCC tumors (P < 0.01). In addition to the above mentioned alterations, several other changes were also seen at lower frequencies. The variations in the DNA copy number changes observed in TCC, SCC, SA, and NSA bladder carcinomas suggest that these tumors have different genetic pathways.