Possible Diagnostic Protein Markers in Schistosoma Related Bladder Diseases.

Sponsor

Assiut University (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05941884

Collaborator

(none)

120

Enrollment

Location

Anticipated Duration (Months)

2.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Schistosomiasis is the second most common parasitic infection affecting humans, endemic in the Middle East, especially Egypt (1), and in 42 African countries (2).

There are 5 main species infecting humans: S. mansoni, S. haematobium, S. japonicum, S. intercalatum, and S. mekongi. S. haematobium is responsible for chronic urogenital infections that may cause serious complications (3). Urinary schistosomiasis is mostly borne in rural and agricultural communities, according to WHO (4)

Condition or Disease	Intervention/Treatment	Phase
Schistosoma Haematobium	Diagnostic Test: Immunohistochemistry staining, Diagnostic Test: microscopic examination of urine

Detailed Description

Bleeding, anemia and chronic renal failure are common presentation. Bladder cancer is associated with schistosomiasis, However the mechanism by which it occurs is still controversial. Chronic interaction with the host immune system as well as association with other carcinogenic agents can lead to the neoplastic transformation (3). The International Agency for Research on Cancer classifies the infection with S. haematobium as a group 1 carcinogen, a definitive cause of cancer (5).

Bladder cancer (BC) is the sixth most prevalent cancer in both genders worldwide. Amongst Egyptian males, bladder cancer is the most common malignancy accounting for 16% with more than 7,900 deaths per year. The main risk factor was urinary schistosomiasis which is more frequent in Upper Egypt (1).

Urothelial carcinoma represents the most common histologic type of BC, accounting for 90% of all cases. Squamous cell carcinoma may develop following bilharziasis infection, in addition other types includes adenocarcinoma and small cell carcinoma were reported (6). The WHO classification includes urothelial papilla, papillary urothelial neoplasm of low malignant potential (PUNLMP), low-grade urothelial carcinoma (LGPUC) and high- grade UC (HGPUC) (7).

Urine cytology is the only established noninvasive adjunct to cystoscopy. Being in close contact with tumor cells and adjacent inflamed urothelium. Thus, immune mediators in urine may serve as biomarkers (8). Urine biomarkers of schistosomal bladder cancer can be used as diagnostic markers in patients, and prognostic indicators of disease survival, and as early detectors of recurrent disease in the monitored patient (9).

Heat shock proteins (HSPs) are synthesized by cells in response to various stress conditions, including carcinogenesis. These molecules have been studied in several malignancies, they may be useful markers for patients with schistosomiasis-associated bladder cancer and may be used for predicting disease progression. (10). HSPs are upregulated when cells are exposed to elevated temperature. In neoplasia, the expression of HSPs is implicated in the regulation of apoptosis and tumor-cell growth, helps tumor to evade immune surveillance. As it has been reported to abort Th1 effector immunity and enhance Th2 down- regulatory immune responses. Thus, downregulate antitumor effector T cells (8). Urine proteome profile provide deeper insights into urogenital schistosomiasis, it's carcinogenesis and highlight potential biomarkers for diagnosis and/or prognosis (11).

Immunohistochemistry (IHC) is currently the most widely used pathological technique for accurate diagnosis of urinary bladder neoplasms. Moreover, identification and validation of the prognostic IHC signature have been reported in various cancer types and proved to be a promising complement in therapeutic planning and patient management (12). As oxidative stress and immune defense systems responsible for microbicide activity are the most representative clusters in urogenital schistosomiasis patients. Proteins involved in immunity, negative regulation of endopeptidase activity, and inflammation were more prevalent in UGS patients with bladder cancer (11).

NF-ƙB was first identified in active B cells by its binding affinity to immunoglobulin enhancer. NF-ƙB serves as dominant modulator of immuno-inflammatory responses. (13). It plays a critical role in normal physiology and bladder cancer progression. NF-ƙB orchestrates protein interactions (PTEN, survivin, VEGF), regulation (CYLD, USP13) and gene expression (Trp 53) resulting in bladder cancer progression, recurrence, and resistance to therapy. Bladder cancer patients have constitutively active NF-ƙB triggered by pro-inflammatory cytokines, chemokines, and hypoxia, augmenting carcinogenesis and progression (14).

Further, Protein kinase C α (PKC) is one of the serine/threonine kinases that regulates a variety of cellular biological process, such as apoptosis. It has been firmly established that PKCs are closely related to process of tumorigenesis, including the initiation and progression of bladder cancer (15). In addition, activated PKC α is involved in bladder cancer cell proliferation, survival, invasion, migration, and anticancer drug resistance (16).

In literature, the evaluation of schistosomal infestation is not precise as it depends on the histopathologic findings, which proved to be less accurate. Most of them focused on the prognostic role of biomarkers rather than their role in diagnosis and pathogenesis.

Our aim in this study is to identify the potential causal relationship between schistosomal infection and levels of NF-kappa-B and Protein kinase C α signaling and bladder cancer development and highlights their role in bladder cancer pathogenesis

Study Design

Study Type:

Observational

Anticipated Enrollment :

120 participants

Observational Model:

Case-Control

Time Perspective:

Other

Official Title:

Possible Diagnostic Protein Markers in Schistosoma Related Bladder Diseases.

Anticipated Study Start Date :

Oct 1, 2023

Anticipated Primary Completion Date :

Jun 30, 2025

Anticipated Study Completion Date :

Oct 30, 2027

Arms and Interventions

Arm	Intervention/Treatment
Schistosoma haematobium cystitis. patient has symptoms suggestive of Schistosoma haematobium infection like terminal hematuria and burning micturition	Diagnostic Test: microscopic examination of urine Urine samples: Mic roscopic examination (detection of S. haematobium egg - egg counting) Detection of HSP 70 Measurements: indirect ELISA will be used to quantify HSP concentrations in urine.
Healthy personnel. as control group	Diagnostic Test: microscopic examination of urine Urine samples: Mic roscopic examination (detection of S. haematobium egg - egg counting) Detection of HSP 70 Measurements: indirect ELISA will be used to quantify HSP concentrations in urine.
Schistosomal bladder cancer. from patient undergone diagnostic cystoscopy and sampling and confirmed pathologically as Schistosomal bladder cancer.	Diagnostic Test: Immunohistochemistry staining, Tissue samples: Histopathological examination: Hematoxylin and Eosin slides will be prepared and examined. The only dependable criterion for the diagnosis of bilharzial infestation is the microscopic detection of Bilharzia ova in pathological sections. Pathology (cystitis- cancer and its grade staging will be reported in accordance with the 2022 World Health Organization Classification of Tumors of the Urinary System (17). To quantify levels of Nuclear factor kappa B and protein kinase c α: Immunohistochemistry according to the manufacturer's instructions. Diagnostic Test: microscopic examination of urine Urine samples: Mic roscopic examination (detection of S. haematobium egg - egg counting) Detection of HSP 70 Measurements: indirect ELISA will be used to quantify HSP concentrations in urine.
non Schistosomal bladder cancer. from patient undergone diagnostic cystoscopy and sampling and confirmed pathologically as non Schistosomal bladder cancer.	Diagnostic Test: Immunohistochemistry staining, Tissue samples: Histopathological examination: Hematoxylin and Eosin slides will be prepared and examined. The only dependable criterion for the diagnosis of bilharzial infestation is the microscopic detection of Bilharzia ova in pathological sections. Pathology (cystitis- cancer and its grade staging will be reported in accordance with the 2022 World Health Organization Classification of Tumors of the Urinary System (17). To quantify levels of Nuclear factor kappa B and protein kinase c α: Immunohistochemistry according to the manufacturer's instructions.
Schistosomal cystitis patients. from patient undergone diagnostic cystoscopy and sampling and confirmed pathologically as Schistosomal cystitis	Diagnostic Test: Immunohistochemistry staining, Tissue samples: Histopathological examination: Hematoxylin and Eosin slides will be prepared and examined. The only dependable criterion for the diagnosis of bilharzial infestation is the microscopic detection of Bilharzia ova in pathological sections. Pathology (cystitis- cancer and its grade staging will be reported in accordance with the 2022 World Health Organization Classification of Tumors of the Urinary System (17). To quantify levels of Nuclear factor kappa B and protein kinase c α: Immunohistochemistry according to the manufacturer's instructions.
healthy bladder tissue from tissue biopsy patient with benign prostatic hyperplasia. as control group	Diagnostic Test: Immunohistochemistry staining, Tissue samples: Histopathological examination: Hematoxylin and Eosin slides will be prepared and examined. The only dependable criterion for the diagnosis of bilharzial infestation is the microscopic detection of Bilharzia ova in pathological sections. Pathology (cystitis- cancer and its grade staging will be reported in accordance with the 2022 World Health Organization Classification of Tumors of the Urinary System (17). To quantify levels of Nuclear factor kappa B and protein kinase c α: Immunohistochemistry according to the manufacturer's instructions.

Outcome Measures

Primary Outcome Measures

NF-kappa-B and Protein kinase Cα [2 years]
Association and changes of NF-kappa-B and Protein kinase Cα as diagnostic markers in chronic schistosomaiasis with or without bladder cancer
heat shock protein [1 year]
Changes of heat shock protein HSP 70 as urinary biomarkers for Schistosomal bladder diseases.

Eligibility Criteria

Criteria

Ages Eligible for Study:

30 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Male and female patients of different age groups known to suffer from cystitis and bladder cancer regardless results from schistosomal infection or any other causes.

Exclusion Criteria:

patients with concomitant other tumours.
patients with other urinary tract infection.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Assiut University Hospital	Assiut		Egypt	Assiut University71515

Sponsors and Collaborators

Assiut University

Investigators

Study Director: Fatma G Sayed, prof, unaffiliation

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:

Samah Mohammad Hussein, Assistant Lecturer at Parasitology department, Assiut University

ClinicalTrials.gov Identifier:

NCT05941884

Other Study ID Numbers:

PDPMSRBD

First Posted:

Jul 12, 2023

Last Update Posted:

Jul 12, 2023

Last Verified:

Jul 1, 2023

Individual Participant Data (IPD) Sharing Statement:

Undecided

Plan to Share IPD:

Undecided

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Urinary Bladder Diseases

Study Results

No Results Posted as of Jul 12, 2023