scholarly journals The role of estradiol metabolism in urogenital schistosomiasis-induced bladder cancer

Tumor Biology ◽  
2017 ◽  
Vol 39 (3) ◽  
pp. 101042831769224 ◽  
Author(s):  
Nuno Vale ◽  
Maria J Gouveia ◽  
Gabriel Rinaldi ◽  
Júlio Santos ◽  
Lúcio Lara Santos ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Schistosoma Haematobium ◽  
Infectious Agent ◽  
Suppressor Gene ◽  
Urogenital Schistosomiasis ◽  
P53 Expression ◽  
Estradiol Metabolism ◽  
Shed Light ◽  
Tumor Suppressor Gene P53

Urogenital schistosomiasis is a neglected tropical disease that can lead to bladder cancer. How urogenital schistosomiasis induces carcinogenesis remains unclear, although there is evidence that the human blood fluke Schistosoma haematobium, the infectious agent of urogenital schistosomiasis, releases estradiol-like metabolites. These kind of compounds have been implicated in other cancers. Aiming for enhanced understanding of the pathogenesis of the urogenital schistosomiasis-induced bladder cancer, here we review, interpret, and discuss findings of estradiol-like metabolites detected in both the parasite and in the human urine during urogenital schistosomiasis. Moreover, we predict pathways and enzymes that are involved in the production of these metabolites emphasizing their potential effects on the dysregulation of the tumor suppressor gene p53 expression during urogenital schistosomiasis. Enhanced understanding of these potential carcinogens may not only shed light on urogenital schistosomiasis-induced neoplasia of the bladder, but would also facilitate development of interventions and biomarkers for this and other infection-associated cancers at large.

scholarly journals IPSE, an Abundant Egg-Secreted Protein of the Carcinogenic Helminth Schistosoma haematobium, Promotes Proliferation of Bladder Cancer Cells and Angiogenesis

2020 ◽  
Author(s):  
Evaristus C. Mbanefo ◽  
Chinwike Terry Agbo ◽  
Yuanlong Zhao ◽  
Olivia K. Lamanna ◽  
Kimberly H. Thai ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Schistosoma Haematobium ◽  
Causal Link ◽  
Urothelial Cell ◽  
Cell Uptake ◽  
Interleukin 4 ◽  
Nuclear Localization Sequence ◽  
Urothelial Cells ◽  
Cell Nuclei ◽  
Urogenital Schistosomiasis

Abstract Background: Schistosoma haematobium, the helminth causing urogenital schistosomiasis, is a known bladder carcinogen. Despite the causal link between S. haematobium and bladder cancer, the underlying mechanisms are poorly understood. S. haematobium oviposition in the bladder is associated with angiogenesis and urothelial hyperplasia. These changes may be pre-carcinogenic events in the bladder. We hypothesized that the Interleukin-4-inducing principle of Schistosoma mansoni eggs (IPSE), an S. haematobium egg-secreted “infiltrin” protein that enters host cell nuclei to alter cellular activity, is sufficient to induce angiogenesis and urothelial hyperplasia. Methods: Mouse bladders injected with S. haematobium eggs were analyzed via microscopy for angiogenesis and urothelial hyperplasia. Endothelial and urothelial cell lines were incubated with recombinant IPSE protein or an IPSE mutant protein that lacks the native nuclear localization sequence (NLS-) and proliferation measured using CFSE staining and real-time monitoring of cell growth. IPSE’s effects on urothelial cell cycle status was assayed through propidium iodide staining. Endothelial and urothelial cell uptake of fluorophore-labeled IPSE was measured. Findings: Injection of S. haematobium eggs into the bladder triggers angiogenesis, enhances leakiness of bladder blood vessels, and drives urothelial hyperplasia. Wild type IPSE, but not NLS-, increases proliferation of endothelial and urothelial cells and skews urothelial cells towards S phase. Finally, IPSE is internalized by both endothelial and urothelial cells. Interpretation: IPSE drives endothelial and urothelial proliferation, which may depend on internalization of the molecule. The urothelial effects of IPSE depend upon its NLS. Thus, IPSE is a candidate pro-carcinogenic molecule of S. haematobium.

A Study on the Etiological Factors of Bilharzial Bladder Cancer in Egypt. 6. The Possible Role of Urinary Bacteria

1982 ◽  
Vol 68 (1) ◽  
pp. 23-28 ◽  
Author(s):  
Abdelbaset Anwer El-Aaser ◽  
Mahmoud Mohamed El-Merzabani ◽  
Nadia Ahmed Higgy ◽  
Abdel E. El-Habet
Keyword(s):  
Escherichia Coli ◽  
Bladder Cancer ◽  
Enzyme Activity ◽  
Nitrate Reductase ◽  
Bacterial Infection ◽  
Schistosoma Haematobium ◽  
Nitrate Reductase Activity ◽  
Reductase Activity ◽  
Glucuronidase Activity

A correlation was obtained between a positive nitrite test in urine and the severity of urinary bacterial infection. Bacteria isolated from the urine of bilharzial or bladder cancer patients were found to be rich in nitrate reductase activity. « Escherichia coli » was the most common microorganism isolated from these specimens. Urine and several urinary constituents activate bacterial nitrate reductase. β-Glucuronidase activity in the urine of patients with chronic « Schistosoma haematobium » infection and bladder cancer was measured and shown to be significantly greater than that of urine of normal control subjects. Urinary bacterial infection was shown to be the source of the increased urinary level of enzyme activity at pH 7.0.

A Study on the Etiological Factors of Bilharzial Bladder Cancer in Egypt: 5-Urinary Nitrite in a Rural Population

1980 ◽  
Vol 66 (4) ◽  
pp. 409-414 ◽  
Author(s):  
Abdelbaset Anwer El-Aaser ◽  
Mahmoud Mohamed El-Merzabani ◽  
Mohamed Nabil El-Bolkainy ◽  
Amal Sami Ibrahim ◽  
Nadia Iskander Zakhary ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Bacterial Infection ◽  
Rural Population ◽  
Schistosoma Haematobium ◽  
Urinary Infection ◽  
Etiological Factors ◽  
Cellular Atypia ◽  
Bladder Carcinogenesis

Urinary nitrite was present in 5.6 % of 2379 individuals from a rural population infested with « Schistosoma haematobium ». A higher frequency was observed in symptomatic patients with active bilharzial cystitis (25 %) and patients with bladder cancer associated with schistosomiasis (66.2 %); conversely, urinary nitrite was absent in normal urban individuals. The frequency of urinary nitrite was higher in females (6.4%) than males (4.6%), and was more frequent in adults than extremes of age. The presence of urinary nitrite was associated with urinary infection and was commonly accompaned by cellular atypia in urine, in the form of dysplasia. Under these circumstances, carcinogenic nitrosamines are liable to be produced in the bladder from urinary nitrite and amines. These observation support the possible role of urinary bacterial infection, commonly associated with bilharzial cystitis, in bladder carcinogenesis.

scholarly journals Cytological and Wet Mount Microscopic Observations Made in Urine of Schistosoma haematobium-Infected Children: Hint of the Implication in Bladder Cancer

2019 ◽  
Vol 2019 ◽  
pp. 1-8
Author(s):  
Patience B. Tetteh-Quarcoo ◽  
Benjamin K. Akuetteh ◽  
Irene A. Owusu ◽  
Solomon E. Quayson ◽  
Simon K. Attah ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Schistosoma Haematobium ◽  
Inflammatory Cells ◽  
Sub Saharan Africa ◽  
Urine Samples ◽  
Urogenital Schistosomiasis ◽  
Cytological Abnormalities ◽  
Sub Saharan ◽  
Carcinoma Of The Bladder ◽  
Infected Urine

Background. Schistosomiasis is the second major human parasitic disease next to malaria, in terms of socioeconomic and public health consequences, especially in sub-Saharan Africa. Schistosoma haematobium (S. haematobium) is a trematode and one of the species of Schistosoma that cause urogenital schistosomiasis (urinary schistosomiasis). Although the knowledge of this disease has improved over the years, there are still endemic areas, with most of the reported cases in Africa, including Ghana. Not much has been done in Ghana to investigate cytological abnormalities in individuals within endemic communities, although there are epidemiologic evidences linking S. haematobium infection with carcinoma of the bladder. Aim. The aim of this study was to identify microscopic and cytological abnormalities in the urine deposits of S. haematobium-infected children. Methodology. Three hundred and sixty-seven (367) urine samples were collected from school children in Zenu and Weija communities. All the samples were examined microscopically for the presence of S. haematobium eggs, after which the infected samples and controls were processed for cytological investigation. Results. S. haematobium ova were present in 66 (18.0%) out of the 367 urine samples. Inflammatory cells (82%, 54/66), hyperkeratosis (47%, 31/66), and squamous cell metaplasia (24%, 16/66) were the main observations made during the cytological examination of the S. haematobium-infected urine samples. Conclusion. Cytological abnormalities in S. haematobium-infected children may play an important role in the severity of the disease, leading to the possible development of bladder cancer in later years, if early attention is not given. Therefore, routine cytological screening for urogenital schistosomiasis patients (especially children) at hospitals in S. haematobium-endemic locations is recommended.

scholarly journals IPSE, an Abundant Egg-Secreted Protein of the Carcinogenic Helminth Schistosoma haematobium, Promotes Proliferation of Bladder Cancer Cells and Angiogenesis

2020 ◽  
Author(s):  
Evaristus C. Mbanefo ◽  
Chinwike Terry Agbo ◽  
Yuanlong Zhao ◽  
Olivia K. Lamanna ◽  
Kimberly H. Thai ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Schistosoma Haematobium ◽  
Causal Link ◽  
Urothelial Cell ◽  
Cell Uptake ◽  
Interleukin 4 ◽  
Nuclear Localization Sequence ◽  
Urothelial Cells ◽  
Cell Nuclei ◽  
Urogenital Schistosomiasis

Abstract Background: Schistosoma haematobium, the helminth causing urogenital schistosomiasis, is a known bladder carcinogen. Despite the causal link between S. haematobium and bladder cancer, the underlying mechanisms are poorly understood. S. haematobium oviposition in the bladder is associated with angiogenesis and urothelial hyperplasia. These changes may be pre-carcinogenic events in the bladder. We hypothesized that the Interleukin-4-inducing principle of Schistosoma mansoni eggs (IPSE), an S. haematobium egg-secreted “infiltrin” protein that enters host cell nuclei to alter cellular activity, is sufficient to induce angiogenesis and urothelial hyperplasia.Methods: Mouse bladders injected with S. haematobium eggs were analyzed via microscopy for angiogenesis and urothelial hyperplasia. Endothelial and urothelial cell lines were incubated with recombinant IPSE protein or an IPSE mutant protein that lacks the native nuclear localization sequence (NLS-) and proliferation measured using CFSE staining and real-time monitoring of cell growth. IPSE’s effects on urothelial cell cycle status was assayed through propidium iodide staining. Endothelial and urothelial cell uptake of fluorophore-labeled IPSE was measured. Findings: Injection of S. haematobium eggs into the bladder triggers angiogenesis, enhances leakiness of bladder blood vessels, and drives urothelial hyperplasia. Wild type IPSE, but not NLS-, increases proliferation of endothelial and urothelial cells and skews urothelial cells towards S phase. Finally, IPSE is internalized by both endothelial and urothelial cells. Interpretation: IPSE drives endothelial and urothelial proliferation, which may depend on internalization of the molecule. The urothelial effects of IPSE depend upon its NLS. Thus, IPSE is a candidate pro-carcinogenic molecule of S. haematobium.

Molecular Pathogenesis of Adenocarcinomas in Barrett’s Esophagus: Role of the Tumor Suppressor Gene p53

1997 ◽  
Vol 20 (1) ◽  
pp. 36-40
Author(s):  
P.M. Schneider ◽  
A.G. Casson ◽  
A.H. Hölscher ◽  
S. Schweighart ◽  
S. Mizumoto ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Barrett’S Esophagus ◽  
Barrett's Esophagus ◽  
Suppressor Gene ◽  
Molecular Pathogenesis ◽  
Tumor Suppressor Gene P53

scholarly journals IPSE, an abundant egg-secreted protein of the carcinogenic helminth Schistosoma haematobium, promotes proliferation of bladder cancer cells and angiogenesis

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Evaristus C. Mbanefo ◽  
Chinwike Terry Agbo ◽  
Yuanlong Zhao ◽  
Olivia K. Lamanna ◽  
Kim H. Thai ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Schistosoma Haematobium ◽  
Causal Link ◽  
Urothelial Cell ◽  
Cell Uptake ◽  
Interleukin 4 ◽  
Nuclear Localization Sequence ◽  
Urothelial Cells ◽  
Cell Nuclei ◽  
Urogenital Schistosomiasis

Abstract Background Schistosoma haematobium, the helminth causing urogenital schistosomiasis, is a known bladder carcinogen. Despite the causal link between S. haematobium and bladder cancer, the underlying mechanisms are poorly understood. S. haematobium oviposition in the bladder is associated with angiogenesis and urothelial hyperplasia. These changes may be pre-carcinogenic events in the bladder. We hypothesized that the Interleukin-4-inducing principle of Schistosoma mansoni eggs (IPSE), an S. haematobium egg-secreted “infiltrin” protein that enters host cell nuclei to alter cellular activity, is sufficient to induce angiogenesis and urothelial hyperplasia. Methods: Mouse bladders injected with S. haematobium eggs were analyzed via microscopy for angiogenesis and urothelial hyperplasia. Endothelial and urothelial cell lines were incubated with recombinant IPSE protein or an IPSE mutant protein that lacks the native nuclear localization sequence (NLS-) and proliferation measured using CFSE staining and real-time monitoring of cell growth. IPSE’s effects on urothelial cell cycle status was assayed through propidium iodide staining. Endothelial and urothelial cell uptake of fluorophore-labeled IPSE was measured. Findings: Injection of S. haematobium eggs into the bladder triggers angiogenesis, enhances leakiness of bladder blood vessels, and drives urothelial hyperplasia. Wild type IPSE, but not NLS-, increases proliferation of endothelial and urothelial cells and skews urothelial cells towards S phase. Finally, IPSE is internalized by both endothelial and urothelial cells. Interpretation: IPSE drives endothelial and urothelial proliferation, which may depend on internalization of the molecule. The urothelial effects of IPSE depend upon its NLS. Thus, IPSE is a candidate pro-carcinogenic molecule of S. haematobium. Summary Schistosoma haematobium acts as a bladder carcinogen through unclear mechanisms. The S. haematobium homolog of IPSE, a secreted schistosome egg immunomodulatory molecule, enhances angiogenesis and urothelial proliferation, hallmarks of pre-carcinogenesis, suggesting IPSE is a key pro-oncogenic molecule of S. haematobium.

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