Entry |
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Name |
Bladder cancer |
Description |
The urothelium covers the luminal surface of almost the entire urinary tract, extending from the renal pelvis, through the ureter and bladder, to the proximal urethra. The majority of urothelial carcinoma are bladder carcinomas, and urothelial carcinomas of the renal pelvis and ureter account for only approximately 7% of the total. Urothelial tumours arise and evolve through divergent phenotypic pathways. Some tumours progress from urothelial hyperplasia to low-grade non-invasive superficial papillary tumours. More aggressive variants arise either from flat, high-grade carcinoma in situ (CIS) and progress to invasive tumours, or they arise de novo as invasive tumours. Low-grade papillary tumors frequently show a constitutive activation of the receptor tyrosine kinase-Ras pathway, exhibiting activating mutations in the HRAS and fibroblast growth factor receptor 3 (FGFR3) genes. In contrast, CIS and invasive tumors frequently show alterations in the TP53 and RB genes and pathways. Invasion and metastases are promoted by several factors that alter the tumour microenvironment, including the aberrant expression of E-cadherins (E-cad), matrix metalloproteinases (MMPs), angiogenic factors such as vascular endothelial growth factor (VEGF).
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Category |
Cancer
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Brite |
Human diseases [BR:br08402]
Cancers
Cancers of the urinary system
H00022 Bladder cancer
Human diseases in ICD-11 classification [BR:br08403]
02 Neoplasms
Malignant neoplasms, except of lymphoid, haematopoietic, central nervous system or related tissues
Malignant neoplasms, stated or presumed to be primary, of specified sites, except of lymphoid, haematopoietic, central nervous system or related tissues
Malignant neoplasms of urinary tract
2C94 Malignant neoplasms of bladder
H00022 Bladder cancer
Tumor markers [br08442.html]
H00022
Cancer-associated carbohydrates [br08441.html]
H00022
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Pathway |
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Network |
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Element |
N00006 | Amplified EGFR to RAS-ERK signaling pathway |
N00011 | Mutation-activated FGFR3 to RAS-ERK signaling pathway |
N00022 | ERBB2-overexpression to RAS-ERK signaling pathway |
N00041 | EGFR-overexpression to RAS-ERK signaling pathway |
N00067 | Deleted p14(ARF) to p21-cell cycle G1/S |
N00071 | Deleted p16(INK4a) to p16-cell cycle G1/S |
N00074 | Loss of RB1 to cell cycle G1/S |
N00075 | Mutation-inactivated RB1 to cell cycle G1/S |
N00077 | HRAS-overexpression to ERK signaling pathway |
N00078 | Mutation-activated HRAS to ERK signaling pathway |
N00115 | Mutation-inactivated TP53 to transcription |
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Gene |
H-ras (activating mutation) [HSA: 3265] [KO: K02833]
FGFR3 (activating mutation) [HSA: 2261] [KO: K05094]
p16/INK4A (homozygous deletion or hypermethylation) [HSA: 1029] [KO: K06621]
p53 (inactivating mutation or deletion) [HSA: 7157] [KO: K04451]
RB1 (deletion or hyperphosphorylation) [HSA: 5925] [KO: K06618]
EGFR (overexpression) [HSA: 1956] [KO: K04361]
ERBB2 (overexpression) [HSA: 2064] [KO: K05083]
RASSF1 (hypermethylation) [HSA: 11186] [KO: K09850]
DAPK1 (hypermethylation) [HSA: 1612] [KO: K08803]
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Carcinogen |
Aluminium production
4-Aminobiphenyl [CPD: C10998]
Arsenic in drinking-water
Auramine, manufacture of
Benzidine [CPD: C16444]
Benzo[a]pyrene [CPD: C07535]
N,N-Bis(2-chloroethyl)-2-naphthylamine (Chlornaphazine)
Coal gasification
Coal-tar pitches [CPD: C16451]
Coal-tars
Herbal remedies containing plant species of the genus Aristolochia
Magenta, manufacture of
2-Naphthylamine [CPD: C02227]
Paving and roofing with coal-tar pitch
Radium-224 and its decay products [CPD: C16455]
Schistosoma haematobium (infection with)
Shale-oils [CPD: C16458]
Tobacco smoking and tobacco smoke
X- and gamma-radiation
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Drug |
Thiotepa [DR: D00583]
Doxorubicin hydrochloride [DR: D01275]
Valrubicin [DR: D02697]
Mitomycin [DR: D00208]
Erdafitinib [DR: D10927] (FGFR3 or FGFR2 genetic alterations)
Cisplatin [DR: D00275]
Nivolumab [DR: D10316]
Pembrolizumab [DR: D10574] (PD-L1 expressed)
Durvalumab [DR: D10808]
Avelumab [DR: D10817]
Atezolizumab [DR: D10773] (PD-L1 expressed)
Enfortumab vedotin [DR: D11525]
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Comment |
ICD-O: 8120/3, Tumor type: Infiltrating urothelial carcinoma
ICD-O: 8120/2, Tumor type: Urothelial carcinoma in situ
ICD-O: 8130/23, Tumor type: Non-invasive papillary urothelial carcinoma, high grade
ICD-O: 8130/21, Tumor type: Non-invasive papillary urothelial carcinoma, low grade
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Other DBs |
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Reference |
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Authors |
Wu XR. |
Title |
Urothelial tumorigenesis: a tale of divergent pathways. |
Journal |
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Reference |
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Authors |
Sugano K, Kakizoe T. |
Title |
Genetic alterations in bladder cancer and their clinical applications in molecular tumor staging. |
Journal |
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Reference |
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Authors |
Wolff EM, Liang G, Jones PA. |
Title |
Mechanisms of Disease: genetic and epigenetic alterations that drive bladder cancer. |
Journal |
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Reference |
|
Authors |
Mitra AP, Datar RH, Cote RJ. |
Title |
Molecular pathways in invasive bladder cancer: new insights into mechanisms, progression, and target identification. |
Journal |
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Reference |
|
Authors |
Schottenfeld D, Beebe-Dimmer JL. |
Title |
Advances in cancer epidemiology: understanding causal mechanisms and the evidence for implementing interventions. |
Journal |
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Reference |
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Authors |
Boffetta P, Jourenkova N, Gustavsson P. |
Title |
Cancer risk from occupational and environmental exposure to polycyclic aromatic hydrocarbons. |
Journal |
|
Reference |
|
Authors |
Luch A. |
Title |
Nature and nurture - lessons from chemical carcinogenesis. |
Journal |
|
Reference |
|
Authors |
Burger MS, Torino JL, Swaminathan S. |
Title |
DNA damage in human transitional cell carcinoma cells after exposure to the proximate metabolite of the bladder carcinogen 4-aminobiphenyl. |
Journal |
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Reference |
|
Authors |
Rossman TG. |
Title |
Mechanism of arsenic carcinogenesis: an integrated approach. |
Journal |
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Reference |
|
Authors |
Vineis P, Pirastu R. |
Title |
Aromatic amines and cancer. |
Journal |
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Reference |
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Authors |
Golka K, Wiese A, Assennato G, Bolt HM. |
Title |
Occupational exposure and urological cancer. |
Journal |
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Reference |
|
Authors |
Abnet CC. |
Title |
Carcinogenic food contaminants. |
Journal |
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Reference |
|
Authors |
Olfert SM, Felknor SA, Delclos GL. |
Title |
An updated review of the literature: risk factors for bladder cancer with focus on occupational exposures. |
Journal |
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Reference |
|
Authors |
Verma DK, Purdham JT, Roels HA. |
Title |
Translating evidence about occupational conditions into strategies for prevention. |
Journal |
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Reference |
|
Authors |
Nortier JL, Vanherweghem JL. |
Title |
Renal interstitial fibrosis and urothelial carcinoma associated with the use of a Chinese herb (Aristolochia fangchi). |
Journal |
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Reference |
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Authors |
Zhou S, Koh HL, Gao Y, Gong ZY, Lee EJ. |
Title |
Herbal bioactivation: the good, the bad and the ugly. |
Journal |
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Reference |
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Authors |
Stern FB, Ruder AM, Chen G. |
Title |
Proportionate mortality among unionized roofers and waterproofers. |
Journal |
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Reference |
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Authors |
Nekolla EA, Kellerer AM, Kuse-Isingschulte M, Eder E, Spiess H. |
Title |
Malignancies in patients treated with high doses of radium-224. |
Journal |
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Reference |
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Authors |
Wogan GN, Hecht SS, Felton JS, Conney AH, Loeb LA. |
Title |
Environmental and chemical carcinogenesis. |
Journal |
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Reference |
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Authors |
Sasco AJ, Secretan MB, Straif K. |
Title |
Tobacco smoking and cancer: a brief review of recent epidemiological evidence. |
Journal |
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Reference |
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Authors |
Berrington de Gonzalez A, Darby S. |
Title |
Risk of cancer from diagnostic X-rays: estimates for the UK and 14 other countries. |
Journal |
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LinkDB |
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