EDCs and male urogenital cancers

2021 ◽  
pp. 521-553
Author(s):  
M.S. Bornman ◽  
N.H. Aneck-Hahn
Keyword(s):  
Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 535
Author(s):  
Anouk E. Hentschel ◽  
Rianne van den Helder ◽  
Nienke E. van Trommel ◽  
Annina P. van Splunter ◽  
Robert A. A. van Boerdonk ◽  
...  

In urogenital cancers, urine as a liquid biopsy for non-invasive cancer detection holds great promise for future clinical application. Their anatomical position allows for the local shedding of tumor DNA, but recent data indicate that tumor DNA in urine might also result from transrenal excretion. This study aims to assess the origin of tumor-associated DNA in the urine of 5 bladder and 25 cervical cancer patients. Besides natural voided urine, paired urine samples were collected in which contact with the local tumor was circumvented to bypass local shedding. The latter concerned nephrostomy urine in bladder cancer patients, and catheter urine in cervical cancer patients. Methylation levels of GHSR, SST, and ZIC1 were determined using paired bladder tumor tissues and cervical scrapes as a reference. Urinary methylation levels were compared to natural voided urine of matched controls. To support methylation results, mutation analysis was performed in urine and tissue samples of bladder cancer patients. Increased methylation levels were not only found in natural voided urine from bladder and cervical cancer patients, but also in the corresponding nephrostomy and catheter urine. DNA mutations detected in bladder tumor tissues were also detectable in all paired natural voided urine as well as in a subset of nephrostomy urine. These results provide the first evidence that the suitability of urine as a liquid biopsy for urogenital cancers relies both on the local shedding of tumor cells and cell fragments, as well as the transrenal excretion of tumor DNA into the urine.


1984 ◽  
Vol 132 (6) ◽  
pp. 1256-1261 ◽  
Author(s):  
Alice S. Whittemore ◽  
Ralph S. Paffenbarger ◽  
Keaven Anderson ◽  
Jeffrey E. Lee

2020 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Leendert H.J. Looijenga ◽  
Theodorus H. Van der Kwast ◽  
David Grignon ◽  
Lars Egevad ◽  
Glen Kristiansen ◽  
...  

2020 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Sofía Canete-Portillo ◽  
Elsa F. Velazquez ◽  
Glen Kristiansen ◽  
Lars Egevad ◽  
David Grignon ◽  
...  

2012 ◽  
Vol 30 (30_suppl) ◽  
pp. 50-50
Author(s):  
Shanna Arnold ◽  
Celestial Jones-Paris ◽  
Amanda Georgia Hansen ◽  
Oluwole Fadare ◽  
Peter Clark ◽  
...  

50 Background: ALCAM (Activated Leukocyte Cell Adhesion Molecule) is thought to be involved in tumor cell adhesion, migration and metastasis. The ectodomain responsible for adhesion is proteolytically shed. Elevated shedding of ALCAM ectodomain is associated with malignant progression. Considering the proximity of urogentical cancer to both urinary secretions and hematogenous circulation we investigated if ALCAM shed into urine and/or blood could act as a prognostic or diagnostic marker of disease and patient outcome. Methods: Shed ALCAM in serum and urine was measured by ELISA while ALCAM shedding in tissues was detected with a unique immunohistochemical approach. ALCAM shedding was correlated with patient parameters including tumor stage, metastasis, recurrence, overall and disease-specific survival. Results: ALCAM shedding was compared across tissue and fluids from normal age-matched healthy adults, non-urological neoplasia, and non-cancer patients. Elevated ALCAM shedding was readily detected in fluids and tissue from patients with urogenital cancers. However, only the detection of shedding in tissue and urine correlated significantly with disease progression and patient outcome. Specifically, shed ALCAM detected in urine collected from bladder cancer patients undergoing cystectomy (Vanderbilt 2000-2010) correlated strongly with patient outcome. Urine ALCAM correlates positively with invasiveness (80%), and is predictive of recurrence as well as survival (HR=10.2 and 2.9). Urinary ALCAM ROC curves show the optimal sensitivity and specificity of predicting recurrence (90 and 68%) and survival (62 and 83%). Conclusions: We show for the first time that cleaved ALCAM is detectable in the urine and that urinary ALCAM is a novel biomarker in urogenital cancers. ALCAM shedding is marker of cancer progression and patient outcome with high specificity and accuracy. Evaluating levels of shed ALCAM in urine offers a unique and effective method to diagnose, assess, and stratify patients with urogenital cancers. We find this correlation particularly exciting because ALCAM is functionally involved in cancer progression and therefore reports on cellular behavior rather than mere presence of neoplastic disease.


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