Screening for urinary markers predicting hematopoietic stem cell injury induced by busulfan using genetically diverse mice

Background:Busulfan(BU)is an alkylating agent used as a conditioning agent prior to hematopoietic stem cell(HSC)transplantation as it is known to be cytotoxic to host hematopoietic stem and progenitor cells.The susceptibility of HSCs to BU injury plays an important role in the myeloablative efficacy of BU.Different susceptibilities were demonstrated in genetically diverse(GD)mice in our preliminary research.Methods:Three strains of GD mice with different susceptibilities to BU-i nduced HSC injury were used for screening biological markers of HSC injury susceptibility in urine.The urine proteins were analyzed using liquid chromatography coupled with tandem mass spectrometry to screen for differentially expressed proteins.Screening for possible biomarkers based on differences in protein expression abundance was validated using enzyme-l inked immunoassay(ELISA).Results:Functional analysis showed that the differential proteins were all involved in a series of biological pathways related to cellular senescence,apoptosis,and angiogenesis;whereas the differential proteins of the high-susceptible strain were enriched for the regulation of bone marrow microenvironment pathways,those of low-susceptible strain were enriched for the proapoptotic effect of GTPase pathways.Based on protein abundance differences,several urinary proteins that may be indicative of susceptibility were screened,and ELISA validation results showed that angiotensin-converting enzyme may be a potential biomarker predicting HSC susceptibility for BU conditioning.Conclusions:This study indicates that urinary protein levels can reflect differences in susceptibility to BU-i nduced HSC injury.Using GD mice to construct genetic difference models will provide preclinical data for screening BU-related biological markers.

Early Results of Urothelial Carcinoma Screening in a Risk Population of Coke Workers:Urothelial Carcinoma among Coke Workers

Objective To present the protocol and the early results of a urothelial carcinoma （UC） screening analysis performed in a risk population of coke workers. Methods Between June 2006 and October 2008, 171 male workers （mean age 43 years）, employed in a Ligurian coke plant （Italiana Coke S.r.l） and exposed to polycyclic aromatic hydrocarbons （PAHs） for a median period of 16 years, underwent screening for UC. Urological evaluation included medical history, physical examination, routine laboratory tests, urine analysis, urinary cytology and uCyt＋ assay. In the event of signs and symptoms suggestive of UC or positive urinary tests, the workers were also subjected to urinary ultrasonography and cystoscopy with biopsy of any suspicious lesions. Results Regarding the laboratory tests, 19/171 （11%） uCyt＋ samples were considered inadequate and were excluded from the outcomes assessment. Overall, urine analysis, cytology and uCyt＋ were positive in 18/152 （12%） subjects who showed no evidence of UC at the scheduled check-ups. No significant association was identified between marker positivity and occupational activity. Conclusions Our results fail to show an increased risk of UC among the coke workers evaluated. However, they will need to be confirmed in the future by a larger enrollment and a longer follow-up in order to assess the definitive risk for UC after exposure to coke.