Naslov
CD4 T Cell Knockout Worsens Lung Cancer and Has No Effect on Cisplatin-Induced AKI in Mice

Autori
Ravichandran, Kameswaran ; Kim, Hyun-Jung ; Ozkok, Abdullah ; Wang, Qian ; Nguyen, Quocan ; Jani, Alkesh ; Nemenoff, Raphael A. ; Li, Howard Y. ; Galešić Ljubanović, Danica ; Edelstein, Charles L.

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
J Am Soc Nephrol / - , 2014

Skup
ASN Kidney Week 2014

Mjesto i datum
Philadelphia (PA), Sjedinjene Američke Države, 11.11.2014. - 16.11.2014

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
CD4 T Cell Knockout; Lung Cancer; Cisplatin-Induced AKI

Sažetak
Background: We have developed a model of 4 week, low dose cisplatin (Cis)-induced AKI in mice with cancer that closely resembles the Cis dosing regimen used in humans with non small cell lung cancer. In the 4 week model of AKI, there is an increase in CD4 T cells that precedes the AKI and tubular injury suggesting that CD4 T cells may play a causative role. The aim of the study was to determine the effect of CD4 T cell depletion on AKI and the growth of lung cancer. Methods: Wild type (WT) C57BL/6 or CD4 T cell -/- mice were injected with lung cancer cells in to the flank at day 1 subcutaneously. Ten days later, Cis (10 mg/kg/week) was given for 4 weeks. Results: The decrease in BUN and SCr in CD4-/- mice vs. WT mice with AKI was not statistically significant. Tumor weight was double in CD4 -/- mice. Cis prevented the increase in tumor volume in WT mice but not in CD4-/- mice. Tumors in CD4- /- mice started enlarging at 1 week and were significantly larger at 4 weeks. To determine the mechanism of increased tumor growth, perforin (perf), granzymeB (grB) and cleaved caspase-3 (CC3) that decrease tumor growth by increasing apoptosis were measured by immunoblot . Perf, GrB were decreased in CD4-/- vs. WT tumors. CC3 was increased by Cis in WT but not CD4-/- tumors. Despite larger tumors, CC3 was increased in CD4- /- vs. WT tumors. Conclusions: CD4-/- mice with AKI are not protected against AKI. Increased tumor growth in CD4-/- tumors is associated with decreased perf and grB. Cis increases CC3 in WT but not CD4-/- tumors ( may explain less effect of Cis in -/- tumors) . CC3 is increased in larger CD4-/- tumors perhaps as a compensatory response.

Izvorni jezik
Engleski

Znanstvena područja
Kliničke medicinske znanosti

POVEZANOST RADA