HAMLET treatment delays bladder cancer development.
OBJECTIVE
HAMLET is a protein-lipid complex that kills different types of cancer cells. Recently we observed a rapid reduction in human bladder cancer size after intravesical HAMLET treatment. In this study we evaluated the therapeutic effect of HAMLET in the mouse MB49 bladder carcinoma model.


METHODS
Bladder tumors were established by intravesical injection of MB49 cells into poly L-lysine treated bladders of C57BL/6 mice. Treatment groups received repeat intravesical HAMLET instillations and controls received alpha-lactalbumin or phosphate buffer. Effects of HAMLET on tumor size and putative apoptotic effects were analyzed in bladder tissue sections. Whole body imaging was used to study HAMLET distribution in tumor bearing mice compared to healthy bladder tissue.


RESULTS
HAMLET caused a dose dependent decrease in MB49 cell viability in vitro. Five intravesical HAMLET instillations significantly decreased tumor size and delayed development in vivo compared to controls. TUNEL staining revealed selective apoptotic effects in tumor areas but not in adjacent healthy bladder tissue. On in vivo imaging Alexa-HAMLET was retained for more than 24 hours in the bladder of tumor bearing mice but not in tumor-free bladders or in tumor bearing mice that received Alexa-alpha-lactalbumin.


CONCLUSIONS
Results show that HAMLET is active as a tumoricidal agent and suggest that topical HAMLET administration may delay bladder cancer development.
Mossberg
Ann-Kristin
AK
Department of Microbiology, Institute of Laboratory Medicine, Lund University, Lund, Sweden.
Hou
Yuchuan
Y
Svensson
Majlis
M
Holmqvist
Bo
B
Svanborg
Catharina
C
D000818:Animals; D004354:Drug Screening Assays, Antitumor; D005260:Female; D007768:Lactalbumin / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D009829:Oleic Acids / Q000627:therapeutic use*; D013997:Time Factors; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000473:pathology
C506422:HAMLET complex, human; D009829:Oleic Acids; D007768:Lactalbumin