title: Bladder cancers respond to intravesical instillation of HAMLET (human alpha-lactalbumin made lethal to tumor cells).
abstract: We studied if bladder cancers respond to HAMLET (human alpha-lactalbumin made lethal to tumor cells) to establish if intravesical HAMLET application might be used to selectively remove cancer cells in vivo. Patients with nonmuscle invasive transitional cell carcinomas were included. Nine patients received 5 daily intravesical instillations of HAMLET (25 mg/ml) during the week before scheduled surgery. HAMLET stimulated a rapid increase in the shedding of tumor cells into the urine, daily, during the 5 days of instillation. The effect was specific for HAMLET, as intravesical instillation of NaCl, PBS or native alpha-lactalbumin did not increase cell shedding. Most of the shed cells were dead and an apoptotic response was detected in 6 of 9 patients, using the TUNEL assay. At surgery, morphological changes in the exophytic tumors were documented by endoscopic photography and a reduction in tumor size or change in tumor character was detected in 8 of 9 patients. TUNEL staining was positive in biopsies from the remaining tumor in 4 patients but adjacent healthy tissue showed no evidence of apoptosis and no toxic response. The results suggest that HAMLET exerts a direct and selective effect on bladder cancer tissue in vivo and that local HAMLET administration might be of value in the future treatment of bladder cancers.
authors.affiliation: Department of Microbiology, Immunology and Glycobiology, Institute of Laboratory Medicine, Lund University, Lund, Sweden.
authors.forename: Ann-Kristin
authors.initials: AK
authors.lastname: Mossberg
authors.forename: Björn
authors.initials: B
authors.lastname: Wullt
authors.forename: Lotta
authors.initials: L
authors.lastname: Gustafsson
authors.forename: Wiking
authors.initials: W
authors.lastname: Månsson
authors.forename: Eva
authors.initials: E
authors.lastname: Ljunggren
authors.forename: Catharina
authors.initials: C
authors.lastname: Svanborg
mesh_terms: D000283:Administration, Intravesical; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D020287:In Situ Nick-End Labeling; D007768:Lactalbumin / Q000008:administration & dosage*; D008297:Male; D009829:Oleic Acids / Q000008:administration & dosage*; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; C506422:HAMLET complex, human; D009829:Oleic Acids; D007768:Lactalbumin