Bladder cancers respond to intravesical instillation of (HAMLET human alpha-lactalbumin made lethal to tumor cells).

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Bladder cancers respond to intravesical instillation of (HAMLET human alpha-lactalbumin made lethal to tumor cells). / Mossberg, Anki; Wullt, Björn; Gustafsson, Lotta; Månsson, Wiking; Ljunggren, Eva; Svanborg, Catharina.

In: International Journal of Cancer, Vol. 121, No. 6, 2007, p. 1352-1359.

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T1 - Bladder cancers respond to intravesical instillation of (HAMLET human alpha-lactalbumin made lethal to tumor cells).

AU - Mossberg, Anki

AU - Wullt, Björn

AU - Gustafsson, Lotta

AU - Månsson, Wiking

AU - Ljunggren, Eva

AU - Svanborg, Catharina

PY - 2007

Y1 - 2007

N2 - We studied if bladder cancers respond to HAMLET (human alpha-lactalburnin 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 a-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. (c) 2007 Wiley-Liss, Inc.

AB - We studied if bladder cancers respond to HAMLET (human alpha-lactalburnin 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 a-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. (c) 2007 Wiley-Liss, Inc.

KW - folding

KW - protein

KW - alpha-lactalbumin

KW - therapeutics

KW - bladder cancer

KW - apoptosis

U2 - 10.1002/ijc.22810

DO - 10.1002/ijc.22810

M3 - Article

VL - 121

SP - 1352

EP - 1359

JO - Acta - Unio Internationalis Contra Cancrum

T2 - Acta - Unio Internationalis Contra Cancrum

JF - Acta - Unio Internationalis Contra Cancrum

SN - 0020-7136

IS - 6

ER -