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

Mossberg, Anki LU ; Wullt, Björn LU ; Gustafsson, Lotta LU orcid ; Månsson, Wiking LU ; Ljunggren, Eva and Svanborg, Catharina LU (2007) In International Journal of Cancer 121(6). p.1352-1359
Abstract
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... (More)
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. (Less)
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author
; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
folding, protein, alpha-lactalbumin, therapeutics, bladder cancer, apoptosis
in
International Journal of Cancer
volume
121
issue
6
pages
1352 - 1359
publisher
John Wiley & Sons Inc.
external identifiers
  • wos:000248976800025
  • scopus:34548073069
ISSN
0020-7136
DOI
10.1002/ijc.22810
project
HAMLET- In vivo effects and mechanisms of tumor cells death
language
English
LU publication?
yes
id
69f4261a-5e18-4a08-9bdd-5375e9877887 (old id 168173)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=17514650&dopt=Abstract
date added to LUP
2016-04-01 12:22:00
date last changed
2022-04-21 06:27:01
@article{69f4261a-5e18-4a08-9bdd-5375e9877887,
  abstract     = {{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.}},
  author       = {{Mossberg, Anki and Wullt, Björn and Gustafsson, Lotta and Månsson, Wiking and Ljunggren, Eva and Svanborg, Catharina}},
  issn         = {{0020-7136}},
  keywords     = {{folding; protein; alpha-lactalbumin; therapeutics; bladder cancer; apoptosis}},
  language     = {{eng}},
  number       = {{6}},
  pages        = {{1352--1359}},
  publisher    = {{John Wiley & Sons Inc.}},
  series       = {{International Journal of Cancer}},
  title        = {{Bladder cancers respond to intravesical instillation of HAMLET (human alpha-lactalbumin made lethal to tumor cells).}},
  url          = {{http://dx.doi.org/10.1002/ijc.22810}},
  doi          = {{10.1002/ijc.22810}},
  volume       = {{121}},
  year         = {{2007}},
}