Taka
Thu, May-22-08, 17:16
A pro-inflammatory pathway may protect against radiation and
kill cancer cells at the same time?
Drug may limit radiation damage
April 10, 2008 Courtesy Science and World Science staff
Re=ADsearch=ADers say they have de=ADvel=ADoped a drug that
pro=ADtects an= =ADi=AD mals=92 bone mar=ADrow and
gas=ADt=ADro=ADin=ADtes=ADti=ADnal cells from de=
=ADstruc=ADtive radia=ADt=ADion.
The com=ADpound pro=ADtects or=ADdi=ADnary cells with=ADout
re=ADduc=ADing t= he ef=AD fec=ADtive=ADness of
radia=ADt=ADion ther=ADa=ADpy against tu=ADmor cells, m=
ak=ADing it a po=ADten=ADtially use=ADful ad=ADjunct to
can=ADcer treat=ADment, the s= ci=ADen=AD tists said.
Radia=ADt=ADion is a key treat=ADment for many can=ADcers, but
drugs that li= m=AD it its dev=ADas=ADtat=ADing ef=ADfects on
healthy cells are needed to re=ADd= uce the some=ADtimes
se=ADvere side ef=ADfects. The new drug, CBLB502, tested in=
mice and mon=ADkeys, works by ac=ADti=ADvat=ADing a well-known
mo=ADlec=ADu= =ADlar mech=ADan=ADism that some can=ADcer cells
use to stave off cell death, said the re=ADsearch=ADers.
The stu=ADdy, by Lyud=ADmila Bur=ADdelya of Ros=ADwell Park
Can=ADcer In=ADs= ti=AD tute in Buf=ADfa=ADlo, N.Y. and
col=ADleagues, is to ap=ADpear in the April = 11 is=ADsue of
the re=ADsearch jour=ADnal Sci=ADence.
One dose of the drug giv=ADen to the an=ADi=ADmals shortly
be=ADfore re=ADce= iv=AD ing radia=ADt=ADion ther=ADa=ADpy
sig=ADnif=ADi=ADcantly re=ADduced radia=AD= t=ADion dam=AD age
to bone mar=ADrow and gas=ADt=ADro=ADin=ADtes=ADti=ADnal cells
and pro= =ADlonged the an=ADi=ADmals=92 sur=ADviv=ADal,
ac=ADcord=ADing to the group. The re=AD= search=ADers al=ADso
said the drug might be use=ADful in radia=ADt=ADion
emer=ADgen=ADcie= s, such as dur=ADing a nu=ADclear plant
mal=ADfunc=ADtion or =93dirty bomb=94 d= etona=AD t=ADion.
Science. 2008 Apr 11;320(5873):226-30. Comment in: Science.
2008 Apr 11;320(5873):163.
An agonist of toll-like receptor 5 has radioprotective
activity in mouse and primate models.
Burdelya LG, Krivokrysenko VI, Tallant TC, Strom E, Gleiberman
AS, Gupta D, Kurnasov OV, Fort FL, Osterman AL, Didonato JA,
Feinstein E, Gudkov AV. Department of Cell Stress Biology,
Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
The toxicity of ionizing radiation is associated with
massive apoptosis in radiosensitive organs. Here, we
investigate whether a drug that activates a signaling
mechanism used by tumor cells to suppress apoptosis can
protect healthy cells from the harmful effects of
radiation. We studied CBLB502, a polypeptide drug derived
from Salmonella flagellin that binds to Toll-like
receptor 5 (TLR5) and activates nuclear factor-kappaB
signaling. A single injection of CBLB502 before lethal
total-body irradiation protected mice from both
gastrointestinal and hematopoietic acute radiation
syndromes and resulted in improved survival. CBLB502
injected after irradiation also enhanced survival, but at
lower radiation doses. It is noteworthy that the drug did
not decrease tumor radiosensitivity in mouse models.
CBLB502 also showed radioprotective activity in lethally
irradiated rhesus monkeys. Thus, TLR5 agonists could
potentially improve the therapeutic index of cancer
radiotherapy and serve as biological protectants in
radiation emergencies. PMID: 18403709
kill cancer cells at the same time?
Drug may limit radiation damage
April 10, 2008 Courtesy Science and World Science staff
Re=ADsearch=ADers say they have de=ADvel=ADoped a drug that
pro=ADtects an= =ADi=AD mals=92 bone mar=ADrow and
gas=ADt=ADro=ADin=ADtes=ADti=ADnal cells from de=
=ADstruc=ADtive radia=ADt=ADion.
The com=ADpound pro=ADtects or=ADdi=ADnary cells with=ADout
re=ADduc=ADing t= he ef=AD fec=ADtive=ADness of
radia=ADt=ADion ther=ADa=ADpy against tu=ADmor cells, m=
ak=ADing it a po=ADten=ADtially use=ADful ad=ADjunct to
can=ADcer treat=ADment, the s= ci=ADen=AD tists said.
Radia=ADt=ADion is a key treat=ADment for many can=ADcers, but
drugs that li= m=AD it its dev=ADas=ADtat=ADing ef=ADfects on
healthy cells are needed to re=ADd= uce the some=ADtimes
se=ADvere side ef=ADfects. The new drug, CBLB502, tested in=
mice and mon=ADkeys, works by ac=ADti=ADvat=ADing a well-known
mo=ADlec=ADu= =ADlar mech=ADan=ADism that some can=ADcer cells
use to stave off cell death, said the re=ADsearch=ADers.
The stu=ADdy, by Lyud=ADmila Bur=ADdelya of Ros=ADwell Park
Can=ADcer In=ADs= ti=AD tute in Buf=ADfa=ADlo, N.Y. and
col=ADleagues, is to ap=ADpear in the April = 11 is=ADsue of
the re=ADsearch jour=ADnal Sci=ADence.
One dose of the drug giv=ADen to the an=ADi=ADmals shortly
be=ADfore re=ADce= iv=AD ing radia=ADt=ADion ther=ADa=ADpy
sig=ADnif=ADi=ADcantly re=ADduced radia=AD= t=ADion dam=AD age
to bone mar=ADrow and gas=ADt=ADro=ADin=ADtes=ADti=ADnal cells
and pro= =ADlonged the an=ADi=ADmals=92 sur=ADviv=ADal,
ac=ADcord=ADing to the group. The re=AD= search=ADers al=ADso
said the drug might be use=ADful in radia=ADt=ADion
emer=ADgen=ADcie= s, such as dur=ADing a nu=ADclear plant
mal=ADfunc=ADtion or =93dirty bomb=94 d= etona=AD t=ADion.
Science. 2008 Apr 11;320(5873):226-30. Comment in: Science.
2008 Apr 11;320(5873):163.
An agonist of toll-like receptor 5 has radioprotective
activity in mouse and primate models.
Burdelya LG, Krivokrysenko VI, Tallant TC, Strom E, Gleiberman
AS, Gupta D, Kurnasov OV, Fort FL, Osterman AL, Didonato JA,
Feinstein E, Gudkov AV. Department of Cell Stress Biology,
Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
The toxicity of ionizing radiation is associated with
massive apoptosis in radiosensitive organs. Here, we
investigate whether a drug that activates a signaling
mechanism used by tumor cells to suppress apoptosis can
protect healthy cells from the harmful effects of
radiation. We studied CBLB502, a polypeptide drug derived
from Salmonella flagellin that binds to Toll-like
receptor 5 (TLR5) and activates nuclear factor-kappaB
signaling. A single injection of CBLB502 before lethal
total-body irradiation protected mice from both
gastrointestinal and hematopoietic acute radiation
syndromes and resulted in improved survival. CBLB502
injected after irradiation also enhanced survival, but at
lower radiation doses. It is noteworthy that the drug did
not decrease tumor radiosensitivity in mouse models.
CBLB502 also showed radioprotective activity in lethally
irradiated rhesus monkeys. Thus, TLR5 agonists could
potentially improve the therapeutic index of cancer
radiotherapy and serve as biological protectants in
radiation emergencies. PMID: 18403709