Ironjustic
Thu, Sep-28-06, 17:15
<<snip>> can overcome resistance to established
chemotherapeutics <<snip>>
A class of iron chelators with a wide spectrum of potent
antitumor activity that overcomes resistance to
chemotherapeutics. Whitnall M, Howard J, Ponka P, Richardson
DR Proc Natl Acad Sci U S A. 2006 Sep 26;
Novel chemotherapeutics with marked and selective antitumor
activity are essential to develop, particularly those that can
overcome resistance to established therapies. Iron (Fe) is
critical for cell-cycle progression and DNA synthesis and
potentially represents a novel molecular target for the design
of new anticancer agents. The aim of this study was to
evaluate the antitumor activity and Fe chelation efficacy of a
new class of Fe chelators using human tumors. In this
investigation, the ligands showed broad antitumor activity and
could overcome resistance to established antitumor agents. The
in vivo efficacy of the most effective chelator identified,
di-2-pyridylketone-4,4,-dimethyl-3-thiosemicarbazone (Dp44mT),
was assessed by using a panel of human xenografts in nude
mice. After 7 weeks, net growth of a melanoma xenograft in
Dp44mT-treated mice was only 8% of that in mice treated with
vehicle. In addition, no differences in these latter animals
were found in hematological indices between Dp44mT-treated
mice and controls. No marked systemic Fe depletion was
observed comparing Dp44mT- and vehicle-treated mice, probably
because of the very low doses required to induce anticancer
activity. Dp44mT caused up-regulation of the Fe-responsive
tumor growth and metastasis suppressor Ndrg1 in the tumor but
not in the liver, indicating a potential mechanism of
selective anticancer activity. These results indicate that the
novel Fe chelators have potent and broad antitumor activity
and can overcome resistance to established chemotherapeutics
because of their unique mechanism of action.
Abstract =B7 PubMed FullText =B7 SFX =B7 GS Clip Export
InterDB =B7
Terms Related =B7 Graph Cites =B7 Scopus =B7 Tag
10.1073/pnas.0604979103
Who loves ya. Tom
Jesus Was A Vegetarian! http://jesuswasavegetarian.7h.com
Man Is A Herbivore! http://tinyurl.com/a3cc3
DEAD PEOPLE WALKING=20 http://tinyurl.com/zk9fk
chemotherapeutics <<snip>>
A class of iron chelators with a wide spectrum of potent
antitumor activity that overcomes resistance to
chemotherapeutics. Whitnall M, Howard J, Ponka P, Richardson
DR Proc Natl Acad Sci U S A. 2006 Sep 26;
Novel chemotherapeutics with marked and selective antitumor
activity are essential to develop, particularly those that can
overcome resistance to established therapies. Iron (Fe) is
critical for cell-cycle progression and DNA synthesis and
potentially represents a novel molecular target for the design
of new anticancer agents. The aim of this study was to
evaluate the antitumor activity and Fe chelation efficacy of a
new class of Fe chelators using human tumors. In this
investigation, the ligands showed broad antitumor activity and
could overcome resistance to established antitumor agents. The
in vivo efficacy of the most effective chelator identified,
di-2-pyridylketone-4,4,-dimethyl-3-thiosemicarbazone (Dp44mT),
was assessed by using a panel of human xenografts in nude
mice. After 7 weeks, net growth of a melanoma xenograft in
Dp44mT-treated mice was only 8% of that in mice treated with
vehicle. In addition, no differences in these latter animals
were found in hematological indices between Dp44mT-treated
mice and controls. No marked systemic Fe depletion was
observed comparing Dp44mT- and vehicle-treated mice, probably
because of the very low doses required to induce anticancer
activity. Dp44mT caused up-regulation of the Fe-responsive
tumor growth and metastasis suppressor Ndrg1 in the tumor but
not in the liver, indicating a potential mechanism of
selective anticancer activity. These results indicate that the
novel Fe chelators have potent and broad antitumor activity
and can overcome resistance to established chemotherapeutics
because of their unique mechanism of action.
Abstract =B7 PubMed FullText =B7 SFX =B7 GS Clip Export
InterDB =B7
Terms Related =B7 Graph Cites =B7 Scopus =B7 Tag
10.1073/pnas.0604979103
Who loves ya. Tom
Jesus Was A Vegetarian! http://jesuswasavegetarian.7h.com
Man Is A Herbivore! http://tinyurl.com/a3cc3
DEAD PEOPLE WALKING=20 http://tinyurl.com/zk9fk