Iron Chelators For Pancreatic Cancer

[ironjustice]

NOVEL THIOSEMICARBAZONE IRON CHELATORS INDUCE UP-REGULATION AND
PHOSPHORYLATION OF THE METASTASIS SUPPRESSOR, NDRG1: A NEW STRATEGY
FOR THE TREATMENT OF PANCREATIC CANCER.
Mol Pharmacol. 2011 Jun 30.
Kovacevic Z, Chikhani S, Lovejoy DB, Richardson DR.
University of Sydney.

Abstract
Pancreatic cancer is an aggressive neoplasm, with a mortality rate
close to 100%.
Currently, the most successful agent for pancreatic cancer treatment
is gemcitabine, although the overall effect in terms of patient
survival remains very poor.
This study was initiated to evaluate a novel class of anti-cancer
agents against pancreatic cancer.
This group of compounds belongs to the dipyridyl thiosemicarbazone
(DpT) class that have been shown to have potent and selective activity
against a range of different neoplasms in vitro and in vivo (Whitnall
M., Howard J., Ponka P. and Richardson D.R. 2006, PNAS 40:14901-6).
We demonstrate for the first time in pancreatic cancer that these
agents increase the expression of the growth and metastasis
suppressor, N-myc down-stream regulated gene 1 (NDRG1), and also its
phosphorylation at Ser-330 and Thr-346 that is important for its
activity against this tumor.
In addition, these agents increased expression of the cyclin-dependent
kinase inhibitor p21(CIP1/WAF1), while decreasing cyclin D1 in
pancreatic cancer cells.
Together, these molecular alterations account, in part, for the
pronounced anti-tumor activity observed.
Indeed, these agents had significantly higher anti-proliferative
activity in vitro than the established treatments for pancreatic
cancer, namely gemcitabine and 5-fluorouracil.
Studies in vivo demonstrated that a novel thiosemicarbazone, namely
di-2-pyridylketone 4-cyclohexyl-4-methyl-3-thiosemicarbazone
hydrochloride (DpC), completely inhibited the growth of pancreatic
cancer xenografts with no evidence of marked alterations in normal
tissue histology.
Collectively, our studies have identified molecular effectors of a
novel and potent anti-tumor agent that could be useful for pancreatic
cancer treatment.

PMID:21719465


Who loves ya.
Tom


Jesus Was A Vegetarian!
http://tinyurl.com/2r2nkh


Man Is A Herbivore!
http://tinyurl.com/a3cc3


DEAD PEOPLE WALKING
http://tinyurl.com/zk9fk

[dr_jeff]

Post by ironjustice
NOVEL THIOSEMICARBAZONE IRON CHELATORS INDUCE UP-REGULATION AND
PHOSPHORYLATION OF THE METASTASIS SUPPRESSOR, NDRG1: A NEW STRATEGY
FOR THE TREATMENT OF PANCREATIC CANCER.
Mol Pharmacol. 2011 Jun 30.
Kovacevic Z, Chikhani S, Lovejoy DB, Richardson DR.
University of Sydney.
Abstract
Pancreatic cancer is an aggressive neoplasm, with a mortality rate
close to 100%.
Currently, the most successful agent for pancreatic cancer treatment
is gemcitabine, although the overall effect in terms of patient
survival remains very poor.
This study was initiated to evaluate a novel class of anti-cancer
agents against pancreatic cancer.
This group of compounds belongs to the dipyridyl thiosemicarbazone
(DpT) class that have been shown to have potent and selective activity
against a range of different neoplasms in vitro and in vivo (Whitnall
M., Howard J., Ponka P. and Richardson D.R. 2006, PNAS 40:14901-6).
We demonstrate for the first time in pancreatic cancer that these
agents increase the expression of the growth and metastasis
suppressor, N-myc down-stream regulated gene 1 (NDRG1), and also its
phosphorylation at Ser-330 and Thr-346 that is important for its
activity against this tumor.
In addition, these agents increased expression of the cyclin-dependent
kinase inhibitor p21(CIP1/WAF1), while decreasing cyclin D1 in
pancreatic cancer cells.
Together, these molecular alterations account, in part, for the
pronounced anti-tumor activity observed.
Indeed, these agents had significantly higher anti-proliferative
activity in vitro than the established treatments for pancreatic
cancer, namely gemcitabine and 5-fluorouracil.
Studies in vivo demonstrated that a novel thiosemicarbazone, namely
di-2-pyridylketone 4-cyclohexyl-4-methyl-3-thiosemicarbazone
hydrochloride (DpC), completely inhibited the growth of pancreatic
cancer xenografts with no evidence of marked alterations in normal
tissue histology.
Collectively, our studies have identified molecular effectors of a
novel and potent anti-tumor agent that could be useful for pancreatic
cancer treatment.

The new anticancer agent might be an iron chelator, but there is nothing
in the abstract that suggest that chelation or iron has anything to do
with its mechanism of action, but there are other mechanisms of action
for the drug.

This is clearly an example of too much knowledge is a dangerous thing.

Jeff

Post by ironjustice
PMID:21719465
Who loves ya.
Tom
Jesus Was A Vegetarian!
http://tinyurl.com/2r2nkh
Man Is A Herbivore!
http://tinyurl.com/a3cc3
DEAD PEOPLE WALKING
http://tinyurl.com/zk9fk

[ken]

Post by dr_jeff
The new anticancer agent might be an iron chelator, but there is nothing
in the abstract that suggest that chelation or iron has anything to do
with its mechanism of action, but there are other mechanisms of action
for the drug.
This is clearly an example of too much knowledge is a dangerous thing.
Jeff

Rusty is a perfect example of why very little knowledge is a dangerous
thing

[ironjustice]

On Jul 2, 8:04 am, dr_jeff <***@msu.edu> wrote: there is nothing
in the abstract that suggest that chelation or iron has anything to
do
with its mechanism of action <<

It's right in the title.

"IRON CHELATORS INDUCE UP-REGULATION AND PHOSPHORYLATION OF THE
METASTASIS SUPPRESSOR, NDRG1"

You must be kind of stupid.

NOVEL THIOSEMICARBAZONE IRON CHELATORS INDUCE UP-REGULATION AND
PHOSPHORYLATION OF THE METASTASIS SUPPRESSOR, NDRG1: A NEW STRATEGY
FOR THE TREATMENT OF PANCREATIC CANCER.
Mol Pharmacol. 2011 Jun 30.
Kovacevic Z, Chikhani S, Lovejoy DB, Richardson DR.
University of Sydney.

Abstract
Pancreatic cancer is an aggressive neoplasm, with a mortality rate
close to 100%.
Currently, the most successful agent for pancreatic cancer treatment
is gemcitabine, although the overall effect in terms of patient
survival remains very poor.
This study was initiated to evaluate a novel class of anti-cancer
agents against pancreatic cancer.
This group of compounds belongs to the dipyridyl thiosemicarbazone
(DpT) class that have been shown to have potent and selective
activity
against a range of different neoplasms in vitro and in vivo (Whitnall
M., Howard J., Ponka P. and Richardson D.R. 2006, PNAS 40:14901-6).
We demonstrate for the first time in pancreatic cancer that these
agents increase the expression of the growth and metastasis
suppressor, N-myc down-stream regulated gene 1 (NDRG1), and also its
phosphorylation at Ser-330 and Thr-346 that is important for its
activity against this tumor.
In addition, these agents increased expression of the cyclin-
dependent
kinase inhibitor p21(CIP1/WAF1), while decreasing cyclin D1 in
pancreatic cancer cells.
Together, these molecular alterations account, in part, for the
pronounced anti-tumor activity observed.
Indeed, these agents had significantly higher anti-proliferative
activity in vitro than the established treatments for pancreatic
cancer, namely gemcitabine and 5-fluorouracil.
Studies in vivo demonstrated that a novel thiosemicarbazone, namely
di-2-pyridylketone 4-cyclohexyl-4-methyl-3-thiosemicarbazone
hydrochloride (DpC), completely inhibited the growth of pancreatic
cancer xenografts with no evidence of marked alterations in normal
tissue histology.
Collectively, our studies have identified molecular effectors of a
novel and potent anti-tumor agent that could be useful for pancreatic
cancer treatment.


PMID:21719465


Who loves ya.
Tom


Jesus Was A Vegetarian!
http://tinyurl.com/2r2nkh


Man Is A Herbivore!
http://tinyurl.com/a3cc3


DEAD PEOPLE WALKING
http://tinyurl.com/zk9fk

[ironjustice]

On Jul 3, 6:29 am, ironjustice <***@rock.com> wrote:
"IRON CHELATORS INDUCE UP-REGULATION AND PHOSPHORYLATION OF THE
METASTASIS SUPPRESSOR, NDRG1" <<

"Doxorubicin (DOX) up-regulated mRNA levels of the iron-regulated
genes transferrin receptor-1 (TfR1) and N-myc downstream-regulated
gene-1 (Ndrg1). This effect was mediated by iron depletion, because it
was reversed by adding iron and it was prevented by saturating the
anthracycline metal binding site with iron."

http://molpharm.aspetjournals.org/content/73/3/833.abstract

" Ndrg-1 is up-regulated in cells following iron (Fe)-depletion using
Fe chelators"

http://www.sciencedirect.com/science/article/pii/S0167488908001791

"Ndrg-1 expression was demonstrated to be regulated by cellular iron
levels and induced by iron chelators."

http://carcin.oxfordjournals.org/content/27/12/2355.full

"Increased Ndrg1 expression following Fe chelation was related to the
permeability and antiproliferative activity of chelators and could be
reversed by Fe repletion."

http://bloodjournal.hematologylibrary.org/content/104/9/2967.full

Post by ironjustice
You must be kind of stupid.
NOVEL THIOSEMICARBAZONE IRON CHELATORS INDUCE UP-REGULATION AND
PHOSPHORYLATION OF THE METASTASIS SUPPRESSOR, NDRG1: A NEW STRATEGY
FOR THE TREATMENT OF PANCREATIC CANCER.
Mol Pharmacol. 2011 Jun 30.
Kovacevic Z, Chikhani S, Lovejoy DB, Richardson DR.
University of Sydney.
Abstract
Pancreatic cancer is an aggressive neoplasm, with a mortality rate
close to 100%.
Currently, the most successful agent for pancreatic cancer treatment
is gemcitabine, although the overall effect in terms of patient
survival remains very poor.
This study was initiated to evaluate a novel class of anti-cancer
agents against pancreatic cancer.
This group of compounds belongs to the dipyridyl thiosemicarbazone
(DpT) class that have been shown to have potent and selective
activity
against a range of different neoplasms in vitro and in vivo (Whitnall
M., Howard J., Ponka P. and Richardson D.R. 2006, PNAS 40:14901-6).
We demonstrate for the first time in pancreatic cancer that these
agents increase the expression of the growth and metastasis
suppressor, N-myc down-stream regulated gene 1 (NDRG1), and also its
phosphorylation at Ser-330 and Thr-346 that is important for its
activity against this tumor.
In addition, these agents increased expression of the cyclin-
dependent
kinase inhibitor p21(CIP1/WAF1), while decreasing cyclin D1 in
pancreatic cancer cells.
Together, these molecular alterations account, in part, for the
pronounced anti-tumor activity observed.
Indeed, these agents had significantly higher anti-proliferative
activity in vitro than the established treatments for pancreatic
cancer, namely gemcitabine and 5-fluorouracil.
Studies in vivo demonstrated that a novel thiosemicarbazone, namely
di-2-pyridylketone 4-cyclohexyl-4-methyl-3-thiosemicarbazone
hydrochloride (DpC), completely inhibited the growth of pancreatic
cancer xenografts with no evidence of marked alterations in normal
tissue histology.
Collectively, our studies have identified molecular effectors of a
novel and potent anti-tumor agent that could be useful for pancreatic
cancer treatment.
PMID:21719465

Who loves ya.
Tom

Jesus Was A Vegetarian!http://tinyurl.com/2r2nkh

Man Is A Herbivore!http://tinyurl.com/a3cc3

DEAD PEOPLE WALKINGhttp://tinyurl.com/zk9fk

[dr_jeff]

Post by dr_jeff
in the abstract that suggest that chelation or iron has anything to do
with its mechanism of action<<
It's right in the title.

I stand correct. There is nothing in the abstract that suggest that iron
chelation has anything to do with the mechanism of action and much to
suggest that it doesn't.

The fact that iron binds to the chemicals seems to have nothing to do
with their mechanism of action.

Jeff

Post by dr_jeff
"IRON CHELATORS INDUCE UP-REGULATION AND PHOSPHORYLATION OF THE
METASTASIS SUPPRESSOR, NDRG1"
You must be kind of stupid.
NOVEL THIOSEMICARBAZONE IRON CHELATORS INDUCE UP-REGULATION AND
PHOSPHORYLATION OF THE METASTASIS SUPPRESSOR, NDRG1: A NEW STRATEGY
FOR THE TREATMENT OF PANCREATIC CANCER.
Mol Pharmacol. 2011 Jun 30.
Kovacevic Z, Chikhani S, Lovejoy DB, Richardson DR.
University of Sydney.
Abstract
Pancreatic cancer is an aggressive neoplasm, with a mortality rate
close to 100%.
Currently, the most successful agent for pancreatic cancer treatment
is gemcitabine, although the overall effect in terms of patient
survival remains very poor.
This study was initiated to evaluate a novel class of anti-cancer
agents against pancreatic cancer.
This group of compounds belongs to the dipyridyl thiosemicarbazone
(DpT) class that have been shown to have potent and selective
activity
against a range of different neoplasms in vitro and in vivo (Whitnall
M., Howard J., Ponka P. and Richardson D.R. 2006, PNAS 40:14901-6).
We demonstrate for the first time in pancreatic cancer that these
agents increase the expression of the growth and metastasis
suppressor, N-myc down-stream regulated gene 1 (NDRG1), and also its
phosphorylation at Ser-330 and Thr-346 that is important for its
activity against this tumor.
In addition, these agents increased expression of the cyclin-
dependent
kinase inhibitor p21(CIP1/WAF1), while decreasing cyclin D1 in
pancreatic cancer cells.
Together, these molecular alterations account, in part, for the
pronounced anti-tumor activity observed.
Indeed, these agents had significantly higher anti-proliferative
activity in vitro than the established treatments for pancreatic
cancer, namely gemcitabine and 5-fluorouracil.
Studies in vivo demonstrated that a novel thiosemicarbazone, namely
di-2-pyridylketone 4-cyclohexyl-4-methyl-3-thiosemicarbazone
hydrochloride (DpC), completely inhibited the growth of pancreatic
cancer xenografts with no evidence of marked alterations in normal
tissue histology.
Collectively, our studies have identified molecular effectors of a
novel and potent anti-tumor agent that could be useful for pancreatic
cancer treatment.
PMID:21719465
Who loves ya.
Tom
Jesus Was A Vegetarian!
http://tinyurl.com/2r2nkh
Man Is A Herbivore!
http://tinyurl.com/a3cc3
DEAD PEOPLE WALKING
http://tinyurl.com/zk9fk

[ironjustice]

On Jul 3, 11:10 am, dr_jeff <***@msu.edu> wrote: The fact that iron
binds to the chemicals seems to have nothing to do with their
mechanism of action. <<

Five studies using iron chelators result in the SAME thing.

You figure iron chelation has nothing to do with it ..

You figure it is coincidence ..

That is very good ..

Let me repeat ..

It seems you are stupid ..

Giiiiiit ..

"Ndrg-1 reduces the invasion and metastasis of breast, colon, prostate
and pancreatic cancer"

"IRON CHELATORS INDUCE UP-REGULATION AND PHOSPHORYLATION OF THE
METASTASIS SUPPRESSOR, NDRG1"

"Doxorubicin (DOX) up-regulated mRNA levels of the iron-regulated
genes transferrin receptor-1 (TfR1) and N-myc downstream-regulated
gene-1 (Ndrg1). This effect was mediated by iron depletion, because
it
was reversed by adding iron and it was prevented by saturating the
anthracycline metal binding site with iron."


http://molpharm.aspetjournals.org/content/73/3/833.abstract


" Ndrg-1 is up-regulated in cells following iron (Fe)-depletion using
Fe chelators"


http://www.sciencedirect.com/science/article/pii/S0167488908001791


"Ndrg-1 expression was demonstrated to be regulated by cellular iron
levels and induced by iron chelators."


http://carcin.oxfordjournals.org/content/27/12/2355.full


"Increased Ndrg1 expression following Fe chelation was related to the
permeability and antiproliferative activity of chelators and could be
reversed by Fe repletion."


http://bloodjournal.hematologylibrary.org/content/104/9/2967.full




- Hide quoted text -
- Show quoted text -

Post by ironjustice
You must be kind of stupid.
NOVEL THIOSEMICARBAZONE IRON CHELATORS INDUCE UP-REGULATION AND
PHOSPHORYLATION OF THE METASTASIS SUPPRESSOR, NDRG1: A NEW STRATEGY
FOR THE TREATMENT OF PANCREATIC CANCER.
Mol Pharmacol. 2011 Jun 30.
Kovacevic Z, Chikhani S, Lovejoy DB, Richardson DR.
University of Sydney.
Abstract
Pancreatic cancer is an aggressive neoplasm, with a mortality rate
close to 100%.
Currently, the most successful agent for pancreatic cancer treatment
is gemcitabine, although the overall effect in terms of patient
survival remains very poor.
This study was initiated to evaluate a novel class of anti-cancer
agents against pancreatic cancer.
This group of compounds belongs to the dipyridyl thiosemicarbazone
(DpT) class that have been shown to have potent and selective
activity
against a range of different neoplasms in vitro and in vivo (Whitnall
M., Howard J., Ponka P. and Richardson D.R. 2006, PNAS 40:14901-6).
We demonstrate for the first time in pancreatic cancer that these
agents increase the expression of the growth and metastasis
suppressor, N-myc down-stream regulated gene 1 (NDRG1), and also its
phosphorylation at Ser-330 and Thr-346 that is important for its
activity against this tumor.
In addition, these agents increased expression of the cyclin-
dependent
kinase inhibitor p21(CIP1/WAF1), while decreasing cyclin D1 in
pancreatic cancer cells.
Together, these molecular alterations account, in part, for the
pronounced anti-tumor activity observed.
Indeed, these agents had significantly higher anti-proliferative
activity in vitro than the established treatments for pancreatic
cancer, namely gemcitabine and 5-fluorouracil.
Studies in vivo demonstrated that a novel thiosemicarbazone, namely
di-2-pyridylketone 4-cyclohexyl-4-methyl-3-thiosemicarbazone
hydrochloride (DpC), completely inhibited the growth of pancreatic
cancer xenografts with no evidence of marked alterations in normal
tissue histology.
Collectively, our studies have identified molecular effectors of a
novel and potent anti-tumor agent that could be useful for pancreatic
cancer treatment.
PMID:21719465

Who loves ya.
Tom

Jesus Was A Vegetarian!
http://tinyurl.com/2r2nkh

Man Is A Herbivore!
http://tinyurl.com/a3cc3

DEAD PEOPLE WALKING
http://tinyurl.com/zk9fk