According to my husband's oncologist and radio-oncologist, no one wants to
spend the money doing trials on his type of astrocytoma, which is somewhat
related to the kind that affects children (I forget the name of that one),
because it is not common enough to bother with. And, of course, the trials that
are being done on the kids, don't take adults. Go figure.
So far, though, he is doing miraculously well with the radiation and Temodar,
better than they even dreamed. He has gone from "maybe two years left", to who
knows, maybe even no tumor. They can't tell, of course, because it is deeply
imbedded in inoperable brain tissue, what his first neurosurgeon called, "the no
fly zone."
Cookie



----- Original Message ----
From: "anne91547@..." <anne91547@...>
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Sent: Saturday, March 15, 2008 8:17:56 AM
Subject: [BrainSurgery@Yahoo] Recent Research about the drug Mifepristone I take
for my recurrent meningioma as an anti-cancer agent

No fascinating new report about my current use SUCCESSFULLY FIGHTING meningioma
brain tumor cell growth with RU 486 (Mifepristone) for another three years now,
( my cynical sarcasm here) but these various other uses truly might be
beneficial and lifesaving for many more people.

I hope and wish (and pray too)for someone who had the money and interest to do
more human clinical trials of Mifepristone on other brain tumors, especially
before radiation therapy for small, residual or slow growing tumors. The one
about how it chemically fights the damages of stress to neurogenesis is truly an
amazing discovery.
GBYAY Anne McGinnis Breen

1: Endocrine. 2007 Oct;32(2):129- 35. Epub 2007 Nov 15.



Progesterone effects on cell growth of U373 and D54 human astrocytoma cell
lines.



González-Agüero G, Gutiérrez AA, González-Espinosa D, Solano JD, Morales R,
González-Arenas A, Cabrera-Muñoz E, Camacho-Arroyo I.

Facultad de Química, Departamento de Biología, Universidad Nacional Autónoma de
México, Mexico DF, 04510, Mexico.

Astrocytomas are the most frequent primary brain tumors and constitute a leading
cause of cancer-related deaths. We studied the effects of progesterone and its
antagonist, RU486, on cell growth of two human astrocytoma cell lines with
different evolution grade (U373, grade III; and D54, grade IV). Progesterone
receptor expression was determined by Western blot. The effects of different
doses of progesterone and RU486 on cell number, cell cycle, and apoptosis were
analyzed for five consecutive days. Progesterone (10 nM) significantly increased
the number of D54 cells from the second day of culture, and the number of U373
cells on days 3-5. RU486 (10 muM) blocked progesterone effects in both
astrocytoma cell lines. Interestingly, RU486 administered without progesterone
significantly reduced the number of cells from the second day of culture in both
cell lines. Progesterone increased S phase of cell cycle in U373 cells (61%, on
day 5). RU486 blocked the
effects of progesterone on cell cycle but administered alone did not
significantly change cell cycle profile. DNA fragmentation (TUNEL) assay showed
that the diminution in the number of astrocytoma cells produced by RU486 was not
by apoptosis. Progesterone receptor isoforms were detected in both cell lines.
Our data suggest that progesterone induces cell growth of human astrocytoma cell
lines through the interaction with its nuclear receptor.

PMID: 18008187 [PubMed - in process]



1: Clin Exp Obstet Gynecol. 2007;34(4):207- 11



Evidence that progesterone receptor antagonists may help in the treatment of a
variety of cancers by locally suppressing natural killer cell activity.



http://www.ncbi. nlm.nih.gov/ pubmed/18225679? ordinalpos= 18&itool=
EntrezSystem2. PEntrez.Pubmed. Pubmed_ResultsPa nel.Pubmed_ RVDocSum



Check JH, Sansoucie L, Chern J, Amadi N, Srivastava M, Larece K.

PURPOSE: To propose a novel concept that progesterone receptor antagonists,
e.g., mifepristone, may prove effective in treating a variety of cancers--even
those not shown to be hormonally dependent or possessing progesterone receptors.
METHODS: Multiple human leukemia cell lines were evaluated for mRNA expression
of an immunomodulatory protein called the progesterone- induced blocking factor
(PIBF) that suppresses natural killer (NK) cell activity during normal
pregnancy. Furthermore, we evaluated the effects of progesterone (P) and
mifepristone in PIBF protein expression. Finally, the effect of mifepristone
treatment of mice with advanced leukemia was evaluated. RESULTS: All tumor cell
lines evaluated were found to express mRNA for PIBF and some were found to even
express the PIBF protein. The addition of P to the media increased the
expression of PIBF and mifepristone downregulated its expression. Treatment of
mice with spontaneous leukemia when they
already had extensive disease seemed to increase the length and quality of
their life. CONCLUSIONS: These data and other experience with mice with lung
cancer and some anecdotal human cancer experience suggest that various cancers
may utilize similar mechanisms used by the fetus to escape NK cell surveillance.
Mifepristone and other progesterone receptor antagonists may deserve a clinical
trial in human cancer even where there is no knowledge of the presence of
progesterone receptors.

PMID: 18225679 [PubMed - indexed for MEDLINE]



1: Eur J Neurosci. 2007 Dec;26(12):3395- 401. Epub 2007 Dec 4

Brief treatment with the glucocorticoid receptor antagonist mifepristone
normalizes the reduction in neurogenesis after chronic stress.

http://www.ncbi. nlm.nih.gov/ pubmed/18052970? ordinalpos= 42&itool=
EntrezSystem2. PEntrez.Pubmed. Pubmed_ResultsPa nel.Pubmed_ RVDocSum

SILS Centre for Neuroscience, University of Amsterdam, Kruislaan 320, 1098 SM,
Amsterdam, The Netherlands.

In rodents, stress suppresses adult neurogenesis. This is thought to involve
activation of glucocorticoid receptors in the brain. In the present study, we
therefore questioned whether glucocorticoid receptor blockade by mifepristone
can normalize the effects of chronic stress on adult neurogenesis. Rats received
mifepristone on the last 4 days of a 21-day chronic unpredictable and
inescapable stress regimen. Neurogenesis was analysed by stereological
quantification of adult-generated cell survival (bromodeoxyuridine) , young
neuronal survival (doublecortin) and cell proliferation (Ki-67). The results
show that only 4 days of mifepristone treatment normalized the stress-induced
reductions in neurogenesis. Importantly, mifepristone by itself had no effect on
neurogenesis. We conclude that, contrary to other compounds interfering with the
effects of chronic stress on neurogenesis, like antidepressants, the normalizing
effects of mifepristone on neurogenesis
are rapid and particularly potent in a high stress environment. This neurogenic
action of mifepristone could potentially contribute to its clinical mechanism of
action.

PMID: 18052970 [PubMed - indexed for MEDLINE]



Arq Bras Endocrinol Metabol. 2007 Nov;51(8):1339- 48

Pharmacological management of Cushing's syndrome: an update.

http://www.ncbi. nlm.nih.gov/ pubmed/18209872? ordinalpos= 19&itool=
EntrezSystem2. PEntrez.Pubmed. Pubmed_ResultsPa nel.Pubmed_ RVDocSum



Dang CN, Trainer P.

Christie Hospital, Manchester, UK.

The treatment of choice for Cushing's syndrome remains surgical. The role for
medical therapy is twofold. Firstly it is used to control hypercortisolaemia
prior to surgery to optimize patient's preoperative state and secondly, it is
used where surgery has failed and radiotherapy has not taken effect. The main
drugs used inhibit steroidogenesis and include metyrapone, ketoconazole, and
mitotane. Drugs targeting the hypothalamic- pituitary axis have been
investigated but their roles in clinical practice remain limited although
PPAR-gamma agonist and somatostatin analogue som-230 (pasireotide) need further
investigation. The only drug acting at the periphery targeting the
glucocorticoid receptor remains Mifepristone (RU486). The management of Cushing
syndrome may well involve combination therapy acting at different pathways of
hypercortisolaemia but monitoring of therapy will remain a challenge.

PMID: 18209872 [PubMed - in process]





1: Gene Ther. 2008 Jan;15(1):1- 11. Epub 2007 Jul 19. Links



Regulated expression of the interferon-beta gene in mice.



Harkins RN, Szymanski P, Petry H, Brooks A, Qian HS, Schaefer C, Kretschmer PJ,
Orme A, Wang P, Rubanyi GM, Hermiston TW.

Department of Gene Technologies, Berlex Biosciences, Richmond, CA, USA.
rick.harkins@ bayer.com

A single plasmid regulated expression vector based upon a mifepristone-
inducible two plasmid system, termed pBRES, has been constructed and tested in
mice using murine interferon-b (mIFNb) as the transgene. The expression of mIFNb
in the circulation was followed by measuring the systemic induction of IP-10, a
validated biomarker for mIFNb in mice. Long-term, inducible expression of mIFNb
was demonstrated following a single intramuscular (i.m.) injection of the pBRES
mIFNb plasmid vector into the hind limb of mice. Induction of mIFNb expression
was achieved by administration of the small molecule inducer, mifepristone
(MFP). Plasmid DNA and mIFNb mRNA levels in the injected muscles correlated with
mIFNb expression as monitored by IP-10 over a 3-month time period. Renewable
transgene expression was achieved following repeat administration of the plasmid
at 3 months following the first plasmid injection. A dose-dependent increase in
expression was
demonstrated by varying the amount of injected plasmid or the amount of the
inducer administered to the mice. Finally, the pBRES plasmid expressing mIFNb
under control of the inducer, MFP, was shown to be efficacious in a murine model
of experimental allergic encephalomyelitis, supporting the feasibility of
gene-based therapeutic approaches for treating diseases such as multiple
sclerosis.

PMID: 17637794 [PubMed - in process]



Cancer Sci. 2008 Mar;99(3):518- 23. Epub 2007 Dec 15

Sex steroid receptors expression and hormone-induced cell proliferation in human
osteosarcoma.

http://www.ncbi. nlm.nih.gov/ pubmed/18081879? ordinalpos= 4&itool=EntrezSy
stem2.PEntrez. Pubmed.Pubmed_ ResultsPanel. Pubmed_RVDocSum



Dohi O, Hatori M, Suzuki T, Ono K, Hosaka M, Akahira J, Miki Y, Nagasaki S, Itoi
E, Sasano H.
Department of Orthopaedic Surgery, Tohoku Kosai Hospital, 2-3-11 Kokubuncho,
Aoba-ku, Sendai, Japan. odohi@.... com

Sex steroid receptors including estrogen receptors (ER), progesterone receptors
(PR), and androgen receptors (AR) have been sporadically reported in human
osteosarcoma or its cell lines. Therefore, sex steroids have been considered to
play some roles in human osteosarcoma, but no systematic and detailed studies
regarding the correlation between the status of these receptors in sarcoma cells
and clinicopathological parameters have been reported. We examined the existence
of ER, PR and AR in 28 cases of osteosarcoma using immunohistochemistr y. We
then characterized the potential influence of sex steroids on cell proliferation
of osteosarcoma cells using MG-63 human osteosarcoma cell line, which expressed
all of these receptors. ER-beta and PR were detected in the great majority of
the cases (23 and 24 cases, respectively) but ER-alpha and aromatase were not
detected in all the cases, and AR was detected only in eight cases. There was a
significant
positive correlation between ER-beta and Ki-67 (MIB1) labeling indexes. The
absence of aromatase in tumors also suggests the relative importance of
concentrations of circulating sex steroids. Proliferation of MG-63 cells was
significantly stimulated by estradiol, progesterone, and 5 alpha-dihydrotestos
terone (DHT), and was significantly suppressed by the addition of fulvestrant
(ICI), mifepristone (RU), and hydroxiflutamide, blockers for ER, PR and AR,
respectively. Sex steroids, particularly estrogen and progesterone, are
considered to play important roles in the regulation of cell proliferation in
human osteosarcoma. In addition, these data suggest the potential for a novel
endocrine therapy in osteosarcoma using clinically available inhibitors of
progesterone and estrogen actions.

PMID: 18081879 [PubMed - in process]



Department of Orthopaedic Surgery, Tohoku Kosai Hospital, 2-3-11 Kokubuncho,
Aoba-ku, Sendai, Japan. odohi@.... com

Sex steroid receptors including estrogen receptors (ER), progesterone receptors
(PR), and androgen receptors (AR) have been sporadically reported in human
osteosarcoma or its cell lines. Therefore, sex steroids have been considered to
play some roles in human osteosarcoma, but no systematic and detailed studies
regarding the correlation between the status of these receptors in sarcoma cells
and clinicopathological parameters have been reported. We examined the existence
of ER, PR and AR in 28 cases of osteosarcoma using immunohistochemistr y. We
then characterized the potential influence of sex steroids on cell proliferation
of osteosarcoma cells using MG-63 human osteosarcoma cell line, which expressed
all of these receptors. ER-beta and PR were detected in the great majority of
the cases (23 and 24 cases, respectively) but ER-alpha and aromatase were not
detected in all the cases, and AR was detected only in eight cases. There was a
significant
positive correlation between ER-beta and Ki-67 (MIB1) labeling indexes. The
absence of aromatase in tumors also suggests the relative importance of
concentrations of circulating sex steroids. Proliferation of MG-63 cells was
significantly stimulated by estradiol, progesterone, and 5 alpha-dihydrotestos
terone (DHT), and was significantly suppressed by the addition of fulvestrant
(ICI), mifepristone (RU), and hydroxiflutamide, blockers for ER, PR and AR,
respectively. Sex steroids, particularly estrogen and progesterone, are
considered to play important roles in the regulation of cell proliferation in
human osteosarcoma. In addition, these data suggest the potential for a novel
endocrine therapy in osteosarcoma using clinically available inhibitors of
progesterone and estrogen actions.

PMID: 18081879 [PubMed - in process]



Brief treatment with the glucocorticoid receptor antagonist mifepristone
normalizes the reduction in neurogenesis after chronic stress.

http://www.ncbi. nlm.nih.gov/ pubmed/18052970? ordinalpos= 42&itool=
EntrezSystem2. PEntrez.Pubmed. Pubmed_ResultsPa nel.Pubmed_ RVDocSum

SILS Centre for Neuroscience, University of Amsterdam, Kruislaan 320, 1098 SM,
Amsterdam, The Netherlands.

In rodents, stress suppresses adult neurogenesis. This is thought to involve
activation of glucocorticoid receptors in the brain. In the present study, we
therefore questioned whether glucocorticoid receptor blockade by mifepristone
can normalize the effects of chronic stress on adult neurogenesis. Rats received
mifepristone on the last 4 days of a 21-day chronic unpredictable and
inescapable stress regimen. Neurogenesis was analysed by stereological
quantification of adult-generated cell survival (bromodeoxyuridine) , young
neuronal survival (doublecortin) and cell proliferation (Ki-67). The results
show that only 4 days of mifepristone treatment normalized the stress-induced
reductions in neurogenesis. Importantly, mifepristone by itself had no effect on
neurogenesis. We conclude that, contrary to other compounds interfering with the
effects of chronic stress on neurogenesis, like antidepressants, the normalizing
effects of mifepristone on neurogenesis
are rapid and particularly potent in a high stress environment. This neurogenic
action of mifepristone could potentially contribute to its clinical mechanism of
action.

PMID: 18052970 [PubMed - indexed for MEDLINE]



Arq Bras Endocrinol Metabol. 2007 Nov;51(8):1339- 48

Pharmacological management of Cushing's syndrome: an update.

http://www.ncbi. nlm.nih.gov/ pubmed/18209872? ordinalpos= 19&itool=
EntrezSystem2. PEntrez.Pubmed. Pubmed_ResultsPa nel.Pubmed_ RVDocSum



Dang CN, Trainer P.

Christie Hospital, Manchester, UK.

The treatment of choice for Cushing's syndrome remains surgical. The role for
medical therapy is twofold. Firstly it is used to control hypercortisolaemia
prior to surgery to optimize patient's preoperative state and secondly, it is
used where surgery has failed and radiotherapy has not taken effect. The main
drugs used inhibit steroidogenesis and include metyrapone, ketoconazole, and
mitotane. Drugs targeting the hypothalamic- pituitary axis have been
investigated but their roles in clinical practice remain limited although
PPAR-gamma agonist and somatostatin analogue som-230 (pasireotide) need further
investigation. The only drug acting at the periphery targeting the
glucocorticoid receptor remains Mifepristone (RU486). The management of Cushing
syndrome may well involve combination therapy acting at different pathways of
hypercortisolaemia but monitoring of therapy will remain a challenge.

PMID: 18209872 [PubMed - in process]





1: Gene Ther. 2008 Jan;15(1):1- 11. Epub 2007 Jul 19. Links



Regulated expression of the interferon-beta gene in mice.



Harkins RN, Szymanski P, Petry H, Brooks A, Qian HS, Schaefer C, Kretschmer PJ,
Orme A, Wang P, Rubanyi GM, Hermiston TW.

Department of Gene Technologies, Berlex Biosciences, Richmond, CA, USA.
rick.harkins@ bayer.com

A single plasmid regulated expression vector based upon a mifepristone-
inducible two plasmid system, termed pBRES, has been constructed and tested in
mice using murine interferon-b (mIFNb) as the transgene. The expression of mIFNb
in the circulation was followed by measuring the systemic induction of IP-10, a
validated biomarker for mIFNb in mice. Long-term, inducible expression of mIFNb
was demonstrated following a single intramuscular (i.m.) injection of the pBRES
mIFNb plasmid vector into the hind limb of mice. Induction of mIFNb expression
was achieved by administration of the small molecule inducer, mifepristone
(MFP). Plasmid DNA and mIFNb mRNA levels in the injected muscles correlated with
mIFNb expression as monitored by IP-10 over a 3-month time period. Renewable
transgene expression was achieved following repeat administration of the plasmid
at 3 months following the first plasmid injection. A dose-dependent increase in
expression was
demonstrated by varying the amount of injected plasmid or the amount of the
inducer administered to the mice. Finally, the pBRES plasmid expressing mIFNb
under control of the inducer, MFP, was shown to be efficacious in a murine model
of experimental allergic encephalomyelitis, supporting the feasibility of
gene-based therapeutic approaches for treating diseases such as multiple
sclerosis.

PMID: 17637794 [PubMed - in process]



Cancer Sci. 2008 Mar;99(3):518- 23. Epub 2007 Dec 15

Sex steroid receptors expression and hormone-induced cell proliferation in human
osteosarcoma.

http://www.ncbi. nlm.nih.gov/ pubmed/18081879? ordinalpos= 4&itool=EntrezSy
stem2.PEntrez. Pubmed.Pubmed_ ResultsPanel. Pubmed_RVDocSum



Dohi O, Hatori M, Suzuki T, Ono K, Hosaka M, Akahira J, Miki Y, Nagasaki S, Itoi
E, Sasano H.
Department of Orthopaedic Surgery, Tohoku Kosai Hospital, 2-3-11 Kokubuncho,
Aoba-ku, Sendai, Japan. odohi@.... com

Sex steroid receptors including estrogen receptors (ER), progesterone receptors
(PR), and androgen receptors (AR) have been sporadically reported in human
osteosarcoma or its cell lines. Therefore, sex steroids have been considered to
play some roles in human osteosarcoma, but no systematic and detailed studies
regarding the correlation between the status of these receptors in sarcoma cells
and clinicopathological parameters have been reported. We examined the existence
of ER, PR and AR in 28 cases of osteosarcoma using immunohistochemistr y. We
then characterized the potential influence of sex steroids on cell proliferation
of osteosarcoma cells using MG-63 human osteosarcoma cell line, which expressed
all of these receptors. ER-beta and PR were detected in the great majority of
the cases (23 and 24 cases, respectively) but ER-alpha and aromatase were not
detected in all the cases, and AR was detected only in eight cases. There was a
significant
positive correlation between ER-beta and Ki-67 (MIB1) labeling indexes. The
absence of aromatase in tumors also suggests the relative importance of
concentrations of circulating sex steroids. Proliferation of MG-63 cells was
significantly stimulated by estradiol, progesterone, and 5 alpha-dihydrotestos
terone (DHT), and was significantly suppressed by the addition of fulvestrant
(ICI), mifepristone (RU), and hydroxiflutamide, blockers for ER, PR and AR,
respectively. Sex steroids, particularly estrogen and progesterone, are
considered to play important roles in the regulation of cell proliferation in
human osteosarcoma. In addition, these data suggest the potential for a novel
endocrine therapy in osteosarcoma using clinically available inhibitors of
progesterone and estrogen actions.

PMID: 18081879 [PubMed - in process]



Department of Orthopaedic Surgery, Tohoku Kosai Hospital, 2-3-11 Kokubuncho,
Aoba-ku, Sendai, Japan. odohi@.... com

Sex steroid receptors including estrogen receptors (ER), progesterone receptors
(PR), and androgen receptors (AR) have been sporadically reported in human
osteosarcoma or its cell lines. Therefore, sex steroids have been considered to
play some roles in human osteosarcoma, but no systematic and detailed studies
regarding the correlation between the status of these receptors in sarcoma cells
and clinicopathological parameters have been reported. We examined the existence
of ER, PR and AR in 28 cases of osteosarcoma using immunohistochemistr y. We
then characterized the potential influence of sex steroids on cell proliferation
of osteosarcoma cells using MG-63 human osteosarcoma cell line, which expressed
all of these receptors. ER-beta and PR were detected in the great majority of
the cases (23 and 24 cases, respectively) but ER-alpha and aromatase were not
detected in all the cases, and AR was detected only in eight cases. There was a
significant
positive correlation between ER-beta and Ki-67 (MIB1) labeling indexes. The
absence of aromatase in tumors also suggests the relative importance of
concentrations of circulating sex steroids. Proliferation of MG-63 cells was
significantly stimulated by estradiol, progesterone, and 5 alpha-dihydrotestos
terone (DHT), and was significantly suppressed by the addition of fulvestrant
(ICI), mifepristone (RU), and hydroxiflutamide, blockers for ER, PR and AR,
respectively. Sex steroids, particularly estrogen and progesterone, are
considered to play important roles in the regulation of cell proliferation in
human osteosarcoma. In addition, these data suggest the potential for a novel
endocrine therapy in osteosarcoma using clinically available inhibitors of
progesterone and estrogen actions.

PMID: 18081879 [PubMed - in process]



[Non-text portions of this message have been removed]




[Non-text portions of this message have been removed]