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.PE\
ntrez.Pubmed.Pubmed_ResultsPanel.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.PE\
ntrez.Pubmed.Pubmed_ResultsPanel.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.PE\
ntrez.Pubmed.Pubmed_ResultsPanel.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@...

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=EntrezSystem2.PEn\
trez.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@...

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 immunohistochemistry. 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-dihydrotestosterone (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@...

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 immunohistochemistry. 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-dihydrotestosterone (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.PE\
ntrez.Pubmed.Pubmed_ResultsPanel.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.PE\
ntrez.Pubmed.Pubmed_ResultsPanel.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@...

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=EntrezSystem2.PEn\
trez.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@...

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 immunohistochemistry. 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-dihydrotestosterone (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@...

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 immunohistochemistry. 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-dihydrotestosterone (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]

 



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