I have just had my article published in the Australian Medical Journal and may be of interest to readers:
The fight for a life-saving drug: a personal perspective
In addition to the above, the following may be of interest re other forms of brain tumours incl post surgery where viable to possibly prevent further growth. See corresponding PR isoforms in human astrocytomas and various others including glioblastomas below. Mifepristone also called RU486 is a very effective progesterone atagonist so it could be useful in the treatment of astrocytomas and other malignant brain tumour which are mostly PR+ (It is now only available via the FMF's Compassionate Use Porgram in the USA or the TGA's Special Access Scheme in Australia. If any patients are interested their oncologist must apply to import the drug), alternatively, clinical trials could be set up to trial it ether as monotherapy, in conjunction with chemotherapy or raditiation therapy. The drug can also overcome p-glycoprotein resistance to chemotherapeutic drugs. It's time that such clinical trials are further progressed.
2001: Progesterone receptor isoforms expression pattern in human astrocytomas
Progesterone receptors (PR) have been detected in human astrocytomas;
however, the expression pattern of PR isoforms in these brain tumors is
unknown. Progesterone receptor isoforms expression was studied in 13
biopsies of astrocytomas (6 grade III, and 7 grade IV) from adult Mexican
patients by using reverse transcription-polymerase chain reaction and
immunohistochemistry. Progesterone receptor expression was observed at mRNA
and at protein levels in 66% and 83% of astrocytomas grade III,
respectively, whereas 100% of astrocytomas grade IV expressed PR. Almost all
PR mRNA content in astrocytomas grades III and IV corresponded to PR-B. The
number of immunoreactive cells expressing PR-B was higher than that
expressing PR-A in 73% of the cases. Estrogen receptor-α protein was only
observed in 33% of astrocytomas grade III, whereas no astrocytomas grade IV
expressed it. These data suggest that PR-B is the predominant isoform
expressed in human astrocytomas grades III and IV, and that estrogen
receptor-α is not expressed in astrocytomas grade IV.
Immunohistochemical analysis of progesterone receptor and ki-67 labeling
index in astrocytic tumors
Intracranial tumors such as meningiomas express steroid hormone
receptors but little is known regarding progesterone receptor (PR) in
astrocytic tumors. The authors evaluated expression of PR in 86 astrocytic
tumors in relation to tumor proliferative potential.
Paraffin embedded tumor sections were stained with polyclonal
antiprogesterone antibody by the peroxidase-antiperoxidase method and with
monoclonal MIB-1-Ki-67 antibody by avidin-biotin complex
Sixty-three of the 86 astrocytic tumors (73%) showed positive PR
immunoreactivity. PR expression was observed in 4 of 9 pilocytic
astrocytomas, 13 of 24 Grade 2 astrocytomas, 15 of 20 anaplastic
astrocytomas, and 31 of 33 glioblastomas. In addition to the tumor cells,
cells of microvascular endothelial proliferation and the smooth muscle of
tumor vessel walls were frequently PR positive. Glioblastomas had a
significantly higher percentage of PR positive cells compared with
anaplastic (P < 0.0008) and low grade (P < 0.0001) astrocytomas. Patients
with PR positive astrocytomas were of an older age than patients with PR
negative astrocytomas (48.71 ± 21.95 years vs. 37.09 ± 24.69 years; P <
0.04). The mean Ki-67 labeling index (LI) was significantly higher in the
high grade (3-4) astrocytomas compared with low grade (1-2) astrocytomas (P
< 0.0001). PR positive astrocytic tumors had higher Ki-67 LI than PR
negative tumors. PR expression was not correlated with tumor recurrence and
The current study suggests that PR in the astrocytic tumors correlates
with histologic grade and PR may participate in the growth of these tumors
and tumor angiogenesis. The measurement of PR in these tumors may indirectly
represent tumor growth potential. Cancer 1997; 80:2133-40. © 1997 American
Progesterone Receptor Expression in Neurofibromas1
Antiprogestins, such as Mifepristone (RU486), are being used currently for
the treatment of other hormonally responsive tumors that express PR,
including breast carcinoma and meningiomas (21) . We propose that
antiprogestins may be useful for the treatment of neurofibromas as an
alternative to surgery, to reduce the size of lesions so that smaller
surgical procedures could be performed, and/or to slow malignant progression
of plexiform neurofibromas.
Please also note other overseas research findings re: use of corticosteroids ie. Dexamethasone & Prednisolone. Mifepristone can overcome that resistance to various chemotherapeutic drugs:
Corticosteroids induce chemotherapy resistance in the majority of tumour cells from bone, brain, breast, cervix, melanoma and neuroblastoma
2007: Mifepristone inhibits ovarian cancer cell growth in vitro and in vivo.
CONCLUSIONS: These preclinical studies show that mifepristone is effective as a single agent in vitro and in vivo, inhibiting the growth of human epithelial ovarian cancer cells. Mifepristone markedly reduces cdk2 activity likely due to increased association of cdk2 with the cdk inhibitors p21(cip1) and p27(kip1) and reduced nuclear cdk2/cyclin E complex availability. Acting as a cytostatic agent, mifepristone promises to be of translational significance in ovarian cancer therapeutics.2007: Mifepristone inhibits ovarian cancer cell growth in vitro and in vivo.
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