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 le phenoxodiol

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Nombre de messages : 15767
Date d'inscription : 23/02/2005

MessageSujet: Re: le phenoxodiol   Dim 17 Mai 2015 - 8:24

mise à jour article de Nov 2014 :


RESULTS:

Here we report that phenoxodiol induces cell cycle arrest in the G1/S phase of the cell cycle, with the resultant arrest due to the upregulation of p21(WAF1) in all the cell lines in response to treatment, indicating that activation of p21(WAF1) and subsequent cell arrest was occurring via a p53 independent manner, with induction of cytotoxicity independent of caspase activation. We found that c-Myc and Cyclin-D1 expression was not consistently altered across all cell lines but Ki-67 signalling expression was decreased in line with the cell cycle arrest.
CONCLUSIONS:

Phenoxodiol demonstrates an ability in prostate cancer cells to induce significant cytotoxicity in cells by interacting with p21(WAF1) and inducing cell cycle arrest irrespective of p53 status or caspase pathway interactions. These data indicate that phenoxodiol would be effective as a potential future treatment modality for both hormone sensitive and hormone refractory prostate cancer.


RÉSULTATS:

Nous rapportons ici que phenoxodiol induit un arrêt du cycle cellulaire en phase G1 / S du cycle cellulaire, résultant du fait que la régulation de p21 (WAF1) est à la hausse dans toutes les lignées de cellules en réponse à un traitement, ce qui indique que l'activation de p21 (WAF1 ) et un arrêt ultérieur de la cellule se produisait par l'intermédiaire d'une manière indépendante de p53, avec l'induction de la cytotoxicité indépendant de l'activation des caspases. Nous avons constaté que c-Myc et la cycline D1 n'ont pas été altéré de manière systématique dans toutes les lignées cellulaires mais que l'expression de Ki-67 a été diminuée en ligne avec l'arrêt du cycle cellulaire.

CONCLUSIONS:

Le Phenoxodiol démontre la capacité pour induire une cytotoxicité significative dans des cellules cancéreuses de la prostate en interagissant avec p21 (WAF1) et pour induire l'arrêt du cycle cellulaire, quel que soit l'état de l'interaction de p53 ou la voie des caspases. Ces données indiquent que le phenoxodiol serait efficace comme futur traitement potentiel à la fois pour le cancer de la sensible aux hormones et le cancer prostate réfractaire aux hormones.

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MessageSujet: Re: le phenoxodiol   Lun 26 Nov 2007 - 2:57

Tuesday, 23 October 2007

Yale Cancer Center sponsors study of phenoxodiol for prostate cancer
Researchers seek to build on previous study indicating investigational drug phenoxodiol prolonged time to progression and PSA doubling time.
(New Haven, Conn., October 22)

Yale researchers have begun recruiting 60 men for a clinical trial investigating an experimental new drug, oral phenoxodiol, as a potential first line therapy for prostate cancer. The study is funded by Yale Cancer Center .

Les chercheurs de Yale ont commencé à recruté 60 hommes pour un essai clinique expérimentant un nouveau médicament, le phenoxodiol, comme un médicament de première ligne contre le cancer de la prostate.


http://www.marshalledwardsinc.com/index04.cfm?section=04&status=1&id=219
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MessageSujet: Re: le phenoxodiol   Mer 9 Mai 2007 - 14:11

L'essai sur le médicament phenoxodiol revient dans l'actualité. Il est dit que le phenoxodiol a un excellent profil de sécurité et que quelques patients ont expérimenté des effets secondaires.

De nouvelles études sont faites égalment pour découvrir le mécanisme par lequel le phenoxodiol agit.


Le phenoxodiol a aussi démontré quelque promesse pour restaurer la sensibilité du cancer ovarien aux médicaments. L'essai sur le cancer de l'ovaire devrait produire ses résultats dans 18 mois ou moins.
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MessageSujet: Re: le phenoxodiol   Mar 28 Nov 2006 - 19:23

La phase III de l'essai clinique connu sous le nom de OVATURE a été mis en route au Royal hopital à MElbourne en Australie. Ce sera un des 60 hopitaux qui participeront à cette étude sur le cancer ovarien pour confirmer l'efficacité du phenoxidiol pour ce qui a trait à une resensibilisation des cellules des patients à une chimio thérapie.


Le nombre total de patients à être traité sera de 470, la mitié seront traité avec le phenoxidiol et le carboplatine et l'autre moitié avec un placebo et la carboplatine. 30 des hopitaus seront aux États-unis, 25 en Europe et 5 en Australie. Une phase II déja conduite avait montré que le phenoxodiol avait un effet sensibilisateur pour la chimio sur les patientes avec un cancer ovarien dont la chimio avaient échouer dans un premier temps.


Le phenoxodiol est un médicament à l'essai et n'est pas commercialisé pour le moment.
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MessageSujet: Re: le phenoxodiol   Sam 22 Avr 2006 - 23:31



Le Phenoxodiol régit les suicides pour les cellules cancéreuses

Will Boggs, MD
Reuters Health
Posting Date: February 22, 2006

Last Updated: 2006-02-22 16:33:12 -0400 (Reuters Health)


Le Phénoxodiol sensibilise les cellules cancéreuses ovariennes aux agents chimiques en modulant les chemins apoptiques et non-apoptiques.


La manipulation de réactions en cascades par les molécules comme le phenoxodiol qui peut déranger la machinerie anti-apoptique dans les cellules cancéreuses présentent un espoir majeur pour le développement qui non seulement prolongeront la vie des patients mais pourrait les guérir selon le docteur Gil Mor de l'université de Yale.

Le docteur Mor et ses collègues cherchent à savoir si le phenoxodiol peut agir comme sensibilisateur aux agents chimiothérapeuthiques et quel est le mécanisme derrière cet effet sensibilisateur.


Le prétraitement des cellules du cancer ovarien avec le phenoxodiol les a sensibilisé aux chimios tels le carboplatine, le paclitaxel et la gemcitabine et a abaissé les doses nécessaires pour exposer les cellules aux chimios


Le phenoxodiol a eu des effets similaires sur un souris xénogreffée injecté avec le cancer de l'ovaire

"À notre connaissance disent les chercheurs c'est le premier cass rapporté d'uen molécule capable de sensibiliser les cellules cancéreuses in vitro et in vivo."

Les monothérapies avec leurs agents chimiothérapeuthiques n'activent pas le caspase-3, notent les chercheurs, mais les cellules traitées avec le phenoxodiol seul ou avant la chimio connaissent une hausse de l'activité de caspase-3.

Les résultats indiquent aussi que le phenoxodiol est associé avec une baisse de la protéine anti-apoptique XIAP.

"Les médicaments avec la capacité de sensibiliser les cellulles cancéreuses à la chimiothérapie vont relver l'effet cytotoxique des chimios conventionnelles et réduire les effets secondaires, ils vont prévenir la résistance et réduire les effets secondaires." dit le docteur Mor " De plus, les médicaments comme le phenoxodiol peut sensibiliser les cellules cancéreuses aux réponses su système immunitaire et dès lors prévenir la rechute.

"Nous continuons à évaluer les méchanismes additionnels que les cellules cancéreuses développent pour bloquer la réponse chimiothérapeuthique et tester le phenoxodiol pour vaincre ces processus" a ajouté le docteur Mor "Nous examinons aussi les premiers signaux en provenance de la cellule après le traitemement au phenoxodiol.
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MessageSujet: Re: le phenoxodiol   Ven 30 Déc 2005 - 14:59

Un article plus complet sur le cancer de la prostate et du phenoxodiol. Les résultats des premières expériences sont quasiment trop beaux. Une autre expérience se déroulera à partir de janvier 2006. C'est un espoir sérieux mais beaucoup d'espoirs sérieux se révèlent décevants...je ne sais pas trop quoi en penser.

Thursday, 17 November 2005


Phenoxodiol delays tumor progression in late stage hormone refractory prostate cancer

Long term Phase Ib/IIa study presented at AACR-NCI-EORTC meeting showed significant anti-tumor effects and no toxicity

Philadelphia - November 17, 2005 -- A new study presented today at the International Conference on Molecular Targets and Cancer Therapeutics in Philadelphia shows that phenoxodiol significantly delays tumor progression in men suffering from late-stage hormone refractory prostate cancer. The meeting is sponsored by the American Association of Cancer Researchers (AACR), the National Cancer Institute (NCI), and the European Organization for Research and Treatment of Cancer (EORTC).

The anti-tumor effect in this Phase Ib/IIa trial was dose-dependent. The trial was designed to end after 24 weeks of treatment, but had to be extended to the current 90 weeks because of the unexpected extended survival in some patients. Patients have been able to remain on phenoxodiol for this extended time without any evidence of toxicity.

Researchers administered various doses (20, 80, 200 and 400 mg) of phenoxodiol to men with metastatic, hormone-refractory prostate cancer to establish what level of anti-cancer effect the oral dosage form of this drug would provide and whether there was a dose-dependent effect. The phenoxodiol was administered in monthly treatment cycles comprised of 3 doses daily for 21 consecutive days followed by 7 days without treatment. The original plan was to treat patients for a maximum of 6 treatment cycles. Except for anti-androgen therapy being continued in those who were receiving it pre-trial, phenoxodiol was the only treatment. The age of the 26 subjects studied ranged from 55 to 85, the Gleason score was mean 8.04 (range 6-9), and the mean baseline PSA level was 56.3 pg/ml.

Response to therapy in these patients was determined on the basis of PSA response (a decline in PSA level compared to baseline of at least 50 percent), PSA doubling time (time for the baseline PSA level to double), and time to progression (length of time that patients remained on phenoxodiol based on PSA levels and clinical assessment).

"The two highest dosages of phenoxodiol provided a significant anti-tumor response in a disease that is normally unresponsive to treatment in its late stages," says Robert Davies, MD, lead investigator of the study and urologist at Sir Charles Gairdner Hospital in Perth, Australia. "We found that the PSA level, an indicator of the level of cancer, decreased. We also saw a clinical response that was prolonged in some patients."

Combining the data from the two lowest dosages (12 patients) and the two highest dosages (14 patients), the number of patients still on therapy after 6 months increased from 1 out of 12 (8.5 percent) to 10 out of 14 (71.4 percent), and the mean time to progression (length of time patients were deemed to be deriving a benefit from therapy) increased from 15 weeks to 47 weeks. This latter figure does not take into account four patients who remain on therapy after 42, 74, 82 and 90 weeks.

In terms of PSA levels, there were no PSA responses in the two lowest dosage groups, but 3 of the 14 in the two highest dosage groups experienced a PSA level reduction of 50 percent or greater from baseline. The PSA doubling time increased from a mean 18 weeks to 43 weeks, not including the 3 of 14 patients who remain on phenoxodiol therapy and whose PSA levels have yet to double. While it was not possible to measure tumor size in this study, an increase in PSA doubling time is generally regarded as reflecting a tumor response.

"The long-term anti-tumor effects and safety demonstrated in this study are very encouraging developments," said Graham Kelly, Ph.D, Chairman of Marshall Edwards, Inc. Professor Kelly presented the data on behalf of the investigators in the 12:30 - 2:30 pm poster session on Thursday, November 17, at the AACR-NCI-EORTC meeting.

A Californian oncologist who referred two patients to the trial agrees that the results are good news, and may impact the way prostate cancer is treated.

"Phenoxodiol represents a unique new class drugs for men with prostate cancer," says Steven Tucker, MD, Director of Prostate and Genitourinary Oncology at The Angeles Clinic & Research Institute in Los Angeles.

"If the clinical benefit seen in these refractory patients can be extended into an earlier disease state, we may be looking at a paradigm shift in the management of advanced prostate cancer,” says Dr. Tucker, who is also an Assistant Clinical Professor of Medicine at the UCLA School of Medicine.

Professor Kelly said that the next stage of development of phenoxodiol for prostate cancer would be to use it in patients who have failed to respond to both hormone therapy and docetaxel therapy.

“On the basis of this data, we would expect that phenoxodiol alone would offer these patients a significant survival benefit, but we also will be interested in testing the ability of phenoxodiol to restore sensitivity to docetaxel in these end-stage patients,” Professor Kelly added.

This next study will be conducted in the U.S. and is planned to commence enrollment in 2006.

About Prostate Cancer

According to data provided by the American Cancer Society (ACS), prostate cancer is one of the most common types of cancer found in American men, second only to skin cancer. ACS estimates that there will be more than 232,000 new cases of prostate cancer in the United States in 2005 and about 30,350 men will die of this disease. One man in 6 will get prostate cancer during his lifetime, and 1 in 34 will die of the disease.

Most cases of prostate cancer are sensitive to male sex hormones (androgen), and blocking of the effect of these hormones is a common therapeutic process. Ultimately, however, most prostate cancers become insensitive to androgens, at which time the tumor is referred to as being ‘hormone refractory. The approved anti-tumor therapy for these patients is docetaxel (Taxotere®), which has been shown to provide a modest extension of survival in some patients, before the tumors become docetaxel-refractory. Hormone-refractory, docetaxel refractory patients represent the end-stage of this disease.

About Phenoxodiol

Phenoxodiol is being developed as a therapy for late-stage, chemo-resistant prostate, ovarian and renal cancers.

Phenoxodiol targets the tumor cell’s cation excretion pump, with the resulting disruption to the cell’s redox potential producing a range of biochemical effects including inhibition of phosphorylation of the key pro-survival sphingosine-1-phosphate and Akt signalling pathways. Inhibition of production of anti-apoptotic proteins including XIAP is a key biochemical outcome.

The mechanism of action of phenoxodiol suggests a potential to be used both as a monotherapy and in combination with standard anti-cancer drugs where it acts to enhance the efficacy of those drugs in chemo-sensitive patients and to restore sensitivity to those drugs in chemo-resistant patients. Phenoxodiol currently is undergoing clinical studies in the US and Australia.

Phenoxodiol is an investigational drug and, as such, is not marketed in the US.

More information about phenoxodiol can be found at www.phenoxodiol.com.

About Marshall Edwards, Inc.

Marshall Edwards, Inc., (Nasdaq: MSHL) has licensed rights to bring phenoxodiol to market globally from its parent company, Novogen Limited. (ASX: NRT; Nasdaq: NVGN). Novogen is developing a range of therapeutics across the fields of oncology, cardiovascular disease and inflammatory diseases based on its phenolic drug technology platform. More information on the Novogen group of companies can be found at www.novogen.com.


Dernière édition par le Mar 28 Nov 2006 - 19:33, édité 1 fois
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MessageSujet: Re: le phenoxodiol   Ven 30 Déc 2005 - 14:38

On parle dans cet article d'un essai de Phenoxodiol pour sensibiliser des cellules cancéreuses ovariennes

Tuesday, 29 November 2005


Phenoxodiol in joint trial with Sanofi-Aventis at Yale

New Clinical Study of Phenoxodiol as Chemo-sensitizer for Docetaxel in Ovarian Cancer Commences at Yale University School of Medicine

Combination therapy study to address major need in jumping hurdle of resistance to standard treatments

(WASHINGTON/SYDNEY– November 28th, 2005) -- Marshall Edwards, Inc. announced today plans for a Phase Ib/IIa clinical study of the investigational anti-cancer drug, phenoxodiol in combination with docetaxel for women with recurrent ovarian cancer. The investigator-initiated clinical study will take place at the Yale University School of Medicine and is supported jointly by Sanofi-Aventis and Marshall Edwards, Inc.

Docetaxel is a second-generation taxane that is commonly used in patients with recurrent or persistent ovarian cancer that have failed other therapies, including the first-generation taxane, paclitaxel. In this setting, docetaxel faces the challenge of a high level of drug resistance that has developed following earlier therapy with paclitaxel and other agents. Under these circumstances, the clinical response rate to any chemotherapeutic is often limited due to the rapid development of chemo-resistance. The purpose of the study is to determine if the addition of phenoxodiol to docetaxel can improve clinical response and survival by delaying or preventing the development of chemo-resistance in women with recurrent ovarian cancer.

The study will enroll 60 women with recurrent epithelial ovarian, fallopian tube or abdominal cavity cancer after treatment with a platinum and paclitaxel. All 60 patients will be given docetaxel by injection weekly; half the patients will also be given oral phenoxodiol daily, and the other half a placebo tablet. Tumor response will be determined on the basis of tumor burden (RECIST criteria) in patients with measurable disease, and tumor marker levels (GCIG criteria) in patients with non-measurable disease. Disease free survival, the time from study enrollment to evidence of disease progression, will also be compared between the two groups. Treatment will continue for one year unless there is evidence of unacceptable toxicity or disease progression.

The rationale behind this study is based on two observations. The first is the demonstration in pre-clinical studies of the potent ability of phenoxodiol to reverse chemo-resistance in human ovarian cancer cells to docetaxel, through the ablation of anti-apoptotic proteins in the tumor cells.1,2 The second is the encouragingly high tumor response rate observed in a current clinical study where phenoxodiol is being used to chemo-sensitize paclitaxel in advanced-stage ovarian cancer patients where the tumor is taxane-resistant or refractory.

“Advanced-stage ovarian cancer is one of the most devastating forms of cancer, with half of the women diagnosed with it dying within five years,” said Dr. Thomas Rutherford, the study’s Principal Investigator. “One of the imperatives facing doctors who treat these patients is to find ways to restore sensitivity to drugs such as taxanes once they start to lose that sensitivity.”

“The highly encouraging pre-clinical and clinical data that we have seen with phenoxodiol when it has been used as a chemo-sensitizer to date, gives us optimism that this strategy will provide the means to improve the survival of these late-stage cancer patients.”

The study is expected to open for enrollment immediately and calls should be directed to 203-785-6956.

About Docetaxel Docetaxel (Taxotere®, Sanofi-Aventis) belongs to the taxane family of anti-cancer agents that is characterized by their ability to inhibit cell division by essentially “freezing” the cell’s internal skeleton which is comprised of microtubules. Microtubules assemble and disassemble during cell growth. Docetaxel blocks their disassembly, thereby preventing the cell from dividing and leading ultimately to its death.

Docetaxel is approved by the FDA (i) for the treatment of women with early stage breast cancer, locally advanced or metastatic breast cancer after failure of prior platinum-based chemotherapy, (ii) for locally advanced or metastatic breast cancer after anthracycline-based therapy, (iii) as a first-line therapy for non-small cell lung cancer, (iv) as a second-line therapy for non-small cell lung cancer following prior treatment with cisplatin, and (v) for hormone-refractory prostate cancer in combination with prednisone.

About Phenoxodiol Phenoxodiol is an investigational drug and, as such, is not marketed in the United States.

Phenoxodiol was granted fast-track status by the FDA in November 2004 for its intended use in women with ovarian cancer.

Phenoxodiol is a novel acting drug that inhibits key pro-survival signalling pathways generated by the sphingomyelin pathway. These pathways (eg. sphingosine-1-phosphate) are over-active in tumor cells, and their inhibition by phenoxodiol leads to the prevention of production of key pro-survival proteins such as XIAP. XIAP, an anti-apoptotic protein, prevents cell death by blocking signals coming from the death receptors on the cell surface. Removal of such anti-apoptotic proteins restores the ability of tumor cells to undergo apoptosis in response to chemotherapy.

The putative primary molecular target of phenoxodiol is a family of proteins expressed on the surface of tumor cells, but not on non-tumor cells. The restriction of expression of that family of proteins to tumor cells is thought to account for the high specificity of phenoxodiol.

Phenoxodiol is able to kill ovarian cancer cells that are highly resistant to standard anti-cancer drugs, as well as being able to restore sensitivity in these cells to standard anti-cancer drugs such as taxanes. These findings have been borne out in recent clinical results showing that some women who have stopped responding to taxane and platinum drugs had disease regression when phenoxodiol was given in combination with their chemotherapy.3

About Ovarian Cancer Ovarian cancer is the most lethal gynecological malignancy, and the fifth leading cause of cancer related death in women in the United States. The American Cancer Society reports that an estimated 25,400 new cases of ovarian cancer will be diagnosed each year in the United States and 14,300 deaths will occur. One in 70 women will develop ovarian cancer and one out of 100 women will die from this disease. This high mortality is due mainly to the inability to detect early disease, with approximately 80% of patients being diagnosed in advanced-staged disease. However, even in those patients diagnosed with Stage I or Stage II disease, the five-year survival rate ranges from 60 to 90 percent depending on the degree of tumor differentiation, and despite treatment advances over the past decade, there has been no advance in overall survival. The reason for this is the high rate of relapse.

Of patients who respond to first-line chemotherapy, less than 10 to 15 percent of these will remain in remission, and most relapsed cases are chemo-resistant. The failure of some ovarian cancers to respond to first-line chemotherapy and the development of resistance to multi-drug therapies represent the major hurdles to effective therapy of ovarian cancer.

About Sanofi-Aventis The Sanofi-Aventis Group is the world's third largest pharmaceutical company, ranking number one in Europe. Backed by a world-class R&D organization, Sanofi-Aventis is developing leading positions in seven major therapeutic areas: cardiovascular, thrombosis, oncology, metabolic diseases, central nervous system, internal medicine, and vaccines. The Sanofi-Aventis Group is listed in Paris (EURONEXT: SAN) and in New York (NYSE: SNY).

About Marshall Edwards, Inc. Marshall Edwards, Inc. (Nasdaq : MSHL) has licensed rights to bring phenoxodiol to market globally from Novogen Limited (Nasdaq : NVGN). Marshall Edwards, Inc. is majority owned by Novogen, an Australian biotechnology company that is specializing in the development of therapeutics based on regulation of the sphingomyelin pathway. Novogen, based in Sydney, Australia, is developing a range of therapeutics across the fields of oncology, cardiovascular disease and inflammatory diseases.

More information on phenoxodiol and on the Novogen group of companies can be found at www.marshalledwardsinc.com and www.novogen.com.
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MessageSujet: Re: le phenoxodiol   Ven 16 Déc 2005 - 15:54

Nov 20, 2005


Hope For Prostate Cancer Patients From Australia

I just saw this exciting news that comes across the Pacific Ocean, from Australia. Good news for those prostate cancer patients, who have lost all hopes. This new drug called phenoxidiol is showing promise as a treatment for prostate cancer, particularly for patients whose cancers have not responded to other forms of treatment.

Patients with hormone-sensitive prostate cancer are given drugs that block the effects of testosterone, but those treatments are usually effective only for a period of time. Eventually the cancer cells learn to defeat the hormonal manipulation and grow despite continuation of hormonal therapy. At this point in the course of their disease, there is nothing much to offer in terms of treatment.

The new drug, phenoxidiol, works by reprogramming cells to encourage cancerous ones to die off. In a trial of 26 patients in the United States, those patients given the highest doses had the best response, with few side effects.

"We found that the PSA level, a measure of the activity level of prostate cancer, decreased and we found that some patients clinically improved," says Urologist Dr Robert Davies.
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MessageSujet: le phenoxodiol   Ven 16 Déc 2005 - 15:45

Des urologues australiens proposent un nouveau médicament contre les cancers de la prostate qui dépendent des hormones : le phenoxodiol. Il reprogramme les cellules cancéreuses pour qu'elles se suicident. Un test sur 26 patients américains a montré une meilleure réponse au fur et à mesure de l'augmentation des doses. Ce médicament permettrait de considérablement améliorer le traitement. Il est en cours de tests sur des cancers ovariens.


autre site qui en parle (en anglais)

p.s. Plus mon médecin s'acharne à me voir mort, plus je m'acharne à me trouver un médicament qui me sauverait.


Dernière édition par le Lun 26 Nov 2007 - 6:14, édité 2 fois
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MessageSujet: Re: le phenoxodiol   Aujourd'hui à 12:26

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