Saturday 30 April 2016

Research into blood pressure drug to treat glioblastoma-initiating cells




Researchers reposition existing prazosin drug to combat glioblastoma     

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Treatments available for glioblastoma—malignant brain tumors—have little effect. An international collaboration led by the Laboratoire Neurosciences Paris-Seine (CNRS/ INSERM/UPMC) tested active ingredients from existing medications and eventually identified one compound of interest, prazosin, on these tumors. Not only did it seem to be effective in this type of cancer, but it also acted on a signaling pathway that is common with other cancers. These promising findings are available online (advance publication) in EMBO Molecular Medicine.

Turning old into new is what recycling is all about—and what is being attempted by an international collaboration of research scientists coordinated by Marie-Pierre Junier and Hervé Chneiweiss at the Laboratoire Neurosciences Paris-Seine (Paris). The researchers chose to study the most common malignant tumors that develop from brain cells, glioblastomas, which represent the fourth most frequent cause of cancer deaths among adults and the second in children. This is due to the inefficacy of current treatments. Indeed, a glioblastoma can resist treatment and reawaken from a very small number of tumor cells called glioblastoma-initiating cells (GIC). It is these cells—whose characteristics and properties resemble those of stem cells—that were targeted in the study.

Rather than trying to discover new compounds, the team opted for repositioning existing drugs. In other words, they tested a collection of substances used for so long to treat other conditions that their patents have now fallen into the public domain. This method makes it possible to develop new active ingredients cheaply and very rapidly. Twelve hundred compounds were thus tested on normal human neural stem cells and on glioblastoma-initiating cells from different aggressive tumors. Twelve of these compounds showed a toxic effect on GIC—and none on the normal neural stem cells. The most effective was prazosin. Tested in mice carrying glioblastoma-initiating cells, prazosin significantly reduced the size of tumors and prolonged survival of the mice by more than 50%.

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This compound, which has been used for many years to treat hypertension, is an alpha-adrenergic receptor antagonist. The researchers nonetheless made a surprising finding: glioblastoma-initiating cells are devoid of these receptors. The compound therefore acts via an "off-target" mechanism, or in other words through another pathway than standard interaction. The scientists thus identified an intracellular signaling molecule, PKCδ, which is over-expressed in GIC when compared with normal neural stem cells. In the presence of prazosin, it is only cleaved in GIC, which leads to their death.

Clinical trials will be initiated this year to confirm these findings. If they are conclusive, the compound could rapidly be introduced to complement existing therapies and improve the management of patients with brain cancer. Already, the scientists have discovered that other cancer cells display altered PKCδ signaling, including those in colorectal, pancreatic and liver cancer. Understanding the mechanism of action of prazosin may therefore pave the way for the development of new potential treatments for other cancers.

Source:

CNRS (Délégation Paris Michel-Ange)

Banerji Protocol

Hi,

Has anyone tried the Banerji protocol? Any success with it? Thanks for sharing your experience.
Noha

Could Optune Novocure cause confusion?

My husband started novocure on april 12th. He was intermittently slightly confused then but very minimal. His tumor volume was 9 oz on February 27th. He has been getting worse by the day to the point now where he can no longer be left alone. He is confused all the time (with some periods of good orientation) and sleeps 80% of the day. His tumor started on bilateral frontal lobes. I know this is probably related to his tumor but could Optune be making him more confused?? That's when he seemed to get worse. Amazingly he has no headaches and is only taking 1mg dex daily plus boswellia and turmeric. Can you share your experiences with optune? My husband and I are both 33 yo and have a 7 and 10 yo. I have to keep my full time job as a RN so I can continue to provide for my family but its just killing me to see my husband declines day by day. We are all overwhelmed and trying to adjust to the changes. My brother in law and his wife, and my father in law are taking turns watching my husband while I'm at work. Please keep us in your prayers as he has a MRI scheduled for today.

Thursday 28 April 2016

I.V. for Vitamin C to boost Chemo and overall Immune strength?

Stephen -
I got a strong recommendation from a leading brain cancer oncologist (he appeared on Ben Williams' documentary) to take I.V. for Vitamin C with observational evidence of it significantly helping the patients. I am working on getting prescription next. I am finding lot of materials on web as well about Vitamin C against cancer, though FDA has not approved it. Any insights on this? thanks!

Clomipramine ?

All -

I hope this finds you well.  Dad is hanging in there.  Not doing great, but not significantly declined so we're happy.

I came across a Facebook post with MRIS showing a sizable tumor shrink.  She says they follow the ketogenic diet and a number of supplements, as well as clomipramine.  I searched here and don't see anything except one post mentioning not to take clomipramine while on boswelia, but that's it.

Does anyone here take it or have thoughts on its use for GBM?  I'm very unfamiliar with it.

Thanks as always.
Annie

Extremely urgent

Dear all,
this blog is always a resource of information, I need to say thank you all.
I am Simone, my sister Lorena has a brain tumor since 2010.
All our story started with a first removal operation for fibril astrocytoma with wide signs of anaplasia, after a first treatment of radiotherapy the situation seamed to be under control.

In the July of 2014 a second relapse tumor appear, she undergone on a second removal operation defined completed of anaplastic astrocytoma. Lorena complains hypoaesthesia at the left hemisphere, at the hand. She began Chemiotherapy with Temozolomide. The molecular analysis shows the IDH1 mutation on the operation area – MGMT not methylate.

The brain Magnetic
resonance of August 2015 with contrast shows a round area that has a contrast at the precuneus level, moreover three tiny area of white substance on the
subcortex region. Suspention of Chemiotherapy after 10 cycles of Temozolomide and start with PCV therapy.

From 2015.11.11 to 2015.11.23 radiosurgery on the enhancement areas in the right occipital parietal area. 24Gy in 3 fractions. Isodose 82%

Here you will find an extract of her medical history of the last few months:

EMERGENCY DEPARTMENT 2015.11.16Partial sensory crisis left hemisphere and headaches in therapy with Keppra and Soldesam
 
MAGNETIC RESONANCE 2016.01.13Serious worsening of the magnetic resonance results. Appearance of a voluminousinjury that involves the white substance periventricular and subcortical in right occipital parietal area.Important progression of the illness as glioblastoma. DOTT.SSA MILANESI VISIT 2016.01.15Toxicity caused by radiosurgery that has to be controlled after cortisone.Magnetic resonance between two months. FIRST AID 2016-03-08Important Nausea and headache.Undergone on a control CATscan without Contrast and Blood ExamCAT medical report“Determined disease progression with hypodensities meaning edemigeno-infiltrating affecting the right parietal-temporal-nuclear region with extension to the splenius of the corpus callosum and the capsule system.Collabimento the right lateral ventricle and shift to the left of the center line of about 11mm”Recommended Steroids Decadron 4 mg x 2  MRI 2016.03.09There is an additional significant progression of neoplastic lesion known, in the right parietal occipital. It shows signs of spreading peri axonal along the perivascular spaces of virchow-robin and periependimale. Marcato is also the involvement of the splenius of the corpus callosum.Coexists edema vasogeninco enhancement resulting in higher compressive effect on the ventricular complex. 2016.03.14Start of MANNITOLO 100 CC  three times a day by injection in addition of DESAMETASONE 8 mg three times a day
 MRI 2016.04.10There is an additional significant progression of neoplastic lesion known, in the right parietal occipital.

The situation is much worse. Now they have a palliative treatment of pain, every week is worse, more and more sleep and struggles to speak, until a week ago could sit and eat and interacted more, is now getting to bed. The doctors have told us that there's nothing left to do.

The edema was treated with mannitol and cortisone, which has not reacted as hoped the doctors.
Do you have tips for us? What more can we do?

Thank you in advance, good luck to everyone..
Best
Simone

Wednesday 27 April 2016

Selegiline vs Prozac

Quick question:  which is proven to be more effective in overcoming BBB for agents to go into the tumor -- Prozac or Viagra or Selegiline?  I have seen many people including Prozac in their cocktail. However, Ben Williams probably indicated in his latest PDF that selegiline could be more effective. Any insights to help select one? thanks, Jinesh

Tuesday 26 April 2016

ICT-107 vs. DC Vaccine trial selection

Thank you Stephen for setting me up on this site.

We are evaluating clinical trials to select one for my mother's GBM treatment. She has not yet started on radiation and Tamodar after the surgery. 

Does anyone on this forum have experience with ICT-107 vaccine (randomized with 50% placebo) or DC Vaccine (phase 1) or stem cell based protocol (personalized by UCSF)?  We have to choose one of these three this week itself as it's bee 4 week since her surgery and we are running out of time. Any insights or pointers to help select one would be highly appreciated. 

1)
Phase 3 Randomized, Double-blind, Controlled Study of ICT-107 in Glioblastoma

2)
Phase I Study of a Dendritic Cell Vaccine for Patients With Either Newly Diagnosed or Recurrent Glioblastoma

3)
An ex USCF doctor has offered to work with us on developing cell based high throughput cancer stem cell protocol. 


Friday 22 April 2016

Artusunate and CMV

Stephen

Do you have any information on the results from this study?  https://clinicaltrials.gov/ct2/show/NCT00284687.  The study looked at the affect artusunate had on CMV.  The CUSP 9 paper mentioned Artusunate was effective against CMV.  If this is indeed correct, then it might be a far less expensive approach to CMV than valcyte.

Mike

Recyclining a Anti Hypertensive Agent to Fight Brain Tumors

Saw this yest and thought may b useful to some of u as I believe they r discussing drugs that r already approved and can b added to someone's cocktail. If it's already been posted I apologize!

https://www.sciencedaily.com/releases/2016/04/160421085706.htm?utm_source=feedburner&utm_medium=email&utm_campaign=Feed%3A+sciencedaily%2Fhealth_medicine%2Fbrain_tumor+%28Brain+Tumor+News+--+ScienceDaily%29

Stephen's edit:  click here to download the full study

Wednesday 20 April 2016

New study on subgroups of 1p/19q codeleted oligodendrogliomas

Uploaded to the library, folder 6 (Pathology)

Click here to view abstract

Seattle Science Foundation Lecture Link Available

Hi -

Finally got the link to the lecture from the event at the Seattle Science Foundation: https://www.youtube.com/watch?v=tEWU6TDoR9Y&list=PLyptnEaqO5i5pTEYxgouH61Twgp3I5vMt&index=1

Dr. Soderberg's presentation was not published per her request.  Apparently it's unpublished data.  To summarize what I got from it, 100% of GBM tumors test positive for CMV.  In Sweden 150 +/- GBM patients were given valcyte.  30 were recurrent, the rest newly diagnosed.  All saw benefit.  It's cheapest (for the US anyway) at Mark's Marine Pharmacy in CA (generic is $800 per month).


Thanks.
Annie

IDH1/IDH2 status?

I've spent some time on the sister site, AstrocytomaOptions, but I'm still not quite sure of the significance of these two markers.

My wife doesn't appear to have either of these mutations and I'm not sure if that's a good or bad thing, or is it merely a status. Does someone that doesn't have these mutations change their cocktails, and if so, in what meaningful way?

Thoughts?

NFIB and Brain Cell Division

The study mentions that there are drugs already available that increase NFIB, but doesn't give specifics.

http://www.brisbanetimes.com.au/queensland/brain-development-protein-could-stop-cancer-growth-queensland-study-finds-20160420-gob1fj.html

Tuesday 19 April 2016

Valcyte/ Valganciclovir

Hi,

Has anyone had success using Valcyte? I read a study suggesting that the CMV virus might have a role to play in GBM. Also the Swedish VIGaS study showed some benefit to adding Valcyte to standard treatment. Can someone please share their opinion/ experience with me?
Many thanks
Noha

Saturday 16 April 2016

Perillyl alcohol trial for GBM

The perillyl alcohol trial sponsored by Neonc is slated to open soon at University of Southern California, Cleveland Clinic, University of Washington (Seattle) and University of Wisconsin.

Click here for trial details

What to avoid during stable period

Sorry for repeating my earlier question, but I thought a broader category would help get us talking. My question is whether anyone is aware of mechanisms of action of melatonin or metformin that might make them undesirable for a low grade oli with deletions to take during stable period (either them not being efficacious apart from cocktail or might exacerbate mutation)?

The larger topic is; What should be avoided during stable period that might exacerbate mutation?

Friday 15 April 2016

CRONaxal?

Does anyone have any experience with this? I've seen it posted by three different people in three different places so I wanted to ask.

http://cronaxal.com/index.html

Thoughts?

Monday 11 April 2016

Corneliu Cocktail Profile

Long time I am not Updated my husband Cocktail, but for a while we set approximately to folowing meds+ suplements:

- TEMOZOLOMIDE  - 5/23
- GRANISETRON      - WITH TEMOZOLOMIDE
- CELECOXIB    - 400 MG/DAY
- VERAPAMIL    - 240 MG/DAY
- OMEPRAZOL    - 40 MG/DAY
- CIMETIDINE   - 400 MG/DAY
- LEVETIRACETAM- 1500 MG/DAY
- DEPAKINE     - 1000 MG/DAY
- PLAQUENIL    - 200  MG/DAY
- MEFORMIN     - 1000 MG/DAY and 2000 mg 5/23 with temozolomide

- FLAXSEED OIL - 3000 MG/DAY
- SUPRADYNE    - 1 TABLET/DAY
- REISHI       - 1800 MG/DAY
- MAITAKE      - 1500 MG/DAY
- ALOE VERA   - 500 mg/day
- MILK THISTLE - 1000 mg/day
- VITAMIN  D3   - 5000 IU/day
- VITAMIN C    - 500 MG/day
- LYCOPENE    - 20 mg/day
- GREEN TEA EXTRACT - 1500 MG/day
- RESVERATROL(PTEROSTILBENE)  - 2 X 50 MG/day
- ASHWAGANDA  - 3 X 125 MG/day
- BOSWELIA    - 1000 MG/day
- VITAMIN B12  - 1000 MCG/day
- FOLIC ACID  - 1600 MCG/day
- SELENIUM     - 200 MCG/DAY
- ASTRAGALUS   - 500 MG/DAY
- TURMERIC    - 2000 MG/ DAY
- MELATONIN - 10 MG/DAY

IF I FORGOT TO MENTION SOMETHING, I WILL COME BACK ....

Monday 4 April 2016

My book about parenting a child with a brain tumour

Hi,

I've written a book about parenting a child with a brain tumour. The story is based on a real one (mine), but to help drive the story along, there's a large helping of fiction too.

I'm hoping it's a good read, even if somewhat difficult. I'm also hoping it proves useful to other parents of children with brain tumours, as well as brain tumour sufferers themselves. 


I know the focus here is mainly GBM, and the story deals with a child who has a Grade 1 Pilocytic Astrocytoma. However, I thought it would still be useful.

It's available to read online for free: 
https://glowkeeper.gitbooks.io/my-abi/content/ 

Take care,

Steve

Honokiol

Hi All,

Anyone here on Honokiol can advise me if it is Ok to take it along with DCA and Avastin as well as immunotherapy PD-1? Have you had success with it?

How much dose should we start with? Should be taken all the time or during chemo days ?

Thanks
Noha

Saturday 2 April 2016

Response to nivolumab (PD-1 antibody) in hypermutated glioblastoma

Click here for the abstract

Treatment of two siblings with multifocal, hypermutated GBM resulting from "biallelic mismatch repair deficiency" leads to "clinically significant responses and a profound radiologic response."

Find the full paper in the Library.

Drug timing

Hi all
Hope everyone is well
I'm trying to work out the best times of when to give dad his cocktail in terms of when drugs peak in the body.
Now they say to have at least a 4 hour fast before taking temodar so what I'm asking is :
Celebrex takes about 2 hours to peak and Viagra takes about 1.2 hours to peak so in order to get these drugs to peak at around the same time of temodar you would be needing to take these whilst on the fasting period, is this aloud ?
Also how long dose it take for temodar to peak ?
And also how long dose other drugs take to peak ?

Friday 1 April 2016

CUSP9v4 details uploaded

I've been conversing with Dr. Richard Kast, who helped devise the CUSP9 protocol.

He sent me details about version 4 (CUSP9v4 - 2016.03.23) and I've uploaded the file to the shared drive for your review. If you, or anyone you know, has started the protocol, can you let me/us know what you think of it and how it's working for you?