Friday, 15 February 2019

GBM recurrence

Dear All,

I request your opinion and advice, since our situation is very difficult. A young adult (19 years old) was diagnosed with the GBM WHO IV (gliosarcoma), and further genetic screening revealed the H3F3A G34 mutation, with ATRX, TP53, PDGFRA and others. The treatment was more or less standard Stupp protocol, with adjuvant TMZ+CCNU (as  in CeTeG trial) after the chemoradiation. After 8 months from diagnosis and the fourth chemo cycle, a diffused regions appeared in MRI scans, which our oncologists interpreted as progression, and in spite of three independent NO opinions from US, Spain and Poland, they decided to switch the chemo to Topotecan+dacarbazine (DICT). That worked for 8 cycles. During that time we tried to enroll in  a few clinical trials but without any success, usually due to the geometry and character of changes, a lack of free places, non-recruiting or closed trials and other circumstances.

Our supplements coctail was rather conservative (PSK, fish oil, melatonin, boswellia, curcumin, berberine, bee products, pterostilbene, ecchinacea, syllimarin) + anti-seizure drugs.

Unfortunately, the last MRI scan made a few days ago shows that the tumor has invaded many parts of the brain, though the primary site is essentially clean. This is a real shock for us, since the previous scan made at the beginning of December, 2018 revealed stabilization and even some improvement when compared with previous scans made on 2-months basis.

Our doctors stand at the opinion that nothing more can be done, and they sent us home (to palliative care).  I feel devastated, they give us at most a few weeks.


- Could be a metronomic TMZ (40-50mg/m^2) beneficial in this situation, as the primary tumor was non-IDH1 and likely non-MGMT, that would be the only thing to do, given that the patient has mood changes, lacks of concentration; or any other salvage chemo, Avastin, Nivolumab?

- Do you know or could you recommend a hospital/center in Europe which could provide a second and reliable opinion (like https://www.ucsfhealth.org/secondopinion/)?
 


Stefan Sobieski

Amazing G47 Delta (Herpes Virus) data from Japan for rGBM

Dear all,

Just came across a very promising phase II trial interim update from Japan, from Daiichi Sankyo's ongoing G47 Delta trial. It looks like this virotherapy is heading for fast-approval in Japan, after achieving amazing interim results in recurrent GBM:

- 1 yr survival was 92.3% (12/13 patients), vs. around 15% in historical comparisons
- Median PFS (16 people) was 8.6 months; Median OS has not been reached yet (but at least 4 with a 2 year follow-up so far)

While a small population, the results were so strong that the company is seeking to bypass the phase III trial altogether and apply in the near future for manufacturing & marketing of the treatment. Expectation would be to reach conclusion of this process within this year. It would be the first virotherapy treatment on the market.

I did not find anything on it in the English web, but here is the Japanese press release (best us web translate, which works reasonably well):

https://www.amed.go.jp/news/release_20190213.html?fbclid=IwAR3rLbU6z4MYkAoqr9trLuXQNMwKG9eLYRJd7v8YJiK-Urfex3on7zGtRtE

Very good news I believe! Hopefully we can get similar good news this year also from TOCA & DcVax. I really feel like 2019 will finally be a game changer for GBM, finally!

Best,
John

P.S. Does anyone have a view how likely it would be to get this treatment approved outside of Japan given these results?


Wednesday, 13 February 2019

Leacadinum

I'm posting this on behalf of a correspondent.

Hello!
We are  searching for medicine against brain tumor.
We found an information about Leacadinum and spoke with its creator Ivars Kalviņš. He is from Lithuania.
It was very effective instrument till 1990’. https://m.lv.sputniknews.ru/Latvia/20170220/3960096/mildronat-latvija-uchenye.html?mobile_return=no (russian articles). https://meduza.io/feature/2016/03/09/etot-preparat-spas-tysyachi-zhizney “after a course of Leacadinum use, the tumor was reduced by approximately 35–40%, metastases to the brain stem disappeared.”

And also we know story of 1 woman with GBM who survived after its using for many years (when is was in production).
Now this medicine is not producing (because of politics or something. It was bad times for USSR and its friendly countries).
We know the owner of the patent. And may be it is possible to order a test batch from him.
In this case we are searching for any information about Leacadinum:
  1. patients true stories
  2. Doctors evidences (doctors should be people after 50-60 years old I  think)
  3. May be someone of you will join us in ordering of test batch (more people=cheaper cost).
And any comments and discussions  will be helpful! 

Especially people from Lithuania are welcome! 

Neo-adjuvant (before surgery) pembrolizumab

Neoadjuvant anti-PD-1 immunotherapy promotes a survival benefit with intratumoral and systemic immune responses in recurrent glioblastoma

http://sci-hub.tw/https://www.nature.com/articles/s41591-018-0337-7



This was a small, randomized trial for recurrent GBM at first or second relapse, who were candidates for surgical debulking and were on steroid doses less than 4 mg per day of dexamethasone or equivalent.  There were 16 patients in each arm. One arm (neoadjuvant) received pembrolizumab (Keytruda) 14 days before surgery, and further doses of pembrolizumab after recovery from surgery. The second arm (adjuvant) received pembrolizumab only after surgery.

The survival advantage of neoadjuvant pembrolizumab was statistically significant (hazard ratio = 0.39, P = 0.04).  Note that it's more difficult to achieve statistical significance in a smaller trial versus a larger one.  Patients in each arm were well-matched for typical prognostic features.

In light of the positive results of this trial, "we intend to expand the current study and pursue further clinical trials with neoadjuvant combination immunotherapeutics."

Tuesday, 12 February 2019

Tumor Monorail

Is there any mention on this site about this Tumor Monorail?  What are your thoughts Stephen?
https://medicalxpress.com/news/2019-02-breakthrough-device-llures-aggressive-brain.html

My husband had a focal seizure at the airport and this week had one while waiting for his f/u MRI at home.  He's never had seizures b4 this.    After 5 yrs tumor free from original GBM diagnosis,  recurrence/surgery one year ago, they now think he could have two tumors!   Time to head south to UCSF for Dr. Berger to weigh in since one tumor site looks close to the ventricle.  :-((  

Also, he's had skin cancer on his head w/2 Moh's surgeries with grafts this last summer and the rashes from that, in itself, could inhibit him having surgery, fearing if any infection could get in his brain if they open him up.     Talk about getting slammed!!!  We are waiting to hear from UCSF for their opinion.  I don't have a good feeling this round.

Candy

19 yr old with GBM, any advice for next step warmly welcomed x

Hello everyone, I've learned so much from this site already but now I have some more detailed information I'm wondering if anyone can help me with some specific advice (I apologise for the long post now)

My 19 year old daughter was in her first tern at Uni when she was diagnosed with Glioblastoma Multiforme in October, She had a craniotomy early November and most of the biggest tumour was removed. She then had the standard 6 weeks of radiotherapy (18 full brain, 12 targeted) with Temozolomide. She's had a month off and just had her first double dose 5/23 chemo (and she's been horribly sick with it and has zero appetite)

We were hoping to go down the DCVax route but it looks as though there might not be enough frozen tumour material to make a full vaccine (and we're gutted)
We had an Oncologica biomarker report and it looks like her mutations are ATM, TSC1 and TP53, her PD-L1 tumour proportion score is 90-95%, PD-L1 positive ICs 1% of tumour area (which I'm told suggests she'd be a good candidate for immunotherapy)

In terms of what Laura's currently taking, she's takes FECO 3 times a day, Keppra, Chloroquine and she's also on the Care Oncology protocol (Metformin, Atorvastatin and Vermox)

Supplement wise she also takes;
Boswellia
Berberine
Bromelain
Longvidia Curcumin
Milk thistle
Melatonin
Artemisia
Vitamin A D K
Resveratrol
Grapeseed

So the reason for the post is to ask if any of you wise people have any suggestions as to where we could look next? I think we might struggle with dendritic cell therapy due to the small sample size but is it possible to get hold of immunotherapy drugs or is that only an option if you're on a trial?

Laura was just getting started in her life and I'll do whatever I can to give her the best possible change of a happy life.
Thanks very much for reading and best wishes to you all
Nicola x


Hi to everybody. My 69-year-old mother was diagnosed with glioblastoma in december 2018. We realized that she was missing a few words in reading, writing and talking and having constantly headache. It was operated on 12/27/18, when approximately 90% of a tumor was removed. She never had any seizures. After the surgery she had a considerable improvement in writing and reading and did not fell any more headaches, despite having presented a little tremor in her hands. Radiation therapy started on 01/23/1919 and was fractionated in 15 sessions. The first cycle (21 days) of temodal (temozolamide - TMZ) chemotherapy was started on 05/02/19.

Since the surgery she has been taking:

- Omeprazole
- Pure (she has hypothyroidism)
-Paroxetine
- Depakene 500 mg twice a day
-dexametazone just one per day
zolpidem

and supplements:
- magnesium chloride
-D vitamin 10,000 cu
- curcurum (curcumin)
-Omega 3
metatonin (15) at night

started recently:
resveratrol
1 clove garlic, raw

and will start:
-Beta Glucan
-artemisinine
-genysteine
sibyllin


We are thinking of associating acetatalozamide with the next cycles of temozolomide.

I would like you, or someone, to evaluate, and please and if possible make some comments and suggestions.

Note: We have not taken the MGMT exam yet.

thanks in advance

Thursday, 7 February 2019

Request for choosing a suitable cocktail



Hi everybody and many thanks to Stephen for adding me to
this wonderful blog.
I have some questions regarding my father situation and it’s
a bit embarrassing cause we don’t have detailed information about the tumor as
many of you have, so I wonder if someone could kindly help me to choose the
best probable cocktail for him while I know that it is just a shot in the dark.

He is 69 years old and last year (March 2018) during working
with probably toxic glue he suddenly fainted out and later he had problem in
his stomach. We went through lots of colonoscopy and other procedures during a
year and he lost more than 10 kg. Finally (at September 2018) we had a MRI that
said low grade glioma (in the LT temporal)
is the first possibility. (I guess since his HDL and LDL cholesterol were 41
and 77 mg/dl in July 2018 the tumor was not aggressive at that time). We’d been
told that because of tumor location it is better to do nothing and just wait.
(I am suspicious about
Finasteride pill that he took for 3 years for his prostate and we recently switched
to Terazosin)
Then in December we had
the second MRI which shows a “51*47*24 mm heterogeneous mass with surrounding edema
and extension to hippocampus region and mass effect on the LT with mild mid
line shift”.
Then we went through a
painful process to decide whether we should take the risk of surgery and
finally we decided not to (which I am still doubtful about it). After a stereotactic
biopsy which only says this:
  •  Microscopy:




Sections reveal fragments
of tissue including an astrocytic neoplasm. The cellularity is high. The cytologic
atypia include unclear hyperchromatism and some pleomorphism with scattered
cells having larger more hyperchromatic nuclie, occasional multinucleated. There
is rather extensive necrosis with prominent vascular and endothelial
proliferation.
  • Diagnosis:







Astrocytoma, anaplastic
with necrosis (glioblastoma multiforme), left temporal and basal ganglia involvement.
 



We started the temodal (120)+ radiotherapy (30 sessions) recently and now he
is in his second week.
He is taking 1 sodium
valproate 500, had around 25 dexamethasone (finished now), 3 phenytoin 100, 2 ranitidine!,
and 1 Terazosin a day.

I am trying to persuade
his Drs: to change ranitidine to cimetidine and maybe adding metformin (since he
had lost many weight I don’t know if they accept this and as someone mentioned
here metformin and cimetidine does not go well together. Am I right? But cutting
his carbohydrate too much is quiet hard so I still like metformin)

Also maybe chloroquine if
they accept.

-         
So the first silly question is that, if he goes well with the first cycle
can we say his tumor is methylated?
-         
Do you think Turmeric curcumin NovaSol could work as a replacement for
Longvida? Because of his weak stomach I thought soft gels might work better.  (https://www.amazon.com/Turmeric-Curcumin-NovaSOL-Bioperine
Softgels/dp/B018GQJQHM/ref=sr_1_2_s_it?s=hpc&ie=UTF8&qid=1533759320&sr=1-2&keywords=NovaSol%C2%AE&dpID=61EqNrydTdL&preST=_SX300_QL70_&dpSrc=srch
)

-         
What would you suggest for such a vague situation for a cocktail or other
therapy? (
  Ttf and vaccine are not available here)


I know most of information I said are useless but I thought it might help for some better guess. 

Many thanks in advance,

Sahel


Tuesday, 5 February 2019

Chemoradiation + PCV + Cannabidiol for IDH1-mut secondary GBM

Case Report: Clinical Outcome and Image Response of Two Patients With Secondary High-Grade Glioma Treated With Chemoradiation, PCV, and Cannabidiol
Dall'Stella et al. 2019

link to full study

Monday, 4 February 2019

Drugs to Combine with CCNU

My husband will soon begin CCNU for recurrence. In reviewing Ben Williams' document, I see that Verapamil and Calcium Channel Blockers like nimodipine have some evidence for augmentation benefit; however, the articles I found (both from his references and my own search) are quite old. Verapamil has more drug interactions than nimodipine. Is there any research about these drugs or other potential augmenters which I might share with his NO? (His NO has generally been supportive of repurposed drugs when I can share relevant studies. His NO does not want to combine CCNU with TMZ despite CeGaT study due to increased toxicity.)

Much gratitude and well wishes to all--
S.

Saturday, 26 January 2019

Advice for a 8 year-old boy with diffuse midline glioma, BRAFV600E and H3K27M mutation

Dear Stephen, dear all,

Anatole, my 8 year-old son has been diagnosed in May 2018 with a diffuse midline glioma on the right thalamus. We are French and based in Stockholm, Sweden. We followed the proposed protocol with the local medical team who works in partnership with Gustave Roussy institute in France but we want to go further now, and we need your advice. The local medical team is not very aware of alternative medication but is willing to help.

Molecular status of the tumour:
BRAFV600E and H3K27M mutation
NF1 and MLH1 mutation
We have little chance to find new targetable alterations by a deeper sequencing. It is possible now that the V600E BRAF mutation is lost in the resistant cells but anyway we do not think it is wise to treat with a V600E BRAF inhibitor which in our experience could speed up tumor growth.  

History:
18/05/09 Diagnosis: MRI tumour size 3.3x3.7x3.7cm, unusual calcification
18/05/16 Biopsy, leading to light hemiparesis
Proton-therapy 18/07/02-18/08/13, 1.8Gy x 30 = 54Gy. Almost fully recovered from hemiparesis
18/09/07 Headaches
18/09/07 MRI tumour size about 4cm
18/09/12 Ventriculostomy
18/09/19 Beginning og Dasatinib (100+70mg/day), after 18/11/06 alternating with Everolimus (5mg/day) every 2 weeks (Biomede protocol)
18/09/22 Beginning of hemiparesis
18/10/03 Wheelchair for walks more than 20m
18/10/12 MRI tumour size 5 to 6cm unsure if pseudoprogession
18/10/22 Beginning of Bevacizumab then once every 2 weeks
18/11/06 Beginning of Everolimus  
18/12/03 MRI tumour size 4 to 5cm unsure if pseudoprogession
18/12/17 Crook for walks less than 20m
19/01/14 MRI tumour size 5x6x5cm
19/01/22 Stop all current chemo (Dasatinib and Everolimus, last Bevacizumab 19/01/02)
24/01/24 PET scan (methyonine)
New plan established by Gustave Roussy Institute: Mebendazol, investigation for debulking of calcification before re-irradiation, eventually ONC201
Any comment on this plan?

Supplements:
Anatole is 30kg 132cm  
D3 vitamin since 18/12/24: escalading from 40µg/d to 100µg/d now
Fish oil since 18/12/24: 1g
Melatonin since 19/01/10: escalading from 2mg/d to 5mg/d now
Turkey tail since 19/01/25: 500mg/d

We plan to add soon:
Longvida Curcumin: 800mg/d
Milk thistle: which dose would you recommend? 
Green tea extract: which dose would you recommend? 
Broccoli sprouts: which dose would you recommend? 
Metformin: Is it worth considering for a child?

Anything else you would find suitable considering his condition (celebrex, chloroquine, clomipramine, berberine, selenium, probiotics, etc?

Diet:
We follow a light low carb diet now (no refined sugar or flour, very limited sugar, no processed food, only bio food). We are planning to begin a ketogenic diet soon, we are ready to change all our habits. We will contact a dietetician specialist in this diet. Anybody else with an experience of ketogenic diet with children?

Thanks to all of you for your precious help, any contribution could help.
Fabrice

Sunday, 20 January 2019

Cannabis oil treatment (THC)

Dear Stephen, dear all!

What do you think about using cannabis oil with a high content of THC component to treat glioblastoma. (Exact component concentration is not known (but declared as high).

Based on recommendations of one doctor, the oil should be applied according to the following scheme (it's also known as Rick Simpson's scheme):
* first day - one drop x 2 times a day;
* then every three days increase intake by one drop in the morning and evening
* reach 24 drops (approximately 1 ml) and take this amount x 2 times a day.

There are a lot of wonderful stories about its anti-cancer effect in the Internet, especially in case of brain tumor. But then I found this research http://cancerres.aacrjournals.org/content/64/6/1943.long#sec-10.

"Treatment of the glioblastoma cell line U373-MG and the lung carcinoma cell line NCI-H292 with nanomolar concentrations of THC led to accelerated cell proliferation that was completely dependent on metalloprotease and epidermal growth factor receptor (EGFR) activity."

"In the light of these results, the use of cannabinoids in cancer therapy has to be reconsidered, because relatively high concentrations of THC induce apoptosis in cancer cells, whereas nanomolar concentrations enhance tumor cell proliferation and may, therefore, accelerate cancer progression in patients."

"Smoking of THC is the most effective route of delivery, as THC is rapidly absorbed after inhalation, and the effects become fully apparent within minutes. Pharmacological activity of smoked THC depends on the depth and length of inhalation. Maximum serum concentrations up to 267 ng/ml (850 nm) are measured after smoking THC, whereas maximum serum concentrations of oral or rectal administered THC or its derivatives as a drug are lower (35–350 nm). Here we observed a proliferative response of glioblastoma and lung cancer cells at concentrations of 100–300 nm THC, whereas THC at micromolar concentrations induced cell death in agreement with previous observations with neuronal cell types and immune cells. These findings indicate that the biological responses to cannabinoids critically depend on drug concentration and cellular context. Taken together, these results have to be taken into account when considering therapeutic applications of cannabinoids. The risk in the medical use of THC or cannabis for the treatment of patients with established tumors is the further acceleration of tumor growth due to the proliferative potential of cannabinoids."
Questions:

1. Has anyone tried to measure THC concentrationt in the blood? Are there any tests for home use that can show the quantitative content of this component in the blood? I know that there are tests for saliva and urine, but how to compare blood concentration and saliva/urine?

2. Perhaps it is easier to measure the THC concentration in one oil drop? And then to estimate what concentration it causes in the blood?

3. Do I understand correctly that THC has a cumulative effect when using daily and in principle it is real to achieve micromolar concentration after some time?

4. Is it possible to avoid the psychotropic effect with micromolar concentration?

5. Is THC effective by itself or only with radiation therapy or chemotherapy?

6. May be it's really better smoking if it allows to achieve more THC concentration? 

I am looking forward to your answers! Thank you!


And please accept my late congratulations with New Year! Let it be full of wonders! Health to all of you and your loved ones!

Irina

Recurrant anaplastic astrocytoma treatment options

Hey all,
Need suggestions for treatment options and supplementation for my brother
His clinical history is-
clinical history date remarks
diagnosed in                                                                                                         september 2009                               assumed to be begnin tumour
                                                      observation through mri 
Tumour surgical resection 18th feb 2016 tumour started to enhance in size
gross resection of more than 95% 
tumour size 7.2x5.5x5.1( anaplastic oligoastrocytoma)
RT PLUS  CONCURRENT TEMOZOLOMIDE 2ndAPRIL 2016 TO 17th MAY 2016 59.4 gy ,33 fractions plus 120 mg temozolomide
Temozolomide june 2016 -december 2016 6 cycles
Recurrence                                                  may-18         
reradiation +concurrant temozolomide 18th jul 18-16th aug 18 36gy, 20 fractions plus 120 mg temozolomide
temozolomide chemo 1st jan 19-5thjan 19 200mg per day for 5 days                              
HIS BIOMARKERS ARE-

BIOMARKER AND GENOMIC FINDING STATUS
MICROSATELLITE STATUS MS-STABLE
TUMOUR MUTATIONAL BURDEN  TMB-LOW (4 MUTS/MB)
ATRX  LOSS
IDH1 R132H
NOTCH1 A465T SUBCLONAL,E450K-SUBCLONAL,R353C-SUBCLONAL
SMARCA4 T910M
TP53 G245S,R273C
MGMT UNMETHYLATED(METHYLATION SCORE-0.49)
ANTIBODY TYPE RESULT
GFAP POSITIVE
IDH1 R132 POSITIVE
KI-67 POSITIVE PROLIFERATIVE INDEX APPROX 10-15%
FISH TEST
1P/19Q CO-DELETION NEGITIVE
EGFR NEGITIVE FOR EGFR AMPLIFICATION
PTEN LOSS POSITIVE (39.3% OF NUCLEI EXAMINED)
His current medications are-

Part of Day Medicine Name Medicine count Notes
PRE MORNING BROMELAIN 500 MG NOW 3 EMPTY STOMACH
TAB PAN 40 MG RT OD 1 STOP ON 30TH JAN 2019
MORNING BREAKFAST CURCUMIN TABLETS 3 NOT WITH AVASTIN OR TAGRISSO/TARCEVA
GLYCEROL 30 ML 1
DIAMOX 250 MG 1
METAFORMIN 500MG 1 TWICE DAILY FROM 1ST FEB
IBUPROFEN 200 MG 1
CBD OIL 2 FULL DROPPERS 1
LEVIPILL 750 MG RT 1
LASILACTONE 20/50 MG RT 1
TAB DEXA 4 MG RT 1 STOP AFTER 21ST JAN
TAB BACLOFEN 5MG RT 1
REFRESH EYE DROP 2 BOTH EYES 2 DROPS
LEVOLIN NEBULISATION .63MG 1 STOP ON 25TH JAN 2019
TAB GLYCOPYRROLATE 1 MG 1 STOP ON 20TH JAN
TO BE ADDED VALGANCICLOVIR 450 MG 2
CHLOROQUINE 250 MG 1
CELEBRAX 200MG 1
WHEY PROTIEN 2 SCOOPS  WHEN RECD FROM USA
GRAPESEED EXTRACT 250 MG 1
STRESS B COMPLEX 2
LUNCH CURCUMIN TABLETS 3
MEBENDAZOLE 100 MG 1 START DOXYCYCLINE ON 18 TH APRIL
GLYCEROL 30 ML 1
IBUPROFEN 200 MG 1
LASIX 40 MG 1
REFRESH EYE DROP 2 DROPS STOP AFTER 21ST JAN
LEVOLIN NEBULISATION .63MG 1 TIME STOP ON 25TH JAN 2019
TAB GLYCOPYRROLATE 1 MG 1 STOP ON 2O TH JAN
TO BE ADDED CELEBRAX 200MG 1
NIGHT CURCUMIN TABLETS 3
ATORVASTATIN 40 MG 1 80 MG FROM 1ST FEB
GLYCEROL 30 ML 1
DIAMOX 250 MG 1
IBUPROFEN 200 MG 1
CBD OIL 2 FULL DROPPERS 1 AFTER HALF HOUR GIVE THC 6 DROPS
THC OIL 6 DROPS 1
LEVIPILL 750 MG 1
LASILACTONE 20/50 MG 1
TAB BACLOFEN 5MG RT 1
REFRESH EYE DROP 1 BOTH EYES
LEVOLIN NEBULISATION .63MG 1 TIME STOP ON 25TH JAN 2019
TAB GLYCOPYRROLATE 1 MG 1 STOP ON 2O TH JAN
TO BE ADDED VALGANCICLOVIR 450 MG 2 STOP ON 9TH FEB 2019
CELEBRAX 200 MG 1
BERBERINE 500 MG 1
BEDTIME ARTEMISIA 500 MG 2 WHEN RECD FROM PATRICE
TAB FRISIUM 5MG RT 1
PLEASE SUGGEST
1.SUPPLEMENTS TO ADD OR TO BE DISCONTINUED
2.AVASTIN OR LOUMUSTINE OR ANY OTHER TRIAL DRUG BEST SUITED FOR HIM
3.ANY OTHER EFFECTIVE THERAPY TO HELP HIS QUALITY OF LIFE.

Saturday, 19 January 2019

Phosphatidylserine

Stephen, are you familiar with the young man from Canada who is a long term survivor of GBM?

Apparently he took Phosphatidylserine but he is not intimating that is the reason for his survival.   Interesting website.



Do you have any thoughts on Phosphatidylserine?



Hope all is well.

Candy

Thursday, 17 January 2019

Temozolomide + mifepristone in rat glioma model


  • Mifepristone, an FDA and Health Canada approved antiprogestogen, used to induce abortion.
  • C6 rat glioma cells implanted into brains of male Wistar rats
  • temozolomide applied to the rats at a dose of 5 mg/kg/day intraperitoneally
  • mifepristone applied to the rats at a dose of 10 mg/kd/day subcutaneous injection
  • rat survival as show below ("sham" refers to rats undergoing sham surgery with no glioma cells implanted)
  • combination of temozolomide + mifepristone was effective where either single agent alone was  ineffective







Wednesday, 9 January 2019

advices on cocktails and corticoids

My father in France - 71 years old - has been diagnosed with a GBM grade IV in September 2018. Before that he has always been in good shape and was very sportive.
He has 3 tumors from 10mm to 40mm and seems to be inoperable. He already had 3 sets of TMZ and he is taking already some supplements I recommended based on my researches on Internet. 
Here is his complete current treatment started 1 month after first diagnosis (time to perform biopsy) :


Temodal3 cycles of 5 days done
Corticoids - Solupred50 to 60 mg / day
Cannabis suppositories1g / day (80% THC)
Chinese herbs and mushrooms (including Artemisia Annua)every day
Vitamin C5g / day
Nutraexpert Lipo HCA dietary suplements containing:
HCA1500 mg / day
Alpha Lipoic Acid1600 mg / day
Capsicum112 mg/ day
Quercetin45 mg/ day
Ginger46 mg/ day
Whey47 mg/ day
Green tea30 mg/ day
Nicotinamid20 mg/ day
Vitamin D325 µg/ 1000 UI
Ketogenic diet
Curcuma (Longvida) : added last week1g / day

Biopsy revealed :

  • IDH1 : negative
  • FGFR3 : negative
  • P53 protein : 15 - 20%
  • no information on MGMT

MRI performed early december has show a slight size increase in the 2 biggest tumors, the oncologist says it is not alarming as the treament started one month after first diagnosis.
Currently my father resists well and tries to keep daily walking activity. Next MRI will be next month. 

I just recently discovered the cocktail approach and your blog and I have some questions.

1. It seems many patients are taking Melatonin 20 mg/ day (forbidden in France at this dosage by the way) and that it could be of good help : sustains the immune system, anti-oxidant, anti inflammatory, leads to cancer cells suicide ... Should I add Melatonin to the treatment ? It seems also that Malatonin is non compliant with corticoids as it inhibits corticoids effects : what do you think ?

2. More globally I fear corticoids may have a negative impact on the different supplements. Is there a mean to sustitute it by anything else ? Is Celebrex an option ? If so at which dosage ? (the inflammation is still important, but decreasing).

3. Would you have any recommandation in other supplements or drugs ? PSK mushroom, Valpoic Acid, Metformin? 

Thank you very much for your precious help.

Saturday, 5 January 2019

Question about TP53 Mutated Tumors and Use of Chloroquine

In reviewing the section on TP53 from Astrocytoma Options, I noted "autophagy inhibition with chloroquine prevented restoration to normal P53 function" and therefore best to avoid autophagy inhibitors. Would someone kindly clarify whether this suggests chloroquine should be avoided for my husband who was found to have TP53 Variants including insertions/deletions? 
We have been using it for its purported benefit for EGFR amplification.
If so, are there other autophagy inhibitors to avoid?
Would Zinc be worth adding? (Tried it briefly in the past and experienced GI upset).

Many thanks and healing wishes to all--

Wednesday, 2 January 2019

Limited activity

My personal computer is out of service and I won’t be able to get a new one until next week at the earliest.  Consequently my blogging and researching abilities will be very limited until then. Thanks for your patience and best wishes to all in the new year!
Stephen

Saturday, 29 December 2018

Alpha lipoic acid and hypoxia

Some patients use alpha lipoic acid in the treatment of glioblastoma. For example, it is part of the Metablock protocol or is accepted to minimize side effects of DCA.

However, this new study contains strange conclusions:

Alpha lipoic acid attenuates hypoxia-induced apoptosis, inflammation and mitochondrial oxidative stress via inhibition of TRPA1 channel in human glioblastoma cell line.

https://www.ncbi.nlm.nih.gov/pubmed/30590317
https://www.sciencedirect.com/science/article/pii/S0753332218355070?via%3Dihub

"More importantly, we found ALA reduced the percentage of apoptotic cells and increased the MTT levels in the cells.
...inhibition of TRPA1-mediated Ca2+ entry through ALA treatment may not be a potential strategy for killing the glioblastoma cancer cells"

As you know, the tumor is very often hypoxic due to the use of Avastin.

Does this mean that alpha-lipoic acid should be avoided if there is a suspicion that the tumor has become hypoxic?

Thursday, 27 December 2018

EGFR-targeting trial or Tagrisso?

Looking at a possible clinical trial for my husband with an ADC (antibody-drug conjugate) called ABBV-321 that targets EGFR.  The trial has identified a maximum dose and is now in the expanded safety phase.  Any one know anything about this?  https://clinicaltrials.gov/ct2/show/NCT03234712

My husband's tumor is showing progression, so if he's deemed eligible for the trial then we'd be choosing between the trial or a combo of CCNU/Avastin/Tagrisso (the latter to target that EGFR amplification).  Choices, choices....


storemytumor.com & vaccine treatment against GBM?

Hello,

Anyone has experience or heard about storemytumor.com?


Can they be trusted? are they good / recommended ?

They offer to save the GBM live tumor, and also send it to 3rd party company (for example in Germany), and make a vaccine (like DCVAX or so)

What do you think? any tips or information will be appreciated!

Thanks
Nimrod, Israel

Wednesday, 26 December 2018

L-lysine supplement for GBM?

Hi All,

Has anyone used L-lysine as part of their cocktail?

We are taking a look at it as a possible way to interfere with arginine. There was a recent study that suggested the amino acid arginine could be used as a fuel source by GBM, and arginine has been implicated in other cancers, as well. https://www.nature.com/articles/s41419-018-1195-4

If I understand correctly, L-lysine may compete with arginine for entry into cells -- thus potentially decreasing the amount of available arginine for fuel.

I read that L-lysine is more commonly used to treat cold sores and to assist in calcium supplementation. Has anyone taken it, and if so at what dose? Any side effects or drug interactions to be aware of? 


Thanks so much!!


Monday, 24 December 2018

A New Diet to Fight GBM

Hello to everyone. We are fighting this disease (grade IV GBM) more than a year and trying to find methods to beat it. I would like to give you some information about the method i found and i hope we will discuss it in a proper way. Before we start, sorry for my bad English.


So, i was wondering what diet is the most effective for fighting GBM. Scientific researches are talking about benefits of a ketogenic diet (KD) - low proteins, low carbs & a lot of fat. First of all i will try to discuss why ketogenic diet has its benefits in curing GBM, and then i should mention its limitations and then i’ll tell you about the alternative diet that i’ve found.


Why KD is showing good results in curing GBM?


  1. Ketones instead of glucose.
    Its proven that our body in ketosis produces ketones out of fat and the brain use ketones instead of glucose. But the tumor can’t eat ketones, so it loses habitual food.
Also, besides simple carbohydrates, KD excludes ALL carbs - including complex carbohydrates. Simple carbs are known evil, that can feed a tumor very quickly. It lowers the blood sugar level - its known that the lower it is, the more is better for curing GBM.


2.  Less protein
The best type of KD for curing GBM is 4:1 - 80% of fat, 15% of proteins and 5% of carbs. There are a lot of researches, proving that lowering protein in the diet can stop the growth of tumors. See China Study: https://www.researchgate.net/publication/324023234_Protein_restriction_and_cancer


3. Less lactate
The level of lactate, glucose breakdown product, in blood is lowering on the ketogenic diet.  I’ve found some researches showing that “Rise in serum lactate can be used as a non-invasive biomarker that correlates with brain tumour grade.”: https://www.ncbi.nlm.nih.gov/pubmed/25172017


These are basic effects of KD, that can influence the growth of GBM. But basically, this diet only increases life expectancy. What if there is some alternative diet, that should have similar effects and should be even more effective?

Many studies have suggested a link between the consumption of cured foods and the development of many diseases - a team of researchers at the National Brain Tumor Foundation has added one more to the list of diseases linked to cured foods: Glioma :


Avoiding cured foods is one of the primary ways we can use to reduce our risk of developing Glioma. So, if you are ever tempted to consume a seemingly delicious and sumptuous plate of cured meat, fish, or even cured vegetables, you should take a moment to consider that you might be increasing your chances of developing Glioma.”


The reasons of it can be explained in such ways:


  1. Nitrites
    Curing is a method of preserving of foods, such as meat, fish, and even vegetables. It involves the addition of salt, sugar, nitrate, and nitrite to raw foods for the purpose of preservation, coloring, and flavoring. In addition, many curing processes also make use of spicing, cooking, and smoking to preserve food items. The nitrite used in the curing process helps to inhibit the growth of clostridium botulinium, a species of gram negative bacteria that cause food poisoning. However, the high nitrite content of cured foods also contribute to the development and growth of cancerous cells in healthy human tissues and organs, including the brain and spinal cord.


  1. Carcinogens
    During the cooking process, the nitrites found in cured foods combines with amines present in meat and fish to form N-nitroso compound, a potent human carcinogen. N-nitroso compounds react with the DNA of healthy glial cells and induce the mutation of these cells into cancerous cells and tumors.
  1. Denaturated proteins
    Most proteins are denatured by heat treatment, and the process is usually irreversible. Denaturation does not break the peptide bonds of the constituent amino acids, but it does disrupt the normal alpha-helix and beta sheets in large proteins, causing them to uncoil and restructure in random shapes.
  2. Less nutrients
During thermal treatment food loses most amount of vitamins and minerals. The following nutrients are often almost fully reduced during cooking:
  • Water-soluble vitamins: Vitamin C and the B vitamins — thiamin (B1), riboflavin (B2), niacin (B3), pantothenic acid (B5), pyridoxine (B6), folic acid (B7) and cobalamin (B8).
  • Fat-soluble vitamins: Vitamins A, D, E and K.
  • Minerals: Primarily potassium, magnesium, sodium and calcium.
  1. Enzymes
    Processing and cooking destroy enzymes in food. In fact, any sustained heat of approximately 118-129 degrees F (48-54 C) destroys virtually all enzymes. This means that, for most of us, the food entering our stomachs is devoid of enzymes. Why is this important? Because enzyme rich foods actually "predigest" in your stomach through the action of their own enzymes in a process called autolytic digestion. Before stomach acid enters the process, you can actually break down as much as 75% of your meal. Without that "autolytic" digestion, you force the body to compensate by over producing stomach acid and digestive enzymes in the pancreas in an attempt to break down the "dead" food.


The bottom line is that eating a diet of cooked and processed food puts incredible stress on the body - particularly on the pancreas since it has to produce massive quantities of digestive enzymes since they did not come with the food itself. The less digestion that takes place before food reaches the small intestine, the greater the stress placed on the endocrine system. If your diet consists of predominantly cooked and processed foods, then supplemental digestive enzymes are the "sine qua non" of minimal good health.


For example, chewing a raw broccoli, with the help of the plant enzyme myrosinase, glucoraphanin is converted into sulforaphane. And during cooking this enzyme is destroying, reducing level of sulforaphane by 80%. https://pubs.acs.org/doi/abs/10.1021/jf062630b?prevSearch=myrosinase+AND+broccoli&searchHistoryKey=


As i mentioned here, there are 5 reasons not to eat cured, cooked food with GBM.
Is there a diet that avoids the consequences of eating processed foods? There is a diet, offerring the list of products with nutrients in their most digestible and natural form.


Let’s take a look at Raw Diet. Or Fruit diet, or Strict-vegan diet, or Plant-based diet (RD). It’s a diet that I find the only suitable and the most natural for a mankind. There are a lot of variations of this diet - I saw many opinions about what you can eat and what not, but the basis is the same:


  • Fruits
  • Vegetables
  • Nuts
  • Seeds
  • Berries
  • Bee products
  • Raw meat and fish (very rarely)


So, what if we compare KD and RD?


  1. Low blood sugar in Raw diet
Raw diet is using to cure diabet:
Too much fat slows everything down in the body including digestion and assimilation of the food you eat. Too much fat will hold sugar in your blood causing your blood sugar to rise. Also Raw diet excludes simple carbs - sugar, flour and so on. Fruit is a whole food - it has not been altered in any way. It contains all of its fiber. Because of this, when fruit with its fiber intact is consumed blood sugar rises at a moderate rate. It is not a problem for our body.
So it is a delusion to think that eating many fruit will cause high blood sugar - plant-based diet reduce blood sugar level.
You don’t need to be concerned about the glycemic index of a particular natural food if it is otherwise nutrient and fiber rich and is part of a healthful diet.
The present of fiber is more important than the glycemic index of a raw, whole, ripe, fresh food.
A low glycemic rating relates to slower digestion and absorption of a food carbohydrates.



2.  Less protein
Plant-based diet and KD have common great idea - limiting any source of protein. I haven’t heard if somebody asked people at ketogenic diet where do they get protein, like it seems to be a problem at vegan diet (only seems to).
In fact, even at using a RD you will get your protein, even animal protein!


In 2016 Nobel Prize in Physiology or Medicine got Yoshinori Ohsumi for discovering and elucidating mechanisms underlying autophagy, a fundamental process for degrading and recycling cellular components. In short, when the protein does not arrive with food, the body take it from dead cells and cells can “eat” themselves to be reborn in a new way.


“The word autophagy originates from the Greek words auto-, meaning “self”, and phagein, meaning “to eat”. Thus,autophagy denotes “self eating”. This concept emerged during the 1960’s, when researchers first observed that the cell could destroy its own contents by enclosing it in membranes, forming sack-like vesicles that were transported to a recycling compartment, called the lysosome, for degradation. Difficulties in studying the phenomenon meant that little was known until, in a series of brilliant experiments in the early 1990’s, Yoshinori Ohsumi used baker’s yeast to identify genes essential for autophagy. He then went on to elucidate the underlying mechanisms for autophagy in yeast and showed that similar sophisticated machinery is used in our cells.


Ohsumi’s discoveries led to a new paradigm in our understanding of how the cell recycles its content. His discoveries opened the path to understanding the fundamental importance of autophagy in many physiological processes, such as in the adaptation to starvation or response to infection. Mutations in autophagy genes can cause disease, and the autophagic process is involved in several conditions including cancer and neurological disease.


Thanks to Ohsumi and others following in his footsteps, we now know that autophagy controls important physiological functions where cellular components need to be degraded and recycled. Autophagy can rapidly provide fuel for energy and building blocks for renewal of cellular components, and is therefore essential for the cellular response to starvation and other types of stress. After infection, autophagy can eliminate invading intracellular bacteria and viruses. Autophagy contributes to embryo development and cell differentiation. Cells also use autophagy to eliminate damaged proteins and organelles, a quality control mechanism that is critical for counteracting the negative consequences of aging.
Disrupted autophagy has been linked to Parkinson’s disease, type 2 diabetes and other disorders that appear in the elderly. Mutations in autophagy genes can cause genetic disease. Disturbances in the autophagic machinery have also been linked to cancer.


Autophagy is a process, wholly dependent on enzymes in the body - if they are not coming with food (cured food doesn’t contain enzymes) the body use enzymes to digest such food, not for autophagy. The fruits and germinated seeds are best sources of enzymes and body doesn’t spend its own enzymes to digest such food - but use them to recycle the body’s cells.


So, as you can see, KD has a great idea to lower the level of protein, but it doesn’t fill the body with nutrients, that are making possible to get the protein inside the body using autophagy.


Besides, autophagy is the main reason of healthy effect of starvation - its proven that starvation is useful in curing GBM:


3.  Less lactate
It is known, that as soon as lactic acid appears in blood, almost all of it (90%) become a fuel for brain, even faster than glucose (it means that tumor also use it as fuel - lactic acid increases the acidity of the microenvironment of the tumor and causing its growth). During vegan diet and RD all lactic acid is recycling by the liver and is NOT using by brain - it’s going to the muscles.


I need to mention that at the beginning of RD the level of lactic acid in blood will increase, because the body will get rid of lactic acid deposits through blood, but then its level will be very low.
So, as you can see, KD and RD is providing almost same effects - but RD is doing it much more effective. And still there are more of it benefits:


What else are the proven benefits of such diet for GBM?
  1. Chlorophyll
A impact study of Chlorophyll on GBM in plant-based diet. From this research: “Vegetable and dietary therapies are previously applied in advanced phases of cancer (Donaldson, 2004). Green vegetable juice is composed of fibers, vitamins, enzymes, and other nutritional elements. Chlorophylls are not only the green pigment of plant cells, but also a crucial requirement for the energy processes of life.
Chlorophyll and its derivatives are very effective in binding with polycyclic aromatic hydrocarbons, heterocyclic amines, aflatoxin, and other hydrophobic molecules. These chlorophyll-carcinogen complexes are much harder to absorb by the body (Donaldson, 2004). Therefore, when green vegetables are consumed, it can be questionable whether the chlorophyll components can affect the cancer cells, which are remote from the gastrointestinal tract. However, in sera of volunteers, who had been taking the supplement, the presence of chlorophyllin, a chlorophyll derivatives has also been detected (Egner et al., 2000), indicating that chlorophyll can function in places other than the digestive tract (Egner et al., 2000). This in-vitro culture model bears the possibility of screening the effect of chlorophyll on the cancerous cells that are remote from the gastrointestinal system.
In conclusion, chlorophylls inhibited the growth of cultured U87 glioblastoma cells with alteration in PTEN phosphorylation, implying their role as a cytostatic agent.
http://www.nchpjournals.com/manuscript/uploads/article_515.pdf


2.  Good bacteries
Fermented foods are some of the healthiest things about eating a raw food diet. Fermented foods are raw and naturally develop probiotics during the period when they undergo fermentation, which happens when oxygen converts some of their nutrients. Probiotics supplied by fermented foods, which are “good bacteria” that reside in your gut, are responsible for nutrient absorption and supporting your immune system. They help you to repopulate your gut with beneficial microbiota after you’ve begun the process of clearing away built-up toxins and waste. Probiotic foods encourage a healthy microbiome, are great for your digestive system, improve immunity, help clear up your skin, and are even beneficial for maintaining hormonal balance and a healthy weight and to prevent digestive disorders, skin issues, candida, autoimmune disease and frequent infections.

3.  Fiber
A large body of literature suggests that eating a variety of foods containing high fiber has a protective effect against many kinds of cancer:
https://www.sciencedirect.com/science/article/pii/S0889858818304520

Real stories about curing brain cancer with Raw diet.


  1. “Within 1 year after I made the change to a plant-based diet I received the news that my tumor was shrinking. However slow, it lost its ability to thrive and that’s due to the nourishment my body was receiving from all of the plant foods I’ve been eating and taking away the tumor’s primary growth factor, animal protein! I must also mention how many other things in my life began to change: my ability to focus improved, my mood stabilized, my skin cleared, and I had much more energy. I felt so much better in all areas of my life.”
    https://nutritionstudies.org/in-control-of-cancer/
  2. The raw food diet helped Megan Sherow overcome her terminal brain cancer, and she is completely cancer-free and healthy now.
    http://sites.bu.edu/ombs/2013/10/24/overcoming-brain-cancer-with-the-raw-food-diet/
  3. It started growing again a few months later. I got a lot of signs to start eating a whole food, plant based diet. It's basically raw vegetables & fruit, nuts/seeds, and absolutely no animal products (meat/eggs/dairy). The MRI in 09/2011 showed no growth and it has been stable since I started this diet.”


4.  “A year of strict whole foods, plant-based diet -  Matt’s most recent MRI scan showed a reduction in the size of his tumor.“ https://my.clevelandclinic.org/patient-stories/141-baseball-coach-battles-brain-tumor-with-lifestyle-change

More useful links: