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.

"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?

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.... & vaccine treatment against GBM?


Anyone has experience or heard about

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!

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.

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:

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.”:

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%.

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.

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:

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.”
  2. The raw food diet helped Megan Sherow overcome her terminal brain cancer, and she is completely cancer-free and healthy now.
  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.“

More useful links:

Monday, 17 December 2018

Retinoic acid for reversing immune evasion in IDH-mutant gliomas

I'm still going through the abstracts from this year's SNO meeting and came across this:

It's tempting to speculate that Ben Williams' use of Accutane (another form of retinoic acid - namely 13-cis retinoic acid) was part of the reason for his excellent response back in 1995. His tumor was since found to be IDH1-mutant. 

This study used ATRA, or all-trans retinoic acid.

ATM mutation

Hi all,

My mom's Caris report showed ATM mutation with "variant frequency" of 52% (EGFR was 59% and PTEN was 17%). Her doctor is suggesting HDAC drug/belinostat trial. Has anyone seen ATM mutation on their genetic report? Is it common in GBM? We may switch her from Keppra to valproic acid as it is also a HDAC drug, or give her both. Thank you for your help!

Saturday, 15 December 2018

Regorafenib superior to lomustine in randomized phase 2 trial for reGBM

This is newsworthy because I expect trials like this to fail in GBM, and I'm very biased against single agent kinase inhibitor trials for GBM, but this one showed regorafenib to actually be superior to lomustine in a randomized phase 2 trial.

Friday, 14 December 2018

When trials change dramatically from their NCT descriptions

I was checking out, "ERC1671/GM-CSF/Cyclophosphamide for the Treatment of Glioblastoma Multiforme".  It's a personalized cancer vaccine, but I can't find any mention of surgery on the NCT site aside from a mention of an injection. No mention of needing a tumor sample either.  If I'd been thinking, I should have been asking how they created the personal vaccine.

I called the program coordinator, and they told me there'd be surgery to get fresh tumor tissue to create the vaccine.  Plus you have to go in to them three times a week for three weeks, followed by a week off, then repeat.  All not mentioned on the NCT site.

The NCT site says that this is double blinded.  Given how everything else in the description seems to be different maybe this is no longer true.  Even if everyone gets the personal vaccine it's not worth the logistics for us (1-2 hour drive each way three times a week ugh).

There was a talk at the UCLA brain tumor conference last May about how a very small percentage of GBM patients take part in a clinical trial.  Not giving the potential trial participant good info doesn't help bring in more recruits.