My surgeon achieved a gross total resection of the tumor, which is worth years and years of longevity.  However, the obnoxious thing about gliomas is that they send tendrils of cells into surrounding tissues, so there’s always the possibility of recurrence hanging over my head for a long time to come.  This isn’t much different from other cancer survivors who have to deal with the uncertainty that one or more rogue cells survived all interventions and are lurking, ready to make mischief again.

I have no intention of waiting patiently for this enemy to return.  It’s basically a differential equation problem: how many glioma cells are there, how rapidly do they divide, versus how effectively are they held in check by the immune system.  Minimizing cell divisions is the key, first because it reduces tumor load and consequently the compound interest carried over; second and more importantly, because every cell division is a chance for an indolent low-grade glioma cell to acquire new bad mutations.  Therefore, every possible effort must be made to shift the balance toward tumor clearance.

The heroes in this battle are my Natural Killer (NK) cells.  NK cells are an essential component of the innate immune system.  T-cells detect infection and pathogens by examining peptides presented on MHC molecules on every cell in the body; if they detect a foreign peptide, they infer that the host cell has been damaged or infected with something bad, and they instruct that cell to self-destruct for the good of the entire body.  To evade T-cell defenses, many viruses and tumors instruct cells to down-regulate MHC expression, and thereby keep themselves hidden from the immune system.  NK cells are the immune system’s response in this evolutionary arms race.

NK cells possess activating and inhibiting receptors on their surface.  If the balance of signaling activity leans towards activating i.e., there are signs that a cell is damaged or not expressing appropriate levels of MHC, NK cells secrete perforin and granzymes, which break holes in the target cell and cause it to self-destruct.  NK cells also secrete cytokines that promote and coordinate a secondary inflammatory response.  Since gliomas play many tricks on the immune system to evade detection, NK cells are the key to finding and eradicating them.  NK_cellsThe nearby image shows a pack of immune cells (orange) attacking a tumor cell.  This reminds me a quote from the Illiad about Achilles’ companions, the Myrmidons:

“Like wolves, carnivorous and fierce and tireless, who rend a great stag on a mountainside and feed on him, their jaws reddened with blood, loping in a pack to drink spring water, lapping the dark rim up with slender tongues, their chops a-drip with fresh blood, their hearts unshaken as ever, and their bellies glutted: such were the Myrmidons and their officers, running to form-up around Achilles.”

Meditation and Visualization:

If NK cells are superman in this story, then stress is their kryptonite.  The activity of NK cells in the blood plummets by orders of magnitude in otherwise healthy medical students before a big exam.  This phenomenon may account for why cancers are so common in recently bereaved spouses, as well providing a mechanistic explanation for the well-established psychological connection between stress and cancer.  It may also explain why depression decreases the median survival time of glioma patients by >60%.  Despair, helplessness, and hopelessness are allies of cancer, and we must guard against them.  I’ve written in some detail about my daily meditation and visualization exercises.  These interventions are useful: stress reduction improves immune function in a variety of cancers and increases survival. Notably, these effects correlate with increased NK cell counts and activity.

Nutraceuticals 1 — Blueberries

“Nutraceutical” is a made-up word to describe using food as medicine.  I’m not entirely comfortable with the supplement culture, especially after my bad reaction to melatonin.  But I do need to eat, so I might as well eat things that are helpful in parallel.  Blueberries and many other berries contain all sorts of useful things like Vitamin C and polysaccharides that increase NK cell counts by an average of 40% when consumed regularly for six or more weeks.  I eat a ton of blueberries these days.

Nutraceuticals 2 — Green Tea

The notion that green tea is anti-cancer is so common, it’s practically cliche. Nevertheless, the epidemiological evidence is clear: drinking multiple cups of green tea per day dramatically decreases your lifelong risk of cancer.  And, I have it on good authority that unpublished data show that green tea extracts are highly effective inhibitors of tumor cell division and spread.  One potential mechanism for this is their down-regulation of the expression of matrix metalloproteinases (MMPs) in tumor cells via catechins in the tea (which incidentally are NOT destroyed by the brewing process, unlike the same compounds in black tea).  This is a good thing to have; as I mentioned above, glioma send tendrils into neighboring tissue which makes them more difficult to eradicate by surgery, radiation, and immune surveillance.  By down-regulating MMPs, green tea helps keep the bad cells right where they are so they can be destroyed, systematically and mercilessly.

Nutraceuticals 3 — Sugar

Like many of the Hughes, I had a bit of a sweet tooth in the past.  Unfortunately, tumor cells thrive on sugar, so I’ve cut my daily cola and most desserts from my diet.  I’ll be damned if I do anything to help these tumor cells out.  I can’t say I miss the soda very much; once you get out of the habit of drinking it, it really isn’t all that great.  I can get my caffeine from green tea.

Chinese Medicine:ganoderma

Our close friends in St. Louis have been kind enough to donate their personal stash of Ganoderma mushrooms to my cause. These are a genus of polyspore mushrooms that contain 60 or more members and have been used for thousands of years in traditional Chinese medicine, earning the names: “mushroom of immortality,” and “the king of all medicinal herbs.”  They are approved for use as adjuvant to chemotherapy in Japan, and many Asian oncologists rave about their medical virtues.  The exact mechanism is unclear, but it’s thought to be a combination of immune modulation via polysaccharides that enhance the activity of lymphocytes including NK cells, as well as intrinsic toxicity to tumor cells.  Pre-clinical studies have demonstrated their efficacy in a variety of cancer models, and on-going clinical trials looks promising. I’ve been drinking Ganoderma tea for a few weeks now; it tastes like a bitter, fishy mushroom broth.  The nearby image shows Carolyn who decided to taste some of the dried mucarolyn_mushroomshrooms, and she didn’t care for it much.  I suspect that its clinical effects may be biased by a self-selection of patients… it takes a great will to live to consume many pints of bitter Ganoderma tea per day.  I also take 1000 mg of vitamin C which is purported to improve the absorption and breakdown of the Ganoderma polysaccharides.

Physical Exercise:

My friend Karyn would be outraged if I did not mention the importance of physical exercise.  Besides a thousand other benefits, including physical rehab and supporting psychological health, short bouts of aerobic exercise activate NK cells. Anecdotally, many oncologists describe how their most exceptional patients — those surviving several standard deviations beyond the median — are typically those who are the most active, lean, and fit.

Cognitive exercise and social interactions:

I wrote earlier about how enriched environments for caged mice increase the activity of NK cells and thereby dramatically decreasing glioma tumor volumes and simultaneously improve survival.  This finding couldn’t possibly be any more delightful.  What a prescription to receive: challenge your mind, read good books, and interact with smart, interesting people, and you’ll improve your overall health and fight cancer at the same time.  It’s like getting paid to eat chocolate.  Given the emerging literature about how valuable cognitive exercise is for a variety of human diseases, including cancer and neurodegeneration, I wonder whether doctors in the near future will routinely prescribe brain games like Lumocity the way they currently scold us to get more physical exercise.

Social Support:

Patients with stable, healthy relationships invariably have better immune function than patients who live alone or in dysfunctional relationships.  In this sense (and many others), Jing is a huge asset in the fight against glioma.  The little girls are as well, and every time they give me a hug or tell me to get better, I imagine my NK cells shifting into a higher gear.  Likewise, this blog has helped enormously — I had no idea I had so many friends and well-wishers.  Literally hundreds of people have contacted me in the last two months to offer their support and prayers.  Both are greatly appreciated, and I’m sure they’re helping my immune system do its duty.

Overall strategy:

When writing a grant in the sciences, it’s advantageous to propose parallel experiments that are technically independent but mutually reinforcing.  Jing and I have constructed the above regimen based on this guiding principle with the intention of increasing the odds that any residual tumor cells are either destroyed by the immune system or held in check permanently.  Realistically, many of these interventions are going to have a smaller impact on my overall health than  conventional Western medicine.  But having completed all the necessary medical interventions, I have no intention of waiting around passively for this glioma to regrow.  Much better to have a plan of attack that shifts the relevant differential equations into a more promising balance.