SNAKE OIL

Somewhere in Northern Wales

In geology and, I suspect, most sciences there exists something often referred to as “gray literature”.  This consists of scientific papers that have not undergone proper peer review before publication.  Often these papers are published in journals nobody has ever heard of, or even journals known to value cash over truth.  Some “gray” papers contain valuable information and/or innovative insights – but most don’t.  Bottom line:  Don’t rely on the gray stuff if you’re fighting for tenure.

Well, Google Alerts has just led me to a bit of gray stuff in the cancer field.  An article printed in “FoodConsumer” (not exactly a well-regarded source for medical research) seems to be telling us that a protein called GcMaf, if used as an immunotherapy agent  may be a “universal cancer cure”.   I don’t know what the Gc part indicates, but Maf stands for ‘Macrophage activating factor”.  As you certainly know, a macrophage is a part of the natural immune system.  They are big, ugly white blood cells that engulf bacteria, etc., and eat them for lunch.  Some people at the “Socrates Institute for Therapeutic Immunology” have been experimenting with this GcMaf stuff and claim to have cured small groups of metastatic prostate and breast cancers, with no failures and no side effects.  There is speculation that GcMaf may also be effective against other cancers, as well as autism and viral infections.

Well, I looked into it.  There really is a Socrates institute; it consists of five guys in Philadelphia.  They have published at least one paper in a reputable journal (Translational Oncology), but withdrew another under peculiar circumstances.  You can obtain GcMaf from a number of sources, and treat yourself at home.   The FDA wants nothing do with it, of course.  One “source”, aptly named Health Nut News, implies that several “Holistic Doctors” pushing this universal cure have turned up dead, under suspicious circumstances.  And so on, and on.

Folks:  You are too smart to fall for this claptrap.  GcMaf may have potential, but that has yet to be demonstrated.  At the moment the only thing it is likely to cure is the relative poverty of a few snake-oil salesmen.

Yes, we do need the FDA, much as I like to vilify it.

http://www.foodconsumer.org/newsite/Non-food/Drug/Gcmaf_a_universal_cancer_cure_1210161151.html

OF CANCER AND CODFISH

Hurricane Ridge, early on

This is a weird one.  The research summarized below was done at Cold Springs Laboratory,  Long Island.  More about that below.  The study is very far from complete – in fact, it might be characterized as a “Gee whiz!  Look at this!” sort of report.  To summarize:

There are these things called “neutrophils” that are part of the immune system.  They are white blood cells that help protect the body from harmful invaders; microbes of various sorts, principally.  They do so by extruding a thing called a “neutrophil extracellular trap (NET)”.  The NET is composed of DNA and enzymes of various (presumably lethal) sorts.  A diagram accompanying the article shows  what looks very much like a fisherman in a little round boat tossing out a net to catch a codfish.

So NETs are good, right?  Well, maybe not always.  The Cold Springs people find that some kinds of metastatic cancer come richly ornamented with NETs.  They speculate that the cancer cells somehow use the NETs to hide from the rest of the immune system.  More seems not to be known.  Much head-scratching is evident.  This is intriguing.  Stay tuned.

Cold Springs is an interesting place, at least to me.  In some of the reading I have done it comes across as a kind of summer camp for molecular biologists.  You know: work hard in the morning, go swimming or play volleyball in the afternoon, have a seminar after dinner, then sit on the porch and knock down a few as the sun sets over New Jersey.  Until recently it was supervised by Jim Watson (yes, that Watson) – until age and a lose tongue conspired against him.

But don’t get me wrong – Cold Springs is an important lab that does important work.  I wish I had played volley ball there.

https://www.cancer.gov/news-events/cancer-currents-blog/2016/nets-metastasis?cid=eb_govdel

COLLATERAL DAMAGE

The Joyce sisters: Heron Island, 2008

Boy, is this a good one!

Sometimes I almost believe that the NYTimes deserves its reputation as the best new source in America; even better than the Breitbart News, the Bellingham Herald, and my personal favorite, The Onion.  The scouting team of Joanne & Dick Ingwall has just sent me a link to this very useful and informative article, which I hereby pass on to you:

http://www.nytimes.com/2016/12/03/health/immunotherapy-cancer.html?smprod=nytcore-ipad&smid=nytcore-ipad-share&_r=0.

The gist of this little gem is this:  immunotherapy is close to being a real breakthrough in cancer treatment, but has some very serious – in fact, potentially fatal – side issues that require urgent address.  This is illustrated by two cringe-generating case studies, accompanied by some simple science that we all can assimilate.  And as an added treat, there is a diagram illustrating how immunotherapy works. I must have read about immunotherapy six dozen times, but now I think I understand it, thanks to this illustration.

(Confession: As a geologist, I thrived on diagrams – maps, etc.  I might have trouble with the printed word, but I got off on pictures.  Toward the end of my career I began to simply scan new publications for useful pictures.  Then I would check to see if I was cited, and – if so – I would read the thing.  That worked because I had graduate students to explain new scientific wrinkles to me.)

So, why should we be surprised that immunotherapy comes with the potential for collateral damage?  The body has ways of protecting itself from its own immune system.  Immunotherapy subverts that protection, with any luck only with regard to the targeted cancer cells.  However, do it imperfectly and your implacable T-cells will also devour your liver, your pancreas, your kidneys, and a whole lot more besides – not that more would be needed.  A significant number of people have died as a result of the side effects of immunotherapy.  Much effort is being expended to find ways to deal with this problem, but the end is not yet in sight.

Some of you know that I am an Egyptophile – I am fascinated by everything about ancient Egypt.  This blog brings into focus the myth of Sekhmet the lion-headed goddess of destruction (and other stuff).  Once Re, her father, told her to kill off a bunch of humans he didn’t like.  As her work progressed she found it so entertaining that she set out to kill all of mankind – and Re couldn’t turn her off!  In desperation he mixed human blood with beer, causing Sekhmet to get drunk and pass out.  Presumably her subsequent hangover was so bad that she gave up on her cat-and-man game, and we all were spared.

We need Re to show us how to shut off our T-cells.

IMMUNOTHERAPY

Linda and friend, off to Europe

Probably 1965

I guess this is worth posting.  It originates with the NCI and is a general description of immunotherapy - what it is, what it does, how you get it, what its side effects are, and so forth – aimed at people who know less about it than you do.  It is boring, but useful, and I can’t think of anything clever to say about it.  Stow it away, & hope you never need it.

https://www.cancer.gov/about-cancer/treatment/types/immunotherapy?cid=eb_govdel

THERE ARE TINY BUGS CRAWLING AROUND INSIDE YOU!

Linda and the author, 2010

Fecal transplants.

Now that I have your attention, let me introduce the Fred Hutch Winter Magazine, which largely is devoted to new developments in studies of what the researchers chose to call the human microbiome. You know what that is:  the trillions of tiny creatures that happily live and die inside us, everywhere, inside and out.  These creatures consist of bacteria, fungi, viruses, and other microscopic uglies left unnamed.  It is said that there are two pounds of these little creatures living in our colons alone.  Another estimate holds that on average each of us plays host to 40 trillion of the things – enough to adorn each cigarette smoked in China last year with 16 of them.  Disgusting, right?  Read on.

Recent research indicates that a lot of what you regard as “you” is strongly influenced by your particular mix of microbes.  Not only your digestion, your propensity to gain weight, or your susceptibility to disease – your microbiome even influences your sex life.  Enough people already know this that an entirely new sub-set of quackery has sprung up.  There is even mention of things called “fecal spas”.  Other equally disgusting practices are discussed.  There are definitely some instances in which messing with the microbiome is useful – it sometimes even helps with cancer.  But too little is known for the amateur to dive in head first.  So, the recommendation is caveat emptor, or for those of us born since the 19^th century, let the buyer beware. 

This really is an interesting article.  You would enjoy reading it..

http://getinvolved.fhcrc.org/site/MessageViewer?em_id=35367.0&dlv_id=35462&printer_friendly=1&s_AffiliateSecCatId=1

I wrote about this topic several years ago:

http://ljb-quiltcutie.blogspot.com/2012/11/microbes-maketh-man.html

A lot seems to have happened since.

Let's be Nice to the FDA

Two happy people on the Nile

Maybe Congress reads this blog, because they are attempting to do something about the FDA, my long-time punching bag. 

  As this Washington Post article explains, FDA is being encouraged – nay, required – to speed up its activities.  More money is provided, and restrictions are loosened, IF THIS BUNCH OF LEGISLATION IS ENACTED INTO LAW.  You would think this would be a slam-dunk; both parties are in favor, and President Obama already has his approval pen in hand.  Yet this matter has been held up for months, and may not survive.  Why?  Why, politics, of course.

To put it succinctly, Democrats want more, and Republicans worry about where the money will come from.  Then there special-interest groups, ranging from the AFL-CIO to the Breast Cancer Alliance, that want specific fiddles.  My opinion: The perfect can be the death of the good.  For God’s sake, let’s get something written into law quickly, ‘cause only the Lord can predict after the inauguration – and even He is scratching his head!

I should add that I now partially comprehend  why the FDA grinds so slowly; not only are they entangled in restrictions, but they are also short-handed.  Apparently they are 700-odd technical staff short, partly because they can’t meet the salaries available in the private sector.  This pending legislation will fix that, if and when.

Read this.

https://www.washingtonpost.com/national/health-science/long-stalled-fda-reform-sits-on-senates-lame-duck-calendar/2016/11/22/14268224-b040-11e6-840f-e3ebab6bcdd3_story.html

BURDEN

A Joyce ceremonial caramel cake

Yum!

Did you know that the number of cigarettes consumed in China this year, if laid end-to-end, would extend to the moon and back nearly four times?  Well, neither did I, and in fact I’m actually not absolutely sure of it – I just made a quick  back-of-the envelope calculation using my cell phone.  But whether that’s right or not isn’t important – the average Chinese smoker consumes 22 cigarettes daily, and the total consumed adds up to a yearly total of 2.5 trillion.  Those numbers alone invite further arithmetic:  for instance, 2.5 trillion cigarettes divided by 22 cigs per day times 365 days per year suggests that there are 311 million smokers in China.  India may be nearly as bad.

So, for your homework:  If all the cigarette butts generated in China were dumped in Nebraska, how deep would the pile be?

All this is meant to introduce today’s topic: why is the worldwide burden of cancer increasing so rapidly?  Apparently it is, you know, as the following link describes:

https://www.cancer.gov/news-events/cancer-currents-blog/2016/global-cancer-symposium?cid=eb_govdel

I am aware that most of you won’t read this link, so I will give you the short answer.  There is higher cancer “burden” (expense, suffering, death) throughout the world because poor countries are getting richer.  Being richer, they can afford better health care.  Better health care means that fewer of their people die of malaria, HIV, syphilis, cholera – etc.  This allows them to live long enough to die of cancer, and it gives them pocket money to buy certain agents of doom, such as cigarettes. 

Hell!  There was more to this blog – as there is more to this article – but my computer just ate it all, every word.  And it is time to watch the Seahawks.

CUBA?

Carolyn, Linda with cousin Elsie

Heron Island, Maine

From my scouting team of J & R Ingwall comes this interesting NYTimes article.

http://www.nytimes.com/2016/11/15/health/cancer-vaccine-cuba-medical-tourism.html?smprod=nytcore-ipad&smid=nytcore-ipad-share&_r=0

 I have never had any desire to visit Cuba.  I visualize it as something like Puerto Rico, but with older cars.  I spent five days in Puerto Rico once, and came back with foot fungus and a queasy belly.  My rule of thumb is, never visit a place with broad-leaf plants and high humidity.  Iceland, yes.  Indonesia, no.

However, it appears that good can emanate from such a sticky paradise as Cuba must be.   Apparently Cuba has a healthy biotech industry.  They have developed and currently market a vaccine called Cimavax which arrests the progress of one kind of lung cancer.  Many Americans currently journey to Havana to get treatment, and to stock up on the stuff to smuggle home.  In the meantime our FDA is effectively sitting on its hands; it will authorize testing sometime soon.  As you know, I don’t like the FDA very much.

Cuba is an anomaly, at least to me.  In most respects it is very poor – but it has an excellent medical system.  Apparently medical doctors there are everywhere, on every street corner, a dime a dozen.  There are so many of them that they are exported to Venezuela, in exchange for oil.  I wish a few thousand of them would come here.  That way maybe I wouldn’t  have to wait a week to see my primary care physician.

OF MICE AND MEDICINE

Normally I introduce a blog entry with a picture of Linda but, in view of our recent election, I will use this shot to illustrate that there places on earth where no one gives a fig about

 Donald Trump

Medieval armies relied on the horse.  During the Napoleonic Wars, navies relied on oak trees.  Today in the war against cancer the one indispensable creature is, of course, the mouse.  I have mentioned mice 27 times in the course of this blog.  For instance, early on I introduced you to the  “transgenic glowing reporter mouse”, and later to the “sublethally irradiated nonobese diabetic severe combined immunodeficient mouse” (poor little devil!).  I also have heard of “nude mice”, although what they are good for is a mystery to me.  There must exist huge mouse farms, devoted to breeding and genetically screwing up these miserable rodents.  I would guess that the proprietors of these diabolic (but essential) establishments have dreams wherein, having died, they report to the Pearly Gates, only to discover that St. Peter is a huge white rat with angry pink eyes and a swishing tail.

Well, in Holland right now they are killing vast quantities of “immune-deficient mice”, for the good of humanity.  Dutch investigators have determined that existing ovarian cancer (OVCA) cell lines do not do an adequate job of mimicking the effect of their drug of the moment, on high grade serous ovarian cancer (HGSOC).  Thus, they have taken to transferring OVCA cells to their mice from actual OVCA patients.  Results from this seemingly cruel but necessary operation they term “Patient-derived tumor xenografts” (PDXs; these guys seem uncommonly fond of acronyms).  Results so far are encouraging, both for OVCA therapy and for prediction.

This article (which is tough going) is of particular interest to me because it deals with epigenetics (which I have written about even more than about mice.)  One form of epigenetic control is to paste a methyl group (CH₃) on a segment of DNA, thereby somehow preventing the expression of a gene.  It appears that HGSOC is accompanied by a distinctive pattern of methylation, and thus can be used as a predictor.  It seems to me that this knowledge also could be used to derive a drug to reverse the effects of methylation – to scrub the DNA double helix free of the little methyl devils, so to speak.

So let’s hope that global warming and sea-level rise don’t first scrub the earth clean of these valuable Dutch labs!

 http://www.science20.com/tushar_tomar/epigenetic_predictors_of_ovarian_cancer-180648

CANCER CAREGIVING: Not much fun.

When Linda's hair fell out during chemo she briefly considered wigs.  She didn't like them, so went to scarves.  I rather like this wig picture, though

I am going to pass along some information that I hope to hell you never need: how to be an effective cancer caregiver.  This information originates with the NCI, not me, so you can rely on its veracity (and, perhaps, curse its bureaucratic construction.)  Here it is:

https://www.cancer.gov/about-cancer/coping/family-friends/family-caregivers-pdq

God knows that being a cancer caregiver is tough.  Carolyn (Linda’s sister) and I shared the work and the misery during Linda’s last few weeks.  Others helped; Bunny Schneider, Linda’s cousin, Florence DiJulio, her best friend, my kids – and lots of others.  Without all of you people, but especially without Carolyn, I would  not have survived.

So glance through the NCI document, then stash it away.  Chances are you will never need it.  With any luck…..

And if you want to help erase this fucking disease from the face of the earth, grab yourself a charity deduction by sending a check to the Fred Hutchinson Cancer Research Institute, in honor of Linda Joyce Beck.

THE WORST JOB IN THE WORLD

Linda and Ella share the bald look

Let’s say you are a bright, hard-working high school senior with very good grades, cogitating on your future.  Being a normal human being you will be looking for a profession that pays well and stands high in societal respect.  Being a naive  kid you aren’t the least bit worried about how long your training will take - and being from a prosperous family – how much it will cost.  Unless you are 6’ 8” or weigh 280 lbs., professional sports aren’t for you.  What to do?  May I make a suggestion?  Go to a good college, major in pre-med, then go to medical school and become a gynecological oncologist.

You won’t have much trouble getting a job, that’s for sure.  The NYTimes presents an article about how scarce gynecological oncologists are at present – and how much more scarce they will be very soon.  Here is the article; it’s well worth reading:

http://www.nytimes.com/2016/11/03/well/live/a-shortage-of-oncologists.html?_r=0

I have no figures about how well GOs are remunerated, but I’ll bet that in monetary terms it’s tons.  As to societal respect, well –Mother Teresa ranks higher, but not by all that much.  However, there are drawbacks.  To become a GO you are required to study and apprentice for what must seem like half your life.  (That eager 18 year old can count on earning her living by age, say, 32 – if all goes well.)  You must deal each day with people who are indisputably very sick.  Some of those people will be terrified, and will lean on you for hope.  And, of course, no matter how good you are, many of your patients will die.

I remember once telling a GO that he had the worst job in the world.  I was distraught, of course – you can guess the circumstances.  I wish I hadn’t said that.  Even more, I wish I had added my profound thanks for taking on such a difficult but essential profession.

Being an oncologist requires a level of courage and dedication that I am sure I never had.

GLOOM

No baby?  No problem

Linda and unknown puppy.  1978

I am escaping the cleaning lady, hiding in my office, reading the Bellingham Herald, and feeling depressed.  Normally I finish the Herald in about three minutes, but this morning it featured an article on AFM, enteroviruses, and the FDA that nailed my attention.  Here it is:

   http://www.bellinghamherald.com/news/local/article112430207.html

(One should note that it originated in the Washington Post.)

First, some vocabulary:

AFM: Acute Flaccid Myelitus.  This is a nasty disease that seems to have flared up recently.  It affects children; 89 so far in the U.S.  It leaves one or more limbs paralyzed, and has other effects.  A little Bellingham boy recently died from it.

Enterovirus.  An RNA virus that usually hangs out in the gut.  One kind of enterovirus causes polio.

RNA.  Aw, you know what that is.

Compassionate-use exception.  Say you are dying, and out there in the Pharma universe there exists a drug that night help.  The problem, however, is that it is not yet approved for your particular condition by the FDA.  You can ask for it, anyway: after all, you are DYING, for Christ’s sake!  Usually the FDA will say “yes” – but not always, as this article makes clear. 

So read the article and see if, like me, it makes you a little bit angry and more than a little bit depressed.

Maybe it’s the gloomy weather outside, and maybe it’s the fact that my hip is hurting – but one passage here almost brought me to tears.   It concerns a clinical trial of the drug preconaril, which was tested as a remedy for sepsis caused by enterovirus – in babies.  It is stated that it cut the risk of death to 23%, compared to 43% in a placebo-controlled comparison group.  I couldn’t help but imagine how I would have felt if my new great grandson Finnegan had been chosen for the control group.  These decisions - placebo or the real stuff - often are made by a computer and may be "double blind", meaning that the person administering the treatment doesn't know what the patient is getting.  I surmise that this is vital to medical sanity: imagine having to give a baby a sugar pill and instead of something that might save its life.  God help us if computers ever develop a conscience.

I will scare up a cheery picture to banish all this gloom.

THANK YOU Mr. Bezos

Linda in Nova Scotia

The rocks behind her should be in Norway

Or maybe Auld Scotland

Here is another reason to patronize Amazon.com.  Jeff Bezos has made an unimaginable amount of money selling first books – then nearly everything, on line.  Unlike some of his fellow billionaires, Jeff has not used his wealth to develop space travel, buy professional sports teams, or even run for president.  Instead, like Bill Gates and Warren Buffet he has chosen to use his wealth to benefit the rest of us.  Fred Hutch has just announced the emergence of a clinic devoted to T-cell therapy, named after and paid for by the Bezos family.  Here is the Hutch news release:

https://outlook.live.com/owa/?path=/mail/inbox/rp

I have written about immunotherapy before (24 times to be exact), and T-cells also should be an old friend (94 times!).  Briefly, T-cell immunotherapy as usually practiced today consists of extracting white blood cells from the patient, isolating those T-cells most inimical to the particular cancer cells in question, modifying these T-cells so as to encourage them to bind with receptors on the cancer cells’ exterior wall, growing billions of them – and injecting them back into the patient.  Simple, huh?  Often this works; sometimes, so far, it doesn’t. 

This is an ultra-hot topic in cancer therapy.  Even the Moonshooters agree.  More on T-cell immunotherapy:

https://www.cancer.gov/about-cancer/treatment/research/car-t-cells

T-cell immunology has been used for melanova for some time.

https://www.seattlecca.org/diseases/melanoma/treatment-options/immunotherapy-melanoma

ONIONS are a girl's best friend

Linda and nephew Cash

2010

Onions are my favorite fruit.  I chop them up and use them with everything – hamburger, soup, chili, scrambled eggs, breakfast cereal.  I have often said that a household without onions is a house without sustenance.  Only bacon, eggs and Reyka vodka rival onions in importance.

Obviously I can’t credit onions for the fact that I have avoided ovarian cancer.  However, some Japanese scientists have shown that onions contain a substance – they call it onionin A (ONA) – that inhibits the growth of OVCA cells in mice.  Apparently ONA does a number on “myeloid-derived suppressor cells”, which, in a manner unexplained, act to favor the growth of tumor cells.  How it works and where we go from here is left unaddressed, but it (this research) seems promising so I thought I’d clue you in.

Oh, by the way – “myeloid” refers to having been derived from bone marrow.  Like blood.

http://www.figo.org/news/compound-onions-could-protect-against-ovarian-cancer-0015395

KNOW YOUR ENEMY; Don't get breast cancer

Linda on the beach

2007

Prepare for a blizzard of blogs.  My Alaskan sub-tribe was here for a few days, featuring Finnegan (as cute and quiet a baby as I can recall), and Seamus (everything a three year old should be, and a lot more) – and, oh yes, their mother Amanda (my oldest grandchild) and James (her husband and my personal jeep mechanic.)  Apparently Seamus is doing fine, thank goodness.  Anyway, after a month of company (both here and in Asheville) my calendar is empty and I am several dozen Google Alerts and NCI Bulletins behind.  I think I will migrate south in mid-December, and in the meantime I have nothing much to do but peck away at this keyboard.

Here is a bit of clear and important advice for women with a family history of breast or ovarian cancer.  Summarizing it for you makes no sense.  Just read the thing, for gosh sake!

http://www.seattletimes.com/life/wellness/when-it-comes-to-breast-cancer-know-your-risks/

DINO: Good news

Linda and Carolyn in Vancouver

I was lucky to have been along

According to the Tea Party, guys like John McCain are RINOs.  This translates as Republican In Name Only.  John – and many other relatively conservative public figures – acquire this designation because they are willing to compromise on occasion, to get things done.  Well, this blog is about DINOs.  These are not about Democrats In Name Only, as you might deduce.  (How about Bill Clinton in the 1990s, compromising on welfare reform and free trade?)  No, as used here, DINO is an RNA molecule that plays a crucial role in the biochemical cascade that enables the tumor-suppressor protein p53 to do its job.  In over half of all cancers, p53 is disabled.  Fooling around with the DINO (Damage Induced NOncoding) RNA, Stanford researchers have determined that p53 can be brought back from the dead and induced to do its job.  Early times, of course, but there is reason to hope.  In the immediate future many mice will die and many grant applications will be submitted, but I am optimistic.

https://www.cancer.gov/news-events/cancer-currents-blog/2016/dino-p53?cid=eb_govdel

PROFILES IN RESEARCH EXCELLENCE: Dr. Varatharasa Thiviyanathan

Linda and me, in Egypt

After chemo her hair grew back gray.  I really liked it.

Let’s get the name business over first.  Hereafter, in this essay, he will be known as Dr. T.  Some research this afternoon suggests that the name is Sri Lankan.  He received his Ph.D. from Purdue University and now works at the University of Texas Medical Center in Houston, where he has been since 1994.  He is a co-author of countless medical research papers (well, 27 since 2000).  More about his history I cannot determine.

As an aside, typing Dr. T’s full name into various search engines is laborious.  I can imagine the poor kid in grammar school, taking exams.  The other kids would be turning in their papers about the time he finished writing his name at the top of the answer sheet!

But who cares how tough his name is to spell; he is doing some great work.  Partially funded by the Rivkin Center, Dr. T is developing a novel sort of address label to deliver nanoparticles of death-dealing drugs directly to cancer cells.  His labels consist of short strands of RNA, especially constructed to zoom in on specific types of cancer cells and, binding to them, deliver their lethal load.

This line of research seems potentially fruitful to me; I have written about nanoparticles before.

However, always remember my abysmal ignorance of most things biological.  If you are curious, Google “aptamer” and go from there.  Me, I’m still tired from my recent trip.

TWO GREAT GUYS

Carolyn and Linda, with their mother

Carolyn has forwarded me this inspiring, even humbling, story of two ordinary guys using their ordinary talents to raise an extraordinary amount of money to fight ovarian cancer.  Makes me wish I were one of them.  Read it.

http://wlos.com/news/person-of-the-week/persons-of-the-week-john-zimmerman-and-taylor-sharp

Wee1: A little bit of good news.

Taking it easy,  Heron Island, Maine

2008, I think

Man, if you need any additional proof that cancer biochemistry is complicated, just Google “Wee1 cancer” and try to read the Wiki entry that pops up!

Saul Rivkin is excited about the emergence of a “new tool” for use in combating ovarian cancer – and when Saul is excited, so am I.  This useful innovation involves a “nuclear kinase” called Wee-1.  As you all know, a kinase is an enzyme that enables anabolic reactions to go by slapping phosphate groups on the substrate – thereby adding energy.  (You did know that, right?)   Well, anyway, Wee1 is in part responsible for guarding the gate between cell-cycle phase G2 and mitosis; cell-splitting, to most of us.  If the cell is too small, Wee1 won’t let it split.  (If it did split, it would croak – to use a technical term.)

It seems that there is another checkpoint in the cell cycle; escape from Gap phase 1 to Interphase depends on the activity of a molecule named TP53, which is mutated (and thus non-functional) in >85% of ovarian tumors  There exists a molecule that “inhibits” Wee1.  So, Saul’s new tool: administer this inhibitor molecule (AZD1775 for the curious), possibly together with an anti-cancer drug.  Absent functional TP53 the cycle relies on Wee1 to prevent midget cells from passing into mitosis.  Apparently they can’t survive (this is my guess), hence are “apoptosed” and ground up for use as nuclear fertilizer.  Moreover, because cancer cells are so quick to multiply, maybe baby cancer cells are unusually small.

Hell, I don’t know – all I am sure of is that Saul thinks this is a very good thing.  I suspect it’s not an earth-shattering discovery – but it helps.

Oh, you wanted to know why the thing is “Wee”.  Well, it was discovered and named in Scotland, where wee means small.  Wee1 weighs 96 kDa.  Is that small?

THE PILL

my guess:

Carolyn's birthday celebration at The Ivanhoe

Ferndale, CA

maybe 2008

When I was in high school telephones were dial-up affairs on the wall, and in many cases required the assistance of a human being (the “operator”, for you under 40.)  It was common knowledge that (shudder?) pot was a sure road to hard-drug addiction, misery, and death.  Nobody drank in high school, only a few would-be hipsters smoked, and as for sex – then as now nobody thought of anything else - but very little occurred.  Oddly enough, the girls didn’t want to get pregnant.  

However, that was before THE PILL.  With the advent of oral birth control it became possible to safely do what nature so vigorously called upon you to do – and not risk the consequences!  To me and my male friends THE PILL was an innovation equivalent in importance  to electricity!*

 

Well, it happens that at that time I was a faithful attendant at several church-sponsored evening youth activity groups.  That was because they had singing, guitar music, apple cider – and girls.  Lots of girls!  At those evening sessions there invariably would be some kind of informal “sermon”, in general laid on by an earnest and devout, well-scrubbed college boy, most likely a seminary student.  Uniformly we hormone-wracked high schoolers were enjoined to lay off sex until we were married.   The poor girls in the group were threatened with societal rejection, not to mention eternal damnation, if they took THE PILL.

Well, some did and some didn’t.  And young married women who wanted a career took the pill, as did women who simply didn’t want any more babies.  THE PILL was even good for guys; we could save on condoms, and delay that inevitable vasectomy. Maybe it WAS more important than electricity!

It turns out that THE PILL brought with it another, entirely unexpected, benefit – it helped protect women from ovarian cancer.  The NYTimes article cited below states that the death rate from OVCA dropped by 16% between 2002 and 2012.  This, the article goes on to say, is the result of less use of hormone therapy – and increased use, many decades ago, of THE PILL!  So, those naughty girls of the 50s not only had more fun – they lived longer!  So much for Protestant orthodoxy.

The same article recognizes that there has been a little improvement in the treatment of ovarian cancer, but not enough to make much difference. And early detection is not even mentioned.

http://www.nytimes.com/2016/09/27/health/ovarian-cancer-death-rate.html?_r=0

*Not that it did us much good.

KALAMAZOO TURNS TEAL

Hunsingers, Joyces, and Becks

Well, by God, good for Kalamazoo, Michigan!  As many of you don’t know – but should – September is Ovarian Cancer Awareness Month.  I told you that weeks ago 

 http://ljb-quiltcutie.blogspot.com/2016/09/the-fda-and-uspstf-strike-again.html 

but only managed to give away four of my teal pins, so far.  However, folks in Kalamazoo managed to turn the whole town teal, or thereabouts.  Kalamazoo is the home if Linda’s brother and his family, which numbers eight (unless some new grandkids have been slipped in without my knowledge.)  All but the ones under six are energetic activists, so I wouldn’t be surprised to learn that some of the teal was laid on by members of the Joyce-Hunsinger clan.  Thanks.

Here is the article:  http://wwmt.com/news/local/turn-the-town-teal-canvases-kalamazoo-to-raise-awareness-of-ovarian-cancer

  

TALC AND THE COURTS

What can I say?  I miss her

Here is an article that many of you won’t like.  It was written by a blogger who happens to be an attorney heavily involved in tort cases concerning the medical profession.  The specifics in this case concern lawsuits directed at Johnson & Johnson over talc and its relationship to ovarian cancer.  He seems to be somewhat skeptical of the way some courts have handled these suits.  His opinion seems to be that the role of the court should be that of “gatekeeper”; that is, they should determine which scientific evidence carries the presumption of validity – is based on experiments conforming to the accepted standards of the discipline.  This would seem to be a tall order for an elderly lawyer turned judge who flunked biology 101, but must be oerformed to prevent the jury (ALL of whom flunked biology 101) from tearing the defending party (often a hate worthy big corporation) into little pieces unjustifiably.  My take on this:

1)      Stop using talc, right now.  I suspect that it contributes to ovarian cancer, but I’m not sure – so don’t take the chance.

2)      If a company has reasonably good evidence that its product is harmful it should stop selling it and run an honest experiment to find out if and why.

3)      If a company knows that its product is harmful but does nothing about it, it should be sued out of existence and its CEO and Board tossed in jail.

4)      If a company sells a product (e.g., asbestos) in good faith, it should not be driven out of existence if, at a later date, harm is detected.  See Johns Manville as a case study.

5)      If I had it to do over again I would, of course, study cancer biology and go into research.  However, I would be sorely tempted to acquire both an M.D and a J.D.  Imagine trying a medical case with yourself as an expert witness!  Such people exist; all are rich and only die when they crash their Aston Martins into a bridge.

http://www.chem.info/blog/2016/09/talc-and-ovarian-cancer-does-reliable-science-even-matter-anymore

BRCA, Rucaparib - and Clovis Pharmaceuticals

At the great Sisters, Oregon quilting frenzy

As no doubt you deduced many months ago, the oft-used acronym BRCA stands for Breast Cancer; medical researcher types seem to like to like to paste together the first two letters of words to designate something.  That, for example, the famous HELA strain of cancer cells received its name from an equally famous patient named Henrietta Lax. 

Anyway, you really don’t want mutated BRCA1 or BRCA2 genes, because they accompany (cause?) a high susceptibility to breast – and, as it turns out – ovarian cancer.  But, if you DO have OVCA (see: ovarian cancer, OVCA) you should then hope that you are  BRCA-positive, because (for reasons I don’t understand) BRCA-positive cases are easier to treat.  The article cited below relates how rucaparib, a PARP inhibitor developed by Clovis Pharmaceuticals has been so successful in treating women with advanced BRCA-positive OVCA that it has been granted fast-track status by the NCI and FDA.  If you know someone in that unfortunate category, tell them to hound their oncodoc to get them in a trial.

http://www.targetedonc.com/news/rucaparib-granted-priority-review-for-ovarian-cancer

Yes, I thought I had read this “news” before – and written about it.  17 months ago!  Boy, Clovis must have a skillful publicity guy!

http://ljb-quiltcutie.blogspot.com/2015/04/cancer-and-stock-market.html

CURE?

Linda contends with the cat from hell!

The latest Fred Hutch magazine has an interesting, but not very clarifying, discussion of what the word “cure” means in oncology.  The article infers that it is a statistical concept, but then fails to clarify.  That may be deliberate; real statistics would either drive us away or bore us to death.  I remember asking Linda’s oncologist about the possibility of a complete cure.  He did a verbal version of a soft-shoe Shuffle off to Buffalo dance routine and introduced the concept of “chronic disease” (see http://ljb-quiltcutie.blogspot.com/2016/08/a-new-approach.html).   I was so ignorant that I thought I’d received an answer!

Well, this Fred Hutch article provides a definition of “cure” that seems logical to me.  You are “cured” when your disease has disappeared and you are no more likely to see it flare up again than the general population is to get it in the first place.  That makes sense to me, although in practice it might be very hard to apply.  Here is a glossary of onco-speak from the article:

If the doctor says                                                            He/she means

Stable disease                                                                 Tumor constant in size or severity

Partial remission                                                             Tumor getting smaller and/or less virulent

Complete remission                                                        Tumor gone.  No evidence of disease

Cure                                                                                 No trace of tumor – which won’t come back*

For my money, the best way to judge how far out of the woods you are is to use a Kaplan-Meier curve based on plentiful data.  Such a plot illustrates the probability that someone with a given disease will be alive at various times after diagnosis.  (I wish to hell that I could draw – and post – an example, but I don’t know how. )  Anyway, plot the probability of being alive on the Y-axis and time on the X-axis,  The curve will fall off toward increased time, and (hopefully) flatten out eventually.  For a nasty bastard like pancreatic cancer it drops rapidly, then flattens near zero; for something like prostate cancer it falls off much less precipitously and begins to flatten out at a much higher probability.  Got that?  Well, never mind, just remember this:  if you have a disease and find that you plot on the near-horizontal part of the curve, for all reasonable purposes you can consider yourself cured

You can get the graph you need by going to the following:  

http://seer.cancer.gov/faststats/selections.php?  And fiddling around for awhile.

As an example, pancreatic cancer victims are “cured” by this definition at 12-15 years, but at that time only about 5% of them are alive.  OVCA patients are considerably more lucky.

*Don’t use this definition.  Use the one in the text, above.

VOLUNTEER? A confession.

Linda at the famous market in Otovalo, Ecuador

About 1988

The elevation there was over 10,000 ft.

Notice the small size of the people.  

When you read these blog entries, at times you may glance at the blurb printed nearby, which purports to explain what I’m on about, as our British friends might say.  Sadly, it no longer is completely true.  Only in a very restricted sense do I continue to volunteer at Fred Hutch or the Rivkin Center.  Advancing age and increased  traffic flow make it inadvisable for me to fire up my sturdy little jeep and tempt fate on I5.  I still stand ready to tackle jobs that I can do at home, but none such seem to materialize.  But I still write this blog, and I hope that counts..  

THE FDA AND USPSTF STRIKE AGAIN!

Cleansing ceremony before mountain adventure

As I prepared to construct this blog a powerful lot of extremely colorful language trickled through my head.  I managed to suppress most of it, but a bit may seep out from time to time.  Forgive me.

Jesus H. Christ!  The news today is that the FDA has joined our old friend the USPSTF in recommending that CA125 should not be used to screen for ovarian cancer.  Not even in its ROCA form.  Not even for post-menopausal women.  Not even if you toss in a family history of ovarian or breast cancer.  Not even if you are positive for BRCA mutations.  Not for nothing, apparently.

And the Ovarian Cancer Research Fund agrees, apparently. 

Add to that the fact that many (most?) doctors either don’t know the OVCA Symptom Index, or don’t think it works (see recent blog about Gilda Radner) and you arrive at the current situation: most OVCA sufferers are diagnosed in Stage IIIc or IV, and have at best a 45% chance of living five more years!

And why not use ROCA or some similar technique?  Cost!  False positives!  Hain’t passed the crucial tests with a high-enough margin of error!  (I just choked back a particularly harsh epithet.)

I appreciate the efforts of our medical experts to protect us from harm.  But can’t we put more of all that brain power and money to work doing something positive?  We could save a lot of lives if we could detect early stage ovarian cancer.  If we had a Cancer Czar, as I have suggested, he or she might be persuaded to make this a priority.  But with the present Moonshot structure – not a chance.

By the way, this being Ovarian Cancer Awareness Month, I will send you a classy teal pin, free of charge, if you promise to (1) wear it, and (2) email me your address.

http://www.foxnews.com/health/2016/09/08/fda-warns-against-widely-used-ovarian-cancer-screening-test.html

GILDA and GENE

First Wedding Anniversary

I had known that Gilda Radner died, at an obscenely early age, of ovarian cancer, but until now I had not realized that Gene Wilder and she were associated and that he spearheaded creation of the Gilda Radner Ovarian Cancer Research Program at Cedars-Sinai hospital in Los Angeles.  Linda, of course, would have known all about it, but lacking her it took Wilder’s death to alert me.  I have spent a frustrating hour trying to read about Wilder’s activism, but to little avail – obscenely irrelevant and obnoxious pop-ups invariably interrupt, just as I am making progress.  Damn capitalism, anyway!

But I seem to have determined that the poor diagnosis Radner experienced was the object of Wilder’s wrath.  Apparently Gilda complained for nearly a year of recognized OVCA symptoms: see

http://ljb-quiltcutie.blogspot.com/2012/09/ovarian-cancer-awarness-month-spread.html

She was told not to worry, apparently, and was offered neither a CA125 test nor an ultrasound.  When Medical Science finally caught on, she was stage IV.

Wilder says that neither he nor Gilda knew anything at all about OVCA symptoms.  Neither, apparently, did one or more doctors.  Those of you who do read this blog have no such excuse.  If your medical authority attempts to give you the brush-off you will, for God’s sake raise well- informed  hell!

Sometimes I wonder it primary care physicians aren’t unduly influenced by all the chatter about how much America spends on health care.  “Ultrasound and CA125 analysis cost money:  maybe we should just wait and see.  After all, there are only 21,000 or so new OVCA cases yearly, out of more than 100 million American women, so the odds are good”.  Please join me in saying, SCREW THAT!

Life is a lot more important than money.

So, I keep coming back to the thought that early detection is, perhaps, the most important current line of OVCA research.  It happens that Linda’s cancer might have been diagnosed early, but for an all-to-human medical error.  When she was diagnosed four months later she was stage IIIc.  She “let go of it (that fact)”, and thus so must I – but sometimes I find that hard to do.

So, thanks, Gene, for your help.  We’ll get the bastard yet!

A NEW APPROACH

Linda and Carolyn

Someplace

When Linda (who would have been 71 today) and I talked to her oncologist after surgery we were told that we should consider her condition a “chronic disease”.  I took that to mean that they could keep it at bay indefinitely.  I was wrong.  What he meant was that he could slow it down, but he couldn’t cure it.

Well, now an effort is being made to truly keep ovarian cancer at bay indefinitely, or at least for a very long time.  The article cited below describes how research workers at Oregon State University as well as the U.K. are testing a new therapeutic technique; they call it “metronomic dosage regimen”.

Take ovarian cancer, for instance.  OVCA chemo traditionally consists of giving the patient the “maximum tolerated dose” of one or more drugs for a brief time, at regular intervals.  The intent here seems to be to kill the damned thing outright; to affect a cure.  However, in advanced OVCA (stages III and IV) this rarely works, and moreover results in massive discomfort.  The metronomic dosage approach would be – in the example discussed – to give a much smaller dose (<33%) at widely spaced intervals – indefinitely.  They suggest using paclitaxel, which attacks cancer cells, and rapamycin, which combats angiogenesis (the ability of a growing tumors to recruit new blood vessels).  These drugs are delivered together by targeted nanoparticles.  The aim here is “to create an environment in which [cancer cells] do not grow easily”.  Complete cure is not ruled out under a metronomic dosage regimen, but it is not necessarily the goal.  Rather, the goal is to place OVCA into the same classification as, say, high blood pressure.  I’ve had high blood pressure for 40 years.

So, let’s fervently hope that this works.  It certainly sounds feasible to me.  My only concerns are that no clinical trial is mentioned, and that the paper was published in a journal I have never heard of.

http://www.medicaldaily.com/cancer-breakthrough-use-chemotherapy-control-not-cure-new-drug-delivery-system-396206

EPIDEMICS

Dinner on the Norsk vessel Vesterhalen

Those glasses of wine were >$10

What is an epidemic, you ask?  Well, most would agree that it is a sudden upsurge in some natural phenomenon – usually a disease.  Take the Black Death, for instance.  It arose suddenly, spread like lightning, and killed half of Eurasia.  Several times, in fact.  The Black Death is what we geologists might term the type locality of epidemics.  Zika might qualify as this sort of epidemic, but for the fact that it is spread by a fat, lazy little toad of a mosquito that is averse to travel.  To contract Zika you have to go to the mosquito, not vice versa.  So, don’t be stupid.

There is another type of epidemic which I will term a “media epidemic.”  Take earthquakes, for example.  The frequency and severity of earthquakes vary over the short term, of course, but the average over periods of years is reasonably constant.  As far as I know there are no long-term trends.  However, the media will leap on any significant seismic event – and then pay unwarranted attention to other such events, wherever they occur and regardless of how insignificant they may be.  The result is to give the false impression that the earth is about to shake itself into a bunch of little pieces!  Once, a long time ago, I was stuck in a mountain hut with three young men in the grip of such a media epidemic; they were sure that we were entering the End of Days.  Being young and foolish I tried to talk them out of it.  When my party left the next morning I believe they were praying for my soul.

Well, the Ingwalls have alerted me to another kind of epidemic – an epidemic of over-diagnosis.    It is only human to celebrate the appearance of a tool or technique that makes your life’s work simpler to accomplish – and to use the hell out of it.  Such it is with all these new imaging gadgets:  ultrasound, MRI, CT, etc.  These and other modalities may allow you to detect more “anomalies”, cancers, for instance, than previously, but they don’t say much at all about their “penetrance” (likelihood to cause trouble.)  This is illustrated by the recent history of thyroid cancer.  In many countries diagnosis of thyroid cancer suddenly has increased many-fold, leading to a proportional increase in the number of surgeries.  However, pathology shows that many (most?) of these surgeries were unnecessary – the “cancer” involved was never going anywhere.  What to do?  How about the old standby, watch and wait?

In passing, it should be easy to distinguish a diagnostic epidemic from a real one.  Just examine the death statistics.   

http://www.nytimes.com/2016/08/23/health/got-a-thyroid-tumor-most-should-be-left-alone.html?smprod=nytcore-ipad&smid=nytcore-ipad-share&_r=0

YOUR MID-TERM EXAM

Linda in front of the temple of Nefertari, Ramses' II chief wife

Of her he wrote, She for whom the sun doth shine.

Right on!

Here is a cheat-sheet to assist you in your efforts to prepare for your mid-term exam in Health Science 401, Cause, Prevention & Cure of Ovarian Cancer.  If you have paid attention in the previous 450 or so lectures there is nothing here that should confuse you.  If something does confuse you ,you can “search” Myrl’sBlog.  And then, again, there is always Wikipedia.

http://www.onclive.com/publications/Oncology-live/2016/vol-17-no-16/genome-sequencing-is-mapping-a-path-to-personalized-treatment-for-ovarian-cancer

But, seriously, this is a darned good summary of things as they stand.  You should read it.  (It’s somewhat long.)  I’m going to study it to see if it needs a bit of explication.

DO NOT GIVE UP

Just before she died

Now here’s one that’s hard to swallow.  A clinical trial – properly conducted and published – seems to be telling us that secondary therapy for advanced ovarian cancer is futile.  To put this in context, compare Linda’s treatment five years ago.  When first diagnosed she was in stage 3c and her CA125 was over 600 (normal is less than 35).  Her initial treatment was surgical debulking – that is, they cut out as much tumor as they could find.  When she recovered from surgery she underwent eight weeks of intensive and thoroughly unpleasant chemotherapy.  Her chemo was administered intravenously.  Nowadays she might have received her chemo through a hole in her stomach – this is now known to be more effective.  Moreover, she might have had chemo before surgery; “neoadjuvant chemo” is preferable in some cases.

After chemo we settled down to wait.  Each month she had a blood draw for measurement of CA125.  For about a year she remained steadily at CA125=8.  Then one day it crept up to 12.  Then 20.  The damned thing was coming back.  Next she underwent a course of an alternative chemo, which slowed her cancer’s growth and gave her a few months of what you might call quasi-remission , and at the end she was on some other drugs, which didn’t help at all.  After diagnosis she lived about three years.

Well, the study described below seems to be telling us not to monitor the progression of the disease, because this has been shown  to be of no value in terms of ultimate mortality.  That is to say, you are no less likely to die if you combat the resurgent disease than if you simply ignore it.  The recommendation seems to be to simply forget about it and thus save yourself worry, discomfort, and expense.

Well, folks, screw that!!  Life is too precious simply to toss it at the wall to see if it sticks.  If I had ovarian cancer – which, thank God is impossible – I would fight the son of a bitch with every weapon I could lay my hands on, and if I died anyway I would know that I had done my best .  That’s what Linda did.

By the way, it hasn’t been easy to write this blog.  Lots of old scabs were scraped off, and I am crying as I finish.  The older I get, the more I realize how inadequate I really am.

I was married to one of the bravest women in the world.

http://www.cancer.gov/news-events/cancer-currents-blog/2016/surveillance-tests-ovarian?cid=eb_govdel