PLEASE READ THIS SECOND FASCINATION LITTLE ESSAY

In Trondheim, Norway

Here is another easy-to-follow article from the NY Times:

http://nyti.ms/1GJRGee

It seems that the American Society of Clinical Oncology is meeting now, in Chicago, leading me to believe that there will be a lot more to report on in the next few weeks.  One of the biggest topics of discussion amongst these people these days is immunotherapy, which we have discussed many times before.  If you read this article – which you should – you will have to remember what is meant by a “checkpoint”, about which I wrote with admirable clarity a few weeks ago:

http://ljb-quiltcutie.blogspot.com/2015/02/please-read-this-fascinating-little.html

You also will benefit by knowing what is meant by “mismatch repair deficiency”.  Briefly: When cells divide they must copy their DNA strands – all several billion “letters” of it.  Inevitably, mistakes are made – darned few, it seems, but some.  These are “mismatches”.  If left alone they constitute a mutation.  Most mutations are benign, but some are lethal.  Thus, evolution has provided us with a complex of proteins that goes down the DNA strand, searching for mistakes.  When one is found, this “mismatch-repair complex” fixes it.  Thus, if one has “mismatch-repair deficiency”, one is up a creek – mutations accumulate, with eventual unpleasant consequences.

The NYTimes article cited above discusses drugs aimed at preventing tumor cells from disguising their malevolent nature under a thick coating of checkpoint proteins (we’ve discussed that before).  Also discussed are drugs to cope with mismatch-repair deficiency, although how they work doesn’t seem to be explained. 

So, these drugs are not exactly the cat’s meow.  First one thing – to date they have only succeeded in buying time – time, in months!   Secondly, they are fiendishly expensive: of the order of $150,000 per year.  Thus, I am not about to leap with joy.  However, the oncologists are excited, so maybe they’re on to something.

This information comes to you courtesy of the research team of Joanne & Dick Ingwall.  As I am their best (well, only) client they plan to move to Bellingham soon, attracted by the mild weather, good fishing, and the aura of subdued excitement.  I am acting as their real estate scout and advisor.



DON'T BE A FINK

In Bergen, Norway

Not many things annoyed Linda, but she was annoyed by the Norwegian love of trolls.

 

Here’s something that strikes me as promising.  Inevitably, it “needs more work”, especially clinical trials, but I like it.  The authors are all from U.C., San Diego and are modest scientists – nobody used the word “breakthrough”.  But maybe it is.

So, before you read this short blurb (I think it is a press release), you need a refresher course in human genetics, which I am about to deliver.  If you quit here you are a fink.  Yes, that means you.

You all know that DNA consists of “code” for genes and a lot more besides.  Genes are “transcribed” into stretches of RNA called messenger RNA, or mRNA.  The mRNA often is extensively “processed”, then transported out of the nucleus to things called ribosomes, where they are “translated” into proteins.  Yeah – you know all that.  This next might be new to some of you, though:

Genes consist of two kinds of stretches of code: exons, which will be “expressed” as protein, and introns, which won’t.  To process a stretch of mRNA means in part to cut out the introns, then stitch together the exons.  The stitching can be quite variable.  For instance, consider a molecular “sentence” such as the following, where “blah” means a stretch of intron:

GoodblahgirlsblahlikeblahbadblahboysblahonblahTuesdays.

If you cut out all the “blahs” and stich the remainder together you get “Good girls like bad boys on Tuesdays.  If that mRNA is taken to a ribosome it can be translated into some kind of protein.  However, the stitching mechanism has variability.  For instance, it could create an mRNA that reads “girls like boys”, or Girls like Tuesdays”.  Sequence can be altered, so that “Boys like bad girls on Tuesdays” is possible.  Each of these “isoforms” can lead to a unique protein.

And now that you know what “mRNA isoforms” means, you can read the article:

http://health.ucsd.edu/news/releases/Pages/2015-05-25-markers-set-stage-for-early-diagnosis-ovarian-cancer.aspx

What these folks have done is relatively simple – if you have the hardware.  They have compared he mRNA isoforms of ovarian cancer patients with those of women free from cancer (they are working with ovarian).  Because mRNA is created in profusion, they can find it relatively easily – apparently they can use a Pap smear.  Presence of cancerous mRNA is (or can be) a biomarker.  Also, because these cancerous mRNAs are coding for proteins, it seems likely that these proteins have something to do with the development of the cancer – hence, provide a clue to various therapies. 

Well, if you have read this far – good for you.  As stated previously – the rest of you are finks.



AN INDECENT PROPOSAL

Mildred and Billie

Welcome to life, little guy.  You may be four hours old.

 

Deer report:  I guess my yard was the obstetrics ward but not the neo-natal nursery.  I have seen neither hide nor hair of Mildred and her two tiny fawns since the day fawn #2 (Willie) was born.  I feel bereft and slighted, but I will bear up   and continue to look out the window every 30 minutes are so).  The camera remains at the ready.

So, while I wait to go to Iceland I am re-watching a Teaching Company course What Science Knows about Cancer.  The teacher is a geeky looking guy (Hey, he’s an academic.  We are supposed to look geeky) but he really knows how to package the info and pass it on to you painlessly.  It comes pretty fast, but – since the lectures are on DVDs, they are repeatable – in whole or in part– as often as needed.  I’m not supposed to do this, but I will:  Who wants to borrow the course?  It consists of 18, 30 minute lectures.  I will mail it to whoever wants it, and applies first, to mebeckjr@gmail.com.  Then, when #1 is done with it, he/she must promise to mail it to #2, etc, etc, until it wears out.  I will give the appropriate addresses.

Now, come on!  Here is your chance to prove to me that you do more than just look at the pretty pictures I post.  Sure, some of you will have a good reason to refuse this splendid offer.  I give you a sampling:

1)      I don’t own a TV, or a DVD player.  Actually, I do, but I don't know how they work.

2)      I cannot possibly look at a geeky guy with a clownishly long necktie for 30 minutes

3)      I have a Ph.D. in medical oncology.

4)      I can’t sit still for 30 minutes at a crack.  (Unless I have a beer in my hand)

5)      I live in Canada, and we don’t have mail service or electricity way up here.

6)      I cannot afford the postage to send it on to the next guy on the list

7)      I think your blog is dumb, but I live in Kansas and it’s the only thing my computer can manage to find

8)      Etc.

Okay, here’s your chance.  Give me a shout.



FOUR YEARS AGO

Linda at a quilting retreat, 2008

Cancer might take her hair, but it couldn't touch her smile.

 

Four years ago today ovarian cancer took my wife Linda, robbing all of us  of a woman of kindly good humor, gentle wit, and radiant beauty.  Linda is gone, but ovarian cancer is still here, as lethal as ever.  During these last four years important advances have been made in understanding the basic biology of ovarian cancer, but a cure still eludes us.  About 14,000 American women will die of ovarian cancer this year – essentially the same as a decade ago.  Really, this is inexcusable.  I somehow believe that a cure is close, but we must keep the pressure on.  Ovarian cancer deserves to become a footnote in books on medical biology.  Please do what you can.





MORE ON EARLY DETECTION

Nice picture

I wish I knew where it was

It is sunny today here in Bellingham, with a high supposedly approaching 70⁰.  I had intended to drive to the Skagit Flats nature spot, to look at birds.  However, I have been outside planting more pole beans for my back yard deer to eat, and it was uncomfortable – there was a cold wind a-blowing out of the frozen  wastelands north of Blaine, so I wimped out and tackled ovarian cancer instead. 

I uncovered two articles of interest.  One concerns ROCA- I wrote about that several times before.  ROCA is a screening protocol, involving monitoring changes in the bio-marker CA 125, together with ultrasound in suspicious cases.  It has been shown to be twice as effective as competing method.  If you are lucky enough to live in the U.K. you will be able to get this monitoring for as little as 150 Pounds ($232.5).  The company that offers this service is called Abcodia.  Apparently, at present the test will be out-of-pocket; however, Abcodia hopes to persuade the NHS to pay for it.  Abcodia will offer the service in the U.S. in the next year or two; I foresee a great and bloody struggle to get it approved and routinely offered here.

Apparently ROCA detects only 85% of all OVCA cases; work is underway to find something for the remaining 15%.  Maybe the next article will help.

The second article concerns work at Arizona State University which indicates that three distinct autoantibodies, if found in a patient’s blood sample, may prove to be a reliable marker of ovarian cancer.  Some quick definitions are in order.  An “antibody” it a molecule that is generated by the immune system to attack an “antigen” – the name antigen merely means something that will provoke an antibody attack.  In general, antibodies are benign, as they are directed at malicious invaders – bacteria and their ilk.  Autoantibodies, on the other hand, are molecules that attack “self” - indigenous proteins. Autoantibodies can be bad news; for instance, they are the cause of auto-immune diseases, such as Lupus.  However, certain kinds of autoantibodies apparently are generated to fight cancerous cells; these are the kind that the ASU people are investigating. 

As always: How early can these methods detect ovarian cancer, and what do we do about it once it’s detected? 

Here are the two URLs

http://newsok.com/researchers-find-potential-clues-to-detecting-ovarian-cancer/article/feed/840393

http://www.ibtimes.co.uk/roca-why-you-should-be-excited-about-150-ovarian-cancer-test-set-launch-this-summer-1501544

 



SGO: The good guys

Linda and Whiskers

Long ago

There exists an outfit called the Society of Gynecological Oncology.  This learned assortment of scientists has recently published, in the journal Cancer, a review of the etiology of ovarian cancer and suggestions for the prevention of the disease.  I am tempted to acquire a copy of that issue, but I am reminded of how little I normally understand of literature written for cancer professionals.  So, I will summarize what I have tracked down and aimed at folks like us who do not understand medical Lithuanian.  Here are some web addresses for you to read at your leisure:

http://www.healio.com/hematology-oncology/gynecologic-cancer/news/online/%7Ba0bc9362-16d7-46ac-a9b0-67452c0f78fd%7D/society-of-gynecologic-oncology-outlines-recommendations-for-ovarian-cancer-prevention

http://onlinelibrary.wiley.com/doi/10.1002/cncr.29347/full

So, here are the highlights, in no particular order.  Much of this reinforces previous suggestions forcefully  advanced previously in this series of blogs.

The median age at diagnosis (of ovarian cancer) is 63; the lifetime risk of contracting ovarian cancer is 1.3%.  (I assume that’s 1.3$ of women, not of everybody.)

Most epithelial ovarian cancer arises in the fallopian tubes, not the ovaries.  No sense having your ovaries removed without taking the fallopian tubes too.

As we have discussed many times before, association and correlation do not establish causation.  Only a “prospective* randomized controlled trial” can establish causation.  Many studies that lack this level of sophistication have subsequently been proven false.  (Enter Dr. Ioannidis, stage left, bearing a laptop:  http://ljb-quiltcutie.blogspot.com/2014/04/metrics-scourge-of-sloppy-science.html )

Use oral contraceptives for as long as possible.

Have your fallopian tubes removed after you hatch your family.

Find out if you are high-risk for ovarian cancer.  See a genetics counselor.  Get your genome investigated for suspicious mutations.

Don’t expect your primary care physician to up to snuff on ovarian cancer.  Take responsibility yourself.  And how do you do that?  By reading my blog, not just enjoying the pictures!

*”Prospective” means that you select a group of people and then follow them for many years.  This is in contradistinction to “Retrospective”, wherein you keep records of a bunch of people throughout  some (long) period of time and then, knowing how they prospered (or didn’t prosper),  go back and see what the differences may be. 



"SURVIVAL" vs "CURE"

Linda and Canada jay

Our skiing years, sometime in the 90s

Somewhere in southern Canada

The NY Times has published a thoughtful little essay by an oncology doc, on the difference between “survival” and “cure”.  Here it is; read it:

http://well.blogs.nytimes.com/2015/05/11/cured-from-cancer-almost/?ref=health

As I read this essay, I couldn’t help but think of what an awful job these oncologists have.  I don’t think I would have had the strength.  I would love to have been a cancer researcher, but the necessity of telling people they are about to die would have killed me.  I guess I am a wus.

By the way, this essay seems to contain one arithmetic mistake.  First person who spots it wins a beautiful ovarian cancer awareness car magnet.

For my trip to Iceland I have bought a fancy camera, and have spent many hours trying to figure out how it works.  Apparently it can do many things that I have never heard of.  Explanations are couched in language I don’t understand, using undefined terms and acronyms.  What in hell is IPO, anyway?. 



IBM goes for the Nobel

Linda in Ireland, at 21

As a college senior she did a "If today is Thursday then we're in Brussels" whirlwind tour of Europe

Long ago I read a science fiction story consisting of a single “scene”, if you will – the presentation of the Nobel Prize in medicine to the curer of cancer.  Turned out to be a computer.

Well, now we know that there will never be a single cure for “cancer”, because each individual tumor is unique, with its own cause and potential cure. (Well, maybe they’re not all literally unique, but there are a heck of a lot of variations within the disease we call cancer.)  Targeted therapy is becoming the rage; deduce what’s wrong by sequencing some genes, then design a cure.  This requires enormous computing power.  And who’s got that?  IBM, of course.  A news item

http://www.bloomberg.com/news/articles/2015-05-05/ibm-expands-watson-health-partnerships-to-help-fight-cancer 

describes how IBM is partnering with 14 cancer centers (Yale and the Mao Clinic were mentioned) to develop analytical techniques  that will enable doctors and medical scientists to build the correct designer drugs.  This sounds like progress to me, but I suspect it will be expensive progress.  I keep worrying that the cost to society of these new medical miracles will turn out to be more than society is willing to pay.

But, anyway – maybe a collection of computer algorithms, not the machine they run on, will get that Nobel.



ROCA: Can't help but help.

What the hell - this is supposed to be downtown Colorado Springs!

"Ho hum.  Myrl's got us lost again"

Fox News, that much maligned conservative news organization (“Friends Don’t Let Friends Watch Fox News”) has, despite its perceived imperfections, published an important news article on ovarian cancer.  Here it is:

http://www.foxnews.com/health/2015/05/05/new-ovarian-cancer-screening-method-can-detect-twice-as-many-cases/

This concerns a massive study conducted in the U.K. that has lasted 14 years so far, and counting.  It is a test of the ROCA (Risk of Ovarian Cancer Algorithm) predictive technique.  ROCA uses CA 125, long known to be elevated in ovarian cancer.  The most common use of CA 125 consists of a simple threshold measure – if CA 125 > 35, get an ultrasound.  (Linda when first tested was over 600.)  The problem with this is that the normal CA 125 level varies from woman to woman.  ROCA overcomes this by establishing a baseline for each individual; markedly elevated readings relative to this baseline triggers ultrasound and other tests.  From the U.K. study results, ROCA would seem to be about twice as effective as other methods.  ROCA is similar to the method recommended by my Hutch group involving Bayesian mathematics.  I suspect that ROCA will win out in the end, if only because it is easier to remember. 

Unanswered so far: how early will ROCA catch the cancer?

I have written about ROC before:

http://ljb-quiltcutie.blogspot.com/2013/01/early-warning-signals-more-progress.html

http://ljb-quiltcutie.blogspot.com/2013/09/roca-foul-weather-and-dogs.html

By the way:  Feliz Cinco de Mayo a todos. 



OF TORTS AND TALCUM POWDER

By the sea, somewhere

Note the antique Geology T-shirt

Also, again, the presence of hair

I have written several  times about the correlation of talc use and the probability of contracting ovarian cancer, most recently on 9/13/13.  The cause-and-effect doesn’t seem to have been mapped out with much certainty; maybe the ultra-small particles of talc manage to infiltrate a woman’s reproductive apparatus and, somehow, promote deleterious mutations.  Asbestos does the same thing, more or less, to lung tissue.  Anyway, how it works doesn’t really matter; don’t use the stuff.  And don’t smother your babies in it, either.

I was led to this topic by an article on a lawsuit being prosecuted by a woman who had contracted ovarian cancer, after a lifetime of using  talcum powder (Johnson & Johnson) in great profusion.  She is suing for a sum that dwarfs the GDP of most African countries.  Her claim is that J & J knew all along that the powder was dangerous, but didn’t stop marketing it.  If this is true, she deserves to win.  But there are several shades of gray here.

Living alone and being bored much of the time, I watch too much TV.  Nearly all of my favorite shows will be interrupted periodically by advertisements for some new drug or other.  You have seen them; 30 seconds of “what this wonderful stuff will do” followed by 2.5 minutes of warnings of possible ill side-effects.  (At the end the couple - and there always is a couple – ends up in some preposterous but suggestive arrangement, as for instance side by side in separate bathtubs!)  What is going on here is obviously  a ”cover-your-ass”  maneuver; if you use the stuff and subsequently grow a horn in the middle of your forehead – tough luck, you were warned. 

So, let’s suppose that J & J discovered long ago that talcum powder was dangerous, but kept it a secret.  Then, sock it to’em  and have no mercy. 

But what if they never realized that their product was dangerous and marketed it in good faith?  Then they should get off scot free – but they must immediately festoon their talc-shakers with warnings.  Indeed, maybe, they should take it off the market entirely.

What seems to be happening here is that J & J has been aware of suspicions amongst researchers that talc contributes to OVCA, but maintains that this is not proved and gone on, business as usual.  This may be legal, but it is unarguably immoral.  They should get soundly whacked.

Astonishingly, an earlier such lawsuit against J & J was decided in the plaintiff’s  favor – but no damages were awarded!  I’d like to have listened to the  jury’s deliberations.

http://www.tampabay.com/news/health/research/womens-use-of-talc-powder-may-be-tied-to-ovarian-cancer/2227722