LINDA'S 70th BIRTHDAY

Linda on her 7th birthday

 

 

This Sunday would have been Linda’s 70^th birthday.  Boy, what a party we would have had!  I would have spent a week by now,  searching for the world’s best funny card.  The table would have groaned from its load of food; my recycle bin would have overflowed with empty wine bottles. Late-comers would have been forced to park two blocks away! Linda’s face would have ached from so much smiling.  And after you all had left I would have squeezed her tight, told her how much I loved her, and how lucky I was to have her to watch over me as I lapsed gradually into grouchy old age.  And we would have been very happy.

Well, of course, none of that happened.  Linda died 4+ years ago. Since that time about 65,000 American women have died of ovarian cancer.  What seems to me to be rapid progress is being made, but the end is not in sight.  I am going to try to help until I get too senile to turn on the computer.  That may be sooner than you think.

Maybe you want to give Linda a birthday present.  Here is the address:

http://getinvolved.fhcrc.org/site/TR/Events/FredHutchinsonCancerResearchCenter?pxfid=2861&fr_id=1050&pg=fund            

I will be in Alaska for the next week or so.  Take this opportunity to browse my blog and catch up on all the good stuff you’ve missed.



FORGET FRANKINFOODS - HOW ABOUT DESIGNER BABIES?

A long time ago

The little boys are daddies now.

You know what a palindrome is, right?  A palindrome is a phrase or sentence (or even a word) that reads the same right-to-left as left-to-right.  “Anna” is a palindrome.  So is “Madam’ I’m Adam”.   A highly unreliable source once told me that the longest palindrome in the English language was supposedly uttered by Napoleon during his first exile: “Able was I ere I saw Elba”

If you know a longer one, please tell me.

So why bother about palindromes?  It turns out that they are very important in genetics.  As you know, the “language” of DNA is written using just four “letters” – called nucleotides:  adenine (a), cytosine (c), guanine (g) and thymine (t).  Thus, a palindromic sequence of DNA might be something like this:  acgttgca.  Apparently the real palindromes in our cells can be much longer than this.  They also seem to function as beacons to guide various molecules of the kind that modify the DNA sequence to the place they need to go to work.  Why this is and how it has come about are well beyond my ken, I’m afraid.  Come November, when it is guaranteed to be cold, wet and gloomy, I plan to curl up with Wikipedia and try to figure this stuff out.  Or maybe I’ll just go to Borrego Springs and work on my tan.

Anyway, the Economist has published several articles on new wrinkles in genomic science – wrinkles you might be tempted to call “genetic engineering”.  Here are the links.  The first is what they call a “Leader”, and amounts to an abbreviated account of something important, with their point of view amply emphasized.  The second is the gist of the article, with all the palindrome stuff.

http://www.economist.com/news/leaders/21661651-new-technique-manipulating-genes-holds-great-promisebut-rules-are-needed-govern-its

http://www.economist.com/news/briefing/21661799-it-now-easy-edit-genomes-plants-animals-and-humans-age-red-pen

It appears that  large numbers of smart people in white coats have developed something they call CRISPR-Cas9.  The CRISPR part is short for “clustered, regularly interspaced palindromic repeats”: the Cas9 is a protein that cuts DNA.  Here, I think, is a CRISPR: acgttgcaBLAHacttgcaBLAHacgttgac – and so on, ad infinitum (or a large number of repeats, whichever comes first.)  Apparently the CRISPR indicates the right spots to enable the Cas9 protein to chop out a gene.  Presumably there will be another gene, a new and improved model, ready to slip into the gap.  Voila:  genetic engineering.

Oh, I forgot.  CRISPR molecules are actually RNA (so you should replace the thymine in the examples above with u, for uracil.) 

Obviously, it takes no great store of imagination to dream up useful application of CRISPR-Cas9 technology.  One relevant to an anti-ovarian cancer blog: Find women who carry a germ-line mutation of the BRCA genes, edit them out, and replace them with a working equivalent.  Using TCGA (The Cancer Genome Atlas) it ought to be possible to wipe out lots of hereditary cancers.  Same with other diseases: Tay Sachs and hemophilia are among those discussed.  Good stuff, for sure.

But, of course, there is a snake hiding in the garden.  If it is possible to “edit out” Tay Sachs, why isn’t equally possible to swap shortness genes for tallness genes?  Or develop a smartness gene and slap it in there, in the right place?  No more short, bald, stupid men.  A world of tall, thin, curvaceous, blond women.  In other words, designer people.  It’s scary, no?  I don’t think I know what “dystopian” means, but I’ll bet it applies here. 

And if you think that designer babies are scary, read this and let your mind run amok. 

http://www.economist.com/news/briefing/21661801-giving-bits-dna-power-edit-themselves-intriguing-and-worrying-possibility



MORE ON TARGETED THERAPY

Linda and her Mom, 1973

 

Linda’s sister Carolyn has sent me this link to an important and interesting news article:

http://www.nbcnews.com/health/cancer/new-kind-cancer-study-shows-tailored-treatment-saves-some-n412436.

The article concerns targeted therapy, which we have considered many times before, e.g.:  http://ljb-quiltcutie.blogspot.com/2014/01/linda-and-carolyn-in-borrego-springs.html

As you certainly know, if you actually READ my blogs, targeted therapy consists of first determining the mutation responsible for the tumor, then somehow undoing its malign effects.  This contrasts with “standard” therapy, which usually consists (after surgery and possibly radiation) of dosing the patient with a cocktail of chemo drugs chosen based on the site of the tumor – ovary, breast, prostate, blood, etc.  Targeted therapy requires gene sequencing, of course, and so is expensive to use – although the cost of sequencing is said to be dropping rapidly.  Targeted therapy depends heavily on research contained in The Cancer Genome Atlas:  http://ljb-quiltcutie.blogspot.com/2012/09/cancer-genome-atlas-progress.html. 

So, as I understand it, the take-away from this current article is something like this: 

1)      There are many types of mutation that are capable of causing cancer, either alone or in combination with other mutations.

2)      These mutations are not necessarily confined to a single organ, although they may be more common in some than in others.

3)      When such a mutation is discovered, and a therapy devised, it makes sense to try it wherever that particular mutation exists.  For instance, a therapy developed for melanoma has been found to be very effective against some kinds of lung cancer.

4)      Unfortunately, many tumors result from multiple mutations.  Consequently, just because a patient has a tumor that displays mutation XYZ it does not follow that a beneficial result from XYZ therapy will certainly occur – other genetic mistakes may still be able to do the job.

One example discussesd in this article concerns a woman with brain cancer, glioblastoma specifically, who has been helped significantly by a drug developed to combat melanoma. As you all probably know, Jimmy Carter has announced that he, too, has cancer in his brain – but his seems to be melanoma proper.  (I didn’t know you could get melanoma internally, but evidently you can.  One more thing to worry about.)  Jimmy is 90 but, if targeted therapies repulses his cancer I’d be glad to see him back in the White House – with a good V.P., of course.

*Carolyn Joyce deserves to be a co-author of this blog.  Not only does she send me links to ideas I should explore, but she also writes intelligent Comments and thereby gives me assurance that at least ONE person is actually reading this stuff.  Thanks, Carolyn.





MORE LIGHT ON CANCER

Linda and Carolyn ready for a hot double date

1967

Some few weeks ago I wrote a blog about an advancement, seemingly an important one, involving a compound – combretastatin,  if you are curious - derived from a tree called the South African bushwillow.  Combretastatin A-4, one type of the stuff, comes in two “isomers” – that is, it comes in two forms with the same chemical formula but different structures.  It appears that one isomer is all but entirely innocuous when applied to cells, but the other is hell on wheels – it prevents proper cell division.  Two clever German scientists have discovered that, by slightly modifying the stuff, they can produce a compound that can be switched from one isomer to the other simply by illuminating it with harmless blue light.  The game plan, then, would seem to be – suffuse the body with the harmless isomer, then use a sharply focused beam of blue light to turn it into the lethal form wherever a piece of tumor is detected.  To me this line of research seems very promising, but it is early days.

Read the article itself at:  http://www.economist.com/news/science-and-technology/21657352-optical-switching-may-abolish-side-effects-cancer-drugs-colourful

and/or my original discussion: http://ljb-quiltcutie.blogspot.com/2015/07/trees-are-our-friends.html

Well, now, more on light.  First of all, reading the first part of this blog you may have thought something along the line of “Well, great – but how do you know where all the bits of metastases are?”  Hurray!  There is a compound called naphthalocyanine which can be administered prior to surgery, which will cause the tumor bits to glow, presumably rendering them easy to zap.      

Now, several equally clever scientists – at Oregon State and U. Nebraska – have developed another therapy employing light.  Their approach is to flood the patient (mice, so far) with a chemical called phthalocyanine (note similarity to the unpronounceable word in the preceding paragraph.)  This compound has the ability to produce “reactive oxygen species” that can kill cells, but only when subjected to a beam of near-infrared light. To render the cancer cells defenseless a “gene therapy” (mostly unexplained) also is administered.  Apparently the cancer cell’s resistance to these “reactive oxygen species” is entrusted to a protein named DJ1.  Also, I surmise, gene therapy in this case consists of producing a superabundance of the right type of siRNA (short interfering RNA, a mysterious (to me) little critter that, as its name implies, interferes with lots of biochemical processes.) So, then, illuminate the tumor for the surgeon, cut out as much as possible, administer this gene therapy stuff to throttle the DJ1, and kill any remaining bad stuff with phthalocyanine and a light beam.  Simple as pie?  Probably not.

So, as I have said many times before: these therapies may not solve the cancer question, but maybe they will.  And, it warms my heart to read about smart people like these people working hard on my number one goal for humanity – the elimination of deaths from ovarian cancer.

Read this:  http://medicalxpress.com/news/2015-08-advance-photodynamic-therapy-approach-ovarian.html

And if you read all the way through this over-long bit of biochemical blundering, I’m proud of you.  Go have a beer.



HAPPY NEWS, FOR ONCE

Linda at 20

At W.M.U.

 

A new study by U.C. Davis scientists amounts to good news for ovarian cancer sufferers.  You faithful readers are aware that OVCA is known as the “silent killer” because symptoms show up so late in the progress of the disease, and that the fraction of OVCA women that are alive five years after diagnosis (the “survival” ratio) is less than 50%.  Now, however, the statistics have been raked through again and a more encouraging observation advanced: Nearly 1/3 of OVCA patients can expect to reach a more distant survival measure – 10 years.  What traits improve your chances?  Detection at a young age, detection at a lower stage, and having a less aggressive type of OVCA.*  Obviously some of these characters are intertwined: Early detection surely correlates with lower grade, for instance.  Anyway, this article (and many others like it is big news in ovarian oncology and does a lot to lighten the OVCA gloom.

http://consumer.healthday.com/cancer-information-5/ovarian-cancer-news-104/1-in-3-women-now-survive-ovarian-cancer-for-at-least-10-years-702201.html

For the record, Linda had none of the above going for her.  She was in her 60s when diagnosed, was at stage 3C, and had the most aggressive form of OVCA: serous epithelial.  I often wonder what she had done to deserve all this bad luck.  Maybe she was just too nice.

*And let's toss quality of care into the mix, although it wasn't mentioned in the article.

 

 



FLAX SEED: Yum!

Linda and Carolyn, in Vancouver, I think

 

Here is a tidbit of interest to all, but especially to those of you who place great importance on diet as a means of avoiding cancer.  There is evidence that eating flax seed will prolong remission in ovarian cancer.  The evidence comes not from humans, or even mice, but chickens.  As you surely remember, a little over three years ago I wrote a blog featuring chickens.  It seems that the poor things get ovarian cancer at an appalling rate, almost certainly because they “ovulate” every day – and, as you know, the more you ovulate the higher your risk of ovarian cancer.  In case you have forgotten this early blog, here it is:

http://ljb-quiltcutie.blogspot.com/2012/07/thoroughly-enjoying-our-norwegian.html

Well, people working at Southern Illinois School of Medicine have determined that, in chickens, eating flax seed prolongs survival.  They wish to extend their experiments to humans and are asking for volunteers.  To qualify you must have ovarian cancer, but be in remission.  Read the article and see what you think.  Here it is:

http://www.news-gazette.com/news/local/2015-08-08/women-sought-clinical-trial-flaxseed-weapon-against-ovarian-cancer.html

Flax seed is said to be far from a dessert food, taste-wise.  I wouldn’t know.

 



CANCER DRUGS COST TOO MUCH, Ch III (Or maybe IV)

Hard at work

 

This blog comes to you from Dick Ingwall via the NY Times.  It contains nothing particularly new, but does summarize well some of the topics we have discussed many times before.  Specifically, it returns once again to the questions “Why do drugs cost so much, and what can we do about it?”

The underlying kernel of reportage here concerns an article published by the Mayo Clinic and signed by 100 of the nation’s top oncodocs (U.W. and Fred Hutch are prominently represented).  Here is the article:

http://www.mayoclinicproceedings.org/article/S0025-6196(15)00430-9/fulltext

And here is the gist:

1)      Cancer will effect one in three adults during their lifetime.  (Does that include skin cancer?)

2)      Recent trends have resulted in 20 to 30% of out-of-pocket expense by cancer patients.  This is after insurance payments.

3)      In 2014 all new cancer drugs approved by the FDA cost over $120,000 per treatment.

4)      Given that the average household gross income in the U.S. is $52,000/year, paying for this 20-30% of $120,000 drugs will leave the patient and his/her family hard up for food and housing.

5)      Because cancer is predominantly a disease of old people, and in view of the fact that old people are accumulating like ants at a picnic, this economic problem is bound to get worse, fast.

And what to do about it?

1)      Create a governmental panel to propose prices, based on need and cost

2)      Allow Medicare to negotiate drug prices directly with Big  Pharma.

3)      Allow another governmental agency, one already created under ObamaCare, to evaluate the drug’s efficacy, and adjust prices accordingly.

4)      Permit importation of drugs from abroad.

5)      Prevent Big Pharma from delaying the introduction of generic drug-equivalents.

6)      Screw around with patenting procedures, ostensibly to make it harder for Big P to get exclusivity in the first place.

7)      Get the right, in-the-know organizations to revise treatment guidelines.

As you know, I am suspicious of governmental panels so much of this leaves me skeptical.  However, there being no practical way to invoke market forces in this industry, something similar to this may be inevitable.

I found this Mayo clinic article by reading a related story in the NY Times.  The Times relates that the Obama Administration (through the agency of Medicare) has reversed itself and approved payment for a cancer drug called Blincyto (actual name blinatumomab; developed by Amgen – don’t you wish you had bought its stock?).  Blincyto combats acute lymphoblastic leukemia, described as being particularly “aggressive”.  A “course” of Blincyto – two 28-day sessions – costs $178,000, not counting hospital expenses.  If you are making $50,000/year and end up paying 20% of the cost, you are out $35,600, or 71.2% of your yearly gross income.  Let’s hope the damned stuff works.

Here is the article:

http://www.nytimes.com/2015/08/09/us/medicare-reversing-itself-will-pay-more-for-an-expensive-new-cancer-drug.html?smprod=nytcore-ipad&smid=nytcore-ipad-share

The moral seems to be – let’s figure out how to stop people from getting acute lymphoblastic leukemia.



SEVERAL (OF MANY) GOOD REASONS NOT TO LIVE IN APPALACHIA

Just back from Hawaii

 

My daughter advised me recently to stop giving people web addresses for cancer articles because they are too busy to read them.  Instead I am supposed to summarize these articles in as few sentences as possible, using words of one syllable whenever such words can be found.  Well, nuts to that: here is the web address of a Newsweek article on the prevalence of cancer in the Appalachian coal country.  It took me seven minutes to read it, and I am a slow reader.  Find the time.

http://www.newsweek.com/2015/07/31/cancer-epidemic-central-appalachia-354857.html

But, if you can’t afford seven minutes, here is the gist of the article, in table form: 

1)      In Appalachia (here, specifically eastern Kentucky) there is an abnormally high incidence rate of several cancers: lung, colorectal, cervical (but apparently not ovarian).

2)      The causes of this cancer epidemic are: poverty, ignorance, smoking, coal mining.

3)      Ignorance contributes to poverty, and also to widespread smoking.

4)      Smoking and inhaling coal dust contribute to lung cancer.

5)      Open-pit coal mining releases numerous carcinogens into the atmosphere.

6)      Kentucky is the 45^th poorest  state in the Union; without coal it would be measurably less well off.

7)      A huge percentage of the nation’s energy supply comes from coal.  This percentage has decreased somewhat in recent decades, but not much. 

8)      Renewables (solar, wind, etc.) have increased dramatically in importance in recent years, but still furnish less than 5% of the nation’s energy needs.

9)      Nuclear and natural gas are poised to take over a very large portion of our energy requirements, but people are afraid of nuclear and Democrats are opposed to pipelines.

10)   There is no easy (or even apparent) solution to the problem of bad health in Appalachia.

Actually, some of the stuff in this table represents my thinking and not anything in the Newsweek article.  You’ll have to read the text, though, to figure out which is which.



GRATEFULL TO HAVE BEEN BAMBOOZLED

 

Back from Egypt

 

Not long ago Newsweek bamboozled me into buying an on-line subscription.  For most news items they are far inferior to the Economist, but they do seem to devote a generous amount of time to health issues.  I say this on the basis of insufficient evidence; what drew me to them in the first place is a special issue on cancer, now or recently on the newsstands.   Here is an example of what you will find in that issue:

http://www.newsweek.com/2015/07/31/childrens-cancer-unprofitable-and-ignored-355135.html

You would do well to read this article.  It examines the economics of developing drugs for children with cancer, which is made unprofitable by the fact that cancer in children is (blessedly) rare.  Apparently some progress is being made, but the hill to climb is very steep.  As noted in the article, the average cost of developing a new drug and bringing it to market is $1.7 billion. 

The Web address for the whole special issue is:

http://www.newsweek.com/2015/07/31/issue.html

Be careful and avoid being bamboozled.

 







INTRAPERITONEAL CHEMOTHERAPY

A (Late) Kalamazoo Fall

 

Okay, this one is going to be heavy, so don’t read it unless you are prepared for a slice of the real world.  I am going to interject Linda’s experiences with the information contained in this article.  Maybe by doing so I will make the situation more real for you, and allow me to come to grips with some painful things that are stuck in my psychic craw.  Be warned.

Chemotherapy is generally administered intravenously, through a needle or a “port” – the latter being a semi-permanent arrangement that allows the stuff to be pumped directly into the heart.  Linda had a port; you can see it in her picture at

 http://ljb-quiltcutie.blogspot.com/2014/02/some-cool-stuff-from-economist.html

However, there is another way to give chemo, one that is strongly recommended by the experts.  It is called intraperitoneal (IP) therapy.  To use IP you drill a hole in the patient’s abdomen and pump the chemo drug directly into the place it is needed.  Then you attach the patient to a machine that tips her about, allowing the drug to slosh into the far corners of the peritoneal cavity.  IP is proven superior to other cancer therapies but is not used in a majority of cases, for reasons described in this article that are not flattering to the medical profession.

Before Linda had her “debulking” operation – it lasted about seven hours – we had been told that she might awaken with a small tube sticking out of her stomach, for the administration of IP chemo.  When she did come out of her drug-induced stupor she immediately looked for that tube and, not finding it, assumed the surgery had found no cancer.  I had told her that I had good news, and she thought that it was that she was cancer free.  What I had meant was that her sister was on her way to stay with us while she recuperated.  That meant that I had to tell her that she had ovarian cancer.  I didn’t know the stage or anything about her prognosis, thank God, or I might have simply lost it all. 

Why didn’t she get IP?  Well, I vaguely remember the surgeon saying that, as the result of a previous major abdominal operation it wouldn’t be effective.  Probably something like that was the case.  One thing I do know, though:  another Bellingham woman operated on at nearly the same time had IP and is still alive. 

I often think about what an awful job being an oncologist would be.  In point of fact, the generality of MDs don’t have it so great, either.  Sure, they are well paid and highly respected, but consider the importance of their decisions.  As a college professor I might decide to give some lad or lass a B when maybe an A would have been appropriate.  Who cares?  They do, but in the long run nothing is ruined.  However, if I tell a woman that some lumps in her abdomen are probably benign and not to worry – and they later turn out to be cancerous – I  have made a mistake of tremendous consequence, one that will follow me for the rest of my life.  MDs face situations like that all the time.  No wonder they screw up now and then.  I will continue to try to cut them lots of slack.

http://www.nytimes.com/2015/08/04/health/ovarian-cancer-abdominal-chemotherapy-underused.html?smprod=nytcore-ipad&smid=nytcore-ipad-share 



TWO NEW WORDS, and possibly a new medicine.

Linda and her sister-in-law Raelyn Joyce

Celebrating New Years in the usual Joyce tradition

 

Wow!  Two impressively big and obscure words in one paragraph!  The article cited below treats of the use of Mullerian inhibitory factor to treat cases of ovarian cancer that have relapsed and are resistant to chemotherapy.  In case you don’t like Mullerian, try Paramesonephric.  Does that help?  Well, all I can say is “Thank God for Wikipedia”. 

So, it works like this.  All embryos originally have two things called Mullerian or Paramesonephric ducts.  In girls these develop into the necessary reproductive machinery; it boys they are “suppressed” by something called Mullerian (or, of course, Paramesonephric) inhibitory factor.  This is a protein, produced in the usual way, by decoding a gene.  It appears that scientists from Harvard and elsewhere have discovered that, by modifying the gene slightly and using a standard virus “vector” they can obtain an abundant supply of a very similar protein which, in mice, (if you want to sound professional you say “in a murine model”) is effective in curbing growth of ovarian cancer.  Why this works is not explained, but just as well:  I wouldn’t understand it anyway and neither, probably, would you.  Let’s just hope it works in people.

Here is the article:

http://news.harvard.edu/gazette/story/2015/07/recurrent-ovarian-cancer-patients-may-have-hope/

So, my two great grandkids were here over the weekend.  They are nearly of an age; approximately 1.7 years old.  They clearly are superior beings, destined for great things.  You can tell that by the way they throw green Asian pears into a bucket of water, say “apple”, and then fish them out again.  I was six before I could do that.



CANCER AND EVOLUTION

In the Galapagos

She loved water.  Not me.  No, wait - that didn't come out right.

The NY Times provides a summary of a recent paper that treats of what you might be tempted to call the “philosophy of cancer”, by which I mean the nature of such aberrations as viewed in light of evolution.  All that sounds thick and stifling, but that would be an unfair assessment of this short article.  You should read it. 

http://www.nytimes.com/2015/07/28/science/cellular-cheaters-give-rise-to-cancer.html?ref=health

The gist, honestly (but perhaps erroneously, in part) summarized

Multicellularity (as in us, fruit flies and grapefruit) has evolved from single-cellularity at least seven times – mostly in braches of life I have never heard of before.  It evolves because it offers certain survival benefits.  However, multicellularity require sacrifice – cells must give up their absolute freedom to behave as they see fit, and instead assume certain definite roles and functions.  What we call cancer is simply one way to describe the result when a cell rebels against these restrictions and begins to do what IT wants to do, rather than what the ORGANISM requires.  The organism has devised many ways to snuff out such a rebellious cell, but sometimes they fail.  And that’s about it. 

I have pondered these concepts for, oh, easily 30 minutes, and I am somewhat puzzled.  Evolution is largely based on natural selection: everything else equal, that unit prospers that is most aptly suited to its environment.  The key is survival.  The authors of this article (web address given below) regard the success of a tumor as a benefit to survival – of the tumor.  However, in the end the organism dies, and so does the tumor.  Rotten kind of “success”, I would say.

Here is the original article.  I am going to study it and see if deeper understanding evolves.  However, my great grandkids are visting (with their mothers, of course), so I have better things to do right now.

http://rstb.royalsocietypublishing.org/content/370/1673/20140219