Thursday, August 27, 2015

LINDA'S 70th BIRTHDAY

Linda on her 7th birthday
 
 
This Sunday would have been Linda’s 70th 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:
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.


Tuesday, August 25, 2015

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.
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. 
 
 
 


Friday, August 21, 2015

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:
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.



Sunday, August 16, 2015

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


Friday, August 14, 2015

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.
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.
 
 


Thursday, August 13, 2015

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


Monday, August 10, 2015

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.