CAR T and OVCA

Caspar Wistar, M.D.

He was a buddy of Ben Franklin

This is very good news, I believe.  My printer seems to agree: when I attempted to print the article (below) it (my printer) stopped working half way through the first page, emitted a terrible scream (of joy?) – and quit working.  I take that to be a good omen.

You remember CAR T, right?  If not, read

http://ljb-quiltcutie.blogspot.com/2017/10/car-t.html

for a refresher course.  In brief, CAR T refers to an immunotheraputic process wherein T cells are targeted at specific cancer cells, then venture forth through the body to find them, and kill them.  So far CAR T has only been used on blood cancers, but now an outfit called ITUS Corporation (of San Jose, California) is preparing to unleash CAR T technology on solid tumors – beginning with our favorite target – ovarian cancer.

From Bio 1a in high school you remember that cells have various proteins attached to their external membrane.  These proteins have specific functions.  For instance, they may signal to glucose molecules to come hither, attach, and be eaten (cells need nutrition, after all.)  Or they may say “hey,  - signals from the pancreas – come over, lock on, and deliver your instructions.  That sort of thing.

Well, some smart people have discovered that a particular protein – they call it “follicle stimulating hormone receptor” (FSHR) – exists only on the ovarian cells of adult women.  In principal, these means that one can extract T cells from an OVCA patient, modify them to recognize (and kill) cells with FSHR proteins on their surfaces – and destroy those (cancerous) cells.  Trials are underway.  Clinical applications: maybe two years away.

My family used to have a saying that went something like “There’s many a slip between the cup and the lip”.  That is certainly true, so we must be aware that this discovery – so simple, so promising – may come to nothing.  But I am greatly encouraged.

So what does Caspar Wistar have to do with any of this?  I will tell you.

Dr. Caspar Wistar was a physician in Philadelphia and a contemporary of Benjamin Franklin.  He was so important that various academic units of the University of Pennsylvania have born his name.  The latest incarnation is the Wistar Institute, which is a biomedical research facility.  The CAR T technology as applied to OVCA was developed in the Wistar labs, using funds provided by you and me  through the NIH.  Wistar Institute does biology, not bio-business, so  presumably they sold  the right of development to ITUS.  However, ITUS has sub-let the actual work to something called the Moffitt Cancer Center.  No wonder the development efforts will cost upwards of $ I million.

I tell you all this to help you understand how the Pharma universe operates.  I withhold judgement.

http://managedhealthcareexecutive.modernmedicine.com/managed-healthcare-executive/news/ovarian-cancer-could-be-next-application-car-t-cell-therapy

Linda, in the mood for Christmas

FRANKENSTUFF

Dr.Francis Collins, Director of the NIH

Former lead guitar for the Rolling Stones

(No, I made that part up)

Dr. Collins is one of my current heroes.

Along with Russell Wilson

Now this sort of scares me.  People at Scripps have created what can only be called “frankenproteins”.  They are excited.  So was Dr. Frankenstein when he zapped his monster into life.  We all know how that turned out.

Not to insult your intelligence, but I want you to recall that our entire heredity is “written” in a code consisting of only four letters:  A, T, C, and G. The “book” containing these letters is the DNA double helix.  Baring errors, in the DNA molecule A always bonds with T, and C with G.  It is the sequence of these A-T and C-G parings that tells a creature to develop into, say, a tadpole, rather than, say,  Donald Trump.

A, T, C, and G are known as nucleotides.   They “code” for the proteins, upon which all life depends.

Well, some adventurous folks at Scripps in San Diego have created two new nucleotides, which they call X and Y (pitiful lake of originality).  X pairs with Y, just like A-T and C-G.  Furthermore, they have inserted the X-Y pair into the bacterium E. coli, and then run the resulting (man-made!) genetic material through the normal DNA-to-protein assembly process.  And - Voila! – A new, totally unnatural, man-made protein walks (slithers, actually) the face of the earth!

The Scripps folk are jubilant, and forecast all sorts of uses for these frankenproteins.  Dr. Collins, Director of NIH and the author of many learned publications, enthusiastically agrees.  So maybe I should be happy with this development.  After all, it is a promising tool, right?  And the Scripps people assure us that it can’t get out of hand:  they have to feed it just to keep it alive.  Yeah, sure.  The original Frankenstein creation learned to go get its own food.  We don’t want to see globs of frankenprotein slithering around the lab, eating the lab rats!

Seriously, this stuff disturbs me a bit.  I think we must proceed very carefully.

By the way, Dr Francis Collins not only runs NIH, which has a budget similar in size to, say, the U.S. Navy – he also has time to author a series of highly informative blogs.  You should get on his mailing list.

https://directorsblog.nih.gov/2017/12/05/adding-letters-to-the-dna-alphabet/

 Linda at the gourd farm.

She delighted in decorating gourds.

RNA

RNA and DNA

Ain't they pretty?

Ever hear of Thomas Jefferson University?  Well, neither had I, until today.  It turns out to be a mostly professional/grad student sort of place, located in Philadelphia.  One of its subdivisions is the Sidney Kimmel Cancer Center, of which I definitely have heard, multiple times.  Out of SKCC emanates an interesting report on a factor contributing to metastasis of ovarian cancer.  It involves something symbolized by lncRNA.  That’s l as in “long”, not “one”.  Those symbols always get twisted up in my brain.

So, you know a lot about RNA, right.  It is a nucleic acid molecule, not much different from DNA.  Most people know RNA as a messenger molecule, functioning to carry information from the genes imbedded in DNA to a ribosome, where it is used to manufacture the protein molecules which keep us all purring along.  You might call such RNAs as “coding RNSs”, because they carry the “code” for the protein’s structure.  Thus, lncRNA stands for “long non-coding RNA”.    Long non-coding RNA is a product off what once was referred to as “junk DNA”, because the product had no obvious use.  Now we know that these ncRNA molecules perform an essential service; they regulate which genes are “expressed”.  Probably some ncRNA is responsible for the fact that you don’t grow toenails in your eyeballs.

Geez!  This was supposed to be a simple little report, but it has gotten well out of hand.  The gist of the matter is that these folks at SKCC have shown that specific lncRNAs are strongly associated with metastasis of OVCA .  They did this using “bioinformatics”, which involves feeding a large mass of data to a computer algorithm, and seeing what comes out.  Read about it, below.  There is a possibility that new therapies could be directed against these particular lncRNAs

In previous blogs I have said that, if had it to do over again, I would go into molecular biology.  However, as I have the small-muscle dexterity of a walrus but am not entirely hopeless at mathematics, I think bioinformatics would be the better choice.

https://www.news-medical.net/news/20171129/Study-provides-new-insights-into-mechanisms-contributing-to-ovarian-cancer.aspx

 Linda and Scottish friend

Isle of Skye  

MORE ON PARP

Double stranded break in DNA, on the right

PARP will fix it, unless we intervene

Here is an update on PARP inhibitors as applied to ovarian cancer.  I have been guilty of runaway enthusiasm for immunotherapy; until immunotherapy proves to be the weapon that eventually eliminates ovarian cancer (as I believe), PARP inhibitor drugs will serve the vital purpose of extending lives.  This article speaks of PFS (progression-free survival) rather than mortality, but surely the two must roughly  correlate.  The article describes several clinical trials, which found that the PARP drugs in general lengthened PFS by one to two years.  In the past I have been scornful of treatments that were not outright cures,  but now I realize I was wrong.  What would I not have given or done to give Linda an extra 18 months  of life?

This article is tough sledding in places, so you should glance at the following glossary before you try:

PARP (Poly ADP ribose polymerase) is a family of proteins that serve to repair double-stranded DNA breaks.  OVCA cancer cells have many such breaks, so if you can screw up the PARP you can inhibit growth of the cancer.

Germline BRCA mutations refers to inherited DNA defects.

Platinum-based, platinum-sensitive:  Most standard OVCA chemo drugs are based on platinum, which most OVCA cancer cells don’t like at all.  Unfortunately, some such cells almost inevitably survive – leading to recurrence.

AE:  Adverse effects, meaning bad side effects

Neutropenia means a deficiency of certain essential white blood cells

Thrombocytopenia seems to be a difficult way to say platlet-deficiency

BRCA “wild type” means unmutated BRCA genes.  For some reason geneticists refer to an undamaged chunk of DNA as “wild”.  They must lead an awfully placid life.

Okay, now give this a try.

https://www.curetoday.com/articles/parp-inhibitors-continue-to-show-promise-in-ovarian-cancer

And for trying, here is an award:

Linda and my Mom, probably 1982

THE ONLY GOOD VIRUS IS A DEAD VIRUS

An adenovirus, presumably dead

Viruses are bad, right?  Well, not necessarily.  Dead or denatured virus is used as a messenger boy, to deliver modified genes to the correct place in the DNA molecule.  How?  Believe me, if I knew I would show off by explaining it to you, at great length.  But I don’t know, so you are spared some – perhaps boring – biology. Give thanks.

Anyway, they do use virus to deliver the goodies, and therein lies a problem you probably didn’t anticipate:  there is an acute shortage of properly prepared virus.  There are entire biotech firms wholly devoted to the preparation of types of properly modified viruses – and they have years of backlog.  It turns out that you don’t fix up medicinal virus in your garage.  It costs hundreds of millions of dollars to get into the game.  That is partially why some new drugs cost so much.  Partially.

All this is explained in the NYTimes article below.  Take a few minutes and read it.

https://www.nytimes.com/2017/11/27/health/gene-therapy-virus-shortage.html?em_pos=medium&emc=edit_sc_20171127&nl=science-times&nl_art=1&nlid=69247603&ref=headline&te=1  

Linda and Ella

WE SPEND TOO MUCH. BUT NOT ON EVERYTHING

Our big Alaska adventure

Photo taken at 11:30 pm

Well, according to the TEA Party we are Taxed Enough Already.  However, I prefer the judgement of Robert Samuelson, a middle-of-the-road NYTimes columnist who maintains that we (Americans) don’t pay enough tax; according to his calculations we borrow 17 cents of every dollar we spend – “we” here being the government.  

This has resulted in a National Debt of $20.44 X 10¹² (trillion)., slightly more than our GDP (Gross Domestic Product).  In other words, we owe more than we make in a whole year!

That can’t be good.

So, we should pay more tax – and we should reduce expenditures, right? 

Well, yes – but let’s leave the NCI (National Cancer Institute) alone.  They have just released upbeat information on a vaccine against ovarian and breast cancer.  Works on mice: human trials in the offing.  Said to be particularly important for women with BRCA mutations.  If you are female, ask about getting the BRCA test.  Really!

.

The link below describes the vaccine.  If you bring it up, notice the column of topics along the right margin.  These are good, non-technical essays on many cancer topics.  Reading them might be a good way to study for my next pop quiz.

https://www.cancer.gov/news-events/cancer-currents-blog/2017/ovarian-cancer-vaccine?cid=eb_govdel

LITTLE GOLDEN BALLS

The Joyce sisters, Humboldt County

The weather outside is frightful, and in here it is far from delightful – my cleaning lady not having been here recently.  I find that after many years of practice I can screw off successfully for much of most days.  However, at irregular intervals feelings of guilt and remorse sweep over me; I am useless, and I really don’t like it.  That’s when I sit down in front of my computer and try to understand cancer biology and research. 

First thing this morning I found an article on using gold nanoparticles to deliver CRISPR/Cas9 to specific locals in the body.  “Nano”, as you know, refers to a unit of length equal to one billionth of a meter .  This is, like, pretty small.  The width of the DNA molecule is about 2.5 nanometers (nM).  A human hair is 80,000 t0 100,000 nM in diameter.  (It is said that those of Donald Trump are far thicker, owing to the yellow goop he applies.).  Anyway, a nanoparticle is damned small.

Small though they are, they can carry CRISPR/Cas9 assemblies to their assigned destinations.  Dead viruses have been used for this task, but, small though a nanoparticle is, apparently viruses are even smaller; several of them are required to deliver the whole CRISPR package, whereas the gold nanoparticle can do it in one load.  This is important, it seems.

Why gold?  Well, for reasons left unexplained, gold can penetrate cell membranes with uncommon ease.  (I could say something clever right here, such as “A little gold will get you most anywhere”, but I won’t.)  Also, gold is tolerated uncommonly well by the human body.  (Supply your own wisecrack.) 

Well, big deal.  I still don’t know how CRISPR actually works.  This deficiency set me to “researching” CRISPR/Cas9, with the customary result.  There are dozens of articles that tell me what I know already: 

https://www.yourgenome.org/facts/what-is-crispr-cas9     is an example.

 And there are thousands of articles that “tell” me what I want to know, but in terms I cannot understand:

https://www.neb.com/tools-and-resources/feature-articles/crispr-cas9-and-targeted-genome-editing-a-new-era-in-molecular-biology    for instance.

.

 I spent several hours beating my brain against this and its ilk, before throwing in the towel and writing this blog.  Maybe I will try again tomorrow.

I did learn some things, though:

Apparently CRISPR is an RNA molecule that functions as a guide, leadung Cas9 to the proper location.

Cas9 is one of several “CRISPR-associated proteins” – enzymes – that like to cut DNA.

If you want to read about the little gold nanoparticles, click on

https://directorsblog.nih.gov/2017/10/10/gene-editing-gold-nanoparticle-delivery-shows-promise/

ARTIFICIAL INTELLIGENCE

Linda clinging to a funny-looking guy

Stephan Hawking is a smart guy.  You know who he is: the Cambridge professor of physics, cosmology and all things difficult who has been confined to a wheelchair most of his life by ALS (Lou Gehrig’s disease) and now communicates, somehow, through a machine.  Hawking has warned strongly against AI (artificial intelligence), sometimes known as machine learning.  This seems to be a method for computers to “educate” themselves; learn new tricks by observing the world around them.  Hawking  believes that this may allow machines, which after all are amoral fabrications made from inorganic stuff, to take over the world and dispense with humans.  I tend (somewhat) to agree; after all, I remember (Terminator) when Skynet became “self-aware” and initiated a war that loosed the likes of Arnold Schwarzennerg on humanity.  There is a (rather bad) book, The Fear Index by Robert Harris, which explores that same theme.  I tend to believe that considerable caution should accompany any attempt to facilitate computer self-education.

So, what does any of that have to do with cancer?  Well, the Director’s Blog by Francis Collins (NIH) recently featured  an article titled “Using machine learning to understand genome function”:

https://directorsblog.nih.gov/2017/10/19/creative-minds-using-machine-learning-to-understand-genome-function/

about a smart mathematically inclined biologist, or perhaps more accurately biologically-inclined mathematician at Stanford, who is using machine learning to understand how the genome works.  His name is Anshul Kundaje, and he is originally from India.  I don’t fully understand the article, but it appears that Dr. Kundaje is applying machine learning to identify significant patterns in huge genomic (and/or epigenomic) data sets.  For instance, artificial intelligence already has been used to identify patterns in brain scans that predict whether a child will develop autism.  AI also has been used to identify the abnormalities associated with Alzheimer’s disease.

Genomics and epigenomics involve huge data sets, far larger than our little brains can wrestle with efficiently, so I guess it makes sense to sic self-educating computers on them.  But, seriously, I think we ought to be cautious in doing so.  I don’t want the Terminator walking into my living room and solving all my health problems, permanently.

NEW TOOLS

Linda and Chestnut tree

Well, I guess you have to make the tools before you can build the house.  For me, the “house” is curing cancer, especially ovarian.  A few potential “tools” are described in the links below.  The first outlines a way to “edit” RNA using CRISPR technology.  The second involves a way to correct single “letter” mistakes in DNA; for instance, replace a C with an A. 

I guess these “tools” are important.  For instance, if a mutated gene was cranking out potentially lethal RNA, perhaps you could “edit” the RNA to, say, go somewhere and quietly croak.  Or, in the case of a point mutation that renders a gene ineffective, maybe you could fix the problem.  How one would do any of this is, of course, way beyond me.  But let us not forget: tools are only worth making if they have a use.  So, quick as we can, let’s build the damned house!

As you can see, blogger hiatus us over.

https://www.nih.gov/news-events/nih-research-matters/crispr-technology-adapted-edit-rna

https://www.economist.com/news/science-and-technology/21730615-it-can-now-edit-individual-genetic-letters-gene-editing-takes-another-step-forward

CAR T

A classical chimera

More than likely you have brushed up against “immunotherapy” and its faithful companion (CAR T therapy) in the news.  Being the curious person you are, no doubt you have asked yourself what CAR T stands for.  Well, the CAR part stands for “chimeric antigen receptor”, and the T part refers to that part of the immune system called T cells (sometimes called “killer T cells” for their ferocious role in the body’s defense system).

Did that help?  Well, maybe not, so I here is an official explanation: “Chimeric antigen receptors are engineered receptors which graft an arbitrary specificity onto an immune receptor cell”. 

Did that do the trick?  Well, hell, of course not.  Who do these people think they’re writing for – Watson and Crick, or maybe Linus Pauling?  Here is all I know:  CAR T therapy is called “chimeric” because it grafts some new stuff onto the patient’s own T cells.  This gives it “specificity”, which means that these T cells now can recognize a particular kind of cancer cell, and gobble it up.  Two (very expensive) drugs are now approved for blood cancers.  One researcher describes these engineered T cells as Pac Men, swimming through the blood stream and zapping the bad guys.

Anyway, CAR T technology is being modified to attack solid tumors, including ovarian.  Some of this work is going on at Fred Hutch.  If you use the link below to follow up on CAR T, soon you will know more than me

Not that that’s saying much.

https://ovariancancernewstoday.com/2017/10/20/ovarian-cancer-gene-therapy-specialist-to-share-more-than-a-million-dollars-in-grants/

AMERICAN EXCEPTIONALISM

Linda with Tarahumara baby, 2009

I think she wanted to bring it home with her

They talk about “American  exceptionalism”.  There is no doubt that we are exceptional in many ways.  We are exceptionally powerful, economically as well as militarily.  We are exceptionally lucky to be situated on North America and not, for instance, West Africa.  We are exceptionally lucky to have a secular state, rather than one based on religion.  Likewise, we are fortunate enough to have the NY Yankees and the New England Patriots to hate.  So, by and large, we should be very  happy to have been born here, rather than in Yemen, for example.

But on some things it seems to me that we are exceptionally stupid.  In school I was taught that our system of government was created by very wise men, and was the best ever devised.  But why, then, do we have total gridlock in Washington and a bunch of clowns for leaders?  Is it the fault of the Founding Fathers, or are we modern voters to blame.  Possibly a bit of both, I believe. 

But one facet of life we approach in an exceptionally stupid way, for sure – our system of providing health care.  What pushed me into this tirade is the fact, which I just learned…

http://www.news.com.au/lifestyle/health/women-with-family-history-of-breast-and-ovarian-cancer-able-to-undergo-free-genetic-tests/news-story/3a2de230422fbca80c93f0ce889a72a8

that in Australia every woman with any risk factors can now get tested for BRCA mutations on the cheap, whereas in this country one actually has to  HAVE the damned disease!  How many American lives are tossed away needlessly each year, in order to save a few bucks?  We need more cancer biologists, and fewer statisticians and economists.  So say I.

I am in a bad mood this morning.

MORE ON HORMONE THERAPY

Linda and a stuffed something

Despite my somewhat ambiguous first name (Myrl), I am male and consequently know about such things as hot flashes, night sweats and sleeplessness (post-menopausal symptoms, apparently) only at second hand.  They seem to be serious enough, however, that hormone therapy – estrogen, progestin – have been prescribed to ease them.  In 1993 a massive study was undertaken to test the safety and efficacy of this drug regimen.  It was terminated prematurely in 2002 because, as I read it, taking estrogen in combination with progestin caused a statistically-significant increase in the incidence if stroke, breast cancer, and blood clots.  On the basis of this result I have advised against hormone therapy multiple times (eg., http://ljb-quiltcutie.blogspot.com/2013/09/free-medical-advice-and-worth-every.html).  So maybe I was wrong.

The massive study referred to above (the Women’s Health Initiative) was continued (after withdrawing the drugs) in the sense that the subsequent histories of the participants were studied.  Big surprise: the placebo group and the group that received the drugs had statistically-significant identical rates of mortality.  I probably know less about statistics than I know about cancer biology, if that is possible, but this sounds weird to me; if the drug-getters had more life-threatening side effects than the placebo group, how come they didn’t die more?  I have to assume that all the stats were done correctly – so what gives?  Did they mix a little Atropa belladonna into the placebo?  Or maybe GMO-enhanced polyunsaturated fructose sugar?  None of these is possible, of course, leaving me baffled.

There are some other important statistics in the article:  http://www.fredhutch.org/en/news/center-news/2017/09/death-risk-menopausal-hormone-replacement.html.  Some of them suggest to me that the culprit here is progestin, and that estrogen alone may be safe and beneficial under certain circumstances.  As always, consult someone who knows.  Maybe several.

QUAKERS AND OVARIAN CANCER

Two of my favorite people

As we all learned many months ago, if ovarian cancer is detected in stages 1 or 2, cure – it not a slam-dunk – is still quite likely.  However, in view of the fact that early stage disease has few obvious symptoms, most OVCA cases are discovered only after the disease has spread.  We also all agreed many months ago that a major new weapon – specifically, an effective test for early stage OVCA – is sorely needed.  Well, here is one, involving cancer DNA in the bloodstream.  Read this little ditty to find out how it works.

https://www.nih.gov/news-events/nih-research-matters/detecting-early-signs-cancer-blood

The catch, as always, is cost.  If a woman’s body doesn’t show obvious signs of distress, how then does one know which women to apply the test to?  Clearly, humankind would be well served if ALL women were tested periodically.  But how much would that cost?  I don’t know, but I would bet – about as much as the U.S. Navy.  And so it won’t happen, at least not soon.

Wouldn’t it be nice if the world were so ordered that we didn’t need a navy – or an army or air force, for that matter?  Think of what could be done with all that money.  The Quakers definitely have the right idea.  Just not the votes.

FREE CAR MAGNET

I ordered some more Ovarian Cancer Awareness car magnets, and to get the volume discount I ended up with a few extra.  If you want one, email me at myrlbeck@msn.com and I will send it free, gratis and for nothing.  They are 8 inches high, cling to your vehic like a barnacle, and further a good cause.  Supply severely limited, so act now.

WHAT YOUR PCP SHOULD KNOW

If you take my picture one more time I"ll whack you with this gourd!

Does your PCP (primary care physician) know all this?  Maybe not; they are busy professionals with family lives of their own.  But they should.  Read this, then give them an oral exam.

https://www.healio.com/internal-medicine/oncology/news/online/%7Bc2f9594d-5f0d-40ea-aa06-3c39774ec0c0%7D/ovarian-cancer-care-what-pcps-need-to-know?page=3

ALAN SANDERSON

Two kids in Evanston

Alan Sanderson, you’re my man!

There is a large lake, Chew Valley Lake, in the Chew Valley district of Somerset, England.  The somewhat comical name (Chew Valley) led me to read an article in the Chew Valley Gazette.  There I met Alan.

Alan lost his wife to ovarian cancer in 2014.  Since then he has devoted much of his time and energy to combatting the disease.  He is a star fundraiser for Ovacome, a leading British charity focused on ovarian cancer.  For instance, he recently organized a 13-mile walk through the Somerset countryside, to raise money for OVCA research and treatment.  In his spare time he gives talks to groups about OVCA symptoms and treatments.

Alan, I envy you the energy and mobility to do what you do.  I have somehow become so old that all I can do is sit on my duff and write this blog.  If you ever visit the Pacific Northwest, I would like to buy you a beer.  Not as good as you would get in your Local, of course, but not bad, either.

Here is the article on Alan:  http://www.chewvalleygazette.co.uk/article.cfm?id=102792&headline=Chew%20Valley%20Challenge%20tackles%20ovarian%20cancer&sectionIs=news&searchyear=2017

And here is some information about Ovacome:

http://www.ovacome.org.uk/

MEDICARE, GENETIC TESTING, AND YOU

Linda in Quito, Ecuador

I have been asked several times if Medicare will pay for genetic testing; specifically, for BRCA mutations.  Such is the extent of my rattle-brainishness that I just now got around to checking.  The short answer is: no.  Until recently, you could be tested if a family member had breast or ovarian cancer.  Not any more; now you actually have to HAVE cancer to get tested!  Seems monumentally short-sighted to me, but what do I know?  I’m just a dumb geologist.

Needless to say, FORCE* is not pleased with this situation.

http://www.facingourrisk.org/understanding-brca-and-hboc/publications/newsletter/archives/2007winter/stricter-medicare-guidelines.php

Neither am I.

*Facing Our Risk of Cancer, Empowered.  Look ,’em up.

CURE

A young Linda

I have been writing this cancer blog for something like five years – and I just now discovered that there is a magazine wholly devoted to cancer: what it is, what it does, and what to do about it.  I am going to explore the magazine more intensely this week-end (no use starting now; Friday beer is less than an hour away.)  But in the meantime, why don’t you form your own opinions.  Just click on

http://www.curetoday.com/

and go from there.

STARVE YOURSELF HEALTHY

At home in Evanston, 1984

As we get older our DNA accumulates epigenetic changes, especially methylation.  (See blog http://ljb-quiltcutie.blogspot.com/2013/08/epigenetic-apocalypse-now-i-warned-you.html, for instance.)   New research demonstrates that “caloric restriction” minimizes these changes.  Thus, cutting lifetime caloric intake by 30% or so is associated with significantly slower ageing, at least in mice and some particularly ugly brand of monkey; the article implies a similar benefit to humans, but no evidence is provided.  The experiment indicates that diet restriction has no effect on telomere shortening, another contributor to senescence (see http://ljb ljb-quiltcutie.blogspot.com/2012/07/relaxing-on-beach-somewhere-1988.html). 

Well, heck, at 84 my DNA is certain to be crowded with methyl groups, and my telomeres mere nubbins.  Thus, caloric deprivation is unlikely to do me much good.  However, to be on the safe side I hereby vow to give up broccoli, cauliflower, raw celery, and humus.  That should so the trick.

https://www.nih.gov/news-events/nih-research-matters/calorie-restriction-slows-age-related-epigenetic-changes

IMMUNOTHERAPY FOR THE REST OF US

Linda and an early quilt

NCI produces a lot of video clips, most of which I consider only marginally worthwhile, or even a bit dumb.  Here, however, is one that vastly repays the effort to create it.  You might call it Cliff Notes – Immunotherapy”.  Watch it.

https://www.youtube.com/watch?v=UOowq2GXN7A

IMPORTANT INFORMATION

\

Two kids in the Olympics

This is largely for guys.

Linda was diagnosed with ovarian cancer about nine years ago.  After she had undergone her truly terrible “debulking” operation, her surgeon met with me to explain the situation.  I am positive that he was a good, well-intentioned man and a surgeon of outstanding skill and experience – but I understood little of what he said, and retained even less.  His explanation did Linda, and me, no good whatsoever.  The fault lay with me:  I didn’t know what to ask.  If, God forbid, your female partner finds herself one if the 22,000 American women diagnosed with ovarian cancer each year, I don’t want you to be at a loss for background and understanding.  We can’t all be research biochemists, but there are certain lay-person summaries that are of great help.  The latest and best was just published in The Economist:

https://www.economist.com/news/leaders/21728893-science-will-win-technical-battle-against-cancer-only-half-fight-closing.

I implore you to read this article.  You may have to buy the current issue (maybe $5.00, you cheapskate!).  Do so, then give it to a friend.  An added benefit would be to enjoy a fresh, British-cynical take on the clown show maturing in Washington.

Of course, if you have studied all 531 of my cancer blogs you would know all this already.  But you haven’t, and I don’t blame you.  After all, who wants to think about cancer when the sun is shining, there are trails to be hiked, and Facebook is filled with cute pictures of crows and little kids?  But read them and think about cancer nonetheless.  Cancer will not go away by itself.

VOODOO MEDICINE

Linda and Ella, a few years ago.

One is now a beautiful little girl.

The other is a beautiful memory

God knows, cancer is a tough beast to kill.  Society has invested prodigious sums of money warring on cancer for at least half a century – with, overall, disappointing results.  As I wrote earlier, with immunotherapy in our quiver, I am feeling cautiously optimistic, but we still have a long way to go.  In the meantime, don’t abandon science for voodoo “cures”.  As this article makes clear, they just don’t work.

https://www.cancer.gov/news-events/cancer-currents-blog/2017/alternative-medicine-cancer-survival

MORE ON DRUG PRICING

Guess where

When I first signed on as a Research Advocate with Fred Hutch I was astonished to learn that they carried economists on their staff.  And even paid them!  My astonishment arose from the fact that, although an honor student in economics at Stanford, I couldn’t remember ever learning anything useful.  But now maybe I get it.

The NYTimes article (below) deals with a new study of drug pricing.  New drugs cost us (society) a lot, as is well known.  The conventional defense against charges of price gouging is: drug development is costly, because costs arising from failed drugs must be included.  Critics respond that in fact all the basic research is handed to Big Pharma gratis, by publically funded research outfits (NIH, Fred Hutch, Sloan Kettering, U. W. Medicine, etc.)  As the article (which you should read) makes clear, the case is complicated.  How, for instance, do you calculate costs when a researcher blunders on something patentable, quits to form his or her own company to exploit it,  runs a few small but encouraging trials, and then is bought out by by Big Pharma for enough money to fund the North Korean nuclear program?

So read the article and tell me what you think.

The article ends with the following chilling observation:

When it comes to drug prices, it does not matter what companies spend on research and development, Dr. Kesselheim said.  The price is based on what the market will bear.

https://www.nytimes.com/2017/09/11/health/cancer-drug-costs.html?em_pos=medium&emc=edit_sc_20170912&nl=science-times&nl_art=2&nlid=69247603&ref=headline&te=1

Ovarian Cancer Awareness Month

Aw, nuts!

September is ovarian cancer awareness month.  Let's be more than aware; let's exterminate the damned disease!

http://www.kulr8.com/story/36315924/what-you-need-to-know-for-ovarian-cancer-awareness-month

COSTS OF CANCER

How could I sell this house and lose this tree?

Especially when I can remember this lady being there.

As if getting cancer is not painful enough to the body and spirit, when it happens you get whacked in the wallet, too.  Copays, deductibles, medicines, etc., are compounded by lost income.  Your hard-working public servants at the NCI refer to this as “financial distress” or, in more extreme cases, “financial toxicity”.  The bottom line is that living can cost you a lot more if you get cancer.  See below:

https://www.cancer.gov/about-cancer/managing-care/track-care-costs/financial-toxicity-pdq

The obvious moral here is – don’t get cancer.  But since that can’t be guaranteed, maybe we ought to look into reorganizing our health care system.

  

Linda's 72nd.

Linda on her 7th birthday

August 30, 1952

Today would have been Linda’s 72^nd birthday.  She is no longer here, of course, but the disease that killed her – ovarian cancer –  still is, and is as cruel and implacable as ever.  Some little progress toward eliminating it has been made in the years since Linda’s death, but not nearly enough.  Now, however, with many  promising results emerging from multiple experiments in immunotherapy,  I  taste blood in the water!  If you want to join me in being in on the kill, please do so through Linda’s Fred Hutch web page:

http://getinvolved.fhcrc.org/site/TR?px=1148821&fr_id=1573&pg=personal

Think of it as a birthday present, to one of the most lovely people any of us has ever known.

BLOGGER HIATUS CONTINUES

Linda in Sedbergh, Cumbria, UK

I am back from England and ready to confront real life once again.  Unfortunately, I returned with a severely damaged rotator mechanism which intermittently turns my right shoulder into a useless source of pain and distraction.  That, plus the fact that I am preparing to “downsize” (= move to a smaller house with no stairs, but also no view) means that there will continue to be a hiatus in my string of blogs.  For how long, I do not know.

But in the meantime, read the following interesting article.  It appears that there are so many therapies that require clinical trials (in immunotherapy and personalized medicine) that there is a critical shortage of patients!

https://www.nytimes.com/2017/08/12/health/cancer-drug-trials-encounter-a-problem-too-few-patients.html?smprod=nytcore-ipad&smid=nytcore-ipad-share

THIS IS IMPORTANT. READ IT.

Carolyn will be here in a few days.  Hooray!

Quite a few years ago I bought some shares of stock in Novartis, a pharmaceutical company based in Switzerland.  I thought I needed some drug company stock to “balance my portfolio”, as my broker is fond of saying.  I would have preferred an American company, but I reasoned that the political climate here was inimical to Big Pharma; too many Elizabeths and Bernies breathing down their collective neck.  The Swiss never let anything stand between them and a healthy profit.  But, whatever.  I wish I had bought a whole lot more.

That by way of providing a somewhat sour introduction to an important cancer story.  We have discussed “immunotherapy” before, many times (29, to be exact).   Well, it appears that the FDA is on the verge of approving an immunotheraputic approach to dealing with a type of leukemia, “B-cell acute lymphoblastic leukemia” to give the malevolent sucker its full name.  In this disease the culprit is cancerous B cells.  B cells are part of the immune system.  The immunological approach involves extracting millions of the patient’s own T cells (another part of the immune system), modify their genetics to teach them that cancerous B cells are “the enemy”, then infusing them back into the patient where, in the pleasing phrase of one Dr. Carl June, they behave like “serial killers”, offing hundreds of thousands of errant B cells.  This treatment is not without side effects and is far from infallible – but it seems to beat alternative treatments (chemo; bone marrow transplants) in most respects.

This type of immunotherapeutic approach has been studied using lab animals for at least a decade.  It gives promise of value defending against other cancers as well:  multiple myeloma and aggressive brain tumors are mentioned.

Oh, by the way: the treatment is estimated to cost $300,000.  That’s a lot of Swiss francs, but clearly beats the alternative.

Here is the article.  Read it!  

https://www.nytimes.com/2017/07/12/health/fda-novartis-leukemia-gene-medicine.html?smprod=nytcore-ipad&smid=nytcore-ipad-share

OVARIAN CANCER CONFERENCE

Linda in Yorkshire

The 20^th Annual Conference on Ovarian Cancer is going on in Chicago at the moment, and many interesting facets of the fight against the disease are being examined.  Here is a discussion of clinical trials of clinical trials and why they are so important.  Especially important are early-stage trials.  Every woman, and every husband, should be aware of this.

http://www.curetoday.com/conferences/20th-ovarian-national-conference/clinical-trials-are-the-way-forward-for-ovarian-cancer-but-they-need-advocates-at-every-level 

For an overview of the state of the battle against the disease, read this:

http://www.curetoday.com/conferences/20th-ovarian-national-conference/the-road-ahead-for-ovarian-cancer

Enjoy your summer, and don’t start any fires. 

A USEFUL NEW TEST

Linda at the Seashore

Apparently there is, or has been, a serious problem determining if an anomalous pelvic mass in a woman is or is not dangerous.   I seem to understand that the evidence currently used in diagnosis is concentration of the protein CA125; if it is high enough, the surgeon goes to work.  All too often, though, the post-operation report goes something like “Woops!  Just a benign growth, after all.  Could have been ignored.  That will be $30,000, please.”  In other words, the statistical “specificity” is poor.

Well, a Brit outfit called Angle has developed a “liquid biopsy” (more commonly referred to as a blood test) that has double the previous specificity.  The test is called the Parsortix test, and how it works is not explained, other than it involves RNA somehow.

Not a cure, not prevention – but useful just the same.

http://www.marketwired.com/press-release/angle-reports-successful-headline-data-us-european-ovarian-cancer-studies-400-patients-aim-agl-2224784.htm

PROFILES in RESEARCH EXCELLENCE: Dr. M. ROBYN ANDERSEN

Linda & grand-niece Ella Henner

The Rivkin Center has announced its grant recipients for 2017.  As you will know if you read every word I post to this blog and have a good memory, MRC awards grants in four categories:  Pilot Studies ($75,000) to allow pursuit of new approaches to conquering ovarian cancer; Scientific Scholar Awards ($60,000) to assist talented newly-minted researcher get started on their careers; Bridge Funding Awards ($30,000) to help young scientists successfully swim the moat and scale the wall that stands between them and the glittering hoard of NCI funding;  Challenge Grants ($150,000 for two years) to explore big-picture ideas. 

For 2017 MRC appears from their web site to have given out 14 grants worth just shy of $1 million.  Not bad for an outfit created by a busy oncodoc in his spare time!  Saul, you are my hero.

But what about Robyn Andersen?  She is one on many who submitted proposals that appealed to me.  I chose her in part because I know her.  She worked with Drs. Urban and Drescher on a mega-colossal project – now sadly defunct – for which I attempted to be useful some years ago.  I have “edited” several of her papers and can say two things: she is a psychologist rather than a biochemist, and she can write long and convolute sentences of unmatched complexity.  I can say one other thing, although perhaps I shouldn’t: she is nice to look at, surrounded as she is by male cancer researchers who look more or less like a younger version of me.

Dr. Andersen’s Rivkin-funded project involves using “meditation-like exercises, along with a smartphone-connected feedback system, to reduce symptoms of stress and anxiety in patients who have completed initial cancer treatment.”  This is important; I know from personal experience.  Linda was brave beyond anything I can imagine, so avoided dumping the anxieties she must have felt on me.  Also, she was simply optimistic and cheerful by nature.  However, late at night when I was asleep I know she suffered.  If Dr. Andersen can mitigate this aspect of the cancer ordeal, she will have made an important contribution.

So, Robyn Andersen was educated at SUNY Stoney Brooke (MA), U. Washington (MPH), and Stoney Brooke again (Ph.D).  She has been with Fred Hutch for at least seven years.  In the past nine years she has published 27 papers if I counted correctly, for many of which she seems to have been the principal author.  That sure as hell beats my output when I was her age.  Way to go, Robyn; keep it up!

MORE USEFUL INFORMATION

Linda in the Mountains

I don’t know what you might do with this information, but potentially it is too valuable to simply delete.  The main part of the article introduces an NCI cancer genome data base that might (should?) be useful for cancer researchers.  Lay-persons such as you and I can give this a skip.  However, running down the side is a list of general cancer topics, and if you investigate them you will find that they are meant for us, not the pros.  A few of the topics are: What is cancer?, Prevention, Early Detection, stuff like that.  Maybe just the thing if you’re stuck indoors on the 4^th because of foul weather.

https://www.cancer.gov/news-events/cancer-currents-blog/2017/gdc-dave-tools?cid=eb_govdel

A LEARNED ESSAY ON STEM CELLS

Daughters Karen and Kristen will re-visit this country with me next month

Sure wish this lady could be with us

 I have mentioned stem cells 47 times in this blog.  It is time to determine if I really know what they are and what they do.  (The smart money is on:  probably not.)  I am going to write this “learned essay” off the top of my head; not even Wikipedia will be involved.  I expect biologically sophisticated readers (e.g., daughter Kristen Beck, niece Rebecca Hunsinger, great friend and benefactor Dr. Joanne Ingwall, paleontology colleague and occasional social critic Dr. Sharron Sussman) to comment, correct, and even chastise, if appropriate.  Failing that I will continue to muddy the waters and roll science back on its haunches – and it will be your fault, not mine.

So, what’nhell is a stem cell?  Well, it is an “undifferentiated” cell that has the capacity to turn into one or more types of specialized cells – liver, muscle, skin, etc.  You read a lot about “embryonic stem cells”.  These little buggers are derived from embryos, natch, and seem to occupy a realm of constant warfare between science and (some flavors of) religion.  This is because they have the capacity to develop into a whole and complete human being.  (There also are murine embryonic stem cells, but nobody worries much about the immortal souls of mice.  Other mammals have ESCs too, of course.)  As I understand it, there are two kinds of ESCs: “omnipotent ESCs, which can give rise to an embryo plus a placenta to nourish it, and “pluripotent ESCs” which can’t do the placenta thing.  I am far from certain about this, but it doesn’t’ matter anyway.  The overriding problem is that there are lots and lots of well-meaning, intelligent people who regard using ESCs in experiments as murder.  I see their point, but disregard it.

Question:  Is a human zygote also an omnipotent ESC? 

There also exist many other kinds of less “potent” stem cells.  These are specialized stem cells (SSC) which can turn into only a single type of cell: liver, say, or blood, muscle, etc.  Actually, they don’t “turn into” anything; rather, they divide, with one daughter being the specialized, working cell in question and the other an exact (it is hoped) copy of the original SSC.  In this way the SSC is essentially immortal and hangs around doing its thing indefinitely.

Question:  I had always thought that ordinary somatic cells divide to replenish its organ.  For instance, if an old liver cell with tattered telomeres received orders (from where?) to croak, its near neighbor, another somatic liver cell, would receive orders to divide, thereby filling the gap.  That must be wrong, right?

Question:  Cancer is said to result from unlucky mutations or groups of such mutations.  Does this mean that the SSC itself is mutated, or its sister the specialized cell?  Or both?

So, I am vaguely aware that it has proved possible to take an SSC and, using almost magical biological sleight of hand, induce it to climb back up the developmental ladder and become equivalent to am ESC.  They call these things iESCs, which codes for “induced embryonic stem cells”, although maybe they should be called induced pluripotent stem cells (iPSC) because they have little to nothing to do with embryos. 

An aside:  If iPSCs are ever used to generate a human being – in effect, a human clone - expect all hell to break loose.

OK, I think that’s all I know about stem cells.  You are to be praised if you read this far.  Thank you.  BUT WAIT:

Overriding big picture question.  When, for instance, a liver SSC divides to make a functional liver cell and a duplicate of itself, if mitosis does its job correctly both daughter cells have identical DNA – although they have profoundly different roles to play.  The difference must be epigenetic. Different genes are silenced in the two sibling cells.  What in Heaven’s name controls this?