I DON'T GET IT

Finn invokes Spring

Okay, I don’t get this.  It must be important; it was just published in Science, which is scientific bigtime.  But the press release (below) leaves me more than a little confused.

So, the authors refer to a property they call “stemness”, which seems to be the ability to self-reproduce by cell division.  At one time I thought that ALL cells could do that, but apparently this attribute is confined to specialized cells – we call them stem cells. 

It seems that his research establishes the following:  There are cancer-fighting T-cells in many (all?) solid tumors.  As they kill cancer cells, the victims exude potassium.  What this article seems to be saying is that the potassium induces “stemness” in the T cells, but the products thereof are –why? – divested of their cancer-killing properties. 

So what these guys have done is to extract tumor-infiltrating lymphocytes (T cells), then cause them to reproduce in a high-potassium environment.  Then they are put back in the bio-system (read: mouse), where they kill tumor. 

Obviously, I don’t get it.  If the potassium-grown T cells within the tumor don’t kill it, why should similar cells grown in vitro to do the trick?  But apparently they do – in mice, at least.

This is touted as “basic research”, and I guess it is.  The more we learn about cancer, the closer we come to a real cure.  Right?

https://www.cancer.gov/news-events/press-releases/2019/stemness-potassium-immunotherapy?cid=eb_govdel

ATRIAL FIBRILLATION: WHO NEEDS IT?

Karen, Canuck, & me

Since I have atrial fibrillation I assume everybody is interested in it.  Here is the result of a study which, unless I am missing something, is not very useful.

https://www.nih.gov/news-events/nih-research-matters/comparing-treatments-atrial-fibrillation

A POTPOURRI OF POORLY UNDERSTOOD BIOLOGY

Spring us in the air!

PFS = Progression-free survival.  Means:  You’ve got it, it will probably get you in then end – but right now you are in remission and this stuff helps prolong it.  A lot better than nothing, certainly, but not what you really want, which is ….

OS = Overall survival.  A lengthened lifetime.  The Holy Grail here is something that prolongs OS indefinitely.  In other words: a cure.   The search still goes on.

PARP = Poly ( ADP-ribose) polymerase.  This is a protein that, among other things, repairs double-stranded breaks in cellular DNA.  Double-stranded breaks (and other imperfections) most commonly occur during cell division.  If a break is not repaired the cell will die.  Thus…

PARPi = PARP inhibitor.  This is a variety of drug that inhibits the activity of PARP.  As cancer cells divide much more frequently than normal cells, PARPi drugs are a weapon against cancer.  There are several already approved by the FDA: olaparib, rucaparib, niraparib, talazoparib.  As far as I can see, these are mainly (only?) useful for cases of OVCA and breast cancer where germ-line mutations of the genes BRCA1, BRCA2 and (something I had never heard of) PALB2 are involved.  Thus, these drugs are not universally useful and, moreover, have nasty side effects.  PARPi treatments are good for PFS, but how they affect OS is questionable. 

PARG = Poly (ADP-ribose) glycohydrolase.  And now we get, at last, to what spurred me to write this blog.  This stuff’s mission in life is to “catabolize” (i.e., get rid of) PARP.  Without it, PARP accumulates, and the cell dies.  So, inhibit PARG , PARP accumulates, and the (cancer) cell croaks.  At least, so reason scientists at U. Manchester, U.K.  The blurb cited below does not make it clear whether PARGi drugs can be useful in OVCA cases not involving BRCA, etc., mutations.  I can’t see why they SHOULD but, hell, as I have said many times before – what do I know?

https://www.eurekalert.org/pub_releases/2019-03/uom-nco031919.php

MOLECULAR GARBAGE BAGS

Yes, we have had rotten winters before

Here is a new word for you: exosome.  Exosomes are tiny molecular trash bags expelled by cells to get rid of waste products, and possibly for other purposes as well.  According to Dr. Collins, NIH Director (in his blog), investigators at U. Kansas have developed a “nanochip” (nano means one millionth of a meter) that can detect exosomes expelled by ovarian cancer cells in their frantic race to reproduce.  It seems to work; it properly detected OVCA in women known to have it, and cleared women known to be free of the disease.  Left unsaid is how early in OVCA development it works.  If stage 1 or even 2, it may be a significant breakthrough.

By the way: you can do far worse with your spare time than to follow Dr. Collins’ blog; not only does he write about interesting and important things, he writes about them well.

https://directorsblog.nih.gov/2019/03/21/detecting-cancer-with-a-herringbone-nanochip/

AN UNCOMFORTABLE DEATH TO CANCER STEM CELLS

Puppy Love

Well, at least we can cure ovarian cancer – in mice – most of the time.

As far back as 8/22/2012 I wrote a blog about cancer stem cells,

https://ljb-quiltcutie.blogspot.com/2012/08/cancer-stem-cells-may-they-rot-int-hell.html

 and the topic has arisen multiple times since.  The down and dirty facts are that standard chemo can kill, say, 99% of OVCA cancer cells – but the remaining 1% have stem-cell-like properties and, surviving, regenerate the malignancy.  Now some smart people at U. Pittsburgh have devised a drug that causes these cancer stem cell bastards to themselves croak.  What this drug does is to prevent the cancer stem cells from expelling toxins they generate in dividing.  In effect, they die of acute constipation!  Serves ‘m right, by golly!

Of course, so far these results apply only to mice; no human trials are reported, yet.

https://www.managedcaremag.com/news/20190314/new-drug-may-prevent-recurrence-improve-survival-ovarian-cancer

P.S.  I try not to become discouraged, but sometimes it is hard.  When I started this blog, some seven years ago, many articles I read began with words like “22,000 women will be diagnosed with ovarian cancer this year, and 15,000 will die of it.  Less than 50% of women with OVCA will survive for five years.”    I still see that language, all the time.

TWO USEFUL ARTICLES

Linda and Viv Hailwood, on a long-ago Howgill hike

The Economist must be the prince of news magazines.  Yes, at times it does suffer from an overdose of British humour and a wanton waste of vowels – note the superfluous  second  “u” in humour – but it covers what is important in the world with clarity, thoroughness,  and, for the most part, a lack of obvious bias ( they do draw the line at the misadventures of our current President, however).  Last week’s edition had two articles that concern medicine that are well worth reading.

The first, 

https://www.economist.com/international/2019/03/02/repurposing-off-patent-drugs-offers-big-hopes-of-new-treatments  

describes efforts to “repurpose” drugs, already approved for one or more conditions, to other uses.  Often, I suspect, genetics suggest possible unsuspected efficacies.  Repurposing a drug costs a hell of a lot less than developing one de novo,  and requires less paperwork – although still, in my view, too much.  Read the link and see if you agree.

A shorter article in the same issue,  https://www.economist.com/business/2019/03/02/global-drugs-firms-are-under-pressure-from-american-politicians , 

examines Big Pharma – a thing we all love to hate – and their pricing policies.  The central question addressed is, “Why do drugs cost more here than almost anywhere else?”.  The answers given will not satisfy you.  Drug pricing is one of those issues, a growing number, about which all I can say is – “There’s a big problem here, but I don’t know what’n hell to do about it.”  When I was younger I would have known - immediately - and like as not been wrong.

GENE THERAPY AND SICKLE-CELL ANEMIA

Alaska cousins

Each 12.5% me

Thanks to my friend Phil Montague for tipping me off to this valuable info-bit.

You probably know what sickle- cell anemia is: an excruciatingly painful disease caused by misshapen red blood cells.  They – the blood cells – get this way because of a genetic mistake involving just one letter of the DNA alphabet.  It turns out that NIH has sponsored research leading to a cure – an actual cure – for sickle-cell anemia.  The process is described in a segment of last Sunday’s 60 Minutes TV show (3/10/19), largely through an interview with Dr. Francis Collins, Director of NIH (see https://ljb-quiltcutie.blogspot.com/2017/12/frankenstuff.html).  If you have a TV you should hasten to watch this program, especially if you are still shaky on how gene therapy works.  (And aren’t we all?). 

Several times previously I have declared Dr. Saul Rivkin to be my hero.  Saul lost his wife to OVCA at an early age; he responded by establishing the Marsha Rivkin Center for Ovarian Cancer Research, while raising at least $15 million for its support.  But to Saul I now add Dr. Collins, who headed the official effort to decode DNA, and now serves in a capacity to greatly influence where medical research funds go.  Dr. Collins is a brilliant scientist, an articulate blogger (see NIH web site) – and he even plays a mean guitar! 

LOSARTAN: GOOD FOR OVCA?

Linda on a birding expedition

I take Losartan for high blood pressure, and it is darned likely that you do, too.  Losartan is an effective drug – even though there was a recent flurry of panic over whether or not it contained trace amounts of some carcinogen or another.  Well, there has arisen some medical evidence that taking Losartan correlates with, and may be responsible for, increased longevity in OVCA patients.  Rodents are dying even now, to test this hypothesis.  This link will fill in some of the details:

https://www.medicalnewsbulletin.com/common-blood-pressure-drug-improve-ovarian-cancer-treatment/ 

We are making progress.

CLINICAL TRIALS: GUIDELINES

In our new house:  1984

I have urged you repeatedly, in my 656 (!) blogs, to be aware of and receptive to the possibility of participating in a cancer clinical trial.  Regrettably, I have not spent many words on other important matters, such as eligibility and feasibility.  For instance: you may be ineligible to participate in a trial if you are too old, too young, or perhaps otherwise too sick.  Also, participating in a trial may not be feasible if it requires you to abandon your husband and twelve kids and move to NY City.  Well, the NCI has finally got around to considering these issues, in this highly useful little essay:

https://www.cancer.gov/news-events/cancer-currents-blog/2019/expanding-clinical-trial-eligibility-criteria?cid=eb_govdel 

Much of the problem, it seems, lies with well-meaning but poorly informed “clinicians” (e.g., your family doc or your oncologist).  Make sure these guys are up to speed.

THE LINDA JOYCE BECK QUILTING COMPETITION

Linda and one of her quilts

Ann Bjorseth, Linda’s long-time very good friend (and my once-upon-a-time girlfriend), alerts me to this news article.  It appears that in Canada they have a very straightforward and effective approach to raising money for a good cause:  play some hockey.  Seems that a woman named Sue Deacon, who loved – and played – hockey died a few years ago, of ovarian cancer.  Her friends responded by organizing the Sue Deacon Cup, a hockey tournament.  So far they have raised a half-million, and are supporting several OVCA research projects.  Of course, my hero Dr. Saul Rivkin has raised about $15 million for the same purpose, largely by sponsoring a foot-race – but Saul has been at it for decades.  By 2030 I hope to see the winner of the Sue Deacon Cup go straight to the Winter Olympics – and win.

But Linda wasn’t much of an athlete, so what should I start in her honor?  A quilting competition?  The Linda Joyce Beck Quilting Super Bowl?  Maybe not, but it sounds nice. 

http://noca.convio.net/site/TR?fr_id=1460&pg=entry  

A CANCER-GENETICS PRIMER

Linda and her Mom, in front of Linda's new mobile home

This was pre-me

This is a Cliff Notes-type summary of cancer genetics.  You know most of this stuff, but a review wouldn't hurt.

https://www.cancer.gov/about-cancer/causes-prevention/genetics?cid=eb_govdel

HACHIMOJI DNA

Marion &^ Linda, in Borrego days of yore.

I am getting in over my head, that’s for sure.  After many encounters with basic genetics I am pretty comfortable with DNA, RNA, proteins, and how they all work together to construct the glory that is us.  I also can tell you glibly about the essence of DNA:  sugar-phosphate support in the form of a twisted ladder, with “rungs” consisting of four “bases”, a, c, g, and t, with t fitting together with a to form one kind of rung, and c mating with g to yield another.  If an accident occurs and a hooks up with g, for instance, the DNA molecule is distorted and – possibly – there’s all hell to pay.

Well, now scientists at several institutions have manufactured four totally new bases, and moreover succeeded in inserting them in natural DNA, to form to form what the call hachimoji  (Japanese for eight letter) DNA.  It seems that HM DNA can be copied onto messenger RNA and then run through a ribosome to produce – what? – new, synthetic proteins perhaps, provided the amino acids called for already exist.  Scary.  In the meantime HM DNA may earn its keep as a data-storage device.  There also is some mention of new drugs.

So, stay tuned.  No telling what the guys in white coats will come up with next.

Oh, best to say that HM DNA is said not to be a threat to escape the lab and attack your house pets.  Seems it has to be fed constantly, just to stay alive.

Lots of useful links to hachimoji  DNA.  Just trust yourself to Google