MORE ON EARLY DETECTION

Linda in an Indian village, northern Mexico

Probably 2010

You all know the following facts:

1    (1)      OVCA is curable if detected in stages 1 or 2.

2     (2)       It is damned hard to detect OVCA in stages 1 or 2.

At least you should know that stuff; I’ve blogged about it for the last six years.

Well, then, this is damned good news.  A lab in Australia has found a test that really seems to work. 

The trick apparently is to inject a “harmless toxin” into the patient.  Somehow or somewhy this toxin gloms onto sugars displayed on the surface of OVCA cells.  For other reasons – also not elucidated – this makes the cancer cells (in the blood stream) easier to detect.  Preliminary results gave a sensitivity of 90% for patients with stage 1 OVCA.  PDG.

So, okay, I don’t know enough about this matter to comment.  Further tests are underway.  Let us hope.

https://www.myhighplains.com/news/new-blood-test-could-detect-ovarian-cancer/1621670198

He did it!! Or did He?

A most beautiful baby

Made the old fashioned way

As we witty little smart-alecks used to say back in junior high school, a big, soft wad of it is about to hit the fan!

Designer babies!  The very thought frightens most of us, and puzzles the rest.  You all are aware of the potential for using “edited” genes to combat disease, especially cancer.  These alterations are applied to “somatic” cells, often using the CRISPR cas9 technology, about which I have written many times.  This use of DNA-modification raises no ethical problems; no potential human life is sacrificed by editing somatic cells, and any such changes cannot be passed on to the next generation.

You also are aware of the ethical battles surrounding the use of embryonic stem cells for any purpose other than to produce babies.  Such “pluripotent” cells have the capacity to turn into anything the body requires.  However, their main biological “purpose” is to turn into a human being.  Thus, some say, sacrificing a stem cell for anything else is tantamount to murder.  Many conferences have been devoted to the ethics of this sort of thing, and emotions run high.  Fortunately it now is possible to chemically coax a mature cell back to its pluripotent state, so with luck it may be possible to leave the embryonic type alone.

It is possible, however, to “edit” the DNA of an embryonic cell – and such an editing job can be inherited.  Therein rests big ethical questions, because editing heritable DNA is the road to designer babies.

In the United States experimenting on this subject is almost universally condemned – and moreover, illegal.  Not so, it appears, in China.

In a southern Chinese technical center, a researcher (they call him He) claims to have successfully added a gene to embryonic DNA that will protect against HIV.  He has yet to publish his results properly, so some skepticism exists.  His method involves processes done in vitro and thus is neither simple nor swift.  However, He says, healthy twin girls have been born with their modified DNA safely aboard.  They, and their descendants, will be resistant to HIV.

By the way, Dr. He was educated at Rice and Stanford.  He is no Chinese witch doctor prescribing ground rhino horn for erectile dysfunction.  Still, great doubt abounds, and all await the definitive publication.  Then, assuming He really did it, an ethical shit-storm inevitably will arise.  I will wait until then to wade into that particular fetid swamp.

https://www.huffingtonpost.com/entry/scientists-in-china-claim-first-gene-edited-babies_us_5bfbfe6fe4b0eb6d93116196

Hippo, YAP, and all that jazz

Linda and the cat from Hell

Okay, here is what I got out of this:

https://medicalxpress.com/news/2018-11-druggable-cancer-pathway-size.html

There is a “pathway” called Hippo that regulates the size of organs in mammals.  For example, by properly screwing around with Hippo you can produce mice with testicles the size of tennis balls; a revolting image.

“Pathway” in the language of the bio-geek refers to a chain of “reactions”; something activates protein A, which in turn activates B, which sets off C –resulting, at the end of the pathway with some newly activated molecule doing something important.

“Druggable” refers to a molecule that can be rendered inactive by a “drug”.  Drugs most often work by attaching themselves to the enemy in question.  To do so requires the enemy to have an irregular external shape, into which the drug can insert itself.  A molecule with a smooth external shape is said to be “undruggable”

Well, a major player in the Hippo pathway is something called YAP.  YAP seems to be especially active in some kinds of cancers, including ovarian.  YAP is a “transcription factor”, which means it helps regulate the rate at which genes are “transcribed” into functional proteins.  If the “function” is harmful, as in promoting cancer growth, it would be nice to be able to shut it down: to zap YAP, so to speak.  Unfortunately, YAP is undruggable.

Ah, but YAP operates through its own pathway, and one step in the pathway “cascade” involves a molecule called NUAK2, which has a shape into which you can insert a “small molecule”, a drug.  Some very smart people in Boston figured this out, and even designed the appropriate drug.  They are going to try it out on mice.  Let us hope.

NEW OVCA DRUG

Linda and Carolyn in Borrego Springs

Just now ten minutes of intense research showed me that AstraZeneca is one of those international drug companies that we so love to hate.  In other words, when we excoriate Big Pharma, as we so often do, AstraZeneca comes in, non-specifically, as one of the culprits.  I have several times said that, unfortunately, we need the bastards – stirring up a personal batch of a cancer drug in your bathtub just isn’t feasible.  There are sharp questions to be asked about their (Big Pharma’s) business practices, for sure, but by and large they are on the side of the angels.  I have written about this subject many times; here is an example:

https://ljb-quiltcutie.blogspot.com/2018/03/financial-toxicity-part-2.html

Well, hell, AZ seems to have gone a long way toward justifying its mercenary capitalist existence by developing, getting approval for, and bringing to market a new drug they call Lynparza (Bio-name, Olaparib).  Olaparib is a PARP inhibitor, useful as a “maintenance” drug in cases of advanced ovarian cancer.  It also seems to be good for breast cancer and certain instances of prostate cancer.  It is specific to cases of defective BRCA genes, but also (unless my hurried research betrays me) can help in cases of non-BRCA OVCA as well.  Olaparib comes equipped with its own collection of side effects (bio-geeks call them AE’s, for Adverse Events), but none appear to be dangerously severe.  Olaparib is not a cure for OVCA, but it provides a good many months, even years, of life.

So, maybe AZ has done a good thing, after all.  Quick:  sell your stock – as we all know, no good deed goes unpunished.

https://www.targetedonc.com/news/olaparib-suitable-for-longterm-maintenance-in-recurrent-ovarian-cancer

By the way, AZ is headquartered in London, but has a big facility in Maryland.

CHECKPOINT THERAPY

Linda, Whiskers, Patches & Me

Two guys who made their names in immunological research won the 2018 Nobel Prize for Medicine and Physiology.  One is from Texas, the other from Kyoto, Japan.  They worked independently, but almost simultaneously they gave intellectual birth to our old friend, the checkpoint inhibitor.  Here is a PDF describing their work.  It is easy to follow and well worth a bit of your time.

https://www.nobelprize.org/uploads/2018/10/press-medicine2018.pdf

In case you need a refresher course in checkpoint inhibitors, you could start here:

https://ljb-quiltcutie.blogspot.com/2016/05/more-progress.html

REVIEW ARTICLE

Linda and her big brother Dick, who just turned (gasp!) 80

Here is a review article.  Much of this stuff you know already, but this helps tie it together.

https://www.cancerresearch.org/immunotherapy/cancer-types/ovarian-cancer

TREE ANGEL

Linda on Heron Island, Maine

Taking a break from chemotherapy

Call me an old softy, but I loved this news article.  (To see it you may have to wade through some obnoxious advertisements.)

https://fox59.com/2018/11/08/lizton-man-honors-late-wife-raises-awareness-for-ovarian-cancer-with-wood-carved-angel/

I wish I had the talent to do something like this.

EPIGENETICS (SORT OF) EXPLAINED

Linda on a bridge near Sitka, Alaska

Mid 1980s

I found this to be useful and interesting.

You all know what the word “epigenetic” means, right?  Simplistically, it refers to things that happen to your genome that effect your health, happiness and/or heredity that do not involve alternation of the c, g, t, a sequences of your DNA. 

One important agent of epigenetics is the attachment of a methyl group (CH₃) to the DNA molecule in such a way as to “silence” a gene (prevent it from being transcribed into a protein.)  You all also know that an error (mutation) in the BRCA genes can lead to breast and/or ovarian cancer.  Well, it transpires that you can have BRCA-related trouble even though your BRCA genes are alive and well.  This can sometimes be attributed to the “methylating”  of the “promoter” region of the BRCA genes, preventing them from being properly activated.  Promoter regions are segments of DNA that are required to set the gene itself in action.

WHY some promoters get silenced while others don’t remains a profound mystery to me.

Anyway, glance at this short and simple essay.

http://www.cancernetwork.com/cancer-and-genetics/epigenetics-brca-and-inherited-cancers-dr-newman-connects-dots

GRAPEFRUIT AND OVARIAN CANCER

Linda in Yorkshire

I often feel sorry for those persons visiting me in Borrego Springs, CA, who are unable to enjoy my delicious Borrego grapefruit owing to having to take statins for high cholesterol.  Now, it turns out, cancer researchers seem to have shown that there is another, offsetting benefit from statins: reduction in the probability of contracting the most deadly form of ovarian cancer.  In a case control study it was shown that statin-users were about 32% less likely to come down with epithelial OVCA than comparable non-users.  I skimmed through the original article and came away with the impression that they (the authors) had leaned over backwards to do the statistics right – although, it is well to remember, I am no statistician. 

So, maybe the use of statins should be encouraged.  I don’t know if statins have occasional nasty side effects, but from their wide use I would guess not.  Thank goodness this doesn’t apply to me: I neither have high cholesterol nor am in danger of contracting ovarian cancer, so I can continue to enjoy my delicious, incredibly inexpensive Borrego grapefruit.

 https://www.mdlinx.com/journal-summaries/hydroxy-methylglutaryl-coa-reductase-inhibitors-ovarian/2018/11/01/7548305/?spec=pharmacy 

BRCA TESTS FOR ALL, Females, that is.

Linda in the mountains

A long time ago.

Is one billion dollars a lot of money?  Well, from my perspective – certainly.  I would bet that nearly all of you faithful readers would concur.  However, there are people who have dozens – even hundreds – of billions of dollars.  With all this wealth sloshing around, it seems to me that we ought to be able to afford to test every female baby for BRCA mutations, at birth.

There are about two million baby girls born each year.  Costs of a genetic screen for cancer-related mutations can range up to five thousand dollars, but simply testing BRCA can be performed for as little as one hundred dollars.  Say $500 a crack to be on the safe side, times two million tests yields a paltry one billion dollars! 

For comparison, the cost of our latest aircraft carrier is about 14 billion, and the annual budget of the NCI is around five billion.

Good God!  Our priorities are totally screwed!  Bitch to your doctors and your Congress-persons.  Forward this blog to the Trumpster.  And, you females – get yourselves tested.