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!

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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.

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 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