A WELL DESERVED BLOGGER HOLIDAY

Grand daughter Olivia

Great grand daughter Evelyn, atop

Daughter Kristen's excellent horse, Buddy
Photo Joe Mortimer

There will be no new blogs for about a week; try to contain your grief.  I have visitors from Alaska (shown above) and I intend to enjoy them to the fullest.  You may well ask: how did a troll like you produce such handsome offspring?  Answer:  Darned if I know; the rest of their forebears must have been pretty exceptional.

THE GENE: An Intimate History

In search of fabric

St. Charles, Missouri

Remember  Rocky?  Of course you do; it was a great movie.  No matter what you think of boxing, Philadelphia, or Sylvester Stallone, Rocky was great.  Do you remember Rocky 2?  Probably not.  It wasn’t bad, really, but it just wasn’t up to the standards of its predecessor.  That seems to be generally the case; sequels are, to some extent, a letdown.

Of course, there are exceptions: The Godfather was one of the best movies of all time – but Godfather 2 was just as good.

Well, sadly, Siddhartha Mukherjee’s new book, The Gene: an Intimate History falls into the Rocky category; compared to his previous triumph, The Emperor of All Maladies, The Gene is over-long,  over-written, and difficult to follow – in fact, soporific.  (My open-the-book to nap interval was about seven minutes, a  record.)  I wish I could praise Mukherjee’s new book, because he is an indisputably brilliant scholar.  I think that winning the Pulitzer Prize with Emperor has made him secretly long to be a poet.  Instead, I hope he goes back to being a fill-time cancer researcher; then, in 20 years, he can write  the Godfather of modern medical  literature.

As to the structure of the book:  He begins with the history of research in genetics – all the way back to Mendel, for Heaven’s sake!  This story has been told before, usually more simply.  There is quite an extensive (and interesting) discussion of eugenics, Nazi and otherwise.  The bulk of the book deals with modern developments in genetic medicine, and is quite up-to-date; even CRISPR Cas9 technology is explained, and rather well at that.  The final few chapters, though, degenerate into medical metaphysics.  I got through them, with the help of much coffee.  I may try them again someday, but not soon.

In short: don’t read this book unless you are an expert in the field, an insomniac or, like me, a masochist. 

HEREDITARY CANCER

Linda and Kristen

Tucson, mid 1980s

 When Linda was diagnosed with ovarian cancer about a decade ago she was not offered genetic testing.  I believe that was because of how little was known about the genetics of ovarian cancer at the time.  Now, it is recommended that every woman be offered BRCA testing upon diagnosis, whether or not there is a family history of breast or ovarian cancer.  This is partly because treatment and prognosis in part are determined by BRCA state.  For instance, it appears certain that patients who are BRCA-positive have longer remissions.  If you have breast or ovarian cancer in your familial history you should study this web site.

https://www.brcainoc.com/?source=OLA_N_H_49&WT.mc_id=OLA_N_H_49&umedium=banner&uadpub=targetedtherapies.onclive.com&ucampaign=2016%20lynparza%20hcp&ucreative=3181706_animated_unbranded_banner_300x250&uplace=dm_ban_oo_con_hlth_flat_intlsp_asco%20meetingovarianspotlight_300x250_fy16_as_nt_noba_dv_nostud_hcp&adid=1#/the-test

(This must be a contender for the title of “most difficult web address to type accurately” in the world.  I wonder what it would look like in Arabic.)

As I have discussed elsewhere, the more OVCA and genetics are parsed, the murkier the connection becomes.  Apparently there are a dozen or so mutated genes that can contribute to ovarian cancer; BRCA1 & 2 merely have the highest “penetrance”.  (Rough definition: the higher the penetrance, the higher the probability of coming down with the disease.) 

If you study the web site you will find a pie diagram that illustrates just how difficult this whole thing of OVCA/genesis turning out to be.  The diagram shows the fraction of hereditary OVCA attributable to certain mutations – BRCA, for instance, is held responsible for ~20%.  The largest piece of the pie - fully 60% - is labeled “unexplained familial risk”.

By the way – health insurance will cover BRCA testing.

SOME RECENT COMMENTS OF INTEREST

Weddell Seal, basking in Antarctic sunshine

This blog isn't worth a picture of Linda

Read 'em all.  What else do you have to do?

More on the benefits of using oral contraceptives - and of having kids. http://www.clinicalendocrinologynews.com/specialty-focus/reproductive-endocrinology/single-article-page/study-confirms-role-of-oral-contraceptives-in-preventing-ovarian-cancer/7d253397f184402b915c6fe19d8c9acd.html on SGO: The good guys

More on the link between lack of exercise and ovarian cancer. Cause and effect rather murky. http://www.oncologynurseadvisor.com/ovarian-cancer/exercise-may-protect-against-epithelial-ovarian-cancer/article/504709/ on THE DEATH OF CANCER?

Will this topic never die? I am so upset that I plan to grill a steak this evening. http://www.cancertodaymag.org/Spring2016/Pages/What's-The-Beef-Cancer-Risk-Meat.aspx on BACON FOREVER!

And here is another use for NIR radiation. Recent experiments indicate that NIR can make the cancer surgeon’s job easier. In OVCA, surgical “debulking” – cutting out all visible tumor – is SOP. It is, however, notably inefficient, because the surgeon must recognize cancerous material “By eye”. Now it appears that help for the surgeon is within sight. Some clever people have developed a chemical that is readily absorbed by OVCA tissue, but by scarcely anything else. This stuff will glow when subjected to NIR, and guide the surgeon’s knife to hidden bits of bad stuff. As always – not a cure, but progress none the less. http://www.news-medical.net/news/20160615/Novel-imaging-technique-may-assist-surgeons-to-improve-visualization-of-ovarian-tumors-during-surgery.aspx on NCI brings you NIR-PIT

I am a sucker for anything having “epigenetic” in the title, so I picked up on this article – but learned darned little. Apparently there is something called “epigenetic medicine”. Maybe someday someone will tell me what it is. http://medicalresearch.com/author-interviews/breast-and-ovarian-cancers-may-have-common-epigenetic-origin/24690/ on EPIGENETIC APOCALYPSE NOW: I warned you.

More on endometriosis. Ladies, you should appreciate me http://thestir.cafemom.com/healthy_living/198268/5_things_you_didnt_know on NOT A GUY THING

More on BSOR, Does your gynecologist know this? http://news.yale.edu/2016/01/21/sparing-ovaries-and-removing-fallopian-tubes-may-cut-cancer-risk-few-have-procedure on FREE MEDICAL ADVICE (and worth every penny)

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A USEFUL WEB SITE

Joyces, Becks, and Ocotillos

Remember Dream Teams?  Specifically, do you remember SU2C – Stand Up to Cancer?  I have blogged about them several times over the past many months.  Probably Dream Team efforts have been swallowed up and digested by the Moonshot by now.  If not, then soon.  Anyway, one of the outfits involved in the ovarian efforts of SU2C has come out with a nifty new web site which you should investigate and possibly bookmark.  Here it is:

http://ovarian.org/

Regarding the picture.  It must have been a cold day in old Borrego Springs.  Two days ago it was rather warmer: 123 degrees, to be exact.

FUN with the Economist

Linda on the Greek island of Rhodes

The Economist has two important stories of interest to us.  The second one deals with the relative cost of drugs.  You may need to “Register” to read them both, but Registration is quick, easy, and free.

Read them.  They’re FUN!

http://www.economist.com/news/science-and-technology/21700125-personalisation-cancer-treatments-leading-better-outcomes

http://www.economist.com/news/science-and-technology/21700373-cancer-drugs-cost-more-america-elsewhere-may-be-just-priced-out

OF WOLVES AND WOODCUTTERS

Linda astride the Mendocino Triple Junction

VBL Therapeutics, based in Israel, has just presented evidence that one of its drugs (VBL-111) is useful in combating thyroid cancer, glioblastoma – and ovarian cancer.  Here is the press release:

https://globenewswire.com/news-release/2016/06/06/846242/0/en/VB-111-Clinical-Data-Presented-at-ASCO-Demonstrate-Significant-Increase-in-Overall-Survival-in-Platinum-Resistant-Ovarian-Cancer.html

But that’s what I want to write about.  No doubt you have read my characterization of the savage pack of tort lawyers that feast on medical mistakes.  To some extent the scene resembles a party of woodcutters in a forest, nervously huddled around a campfire while all around them twin eye-shaped pairs of lights blink on and off.  The sound of gentle drooling is distinctly evident.

God help the axman who has to go into the shadows to pee.

No doubt the “wolves” in this scene would prefer to be seen as trailing a migrating herd of caribou, weeding out the old, weak and undeserving, thereby bettering caribou in particular and the world in general.  Well, maybe.

As often is the case, there is some truth in both characterizations.  However, there can be no doubt that wolf-scrutiny inculcates caution.  Here, for instance, is VBL Therapeutics’ effort to cover its ass:

Forward Looking Statements:
This press release contains forward-looking statements. All statements other than statements of historical fact are forward-looking statements, which are often indicated by terms such as “anticipate,” “believe,” “could,” “estimate,” “expect,” “goal,” “intend,” “look forward to”, “may,” “plan,” “potential,” “predict,” “project,” “should,” “will,” “would” and similar expressions. These forward-looking statements include, but are not limited to, statements regarding the clinical development of VB-111 and its therapeutic potential and clinical results, including statements related to the Phase 3 pivotal trial for rGBM. These forward-looking statements are not promises or guarantees and involve substantial risks and uncertainties. Among the factors that could cause actual results to differ materially from those described or projected herein include uncertainties associated generally with research and development, clinical trials and related regulatory reviews and approvals, and the risk that historical clinical trial results may not be predictive of future trial results. A further list and description of these risks, uncertainties and other risks can be found in the Company's regulatory filings with the U.S. Securities and Exchange Commission. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. VBL Therapeutics undertakes no obligation to update or revise the information contained in this press release, whether as a result of new information, future events or circumstances or otherwise.

That should keep the wolves at bay, by God!

FUN FACTS about the MOONSHOT

With Linda Dennis 

Park Place Market, 2010

It certainly is obvious that users of Facebook are searching for entertainment, not enlightenment.  Recently I posted a short essay to my blog ("Fun Facts about Biology") in which I suggested that I planned to accumulate a list of articles that are interesting from a scientific viewpoint  but lacked “specificity” regarding ovarian cancer and hence did not merit a blog of their own.  Almost immediately upon reposting to Facebook it accumulated 60 hits – and the number continues to rise.  Certainly the word “Fun” did the trick.  I may post something of the order of  “Fun observations of our dismal, expensive, tragic failure to cure cancer of the earlobe” and see if the Fun phenomenon reasserts itself.

On a more serious note, it appears that the Moonshot people are making progress.  A central repository for genomic data is coming into existence at the University of Chicago.  A vast and expensive array of computers will receive, categorize, organize – and share – DNA data bases from around the world.  This should allow quick and efficient access to vital data for researchers everywhere.

As noted recently, there is some discouragement about the practical value of cancer genomes and associated mutations:

http://ljb-quiltcutie.blogspot.com/2016/06/so-many-genes-so-little-time.html

However, more knowledge must surely help, at least a bit.

Here is the link:  http://www.cancer.gov/news-events/press-releases/2016/genomic-data-commons-launch?cid=eb_govdel

SO MANY GENES, SO LITTLE TIME

Carolyn's wedding

Note sign in background

ASCO, The American Society of Clinical Oncologists, is holding its annual meeting right now, which means that my web-based tip sheet is flooded with articles on ovarian cancer – most of which either cost money to read, or are beyond my comprehension.  Here is one that is neither.

A report presented by a Stanford researcher, based on a data set of 100,000 women, reports that an additional 11 genes have been identified that (when mutated, I presume) contribute to the probability of contracting ovarian cancer.  This brings the total to 25 – and, probably, still counting.  Three of these are well understood; BRCA1,2 and something called Lynch syndrome (of which I had never heard until today).  Lynch syndrome is more commonly associated with colon cancer and, like the BRCA genes, involves the disabling of a DNA damage-repair gene.  The “odds ratios” (think of the relative probabilities of contracting OVCA) vary from 12 for BRCA1 to almost nothing.  Oddly, and to the surprise of the investigators, a gene called STK11 came in at 4, almost as high as BRCA2. It doesn’t appear to be clear WHY many of these genes are bad, only that they are.  So what to think?

Well, Jim Watson (yes, that Jim Watson) said it best (I paraphrase):  “We all thought that determining which genes are responsible for diseases would yield a major therapeutic  pay off, but it hasn’t”.  (Watson is well known for “off-the-wall-isms”, AKA gaffes, but this isn’t one of them.)  He is right.

That there are two dozen genes that contribute to OVCA is interesting, but also discouraging.  To make use of this information it would be necessary to determine what each gene does, then devise a drug to interfere with or undo its malign effect.  This would cost unimaginable sums of money, might result in therapy involving several dozen drugs – and would be only marginally effective since most cases of OVCA are sporadic – that is, the result of bad luck rather than bad genes.  Better to concentrate in immunotherapy or personalized therapy. Put the money on the fastest horse.  You agree, I assume – Mr. Right Honorable VP Joe Biden Sir?  (You do read my blogs, right?)

Ladies - after you have had so many babies that you can't tolerate the thought of having any more - have your Fallopian tubes removed at the first opportunity.

Or so it seems to me.

http://www.medpagetoday.com/clinical-context/GynecologicCancers/58322

FUN FACTS about BIOLOGY

Joshua and the Joyce Family

From time to time I stumble upon captivating articles that have no direct relevance to the mission of this blog: to search out important developments in our war on ovarian cancer and pass what I learn on to you.  Usually I attempt to persuade myself that the article in question has enough bearing on OVCA to justify slipping it in somewhere as a “Comment”.  However, sometimes I simply sigh and,  hit the “Delete” button.

Well, I have  just encountered a little essay that I don’t want to delete, regardless of its irrelevance.  It is about genes, and it was written by the Director of the NIH.  So….I’m going to start a blog-bit I might call Fun Facts about Biology, to use as a repository for any intriguing-but-irrelevant bio tidbits I run across,  All of you many biological aficionados should remember to check back now and then.  I will alert you to new Fun Facts by sticking FFaB at the bottom of new entries.  Well, that sounds stupid, but you know what I mean.

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Here is an introduction to duplicated genes, pseudogenes, and evolution:

https://directorsblog.nih.gov/2016/05/31/gene-duplication-new-analysis-shows-how-extra-copies-split-the-work/

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Mukherjee to the rescue:

Seventy five readers so far have clicked on this link, expecting to pass some innocent time enjoying “Fun Facts about Biology”.  They were disappointed.  To partially rectify this error, I offer the following assortment on Fun Facts, all taken from pp. 322=326 of Siddhartha Mukherjee’s new book The Gene: An intimate history.

The gene is like a book written with only four letters: A,T,C,G.  Our genome contains over three billion of these letters, strung together without punctuation or explanatory cartoons.  Scientists have been known to go mad from prolonged reading of this book.

This tedious collection of letters encodes about 20,800 genes.  Worms have nearly as many – and both wheat and rice have more.  Gorillas and humans share about 96% of our genomes in common.  However, gorillas have 24 chromosomes whereas we have only 23.  As Mukherjee says, somewhere in evolutionary time we lost a chromosome, but gained a thumb.  He is clever.

The conspicuous difference between us on the one hand, and rice and wheat (“breakfast cereal”, says Mukherjee) on the other rests not in our genes, but in how we use them.  This leads to such deep and abstruse subjects as epigenetics and the true meaning  of “junk” DNA.  No one can twist such stuff into a Fun Fact.

There are 155 separate genes that control our sense of smell.  Dogs have smelling ability thousands of times better than humans.  Does that call for more genes?  Pretty surely not; they probably just use them better.  Given the state of my kitchen counters I am glad I am not a dog.

Lots more interesting stuff in Mukherjee’s book.  Read it sometime.

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  So, which is the scariest?

                Donald Trump as President
                Britain pulling out of the European Union

                Contagious cancer

Whatever: the NYTimes has argued against all three.  One has just happened, one is still undecided, and one – the scariest, really – turns out to possible.  Tasmanian Devils and dogs have been known to suffer from a type of transmissible cancer for years.  Now it turns out that our ocean waters are fairly aswim with free-floating cancer cells just waiting to infect all kinds of shell fish.  So far these cancers have not learned how to cross over to humans, but who knows?  I plan to eat as many clams, mussels and oysters as possible before they do.

http://www.nytimes.com/2016/06/28/science/contagious-cancer-clams.html?smprod=nytcore-ipad&smid=nytcore-ipad-share&_r=0

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I know you’re too wise to fall for this crap, but read this article to verify that, yes, we still need the FDA

http://www.latimes.com/science/sciencenow/la-sci-sn-unapproved-stem-cell-treatments-20160630-snap-story.html

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Here is a good one:

http://online.wsj.com/articles/sperm-can-carry-dads-stress-as-well-as-his-genes-1409938666

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Here is an interesting bio-article you should read.  It goes some way toward explaining how it is possible to determine how human races originated, migrated, and intermingled.  It also offers some hope for diagnosis and treatment of some diseases.  What you must know:

1)      The human genome consists of perhaps 3 billion “letters”.  To sequence the whole thing currently costs about $1000.

2)      Only a small fraction of the genome actually consists of genes, the blueprints for proteins.

3)      Of these genes, more than half of their “letters “code for “introns”, which must be cut out before the gene can be converted into something functional.  These introns separate “exons” which, after the introns are cut out must be stitched together and transported to a ribosome for protein synthesis.

But of course you knew all this already.  Anyway:

4)      It is much cheaper to sequence exons than whole genomes, because they amount to only ~1% of the 3 billion letters.  If a whole genome sequencing costs $1000, then an exon study should cost only about ten bucks.  Fat chance!

5)      How they do any of this is beyond my pay grade.

https://www.nih.gov/news-events/nih-research-matters/catalogue-human-genetic-diversity-expands

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What is a "knockout mouse?"  Why do they knock the little fellows out, and how so they do it?  What justifies this act od unrepentant cruelty?  Which genes are essential for life?  All that and more on 60 minutes - no, I mean by clicking on:

https://directorsblog.nih.gov/2016/09/20/of-mice-and-men-study-pinpoints-genes-essential-for-life/
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Tricking diseased cells into making their own poison:

https://directorsblog.nih.gov/2016/10/06/creative-minds-can-diseased-cells-help-to-make-their-own-drugs/

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More fun stuff about our micribiome and what it's good (and bad) for.  Did you know that we carry around about 2 pounds worth oj bacteria, fungi and other creepy-crawlers?

https://www.nih.gov/news-events/nih-research-matters/infant-gut-microbes-linked-allergy-asthma-risk
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Medical science stumbles forward, aided by monkeys

https://directorsblog.nih.gov/2016/11/01/mock-siv-treatment-post-for-updating-with-fcs-edit/

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You’ve heard of Intelligent Design?  Well, I find arguments in its favor unconvincing.  However, I am beginning to believe in a corollary:  Malevolent Design.  Evidence for MD consists of all the ways that cancer cells have evolved to protect themselves: to allow them  to go forth, be fruitful, and multiply in the face of everything the body’s defense system throws against them.  It always has been a mystery how cancer cells obtained the energy to do their dirty work.  Well, here – apparently – is one way.  Read the article: you will learn some important stuff.

https://www.cancer.gov/news-events/cancer-currents-blog/2016/cancer-metabolism-lactate?cid=eb_govdel

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Another very good reason not to horse around with the Zika virus

https://directorsblog.nih.gov/2016/11/08/could-zika-virus-have-lasting-impact-on-male-fertility/

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The hot bio=topics of 2018

https://directorsblog.nih.gov/2019/01/02/biomedical-research-highlighted-in-science-magazines-2018-breakthroughs/

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A MULTI-PURPOSE DRUG?

Playing with Cash

2010

Okay, so here is a drug to ponder upon, harass your doc about, and remember.  It is one of a class of pain killer drugs known as non-steroidal anti-inflammatory – NSAID in shortened med-speak.  The name of the stuff is Diclofenac, and it is prescribed for arthritic pain, post-op pain, migraines, etc.  Note prescribed; you can’t buy it over the counter.  There exists some evidence that it not only helps prevent cancer (as do asprin and other NSAIDs), but also is somewhat effective as therapy against existing cancer, especially the metastatic kind.  Ovarian is mentioned explicitly.  So, if your primary care physician is pen-in-hand over a prescription form, ask him/her about Diclofenac.

http://health.usnews.com/health-news/health-wellness/articles/2016-01-13/common-painkiller-fights-cancer

Not a panacea, for sure, but maybe it will help.