REMISSION, RELAPSE

Happy

Far too many ovarian cancer histories go like this.  First, the cancer is diagnosed, often by accident (OVCA symptoms are notoriously subtle), and found to be in an advanced state (Linda was stage 3C, indicating that the original tumor had spread throughout her abdomen.)  The first therapeutic step involves so-called “debulking surgery” – all visible traces of the cancer are cut out.  Next comes “adjuvant chemotherapy”, involving a cocktail of drugs that, hopefully, will kill any remaining cancer cells.  Workhorses among these drugs often are platinum-based.  Normally this puts the patient into “remission” – that is, no trace of the disease can be detected.  (Remission often is monitored by periodic determination of the level of the protein CA 125 in the blood.  “Normal”, which varies considerably, ranges from 0 to 30 or so; Linda was at 650 when diagnosed and at 6 after treatment.)

In remission the patient can live a normal life.   Her hair grows back, she regains strength and mobility, she can be happy.  However, after a few months or years in all too many cases remission is gradually lost.  In Linda’s case her CA 125 count remained at 6 for about two years.  Then, one month it rose to 8.  No problem, right?  The next month it was 15.  The cancer was coming back.

Apparently the cisplatin-based drug cocktail was effective initially, but had left behind a few cancer cells that were “immune”, rendering it futile to repeat the original chemotherapy.  In Linda’s case another selection of drugs was tried, resulting in only a short, partial remission.

Well, researchers at the University of Michigan may have discovered a way to deal with this apparent immunity.  They found that fibroblasts (a type of cell involved in connective tissue) located in the tumor’s microenvironment acted to prevent buildup of platinum in the cell.  They also found that immune T cells could pry open the fibroblast barrier, thereby allowing the platinum poison in to kill the cell.  (Mice, again, of course.)  My reading of this is two-fold.  Maybe administering T cell based immunotherapy along with standard platinum-based chemo would wipe the cancer out in one fell swoop.  Barring that, maybe T-cells would make it possible to use the same drugs after an initial remission, thereby prolonging remission indefinitely.  More I cannot say; there are important parts of these two articles that I don’t understand.

And here is something else I don’t understand: how in heck are we supposed to understand “relapse”?  I have written about “cancer stem cells”; are there such, and how do they operate?  Also I keep reading about the accelerated rate of mutation in cancers, presumably making it difficult to eradicate the beast completely before it changes.  Now I read that an army of misguided fibroblasts promote relapse by combating cisplatin.  Are all of these things true?  If so, God help us.

http://www.genengnews.com/gen-news-highlights/t-cells-help-reverse-ovarian-cancer-drug-resistance/81252753/

http://www.siasat.com/news/reversing-chemo-resistance-ovarian-cancer-immune-cells-961322/

May 22, 2016

In our hearts forever

Today is the fifth anniversary of Linda’s death.  I don’t feel up to writing something new, so I will modify and re-post a blog from three years ago.

On this fifth anniversary of Linda’s death I can do no better than to repeat what I wrote on May22, 2011.

My beloved companion of 30+ years left today at 4:20 pm.  She had struggled bravely for days, but in the end her going was peaceful and, in its way, almost beautiful,  If there is a heaven she is surely there, with the mother she hasn’t seen for five years and the father she has missed for over fifty years.  There will be a celebration of life but I don’t know when*; you will all be informed.  Hospice House is a wonderful institution.  Your friendship is a great blessing.  Life can be painful, but I guess it’s worth the effort.
*****************************************************************************

As for me now, the pain is still here, but I have learned to deal with it.  And I continue to work to the best of my poor ability to hasten, if by only a few hours, that wonderful day when no woman ever again has to suffer what Linda suffered, and no man will be forced to stand by, helpless, and experience the agony of watching his beloved wife die of ovarian cancer, and be powerless to intervene.

If you would like to make a donation to ovarian cancer research, please do it through Linda’s tribute page:

http://engage.fredhutch.org/site/TR/PersonalFundraisingPages/General?px=1148821&pg=personal&fr_id=1573

*It was held on July 24^th, 2011.  About 65 people attended - a small fraction of those who loved her.

DULL BUT IMPORTANT

Heron Island, Maine

HERE are some useful facts:

                Amino acids are organic molecules.  There are 20 of them.  They have names like tyrosine and glutamine.  They all contain a carboxyl group (CO₂^-) and a methyl group (NH₂₎).  They differ in what are called “side chains”.

                Proteins are long strings of amino acids.  The sequence of amino acids in a protein determines its shape, which in turn determines its function.

                The amino acids in a protein are held together by something called a peptide bond.  In chemistry, “bonds” stick things together. How it occurs in this particular instance is of no earthly interest to us.

                Because proteins are strings of amino acids held together by peptide bonds, sometimes they are called polypeptides

Polypeptides may have hundreds or thousands of peptide bonds; the ones we are going to discuss have five.

Now, wasn’t that fascinating?

Having written the above, I took the trouble to actually READ the article, and guess what?  I needn’t have bothered.  Here, see for yourself:  http://medicalxpress.com/news/2016-03-small-peptides-ovarian-cancer-fronts.html

Here is the gist.  Scientists from Boston, Norway and Cornell have developed a new prospective weapon against ovarian cancer.  Back in 2009 they determined that a protein called prosaposin was effective in blocking angiogenesis (formation of blood vessels) and inflammation in the “microenvironment” of solid tumors.  From this stuff (prosaposin) they extracted a five-amino acid chunk  they call a psaptide.  .  Then they modified this little devil in two different ways, both of which make it more potent. This psaptide works by “stimulating” some substance called thrombospondin-1 (TSP-1), which does the actual work; kill cancer cells

I love these medical words: they drive Spellcheck crazy.

Anyway, many mice have died and the stuff looks promising.  Make it so!

OPTIMISM?

Oregon Coast, 2007

Now here’s an optimistic take on cancer.  At least for most of you; for me it’s irrelevant:

http://www.fool.com/investing/general/2016/03/13/could-cancer-deaths-really-be-eliminated-for-peopl.aspx.

Warning:  The origin of this article is Motley Fool, a stock market pub.  Its purpose is to alert you to potential profits in Pharma stocks.  So, if you don’t have money smoldering in your pocket, only read the first page.

The gist of the article is as follows:  Two optimistic Brit onco-scientists predict that cancer will be eliminated in people under 80 – by the year 2050.  As I already am over 80, and would be 117 years old in 2050, they are not talking to me.  But my kids, grandkids and great grandkids will be here then, so I hope they (the onco-docs) are right.  Here are the reasons for their optimism: 

1)      Reduction in smoking rates.

2)      Personalized medicine, based on genetics.

3)      Earlier diagnosis.

4)      Better drugs.

5)      Healthier lifestyles: less obesity, more exercise, less booze, lots of red wine.  (No – I made that last bit up.)

As to #4 – they will tell you what to buy to get in on the bonanza.

In passing, Dr. Vince DeVita – author of The Death of Cancer  (http://ljb-quiltcutie.blogspot.com/2016/03/warts-and-all.html) probably would agree with this assessment – although not necessarily with the stock tips.

I AM CONFUSED

Maine clam bake

Okay, this is getting ridiculous.  I used to think that all it took to start a cancer is a mutation in a single important gene.  Take the “tumor suppressor” gene TP53, for instance, TP53 codes for the protein p53, the so-called “angel of death”.  P53 tells defective cells when to die.  Absent a functional TP53 gene, a cell will just go on dividing without limit – turn cancerous.  Or so I thought,

Well, it turns out otherwise.   Some people at UW and Fred Hutch have developed a super-fast, super-accurate method of sequencing DNA, and have found loads of mutated cancer-relevant genes in perfectly healthy people.  People with cancer have more, but it appears that we all have some.  So, I don’t get it; what caused Linda to get cancer, but not me?  The article refers to something called the burden of potentially cancerous mutations, but doesn’t explain it.  Maybe if I went to medical school…….

http://medicalxpress.com/news/2016-05-prevalent-cancer-associated-mutations-apparently-healthy.html