KILLER T-CELLS: works on mice, why not us?

Linda and her sister Carolyn, 1951

There is an Interesting article in the April 23^rd issue of The New Yorker, entitled “The T-Cell Army”.  It is part history and part reportage; the recent history of novel cancer treatments and what is going on right now.  It is mainly concerned with two directions in cancer therapy research: individually targeted therapies based on the cancer’s genome, and immunotherapy.  Emphasis is on the latter.

Like nearly everything I have learned in the past few months about how cells work, how DNA does its job, what causes cancer, etc., immunotherapy turns out to be vastly more complicated than it ought to be: full employment for herds of biochemists, but frustration for guys like me.  What I thought I knew about the immune system and cancer was that the immune system is programmed to distinguish between “Self” and “Non-Self” and attack only the latter.  As cancer is a piece of Self gone wild, the immune system stands by and watches as it destroys the body.  Well, yes and no.

As part of the immune response the body generates various kinds of cells: neutrophils, macrophages and T-cells (sometimes called Killer T-cells, a name I really like) and, probably lots more; remember that my biology reference books is “the Complete Idiots guide to College Biology”.    Neutrophils and macrophages attack a particle of Non-Self (a virus, for instance) by swallowing it whole and then digesting it at leisure.  Killer T-cells, by contrast, attack from the outside; all guns blazing – firing enzymes.  Unfortunately, T-cells need to be persuaded to attack tumor cells.  It appears that there is a protein (CTLA-4) attached to the surface of the T-cell that must  be neutralized with an antibody before the T-cell will attack a tumor.  Other proteins that need to be mollified or tricked also are mentioned; no doubt the case is more complicated than anyone thinks.  Nevertheless several therapies have been devised, largely by using our friend the mouse, that are proving effective against metastatic melanoma.  The side-effects described are horrible, however; another reason to stay out of tanning beds.

At any rate, the article gives one further reason to hope.  As with most New Yorker essays there are numerous little anecdotal interjections; these serve to lighten the biochemical gloom.  Mostly they are about patients and their (often quite favorable) outcomes.   I recommend that you buy the mag and read the article.  I find with The New Yorker in general that its chief attraction is its cartoons, and that many articles lead one to suspect that the authors are paid by the word.  Not so here.  But, as the stupid magazine will cost you $6.00, maybe go to the library.  

BRIBERY. And nothing about OC.

                                             1984, in the dead of an Illinois winter.
 We were on Sabbatical at Northwestern University. Yes, I was missing most of a tooth.  She loved me anyway.

Did you know that I can “track” the number of pages read on my blog? That is, I can tell how many times each entry has been looked at, although I can’t tell who did the looking.  These statistics tell me one very important fact – you are looking at my blog mainly to see pictures of my beautiful wife.  Oh, sure, you might read the accompanying text, but it’s mainly Linda you want to see.  I forgive you.  I feel the same myself.
 

The reason I know this is that the entry LINDA ON HER WEDDING DAY has three times as many “hits” as the next highest entries.  Also, the ones with no pictures are at the bottom of the list.  I will swallow my humiliation and push on.
 

So, I am going to bribe you.  It seems that you want to see pictures of Linda on her wedding day.  I have three more.  (Incidentally, I’m in them, too.)  I plan to use them on anniversaries.  However, to drum up enthusiasm I promise to post the best picture of all just as soon as my total of Followers reaches a respectable number - say, a dozen.  To become a Follower you first must get a Google account, which is free but can be a nuisance.  Thereafter, Carolyn tells me, it is simple. 

My faithful editor and research assistant Dick Ingwall has pointed me toward an interesting article in the New Yorker which I will be writing about in a few days.  I am headed back to Bellingham next week.

MEDICAL ECONOMICS

Linda and Viv Hailwood on a hard hike over Howgill Fell, Yorkshire Dales National Park.  Linda had a small stream named after her on that occasion ("Linda Beck", Beck being the local dialect for small stream.

The group I work with at the Hutch has as one of its principal interests the development of tests to permit early detection of ovarian cancer.  I have just run on a review article on the need for such tests for cancer in general.  In case you want to read it yourself, the citation (done like a geologist would do) is Etzione, R., et al, The case for early detection: Nature Reviews, v. 3, pp. (well, they don’t give the page numbers) April 2003.  It is well written, comprehensible for the most part, and blessedly short.  My only real complaint (more of a peevish quibble, really) is that it is hard to read on a computer.  For you Kindle experts it should be a piece of cake.

I have several things from this article to pass on.  By this time it should not be necessary for me to remind you that I am a geologist, not a biochemist, and may occasionally (or more often ?) get things wrong.  This is your last warning; don’t believe anything I say without serious thought, and don’t act on anything I say without consulting an expert.

The first thing, I can’t get wrong.  The authors present us with a graph showing the 5- and 10-year survival frequencies of victims of breast, colorectal, lung and prostate chance, contrasting these frequencies in people whose cancers were discovered when they were localized with frequencies after the cancer had spread.  As you might expect, the former had a much better result than the latter.  Consider breast cancer for example.  For women diagnosed in the period 1993-97, the five-year survival frequency was about 20% if the cancer had spread (was “distant”) but 95% if it hadn’t (was “local”).  For prostate cancer the benefit of early detection was even more pronounced.  Even lung cancer showed this trend, but the actual numbers were definitely pretty dismal.  My take-home from this is that what we (my group, at the Hutch) are doing is worth the time, effort and money – and then some.

Those same graphs showed how survival numbers increased in the interval  1972 to about 1997.  This must reflect improvements in treatment – drugs, radiation, surgery, voodoo, whatever.  There was noticeable, consistent improvement shown – but in terms of  years of life saved it couldn’t compare to the benefit of early detection. 

I have a few more things to say, but I am getting impatient with my typing problems and a gin and tonic is waiting.  I may post more on this article in a day or two.

A BOOK (well, small article) REPORT

On Santorini, 1983

The group I work with at the Hutch has as one of its principal interests the development of tests to permit early detection of ovarian cancer.  I have just run on a review article on the need for such tests for cancer in general.  In case you want to read it yourself, the citation (done like a geologist would do) is Etzione, R., et al, The case for early detection: Nature Reviews, v. 3, pp. (well, they don’t give the page numbers) April 2003.  It is well written, comprehensible for the most part, and blessedly short.  My only real complaint (more of a peevish quibble, really) is that it is hard to read on a computer.  For you Kindle experts it should be a piece of cake.
 

I have several things from this article to pass on.  By this time it should not be necessary for me to remind you that I am a geologist, not a biochemist, and may occasionally (or more often ?) get things wrong.  This is your last warning; don’t believe anything I say without serious thought, and don’t act on anything I say without consulting an expert.
 

The first thing, I can’t get wrong.  The authors present us with a graph showing the 5- and 10-year survival frequencies of victims of breast, colorectal, lung and prostate chance, contrasting these frequencies in people whose cancers were discovered when they were localized with frequencies after the cancer had spread.  As you might expect, the former had a much better result than the latter.  Consider breast cancer for example.  For women diagnosed in the period 1993-97, the five-year survival frequency was about 20% if the cancer had spread (was “distant”) but 95% if it hadn’t (was “local”).  For prostate cancer the benefit of early detection was even more pronounced.  Even lung cancer showed this trend, but the actual numbers were pretty dismal.  My take-home from this is that what we (my group, at the Hutch) are doing is worth the time, effort and money – and then some.

Those same graphs showed how survival numbers increased in the interval  1972 to about 1997.  This must reflect improvements in treatment – drugs, radiation, surgery, voodoo, whatever.  There was noticeable, consistent improvement shown – but in terms of  years of life saved it couldn’t compare to the benefit of early detection. 
 

I have a few more things to say, but I am getting impatient with my typing problems and a gin and tonic is waiting.  I may post more on this article in a day or two.

IF IT AIN'T BROKE, DON'T FIX IT

Sorry.  The new blog isn't doing its thing (attracting hoards of new readers) so in the interest of simplicity I'm going to exterminate it, transfer its postings to this blog, and carry on as before.  So, from now on  just Google Myrl'sBlog and you're in.  Again, sorry.  Myrl

A CHANGE OF NAME ONLY

                                                          Linda with Butch, about 1993

So, here we go.  In order to have my blog come up when people Google "ovarian cancer" I have, in a sense, changed its name.  Actually, what I did was open a new blog named "FIGHT BACK against OVARIAN CANCER", with Web address WWW.QUILTCUTIE.BLOGSPOT.COM.  If this works I will put my new "postings" there, so this will be the last one for this blog (assuming I remember.)  If this doesn't work I will just delete the new blog and come back to this one.  Wish me luck.  Myrl

GOOD THINGS COME IN TINY PACKAGES

                                                     Linda on our 1991 Alaska trip.

Owing to the  fact that I am famously  inept where computers are concerned, I was unable to read an article about nanoparticles in cancer research that was the feature story  in the latest NCI Cancer Bulletin.  However, owing to the fact that it is too hot outside to do anything healthy or fun I have spent the day messing with my trusty Toshiba, and I finally stumbled on the correct maneuver. I am glad that I did, for the article is interesting, readable, and relevant.  Go read it yourself.*

Nanoparticles are little globs of biochemical stuff that are used in various ways in modern medicine.  They are called “nano..” because they are less than 100 nanometers in diameter.  A nanometer is a unit of length equal to one billionth of a meter.   How they make nanoparticles I haven’t a clue, but they do.  And  they’re useful.    For instance, nanoparticles can be used to package chemo drugs and deliver them directly to a specific tumor, rather than (as in conventional chemotherapy) using the blood stream to suffuse the body with the drug in the hope that some of it gets to where it’s needed.  Apparently doing chemo using nanoparticles reduces side effects.   I may not entirely understand this, but it seems that one can festoon the exterior of the nanoparticles with a protein that will act as a “ligand” and bind to receptors on the surface of the tumor cells – and to nothing else.  Some prospective drugs are of proven efficacy against cancer but have such fearsome side-effects that they can’t be used.  It was suggested that these might be packaged in nanoparticles, delivered to the tumor, and do no harm otherwise.  Make it so.

I wish that more of you would go to the trouble of becoming “Followers”.  So far I have only two, which makes me feel like the drum major of the world’s smallest band.  If you don’t know how to become a Follower, neither do I.   Maybe Carolyn will post a “Comment” to this blog entry explaining how it’s done.

*I gave you the web address in an earlier post.

NCI PUBLICATIONS.

Most likely this was Linda's first backpack trip.  We over-nighted on Cougar Divide.  For purposes of location Linda is looking at Skyline Divide, with Mt. Baker to her left and Mt. Shuksan in the distance.  She wasn't an enthusiastic back-packer but she was game.  Probably about 1984.

Well, I was going to go outside and walk, hit golf balls, or maybe clip my bushes – but it has reached 102.7 degrees on my patio, with no signs of cooling off – so I decided to read about cancer instead.

Fiddling around with my trusty Toshiba and with the aid of Google I discovered the NCI (National Cancer Institute) Publications Locator.  If you google that and open the proper web site you will find an overwhelming richness of highly comprehensible articles on all sorts of cancer topics.  I just read the essay on BRCA1 & 2 mutations and the risk of breast/ovarian cancer.   You should all do likewise.  I won’t attempt a summary; read it yourself.

I am also reading “The Immortal Life of Henrietta Lacks “, of which some of you will have heard.  I am almost through with it, and when I am I will write a blurb.  At present, my own personal jury is out, so to speak.  One thing’s for sure; light-hearted entertainment it ain’t.

You all know that I am a Research Advocate, advocating as best I can for more (and better?) cancer research.   Partially, I guess, that means urging everyone to hold the feet of any politician threatening to de-fund NIH, NCI, or similar agencies to a very hot fire.  The government spends too much of our money, and spends some of it unwisely – but cancer research should be the last thing cut.  That takes care of the “more” part of the first sentence.  My gut feeling is that we need to work on the “better” part, too, although I’m not sure what that would entail.  Check back later.

Oh, good, it’s down to 102.4.

IT'S TOO HOT TO HIKE!

Linda at 20, attending Western Michigan University.  I was lucky some college boy didn't snatch her up!

You really ought to read the NCI Cancer Bulletin (www.cancer.gov/ncicancerbulletin).  I know – nobody wants to think about cancer any more than they have to.  Hell, I spent most of a lifetime trying NOT to think about cancer.  Let’s face it; cancer scared the heck out of me.  It still does.  But, since Linda got sick I think about it all the time.  I hate cancer and I want to wipe it from the face of the earth.  Be that as it may, from time to time there is good stuff in the NCI Bulletin: some encouraging, a little discouraging (and, unfortunately, some downright incomprehensible.)  For instance, in the current issue there is a report of a study of ways to deny solid tumors their needed blood supply.  Apparently this kind of tumor sends out a chemical signal causing blood vessels to form, thereby supplying the interior of the beast with blood.  By blocking those chemical signals one can starve the inside to death, while killing the outside with chemo.  It sounds promising.      

Another article in the NCICB concerns over-diagnosis of breast cancer (in a Norwegian study).  The conclusion of the study was that as many as 25% of women who tested positive (mammography) actually had little, benign things that never would have caused them harm.  Thus, one is supposed to conclude, Norway’s mammogram program caused a lot of unnecessary anxiety, medical activity, and expense.  This is somewhat reminiscent of the prostate cancer arguments I blogged about earlier.  My take??  For every “false positive” there were three women whose lives may have been saved.  Until the people in white coats come up with something cheaper and more accurate, keep getting those exams.

Then there is an “interview” with Dr. Lowell Schnipper (a surgeon?) of Harvard, who is Chair of a Cost of Cancer Care Task Force.  Their report concludes that many tests are performed that are not necessary, or even logical.  The article gives a list – I will let you read them for yourself.  Dr. Schnipper expends considerable effort trying to convince us that it is not COST that is driving these suggestions, but mainly consideration of optimal patient care.  No doubt that is true – but I can’t help but think of the huge pack of tort lawyers circling like wolves just outside the fire-light, waiting for a physician to screw up.  If medical folks didn’t do “c.y.a” procedures at times they’d be more than human.

And, finally, there was an interesting article about a new technique to study brain tumors without doing surgery.  It wasn’t clear to me why they wanted the information.  The technique sounded very expensive.  Maybe I should read it again.

It is over 90 on my patio (in Borrego Springs, CA) right now.  I may be back in Bellingham sooner than planned.   

Wastin away in Melanoma-ville.....

                                          Thanksgiving, 1981.  See, I was, too, taller than her.

.....searchin  for my lost bottle of sunblock.  Not as catchy as the original lyrics, maybe, but more relevant to my current lifestyle.  For one thing, I’m mostly drinking vodka and grapefruit juice.  For another, the sun here, in the desert, in mid-April, is such as to peal the skin off your unprotected body part, so I’m indoors most of the day.  Yeah, sure – I’m a PNW weather wimp.  It hit 96 on my patio a few hours ago; in partial shade.  I may be home earlier than expected.

You all know that melanoma is deadly, that you are at greater risk of getting it if you have a fair complexion, and that all that sun-tanning you did as a youth was stupid.   All you can do now is use sun block, wear long-sleeved shirts, and scrutinize your moles.  In my case – I’ve had two friends die of melanoma – I agonize over every black spot I detect, no matter how tiny.  To my shame I went to my doctor recently with a tiny, circular black spot.  He sighed, and removed a blackhead.   I get professionally evaluated (dermatologist) once/year.  She freezes (or cuts) off the other, less deadly kinds of skin cancers, and then reassures me that all is well otherwise.  I recommend this practice to everybody.  It gives you blessed peace of mind - until the next time you see a dark-colored mole.

 I recently saw a list of symptoms that should send you running to your doctor.  Here they are

A mole, sore, lump, or growth on the skin can be a sign of melanoma or other skin cancer. A sore or growth that bleeds, or changes in skin coloring may also be a sign of skin cancer.

The ABCDE system can help you remember possible symptoms of melanoma:

• Asymmetry: One half of the abnormal area is different from the other half.
• Borders: The edges of the growth are irregular.
• Color: Color changes from one area to another, with shades of tan, brown, or black, and sometimes white, red, or blue. A mixture of colors may appear within one sore.
• Diameter: The spot is usually (but not always) larger than 6 mm in diameter -- about the size of a pencil eraser.
• Evolution: The mole keeps changing appearance.

Note that blackheads don’t qualify.

P.S.  As I am supposed to be a Research Advocate, I decided that I was honor bound to do some research on the subject of sunshine, sunblock, and melanoma.   Literature, research, naturally.  I almost wish I hadn’t, because what I found was confusing, contradictory, and discouraging.  Much of the following comes from scanning articles found using Google Scholar*.  Try clicking on the following link and get involved yourself:

http://scholar.google.com/scholar?start=10&q=melanoma+research+articles&hl=en&as_sdt=0,5&as_vis=1

Always remembering the severely limited understanding I bring to anything bio-medical, my take-away from several hours of reading is more-or-less as follows:

a)      Very many groups are working on the genetics of melanoma, which appears to be complicated.

b)      Ditto, drugs to retard the spread of metastatic melanoma.

c)       Exposure to sunlight increases the likelihood of contracting melanoma, at least in Caucasians.

d)      Slobbering sunscreen on your exposed body parts does not prevent melanoma and – for God’s sake!  - may even increase it.

e)      Some families have a genetic predisposition to melanoma.

f)       So, in general, cover up, watch your warts, and keep company with a good dermatologist. 

*My knowledge of Google Scholar is owing a tip from my faithful editor, Dick Ingwall

THE GENOME AND CANCER

                                                          The Wyoming death march

Of all the stupid whims I ever inflicted on Linda, this might be the worst.  We were camping in Wyoming and I noticed (on my TOPOGRAPHIC MAP!) that there was a lake about 3 miles away, so I suggested that we take a little hike and see it.  I guess I forgot to notice that it was also 3000 ft. below our campground, hence going there - and coming back - would entail a mighty climb.  This picture shows her at the top of the climb, no doubt trying to convince herself that I meant well and she could put up with me for a few more years!  To make the fiasco even  worse, we were followed up the traill by some bozo with a pistol, who kept taking pot-shots at anything that moved.  Linda hated guns.  We turned the bozo in - I hope they threw the book at him.  Anyway...

There is a very interesting article in the current NCI Cancer Bulletin  which I will summarize for you, although you would be better served by reading it yourself: (http://www.cancer.gov/ncicancerbulletin,) and read the “Conversation” with Dr. Bert Vogelstein of Johns Hopkins University about his Whole Genome Sequencing project.  Vogelstein and co-authors used data from the Swedish Twin Registry (who would have guessed there was such a thing?) to predict what value whole genome sequencing will have – in the future – in mitigating the effects of cancer and other disease.  My take-away message from this work is that we should double and then redouble our efforts to detect cancer early, and to identify and insofar as is possible eliminate  environmental  factors that contribute to its cause.   First, genome studies are expensive:  ~$5000 now, but perhaps ~$1000 in a few years.  Second, most cancers are not caused by heredity, so getting a clean bill of health on a genome study might lead to a false sense of security.  And, finally, many (most?) people with suspicious heredity still will not contract cancer; why condemn the poor sods to a lifetime of worry? 

There are many references in this article to ovarian cancer.  Did you know that obesity is an adverse “environmental factor” for OC?  I certainly didn’t.

WITH LUCK, HERE ARE THE LINKS

http://www.nytimes.com/2012/03/21/health/research/studies-link-aspirin-daily-use-to-reduced-cancer-risk.html?_r=1&scp=2&sq=aspirin%20cancer&st=cse#

AND

http://well.blogs.nytimes.com/2012/03/26/how-much-aspirin-is-too-much-of-a-good-thing/?scp=1&sq=aspirin%20cancer&st=csehttp://well.blogs.nytimes.com/2012/03/26/how-much-aspirin-is-too-much-of-a-good-thing/?scp=1&sq=aspirin%20cancer&st=cse

ASPIRIN TO THE RESCUE?

                                         
                                               Linda at her Mom's apartment in Kalamazoo, 1999.

Remember you read it here first!  A massive study ("tens of thousands of men and women") conducted in Britain and reported by researchers based at Oxford University seems to show that aspirin, at least in large doses swallowed every day,is effective against many types of cancer - in fact, incredibly effective in some cases.  After five years an overall reduction of 37% in cancer-related deaths was observed.  So let's all raid the drugstores and start dosing ourselves, right?  No, maybe not.  There is ample evidence to incriminate aspirin (in large doses?) in increases in gastrointestinal bleeding and even something as nasty as hemorrhagic stroke.  Better talk to your doctor first.  (Of course, you knew that anyway.)

This study seems to controvert a similar study done in America that showed no effect of aspirin on cancer rates.  However, the American study involved smaller doses taken only every second day.  So maybe it's the dosage that counts.  Stay tuned - this is a big deal and will be all over the news media.

I got most of this information from two articles published in the NY Times, and if I weren't so technologically incompetent I would give you the links.  I will continue to try.