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DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: derekb.lowe@gmail.com Twitter: Dereklowe

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December 7, 2005

The Hard News on Cancer

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Posted by Derek

I can recommend this grim but well done article from last weekend's New York Times magazine. It's on the death from cancer of the author and critic Susan Sontag, written by her son.

He spent a lot of time with physicians and researchers during her last illness, and it wasn't time wasted. The article is a very good summary of the current state of the art in cancer research, and doesn't try to paper over the disagreements abpit how far along we are:

". . .advances in cancer treatment and, indeed, in the fundamental understanding of how cancer works have come far more slowly than many people expected. Periodically since 1971, when President Nixon declared his war on cancer, the sense that the corner is about to be turned takes hold. We appear to be in such a moment today. The National Cancer Institute has recently put forward ambitious benchmarks for progress in cancer research and treatment. As its director, Dr. Andrew von Eschenbach, a respected surgeon and a cancer survivor himself (he is also acting head of the Food and Drug Administration), put it recently: "The caterpillar is about to turn into a butterfly. I have never known more enthusiasm among cancer researchers. It's a pivotal moment." The suffering of cancer, he argued, will be well on its way to being alleviated by 2015.

The media have mostly echoed this optimism. It is not unusual to read about the latest "breakthrough" in cancer treatment, both in terms of understanding the basic biological processes involved and with regard to innovative new drug therapies. . . "

Exactly so, and that's one of the things that worries me. I know that it's in the interest of academic and industrial researchers to say that they're making great progress, but let's face it: great progress isn't being made all the time, everywhere, by everyone. You wouldn't know it to look at the press releases, though. It upsets me to see the words "cure" and "breakthrough" thrown around by both scientists and journalists who should really know better. It's understandable that such words should come to be devalued eventually, but we don't have to help devalue them as quickly as possible, do we?

David Sontag quotes Harold Varmus at Sloan-Kettering with some reasonably optimistic statements, but then says:

"Other research scientists seemed far more pessimistic when I spoke with them. Dr. Lee Hartwell, also a Nobel laureate, is president and director of the Hutchinson Center. He has urged that the focus in cancer treatment shift from drug development to the new disciplines of genomics and, above all, proteomics, the study of human proteins. Though he acknowledged the profound advances in knowledge made over the past two decades, Hartwell emphasized a different question: "How well are we applying our knowledge to the problem? The therapy side of things has been a pretty weak story. There have been advances: we cure most childhood leukemias with chemotherapy, for one thing. But the progress has been surprisingly weak given the huge expenditures that we've made. We're spending over $25 billion a year improving cancer outcomes, if you include the spending of the pharmaceutical companies. So you've got to ask yourself whether this is the right approach."

. . .Some researchers are even more skeptical. Mark Greene, the John Eckman professor of medical science at the University of Pennsylvania and the scientist whose lab did much of the fundamental work on Herceptin, the first important new type of drug specifically designed to target the proteins in the genes that cause cells to become malignant, agrees with Hartwell. The best way to deal with cancer, he told me, is to "treat early, because basic understanding of advanced cancer is almost nonexistent, and people with advanced cancer do little better now than they did 20 years ago."

I come down more on this side of things, myself. When we talk about the progress that we've made against cancer, we're almost always talking about the amount of knowledge we've accumulated. Measuring progress by how well we keep people from dying of the disease is more sobering, because the rate of exchange between those two currencies is rather poor. And we should keep in mind that much of the improvement in those numbers is due to early detection, often coupled with surgery. We need to do better.

Comments (27) + TrackBacks (0) | Category: Cancer


COMMENTS

1. pipet on December 8, 2005 12:47 AM writes...

so there isn't any progress..but what about Anders work http://www.lub.lu.se/cgi-bin/show_diss.pl/med_352.html? have you heard anything more about this or has it hit a deadend? it seems hard to believe that a protein thats in mothers milk would be toxic.

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2. Cancer Chemist on December 8, 2005 8:11 AM writes...

Having been in the cancer business for 15+ years, I wish I could say a "cure" is just around the corner. However, I am not that optimistic. I think I can say that there will be new TREATMENTS in the coming years. Some of them will be less toxic than standard chemo and others will not. Another thing to keep in mind is that death is not necessarily caused by the primary tumor, but by the metastases that migrate to key organs like the liver & brain. IMO, new, better detection methods for early, small cancers followed by surgery and/or chemo (old or new) will do more to help cancer patients.

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3. jkm on December 8, 2005 10:30 AM writes...

Cancer Chemist brings to mind another pertinent point. Many cancer patients die from side effects of the treatment rather than the cancer itself, and I would be curious to know how those statistics break out and what research is being conducted on ways to improve such devastating problems as infection, respiratory distress, etc.

It has been my experience in dealing with two parents with cancer that there exist vast differences in protocol related to managing treatment effects. Those that proactively fight problems fare much better than those that react to them, yet reaction to side effects seems to be more common. Even in such world-renowned research and educational facilities as MD Anderson, while patients greatly benefit from the wisdom, experience, and trials of specialized physicians, if a patient becomes hospitalized due to side effects of treatment (for infection, for example), current therapies often fail.

As more and more patients are living longer with cancer, I can't help but wonder how much more that statistic can improve if we can develop not only less-toxic treatments, but also better treatments and/or protocols for the side effects (until a cure comes along, of course).

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4. JSinger on December 8, 2005 11:40 AM writes...

so there isn't any progress..but what about Anders work...?

I don't know anything about that specifically, but compounds that kill cancer cells in a dish are a dime a dozen. There's a huge gap between that and a real therapy, which is precisely the point Derek was initially making.

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5. dave s on December 8, 2005 11:54 AM writes...

My wife was cured of breast cancer last year by, yes, early detection and surgery. I don't know as anything happened for her which couldn't have happened for a breast cancer patient fifteen years ago (except for the postsurgery course of tamoxifen) but she and I and the kids are thrilled to have her around for the next thirty years, and she is nagging all her buddies to have their regular mammograms.

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6. ANDY LOZANO on December 8, 2005 2:04 PM writes...

I'M PRETTY MUCH A LEY PERSON ,WHEN IT COMES TO
CANCER . ALTHOUGHT I HAVE HAD MY SHARE OF IT .
MY MOTHER DIED OF MULTIBLE MYELOMA AND MY AUNT DIED OF WELL WHAT THEY SAY WAS OVARIAN CANCER
I BEG TO DIFFER . SHE RAELLY DIED FROM THE AFTER EFFECTS OF THE RADIATION SHE WAS GIVEN.THEY GAVE HER ENOUGH FOR AN ELEPHANT.SINCE THAT POINT IN MY LIFE I HAVE BEEN LOOKING AT OTHER ALTERNITIVES IN CASE SOMTHING WERE TO HAPPEN TO ME OR MY FAMILY.
ANTIOXIDENTS ARE ANSWER FOR A CURE. IF CANCER
CAN'T LIVE IN THAT ENVIROMENT THEN USE COMMON
SENSE . LETS BE SURE WHAT I AM SAYING NOW.
DOING THIS FOR LOCALIZED CANCERS SHOULD BE FIARLY EASY . STARVE THE TUMER OR TUMERS OF OXYGEN
THEN REMOVE THEM EASY QUESTION ANSWERED
# 2 FOR CANCERS THAT HAVE SPREAD THREW OUT THE BODY TO DIFFERENT ORGANS , IT'S GOING TO BE A LITTLE MORE CHANLENGING . THE ANSWER WOULD BE
TO COMPLETLY INCUBATE THE BODY TO THE POINT OF DEATH .THEN BY USING LIFE SUSTIANING MACHINES KEEP THE ORGANS THAT NEED TO BE SUSTIANED ALIVE
WITH THE MACHINES . THOSE ORGANS WERE THE CANCER HAS SPREAD NEED TO BE BOMBARDED WITH ANTIOXIDENTS AND OR STARVED OF OXYGEN JUST LONG ENOUGH TO KILL THE CANCER . THEN THEY WILL REMOVE WHAT EVER VISIBLE SIGNS ARE LEFT.THEN THAT ORGAN WILL THEN BE PUT ONTO A LIFE SUSTIANING MACHINES AS WELL.
EACH CANCEROUSE ORGAN MUST HAVE THIS DONE BEFORE THE PATIENT IS ALLOWED TO COME OUT FROM BEING COMATOST.SOMETHING SIMULIAR TO THIS WOULD WORK.THE COST FOR THUSANDS OF OPERATIONS LIKE
THIS. WOULD BE COMPARABLE TO THE 25 BILLION IN RESEARCH YEAR. IF I EVER GET CANCER THIS IS WHAT I WOULD LIKE DONE TO ME. IN MY OPINION 90% OF PROBLEMS ARE SOLVED BY COMMON SENSE THINKING
WHICH NO MANY SMART POEPLE HAVE . THERE ARE PEOPLE THAT WORK FOR THE GOVENMENT .THAT ARE THERE JUST TO THINK . SERIOUSE THEY PUT THEM IN WHAT THEY CALL THINK TANKS VERY,VERY SMART POEPLE
BUT THEY CAN'T TIE THERE OWN SHOE'S

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7. Timothy on December 8, 2005 2:19 PM writes...

A vitamin pusher whose capslock got stuck, is there anything worse?

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8. Anonymous on December 8, 2005 2:19 PM writes...

"THE ANSWER WOULD BE TO COMPLETLY INCUBATE THE BODY TO THE POINT OF DEATH .THEN BY USING LIFE SUSTIANING MACHINES KEEP THE ORGANS THAT NEED TO BE SUSTIANED ALIVE WITH THE MACHINES..."

Wow, so simple, it just might work. But I wonder why they've never tried this before...

"IF I EVER GET CANCER THIS IS WHAT I WOULD LIKE DONE TO ME."

Excellent! I think you definitely should.

IN MY OPINION 90% OF PROBLEMS ARE SOLVED BY COMMON SENSE THINKING
WHICH NO MANY SMART POEPLE HAVE . THERE ARE PEOPLE THAT WORK FOR THE GOVENMENT .THAT ARE THERE JUST TO THINK . SERIOUSE THEY PUT THEM IN WHAT THEY CALL THINK TANKS VERY,VERY SMART POEPLE
BUT THEY CAN'T TIE THERE OWN SHOE'S

Are you in a think tank?
How did you arrive at this web site??

Permalink to Comment

9. Katherine on December 8, 2005 3:01 PM writes...

That's a great mental picture... everyone at Brookings walking around with their shoes untied.

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10. ANDY on December 8, 2005 3:02 PM writes...

Are you in a think tank?

TO ANSWER YOUR QUESTION , IS YOUR NOT VERY FUNNY.

THAT'S JUST MY OPINION, BUT I GUESS YOU WILL TAKE IT TO HEART AND REPLY WITH SOME WISE REMARK.I GUESS YOUR ONE OF THOSE PEOPLE WHO THINKS HE KNOWS IT ALL!
DO YOU HAVE A BETTER OPINION ON WHAT SHOULD BE TRIED TO CURE CANCER , MAYBE YOU'VE BEEN HIDDING IT FOR SIXTY YEARS.

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11. LNT on December 8, 2005 3:12 PM writes...

Here's a question: Everyone must die from something. As we (pharmaceutical companies/doctors) are able to "cure" (or treat) more an more diseases, people are living longer and longer. Of course, age is a key factor in cancer risk. Thus, adjusted for age, we may be effectively reducing the rate of cancer deaths. But due to the increasing age of the population, the overall death rate from cancer has remained the same. Does anyone know if my "theory" is correct?

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12. Paul on December 8, 2005 3:35 PM writes...

Take your caps lock off, you're SHOUTING AT US & it HURTS OUR EYES.

The point I wish to make is that antioxidants are to prevent oxidation, not remove oxygen. Oxidative reactions are potentially harmful, & may cause a cascade of tissue-damaging free radical reactions (as I understand it). Simply starving the tissue of oxygen is something different & would be detrimental to the tissue before the tumour, I suspect.

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13. RKN on December 8, 2005 4:22 PM writes...

Andy,

Google: spontaneous remission, and then click "I'm Feeling Lucky"

You'd have to be.

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14. pipet on December 8, 2005 7:04 PM writes...

I don't know anything about that specifically, but compounds that kill cancer cells in a dish are a dime a dozen. There's a huge gap between that and a real therapy, which is precisely the point Derek was initially making.


well I know that alcohol could probably kill a cancer cell - so what? the key here is that the protein extracted from milk is able to cause apoptosis in cancer cells and only in cancer cells from what I recall. and it isn't obvious to me why such a protein that is already prevalent in mother's milk would have any toxicity problems. the only things that I can think of that might make it unpalatable as a treatment are that it's a protein which maybe the only way you can get it into the body is via injection.

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15. ANDY on December 8, 2005 7:25 PM writes...


Does anyone know if my "theory" is correct?

MY PERSONEL OPINION PROBERBLY WOULDN'T MATTER
TO CERTIAN PEOPLE . SOME OF THE MEDICINES THAT WE ALL HAVE TO TAKE ONCE IN WHILE ARE FANTASTIC
FOR FIGHTING OFF SMALL DESEASES , BUT WE ALL KNOW ONE THING . THIS WORLD WASN'T BUILT BY PEOPLE WHO WERE SO OPTIMISTIC AND WENT WITH WHAT THEY LEARNED FROM A BOOK . ALL I'M SAYING IS THAT THE MEDICAL AND PHARMACEUTICAL COMPANIES HAVE A LOT OF CATCHING UP TO DO ,IF THEY WANT TO MIANTIAN THE DIGNITY THAT OTHER INDUSTRIES HAVE ENJOYED YEARS. MUST ALL OTHER INDUSTRIES ARE COMPLIMENTED ON THERE PROGRESS , BY NOT JUST THERE COALEGES AND COMPETITORS BUT MOSTLY FROM THE GERNERAL PUBLIC.
HOW ABOUT THOSE PEOPLE IN CAL THAT WENT TO SPACE WITH THAT EXPERIMENTAL PLANE .WHAT A LEAP TOWARD THE FUTURE AND WHAT A MONEY SAVER.THESE GUYS AREN'T JUST NUMBERS ANYMORE . GUYS LIKE THAT IS WHY WE ALL HAVE THE THE AMENITIES WE HAVE AND ENJOY EVERY DAY. GUYS LIKE THAT SHOULD BE PRIASED AND APPLUADED UPON. THEY SHOULD HAVE A RISK TAKERS HALL OF FAME .NOT A PLACE JUST TO KEEP THEIR INVENTION WE THIER DEAD , BUT A PLACE SO THAT PEOPLE CAN KNOW THE REAL RISK THAT WAS INVOLVED IN AN EXPERIMENT LIKE THAT WHAT ABOUT SOME OF THESE HYBIRD CARS THAT ARE ON THE MARKET NOW.EVERY ONES LIKE THATS , ITS A GOOD CAR. THE ONLY REASON IT'S ON THE MARKET IS BECAUSE IT RUNS PARTIALLY ON FUEL ( GAS ).SOMEONE EVEN INVENTED A CAR THAT RAN ON WATER.NO ONE WORIES WHAT HAPPENED TO THAT INVENTION . YOU DON'T HEAR PEOPLE SAYING THOSE DAM CAR MANUFACTURERS BLA BLA BLA.BECAUSE ITS NOT GOING TO ( KILL ) ANYONE TO PAY A LITTLE MORE FOR GAS. I DON'T WANT YOU TO COP AN ATTITUDE OR ANYTHING , BUT THE APLLAUSE THE PHARMACEUTICAL AND MEDICAL DOCTORS GET IS MOSTLY FROM IN HOUSE SUCH AS FROM COLLEAGES , YOU KNOW FROM PEOPLE IN THIER OWN INDUSTRY . HAVING SAID A FEW WORDS.
IF YOU HAVE A BETTER IDEA FOR A CANCER CURE YOU SHOULD STEP UP TO THE PLATE AN MAYBE YOU'LL BE IN THAT HALL OF FAME SOMEDAY, BUT DON'T BE A HEPACRIT

Permalink to Comment

16. Derek Lowe on December 8, 2005 8:52 PM writes...

Andy, I can assure you that all kinds of people are trying out all kinds of ideas for cancer treatments. Some pretty wild stuff is being looked at, because the disease can be so terrible (and the treatment options can be so few). And of course, any company that comes up with an effective treatment will also make a lot of money, which hasn't escaped our attention, either.

The run-on-water car is unfortunately a myth. Water can't be burned as a fuel - chemically, it's already burned.
As for your idea, many tumors are already deprived of oxygen in the middle parts of their tissue, and manage to survive. They're pretty tough. If you tried to kill cancer cells by depriving a tissue of oxygen, the cancer cells would probably be the last ones to die, which is the opposite of what you want.

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17. ANDY on December 9, 2005 12:11 AM writes...

THANK YOU FOR YOUR REPLY . THE POINT REALLY IS TO MAKE CURES FOR CANCER AND OTHER DESEASES A REALITY, IF SOMEONE DOESN'T COME OUT SOON WITH A CURE FOR AT LEAST ONE LETHAL DESEASE . THINGS IN THIS WORLD COULD BOIL OVER AND BECOME 10 FOLD OR MORE. IF THIS HAPPENS IT'S NOT GOING MATTER HOW GOOD PEOPLE TAKE CARE OF THEM SELVES . WHAT WILL THEY DO IF SOMETHING HAPPENS LIKE THIS. FIND AN ISLAND AND STICK EVERYONE THATS SICK THERE,LIKE THEY DID WITH LEPARDSEY.

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18. The Novice Chemist on December 9, 2005 1:10 AM writes...

This guy HAS to be a parody.

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19. sylvia on December 9, 2005 3:42 AM writes...

These cancer cells seem to be more intelligent than the grey cells of our scientists. It high time the grey cells convened to fight these invaders. Praying it to happen soon!

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20. TFox on December 9, 2005 11:48 AM writes...

What with world death rates constant (as reported the Onion long ago), "cure" is never a final solution, and is the wrong goal. The right goal has always been "die of somebody else's specialty". A friend has had NHL for many years, remissions and recurrence, stem cell transplant, the works. His doctor recently started harassing him about his diet, exercise and cholesterol. In other words, heart disease is now more likely to kill him than his cancer. That's the goal, that's the success story, and I suspect that there are a lot of other success stories like him walking around, even if none of them can be counted as "cured".

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21. mein on December 11, 2005 12:14 PM writes...

TFox, was your friend ever treated with Rituxan?

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22. beloml on December 12, 2005 1:57 PM writes...

The Novice Chemist: "This guy HAS to be a parody."

Don't you mean PERIDY?

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23. Susan on December 13, 2005 5:24 AM writes...

You've written a lot of interesting things here. Maybe for it doesn't mean much, but it's useful to read. Thanks for that.

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24. Mikie on December 14, 2005 5:01 PM writes...

Problem: Cancer is not one disease, it is many different genetic problems.
My money is on proteomics and DNA microarray profiling.
Having said that I still think it will be years
before anything approaching a breakthrough in treatment occurs.

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25. Jan on December 16, 2005 6:55 PM writes...

How's this for some indication of progress right around the corner? Go google zactima (aka zd6474) and medullary thyroid cancer. It is an example of molecularly targeted therapy in treating cancer. This is rare type of cancer, sometimes a component of MEN2A and MEN2b, both genetically inherited diseases, which has been a surgically-treated disease with no effective chemotherapy or radiation treatments. A phase II trial of zd6474 (a tyrosine kinase inhibitor) in the meduallry thyroid cancer patients resulted in a median fall in the tumor marker by 80%. 100% of the patients experienced over a 50% decrease in the tumor marker, some by as much as 99%. Objective decreases in tumor size have also been documented.

ALthough it is too early to tell the exact impact this will have on survival, it isn't difficult to see targeted therapies will eventually bring a different mode of treatmetnt to the cancer patient.

You scientists keep going! It may take a while but soon the pieces will come together.

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26. Shmoo on December 18, 2005 1:26 PM writes...

Andy, I think Mikie summed it up very effectively:

“Problem: Cancer is not one disease, it is many different genetic problems.”

Cancer is a very complex disease with a complex genesis and lifecycle. Even more frustrating is the fact that its causes and progression is often very different from person to person. Whenever you see a media blurb about a “cure” or a “breakthrough” by medical researchers you are seeing what is most likely an exciting new possibility targeting a specific part of the cancer lifecycle. In the past, the only treatments available were chemotherapy and/or radiation treatments that targeted the whole body and just happened to kill cancer cells a little better. The exciting part for cancer researchers is that we are developing a whole new toolbox for attacking cancer. None of these “breakthroughs” will be a cure in itself, but the hope is that as we develop more targeted therapeutics, we will be able to use the best combination to tackle each individual case.

Andy, one big problem with cancer research is that there are no really good models for cancer. As JSinger put it:

“…compounds that kill cancer cells in a dish are a dime a dozen…”

We can effectively kill cancer cells in a Petri dish. We even put tumors into mice, feed them these therapeutics, and watch the implanted tumors stop growing or disappear. The problem is that this doesn’t effectively mimic the disease in a human patient and these treatments are often ineffective in human cancer patients. Part of the “toolbox” we are developing will help us match the correct therapeutic with the correct patient, but our success rate will always be hampered until we develop better models.

On a separate topic, I think this dialogue with Andy raises another important topic. Whether Andy is real or someone trying to cause trouble, it highlights the fact that the pharmaceutical industry does a horrible job at educating the public about what we do. Most researchers are keenly aware of this problem, but the folks in corporate don’t seem to grasp this. GSK has a nice try with some of their commercials, but it just puts a friendly face on a scientist and doesn’t really educate people about what is really involved in making a drug. The current backlash against the pharmaceutical industry may not have occurred if people really understood what was involved in the whole process. The initial response to Andy was basically “you are a moron” rather than a quick explanation of where he was misinformed. I feel like big pharma often treats their customers in a similar manner. We obviously need to do a better job of explaining what pharmaceutical research has done for the whole world and how we do it. What are people’s opinions on how we should do this? Derek, is this a forum you have covered in the past?

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27. tina on December 25, 2005 6:44 AM writes...

Mikie: Cancer terrible illness. Do not give My God to whom to know about illness.

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