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Pancreatic Cancer's Achilles' Heel
ScienceNOW Daily News ^ | 21 May 2009 | Stephanie Pappas

Posted on 05/23/2009 10:05:08 PM PDT by neverdem

Enlarge ImagePicture of tumor

Blocked. Chemo drugs (green) can't penetrate a pancreatic tumor (blue). White stroma (insert) separates blood flow from tumor cells (light brown).

Credit: Stefanie Reichelt, Michal Al Jacobetz, and Kenneth P. Olive; (inset) Kenneth P. Olive

Almost 95% of pancreatic cancer patients die within 5 years of diagnosis, and traditional chemotherapy does little to save their lives. Now, cancer researchers think they know why--and how they might get around the tumor's defenses. The work "has huge ramifications for how we approach therapy of this disease," says Margaret Tempero, an oncologist at the University of California, San Francisco.

Cancers almost always grow in the duct system of the pancreas, a spongy handful of tissue nestled against the stomach that produces digestive enzymes and hormones such as insulin. Although these tumors are deadly when they spread to other parts of the body, malignant cells are surprisingly sparse in the pancreas. Biopsies typically turn up a few scattered cancer cells amid masses of stroma, webs of tough, fibrous connective tissue that look like a "big piece of gristle," says oncologist David Tuveson of the Cambridge Research Institute in the United Kingdom.

That gristle, Tuveson and his colleagues found, shields pancreatic tumors from blood-transported treatments like chemotherapy. Using mice genetically engineered to develop pancreatic cancer, the team mapped the blood supply of tumors using chemical tracers to mark blood flow. They found very few blood vessels and just a third as much circulation as in normal tissue. Human pancreatic cancer samples told a similar story: lots of fibrous tissue, few blood vessels.

If his team could shrink the stroma, Tuveson wondered, could doctors target the cancer cells hiding inside? The group focused on the whimsically named hedgehog signaling pathway, which helps organize the structure of organisms during embryonic development and promotes the growth of stroma. The researchers treated mice with IPI-926, a drug that suppresses the hedgehog pathway. Other mice got a common chemotherapy drug, whereas yet another group got IPI-926 and the chemo drug.

As the researchers had hoped, IPI-926 dramatically shrank the stroma. And there was a bonus: The drug also increased the number of blood vessels inside the tumors by threefold to fourfold. Feeding a tumor with extra blood might normally promote cancer growth, but in the case of pancreatic cancer, it was good for drug delivery; mice given a combination of chemo and IPI-926 nearly doubled their survival, from a median of 11 days to 25 days, the researchers report online today in Science. It's not a cure, Tuveson cautions, but the results leave him optimistic. "If we were to double the survival of pancreas cancer patients that had advanced disease, instead of dying in 6 months, they'd die in 12 months," he says. Compared with previous medical interventions, "that would be a bigger impact than we've ever seen."

Although other factors besides blood flow might affect chemotherapy resistance, the study "demonstrates pretty nicely that the cancer cell is not the only thing we need to be worried about," says oncologist James Abbruzzese of the M. D. Anderson Cancer Center in Houston, Texas. "We really should be paying more attention to these cancer-stroma interactions." The next step, he and Tempero say, is to find out if IPI-926 has any potential as a drug for humans and if it is safe to use on tumors outside the pancreas.


TOPICS: Culture/Society; News/Current Events; Testing
KEYWORDS: cancer; hedgehog; hedgehogsignaling; pancreaticcancer
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To: Talisker
Not to mention that many states have laws allowing physicians only the use of surgery, chemo or radiation therapy for cancer, and specifically disallow any alternative treatment. Yeah, that's for patient protection, right? Not any other illness, just cancer.

Meme? Or industry protection?

21 posted on 05/24/2009 3:58:02 AM PDT by Talisker (When you find a turtle on top of a fence post, you can be damn sure it didn't get there on it's own.)
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To: wardaddy

Chemo is not what it used to be.

I have had nine months os what is said to be brutal chemo. Not one day of nausea, no pain, I feel good, life is good and the last six months have been among the happiest.

No pain, needle sticks to ports aren’t a big deal and my major complaint is eating like a lumberjack and that I can go off traveling for weeks.

While no cure may exist, some people can rock along pretty well for more than a couple of years with stable disease.

CHemo has its complications but it is remarkably easier than I thought it would be. I would do this forever if I could live out my natural life.

Before anyone rejects a chemo protocol, they should get opinions of other people on it.


22 posted on 05/24/2009 4:30:19 AM PDT by cajungirl (no)
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To: cajungirl

major complaint is I cant go off traveling for more than two weeks,,I mistyped.


23 posted on 05/24/2009 4:32:04 AM PDT by cajungirl (no)
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To: cajungirl; wardaddy

Wardaddy, as cajungirl noted, results of chemo and radiation vary widely.

I was diagnosed with colon cancer in 1996, when I was a young 42 years old. I had surgery to remove the tumor 5 days after diagnosis, and I began radiation therapy 30 days, and chemo one week after that.

My side affects were fairly mild. My hair did not fall out, though I was down to shaving only once a week, and I didn’t need a haircut for two months. I do not recall experiencing more than brief mild nausea. I did, however, have frequent diarrhea. I subsisted on a diet of rice and chicken soup for six weeks.

I once talked with a young man of 26 who was going through severe side affects from the same regimen I was in the final stages of. He had the same colon cancer with the tumor in the same location. He was treated by the same oncologist and surgeon, with the same treatments. He had lost all his hair, suffered from constant nausea, had severe diarrhea and his white and red blood cell counts had crashed.

My point here is that experiences vary widely. Yes, one may die in utter misery, killed by the supposed treatment. One may also have less severe symptoms, and live many more years in comparative comfort. I have known people go both ways.


24 posted on 05/24/2009 5:10:25 AM PDT by jimtorr
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To: jimtorr

Ditto what you said.

I have read only 40 percent of people can finish the chemo I am doing but while not a piece of cake, it is very much easier than anticipated. Amazes me.


25 posted on 05/24/2009 5:36:24 AM PDT by cajungirl (no)
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To: KoRn
Nice thoughts.

It would help our society if they saw how much money is contributed by very very rich people to fight cancer. For example, at UT Southwestern Medical school three research and treatment buildings with over a million sq ft of space have been built with PRIVATE FUNDS. People like Boone Pickens and Harrold Simmons - good conservative leaders have DONATED over 100 million towards two of those buildings.

If you looked at the medical charts of the people in treatment you'll see every nationality, every economic level - from private pay themselves to public medicare or county hospital coverage. Nobody at any age or any income is left out of the most advanced care in the world and the buildings come from those 1% evil conservate evil rich people.

Too bad that a 60 minutes story or a 20/20 story does not tell the world about the wonderful things done by volunteers and conservative charities. But that would ruin the social liberal's picture of private vs. public money to help thiose in need. I'll vote for PRIVATE.

26 posted on 05/24/2009 7:16:16 AM PDT by q_an_a
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To: MarineMom613

I lost my 76yo father to pancreatic cancer in December, 6 months after diagnosis. He chose to do chemo because he was a caregiver for a family member and wanted to do that as long as possible. If I had it to do over, I don’t know that I would have encouraged him to do chemo. But like your mom, once he made up his mind about something...


27 posted on 05/24/2009 7:30:05 AM PDT by Palmettomom
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To: MaxMax

Go to a doctor.


28 posted on 05/24/2009 7:33:19 AM PDT by 2111USMC
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To: cajungirl

As my medical oncologist described most cancer therapies to me, they are mostly a balancing act between killing the cancer and killing the patient.

I had a lot of weird symptoms that I didn’t get into above. Strange allergic reactions, for no apparent reason.

The chemo line had to be run up a vein from my arm into the major vein leading to my heart. I had a severe vaso vagal reaction to the movement of the tube up the vein. Every time the technician moved the line a few inches, all my veins would clamp down, and my blood pressure would drop from a normal 80/120 to 40/60.

I developed an infection in my spit glands, and they swelled up so far that it looked like I was storing nuts for the winter, or had the mumps. Nobody in my oncologists practice had seen the like, and he had to get the answer off the internet!

At one point, my small intestine decided to close up shop. I couldn’t even drink a full glass of water without vomiting it back up. It tasted like beef-noodle soup, by the way. By the time I got a stomach x-ray the next day, the intestine had begun to open up again. The doctor never did have a clue why that happened. He was more interested in where I had the smoked salmon breakfast the day before.

When I moved out of California and said goodbye, the medical and radiation oncologists both thanked me for providing them with an interesting case.


29 posted on 05/24/2009 7:40:31 AM PDT by jimtorr
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To: jimtorr
blood pressure would drop from a normal 80/120 to 40/60

Ummm, that should be "120/80 to 60/40".

30 posted on 05/24/2009 7:47:09 AM PDT by jimtorr
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To: jimtorr

Oh man,,you have been thru it. Sometimes I get the feeling my oncologist will be glad to be rid of me. I ask a lot of questions and am very leery of things.

So far the chemo has not been awful. I do notice I am not up to snuff, tired alot and my tolerance for exercise is very poor.

Sounds like you had a salivary gland stone, one in the duct.


31 posted on 05/24/2009 8:25:37 AM PDT by cajungirl (no)
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To: Talisker; Sandreckoner; informavoracious; larose; RJR_fan; Prospero; Conservative Vermont Vet; ...

“... ever see a business that big voluntarily ended?”

AT&T, Smith-Corona, Tower Records, soon GM/Chrysler. Big often fails, it happens.

Big Medicine a century ago fed off infectious diseases, TB and polio leap to mind. Where are they now?


32 posted on 05/24/2009 8:30:25 AM PDT by narses (http://www.theobamadisaster.com/)
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To: xkaydet65

“The gay community’s determination to have unfettered sex is the driving force behind the spending on HIV to the detriment of diseases like pancreatic cancer.”

I agree completely, but would like to gently point out that we do ourselves harm when we cede to them the battle of words without firing a shot.

I do not use the word “gay” to indicate that a person is a sodomite, a rump ranger, a butt pirate, or a rug muncher. I will not join in the conspiracy to pretend that there is “nothing wrong with that.”

There is.


33 posted on 05/24/2009 9:03:34 AM PDT by dsc (A man with an experience is never at the mercy of a man with an argument.)
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To: cajungirl
I do notice I am not up to snuff, tired alot and my tolerance for exercise is very poor.

It sounds like your red blood cell count might be pretty low.

Sounds like you had a salivary gland stone, one in the duct.

It was most likely an infection. The Dr. treated it with massive antibiotics. He started the course with a full IV unit. Of course, all the time the IV was plugged into my arm my sinuses were pouring out snot and I was constantly sneezing.

I was not as miserable as it might appear. All of these strange things were isolated, and I was comfortable most of the time. I just had to learn techniques to limit the more unpleasant events.

Then one day six weeks after the full-time chemo ended, I woke up with no discomfort, feeling energetic for the first time in months, and ravenous. The world became a wonderful place again, and I praised God for being alive once more.

I hope you can experience the same thing.

34 posted on 05/24/2009 9:53:09 AM PDT by jimtorr
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To: KoRn
It boggles the mind that so much effort is spent researching AIDS and other STDs, which already have a cure through behavioral prevention(for the most part), while there is a deadly disease like Cancer that can strike anyone at any time.

If only the panoply of cancer were one disease. There are over two hundred types of cells in the human body, IIRC. Each has the potential for multiple mutations causing the molecular genetics to go wild causing uncontrolled growth, invasion and ofter spreading to distant parts of the body, i.e. metastasis.

35 posted on 05/24/2009 11:08:33 AM PDT by neverdem (Xin loi minh oi)
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To: diamond6
I don’t mean to be a pessamist, but, will cancer ever really be cured? There’s too much money to be made with chemotherapy and “cancer research”.

See comment# 35. Cancer is just a convenient name for all of the aberations of adult stem cell reproduction plus whatever else causes cells to go wild. Think of induced pluripotent stem cells by accident.

36 posted on 05/24/2009 11:21:48 AM PDT by neverdem (Xin loi minh oi)
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To: neverdem

Not just pancreatic cancers can screw up someone’s life pretty good...

3 years ago - came down with gall stone induced necrotic pancreatitis - was in a coma & on a ventilator for over a month... finally recovered enough to get a job and work again 16 months later.


37 posted on 05/24/2009 11:30:40 AM PDT by Keith in Iowa (ESPN MNF: 3 Putzes talking about football on TV while I'm trying to watch a game.)
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To: cajungirl

I don’t know what sort of chemo you took but I have dealt with two family members dying in the past 14 months with chemo treatment up to the futility point...Sarah Cannon Cancer Center

You werefortunate and I am thankful for that.

That is not anything like what I dealt with as caregiver.

My mother took a triplicate dose which included Avastin (blood agent)which caused stroke a after stroke after stroke. and the chemo was just awful though she didn’t vomit much...just the runs constantly.

My aunt nearby who my wife helped more than I admittedly could not stop vomiting till the end and she died extremely messed up from 5 months of cycling.

My mother actually gained a few months from a severe juice diet which I think shocks the cancer and bewilders it....we had one of those 2000 dollar juicers and juiced veggies and fruits non stop

Chemo is like a poison, you hope it kills more of the cancer than the good stuff.

I’m genuinely happy it worked for you and I did not know you were even sick but your experience is not what I dealt with.

I’ve had two heart surgeries and thought they were hard on me but they were a walk in the park compared to what I saw chemo did to my mother and aunt.

Another relative after seeing all this got sick recently and she passed on all of it and died 5 months later comfortably.

Mother would just lie on the sofa all day and eat broth....very very weak. She had colon cancer that had spread. Ditto my aunt. Other relative had advanced breast cancer.

and the bigger variable....all were old...mid 70s..and all were late stage, the Onc told us there only months or maybe 18 months tops left. Mother made a year. My aunt ...two years.

The oncologist made it clear that treatments varied by age and motivation (will). With children one will try anything as I know I sure would God forbid.

I sure hope things continue for good for you CG. As I stated before I would take even mean Chemo if it had good chances but I don’t think I would for just a a year but everyone is different. ...my aunt who rejected it was very devout Christian and had lost her husband of 50+ years two years ago..which contributes I think. My mother had a strong will to live, bless her heart she had lived with a big fear of dying all her life but as God works she did come to accept it near the end but she fought like hell. ....I would certainly take another open heart for a few years...


38 posted on 05/24/2009 11:50:10 AM PDT by wardaddy
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To: jimtorr
I think it depends on age, what sort of cancer and the chemo used....and most important...viability.

My experiences as a family member in the past year or so were Godawful....and both family members regretted taking it.

I am glad both you and CG survived and had few complications...that is wonderful.

I'm not faced with cancer yet though as I noted I've had two open hearts in 2004/2005 from congenital anomaly and that's about a year for full recovery first time (if no damage) and the second time I'm not so sure you ever completely get over it pain wise and scar tissue and lung deflation etc but still even with 75% pumping rate the quality of life is rather good.

I would use the same parameters on choosing chemo but then again....there is so much consideration...one’s affairs, children, otherwise health and so forth

I still think given less than a few years I would not want to waste a lot of that going through what my mother did but given good chances or tolerating chemo well then it's another story....you don't know till you're faced with it.

My first heart surgery was down to hours of survival left...lol...that doesn't leave a lot of room for what if? but cancer treatment is a different animal

I'm just happy it worked for yall

39 posted on 05/24/2009 12:04:17 PM PDT by wardaddy
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To: cajungirl; neverdem

I am so glad that you had a positive experience re: chemo. Cancer scares the hell out of me, my mother died of it (ovarian cancer at 52), my sister is in remission (diagnosed with Hodgkins in her early twenties); my dad has been diagnosed with prostate, melanoma and squammous skin cancer. It’s all over my family unfortunately; and I will be the first person to say that I hope I’m wrong about the money making aspect; I want this evil disease cured badly.


40 posted on 05/24/2009 1:50:12 PM PDT by diamond6 (Is SIDS preventable? www.Stopsidsnow.com)
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