Thyroid Cancer Awareness Month

My mother has half a neck (missing the right sterno-cleito-mastoid muscle). She’s quite a stunning woman, tall, shapely, and she holds herself with a certain presence. With her grace and pride and sharp intelligence, she might almost be intimidating to an insecure person who first meets her, and it’s the rare person who notices this missing body part.

She has thyroid cancer to thank for the loss.

Some days I don’t feel we’ve come too far in cancer treatment—but I must hand it to the medical community. They have definitely made some progress in treating thyroid cancer–you don’t donate half your neck to the cause of thyroid cancer wellness any more.

My guess is that you weren’t worried. Thyroid cancer isn’t big on people’s radar—probably because it’s rare compared to some of the other ‘big name’ cancers.  In 2010 in the U.S., the American Thyroid Association estimated that around 45,000 people were diagnosed with thyroid cancer.  Compare that to 140,000 who received a diagnosis of colon cancer, and over 200,000 patients who were diagnosed with breast cancer.  Truly, it’s hard to keep up with the Joneses.

BUT. . .it is actually the fastest increasing cancer in both men and women. Everyday Health notes that it is also different from many adult cancers in that it is commonly diagnosed in younger people (although, I must interrupt here, their definition of ‘younger people’ should bring a smile; it’s coming:) almost 2 of 3 cases are found in people between the ages of 20 and (you ready for this?) 55. And although the initial statistics really look great, there is definitely cause for caution.

According to Cancer.net, five-year survival rate (the percentage of people who survive at least five years after the cancer is detected, excluding those who die from other diseases) for all stages of thyroid cancer is about 98%. For cancer that has spread to the regional lymph nodes, the five-year survival rate is 97%. However. .  the five-year survival rate for cancer that has spread outside the thyroid–to other body parts–that’s a much lower 54%.

So what should we really do for thyroid cancer, and for awareness of this disease that takes a backseat to more ‘dramatic’ cancers?

Well, it’s always touching when the government tries to help.

On June 12—really—in Harrisburg, PA—the Senate President Pro Tempore (it’s crucial to have a really important sounding name), one Joe Scarnati, a Republican—sponsored a resolution designating September 2012 as “Thyroid Cancer Month” in Pennsylvania.

Yes, it’s true that for years people had been working on thyroid awareness—and in that self-same month—but now we have a resolution, or at least Pennsylvanians do—adopted unanimously.

While it’s true that you could say, “too little, too late,” you could just as easily say, “the more the merrier,”

Now—there’s the bad news and the good news about treatment, depending on how you feel about body parts coming and going.  Really, once you’re diagnosed with thyroid cancer, something’s going to go. One of the more common treatments does indeed involve removing things–but, called a thyroidectomy, docs stick to removing the thyroid gland.  If you’ve potentially got some metastasis, or the doctor aims big, he may also remove lymph nodes in the neck, in order to check them for cancer cells.

Now, I don’t want anyone to be disappointed, but, bad as this may sound, no doctor today treats a young woman’s thyroid cancer by cutting out the major muscles.  If that’s what you’d always hoped for, I’d consider looking into underdeveloped countries for treatment.  My mother got what I assume was standard of care for the 1960s—although they sure took a whole lot of extra stuff.  Extreme caution, I guess.

Anyway, back to the month. Thyroid Cancer Awareness Month–which is actually observed world-wide–began at the initiation of ThyCa: (Thyroid Cancer Survivors’ Association) in 2000 as a week, in 2003 it grew to a whole month. And their page, “September Is Thyroid Cancer Awareness Month Free Materials Available Year-Round,” is really where you want to be if you want to do something–or just learn something–in honor of Thyroid Cancer Awareness month.

From the Top 10 Things to Know About Thyroid Cancer (more than 2/3 of people with thyroid cancer are women) to the article New Thyroid Cancer Diagnoses Will Set Record High Total in 2013 to lists of support groups, the site has just about everything you need to raise your own awareness–and to equip yourself to help raise others’.

The Drug That’s Getting a Second Chance: Thioridazine and Cancer Stem Cells

Even when still available, Thioridazine was anything but a first-line drug in treating psychosis or schizophrenia–and that was before it was withdrawn from the market.

In the class of the first-generation or ‘typical’ antipsychotics, its main purpose was to treat the symptoms of schizophrenia–but the National Institute of Health felt it was dangerous enough that they asserted it should only be used with people who had been treated with at least two other medications, with no results, or had experienced severe side effects with the other choices.

Even after the NIH’s restrictions, things went poorly. Known in the U.S. as Mellaril, it eventually was determined that its adverse side effect profile, including risk of cardiac arrhythmias, and, even according to its manufacturers, “sudden death,” was so severe that its manufacturer, Novartis, discontinued the drug worldwide in 2005.

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“Everybody deserves a second chance in this world.”

Thus went American actress Shannen Doherty’s philosophy. I’m not sure I’ve totally bought into her belief, but in this case the essence of it applies to medicines.

Think no further than thalidomide, used to treat nausea in pregnant women. The birth defects it caused in the fetus still haunt the public psyche. It seemed the drug could never be redeemed.

And today we use it to treat cancer, multiple myeloma, to be specific, with good results. It is a rehabilitated drug. And the possibilities researchers see for it couldn’t come at a better time.

The Cancer Prevention Coalition claims that overall five-year survival rates for all cancers have remained virtually static since 1970, from 49 to 54%, and incidences of a number of cancers are up. Lung cancer is up 30%, liver cancer 104%, brain cancer 50%–and, more relevant here, acute myeloid leukemia has increased 16%.

More and more scientists believe cure rates will improve by treating the rare and chemotherapy-resistant cancer stem cells.

Cancer stem cells exist within tumors and can replicate and turn into all types of cancer cells. But unlike normal stem cells, they don’t change into stable, non-dividing cell types. It’s a difficult situation, and much treatment has focused on wiping out the cancer cells–along with whatever else is around it–in an effort to stop the progression of the illness.

 Re-enter the formerly discredited thioridazine.
Thioridazine, like many psychotropic medications, targets the brain’s dopamine receptors. And, sure enough, leukemia stem cells express a dopamine receptor on their surface (as do breast cancer stem cells, in fact)-something no self-respecting normal blood stem cell would consider. In the lab, thioridazine located these cells.

That ability to locate the expressed dopamine receptors is a cause for hope. Scientists could use these dopamine receptors as a biomarker, thus allowing early detection and treatment of breast cancer and leukemia.

And although the drug does not kill the cancer stem cells, according to Medical News Today ,it

encourages them to differentiate and therefore exhausts the number of self-renewing cells.

And–better yet– unlike chemo and radiation, it seems to have no effects on non-cancerous cells at all.

Now this all seemed pretty promising–and pretty clear, really–as I read the reviews of the research. But I felt put in my place by the actual article, which seemed to have been written for a competition in abstruseness, and required me to re-read each line several times until I could interpret it into usable language. We do owe it to the authors to make some of their own words heard, though. Just hang on through the rough patches. The researchers summarize their fundings thus

. . . assays for both human CSCs and normal stem cells that are amenable to robust biological screens are limited. Using a discovery platform that reveals differences between neoplastic and normal human pluripotent stem cells (hPSC), we identify small molecules from libraries of known compounds that induce differentiation to overcome neoplastic self-renewal. [So far so good, if you can get over ‘neoplastic’ and ‘pluripotent,’ not words in everyone’s daily vocabulary-and the next part is smooth-sailing:] Surprisingly, thioridazine, an antipsychotic drug, selectively targets the neoplastic cells, and impairs human somatic CSCs capable of in vivo leukemic disease initiation while having no effect on normal blood SCs. The drug antagonizes dopamine receptors that are expressed on CSCs and on breast cancer cells as well. [And then we come to crescendo of acronym-abounding utterance:]  These results suggest that dopamine receptors may serve as a biomarker for diverse malignancies, demonstrate the utility of using neoplastic hPSCs for identifying CSC-targeting drugs [you with me here? We all together on those neoplastic hPSCs?], and provide support for the use of differentiation as a therapeutic strategy.

Well, having given the authors their due, we’re ready to address the final issue and close:

What now?

Bhatia and his team want the drugs available for patients use as soon as possible. So they’re ready for the next step, which is actual clinical trials, to be conducted on patients with acute myeloid leukemia who have relapsed after chemotherapy. The trials have already been designed.

Bhatia hopes to be able to put their cancer in to remission, and, more so, by targeting those cancer stem cells, actually prevent the cancer from coming back.

The drug that had to leave the schizophrenia-treatment theater, tail between its legs, may yet have a triumphant return in the world of cancer treatment. And not a moment too soon.

A Cell Donation Day That Will Live in Infamy–Part II

So back to Henrietta Lacks and her overly hardy–some say virulent–cervical cancer cells. You may recall from last post that Ms. Lacks’ cells, entitled HeLa, were taken without her permission, and without recompense to the family. They were nabbed by one Dr. George Gey, head of tissue research at Johns Hopkins, where Ms. Lacks was treated. And with his propogation of her cancerous tissues he created the closest thing we have to human immortality–a cell line that never quits.

Dr. Alan Cantwell, cancer and AIDS researcher, writes [in a truly odd piece, if truth be told] of how astonished researchers of the day were:

For some unknown reason, Henrietta’s cancer cells continued to grow vigorously. The cells did not age. Instead, if fed properly they could live and multiply indefinitely. Amazingly, her new tissue culture “cell line” proved to be “immortal.” These malignant cells became the first successful human tissue culture cell line in medical history-the now famous HeLa cell line. . .

Gey, somewhat stingy in offering the Lacks family anything, was extremely generous in sharing the HeLa cells. HeLa divided and conquered in labs throughout the world as researcher transferred them to researcher, even across international boundaries.

And then it came back to bite the scientists, and set back cancer research years.

In 1966, Stanley Gartler, a cell and molecular biologist, became the first to reveal a very unpleasant truth to the cancer research community. After locating a gene specific to African-Americans in 18 separate supposedly Caucasian cell lines, Gartler came to the conclusion that HeLa was overtaking these cells.


Forty different human cell culture lines, used extensively in labs worldwide, were contaminated with HeLa. Millions of dollars worth of published cancer research experiments were ruined. “Liver cells” and “monkey cells” used in cancer experiments turned out to be Henrietta’s cervical cancer in disguise (see Cantwell).
And then it got even worse. In 1974, a cell culture expert by the name of Walter Nelson-Rees discovered widespread contamination of cell lines with HeLa, and had the moxie to share his findings–publicly. Rees, co-author of “Henrietta Lacks, HeLa cells, and cell culture contamination,” found that

And things didn’t stay close to home. In that same year, 5 cell lines claimed to be of human lineage were sent here from the Soviet Union. All of the lines were discovered to be of HeLa origin (see Lucey & Rees).

It was a complete fiasco.

DSC_5858

Writes Stephen O’Brien from the Laboratory of Genomic Diversity, National Cancer Institute,  in Maryland, of that time:

Human emotions were on edge, red faces were appearing in the most prestigious laboratories, and discussions of the problem rapidly lost any semblance of civility. The cost, both monetary and to science, of cell line mix-ups is considerable. Hundreds of scientific reports based on fraudulent cell lines were published, and tainted research, estimated in value well in excess of 10 million dollars, was discredited. Each incident of cell contamination had a lead researcher’s name attached, and all were branded with Nelson-Rees’ “scarlet letter,” even if they had not actually caused the mix-up. Careers were derailed, epithets were slung, and science stumbled [italics mine].

And with that anger, and the threat to careers and financing, came the downfall, not of sloppy cancer research practices, but of Nelson-Rees.

An editorial published Nature, called him a “self-appointed vigilante,” his published work was referred to as the ‘hit list’ because of how damaging it could be to reputations, and he even received an anonymous telegram offering him a one-way ticket to South Africa.

Nelson-Rees bowed under the pressure and retired, and the tremendous hubbub he had created subsided for a bit. There was simply too much riding on it for the research community as a whole to accept his findings.

And, although some safeguards have been put into place to try to prevent such widescale contamination nowadays (in fact, HeLa’s unparalleled aggressiveness is so great that if a lab wants to use it, they’re not currently allowed to use any other cell line), the mess-ups continue.

The Wall Street Journal opens its article on cell contamination with the story of cancer researcher Robert Mandic, who spent years studying a rare head-and neck cancer, and finally had his article published on the topic in Oral Oncology. Turns out, he learned, he had been studying nothing other than Ms. Lacks’ cervical cancer cells. [He notified the journal which withdrew the article.]

In the 2010 article “Check your cultures! A list of cross-contaminated or misidentified cell lines,” the authors write that “Cross-contamination, in which the contaminant is another cell line, was first recognized in the 1950s but, disturbingly, remains a serious issue today.” And my guess is you won’t be surprised who the biggest culprit is.

The researchers put together a list of 360 known cross-contaminated cell lines. The most common? HeLA, contaminating 106/360, or 29%, of human cell lines.

Some scientists despair of ever being clear of the contamination.  They suggest that one of the biggest hurdles in finding a cancer cure isn’t even in penetrating the mysteries of tumor growth itself–but in scientists’ refusal to address the issue forthrightly.

John Masters, a professor at the Institute of Urology at the University College London, has had more than enough, and is skeptical that researchers will finally take notice, as he told the Journal:

Screaming and shouting, it doesn’t do any good. No one takes any notice for reasons I don’t understand. The whole ethos of science is to strive for the truth and produce a balanced argument about the evidence. Yet, all this crap is being produced.

Not to be outdone by that statement, he writes in his article “HeLa cells 50 years on: the good, the bad and the ugly,” that in the cancer community, “chaos reigns and fraud —unwitting or deliberate — is condoned.”

Inspiring, right? Breeds confidence in the system. It’s hard to explain it.

Could it be a last laugh on the part of Henrietta Lacks, perhaps? She received nothing for her contribution–but her ability to replicate and take over, messing with the scientific powers that be, continues on, unabated.

References

Capes-Davi A. Check your cultures! A list of cross-contaminated or misidentified cell lines. International Journal of Cancer 2010; 127(1):1-8.

Cantwell A. Immortal HeLa Cells And The Continuing Contamination Of Cancer And Vaccine Research, 2-7-10 at http://www.rense.com/general89/immot.htm.

Fung B. ‘Oops, Wrong Cancer': How Contaminated Cell Lines Produce Bad Research. The Atlantic; April 23, 2012.

Lucey BP, Nelson-Rees WA, Hutchins GM. Henrietta Lacks, HeLa cells, and cell culture contamination. Archives of Pathology & Laboratory Medicine 2009; 133(9):1463-7.

Marcus AD. Lab Mistakes Hobble Cancer Studies But Scientists Slow to Take Remedies. Wall Street Journal; April 20, 2011.

Masters JR. HeLa cells 50 years on: the good, the bad and the ugly. Nature Reviews Cancer 2002; 2:315-319.

Ncayiyana DJ. The extraordinary story of the life after death of Henrietta Lacks. South African Medical Journal 2011; 101(3):141.

O’Brien SJ. Cell culture forensics. Proceedings of the National Academy of Sciences 2001;  98(14): 7656–7658.

 

A Cell Donation Day That Will Live in Infamy–Part I

Henrietta Lacks was young, poor, unassuming, African-American. From Virginia, she earned her living as a tobacco farmer, happily married, had five children, and died of cervical cancer at 31.

But her story doesn’t end there. In pain and bleeding as the cancer took its toll, she was tested for syphilis and treated for venereal disease–but certainly failed to receive state of the art cancer treatment.

Her illness’ progression may have been complicated by having exactly one treatment location: In 1951, Johns Hopkins was the only hospital nearby that treated black patients. The cancer had metastasized–there was little to be done, and Ms. Lacks died in the hospital.

She was buried without a tombstone in the family cemetery, and to this day the exact location of her burial site is not known.

But, dead as she was as an early age, her body lost to the generations, Henrietta Lacks actually has a form of immortality more pervasive than anyone could have imagined.

Before she died–and without asking or even telling her–doctors took some of her tumor cells for research.

And Ms. Lacks, who, in life, was a solid, decent human being, but not extraordinary, gave to scientists something they’d been longing for, but had never been able to find–cells that could be kept alive and grown in the lab. Named HeLa cells (code for Henrietta Lacks, they were the first line of cells not to die off in the lab. This wonder cells would be shared with countless researchers throughout the years.

Keeping the cells alive was complicated procedure, to be sure, with the makings of a horror movie. Michael Gold, in his 1986 book A Conspiracy of Cells shares the requisite cellular diet (and you know I couldn’t make this up):

1. Blood from a human placenta [I didn’t ask whose]
2. Ground-up remains of a three-week-old unborn cattle embryo [for real]–and. . .
3. Fresh chicken plasma from the blood of a live chicken heart

I don’t know the chef that concocted this diet plan–but success made up for how grotesque it was.  The cells flourished beyond all expectation or hope.

These  cells lived and grew–and went on to become the first successful human cell line–ever. And they grew and grew–until there were trillions upon trillions of them. They seem to have played a role in almost every important cellular experiment for decades after their ‘birth’ in the lab.

Salk used them to research his Polio vaccine, they have been used to help develop medicines to fight cancer, the flu, and Parkinson’s disease, and have been part of the research developing gene mapping and cloning. Ms. Lacks’ cells were there, testing the effects of atomic radiation–and (and I’m not sure why on this one; my research lags behind here) they were sent into outer space.

A few posthumous honors have been granted the woman who unknowingly changed the face of medical research forever. In 1996 the state of Georgia and the mayor or Atlanta recognized Ms. Lacks for her posthumous contributions to medicine research. Just this past year Morgan State university granted her a posthumous honorary degree. And in the fall of 2013 a new school specializing in bioscience will open in Vancouver, Washington, named the Henrietta Lacks Health and Bioscience High School. Thanks. A lot.

But as the cell-explosion continued, and lab after lab worked on Ms. Lacks’ cells, no one bothered to tell the Lacks family about their wife and mother’s contribution. No one in Lacks’ family ever knew any of this for more than 20 years. When they were finally told in the 1970s, they were stunned, then angry. “That’s the main thing that’s troubl[ing],” they said. “Why was it kept such a secret?”

Companies that sold HeLa cells made billions, while the Lacks family remained poor–and numbers of them don’t even have health insurance.

To this day, no apologies were ever made, and no recompense has ever been offered to Ms. Lacks’ family.

But the story doesn’t end there.

HeLa grows so fast, and is so viable–and was shared so generously–that it shows up in all sorts of places that it shouldn’t. Researcher after researcher believed himself to be studying one form of cancer, only to find out–really quite late–that he was analyzing a certain hardy strain of cervical cancer cells. The phenomenon has ruined hundreds of research studies–and wasted millions of dollars..

Almost as if Ms. Lacks seeks posthumous revenge for the invasion of her cellular line, there is now a controversy throughout the medical research community, raising the question: Exactly how many labs and strains have HeLa cells contaminated–and how can the labs ever clean up from the massive contamination by the cervical cancer cells fed on placenta blood and embryo?

Let’s examine the havoc wreaked by HeLa in the next post.

References