 in leukemia patients. But how common is this phenomenon?)
Lethal signals: Physicians know abnormal stem cells can give rise to cancer cells (stained purple) in leukemia patients. But how common is this phenomenon?
Image: Joaquin Carrillo-Farga Photo Researchers, Inc.
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The Best Science Writing Online 2012
Showcasing more than fifty of the most provocative, original, and significant online essays from 2011, The Best Science Writing Online 2012 will change the way...
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On a sweltering August evening in 2009 Pat Elliott noticed that her feet seemed swollen. Because she had been standing for hours while teaching a workshop in Phoenix, she was not surprised. “I thought it was the heat,” she says. But her feet hurt, too, so Elliott decided to play it safe and called her doctor, who suggested she come in for some tests. Days later the marketing professional learned that she had developed an uncommon form of blood cancer called chronic myelogenous leukemia (CML).
Elliott’s cancer is the result of a genetic change that arose in one or more stem cells in her bone marrow. (Normally these stem cells give rise to various blood cells in the body.) The defect caused the stem cells and their progeny to produce an abnormal enzyme known as Bcr-Abl. This enzyme signals the marrow to produce too many immature white blood cells and allows them to persist longer than they should. The proliferating blood cells then crowd out healthy cells, damage the bone marrow and allow infections to take hold. Once these abnormal cells enter the bloodstream, they can also cause the spleen to swell and damage other organs. The pain and swelling in Elliott’s feet most likely resulted from kidney problems caused by her disease. CML usually starts off being fairly innocuous, especially if treated. It can, however, become aggressive and lethal if left untreated.
To keep her disease in check, Elliott takes a bright yellow pill daily. The medication, called imatinib (sold under the brand name Gleevec), binds to the abnormal enzyme and shuts off the proliferation signal. Without this enzyme, the extra white blood cells mature normally and die as they should. Indeed, a recent study suggests that CML patients who live at least two years after starting imatinib treatment can look forward to a normal life span. But the pill is not a cure. A small number of long-lived cancer cells persist inside Elliott’s body. If she stops taking her medication, the cancer will return.
Although imatinib keeps Elliott—and some 22,000 other CML patients in the U.S.—alive and healthy, the drug’s inability to eradicate the cancer suggests that perhaps the standard model that most researchers use to visualize how tumors grow—and the treatments that have arisen from that model—is flawed. An alternative hypothesis has recently gained traction; if it proves to be more accurate, physicians may need to adjust their therapeutic approaches, targeting their treatments to destroy particular subsets of cells within the tumor.
Two Models
Oncologists have long worked under the assumption that most tumors develop from a single cell. After a series of genetic mutations, which occur as a result of exposure to radiation, cigarette smoke, dietary choices or a genetic predisposition, this single cell begins to divide uncontrollably into more cells. Each succeeding generation of cells accumulates more genetic mistakes that make the tumor grow bigger, invade local tissues and eventually spread (metastasize) to other parts of the body. Under the standard model of cancer growth, once a tumor has gained the ability to spread, any one of the founding cell’s descendants can break off and form a new mass—which is why health authorities emphasize early diagnosis and the need to destroy all tumor cells to prevent a recurrence.
The alternative view proposes that only a handful of the cells in a tumor—known as cancer stem cells—have the ability to grow uncontrollably and spread. These cells renew themselves indefinitely (essentially making close duplicates of themselves) and also give rise to a mix of cells having different properties and a finite life span. In this way, cancer stem cells resemble the normal stem cells sprinkled throughout the body that replace old or damaged tissues, such as skin or the lining of the intestine. Unlike normal stem cells, however, cancer stem cells ignore any and all chemical signals that tell them to stop dividing. According to this alternative conception, most cells in the tumor will eventually die and so should be less dangerous. The few stem cells in the tumor, however, would be particularly deadly: if even a single cancer stem cell survived the initial therapy, it could give rise to a whole new tumor weeks, months or even years later.
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14 Comments
Add CommentMy theory is that there is no such thing as "dormancy". Patients may sometimes avoid relapse if every single cancerous cell had been eliminated. That's the easy part. The real problem is that the original cause of mutation is difficult to eliminate. For example, an Australian who works outdoors can have a melanoma lesion on the bridge of his nose completely ablated by laser, but a year later the melanoma returns in the same spot. And some brilliant cancer researcher assumes that the original cancer had not been completely eradicated as hoped, and he calls this "dormancy", but lacks an explanation for the purpose or the mechanism for "dormancy". Did this Australian quit his job as a surveyor for a mining company? Of course not, otherwise how would he be able to afford "cancer therapy"? Thus, why complicate the matter with talk of "dormancy" when it is obvious even to a child that having melanoma means that surrounding cells have incurred so much DNA damage that they will also eventually develop malignancy if exposure to UV continues. We can see a similar pattern in other cancers as well. In cervical cancer, you can excise the tumors, but not the HPV virus. In colon cancer, you can also get rid of all cancerous cells, but can you stop the neurotic anxiety caused by greed and financial mismanagement? In gliomas, how do you get the patient to stop pursuing advanced degrees with no intention of ever contributing to science? How is it that these so called "scientists" keep assuming that cancer cells are invariably surrounded by absolutely normal cells?
Reply | Report Abuse | Link to thisAn explanation for the fundamental development of tumors (cellular transformation-cancer) is in the "Warburg effect". The URL for the Wikipedia article explaining the same is:
Reply | Report Abuse | Link to thishttp://en.wikipedia.org/wiki/Warburg_effect
In papers presented before the Texas Medical Association, I further hypothesized that because lactate (hydrogenated pyruvate) and alanine have the same number of valence electrons and the same molecular weight in their natural biological states, the enzyme feedback mechanism responsible for the alanine transaminase reaction which produces alanine from pyruvate (alanine transaminase)mistakes lactate for alanine with only a minimal aberrant change in this enzyme resulting in the Warburg effect. However, although the Warburg effect is almost universal in Cancer, my hypothesis remains just a hypothesis.
How Do Tumors Originate? That is the Prime Question!
Reply | Report Abuse | Link to thisTake a look on Rumyantsev S. Hypothesis: Towards the origin of cancer epidemics and pathogenesis. Journal of Carcinogenesis 2010;9:1-7.
In contrast to the current 50-year-old hypothesis of mutant maternal tumor and its subsequent metastasis, the revealed set of evidences allowed hypothesize that potentially cancerous cell clone spreads in human population and settles some persons' bodies during cross-fertilization of parents with genetically incongruent regulators of cell dividing and tissue growth. The clone is formed and distributed in the offspring's body before postnatal ontogenesis and for many decades exists in it like sleeping populations of smallest sizes. But at a relevant time of an individual's life (mainly after 40 years of age), according to a specific program of the clone ontogenesis, the populations come into sight as constitutionally immune against prevailing regulators of cell reproduction and begin to multiple uncontrollably thus initiating the cancerous growth. The new view of cancer origin and pandemic spread supplies a framework for understanding the genetic nature of cancer epidemics and its rising incidence in the current worldwide population. It also forces one to reconsider the perspective of future investigations and reassess both the means and methods for cancer prevention and healing.
Cancer stem cell is a very important concept in cancer research. So far there is a lot of confusion in the field because people messed up three totally different concepts: embryonic stem cells, adult stem cells (either in bone marrow/circulation or residing in a specific tissue or organ) and cancer stem cells. Even no one undoubtedly purified cancer stem cells, there are already tons of thousand original research articles published in many prestigious biomedical journals on the topic. It became a white hot field even without any standard cell. That’s why you face this situation, “Cancer Stem Cells: Somewhere, Everywhere, or Nowhere?” (see link at http://www.conferencemedia.net/store/stores/aacr/aacr-101st-annual-meeting-2010-washington-dc/cancer-stem-cells-somewhere-everywhere-or-nowhere.htm ). When I attended an important stem cell meeting, I found one speaker frequently and freely changed those three concepts and I had to rush out within few minutes. Another famous scholar tried to solve so many confusions in the field, but he ended up losing himself in a complex web within few minutes after he started talking.
Reply | Report Abuse | Link to thisIn order to solve this problem the scientists and doctors really need to have a brand new mindset and fundamentally different view toward cancers. Some good viewpoints can be found at www.thedoctorxproject.com and http://www.nature.com/embor/journal/v9/n1/full/7401147.html ). Until one group can clearly show the unique characters of cancer stem cells, a lot of valuable resources will be wasted in an endless debate on some basic questions of this very interesting and critical important aspect in conquering cancer.
It appears that normal cellular reproduction is a healthy form of 'cancer' and the termination of that healthy 'cancer' -- resulting in cellular death -- is caused by unknown genetic abnormalities.
Reply | Report Abuse | Link to thisSuppose scientists, in curing abnormal cancer, allow the healthy form of 'cancer' in humans to allow cellular reproduction to continue indefinitely. Perhaps that is why trees lives for thousands of years; their cells do not contain genetic abnormalities resulting in early termination of cellular reproduction. And yet trees terminate their lives because they keep growing until gravity prevents further growth, causing them to crash to Earth.
There's an old adage "Be careful what you ask for because you might get it." Suppose science removes the barriers to aging and humans live for thousands of years. Now suppose humans grow slowly like trees, so slowly nobody notices their miniscule increase in size from year to year. Their hair and finger nails get thicker over the centuries and they grow a few inches taller, until friends start noticing the difference compared to youth under the age of 100. Not until they passed the age of 1,000 would the tragic truth of their mortality become apparent when reaching 7 feet in height, with abnormally thick strands of hair and freakishly thick finger nails. At the age of 2,000 perhaps they're too large and heavy to easily walk in Earth's gravity. Like trees, perhaps the fate of humans is sealed, one way or the other?
If my suspicions that humans were never born to live forever is right, then perhaps Kurzweil is right; the future of humanity is in cyborg technologies. Either that, or one must just let go of the fear of death and trust in a higher power, 'God' as it were, that is beyond the scope of limited human mental capacity to comprehend the scope and grandeur of physics.
Reply | Report Abuse | Link to thisHere is how I will explain it for elementary students. Imagine on streets of Huston from point A to point B there are 100 alternative routs. Evolutionary pressure based on any factors (light (all kind), humidity, oxygen concentration, food etc) selects a set of routs that satisfies what we call the internal clock of linage of cells. What sets up that internal clock is pure interference of particles/strings/waves.
Reply | Report Abuse | Link to thisNow, genomic capacity is a reflection of that internal clock and as cells run out of phase time wise, an event that appears in time 0.0001 may appear again in time 0.001. Time is unifying (propagating)the classic 3 dimensions-- energy, mass, space.
1. One shell know that the origin of carbon signaling/interference of space A may affect space B. Therefore space A and B are entangled. In other words, if Mom call you on phone and you were blind, she could perfectly navigate you if a blind kid lost his leading dog.
2. The resistance of genome (that is so called oncogenes and tumor suppressors - generally transcription factors interact in a definite way that runs time forward, but remember forward can be in path A, from 1 to 100 B, That is essentially the resistance of time trick. Catching time in biology is highly problematic at that level due I shell say old fashioned paradigm.
3. Passing a trait, that is a "so called" bad genes, from generation to generation may be expressed solely due your behavior and interaction with environment. cancer cells are like states that get out of prison. To suppress those states one must act in a way that can increase capacitance. But that is tricky as there are always two constants (entropy and negentropy) that may be in independent spaces.
4. Personal screening as they do in advance hospitals attempt to identify what mediates routs , or as we should say which piece of protein loops back to a non coding RNA. Non coding RNA have the 2 main purposes, to generate methylome and to degrade piece of protein which is actually the same.Note matter converts as quickly as space diminishes.
5. The notion of stem cell is partially true although a stem cell have different grading (scaling) and each me emerge into a distinct for due again interference of all matter over time.For more details on it look below:
http://www.wseas.us/e-library/conferences/2011/Cambridge/MEDICAL/MEDICAL-09.pdf
I am interested in reading your research presented at Texas Medical Association meeting; however, your name does not appear in your comment. Can you please post a complete reference so that I can read it? Thanks,
Reply | Report Abuse | Link to thisJay Thakar, Ph.D.
jhthakar@gmail.com
Zero gravity or microgravity would solve the problem. One would wonder how children of centuries old giants would develop though.
Reply | Report Abuse | Link to thisThat wasn't very elementary seeming to me.
Reply | Report Abuse | Link to thisWhat struck me was "...At the time, Chang was working with patients at Ben Taub General Hospital in Houston, which serves the region’s 1.5 million uninsured residents." Dear Governor Perry, is this what you call a successful economy. What would the country do if you were president? Pray for care, I assume.
Reply | Report Abuse | Link to thisWhat struck me was "...At the time, Chang was working with patients at Ben Taub General Hospital in Houston, which serves the region’s 1.5 million uninsured residents." 1.5 Million uninsured residents!!!! Dear Governor Perry, is this what you call a successful economy. What would the country do if you were president? Pray for care, I assume.
Reply | Report Abuse | Link to thisI think the new theory in on the right track. Whatever mechanism is responsible for the development of embrionic stem cells into specialised healthy organ cells must be responsible for the development of uncontrollable cancer cells. Therefore,if we understand the first, we will understand the second. I think chemical information links between the cells and environmental (mother's before the birth and world's after the birth) effects on the chemical composition of cells are important.
Reply | Report Abuse | Link to thishttp://www.kptv.com/story/22201775/ohsu-nano-particle-research-could-revolutionize-disease-treatment research and hope
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