Hallmarks of cancer

English: Cancer cells photographed by camera a...

English: Cancer cells photographed by camera attached to microscope in time-lapse manner. (Photo credit: Wikipedia)

II was inspired to add another blog today after a friend/former colleague of mine came in to see me and mentioned he had been reading my blog (thanks Allan).  So, today I have decided to embark on describing the hallmarks of cancer as we now understand them (hopefully using simple words and concepts as some of this does get kinda’ murky).

In 2000, a well known cancer scientists named R. Weinberg and his colleague published a review of the major hallmarks of all cancer cells (and thus of cancer itself).  In that original publication, he described six hallmarks, that was an increase in the previously established two.  There are now about eight that are widely accepted.  So, let’s start with the original two.

We all have normal tissues and cells in our body and many of the cells turnover relatively frequently.  Cellular turnover refers tot he process of dying and dividing cells.  Thus, new cells are made from dividing older cells and other old cells die off.  As the new cells are made, some of them may acquire new mutations.  Some of the cells may also have old mutations or may even harbor mutations that were inherited.  If these mutations affect the survival of the cells than we call them oncogenes (#1 hallmark).  If these mutations prevent the killing (or what is known as apoptosis, or programmed cell death) then the cells don’t die when they are supposed to (the #2 hallmark of cancer).  We have known for many years that all cancer cells derive from cells that keep growing and that don’t die.

Later, we started to appreciate that there were some other characteristics that we could ascribe to all cancer cells in addition to these two.  Instead of needing to turn on and off growth signals like normal cells, cancer cells are self sufficient in growth signals.  That means that the signals that make the cells grow, don’t turn off.  As long as their is cellular energy, then the cells keeps going.  That is hallmark #3.  Another attribute that all cancer cells have is that they are actually insensitive to growth signals, this is in addition to the fact they they evade death signals.  So, the signals that they receive from death inducing agents are either ignored or fuel growth or expansion. That is the 4th hallmark.  Two additional changes occur that are universal to all cancers, but some early cancers may not progress o this state.  One of these is the promotion of sustained blood supply to the tumor and thus the cancer cell (supplying it with nutrients and oxygen, etc.).  This 5th hallmark is also known as angiogenisis.  Looking at cancers that have advanced it is clear that they have increased vascular supply than the surrounding tissues.  Finally, the 6th hallmark of cancer is that of tissue invasion.  Aggressive cancers and the cells that make them up typically run out of food supply and become more aggressive and seek out new areas of the body.  In order to do so they need to secret products that help them ‘digest’ their environment and all of the fibrotic material that accumulates.  This 6th hallmark of cancer is also referred to as metastasis.  The cancer is usually more aggressive and serious once it has moved onto and latches onto its new location.  It is also much harder to treat.

Two newly recognized and agreed upon processes occur in cancers as well (and thus the cells that make them up).  The 7th hallmark of cancer is the ability of the cancer cells to escape the immune response.  Normally, the immune response would look at mutated proteins (that are found in most cancer cells) and try to destroy them.  However, cancer cells evolve many unique ways to evade immune destruction and recognition.  Finally, the 8th hallmark of cancer cells is something called metabolic reprogramming.  This basically means that the metabolism of the cells itself no longer mirror what the normal cell has.  The genes, energy usage, and most metabolic processes have permanently changes into a more aggressive, energy hungry pro-growth state.

Thus, as you can see, cancer is not so simple.  The cells that make up the cancer have changed in so many ways.  This is partially why it is so hard to eliminate cancer once it has taken hold.  There are quite a number of pathways involved in all 8 of these processes.  Since the early 80’s we have really learned a lot about cancer; certainly we have learned how complicated they are.  We have developed drugs against every single one of these 8 hallmarks, but we have not been able to cure most cancers and permanently eliminate many tumors (especially of caught late).

Thank you for reading and i do hope that is made cancer a bit more easy to understand.
Do visit www.cancermadesimple.com for more information.

Dr. C

Oh snap, what’s a SNP?

A Single Nucleotide Polymorphism is a change o...

A Single Nucleotide Polymorphism is a change of a nucleotide at a single base-pair location on DNA. Created using Inkscape v0.45.1. (Photo credit: Wikipedia)

OK, I don’t like it either, but scientist use so many big words and then they use so many acronyms and often think that the rest of the world uses them also.  Not only does the rest of the world have little clue about what most of them talk about, they certainly don’t know/understand/recognize the acronyms and terms.  There is said it.  Let angry scientist yell at me…won’t stop it from being true.

So, today I thought I might demystify (if possible) a term we use all the time and in this case, an acronym also.  SNP.  SNPs stand for Single Nucleotide Polymorphisms.  What?  Yes, they are a single change at the nucleotide level (one of the four letter codes that represent the entirety of our DNA, an A,C, T or G) of the DNA.  You might have heard about a mutation, which can also be a result of a change at the single nucleotide at the DNA level also.  Let me explain.

We have over 3 billion nucleotides that in essence make up the entirety of our DNA makeup.  You and I are different, so we express that DNA differently, but essentially we all have quite a similar 3 billion sequence code.  The DNA is where our functional proteins come from, although the steps to get from a piece of DNA to a protein is quite complex.  You get your DNA from your mom and dad (a combination of them) as your parents did from their parents.  So, you see, the DNA is going to be different in all of us as the mix we get from our parents is unique.  But, in general all of us who get blue eyes (let’s keep blue simple..but we know there might be many shades of blue) essentially have the same blue pigment at the DNA level and thus code for a blue protein (pigment).  Now, let’s say there is a random mutation that changes one nucleotide (again the building blocks of the DNA itself) in the blue gene.  That mutation might result in no color being made, or a different color, or even the same color if the mutation is in an unimportant part of the gene.   The point is that this mutation is random.  And it might not even occur in the cells of the eye or not even in the cells that will be given to your offspring.  It means that that mutation would only be passed down to future generations if it was in the sex cells (sperm or eggs).  If not, than it is random and a single incident mutation.

A SNP on the other hand is handed down.  It is a single nucleotide change that sticks in the chromosome (the way the DNA is bundled together….the structural unit of DNA) that is passed down through subsequent generations.  So, a SNP is a change that is maintained at the genomic level.  Have you ever heard that you can not simply give your organ to someone else, as their body may very well reject it.  Well, that is due to the presence of SNPs in the genes of the body that are known as transplant antigens.  So, your mom and dad gave you a mix of their own SNPs in their transplant antigens and you will give your future offspring a unique mix as well.  However, overall in a population, a certain number of SNPs will be present.  In other population, let’s say Asia, another set of SNPS are more frequent.  A SNPs is not a random mutation.  It is a difference in the nucleotide level (a single one) in the population due to mixing of that population over time.

So for transplants (giving someone your liver for example) you can only give the organ to a person who has the exact same set of polymorphisms in your transplant antigens.  If you have different ones that the recipient, then they will likely reject your liver (or rather their own immune system will try to remove it).

SPS are found all over the genome.  The one’s I was referring to above are functional, they actually have a known consequence.  There are many other SNPS that lie in regions where there is no known function (for example that do not code for protein).  However, if you read my post last week, you will note that those regions may not be junk at all and may be functional…in ways we don’t fully understand yet.

In summary, SNPs are single nucleotide changes that are in the DNA that are acquired by hereditary properties and exist in groups of people in a population.  Some may be functional and some non functional.  They are not mutations in that they are not random and must be inherited.  Over millions of years, some SNPS can be lost, but usually the whole set of SNPs in the genome are thought to be kept in the population (as long as the population does not die-off of course)!

I hope that was helpful and the next time you see SNP will you feel a tad bit more enlightened.

Dr. C

 

The new human genome!

A slight mutation in the matched nucleotides c...

A slight mutation in the matched nucleotides can lead to chromosomal aberrations and unintentional genetic rearrangement. (Photo credit: Wikipedia)

So this week, in over 30 different journals, a detailed study was reported on the nature of the over 3 billion nucleotides (the fundamental building blocks of genes and thus of DNA) that make up the human genome.  In the turn of this century, the human genome was completely sequenced (identified at the nucleotide level).  At that time it was thought that only 1.5% of those 3 billion plus nucleotides were functional and directly coded for proteins.  Much of the remaining 98.5% of the human DNA material in all of our chromosomes where thought to be junk DNA, thus serving little to no function.

However, this has been challenged greatly by new studies published this week suggested that as much as 80% of all the DNA in our cells are functional.  They define functional as the following: nucleotides that do not code for proteins but that does for RNA that is not translated in proteins (but can be regulatory in nature), nucleotides that themselves bind proteins, or nucleotides that affect the shape of the DNA in one way or another.  Thus is a far cry from the thought that most of the genome in our bodies is junk.

What does this mean in the real world and will it revolutionize medicine and science. It certainly means that labs all around the world working on their favorite gene or gene location will pay a lot more attention to sequences outside of the traditional gene unit (usually includes, enhancer, promoters and the introns and exons of the genes themselves).  More and more data will probably come out from labs on novel regulatory mechanisms from far away gene sequences and so on.  However, clinically t is doubtful that this new finding will bear any direct relevance to treatment and disease.  Just as the impact of the human genome was rather weak after the initial wave of euphoria, this too will pass.

Human genome

Human genome (Photo credit: Wikipedia)

Why medical community still doubts herbal remedies

English: Herbal remedies for sale in San Juan ...

English: Herbal remedies for sale in San Juan de los Lagos, Mexico (Photo credit: Wikipedia)

We have all heard it:  herbal remedies can’t be wrong, they have been used for thousands of years.  In fact, it’s true…many cultures, tribes, medicine men, etc. have been using and in essence prescribing natural plant based herbal remedies for many many years….in fact, much longer than that of modern medicine/pharmaceuticals.
So why then is the medical community reluctant to embrace herbal medicines and remedies.  Although it’s fun to poke fun of doctors, medical administrators, insurance companies, and pharmaceutical executives, the universal distrust in these types of remedies is not unfounded.  Here is a small list of reasons: 1) Many herbal remedies were found to have good affects on one particular ailment (such as stomach discomfort) and then prescribed and suggested to work in other organ system (the liver, lungs, etc.) with little or no evidence.  2) Many herbal remedies have been linked to visual cues in how they were assigned to work.  For example, it is common to find that red fruits or seed products are often given to women for bleeding conditions as blood is red and so is the remedy.  3) Many herbal remedies over the years are assigned to work on various parts of the bodies as they were harvested in certain ways- functional links.  For example, the Cantonese believe that eating pig brain will make you smart, or if you have impotency- eating of dried and ground up ox testicles will help.  Although these are not plant remedies, these types of functional or anatomical links have dominated traditional remedies.  4) The vast majority of remedies, even though many have commonalities from independent groups around the world and have been used by millions, have no properly controlled studies to show that they actually work. 5) They are prescribed and administered in widely varying fashion. The list goes on and on and these objections are fair.  That does not mean that herbal remedies don’t work, it just means we have a long way to go before modern practitioners will embrace them.

The last time that a medical compound was successfully derived from a plant and used in clinical medicine was in 1967.  That agent/drug was Taxol.  That was a long time ago?  For a while people just stopped looking for them.  However, many are now pursuing this newly popular science; namely plant medicinal chemistry with newer techniques.  Who knows, maybe one of our next blockbusters will come from a herb, plant or natural product.   It might not only save lives but also teach us identify the chemical component that works in the plant itself.

The skinny on health Supplements

daily dose

Supplements….do they actually work?  Are we wasting hundreds of dollars a year or more on products that are useless or are we spending good money on products that will benefit us and prevent us from getting ill…or better still keep cancer at bay?  This is a very VERY difficult question to answer.  I unfortunately will not give you the best answer but help point you in a direction that will help.

There are hundreds of supplemental products out there that claim to help with sleeplessness, eye sight, brain development (cognitive function), over immune health, and energy…just to name a few.  Some of these are mixtures of herbs such as fruit concoctions that are sold for various ailments and other products are vitamins, or single agents such as vitamin C, garlic, folic acid, etc.  If you have noticed, these supplements are getting more and more expensive as demand increases.  Multiple brands are competing against each other for the same product.  For example, in health care store and most pharmacies, you will see sever different companies selling fish or linseed oil that are high in omega 3 fatty acids.  The prices can differ significantly as some manufactures claim that they have more active ingredients, etc. 

However, as a consumer who is subjected to tons of adds in the newspaper, TV, and peer pressure (usually…or almost exclusively from people who have no expertise in health sciences) we are constantly pressured to take these.  How do we know what is real and what is pure crap and marketing.  As a rule of thumb, the vast majority of information out there is pure marketing…and if studies are referred to…they are typically very week and prove nothing.  That’s just a rule of thumb.  That does not mean that Omega 3 fatty acids are bad for you…for example.  It just might mean that the evidence that they actually lower blood cholesterol might be weak at best.  So, spend money at your own risk. 

Ok, this is not very helpful I know…so let me help you a little bit more.  There is a group out there who have looked at the most common supplements out there such as iron, different omega, vitamins, chocolate, green tea, honey, iron, glucosamine, and others and tried to help you determine how much evidence supports their use for the indications recommended in a help visualization.  Please see the following visual miscellanium health supplement website to see this tool: http://www.informationisbeautiful.net/play/snake-oil-supplements/

the authors of this tool have nicely ranked various health supplements in such a way that it is easy to visually see which products are likely to work and those that have no or weak evidence.  And it makes it easy to see how many studies have been done for each of the products in questions.  For example, folic acid for the prevention of birth defects is very strong and is in fact supported by the clinical community and ranked very high in this visualization.  However, vitamin C for colds is in the middle of the chart…and data suggests that the evidence for prevention of colds using vitamin C is quite weak….despite the huge number of studies that have been done.  So, saving money by not buying this product to prevent colds may be a good idea.  There are some products or supplements that show no benefits at all after the evidence has been examined.  These items are at the bottom of the chart and would be a waste of money.  An example of this would be garlic for the prevention of cancer….the evidence for this is severely lacking.  Another example is the use of coenzyme Q10 for diabetes…..zero benefit. 

So, this helpful visualization tool is backed up evidence.  Scientific publications over many years have been analyzed for each of these products.  Some products have multiple claims….some are thought to prevent cancer and colds, etc.  Remember, when ads on the TV claim that certain health products can prevent cancer, can prevent colds, and so on and so forth, you are wise to dismiss this altogether.  It is simply not true. 

In this chart the authors have drawn a ‘worth it line’.  This means that items above this line have evidence that support the claims of the manufacturer, while items below this line have less or no evidence.  Thus, green tea is below the line because the data on this is mixed…alot of data shows little benefits and some data shows benefits…conflicting at best.  I ask you to think about the following: which one would be more harmful if you took too much….green tea or certain vitamins like vitamin B2.  You would have to drink gallons of green tea before your body would be damaged by that beverage.  The liver and kidneys can handle large amounts of green tea before they might shut down.  However, vitamins in large amounts (are not only useless) can be damaging.  These are single compounds whereas tea has many thousands of compounds in tiny amounts.  So, remember this when you take supplements…some will hurt you if you take too much.  In fact, most of us get most of the vitamins and minerals we need in our food, and the extra we take in supplements add little benefit and potentially causes harm.  So, be careful when consuming these. 

So taken together….the health supplement fad is here to stay for a long time.  It is a huge money-making revenue stream for many companies.  The more claims the manufactures/companies can make the better the sales.  At the moment there is very little regulation that prevents companies for overstating the claims of their products.  These products are not regulated by the FDA which insists on hard evidence.  So, take these with caution.  Do not take too much of any one supplement…use moderation.  Take a look at the link I showed you for more information on the evidence or lack of it, for the item you take or wish to take.  In short…..be careful.

Thanks for reading and as usual, please leave me a comment or two.  Let me know what you think?  I want to make one more comment and that is that my blog is written by me and I DO NOT pay others to write as is very common.  Please do visit my web page for more information.  Cancer Made Simple

Cancer prognosis and statistics

Cancer A~

Image via Wikipedia

As I have mentioned before, cancer has a lot to do with number.  Risk, prognosis, and so on are rooted in some simple types of math.  Statistics are often thought of as cold unfeeling facts that do not help much.  The first part may be true but the last part is far from truth.  However, psychology is very important when people talk about cancer with one another.  statistics (if the numbers are good) help to overcome issues related to bias and personal feeling about things so that we can get a better handle on certain issues related to cancer.  Many of us (if not all) fall into recognizable patterns often; how many times have we heard someone tell us, my friend or relative was cured of this or that.  Most likely we remember that fact and rely on that treatment issue without much thought.  We may even rely on one persons recommendation to take a certain supplement because they swear how he/she has overcome some serious complications etc.  It’s natrual to think like this, but it’s also a bit destructive.  The ‘n’ of one is not a powerful statistic at all.  Anecdotal evidence…many people have told me this or that, is also easy to rely on.  What we miss in the ‘n’ of one or the anecdotal evidence is the others who took the same drug/supplement that had no benefits.  Or we fail to realize that the person who is telling us the evidence is biased or perhaps not accurate at all.  This is often the case for most folks who are promoting self-help, alternative medicines, or supplements…that all too often have little evidence for being effective. 

So what do we do about all of this….well think.  Ask yourself about the evidence before you start buying expensive supplements.  If the person selling you the stuff or your relative who believes in some remedy for the common cold…please ask them to produce some rational evidence to you. 

So what is prognosis?  It is a guess that doctors give that is often based on statistics from a large or even small group of patients who have had the same conditions as you.  More specifically, for cancer patients it is the prediction of the future course and outcome of a cancer and an indication of the likelihood of recovery from that cancer.  So, from this you might guess a few things.  A prognosis is not fact…it’s an educated guess.  A prognosis (an estimate for example of how long you have to live with a particular treatment for example) is limited by the ‘power’ of the number of individuals who have been previously analyzed.  So, if it’s the common forms of breast cancer the prognosis might be really accurate as there is a huge patient number that allow for very good statistical interpretation.  If it’s mesothelioma, a much more rare cancer, the prognostication might not be very accurate.  Furthermore, no two people are alike…our immune systems are different, are genetics are different, and out habits (such as eating, etc.) and thus we might not respond at all like the average patient.  So, a given prognosis is an estimate…but not final or finite.  It is a rough guideline.  Put it this way, if good statistical information is available…why not put some faith in it and listen to the doctor who gives you an estimate about your response?  If the statistical information is weak or based on one person’s advice or anecdotal evidence, why not questions the information and rely less on it?  Keep an open mind but don’t ignore previously recorded evidence.  A good prognosis will boost your confidence and have a positive impact on your thinking and a negative/poor prognosis will sap your confidence and perhaps may even have a negative impact on your health. 

This leads me to my final comment…statistics can be cold numbers that don’t reveal everything.  If the doctor gives you a poor prognostic for your survival with cancer X, you may wish to ask him what he uses for evidence.  How large is the sample size or the trial size that he is using?  He will know that information or can find it fairly quickly.  Do not give up just because you have been told your prognosis is poor.  The evidence behind that prognosis is poor and you may respond differently (the mean may not tell the whole story).  Ask more questions the more negative the news is…you owe it to yourself!!

Ok, I think I will stop now…please do ask me to clarify anything if you wish!  Thanks for reading.  Do look at cancer made simple for more information!!! 

Dr. C

The placebo effect or the placebo response

Placebo Effect (Doctor Who)

Image via Wikipedia

Evidence-based medicine for all it’s ugly by products, is here to stay.  This means that any therapies/medicines/approaches to helping patients with illness must be proven by outcomes in a controlled and documented manner.  That means just simply saying, ‘see it works’ will not cut it.  Since 1993, when the Cochrane Collaboration was formed and recommended that all studies be conducted as full ‘ Randomized Control Studies’, evidence-based medicine has dominated Western thinking.  Those who have promoted that we treat patients the same way as we have always done without properly conducting trials when possible are of course not happy with this type of medicine.  Those who promote ‘complimenary and alternative medicine or CAM‘ are also not too happy, as many state that the effectiveness of that type of therapy is based on hundreds of years of experience. However, many supporters of CAM have been conducting randomized control trials to address these concerns about real efficacies.  So far, no CAM therapies have been proven effective after these trials are done.

So this is where placebos come in to play.  A placebo is an agent that is given to a patient that does NOT contain the active ingredient or ‘device’ being tested in the experimental arm.  So, if for asthma medication treatment study that could be the inhaled drug albuterol as the experimental agent and inhaled air as a placebo.  A placebo is designed to act as a type of control.  However, it is not a true control as if it is inhaled (even air) it may be perceived to provide some benefit by the patient.  A true control would be non-intervention or nothing.  So inhaled albuterol, inhaled air as a placebo and nothing as a true negative control is a great example of a randomized control trial design.  The patient does not know which one he/she is given (the placebo or albuterol) but will know if they are in the nothing treatment arm. 

This is actually a true study designed to look at the placebo effect.  This particular study published in the New England Journal of Medicine and compared the effects of inhaled asthma drug, placebo, acupuncture, and no treatment conditions.  The interesting thing is that when all of these were compared the placebo, the acupuncture and even the no treatment conditions all showed strong subjective responses.  This means that when patients were asked how these treatments made them feel about their asthma, they were very positive in their answers.  The drug was slightly higher at about 50% subjective responses while the acupuncture and placebo were both at about 45%, not much lower.  The lowest response came from those with no intervention; 21% of those folks felt that no treatment made them feel much better.  Seems good right?  Wow, seems like we can avoid expensive drugs and just take inhaled air or go see an acupuncturist right?

No, it turns out that the second set of data is what really makes people stand up and take notice.  When you actually measure the amount of air that gets in through the lungs (by an accepted lung air measuring medical device) the data looks completely different. When they actually measure physiologic response; ONLY the inhaled drug works well and gives a measurable response.  Whereas all three other treatment (or lack of it) gave the same low response.  So, the body really does react to the drug and only very little to the non drugs (or the placebo effect). There was actually no difference in physiologic or objective responses between the non-intervention or the placebo or acupuncture.  They were the same.  The body derives zero benefit from these as compared to no treatment.  

So, not to trash the CAM believers in any way…this is only one study on Asthma and not the definitive study on all other indications where traditional chinese medicine or other CAMs may have some effects (positive not negative).  But, this is fairly drastic news for those who propose that the placebo effect may explain how CAM works…as the placebo effect (in this case) is a fallacy.  It also underscores something else very important….that is, subjective responses (I feel, he feel, she feels) are very dangerous and recording them may not be the best measurement when looking at medications and treatments.  This is a big issue now?  Do we look at objective or subjective measurements?  For evidence-based medicine, the answer is clearly objective outcomes. 

Thank you for reading…Dr. G Cancer Made Simple