Wednesday, October 29, 2014

EBOLA and the firefighters

This Ebola thing has everyone worried stiff.

Besides the mangling, the bungling and the bumbling that goes on and still does in circles of high intellect, this entire exercise is a human failing of fear. This fear is furthered by information asymmetry that plagues the senses of the many. The intangible thoughts are housed in intangible silos of il-logic. It is neither the blue pill or the red pill, but the mere act of thinking that throws us into the ethereal world of intubated existence based on nonsensical force-feed.

Assuming that you dear reader are reasonably versed in the language of today, where fear mongering is a game for thrones and every word is crafted to incite the amygdala to release some synaptic electrical impulse, then surely you realize that Ebola by in itself in the U.S. is not too much a cause for concern.

However and here is the however that everyone shudders to bring to the fore in their mind’s eye; West Africa is in trouble, a shaky economic foundation, a paltry infrastructure and a government by, for and of the government. Those countries are going to need a lot of our hard earned tax dollars in the future via the United Nations or through its barbed tongue of ridicule invoking redistribution of wealth. Now where does that leave us over here in the scrutinized, carefully configured and elegantly crafted western world? Through the worm hole of cognitive dissonance, doesn't it?

Getting back to the facts here are some that we should chew upon:

1.      1.  Ebola is a virus.
2.       2. Ebola is contagious through body fluids including saliva.
3.       3. Ebola does not spread through air – unless you are within 3 feet of a coughing infected individual or if it decides to mutate. It hasn't yet, has it? Don’t think so.But it can be aerosolized (mixed with air as in a cough associated saliva being dispersed out of the trachea at 70-200 mph with 40,000 droplets ).
4.       4. Of the 10,100 or so infected 4990 have perished, a mortality rate just under 50%.
5.       5. ONE diseased individual traveler from Liberia died on the US soil.

Now for some stubborn facts in the United States:

1.      1.  Lightning Strikes kills 6000 people annually.
2.      2.  Car wrecks kill 43,000 people or 24/100,000 hours of driving per annum.
3.      3.  General Aviation killed 444 in 2013 or 0.04% or 0.65 fatalities/100,000 flight hours
4.      4.  Tornadoes killed 908 people in 2013.

You get the drift…

Now what gives Ebola such an overwhelming emotional force that makes everyone tremble with anguish and fear?

Therein are the twin slaps of human frailty and desire. Something sinister comes this way and we don’t know what it is. If you were to peek in the theaters, they are filled with thrill seekers watching zombie movies and other blood curdling suspenseful artistic endeavoring to make one jump off the seat. Another place to look at the long lines is the bungee-jumping sites, “free fall” at adventure parks and the like. The thrill from these bete-noir is something to gloat about, but, they are a “known, known.” The risks are reasonably well mitigated and the thrill lasts a few minutes. But with Ebola there is something surreptitious, something alien, something to be feared because it cannot be easily seen, touched nor controlled.

Everyone talks about it without foundation, as an expert. From lawyers to engineers, from radio talk show hosts to TV hosts, from political pundits to artists all have an opinion to express. And the conversation thus grows and grows till it comes out of the pores of every editor of a newspaper, magazine because fear sells and they need to sell. Interestingly "experts' convey the deaths associated with Influenza as a more serious event of which we should be more concerned. Really? Influenza has a mortality rate of just under 0.01% with its annual pandemic march! Imagine Ebola on that scale?  This vortex, vicious in its intensity consumes the minds of all and then it fades as all vortices eventually do. The mental discourse moves on as this one will too.

But seriously what drives us, is the invisibility of the hazard (the risk) and its unknown quantity. It can arrive in any form, on an airplane, in the movie theater, in a crowded bus or on a stretcher in the Emergency Room of a hospital. These unknowns drive us; the quantifiers with wearables, up the proverbial wall. We want to know, to be able to see the risk and mitigate it by donning the “no skin visible, paper garments!” We want easy, identifiable transparency within the microscopic world of the microbial. We feel given our lofty sense of “know” that is how it should be. Only nature does not behave that way. Now does it?

What will Ebola do? It will do what is written in it's RNA code, namely, to go forth and multiply and survive! Ebola will over time find a happy medium of existence but before it does that there will be the parabolic curve. Every epidemiologist like a firefighter worth her/his salt would know to curb an epidemic or to douse the flame they need to burn a ring around the site. Well in our loftiest of thinking we keep expanding the index sites. What utter rubbish emanating from faulty reasoning. Sometime I wonder...

So take a deep breath and let the lawyer spokesperson spin it the way it will become music to all our ears. Let us continue to widen the circle of the exposed by not “nipping it in the bud.” Let us look for vaccines first rather than prevent the clustering so with the immune selective pressures we can force it to mutate. Let us give some free reign to the virus in the meantime and maybe it will douse its own flames as the HIV did. But then, I digress…

Ah we of such lofty thoughts and ideals don’t see the ground we walk upon.

Sunday, October 26, 2014

CANCER and the DEVIL in Tasmania

I was always fascinated by the cartoon character of the Tasmanian Devil. It has the classic lines of a naughty, rowdy, energetic devilish sort of look to it.

But then I found out after some reading that these are actually carnivorous marsupials and exist in the real world in Tasmania. They have a stocky and muscular build covered by a black fur, exude a pungent odour, are extremely loud with a annoying screech, a very keen sense of smell, and they feed with an unmatched ferocity. These creatures actually exist but have a shortened life span. Most die by four years of age. In the 1996 it was discovered that the Tasmanian Devils were developing a devil facial tumor disease (DFTD) that restricted their ability to feed and the cause of death was from starvation and organ failure. The facial tumors when studies revealed molecular characteristics of the Schwann nerve cell.

The declining population of the Tasmanian Devil was attributed to the DFTD. 

The devils are a promiscuous lot and those dominant keep a tight control on their female counterparts. The mating process leads to a lot of biting among the competitors and the male and females. The biting was noted to be the mode of transmission of the DFTD. SO here was a cancer that was transmitted by contact in a marsupial. Interestingly facing extinction the females that normally became sexually active at 2 years of age now started to become pregnant at age 1 and then soon died after the mating period by age 2 or 3. The population of the devils rapidly decreased raising an alarm and thus rendering the Tasmanian Devil as endangered species in 2004.

What interests us is the mode of transmission. Up until now we humans were peripherally interested in this phenomenon. ”Ah the poor devils, what a terrible fate to suffer from their sexual appetite,” one would say and move on. But then this article appeared about breast cancer cells and suddenly the alarm bells should be going on. The bell has been rung and cannot be un-rung!

It turns out that breast cancer cells based on this study exude exosomes, encapsulated vesicles, with their waste-products of short fragments of their RNAs. These exosomes when transplanted or via endo-phagacytosis find themselves within the interior of a normal cell have the capacity to override the nuclear machinery of that cell and convert it into a cancerous cell. It has been previously known that the exosomes transfer chemotherapy resistance, but this is the first link of transfer tumorogenesis. 

This finding has tremendous relevance to our way of thinking. Cancer transmission is more than genetic mutations passed down through generations or acquired sporadically through external influences such as chemicals and viruses and other such products of nature and man. It now appears that cancer cells by virtue of their ability to discard their effete products can do the same! ( ) and ( )

Maybe it is time to rethink our strategies and include a mechanism to subvert the cancer cell exosome production and extrusion and it's accumulated detritus that would choke off a cancer cell’s survival. Maybe?

Interesting to ponder upon, don’t you think?

Saturday, October 18, 2014

The BIG DATA Factory

We clamber for proof
Through the muddiest of spoofs
Living dangerously amidst
The high flying acts

There are ventures galore
Inspired by the vultures of yore
Singing songs without
Beginning or end

In what becomes a tale
Of words that have gone stale
Building castles of glass
That shatter with light

The monster within
Hides it's spectral kin
Forcing the ball and chain
To wreak havoc through gain

From the lofty sight
Where blindness alights
And numbers flow
With outcomes that glow

The wisdom of a few
Finally askance and askew
Turns to search the truth
Hidden deep in their soul

Might one find the fare
That lay hidden in despair
In the catacombs of dust
Filled with shards of rust

The mountain of data
Bury the layers of strata
And only shows the glint
Of someone else's dint

Where are we today
How far did we stray
Where more do we go
Before we lose sight of the goal

That intellect of man
Was made to enhance the clan
And not live in despair
Under shadows of disrepair

Where Big Data lives
And all bow to its gives
Of false gods and premise
As truth lies asleep

Only if p had values
And Odds held ratios
Standards showed no Deviation
Truth would compel us more

To find a needle in the stack of hay
That grows bigger each day
Where no light can shine
And darkness fills the decline

Only time will tell
How this deep dark well
Will unfold its truths
To those who live for proofs

Time marches on
As decay becomes the norm
Through the pseudo in science
Fills ignorance’s blithe

One day soon
When a few stop to swoon
And come to realize
That there are gremlins inside

This big data factory
That hides truth and reality
Under the guise of wisdom
To someone's narcissism

And all that was termed good
Is but darkness under the hood
Where the select flourish
From lies that self-nourish

It might be time
To climb the shoulders of giants
Remember their toil
And the sacrifices they made

See further than you've seen
Dream bigger than you've dreamt
Live better than you've lived
And think inspired!

Intuition beats the miscellany
Of numbers and bits
One piece is never all
And all is not one bit

Science lives through reason
As reason flows in logic
Both are parts of science
Both are parts of the whole

Marry logic to reason
And reason to thought
What then is in store
Is our future life's lore.

Looking for the needle?
Take this exit...

Thursday, October 16, 2014


When intellect was grace and each word imbued with wisdom, humanity craned its collective head to listen. The likes of Newton, Gallileo and Einstein, all were venerated for their reach into the hidden secrets of science and society, so much so that their bones, fingers and brain respectively, were held in awe for centuries.

Sometime in the 20th century a different core of “intellectuals” emerged. These were driven by sycophants, adoring groups and the easily influenced. Joseph Goebbels spoke of the Fuhrer as the “natural, creative instrument of divine fate.” This knee-bending worship led to the creation of tyranny that took seven years of war to demolish. And yet that same thought continues today. From the “broken individuals” who find fame and wealth in Hollywood to the young minds that create magic on a silicon wafer we are engulfed by a sea of the "adoring" and the “adored.”

Equally we find it emotionally satisfying to pin the hopes of the planet earth on the worship of a single human being, who flawed in his humanity, as all humans are, is made to be the one to stop the ocean levels to rise. When reality, cuffed and bound, eventually staggers in, the disappointment is great.

Besides our desire to adore and worship humans, we also have this uncanny want to put non-human entities on the pedestals. The oft-mentioned and mostly deferred to even in the echelons of medicine is the much adored Centers of Disease Control or CDC. The fault lines of this entity of late suggest that even though the brick and mortar in Atlanta has an imposing visage, it is still governed by a group of fallible human beings. The “hissing doorways” in their Level Four containment centers. The highly infectious bacterial agents lying in containers outside of containment areas and the recent debacle in Ebola virus strategies point to the failings of such pedestal exposed ornamental worship, especially when politics and personal fame override the charter of such entities.

Enough with this hero worship. We should finally come to an understanding that what is at play is “… a walking shadow, a poor player, that struts and frets his hour upon the stage, and then is heard no more. It is a tale told by an idiot, full of sound and fury, signifying nothing.”

Maybe we should encourage all to gain access to their potential and reap the rewards from the intellect of the many rather than venerate one to the exclusion of the many and make him or her the tyrant that any hero-worship is wont to. Maybe it is time to do some critical thinking on our own rather than rely on some propped-up patron.

Maybe we should let meritocracy rise above mediocrity for those that strive. If we are careful not to suppress it through arbitrary means for fear of loss of political power and self-enrichment and put natural constraints against limitless power, we just might have a functional society. It might be time to let Kant’s “Reason” rise to the surface in our thinking and analyses and Bentham’s “greatest happiness principle” to espouse the “nonsense on stilts” of the natural law. 

Sunday, October 5, 2014


Sometime ago an elderly man in his 80s walked into a hospital Emergency Room. He had a fever and associated symptoms of influenza. The symptoms cleared after two days in the hospital. Yet he stayed on in the hospital, moving from the Internal Medicine unit to the Intensive Care unit and thence to the Orthopedic unit and finally to the rehabilitation unit.

The crossroads of guidelines and mandates and the cross-currents of ambiguous thoughts create the bed where the conflicts between implied welfare and the resulting seeds of disastrous medicine take root.

On the third day, the potential day of his discharge he (our patient) became slightly confused. The order for an MRI was placed immediately and the results within 24 hours were negative for any pathology. The confusion continued and with it he developed a minor headache. Acetoaminophen (Tylenol) was prescribed that helped abate the headache temporarily. The confusion continued till the fifth day when he became slightly irritable. The reporting nurse asked the physician for assistance and that help came in the form of a sedative tranquilizer. The irritability subdued a bit but for the patient’s sake he had wrist restraints placed on him to protect him from falling off the bed at night.

On the seventh day, he developed constipation and an enema was ordered. During the daytime with assistance he walked to the toilet to relieve himself. Upon returning he had difficulty maintaining his balance and fell on the floor, in spite of the assistance. He was helped onto his bed. He laid there for 12 hours undisturbed due to his ordeal. On the eighth day while changing the bed sheets and rolling him over, the nurse determined his left leg was abnormally rotated. X-Rays were called for and a diagnosis of a left hip fracture was made.

After recovering from his surgery and a short stint in the Intensive Care Unit he was transferred to the orthopedic unit. All medications were renewed as before. His blood sugar levels rose requiring periodic dosing with Insulin for control. His mental disorientation waxed and waned along with the rising and falling tides of headache.

On the fourteenth day, the patient’s daughter asked the nurse what medication her father was being given. A list was proffered reluctantly. She questioned the need for the Statin drugs and a host of others including, Thorazine, Compazine, Insulin. She received appropriate answers for each of the medication and their need.

On the fifteenth day, the daughter asked that no further Statin be given to her father. The health care workers protested but the physician acquiesced to the daughter’s demand. The Statin was discontinued and on day twentieth her father was back to his former mental frame. He was discharged for home on day 21 with outpatient rehabilitation services.

This drama plays out in our institutions and at homes daily. In this case the need for the Statin to lower Cholesterol was a requirement at the institution based on the set guidelines.  Not heeding to the guideline would not win the hospital some useless award for the hospital and potentially risk the wrath of Insurers who would heave a financial penalty upon it. So they followed their protocol to the “T.” A Perfect Score! Yet, the entire chain of reactive medicine stems from the use of that particular drug in this case. Speaking of harm in medicine, maybe it is time to find the keys to that harm where there is no lamplight.

Trace back the history and you will see the folly in the Universal Guidelines that litter the medical scene. Population medicine harms the individual in such subtle ways that more harm follows if not for a careful and dedicated daughter in this case. How many daughters would question such benevolent dictates of the guidelines? Not many, I venture.

So, clearly much is to be reflected upon in our current state of medicine. As physicians are being trained to abrogate their right as critical thinkers, and legions of notepad -carriers scour the halls of the hospitals and other medical facilities in hopes of finding fault, something is gravely wrong in the field of medicine. The “evidence” we all seek to mollify our desire for the “best” practice of medicine through the lens of such correlational science is harming the very people we seek to heal.

Maybe it is time to rethink?

Monday, September 29, 2014


“Paint with an airbrush!”
“Yes but all that paint-scatter?”
“Mask the edges!”
An un-blinded Algorithm

We employ methodologies with limited views and with one broad stroke of the brush to wipeout any hidden flaws. The truth seeks but under the colossal weight of dried ink it remains muffled and hidden, like a masterpiece painting it lies submerged under the spray of a modern airbrushed abstract. Eventually the leveling scythe of assumptions and probability science shows its obverse edge.
What if… we had a blind algorithm that went about sniffing through large pieces of data, snaking its way and exploiting each path, determining the cost of each path and all successor events that preceded and followed in each of those paths to arrive at a goal that no one pre-selected, in other words, blind vectoring into a sea of options. The blind algorithm would blind the researcher and would dive down into the sea of amorphous data. The Artificial Intelligence would guide it through the maze just as a modern day Robotic vacuum cleaner dodges and bumps against furniture in a room. This would prevent the ebb and fracture of the scientific culture currently in progress.

O God, I could be bounded in a nutshell, and count myself a
king of infinite space—were it not that I have bad dreams.

Which dreams indeed are ambition, for the very
substance of the ambitious is merely the shadow of a dream.

What would happen?

We might get results that would surprise us all. It might eliminate certain prejudices of thought. It might conflate some, inflate others and deflate concretely held paradigms. It might through aggregation of such information form a shape more akin to reality then prophesied through the false gods of statistical fiat.

What then?

Would humanity consider those potential alternatives via a more clear vision rather than the dark lenses of doubt? I am afraid so. The well entrenched busy-bodies would still want to extract their pound of flesh, but their premise would be mortally weakened. Their narcissistic grist would be reduced and their mills dried would seek redemption. To reduce the risk of such posturing or "gaming" the system with the algorithm, one might consider sending a second algorithm-bot which could constantly modify the prime algorithm's behavior when under threat from outside manipulations.

Humans love to seek the truth; beneath the stone, the dark side of the moon, the distance from the moon and the elliptical orbit of the planets. They desire real evidence but often fail in their goals mired in the gutter of soft, pliable and manipulated evidence. Medical literature is bugged with a significant amount of pseudo-science. This form of pseudoscience comes from selected variable sources that attempt to create a reality that is nonexistent. These useless dribblings on our zeitgeist mar the tattered tapestry of our being even further.

A blind algorithm run amuck in a Data-warehouse would produce some sparks of discontent as it bumps against dead ends, ricochets through the “bump and grind” and the stochastic information finds the critical path to a heretofore unrealized solution. This ultimate critical path would use efficiency, expediency and find pecuniary limits to realize the least resistant and best pathway. Or, then it might just prove an existing paradigm. Such a confirmation would equally have immense credibility and usage. The flowering colorful proofs from random analytics would shed more light and do more for humanity than the gunmetal gray of a postured regulatory missive!

Imagine if a large pool of patient data demographics that included age, sex, race etc. and in addition family history, dietary history, exercise habits, thrill seeking or a quiet lifestyle, use of any prescribed and over the counter medication and myriad of other information is floating around in the dark unreflective waters. The blind algorithm would tease outputs that we may not have contemplated. Instead of selected data, univariate analytics or even controlled multivariate analytics, the randomness of “chew and spit” of the esoteric data for the “right taste” could/would reveal outputs of immeasurable weights and benefit…or not. It certainly would be worth the endeavor.  variables would then indeed be variables, not chosen and picked like fruit from a tree, the correlations would indeed be obvious and used within the algorithm and the regressions would point to the future with a focused light. The p-values would have meaning and the Confidence Intervals would be tightly bound. Even Fat tails would be obvious and not hidden under the weight of mathematical jujitsu to make “nice.”

Studies of coffee, chocolate and red wine proving goodness for the heart created through selected dataset by those industries to prove the primary aim of the researcher would indeed be a thing of the past. As John Ioannidis points out currently 54% of the studies are not validated or reproducible lends further credence to blinding the algorithm for real “Evidence’ in Evidence Based Medicine!
In the end, the numbers themselves do not deny us our humanity but the calculated decision to stop being human but the complete devotion to reliance on an obtuse and self-motivated junk science.
Let us therefore use the combinatorial force of computer science for the purpose it was designed. Let us start looking for the keys to reality in the dark and not only under the lamplights. Let us use Big Data for all its worth! 

We all have dreams…

Wednesday, September 17, 2014


 The Cancer Prevention Study II (CPS II) examined the risk of cancer mortality in obese men and women in the U.S. They reported that obesity is associated with a significant increase in mortality from multiple cancers, including esophageal, colorectal, liver, gallbladder, pancreatic, breast, endometrial, cervical, ovarian, renal, brain, kidney, and prostate cancer; non-Hodgkin lymphoma; and multiple myeloma.

 It has been estimated that overall overweight and obesity cause approximately 20% of all cancer cases.  International Agency for Research on Cancer has reported that obesity causes 39% of endometrial cancer cases.

Asia-Pacific Cohort Collaboration set out to to specifically examine the association of cancer mortality with BMI. They reported a significant increase in the risk of mortality from colon, rectal, postmenopausal breast, ovarian, cervical, and prostate cancer and leukemia in overweight and obese individuals from this population.

The CPS II study examined the association between diabetes and cancer mortality in 467,922 men and 588,321 women in the U.S. After 16 years of follow-up, they found a significantly increased risk of mortality from bladder, colon, pancreatic, and liver cancer in men and from pancreatic, colon, and breast cancer in women with diabetes. In the CPS II study, an inverse association was found between diabetes and prostate cancer mortality.

After 26 years of follow-up, in addition to finding an increased risk of mortality from bladder, pancreatic, breast, liver, and colon cancers, they reported that diabetes was associated with an increased risk of oral and pharyngeal cancer, breast cancer in men, and endometrial cancer in women.
The Metabolic Syndrome and Cancer Project (Me-Can) cohort in Austria, Sweden, and Norway is examining the association between the metabolic syndrome as a whole and its individual components on the risk of cancer. From this cohort, the investigators have reported that higher glucose levels were associated with an increased risk of liver, gallbladder, respiratory, and thyroid cancer and multiple myeloma in men, and pancreas, bladder, endometrial, cervical, and stomach cancer in women.

Syllogisms aside, if infections cause inflammations, by Giuseppe Peano’s logic, cancer must to some degree come from an infection.

A more apt question would be; does inflammation promote cancer? The answer to this statement is more apt to be a yes.

The most well-known is the disease Ulcerative Colitis. In this disease there is generalized inflammation of the colon.  This constant inflammation leads to intestinal crypt deformation and a 43% chance of colon cancer within 25-35 years.

PMNs produce enzymes/cytokines to evoke the inflammatory and immune response. The immune cells are provoked via a protein product liberated by the (TAM1) or T cell activated Macrophages. This product is called TNFa. TNFa promotes another agent called NFkB that sends signals to the immune system via IL6 (a cytokine). This signal essentially motivates the immune system with an “intruder alert” warning.

In the immune system, the NFkB is designed to eradicate the potential for injury but in the tissues the mischief it creates is a whole different ballgame.

This leads to the continuous inflammatory response and further production of the TNFa and by shared cross-talk the production of NFkB in the infected tissue cells. 

The overabundance of the NFkB leads to signaling via the STAT3 and IL6. The latter agent induces COX2, which stimulates the Prostaglandin E or PGE. This final agent then provokes the inflammatory response. The continued inflammation leads to a constant provocation of the tissue cells and a self-sustained vicious cycle of cytokine production that induces the cells to grow or proliferate. Somewhere in that confluence of this potpourri of enzymes, a genetic mutation lives or occurs and a cancer is born.

It appears that the NFkB causes about 500 different reversible and irreversible actions within the cellular DNA through epigenetics (Modulating the gene function by virtue of minor or major pressures from micro RNA, Histones etc. imposed on the genome) So not only is this cascade in flow, but other mechanisms are also being cumulated and promoted.

Specific COX-2 inhibitors (Celexecob) including aspirin and other NSAIDs (Advil. Aleve etc.) the increased incidence of polyp formation and cancer is reduced many-fold in patients with ulcerative colitis, in Familial Polyposis Coli and Inflammatory Bowel Disease.

Interestingly, the mitochondria undergo stresses via infection and inflammation by releasing Reactive Oxygen Species (ROS) and Reactive Nitrogen Species (RNS). 80% of all ROS is produced by the mitochondria. These reactive or nascent radical elements (when released within the mitochondria) lead to damage to the mitochondrial DNA (mtDNA), which leads to loss of energy needed for cell growth and function, cell senescence and finally cell death. In the aging process, mtDNA damage occurs over decades. While in infection-inflammation scenario the time is shorter. These ROS and RNS liberations are directly related to the TNFa and NFkB production.

Breast Implants: Recent studies have shown a higher risk of Malignant Lymphoma arising in the breasts of patients with breast implants. Questions remain as to the inflammatory link as the probable causality.

Mutation of the c-Myc and the K-Ras genes lead to the production of TNFa and NFkB, both within the tissue cells and the mitochondria spontaneously thus liberating the ROS and RNS (Oxidative Stressors)

Aspirin. A large meta-analysis of eight studies done by Rothwell et al revealed that those individuals talking daily aspirin had a 60% lower risk of colo-rectal cancer and a 30% lowered risk of other solid malignancies.

Natural agents: Fruits, vegetables, legumes and spices are notable in their ability to reduce inflammatory response.

Curcumin used in curry has been shown to decrease the levels of Y+TNFa and NFkB in the blood of individuals consuming curcumin when exposed to inflammatory provocations. In addition there was a reduction by 40% of abnormal crypt formation in the intestines of patients with inflammatory bowel disease (IBD), which also is proof positive.

Green Tea, Red wine, grape juice and other bioflavonoid also reduce the ROS liberation and the inflammatory response.

Hippocrates: Let food be thy medicine and medicine be thy food.”

Potential mechanisms:
Increased insulin secretion from the pancreas into the portal circulation may lead to increased hepatic growth hormone–mediated synthesis of IGF-1. High-normal levels of insulin, C-peptide, and IGF-1 have been associated with an increased risk of certain cancers in epidemiological studies.

An analysis of 12 prospective studies reported that men with serum IGF-1 levels in the highest quintile of the population range had an odds ratio of 1.38 for developing prostate cancer, compared with men with the lowest IGF-1 levels not all studies have reported positive findings.

In vitro, both IGF-1 and insulin stimulate the proliferation of tumor cells lines. In vivo animal studies have demonstrated that endogenous hyperinsulinemia increases the growth and metastasis of mammary tumors, while increased circulating IGF-1 levels increased the growth and metastases of colon cancers in mice.

Many tumors are known to overexpress the IR, and some studies have reported that higher expression of the IR is associated with a worse prognosis.

Therefore, in obesity, diabetes, and the metabolic syndrome, glucose may be playing a role in concert with hyperinsulinemia, inflammation, adipokines, and altered estrogen levels.

Similarly, increased endogenous estrogen levels have been reported to increase the risk of postmenopausal breast cancer twofold. Obesity has long been known to be associated with increased circulating estrogen levels, due to increased aromatase activity in adipose tissue. In addition, insulin-resistant women have suppressed hepatic production of sex hormone–binding globulin, leading to increased levels of free estrogen. More recent studies have also demonstrated that obese women express increased levels of aromatase in breast stromal tissues, the expression of which is increased by inflammatory mediators including TNF-α, IL-1β, prostaglandin E2, and cyclooxygenase-2 (COX-2)
The estrogen receptor (ER) and IGF-1R are known to have significant cross-talk in the normal mammary gland and breast cancer.

Obesity is considered a state of chronic inflammation. In obesity, adipocytes increase in size and have a greater number of macrophages. Adipose tissue macrophages secrete a number of inflammatory molecules including IL-6 and TNF-α.

Increased IL-6 levels have been implicated in the pathogenesis of hepatocellular carcinoma and ovarian, prostate, and breast cancer.

IL-6 has also been implicated in the development of breast cancer metastases by inducing changes in cells that lead them to have greater invasive and migration properties: a phenomenon known as epithelial-mesenchymal transition. TNF-α has also been seen to play a role in tumor promotion. TNF-α is associated with increased colon tumor growth in animal models and with more aggressive prostate cancer and in breast adipose tissue has been shown to increase the expression of aromatase. 
Studies have demonstrated cross-talk between IL-6 and epidermal growth factor receptor signaling in epidermal growth factor receptor–driven breast cancer.

Knocking down IL-6 was also associated with a decrease in the number of tumor-associated macrophages. Tumor-associated macrophages are a source for cytokines and TNF-α and may contribute to tumor growth and metastases.

Low adiponectin levels and high leptin have been associated with an increased risk of colorectal cancers in a cohort study nested within the Women’s Health Initiative cohort. Leptin is also a proangiogenic factor and increases the expression of matrix metalloproteases (MMP-2 and MMP-9) that are important for cell invasion.

The bottom line is simple: Obesity is linked with chronic Inflammation and the latter drives the wheel of misfortune (cancer).

"Live Long and Prosper: Eat less (consider fasting a few days a month a prelude to healthy living), Exercise more (Walking daily for an hour) and De-stress a bit (don't take everything seriously)."


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