Sunday, February 19, 2017

The FUTURE...?

A sunny day or a cloudy day, both stem from the same nature. Success and failure are fugue states in a quantum foam that collapse into perceived outcomes. But beneath it all is the daunting spirit of humanity to forge ahead.

Whether by words or by deeds, humans continue to imagine the future. Through science that retracts sometime from editing or art that gets plagiarized, the incremental advance of what endures, continues in the pursuit of the future.

Immunity was masqueraded in scientific circles to help in the fight against cancer many years ago alas without the tools of molecular technology. What were considered miraculous cures in cancer (no less miracles today) seem to have walked the less traveled path through the eye of the immune surveillance needle. 

Today inhibiting the Immune cellular dysfunction and enhancing the killer cell function by coopting the over-expression of the cancer cells’ exposed vulnerability, we can control and collapse the structure of this infirmity.

Many years ago, the movie Minority Report image manipulation on virtual screens has turned into a reality as two-year-old toddlers know how to do that effortlessly. 

Indeed, the convergence of technology and knowledge of molecular biology of the state of the cell and its future is determinable. For instance, today, disrupting certain cell-surface signals within the wayward cancer cell, one can propel these life-threatening mischief mongers into self-destruction (apoptosis) or targeted for cannibalism (autophagy).

Medicine continues to press against current self-imposed limits. Today’s evidentiary basis of care continues to morph into tomorrow’s therapy.

We can peer with a hand-held ultrasound into the body with amazingly accurate diagnoses. What was the realm of listening with a stethoscope can now be fairly accurately determined by sound-waves. 

Wearables are proliferating as engineering scientists and biology experts merge their respective disciplines into creating gizmos, which record vital signs that transmit to a machine and the machine via algorithms deciphers change and demands a human intervention (for now). 

Some foretell about days ahead when the human eye and touch will be a thing of the past in healthcare, but that is ways away. Humans need humans. Trust and empathy are not borne of an algorithm, yet the latter can be faked by a machine defying the Turing test almost akin to a sociopath’s maneuverings. Perhaps when we have silicon embedded in our brains to enhance our intellect and function and we can tweak function as we do today with heart defibrillators then maybe we will have arrived at the Start Trek Hologram-doctor who can cure illness with a magic gizmo wand. 

Presently however, we remain consigned to testing our technological limits of embedding gold nanowires and nano-discs to warn us of our health threats that might be inhabiting the human body. are restricted to research science. The trend to recognizing cell free DNA in a patient's blood to determine a cancer's state in the body is however in use today,

Meanwhile outside of the human body and its blood vessel highways, the streets and roads are getting ready to accommodate driverless vehicles, and air-transport drone machines to ease the burden of human travel. meanwhile, technology and Moore’s Law is constantly fanning the flames of better processing power to allow us to speed across the ends of the earth and see a holographic fellow human being in an instant with a simple act of pressing the Return button on the computer, hand held device or virtual reality device.

From the world of IFTTT we are slowly marching towards a machine driven Artificial Intelligence that will one day upend the way we live and function. Asimov’s dream just might come true and Robot Laws might yet have to be enacted to protect humanity itself from this self-recognizing robotic entity. When armies of robots designed to help the aging human race and arm themselves for self-preservation, humanity will face a test. Perhaps the soft tentacles of the gooey brain cells merged with the silicon or ceramic or biological wafer charmed by a quantum computer CPU in each cybernaut might organize the next coming of a new race? Or perhaps the endeavor might devolve this utopian future into a dystopian dust bowl. Time will tell, if there is a robot to record such history.

For its own survival, humanity will hurtle in deep sleep through deep space to reach and populate distant planets. Colonies on the Moon and Mars and perhaps on Kepler 22b might herald us into populating new planets. 

Perhaps the art of imagination will tailor the future, determined by the reality of worm-holes and tesseracts (currently in our art and inspired via mathematics), which might give us an eye into these distant lands.

With every turn of the screw…and time…

The universe awaits.

Monday, February 13, 2017


Ever wonder why 5 percent (5%) of metastatic cancer the primary site is never found! There is some enlightenment on the subject and is the purpose of this discourse.

Here are some well-known fact:

Experimental data from Ductal Carcinoma In Situ (DCIS) suggest that after “curative” treatment shows 2 -3% of cases will develop metastasis in spite of no residual primary. This is indeed the launch-pad for the inquiry.

We know that cancer cells have single or multiple constraints, which prevent them from progressing. The most important of these constraints is the Tumor suppressor genes. An example of that is the BRCA1. A mutation in that gene (disabling the function of the gene) leads to a higher risk of developing breast cancer. Consider the tumor suppressor gene as brakes in a car. Juxtaposed to the brake is the accelerator; the oncogene. An oncogene when overexpressed (driver with a lead foot) within the cell leads to cancer formation and promotion. An example of the oncogene would be HER 2-neu (erbB-2) in breast and stomach cancer. And MYC gene in lymphomagenesis.

Now researchers have tied the two processes together to come up with a composite concept in breast cancer-genesis.

The proposal based on experimental data suggests both the brake and acceleration process sequentially can go awry leading to the formation of the breast cancer cell. The tumor suppressor gene proposed in this experimental data is p38 gene (P38 mitogen-activated protein kinases are a class of mitogen-activated protein kinases (MAPKs) that are responsive to stress stimuli, such as ultraviolet and irradiation, heat shock, and osmotic shock, and are involved in cell differentiation, apoptosis and autophagy. -Wikipedia), while HER 2-neu is the promoter oncogene. The latter leads to the initiation of the Epithelial Mesenchymal Transition (EMT). It is here that the transformed cell “by melting down of the barriers and cross talk between the EP tissues” causes the transition of the breast cancer cell into distant organs. Additionally, the Progesterone Receptors play a big role in allowing mammary cells to move through the mammary gland, hollow out a tubular and the branching network of milk ducts, where the cancer cell develops. These cancer cells, migrate through tissues and via blood vessels to distant organs (liver, bones, lungs etc.) still in their G0/G1 phase and can sit around until further stimuli (stressors: hormones, smoking, drinking, diet etc.) appear, which cause them to go forth and multiply (metastasis) (2).

If the p38 is turned off and the HER 2-neu is constantly turned on (no brake, only accelerator) one can conceptualize a progressive proliferation of the mammary cell turned cancerous forming a nidus to spread via the EMT into other tissues, lymphatic spaces and blood vessels.  The Klein group showed in mice that 80% of metastasis originated from the early spread cells and not from the large tumors and the mechanism of spread was more efficient in early lesions than in large tumors (1).

Inherent in this experimental data is the suggestion that not only size of the primary tumor (where a growing primary tumor is known to cause spread to the adjacent lymphatics and lymph-nodes in a somewhat linear fashion – as most text books equate size equals the potential of stage of the disease) but also the molecular changes within the cancer cell have a part to play both in growth and spread. Hence the cases where metastases are noted first and then through elaborate histological/immunological/molecular diagnostics the primary source of the cancer is determined, are the very seeds of oncogeny.

The benefit of this understanding is both a study in ontogeny and oncogeny of the breast cell. The tautological basis of the experimental data is self-evident. From these basic science experiments, will come the genesis of better management of cancer. Determining the presence via impregnated none discs and nanowires to launch an investigation into potential sites where these wayward cells hide and molecularly targeting them to end them.

Notwithstanding the lead time bias issues, the logic here also explains the fallacy in the “time to spread” argument. It is suggested that 2/3rd of the life history of the cancer is already lived when the diagnosis is made in most cases. It is suggested in these experiments, the growth from 1 million cells (barely visible or causing signs and symptoms) to 1 billion cells (obvious tumors visible on radiological diagnostic tests), where most analyses are undertaken, time in the growth question does not appear to be a linear process and may also be dependent on molecular/hormonal/other stressor issues than believed.

Understanding reality is All.

“It was the lark, the herald of the morn,
No nightingale. Look, love, what envious streaks
Do lace the severing clouds in yonder east.
Night’s candles are burnt out, and jocund day
Stands tiptoe on the misty mountain tops.” - Shakespeare

Christoph A. Klein. Early dissemination seeds metastasis in breast cancer. Nature, 2016.
Julio A. Aguirre-Ghiso. Mechanism of early dissemination and metastasis in Her2 mammary cancer. Nature, 2016.